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The thyroid gland contains spherical follicles(50–500 µm in diameter). Follicle cells synthe-size the two iodine-containing thyroid hor-mones thyroxine (T4, tetraiodothyronine) andtriiodothyronine (T3). T3 and T4 are bound tothe glycoprotein thyroglobulin ( B2) andstored in the colloid of the follicles ( A1, B1).The synthesis and release of T3/T4 is controlledby the thyroliberin (= thyrotropin-releasinghormone, TRH)-thyrotropin (TSH) axis ( A,and p. 272ff.). T3 and T4 influence physicalgrowth, maturation and metabolism. The par-afollicular cells (C cells) of the thyroid glandsynthesize calcitonin ( p. 294).

Thyroglobulin, a dimeric glycoprotein (660 kDa) issynthesized in the thyroid cells. TSH stimulates thetranscription of the thyroglobulin gene. Thyro-globulin is stored in vesicles and released into the col-loid by exocytosis ( B1 and p. 30).

Iodine uptake. The iodine needed for hormonesynthesis is taken up from the bloodstream asiodide (I–). It enters thyroid cells through sec-ondary active transport by the 2Na+-I– symportcarrier (NIS) and is concentrated in the cell ca.25 times as compared to the plasma ( B2).Via cAMP, TSH increases the transport capacityof basolateral I– uptake up to 250 times. Otheranions competitively inhibit I– uptake; e.g.,ClO4

–, SCN– and NO2–.

Hormone synthesis. I– ions are continuouslytransported from the intracellular I– pool to theapical (colloidal) side of the cell by a I–/Cl– anti-porter, called pendrin, which is stimulated byTSH. With the aid of thyroid peroxidase (TPO)and an H2O2 generator, they are oxidized to el-ementary I2

0 along the microvilli on the colloidside of the cell membrane. With the help ofTPO, the I0 reacts with about 20 of the 144 ty-rosyl residues of thyroglobulin ( C). Thephenol ring of the tyrosyl residue is therebyiodinated at the 3 and/or 5 position, yielding aprotein chain containing either diiodotyrosine(DIT) residues and/or monoiodotyrosine (MIT)residues. These steps of synthesis are stimu-lated by TSH (via IP3?) and inhibited bythiouracil, thiocyanate, glutathione, and otherreducing substances. The structure of the thy-roglobulin molecule allows the iodinated ty-rosyl residues to react with each other in thethyrocolloid. The phenol ring of one DIT (orMIT) molecule links with another DIT

molecule (ether bridges). The resulting thyro-globulin chain now contains tetraiodothy-ronine residues and (less) triiodothyronine resi-dues ( C). These are the storage form of T4 andT3.

TSH also stimulates T3 and T4 secretion. Theiodinated thyroglobulin in thyrocolloid are re-absorbed by the cells via endocytosis ( B3,C). The endosomes fuse with primary lyso-somes to form phagolysosomes in which thy-roglobulin is hydrolyzed by proteases. Thisleads to the release of T3 and T4 (ca. 0.2 and1–3 mol per mol of thyroglobulin, respec-tively). T3 and T4 are then secreted into thebloodstream ( B3). With the aid of deiodase,I– meanwhile is split from concomitantly re-leased MIT and DIT and becomes reavailablefor synthesis.

Control of T3/T4 secretion. TSH secretion bythe anterior pituitary is stimulated by TRH, ahypothalamic tripeptide ( p. 282) and in-hibited by somatostatin (SIH) ( A and p. 272).The effect of TRH is modified by T4 in theplasma. As observed with other target cells,the T4 taken up by the thyrotropic cells of theanterior pituitary is converted to T3 by 5′-deio-dase. T3 reduces the density of TRH receptors inthe pituitary gland and inhibits TRH secretionby the hypothalamus. The secretion of TSH andconsequently of T3 and T4 therefore decreases(negative feedback circuit). In neonates, coldseems to stimulate the release of TRH via neu-ronal pathways (thermoregulation, p. 226).TSH is a heterodimer (26 kDa) consisting of anα subunit (identical to that of LH and FSH) anda subunit. TSH controls all thyroid gland func-tions, including the uptake of I–, the synthesisand secretion of T3 and T4 ( A-C), the bloodflow and growth of the thyroid gland.

Goiter (struma) is characterized by diffuse or nodu-lar enlargement of the thyroid gland. Diffuse goitercan occur due to an iodine deficiency, resulting inT3/T4 deficits that ultimately lead to increased secre-tion of TSH. Chronic elevation of TSH leads to theproliferation of follicle cells, resulting in goiterdevelopment (hyperplastic goiter). This prompts anincrease in T3/T4 synthesis, which sometimes nor-malizes the plasma concentrations of T3/T4 (euthyroidgoiter). This type of goiter often persists even afterthe iodide deficiency is rectified.

Hypothyroidism occurs when TSH-driven thy-roid enlargement is no longer able to compensate forthe T3/T4 deficiency (hypothyroid goiter). This type of

Thyroid Hormones

Iron deficiency, Graves’ disease, goiter, radiotherapy and damage by radioiodine


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Plate 11.11 Thyroid Hormones I

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goiter can also occur due to a congenital distur-bance of T3/T4 synthesis (see below) or thyroid in-flammation. Hyperthyroidism occurs when a thy-roid tumor (hot node) or diffuse struma (e.g., inGrave’s disease) results in the overproduction ofT3/T4, independent of TSH. In the latter case, an auto-antibody against the TSH receptor binds to the TSHreceptor. Its effects mimic those of TSH, i.e., it stimu-lates T3/T4 synthesis and secretion.

T3/T4 transport. T3 and T4 occur at a ratio of1 : 40 in the plasma, where 99% of them(mainly T4) are bound to plasma proteins: thy-roxine-binding globulin (TBG), thyroxine-bind-ing prealbumin (TBPA), and serum albumin.TBG transports two-thirds of the T4 in theblood, while TBPA and serum albumin trans-port the rest. Less than 0.3% of the total T3/T4 inblood occurs in an unbound (free) form, al-though only the unbound molecules have aneffect on the target cells. Certain drugs split T3

and T4 from protein bonds, resulting in in-creased plasma concentrations of the free hor-mones.

Potency of T3/T4. T3 is 3–8 times morepotent than T4 and acts more rapidly (half-lifeof T3 is 1 day, that of T4 7 days). Only ca. 20% ofall circulating T3 originate from the thyroid;the other 80% are produced by the liver, kid-neys, and other target cells that cleave iodidefrom T4. The conversion of T4 to T3 is catalyzedby microsomal 5′-deiodase, which removesiodine from the 5′ position on the outer ring( D). T3 is therefore the more potent hor-mone, while T4 is mainly ascribed a storagefunction in plasma.

The inactive form of T3 called reverse T3 (rT3) is pro-duced from T4 when the iodine is split from the innerring with the aid of a 5- (not 5′-)deiodase. Approxi-mately equal amounts of T3 and rT3 are normally pro-duced in the periphery (ca. 25 µg/day). When a per-son fasts, the resulting inhibition of 5′-deiodasedecreases T3 synthesis (to save energy, see below)while rT3 synthesis increases. Pituitary 5′-deiodase isnot inhibited, so TSH secretion (unwanted in thiscase) is suppressed by the negative feedback.

T3/T4 receptors are hormone-sensitive tran-scription factors located in the cell nuclei. Hor-mone–receptor complexes bind to regulatorproteins of certain genes in the nuclei and in-fluence their transcription.

The actions of T3/T4 are numerous andmainly involve the intermediate metabolism.The thyroid hormones increase the number ofmitochondria and its cristae, increase Na+-K+-ATPase activity and modulate the cholesterolmetabolism. This results in an increase inenergy turnover and a corresponding rise in O2

consumption and heat production. T3 alsospecifically stimulates heat production by in-creasing the expression of the uncoupling pro-tein thermogenin in brown fat ( p. 224). T3

also influences the efficacy of other hormones.Insulin, glucagon, GH and epinephrine losetheir energy turnover-increasing effect in hy-pothyroidism, whereas the sensitivity to epi-nephrine increases (heart rate increases, etc.)in hyperthyroidism. T3 is thought to increasethe density of -adrenoceptors. T3 also stimu-lates growth and maturation, especially of thebrain and bones.

Cretinism occurs due to neonatal T3/T4 deficienciesand is marked by growth and maturation disorders(dwarfism, delayed sexual development, etc.) andcentral nervous disorders (intelligence deficits,seizures, etc.). The administration of thyroid hor-mones in the first six months of life can prevent or re-duce some of these abnormalities.

Iodine metabolism ( D). Iodine circulates inthe blood as either (1) inorganic I– (2–10 µg/L),(2) organic non-hormonal iodine (traces) and(3) protein-bound iodine (PBI) within T3 and T4

(35–80 µg iodine/L). The average daily require-ment of iodine is ca. 150 µg; larger quantitiesare required in fever and hyperthyroidism (ca.250–500 µg/day). Iodine excreted from thebody must be replaced by the diet ( D). Seasalt, seafood, and cereals grown in iodine-richsoil are rich in iodine. Iodized salt is often usedto supplement iodine deficiencies in the diet.Since iodine passes into the breast milk, nurs-ing mothers have a higher daily requirement ofiodine (ca. 200 µg/day).

Thyroid Hormones (continued)

Hyperthyroidism, hypothyroidism, cretinism, myxedema, iodide uptake inhibitorsDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.12 Thyroid Hormones II

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Calcium, particularly ionized calcium (Ca2+),plays a central role in the regulation of numer-ous cell functions ( pp. 36, 62ff., 194, 278).Calcium accounts for 2% of the body weight.Ca. 99% of the calcium occurs in bone while 1%is dissolved in body fluids. The total calciumconc. in serum is normally 2.1–2.6 mmol/L. Ca.50% of it is free Ca2+ (1.1–1.3 mmol/L) while ca.10% is bound in complexes and 40% is bound toproteins (mainly albumin; p. 180).

Calcium protein binding increases as the pHof the blood rises since the number of Ca2+

binding sites on protein molecules also riseswith the pH. The Ca2+ conc. accordinglydecreases in alkalosis and rises in acidosis (byabout 0.21 mmol/L Ca2+ per pH unit). Alkalosis(e.g., due to hyperventilation) and hypocal-cemia (see below) can therefore lead to tetany.

The calcium metabolism is tightly regulatedto ensure a balanced intake and excretion ofCa2+ ( A). The dietary intake of Ca2+ providesaround 12–35 mmol of Ca 2+ each day (1 mmol= 2 mEq = 40 mg). Milk, cheese, eggs and“hard” water are particularly rich in Ca2+.When calcium homeostasis is maintained,most of the ingested Ca2+ is excreted in thefeces, while the remainder is excreted in theurine ( p. 180). When a calcium deficiencyexists, up to 90% of the ingested Ca2+ is ab-sorbed by the intestinal tract ( A and p. 264).

Pregnant and nursing mothers have higher Ca2+ re-quirements because they must also supply the fetusor newborn infant with calcium. The fetus receivesca. 625 mmol/day of Ca2+ via the placenta, andnursed infants receive up to 2000 mmol/day via thebreast milk. In both cases, the Ca2+ is used for boneformation. Thus, many women develop a Ca2+ defi-ciency during or after pregnancy.

Phosphate metabolism is closely related to cal-cium metabolism but is less tightly controlled.The daily intake of phosphate is about 1.4 g;0.9 g of intake is absorbed and usually excretedby the kidneys ( p. 180). The phosphate con-centration in serum normally ranges from0.8–1.4 mmol/L.

Calcium phosphate salts are sparinglysoluble. When the product of Ca2+ conc. timesphosphate conc. (solubility product) exceeds acertain threshold, calcium phosphate starts toprecipitate in solutions, and the deposition ofcalcium phosphate salts occurs. The salts are

chiefly deposited in the bone, but can also pre-cipitate in other organs. The infusion ofphosphate leads to a decrease in the serum cal-cium concentration since calcium phosphateaccumulates in bone. Conversely, hypo-phosphatemia leads to hypercalcemia (Ca2+ isreleased from bone).

Hormonal control. Calcium and phosphatehomeostasis is predominantly regulated byparathyroid hormone and calcitriol, but also bycalcitonin to a lesser degree. These hormonesmainly affect three organs: the intestines, thekidneys and the bone ( B and D).

Parathyrin or parathyroid hormone (PTH) isa peptide hormone (84 AA) secreted by the par-athyroid glands. Ca2+ sensors in cells of the para-thyroid glands regulate PTH synthesis andsecretion in response to changes in the plasmaconcentration of ionized Ca2+ ( p. 36). MorePTH is secreted into the bloodstream wheneverthe Ca2+ conc. falls below normal (hypo-calcemia). Inversely, PTH secretion decreaseswhen the Ca2+ level rises ( D, left panel). Theprimary function of PTH is to normalizedecreased Ca2+ conc. in the blood ( D). This isaccomplished as follows: (1) PTH activatesosteoclasts, resulting in bone breakdown andthe release of Ca2+ (and phosphate) from thebone; (2) PTH accelerates the final step of cal-citriol synthesis in the kidney, resulting in in-creased reabsorption of Ca2+ from the gut; (3) inthe kidney, PTH increases calcitriol synthesisand Ca2+ reabsorption, which is particularly im-portant due to the increased Ca2+ supply result-ing from actions (1) and (2). PTH also inhibitsrenal phosphate reabsorption ( p. 180), result-ing in hypophosphatemia. This, in turn, stimu-lates the release of Ca2+ from the bone or pre-vents the precipitation of calcium phosphate intissue (solubility product; see above).

Hypocalcemia occurs due to a deficiency (hypo-parathyroidism) or lack of efficiency (pseudohypo-parathyroidism) of PTH, which can destabilize theresting potential enough to produce muscle spasmsand tetany. These deficiencies can also lead to a sec-ondary calcitriol deficiency. An excess of PTH (hyper-parathyroidism) and malignant osteolysis overpowerthe Ca2+ control mechanisms, leading to hypercal-cemia. The long-term elevation of Ca2+ results in cal-cium deposition (e.g., in the kidneys). Ca2+ conc. ex-ceeding 3.5 mmol/L lead to coma, renal insufficiencyand cardiac arrhythmias.

Calcium and Phosphate Metabolism

Hypercalcemia, hypocalcemia, tetanus, vitamin D deficiency and substitution, osteomalaciaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.13 Calcium Metabolism I

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Calcitonin (CT), or thyrocalcitonin, is a pep-tide hormone (32 AA). It is mainly synthesizedin the parafollicular cells (C cells) of the thy-roid gland, which also contain Ca2+ sensors( p. 36). Hypercalcemia increases the plasmacalcitonin conc. ( D, right panel), whereascalcitonin can no longer be detected when thecalcium conc. [Ca2+] falls below 2 mmol/L. Cal-citonin normalizes elevated serum Ca2+ conc.mainly by acting on bone. Osteoclast activity isinhibited by calcitonin (and stimulated byPTH). Calcitonin therefore increases the up-take of Ca2+ by the bone—at least temporarily( D5). Some gastrointestinal hormones accel-erate calcitonin secretion, thereby enhancingthe postprandial absorption of Ca2+ by bone.These effects (and perhaps the restraining ef-fect of calcitonin on digestive activities) func-tion to prevent postprandial hypercalcemiaand the (unwanted) inhibition of PTH secre-tion and increased renal excretion of the justabsorbed Ca2+. Calcitonin also acts on the kid-neys ( D6).

Calcitriol (1,25-(OH)2-cholecalciferol) is alipophilic, steroid-like hormone synthesizedas follows ( C): Cholecalciferol (vitamin D3)is produced from hepatic 7-dehydrocholesterolin the skin via an intermediate product (pre-vitamin D) in response to UV light (sun, tan-ning lamps). Both substances bind to vitaminD-binding protein (DBP) in the blood, butcholecalciferol is preferentially transportedbecause of its higher affinity. Previtamin Dtherefore remains in the skin for a while afterUV light exposure (short-term storage). Cal-cidiol (25-OH-cholecalciferol) and calcitriolbind to DBP. An estrogen-dependent rise inDBP synthesis occurs during pregnancy.

Cholecalciferol (vitamin D3) is administered tocompensate for inadequate UV exposure. The rec-ommended daily dosage in children is approximately400 units = 10 µg; adults receive half this amount.Plant-derived ergocalciferol (vitamin D2) is equallyeffective as animal-derived vitamin D3. The followingactions apply for both forms.

Cholecalciferol is converted to calcidiol (25-OH-cholecalciferol) in the liver. Vitamin D ismainly stored as calcidiol because the plasmaconc. of calcidiol is 25 µg/L, and its half-life is15 days. Calcitriol (1,25-(OH)2-cholecalciferol),the hormonally active form, is mainly synthe-

sized in the kidneys ( C), but also in theplacenta. The plasma conc. of calcitriol is regu-lated by renal 1-α-hydroxylase (final step ofsynthesis) and by 24-hydroxylase, an enzymethat deactivates calcitriol.

The calcitriol concentration rises in response to hy-pocalcemia-related PTH secretion ( D2), tophosphate deficiency and to prolactin (lactation). Allthree inhibit 24-hydroxylase and activate 1-α-hy-droxylase. It decreases due to several negative feed-back loops, i.e. due to the fact that calcitriol (a)directly inhibits 1-α-hydroxylase, (b) inhibits para-thyroid hormone secretion, and (c) normalizes the(decreased) plasma conc. of Ca2+ and phosphate byincreasing the intestinal absorption of Ca2+ andphosphate (see below). Calcium and phosphate in-hibit 1-α-hydroxylase, while phosphate activates 24-hydroxylase.

Target organs. Calcitriol’s primary target is thegut, but it also acts on the bone, kidneys,placenta, mammary glands, hair follicles, skinetc. It binds with its nuclear receptor and in-duces the expression of calcium-binding pro-tein and Ca2+-ATPase ( pp. 280 and 36). Cal-citriol has also genomic effects. Calcitriol in-creases the intestinal absorption of Ca2+ ( D4)and promotes mineralization of the bone, but anexcess of calcitriol leads to decalcification ofthe bone, an effect heightened by PTH. Cal-citriol also increases the transport of Ca2+ andphosphate at the kidney ( p. 178), placentaand mammary glands.

In transitory hypocalcemia, the bones act as a tem-porary Ca2+ buffer ( D) until the Ca2+ deficit hasbeen balanced by a calcitriol-mediated increase inCa2+ absorption from the gut. If too little calcitriol isavailable, skeletal demineralization will lead toosteomalacia in adults and rickets in children. Vi-tamin D deficiencies are caused by inadequate di-etary intake, reduced absorption (fat maldigestion),insufficient UV light exposure, and/or reduced 1-α-hydroxylation (renal insufficiency). Skeletal deminer-alization mostly occurs due to the prolonged in-crease in parathyroid hormone secretion associatedwith chronic hypocalcemia (compensatory hyper-parathyroidism).

Calcium and Phosphate Metabolism (continued)

Rickets, osteoporosis, arrhythmias, goiter surgery, nephrocalcinosis, paresthesiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.14 Calcium Metabolism II

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Cholesterol is the precursor of steroid hor-mones ( A). Cholesterol is mainly synthe-sized in the liver. It arises from acetyl-coenzyme A (acetyl-CoA) via a number of in-termediates (e.g., squalene, lanosterol) and istransported to the endocrine glands by lipo-proteins ( p. 258). Cholesterol can be synthe-sized de novo also in the adrenal cortex, butnot in the placenta ( p. 306). Since only smallquantities of steroid hormones are stored inthe organs of origin, i.e., the adrenal cortex,ovaries, testes and placenta ( p. 306), theymust be synthesized from the cellularcholesterol pool as needed.

Cholesterol contains 27 carbon atoms. Preg-nenolone (21 C atoms; A, a), the precursor ofsteroid hormones, arises from cholesterol vianumerous intermediates. Pregnenolone alsoyields progesterone ( A, b), which is notonly a potent hormone itself (female sex hor-mone; p. 300ff.), but can act as the precursorof all other steroid hormones, i.e., (1) theadrenocortical hormones with 21 carbonatoms ( A, yellow and orange fields); (2)male sex hormones (androgens, 19 carbonatoms) synthesized in the testes ( p. 308),ovaries and adrenal cortex ( A, green andblue fields); and (3) female sex hormones(estrogens, 18 carbon atoms; p. 300ff.) syn-thesized in the ovaries ( A, red zones).

The precursors for steroid hormone synthe-sis are present in all steroid hormone glands.The type of hormone produced and the site ofhormone synthesis depend on (1) the type ofreceptors available for the superordinate con-trol hormones (ACTH, FSH, LH, etc.) and (2) thedominant enzyme responsible for changingthe structure of the steroid molecule in thehormone-producing cells of the gland in ques-tion. The adrenal cortex contains 11-, 17- and21-hydroxylases—enzymes that introduce anOH group at position C21, C17 or C11, respec-tively, of the steroid molecule ( A, top leftpanel for numerical order). Hydroxylation atC21 ( A, c)—as realized in the glomerularzone of the adrenal cortex—makes the steroidinsensitive to the effects of 17-hydroxylase. Asa result, only mineralocorticoids like corti-costerone and aldosterone (A, d ⇒ e; see alsop. 184) can be synthesized. Initial hydroxyla-tion at C17 ( A, f or g) results in the synthesis

of glucocorticoids—realized mainly in thefascicular zone of the adrenal cortex ( A, h ⇒ j⇒ k)—and 17-ketosteroids, steroids with aketo group at C17 ( A, l and m). Glucocorti-coids and 17-ketosteroids can therefore besynthesized from 17α-hydroxypregnenolonewithout the aid of progesterone ( A, n ⇒ h ⇒j).

The estrogens ( p. 304) estrone andestradiol can be directly or indirectly synthe-sized from 17-ketosteroids ( A, o ⇒ p); theyare produced indirectly by way of testosterone( A, q ⇒ r ⇒ p). The true active substance ofcertain target cells for androgens (e.g., in theprostate) is either dihydrotestosterone orestradiol ; both are synthesized from testo-sterone ( A,s and A,r, respectively).

17-ketosteroids are synthesized by the gonads(testes and ovaries) and adrenal cortex. Since theyare found in the urine, the metyrapone test of pitui-tary function is used to assess the ACTH reserve basedon urinary 17-ketosteroids levels. ACTH secretion isnormally subject to feedback control by glucocorti-coids ( p. 298). Metyrapone inhibits 11-hydroxy-lase activity ( A, d and j), which leaves ACTH un-suppressed in healthy subjects. Urinary 17-ke-tosteroid levels should therefore increase after mety-rapone administration. An abnormality of ACTHsecretion can be assumed when this does not occurin patients with a healthy adrenal cortex.

Degradation of steroid hormones occursmainly in the liver. Their OH groups are usuallylinked to sulfate or glucuronic acid moleculesand the coupling products are ultimately ex-creted in the bile or urine ( pp. 160, 183 and250). The chief urinary metabolite of the estro-gens is estriol, while that of the gestagens(mainly progesterone and 17α-hydroxypro-gesterone) is pregnanediol ( p. 306). Preg-nanediol levels in urine can be measured toconfirm or exclude pregnancy (pregnanedioltest).

Chronically increased estrogen levels due,for example, to decreased estrogen degrada-tion secondary to liver damage, can lead tobreast development (gynecomastia) in themale, among other things. For normal estrogenranges, see table on p. 304.

Biosynthesis of Steroid Hormones

Endocrine disease, virilization, congenital adrenal hyperplasiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.15 Biosynthesis of Steroid Hormones

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The mineralocortico(stero)ids aldosterone,corticosterone and 11-desoxycorticosterone( pp. 184ff. and 296) are synthesized in theglomerular zone of the adrenal cortex ( A1),whereas the glucocortico(stero)ids cortisol(hydrocortisone) and cortisone ( p. 296,small quantities) are synthesized in the fascic-ular zone ( A2). Androgens are synthesizedin the reticular zone of the adrenal cortex (A3). One of the androgens is dehydroepian-drosterone (DHEA), which is used (partly in itssulfated form, DHEA-S) to synthesize varioussex hormones in other tissues ( p. 306).

Cortisol transport. Most of the plasma corti-sol is bound to transcortin, or cortisol-bindingglobulin (CBG), a specific transport proteinwith a high-affinity binding site for cortisol.Cortisol is released in response to confor-mational changes of CBG due to inflammationetc.

CRH and ACTH regulate cortisol synthesisand secretion ( A4, A5; see also p. 272). ACTHensures also structural preservation of theadrenal cortex and supplies cortisol precur-sors, e.g., by forming cholesterol from itsesters, by de novo synthesis of cholesterol andby converting it to progesterone and 17α-hy-droxyprogesterone ( pp. 258 and 296). ACTHsecretion is stimulated by CRH and epineph-rine and inhibited (negative feedback control)by cortisol with or without the aid of CRH ( A;see also p. 275 A).

A circadian rhythm of CRH secretion and thus ofACTH and cortisol secretion can be observed. Thepeak secretion is in the morning ( B, mean values).Continuous hormone conc. sampling at short inter-vals have shown that ACTH and cortisol are secretedin 2–3-hour episodes ( B).

Receptor proteins ( p. 280) for glucocorti-coids can be found in virtually every cell. Glu-cocorticoids are vital hormones that exertnumerous effects, the most important ofwhich are listed below.

Carbohydrate and amino acid (AA) metabo-lism (see also pp. 285 A and 287 C): Cortisoluses amino acids (AA) derived from proteindegradation to increase the plasma glucoseconcentration (gluconeogenesis), which canlead to the so-called steroid diabetes in ex-treme cases. Thus, cortisol has a catabolic ef-

fect (degrades proteins) that results in the in-creased excretion of urea.

Cardiovascular function: Glucocorticoidsincrease myocardial contractility and vasocon-striction due to enhancement of cate-cholamine effects ( pp. 196 and 216). Theseare described as permissive effects of cortisol.Cortisol increases the synthesis of epinephrinein the adrenal medulla ( A6) and of angioten-sinogen in the liver ( p. 186).

Especially when administered at highdoses, glucocorticoids induce anti-inflam-matory and anti-allergic effects because theystabilize lymphokine synthesis and histaminerelease ( p. 100). On the other hand, inter-leukin-1, interleukin-2 and TNF-α (e.g., insevere infection) leads to increased secretionof CRH and high cortisol conc. (see below).

Renal function: Glucocorticoids delay the excretionof water and help to maintain a normal glomerular fil-tration rate. They can react also with aldosterone re-ceptors but are converted to cortisone by 11-hy-droxysteroid oxidoreductase in aldosterone targetcells. Normal cortisol conc. are therefore ineffectiveat the aldosterone receptor. High conc., however,have the same effect as aldosterone ( p. 184).

Gastric function: Glucocorticoids weaken theprotective mechanisms of the gastric mucosa. Thus,high-dose glucocorticoids or stress (see below) in-crease the risk of gastric ulcers ( p. 244).

Cerebral function: High glucocorticoid conc.change hypothalamic ( A) and electrical brain ac-tivity (EEG) and lead to psychic abnormalities.

Stress: Physical or mental stress increases cor-tisol secretion as a result of increased CRHsecretion and increased sympathetic tone( A). Many of the aforementioned effects ofcortisol therefore play a role in the body’s re-sponse to stress (activation of energy metabo-lism, increase in cardiac performance, etc.). Insevere physical (e.g., sepsis) or mental stress(e.g., depression), the cortisol plasma conc. re-mains at a very high level (up to 10 times thenormal value) throughout the day.

Adrenal Cortex and Glucocorticoid Synthesis

Addison disease, Cushing disease, immune suppression, anti-inflammatory and antiallergictherapyDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.16 Adrenal Cortex and Glucocorticoid Synthesis

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Oogenesis. The development of the female gametes(ova) extends from the oogonium stage to the pri-mary oocyte stage (in the primordial follicle),starting long before birth. Oogenesis therefore oc-curs much sooner than the corresponding stagesof spermatogenesis ( p. 308). The fetal phase ofoogenesis is completed by the first week of gesta-tion; these oocytes remain latent until puberty. Inthe sexually mature female, a fertilizable ovumdevelops in the graafian follicles approximately every28 days.

Menstrual cycle. After the start of sexual matu-ration, a woman starts to secrete the followinghormones in a cyclic (approx.) 28-day rhythm( A1, A2). Gonadoliberin (= gonadotropin-re-leasing hormone, Gn-RH) and dopamine (PIH)are secreted by the hypothalamus. Follicle-stimulating hormone (FSH), luteinizing hor-mone (LH) and prolactin (PRL) are released bythe anterior pituitary. Progesterone, estrogens(chiefly estradiol, E2) and inhibin are secretedby the ovaries. Gn-RH controls the pulsatilesecretion of FSH and LH ( p. 302), which inturn regulate the secretion of estradiol andprogesterone. The female sex functions arecontrolled by the periodic release of hor-mones, the purpose of which is to produce afertilizable egg in the ovaries each month( A4) and produce an environment suitablefor sperm reception (fertilization) and implan-tation of the fertilized ovum (nidation) ( A5).This cyclic activity is reflected by the monthlymenses (menstruation) which, by definition,marks the start of the menstrual cycle.

Girls in Central Europe usually have their first men-strual period (menarche) around the age of 13. Byabout age 40, the cycle becomes increasingly irregu-lar over a period of up to 10 years (climacteric) as theend of the reproductive period nears. The lastmenses (menopause) generally occurs around theage of 48–52.

A menstrual cycle can last 21–35 days. The sec-ond half of the cycle (luteal phase = secretoryphase) usually lasts 14 days, while the first half(follicular phase = proliferative phase) lasts7–21 days. Ovulation separates the two phases( A). If the cycle length varies by more than2–3 days, ovulation generally does not occur.Such anovulatory cycles account for 20% of allcycles in healthy females.

In addition to general changes in the bodyand mood, the following changes occur in the

ovaries, uterus and cervix during the men-strual cycle ( A):

Day 1: Start of menstruation (lasting about2–6 days).

Days 1–14 (variable, see above): The follicu-lar phase starts on the first day of menstrua-tion. The endometrium thickens to becomeprepared for the implantation of the fertilizedovum during the luteal phase ( A5), andabout 20 ovarian follicles mature under the in-fluence of FSH. One of these becomes the dom-inant follicle, which produces increasing quan-tities of estrogens ( A4 and p. 300). The smallcervical os is blocked by a viscous mucousplug.

Day 14 (variable, see above): Ovulation. Theamount of estrogens produced by the follicleincreases rapidly between day 12 and 13( A2). The increased secretion of LH in re-sponse to higher levels of estrogen leads toovulation ( A1, A4; see also p. 302). The basalbody temperature (measured on an emptystomach before rising in the morning) risesabout 0.5C about 1–2 days later and remainselevated until the end of the cycle ( A3). Thistemperature rise generally indicates that ovu-lation has occurred. During ovulation, the cer-vical mucus is less viscous (it can be stretchedinto long threads—spinnbarkeit) and the cervi-cal os opens slightly to allow the sperm to en-ter.

Days 14–28: The luteal phase is character-ized by the development of a corpus luteum( A4), which secretes progesterone, ( A2);an increase in mucoid secretion from theuterine glands also occurs ( A5). The endo-metrium is most responsive to progesteronearound the 22nd day of the cycle, which iswhen nidation should occur if the ovum hasbeen fertilized. Otherwise, progesterone andestrogens now inhibit Gn-RH secretion( p. 302), resulting in degeneration of thecorpus luteum. The subsequent rapid decreasein the plasma concentrations of estrogens andprogesterone ( A2) results in constriction ofendometrial blood vessels and ischemia. Thisultimately leads to the breakdown and dis-charge of the uterine lining and to bleeding,i.e., menstruation ( A5).

Oogenesis and the Menstrual Cycle

Family planning, suppression of ovulation, hormone deficiencies (menopause, anorexia)Despopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.17 Menstrual Cycle

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In sexually mature women, gonadoliberin orgonadotropin-releasing hormone (Gn-RH) issecreted in one-minute pulses every60–90 min in response to signals from variousneurotransmitters. This, in turn, induces thepulsatile secretion of FSH and LH from theanterior pituitary. If the rhythm of Gn-RHsecretion is much faster or continuous, lessFSH and LH will be secreted, which can resultin infertility. The LH : FSH secretion ratiochanges during the course of the menstrualcycle. Their release must be therefore subjectto additional factors besides Gn-RH.

The secretion of LH and FSH is, for example, subjectto central nervous effects (psychogenic factors,stress) mediated by various transmitters circulatingin the portal blood in the hypothalamic region, e.g.,norepinephrine (NE) and neuropeptide Y (NPY) aswell as by ovarian hormones, i.e., by estrogens(estrone, estradiol, estriol, etc.), progesterone andinhibin. Ovarian hormones affect Gn-RH secretion in-directly by stimulating central nerve cells that acti-vate Gn-RH-secreting neurons by way of neu-rotransmitters such as norepinephrine and NPY andinhibit Gn-RH secretion by way of GABA and opioids.

FSH production again increases toward theend of the luteal phase ( p. 301, A1). In theearly follicular phase ( A1), FSH induces theproliferation of the stratum granulosum inabout 20 follicles and stimulates the secretionof aromatase in their granulosa cells. Aro-matase catalyzes the conversion of the andro-gens testosterone and androstenedione toestradiol (E2) and estrone (E1) ( p. 297 A,steps r and o). Estrogens are synthesized intheca cells and absorbed by granulosa cells. Al-though relatively small amounts of LH aresecreted ( A1 and p. 301 A1), this is enough toactivate theca cell-based enzymes (17-hy-droxysteroid dehydrogenase and C17/C20-lyase) that help to produce the androgensneeded for estrogen synthesis. The follicle-based estrogens increase their own FSH recep-tor density. The follicle with the highest estro-gen content is therefore the most sensitive toFSH. This loop has a self-amplifying effect, andthe follicle in question is selected as the domi-nant follicle around the 6th day of the cycle( A2). In the mid-follicular phase, estrogensrestrict FSH and LH secretion (via negativefeedback control and with the aid of inhibin; A2) but later stimulate LH receptor produc-

tion in granulosa cells. These cells now alsostart to produce progesterone (start of luteini-zation), which is absorbed by the theca cells( A3) and used as precursor for further in-crease in androgen synthesis ( p. 297 A, stepsf and l).

Inhibin and estrogens secreted by the dominant fol-licle increasingly inhibit FSH secretion, therebydecreasing the estrogen production in other follicles.This leads to an androgen build-up in and apoptosisof the unselected follicles.

Increasing quantities of LH and FSH are re-leased in the late follicular phase ( A3), caus-ing a sharp rise in their plasma concentrations.The FSH peak occurring around day 13 of thecycle induces the first meiotic division of theovum. Estrogens increase the LH secretion(mainly via the hypothalamus), resulting inthe increased production of androgens andestrogens (positive feedback) and a rapid rise inthe LH conc. (LH surge). The LH peak occursaround day 14 ( A2). The follicle rupturesand discharges its ovum about 10 hours later(ovulation). Ovulation does not take place ifthe LH surge does not occur or is too slow.Pregnancy is not possible in the absence ofovulation.

Luteal phase ( A4). LH, FSH and estrogenstransform the ovarian follicle into a corpus lu-teum. It actively secretes large quantities ofprogesterone (progestational hormone),marking the beginning of the luteal phase( A). Estrogens and progesterone now inhibitthe secretion of FSH and LH directly and in-directly (e.g., through inhibition of Gn-RH; seeabove), causing a rapid drop in their plasmaconc. This negative feedback leads to a markeddrop in the plasma conc. of estrogens and pro-gesterone towards the end of the menstrualcycle (approx. day 26), thereby triggering themenses ( p. 301, A2). FSH secretion starts torise just before the start of menstruation( A4).

Combined administration of estrogens and ge-stagens during the first half of the menstrual cycleprevents ovulation. Since ovulation does not occur,pregnancy cannot take place. Most contraceptiveswork according to this principle.

Hormonal Control of the Menstrual Cycle

Infertility, menstrual cycle abnormalities, suppression of ovulation, signs of pregnancyDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.18 Hormonal Control of the Menstrual Cycle

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Estrogens are steroid hormones with 18 car-bon atoms. Estrogens are primarily synthe-sized from the 17-ketosteroid androstene-dione, but testosterone can also be a precursor( p. 297 A). The ovaries, (granulosa and thecacells), placenta ( p. 304), adrenal cortex, andin Leydig’s cells (interstitial cells) of the testes( p. 308) are the physiological sites of estro-gen synthesis.. In some target cells for testo-sterone, it must first be converted to estradiolto become active.

Estradiol (E2) is the most potent estrogen(E). The potencies of estrone (El) and estriol (E3)are relatively low in comparison (E2 : E1 : E3 =10 : 5 : 1). Most estrogens (and testosterone)circulating in the blood are bound to sex hor-mone-binding globulin (SHBG). Estriol (E3) isthe chief degradation product of estradiol (E2).

Oral administration of estradiol has vir-tually no effect because almost all of the hor-mone is removed from the bloodstream duringits first pass through the liver. Therefore, otherestrogens (with a different chemical structure)must be used for effective oral estrogen ther-apy.

Actions of Estrogens. Although estrogensplay a role in the development of female sexcharacteristics, they are not nearly as impor-tant as the androgens for male sexual develop-ment ( p. 308). The preparatory action ofestrogen is often required for optimal pro-gesterone effects (e.g., in the uterus; seebelow). Other important effects of estrogens inhuman females are as follows. Menstrual cycle. Estrogens accelerate matu-ration of the ovarian follicle during the men-strual cycle ( p. 306 and table). In the uterus,estrogen promotes the proliferation (thicken-ing) of the endometrium and increases uterinemuscle contraction. In the vagina, estrogenthickens the mucosal lining, leading to theincreased discharge of glycogen-containingepithelial cells. The liberated glycogen is usedfor an increased production of lactic acid byDöderlein’s bacillus. This lowers the vaginalpH to 3.5–5.5, thereby reducing the risk ofvaginal infection. In the cervix, the mucousplug sealing the cervical os functions as a bar-rier that prevents sperm from entering theuterus. Estrogens change the consistency ofthe cervical mucus, making it more conducive

to sperm penetration and survival, especiallyaround the time of ovulation. Fertilization. In the female body, estrogensprepare the sperm to penetrate and fertilizethe ovum (capacitation) and regulate thespeed at which the ovum travels in the fal-lopian tube. Extragonadal effects of estrogen. Duringpuberty, estrogens stimulate breast develop-ment, induces changes in the vagina and in thedistribution of subcutaneous fat, and (togetherwith androgens) stimulate the growth of pubicand axillary hair.

Since estrogens increase the coagulability ofthe blood, the administration of estrogens(e.g., in contraceptives) increases the risk ofthrombosis.

Estrogens also promote renal salt and waterretention. Estrogens slow longitudinal bonegrowth, accelerate epiphyseal closure (in menand women) and increase osteoblast activity.Estrogen deficiencies in menopause con-sequently lead to the loss of bone mass (osteo-porosis). Estrogens induce a decrease in LDLand a rise in VLDL and HDL concentrations( p. 256ff.), which is why arteriosclerosis isless common in premenopausal women thanin men. Estrogen also makes the skin thinnerand softer, reduces the sebaceous glands, andincreases fat deposits in subcutaneous tissue.Lastly, estrogen influences a number of centralnervous functions, e.g., sexual response, socialbehavior, and mood.

Plasma concentrations of estradiol and progesterone(ng/mL)

Phase Estradiol Progesteron

WomenEarly follicular phase 0.06 0.3Mid- and late follicularphase

0.1 ⇒ 0.4 1.0

Ovulation 0.4 2.0Mid-luteal phase 0.2 8–16Pregnancy 7–14 40 ⇒ 130Day 1 after parturition 20

Men 0.05 0.3

Progesterone

Progesterone, the most potent progestational(pregnancy-sustaining) hormone, is a steroid

Estrogens, Progesterone

Amenorrhea, osteoporosis, vaginal infections, virilization, thrombosis, contraceptionDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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hormone (21 C atoms) synthesized fromcholesterol via pregnenolone ( p. 297). It isproduced in the corpus luteum, ovarian fol-licles and placenta ( p. 306) of the female,and in the adrenal cortex of males and females.Like cortisol, most circulating progesterone isbound to cortisol-binding globulin (CBG =transcortin). Like estradiol (E2), most pro-gesterone is broken down during its first passthrough the liver, so oral doses of progesteroneare almost completely ineffective. Pregnane-diol is the most important degradation productof progesterone.

Actions of progesterone. The main functionsof progesterone are to prepare the female geni-tal tract for implantation and maturation ofthe fertilized ovum and to sustain pregnancy( see table). Progesterone counteracts manyof the effects induced by estrogens, but variouseffects of progesterone depend on the prepara-tory activity or simultaneous action of estro-gens. During the follicular phase, for example,estrogens increases the density of pro-gesterone receptors, while simultaneousestrogen activity is needed to induce mam-mary growth (see below). The uterus is the chief target organ of pro-gesterone. Once estrogen induces endometrialthickening, progesterone stimulates growth ofthe uterine muscle (myometrium), restruc-tures the endometrial glands ( p. 300), altersthe blood supply to the endometrium, andchanges the glycogen content. This representsthe transformation from a proliferative en-dometrium to a secretory endometrium, witha peak occurring around day 22 of the cycle.Progesterone later plays an important role inthe potential implantation (nidation) of thefertilized ovum because it reduces myometrialactivity (important during pregnancy), nar-rows the cervical os, and changes the con-sistency of the cervical mucous plug so that itbecomes virtually impregnable to sperm. Progesterone inhibits the release of LH during theluteal phase. The administration of gestagens likeprogesterone during the follicular phase inhibits ovu-lation. Together with its effects on the cervix (seeabove) and its inhibitory effect on capacitation( p. 304), progesterone can therefore have a con-traceptive effect (“mini pill”).

High levels of progesterone have an anes-thetic effect on the central nervous system.

Progesterone also increases the suscepti-bility to epileptic fits and exerts thermogenicaction, i.e., it raises the basal body temperature( p. 300). In addition, a decrease in the pro-gesterone concentration is also believed to beresponsible for the mood changes and depres-sion observed before menstruation (premen-strual syndrome, PMS) and after pregnancy(postpartum depression). In the kidneys, progesterone slightly inhib-its the effects aldosterone, thereby inducingincreased NaCl excretion.

Prolactin and Oxytocin

The secretion of prolactin (PRL) is inhibitedby prolactin-inhibiting hormone (PIH =dopamine) and stimulated by thyroliberin(TRH) ( p. 272). Prolactin increases the hy-pothalamic secretion of PIH in both men andwomen (negative feedback control). Con-versely, estradiol (E2) and progesterone inhibitPIH secretion (indirectly via transmitters, asobserved with Gn-RH; see above). Con-sequently, prolactin secretion rises signifi-cantly during the second half of the menstrualcycle and during pregnancy. Prolactin (to-gether with estrogens, progesterone, glucocor-ticoids and insulin) stimulate breast enlarge-ment during pregnancy and lactogenesis afterparturition. In breast-feeding, stimulation ofthe nerve endings in the nipples by the suck-ling infant stimulates the secretion of prolactin(lactation reflex). This also increases release ofoxytocin which triggers milk ejection and in-creases uterine contractions, thereby increas-ing lochia discharge after birth. When themother stops breast-feeding, the prolactinlevels drop, leading to the rapid stoppage ofmilk production.

Hyperprolactinemia. Stress and certain drugs in-hibit the secretion of PIH, causing an increase in pro-lactin secretion. Hypothyroidism ( p. 290) can alsolead to hyperprolactinemia, because the associatedincrease in TRH stimulates the release of prolactin.Hyperprolactinemia inhibits ovulation and leads togalactorrhea, i.e., the secretion of milk irrespective ofpregnancy. Some women utilize the anti-ovulatoryeffect of nursing as a natural method of birth control,which is often but not always effective.

Progesterone, Prolactin, Oxytocin

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Beside its other functions, the placenta pro-duces most of the hormones needed duringpregnancy ( p. 222). Ovarian hormones alsoplay a role, especially at the start of pregnancy( A).

Placental hormones. The primary hormonesproduced by the placenta are human chorionicgonadotropin (hCG), corticotropin-releasinghormone (CRH), estrogens, progesterone,human placental lactogen (hPL), and pro-opiomelanocortin (POMC; p. 282). hCG isthe predominant hormone during the firsttrimester of pregnancy (3-month period calcu-lated from the beginning of the last menses).Maternal conc. of hPL and CRH-controlledestrogens rise sharply during the thirdtrimester ( B). Placental hormones are dis-tributed to mother and fetus. Because of theclose connection between maternal, fetal andplacental hormone synthesis, they are jointlyreferred to as the fetoplacental unit ( A).

Human chorionic gonadotropin (hCG) (a)stimulates the synthesis of steroids like DHEAand DHEA-S by the fetal adrenal cortex (seebelow); (b) suppresses follicle maturation inthe maternal ovaries, and (c) maintains theproduction of progesterone and estrogen inthe corpus luteum ( A1) until the 6th week ofgestation, i.e., until the placenta is able to pro-duce sufficient quantities of the hormones.

Most pregnancy tests are based on the fact thathCG is detectable in the urine about 6–8 days afterconception. Since the levels of estrogen and pro-gesterone greatly increase during pregnancy (seetable on p. 304), larger quantities of these hormonesand their metabolites estriol and pregnanediol are ex-creted in the urine. Therefore, their conc. can also bemeasured to test for pregnancy.

In contrast to other endocrine organs, theplacenta has to receive the appropriate precur-sors (cholesterol or androgens, p. 296) fromthe maternal and fetal adrenal cortex, respec-tively, before it can synthesize progesteroneand estrogen ( A2). The fetal adrenal cortex(FAC) is sometimes larger than the kidneys andconsists of a fetal zone and an adult zone. Theplacenta takes up cholesterol and preg-nenolone and uses them to synthesize pro-gesterone. It is transported to the fetal zone ofthe FAC, where it is converted to dehydroepian-drosterone (DHEA) and dehydroepian-drosterone sulfate (DHEA-S). DHEA and DHEA-S

pass to the placenta, where they are used forestrogen synthesis. Progesterone is convertedto testosterone in the testes of the male fetus.

Human placental lactogen (hPL = human chorionicsomatomammotropin, HCS) levels rise steadilyduring pregnancy. Like prolactin ( p. 305), hPLstimulates mammary enlargement and lactogenesisin particular and, like GH ( p. 282), stimulatesphysical growth and development in general. hPLalso seems to increase maternal plasma glucoseconc.

Corticotropin-releasing hormone (CRH)secreted by the placenta seems to play a keyrole in the hormonal regulation of birth. Theplasma levels of maternal CRH increase ex-ponentially from the 12th week of gestationon. This rise is more rapid in premature birthsand slower in post-term births. In other words,the rate at which the CRH concentration risesseems to determine the duration of the preg-nancy. Placental CRH stimulates the release ofACTH by the fetal pituitary, resulting in in-creased cortisol production in the adult zoneof FAC; this again stimulates the release of CRH(positive feedback). CRH also stimulates lungdevelopment and the production of DHEA andDHEA-S in the fetal zone of FAC.

The maternal estrogen conc. rises sharplytowards the end of the pregnancy, therebycounteracting the actions of progesterone, in-cluding its pregnancy-sustaining effect. Estro-gens induce oxytocin receptors ( p. 305), α1-adrenoceptors ( p. 84ff.), and gap junctionsin the uterine musculature ( p. 16ff.), anduterine cells are depolarized. All these effectsincrease the responsiveness of the uterinemusculature. The simultaneous increase inprogesterone synthesis triggers the produc-tion of collagenases that soften the taut cervix.Stretch receptors in the uterus respond to theincrease in size and movement of the fetus.Nerve fibers relay these signals to the hypo-thalamus, which responds by secreting largerquantities of oxytocin which, in turn, increasesuterine contractions (positive feedback). Thegap junctions conduct the spontaneous im-pulses from individual pacemaker cells in thefundus across the entire myometrium at a rateof approximately 2 cm/s ( p. 70).

Hormonal Control of Pregnancy and Birth

Pregnancy test, preeclampsia, placental failure, depression, endometriosisDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.19 Hormonal Control of Pregnancy and Birth

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Androgens (male sex hormones) are steroidhormones with 19 C atoms. This group in-cludes potent hormones like testosterone (T)and 5α-dihydrotestosterone (DHT) and lesspotent 17-ketosteroids (17-KS) such as DHEA( p. 296). In males, up to 95% of testosteroneis synthesized by the testes ( A2) and 5% bythe adrenal cortex ( Al). The ovaries andadrenal cortex synthesize testosterone infemales. The plasma testosterone conc. inmales is about 15 times higher than in females,but decreases with age. Up to 98% of testos-terone circulating in blood is bound to plasmaproteins (albumin and sex hormone-bindingglobulin, SHBG; A2).

The testes secrete also small quantities of DHT andestradiol (E2). Larger quantities of DHT (via 5-α-re-ductase) and estradiol are synthesized from testos-terone (via aromatase) by their respective targetcells. A portion of this supply is released into theplasma. DHT and testosterone bind to the same in-tracellular receptor. Estradiol influences many func-tions in the male, e.g., epiphyseal cartilage andejaculate formation and pituitary and hypothalamicactivity.

Testosterone secretion is regulated byluteinizing hormone (= LH, also called ICSH, p. 271), the pulsatile secretion of which iscontrolled by Gn-RH at 1.5- to 2-hourly inter-vals, as in the female. LH stimulates the releaseof testosterone from Leydig’s cells (interstitialcells) in the testes ( A2), whereas testos-terone and estradiol inhibit LH and Gn-RHsecretion (negative feedback).

Gn-RH also induces the release of FSH,which stimulates the secretion of inhibin andinduces the expression of androgen-bindingprotein (ABP) in Sertoli cells of the testes( A3). Testosterone cannot induce spermato-genesis without the help of ABP (see below).FSH also induces the formation of LH receptorsin the interstitial cells of Leydig. Testosterone,DHT, estradiol and inhibin inhibit the secretionof FSH (negative feedback; A). Activin, thephysiological significance of which is still un-clear, inhibits FSH secretion.

Apart from the important effects of testos-terone on male sexual differentiation, sper-matogenesis and sperm growth as well as onthe functions of the genitalia, prostate andseminal vesicle (see below), testosterone also

induces the secondary sex characteristics thatoccur in males around the time of puberty, i.e.,body hair distribution, physique, laryngeal size(voice change), acne, etc. In addition, testos-terone is necessary for normal sex drive (li-bido), procreative capacity (fertility) and coitalcapacity (potentia coeundi) in the male. Testos-terone also stimulates hematopoiesis and hasanabolic properties, leading to increasedmuscle mass in males. It also has centralnervous effects and can influence behavior—e.g., cause aggressiveness.

Sexual development and differentiation. Thegenetic sex ( B) determines the development of thesex-specific gonads (gamete-producing glands). Thegerm cells (spermatogonia; see below) then migrateinto the gonads. The somatic sex is female when thesubsequent somatic sex development and sex differ-entiation occurs in the absence of testosterone( C). Male development requires the presence oftestosterone in both steps ( C) with or without theaid of additional factors (e.g., calcitonin gene-relatedpeptide, CGRP?) in certain stages of development(e.g., descent of testes into scrotum).High conc. of testosterone, either natural or syn-thetic (anabolic steroids), lead to masculinization(virilization) of the female ( C).

Testicular function. Spermatogenesis occurs inseveral stages in the testes (target organ of tes-tosterone) and produces sperm (spermatozoa)( A3). Sperm are produced in the seminifer-ous tubules (total length, ca. 300 m), theepithelium of which consists of germ cells andSertoli cells that support and nourish the sper-matogenic cells. The seminiferous tubules arestrictly separated from other testicular tissuesby a blood–testis barrier. The testosterone re-quired for sperm maturation and semen pro-duction ( p. 310) must be bound to andro-gen-binding protein (ABP) to cross the barrier.

Spermatogonia ( B) are primitive sex cells. Atpuberty, a spermatogonium divides mitotically toform two daughter cells. One of these is kept as a life-time stem cell reservoir (in contrast to oogonia in thefemale; p. 300). The other undergoes several divi-sions to form a primary spermatocyte. It undergoesa first meiotic division (MD1) to produce two second-ary spermatocytes, each of which undergoes a sec-ond meiotic division (MD2), producing a total of fourspermatids, which ultimately differentiate into sper-matozoa. After MD1, the spermatocytes have asingle (haploid) set of chromosomes.

Androgens and Testicular Function

Infertility, intersexuality, anabolic steroids, hormone therapy, DHT receptor defectDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.20 Androgens and Testicular Function

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Sexual response in the male ( A1). Impulsesfrom tactile receptors on the skin in the genitalregion (especially the glans penis) and otherparts of the body (erogenous areas) are trans-mitted to the erection center in the sacral spinalcord (S2–S4), which conducts them to para-sympathetic neurons of the pelvic splanchnicnerves, thereby triggering sexual arousal.Sexual arousal is decisively influenced bystimulatory or inhibitory impulses from thebrain triggered by sensual perceptions, imagi-nation and other factors. Via nitric oxide( p. 280), efferent impulses lead to dilatationof deep penile artery branches (helicine arter-ies) in the erectile body (corpus cavernosum),while the veins are compressed to restrict thedrainage of blood. Moreover, voluntary and in-voluntary contractions ot the ischiocavernosusmuscle increase the pressure in the erectilebody well above the systolic blood pressure.This causes the penis to stiffen and rise (erec-tion). The ejaculatory center in the spinal cord(L2 –L3) is activated when arousal reaches acertain threshold ( A2). Immediately prior toejaculation, efferent sympathetic impulsestrigger the partial evacuation of the prostategland and the emission of semen from the vasdeferens to the posterior part of the urethra.This triggers the ejaculation reflex and is ac-companied by orgasm, the apex of sexual ex-citement. The effects of orgasm can be feltthroughout the entire body, which is reflectedby perspiration and an increase in respiratoryrate, heart rate, blood pressure, and skeletalmuscle tone. During ejaculation, the internalsphincter muscle closes off the urinary bladderwhile the vas deferens, seminal vesiclesand bulbospongiosus and ischiocavernosusmuscles contract rhythmically to propel thesemen out of the urethra.

Semen. The fluid expelled during ejacula-tion (2–6 mL) contains 35–200 million spermin a nutrient fluid (seminal plasma) composedof various substances, such as prostaglandins(from the prostate) that stimulate uterine con-traction. Once semen enters the vagina duringintercourse, the alkaline seminal plasma in-crease the vaginal pH to increase sperm motil-ity. At least one sperm cell must reach theovum for fertilization to occur.

Sexual response in the female ( A2). Dueto impulses similar to those in the male, theerectile tissues of the clitoris and vestibule ofthe vagina engorge with blood during the erec-tion phase. Sexual arousal triggers the releaseof secretions from glands in the labia minoraand transudates from the vaginal wall, both ofwhich lubricate the vagina, and the nipples be-come erect. On continued stimulation, afferentimpulses are transmitted to the lumbar spinalcord, where sympathetic impulses trigger or-gasm (climax). The vaginal walls contractrhythmically (orgasmic cuff), the vaginalengthens and widens, and the uterus becomeserect, thereby creating a space for the semen.The cervical os also widens and remains openfor about a half an hour after orgasm. Uterinecontractions begin shortly after orgasm (andare probably induced locally by oxytocin). Al-though the accompanying physical reactionsare similar to those in the male (see above),there is a wide range of variation in the or-gasmic phase of the female. Erection and or-gasm are not essential for conception.

Fertilization. The fusion of sperm and egg usuallyoccurs in the ampulla of the fallopian tube. Only asmall percentage of the sperm expelled during ejacu-lation (1000–10 000 out of 107 to 108 sperm) reachthe fallopian tubes (sperm ascension). To do so, thesperm must penetrate the mucous plug sealing thecervix, which also acts as a sperm reservoir for a fewdays. In the time required for them to reach the am-pullary portion of the fallopian tube (about 5 hours),the sperm must undergo certain changes to be ableto fertilize an ovum; this is referred to as capacita-tion ( p. 304).

After ovulation ( p. 300ff.) the ovum enters thetube to the uterus (oviduct) via the abdominal cavity.When a sperm makes contact with the egg (viachemotaxis), species-specific sperm-binding recep-tors on the ovum are exposed and the proteolyticenzyme acrosin is thereby activated (acrosomal re-action). Acrosin allows the sperm to penetrate thecells surrounding the egg (corona radiata). The spermbind to receptors on the envelope surrounding theovum (zona pellucida) and enters the egg. The mem-branes of both cells then fuse. The ovum now under-goes a second meiotic division, which concludes theact of fertilization. Rapid proteolytic changes in thereceptors on the ovum (zona pellucida reaction)prevent other sperm from entering the egg. Fertiliza-tion usually takes place on the first day after inter-course and is only possible within 24 hours after ovu-lation.

Sexual Response, Intercourse and Fertilization

Erectile dysfunction, paraplegiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 11.21 Sexual Response

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The brain and spinal cord make up the centralnervous system (CNS) ( A). The spinal cord isdivided into similar segments, but is 30%shorter than the spinal column. The spinalnerves exit the spinal canal at the level of theirrespective vertebrae and contains the afferentsomatic and visceral fibers of the dorsal root,which project to the spinal cord, and the effer-ent somatic (and partly autonomic) fibers ofthe anterior root, which project to the periph-ery. Thus, a nerve is a bundle of nerve fibersthat has different functions and conducts im-pulses in different directions ( p. 42).

Spinal cord ( A). Viewed in cross-section,the spinal cord has a dark, butterfly-shapedinner area (gray matter) surrounded by alighter outer area (white matter). The fourwings of the gray matter are called horns(cross-section) or columns (longitudinal sec-tion). The anterior horn contains motoneurons(projecting to the muscles), the posterior horncontains interneurons. The cell bodies of mostafferent fibers lie within the spinal ganglionoutside the spinal cord. The white matter con-tains the axons of ascending and descendingtracts.

Brain ( D). The main parts of the brain arethe medulla oblongata ( D7) pons ( D6),mesencephalon ( D5), cerebellum ( E), di-encephalon and telencephalon ( E). Themedulla, pons and mesencephalon are collec-tively called the brain stem. It is structurallysimilar to the spinal cord but also contains cellbodies (nuclei) of cranial nerves, neurons con-trolling respiration and circulation ( pp. 132and 214ff.) etc. The cerebellum is an importantcontrol center for balance and motor function( p. 328ff.). Pons and cerebellum form themetencephalon.

Diencephalon. The thalamus ( C6) of thediencephalon functions as a relay station formost afferents, e.g., from the eyes, ears andskin as well as from other parts of the brain.The hypothalamus ( C9) is a higher auto-nomic center ( p. 332), but it also plays adominant role in endocrine function( p. 268ff.) as it controls the release of hor-mones from the adjacent hypophysis ( D4).

The telencephalon consists of the cortexand nuclei important for motor function, thebasal ganglia, i.e. caudate nucleus ( C5), puta-

men ( C7), globus pallidus ( C8), and partsof the amygdala ( C10). The amygdaloid nu-cleus and cingulate gyrus ( D2) belong to thelimbic system ( p. 332). The cerebral cortexconsists of four lobes divided by fissures (sulci),e.g., the central sulcus ( D1, E) and lateral sul-cus ( C3, E). According to Brodmann’s map,the cerebral cortex is divided into histologi-cally distinct regions ( E, italic letters) thatgenerally have different functions ( E). Thehemispheres of the brain are closely connectedby nerve fibers of the corpus callosum ( C1,D3).

Cerebrospinal Fluid

The brain is surrounded by external and inter-nal cerebrospinal fluid (CSF) spaces ( B). Theinternal CSF spaces are called ventricles. Thetwo lateral ventricles, I and II, ( B, C2) areconnected to the IIIrd and IVth ventricle and tothe central canal of the spinal cord ( B). Ap-proximately 650 mL of CSF forms in the choroidplexus ( B, C4) and drains through thearachnoid villi each day ( B). The blood–brainbarrier and the blood–CSF barrier prevents thepassage of most substances except CO2, O2,water and lipophilic substances. (As an excep-tion, the circumventricular organs of the brainsuch as the organum vasculosum laminae ter-minalis (OVLT; p. 282) and the area postrema( p. 282) have a less tight blood–brain bar-rier.) Certain substances like glucose andamino acids can cross the blood–brain barrierwith the aid of carriers, whereas proteins can-not. The ability or inability of a drug to crossthe blood–brain barrier is an important factorin pharmacotherapeutics.

Lesions that obstruct the drainage of CSF(e.g. brain tumors) result in cerebral compres-sion; in children, they lead to fluid accumula-tion (hydrocephalus).

Neurologic and psychiatric disease, hydrocephalus, CSF penetrability

Central Nervous System


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Plate 12.1 Central Nervous System

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With our senses, we receive huge quantities ofinformation from the surroundings (109 bits/s). Only a small portion of it is consciously per-ceived (101–102 bits/s); the rest is either sub-consciously processed or not at all. Conversely,we transmit ca. 107 bits/s of information to theenvironment through speech and motor activ-ity, especially facial expression ( A).

A bit (binary digit) is a single unit of information (1byte = 8 bits). The average page of a book containsroughly 1000 bits, and TV images convey more than106 bits/s.

Stimuli reach the body in different forms ofenergy, e.g., electromagnetic (visual stimuli) ormechanical energy (e.g., tactile stimuli).Various sensory receptors or sensors for thesestimuli are located in the five “classic” senseorgans (eye, ear, skin, tongue, nose) at the bodysurface as well as inside the body (e.g., pro-priosensors, vestibular organ). (In this book,sensory receptors are called sensors to distin-guish them from binding sites for hormonesand transmitters.) The sensory system extractsfour stimulatory elements: modality, intensity,duration, and localization. Each type of sensoris specific for a unique or adequate stimulusthat evokes specific sensory modalities such assight, sound, touch, vibration, temperature,pain, taste, smell, as well as the body’s positionand movement, etc. Each modality has severalsubmodalities, e.g., taste can be sweet or bitter,etc.

In secondary sensors (e.g., gustatory and auditorysensors), sensor and afferent fibers are separated bya synapse, whereas primary sensors (e.g., olfactorysensors and nocisensors) have their own afferentfibers.

A stimulus induces a change in sensor potential(transduction), which results in depolarizationof the sensor cell (in most types; B1) or hy-perpolarization as in retinal sensors. Thestronger the stimulus, the greater the ampli-tude of the sensor potential ( C1). Once thesensor potential exceeds a certain threshold, itis transformed into an action potential, AP( B1; p. 46ff.).

Coding of signals. The stimulus is encodedin AP frequency (impulses/s = Hz), i.e., thehigher the sensor potential, the higher the APfrequency ( C2). This information is decoded

at the next synapse: The higher the frequencyof arriving APs, the higher the excitatory post-synaptic potential (EPSP; 50ff.). New APs arefired by the postsynaptic neuron when theEPSP exceeds a certain threshold ( B2).

Frequency coding of APs is a more reliable way oftransmitting information over long distances thanamplitude coding because the latter is much moresusceptible to change (and falsification of its infor-mation content). At the synapse, however, the signalmust be amplified or attenuated (by other neurons),which is better achieved by amplitude coding.

Adaptation. At constant stimulation, most sen-sors adapt, i.e., their potential decreases( p. 358). The potential of slowly adaptingsensors becomes proportional to stimulusintensity (P sensors or tonic sensors). Fast-adapting sensors respond only at the onset andend of a stimulus. They sense differentialchanges in the stimulus intensity (D sensors orphasic sensors). PD sensors have both charac-teristics ( p. 316).

Central processing. In a first phase, inhibi-tory and stimulatory impulses conducted tothe CNS are integrated—e.g., to increase thecontrast of stimuli ( D; see also p. 360). In thiscase, stimulatory impulses originating fromadjacent sensors are attenuated in the process(lateral inhibition). In a second step, a sensoryimpression of the stimuli (e.g. “green” or“sweet”) takes form in low-level areas of thesensory cortex. This is the first step of subjec-tive sensory physiology. Consciousness is aprerequisite for this process. Sensory impres-sions are followed by their interpretation. Theresult of it is called perception, which is basedon experience and reason, and is subject to in-dividual interpretation. The impression“green,” for example, can evoke the perception“There is a tree” or “This is a meadow.”

Absolute threshold ( pp. 346ff., 358, 368),difference threshold ( pp. 346ff., 358, 374),spatial and temporal summation ( pp. 52,358), receptive field ( p. 360), habituationand sensitization are other important conceptsof sensory physiology. The latter two mecha-nisms play an important role in learningprocesses ( p. 340).

Stimulus Reception and Processing

Demyelination, multiple sclerosis, neuritis, sensory abnormalitiesDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.2 Stimulus Reception and Processing

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Somatovisceral sensibility is the collectiveterm for all sensory input from receptors orsensors of the body (as opposed to the sensoryorgans of the head). It includes the areas ofproprioception ( p. 318), nociception ( p.320), and skin or surface sensitivity.

The sense of touch (taction) is essential forperception of form, shape, and spatial nature ofobjects (stereognosis). Tactile sensors are lo-cated predominantly in the palm, especially inthe fingertips, and in the tongue and oral cav-ity. Stereognostic perception of an object re-quires that the CNS integrate signals from ad-jacent receptors into a spatial pattern andcoordinate them with tactile motor function.

Mechanosensors. Hairless areas of the skincontain the following mechanosensors ( A),which are afferently innervated by myelinatednerve fibers of class II/A ( p. 49 C): The spindle-shaped Ruffini’s corpuscle( A3) partly encapsulates the afferent axonbranches. This unit is a slowly adapting (SA)pressosensor of the SA2 type. They are P sen-sors ( p. 314). Thus, the greater the pressureon the skin (depth of indentation or weight ofan object), the higher the AP frequency ( B1). Merkel’s cells ( A2) are in synaptic contactto meniscus-shaped axon terminals. Thesecomplexes are pressure-sensitive SA1 sensors.They are PD sensors (combination of B1 andB2) since their AP frequency is not only de-pendent on the pressure intensity but also onthe rate of its change (dp/dt). Meissner’s corpuscles ( A1) are composedof lamellar cell layers between which club-shaped axons terminate. This unit represents arapidly adapting pressure sensor (RA sensor)that responds only to pressure changes, dp/dt(pure D sensor or velocity sensor). The RA sen-sors are specific for touch (skin indentation of10–100 µm) and low-frequency vibration (10–100 Hz). Hair follicle receptors ( A5), whichrespond to bending of the hairs, assume thesefunctions in hairy areas of the skin. Pacinian corpuscles ( A4) are innervatedby a centrally situated axon. They adapt veryrapidly and therefore respond to changes inpressure change velocity, i.e. to acceleration(d2p/dt2), and sense high-frequency vibration(100–400 Hz; indentation depths 3 µm). TheAP frequency is proportional to the vibration

frequency ( B3). These accelaration sensorsalso play a role in proprioception ( p. 318).

Resolution. RA and SA1 sensors are denselydistributed in the mouth, lips and fingertips,especially in the index and middle finger(about 100/cm2). They can distinguish closelyadjacent stimuli as separate, i.e., each afferentaxon has a narrow receptive field. Since the sig-nals do not converge as they travel to the CNS,the ability of these sensors in the mouth, lipsand fingertips to distinguish between twoclosely adjacent tactile stimuli, i.e. their resolu-tion, is very high.

The spatial threshold for two-point discrimina-tion, i.e., the distance at which two simultaneousstimuli can be perceived as separate, is used as ameasure of tactile resolution. The spatial thresholdsare roughly 1 mm on the fingers, lips and tip of thetongue, 4 mm on the palm of the hand, 15 mm onthe arm, and over 60 mm on the back.

SA2 receptors and pacinian corpuscles have abroad receptive field (the exact function of SA2 re-ceptors is not known). Pacinian corpuscles are there-fore well adapted to detect vibrations, e.g., earthtremors.

Two types of thermosensors are located in theskin: cold sensors for temperatures 36 C andwarm sensors for those 36 C. The lower thetemperature (in the 20–36 C range), thehigher the AP frequency of the cold receptors.The reverse applies to warm receptors in the36–43 C range ( C). Temperatures rangingfrom 20 to 40 C are subject to rapid adapta-tion of thermosensation (PD characteristics).Water warmed, for example, to 25 C initiallyfeels cold. More extreme temperatures, on theother hand, are persistently perceived as coldor hot (this helps to maintain a constant coretemperature and prevent skin damage). Thedensity of these cold and warm sensors inmost skin areas is low as compared to themuch higher densities in the mouth and lips.(That is why the lips or cheeks are used fortemperature testing.)

Different sensors are responsible for thermoceptionat temperatures exceeding 45 C. These heat sen-sors are also used for the perception of pungent sub-stances such as capsaicin, the active constituent ofhot chili peppers. Stimulation of VR1 receptors(vanilloid receptor type 1) for capsaicin mediates theopening of cation channels in nociceptive nerveendings, which leads to their depolarization.

Sensory Functions of the Skin

Neural and spinal cord lesions, dissociated disorder of sensation, paresthesia, anesthesia,hypesthesia, dysesthesiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.3 Sensory Functions of the Skin, Proprioception I

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Proprioception is the mechanism by which wesense the strength that our muscles develop aswell as the position and movement of our bodyand limbs. The vestibular organ ( p. 348) andcutaneous mechanosensors ( p. 316) assistthe propriosensors in muscle spindles, jointsand tendons. Sensors of Golgi tendon organsare located near muscle–tendon junctions.Muscle spindles ( A1) contain proportional(P) and differential (D) sensors for monitoringof joint position and movement. The velocity ofposition change is reflected by a transient risein impulse frequency (D sensor; p. 317 D1,spike), and the final joint position is expressedas a constant impulse frequency (P-sensor, p. 317 D2, plateau). Muscle spindles func-tion to regulate muscle length. They lie parallelto the skeletal muscle fibers (extrafusal musclefibers) and contain their own muscle fibers (in-trafusal muscle fibers). There are two types ofintrafusal muscle fibers: (1) nuclear chainfibers (P sensors) and (2) nuclear bag fibers (Dsensors). The endings of type Ia afferent neu-rons coil around both types, whereas type IIneurons wind around the nuclear chain fibersonly (neuron types described on p. 49 C). Theseannulospiral endings detect longitudinalstretching of intrafusal muscle fibers and re-port their length (type Ia and II afferents) andchanges in length (Ia afferents) to the spinalcord. The efferent γ motoneurons (fusimotorfibers) innervate both intrafusal fiber types, al-lowing variation of their length and stretchsensitivity ( A1, B1).

Golgi tendon organs ( A2) are arranged inseries with the muscle and respond to the con-traction of only a few motor units or more.Their primary function is to regulate muscletension. Impulses from Golgi tendon organs(conveyed by type Ib afferents), the skin andjoints, and muscle spindles (some of which aretype Ia and II afferent fibers), as well as de-scending impulses, are jointly integrated intype Ib interneurons of the spinal cord; this isreferred to as multimodal integration ( D2).Type Ib interneurons inhibit α motoneurons ofthe muscle from which the Ib afferent inputoriginated (autogenous inhibition) and activateantagonistic muscles via excitatory inter-neurons ( D5).

Monosynaptic stretch reflex ( C). Musclesspindles are also affected by sudden stretchingof a skeletal muscle, e.g. due to a tap on the ten-don attaching it. Stretching of the musclespindles triggers the activation of type Ia affer-ent impulses ( B2, C), which enter the spinalcord via the dorsal root and terminate in theventral horn at the α motoneurons of the samemuscle. This type Ia afferent input thereforeinduces contraction of the same muscle byonly one synaptic connection. The reflex timefor this monosynaptic stretch reflex is there-fore very short (ca. 30 ms). This is classified as aproprioceptive reflex, since the stimulation andresponse arise in the same organ. The mono-synaptic stretch reflex functions to rapidly cor-rect “involuntary” changes in muscle lengthand joint position.

Supraspinal activation ( B3). Voluntarymuscle contractions are characterized by co-activation of α and γ neurons. The latter adjustthe muscle spindles (length sensors) to a cer-tain set-point of length. Any deviations fromthis set-point due, for example, to unexpectedshifting of weight, are compensated for by re-adjusting the α-innervation (load compensa-tion reflex). Expected changes in musclelength, especially during complex movements,can also be more precisely controlled by (cen-trally regulated) γ fiber activity by increasingthe preload and stretch sensitivity of the intra-fusal muscle fibers (fusimotor set).

Hoffmann’s reflex can be also used to test thestretch reflex pathway. This can be done by position-ing electrodes on the skin over (mixed) musclenerves and subsequently recording the muscle con-traction induced by electrical stimuli of different in-tensity.

Polysynaptic circuits, also arising from type II af-ferents complement the stretch reflex. If a stretch re-flex (e.g., knee-jerk reflex, C, D) occurs in an ex-tensor muscle, the α motoneurons of the antagonis-tic flexor muscle must be inhibited via inhibitory Ia in-terneurons to achieve efficient extension ( D1).

Deactivation of stretch reflex is achieved by in-hibiting muscle contraction as follows: 1) The musclespindles relax, thereby allowing the deactivation oftype Ia fibers; 2) the Golgi tendon organs inhibit theα motoneurons via type Ib interneurons ( D2); 3)the α motoneurons are inhibited by the interneurons(Renshaw cells; D4) that they themselves stimu-lated via axon collaterals (recurrent inhibition; D3;p. 323 C1).

Proprioception, Stretch Reflex

Diagnostic proprioceptive reflexes, areflexia, hyperreflexia, spasticityDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.4 Proprioception II, Stretch Reflex

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Pain is an unpleasant sensory experience as-sociated with discomfort. It is protective inso-far as it signals that the body is beingthreatened by an injury (noxa). Nociception isthe perception of noxae via nocisensors, neuralconduction and central processing. The painthat is ultimately felt is a subjective ex-perience. Pain can also occur without stimula-tion of nocisensors, and excitation of nocisen-sors does not always evoke pain.

All body tissues except the brain and livercontain sensors for pain, i.e., nocisensors ornociceptors ( A). Nocisensors are bead-likeendings of peripheral axons, the somata ofwhich are located in dorsal root ganglia and innuclei of the trigeminal nerve. Most of thesefibers are slowly conducting C fibers ( 1 m/s);the rest are myelinated Aδ fibers (5–30 m/s;fiber types described on p. 49 C).

When an injury occurs, one first senses sharp “fastpain” (Aδ fibers) before feeling the dull “slow pain”(C fibers), which is felt longer and over a broaderarea. Since nocisensors do not adapt, the pain canlast for days. Sensitization can even lower thestimulus threshold.

Most nocisensors are polymodal sensors (Cfibers) activated by mechanical stimuli, chemicalmediators of inflammation, and high-intensity heator cold stimuli. Unimodal nociceptors, the lesscommon type, consist of thermal nocisensors (Aδfibers), mechanical nocisensors (Aδ fibers), and “dor-mant” nocisensors. Thermal nocisensors are activatedby extremely hot ( 45 C) or cold ( 5 C) stimuli( p. 316). Dormant nocisensors are chiefly locatedin internal organs and are “awakened” after pro-longed exposure (sensitization) to a stimulus, e.g.,inflammation.

Nocisensors can be inhibited by opioids(desensitization) and stimulated by prosta-glandin E2 or bradykinin, which is released inresponse to inflammation (sensitization; A).Endogenous opioids (e.g., dynorphin, enke-phalin, endorphin) and exogenous opioids(e.g., morphium) as well as inhibitors of pros-taglandin synthesis (e.g. acetylsalicyclic acid[Aspirin]; p. 271) are therefore able to alle-viate pain (analgesic action).

Inflammatory sensitization (e.g., sunburn) lowersthe threshold for noxious stimuli, leading to excessivesensitivity (hyperalgesia) and additional painresulting from non-noxious stimuli to the skin (allody-nia), e.g., touch or warm water (37 C). Once thenocisensors are stimulated, they start to release neu-

ropeptides such as substance P or CGRP (calcitoningene-related peptide) that cause inflammation ofthe surrounding vessels (neurogenic inflamma-tion).

Projected pain. Damage to nociceptive fiberscauses pain (neurogenic or neuropathic) that is oftenprojected to and perceived as arising from the pe-riphery. A prolapsed disk compressing a spinal nervecan, for example, cause leg pain. Nociceptive fiberscan be blocked by cold or local anesthesia.

Nociceptive tracts ( C1). The central axons ofnociceptive somatic neurons and nociceptiveafferents of internal organs end on neurons ofthe dorsal horn of the spinal cord. In manycases, they terminate on the same neurons asthe skin afferents.

Referred pain ( B). Convergence of somatic andvisceral nociceptive afferents is probably the maincause of referred pain. In this type of pain, noxiousvisceral stimuli cause a perception of pain in certainskin areas called Head’s zones. That for the heart, forexample, is located mainly in the chest region. Myo-cardial ischemia is therefore perceived as pain on thesurface of the chest wall (angina pectoris) and oftenalso in the lower arm and upper abdominal region.

In the spinal cord, the neuroceptive afferentscross to the opposite side (decussation) andare conducted in the tracts of the anterolateralfuniculus—mainly in the spinothalamic tract—and continue centrally via the brain stemwhere they join nociceptive afferents from thehead (mainly trigeminal nerve) to thethalamus ( C1). From the ventrolateralthalamus, sensory aspects of pain are pro-jected to S1 and S2 areas of the cortex. Tractsfrom the medial thalamic nuclei project to thelimbic system and other centers.

Components of pain. Pain has a sensory componentincluding the conscious perception of site, durationand intensity of pain; a motor component (e.g., defen-sive posture and withdrawal reflex; p. 322), an au-tonomic component (e.g., tachycardia), and an affec-tive component (e.g., aversion). In addition, painassessments based on the memory of a previouspain experience can lead to pain-related behavior(e.g., moaning).

In the thalamus and spinal cord, nociceptioncan be inhibited via descending tracts with theaid of various transmitters (mainly opioids).The nuclei of these tracts ( C2, blue) are lo-cated in the brain stem and are mainly acti-vated via the nociceptive spinoreticular tract(negative feedback loop).

Nociception and Pain

Inflammation, Head’s zones, phantom pain, peripheral and central pain reliefDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.5 Nociception and Pain

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Unlike proprioceptive reflexes ( p. 318),polysynaptic reflexes are activated by sensorsthat are spatially separate from the effectororgan. This type of reflex is called polysynaptic,since the reflex arc involves many synapses inseries. This results in a relatively long reflextime. The intensity of the response is depend-ent on the duration and intensity of stimulus,which is temporally and spatially summated inthe CNS ( p. 52). Example: itching sensationin nose ⇒ sneezing. The response spreadswhen the stimulus intensity increases (e.g.,coughing ⇒ choking cough). Protective reflexes(e.g., withdrawal reflex, corneal and lacrimalreflexes, coughing and sneezing), nutrition re-flexes (e.g., swallowing, sucking reflexes), loco-motor reflexes, and the various autonomic re-flexes are polysynaptic reflexes. Certain re-flexes, e.g., plantar reflex, cremasteric reflexand abdominal reflex, are used as diagnostictests.

Withdrawal reflex ( A). Example: A painfulstimulus in the sole of the right foot (e.g., step-ping on a tack) leads to flexion of all joints ofthat leg (flexion reflex). Nociceptive afferents( p. 320) are conducted via stimulatory inter-neurons ( A1) in the spinal cord to mo-toneurons of ipsilateral flexors and via inhibi-tory interneurons ( A2) to motoneurons ofipsilateral extensors ( A3), leading to their re-laxation; this is called antagonistic inhibition.One part of the response is the crossed exten-sor reflex, which promotes the withdrawalfrom the injurious stimulus by increasing thedistance between the nociceptive stimulus(e.g. the tack) and the nocisensor and helps tosupport the body. It consists of contraction ofextensor muscles ( A5) and relaxation of theflexor muscles in the contralateral leg ( A4,A6). Nociceptive afferents are also conductedto other segments of the spinal cord (ascend-ing and descending; A7, A8) because differ-ent extensors and flexors are innervated bydifferent segments. A noxious stimulus canalso trigger flexion of the ipsilateral arm andextension of the contralateral arm (doublecrossed extensor reflex). The noxious stimulusproduces the perception of pain in the brain( p. 318).

Unlike monosynaptic stretch reflexes, poly-synaptic reflexes occur through the co-activa-tion of α and γ motoneurons ( p. 318). The re-flex excitability of α motoneurons is largelycontrolled by supraspinal centers via multipleinterneurons ( p. 326). The brain can there-fore shorten the reflex time of spinal cord re-flexes when a noxious stimulus is anticipated.

Supraspinal lesions or interruption of descendingtracts (e.g., in paraplegics) can lead to exaggerationof reflexes (hyperreflexia) and stereotypic reflexes.The absence of reflexes (areflexia) corresponds tospecific disorders of the spinal cord or peripheralnerve.

Synaptic Inhibition

GABA (γ-aminobutyric acid) and glycine( p. 55f.) function as inhibitory transmittersin the spinal cord. Presynaptic inhibition ( B)occurs frequently in the CNS, for example, atsynapses between type Ia afferents and α mo-toneurons, and involves axoaxonic synapses ofGABAergic interneurons at presynaptic nerveendings. GABA exerts inhibitory effects at thenerve endings by increasing the membraneconductance to Cl– (GABAA receptors) and K+

(GABAB receptors) and by decreasing the con-ductance to Ca2+ (GABAB receptors). Thisdecreases the release of transmitters from thenerve ending of the target neuron ( B2),thereby lowering the amplitude of its post-synaptic EPSP ( p. 50). The purpose of pre-synaptic inhibition is to reduce certain in-fluences on the motoneuron without reducingthe overall excitability of the cell.

In postsynaptic inhibition ( C), an inhibi-tory interneuron increases the membrane con-ductance of the postsynaptic neuron to Cl– orK+, especially near the axon hillock, therebyshort-circuiting the depolarizing electricalcurrents from excitatory EPSPs ( p. 52ff.).

The interneuron responsible for postsynap-tic inhibition is either activated by feedbackfrom axonal collaterals of the target neurons(recurrent inhibition of motoneurons via gly-cinergic Renshaw cells; C1) or is directly ac-tivated by another neuron via feed-forwardcontrol ( C2). Inhibition of the ipsilateral ex-tensor ( A2, A3) in the flexor reflex is an ex-ample of feed-forward inhibition.

Polysynaptic Reflexes

Diagnostic polysynaptic reflexes, areflexia, hyperreflexia, spasticity, spinal cord lesionsDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.6 Polysynaptic Reflexes, Synaptic Inhibition

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The posterior funiculus–lemniscus system( C, green) is the principal route by which thesomatosensory cortex S1 (postcentral gyrus)receives sensory input from skin sensors andpropriosensors. Messages from the skin (su-perficial sensibility) and locomotor system(proprioceptive sensibility) reach the spinalcord via the dorsal roots. Part of these primarilyafferent fibers project in tracts of the posteriorfuniculus without synapses to the posteriorfunicular nuclei of the caudal medulla oblon-gata (nuclei cuneatus and gracilis). The tractsof the posterior funiculi exhibit a somatotopicarrangement, i.e., the further cranial the originof the fibers the more lateral their location. Atthe medial lemniscus, the secondary afferentsomatosensory fibers cross to the contralateralside (decussate) and continue to the post-erolateral ventral nucleus (PLVN) of thethalamus, where they are also somatotopicallyarranged. The secondary afferent trigeminalfibers (lemniscus trigeminalis) end in the post-eromedial ventral nucleus (PMVN) of thethalamus. The tertiary afferent somatosensoryfibers end at the quaternary somatosensoryneurons in the somatosensory cortex S1. Themain function of the posterior funiculus–lem-niscus pathway is to relay information abouttactile stimuli (pressure, touch, vibration) andjoint position and movement (proprioception)to the brain cortex via its predominantlyrapidly conducting fibers with a high degree ofspatial and temporal resolution.

As in the motor cortex ( p. 327 B), eachbody part is assigned to a corresponding pro-jection area in the somatosensory cortex S1( A) following a somatotopic arrangement( B). Three features of the organization of S1are (1) that one hemisphere of the brain re-ceives the information from the contralateralside of the body (tracts decussate in the mediallemniscus; C); (2) that most neurons in S1receive afferent signals from tactile sensors inthe fingers and mouth ( p. 316); and (3) thatthe afferent signals are processed in columnsof the cortex ( p. 335 A) that are activated byspecific types of stimuli (e.g., touch).

Anterolateral spinothalamic pathway ( C;violet). Afferent signals from nocisensors,thermosensors and the second part of pressureand touch afferent neurons are already relayed

(partly via interneurons) at various levels ofthe spinal cord. The secondary neurons cross tothe opposite side at the corresponding seg-ment of the spinal cord, form the lateral andventral spinothalamic tract in the anterolateralfuniculus, and project to the thalamus (PLVN).The tertiary afferent fibers then reach the so-matosensory cortex S1.

Descending tracts (from the cortex) can in-hibit the flow of sensory input to the cortex atall relay stations (spinal cord, medulla oblon-gata, thalamus). The main function of thesetracts is to modify the receptive field and ad-just stimulus thresholds. When impulses fromdifferent sources are conducted in a commonafferent, they also help to suppress unimpor-tant sensory input and selectively processmore important and interesting sensory mo-dalities and stimuli (e.g., eavesdropping).

Hemiplegia. ( D) Brown–Séquard syndrome occursdue to hemisection of the spinal cord, resulting inipsilateral paralysis and loss of various functionsbelow the lesion. The injured side exhibits motor pa-ralysis (initially flaccid, later spastic) and loss of tactilesensation (e.g., impaired two-point discrimination, p. 316). An additional loss of pain and tempera-ture sensation occurs on the contralateral side (disso-ciated paralysis).

Reticular activating system. ( E) The sensoryinput described above as well as the input fromthe sensory organs are specific, whereas thereticular activating system (RAS) is an un-specific system. The RAS is a complex process-ing and integrating system of cells of the retic-ular formation of the brainstem. These cells re-ceive sensory input from all sensory organs andascending spinal cord pathways (e.g., eyes,ears, surface sensitivity, nociception), basalganglia, etc. Cholinergic and adrenergic outputfrom the RAS is conducted along descendingpathways to the spinal cord and along ascend-ing “unspecific” thalamic nuclei and “un-specific” thalamocortical tracts to almost allcortical regions ( p. 335 A), the limbic systemand the hypothalamus. The ascending RAS orARAS controls the state of consciousness andthe degree of wakefulness (arousal activity; p. 338).

Central Conduction of Sensory Input

Neural and spinal cord lesions, dissociated disorder of sensation, paresthesia, anesthesia,hypesthesia, dysesthesiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.7 Central Conduction of Sensory Input

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Coordinated muscular movements (walking,grasping, throwing, etc.) are functionally de-pendent on the postural motor system, which isresponsible for maintaining upright posture,balance, and spatial integration of body move-ment. Since control of postural motor functionand muscle coordination requires the simul-taneous and uninterrupted flow of sensory im-pulses from the periphery, this is also referredto as sensorimotor function.

α motoneurons in the anterior horn of thespinal cord and in cranial nerve nuclei are theterminal tracts for skeletal muscle activation.Only certain parts of the corticospinal tractand type Ia afferents connect to α mo-toneurons monosynaptically. Other afferentsfrom the periphery (propriosensors, nocisen-sors, mechanosensors), other spinal cord seg-ments, the motor cortex, cerebellum, andmotor centers of the brain stem connect to αmotoneurons via hundreds of inhibitory andstimulatory interneurons per motoneuron.

Voluntary motor function. Voluntary move-ment requires a series of actions: decision tomove ⇒ programming (recall of stored sub-programs) ⇒ command to move ⇒ executionof movement ( A1–4). Feedback from affer-ents (re-afferents) from motor subsystems andinformation from the periphery is constantlyintegrated in the process. This allows for ad-justments before and while executing volun-tary movement.

The neuronal activity associated with the first twophases of voluntary movement activates numerousmotor areas of the cortex. This electrical brain activ-ity is reflected as a negative cortical expectancypotential, which can best be measured in associa-tion areas and the vertex. The more complex themovement, the higher the expectancy potential andthe earlier its onset (roughly 0.3–3 s).

The motor cortex consists of three main areas( C, top; see p. 313 E for area numbers):(a) primary motor area, M1 (area 4), (b) premo-tor area, PMA (lateral area 6); and (c) sup-plementary motor area, SMA (medial area 6).The motor areas of the cortex exhibit somato-topic organization with respect to the targetmuscles of their fibers (shown for M1 in B) andtheir mutual connections.

Cortical afferents. The cortex receivesmotor input from (a) the body periphery (via

thalamus ⇒ S1 [ p. 325 A] ⇒ sensory asso-ciation cortex ⇒ PMA); (b) the basal ganglia(via thalamus ⇒ M1, PMA, SMA [ A2] ⇒ pre-frontal association cortex); (c) the cerebellum(via thalamus ⇒ M1, PMA; A2); and (d)sensory and posterior parietal areas of the cor-tex (areas 1–3 and 5–7, respectively).

Cortical efferents. ( C, D, E, F) Motor out-put from the cortex is mainly projected to (a)the spinal cord, (b) subcortical motor centers(see below and p. 330), and (c) the con-tralateral cortex via commissural pathways.

The pyramidal tract includes the corticospi-nal tract and part of the corticobulbar tract.Over 90% of the pyramidal tract consists of thinfibers, but little is known about their function.The thick, rapidly conducting corticospinaltract ( C) project to the spinal cord fromareas 4 and 6 and from areas 1–3 of the sensorycortex. Some of the fibers connect mono-synaptically to α and γ motoneurons re-sponsible for finger movement (precisiongrasping). The majority synapse with inter-neurons of the spinal cord, where they in-fluence input from peripheral afferents as wellas motor output (via Renshaw’s cells) andthereby spinal reflexes.

Function of the Basal Ganglia

Circuitry. The basal ganglia are part of multipleparallel corticocortical signal loops. Associ-ative loops arising in the frontal and limbic cor-tex play a role in mental activities such asassessment of sensory information, adapta-tion of behavior to emotional context, motiva-tion, and long-term action planning. The func-tion of the skeletomotor and oculomotor loops(see below) is to coordinate and control thevelocity of movement sequences. Efferent pro-jections of the basal ganglia controlthalamocortical signal conduction by (a) at-tenuating the inhibition (disinhibiting effect,direct mode) of the thalamic motor nuclei andthe superior colliculus, respectively, or (b) byintensifying their inhibition (indirect mode).

The principal input to the basal gangliacomes from the putamen and caudate nucleus,which are collectively referred to as the stri-atum. Neurons of the striatum are activated bytracts from the entire cortex and use glutamateas their transmitter ( D). Once activated,

Movement

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Plate 12.8 Movement I

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neurons of the striatum release an inhibi-tory transmitter (GABA) and a co-transmitter—either substance P (SP) or enkephalin (Enk., D; p. 55). The principal output of the basalganglia runs through the pars reticularis of thesubstantia nigra (SNr) and the pars interna ofthe globus pallidus (GPi), both of which are in-hibited by SP/GABAergic neurons of the stri-atum ( D).

Both SNr and GPi inhibit (by GABA) the ventrolateralthalamus with a high level of spontaneous activity.Activation of the striatum therefore leads to disinhi-bition of the thalamus by this direct pathway. If,however, enkephalin/GABA-releasing neurons of thestriatum are activated, then they inhibit the pars ex-terna of the globus pallidus (GPe) which, in turn, in-hibits (by GABA) the subthalamic nucleus. The sub-thalamic nucleus induces glutamatergic activation ofSNr and GPi. The ultimate effect of this indirectpathway is increased thalamic inhibition. Sincethe thalamus projects to motor and prefrontal cor-tex, a corticothalamocortical loop that influencesskeletal muscle movement (skeletomotor loop) viathe putamen runs through the basal ganglia. Anoculomotor loop projects through the caudate nu-cleus, pars reticularis and superior colliculus and is in-volved in the control of eye movement ( pp. 348,366). Descending tracts from the SNr project to thetectum and nucleus pedunculus pontinus.

The fact that the pars compacta of the substantianigra (SNc) showers the entire striatum withdopamine (dopaminergic neurons) is of pathophy-siological importance ( D). On the one hand,dopamine binds to D1 receptors (rising cAMP levels),thereby activating SP/GABAergic neurons of the stri-atum; this is the direct route (see above). On theother hand, dopamine also reacts with D2 receptors(decreasing cAMP levels), thereby inhibitingenkephalin/GABAergic neurons; this is the indirectroute. These effects of dopamine are essential fornormal striatum function. Degeneration of morethan 70% of the dopaminergic neurons of the parscompacta results in excessive inhibition of the motorareas of the thalamus, thereby impairing voluntarymotor function. This occurs in Parkinson’s diseaseand can be due genetic predisposition, trauma (e.g.,boxing), cerebral infection and other causes. Thecharacteristic symptoms of disease include povertyof movement (akinesia), slowness of movement(bradykinesia), a festinating gait, small handwriting(micrography), masklike facial expression, muscularhypertonia (rigor), bent posture, and a tremor of rest-ing muscles (“money-counting” movement ofthumb and fingers).

Function of the Cerebellum

The cerebellum contains as many neurons asthe rest of the brain combined. It is an impor-tant control center for motor function that hasafferent and efferent connections to the cortexand periphery ( F, top panel). The cerebel-lum is involved in the planning, execution andcontrol of movement and is responsible formotor adaptation to new movementsequences (motor learning). It is also cooper-ates with higher centers to control attention,etc.

Anatomy ( F, top). The archeocerebellum (floc-culonodular lobe) and paleocerebellum (pyramids,uvula, paraflocculus and parts of the anterior lobe)are the phylogenetically older parts of the cerebel-lum. These structures and the pars intermedia formthe median cerebellum. The neocerebellum (poste-rior lobe of the body of the cerebellum) is the phylo-genetically younger part of the cerebellum andforms the lateral cerebellum. Based on the origin oftheir principal efferents, the archicerebellum and ver-mis are sometimes referred to as the vestibulocerebel-lum, the paleocerebellum as the spinocerebellum, andthe neocerebellum as the pontocerebellum. The cere-bellar cortex is the folded (fissured) superficial graymatter of the cerebellum consisting of an outermolecular layer of Purkinje cell dendrites and their af-ferents, a middle layer of Purkinje cells (Purkinje so-mata), and an inner layer of granular cells. The outersurface of the cerebellum exhibits small, parallel con-volutions called folia.

The median cerebellum and pars intermedia ofthe cerebellum mainly control postural andsupportive motor function ( F1,2) and oculo-motor function ( pp. 348 and 366). Input:The median cerebellum receives afference cop-ies of spinal, vestibular and ocular origin andefference copies of descending motor signals tothe skeletal muscles. Output from the mediancerebellum flows through the intracerebellarfastigial, globose, and emboliform nuclei tomotor centers of the spinal cord and brainstem and to extracerebellar vestibular nuclei(mainly Deiter’s nucleus). These centers con-trol oculomotor function and influence loco-motor and postural/supportive motor functionvia the vestibulospinal tract.

The lateral cerebellum (hemispheres)mainly takes part in programmed movement( F3), but its plasticity also permits motoradaptation and the learning of motorsequences. The hemispheres have two-way

Movement (continued)

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Plate 12.9 Movement II

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connections to the cortex. Input: a. Via thepontine nuclei and mossy fibers, the lateralcerebellum receives input from cortical cen-ters for movement planning (e.g., parietal, pre-frontal and premotor association cortex; sen-sorimotor and visual areas). b. It also receivesinput from cortical and subcortical motor cen-ters via the inferior olive and climbing fibers(see below). Output from the lateral cerebel-lum projects across motor areas of thethalamus from the dentate nucleus to motorareas of the cortex.

Lesions of the median cerebellum lead to distur-bances of balance and oculomotor control (vertigo,nausea, pendular nystagmus) and cause trunk andgait ataxia. Lesions of the lateral cerebellum lead todisturbances of initiation, coordination and termina-tion of goal-directed movement and impair the rapidreprogramming of diametrically opposing move-ment (diadochokinesia). The typical patient exhibitstremor when attempting voluntary coordinatedmovement (intention tremor), difficulty in measuringthe distances during muscular movement (dys-metria), pendular rebound motion after stopping amovement (rebound phenomenon), and inability toperform rapid alternating movements (adiado-chokinesia ).

The cerebellar cortex exhibits a uniform neuralultrastructure and circuitry. All output fromthe cerebellar cortex is conducted via neuritesof approximately 15 106 Purkinje cells. TheseGABAergic cells project to and inhibit neuronsof the fastigial, emboliform, dentate, andlateral vestibular nuclei (Deiter’s nucleus; F,right panel).

Input and circuitry: Input from the spinal cord(spinocerebellar tracts) is relayed by the inferior oliveand projected via stimulatory (1 : 15 diverging)climbing fibers that terminate on a band of Purkinjecells extending across the folia of the cerebellum,forming the sagittal excitatory foci. The climbingfibers use aspartate as their transmitter. Serotoniner-gic fibers from the raphe nuclei and noradrenergicfibers from the locus caeruleus terminate also on theexcitatory foci. Mossy fibers (pontine, reticular andspinal afferents) excite the granular cells. Their axonsform T-shaped branches (parallel fibers). In themolecular layer, they densely converge (ca. 105 : 1)on strips of Purkinje cells that run alongside thefolium; these are called longitudinal excitatory foci. Itis assumed that the climbing fiber system (at the“crossing points” of the perpendicular excitatoryfoci) amplify the relatively weak signals of mossyfiber afferents to Purkinje cells. Numerous inter-

neurons (Golgi, stellate and basket cells) heightenthe contrast of the excitatory pattern on the cerebel-lar cortex by lateral and recurrent inhibition.

Postural Motor Control

Simple stretch reflexes ( p. 318) as well as themore complicated flexor reflexes and crossedextensor reflexes ( p. 322) are controlled atthe level of the spinal cord.

Spinal cord transection (paraplegia) leads to an ini-tial loss of peripheral reflexes below the lesion(areflexia, spinal shock), but the reflexes can later beprovoked in spite of continued transection.

The spinal reflexes are mainly subordinate tosupraspinal centers ( E). Postural motorfunction is chiefly controlled by motor centersof the brain stem ( E1), i.e., the red nucleus,vestibular nuclei (mainly lateral vestibular nu-cleus), and parts of the reticular formation.These centers function as relay stations thatpass along information pertaining to posturaland labyrinthine postural reflexes required tomaintain posture and balance (involuntary).Postural reflexes function to regulate muscletone and eye adaptation movements ( p.349 B). Input is received from the equilibriumorgan (tonic labyrinthine reflexes) and frompropriosensors in the neck (tonic neck reflexes).The same afferents are involved in postural re-flexes (labyrinthine and neck reflexes) thathelp to maintain the body in its normal posi-tion. The trunk is first brought to its normalposition in response to inflow from neck pro-prioceptors. Afferents projecting from thecerebellum, cerebral motor cortex ( C), eyes,ears, and olfactory organ as well as skin recep-tors also influence postural reflexes. Sta-tokinetic reflexes also play an important role inthe control of body posture and position. Theyplay a role e.g. in startle reflexes and nystag-mus ( p. 366).

Descending tracts to the spinal cord arising fromthe red nucleus and medullary reticular formation(rubrospinal and lateral reticulospinal tracts) have agenerally inhibitory effect on α and γ motoneurons( p. 318) of extensor muscles and an excitatory ef-fect on flexor muscles ( E2). Conversely, the tractsfrom Deiter’s nucleus and the pontine areas of the re-ticular formation (vestibulospinal and medial reti-culospinal tracts) inhibit the flexors and excite the αand γ fibers of the extensors.

Movement (continued)

Cerebellar lesions (e.g. multiple sclerosis), ataxia, nystagmus, balance disturbancesDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.10 Movement III

Transection of the brain stem below the red nucleusleads to decerebrate rigidity because the extensor ef-fect of Deiter’s nucleus predominates.

The integrating and coordinating function ofthe sensorimotor system can be illustrated in twotennis players. When one player serves, the body ofthe other player moves to meet the ball (goal-directedmovement) while using the right leg for support andthe left arm for balance (postural motor control). Theplayer keeps his eye on the ball (oculomotor control)and the visual area of the cortex assesses the tra-

jectory and velocity of the ball. The associative cere-bral cortex initiates the movement of returning theball while taking the ball, net, other side of the court,and position of the opponent into consideration.Positional adjustments may be necessary when re-turning the ball. Using the movement concept pro-grammed in the cerebellum and basal ganglia, themotor cortex subsequently executes the directedmovement of returning the ball. In doing so, theplayer may “slice” the ball to give it an additionalspinning motion (acquired rapid directed movement).

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The hypothalamus coordinates all autonomicand most endocrine processes ( p. 266ff.)and integrates signals for control of internalmilieu, sleep–wake cycle, growth, mental/physical development, reproduction and otherfunctions. The hypothalamus receives numer-ous sensory and humoral signals ( A). Pep-tide hormones can circumvent the blood–brain barrier by way of the circumventricularorgans ( p. 282).

Afferents. Thermosensors for control of bodytemperature ( p. 226), osmosensors for regulationof osmolality and water balance ( p. 168), and glu-cose sensors for maintenance of a minimum glucoseconcentration are located within the hypothalamus.Information about the current status of the internalmilieu is neuronally projected to the hypothalamusfrom distant sensors, e.g., thermosensors in the skin,osmosensors in the liver ( p. 170), and stretch sen-sors in the cardiac atria ( p. 216ff.). The hy-pothalamus/circumventricular organs also containreceptors for various hormones (e.g., for cortisol andangiotensin II), some of which form part of controlloops for energy metabolism and metabolichomeostasis (e.g., receptors for cortisol, ACTH, CRH,leptin, and CCK). For functions related to growth andreproduction, the hypothalamus receives hormonalsignals from the gonads and input from neuronal af-ferents that report cervical widening at the begin-ning of the birth process and breast stimulation(suckling reflexes), among other things.

The limbic system ( A) and other areas of thebrain influence hypothalamic function. Thelimbic system controls inborn and acquiredbehavior (”program selection”) and is the seatof instinctive behavior, emotions and motiva-tion (“inner world”). It controls the expressionof emotions conveying important signals to theenvironment (e.g., fear, anger, wrath, discom-fort, joy, happiness). Inversely, signals from theenvironment (e.g., odors) are closely as-sociated to behavior.

The limbic system has cortical components (hippo-campus, parahippocampal gyrus, cingulate gyrus,parts of olfactory brain) and subcortical components(amygdaloid body, septal nuclei, anterior thalamicnucleus). It has reciprocal connections to the lateralhypothalamus (chiefly used for recall of “programs”,see below) and to the temporal and frontal cortex.

Its connections to the cortex are primarilyused to perceive and assess signals from the“outer world” and from memories. Processing

of both types of input is important for be-havior.

Programmed behavior ( A). The lateralhypothalamus has various programs to controllower hormonal, autonomic and motorprocesses. This is reflected internally bynumerous autonomic and hormonal activities,and is reflected outwardly by different types ofbehavior.

Different programs exist for different behavioral re-actions, for example: Defensive behavior (“fight or flight”). This pro-gram has somatic (repulsive facial expression andposture, flight or fight behavior), hormonal (epi-nephrine, cortisol) and autonomic (sympatheticnervous system) components. Its activation resultsin the release of energy-rich free fatty acids, the inhi-bition of insulin release, and a decrease in blood flowto the gastrointestinal tract as well as to rises in car-diac output, respiratory rate, and blood flow to theskeletal muscles. Physical exercise. The components of this pro-gram are similar to those of defensive behavior. Nutritive behavior, the purpose of which is toensure an adequate supply, digestion and intake offoods and liquids. This includes searching for food,e.g. in the refrigerator, activation of the parasympa-thetic system with increased gastrointestinal secre-tion and motility in response to food intake, post-prandial reduction of skeletal muscle activity andsimilar activities. Reproductive behavior, e.g., courting a partner,neuronal mechanisms of sexual response, hormonalregulation of pregnancy ( p. 306), etc. Thermoregulatory behavior, which enables usto maintain a relatively constant core temperature( p. 226), even in extreme ambient temperaturesor at the high level of heat production during strenu-ous physical work.

Monoaminergic neuron systems contain neu-rons that release the monoamine neu-rotransmitters norepinephrine, epinephrine,dopamine, and serotonin. These neuron tractsextend from the brain stem to almost all partsof the brain and play an important role in theoverall regulation of behavior. Experimentalactivation of noradrenergic neurons, for ex-ample, led to positive reinforcement (liking,rewards), whereas the serotoninergic neuronsare thought to be associated with dislike. Anumber of psychotropic drugs target mono-aminergic neuron systems.

Hypothalamus, Limbic System

Endocrine and psychiatric disease, insomnia, effects of psychoactive drugsDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.11 Hypothalamus, Limbic System

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Proper function of the cerebral cortex is essen-tial for conscious perception, planning, action,and voluntary movement ( p. 324ff.).

Cortical ultrastructure and neuronal cir-cuitry ( A). The cerebral cortex consists of sixlayers, I–VI, lying parallel to the brain surface.Vertically, it is divided into columns andmodules (diameter 0.05–0.3 mm, depth1.3–4.5 mm) that extend through all six layers.

Input from specific and unspecific areas of thethalamus terminate mainly on layers IV and on layersI and II, respectively ( A3); those from other areasof the cortex terminate mainly on layer II ( A2). Thelarge and small pyramidal cells ( A1) comprise80% of all cells in the cortex and are located in layersV and III, respectively (glutamate generally serves asthe transmitter, e.g., in the striatum; p. 327 D).The pyramidal cell axons leave the layer VI of their re-spective columns and are the sole source of outputfrom the cortex. Most of the axons project to otherareas of the ipsilateral cortex (association fibers) or toareas of the contralateral cortex (commissural fibers)( A2); only a few extend to the periphery ( A4and p. 327 C). Locally, the pyramidal cells are con-nected to each other by axon collaterals. The princi-pal dendrite of a pyramidal cell projects to the upperlayers of its column and has many thorn-likeprocesses (spines) where many thalamocortical,commissural and association fibers terminate (seealso p. 342ff.). The afferent fibers utilize varioustransmitters, e.g., glutamate norepinephrine,dopamine, serotonin, acetylcholine and histamine.Inside the cerebral cortex, information is processedby many morphologically variable stellate cells( A1), some of which have stimulatory effects (VIP,CCK and other peptide transmitters), while othershave inhibitory effects (GABA). Dendrites of pyra-midal and stellate cells project to neighboringcolumns, so the columns are connected by thou-sands of threads. Plasticity of pyramidal cell syn-apses — i.e., the fact that they can be modified inconformity with their activity pattern — is importantfor the learning process ( p. 340).

Cortical potentials. Similar to electrocardio-graphy, collective fluctuations of electricalpotentials (brain waves) in the cerebral cortexcan be recorded by electroencephalographyusing electrodes applied to the skin over thecranium ( B). The EPSPs contribute the mostto the electroencephalogram (EEG) whereasthe share of the relatively low IPSPs ( p. 50ff.)generated at the synapses of pyramidal celldendrites is small. Only a portion of therhythms recorded in the EEG are produced

directly in the cortex (α and γ waves in con-scious perception; see below). Lowerfrequency waves from other parts of the brain,e.g. α waves from the thalamus and θ wavesfrom the hippocampus, are “forced on” thecortex (brain wave entrainment).

By convention, downward deflections of the EEG arepositive. Generally speaking, depolarization (excita-tion) of deeper layers of the cortex and hyperpolari-zation of superficial layers cause downward deflec-tion (+) and vice versa.

Brain wave types. The electrical activity levelof the cortex is mainly determined by thedegree of wakefulness and can be distin-guished based on the amplitude (a) andfrequency (f) of the waves ( B, C). α Waves(f 10 Hz; a 50 µV), which predominatewhen an adult subject is awake and relaxed(with eyes closed), are generally detected inmultiple electrodes (synchronized activity).When the eyes are opened, other sensory or-gans are stimulated, or the subject solves amath problem, the α waves subside (αblockade) and waves appear (f 20 Hz). Theamplitude of waves is lower than that of αwaves, and they are chiefly found in occipital( B) and parietal regions when they eyes areopened. The frequency and amplitude of waves varies greatly in the different leads(desynchronization). Waves reflect the in-creased attention and activity (arousal activ-ity) of the ascending reticular activating system(ARAS; p. 324 and 338). γ Waves ( 30 Hz)appear during learning activity. Low-frequency θ waves appear when drowsinessdescends to sleep (sleep stages A/B/C; D);they transform into even slower δ wavesduring deep sleep ( C, D).

The EEG is used to diagnose epilepsy (local-ized or generalized paroxysmal waves andspikes; C), to assess the degree of brainmaturation, monitor anesthesia, and to deter-mine brain death (isoelectric EEG).

Magnetoencephalography (MEG), i.e. recordingmagnetic signals induced by cortical ion currents,can be combined with the EEG to precisely locate thesite of cortical activity (resolution a few mm).

Cerebral Cortex, Electroencephalogram (EEG)

Cerebral lesions (scars, tumors, hypoxia), epilepsy, sleep disorders, EEG diagnosisDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.12 Cerebral Cortex, EEG, Stages of Sleep

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The daily sleep–wake cycle and other circadianrhythms (diurnal rhythms) are controlled byendogenous rhythm generators. The central bio-logical clock (oscillator) that times theseprocesses is located in the suprachiasmatic nu-cleus (SCN) of the hypothalamus ( A). The en-dogenous circadian rhythm occurs in cycles ofroughly 24–25 hours, but is unadulterated onlywhen a person is completely isolated from theoutside influences (e.g., in a windowless base-ment, dark cave, etc.). External zeitgebers (en-training signals) synchronize the biologicalclock to precise 24-hour cycles. The zeitgeberslows or accelerates the endogenous rhythm,depending on which phase it is in. It takesseveral days to “reset” the biological clock, e.g.,after a long journey from east to west (jet lag).

The main external zeitgeber for 24-hoursynchronization of the sleep–wake cycle isbright light (photic entrainment). Light stimuliare directly sensed by a small, melanopsin-containing fraction of retinal ganglion cellsand conducted to the SCN via the retinohy-pothalamic tract ( A2, 3).

Signals from the zeitgeber also reaches theepiphysis (pineal body, pineal gland), where itinhibits the secretion of melatonin which ishigh at night. Since it exerts its effects mainlyon the SCN, administration of melatoninbefore retiring at night can greatly reduce thetime required to “reset” the biological clock.The main reason is that it temporally “deacti-vates” the SCN (via MT2 receptors), thereby ex-cluding most nocturnal neuronal input (exceptlight stimuli).

Important genetic “cogwheels” of the central bio-logical clock of mammals were recently discovered( A1). Neurons of the SCN contain specific proteins(CLOCK and BMAL1), the PAS domains of which bindto form heterodimers. The resulting CLOCK/BMAL1complexes enter the cell nuclei, where their pro-moter sequences (E-box) bind to period (per) oscilla-tor genes per1, per2, and per3, thereby activatingtheir transcription. After a latency period, expressionof the genes yields the proteins PER1, PER2, andPER3, which jointly function as a trimer to block theeffect of CLOCK/BMAL1, thereby completing thenegative feedback loop. The mechanism by whichthis cycle activates subsequent neuronal actions(membrane potentials) is still unclear.

Via various effector systems of the CNS( A4), the coupled cells of the SCN ( A)

bring about circadian rhythms of hormonesecretion ( p. 298), core temperature( p. 226 and 387 C), reception of food, andphysical exercise ( p. 232) as well as sleep–wake cycles ( A5, B and p. 339).

Various stages of sleep can be identified inthe EEG (p. 334 and 335 D). When a normalperson who is awake, relaxed and has the eyesclosed (α waves) starts to fall asleep, the levelof consciousness first descends to sleep phase A(dozing), where only a few isolated α wavescan be detected. Drowsiness further descendsto sleep stage B (or 1), where θ waves appear,then to stage C (or 2) where a burst of fastwaves (sleep spindles) and isolated waves (Kcomplexes) can be recorded, and ultimately tothe stages of deep sleep (stages D/E or 3/4),characterized by the appearance of δ waves.Their amplitude increases while theirfrequency drops to a minimum in phase E( p. 335 D).

This phase is therefore referred to as slow-wave sleep (SWS). The arousal threshold ishighest about 1 hour after a person falls asleep.Sleep then becomes less deep and the first epi-sode of rapid eye movement ( REM) occurs. Thiscompletes the first sleep cycle. During REMsleep, most of the skeletal muscles becomeatonic (inhibition of motoneurons) while thebreathing and heart rate increase. The face andfingers suddenly start to twitch, and penileerection and rapid eye movements occur. Allother stages of sleep are collectively referred toas non-REM sleep (NREM). Sleepers arousedfrom REM sleep are more often able to describetheir dreams than when aroused from NREMsleep. The sleep cycle normally lasts about90min and is repeated 4–5 times each night( p. 333 D).

Towards morning, NREM sleep becomesshorter while the REM episodes increase from10min to 30min.

Infants sleep longest (about 16 hours/day, 50% REM),10-year-olds sleep an average 10 hours (20% REM),young adults sleep 7–8 hours a day, and adults over 50sleep an average 6 hours (both 20 % REM). The pro-portion of SWS decreases in favor of stage C sleep.

When a person is deprived of REM sleep, the du-ration of the next REM phase increases. The first twoto three sleep cycles (core sleep) are essential. Totalsleep deprivation leads to death, but the reason isstill unclear.

Circadian Rhythms, Sleep–Wake Cycle

Delayed sleep phase insomnia, somnolence, sleep apnea, shift work, jetlagDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.13 Circadian Rhythms, Sleep–Wake Cycle

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Consciousness, Sleep

Insomnia, narcolepsy, somnambulism, hypersomnia, depression

Consciousness. Selective attention, abstractthinking, the ability to verbalize experiences,the capacity to plan activities based on ex-perience, self-awareness and the concept ofvalues are some of the many characteristics ofconsciousness. Consciousness enables us todeal with difficult environmental conditions(adaptation). Little is known about the brainactivity associated with consciousness andcontrolled attention (LCCS, see below), but wedo know that subcortical activation systemssuch as the reticular formation ( p. 324, A1)and corticostriatal systems that inhibit the af-ferent signals to the cortex in the thalamus( p. 328) play an important role.

Attention. Sensory stimuli arriving in thesensory memory are evaluated and comparedto the contents of the long-term memorywithin fractions of a second ( p. 341 C). Inroutine situations such as driving in traffic,these stimuli are unconsciously processed (au-tomated attention) and do not interfere withother reaction sequences such as conversationwith a passenger. Our conscious, selective (con-trolled) attention, on the other hand, is stimu-lated by novel or ambiguous stimuli, the reac-tion to which (e.g., the setting of priorities) iscontrolled by vast parts of the brain called thelimited capacity control system (LCCS). Sinceour capacity for selective attention is thereforelimited, it normally is utilized only in stresssituations.

Consciousness and attention are linked towakefulness, which is maintained in the reticu-lar formation of the brain stem by multiple neu-ron groups that transmit nonspecific ascendingactivating impulses via the thalamus to wideareas of the forebrain: the ascending reticularactivating (arousal) system (ARAS, A1 andp. 324 and 325 E). The transmitter in thesefibers is acetylcholine (ACh) from the medial

parabrachial nucleus, the lateroposterior andpedunculopontine tegmental nuclei ( A1,LTN, PPN). Alongside this cholinergic system, amonoaminergic system also operates, whichconsists of the locus caeruleus ( A1, LC) withnorepinephrine (NE), the raphe nuclei withserotonin (= 5-hydroxytryptamine, 5-HT), theventral periaqueductal gray substance ( A,vPAG) with dopamine and the tuberomamillarnucleus ( A, TMN) with histamine as trans-mitters. In the awake state both systems arehighly active (see Table) and the sleep/wakeswitch in the hypothalamus (LH), where thetransmitter orexin (= hypocretin) activates theaminergic system ( A ).

Sleep is a state of physiologic recovery, reg-ularly repeated at night. The day/night rhythmis associated with an altered state of con-sciousness. Here REM sleep shows considera-ble differences from NREM sleep ( p. 336 andTable). These two forms of sleep are mutuallyexclusive, i.e., the sleeping brain can eitherprocess perceptions from endogenous sources(REM sleep with hallucinatory illusions; exo-genous sensibility is blocked) or it can perceiveand (persistently) “think over” external infor-mation (see Table) but not both at the sametime.

Sleep is a regulated process. The central bio-logical clock located in the suprachiasmatic nu-cleus (SCN) of the hypothalamus ( p. 336 and337 A) is responsible for timing this process.During REM sleep only the aminergic ARAS isswitched off (and the cholinergic system isstrongly activated), while during NREM sleepthe central biological clock inhibits both sys-tems equally ( Table and A, bottom). At nightthe SCN controls, in particular, neurons in theventrolateral preoptic nucleus (VLPO). Its acti-vation causes the switchover to the “sleep”state by inhibiting both the stabilizing LH and

Awake NREM sleep REM sleep

Sensitivity, perception Active(exogenic stimulation)

Sluggish to absent Active(endogenic stimulation)

Thought Logical, progressive Logical, persistent Illogical, bizarre

Motor system activity Uninterrupted, deliberate Episodic, involuntary Brain pathways active butα motoneurons inhibited

ARAS activity Cholinergic and amin-ergic

Cholinergic and amin-ergic

Cholinergic, amin-ergic 0

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Plate 12.14 Sleep–Wake Cycle

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Consciousness, Sleep (continued)

Hypnotic/sedative medication, dependence and poisoning, disorders of consciousness, stupor

the aminergic ARAS (LC, RN, vPAG, TMN) viathe transmitters galanin and gamma-aminobutyric acid (GABA; A, bottom).

The functions of sleep are homeostasis (re-plenishment of energy reserves with high par-asympathetic involvement) and consolidation(stabilization) of acquired procedural knowl-edge (spoken language, motor functions; seebelow). Dreaming appears to be involved inthe consolidation process. Dreams includefragmentary episodic memories, which stempartly from experiences while awake duringthe previous 1 to 6days and are emotionallystructured. The high rate of REM sleep in in-fants (p. 336) suggests that it is important fordevelopment of the brain. In adults the extentof REM sleep phases increases throughout thenight (p. 335 D) and without an alarm, we usu-ally awake from REM sleep. Alertness is no-tably higher when awaking from REM sleepthat when woken from deep sleep, so anotherfunction of REM sleep may be to prepare us forbeing awake (activation of brain stem activity).

Sleep disorders include (in addition to sleep rhythmabnormalities) hypersomnia, i.e. severe daytimetiredness despite sleeping at night. Narcolepsy is anexample of such a disorder, in which (as a con-sequence of encephalitis or congenital Gélineau syn-drome) ARAS stabilization by the LH is absent (A,bottom). Without any warning, sleeping spells ofminutes at a time occur during the day, as the desta-bilized sleep/wake switch suddenly flips to “sleep.”Insomnia (sleeplessness) can have numerous causes,including damage to the VLPO (e.g. encephalitis; A,top). Parasomnias are disturbed sleep behaviors suchas sleepwalking (somnambulism) or bedwetting(nocturnal enuresis).

How easily one can be woken from sleep dependson the sleep phase, and generally we can quickly re-member what was happening just before fallingasleep. In contrast, during unconsciousness, whetherbrief (fainting, syncope) or prolonged (coma), suchas following brain injury, O2 or glucose deficiency,poisoning etc., the patient cannot be woken and willoften have retrograde amnesia (see below).

Learning, Memory, Language

The implicit memory (procedural memory B, brown area) stores skill-related informa-tion and information necessary for associativelearning (conditioning of conditional reflexes; p. 236) and non-associative learning (habit-

uation and sensitization of reflex pathways).This type of unconscious memory involves thebasal ganglia (procedural memory, e.g. learn-ing of skills and procedures), cerebellum(motor reflexes in associated learning), neo-cortex (priming, e.g. ability to complete partialtexts based on previously acquired knowl-edge), amygdaloid body (emotional reactions)and other structures of the brain.

The neuronal circuits of the implicitmemory ( B) are largely independent fromthose of the explicit memory. The latter is af-fected particularly by damage to the hippo-campus (e.g., retrograde amnesia), while theimplicit memory continues to function nor-mally. Conversely, atrophy of the amygdala.e.g., in Urbach–Wiethe disease, leads to defi-cits of emotional memory (problems with in-terpretation and expression of emotions).

The explicit memory (declarative/knowl-edge memory) stores facts (semantic knowl-edge) and experiences (episodic knowledge,especially when experienced by selective at-tention) and consciously renders the data.Storage of information processed in the uni-and polymodal association fields is the re-sponsibility of the temporal lobe system (hip-pocampus, perirhinal, entorhinal and parahip-pocampal cortex, B, green area). It estab-lishes the temporal and spatial context sur-rounding an experience and recurrently storesthe information back into the spines of corticaldendrites in the association areas ( D). Therecurrence of a portion of the experience thensuffices to recall the contents of the memory.

Explicit learning ( C) starts in the sensorymemory, which holds the sensory impressionautomatically for less than 1 s. A small fractionof the information reaches the primarymemory (short-term memory), which can re-tain about 7 units of information (e.g., groupsof numbers) for a few seconds. In most cases,the information is also verbalized. Long-termstorage of information in the secondarymemory (long-term memory) is achieved byrepetition (consolidation). The tertiary memoryis the place where frequently repeated impres-sions are stored (e.g., reading, writing, one’sown name); these things are never forgotten,and can be quickly recalled throughout one’slifetime.


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Plate 12.15 Memory, Learning

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Learning, Memory, Language (continued)

Amnesia, Alzheimer disease, speech disorders, aphasia

The mechanism correlating with primary (short-term) memory is likely to be the impulses circulatingin the neuronal tracts, while biochemical mechanismsare predominantly involved in long-term memory.Repeated excitation causes reinforcement lastinghours or days of synaptic connections (early LTP,long-term potentiation) at the spines of cortical den-drites ( D, top). Long-term genomic changes even-tually result from this reinforcement (late-phaseLTP). Synaptic transmission at specific synapses isthus enhanced and the learned information consoli-dated.

Mechanisms for LTP. Once ionotropic receptorsfor AMPA (α-amino-3-hydroxy-5-methyl-4-isoxa-zolepropionic acid), which are permeable for Na butnot for Ca2, are activated by the presynaptic releaseof glutamate at glutamatergic axodendritic synapsesof cortical pyramidal cells ( p. 55 F), influxing Na+

depolarizes the postsynaptic membrane and a nor-mal EPSP results ( D1 and p. 50ff). Glutamate alsobinds to the ionotropic NMDA (N-methyl–asparticacid) receptor. The ion channels of the NMDA recep-tors are in principle permeable to Ca2, but at normalEPSP are blocked by Mg2. If the neuron is furtherdepolarized by increased activity via the dendriticsynapses, the Mg2 is relieved and Ca2 can flow intothe cell. The cytosolic Ca2+ concentration [Ca2+]i thenrises. If this is repeated often enough, calmodulinmediates the autophosphorylation of CaM kinase II( D2 and p. 36), which persists even after the[Ca2+]i falls back to normal. CaM kinase II phosphory-lates AMPA receptors (increases their conductivity)and promotes their insertion into the postsynapticmembrane, thereby enhancing synaptic transmis-sion over longer periods of time (early LTP).Frequent, marked increases in [Ca2]i concentrationresults in long-term prolongation (late LTP), becausethis activates adenylate cyclase, and increased cAMPis released ( D3). The cAMP and MAP (mitogen-ac-tivated protein) kinases are then activated andphosphorylate transcription factors (CREB = cAMPresponse element binding protein) in the cell nu-cleus. These in turn activate promoters (CRE), and inthis manner resting synapses are mobilized and newproteins are synthesized.

Amnesia (memory loss). Retrograde amnesia(loss of memories of past events) is characterized bythe loss of primary memory and (temporary) diffi-culty in recalling information from the secondarymemory due to various causes (concussion, electro-shock, etc.). Anterograde amnesia (inability to formnew memories) is characterized by the inability totransfer new information from the primary memoryto the secondary memory (Korsakoff’s syndrome,which occurs mainly with alcoholism).

Language is a mode of communication used (1)to receive information through visual andaural channels (and through tactile channels inthe blind) and (2) to transmit information inwritten and spoken form (see also p. 372). Lan-guage is also needed to form and verbalizeconcepts and strategies based on consciouslyprocessed sensory input. Memories can there-fore be stored efficiently. The centers for for-mation and processing of concepts and lan-guage are unevenly distributed in the cerebralhemispheres. The left hemisphere is usuallythe main center of speech in right-handed in-dividuals (“dominant” hemisphere, largeplanum temporale), whereas the right hemi-sphere is dominant in 30–40% of all left-hand-ers. The non-dominant hemisphere is impor-tant for word recognition, sentence melody,and numerous nonverbal capacities (e.g.,music, spatial thinking, face recognition).

This can be illustrated using the example of patientsin whom the two hemispheres are surgically discon-nected due to conditions such as otherwise un-treatable, severe epilepsy. If such a split-brainpatient touches an object with the right hand (re-ported to the left hemisphere), he can name the ob-ject. If, however, he touches the object with the lefthand (right hemisphere), he cannot name the objectbut can point to a picture of it. Since complete sepa-ration of the two hemispheres also causes manyother severe disturbances, this type of surgery isused only in patients with otherwise unmanageable,extremely severe seizures.


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Plate 12.16 Memory, Learning II

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The central nervous system contains around1011 nerve cells and 10 times as many glia cellssuch as oligodendrocytes, astrocytes, ependy-mal cells, and microglia ( A). Oligodendro-cytes (ODC) form the myelin sheath that sur-rounds axons of the CNS ( A).

Astrocytes (AC) are responsible for extra-cellular K+ and H+ homeostasis in the CNS. Neu-rons release K+ in response to high-frequencystimulation ( B). Astrocytes prevent an in-crease in the interstitial K+ concentration andthus an undesirable depolarization of neurons(see Nernst equation, Eq. 1.18, p. 32) by takingup K+, and intervene in a similar manner withH+ ions. Since AC are connected by gap junc-tions ( p. 16ff.), they can transfer their K+ orH+ load to nearby AC ( B). In addition to form-ing a barrier that prevents transmitters fromone synapse from being absorbed by another,AC also take transmitters up, e.g. glutamate(Glu). Intracellular Glu is converted to glu-tamine (GluNH2), then transported out of thecell and taken up by the nerve cells, which con-vert it back to Glu (transmitter recycling; B).

Some AC have receptors for transmitters such asGlu, which triggers a Ca2+ wave from one AC toanother. Astrocytes are also able to modify the Ca2+

concentration in the neuronal cytosol so that the twocell types can “communicate” with each other. ACalso mediate the transport of materials betweencapillaries and neurons and play an important part inenergy homeostasis of the neurons by mediating gly-cogen synthesis and breakdown.

During embryonal development, the longprocesses of AC serve as guiding structures that helpundifferentiated nerve cells migrate to their targetareas. Glia cells also play an important role in CNSdevelopment by helping to control gene expressionin nerve cell clusters with or without the aid ofgrowth factors such as NGF (nerve growth factor),BDGF (brain-derived growth factor), and GDNF (glialcell line-derived neurotropic factor). GDNF alsoserves as a trophic factor for all mature neurons.

Cell division of glia cells can lead to scarring(epileptic foci) and tumor formation (glioma).

Immunocompetent microglia ( A) assumemany functions of macrophages outside the CNSwhen CNS injuries or infections occur ( p. 94ff.).Ependymal cells line internal hollow cavities of theCNS ( A).

Sense of Taste

Gustatory pathways. The taste buds ( D) con-sist of clusters of 50–100 secondary sensorycells on the tongue (renewed in 2-week cy-cles); humans have around 5000 taste buds.Sensory stimuli from the taste buds are con-ducted to endings of the VIIth, IXth and Xthcranial nerves, relayed by the nucleus tractussolitarii, and converge at a high frequency on(a) the postcentral gyrus via the thalamus( p. 325 B, “tongue”) and (b) the hypotha-lamus and limbic system via the pons ( C).

The qualities of taste distinguishable inhumans are conventionally defined as sweet,sour, salty, and bitter. The specific taste sensorcells for these qualities are distributed over thewhole tongue but differ with respect to theirdensities. Umami, the sensation caused bymonosodium-L-glutamate (MSG), is nowclassified as a fifth quality of taste. MSG ischiefly found in protein-rich foods.

Taste sensor cells distinguish the types of taste asfollows: Salty: Cations (Na+, K+, etc.) taste salty, butthe presence of anions also plays a role. E.g., Na+ en-ters the taste sensor cell via Na+ channels anddepolarizes the cell. Sour: H+ ions lead to a morefrequent closure of K+ channels, which also has adepolarizing effect. Bitter: A family of 50 genescodes for a battery of bitter sensors. A number ofsensory proteins specific for a particular substanceare expressed in a single taste sensor cell, making itsensitive to different bitter tastes. The sensory inputis relayed by the G-protein α-gustducin. No nuancesbut only the overall warning signal “bitter” is per-ceived. Umami: Certain taste sensor contain ametabotropic glutamate receptor, mGluR4, thestimulation of which leads to a drop in cAMP conc.

Taste thresholds. The threshold (mol/L) forrecognition of taste stimuli applied to thetongue is roughly 10– 5 for quinine sulfate andsaccharin, 10– 3 for HCl, and 10– 2 for sucroseand NaCl. The relative intensity differentialthreshold ∆I/I ( p. 358) is about 0.20. Theconcentration of the gustatory stimulus deter-mines whether its taste will be perceived aspleasant or unpleasant ( E). For the adapta-tion of the sense of taste, see p. 347 C.

Function of taste. The sense of taste has aprotective function as spoiled or bitter-tastingfood (low taste threshold) is often poisonous.Tasting substances also stimulate the secretionof saliva and gastric juices ( pp. 238, 244).

Glia

Hepatic encephalopathy, disorders of CSF transmitter metabolism, ageusia, dysgeusiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.17 Glia, Sense of Taste

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The neuroepithelium of the olfactory regioncontains ca. 107 primary olfactory sensor cells( A1) which are bipolar neurons. Their den-drites branch to form 5–20 mucus-coveredcilia, whereas the axons extend centrally inbundles called fila olfactoria ( A1,2). Ol-factory neurons are replenished by basal celldivision in 30–60-day cycles. Free nerveendings (trigeminal nerve) in the nasal mucosaalso react to certain aggressive odors (e.g., acidor ammonia vapors).

Olfactory sensors. Odorant molecules (Mr

15–300) are transported by the inhaled air tothe olfactory region, where they first dissolvein the mucous lining before combining withreceptor proteins in the cilial membrane. Theseare coded by a huge family of genes (500–750genes distributed in most chromosomes),whereby probably one olfactory sensor cellonly expresses one of these genes. Since only apart of the sequence of about 40% of thesegenes is expressed, humans have roughly 200–400 different sensor cell types. Olfactory re-ceptors couple with Gs-proteins (Golf proteins; B and p. 276ff.) that increase the conductiv-ity of the sensor cell membrane to cations,thereby increasing the influx of Na+ and Ca2+

and thus depolarizing the cell.Sensor specificity ( A3). Olfactory sensor

cells recognize a very specific structural fea-ture of the odorant molecules they are sensi-tive to.

The cloned receptor 17 of the rat, for example, reactswith the aldehyde n-octanal but not to octanol, oc-tanoic acid, or aldehydes which have two methylgroups more or less than n-octanal. In the case ofaromatic compounds, one sensor recognizeswhether the compound is ortho, meta or para-substi-tuted, while another detects the length of the sub-stituent regardless of where it is located on the ring.The different molecular moieties of an odorantmolecule therefore activate different types of sen-sors ( A3, top right). Jasmine leaves and wine con-tain several dozens and hundreds of odorants, re-spectively, so their overall scent is a more complexperception (integrated in the rhinencephalon).

Olfactory pathway ( A2). Axons of (ca. 103)same-type sensors distributed over the ol-factory epithelium synapse to dendrites oftheir respective mitral cells (MC) and bristlecells (BC) within the glomeruli olfactorii of theolfactory bulb. The glomeruli therefore func-

tion as convergence centers that integrate andrelay signals from the same sensor type. Theirrespective sensor protein also determineswhich glomerulus newly formed sensor axonswill connect to. Periglomerular cells and granu-lar cells connect and inhibit mitral and bristlecells ( A2). Mitral cells act on the same recip-rocal synapses ( A, “+/–”) in reverse directionto activate the periglomerular cells and granu-lar cells which, on the other hand, are inhibitedby efferents from the primary olfactory cortexand contralateral anterior olfactory nucleus( A2, violet tracts). These connections enablethe cells to inhibit themselves or nearby cells(contrast), or they can be disinhibited byhigher centers. The signals of the axons of mi-tral cells (1) reach the anterior olfactory nu-cleus. Its neurons cross over (in the anteriorcommissure) to the mitral cells of the con-tralateral bulb and (2) form the olfactory tractprojecting to the primary olfactory cortex (pre-piriform cortex, tuberculum olfactorium, nu-cleus corticalis amygdalae). The olfactoryinput processed there is relayed to the hy-pothalamus, limbic system (see also p. 332),and reticular formation; it is also relayed to theneocortex (insula, orbitofrontal area) eitherdirectly or by way of the thalamus.

Thresholds. It takes only 4 10-15 g ofmethylmercaptan (in garlic) per liter of air totrigger the vague sensation of smell (percep-tion or absolute threshold). The odor can beproperly identified when 2 10– 13 g/L is pres-ent (identification threshold). Such thresholdsare affected by air temperature and humidity;those for other substances can be 1010 timeshigher. The relative intensity differentialthreshold ∆I/I (0.25) is relatively high( p. 358). Adaptation to smell is sensor-de-pendent (desensitization) and neuronal ( C).

The sense of smell has various functions.Pleasant smells trigger the secretion of salivaand gastric juices, whereas unpleasant smellswarn of potentially spoiled food. Body odorpermits hygiene control (sweat, excrement),conveys social information (e.g., family,enemy; p. 332), and influences sexual be-havior. Other aromas influence the emotionalstate.

Sense of Smell

Conductive hyposmia (tumor, foreign body), skull base fracture, anosmia, parosmiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.18 Sense of Smell

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Anatomy. Each of the three semicircular canals( A1) is located in a plane about at right angles tothe others. The ampulla of each canal contains aridge-like structure called the crista ampullaris( A2). It contains hair cells (secondary sensorycells), the cilia of which ( A3) project into a gelat-inous membrane called the cupula ( A2). Each haircell has a long kinocilium and ca. 80 stereocilia of vari-able length. Their tips are connected to longer adja-cent cilia via the ”tip links” ( A3).

Semicircular canals. When the cilia are in aresting state, the hair cells release a transmit-ter (glutamate) that triggers the firing of actionpotentials (AP) in the nerve fibers of the vesti-bular ganglion. When the head is turned, thesemicircular canal automatically moves withit, but endolymph in the canal moves moresluggishly due to inertia. A brief pressure differ-ence thus develops between the two sides ofthe cupula. The resultant vaulting of thecupula causes the stereocilia to bend ( A2)and shear against each other, thereby changingthe cation conductance of the hair cell mem-brane. Bending of the stereocilia towards thekinocilium increases conductivity and allowsthe influx of K+ and Na+ along a high electro-chemical gradient between the endolymphand hair cell interior (see also pp. 372). Thus,the hair cell becomes depolarized, Ca2+ chan-nels open, more glutamate is released, and theAP frequency increases. The reverse occurswhen the cilia bend in the other direction(away from the kinocilium). The semicircularcanals function to detect angular (rotational)accelerations of the head in all planes (rotation,nodding, tilting sideways). Since normal headmovements take less than 0.3 s (acceleration⇒ deceleration), stimulation of the semicircu-lar canals usually reflects the rotational veloc-ity.

The pressure difference across the cupula disappearswhen the body rotates for longer periods of time.Deceleration of the rotation causes a pressuregradient in the opposite direction. When bending ofthe cilia increased the AP frequency at the start of ro-tation, it decreases during deceleration and viceversa. Abrupt cessation of the rotation leads to ver-tigo and nystagmus (see below).

The saccule and utricle contain maculae ( A1,A4) with cilia that project into a gelatinousmembrane ( A4) with high density ( 3.0)calcite crystals called statoconia, statoliths or

otoliths. They displace the membrane andthereby bend the embedded cilia ( A4) dueto changes of the direction of gravity, e.g. whenthe head position deviates from the perpen-dicular axis. The maculae respond also to otherlinear (translational) accelerations or decelera-tions, e.g. of a car or an elevator.

Central connections. The bipolar neurons ofthe vestibular ganglion synapse with the vesti-bular nuclei ( A, B). Important tracts extendfrom there to the contralateral side and to ocu-lar muscle nuclei, cerebellum ( p. 328), mo-toneurons of the skeletal muscles, and to thepostcentral gyrus (conscious spatial orienta-tion). Vestibular reflexes (a) maintain thebalance of the body (postural motor function, p. 330) and (b) keep the visual field in focusdespite changes in head and body position(oculomotor control, B and p. 366).

Example ( C): If a support holding a test subject istilted, the activated vestibular organ prompts thesubject to extend the arm and thigh on the decliningside and to bend the arm on the inclining side tomaintain balance ( C2). The patient with an im-paired equilibrium organ fails to respond appro-priately and topples over ( C3).

Since the vestibular organ cannot determinewhether the head alone or the entire bodymoves (sense of movement) or changed posi-tion (postural sense), the vestibular nucleimust also receive and process visual informa-tion and that from propriosensors in the neckmuscles. Efferent fibers project bilaterally tothe eye muscle nuclei, and any change in headposition is immediately corrected by opposingeye movement ( B). This vestibulo-ocular re-flex maintains spatial orientation.

Vestibular organ function can be assessed by testingoculomotor control. Secondary or postrotatory nys-tagmus occurs after abrupt cessation of prolongedrotation of the head around the vertical axis (e.g., inan office chair) due to activation of the horizontalsemicircular canals. It is characterized by slow hor-izontal movement of the eyes in the direction of rota-tion and rapid return movement. Rightward rotationleads to left nystagmus and vice versa ( p. 366). Ca-loric stimulation of the horizontal semicircular canalby instilling cold (30 C) or warm water (44 C) in theauditory canal leads to caloric nystagmus. Thismethod can be used for unilateral testing.

Sense of Balance

Damage to semicircular canals or maculae (ischemia, Meniere’s disease), nystagmus, dizzinessDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.19 Sense of Balance

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Light entering the eye must pass through thecornea, aqueous humor, lens and vitreous body,which are collectively called the optical ap-paratus, before reaching the retina and itslight-sensitive photosensors ( A). This pro-duces a reduced and inverse image of the visualfield on the retina. All parts of the apparatusmust be transparent and have a stable shapeand smooth surface to produce an undistortedimage, which is the main purpose of tear fluidin case of the cornea. Tears are secreted bylacrimal glands located in the top outer por-tion of orbit and their mode of production issimilar to that of saliva ( p. 238). Tears aredistributed by reflex blinking and then passthrough the lacrimal puncta and lacrimalcanaliculi (or ducts) of the upper and lowereyelid into the lacrimal sac and finally draininto the nasal sinuses by way of the nasolacri-mal duct. Tear fluid improves the opticalcharacteristics of the cornea by smoothing un-even surfaces, washing away dust, protecting itfrom caustic vapors and chemicals, and pro-tects it from drying out. Tears lubricate theeyelid movement and contain lysozyme andimmunoglobulin A ( pp. 96ff. and 234),which help ward off infections. In addition,tears are a well known mode of expressingemotions.

The entry of light into the eye is regulatedby the iris ( A; p. 359 C1), which containsannular and radial smooth muscle fibers.Cholinergic activation of the sphincter muscleof pupil leads to pupil contraction (miosis), andadrenergic activation of the dilator muscle ofpupil results in pupil dilatation (mydriasis).

The bulbus (eyeball) maintains its shape dueto its tough outer coat or sclera ( C) and in-traocular pressure which is normally10–21 mmHg above the atmospheric pressure.The drainage of aqueous humor must balanceits production to maintain a constant ocularpressure ( C). Aqueous humor is produced inthe ciliary process of the posterior ocular cham-ber with the aid of carbonic anhydrase and ac-tive ion transport. It flows through the pupilinto the anterior ocular chamber and drainsinto the venous system by way of the trabecu-lar meshwork and Schlemm’s canal. Aqueoushumor is renewed once every hour or so.

Glaucoma. Obstruction of humor drainage canoccur due to chronic obliteration of the trabecularmeshwork (open-angle glaucoma) or due to acuteblock of the anterior angle (angle-closure glaucoma)leading to elevated intraocular pressure, pain, retinaldamage, and blindness. Drugs that decrease humorproduction (e.g. carbonic anhydrase inhibitors) andinduce meiosis are used to treat glaucoma.

The lens is held in place by the ciliary zonules( C). When the eye adjusts for far vision, thezonules are stretched and the lens becomesflatter, especially its anterior surface ( D,top). When looking at nearby objects (near vi-sion), the zonules are relaxed due to contrac-tion of the ciliary muscle, and the lens reas-sumes its original shape due to its elasticity( D , bottom, and p. 352).

The retina lines the interior surface of thebulbus except the anterior surface and the sitewhere the optical nerve ( A) exits the bulbusvia the optic papilla ( A). The fovea centralis( A) forms a slight depression across fromthe pupillary opening. The retina consists ofseveral layers, named from inside out as fol-lows ( E): pigmented epithelium, photosen-sors (rods and cones), Cajal’s horizontal cells,bipolar cells, amacrine cells, and ganglioncells. The central processes of the ganglioncells (n 106) exit the bulbus as the opticalnerve (retinal circuitry; p. 361ff.).

Photosensors. Retinal rods and cones have alight-sensitive outer segment, which is con-nected to a inner segment by a thin connectingpart ( p. 355 C1). The inner segment containsthe normal cell organelles and establishes syn-aptic contact with the neighboring cells. Theouter segment of the rod cells contains ca. 800membranous disks, and the plasma membraneof the outer segment of the cones is folded.Visual pigments are stored in these disks andfolds ( p. 354).

The outer segment is continuously regenerated;the old membranous disks at the tip of the cell areshed and replaced by new disks from the inner seg-ment. The phagocytic cells of the pigmentedepithelium engulf the disks shed by the rods in themorning, and those shed by the cones in the eve-ning. Some ganglion cells contain a light-sensitivepigment ( p. 336).

Eye Structure, Tear Fluid, Aqueous Humor

Glaucoma, cataracts, tear fluid drainage abnormalities, retinal detachmentDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.20 Eye Structure, Tear Fluid, Aqueous Humor

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Physics. The production of an optical image isbased on the refraction of light rays crossing a spheri-cal interface between air and another medium. Sucha simple optical system illustrated in plate A has ananterior focal point (Fa) in air, a posterior focal point(Fp), a principal point (P), and a nodal point (N). Lightrays from a distant point () can be regarded as par-allel. If they enter the system parallel to its opticalaxis, they will converge at Fp ( A1, red dot). If theyenter at an angle to the axis, then they will form animage beside Fp but in the same focal plane ( A1,violet dot). Light rays from a nearby point do not en-ter the system in parallel and form an image behindthe focal plane ( A2, green and brown dots).

The optical apparatus of the eye consists ofmultiple interfaces and media, and is thereforea complex optical system. It can, however, betreated as a simple optical system. Light raysfrom a focused object (O) pass through N anddiverge at angle α until they reach the retinaand form an image (I) there ( A2).

Two points separated by a distance of 1.5 mm and lo-cated 5 m away from the eye (tan α = 1.5/5000; α =0.0175 degrees 1′) will therefore be brought intofocus 5 µm apart on the retina. In a person with nor-mal vision ( p. 356), these two points can be distin-guished as separate because 5 µm corresponds tothe diameter of three cones in the fovea (two arestimulated, the one in between is not).

Accommodation. When the eyes are adjustedfor far vision, parallel light rays from a distantpoint meet at Fp ( B1, red dot). Since the ret-ina is also located at Fp, the distant point isclearly imaged there. The eye adjusted for farvision will not form a clear image of a nearbypoint (the light rays meet behind the retina, B1, green dot) until the eye has adjusted fornear vision. In other words, the curvature ofthe lens (and its refractive power) increasesand the image of the nearby point moves to theretinal plane ( B2, green dot). Now, the dis-tant point cannot not be sharply imaged sinceFp does not lie in the retinal plane any more( B2).

The refractive power of the eye is the recip-rocal of the anterior focal length in meters, andis measured in diopters (dpt). In accommoda-tion for far vision, focal length = anterior focalpoint (Fa)–principal point (P) = 0.017 m ( B1).Thus, the corresponding refractive power is1/0.017 = 58.8 dpt, which is mainly attributableto refraction at the air–cornea interface (43

dpt). In maximum accommodation for near vi-sion in a young person with normal vision (em-metropia), the refractive power increases byaround 10–14 dpt. This increase is called rangeof accommodation and is calculated as 1/nearpoint –1/far point (m–1 = dpt). The near pointis the closest distance to which the eye canaccommodate; that of a young person withnormal vision is 0.07–0.1 m. The far point is in-finity () in subjects with normal vision. Therange of accommodation to a near point of0.1 m is therefore 10 dpt since 1/ = 0.

The refractive power around the edge of the opticalapparatus is higher than near the optical axis. Thisspherical aberration can be minimized by narrow-ing the pupils.

The range of accommodation decreases aswe grow older (to 1–3.5 dpt in 50-year-olds)due to the loss of elasticity of the lens. Thisvisual impairment of aging, called presbyopia( C1–3), normally does not affect far vision,but convex lenses are generally required fornear vision, e.g., reading.

Cataract causes opacity of the lens of one or botheyes. When surgically treated, convex lenses (glassesor artificial intraocular lenses) of at least + 15 dptmust be used to correct the vision.

In myopia (near-sightedness), rays of light en-tering the eye parallel to the optical axis are broughtto focus in front of the retina because the eyeball istoo long ( C4). Distant objects are therefore seenas blurred because the far point is displaced towardsthe eyes ( C5). Myopia is corrected by concavelenses (negative dpt) that disperse the parallel lightrays to the corresponding extent ( C6 ). Example:When the far point = 0.5 m, a lens of [– 1/0.5] = [– 2dpt] will be required for correction ( C7). In hyper-opia (far-sightedness), on the other hand, the eye-ball is too short. Since the accommodation mecha-nisms for near vision must then be already used tofocus distant objects ( C8), the range of accommo-dation no longer suffices to clearly focus nearby ob-jects ( C9). Hyperopia is corrected by convex lenses(+ dpt) ( C10–11).

Astigmatism. In regular astigmatism, the cornealsurface is more curved in one plane (usually the verti-cal: astigmatism with the rule) than the other, creat-ing a difference in refraction between the twoplanes. A point source of light is therefore seen as aline or oval. Regular astigmatism is corrected by cy-lindrical lenses. Irregular astigmatism (caused byscars, etc.) can be corrected by contact lenses.

Optical Apparatus of the Eye

Myopia, hyperopia, presbyopia, astigmatism, glasses and contact lensesDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.21 Optical Apparatus of the Eye

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Visual acuity is an important measure of eyefunction. Under well-lighted conditions, thenormal eye should be able to distinguish twopoints as separate when the light rays emittedby the point objects converge at an angle (α) of1 min (1/60 degree) ( A and p. 352). Visualacuity is calculated as 1/α (min– 1), and is 1/1 insubjects with normal vision.

Visual acuity testing is generally performed usingcharts with letters or other optotypes (e.g., Landoltrings) of various sizes used to simulate different dis-tances to the test subject. The letters or rings areusually displayed at a distance of 5 m ( A). Visualacuity is normal (1/1) if the patient recognizes lettersor ring openings seen at an angle of 1 min from a dis-tance of 5 m. Example: It should be possible to iden-tify the direction of the opening of the middle ringfrom a distance of 5 m and that of the left ring from adistance of 8.5 m ( A). If only the opening of theleft ring can be localized from the test distance of5 m, the visual acuity is 5/8.5 = 0.59.

Photosensors or photoreceptors. The light-sensitive sensors of the eye consist of approxi-mately 6 · 106 rods and 20 times as many cones( p. 351 E) distributed at variable densitiesthroughout the retina ( B1). (Certain gan-glion cells also contain a light-sensitive pig-ment; p. 336). The fovea centralis is exclu-sively filled with cones, and their densityrapidly decreases towards the periphery. Rodspredominate 20–30 degrees away from thefovea centralis. Approaching the periphery ofthe retina, the density of the rods decreasescontinuously from 1.5 105/mm2 (maximum)to about one-third this value. No photosensorsare present on the optic disk, which is thereforereferred to as the blind spot in the visual field.

Clear visualization of an object in daylightrequires that the gaze be fixed on it, i.e., that animage of the object is produced in the foveacentralis. Sudden motion in the periphery ofthe visual field triggers a reflex saccade( p. 366), which shifts the image of the objectinto the fovea centralis. Thereby, the retinalarea with the highest visual acuity is selected( B2, yellow peak), which lies 5 degrees tem-poral to the optical axis. Visual acuitydecreases rapidly when moving outward fromthe fovea ( B2, yellow field), reflecting thedecreasing density of cone distribution ( B1,red curve). In a dark-adapted eye, on the otherhand, the sensitivity of the retina ( B2, blue

curve) is completely dependent on the rod dis-tribution ( B1, purple curve). The color-sen-sitive cones are therefore used for visual per-ception in daylight or good lighting (day vision,photopic vision), while the black and white-sensitive cones are used to visualize objects indarkness (dim-light vision, night vision, scotop-tic vision). The high light sensitivity in night vi-sion is associated with a high loss of visual acu-ity ( p. 360).

Photosensor Function

Light-absorbing visual pigments and a varietyof enzymes and transmitters in retinal rods andcones ( C1) mediate the conversion of lightstimuli into electrical stimuli; this is calledphotoelectric transduction. The membranousdisks of the retinal rods contain rhodopsin( C2), a photosensitive purple-red chromo-protein (visual purple). Rhodopsin consists ofthe integral membrane protein opsin and thealdehyde 11-cis-retinal. The latter is bound to alysine residue of opsin which is embedded inthis protein; it is stably kept in place by weakinteractions with two other amino acid resi-dues. Photic stimuli trigger a primary photo-chemical reaction in rhodopsin (duration,2 · 10– 14 s) in which 11-cis-retinal is convertedto all-trans-retinal ( C3). Even without con-tinued photic stimulation, the reaction yieldsbathorhodopsin, the intermediates lumirho-dopsin and metarhodopsin I, and finally meta-rhodopsin II within roughly 10– 3 s ( D1).

Metarhodopsin II (MR-II) reacts with a Gs-protein ( p. 276) called transducin (Gt-pro-tein), which breaks down into αs and γ sub-units once GDP has been replaced by GTP( D1). Activated αs-GTP now binds the inhibi-tory subunit of cGMP phosphodiesterase (IPDE)( D2). The consequently disinhibited phos-phodiesterase (PDE) then lowers the cytosolicconcentration of cyclic guanosine mono-phosphate (cGMP). The activation of a singleretinal rhodopsin molecule by a quantum oflight can induce the hydrolysis of up to 106

cGMP molecules per second. The reaction cas-cade therefore has tremendous amplifyingpower.

In darkness ( D, left), cGMP is bound tocation channels (Na+, Ca2+) in the outer seg-ment of the photosensor, thereby keepingthem open. Na+ and Ca2+ can therefore enter

Visual Acuity, Photosensors

Eyesight test, retinal detachment, diabetic retinopathy, occlusion of central retinal artery


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Plate 12.22 Visual Acuity, Photosensors I

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the cell and depolarize it to about – 40 mV( D3, D4). The Ca2+ entering the outer seg-ment is immediately transported out of thecell by a 3 Na+/Ca2+ exchanger ( p. 36), so thecytosolic Ca2+ concentration [Ca 2+]i remainsconstant at ca. 350–500 nmol/L in darkness( D6). If the cytosolic cGMP concentrationdecreases in response to a light stimulus( D2), cGMP dissociates from the cationchannels, allowing them to close. The photo-sensor then hyperpolarizes to ca. – 70 mV (sen-sor potential: D, right). This inhibits the re-lease of glutamate (transmitter) at the sensorpedicle ( D5), which subsequently causeschanges in the membrane potential indownstream retinal neurons ( p. 362).

Deactivation of Photic Reactions andRegeneration Cycles

Rhodopsin ( E2). Rhodopsin kinase (RK)competes with transducin for bindings sites onmetarhodopsin II (MR-II); the concentration oftransducin is 100 times higher ( E2, right).Binding of RK to MR-II leads to phosphoryla-tion of MR-II. As a result, its affinity to trans-ducin decreases while its affinity to anotherprotein, arrestin, rises. Arrestin blocks thebinding of further transducin molecules toMR-II. All-trans-retinal detaches from opsin,which is subsequently dephosphorylated andre-loaded with 11-cis-retinal.

Vitamin A. In the photosensor, all-trans-ret-inal ( E1) is reduced to all-trans-retinol (= vi-tamin A), which is transported into the pig-mented epithelium (PE). When light is pres-ent, it is esterified and with membrane-boundRPE65 (mRPE65) and an isomerohydrolase(IMH) ultimately restored to 11-cis-retinalwhich binds to opsin again in the photosensor( E2). In darkness, Vitamin A binds to thesoluble protein RPE65 (sRPE65) in the PE andstored until required when light returns.Lecithin retinol acyltransferase (LRAT) is re-sponsible for the sRPE65 to mRPE65 conver-sion.A chronic deficiency of vitamin A1 leads tonight blindness ( p. 358). RPE65 mutationscause certain forms of retinitis pigmentosa,e.g., congenital blindness.

Transducin ( E3). Since the GTPase activityof αs-GTP breaks down GTP into GDP + Pi, themolecule deactivates itself. The αs-GTPmolecule and γ subunit then rejoin to formtransducin. GAP (GTPase-activating protein)accelerates the regeneration of transducin.Phosducin, another protein, is phosphorylatedin the dark ( D6) and dephosphorylated inlight ( D7). The latter form binds to the γsubunit ( D7, E3), thereby blocking the re-generation of transducin. This plays a role inlight adaptation (see below). Phosphodiesterase (PDE). In the course oftransducin regeneration, the inhibitory sub-unit of cGMP phosphodiesterase (IPDE) is re-leased again and PDE is thus inactivated. cGMP. Since the 3 Na+/Ca2+ exchanger stillfunctions even after photostimulation-in-duced closure of Ca2+ channels, the [Ca2+]i

starts to decrease. When a threshold of ca.100 nmol/L is reached, the Ca2+-binding pro-tein GCAP (guanylyl cyclase-activating pro-tein) loses its 4 Ca2+ ions and stimulates guany-lyl cyclase, thereby accelerating cGMP synthe-sis. Thus, the cGMP concentration rises, thecation channels re-open, and the sensor isready to receive a new light stimulus. This Ca2+

cycle therefore mediates a negative feedbackloop for cGMP production.

Ca2+ Ions and Adaptation (see also p. 358)

In the dark, the [Ca2+]i is high, and calmodulin-bound Ca2+ ( p. 36) stimulates the phospho-rylation of phosducin with the aid of cAMP andphosphokinase A ( D6). In light, the [Ca2+]i islow; phosducin is dephosphorylated and rapidregeneration of transducin is not possible( D7, E3). Moreover, Ca2+ accelerates thephosphorylation of MR-II in light with the aidof another Ca2+ binding protein, recoverin( E2). Ca2+ is therefore essential for the adap-tation of photosensors ( p. 358).

Although they contain similar enzymes andtransmitters, the photosensitivity of the conesis about 100 times less than that of the rods.Thus, the cones are unable to detect a singlequantum of light, possibly because photic re-actions in the cones are deactivated tooquickly.

Visual Acuity, Photosensors (continued)

Retinitis pigmentosa, macular degenerationDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.23 Photosensors II

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The eye is able to perceive a wide range of lightintensities, from the extremely low intensityof a small star to the extremely strong intensityof the sun glaring on a glacier. The ability of theeye to process such a wide range of luminance(1 : 1011) by adjusting to the prevailing light in-tensity is called adaptation. When going fromnormal daylight into a darkened room, theroom will first appear black because its lumi-nance value (measured in cd · m-2) is lowerthan the current ocular threshold. As thestimulus threshold decreases over the nextfew minutes, the furniture in the room gradu-ally becomes identifiable. A longer period ofadaptation is required to visualize stars. Themaximum level of adaptation is reached inabout 30 min ( A). The minimum light inten-sity that can just be detected after maximumdark adaptation is the absolute visual thresh-old, which is defined as 1 in A and B.

The retinal adaptation curve exhibits a(Kohlrausch) break at roughly 2000 the ab-solute threshold ( A, blue curve). This corre-sponds to the point where the excitationthreshold of the cones is reached (thresholdfor day vision). The remainder of the curve isgoverned by the somewhat slower adaptationof the rods ( A, violet curve). The isolated rodadaptation curve can be recorded in patientswith complete color blindness (rod monochro-matism), and the isolated cone adaptationcurve can be observed in night blindness(hemeralopia, p. 356).

Differential threshold (or difference limen).The ability of the eye to distinguish the differ-ence between two similar photic stimuli is animportant prerequisite for proper eyesight. Atthe lowest limit of discriminative sensibilityfor two light intensities I and I′, the absolutedifferential threshold (∆ I) is defined as I minusI′. The relative differential threshold is calcu-lated as ∆ I/I, and remains relatively constantin the median stimulus range (Weber’s rule).Under optimal lighting conditions (approx. 109

times the absolute threshold; B), ∆ I/I is verysmall (0.01). The relative differential thresholdrises greatly in dark adaptation, but also risesin response to extremely bright light. Sun-glasses decrease the differential threshold inthe latter case.

The mechanisms for adaptation of the eyeare as follows ( C): Pupil reflex ( C1). Through reflexive re-sponses to light exposure of the retina( p. 365), the pupils can adjust the quantityof light entering the retina by a factor of 16.Thus, the pupils are larger in darkness than indaylight. The main function of the pupil reflexis to ensure rapid adaptation to suddenchanges in light intensity. Chemical stimuli ( C2) help to adjust thesensitivity of photosensors to the prevailinglight conditions. Large quantities of light leadto a prolonged decrease in the receptor’s cyto-solic Ca2+ concentration. This in conjunctionwith the activity of recoverin and phosducinreduces the availability of rhodopsin ( p.354ff.). It therefore decreases the probabilitythat a rhodopsin molecule will be struck by anincoming light ray (photon) or that a meta-rhodopsin II molecule will come in contactwith a transducin molecule. When the lightintensity is low, large concentrations ofrhodopsin and transducin are available and thephotosensors become very light-sensitive. Spatial summation ( C3). Variation of reti-nal surface area (number of photosensors) ex-citing an optic nerve fiber causes a form of spa-tial summation that increases with darknessand decreases with brightness ( p. 360). Temporal summation ( C4). Brief sub-threshold stimuli can be raised above thresh-old by increasing the duration of stimulation(by staring at an object) long enough to triggeran action potential (AP). Thereby, the productof stimulus intensity times stimulus durationremains constant.

Successive contrast occurs due to “localadaptation.” When a subject stares at the cen-ter of the black-and-white pattern ( D) forabout 20 s and suddenly shifts the focus to thewhite circle, the previously dark areas appearto be brighter than the surroundings due tosensitization of the corresponding areas of theretina.

Adaptation of the Eye to Different Light Intensities

Vitamin A deficiency, night blindness, rod monochromasiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.24 Adaptation to Light Intensity

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Light stimuli hyperpolarize the sensor poten-tial of photosensors ( A, left) from ca. – 40 mVto ca. – 70 mV (maximum) due to a decrease inconductance of the membrane of the outersensor segment to Na+ and Ca2+ ( p. 354ff.).The potential rises and falls much moresharply in the cones than in the rods. As inother sensory cells, the magnitude of the sen-sor potential is proportional to the logarithmof stimulus intensity divided by threshold-intensity (Fechner’s law). Hyperpolarizationdecreases glutamate release from the receptor.When this signal is relayed within the retina, adistinction is made between “direct” signalflow for photopic vision and “lateral” signalflow for scotopic vision (see below). Actionpotentials (APs) can only be generated in gan-glion cells ( A, right), but stimulus-depend-ent amplitude changes of the potentials occurin the other retinal neurons ( A, center).These are conducted electrotonically acrossthe short spaces in the retina ( p. 48ff.).

Direct signal flow from cones to bipolar cells is con-ducted via ON or OFF bipolar cells. Photostimulationleads to depolarization of ON bipolar cells (signal in-version) and activation of their respective ON gan-glion cells ( A). OFF bipolar cells, on the other hand,are hyperpolarized by photostimulation, which hasan inhibitory effect on their OFF ganglion cells.”Lateral” signal flow can occur via the followingpathway: rod ⇒ rod–bipolar cell ⇒ rod–amacrinecell ⇒ ON or OFF bipolar cell ⇒ ON or OFF ganglioncell. Both rod–bipolar cells and rod–amacrine cellsare depolarized in response to light. Rod–amacrinecells inhibit OFF bipolar cells via a chemical synapseand stimulate ON bipolar cells via an electrical syn-apse ( p. 50).

A light stimulus triggers the firing of an AP inON ganglion cells ( A, right). The APfrequency increases with the sensor potentialamplitude. The APs of ON ganglion cells can bemeasured using microelectrodes. This data canbe used to identify the retinal region in whichthe stimulatory and inhibitory effects on APfrequency originate. This region is called thereceptive field (RF) of the ganglion cell. Retinalganglion cells have concentric RFs comprisinga central zone and a ringlike peripheral zonedistinguishable during light adaptation ( B).Photic stimulation of the center increases theAP frequency of ON ganglion cells ( B1).Stimulation of the periphery, on the other

hand, leads to a decrease in AP frequency, butexcitation occurs when the light source isswitched off ( B2). This type of RF is referredto as an ON field (central field ON). The RF ofOFF ganglion cells exhibits the reverse re-sponse and is referred to as an OFF field (cen-tral field OFF). Horizontal cells are responsiblefor the functional organization of the RFs( p. 350). They invert the impulses from pho-tosensors in the periphery of the RF and trans-mit them to the sensors of the center. The op-posing central and peripheral responses leadto a stimulus contrast. At a light–dark inter-face, for example, the dark side appears darkerand the light side brighter. If the entire RF is ex-posed to light, the impulses from the centerusually predominate.

Simultaneous contrast. A solid gray circle appearsdarker in light surroundings than in dark surround-ings ( C, left). When a subject focuses on a black-and-white grid ( C, right), the white grid lines ap-pear to be darker at the cross-sections, black gridlines appear lighter because of reduced contrast inthese areas. This effect can be attributed to a variablesum of stimuli within the RFs ( C, center).

During dark adaptation, the center of the RFsincreases in size at the expense of the pe-riphery, which ultimately disappears. Thisleads to an increase in spatial summation( p. 359 C3), but to a simultaneous decreasein stimulus contrast and thus to a lower visualacuity ( p. 355 B2).

Color opponency. Red and green light (orblue and yellow light) have opposing effects inthe RFs of ganglion cells ( p. 364) and morecentrally located cells of the optic tract( p. 363 E). These effects are explained byHering’s opponent colors theory and ensurecontrast (increase color saturation; p. 362)in color vision. When a subject focuses on acolor test pattern ( p. 365 C) for about 30 minand then shifts the gaze to a neutral back-ground, the complementary colors will beseen (color successive contrast).

RFs of higher centers of the optic tract (V1,V2; p. 366) can also be identified, but theircharacteristics change. Shape (striate or angu-lar), length, axial direction and direction ofmovement of the photic stimuli play impor-tant roles.

Retinal Processing of Visual Stimuli

Retinal disease, optic nerve lesions (e.g. multiple sclerosis)Despopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.25 Retinal Processing of Visual Stimuli

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White light passing through a prism is splitinto a color spectrum ranging from red to vio-let (colors of the rainbow). Red is perceived at awavelength (λ) of 650–700 nm, and violet ataround 400–420 nm ( A). The eye is sensitiveto waves in this λ range. Perception of whitelight does not require the presence of all colorsof the visible spectrum. It is sufficient to havethe additive effects (mixing) of only two com-plementary colors, e.g., orange (612 nm) andblue light (490 nm).

A color triangle ( B) or similar test panel can beused to illustrate this effect. The two upper limbs ofthe triangle show the visible spectrum, and a whitedot is located inside the triangle. All straight linespassing through this dot intersect the upper limbs ofthe triangle at two complementary wavelengths(e.g., 612 and 490 nm). Additive color mixing( C): The color yellow is obtained by mixing roughlyequal parts of red and green light. Orange is pro-duced by using a higher red fraction, and yellowishgreen is obtained with a higher green fraction. Thesecolors lie between red and green on the limbs of thecolor triangle. Similar rules apply when mixing greenand violet ( B and C). The combination of red withviolet yields a shade of purple not contained in thespectrum ( B). This means that all colors, includingwhite, can be produced by varying the proportionsof three colors—e.g. red (700 nm), green (546 nm)and blue (435 nm) because every possible pair ofcomplementary colors can be obtained by mixingthese three colors of the spectrum.

Subtractive color mixing is based on the op-posite principle. This technique is applied when colorpaints and camera filters are used. Yellow paints orfilters absorb (“subtract”) the blue fraction of whitelight, leaving the complementary color yellow.

Light absorption. Photosensors must be able toabsorb light to be photosensitive. Rods( p. 354) contain rhodopsin, which is re-sponsible for (achromatic) night vision.Rhodopsin absorbs light at wavelengths of ca.400–600 nm; the maximum absorption value(λmax) is 500 nm ( E1). Relatively speaking,greenish blue light therefore appears brightestand red appears darkest at night. Wearing redglasses in daylight therefore leaves the rodsadapted for darkness. Three types of color-sen-sitive cones are responsible for (chromatic)day vision ( E1): (1) S cones, which absorbshort-wave (S) blue-violet light (λmax =420 nm); (2) M cones, which absorb medium-wave (M) blue-green to yellow light (λmax =

535 nm), and (3) L cones, which absorb long-wave (L) yellow to red light (λmax = 565 nm).(The physiological sensitivity curves shown inE1 make allowances for light absorbed by thelens.) Ultraviolet rays (λ max 400 nm) and in-frared rays (λmax 700 nm) are not visible.

Sensory information relayed by the threetypes of cones (peripheral application of thetrichromatic theory of color vision) and trans-duction of these visual impulses to brightnessand opponent color channels ( E2 and p. 360)in the retina and lateral geniculate body (LGB)enables the visual cortex ( p. 364) to recog-nize different types of colors. The human eyecan distinguish 200 shades of color and differ-ent degrees of color saturation. The absolutedifferential threshold for color vision is 1–2 nm( D, “normal”).

Color perception is more complex. White paper, forexample, will look white in white light (sunlight), yel-low light (light bulb) and red light. We also do notperceive the different shades of color in a house thatis partially illuminated by sunlight and partially in theshade. This color constancy is the result of retinaland central processing of the retinal signal.

There is a similar constancy of size and shape:Although someone standing 200 meters awaymakes a much smaller image on the retina than at2 meters’ distance, we still recognize him or her as aperson of normal height, and although a square tablemay appear rhomboid in shape when viewed fromthe side, we can still tell that it is square.

Color blindness occurs in 9% of all men and in0.5% of women. The ability to distinguish certaincolors is impaired or absent in these individuals, i.e.,they have a high differential threshold for color ( D).Various types of color blindness are distinguished:protanopia (red blindness), deuteranopia (greenblindness), and tritanopia (blue-violet blindness).Protanomaly, deuteranomaly and tritanomaly arecharacterized by decreased sensitivity of the conesto colored, green and blue, respectively. Color visionis tested using color perception charts or an anomalo-scope. With the latter, the subject has to mix twocolor beams (e.g., red and green) with adjustable in-tensities until their additive mixture matches aspecific shade of color (e.g. yellow, C) presentedfor comparison. A protanomal subject needs a toohigh red intensity, a deuteranomal person a too highgreen intensity. Protanopes perceive all colors withwavelengths over approx. 520 nm as yellow.

Color Vision

Color vision test, color anopsia and anomaliesDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.26 Color Vision

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The visual field ( A) is the area visualized bythe immobile eye with the head fixed.

The visual field is examined by perimetry. The sub-ject’s eye is positioned in the center of the perimeter,which is a hollow hemispherical instrument. The sub-ject must then report when laterally flashed points oflight appear in or disappear from the visual field.

An area of lost vision within the visual field is ascotoma. Lesions of the retina, or of the centralvisual pathway can cause scotoma.

The blind spot ( A) is a normal scotoma occur-ring at 15 degrees temporal and is caused by nasal in-terruption of the retina by the optic disk( p. 355 B). In binocular vision ( p. 367 A), theblind spot of one eye is compensated for by theother. The visual field for color stimuli is smaller thanthat for light–dark stimuli. If, for example, a red ob-ject is slowly moved into the visual field, the move-ment will be identified more quickly than the color ofthe object.

The retina contains more than 108 photosen-sors connected by retinal neurons ( p. 360)to ca. 106 retinal ganglion cells. Their axonsform the optic nerve. The convergence of somany sensors on only a few neurons is particu-larly evident in the retinal periphery (1000 : 1).In the fovea centralis, however, only one or afew cones are connected to one neuron. Due tothe low convergence of impulses from thefovea, there is a high level of visual acuity witha low level of light sensitivity, whereas thehigh convergence of signals from the periph-ery produces the reverse effect (cf. spatial sum-mation; p. 359 C3).

Ganglion cells. Three types of ganglion cellscan be found in the retina: (1) 10% are M (or αor Y) cells of the magnocellular system; theirfast-conducting axons emit short phasic im-pulses in response to light and are very sensi-tive to movement; (2) 80% are the P (or or X)cells of the parvicellular system; their thinaxons have small receptive fields (high spatialresolution), persistently react to constant light(tonic reaction), and therefore permit patternand color analysis. Both types have equal den-sities of ON and OFF cells ( p. 360). (3) 10%are γ (or W) cells of the coniocellular system;their very thin axons project to the mesen-cephalon and regulate pupil diameter (seebelow) and reflex saccades ( pp. 354, 366).

Objects located in the nasal half of the visualfield of each eye ( B, blue and green) are im-aged in the temporal half of each retina and

vice versa. Along the visual pathway, fibers ofthe optic nerve from the temporal half of eachretina remain on the same side ( B, blue andgreen), whereas the fibers from the nasal halfof each retina decussate at the optic chiasm( B, orange and red). Fibers from the foveacentralis are present on both sides.

Lesions of the left optic nerve for instance cause defi-cits in the entire left visual field ( B, a), whereas le-sions of the left optic tract produce deficits in theright halves of both visual fields ( B, c). Damage tothe median optic chiasm results in bilateral temporaldeficits, i.e., bitemporal hemianopia ( B, b).

Fibers of the optic tract extend to the lateralgeniculate body ( B) of the thalamus, the sixlayers of which are organized in a retinotopicmanner. Axons of the ipsilateral eye terminateon layers 2, 3 and 5, while those of the con-tralateral eye terminate on layers 1, 4 and6. The M cell axons communicate with cells ofmagnocellular layers 1 and 2, which serve as arelay station for motion-related stimuli that arerapidly conducted to the motor cortex. The Pcell axons project to the parvocellular layers3–6, the main function of which is to processcolors and shapes. The neurons of all layersthen project further through the optic radia-tion (arranged also retinotopically) to the pri-mary visual cortex (V1) and, after decussating,to further areas of the visual cortex (V2–5) in-cluding pathways to the parietal and temporalcortex. Magnocellular input reaches theparietal cortex also via the superior colliculi(see below) and the pulvinar.

The primary visual cortex (V1) is divided depth-wise(x-axis) into six retinotopic layers numbered I to VI( p. 335 A). Cells of the primary visual cortex are ar-ranged as three-dimensional modular hyper-columns (3 1 1 mm) representing modules foranalysis of all sensory information from correspond-ing areas of both retinas ( p. 360). Adjacent hyper-columns represent neighboring retinal regions. Hy-percolumns contain ocular dominance columns (y-axis), orientation columns (z-axis), and cylinders (x-axis). The dominance columns receive alternatinginput from the right and left eye, orientationcolumns process direction of stimulus movementand cylinders receive information of colors.

Color, high-resolution stationary shapes, mo-vement, and stereoscopic depth are processedin some subcortical visual pathways, and from

Visual Field, Visual Pathway, Central Processing of Visual Stimuli

scotoma (injury, tumor, multiple sclerosis), pituitary tumors, aneurysmDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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V1 onward in separate information channels.These individual aspects must be integrated toachieve visual perception. In diurnally activeprimates like humans, over half of the cortex isinvolved in processing visual information. On asimplified scale, the parietal cortex analyzesthe “where” and involves motor systems, andthe temporal cortex takes care of the “what” ofvisual input comparing it with memory.

Axons of the optic tract (especially those ofM and γ cells) also project to subcortical re-gions of the brain such as the pretectal region,which regulates the diameter of the pupils (seebelow); the superior colliculi ( B), which areinvolved in oculomotor function ( p. 366);the hypothalamus, which is responsible for cir-cadian rhythms ( p. 336).

The pupillary reflex is induced by suddenexposure of the retina to light ( p. 356). Thesignal is relayed to the pretectal region; fromhere, a parasympathetic signal flows via theEdinger–Westphal nucleus, the ciliary gan-glion and the oculomotor nerve, and inducesnarrowing of the pupils (miosis) within lessthan 1 s. Since both pupils respond simul-taneously even if the light stimulus is uni-lateral, this is called a consensual light response.Meiosis also occurs when the eyes adjust fornear vision (near-vision response p. 366).

The corneal reflex protects the eye. An ob-ject touching the cornea (afferent: trigeminalnerve) or approaching the eye (afferent: opticnerve) results in reflex closure of the eyelids.

Plate 12.27 Visual Field, Visual Pathway

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Eye Movements, Stereoscopic Vision, Depth Perception

Conjugated movement of the eyes occurs whenthe external eye muscles move the eyes in thesame direction (e.g., from left to right),whereas vergence movement is characterizedby opposing (divergent or convergent) eyemovement. The axes of the eyes are parallelwhen gazing into the distance. Fixation of thegaze on a nearby object results in convergenceof the visual axes. In addition, the pupil con-tracts (to increase the depth of focus) and ac-commodation of the lens occurs ( p. 352).The three reactions are called near-vision re-sponse or convergence response.

Strabismus. A greater power of accommodation fornear vision is required in hyperopia than in normal vi-sion. Since accommodation is always linked with aconvergence impulse, hyperopia is often associatedwith squinting. If the visual axes wander too farapart, vision in one eye will be suppressed to avoiddouble vision (diplopia). This type of visual impair-ment, called strabismic amblyopia, can be either tem-porary or chronic.

Saccades. When scanning the visual field, theeyes make jerky movements when changingthe point of fixation, e.g., when scanning a lineof print. These quick movements that last10–80 ms are called saccades. Displacement ofthe image is centrally suppressed during theeye due to saccadic suppression. A person look-ing at both of his or her eyes alternately in amirror cannot perceive the movement of his orher own eyes, but an independent observercan. The small, darting saccades function tokeep an object in focus.

Objects entering the field of vision are re-flexively imaged in the fovea centralis( p. 354). Slow pursuit movements of theeyes function to maintain the gaze on movingobjects. Nystagmus is characterized by a com-bination of these slow and rapid (saccade-like)opposing eye movements. The direction ofnystagmus (right or left) is classified accordingto the type of rapid phase, e.g., secondary nys-tagmus ( p. 348). Optokinetic nystagmus oc-curs when viewing an object passing acrossthe field of vision, e.g., when looking at a treefrom inside a moving train. Once the eyes havereturned to the normal position (return sac-cade), a new object can be brought into focus.

Damage to the cerebellum or organ ofbalance ( p. 348) can result in pathologicalnystagmus.

The brain stem is the main center re-sponsible for programming of eye movements.Rapid horizontal (conjugated) movementssuch as saccades and rapid nystagmus move-ment are programmed in the pons, whereasvertical and torsion movements are pro-grammed in the mesencephalon. The cerebel-lum provides the necessary fine tuning( p. 328). Neurons in the region of theEdinger–Westphal nucleus are responsible forvergence movements.

In near vision, depth vision and three-di-mensional vision are primarily achievedthrough the coordinated efforts of both eyesand are therefore limited to the binocular fieldof vision ( A). If both eyes focus on point A( B), an image of the fixation point is pro-jected on both foveae (AL, AR), i.e., on the corre-sponding areas of the retina. The same appliesfor points B and C ( B) since they both lie on acircle that intersects fixation point A and nodalpoints N ( p. 353 B) of the two eyes (Vieth–Müller horopter). If there were an imaginarymiddle eye in which the two retinal regions (inthe cortex) precisely overlapped, the retinalsites would correspond to a central point AC AL + AR ( C). Assuming there is a point D out-side the horopter ( C, left), the middle eyewould see a double image (D′, D″) instead ofpoint D, where D′ is from the left eye (DL). If Dand A are not too far apart, central processingof the double image creates the perceptionthat D is located behind D, i.e., depth perceptionoccurs. A similar effect occurs when a point E( C, right) is closer than A; in this case, the E′image will arise in the right eye (E′R) and E willbe perceived as being closer.

Depth perception from a distance. Whenviewing objects from great distances or withonly one eye, contour overlap, haze, shadows,size differences, etc. are cues for depth percep-tion ( D). A nearby object moves across thefield of vision more quickly than a distant ob-ject, e.g., in the case of the sign compared tothe wall in plate D). In addition, the moon ap-pears to migrate with the moving car, whilethe mountains disappear from sight.

Squints, strabismic amblyopia, monophthalmia, scotoma (retinal and visual pathwayabnormalities)Despopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.28 Stereoscopic Vision, Depth Perception

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Sound waves are the adequate stimulus for theorgan of hearing. They arise from a soundsource such as a gong ( A1) and are con-ducted in gases, liquids, and solids. The air isthe main carrier of sound.

The air pressure rises and falls rhythmically at thesound source. These pressure waves (sound waves)travel at a characteristic sound velocity (c) in differ-ent materials, e.g., at 332 m/s in air of 0 C. A graphicrecording of sound waves ( A1) will producewaveform curves. The wavelength (λ) is the dis-tance between the top of one wave and the identicalphase of the succeeding one, and the maximum de-viation of pressure from baseline is the amplitude(a) ( A1). Enlargement (reduction) of wavelengthwill lower (raise) the tone, whereas a fall (rise) inamplitude will produce a quieter (louder) tone( A1). The pitch of a tone is defined by itsfrequency (f), i.e., the number of sound pressureoscillations per unit time. Frequency is measured inhertz (Hz = s– 1). Frequency, wavelength and thesound velocity are related:

f (Hz) ⋅ λ (m) = c (m ⋅ s – 1). [12.1]

A pure tone has a simple sinus waveform. The tonesemanating from most sound sources (e.g., musicalinstrument, voice) are mixtures of different frequen-cies and amplitudes that result in complex periodicvibrations referred to as sound ( A2). The fun-damental (lowest) tone in the complex determinesthe pitch of the sound, and the higher ones deter-mine its timbre (overtones). An a1 (440 Hz) sung by atenor or played on a harp therefore has a differentsound than one produced on an organ or piano. Theoverlap of two very similar tones produces a distincteffect characterized by a beat tone of a much lowerfrequency ( A3, blue/red).

Audibility limits. Healthy young persons canhear sounds ranging in frequency from 16 to20 000 Hz. The upper limit of audibility candrop to 5000 Hz due to aging (presbycusis). At1000 Hz, the absolute auditory threshold orlowest sound pressure perceived as sound is3 · 10– 5 Pa. The threshold of sound isfrequency-dependent ( B, green curve). Thethreshold of hearing for a tone rises tre-mendously when other tones are heard simul-taneously. This phenomenon called masking isthe reason why it is so difficult to carry on aconversation against loud background noise.The ear is overwhelmed by sound pressuresover 60 Pa, which corresponds to 2 · 106 timesthe sound pressure of the limit of audibility at1000 Hz. Sounds above this level induce thesensation of pain ( B, red curve).

For practical reasons, the decibel (dB) is usedas a logarithmic measure of the sound pressurelevel (SPL). Given an arbitrary reference soundpressure of po = 2 · 10– 5 Pa, the sound pressurelevel (SPL) can be calculated as follows:

SPL (dB) = 20 · log (px/po) [12.2]

where px is the actual sound pressure. A ten-fold increase in the sound pressure thereforemeans that the SPL rises by 20 dB.

The sound intensity (I) is the amount of soundenergy passing through a given unit of area per unitof time (W · m-2). The sound intensity is proportionalto the square of px. Therefore, dB values cannot becalculated on a simple linear basis. If, for example,two loudspeakers produce 70 dB each (px = 6.3 · 10-2

Pa), they do not produce 140 dB together, but a mere73 dB because px only increases by a factor of 2when the intensity level doubles. Thus, 2 · 6.3 · 10–2

Pa has to be inserted for px into Eq. 12.2.

Sound waves with different frequencies butequal sound pressures are not subjectively per-ceived as equally loud. A 63 Hz tone is only per-ceived to be as loud as a 20 dB/1000 Hz refer-ence tone if the sound pressure of the 63 Hztone is 30-fold higher (+ 29 dB). In this case, thesound pressure level of the reference tone(20 dB/1000 Hz) gives the loudness level of the63 Hz tone in phon (20 phon) as at a frequencyof 1000 Hz, the phon scale is numericallyequals the dB SPL scale ( B). Equal loudnesscontours or isophones can be obtained by plot-ting the subjective values of equal loudness fortest frequencies over the whole audible range( B, blue curves). The absolute auditorythreshold is also an isophone (4 phons; B,green curve). Human hearing is most sensitivein the 2000–5000 Hz range ( B).

Note: Another unit is used to describe how a tone ofconstant frequency is subjectively perceived aslouder or less loud. Sone is the unit of this type ofloudness, where 1 sone = 40 phons at 1000 Hz. 2sones equal twice the reference loudness, and 0.5sone is 1/2 the reference loudness.

The auditory area in diagram B is limited bythe highest and lowest audible frequencies onthe one side, and by isophones of the thresh-olds of hearing and pain on the other. Thegreen area in plate B represents the range offrequencies and intensities required for com-prehension of ordinary speech ( B).

Physical Principles of Sound—Sound Stimulus and Perception

Sound-induced injury (earphones, disco, construction noise, explosions), hearing loss in theelderlyDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.29 Sound Physics and Thresholds

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Sound waves are transmitted to the organ ofhearing via the external ear and the auditorycanal, which terminates at the tympanic mem-brane or eardrum. The sound waves are con-ducted through the air (air conduction) and setthe eardrum in vibration. These are trans-mitted via the auditory ossicles of the tympaniccavity (middle ear) to the membrane of the ovalwindow ( A 1,2), where the internal or innerear (labyrinth) begins.

In the middle ear, the malleus, incus andstapes conduct the vibrations of the tympanicmembrane to the oval window. This ensuresthat the sound is conducted from the low waveresistance/impedance in air to the high re-sistance in fluid with as little loss of energy aspossible. This impedance adaptation occurs atf 2400 Hz and is based on a 22-fold pressureamplification (tympanic membrane area/ovalwindow area is 17 : 1, and leverage arm actionof the auditory ossicles amplifies force by a fac-tor of 1.3).

Impairment of impedance transformingcapacity due, e.g., to destruction of the ossicles,causes roughly 20 dB of hearing loss (conduc-tion deafness).

Muscles of the middle ear. The middle ear containstwo small muscles—the tensor tympani (insertion:manubrium of malleus) and the stapedius (insertion:stapes)—that can reflectively attenuate low-frequency sound (i.e., protect the ear from loudsounds, among other functions).

Bone conduction. Sound sets the skull in vibra-tion, and these bone-borne vibrations are conducteddirectly to the cochlea. Bone conduction is fairly in-significant for physiological function, but is useful fortesting the hearing. In Weber’s test, a vibratingtuning fork (a1) is placed in the middle of the head. Aperson with normal hearing can determine the loca-tion of the tuning fork because of the symmetricalconduction of sound waves. A patient with unilateralconduction deafness will perceive the sound as com-ing from the affected side (lateralization) because ofthe lack of masking of environmental noises in thatear (bone conduction). A person with sensorineuraldeafness, on the other hand, will perceive the soundas coming from the healthy ear because of sound at-tenuation in the affected internal ear. In Rinne’s test,the handle of a tuning fork is placed on one mastoidprocess (bony process behind the ear) of the patient(bone conduction). If the tone is no longer heard, thetines of the tuning fork are placed in front of the ear(air conduction). Individuals with normal hearing orsensorineural deafness can hear the turning fork in

the latter position anew (positive test result),whereas those with conduction deafness cannot(test negative).

The inner ear consists of the equilibrium organ( p. 348) and the cochlea, a spiraling bony tubethat is 3–4 cm in length. Inside the cochlea is an en-dolymph-filled duct called the scala media (cochlearduct); the ductus reuniens connects the base of thecochlear duct to the endolymph-filled part of theequilibrium organ. The scala media is accompaniedon either side by two perilymph-filled cavities: thescala vestibuli and scala tympani. These cavitiesmerge at the apex of the cochlea to form the heli-cotrema. The scala vestibuli arises from the oval win-dow, and the scala tympani terminates on the mem-brane of the round window ( A2). The compositionof perilymph is similar to that of plasma water( p. 93 C), and the composition of endolymph issimilar to that of the cytosol (see below). Perilymphcirculates in Corti’s tunnel and Nuel’s spaces ( A4).

Organ of Corti. The 10 000–12 000 externaland 3500 internal hair cells (HCs) that both situpon the basilar membrane are the sensorycells of the hearing organ ( A4). Their struc-ture is very similar to the HCs of the vestibularorgan ( p. 348). Every HC has approx. 80stereocilia, but the kinocilia are absent or rudi-mentary.

There are three rows of slender, cylindrical outer haircells. The tips of their stereocilia are firmly attached tothe tectorial membrane and surrounded by en-dolymph, whereas their cell bodies float in perilymphof Nuel’s spaces ( A4). The outer hair cells are princi-pally innervated by efferent, mostly cholinergic neu-rons from the spiral ganglion (NM-cholinoceptors; p. 82). The pear-shaped inner hair cells are ar-ranged in a single row and are almost completely sur-rounded by supporting cells. Only their cilia projectfreely into the endolymph. The inner hair cells are sec-ondary sensory cells and synapse with over 90% of theafferent fibers of the spiral ganglion.

Inner ear potentials ( p. 375 C). On the ciliaside, the hair cells border with the endolymph-filled space, which has a potential difference(endocochlear potential) of ca. 80 to 110 mVrelative to perilymph ( p. 375 C). This poten-tial difference is maintained by an active trans-port mechanism in the stria vascularis. Sincethe cell potential of outer (inner) hair cells is–70mV (40mV), a potential difference ofroughly 150–180mV (120–150mV) prevailsacross the cell membrane occupied by cilia(cell interior negative). Since the K conc. inthe endolymph and hair cells is roughly equal

Conduction of Sound, Sound Sensors

Liminal audiometry, eardrum injury (e.g. diving) otitis mediaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.30 Conduction of Sound, Sound Sensors I

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(140mmol/L), the prevailing K equi-librium potential is ca. 0mV ( p. 32).

Sound conduction in the inner ear. The stapesmoves against the membrane of the oval win-dow membrane, causing it to vibrate. These aretransmitted via the perilymph to the mem-brane of the round window ( A2). The wallsof the endolymph-filled cochlear duct, i.e. Re-issner’s membrane and the basilar membrane( D1) give against the pressure wave (migrat-ing wave, B and C). It can therefore take a“short cut” to reach the round window withoutcrossing the helicotrema. Since the cochlearduct is deformed in waves, Reissner’s mem-brane and the basilar membrane vibrate alter-nately towards the scala vestibuli and scalatympani. The velocity and wavelength of themigrating wave that started at the oval win-dow decrease continuously ( B), while theiramplitude increases to a maximum and thenquickly subsides ( B, envelope curve). (Thewave velocity is not equal to the velocity ofsound, but is much slower.) The site of themaximum excursion of the cochlear duct ischaracteristic of the wavelength of the stimu-lating sound. The higher the frequency of thesound, the closer the site is to the stapes ( C).

Outer hair cells. Vibration of the cochlearduct causes a discrete shearing (of roughly0.3 nm) of the tectorial membrane against thebasilar membrane, causing bending of thestereocilia of the outer hair cells ( D1). This ex-erts also a shearing force between the cilia ofthe individual external hair cell. This bending inone direction activates the “tip links” ( p. 349A3), and causes mechanosensitive cation chan-nels (MET channels) in the stereociliary mem-branes to open allowing K+ ions driven by the150–180 mV mentioned above to enter anddepolarize the outer hair cells (mechanoelec-tric transduction MET). This causes the outerhair cells to shorten in sync with stimulation.Repolarization is achieved by the opening oftension-dependent K channels (KCNQ4) onthe perilymph side of the HC. The outflowing K

is taken up by K-Cl– cotransporters (KCC4) insupporting cells and recirculated via gap junc-tions to the stria vascularis. The subsequentbending of the stereocilia in the opposite direc-tion causes hyperpolarization (closure of theMET channels) and extension of the outer HCs.

This extremely fast tension-sensitive electro-motility of the outer hair cells (up to 20kHz, i.e.2·104 times/s) is produced by the motor proteinprestin. Cl– and HCO3

– ions are stored in prestin,dependent on the tension, and therefore act astension sensors. Their presence changes thedensely packed conformation of the prestin,which results in extension of the outer HCs. Atthe site of maximum reaction to the soundfrequency the electromotility of the outer HCscauses endolymph waves in the subtectorialspace, which in turn also bends the stereociliaof the inner hair cell ( D3). Their depolariza-tion triggered by the opening of the MET chan-nels is the sensor potential for the inner HCs,which via opening of basolateral Ca2 channelsincreases the cytosolic Ca2 concentration. Thisleads to transmitter release (glutamate cou-pling to AMPA receptors; p. 55 F) and the sub-sequent conduction of impulses to the CNS( D2, 3).

The outer hair cell electromotility con-tributes to the cochlear amplification (ca. 100-fold or 40dB amplification), which occursbefore sound waves reach the actual sound sen-sors, i.e. inner hair cells. This explains the verylow threshold within the very narrow location(0.5mm) and thus within a very smallfrequency range.

The vibrations in the internal ear set off an outwardemission of sound. These evoked otoacoustic emis-sions can be objectively measured by placing a micro-phone in front of the tympanic membrane, e.g., totest internal ear function in infants and other individu-als incapable of reporting their hearing sensations.

Subjective hearing tests are performed using anaudiometer. The patient is presented sounds ofvarious frequencies and routes of conduction (bone,air). The sound pressure is initially set at a level underthe threshold of hearing and is raised in incrementsuntil the patient is able to hear the presented sound(threshold audiogram). If the patient is unable to hearthe sounds at normal levels, he or she has an hearingloss, which is quantitated in decibels (dB). Inaudiometry, all frequencies at the normal thresholdof hearing are assigned the value of 0 dB (unlike thediagram on p. 369 B, green curve). Hearing loss canbe caused by presbycusis ( p. 368), middle ear in-fection (impaired air conduction), and damage tothe internal ear (impaired air and bone conduction)caused, for example, by prolonged exposure to ex-cessive sound pressure, by ototoxic medication(blockage of stria vascularis by loop diuretics), or bydefects of the KCNQ4 or KCC4 genes.

Conduction of Sound, Sound Sensors (continued)

Acoustic trauma, idiopathic hearing loss, infection, toxins, drugs, ischemia, tinnitusDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Plate 12.31 Conduction of Sound, Sound Sensors II

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Various qualities of sound must be coded forsignal transmission in the acoustic pathway.These include the frequency, intensity anddirection of sound waves as well as the dis-tance of the sound source from the listener.

Frequency imaging. Tones of variousfrequencies are “imaged” along the cochlea( p. 373 C), conducted in separate fibers ofthe auditory pathway and centrally identified.Assuming that a tone of 1000 Hz can just bedistinguished from one of 1003 Hz (resem-bling true conditions), the frequency differ-ence of 3 Hz corresponds to a relativefrequency differential threshold of 0.003( p. 358). This fine differential capacity ismainly due to frequency imaging in thecochlea, amplification by its outer hair cells( p. 372), and neuronal contrast along theauditory pathway ( p. 315 D). This finetuning ensures that a certain frequency has aparticularly low threshold at its “imaging” site.Adjacent fibers are not recruited until highersound pressures are encountered.

Intensity. Higher intensity levels result inhigher action potential frequencies in afferentnerve fibers and recruitment of neighboringnerve fibers ( A). The relative intensity differ-ential threshold is 0.1 ( p. 358), which is verycrude compared to the frequency differentialthreshold. Hence, differences in loudness ofsound are not perceived by the human earuntil the intensity level changes by a factor ofover 1.1, that is, until the sound pressurechanges by a factor of over √1,1 = 1,05.

Direction. Binaural hearing is needed toidentify the direction of sound waves and isbased on the following two effects. (1) Soundwaves that strike the ear obliquely reach theaverted ear later than the other, resulting in alag time. The change in direction that a normalhuman subject can just barely detect (directionthreshold) is roughly 3 degrees. This angledelays the arrival of the sound waves in theaverted ear by about 3 · 10-5 s ( B, left). (2)Sound reaching the averted ear is also per-ceived as being quieter; differences as small as1 dB can be distinguished. A lower sound pres-sure results in delayed firing of actions poten-tials, i.e., in increased latency ( B, right). Thus,the impulses from the averted ear reach theCNS later (nucleus accessorius, D5). Effects

(1) and (2) are additive effects ( B). The exter-nal ear helps to decide whether the sound iscoming from front or back, above or below.Binaural hearing also helps to distinguish acertain voice against high background noise,e.g., at a party. Visibility of the speaker’s mouthalso facilitates comprehension.

Distance to the sound source can be deter-mined because high frequencies are at-tenuated more strongly than low frequenciesduring sound wave conduction. The longer thesound wave travels, the lower the proportionof high frequencies when it reaches thelistener. This helps, for instance, to determinewhether a thunderstorm is nearby or far away.

Auditory pathway ( D). The auditorynerve fibers with somata positioned in the spi-ral ganglion of the cochlea project from thecochlea ( D1) to the anterolateral ( D2),posteroventral and dorsal cochlear nuclei( D3). Afferents in these three nuclei exhibittonotopicity, i.e., they are arranged accordingto tone frequency at different levels of com-plexity. In these areas, lateral inhibition( p. 315 D) enhances contrast, i.e., suppressesnoise. Binaural comparison of intensity andtransit time of sound waves (direction ofsound) takes place at the next-higher stationof the auditory pathway, i.e. in the superiorolive ( D4) and accessory nucleus ( D5). Thenext stations are in the nucleus of lateral lem-niscus ( D6) and, after most fibers cross overto the opposite side, the inferior quadrigeminalbodies ( D7). They synapse with numerousafferents and serve as a reflex station (e.g.,muscles of the middle ear; p. 372). Here,sensory information from the cochlear nucleiis compared with spatial information from thesuperior olive. Via connections to the superiorquadrigeminal bodies ( D8), they also ensurecoordination of the auditory and visual space.By way of the thalamus (medial geniculatebody, MGB; D9), the afferents ultimatelyreach the primary auditory cortex ( D10) andthe surrounding secondary auditory areas( p. 313 E, areas 41 and 22). Analysis of com-plex sounds, short-term memory for compari-son of tones, and tasks required for “eaves-dropping” are some of their functions.

Central Processing of Acoustic Information

Cerebral hemorrhage, trauma or tumor (e.g. Cerebellopontine angle tumor), hearing aidsDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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The human voice primarily functions as ameans of communication, the performance ofwhich is based on the human capacity of hear-ing ( p. 369 B). As in wind instruments, thebody contains a wind space (trachea, bronchi,etc.). Air is driven through the space betweenthe vocal cords (rima glottidis) into the airspace (passages above the glottis), which setsthe vocal cords into vibration. The air spaceconsists of the throat and oronasal cavities( A). The range of the human voice is so im-mense because of the large variety of musclesthat function to modulate the intensity of theairstream (loudness), tension of the vocalcords, shape/width of the vocal cords (fun-damental tone) and size/shape of the air space(timbre, formants) of each individual.

Joints and muscles of the larynx function toadjust the vocal cords and rima glottidis. Astream of air opens and closes the rima glot-tidis and sets off the rolling movement of thevocal cords ( B). When a deep tone is pro-duced, the fissure of the glottis remains closedlonger than it opens (ratio of 5 : 1 at 100 Hz).This ratio drops to 1.4 : 1 in higher tones(400 Hz). The rima glottidis remains openwhen whispering or singing falsetto ( C,blue).

Motor signals originate in the motosensorycortex ( p. 327 C/B, tongue/throat) and areconducted via the vagus nerve to the larynx.Sensory impulses responsible for voice pro-duction and the cough reflex are also con-ducted by the vagus nerve. Sensory fibers fromthe mucosa and muscle spindles of the larynx( p. 318) continuously transmit informationon the position and tension of the vocal cordsto the CNS. These reflexes and the close con-nection of the auditory pathway with bulbarand cortical motor speech centers are impor-tant for fine adjustment of the voice.

Vowels ( D). Although their fundamental frequen-cies are similar (100–130 Hz), spoken vowels can bedistinguished by their characteristic overtones (for-mants). Different formants are produced by modify-ing the shape of oral tract, i.e., mouth and lips ( D).The three primary vowels [a:], [i:], [u:] make up thevowel triangle; [œ:], [ɔ:], [ø:], [y:], [æ:], and [ε] areintermediates ( D).

The phonetic notation used here is that of the In-ternational Phonetic Society. The symbols mentionedhere are as follows: [a:] as in glass; [i:] as in beat; [u:] as

in food; [œ:] as in French peur; [ɔ:] as in bought; [ø:]as in French peu or in German hören; [y:] as in Frenchmenu or in German trüb; [æ:] as in bad; [ε:] as in head.

Consonants are described according to their siteof articulation as labial (lips, teeth), e.g. P/B/W/F/M;dental (teeth, tongue), e.g. D/T/S/M; lingual (tongue,front of soft palate), e.g. L; guttural (back of tongueand soft palate), e.g. G/K. Consonants can be also de-fined according to their manner of articulation, e.g.,plosives or stop consonants (P/B/T/D/K/G), fricatives(F/V/W/S/Ch) and vibratives (R).

The frequency range of the voice, includingformants, is roughly 40–2000 Hz. Sibilants like/s/ and /z/ have higher-frequency fractions. In-dividuals suffering from presbyacusis or otherforms of sensorineural hearing loss are oftenunable to hear sibilants, making it impossiblefor them to distinguish between words like“bad” and “bass.” The tonal range (fundamen-tal tone, C) of the spoken voice is roughly oneoctave; that of the singing voice is roughly twooctaves in untrained singers, and over threeoctaves in trained singers.Language (see also p. 342). The main com-ponents of verbal communication are (a) audi-tory signal processing ( p. 374), (b) centralspeech production and (c) execution of motorspeech function. The centers for speech com-prehension are mainly located in the posteriorpart of area 22, i.e., Wernicke’s area( p. 313 E).

Lesions of it result in a loss of language comprehen-sion capacity (sensory aphasia). The patient willspeak fluently yet often incomprehensibly, but doesnot notice it because of his/her disturbed compre-hension capacity. The patient is also unable to under-stand complicated sentences or written words.

The centers for speech production are mainlylocated in areas 44 and 45, i.e., Broca’s area( p. 313 E). It controls the primary speechcenters of the sensorimotor cortex.

Lesions of this and other cortical centers (e.g., gyrusangularis) result in disorders of speech production(motor aphasia). The typical patient is eithercompletely unable to speak or can only express him-self in telegraphic style. Another form of aphasia ischaracterized by the forgetfulness of words (anomicor amnestic aphasia). Lesions of executive motor cen-ters (corticobulbar tracts, cerebellum) cause variousspeech disorders. Auditory feed back is extremely im-portant for speech. When a person goes deaf, speechdeteriorates to an appreciable extent. Children borndeaf do not learn to speak.

Voice and Speech

Laryngeal disease, vocal cord paralysis and inflammation, hoarseness, aphasiaDespopoulos/Silbernagl, Color Atlas of Physiology, 6th Edition. All rights reserved. ©2009 Thieme Publishers

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Physiology is the science of life processes andbodily functions. Since they are largely basedon physical and chemical laws, the investiga-tion, understanding, assessment, and manipu-lation of these functions is inseparably linkedto the measurement of physical, chemical, andother parameters, such as blood pressure,hearing capacity, blood pH, and cardiac output.The units for measurement of these parame-ters are listed in this section. We have givenpreference to the international system of SIunits (Système International d’Unités) for uni-formity and ease of calculation. Non-SI unitswill be marked with an asterisk. Conversionfactors for older units are also listed. Compli-cated or less common physiological units (e.g.,wall tension, flow resistance, compliance) aregenerally explained in the book as they appear.However, some especially important termsthat are often (not always correctly) used inphysiology will be explained in the Appendix,e.g., concentration, activity, osmolality,osmotic pressure, oncotic pressure, and pH.

The seven base units of the SI system.

Unit Symbol Dimension

Meter m length

Kilogram kg mass

Second s time

Mole mol amount of substance

Ampere A electric current

Kelvin K temperature (absolute)

Candela cd luminous intensity

The base units are precisely defined autono-mous units. All other units are derived by mul-tiplying or dividing base units and are there-fore referred to as derived units, e.g.:— Area (length · length): m · m = m2

— Velocity (length/time): m/s = m · s–1.

If the new unit becomes too complicated, it isgiven a new name and a corresponding sym-bol, e.g., force = m · kg · s–2 = N ( Table 1).

Fractions and Multiples of Units

Prefixes are used to denote decimal multiplesand fractions of a unit since it is both tediousand confusing to write large numbers. We gen-erally write 10 kg (kilograms) and 10µg (mi-crograms) instead of 10 000 g and 0.00001 g,for example. The prefixes, which are usuallyvaried in 1000-unit increments, and the corre-sponding symbols and conversion factors arelisted in Table 2. Prefixes are used with baseunits and the units derived from them( Table 1), e.g., 103 Pa = 1 kPa. Decimal incre-ments are used in some cases (e.g., da, h, d, andc; Table 2). Time is given in conventionalnondecimal units, i.e., seconds (s), minutes(min), hours (h), and days (d).

Length, Area, Volume

The meter (m) is the SI unit of length. Otherunits of length have also been used.

Examples:1 ångström (Å) = 10-10 m = 0.1 nm1 micron (µ) = 10-6 m = 1µm1 millimicron (mµ) = 10-9 m = 1 nm

American and British units of length:1 inch = 0.0254 m = 25.4 mm1 foot = 0.3048 m1 yard = 3 feet = 0.9144 m1 (statute) mile = 1609.344 m 1.61 km1 nautical mile = 1.853 km

The square meter (m2) is the derived SI unit ofarea, and the cubic meter (m3) is the corre-sponding unit of volume. When denoting thefractions or multiples of these units with pre-fixes (Table 2), please note that there are somepeculiarities.

Examples:1 m = 103 mm, but1 mm2 = 106 mm2, and1 m3 = 109 mm3

The liter (L or l)* is often used as a unit ofvolume for liquids and gases:

1 L = 10–3 m3 = 1 dm3

1 mL = 10–6 m3 = 1 cm3

1µL = 10–9 m3 = 1 mm3.

Dimensions and Units


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Table 1 Derived units based on SI base units m, kg, s, cd, and A

Coulomb C electrical charge s · A

Farad F electrical capacitance C · V–1 = m–2 · kg–1 · s4 · A2

Hertz Hz frequency s–1

Joule J heat, energy, work N · m = m2 · kg · s–2

Lumen lm light flux cd · sr

Lux lx light intensity Im · m–2 = cd · sr · m–2

Newton N force m · kg · s–2

Ohm Ω electrical resistance V · A–1 = m2 · kg · s-3 · A–2

Pascal P pressure N · m–2 = m–1 · kg · s–2

Siemens S conductivity Ω–1 = m–2 · kg–1 · s3 · A2

Steradian sr measure of solid angle1 1 (m2 · m–2)

Tesla T magnetic flux density Wb · m–2 = kg · s–2 · A–1

Volt V electric potential W · A–1 = m2 · kg · s-3 · A–1

Watt W electric power J · s–1 = m2 · kg · s-3

Weber Wb magnetic flux V · s = m2 · kg · s–2 · A–1

1 The solid angle of a sphere is defined as the angle subtended at the center of a sphere by an area (A) on itssurface times the square of its radius (r2). A steradian (sr) is the solid angle for which r = 1 m and A = 1 m2,that is, 1 sr = 1 m2/m–2.

Table 2 Prefixes for fractions and multiples of units of measure

Prefix Symbol Factor Prefix Symbol Factor

deca- da 101 deci- d 10–1

hecto- h 102 centi- c 10–2

kilo- k 103 milli- m 10–3

mega- M 106 micro- µ 10–6

giga- G 109 nano- n 10–9

tera- T 1012 pico- p 10–12

peta- P 1015 femto- f 10–15

exa- E 1018 atto- a 10–18


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Conversion of American and British volume units intoSI units:

1 fluid ounce (USA) = 29.57 mL1 fluid ounce (UK) = 28.47 mL1 liquid gallon (USA) = 3.785 L1 liquid gallon (UK) = 4.546 L1 pint (USA) = 473.12 mL1 pint (UK) = 569.4 mL

Velocity, Frequency, Acceleration

Velocity is the distance traveled per unit time(m · s–1). This is an expression of linear velocity,whereas “volume velocity” is used to expressthe volume flow per unit time. The latter is ex-pressed as L · s–1 or m3 · s–1.

Frequency is used to describe how often aperiodic event (pulse, breathing, etc.) occursper unit time. The SI unit of frequency is s–1 orhertz (Hz). min–1 is also commonly used:

min–1 = 1/60 Hz 0.0167 Hz.Acceleration, or velocity change per unit

time, is expressed in m · s–1 · s–1 = m · s–2. Sincedeceleration is equivalent to negative accelera-tion, acceleration and deceleration can both beexpressed in m · s–2.

Force and Pressure

Force equals mass times acceleration. Weight isa special case of force as weight equals masstimes acceleration of gravity. Since the unit ofmass is kg and that of acceleration m · s–2, forceis expressed in m · kg · s–2 = newton (N). Theolder units of force are converted into N as fol-lows:

1 dyn = 10-5 N = 10µN1 pond = 9.8 · 10-3 N = 9.8 mN.Pressure equals force per unit area, so the SI

unit of pressure is N · m–2 = pascal (Pa).However, the pressure of bodily fluids is usu-ally measured in mm Hg. This unit and otherunits are converted into SI units as follows:

1 mm H2O 9.8 Pa1 cm H2O 98 Pa1 mm Hg = 133.3 Pa = 0.1333 kPa1 torr = 133.3 Pa = 0.1333 kPa1 technical atmosphere (at) 98.067 kPa1 physical atmosphere (atm) = 101.324 kPa1 dyne · cm–2 = 0.1 Pa1 bar = 100 kPa.

Work, Energy, Heat, Power

Work equals force times distance, N · m = J(joule), or pressure times volume, (N · m–2) · m3

= J. Energy and heat are also expressed in J.Other units of work, heat, and energy are

converted into J as follows:1 erg = 10-7 J = 0.1µJ1 cal 4.185 J1 kcal 4185 J = 4.185 kJ1 Ws = 1 J1 kWh = 3.6 · 106 J = 3.6 MJ.Power equals work per unit time and is ex-

pressed in watts (W), where W = J · s–1. Heatflow is also expressed in W. Other units ofpower are converted into W as follows:

1 erg · s–1 = 10–7 W = 0.1µW1 cal · h–1 = 1.163 · 10-3 W = 1.163 mW1 metric horse power (hp) = 735.5 W =

0.7355 kW.

Mass, Amount of Substance

The base unit of mass is the kilogram (kg),which is unusual insofar as the base unit bearsthe prefix “kilo”. Moreover, 1000 kg is definedas a metric ton* instead of as a megagram.Weight is the product of mass and gravity (seeabove), but weight scales are usually cali-brated in units of mass (g, kg).

British and American units of mass are converted intoSI units as follows.

Avoirdupois weight:1 ounce (oz.) = 28.35 g1 pound (lb.) = 453.6 gApothecary’s and troy weight:1 ounce = 31.1 g1 pound = 373.2 g.

The mass of a molecule or an atom (molecularor atomic mass) is often expressed in daltons(Da)*. 1 Da = 1/12 the mass of a 12C atom, equi-valent to 1 g/Avogadro’s constant = 1 g/(6.022· 1023):

1 Da = 1.66 · 10-24 g1000 Da = 1 kDa.

Dimensions and Units (continued)


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The relative molecular mass (Mr), or molecu-lar “weight”, is the molecular mass of a sub-stance divided by 1/12 the mass of a 12C atom.Since Mr is a ratio, it is a dimensionless unit.

The amount of substance, or mole (mol), isrelated to mass. One mole of substance con-tains as many elementary particles (atoms,molecules, ions) as 12 g of the nuclide of a 12Catom = 6.022 · 1023 particles. The conversionfactor between moles and mass is therefore:1 mol equals the mass of substance (in grams)corresponding to the relative molecular, ionic,or atomic mass of the substance. In otherwords, it expresses how much higher the massof the atom, molecule, or ion is than 1/12 thatof a 12C atom.

Examples:— Relative molecular mass of H2O: 18

1 mol H2O = 18 g H2O.— Relative atomic mass of Na: 23

1 mol Na+ = 23 g Na+.— Relative molecular mass of CaCl2:

= 40 + (2 · 35.5) = 111 1 mol CaCl2 = 111 g CaCl2.

(CaCl2 contains 2 mol Cl– and 1 mol Ca2+.)

The equivalent mass is calculated as moles dividedby the valency of the ion in question and expressed inequivalents (Eq)*. The mole and equivalent values ofmonovalent ions are identical:

1 Eq Na+ = 1/1 mol Na+.For bivalent ions, equivalent = 1/2 mole:1 Eq Ca2+ = 1/2 mole Ca2+ or 1 mole Ca2+ = 2 Eq

Ca2+.The osmole (Osm) is also derived from the mole

(see below).

Electrical Units

Electrical current is the flow of charged parti-cles, e.g., of electrons through a wire or of ionsthrough a cell membrane. The number of par-ticles moving per unit time is measured inamperes (A). Electrical current cannot occurunless there is an electrical potential differ-ence, in short also called potential, voltage, ortension. Batteries and generators are used tocreate such potentials. Most electrical poten-tials in the body are generated by ionic flow( p. 32). The volt (V) is the SI unit of electricalpotential ( Table 1).

How much electrical current flows at agiven potential depends on the amount of elec-trical resistance, as is described in Ohm’s law

(voltage = current · resistance). The unit ofelectrical resistance is ohm (Ω) ( Table 1).Conductivity is the reciprocal of resistance(1/Ω) and is expressed in siemens (S), where S= Ω–1. In membrane physiology, resistance isrelated to the membrane surface area (Ω · m2).The reciprocal of this defines the membraneconductance to a given ion: Ω–1 · m–2 = S · m–2

( p. 32).Electrical work or energy is expressed in

joules (J) or watt seconds (Ws), whereas electri-cal power is expressed in watts (W).

The electrical capacitance of a capacitor,e.g., a cell membrane, is the ratio of charge (C)to potential (V); it is expressed in farads (F)( Table 1, p. 379).

Direct current (DC) always flows in one direction,whereas the direction of flow of alternating current(AC) constantly changes. The frequency of one cycleof change per unit time is expressed in hertz (Hz).Mains current is generally 60 Hz in the USA and 50 Hzin Europe.

Temperature

Kelvin (K) is the SI unit of temperature. Thelowest possible temperature is 0 K, or absolutezero. The Celsius or centigrade scale is derivedfrom the Kelvin scale. The temperature indegrees Celsius (C) can easily be convertedinto K:

C = K - 273.15.In the USA, temperatures are normally given indegrees Fahrenheit (F). Conversions betweenFahrenheit and Celsius are made as follows:

F = (9/5 · C) + 32C = (F - 32) · 5/9.

Some important Kelvin, Celsius, and Fahren-heit temperature equivalents:

K C F

Freezing point of water + 273 0 + 32

Room temperature 293–298

20–25

68– 77

Body core temperature 310 37 98.6

Fever 311–315

38–42

100–108

Boiling point of water(at sea level)

373 100 212


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Concentrations, Fractions, Activity

The word concentration is used to describemany different relationships in physiology andmedicine. Concentration of a substance X isoften abbreviated as [X]. Some concentrationsare listed below:—Mass concentration, or the mass of a sub-stance per unit volume (e.g., g/L = kg/m3)—Molar concentration, or the amount of a sub-stance per unit volume (e.g., mol/L)—Molal concentration, or the amount of sub-stance per unit mass of solvent (e.g., mol/kg H2O).

The SI unit of mass concentration is g/L (kg/m3,mg/L, etc.). The conversion factors for olderunits are listed below:

1 g/100 mL = 10 g/L1 g% = 10 g/L1 % (w/v) = 10 g/L1 g‰ = 1 g/L1 mg% = 10 mg/L1 mg/100 mL = 10 mg/L1µg% = 10µg/L1γ% = 10µg/L.Molarity is the molar concentration, which

is expressed in mol/L (or mol/m3, mmol/L,etc.). Conversion factors are listed below:

1 M (molar) = 1 mol/L1 N (normal) = (1/valency) · mol/L1 mM (mmolar) = 1 mmol/L1 Eq/L = (1/valency) · mol/L.

In highly diluted solutions, the only differencebetween the molar and molal concentrationsis that the equation “1 L H2O = 1 kg H2O” holdsat only one particular temperature (4C). Bio-logical fluids are not highly diluted solutions.The volume of solute particles often makes upa significant fraction of the overall volume ofthe solution. One liter of plasma, for example,contains 70 mL of proteins and salts and only0.93 L of water. In this case, there is a 7% differ-ence between molarity and molality. Differ-ences higher than 30% can occur in intracellu-lar fluid. Although molarity is more commonlymeasured (volumetric measurement), molal-ity plays a more important role in biophysicaland biological processes and chemical reac-tions.

The activity (a) of a solution is a thermodynamicmeasure of its physicochemical efficacy. In physi-ology, the activity of ions is measured by ion-sensi-

tive electrodes (e.g., for H+, Na+, K+, Cl -, or Ca2+). Theactivity and molality of a solution are identical whenthe total ionic strength (µ) of the solution is verysmall, e.g., when the solution is an ideal solution. Theionic strength is dependent on the charge and con-centration of all ions in the solution:

µ 0.5 (z12 ⋅ c1 + z2

2 ⋅ c2 + . . . + zi2 ⋅ ci) [13.1]

where zi is the valency and ci the molal concentrationof a given ion “i”, and 1, 2, etc. represent the differenttypes of ions in the solution. Owing to the high ionicstrength of biological fluids, the solute particles in-fluence each other. Consequently, the activity (a) of asolution is always significantly lower than its molarconcentration (c). Activity is calculated as a = f · c,where f is the activity coefficient.

Example: At an ionic strength of 0.1 (as it is thecase for a solution containing 100 mmol NaCl/kg H2O), f = 0.76 for Na+. The activity important inbiophysical processes is therefore roughly 25% lowerthan the molality of the solution.

In solutions that contain weak electrolyteswhich do not completely dissociate, the molal-ity and activity of free ions also depend on thedegree of electrolytic dissociation.

Fractions (“fractional concentrations”) arerelative units:— Mass ratio, i.e., mass fraction relative to total

mass— Molar ratio— Volume ratio, i.e. volume fraction relative to

total volume. The volume fraction (F) iscommonly used in respiratory physiology.

Fractions are expressed in units of g/g, mol/mol, and L/L respectively, i.e. in “units” of 1,10–3, 10–6, etc. The unabbreviated unit (e.g.,g/g) should be used whenever possible be-cause it identifies the type of fraction in ques-tion. The fractions %, ‰, ppm (parts per mil-lion), and ppb (parts per billion) are used for alltypes of fractions.

Conversion:1% = 0.011‰ = 1 · 10–3

1 vol% = 0.01 L/L1 ppm = 1 · 10–6

1 ppb = 1 · 10–9

Osmolality, Osmotic / Oncotic Pressure

Osmolarity (Osm/L), a unit derived frommolarity, is the concentration of all osmoticallyactive particles in a solution, regardless ofwhich compounds or mixtures are involved.



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However, measurements with osmometers aswell as the biophysical application of osmoticconcentration refer to the number of osmolesper unit volume of solvent as opposed to thetotal volume of the solution. This and the factthat volume is temperature-dependent are thereasons why osmolality (Osm/kg H2O) is gen-erally more suitable.

Ideal osmolality is derived from the molalityof the substances in question. If, for example,1 mmol (180 mg) of glucose is dissolved in 1 kgof water (1 L at 4C), the molality equals1 mmol/kg H2O and the ideal osmolalityequals 1 mOsm/kg H2O. This relationshipchanges when electrolytes that dissociate areused, e.g., NaCl Na+ + Cl–. Both of these ionsare osmotically active. When a substance thatdissociates is dissolved in 1 kg of water, theideal osmolality equals the molality times thenumber of dissociation products, e.g., 1 mmolNaCl/kg H2O = 2 mOsm/kg H2O.

Electrolytes weaker than NaCl do not disso-ciate completely. Therefore, their degree ofelectrolytic dissociation must be considered.

These rules apply only to ideal solutions, i.e.,those that are extremely dilute. As mentionedabove, bodily fluids are nonideal (or real) solu-tions because their real osmolality is lowerthan the ideal osmolality. The real osmolalityis calculated by multiplying the ideal osmolal-ity by the osmotic coefficient (g). The osmoticcoefficient is concentration-dependent andamounts to, for example, approximately 0.926for NaCl with an (ideal) osmolality of300 mOsm/kg H2O. The real osmolality of thisNaCl solution thus amounts to 0.926 · 300 =278 mOsm/kg H2O.

Solutions with a real osmolality equal tothat of plasma ( 290 mOsm/kg H2 O) are saidto be isosmolal. Those whose osmolality ishigher or lower than that of plasma are hyper-osmolal or hyposmolal.

Osmolality and Tonicity

Each osmotically active particle in solution (cf.real osmolality) exerts an osmotic pressure (π)as described by van’t Hoff’s equation:

π = R · T · cosm [13.2]

where R is the universal gas constant (8.314 J ·K–1 · Osm–1), T is the absolute temperature in K,and cosm is the real osmolality in Osm · (m3

H2O)–1 = mOsm · (L H2O)–1. If two solutions ofdifferent osmolality (∆cosm) are separated by awater-permeable selective membrane, ∆cosm

will exert an osmotic pressure difference (∆π)across the membrane in steady state if themembrane is less permeable to the solutesthan to water. In this case, the selectivity of themembrane, or its relative impermeability tothe solutes, is described by the reflectioncoefficient (σ), which is assigned a value be-tween 1 (impermeable) and 0 (as permeable aswater). The reflection coefficient of a semi-permeable membrane is σ = 1. By combiningvan’t Hoff’s and Staverman’s equations, theosmotic pressure difference (∆π) can be calcu-lated as follows:

∆π = σ · R · T · ∆cosm. [13.3]

Equation 13.3 shows that a solution with thesame osmolality as plasma will exert the sameosmotic pressure on a membrane in steadystate (i.e., that the solution and plasma will beisotonic) only if σ = 1. In other words, the mem-brane must be strictly semipermeable.

Isotonicity, or equality of osmotic pressure,exists between plasma and the cytosol of redblood cells (and other cells of the body) insteady state. When the red cells are mixed in aurea solution with an osmolality of290 mOsm/kg H2O, isotonicity does not pre-vail after urea (σ 1) starts to diffuse into thered cells. The interior of the red blood cellstherefore becomes hypertonic, and water isdrawn inside the cell due to osmosis ( p. 24).As a result, the erythrocytes continuouslyswell until they burst.

An osmotic gradient resulting in the sub-sequent flow of water therefore occurs in allparts of the body in which dissolved particlespass through water-permeable cell mem-branes or cell layers. This occurs, for example,when Na+ and Cl– pass through the epitheliumof the small intestine or proximal renal tubule.The extent of this water flow or volume flow Jv(m3 · s–1) is dependent on the hydraulic conduc-tivity k (m · s–1 · Pa–1) of the membrane (i.e., itspermeability to water), the area A of passage(m2), and the pressure difference, which, inthis case, is equivalent to the osmotic pressuredifference ∆π (Pa):

Jv = k · A · ∆π [m3 · s–1]. [13.4]


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Since it is normally not possible to separatelydetermine k and A of a biological membrane orcell layer, the product of the two (k · A) is oftencalculated as the ultrafiltration coefficient Kf

(m3 s–1 Pa–1) (cf. p. 152).The transport of osmotically active particles

causes water flow. Inversely, flowing waterdrags dissolved particles along with it. Thistype of solvent drag ( p. 24) is a form of con-vective transport.

Solvent drag does not occur if the cell wall isimpermeable to the substance in question (σ =1). Instead, the water will be retained on theside where the substance is located. In the caseof the aforementioned epithelia, this meansthat the substances that cannot be reabsorbedfrom the tubule or intestinal lumen lead toosmotic diuresis ( p. 174) and diarrhea re-spectively. The latter is the mechanism of ac-tion of saline laxatives ( p. 264).

Oncotic Pressure / Colloid Osmotic Pressure

As all other particles dissolved in plasma, mac-romolecular proteins also exert an osmoticpressure referred to as oncotic pressure or col-loid osmotic pressure. Considering its contribu-tion of only 3.5 kPa (25 mm Hg) relative to thetotal osmotic pressure of the small molecularcomponents of plasma, the oncotic pressureon a strictly semipermeable membrane couldbe defined as negligible. However, within thebody, oncotic pressure is so important becausethe endothelium that lines the blood vesselsallows small molecules to pass relatively easily(σ 0). According to equation 13.3, theirosmotic pressure difference ∆π at the en-dothelium is virtually zero. Consequently, onlythe oncotic pressure difference of proteins iseffective, as the endothelium is either partly orcompletely impermeable to them, dependingon the capillary segment in question. Becausethe protein reflection coefficient σ 0 and theprotein content of the plasma (ca. 75 g/L) arehigher than that of the interstitium, these twofactors counteract filtration, i.e., the bloodpressure-driven outflow of plasma water fromthe endothelial lumen, making the en-dothelium an effective volume barrier be-tween the plasma space and the interstitium.

If the blood pressure drives water out of theblood into the interstitium (filtration), the

plasma protein concentration and thus the on-cotic pressure difference π will rise ( pp.152, 210). This rise is much higher than equa-tion 13.3 leads one to expect ( A). The differ-ence is attributable to specific biophysicalproperties of plasma proteins. If there is a pres-sure-dependent efflux or influx of water out ofor into the bloodstream, these relatively highchanges in oncotic pressure difference auto-matically exert a counterpressure that limitsthe flow of water.

pH, pK, Buffers

The pH indicates the hydrogen ion [H+] con-centration of a solution. According to Sörensen,the pH is the negative common logarithm ofthe molal H+ concentration in mol/kg H2O.

Examples:1 mol/kg H2O = 100 mol/kg H2O = pH 0,0.1 mol/kg H2O = 10–1 mol/kg H2O = pH 1,and so on up to 10-14 mol/kg H2O = pH 14.

Since glass electrodes are normally used to measurethe pH, the H+ activity of the solution is actuallybeing determined. Thus, the following rule applies:

pH = – log (fH · [H+]),where fH is the activity coefficient of H+. Consideringits ionic concentration (see above), the fH of plasma is 0.8.

The logarithmic nature of pH must be con-sidered when observing pH changes. For ex-ample, a rise in pH from 7.4 (40 nmol/kg H2O)to pH 7.7 decreases the H+ activity by 20 nmol/kg H2O, whereas an equivalent decrease (e.g.,from pH 7.4 to pH 7.1) increases the H+ activityby 40 nmol/kg H2O.

The pK is fundamentally similar to the pH. Itis the negative common logarithm of the disso-ciation constant of an acid (Ka) or of a base (Kb):

pKa = log Ka

pKb = log Kb.For an acid and its corresponding base,

pKa + pKb = 14, so that the value of pKa can bederived from that of pKb and vice versa.

The law of mass actions applies when aweak acid (AH) dissociates:

AH A– + H+ [13.5]

It states that the product of the molal concen-tration (indicated by square brackets) of thedissociation products divided by the concen-tration of the nondissociated substance re-mains constant:



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Ka =[A–] · [H+]

[AH][13.6]

Converted into logarithmic form (and insert-ing H+ activity for [H+]), the equation is trans-formed into:

log Ka = log[A–][AH]

+ log ([H+] · fH) [13.7]

or

log ([H+] · fH) = log Ka + log[A–][AH]

[13.8]

Based on the above definitions for pH and pKa,it can also be converted into

pH = pKa + log[A–][AH]

[13.9]

Because the concentration and not the activityof A– and AH is used in equation 13.9, pKa isconcentration-dependent in nonideal solu-tions.

Equation 13.9 is the general form of theHenderson–Hasselbalch equation ( p.138ff.), which describes the relationship be-tween the pH of a solution and the concentra-tion ratio of a dissociated to an undissociatedform of a solute. If [A–] = [AH], then the concen-tration ratio is 1/1 = 1, which corresponds topH = pKa since the log of 1 = 0.

A weak acid (AH) and its dissociated salt(A–) form a buffer system for H+ and OH– ions:

Addition of H+ yields A– + H+ AHAddition of OH– yields AH + OH– A– + H2O.The buffering power of a buffer system is

greatest when [AH] = [A–], i.e., when the pH ofthe solution equals the pKa of the buffer.

Example: Both [A–] and [AH] = 10 mmol/L and pKa =7.0. After addition of 2 mmol/L of H+ ions, the [A–]/[AH] ratio changes from 10/10 to 8/12 since 2 mmol/L of A– are consequently converted into 2 mmol/L ofAH. Since the log of 8/12 -0.18, the pH decreases

A. Physiological signification of deviations on oncotic pressure of plasma from van’tHoff’s equation. A loss of water from plasma leads to a disproportionate rise in oncoticpressure, which counteracts the water loss. Conversely, the dilution of plasma due to theinflux of water leads to a disproportionate drop in oncotic pressure, though less pro-nounced. Both of these are important mechanisms for maintaining a constant bloodvolume and preventing edema. (Adapted from Landis EM u. Pappenheimer JR. Handbookof Physiology. Section 2: Circulation, Vol. II. American Physiological Society: WashingtonD.C. 1963, S. 975.)


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by 0.18 units to pH 6.82. If the initial [A–] /[AH] ratiohad been 3/17, the pH would have dropped from aninitial pH 6.25 (7 plus the log of 3/17 = 6.25) to pH5.7 (7 + log of 1/19 = 5.7), i.e., by 0.55 pH units afteraddition of the same quantity of H+ ions.

The titration of a buffer solution with H+ (orOH–) can be plotted to generate a bufferingcurve ( B). The steep part of the curve repre-sents the range of the best buffering power.The pKa value lies at the turning point in themiddle of the steep portion of the curve. Sub-stances that gain (or lose) more than one H+

per molecule have more than one pK value andcan therefore exert an optimal buffering actionin several regions. Phosphoric acid (H3PO4)donates three H+ ions, thereby successivelyforming H2PO4

–, HPO42–, and PO4

3–. The bufferpair HPO4

2–/H2PO4– with a pKa of 6.8 is impor-

tant in human physiology ( p. 177ff.).The absolute slope, d[A–]/d(pH), of a buff-

ering curve (plot of pH vs. [A–]) is a measure ofbuffering capacity (mol · L–1 · [∆pH]–1; p.138).

Powers and Logarithms

Powers of ten are used to more easily and con-veniently write numbers that are much largeror smaller than 1.

Examples:100 = 10 · 10 = 102

1000 = 10 · 10 · 10 = 103

10 000 = 10 · 10 · 10 · 10 = 104, etc.In this case, the exponent denotes the

amount of times ten is multiplied by itself. Ifthe number is not an exact power of ten (e.g.,34 500), divide it by the next lowest decimalpower (10 000) and use the quotient (3.45) as amultiplier to express the result as 3.45 · 104.

The number 10 can also be expressed ex-ponentially (101). Numbers much smaller than1 are annotated using negative exponents.

Examples:1 = 10 10 = 100

0.1 = 10 10 10 = 10–1

0.01 = 10 10 10 = 10-2, etc.Similar to the large numbers above, num-

bers that are not exact powers of ten are ex-pressed using multipliers, e.g.,

0.04 = 4 · 0.01 = 4 · 10-2.Note: When writing numbers smaller than

1, the (negative) exponent corresponds to the

position of the 1 after the decimal point; there-fore, 0.001 = 10-3. When writing numbersgreater than 10, the exponent corresponds tothe number of decimal positions to the left ofthe decimal point minus 1; therefore, 1124.5 =1.245 · 103.

Exponents can also be used to representunits of measure, e.g., m3. As in the case of 103,the base element (meters) is multiplied by it-self three times (m · m · m; p. 378). Negativeexponents are also used to express units ofmeasure. As with 1/10 = 10–1, 1/s can be writ-ten as s–1, mol/L as mol · L–1, etc.

There are specific rules for performing cal-culations with powers of ten. Addition andsubtraction are possible only if the exponentsare identical, e.g.,

(2.5 · 102) + (1.5 · 102) = 4 · 102.Unequal exponents, e.g., (2 · 103) + (3 · 102),

must first be equalized:(2 · 103) + (0.3 · 103) = 2.3 · 103.


B. Buffering Curve. Graphic representation ofthe relationship between pH and the concentra-tion ratio of buffer acid/buffer base [AH]/[A–] as afunction of pH. The numerical values are roughlyequivalent to those of the buffer pair acetic acid/acetate (pKa = 4.7). The buffering power of abuffer system is greatest when [AH] = [A–], i.e.,when the pH of the solution equals the pKa of thebuffer (broken lines).

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Logarithms, Graphic Representation of Data

The exponents of the multiplicands areadded together when multiplying powers of10, and the denominator is subtracted from thenumerator when dividing powers of ten.

Examples:102 · 103 = 102+ 3 = 105

104 102 = 104 - 2 = 102

102 104 = 102 - 4 = 10-2

The usual mathematical rules apply to themultipliers of powers of ten, e.g.,

(3 · 102) · (2 · 103) = (2 · 3) · (102+ 3) = 6 · 105.Logarithms. There are two kinds of loga-

rithms: common and natural. Logarithmic cal-culations are performed using exponentsalone. The common (decimal) logarithm (logor lg) is the power or exponent to which 10must be raised to equal the number in ques-tion. The common logarithm of 100 (log 100) is2, for example, because 102 = 100. Decimallogarithms are commonly used in physiology,e.g., to define pH values (see above) and to plotthe pressure of sound on a decibel scale( p. 369).

Natural logarithms (ln) have a natural baseof 2.71828. . ., also called base e. The commonlogarithm (log x) equals the natural logarithmof x (ln x) divided by the natural logarithm of10 (ln 10), where ln 10 = 2.302585. The follow-ing rules apply when converting between nat-ural and common logarithms:

log x = (ln x)/2.3ln x = 2.3 · log x.When performing mathematical operations

with logarithms, the type of operation is re-duced by one rank—multiplication becomesaddition, potentiation becomes multiplica-tion, and so on.

Examples:log (a · b) = log a + log blog (a/b) = log a - log blog an = n · log alog n

a = (log a)/nSpecial cases:log 10 = ln e = 1log 1 = ln 1 = 0log 0 = ln 0 =

Graphic Representation of Data

Graphic plots of data are used to provide aclear and concise representation of measure-ments, e.g., body temperature over the time ofday ( C). The axes on which the measure-ments (e.g., temperature and time) are plottedare called coordinates. The vertical axis is re-ferred to as the ordinate (temperature) and thehorizontal axis is the abscissa (time). It is cus-tomary to plot the first variable x (time) on theabscissa and the other dependent variable y(temperature) on the ordinate. The abscissa istherefore called the x-axis and the ordinate they-axis. This method of graphically plotting datacan be used to illustrate the connection be-tween any two related dimensions imaginable,e.g., to describe the relationship betweenheight and age, lung capacity and intrapulmo-nary pressure, etc. ( p. 117).

Plotting of data makes it easier to determinewhether two variables correlate with eachother. For example, the plot of height (ordi-nate) over age (abscissa) shows that the heightincreases during the growth years and reachesa plateau at the age of about 17 years. Thismeans that height is related to age in the firstphase of life, but is largely independent of agein the second phase. A correlation does notnecessarily indicate a causal relationship. Adecrease in the birth rate in Alsace-Lorraine,for example, correlated with a decrease in thenumber or nesting storks for a while.

When plotting variables of wide-ranging di-mensions (e.g., 1 to 100 000) on a coordinate

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C. Illustration of how to plot data on a coordi-nate system. The plot in this example shows therelationship between body temperature (rectal,at rest) and time of day.


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system, it can be impossible to plot smallvalues individually without having the axesbecome extremely long. This problem can besolved by plotting the data as powers of 10 orlogarithms. For example, 1, 10, 100, and 1000are written as 100, 101, 102, and 103 or as loga-rithms 0, 1, 2, and 3. This makes it possible to

obtain a relatively accurate graphic represen-tation of very small numbers, and all the num-bers fit on an axis of reasonable length(cf. sound curves on p. 369 B).

Correlations can be either linear or non-linear. Linear correlations ( D1, violet line)obey the linear relationship

Graphic Representation of Data (continued)

D. Types of functions. D1: Linear function (violet), exponential function (red), logarithmic function(blue), and power function (green) showing linear plotting of data on both axes. The three curves can bemade into a straight line (linearized) by logarithmically plotting the data on the y-axis (D2: exponentialfunction) or on the x-axis (D4: logarithmic function) or both (D3: power function).

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Graphic Representation of Data

y = ax + b,where a is the slope of the line and b is thepoint, or intercept (at x = 0), where it intersectsthe y-axis.

Many correlations are nonlinear. For sim-pler functions, graphic linearization can beachieved via a nonlinear (logarithmic) plot ofthe x and/or y values. This allows for the ex-trapolation of values beyond the range ofmeasurement (see below) or for the genera-tion of calibration curves from only two points.In addition, this method also permits the cal-culation of the “mean” correlation of scatteredx-y pairs using regression lines.

An exponential function ( D1, red curve),such as

y = a · eb · x,can be linearized by plotting ln y on the y-axis( D2):

ln y = ln a + b · x,where b is the slope and ln a is the intercept.

A logarithmic function ( D1, blue curve),such as

y = a + b · ln x,can be linearized by plotting ln x on the x-axis( D4), where b is the slope and a is the inter-cept.

A power function ( D1, green curve), suchas

y = a · xb,can be graphically linearized by plotting ln yand ln x on the coordinate axes ( D3) be-cause

ln y = ln a + b · ln x,where b is the slope and ln a is the intercept.

Note: The condition x or y = 0 does not exist on loga-rithmic coordinates because ln 0 = . Nevertheless,ln a is still called the intercept in the equation whenthe logarithmic abscissa ( D3,4) is intercepted bythe ordinate at ln x = 0, i.e., x = 1.

Instead of plotting ln x and/or ln y on the x- and/ory-axis, they can be plotted on logarithmic paper onwhich the ordinate or abscissa (semi-log paper) orboth coordinates (log-log paper) are plotted in loga-rithmic units. In such cases, a is no longer treated asthe intersect because the position of a depends onsite of intersection of the x-axis by the y-axis. Allvalues 0 are possible.

Other nonlinear functions can also be graphi-cally linearized using an appropriate plottingmethod. Take, for example, the Michaelis–Menten equation ( E1), which applies to

many enzyme reactions and carrier-mediatedtransport processes:

J = Jmax ·C

KM + C[13.10]

where J is the actual rate of transport (e.g., inmol · m–2 · s–1), Jmax is the maximal transportrate, C (mol · m–3) is the actual concentration ofthe substance to be transported, and KM is theconcentration (half-saturation concentration)at 1/2 Jmax.

One of the three commonly used linearrearrangements of the Michaelis–Mentenequation, the Lineweaver–Burk plot, states:

1/J = (KM/Jmax) · (1/C) + 1/Jmax, [13.11]

Consequently, a plot of 1/J on the y-axis and1/C on the x-axis results in a straight line( E2). While a plot of J over C ( E1) does not

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permit accurate extrapolation of Jmax (becausean infinitely high concentration of C would berequired), the linear rearrangement ( E2)makes it possible to generate a regression linethat can be extrapolated to C = from themeasured data. Since 1/C is equal to 1/ (= 0),1/Jmax lies on the y-axis at x = 0 ( E2). Thereciprocal of this value is Jmax. Insertion of 1/J =0 into equation 13.11 yields

0 = (KM/Jmax) · (1/C) + 1/Jmax [13.12]

or 1/KM = 1/C, so that KM can be derived fromthe negative reciprocal of the x-axis intersect,which corresponds to 1/J = 0 ( E2).

The Greek Alphabet

α Α alpha Β betaγ Γ gammaδ ∆ deltaε Ε epsilon zetaη Η eta, θ Θ thetaι Ι iotaκ Κ kappaλ Λ lamdaµ Μ muν Ν nu xi omicronπ Π pi Ρ rhoσ, ς Σ sigmaτ Τ tauυ Υ upsilonφ Φ phi+ , chiψ Ψ psiω Ω omega

Reference Values in Physiology

Total body and cells

Chemical composition of 1 kg fat-free bodymass of an adult

720 g water, 210 g protein, 22.4 g Ca, 12 g P,2.7 g K, 1.8 g Na, 1.8 g Cl, 0.47 g Mg

Distribution of water in adult (child) aspercentage of body weight (cf. p. 168)

Intracellular: 40% (40%); interstitium: 15%(25%); plasma: 5% (5%)

Ion concentrations in ICF and ECF See p. 93 C

Cardiovascular system

Weight of heart 250–350 gCardiac output at rest (maximal) 5–6 L/min (25 L/min); cf. p. 188Resting pulse = sinus rhythm 60–75 min-1 or bpmAV rhythm 40–55 min-1

Ventricular rhythm 25–40 min-1

Arterial blood pressure (Riva–Rocci) 120/80 mm Hg (16/10.7 kPa) systolic/diastolicPulmonary artery pressure 20/7 mm Hg (2.7/0.9 kPa) systolic/diastolicCentral venous pressure 3–6 mm Hg (0.4–0.8 kPa)Portal venous pressure 3–6 mm Hg (0.4–0.8 kPa)Ventricular volume at end of diastole/systole 120 mL/40 mLEjection fraction 0.67Pressure pulse wave velocity Aorta: 3–5 m/s; arteries: 5–10 m/s;

veins: 1–2 m/sMean velocity of blood flow Aorta: 0.18 m/s; capillaries: 0.0002–0.001 m/s;

venae cavae: 0.06 m/s

Graphic Representation of Data (continued)


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Blood flow in organs at rest

(See also pp. 189 A, 215 A) % of cardiac output per gram of tissueHeart 4% 0.8 mL/minBrain 13% 0.5 mL/minKidneys 20% 4 mL/minGI tract (drained by portal venous system) 16% 0.7 mL/minLiver (blood supplied by hepatic artery) 8% 0.3 mL/minSkeletal muscle 21% 0.04 mL/minSkin and miscellaneous organs 18% —

Lungs and gas transport Men WomenTotal lung capacity (TLC) 7 L 6.2 LVital capacity (VC); cf. p. 112 5.6 L 5 LTidal volume (VT) at rest 0.6 L 0.5 LInspiratory reserve volume 3.2 L 2.9 LExpiratory reserve volume 1.8 L 1.6 LResidual volume 1.4 L 1.2 LMax. breathing capacity in 30 breaths/min 110 L 100 LPartial pressure of O2 Air: 21.17 kPa (159 mm Hg)

Alveolar: 13.33 kPa (100 mm Hg)Arterial: 12.66 kPa (95 mm Hg)Venous 5.33 kPa (40 mm Hg)

Partial pressure of CO2 Air: 0.03 kPa (0.23 mm Hg)Alveolar: 5.2 kPa (39 mm Hg)Arterial: 5.3 kPa (40 mm Hg)Venous: 6.1 kPa (46 mm Hg)

Respiratory rate (at rest) 16 breaths/minDead space volume 150 mLOxygen capacity of blood 180–200 mL O2/L blood = 8–9 mmol O2/L bloodRespiratory quotient 0.84 (0.7–1.0)

Kidney and excretion

Renal plasma flow (RPF) 480–800 mL/min per 1.73 m2 body surfacearea

Glomerular filtration rate (GFR) 80–140 mL/min per 1.73 m2 body surface areaFiltration fraction (GFR/RPF) 0.19Urinary output 0.7–1.8 L/dayOsmolality of urine 250–1000 mOsm/kg H2ONa+ excretion 50–250 mmol/dayK+ excretion 25–115 mmol/dayGlucose excretion 300 mg/day = 1.67 mmol/dayNitrogen excretion 150–250 mg/kg/dayProtein excretion 10–200 mg/dayUrine pH 4.5–8.2Titratable acidity 10–30 mmol/dayUrea excretion 10–20 g/day = 166–333 mmol/dayUric acid excretion 300–800 mg/day = 1.78–6.53 mmol/dayCreatinine excretion 0.56–2.1 g/day = 4.95–18.6 mmol/day


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Nutrition and metabolism Men WomenEnergy expenditure during various activities Bed rest 6500 kJ/d

(1550 kcal/d)5400 kJ/d(1300 kcal/d)

Light office work 10 800 kJ/d(2600 kcal/d)

9600 kJ/d(2300 kcal/d)

Walking (4.9 km/h) 3.3 kW 2.7 kW Sports (dancing, horseback riding, swimming) 4.5–6.8 kW 3.6–5.4 kWFunctional protein minimum 1 g/kg body weightVitamins, optimal daily intake(IU = international units)

A: 10 000–50 000 IU; D: 400–600 IUE: 200–800 IU; K: 65–80µg; B1, B2, B5, B6:25–300 mg of each; B12: 25–300µg; folate:0.4–1.2 mg; H: 25–300µg; C: 500–5000 mg

Electrolytes and trace elements,optimal daily intake

Ca: 1–1.5 g; Cr: 200–600µg; Cu: 0.5–2 mg;Fe: 15–30 mg: I: 50–300µg; K+: 0.8–1.5 g;Mg: 500–750 mg; Mn: 15–30 mg;Mo: 45–500µg; Na+: 2 g; P: 200–400 mg;Se: 50–400µg; Zn: 22–50 mg

Nervous Systems, muscles

Duration of an action potential Nerve: 1–2 ms; skeletal muscle: 10 ms;myocardium: 200 ms

Nerve conduction rate See p. 49 C

Blood and other bodily fluids (see also Table p. 88)

Blood (in adults) Men: Women:Blood volume (also refer to table on p. 88) 4500 mL 3600 mLHematocrit 0.40–0.54 0.37–0.47Red cell count (RBC) 4.5–5.9 · 1012/L 4.2–5.4 · 1012/LHemoglobin (Hb) in whole blood 140–180 g/L 120–160 g/L

(2.2–2.8 mmol/L) (1.9–2.5 mmol/L)Mean corpuscular volume (MCV) 80–100 fLMean corpuscular Hb concentration (MCHC) 320–360 g/LMean Hb concentration in single RBC (MCH) 27–32 pgMean RBC diameter 7.2–7.8µmReticulocytes 0.4–2% (20–75 · 109/L)Leukocytes (also refer to table on p. 88) 3–11 · 109/LPlatelets 170–360 · 109/L 180–400 · 109/LErythrocyte sedimentation rate (ESR) 10 mm in first hour 20 mm in first hour

ProteinsTotal 66–85 g/L serumAlbumin 35–50 g/L serum 55–64 % of totalα1-globulins 1.3–4 g/L serum 2.5–4 % of totalα2-globulins 4–9 g/L serum 7–10% of total-globulins 6–11 g/L serum 8–12% of totalγ-globulins 13–17 g/L serum 12–20% of total

Coagulation (See p. 102 for coagulation factors)Thromboplastin time (Quick) 0.9–1.15 INR (international normalized ratio)Partial thromboplastin time 26–42 sBleeding time 6 min

Reference Values in Physiology (continued)


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Parameters of glucose metabolismGlucose concentration in venous blood 3.9–5.5 mmol/L (70–100 mg/dL)Glucose concentration in capillary blood 4.4–6.1 mmol/L (80–110 mg/dL)Glucose concentration in plasma 4.2–6.4 mmol/L (75–115 mg/dL)Limit for diabetes mellitus in plasma 7.8 mmol/L ( 140 mg/dL)HBA1c (glycosylated hemoglobin A) 3.2–5.2%

Parameters of lipid metabolismTriglycerides in serum 1.71 mmol/L ( 150 mg/dL)Total cholesterol in serum 5.2 mmol/L ( 200 mg/dL)HDL cholesterol in serum 1.04 mmol/L ( 40 mg/dL)

Substances excreted in urineUrea concentration in serum 3.3–8.3 mmol/L (20–50 mg/dL)Uric acid concentration in serum 150–390µmol/L (2.6–6.5 mg/dL)Creatinine concentration in serum 36–106µmol/L (0.4–1.2 mg/dL)

BilirubinTotal bilirubin in serum 3.4–17µmol/L (0.2–1 mg/dL)Direct bilirubin in serum 0.8–5.1µmol/L (0.05–0.3 mg/dL)

Electrolytes and blood gasesOsmolality 280–300 mmol/kg H2OCations in serum: Na+ 135–145 mmol/L

K+ 3.5–5.5 mmol/LIonized Ca2+ 1.0–1.3 mmol/LIonized Mg2+ 0.5–0.7 mmol/L

Anions in serum: Cl- 95–108 mmol/LH2PO4

- + HPO42- 0.8–1.5 mmol/L

pH 7.35–7.45Standard bicarbonate 22–26 mmol/LTotaL buffer bases 48 mmol/LOxygen saturation 96% arterial; 65–75%

mixed venousPartial pressure of O2 at half saturation (P0.5) 3.6 kPa (27 mmHg)

Cerebrospinal fluid

Pressure in relaxed horizontal position 1.4 kPa (10.5 mmHg)Specific weight 1.006–1.008 g/LOsmolality 290 mOsm/kg H2OGlucose concentration 45–70 mg/dL (2.5–3.9 mmol/L)Protein concentration 0.15–0.45 g/LIgG concentration 84 mg/dLWhite cell count 5 WBC/µL


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1. Fick’s law of diffusion for membrane trans-port (see also p. 20ff.)

Jdiff = F · D ·∆C∆x

[mol · s–1]

Jdiff = net diffusion rate [mol · s–1];A = area [m2];D = diffusion coefficient [m2 · s–1];∆C = concentration difference [mol · m–3];∆x = membrane thickness [m]

Alternative 1:Jdiff

F= P · ∆C [mol · m–2 · s–1]

P = permeability coefficient [m · s–1];Jdiff, A and ∆C; see above

Alternative 2 (for gas diffusion)V.

diffF = K · ∆P

∆x [m · s–1]

V.

diff = net diffusion rate [m3 · s–1];K = Krogh’s diffusion coefficient [m2 · s-1 · Pa-1]∆P = partial pressure difference [Pa]

2. Van’t Hoff–Stavermann equation(see also p. 388)

∆π = σ · R · T · ∆cosm [Pa]

∆π = osmotic pressure difference [Pa]σ = reflection coefficient [dimensionsless]R = universal gas constant [8.3144J · K–1 ·mol–1];T = absolute temperature [K];∆cosm = concentration difference ofosmotically active particles [mol · m–3].

3. Michaelis-Menten equation(see also pp. 28, 389ff.)

Jsat = Jmax · CKM + C [mol · m–2 · s–1],

Jsat = substrate transport (turnover)[mol · m–2 · s–1];Jmax = maximum substrate transport(turnover) [mol · m–2 · s–1];C = substrate concentration [mol · m–3];KM = Michaelis constant = substrateconcentration at 1/2 Jmax [mol · m–3].

4. Nernst equation (see also p. 32)

Ex = –61 · zx–1 · log [X]i

[X]a[mV]

Ex = equilibrium potential of ion X [mV];zx = valency of ion X;[X]i = intracellular concentration of ion X[mol · m–3][Xo] = extracellular concentration of ion X[mol · m–3].

5. Ohm’s Law (see also pp. 32, 188)

a. For ion transport at membrane

Ix = gx · (Em – Ex) [A · m–2]

Ix = ionic current of ion X per unit areaof membrane [A · m–2];gx = conductance of membrane to ion X[S · m–2];Em = membrane potential [V];Ex = equilibrium potential of ion X [V]

b. For blood flow:

Q.

= ∆PR [L · min–1]

Q.

= flow rate (total circulation:cardiac output, CO) [L · min–1]∆P = mean blood pressure difference(systemic circulation: Paorta –Pvena cava;lesser circulation: Ppulmonary artery –Ppulmo-

nary vein) [mmHg]R = flow resistance (systemic circula-tion:total peripheral resistance = TPR)[mmHg · min · L–1].

6. Respiration-related equations(see also pp. 106, 120)a. Tidal volume (VT):

VT = VD + VA [L]b. Respiratory volume per time

(V.

E oder V.

T):V.

E = f · VT = (f · VD) + (f · VA) =V.

D + V.

A [L · min–l]c. O2 consumption, CO2 emission,

and RQ (total body:)V.

O2= V.

T (FIO2 – FEO2) = CO · avDO2 [L · min–1]V.

CO2 = V.

T · FECO2 [L · min–1]

RQ = V.

CO2

V.

O2

Important Equations in Physiology


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Important Equations in Physiology

VD = dead space [L];VA = alveolar fraction of VT [L];f = respiration rate [min–1];V.

D = dead space ventilation [L · min–1];V.

A = alveolar ventilation [L · min–1];V.

O2 = O2 consumption [L · min–1];V.

CO2 = CO2 emission [L · min-1];FIO2 = inspiratory O2 fraction [L/L];FEO2 = exspiratory O2 fraction [L/L];FECO2 = exspiratory CO2 fraction [L/L];RQ = respiratory quotient (dimensionless)

d. O2 consumption and CO2 emission (organ):V.

O2 = Q.

· avDO2 [L · min–1]V.

CO2 = Q.

· avDCO2 [L · min–1]

Q.

= blood flow in organ [L · min–1]avDO2, avDCO2 = arteriovenousO2 and CO2 difference in total circulationand organ circulation [L/L blood]

e. Fick’s principle:

CO =V.

O2

avDO2

[L · min–1]

CO = cardiac output [L · min–1]>

f. Gas partial pressure ↔ gas concentra-tion in liquids:[X] = α · Px [mmol/L plasma]

[X] = concentration of gas X [mmol · L–1]α = (Bunsen’s) solubility coefficient[mmol · L–1 · kPa–1]PX = partial pressure of gas X [kPa]

g. Bohr’s formula (see also p. 115)

VD = VT(FACO2 – FECO2)

FACO2

VD = dead space [L];VT = tidal volume [L];FACO2 = alveolar CO2 fractionFECO2 = exspiratory CO2 fraction [L/L]

h. Alveolar gas equation (see also p. 136)

PAO2 = PIO2 – PAO2

RQ[kPa]

PAO2 and PIO2 = alveolar and inspiratory par-tial pressure of O2 [kPa]PACO2 = alveolar partial pressure of CO2 [kPa]RQ = respiratory quotient [dimensionless].

7. Henderson–Hasselbalch equation(see also pp. 138ff., 385)a. General equation:

pH = pKa + log[A–][AH]

b. for bicarbonate/CO2 buffer (37 oC):

pH = 6,1 +[HCO3

–]α · PCO2

pH = negative common logarithm ofH+ activitypKa = negative common logarithm ofdissociation constant of buffer acid indenominator (AH or CO2)[A–] and [HCO3

–] = buffer base concentra-tion; α · PCO2 = [CO2]; see Equation 6f.

8. Equations for renal function(see also p. 150ff.)

a. Clearance of a freely filtrable substance X(CX):CX = V

.U · UX

PX[L · min–1]

b. Renal plasma flow

RPF = V.

U · UPAH0,9 · PPAH

[L · min–1]

c. Renal blood flow (RBF):

RBF = RPF1 – HCT [L · min–1]

d. Glomerular filtration rate (GFR):

GFR = V.

U · UInPIn

[L · min–1]

e. Free water clearance (CH2 O)

CH2O = V.

U · (1 – UosmPosm

) [L · min–1]

f. Filtration fraction

FF = GFRRPF [dimensionless]

g. Fractional excretion of substance X (FEX):FEX = CX

GFR [dimensionless];

h. Fractional reabsorption of substance X(FRX):FRX = 1 – FEX [dimensionslos];

V.

U = urinary excretion rate [L · min-1]UX, UPAH, UIn = urinary concentration ofsubstance X, para-aminohippuric acid, andindicator (e.g., inulin, endogenous crea-tinine) [mol · L-1] or [g · L-1 ]


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Uosm = osmolality of urine [Osm · L-1]PX, PPAH, PIn = plasma concentration of sub-stance X, para-aminohippuric acid, and in-dicator (e.g., inulin, endogenous crea-tinine) [mol · L-1] or [g · L-1 ]Posm = osmolality of plasma [Osm · L-1]HCT = hematocrit [L of blood cells/L ofblood]

9. Equations for filtration(see also pp. 152, 208)a. Effective filtration pressure at capillaries

(Peff)Peff = Pcap – Pint – πcap + πint [mmHg]

b. Effective filtration pressure at capillariesof renal glomerulus:Peff = Pcap – PBow – πcap [mmHg]

c. Filtration rate (Q.

at glomerulus = GFR)Q.

= Peff · F · k [m3 · s –1]

Pcap (Pint) = hydrostatic pressure in capillaries(interstitium) [mm Hg]πcap (πint) = oncotic pressure in capillaries(interstitium) [mm Hg]Peff = mean effective filtration pressure [mm Hg]A = area of filtration (m2)k = permeability to water (hydraulic conduc-tance) [m3 · s-1 · mm Hg-1]

10. Law of Laplace(see also pp. 118, 188, and 210)

a. Elliptical hollow body (with radii r1 and r2)

Ptm = T ( 1r1

+ 1r2

) [Pa];

b. Elliptical hollow body, considering wallthickness:

Ptm = S · w ( 1r1

+ 1r2

) [Pa];

c. Spherical hollow body (r1 = r2 = r):

Ptm = 2 Tr [Pa] or Ptm = 2 S · w

r [Pa];

d. Cylindrical hollow body(r2 , therefore 1/r2 = 0):

Ptm = Tr [Pa] or Ptm = S · w

r [Pa]

Ptm = transmural pressure [Pa]T = wall tension [N · m-1]S = wall tension [N · m-2]w = wall thickness [m]

11. Equations for cardiovascular function(see also items 2, 5b, 6c, and 9 as well asp. 188ff.)a. Cardiac output (CO):

CO = f · SV [l · min–1]

b. Hagen–Poiseuille equation

R = 8 · l · ηπ · r4 ;

f = heart rate [min-1]SV = stroke volume [L]R = flow resistance in a tube [Pa · s · m-3] ofknown length l [m] and inner radius r [m]η = viscosity [Pa · s]

Important Equations in Physiology (continued)


397

13A

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Further Reading

Physiology

Boron WF, Boulpaep EL. Medical Physiology: ACellular and Molecular Approach. Philadelphia:Saunders; 2004

Guyton AC, Hall JE.Textbook of Medical Physiology.Philadelphia: Saunders 2005

Hall JE. Guyton & Hall Physiology Review. St. Louis:C.V. Mosby; 2005

Koeppen BM, Stanton BA. Berne and Levy Physi-ology. St. Louis: Mosby; 2008

Levy MN, Stanton BA, Koeppen BM. Berne andLevy Principles of Physiology. St. Louis: Mosby;2005

Widmaier EP, Raff H, Strang KD. Vander, Sherman,Luciano’s Human Physiology: The Mechanisms ofBody Function. New York: McGraw Hill; 2003

Cell Physiology

Alberts B, Bray D, Lewis J. Molecular Biology of theCell. 4th ed. Taylor & Francis; 2002

Lodish H, Berk A, Kaiser CA, Krieger M. MolecularCell Biology. New York: Palgrave Macmillan;2007

Neurophysiology, Muscle

Bear M, Paradiso M, Connors BW. Neuroscience:Exploring the Brain. Baltimore: Lippincott Wil-liams & Wilkins; 2006

Kandel ER, Schwartz JH, Jessell T. Principles ofNeural Science. New York: McGraw-Hill; 2000

Respiration

West JB. Respiratory Physiology: The Essentials.Baltimore: Lippincott Williams & Wilkins;2008

Exercise and Work Physiology

McArdle WD, Katch FI, Katch VL. Exercise Physi-ology: Energy, Nutrition, and Human Perform-ance. 6th ed. Philadelphia: Lippincott Williams& Wilkins; 2006

West JB, Schoene RB, Milledge JS. High AltitudeMedicine and Physiology. London: Hodder Ar-nold; 2007

Wilmore JH, Costill DL. Physiology of Sport and Ex-ercise. London: Human Kinetics; 2005

Heart and Circulation

Hurst JW, Alexander RW, Schlant RC. Hurst’s TheHeart, Companion Handbook. New York:McGraw-Hill 2003

Katz AM. Physiology of the Heart. Philadelphia:Lippincott Williams and Wilkins 2005

Renal, Electrolyte and Acid-BasePhysiology

Alpern RJ, Hebert SC. Seldin and Giebisch’s The Kid-ney. Vols. 1 & 2: Physiology and Pathophysiology.Amsterdam: Elsevier Books 2007

Halperin ML, Goldstein MB. Fluid, Electrolyte andAcid-Base Physiology: A Problem-Based Ap-proach. Philadelphia: Saunders; 2006

Navar LG, Eaton DC, Pooler JP. Vander’s Renal Phys-iology. New York: McGraw Hill; 2008

Gastrointestinal Physiology

Barret KE. Gastrointestinal Physiology. New York:McGraw-Hill; 2006

Johnson R, Barrett KE, Ghishan FK. Physiology ofthe Gastrointestinal Tract: Vols 1 & 2. LeonardAcademic Press 2006

Johnson LR. Gastrointestinal Physiology. LeonardMosby; 2006

Endocrinology

Kronenberg HM, Melmed S, Kenneth S. PolonskyKS, Larsen PR. Williams Textbook of En-docrinology. Philadelphia: Saunders; 2007

Strauss JF und Barbieri RL. Yen & Jaffe’s Reproduc-tive Endocrinology. Physiology, Pathophysiologyand Clinical Management. Philadelphia:Saunders; 2004

Reproduction an Sexual Physiology

Leung PCK, Armstrong DT, Ruf KB, Moger WH. En-docrinology and Physiology of Reproduction.Heidelberg: Springer 2007

Neill JD. Knobil and Neill’s Physiology of Reproduc-tion. Amsterdam: Academic Press; 2005

Animal Physiology

Hill RW, Wyse GA, Anderson M. Animal Physi-ology. Palgrave Macmillan; 2004

Randall DJ, Burggren W, French K. Eckert AnimalPhysiology. Palgrave Macmillan; 2002


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Pathophysiology, Pathology

Kumar V, Abbas AK, Fausto N, Mitchell R. Robbins’Basic Pathology. Philadelphia: Saunders 2007

McPhee SJ, Ganong WF. Pathophysiology of Dis-ease: An Introduction to Clinical Medicine. NewYork: McGraw-Hill; 2005

Price SA, McCarty Wilson L. Pathophysiology.Clinical Concepts of Disease Processes. Elsevier,Oxford 2003

Silbernagl S, Lang F. Color Atlas of Pathophysiology(Flexibook). Thieme Medical Publishers 2000

Pharmacology

Brunton LL, Lazo JS, Parker K. Goodman and Gil-man’s the Pharmacological Basis of Therapeutics.B& T 2005

Champe PC, Finkel R, Cubeddu L. PharmacologyPhiladelphia: Lippincott Raven; 2008

Rang P, Dale MM, Ritter JM, Flower RJ. Pharma-cology. Edinburgh: Churchill Livingstone; 2007

Dictionaries

Dorland NW. Dorland’s Illustrated Medical Dic-tionary. Philadelphia: Saunders; 2007

Dumith K, Breskin M, Seeman R. McGraw-HillMedical Dictionary for Allied Health. New York:McGraw Hill; 2007

Martin E. Concise Medical Dictionary. Oxford Uni-versity Press; 2007

Further Reading (continued)


399

Index, Abbreviations

A

a (atto-, submultiple of a unit)379

A (ampere), unit 381band, muscle 60

AA (amino acids) 184, 298Abdominal muscles 108

pressure 108, 266reflex 322

Aberration, spherical 352AB0 system 100Absolute threshold, eye 358

smell 346ear 368

Absorption, intestinal, of aminoacids 260

carbohydrates 260electrolytes 264fat 254iron 90lipids 254peptides 260vitamins 262

Abstract thinking 340ABP (androgen-binding protein)

308ACAT (acyl-CoA-cholesterol acyl

transferase) 258Acceleration (unit) 380

angular (rotational) 348detection 348linear (translational) 348sensor 316, 348

Accessory nucleus 374Accident, electrical 202Acclimatization 226Accommodation, eye 348, 352

range 348, 352reflex, intestine 246

rectum 266stomach 242

ACE (angiotensin-convertingenzyme) 186inhibitor 186

A cells, islets of Langerhans 284,286

Acenocumarol 104Acetate, conjugates 160Acetazolamide 174Acetone 286Acetylcholine 34, 52, 78 ff., 238,

244antagonists 82cerebral cortex 334control of circulation 214ff.coronary vasodilatation 212esophagus 240esterase 56, 82

Acetylcholine (cont.)gastrointestinal tract 236heart action 196motor end plate 56NO-synthase activation 82pankreas 248parietal cells 244release 82receptors cholinoceptors

second messenger 55 F, 276,278

synthesis 82Acetylcholinesterase 56, 82

synaptic cleft 82Acetyl coenzyme A 286A chain, insulin 284Achalasia 240Acetylsalicylic acid 104

cyclooxygenase inhibition271

Achromat 362Acid, fixed 176

production 176titratable 176, 180

Acid–base balance 138, 142compensatory mechanisms

142disturbances 142, 146, 178kidney 176liver 178metabolic disturbances 142normal parameters 142regulation 142respiratory disturbances 144

status, assessment 146Acidosis 142

hyperkalemic 182influence on protein-bound

Ca2 292K concentration, plasma 182lact- 76metabolic 142, 264, 286nonrespiratory (metabolic)

142, 264, 286in diarrhea 264phosphaturia 180renal tubular 142, 178respiratory 126, 142, 144

Acini, salivary gland 238Acne 308Aconitase, iron absorption 90Acoustic information, central

processing 374pathways 374thresholds 368, 374

Acrosomal reaction 310ACTH corticotropinACTH reserve 296Actin 14, 30, 56, 58, 62, 70, 82

Actin (cont.)filament 14, 60molecular structure 60myosin interaction 68smooth muscle 70skeletal muscle 60

Action potential 42, 62all-or-none depolarization

46depolarization phase 46heart 59 A, 194, 196overshoot 46pacemaker, heart 194postsynaptic neurons 82propagation 48purkinje fibers 202repolarization phase 46retina 360skeletal muscle 56, 59 Asmooth muscle 59 A

Activating energy 40Activation system, subcortical

340Active immunization 94

transport 26, 44Activin, FSH secretion 308Activity coefficient 382Acuity, visual 354Acyl-CoA-cholesterol acyl trans-

ferase (ACAT) 258Adam-Stokes attack 202Adaptation, eye 360,

sensors 314smell 346taste 344thermosensation 316

ADCC (antigen-dependent cell-mediated cytotoxicity) 96

Addison’s disease 184Adenin 8Adenohypophysis 270, 282Adenosine, coronary vasodilata-

tion 212second messenger of 276

Adenosine diphosphate ADPmonophosphate AMPtriphosphate ATP

Adenylate cyclase 37 C1, 276, 278inhibition with acetylcholine

82ADH adiuretinAdhesion molecule (VLA-4) 98Adhesion, platelets 102Adiadochokinesis 330Adiuretin 24, 162, 271, 282

activated Cl–-channels 162deficiency 166effects 214, 282


400

Adiuretin (cont.)receptor types 24, 55 F, 166,

282salt/water homeostasis 173 Esecond messenger 24, 55 Fsecretion 220

ADP 72role in autoregulation 214

ADP-ribosylation factor (ARF) 30Adrenal cortex 256, 274, 296,

305, 308androgens 308fetal 306glucocorticoids 298HDL receptors 256hormone synthesis 296 ff.,

306progesterone 305zones 296, 298

medulla 78, 86, 270, 274, 298hormones 86

Adrenaline epinephrineAdrenergic transmission 84Adrenoceptors 84, 214, 216

α- 84, 214f.α1- 80ff., 216, 278, 306

renin secretion 186α2- 52, 80ff., 86, 146, 232, 250

insulin secretion 284second messenger 55, 276

agonists 87 Bantagonists 87 B- 86, 214f.1-, renin secretion 186

second messenger 85ff., 2762-, 85ff., 286

coronary vasodilatation 212second messenger 55, 85ff.,

276salivary glands 238

3-, fatty tissue 84, 224second messenger 55, 276stomach 244

distribution 81, 87 BG- proteins 55, 87 Bkidney 216localisation 81ff.receptor types 84ff.skin 216types 84, 87 Buterus 306

Adrenocortical hormones 296insufficiency 184tumor 218

Adrenocorticotropic hormone corticotropin

AE1 (= Anion exchanger 1) 176Aerobic glucose metabolism 72Affinity, transport system 28Afterload, heart 206

maxima, curve 205Afterloaded contraction 66

heart 204

Agglutination, red blood cells100

Aggregation, platelets 102AIP (aldosterone-induced pro-

teins) 184Air, composition 107 A, 391

sound conduction 370Air space, voice 376Airway resistance 134A-kinase (proteinkinase A, PKA)

84, 276Akinesia 328Alanine, glucagon secretion 286Alarm reaction 86, 332Albumin 92, 154, 158, 270, 308

bilirubin binding 252calcium binding 292pressure, oncotic 210renal filtration 154

reabsorption 158testosterone binding 308T3/T4 transport 290

Alcohol, energy source 228Aldosterone 162, 170, 184 ff., 186,

218antagonists 174deficiency 184deficit 172degradation 185 Deffects 184induced protein (AIP) 184K metabolism 182Na-transport, intestinal 264

tubular 182ff.receptor 174

glucocorticoids 298secretion 184, 185 Dsynthesis 296

Alkaline phosphatase 252Alkalosis 142

Ca2 concentration, serum 292hypokalemic 174, 182K plasma concentration 182metabolic 142non-respiratory 142phosphate reabsorption, renal

180respiratory 142, 144

high altitude 136vomiting 240

Allergens 98, 100Allergy 100

anaphylactic shock 220delayed type hypersensitivity

100immediate reaction 100

Allodynia 320All-or-none-response 46, 66, 194all-trans-retinal 354, 356Alternating current 50, 381Altitude gain 136Alveolar gas 114

Alveolar gas (cont.)partial pressures 120equation 120, 136, 395

exchange 120, 124pressure (PA) 108, 116

Alveolar ventilation 106, 114,120 ff.

Alveoli 106, 118ff.cell types 118contact time 120diffusion distance 120surface 118

tension 118Amacrine cells, retina 350, 360Ambient temperature pressure

H2O-saturated (ATPS) 112Amenorrhea 232Amiloride 174L-Amino acid decarboxylase 84Aminoaciduria 260Amino acids (AA) 242, 260, 184,

186, 298co-transport with Na 158,

260essential 228glucagon secretion 286gluconeogenesis from 284influence on insulin release

284ff.intestinal absorption 260,

264metabolism, cortisol effect

298pylorus, effect on 242renal transport 156, 158storage 286transmitter 55 F

γ-aminobutyric acid (GABA) 52,322

p-aminohippurate 150, 160Aminopeptidases, small intestine

260Ammonia NH3

Ammonium NH4

Amnesia 340Amount of substance, unit 3815’-AMP 278AMP, cyclic 84, 288

adrenergic transmission 84TSH 288

AMPA receptors glutamateAmpere (A), unit 381Amplification, cochlear 372Ampulla, labyrinth 348Amygdala 346α-amylase 260Amylopectin 260Amylose 260Anabolic action 282

insulin 286STH 282testosterone 308


401

Anaerobic glycolysis 72threshold 72

Analgesic action 320Anal sphincters 266Anaphylaxis 100Anastomoses, arteriovenous 226Androgen-binding protein 308Androgens 302, 308

adrenal cortex 296synthesis 296, 308

follicle 302Androstenedione 302Anemia 228, 262

hyperchromic 90hypochromic, iron deficiency

90pernicious 262sickle cell 92

Anergy 98ANF AtriopeptinAngina pectoris 320

ECG 200Angiotensin I 186

lung 106Angiotensin II (AT II) 158, 170,

184, 186, 214aldosterone secretion 184effects 186, 214, 218CSF 168degradation, renal 158receptors 186second messenger 276thirst 172

Angiotensin-converting enzyme(ACE) 186

Angiotensinogen 186synthesis, cortisol effect 298

Ångström (unit) 378Anion exchange, red blood cells

124Anion exchanger 1 (= AE1) 176Anode 50Anomaloscope 362Anovulatory cycle 300Anoxia ( also hypoxia) 130, 134ANP AtriopeptinANS (Autonomic nervous system)

78ff., 196, 214ff., 236, 268, 332Anterior pituitary 270, 282Anterolateral funiculus, tracts

320, 324Antibodies ( also immuno-

globulins) 94, 98, 100Anticoagulants 104Anticodon 8, 10Antidiuresis 164, 166Antidiuretic hormone adi-

uretinAntigen-antibody complex 98

allergy 100presentation 96, 98

Antigen-dependent cell-medi-ated cytotoxicity (ADCC) 96

Antigens 94, 98incomplete 100presentation 96, 98thymus-dependent (TD) 98thymus-independent (TI) 98

Antihemophilic factors 102Antiovulatory effect 305α2-Antiplasmin 104Antiport, definition 26Antipyrine 168Antithrombin 104Antrum, stomach 242α1-Antitrypsin 104Anulospiral endings 318Anuria 164Anus 266Aorta 190

blood flow velocity 192flow rate 193 Apressure 192, 206

influence on heart functions206

sensors 216valves 192

APC (antigen-presenting cells)96, 97 B, 98

Aphasia 376Apnea 108, 132Apolipoproteins 92, 256Apomorphine 240Apoptosis 98, 274, 302Apotransferrin 90, 92Apparatus, juxtaglomerular 174,

186Aprotinin 105 CAQP AquaporinsAquaporins 24, 166, 176Aqueous humor 350Arachidonic acid 270, 278Arachnoid villi 312ARAS (ascending reticular acti-

vating system) 324, 334, 338ff.Archeocerebellum 328Area prostrema, chemosensors

240Areflexia 322, 330ARF (ADP-ribosylation factor) 30Arginine 176, 228, 260, 284, 286

glucagon secretion 286intestinal absorption 260insulin release 284

Aromatase 302, 308Arousal activity 334Arrhenius 40Arrhythmia 220ff

absolute 202Arrestin 356Arsenic (As) 228Arteries ( also artery) 188 ff.,

190arcuate 150bronchial 188compliance 190

Arteries (cont.)coronary, myocardial perfusion

188interlobular 150pressure 208umbilical 222

Arteriole 188 ff.afferent 186efferent 186

Arteriosclerosis 210, 212, 304coronary artery 212hypertension 218

Artery ( also arteries), carotid,pressure sensors 216interlobular 150pulmonary 122

pressure 122fetus 221 B

Ascending reticular activatingsystem (ARAS) 324, 334

Ascites 210Ascorbate vitamin CAspartate 176, 260

intestinal absorption 260receptor types 55 Fsecond messenger 55 F

Aspirin 104, 270, 320Associative cortex 326, 331, 340Asthma 100, 118Astigmatism 352Astrocytes 344Astrup method 146at, conversion into SI unit 380AT I receptor 186AT II (Angiotensin II) 158, 170,

184, 186, 214receptor 186

Ataxia 330Atelectasis 118Atenonol 87 BAtherosclerosis Arteriosclero-

sisatm, conversion into SI unit 380Atmosphere, physical, 380

technical, 380Atomic mass 380ATP 41, 64, 72, 86, 230

control of K channels 284coronary vasodilatation 212cotransmitter 84creatine phosphate 230free enthalpy 41gain, glucose 73 Bneurotransmitter 86production 12

aerobic 41, 72anaerobic 72

supply of energy, muscle 72synthesis 12transport, active 26tubular epithelium 154

ATPase ( also Na-K-ATPase,Ca2-ATPase) 26, 58, 72, 84


402

ATPS (Ambient temperaturepressure H2O-saturated) 112

ATP-synthetase 17Atrial fibrillation 202

flutter 202septal defect 222tachycardia 202

Atriopeptin (ANF, ANP) 152, 162,172 184, 220aldosterone secretion 184receptor 280

Atrioventricular (AV) block 162,202node 194, 196valves 192

Atrophy, compensatory 274Atropine 82

transport, tubular 160Attention 328, 340

automated 340EEG 334selective 340

Atto- (submultiple of a unit) 379Audiometer 372Auditory canal 370

pathway 374threshold 345

Auerbach plexus (myentericplexus) 246

Autoantibody 100TSH receptor 290

Autogenous inhibition 318Autoimmune disease 94Automaticity, heart 194Autonomic nervous system (ANS)

78ff., 196, 214ff., 236, 268, 332Autophagia 12Autophagic vacuole 12Autophagosomes 12Autophosphorylation, receptor

tyrosine kinase 280Autoreceptor 86

presynaptic 52, 82, 146Autoregulation 4, 214

coronary 212gastrointestinal 234renal 150

Auxotonic contraction 66AV atrioventricularavDO2 (arterial venous O2 differ-

ence) 106, 107 AaVF (ECG leads) 198aVL (ECG leads) 198Avogadro’s constant (NA) 20, 380aVR (ECG leads) 198Axolemma 42Axon 42

capacitive flow of charge 48conduction velocity 48, 49 Cdiameter 48hillock 42membrane capacity 48

Axon (cont.)myelin sheath 42nodes of Ranvier 42reflexes 216saltatory conduction 48

Axonal transport 42, 282

B

B7 protein 98B cells, islets of Langerhans 284

lymphocytes 94, 98B chain, insulin 284B lymphocytes 94, 98Bacteria, defense 94ff., 244

intestinal 234, 242, 252, 266lysis 94

Bainbridge reflex 218Balance, body 330, 348

glomerulo-tubular 166Bar (unit) 380Barbiturates, tubular secretion

160Barium contrast medium 266Barotrauma 134, 110Barrier, blood–brain 18, 232, 240,

312, 332blood-CSF 18, 312

Basal body temperature 300Basal ganglia 312, 326

labyrinth of tubule cells 154metabolic rate 228

Base, DNA 8excess 142

measurement 146triplet, mRNA 8units, SI system

Basilar membrane 370, 372Basket cells 330Basolateral membrane, tubule

cell 162Basophilic granulocytes 100Bathorhodopsin 354Bayliss effect 214BDGF (brain-derived growth fac-

tor) 344Beat tone 368Behavior, defensive 332

nutritive 332programmed, hypothalamus

332reproductive 332thermoregulation 226, 332

BEI iodineBel 345Beriberi 228Bicarbonate HCO3

–

Bicycle ergometry 76Bilayer of membranes 14Bile 234, 250 ff., 258, 262

acid bile salts

Bile (cont.)bilirubin excretion 252canaliculi 250components 250ductules 250excretory function 250formation 250hepatic 250salts 160, 248, 250, 254, 258

absorption, terminal ileum254

body pool 250carrier 250conjugated 250, 254enterohepatic circulation

254function 254primary 250secondary 250synthesis 250

steroid hormone excretion 296Bilirubin 250, 252

direct 252diglucuronide 252excretion 252indirect 252

Biliverdin 252Binary digit 314Biologic clock 226, 336Biotin, intestinal absorption 262Biotransformation 234, 252Bipolar cells, retina 350Birth 94, 306, 222

circulation during 2222,3-Bisphosphoglycerate (2,3

BPG) 128, 138Bit 314Bitemporal hemianopia 364Bitter sensors 344Bladder, urinary 70, 79ff., 148

control 79ff., 310Bleeding 220

time 102Blind spot, eye 354, 364Blindness 350Blinking 350Blood 88ff.

brain barrier 18, 232, 240, 282,312, 332

cells 88clotting 102

activation 102, 104endogenous 102exogenous 104

coagulation disorders 228estrogen effects 304factors 102

composition 88CSF barrier 18, 126, 312fibrinolysis 102

Blood flow 122, 214, 234brain, control 214


403

Blood flow (cont.)central regulation 216coronaries 212, 214gastrointestinal 234lungs 122, 188muscle 216properties 92rate 190regulation, neuronal 216renal 150skin 214, 216, 226velocity 92, 190, 192

vessel segments 191 Afunction 88ff.glucose 284, 286groups 100HCO3

– concentration 142, 146hormone transport 270lipids 258loss 90, 175, 220pH 138

puffer 138, 144normal range 142measurement 146

pressure 74, 86, 186, 190, 204,208, 214, 216arterial 208

amplitude 208angiotensin II effect 186fetal 222mean 190, 191 A, 208measurement 208normal range 208physical work 74regulation 218

renin-angiotensin sys-tem 186

salt deficit 172sensors 216shock 220

control 216, 218diastolic 208pulmonary 122, 208sensors 216systolic 192, 208venous 206

sugar 284ff.testis barrier 308transfusion 100vessels 190, 214ff.

autoregulation 214chemosensors 214cross-sectional area 191 Adiameter 191 Afunction 190ff.holding capacity 191 Anervous control 216precapillary sphincter 190skin 226wall tension 190

viscosity 92, 190high altitudes 136

Blood flow (cont.)volume 88, 184, 188, 190, 208

central 206determination 168distribution 189 Aendurance athletes 77 Cmeasurement 168sensors 216total 188

B-lymphocytes 94, 98BMAL1 336BMI (body mass index) 232BMR (basal metabolic rate) 228Body fluids 92, 168

compartments 168measurement 168

homeostasis 168osmolality 170

mass index (BMI) 232plethysmography 114temperature 132, 224, 226,

300, 332, 381, 387 Ccircadian variation 226,

387 Cmeasurement 226menstrual cycle 300pressure saturated (BTPS)

112respiration 132set point 226

water body fluidsweight 232

regulatory mechanism 232,282

Bohr effect 128equation, dead space 114, 115 A

Boiling point, water 381Bomb calorimeter 230Bone 292, 294

break down 292calcitonin effect 294calcitriol effect 294conduction, sound 370estrogen effects 304growth 304marrow 88, 90, 94

Fe homeostasis 90megakaryocytes 102preprocessed precursor cells

94metabolism 292mineralization 294PTH effect 292

Botulinum toxin 56Bowman’s capsule 148Bradycardia, sinus 202Bradykinesia 328Bradykinin 186, 210, 216, 271,

320coronary vasodilatation 212salivary glands 238second messenger 278

Bradypnea 108Brain 312ff.

anatomy 312blood flow 188

regulation 214cortex

afferents 326area 1 311 E, 326, 327 Carea 2 311 E, 326, 327 Carea 3 311 E, 326, 327 Carea 4 311 E, 326, 327 Carea 5 311 E, 326, 327 Carea 6 331 E, 326, 327 Carea 7 311 E, 326, 327 Carea 22 311 E, 376area 44 311 E, 376area 45 311 E, 376area MI 326, 327 Carea PM 326, 327 Carea S1 320, 324, 325 Aarea S2 320, 325 Aarea SMA 326, 327 Casssociation areas 330, 340auditory 374Brodman’s areas 313 Ecolumns 334corticocortical signal loops

326cortical afferents 326

efferents 326ultrastructure 334

motor 326, 330motosensory 376neuronal circuitry 334orbitofrontal area 346organisation 334potentials 334prefrontal association 326premotor area (PMA) 326prepiriform 346primary motor area (MI) 326pyramidal cells 334scarring 344sensory association 326

input 324supplementory motor area

(SMA) 326death, diagnosis 334derived growth factor (BDGF)

344glucose deficit 244glutamate, transmitter 340hemisphere, dominant 342metabolism 284nerve cells 344, 346, 365stem ( also medulla oblong-

ata, pons, and midbrain) 312,320motor centers 326, 330

survival time, anoxia 130visual areas 330, 360, 362, 364


404

Breathing capacity, maximum(MBC) 118flat 120gas ( also O2 and CO2) 106mechanics 108

Breast 304, 305development 306

estrogen effect 304progesterone effect 305prolactin effect 305

enlargement 306feeding 305iodine 290

Brightness channel, visual path-ways 362

Bristle cell, olfactory bulb 346Broca’s area 376Brodman’s map 312Bronchi 376

epithelium 110innervation 79ff.

Bronchial mucus 110tree 188

Bronchitis 118Brown fat 226, 290Brown–Sequard syndrom 324Brunner’s glands 246Brush border 9f., 154, 158

intestinal mucosa 246renal tubule 154stomach, parietal cells 244

BSC (bumetanide-sensitive co-transporter) 162NH4

reabsorption 178BSEP (bile salt export pump) 250,

252BTPS (body temperature pressure

saturated) 112α-BTX (α-bungarotoxin) 56Buffer 124, 138, 140, 142, 144,

384f.base 140

blood 138concentration 138, 142total 146

capacity 138, 140closed system 140curve 386 Bhemoglobin 124, 128non-bicarbonate 126, 140, 144open system 140titration curve 386

Bulb, ocular 350Bumetanide 174Bundle of His 194Bundle-branch 202

block 202α-bungarotoxin (α-BTX) 56Bunsen solubility coefficient 126Bunte glass burette 114Burning 220

Butanol-extractable iodine (BEI)290

Byte 314

C

c (submultiple of a unit) 373C17/C20-lyase 302C cells, thyroid gland 294C, conversion to F 381Ca2 ( also Calcium) 36, 228,

264absorption, intestine 264, 280,

292, 294antagonists 196ATPase 17 A, 17 B2, 26, 36, 180,

294heart 196muscle 64renal 180

balance 292calmodulin-dependent protein

kinase II 36, 50cell regulation 36channels 36, 62, 180, 354

activation 278-adrenoceptors 84hair cells 348heart muscle 63 B3, 65 D,

196inhibition 84, 278muscle 62photosensors 354regulation 36renal 180ryanodine-sensitive 196voltage-gated 196

clotting process 102complexed 292concentration 50

cytosolic 36, 66, 238adrenergic transmission

84electromechanical coupling 62,

196epinephrine 87 B

exocytosis 30extracellular 36, 46heart 196intracellular 36, 278

muscle 63Bsmooth 70, 71Bnorepinephrine 87 Boscillations 36photosensors 356, 358

muscle fibers 62, 64, 196neurons 340, 344serum 292

conductance, GABAB receptors322

daily requirement 228, 292

Ca2 (cont.)darkness-induced 356deficiency 292equilibrium potential 44excretion 180, 292exocytosis 30fat absorption 254fetal 292free 180, 292hormone release 282intake 292intestinal absorption 264, 292,

294intracellular stores 36ionized 180, 292light sensors 358metabolism 180, 292milk 292muscle contraction 60ff/3 Na antiport 36plasma 180, 292pregnancy 292protein bound 180, 290, 292,

294reabsorption, renal 156, 180

paracellular 174renal excretion 180saliva 238sensors 36, 294

kidney 180serum 292smooth muscle 70solubility 292store, intracellular 10,36

IP3 278myocard 196skeletal muscle 60

third messenger 278trigger effect 62urine 292, 180

CaBP (calcium-binding protein)264, 280, 294

Cabrera circle (ECG) 200Caffeine 278Caisson disease 134Cajal cells 242, 246Cajal’s horizontal cells, retina

350, 360cal (calorie), unit 380Calcidiol (25-OH-cholecalciferol)

158, 294Calciol (= cholecalciferol =

Vitamin D) 262, 294Calcitonin 36, 37 C2, 276, 288,

292, 294gene-related peptide (CGRP)

216, 236, 308, 320Calcitriol (1,25-(OH)2 -cholecal-

ciferol, D-hormone) 158, 264,270, 280, 292 f., 294deficiency 292nuclear receptor 280


405

Calcitriol (cont.)PTH effect on formation 292

Calcium also Ca2

Calcium-binding protein (CaBP)264, 280, 294

Calcium oxalate, urinary stones180

Calcium phosphate, solubilityproduct 292

urinary stones 180Caldesmon 70Calmodulin 36, 278, 280, 340

smooth muscle 70photo sensors 356

Calmodulin-dependent proteinkinase II 36, 50neurons 340

Caloric equivalent 230value, physical 230

Calorie 230conversion into SI unit 380

Calorimetry 230cAMP AMP, cyclicCanaliculi 250

bile 250lachrymal 350parietal cells 244

Canals, semicircular 348Can sugar saccharose 260Capacitation of sperm 304, 310Capacitive current, membrane

48Capacity, buffering 140

electric, nerve 48Capillaries 190

blood pressure in 150, 211 Blung 210

characteristics 190diffusion processes 210exchange processes 210, 383filtration 210fluid exchanges 210glomerular 150peritubular 150, 151 A, 166permeability 210, 383pulmonary 106, 122reabsorption 210

Capsaicin sensors 316, 320Carbamate, CO2 transport in

blood 124Carbohydrate 228, 230, 248, 260,

284, 298absorption, intestinal 260caloric equivalent 230digestion 260

pancreatic enzymes 248energy substrate 230metabolism 284

cortisol effect 298nutrition 228

Carbon dioxide CO2

monoxide (CO) 128

Carbonic anhydrase 124, 176, 238gastric 244inhibitors 142, 174, 350pancreas 248red blood cells 124renal 176salivary glands 238

γ-carboxylation 102Carboxylesterase 248, 254, 258Carboxypeptidase 260Cardia 242Cardiac ( also heart)

arrest 202arrhythmias 182, 202cycle 192failure 206index 188muscle 68output (CO) 70, 74, 122, 136,

188, 190, 206, 208, 220, 222fetus 222

paralyis 200valves 192work 204

Carnosine 158Carrier 22

affinity to 28free fatty acids 254liver cells 252passive 28transport 158

CART (cocaine andamphetamine-regulated tran-script) 232

Cartilage 282Catabolism, cortisol 298Catalase 14, 96Cataract 352, 364Catecholamines 84, 270, 276

receptor types 55 FCatechol-O-methyltransferase

(COMT) 86Cathode 50cBAT (canalicular bile acid trans-

porter) 250CBG (cortisol binding-globulin =

transcortin) 298, 305C cells, parafollicular 36, 288CCK CholecystokininCD4 protein 98CD8 protein 98CD28 protein 98CD40 ligand 98CD40 protein 98CD45 receptor 280CD95 protein (= Fas) 98Cecum 234, 266Cell(s) 8 ff.

antigen-presenting (APC) 98body 42chief 242dendritic 96dedifferentiation 274

Cell(s) (cont.)differentiation 274division 8excitable 42expansion 170fat 256ganglion, retina 350, 364granular 328granulosa 302killer 96, 98Leydig, interstitial 308mast 100, 258membrane 2, 8, 14

function 2, 14ion conductance 32proteins 14structure 14permeability 2

migration 30, 58neuroendocrine 268nuclear pores 10nucleus 8, 290

structure and function 8ff.organelles 8f.pacemaker 246parietal 242, 244principal (chief) 162, 182replacement 246retina 364Sertoli 308shrinkage 170structure and function 8ff.T-helper 98

Cellulose 228, 266Celsius, conversion to F 381Centi- (submultiple of a unit)

379Central blood volume 206

canal 312chemosensors 126nervous system (CNS) 305,

312 ff.anatomy 312autonomic centers 78

venous pressure 188, 192, 206shock 220

Centralization, circulation 220Centrosome 14Cerebellum 312, 324, 326, 328 ff.,

330, 348, 366, 376eye movement 366lesions 330nystagmus 366speech 376

Cerebrosides 14Cerebrospinal fluid (CSF) 126,

144, 168, 312CO2 126, 144pH 126, 144

Cerebral cortex 312function, glucocorticoid effect

298


406

Ceruloplasmin, iron oxidation 90Cervix uteri 300, 304

menstrual cycle 300os 300, 305progesterone effects 305

cGMP GMP, cycliccGMP phosphodiesterase, retina

354CGRP (calcitonin gene-related

peptide) 216, 236, 308, 320gallbladder 250second messenger 276stomach 244

Chamber, eye 350Channels, ion 34Chaperone protein 10Chemokines 94, 268, 276

receptors 94Chemosensors 142

area postrema 240central 126, 132, 144for glucose 284respiratory control 132small intestine 242

Chemotaxis 94, 310Chenodeoxycholic acid 250Chest 108Chest leads (ECG) 198Chiasma, optic 364Chief (principal) cells, kidney 162

stomach 242, 244Chinin, taste 344Chloramphenicol 252Chloride Cl-

CHO (cholesterol) 14, 114, 256,270, 296, 305

Cholagogue 250Cholates ( also bile salts) 250Cholecalciferol (calciol = Vitamin

D) 262, 294formation in skin 294

25-OH-cholecaliferol (calcidiol)158

1,25 (OH)2 -cholecalciferol (cal-citriol, D-hormone) 294

Cholecystokinin (CCK) 232, 236,242, 250cerebral cortex 334esophagus 240gallbladder 250pancreas secretion 248receptors

gallbladder 250hypothalamus 332pancreas 248stomach 244types 55 F

second messenger 55 F, 278stomach 244

Cholera toxin 264, 278Choleresis 250Cholesterol (CHO) 14, 114, 256,

270, 296, 305

Cholesterol (CHO) (cont.)bile 250crystals 250esters 254, 258

hydrolase 254LDL 256lipoproteins 256

feces 258LDL 256lipoproteins 258membranes 14micelles 250steroid hormone synthesis

296storage 257 Bsynthesis 258

Cholesterol-7α-hydroxylase 250Cholic acids (cholates) 250Choline 82, 160

acetyl transferase 82nerve terminals 82tubular transport 160

Cholinesterase 56inhibitors 56

Cholinoceptors 82antagonist 82heart 196ionotropic 56M-types, second messenger

276, 278nicotinergic 56salivary glands 238stomach 244types 55 F, 56

Chorda tympani 345 CChorionic gonadotropin, human

(HCG) 306Choroid plexus 312Christmas factor 102Chromium (Cr) 228, 230Chromatin 8Chromosomes 8

single set (haploid) 308Chronotropism, heart 196Chylomicron 256, 262

remnants 256, 258Chyme 234, 260

pH 242Chymotrypsin 248, 260Chymotrypsinogen 248Cilia, bronchial 58, 110

hair cells 348, 370Ciliary body 70

muscle 350process 350zonules 350

Circulation, blood 188ff., 214ff.autoregulation 214

Bayliss-effect 214hormonal 214myogenic effect 214neuronal 216

Circulation, blood (cont.)local metabolic effect 214sympathetic nervous sys-

tem 216birth 222centralisation, flow 216, 220control 214coronary 212fetal 222portal 234pulmonary 188, 190pulse wave velocity 192regulation 214, 216ff.resistances 187 A, 190, 208total peripheral resistance

208venous return 206

cholehepatic 250enterohepatic 250, 254

bile salts 254bilirubin 252

Circulatory “center” 216failure 218reflexes, homeostatic 218sensors 216shock 220

Circumventricular organs 282,312, 332

11-cis retinal 354Cisterns, endoplasmic reticulum

10Citrate 12, 102

complex former 180cycle 12, 73 B3inhibition of blood clotting

102renal excretion 176

Citric acid citrateCl- 384

absorption in intestine 264balance, body 172channels, lysosomes 14

tubular 162concentration, intracellular 44conductance, membrane 34, 44distribution, active/passive 34equilibrium potential 44excretion 162renal handling 156, 162secretion in intestine 264

in pancreas 248salivary glands 238

stomach, parietal cells 244Clarifying factor HeparinClathrin 14, 28Claudins 18Clearance factor (heparin) 258

esophagus 240renal 152

Cleft, synaptic 42, 56, 82Climacteric 300Climax 310


407

Climbing fibres, cerebellum 330Clitoris 310CLOCK 336Clock, biologic 226, 242, 336, 360Clonal selection 98Clonidine 84, 87 BClosed system, thermodynamics

41buffer 140

Clothing 226Clotting, blood ( also coagula-

tion) 102ff.disorders 228

cmH2O, conversion into SI unit380

cMOAT (canalicular multispecificorganic anion transporter) 252

CNS central nervous systemCO (carbon monoxide) 128

binding to hemoglobin 129 CCO also cardiac outputCO2 (carbon dioxide) 106, 120,

266binding, blood 124ff.buffer system 138concentration

blood 124ff.influence of O2 saturation

126cerebrospinal fluid 126, 144influence O2 saturation 126

chemosensors 134, 144chronic retention 132diffusion, tissue 130dissociation curve 126dissolved in plasma 124ff.distribution in blood 124elimination 106/HCO3

- buffer 138, 140Krogh’s diffusion coefficient

120large intestine 266partial pressure 124

alveolar 120diving 134

blood 126increased 144

chemical respiratorystimulant 132

chronical increase 132hyperventilation 120normal range 142regulation by respiration

140venous blood 120

plasma 124ff., 138, 144production 142, 230response curve 132solubility coefficient 126total 126transport, blood 124

α-γ-Coactivation 318, 322

Coagulation, disseminatedintravascular 104

Coated pits 28Coatomer 30Coatomer-coated vesicles 30Cobalamines (vitamin B 12) 90,

92, 228, 262absorption 262deficiencies 90, 262receptor 28storage 262transport proteins 262

Cobalt (Co) 228Cocaine and amphetamine-regu-

lated transcript (CART) 232Cochlea 370, 374Cochlear duct scala media

amplifier 372nucleus 374

Code, genetic 8Coding, neuronal signals 314Codogen 8Codon 10Coital capacity, testosterone 308Cold sensors 226, 316Colipase 248, 254Collaps, orthostatic 206Collagen 102, 103 ACollaterals, axon 42Collecting duct 148, 162, 166, 176Colliculus superior 328Colloid, thyroid 288Colloidal osmotic pressure 92, 384Colon 264, 266

H2O absorption 264K secretion 264

Color blindness 358, 362constancy 362opponency 360perception 362triangle 362vision 362

contrast 360Colors, additive mixture 362

complementary 362subtractive mixture 362

Comfort zone (ambient tempera-ture) 226, 228

Compensation, renal 144respiratory 142

Compensatory atrophy 274hypertrophy 274pause 202

Competitive inhibition 56Complement cascade 96

factors 94, 96Complementary colors 362Compliance

blood vessels 190, 208lung and thorax 116, 118

measurement 112COMT (catechol-O-methyl-

transferase) 86

Concentration, units 378f.Conception 310Conditioned reflexes 238, 244Conductance 46, 381

electrical 22for Cl- 44for K 44hydraulic 24ionic 32unit 381

Conduction, atrioventricular(ECG) 200deafness 370defects, heart 202heart 194, 196, 202heat 224nerve fibres 42, 50saltatory, nerve 48velocity, measurement 50

Conductivity conductanceCones 350, 354, 356, 362

adaptation 358classes 362density 354light absorption maximum 362

Conjugate eye movement 366Conjugation processes 160

with glucuronic acid in liver150, 252

with glutathione in liver 160,252

Connectin (= titin) 60, 66Connexin 16, 19 CConnexons 16Conn’s syndrome 184Consciousness 324, 338Consensual light response 365Consolidation, memory 340Consonants 376Constancy, of color 362

of shape 362of size 362

Constipation 266Contact phase, blood clotting 103

B2Contraceptives 302, 305Contractility, heart muscle 196Contraction, afterloaded 66

auxotonic 66isometric 64, 66isotonic 64, 66velocity, skeletal muscle 68

myocard 206Contracture 66Contrast, auditory pathway 374

enhancement 374of stimuli 314, 330retina 360simultanous 360successive 358, 360

Control circuit 4humoral 274


408

Control circuit (cont.)system 4

Controller 4Convection 24, 224Converting enzyme, angiotensin-

(ACE) 186Convergence of signals 364

response, eyes 366Cooperativity, positive, hemoglo-

bin 128Copper (Cu) 228Coprosterol 258Core sleep 336

temperature 224, 226Cornea 350, 352Corneal reflex 322, 364Corona radiata 310Coronary blood flow 212

insufficiency 212reserve 212

Corpus amygdaloideum 312, 332,340callosum 312geniculatum laterale 362, 364

mediale 374luteum 300, 302

pregnancy 306progesterone production 305

stomach 242Correlations 389Corresponding areas, retina 366Cortex, auditory 374

associative 328cerebellum 328cerebral 334, 312, 328frontal 332

Corticoids, albumin binding 270globulin binding 270, 305

Corticoliberin (= CRH) 232, 271,274, 276, 282, 298, 306birth 306cortisol secretion 298placenta 306receptors, hypothalamus 332second messenger 276secretion, interleukin effect

298Corticosterone 184

synthesis 296Corticotropin (ACTH) 271, 274,

282, 296, 298aldosterone synthesis 184cortisol synthesis 298receptors, hypothalamus 332second messenger 276releasing factor corti-

coliberinhormone corticoliberin

Corti’s tunnel 370Cortisol 92, 184, 258, 274, 282,

298binding-globulin (CBG) 298,

305

Cortisol (cont.)effect, permissive 298fight or flight 332hypothalamus 332precursors 298stress 298synthesis 298transport 298

Cortisone 298Cotransmitter 52, 84, 86, 328Cotransport, definition 26Costimulatory signal 98Coughing 132, 322, 376Coumarin 104Countercurrent exchange, heat

226kidney 164

system 164Countertransport 26Coupling, electromechanical 62COX (cyclooxygenase) 104, 264,

271CPPV (continuous positive pres-

sure ventilation) 110Creatine 72Creatine phosphate 72, 76, 230

muscle reserve 73 Bstandard free enthalpy 41

clearance, endogenous 152Cretinism 290CRF cortiboliberinCRH corticoliberinCrigler-Najjar syndrome 252Cristae, mitochondria 12Crista, ampulla 348Cross test, blood types 100Crypts, large intestine 266

small intestine 246, 264Crypts of Lieberkühn 246, 264CSF cerebrospinal fluidCupula 348Curare 56,110Current, alternating 50, 381

direct 50, 381endplate 56miniature endplate 56unit 381

Current-voltage curve 33 B3, 34CVP (central venous pressure)

192, 206Cyanide 130Cyanosis 110, 130Cyclic AMP AMP, cyclic

GMP GMP, cyclicCyclooxygenase (COX) 244, 271

inhibitors 104Cyclosporin A 98Cystic fibrosis 110, 248Cystine 158, 176Cystinuria 158, 260Cytochrome oxidase 130Cytochrome P450-epoxygenase

271

D

d (submultiple of a unit) 379da (multiple of a unit) 379DAG (Diacylglycerol) 36, 82, 84,

276, 278Dalton (Da), unit 380Dalton’s law 106Dark adaptation, eye 354, 358,

360receptive field 360

Darkness-induced Ca2 356Dead space, artificial respiration

110functional, respiration 114,

122, 134increase 120

functions 114snorkel breathing 134ventilation 106volume (VD) 114

Deafness 370f., 376Debré-Toni-Fanconi syndrome

158Deca- (multiple of a unit) 379D cells, islets of Langerhans 284,

286stomach 244

DCT (distal convoluted tubule)148

DCT1 (= Divalent cation trans-porter 1) 90

Deceleration, unit 380Deci- (submultiple of a unit) 379Decibel (dB), unit 368Decompression sickness 134Decurarinization 56Dedifferentiation, cells 274Defecation 266Defense mechanism 96 ff., 234,

332intestine 234

Defensins 96Defibrillation 202Deflation reflex 132Deglutition 240Degrees Celcius 381

Fahrenheit 3817-dehydrocholesterol 294

Cytokines 268, 270, 276cortisol 298receptors 280

Cytokinesis 58Cytolysis 96Cytoplasm 8Cytosin 8Cytosis 28, 58Cytoskeleton, migration 30Cytosol 8

ions 45 B, 93 C


409

Dehydroepiandrosterone (DHEA)297, 306, 308adrenal cortex 298sulfate (DHEA-S) 306

Deiodinase 288, 290Deiter’s nucleus 328, 330Delayed immune reaction 100Deletion, clonal 94Dendrites 42Deoxycholate 250Depth perception, visual 364Depolarization 46, 66

action potential 46permanent, muscle 56, 60smooth muscle 70

Derepression 8Dermatitis, allergy 100Dermographism 216Desensitization 52, 278, 320

smell sensors 346Desmin filaments 14Desoxycorticosterone 297Desoxyribonucleic acid DNADesoxyribose 8Detoxication processes 160Deuteranomaly 362Deuteranopia 362Dextrin, α-limit 260DHEA dehydroepian-

drosteroneDHPR (dihydropyridine receptor)

62, 63 B, 65 DDHT (5α-dihydrotestosterone)

308Diabetes insipidus 166, 220

mellitus 142, 158, 220, 232,286coma 220osmotic diuresis 174type II, obesity 232

Diacylglycerol (DAG) 36, 82, 84,276, 278

Diacylglycerol lipase 271, 278Diadochokinesia 330Diapedesis 94Diaphragm 108Diarrhea 138, 142, 173, 260, 264,

266acid–base balance 138lactase deficiency 260salt and water homeostasis

175 BDiastole, heart 192Diastolic depolarization 194Diathermy 50Dicarboxylates, tubular transport

158, 160Diencephalon 312Diet 228

induced thermogenesis (DIT)230

vegetarian 142

Differential threshold, sound,frequency 374

intensity 374optical 358smell 346taste 344

Differentiation, cells 274Diffusion 20, 210

capacity 22capillaries 210coefficient (D) 20

Krogh’s (K) 22conductance 22distance 20driving force 20, 22equilibrium 20faciliated 23, 158, 260Fick’s first law 20, 22, 120gas 22ions 22net 20non-ionic 22, 156, 178potential 22, 32, 44rate 20“simple” 20unidirectional 20

Digestion 234, 238, 254, 260carbohydrates 238, 260impaired 248lipids 254organs 234proteins 260

Digitalis 196Dihydropyridine receptor (DHPR)

62, 63 B, 65 Dheart 196

5α-Dihydrotestosteron (DHT)308synthesis 296testes 308

1,25-dihydroxycholecaliciferol calcitriol

Diiodotryrosin residues (DIT) 288Dilator muscle, pupil 350Dim-light vision 354Diopters (dpt) 352Dipeptidases 260Dipeptides 158, 260Diplopia 366Direct bilirubin 252Disaccharide, digestion 260Disinhibition 346

thalamus 328Dissociation constant 384f.Distal stomach 242

tubule 148, 162, 166, 180Distant hearing 374

vision 366DIT (diet-induced thermogene-

sis) 230DIT (diiodotyrosine residues) 288Diuresis 164, 174

Diuresis (cont.)osmotic 174, 178

influence on K excretion184

salt and water homeostasis175 B

Diuretics 174, 184, 220influence on Ca2 reabsorption

180K excretion 174, 184

osmotic 174tubular secretion of 156, 160,

174Diurnal rhythm 336Divalent cation tranporter

(= DCT1) 90Divalent metal transporter

(= DMT1) 90Diving 134

oxygen toxicity 136DMT1 (= Divalent metal trans-

porter) 90DNA (desoxyribonucleic acid) 8

double helix 8DNAses, pancreas 248Döderlein bacilli 304Dominance columns, ocular 364L-Dopa 84Dopamine 84, 270, 271, 276, 282,

305, 328cerebral cortex 334menstrual cycle 300neurons 332receptor, striatum 328second messenger 276synthesis 84transmitter 328

Dopamine--hydroxylase 84Dorsal root, spinal cord 324Double helix, DNA 8

vision 366Down regulation, hormon recep-

tors 30Na-phosphate symport car-

rier 180Drinking 170Driving “force” 20, 38

pressure difference 108Dromotropism, heart 196D (differential)-Sensor 314, 316,

318Dubin–Johnson syndrome 252Duchenne muscular dystrophy

60Duct, collecting 176Ductus arteriosus 222

patent 222venosus 222

Duodenum ( also intestine)236, 246, 260gastrin production 236GIP production 236secretin production 236


410

Dwarfism, T3/T4 deficiency 290Dynamic work, negative 74

positive 74Dyne, conversion into SI unit 380Dynein 58Dynorphin 86, 320Dysmetria 330Dyspnea 108Dystrophin 60

E

E (multiple of a unit) 379E1 estroneE2 estradiolE3 estriolEar 368, 370, 372, 374

drum 370in diving 134

Eavesdropping 374ECF extracellular fluidECL (enterochromaffin-like cells)

244ECG (electrocardiogram) 192,

198 ff.atrial depolarization 198cardiac cycle 192electrical axis 200electrolyte disturbances 200integral vector 198leads 198myocardial infarction 200ventricular depolarization 198

repolarisation 198Ectopic pacemaker, heart 202Edema 174, 210

causes 210extracellular 174, 210intracellular 174local 304pulmonary 118, 120, 122, 132,

144, 174, 210Edinger–Westphal nucleus 366EDHF (endothelium-derived

hyperpolarizing factor) 216EDTA (ethylen-

dinitrilotetraacetat), bloodclotting 102

EDV (end diastolic volume) 192,204

EEG (electroencephalogram) 33411,12-EET (Epoxyeicosatrienoate)

216, 271EGF (epidermal growth factor)

280Eicosanoids 216, 271, 274, 278Einthoven leads (ECG) 198, 200Ejaculate 310Ejaculation 310Ejaculatory center 310Ejection fraction 192

phase, heart 192, 204

Elastase 260Electrocardiogram ECGElectrochemical gradient 26

potential 32Electrodiffusion 22, 34Electroencephalogram EEGElectrolyte homeostasis 168ff.Electromotility, outer hair cells

372Electrophoresis 93 BElectrotonic transmission 48,

54 DEmbolisms 104

diving 134Eminence, median 282Emission, sperms 310Emissions, evoked otoacoustic

372Emotions 340

expression 332limbic system 332

Emphysema 114, 118Emptying rates, gastrointestinal

tract 235, 242Emulsification of fats 254Encoding, information 314End diastolic pressure 204

volume (EDV) 192, 204systolic volume (ESV) 192, 204,

222Endergonic reaction 38Endings, annulospiral 318Endocrine cells 270

gland 270growth 274

system 268ff.Endocytosis 12, 28, 90, 288

receptor-mediated 12kidney 158

thyroid gland 288transferrin 90

Endolymph 348, 370Endometrium 305Endopeptidases 244, 248, 260

gastric juice 244renal tubule 158

Endoplasmic reticulum 10, 12, 26Endorphin 282, 320Endosomes 12

receptors 28transcytosis 28

Endothel(ium) 102, 168exchange processes 210function 18heparin source 256lipoprotein lipase (LPL) 256,

258NO synthase 82

Endothelium-derived hyper-polarizing factor (EDHF) 216

Endothelin 214, 282second messenger 278

Endothermic reaction 38

Endplate current 56motor 56

blocking substances 56reversal potential 56

potential (EPP) 56Endurance limit 72Enema 266Energy, activating 39

basic daily 228chemical 230expenditure, total (TEE) 228homeostasis 232metabolism 38, 224, 230, 284

cortisol effect 298need 228production 38, 230reserves 284sources 228storage 232substrates 72, 228 ff., 256, 284turnover 38, 228, 230units 380

Enkephalin 52, 86, 236, 260, 328ENS (enteric nervous system)

236Enteroglucagon (= GLP-1) 284,

286Enterohepatic circulation 250,

252Enteropeptidase 248Enthalpy 38Entrainment, brainwaves 334Entropy 38Enuresis, nocturnal 338Environment, internal 2, 78, 268Enzyme, function 40Ependymal cells 344EpETrE (= Epoxyeicosatrienoates

EE) 271Epidermal growth factor (EGF)

280Epilepsy, EEG 334Epinephrine (= adrenalin) 84 ff.,

160, 196, 214, 258, 270, 276,284, 290adrenal medulla 86circulatory shock 220coronary vasodilatation 212defensive behavior 332heart 196influence on insulin release

284on K uptake 182

lipolysis 220metabolic effect 285 A, 287 Cpheochromocytoma 218production, cortisol influence

298receptor types adrenocep-

torssecond messengers

adrenoceptors


411

Epinephrine (= adrenalin) (cont.)synthesis 84tubular transport 160vasoactivity 214

Epiphysis (= pineal gland) 336Epiphysis (of bones), estrogens

304testosterone 308

Epithel, function 18Epithelium 168Epoxyeicosatrienoates (EpETrE =

EE) 27111,12-Epoxyeicosatrienoic acid

(11,12 EET) 216EPP (endplate potential) 56EPSP (excitatory postynaptic

potential) 52, 56, 82, 322cerebral cortex 334early 82late 82peptidergic 82

Eq (equivalent), unit 381Equilibrium organ 330, 348

nystagmus 366concentration 32constant (K) 40potential 32, 44

ions 45 BEquivalent, caloric 230

mass 381ER endoplasmic reticulumErection, genital organs 216, >310Erg, conversion into SI unit 380Ergocalciferol 294Ergometry 76Erogenous areas 310Erythroblasts 90Erythrocytes 88, 90

crenation 92effect of hypertonicity 88, 100,

124, 128fluidity 92life span 88maturation 88mean corpuscular hemoglobin

(MCH) 88concentration (MCHC)

88volume (MCV) 88

metabolism 284pH 126proliferation 88viscosity 92

Erythropoiesis 90cobalamin 90folic acid 90high altitude 136inefficient 90

Erythropoietin 88, 148, 220Escalator, cilial 110Esophagus 234, 240, 242

ECG leads 198

Esophagus (cont.)pleural pressure, measurement

108sphincter 240

Essential amino acids 228fatty acids 228

Estradiol (E2) 296, 300, 302, 304,308synthesis 296testis 308

Estriol (E3) 296, 302, 304, 306Estrogens 270, 296, 300, 302,

304, 306actions 304comparison 304degradation 304menstrual cycle 300oral therapy 304placenta 306synthesis 296, 304

Estrone (E1) 302, 304synthesis 296

ESV (end systolic volume) 192,204

Euler–Liljestrand mechanism Hypoxic vasoconstriction

Euphoria, diving 134Evans blue, indicator 168Evaporation of water, heat loss

224Exa- (multiple of a unit) 379Exchange carrier, Na/H 26f.,

162, 176f., 278Excitable cells 42, 44, 46Excitatory postsynaptic potential

(EPSP) 52, 56, 82, 322Excretion ( also kidney) 160,

176fractional 152

Exercise 72, 76, 107, 120, 284cardiac output 76, 74O2 uptake 74respiration 74

Exergonic reaction 38Exocrine glands 248Exocytosis 28f., 30, 50, 86, 288

epinephrine 86constitutive 30glucagon 286salivary enzymes 238thyroid glands 288

Exopeptidases 248Exothermic Reaction 38Expansion, clonal 94, 98Expectancy potential, cortical

326Expiration 108

maximum flow rate 118muscle 108, 132pressure difference, driving

force 108work 116

Expiratory curves, maximal 117

Expiratory curves, maximal (cont.)flow, maximum 118volume, forced 118

first second (FEV1) 118relative 118

Expired air 107 AExponent, calculation with 386 f.Export protein, synthesis 12External auditory canal 370

intercostal muscle 108Extracellular fluid (ECF) ( also

H2O) 34, 93 C, 148, 152, 168indicators 168ions 93 C

Extrafusal fibers, muscle 318Extrasystole 202Eye ( also visual, retina and

opt. . . ), accommodation 350,352adaptation to light 358blind spot 354color vision 362dark adaptation 362far point 350focal lenght 352

point 352intraocular pressure 352light rays, physics 352movements 366muscles, external 366near point 350nodal point 350optical axis 352photochemistry 354postural motor control 330reflex movements 348refraction 352structure 350

Eyelids 365

F

F (Faraday constant) 22, 32 F(fluorine) 228

f (submultiple of a unit) 379F, conversion to C 381Facilitated diffusion 158Fåhraeus–Lindqvist effect 92Fahrenheit, conversion 381Fallopian tube 310Falsetto 352Fanconi–Debré-Toni syndrome

158Faraday constant (F) 22, 32Far point, vision 350, 352Farsightedness 352Fas (= CD95) 98

ligand 98Fascicular zone, adrenal cortex

296Fasting 284

T3 synthesis 290


412

Fat 230, 254, 258, 284absorption, intestine 254brown 226, 290caloric equivalent 230cells 258chemical structure 229 Bdaily intake 254depots 232, 284digestion 238, 254

phases 255 Bemulsification 242, 254energy substrate 230metabolism, insulin 286

Fatigue 72, 76Fat-soluble vitamins 254, 262Fattened animals 286Fatty acids 212, 254, 256, 264,

284, 286cyclooxygenase 271essential 228free (FFA) 284

carrier 254glucagon action 286lipoprotein lipase 256myocard metabolism 212sources 259 Dstorage 259 Dtarget sites 258transport in blood 256uptake in cells 256

supply of energy 72liver 256, 286

Fe (iron) 88, 90, 92, 128, 228, 264absorption in intestine 90carrier, intestinal mucosa 90deficiency 90functional 90hemoglobin 128

degradation 252intake 90, 228metabolism 90overload 90poisoning 90pool 90recycling 90storage 90transferrin 90transport, plasma 90

FE (fractional excretion) 152Feces 252, 264, 266Fechner’s law 360Feedback, control, hormones 274

negative 4, 274, 288, 302, 308,320TSH secretion 290

neuroendocrine 274positive 274, 302, 306tubuloglomerular (TGF) 174,

186Feet, conversion into SI unit 378Femto- (submultiple of a unit)

379

Ferrireductase 90Ferritin 90Ferroportin 1 (= IREG1) 90Fertility 308Fertilization 310Fetal circulation 222

zone, adrenal cortex 306Fetoplacental unit 306Fetus 222

O2 supply 222FEV1 (forced expiratory volume,

first second) 118Fever 100, 226, 290FF (filtration fraction) 24, 152,

395FGF (fibroblast growth factor)

280Fiber nerve, neuron, motor

neuron and muscleFibers, diet 266Fibrillation, atrial 202

ventricular 202Fibrin 102, 104Fibrinogen 102, 104Fibrinolysis 102, 104Fibrinopeptides 104Fibrin-stabilizing factor 102, 104Fibroblast 94

interferons, release 96migration 30

Fibroblast growth factor (FGF)280

Fibronectin 102Fick’s first law of diffusion 20,

120, 394Fick’s principle 106, 130, 395

kidney 150Field, receptive 316, 360

visual 364Fila olfactoria 346Filament sliding, smooth muscle

71 Bstriated muscle 62

Filling phase, heart 192pressure, receptors for, heart

216Filtration 24

capillaries 210coefficient 210equilibrium 150fraction, glomerular (FF) 24,

152, 395glomerular 148pressure, effective 210

kidney 152shock 220

First messenger hormonesFitzgerald factor 102Fixed acids 176Fletcher factor 102Flexion reflex 322Flexor muscles 330

withdrawal reflex 322

Floccunodular lobe 328Flow rate, blood 190

unit 380resistance, blood circulation

190velocity 190

unit 380Fluid compartments 168

measurement 168Fluid exchange, capillaries 210

extracellular 168intracellular 92, 168ounce, conversion into SI unit

380Fluidity of erythrocytes 92Fluorine (F) 228Flutter, atrial 202Folic acid 90, 228, 262

absorption, intestine 262daily requirement 262deficiencies 90storage 262

Follicle, dominant 300, 302, 305graafian 300primordial 300progesteron synthesis 305stimulating hormone

follitropinthyroid gland 288

Follicle-stimulating hormone-releasing hormone gonadoliberin

Follicular phase 300, 302Follitropin (FSH) 271, 300, 302,

308man 308menstrual cycle 300peak 302receptor density 302second messenger 276secretion, activin 308

DHT 308estrogens 302, 308inhibin 302, 308neuropeptid Y 302norepinephrine 302progesterone 302pulsatile 300testosterone 308

Food deprivation, energy reserve284

Foot, conversion into SI unit 378Foramen ovale 222

patent 222Force, unit 380Forced expiratory volume (FEV)

118vital capacity 118

Force–velocity curve, muscle 68Forgetfulness of words 376Formant 376Formatia reticularis 240, 324,

330, 346


413

Formatia reticularis (cont.)vomiting center 240

Formic acid, non-ionic diffusion22

Forskolin 278Fovea centralis, retina 350, 354,

364Fraction, respiration gas 106

units 382Fractional concentration frac-

tionexcretion (FE) 152, 154

Frank–Starling mechanism, heart68, 204, 206, 218, 220

FRC (functional residual capacity)112, 114, 116

Free enthalpy 38fatty acids 212, 254, 256water, urine 174

Freezing point, H2O 381Frequency, fundamental 368, 376

inotropism 196, 206unit 380

Fructose, intestinal absorption260renal reabsoption 158

FSF (fibrin-stabilizing factor) 102FSH follitropin

/LH-RH gonadoliberinFuel value, physiological 230Functional minimum, protein

intake 228residual capacity (FRC) 112,

114, 116Fundamental frequency, vowels

376Fundus, stomach 242Fungi, defense against 94Funicular myelosis 262Furosemide 174Fusimotor set 318

G

∆G (free enthalphy) 38G (multiple of a unit) 379g (membrane conductance) 32GABA (γ-aminobutyric acid) 34,

52, 286, 322, 328 f.cerebral cortex 334Gn-RH secretion 302receptors 52, 55 F, 322second messenger 55 F, 276

Galactorrhea 305Galactose, intestinal absorption

260renal reabsorption 158

Galanin 52, 86insulin secretion 284

Gall bladder 250stones 250

posthepatic jaundice 252

Gallon, conversion into SI unit380

Ganglia, vegetative 78, 83 Aneurotransmission 83 A

Ganglion cells, retina 350, 360,364

vestibular 348GAP (GTPase-activating protein)

356Gap junction 18, 58

astrocytes 344heart muscle 194regulation 37 Asmooth muscle 70uterus 306

Gas constant 20, 24, 32equation, alveolar 120, 136,

395ideal 112exchange 106, 120

impairment 120Gases 106, 266Gastric ( also stomach) acid

244function, glucocorticoid effect

298inhibitory peptide (obsolete

name for GIP) 242juice 240, 244, 260

pH 244reflux 240

mucosa, protection 244secretion 244ulcers 244

Gastrin 236, 242, 244esophagus 240insulin secretion 284second messenger 278stomach 236, 242

Gastrin-releasing peptide GRPGastrocolic reflex 266Gastrointestinal (GI) tract 78,

234 ff.bacteria 242, 266blood flow 188, 234hormones 236interdigestive phase 242neuronal and hormonal inte-

gration 236neurotransmitters 236passage time 234, 235 A

Gauer–Henry reflex 172GCAP (guanylyl cyclase-activat-

ing protein) 356G cells, antrum 244GDNF (glial cell line-derived neu-

rotropic factor) 344GDP (guanosine diphosphate)

276, 278transducin 354

Gene expression 8regulation 12

Genetic code 8Genital tract 216, 300, 308

female 300male 308

innervation 79ff.Germ cell 308Gestagens 305GFR glomerular filtrationGH (growth hormone) soma-

totropinGH-IH somastotatinGH-RH somatoliberinGI gastrointestinalGibbs–Donnan distribution 44Gibbs-Helmholtz equation 38Giga- (multiple of a unit) 379GIP (glucose-dependent

insulinotropic peptide) 236,242esophagus 240insulin seretion 284stomach 244

Glands, Brunner 246bulbo-urethral 311endocrine 270exocrine 248gastrointestinal 234ff., 246,

264parathyroid 238pineal 336salivary 216sublingual 206, 238submandibular 238sweat 224

Glasses 352Glaucoma 350Glia 344Glial cell line-derived neu-

rotropic factor (GDNF) 344Glioma 344Globulin 92

cortisol-binding 298testosterone-binding 309thyroxin-binding 290

Globus pallidus 312Glomera aortica 132

carotica 132Glomerular filter 148

zone, adrenal cortex 296, 298Glomeruli olfactorii 346Glomerulotubular balance 166Glomerulus, renal 148

filtration 154, 156pressure 150rate (GFR) 152

GLP-1 (glucagon-like peptide =enteroglucagon) 284, 286

Glucagon 232, 258, 274, 276, 284,286, 290actions 283 A, 286, 287 Cgluconeogenesis 286influence on insulin release

284


414

Glucagon (cont.)lipolysis 258second messenger 276secretion 286

Glucagon-like peptide (GLP-1)232, 284, 286

Glucocorticoids ( also cortisol)298receptors 10, 298synthesis 296, 298

Gluconeogenesis 72, 284, 286renal 148

Glucose 72, 154 ff., 174, 212, 230,260, 286aerobic oxidation 72, 284anaerobic degradation 142, 284blood 284caloric equivalent 230

value 230carriers 22, 26, 156, 158, 260,

264, 286chemosensors 284co-transport with Na 264deficiency 244energy substrate 72, 212glucagon secretion 286intestinal absorption 260, 264metabolism 72, 284, 298

influence of cyclic AMP 276muscle 72myocard 212osmotic diuresis 174plasma concentration 284

pregnancy 306regulation 274

production 72, 148, 284, 286renal reabsorption 156, 158storage 284uptake 86

Glucose-dependentinsulinotropic peptide (GIP)236

Glucose-6-phosphate 41, 72Glucosuria 158, 174, 286Glucuronic acid 160, 252, 296

conjugates, carrier 252steroid hormones 296

Glucuronides 156, 160Glucuronyl transferase 252GLUT (Glucose transporter) 23,

158, 260, 286GLUT2 158, 260GLUT4 286GLUT5 158, 260Glutamate 34, 52, 176, 260, 276

AMPA-receptors 55 F, 340cochlear transmitter 372

astrocytes 344dehydrogenase, renal 178genetic code 8intestinal absorption 260long-term potentiation 340

Glutamate (cont.)NH4

excretion 180NMDA receptor 52, 55 F, 340receptor types 55 Fsecond messenger 55 F, 276,

278taste quality 344transmitter function 328, 340

hair cells 348photosensors 356, 360

Glutaminase, kidney 178Glutamine 178

astrocytes 344formation, hepatic 180gluconeogenesis 284renal metabolism 178

Glutathione 158, 160, 288conjugates 252

secretion 160conjugation 160, 252S-transferase 252

Glycerol 284, 286Glycine 34, 52, 250, 257

conjugation 252receptor 52, 55 Fsecond messenger 55 Ftransmitter function 322

Glycocalyces 12, 14Glycogen 58, 72, 248, 284

metabolism 284phosphorylase 276skeletal muscle 58, 73 Bsynthase 276synthesis 276

Glycogenesis 284, 286Glycogenolysis 72, 85, 276, 284,

286STH 282

Glycolipids 14Glycolysis 142, 284

anaerobic 72muscle 72

Glycoprotein 276, 288hormones 276

Glycosylation 12GMP, cyclic 270, 276, 280, 354,

356photosensors 356

GnRH gonadoliberinGNRP (guanine nucleotide-

releasing protein) 30Goal-directed movement 330Goblet cells 246, 266Goiter 274, 288, 290Goldberger leads, ECG 198, 200Golgi apparatus 12, 288

cells, cerebellum 330tendon organs 318

Gonadoliberin (GnRH) 232, 271,282, 300, 302, 308menstrual cycle 300, 302

Gonadotropic hormone-releasinghormone gonadoliberin

Gonatropin-releasing hormone(GnRH) gonadoliberin

Gonads 296, 308G proteins 37 C1, 55 F, 84, 276,

278, 344adrenoceptors 84, 87 Bsubunits 276types, Gi 36, 82, 84, 276

Go 36, 278Golf 346Gq 82, 278Gs 84, 276, 346, 354Gt (transducin) 354

Graafian follicle 300Gradient, electrochemical 26, 32,

44Granular cells, cerebellum 330,

346olfactory bulb 346

Granular mesangial cells 186Granules, secretory 270Granulocytes 88, 104

basophilic 100, 256eosinophilic 94neutrophilic 30, 94

allergy 100immune defense 94migration 30

production 94Granulosa cells 302Granzyme B 98Graves’ diseases 290Grey matter, spinal cord 312GRH somatoliberinGrowth 284, 286, 290, 308, 332

factors 88, 234, 270, 280, 282,344nerval 344receptor types 270, 280

hormone somatotropinrelease-inhibiting hormone

(or factor) somatostatinreleasing factor (or hor-

mone) somatoliberininfluence of thyroid hormones

290insulin 286T3/T4 290

GRP (gastrin-releasing peptide)86, 232, 236, 242, 244second messenger 278stomach 244

GSC (glomerular sieving coeffi-cient) 154

GTP (guanosine triphosphate)276, 278, 280transducin 354

GTPase 278transducin 356

GTPase-activating protein (GAP)356

Guanine 8


415

Guanine nucleotide-releasingprotein (GNRP) 30

Guanosinediphosphate GDPmonophosphate, cyclic GMP,

cyclictriphosphate GTP

Guanosylmonophosphate GMP

Guanylyl cyclase-activating pro-tein (GCAP) 356

Guanylyl cyclase, coronary arter-ies 212

cytoplasmatic 280retina 356

α-gustducin 344Gut 236 ff.

absorption, amino acids 264Ca2 264Cl- 264

mechanisms 265 Dglucose 264Mg2 264Na 264

mechanisms 265 Dphosphate 264H2O 264

mechanism 265 Bbacteria 234, 252, 266Brunner’s glands 246calcitriol effect 294CCK production 236defecation 266gases 266motility 246structure 246

Gynecomastia 296Gyrus, angularis 376

cingulate 312, 332parahippocampal 332postcentral 324, 344

H

h (multiple of a unit) 379H zone, muscle 62H 138, 140, 142, 144, 244

buffering 138, 140, 142, 144chemosensors 132concentration, blood 138

normal range 142excretion 176

renal 142gradient 158Na antiport 26 ff., 161 C, 162,

176 ff.secretion, renal 176symport 158, 260uniporter (UCP) 224, 232

H-K-ATPase 26f., 28, 176, 184,244

collecting duct 176, 184

H-K-ATPase (cont.)colon 264

production 176renal excretion 176secretion, gastric 244

renal tubular 176H-ATPase 14, 26, 176

lysosomes 14H-iron cotransport 90H-peptide cotransport 26 ff.,

158, 260H-phosphate cotransport 17 B2H-pyruvate cotransport 17 B2H2 (hydrogen), large intestine

266Habituation 340Hageman factor 102Hagen–Poiseuille’s equation 190,

396Hair cells 58, 348

inner 370outer 370, 374

electromotility 372vestibular ganglion 348

follicle sensors 316Haldane effect 124, 126Hamburg shift 124Haptenes 100Haptoglobin 90Haustration 266Hay fever 100hBSEP (human bile salt export

pump) 250H (histamine) cells, stomach 244hCG (human chorionic

gonadotropin) 306hCL (human placental lactogen)

306HCl (hydrochloric acid) 142, 240

gastric 240, 244, 260production in metabolism 176

HCO3– (bicarbonate) 124, 126,

140, 146, 238, 264blood 142

concentration, actual 142, 146measurement 146

normal range 142, 146standard 142

measurement 146buffer system 138/Cl– antiport 124/CO2 buffer 140, 144CO2 transport, blood 124erythrocytes 124excretion 138, 142, 144, 174,

178high altitude 136

gastric mucosa 244intestinal absorption 264loss, diarrhea 264plasma 142, 146production, amino acid metab-

olism 178

HCO3– (bicarbonate) (cont.)

renal 145 B2renal reabsorption 156, 176saliva 238secretion 244, 248

bile ducts 250pancreas 248salivary glands 238

stomach 244titration curve 147

HCP1 (= Heme carrier protein 1)90

hCS (human chorionic soma-totropin) 306

HDL (high density lipoproteins)256, 258estrogen effect 304

Head’s reflex 132Head’s zones 320Hearing ( also sound) 368ff.

audibility limit 368auditory cortex 374

pathway 374, 376binaural 374cochlear amplification 372, 374direction 374

threshold 374loss 370, 372sensors 370ff.thresholds 368, 372, 374

Heart ( also cardiac and myo-card) 86, 188, 212action potential 194, 195 Aafterload 204, 206all-or-none contraction 68, 194arrhythmias 182atrial contraction 192

flutter 202fibrillation 202septum defect 222tachycardia 202

atrioventricular block 202node 194valves 192

automaticity 194autonomic nervous system 196beats heart ratebundle of His 194cholinergic transmission 83 Bconduction 194, 196, 202

disturbances 202system 194velocity 197 C

contractility 196, 206influences 196, 298

coronary blood flow 188, 192,214, 212vessels 212, 214

cycle 192diastolic time 192ejection fraction 192

phase 204


416

Heart (cont.)electric activity, action poten-

tial 58, 194arrhythmias 182, 202AV block 202AV rhythm 194bundle branch block 202cholinoceptors 82chronotropism 196dromotropism 196ECG 198ectopic 202electrolyte disturbances

200extrasystoles 202

impulse generation 194disturbances 202

inotropism 196, 206pacemaker 194

diastolic depolarization194

ectopic 194potential 194

reentry 196, 202spreading time 197 Cvulnerable phase 195 A,

202electrical axis 200end diastolic volume (EDV)

192, 204systolic volume (ESV) 192,

204influence of aortic pres-

sure 206energy sources 212exercise 74failure 210, 218, 220

cause of edema 210salt and water homeostasis

175 Efilling phase 204Frank–Starling mechanism 68frequency heart rateglycosides 196influence of Ca2 196inotropism 196, 206isovolumetric contraction 192,

204muscle 46, 58, 68, 194ff.

action potential 46, 59 Aadrenoceptors 216blood flow 188Ca2-ATPase 196Ca2 channels 196Ca2 concentration, cytosolic

196contraction 59 A

isovolumetric 192velocity 206

dihydro-pyridine receptors196

ECG 198

Heart (cont.)electromechanical coupling

196frequency inotropism 206impulse generation 194infarction 220

ECG 200influence of Ca2 196

contractility 196inotropism 196, 206ischemia, ECG 200isotonic peaks 205isovolumetric peaks

205metabolism 212Na/Ca2 exchange carrier

196Na-K-ATPase 196O2 supply 212tension-time index 212

mechanics 204metabolic activity 212O2 supply 212output, cardiac (CO) 74, 106,

122, 188, 190, 220fetus 222high altitude 136maximum 77 C

endurance, athlets 77 Cphysical work 74shock 220

power 204preload 204, 206pressure–volume diagram 68

relation 204work 204

Purkinje fibers 194rate 74, 136, 188, 196, 290

AV block 202blood pressure regulation 4,

220fetus 222high altitude 136influence of Ca2 influx 196maximum 77 C

endurance, athlet 77 Cnormal 188physical work 74shock 220T3/T4 effect 290

reentry 196reflexes 218resting pressure–volume curve

204semilunar valves 192sinoatrial node 194

rhythmicity 194threshold potential 194

sounds 192, 193 Astroke volume 188, 192, 204,

206maximum 77 C

Heart (cont.)endurance, athlet 77 C

measurement 106regulation 206training 76

ventricles, stretch sensors 216ventricular diastolic volume

192pressure 192

curve 193 Awork diagram 204

volume load 206weight, endurance athlet 77 Cwork 204

Heat 224, 230, 290countercurrent exchange 164flow, external 224

internal 224loss by evaporation of water

224of maintenance 74production 224, 230, 290

energy metabolism 230influence of thyroid hor-

mones 290sensors ( also warm sensors)

316unit 381

Heat shock proteins (HSP) 280Hecto- (multiple of a unit) 379Helicine arteries 310Helicotrema 370, 372Helium 114Helium dilution, measurement of

residual volume 114Helper cells, T- 98Hematocrit 88, 150, 168

blood viscosity 92high altitude 136

Hematopoiesis 88testosterone 308

Heme 88, 128Fe(II) 90oxygenase 90

Heme carrier protein 1 (= HCP1)90

Hemeralopia night blindnessHemochromatosis 90Hemoglobin 88, 90, 92, 124, 126,

128, 138, 140, 146, 252blood puffer 124, 128, 138, 140,

146carbamate 124concentration, blood 128degradation 252fetal 128synthesis 10, 90types 128

Hemolysis 88, 100, 252fetus 100prehepatic jaundice 252

Hemopexin 90


417

Hemophilia 104Hemoproteins 252Hemorrhage 220Hemorrhagic diatheses 104Hemosiderin 90Hemostasis 102 ff.Henderson–Hasselbalch equation

138, 139 A, 140, 146, 385, 395Henry-Gauer reflex 172, 220Heparin 104, 256Hepatic liverHepatocyte growth factor (HGF)

280Hepcidin 90Hephaestin 90Hering–Breuer reflex 132Hering’s opponent color theory

360Hertz, unit 368, 380HGF (hepatocyte growth factor)

280hGH chorionic growth hor-

moneHLA protein (human leukocyte

antigen) 96, 98High altitude 130, 132

respiration 136erythropoietin secretion 88hypoxic hypoxia 130

density lipoproteins (HDL) 258pressure system 188

Hippocampus 332, 340Hippurate, transcellular secre-

tion, renal 156Histamine 70, 100, 160, 210, 214,

216, 220, 236, 244, 271, 276,278allergy 100cerebral cortex 334coronary vasodilatation 212gastrointestinal tract 236gastric juice secretion 244influence on vessel permeabil-

ity 216receptors, types 55 F

H1 – 214, 278H2- 244, 276

second messenger 276shock 220tubular transport 160vasodilator 216

Histidine 176, 2283-HMG-CoA-reductase 258HMK (high-molecular-weight

kininogen) 102hNaDC-1 (human Na-dicar-

boxylate transporter) 160hNBC (human Na-bicarbonate

cotransporter) 162, 176H2O ( also extracellular fluid

and body fluid), balance 148,166, 168

H2O (cont.)disturbances 174, 175 E

clearance 164concentration 24daily intake 168, 264deficit 170, 182diffusion 24diuresis 164, 166, 174

maximum 166urea excretion 166

excess 172excretion, feces 264

renal kidney, excretionflow, osmotic 24free, urine 164, 174homeostasis 168intake 168intestinal absorption 264intoxication 172losses 170partial pressure 106permeability 210reabsorption 154, 164renal handling 166, 170regulation 170transport 24turnover 168

Hoffmann’s reflex 318Homeostasis 2, 4, 214, 268Homeothermy 224Horizontal cells, retina 350, 360Hormone(s) 236, 268, 270

abbreviations 270, 271adrenocorticotropic (= ACTH)

271aglandotropic 268, 282anabolic 308autocrine 268binding proteins 270catecholamines 276chemical structure 270down regulation 30endocrine 268, 270feedback mechanism 274femal sex 296, 300, 304follicle-stimulating (= FSH) 271gastrointestinal 236gland, atrophy 274

hypertrophy 274influence of hormonal medi-

cation 274glandotropic 268, 271, 282glycoprotein 276, 270hierarchy 270hypothalamic 270, 282lactogenic 271lipophilic 270male sex 308mammotropic 271medication 274α-melanocyte-stimulating hor-

mone (α-MSH) 271

Hormone(s) (cont.)menstrual cycle 302natriuretic 172nomenclature 271pancreatic 284paracrine 268, 270peptide 270, 276

placenta 306pregnancy 306principle functions 274receptors 268, 270, 276ff.second messengers 276ff.steroid 250, 270

placenta 306therapeutic administration 274thyroid 288

stimulating (TSH) 271tissue 270transport, blood 270types 270

Horopter 366Horse power (hp), metric, unit

3805-HPETE (= 5-hydroperoxyeico-

satetraenoate) 271hPL (human placental lactogen)

306H2SO4 (sulfuric acid) production

142, 176HSP (heat shock protein) 280H1(istamine)-receptor, second

messenger 55 F, 214, 278H2-receptor, second messenger

55 F, 276Hüfner number 128Human chorionic gonadotropin

(hCG, HCG) 306somatotropin (hCS) 306

leukocyte-associated antigen(HLA) 96

Na-bicarbonate cotransporter(hNBC) 162, 176

placental lactogen (hPL, HPL)306

Humidity, air 224, 226Humor, aqueous 350Hunger 142

edema 210energy reserves 284metabolic effect 285 A

Hydraulic filter, arteries 190Hydrocarbon continuum 254Hydrocephalus 312Hydrochloric acid HClHydrocortisone cortisolHydrogen ion H and pH

peroxide 94-Hydroxybutyrate 1421α-Hydroxylase, calcitriol syn-

thesis 29411-Hydroxylase

adrenal cortex 296


418

17-Hydroxylaseadrenal cortex 296

21-Hydroxylaseadrenal cortex 296

24-Hydroxylase, calcidiol 29417-Hydroxysteroid dehydro-

genase 30211-Hydroxysteroid oxidoreduc-

tase 184, 298Hyperalgesia 320Hyperaldosteronism 184, 240Hyperaminoaciduria 158Hyperbicarbonaturia, osmotic

diuresis 174Hypercalcemia 180, 200, 292, 294

ECG 200renal phosphate reabsorption

180Hypercapnia 144Hypercholesterolemia 258Hypercolumns, cerebral cortex

364Hyperemesis gravidarum 240Hyperemia, reactive 214Hyperglycemia 286

osmotic diuresis 174Hyperkalemia 62, 142, 182ff.,

200ECG 200

Hyperlipoproteinemia 258Hypermagnesiemia 180Hyperopia 352Hyperosmolality, extracellular

fluid 174Hyperoxia 136Hyperparathyroidism 294Hyperpnea 108Hyperpolarization, action poten-

tial 46afterpotential 46photo sensors 360

Hyperprolactinemia 305Hyperreflexia 322Hypersensitivity, delayed type

100immediate type 100

Hypertension 186, 208, 218renal 186, 218resistance 218

Hyperthermia, malignant 62Hyperthyreoidism 290Hypertrophy, compensatory 274Hyperventilation 108, 120, 136,

144, 292diving 134high altitude 136H2O losses 168non-respiratory acidosis 142salt and water homeostasis

175 EHypervitaminosis 228Hypervolemia 180

Hypocalcemia 180, 200, 292, 294ECG 200renal phosphate reabsorption

180Hypocapnia 144Hypoglycemia 86, 286

glucagon secretion 286Hypokalemia 174, 200, 264

diarrhea 264ECG 200vomiting 240

Hyponatremia 172Hypoparathyroidism 292, 294Hypophosphatemia 292, 294Hypopnea 108Hypotension 208

orthostatic 184Hypothalamus 78, 134, 170, 226,

232, 268, 270, 282, 302, 312,332, 364, 365afferents 332angiotensin II 186body weight 232function 268hormones, regulation 270, 282limbic system 346nuclei, arcuate 232

dorsomedial 232lateral 232paraventricular 226magnocellular 282ventromedial 226

osmosensors 170smell 346somatostatin secretion 288testosterone effect 308thermoregulation 224, 226TRH secretion 288

Hypothyreosis 290, 305Hypoventilation 108, 144Hypovitaminosis 228Hypovolemia 220

chronic vomiting 240shock 220

Hypoxia 130, 136, 142autoregulation 212brain 188fetus 222vasoconstriction 122, 214, 222

Hypoxic vasoconstriction, lung122

Hz, unit 380

I

I band, muscle 62ICAM (intercellular adhesion

molecule) 96ICF intracellular fluidICSH (= LH) lutropinIcterus 252

IDDM (insulin-dependent dia-betes mellitus) 286

IDL (intermediate-density lipo-proteins) 256, 258

IEL (intraepithelial lymphocytes)234

IgA (immunoglobulin A) 98, 234,238, 350

IgE (immunoglobulin E) 93, 98,100

IGF-1 (insulinlike growth factor)280, 282

IgG (immunoglobulin G) 93, 98IgM (immunoglobulin M) 93, 98,

100IL InterleukinIleum ( also intestine) 234, 246

bile salt reabsorption 250cobalamin absorption 262

Immune defense 94ff., 234, 246antigen presentation 96cellular 94, 234gastrointestinal 234, 246specific 98

cellular 96humoral 98

unspecific 94response, delayed 96secondary antigen contact

100Immunity 94

nonspecific 94specific 98

Immunization 100active 94passive 94

Immunoglobulins (Ig) 93 f., 94,98, 234class switching 98concentration, serum 93 DIgA 98, 234, 350

saliva 238IgE 93, 98, 100IgG 93, 98IgM 93, 98

AB0 system 100function 94placental barrier 92receptors 96infections 94

Immunologic tolerance, central94peripheral 98

Immunological memory 94Immunosuppression 98Impedance matching, middle-ear

370Implantation of fertilized ovum

300Impotence 305Inch, conversion into SI unit 378Incus 370


419

Indicator dillution technique 168Indifference point, hydrostatic

206Indirect bilirubin 252Indoor climate 226Induction, hormon-dependent

280Infarction, myocardial 200Inflammation 96, 100, 271, 320

neurogenic 320Information 314

encoding 314storage 340unit 314

Inhibin 302, 308FSH secretion 308menstrual cycle 300

Inhibition, antagonistic 322autogenic 318competitive 28, 56descending 320feed-forward 322lateral 314, 374

acoustic pathway 374postsynaptic 322presynaptic 322recurrent 318, 322

Inhibitory postsynaptic potential(IPSP) 52

Inner ear 370ff.Inositol-1,4,5-trisphosphate (IP3)

82, 84, 270, 276, 278Inotropism, heart muscle 196,

206Inspiration 108, 110, 206

pressure differences, drivingforce 108

work 116Inspiratory pressure, maximum

116Inspired air, composition 107 AInstinctive behavior, limbic sys-

tem 332Insulin 182, 232, 256 ff., 258, 270,

274ff., 276, 284ff, 286, 290anabolic effects 286deficiency, diabetes 286degradation 284effects 182, 285 A, 286, 287 Chalf-life 284K homeostasis 182lipoproteinlipase 256lipolysis 258overdose 220receptor 270, 280regulation of secretion 284secretion 284

amino acids 2842-adrenoceptors 84GIP 236inhibition 332

synthesis 284

Insulin-like growth factors(IGFs) 280, 282

Insulin receptor substrate-1(IRS-1) 280, 286

Integration of body functions268, 312

Intention tremor 330Intercalated cells, tubule 176, 184Intercellular adhesion molecule

(ICAM) 96Intercostal muscles 108Intercourse 310Interdigestive phase 242

motility 236Interferon (IFN) 95f.

IFNγ 95, 98Interleukin (IL) 94, 226, 234

IL1 298IL2 98, 298IL4 98IL5 98IL6 90, 98IL8 94

Intermediate filaments 14type, heart axis 200

Internal clock 242, 336heat flow 224, 226intercostal muscles 108milieu 268tissue respiration 130

Interneuron 318, 322, 326inhibitory 322stimulatory 322

Interstice 45 B, 92, 93 C, 168Interstitial cell-stimulating hor-

mone (ICSH) lutropinfluid 92, 93 C, 168

Internode region 48Intestinal absorption ( also

absorption) 246ff.amino acids 260Ca2 264, 294electrolytes 264glucose 260vitamins 262water 264

bacteria 266blood flow 234glands 246, 264lymph 234, 256movements 246neurons 246phase in gastric secretion 244

Intestine 234Cl- secretion 265defense mechanism 234lymphatics 234mucosal surface 246small 242

structure 246passage time 234

Intracellular fluid 168composition 92

Intracellular fluid (cont.)ions 93 C

Intraesophageal leads (ECG) 198Intrafusal fibers, muscle 318Intrapleural pressure 108Intrapulmonic pressure 108Intrathoracic pressure 108Intrinsic factor 262

cobalamin deficiency 90gastric juice 244

Intron 8Inulin, indicator for extracellular

space 168kidney, clearance 152, 154

5-iodinase 288Iodine/Iodide, butanol-

extractable (BEI) 288 ff.daily requirement 228, 290

Ion channels 32, 34control 34, 278

with ligands 34, 55 Fdiffusion 22open-probability 34, 46, 50pump (ATPases) 26

Ionic conductance 32, 381current 32, 381

Ions ( also individual ions) 381body fluid 93 Cconcentrations 45 B

IP3 (inositol-1,4,5-trisphophate)82, 276, 278IP3 receptor-associated cGMP

kinase substrate (IRAG) 280IPPV (intermittant positive pres-

sure ventilation) 110IPSP (inhibitory postsynaptic

potential) 52cerebral cortex 334peptidergic 82

IRAG (= IP3 receptor-associatedcGMP kinase substrate) 280

IREG1 (= Ferroportin 1) 90Iris 350Iron ( also Fe)Iron lung 110IRS-1 (insulin receptor substrate-

1) 280Ischemia 130, 200Islets of Langerhans 284Isoleucin 228Isomaltase 260Isophones 368Isoprenaline 84, 87 BIsotonic peak curve 204Isovolumetric contraction, heart

192relaxation, heart 192

work diagram 205peak curve 204

IP3 (inositol-1,4,5-trisphosphate)276, 278receptor-associated cGMP

kinase substrate 280


420

J

J (Joule), unit 300, 380JAM (junction adhesion

molecule) 18Jaundice 252Jejunum ( also intestine) 236,

246Jet lag 336JGA (juxtaglomerular apparatus)

174, 186Joint position, information on

318Joule (J), unit 300, 380J sensors 132Junctions, tight 154Juxtaglomerular apparatus (JGA)

174, 186

K

k (multiple of a unit) 379K (dissociation constant) 384f.K (Kelvin), unit 381K, absorption 182

balance 182in intestine 264adaptation 184balance 184

effect of aldosterone 184cellular uptake, influences on

182channels, activation 32ff.

adrenoceptors 84G-proteins 278

ATP-controlled 284collecting duct 182conductance, action poten-

tial 44, 46GABAB receptors 322hair cells 348pacemaker cells, heart 194resting potential 44

voltage-gated 46renal 162, 182

concentration, intracellular 26,44

contracture, skeletal muscle 66deficiency 174, 182diffusion 32distribution 286equilibrium potential 44excretion 174, 182, 184

diuretics 174influence 184

intake, high 182loss 264outflow, motor end plate 56renal handling 156, 182ff.role in autoregulation 214secretion, intestine 264

K, absorption (cont.)saliva 238tubule 174

stomach, parietal cells 244KM (Michaelis–Menten constant)

28Kallidin 216Kallikrein 104, 216

salivary gland 238Karyocytes 88Karyolymph 8kcal, conversion into SI unit 380Kelvin (K), unit 381Keratin filaments 14Kerckring’s fold 246α-Ketoglutarate, renal produc-

tion 178renal transport 160

Ketosis 28617-ketosteroids 296, 304, 308

synthesis 296Kidney ( also tubule and renal)

148ff., 294acid base balance 138, 176α1-adrenoceptors 216ADH receptors 166aldosterone effect 184anatomy 148, 149 A, Baquaporin (AQP) 166ATP 154atriopeptin effect 152autoregulation 150, 214

range of 151 Cbalance glomerulotubular 166blood flow 150, 188

measurement 150medullary 174

Ca2 excretion 180, 294sensors 180

calcitriol synthesis 294capillaries 148f., 151 A, 164,

186pressure 151 Bhypertension 218

circulation 150clearance 152, 395

ratio of 152water 164

concentration and dilution164, 395mechanism 164, 166

conjugation process 160connecting tubule 166cortex 164, 166countercurrent exchange 164diuresis 174, 178endopeptidase 158energy metabolism 150excretion

ammonia/ammonium 76,176

Ca2 180

Kidney (cont.)electrolytes 157 Dfractional (FE) 152f.H 142, 176

titratable acid 180HCO3

– 138, 144Mg2 180organic substances 157 D,

158, 160phosphate 178f.steroid hormones 296urobilinogen 252water 154, 157 D, 164

glucocorticoid effect 298extraction fraction 152filtration 148, 152

amount of a substances 158dissolved substances 154equilibrium 152fraction (FF) 152pressure, effective 152, 396

function 148ff.glomerular filtration rate (GFR)

150glucocorticoid effect 298

glomerulotubular balanceglomerulus 148 ff.glucocorticoid effect 298glutaminase 178glutamine 178H-K-ATPase 176, 183 B4H-ATPase 176H-excretion 142, 176H-secretion 176handling of amino acids 158

angiotensin 158Ca2 180, 294diuretics 156drugs 156glucose 158glucuronides 156glutathione 158H 144, 176HCO3

– 142, 176K 156, 182ff.lactate 158Na 156, 162, 172oxalate 158peptides 158phosphate 178, 180, 292,

294proteins 158urea 166uric acid 156, 158

inulin clearance 152, 154juxtaglomerular apparatus 186juxtamedullary nephrons 150K channels 162

homeostasis 182loop of Henle 164loss 174

Ca2-reabsorption 180


421

Kidney (cont.)Mg2 reabsorption 180Na transport 162water permeability 166

medulla 150medullary blood flow 166, 174metabolism 150, 284Mg2 sensors 180Na channels 174Na-K-ATPase 154, 156, 162

function 154nephron types 148, 166O2 consumption 150PAH clearance 150pH homeostasis 142, 176plasma flow 150potential, transepithelial 156,

162PTH effect 180reabsorption

Ca2 174, 292Cl– 162electrolytes 157 Dfractional 154D-glucose 158HCO3

– 176K 182Mg2 174Na 162

collecting duct 184driving force 156

organic substances 157 D,158

phosphate 180PTH effect 294

water 154, 164renal failure 142, 178

vitamin D 294renin 186secretion 156

K 174, 182organic substances 160

solvent drag 162structure 148tight junctions 154transport processes 154 ff., 155

B,Ctubuloglomerular feedback

(TGF) 174ultrafiltrate 154urea 166

Killer cells, natural 94, 96T-killer cells 98

Kilo- (multiple of a unit) 379Kilowatt hour (kWh), conversion

into SI unit 380Kinase cascades 276Kinesia 240Kinesin 42, 58, 62Kininogen 102, 216, 238

high-molecular-weight (HMK)102

salivary gland 238

Kinocilium 348Knee jerk reflex 318Kohlrausch’s fold 266Kohlrausch break 358Korotkow sounds 208Korsakoff syndrome 342Krebs cycle citrate cycleKrogh’s diffusion coefficient 22,

120, 394Krogh’s cylinder model 130Kupffer cells 96, 234kWh (kilowatt hour), unit 380

L

Labia minora, glands 310Labyrinth 370

basal, tubulus epithelium 154Labyrinth reflexes, tonic 330Lacrimal canaliculi 350

glands 350sac 350

Lactacidosis 72, 76Lactase 260Lactate 72, 73 B2, 74, 142, 176,

284concentration in plasma 76glugoneogenesis from 284muscle metabolism 72myocard metabolism 212physical work 76renal reabsorption 156, 158vagina 304

Lactation 294reflex 305

Lactic acid lactateLactogenesis 305, 306Lactose 260Lamellipodia 30L-amino acids amino acidsLandolt rings 355 ALangerhans cells 96Language 340, 342, 376Lanosterol 296Laplace’s law 118, 190, 204, 212,

396Large intestine 234, 266Larynx 376

testosterone 308Lateral geniculate body 362, 364

lemniscus 374signal flow, retina 360

Lateralization, sound 370Latency, hearing 374Law of mass actions 385Laxatives 264LCCS (limited capacity control

system) 340LCAT (lecithin cholesterol acyl

transferase) 256LDL (low density lipoproteins)

256, 258, 304

LDL (low density lipoproteins)(cont.)estrogen effect 304receptors 256, 258

L-dopa 84Learning 340Lecithin 14, 250, 254

bile 250cholesterol acyl transferase

(LCAT) 256Left axis deviation (heart) 200Lemniscus, medial 324

trigeminalis 324Length, units 378Lens 350, 352Leptin 232

receptors 232, 332Leucine 228

insulin release 284Leu-enkephalin 236Leukocytes 88

interferon secretion 96Leukotriene 270, 271

allergy 100second messenger 278

Lewis’s response 216Leydig cells 304, 308LFA 1 (lymphocyte function-

associated antigen 1) 98LH lutropinLHRH gonadoliberinLibido 308Lids 350Light, adaptation 356, 360

sensors 350stimuli 360wavelength 362

Light chain protein, myosin II 60Lignin 228, 266Limb leads (ECG) 198Limbic system 312, 332α-limit dextrin 248, 260Limited capacity control system

(LCCS) 340Linear velocity, unit 380Linoleic acid 228Lipase 248, 254, 258

acid 258gastric fundus 254hepatic 256in human milk 254lingual 254non-specific 254pancreatic 254saliva 238

Lipid membrane 14Lipids 254, 258

absorption 254digestion 254distribution 256storage 256synthesis 12, 13 F, 284


422

Lipogenesis 284Lipolysis 86, 224, 248, 258, 284,

286influence 258insulin effect 286STH effect282stimulation, thermoregulation

224Lipoproteinlipase (LPL) 256, 258

insulin effect 286thermoregulation 224

Lipoproteins 256 ff.receptors 28, 256

Lipostasis 232Lipoxygenase 271Liter, definition 378f.Lithocholate 250Liver 90, 160, 178, 234, 250, 252,

284acid–base homeostasis 144,

178bypass 234calcidiol synthesis 294coagulation factors, synthesis

102conjugation process 160damage, blood clotting 104excretory function 160, 250ff.fatty 256Fe homeostasis 90fetal blood cell formation 88formation of 7-dehydro-

cholesterol 294gluconeogenesis 284glutamine formation 178glycogenesis 284icterus 252jaundice 252metabolism 284steroid hormones, degradation

296urea production 178

Load, filtered 158Locus coeruleus 330Logarithms, calculations 386 f.Longitudinal tubules, muscle 60Long-term potentiation (LTP) 340Loop, cortico-thalamo-cortical

328diuretics 174, 180oculomotor 326, 328skeletomotor 328

Loop of Henle 148, 164, 166, 180Loudness 368, 376

level 368voice 376

Low density lipoproteins (LDL)258

Low pressure system 188LRH gonadoliberinLTH prolactinLTP (long-term potentiation) 340

Luminous intensity, unit 378Lumirhodopsin 354Lung ( also pulmonary) 106,

108, 110, 112acid base balance 138ff.alveolar contact time 141 Bblood flow 106, 122, 188

fetus 222, 221 Bbronchial, obstruction 120capacity, total (TCL) 112, 113 Acapillaries 106

blood pressure 122disease, obstructive 118

restrictive 118edema 118, 120, 122, 132, 144,

174, 210fetal 222function tests, dynamic 112,

118gas exchange 120ff.hypoxic vasoconstriction 122inflation 118iron 110, 111 A2O2 diffusion capacity 22opening pressure 118perfusion lung, blood

flow122stretch receptors 132surface tension 118total capacity (TCL) 112ventilation/perfusion ratio 122volumes 112ff.

measurement 112ff.Lung and thorax

compliance 116, 118pressure–volume relationship

116Luteal phase 300, 302Luteinization 302Luteinizing hormone (LH)

lutropinreleasing hormone (LTH)

gonadoliberinLuteotropic hormone (LTH)

prolactinLuteotropin (LTH) prolactinLutropin 271, 282, 296, 308

menstrual cycle 300peak 302receptor, cells of Leydig 308secretion, pulsatile 300

Lymph flow 210, 211 Bintestinal 234, 256nodes 88, 96vessels 246

Lymphocyte function-associatedantigen 1 (LFA 1) 98

Lymphocytes 88, 94B- 94, 98

activation 98clonal selection 98differentiation 98

clonal deletion 94

Lymphocytes (cont.)expansion 94selection 94

intraepithelial (IEL) 234naive 94T- 94

“armed” 94, 96CD4 98CD8 98cytotoxic cells 98clonal expansion 98

selection 98differenziation 98naive 96T helper cells 98TH1 cells 98TH2 cells 98T killer cells 94, 98, 234receptor 98

Lymphocytopoiesis 88Lymphokins, cortisol 298Lysine 176, 228, 260

intestinal absorption 260Lysis, bacterial 94Lysosomes 12, 14, 26f., 28, 288Lysozyme 94, 96, 234

renal rabsorption 158saliva 238tears 350

M

µ (submultiple of a unit) 379M (multiple of a unit) 379m (submultiple of a unit) 379M line, muscle 60α2-Macroglobulins 104Macrophages 30, 94, 96, 98, 226,

252activation 96break down of red blood cells

88hemoglobin degradation 252immune defense 94, 96iron metabolism 90migration 30respiratory tract 110

Macula densa 148, 174, 186Maculae 348Magnesium Mg2

Magnetoencephalography (MEG)334

Maintenance heat 74Major histocompatibility com-

plex (MHC) 96, 98Malabsorption, folic acid 90Maldigestion, enzyme deficit 248Malpighian bodies 148Malleus 370Maltase 260Maltose 248, 260


423

Maltotriose 248, 260Mammary glands 294Mammatropic hormone pro-

lactinManganese (Mn) 228Mannitol, osmotic diuresis 174Mannose-6-phosphate 12, 14Mannose-binding protein (MBP)

96MAO (monoamine oxidase) 86MAP kinase (mitogen-activated

protein kinase) 278Margination 94Masking, sound 368Masklike facial expression 328Mass, units 380Mass actions, law 385Mass concentration 382Mass movement, large intestine

266Mast cells 104, 258

allergy 100Maturation, influence of thyroid

hormones 290sexual 300, 308

Matrix, extracellular 14Maximal breathing capacity

(MBC) 118Maximum diastolic potential

(MDP) 194MBC (maximal breathing capac-

ity) 118MBP (mannose-binding protein)

96M cells, mucosal epithelium 234MCH (mean corpuscular

hemoglobin) 88 f., 89 CMCHC (mean corpuscular

hemoglobin concentration) 88,89 C

MCV (mean corpuscular volume)88, 89 C

MDR1 (multidrug resistance pro-tein 1) 252

MDR3 252Measles 94Mechano-electric transduction

(= MET) 372Mechanosensors, skin 316, 318Medial geniculate body 374Mediators 270Medications, bile excretion 250Medulla, adrenal 274

oblongata 132, 312, 324circulatory “center” 216rhythm generator, respira-

tion 132vomiting center 240

MEG (magnetoencephalography)334

Mega- (multiple of a unit) 379Megakaryocytes 88, 102

Meiosis 308Meiotic division, spermatocyte

308first, ovum 302second, ovum 310

Meissner’s corpuscles 316Meissner’s plexus (plexus sub-

mucous) 246α-Melanocortin (=α-MSH =

α-melanotropin) 232, 271, 282Melanocortin receptor (MC4

receptor) 232Melanocytes 282Melanocyte-stimulating hor-

mone melanotropinα-Melanocyte-stimulating hor-

mone (α-MSH) 232, 271, 282Melanopsin 336Melanotropin (α-MSH) 232, 271,

282release-inhibiting factor

melanostatinreleasing hormone

melanoliberinMelatonin 336

second messenger 276, 278Membrane

basolateral 162, 182capacity, nerve 48conductance 32

fractional 32electric properties 42, 52function 2permeability for K 46, 182

influence of cyclic AMP276

for Na 46, 56, 162postsynaptic 42, 50potential 32, 44, 48

photosensors 360renal tubule 156smooth muscle 70

presynaptic 42, 50proteins, glycosylation 12

synthesis 12structure 14transport 16 ff.

active 26f.carrier-mediated 22f.intracellular 16non-ionic 22paracellular 18passive 20potential, driving force 22,

32Memory 340

immunological 94knowledge 340loss 340motoric 328short-term 340, 374

Menaquinone (Vitamin K2) 262

Menarche 300Menopause 300, 304Menses 282, 300f.Menstrual cycle 226, 300, 302,

305body temperature 226, 300hormonal control 302interactions 302

Menstruation 282, 300f.Mercapturic acids 252Merkel’s cells 316Merosin 60Mesencephalon 312Mesentery 246Messenger, first ( also hor-

mones) 270, 276ribonucleic acid mRNAsecond 270, 276substances 268third 270

MET (= Mechano-electric trans-duction) 372

MET channels 372Metabolic alkalosis, 142

rate 228, 230basal (BMR) 228total 228

Metabolism, amino acids 158bone 176, 294carbohydrate 284, 298energy 72, 286glucose 284, 298heart 212iron 90lipids 256, 284muscle 256

Metarhodopsin I 354Metarhodopsin II 354, 358

phosphorylation 356Metastasization 30Met enkephalin 236Methan, intestine 266Methemoglobin (MetHb) 128

reductase 128Methionine 176, 228Methotrexate 2625-Methyltetrahydrofolic acid 262Methopyrapone 296Metopyrone 296Mg2 180, 264, 276

absorption, intestine 264inhibition of Ca2 channels, 50CNS 340excretion, renal 180plasma concentration 180renal reabsorption 156, 174,

180sensors, kidney 180

mGLU-receptors, secondmessenger 276, 278

MgSO4 250MHC (major histocompatibility

complexes) 96


424

MHC proteins 96, 98MI (cortex area) 326Micelle, bile 250

intestine 254, 262Michaelis constant 28Michaelis-Menten constant (KM)

28, 158, 389f., 394kinetics 28, 158, 389 f., 394renal glucose tranport 158

Micro- (submultiple of a unit)379

Microfilaments 14, 16Microglia 96, 344Micrography 328α1-Microglobulin, renal reab-

sorption 1582-Microglobulin, renal reabsorp-

tion 158Micron, conversion into SI unit

378Microtubules 14Micturition 79ff., 148Middle ear 370MIF melanostatinMigrating motor complex (MMC)

242Migrating wave 372Migration 30

phagocytes 94MIH melanostatinMile, conversion into SI unit 378Milk 254, 262, 292

Ca2 292ejection 282, 305fat 254human, lipase 254lactation reflex 305oxytocin 305production 305prolactin 305sugar (lactose) 260

Milli (submultiple of a unit) 379Mineralcorticoids ( also

aldosterone) 184, 298production 296

Minerals, intake 228intestinal absorption 264nutrition 228

Miniature endplate current 56,57 B2

Mini-pill 305Miosis 350, 364f.MIT (monoiodotyrosine residue)

288Mitochondria 12, 290

critical O2 pressure 130skeletal muscle 58, 63 Astructure and function 12T3/T4 effect 290thermal balance 224

Mitral cells, olfactory bulb 346valves 192

MLCK (myosin light chain kinase)36

MMC (migrating motor complex)242

mmHg, conversion into SI unit380

Mobilferrin 90Modification, posttranscriptional

10posttranslational 12, 270

Mol, unit 380f.Molality 380ff.Molarity 380ff.Molecular layer 328, 330

“weight”, unit 380f.Molybdenum (Mo) 2282-Monoacylglycerol 248, 254Monoamine oxidase (MAO) 86Monoaminergic pathways sys-

tem 332Monocytes 88, 94, 96Monoiodotyrosin residue (MIT)

288Mononuclear phagocytotic sys-

tem (MPS) 96Monosaccharides ( also glu-

cose) 260Monooxigenases 252Monosynaptic stretch reflex 318Morning sickness 240Morphine 320

tubular transport 160Moss fibre, cerebellum 330Motilin 242

esophagus 240interdigestive motility 236secretion 236

Motility, molecular basis 58Motion sickness 240Motivation, limbic system 332Motor activity 56ff., 318ff., 326

basal ganglia 326cerebellum 328 f.influence on circulation 74pyramidal tract 326voluntary motor function

326postural motor control 330

aphasia 376cortex 326 ff.end-plate 56function, control center 328

supportive 328neuron 42, 58

α- 322, 326γ- 318, 322

paralysis 324proteins 58, 62

system 326unit 58, 66

recruitment 58types 58

Mouth-to-mouth resuscitation110

MPS (mononuclear phagocytoticsystem) 96

MRF melanoliberinMRH melanoliberinmRNA (messenger ribonucleic

acid) 8MRP2 (multi-drug-resistance

protein type 2) 160, 252MSH also melanotropinα-MSH (α-melanocyte-stimulat-

ing hormone) 232, 271, 282Mucoviscidosis 248Mucus 110, 238, 246

bronchial 110cervical os 300intestine 244, 246, 266neck cells (MNC), stomach 242saliva 238stomach 244

Müller’s maneuver 116Multidrug resistance protein 1

(MDR1) 160, 2523 (MDR3) 252

Multi organ failure 220Muramidase lysozymeMuscarine 82Muscle(s) 42, 44, 46, 56ff., 58,

59 A, 256abdominal 108activity, heat production 226ATP 72afterloaded contraction 66bulbocavernosus 310cardiac 46, 194ff.ciliary 350contractile machinery 60ff.contraction 66

afterloaded 66, 204auxotonic 66ff.isometric 66isotonic 66role of Ca2 64

dilator 350energy supply 72, 256, 285extensibility 66

titin 68fatigue 76fiber 60 ff.force-velocity diagram 68hypertrophy 76inspiratory 108intercostal 108ischiocavernosus 310length-force curve 68length, regulation 318mechanical features 66metabolism 284middle ear 370multi-unit type 70myofibrils 60


425

Muscle(s) (cont.)O2 extraction 72pump 206puborectal 266reflexes 318relaxants 56respiratory 108, 132resting length 68

force 68tension curve 66

single-unit type 70short-term high performance

72skeletal 56 ff.smooth 70

action potential 59 Acaldesmon 70contraction 70M3-receptors 82

softening effect of ATP 64soreness 76spindle 318sphincter 350stapedius 370stiffness 76striated ( also skeletal

muscle, heart muscle) 59 ff.contraction, molecular

mechanism 62cycle 64

summation of excitation 66tension, regulation 318tensor tympani 370tone 66types of contractions 66weakness 56

Muscular dystrophies 60Myasthenia gravis 118Mycobacteria, immune defense

96Mydriasis 350Myelin 42, 48

sheath, nerve fibers 42, 48Myelopoiesis 88Myelosis, funicular 262Myenteric plexus 246Myocard heartMyocardial function 192ff.

infarction 200, 220metabolism 212O2 consumption 212oxygen supply 212

Myofibrils 60Myogenic tonus 70Myoglobin 58, 72, 90, 128Myometrium uterusMyopia 352Myosin 58, 60

light chain kinase (MLCK) 36smooth muscle 70

Myosin I 30Myosin II 58, 60

Myosin II (cont.)striated muscle 60ff.smooth muscle 70

Myotonia 62

N

n (submultiple of a unit) 379N (newton), unit 380N (nitrogen), balance 228N2 dissolved in plasma 134

role in diving 134toxicity 134

Na 56, 158, 162, 172, 184, 186,260, 384absorption in intestine 264antiport carrier 26 f.balance, effect of aldosterone

184bicarbonate cotransporter 3

(= NBC3) 176body content, total 172channels 46, 56, 174, 264, 354

activation 46collecting duct 162, 182conductance 46

action potential 46inactivation 46intestine 264kidney 162, 174photosensors 354resting potential 46voltage-gated, heart 194

Cl– symportcarrier 26concentration, cytosolic 26, 44co-transport 260distribution 93excretion, renal 162feces 264/H antiport carrier (= Na/H

exchanger, NHE) 26, 28, 162,176, 178, 248

kidney 176PKC (protein kinase C)

278stomach, parietal cells

244influx, motor end plate 56intake, hypertension 218renal reabsorption 156

handling 162retention 218saliva 238symport carrier 26 f.

amino acids 260bile salts 250Cl– 28, 162, 174, 238glucose 156 f., 260HCO3

– (hNBC) 162, 176intestine 264iodide (NIS) 288

Na (cont.)phosphate (NaPi) 180vitamins 262

transport 44, 162, 172, 268paracellular 238

tubular resorption 162Na-Ca2 antiport carrier 36, 196

kidney 180, 184myocard 196photosensors 356

Na-2 Cl–-K-cotransport 238inhibition 174kidney 162saliva 238

Na-K-ATPase ( also ATPase)26, 28, 46, 182, 244, 290cardiac glycosides 26, 196electrogenicity 46hyperpolarizing afterpotential

46heart muscle 196ouabain 26phosphorylation 26renal collecting duct 182

tubule 154, 156, 162resting potential 44salt reabsorption, intestine 264stomach, parietal cells 244T3/T4 effect 290transport cycle 26

Na-taurocholate cotransportingpolypeptide (NTCP) 250

NaCl, homeostasis 172disturbances 174regulation 172

deficiency 172excess, counter regulation 172hypertension 218reabsorption, salivary glands

238sense of taste 344uptake 172

NADH 39 CNaPi (Na-phosphate symport

carrier) 180nano- (submultiple of a unit) 379Narcolepsy 340Natriuretic hormone 172Natural killer cells 94, 96Nausea 240, 330NBC (= Na-bicarbonate cotrans-

porter) 176, 248Near point, eye 324, 352

sightedness 352vision 350

response 365, 366Necrosis 98Neck reflex, tonic 330Neocerebellum 328Neostigmine 56Nephrine 148Nephrocalcin 180


426

Nephron 148, 150cortical 150juxtamedullary 150sections 148structure 148transport processes 154

Nernst equation 32, 44, 394Nerve ( also neuron and ner-

vus) 78, 84, 312antidromic conduction 48cell 42cholinergic 78, 82conduction velocity 48endings, free, smell 346fiber 42, 48

diameter 42, 49 Cmyelinated 42, 48unmyelinated 42, 48

fibers Ia 318Ib 318Iia 318

glossopharyngeal 132neurosecretory 282optical 350pelvic splanchnic 310stimulation 50structure 42trigeminal 320, 324, 346, 365

Nerve growth factor (NGF) 42,280, 344

Nervous system 42autonomic 78ff., 80/81 A, 82,

268centers 78cotransmitter 86innervation, organs 78peripheral 268

central 268, 312enteric 236, 268somatic 268

Nervus opticus 350, 365vagus 132, 244, 250, 376

Net diffusion 20Neuroendocrine system 268ff.,

282 ff.Neurofibrils 42Neurofilaments 14Neurogenic tonus 70Neurohypophysis 270, 282Neuron ( also nerve) 42, 50

Aδ 320adrenergic 78ff., 332axolemma 42axon 42axon hillock 42axonal transport 42Ca2 conductance 44cholinergic 78ff.Cl–-conductance 44collaterals 42conduction velocity 48, 49 Ccortex area 334

Neuron (cont.)dendrites 42diameter 49 Cdopaminergic 328, 332GABAergic 328glutamatergic 328Ia- 318, 322, 326Ib- 318II- 318instestinal 246internal longitudinal resistance

48membrane capacity 48α-motor 322γ-motor 322motoric 326, 330neurosecretory 282nitrogenergic 280parasympathetic 78, 82postganglionic 78, 82preganglionic 78, 82sensoric 314ff.serotoninergic 332soma 42summation, spatial 52

temporal 52structure 42, 43 A1sympathetic 78, 82, 84terminal buttons 42

action potential 48transmission, electrotonic 48visceral afferent 78, 236, 268

Neuropeptid Y (NPY) 84, 86, 232,282, 302cotransmitter 84receptor types 55 Fsecond messenger 55 F, 276

Neurosecretion 282Neurotensin 55 F

second messenger 278Neurotransmitter 42, 50, 52, 55 F,

236, 268autonomic nervous system

78ff.excitatory 52exozytosis50function 42inhibitory 52ionotropic 34, 55 Fmetabotropic 34, 55 Frelease 50re-uptake 52termination of action 54 E

Neurotubuli 42Newborn 93 D, 94, 118, 128, 136,

222, 226, 252, 290, 307distress syndrome 118

Newton (N), unit 380NF-κB (necrosis factor) 278NGF (nerve growth factor) 42,

280, 344NH3 22, 156, 176, 180

NH3 (cont.)diffusion 22production 178renal cellular secretion 156,

176 f.renal excretion 176secretion, renal tubular 178transporter 178

NH4 145 B2, 176ff.

excretion 178ff.nonionic transport 176production 178

NHE3 Na/HAntiportcarrier248

Niacin, intestinal absorption262

Niacinamide 228Nickel (Ni) 228Nicotine 82Nidation 300, 305NIDDM (non-insulin dependent

diabetes mellitus) 286Night blindness 228, 356, 358Nipples, erection 310NIS (2 Na-I–-symport carrier)

288Nitric oxide NO

synthase (NOS) 82, 280Nitrogen N and N2

NM-receptors 82NN-receptors 82NO 74, 86, 94, 212, 214, 216, 240,

280coronary vasodilatation 212erection 310immune defense 94synthase 82, 280

Nociception 320, 322, 324tract 320

Nocisensors 320, 324Nodal point, eye 352Nodes of Ranvier 42, 48Noise suppression, auditory

pathway 374Non-bicarbonate buffers 126,

138, 140, 144f.Non-ionic diffusion 22, 156, 178Norepinephrine ( also cate-

cholamines) 52, 78, 84, 196,232, 238, 270, 282, 302adrenal medulla 86cerebral cortex 334coronary vasodilatation 212extraneuronal uptake 86heart 196inactivation 86insulin secretion 284intestinal tract 236neurons 332pheochromocytoma 218receptor types 55 Frelease 84


427

Norepinephrine (cont.)re-uptake 86saliva secretion 238second messenger 55 F, 276,

278synthesis 84thermoregulation 224

NOS (nitric oxide synthase) 82,280

NPY (Neuropeptid Y) 84, 86, 232,282, 302cotransmitter 84receptor types 55 Fsecond messenger 55 F, 276

NREM (non-REM) sleep 336NTCP (Na taurocholate

cotransporting polypeptide)250

Nuclear bag fibers 318chain fibers 318envelope 10pores 10

function 16signal sequences 10

receptors, calcitriol 294Nucleolus 8, 10Nucleotides 8Nucleus/nuclei, accessory 374

amygdaloid 332anterior olfactory 346arcuate 232caudate 312, 328cuneatus 324Deiter 328, 330dentate 330emboliformis 330fastigial 330gracilis 324lateral, lemniscus 374localisation signal 10olivaris superior lateralis 370paraventricular 232pedunculus pontinus 328RNA synthesis 8red 330septal 332subthalamic 328suprachiasmatic (SCN) 336thalamic, anterior 332tractus solitarii 170, 344vestibular 348

Nuel’s spaces 370Nursing mother, Ca2 require-

ment 292Nutrition 228

integration 236, 332passage time, stomach 235,

242reflex 322vegetarian 142

Nystagmus 366caloric 348

Nystagmus (cont.)optokinetic 366pathological 366postrotatory 348

O

Ω (ohm), unit 381O2 (Oxygen) 72, 106

arterio-venous difference 132,212

in myocard 212artificial respiration 132binding curve

in blood 126, 128fetal hemoglobin 222, 129 Cmyoglobin 129 C

breathing 136capacity of blood 126, 128chemosensors 132, 136concentration, blood, maxi-

mum 128difference, heart muscle 212

consumption 106, 120, 150,230, 290heart muscle 212maximum 74, 76measurement 112, 120organs 130, 189 Arenal 150T3/T4 effect 290

debt 72deficiency 72,130, 136, 212, 214

ventilation 136demands 72, 74, 130

heart muscle 212increased 130organ difference 130

difference, alveolar-arterial122arteriovenous 74, 106, 130

diffusion 21 A, 130lung 22tissue 130

dissociation curve 128fetal hemoglobin 222

dissolved in plasma 128extraction 72f., 130, 212

coefficient 212heart muscle 212exercise 74organs, difference 130skeletal muscle 72

half saturation pressure 128high altitude 136Krogh’s diffusion coefficient

22, 120partial pressure 20

alveolar 120, 128diving 134

arterial blood 128

O2 (Oxygen) (cont.)chemical respiratory stimu-

lant 132critical, mitochondria 130high altitude 136hyperventilation 120mixed venous blood 120, 128

plasma 132radicals, immune defense 94role in autoregulation 214saturation (SO2 ) 126, 128

fetus 222, 221 Ainfluence on CO2 binding

curve 126solubility coefficient 128

in plasma 126supply, fetus 222

myocard 212therapy 136toxicity 134, 136

diving 136transport in blood 128uptake, exercise 74

maximum 72, 76, 77 Cendurance athlet 77 C

OAT1 (organic anion transportertype 1) 160, 270

Obesity 232Occludins 18OCT (organic cation transporter)

160Ocular chamber 350

muscle, nuclei 348pressure, internal 322

Oculomotor control 328, 331,348

Odorant molecules 346OFF-bipolar cells 360

field (central) 360ganglion cells 360, 364

OH–-ions 138ff.Ohm (Ω), unit 381Ohm’s law 32, 116, 190

ion transport 32, 394circulation 190, 394ventilation 116

Oil-and-water partition coeffi-cient 20

Olfactory epithelium 346pathway 346sensor cells, primary 346tract 346

Oligodendrocytes 42, 344Oligopeptides, digestion 260

renal handling 158Oligosaccharides 260Oliguria 164

shock 220Olive inferior 330

superior 374Oncotic pressure 24, 94, 152, 166,

210, 384


428

Oncotic pressure (cont.)influence on capillary fluid

exchange 210, 385plasma 152

One-half maximum velocity con-stant (KM) 28

ON-bipolar cells 360field (central) 360ganglion cells 360, 364

Oocyte stage, primary 300Oogenesis 300Oogonia 300, 308Open-probability, ion channels

34Open system, thermodynamics

40Opioids 276, 282

endogenous 320exogenous 320Gn-RH secretion 302receptor types 55 F

gastointestinal tract 236second messenger 55 F, 276

Opponent color channel 362Opsin 354, 356Opsonization 94, 96Optic chiasm 364

nerve 364lesion 364

tract 360, 364Optical apparatus 350

nerve 350system, simple 352

Optokinetic nystagmus 366Orexin 232Organ of balance 366

Corti 370Organelles 8Organs, blood flow 187 A, 214,

216fetus 221 Atransplanted 98

Organum vasculosum laminaeterminalis (OVLT) 282, 312,332

Orgasm 310Orgasmic cuff 310Ornithine 260Orthopnea 108Orthostasis 5 C, 6 f., 206, 218Orthostatic hypotension 184

reflex 7 E, 206, 218Oscillation, unstable 6Osmol 383Osmolality, plasma 92

unit 383urine 164, 174

Osmolarity 383saliva 238unit 383

Osmolytes, organic 170Osmometer 383

Osmoregulation 170Osmosensors 170, 274, 332Osmosis 24Osmotic coefficient 383ff.

diuresis 174, 178effect on K excretion 184

pressure 24, 383colloidal 92, 383

Ossicles, auditory 370Osteoclasts 292, 294Osteolysis, malignant 294Osteomalacia 294Osteoporosis 304Otoliths 348Ouabain 26, 172Ounce, conversion into SI unit

380Outer ear 370Oval window 370, 372Ovaries 256, 270, 296, 300, 308

HDL receptor 256menstrual cycle 300pregnancy 306production, fertiliziable egg

300testosterone production 308

Overshoot, action potential 46Overtone 368Overweight 228, 232OVLT (organum vasculosum

laminae terminalis) 170, 282,312, 332

Ovulation 300, 302, 304antiovulatory effect 305inhibitors 302

Ovum 300, 304first meiotic division 302second meiotic division 310implantation 300, 305

Oxalate 102, 158, 160, 264inhibition, blood clotting 102renal secretion 158, 160

Oxidation, biological molecules41of glucose, aerobic 72

-oxidation 2582-oxoglutarate 178-oxybutyric acid (286Oxygen O2

Oxygenation 128Oxyntic cells parietal cellsOxytocin 172, 271, 276, 282, 305,

306receptors 55 Fsecond messenger 55 F, 276,

278uterus 306, 310

P

P progesteroneP0.5 (half saturation pressure) 128PA (alveolar pressure) 108P (proportional)-Sensors 316P (multiple of a unit) 379p (submultiple of a unit) 379P wave, ECG 198Pa (Pascal), unit 380Pacemaker 70, 242

heart 194, 196, 202artifical 202tertiary 194ventricular 194, 202

intestine, motility 246potential, heart 194stomach 242

Pacinian corpuscles 316PAF (platelet-activating factor)

100, 102PAH p-aminohippuratePain 320, 322, 324

assessments 320components 320post-exercise muscle ache 77 Drelated behavior 320

Palaeocerebellum 328Pallidum 312, 328Pancreas 234, 248

cell types 284, 286enzymes 248exocrine 248gastrin release 254hormones 284, 286islets 270juice 248, 254somatostatin 286

Pancreatic lipase 254necrosis, acute 248polypeptide 284secretions 248

Pantothenic acid 228Papilla nervi optici 350, 364Para-aminohippurate (PAH) 150,

160Paracellular transport 154Paracrine action of hormones

284Paraflocculus 328Parallel fibres, cerebellum 330Paralysis 62

dissociated 324Paraplegia 322, 330Parasites, defense against 94Parasympathetic fibers, genital

tract 216heart 196innervated organs 82

ganglia 78 ff.nervous system, gastrointesti-

nal tract 236


429

Parasympathetic fibers, genitaltract (cont.)

saliva secretion 238stimuli, salivary glands, blood

flow 216Parathormone parathyrinParathyrin (PTH) 36, 37 C3, 180,

292calcitriol 294chemistry 292deficiency 292effects 292influence on Ca2and

phosphate excretion 180regulation 292renal Ca2 reabsorption 180

Parathyroid glands, 270 292hormone parathyrin

Paravertebral ganglionic chain 78Parkinson’s disease 328Parietal cells, gastric 242, 244Parotid glands 238Pars recta, renal tubule 148Partial pressure 106, 120

Dalton law 106Parvalbumin, muscle fibers 64Pascal (Pa), unit 380PAS domains 336Passive immunization 94Patch-clamp technique 34Pause, compensatory 202

post-extrasystolic 202PBI iodinePCT (proximal convoluted

tubule) 164PDGF (platelet-derived growth

factor) 102, 280PD-Sensors 314, 316Peak expiratory pressure 116

inspiratory pressure 116Pendrin 176Pendular movements, intestine

motility 246nystagmus 330

Penicillin, tubular secretion 156Penis 310

erection 280REM sleep 336

Pepsins 240, 244, 260Pepsinogens 244, 260PepT1 (peptide transporter 1),

intestine 260PepT2, kidney 158Peptidase 158, 244, 248, 260Peptide(s), catabolism, renal 148

carrier PepT1 260PepT2 158

digestion 260hormones 270, 276, 306

placenta 306messenger 276renal reabsorption 156, 158

Peptide(s), catabolism, renal(cont.)

handling 128transmitter 55 F

Peptide-H-symport carrier 28,158, 260

PER 336Perception, visual 314

color 362form 316shape 316spatial nature 316

Perfusion, cerebral 188pulmonary 120

imbalance 120, 122, 130Performance limit 76Periglomerular cells 346Perilymph 370, 372Perimeter 364Peripheral resistance 190, 208

influence on heart function208

Peristalsis 236esophagus 240intestine 246

large 266stomach 242ureter 148

Permeability, Ca2 82Cl– 44coefficient (P) 22K 44, 56, 82Na 44, 56, 82

Peroxidase, thyroid (TPO) 288Peroxisomes 14Perspiratio insensibilis 224Perspiration 224

water losses 168Pertussis toxin 278Peta- (multiple of a unit) 379Peyer’s patches 234pH 138, 146, 384

blood 132, 138buffer 138normal range 142

cerebrospinal fluid 126, 132clearance, esophagus 240erythrocytes 126esophagus 240homeostasis, kidney 176

role of liver 178influence on diffusion 22

on protein bound Ca2 292measurement 146plasma 126, 136, 138, 142

K metabolism 182saliva 238tubule lumen 176urine 156

Phagocytes 94Phagocytosis 12, 28, 96Phase, vulnerable, heart 202

Phenol red, tubular secretion 160Phenprocoumon 104Phentolamine 84Phenylalanine 228Phenylephrine 87 BPhenylethanolamine-N-methyl-

transferase 84Pheochromocytoma 218Phon 368Phosducin 356, 358Phosphatase 278

alkaline 252Phosphate 138, 158, 177, 180,

292, 294absorption, intestine 264blood buffer 138calcium complex former 180concentration, serum 292deficiency 180, 294DNA 8excess 180excretion 178, 180, 294H secretion 178homeostasis 292intake 292intestinal absorption 294metabolism 292plasma 292renal reabsorption 158solubility 292

Phosphadidylcholine (lecithin)14, 250, 254bile 250

Phosphatidylethanolamine 14Phosphadidylinositol-4,5-bis-

phosphate (PIP2) 278Phosphatidylserine 14Phosphaturia 180Phosphodiesterase 278, 354, 356

cGMP-specific 280Phospholipase A2 248, 254Phospholipase C (PLC) 37 C1,

82, 84, 278Phospholipids 254, 256

blood clotting 102lipoproteins 256cell membrane 14

Phosphoric acid ( alsophosphate) 142, 176

Phosphorylation 276Photochemistry, eye 354Photosensors 350, 352, 354

retinal distribution 354sensor potential 360

Photopic vision 354Phyllochinone 262Physical activity 72ff.

energy reserve 284exercise capacity 76

core temperature 226energy supply 228heat production 224


430

Physical activity (cont.)measure 74measurement 76work 72 ff., 142, 284

activation of the sympatheticnervous system 74

heat production 224O2 consumption 74threshold, aerobic 76

anaerobic 76ventilation 74

respiratory control 74, 133A5

unit 380Physiologic integration 268Phytin 264Pico- (submultiple of a unit) 379PIF prolactostatinPigmented epithelium 350PIH (prolactin-release inhibiting

hormone) dopaminePineal body (= pineal gland =

epiphysis) 336Pinocytosis 28PIP2 (phosphadidylinositol-4,5-

bisphosphate) 278Pirenzepine 82Pituitary gland 282, 288

anterior 270, 282influence of neu-

rotransmitters 282TSH secretion 288TRH receptors 288

hormones 270posterior 182, 270, 282

ADH secretion 172hormone secretion 282

testosterone effect 308pKa value 138, 140, 384f.PKA (proteinkinase A = A kinase)

84, 276PKC (proteinkinase C) 36, 37 C1,

70, 84, 278PKG (proteinkinase G) 280PKK (prekallikrein) 102Placenta 100, 222, 294, 304, 306Placental barrier, function 306

hormones 306immunoglobulins 92transfusion 222

Plasma 88, 92albumin 92cells 94, 98CO2 124components 88, 92factors 100globulins 92osmolality 92, 171proteins 88, 92, 154, 158, 383f.

binding 24, 25 C, 88, 154Ca2 180, 292blood puffer 138

Plasma (cont.)function 88, 92, 383f.types 92

pH 126thromboplastin antecedent

(PTA) 102volume 172

measurement 168salt deficiency 172

Plasmin 104Plasminogen 104Plasticity of smooth muscle 70

pyramidal cells 334Platelet(s) ( also Thrombo-

cytes) 88, 102activating factor (PAF) 100, 102activation 102aggregation 102

inhibitors 104derived growth factor (PDGF)

102, 280PLC (Phospholipase C) 37 C1, 82,

84, 278Plethysmography 114Pleura 108

pressure (Ppl) 108Plexus myentericus (Auerbach)

236, 246submucous (Meissner) 236,

246PMA (premotor area) 326Pneumothorax 110

diving 134types 110

Podocytes, glomerulus 148Poikilothermy 224Point, low 72Polkissen 186Polyethylene glycol, intestine 264Polypeptide, pancreatic 284Polyribosomes 10Polysaccharides, chemical struc-

ture 227 Bdigestion 260

Polysomes 10Polysynaptic reflexes 322Polyuria 164POMC (pro-opiomelanocortin)

232, 282placenta 306

Pond, conversion into SI unit 380Pons 132, 312

eye movement 366Pontocerebellum 328Porphyrin 128Portal circulation 234, 250

hypothalamus 282vein 210, 234

Positive pressure ventilationcontinuous (CPPV) 110intermittent (IPPV) 110

Postcentral gyrus 324

Posterior funiculus, nuclei 324Postextrasystolic pause 202Postsynaptic inhibition 322

membrane 42, 50Posttranslational modification

10, 12Posttransscriptional modification

12Postural control 330

motor function 326, 328, 330,348system 326

reflex 330labyrinthine 330

Posture 326, 330maintaining 326

Potassium K

Potentia coeundi 308Potential, action 46ff., 48

unit 381diffusion 44electrochemical 32end-plate 56equilibrium 44excitatory postsynaptic (EPSP)

52, 56, 322inhibitory prostynaptic (IPSP)

52, 82, 334maximum diastolic, heart

pacemaker 194resting membrane 44reversal 47 B, 56threshold 46, 48transepithelial 156, 182

lumen-neagtive (LNTP) 162,238, 264

lumen-positive (LPTP) 162,174, 180, 182

Pound, conversion into SI unit380

Power, unit 380Powers of ten, calculation with

386 f.PP (pulse pressure) 196, 208ppb (parts per billion), unit 382ppm (parts per million), unit 382Ppl (pleural pressure) 108PQ interval, ECG 198PQ segment, ECG 198Prader-Willi syndrome 232Prazosin 87 BPrealbumin, thyroxin-binding

(TBPA) 290Precapillary sphincter 190Pregnancy 90, 262, 292, 294, 302,

304Ca2 292central venous pressure 206hormon concentrations 304hormonal control 306, 332nausea 240Rh system 100


431

Pregnancy (cont.)tests 296, 306vitamin D-binding protein 294vomiting 240

Pregnanediol 296, 305, 306Pregnenolone 296, 305

17-OH 296Prekallikrein (PKK) 102Preload, heart 204, 206Prepotential, heart 194Preproinsulin 284Presbyacusis 368, 372, 376Presbyopia 352Presentation of antigens 96Pressure (unit) 380Pressure, arterial sensors 216

capillary 210central venous (CVP) 192, 206colloidal osmotic 384diuresis 172, 174hydrostatic 210

feet 210internal ocular 350intrapleural 108intrapulmonic 108intrathoracic 108oncotic 24, 210, 166, 384

peritubular capillaries 166plasma 152

osmotic 24, 384transmural 190transpulmonary 108transthoracic 108ventricular 192, 204volume curve, heart 68

lung and thorax 116wave, pulse wave 192

Pressosensors, arterial 316skin

Prestin 372Presynaptic inhibition 322

membrane 42, 50Pretectal region 365Previtamin D 294Primary, response, antigen con-

tact 94saliva 238urine 164

Principal cells, kidney 162, 182point, optical apparatus 352

PRL prolactinProaccelerin 102Probenecid 160Procarboxypeptidase 248Process, ciliary 350Procolipase 248, 254Proconvertin 102Procreative capacity 308Proelastase 248Progesterone 132, 296, 300, 302,

305, 306actions 294, 305, 306

Progesterone (cont.)chemistry 305degradation 305esophagus sphincter 240menstrual cycle 30017-OH- 296placenta 306plasma concentration 304

transport 305production 296, 305respiration 132secretion rate 305

Proglucagon 286intestinal 284

Proinsulin 282, 284Prolactin 270, 271, 276, 282, 305,

308lactation reflex 305menstrual cycle 300receptor 280release inhibiting hormone

prolactostatin 270ff., 282,300, 305

secretion, pulsatile 300TRH effect 305

Prolactostatin (PIH = dopamine)270ff., 282, 300, 305

Proliferation 274lymphocytes 94

Proliferative phase, menstrualcycle 300

Prolipase 248Pro-opiomelanocortin (POMC)

232, 282, 306Prophospholipase A2 254Proportional sensors 314, 316,

318Proprioception 316, 318, 324Propriosensors 318, 326

neck 330Prostacyclin (PGI2) 104, 216, 270,

271Prostaglandin(s) (PG) 162, 234,

236, 244, 270, 276, 278autoregulation 214E2 216, 320

fever 226effects 271F2α–216fetal circulation 222HCO3

– secretion, stomach 244I2 (Prostacyclin) 104, 216, 270,

271coronary vasodilatation 212

intestine 264prostate 310second messenger 276, 278synthesis 271

inhibition 271, 320uterus 306, 310

Prostate 308, 310Protanomaly 362

Protanopia 362Proteases, pancreatic juice 248,

260Protective reflexes 240, 322Protein C 104

S 104Protein 154, 148, 228, 230

absorption, intestine 260binding 24, 154bound iodine 288, 290caloric equivalent 230capillary permability 210catabolism, renal 148chemical structure 229 Bconcentration in cerebrospinal

fluid 144digestion 248, 260

enzymes 244, 248energy supply 230filtrability, glomerulus 154functional minimum 228hormones 270kinase A (PKA) 84, 276kinase C (PKC) 36, 37 C1, 70, 84,

278kinase G (PKG) 280kinase II (calmodulin-depend-

ent protein) 36, 50kinase, tyrosine specific 284minimum intake 228nuclear, nuclear pores 10nutrition 228phosphorylated 276plant 228plasma 92, 158renal reabsorption 156synthesis 10, 13 F

influence of cyclic AMP 276Proteinuria 158, 210Proteolysis 248Prothrombin 102, 104Protons H

Proximal stomach 242P (proportional)-Sensors 314,

316, 318Pseudohypoparathyroidism 292Psychotropic drugs 332PTA (plasma thromboplastin

antecedent) 102Pteroylglutamate acid 262Pteroylpolyglutamate hydrolase

262PTH parathyrinPtyalin 238, 260Puberty 304

spermatogonia 308Puborectal muscles 266Pudendal nerve 266Pulmonary ( also lung) artery

122, 188, 192partial pressures 122pressure 120, 192, 208


432

Pulmonary artery (cont.)blood flow 122capillaries 106, 122, 124circulation 188, 190

resistance 208edema 118, 120, 122, 132, 144,

174, 210infarction 120stretch receptors 132valves 192ventilation, exercise 74ventilation/perfusion ratio 122

Pulse pressure (PP) 192, 208receptors 216

wave, velocity (PWV) 192Puncts, lacrimal 350Pupilla 350, 352

contraction 350dilatation 350, 358, 364role in adaptation to light 358

Pupillary reflex 358, 364Purine, receptor types 55 F

second messenger 55 FPurkinje cells, cerebellum 328,

330fibers 194

action potential 202Pursuit eye movement 366Putamen 316, 326, 328P wave (ECG) 192, 198PWV (pulse wave velocity) 192Pylorus 242Pyramidal cells, motosensory

cortex 334tract 326

Pyridoxal 262Pyridoxamine 262Pyridoxine 262Pyrogens 226Pyruvate 73 B2Pyruvic acid 73 B2

Q

Q10 value 40QRS axis, ECG 200QRS complex, ECG 198QRS vector, mean 198, 200QT interval, ECG 198, 200Quinidine, tubular transport 160Quinine 344Quotient, respiratory 120, 136,

230Q wave, ECG 198, 200

abnormalities 200

R

R (gas constant) 20, 32, 34, 112R wave, ECG 198Radiation 224, 226Rahn valve 114Raphe nuclei 330RAS (renin-angiotensin system)

170, 186, 220RA sensor (rapidly adapting pres-

sure sensor) 316Rate constant 40RBC (red blood cell) erythro-

cyteRBF (renal blood flow) kidneyRCC (red cell count) 90Reabsorption, capillaries 210

renal tubule 148, 152ff., 162,176ff., 182ff.

Reaction, acrosomal 310coupled 41endergonic 38endothermic 38equilibrium constant 40exergonic 38exothermic 38hypersensitivity (allergy) 100rate of 40

constant 40Reactive hyperemia 214Reading 340

presbyopia 352Rebound effect 274

phenomenon 330Receptive field 316, 360

retina 360relaxation 240, 242

Receptor (sensory receptors sensors) 6, 55 F, 270, 314acetylcholin cholinoceptor

second messenger 276f.ADH 55 F, 214adrenalin adrenoceptorsadrenergic adrenoceptorsangiotensin II 214CCK 55 F

gallbladder 250stomach 244

cobalamine 28cholinergic 82dopamin 250epinephrine adrenoceptorsendothelin 214G protein-dependent 52guanylyl cyclase 280histamin 55 F, 214, 244, 276,

278hormone 268, 270, 276immunoglobulins 96insulin 270, 284internalization 52ionotropic 52, 55 F, 82

Receptor (cont.)LDL 28mediated endocytosis 12f.metabotropic 52, 55 F, 82noradrenaline adrenocep-

torsnorepinephrin adrenocep-

torsproteins 270, 280, 298recycling 12, 13 F, 29 Cserine/threonine kinase

280synapse 50, 55 Ftransferrin 90tyrosinkinase 280, 284tyrosine phophatases 280

Recoverin 356, 358Recruitment, motoric unit 58

acoustic neurons 374Rectum 234, 266Recurrent inhibition 318, 322Red blood cells erythrocytes5α-Reductase, testosteron 308Reentry, excitation, heart 196,

202Reference values 396 ff.Reflection coefficient (σ) 24, 210,

383Reflex 78, 318ff.

abdominal 322absence of 322accomodation 242arc 78autonomic 322conditioned 238, 244

saliva secretion 238consensual 365corneal 322

crossed 322diagnostic 322endogenous 236extensor 322flexion 322gastrocolic 266gastrointestinal tract 236Henry–Gauer 220Hoffmann’s 318knee jerk 318labyrinthine postural 330load compensation 318locomotor 322monosynaptic 318neck, tonic 330nutrition 322orthostatic 206peristaltic 236, 246plantar 322polysynaptic 322postural 330proprioceptive 318protective 240, 322pupillary 365


433

Reflex (cont.)spreading 322statokinetic 330time 318, 322tone 66

labyrinth 330vagovagal, esophagus 240vestibulo-ocular 348withdrawal 322

Refraction, eye 352Refractive power 352Refractory period (action poten-

tial) 46absolute 46relative 46heart 202

Regulation 4, 268Reissner’s membrane 372Relaxation, receptive 240, 242Relaxin 170Release-inhibiting hormones

270, 271, 282Releasing hormones 270, 271,

282REM sleep (rapid eye movement)

336Remnants of chylomicrons 258

of VLDL 256Renal ( also kidney) artery, ste-

nosis 186blood flow 150failure 142, 178function, glucocorticoid effect

298Renin 148, 186

hypertension 218Renin-angiotensin system (RAS)

170, 186, 220control 186

Renshaw cells 318, 322, 326Replication, cell 8Repolarisation (action potential)

46Repressor protein 8Reproduction 300ff., 332RES (Reticuloendothelial system)

( also macrophage and mon-onuclear phagocytotic system)96

Reserve volume, expiratory 112inspiratory 112

Residual capacity, functional(FRC) 112, 114, 116volume (RV) 112, 114

Resistance peripheral 188, 208hypertension 218

unit 381vessels 188, 190

Respiration ( also respiratory)106artificial 110control 132

Respiration (cont.)dead space 110, 114effects of diving 134functions 106high altitude 132, 136influence on venous return

110internal 106mechanical 110mechanics 108, 110, 112, 144,

116mouth-to-mouth 110muscles 108pressure–volume relationships

116work of breathing 116

Respiratory acidosis 144alkalosis 142, 144air, purification 110chain 12, 73 B3compensation 142control 132, 216drive, high altitude 136

insufficient 144equivalent 74, 106exchange rate 120muscles 132quotient (RQ) 120, 136, 230rate 106, 118sensors 132stimulants 132volumes 112

conversion 112standardization 112

ways, flow resistance 116Response, local 46Resting expiratory level 112

membrane potential 44metabolic rate 228position, respiration 112pressure–volume curve, heart

204lung and thorax 116skeletal muscle 66

tidal volume 112, 114, 118tremor 228

Resuscitation 110Reticular zone, adrenal cortex

298Reticuloendothelial system (RES)

( also macrophage) 96Reticulocytes 88Reticulum, endoplasmic 10, 12,

sarcoplasmic 60, 196Retina ( also visual and eye)

350, 352, 362, 364contrast of a stimulus 360corresponding points 366ganglion cells 360, 364processing of visual stimuli

360receptive field 360

Retina (cont.)sensors 350, 354

potential 36011-cis-Retinal 354Retinol 262, 356Return, venous 206Reversal potential 47 B, 56Reverse-T3 (rTr3) 290Rhesus system 100Rhinencephalon 346Rhodopsin 354, 356, 358, 362

kinase 356Rhythm, circardian 298, 336

diurnal 336generator 336

Rhythmicity, heart 194Riboflavin, intestinal absorption

262Ribonucleic acid RNARibose 8Ribosomal ribonucleic acid

rRNARibosomes 10Rickets 228, 294Rigidity, decerebrate 330Right axis deviation (heart) 200Rigor complex 64

mortis 64, 328Rinne’s test 370Riva-Rocci (blood pressure

measurement) 208RNA (ribonucleic acid) 8ff.RNA polymerases 8RNAses, pancreas 248Rods 350, 354, 356, 362

adaptation 358monochromatism 358light absorption maximum 362

Roots, spinal cord 312Rotation, sensors 348Round window, ear 370, 372RPF (renal plasma flow) kid-

neyRQ respiratory quotientrRNA (ribosomal ribonucleic

acid) 8, 10rTr3 (reverse-T3) 290Ruffini’s corpuscle 316RV (residual volume) 112, 114R wave (ECG) 198Ryanodine receptors (RYR) 62, 64RYR 65 DRYR1 63 BRYR2 63 B

S

σ (reflection coefficient) 24, 383S hormones glucocorticoids

and cortisolS wave, ECG 198


434

S (siemens), unit 381SA sinoatrialSA1 (slow adapting pressosensor)

316SA2 316Saccadic eye movement 366Saccharin, taste 344Saccharase 260Saccharose 260Saccule 348Salbutamol 87 BSaliva 234, 238, 260, 262

primary 238secondary 238

Salivary glands 238blood flow 216

Salt ( also Na and Cl–), balance148, 162, 170

disturbances 170, 174, 175 Eregulation 170

excretion 162, 172role in hypertension 218

retention 172, 184Saltatory conduction 48Saluretics 174Sarcoglycans 60Sarcolemma 56, 60Sarcomere 60f.

resting length 68Sarcoplasm 60Sarcoplasmic reticulum 60Sarcosomes 60Satiety peptides 232Scala media 370

tympani 370, 372vestibuli 370, 372

Scalene muscles 108Scavenger receptors, LDL 258Schlemm’s canal 350Schwann cells 42Sclera 350Sclerosis 218SCN (suprachiasmatic nucleus)

336Scotoma 364Scotopic vision 354Scurvy 228Second messenger 270, 276, 278

adrenoceptors 84f.M-cholinoceptors 82neurotransmitter receptors

52, 55 CSecondary active cotransport

with Na 26, 260of Cl- 264

response, immune defense 94saliva 238

Secretin 236, 242, 248, 276esophagus 240insulin secretion 284pancreas secretion 248second messenger 276stomach 244

Secretion, renal kidneyconstitutive 13 F

Secretory granules 12, 270phase, menstrual 300

Segmentation (intestine) 246Seizures 136Selectins 14, 98Selection, clonal 98Selenium (Se) 228Self-awareness 340Semen emission 310

production 308Semilunar valves, heart 192Seminal vesicles, testosterone

effect 308, 310Seminiferous tubules 308Senses 314, 316, 324, 344, 346,

348balance 348chemical 344hearing 368ff.movement 318, 348position 318, 348smell 346somatovisceral 316strength 318taste 344touch 316vision 350ff.

Sensibility, somatovisceral 316Sensitization 94, 320

reflex pathways 340Rh blood groups 100

Sensor(s) 314, 342blood pressure 216

volume 216cold 226D- 316, 318filling pressure 216heat 316light sensitive 350olfactory 346potential 314

photosensors 356, 360primary 314, 346P- 316pressure 316proprioceptive 318pulse rate 216retina 350, 354secondary 314, 344, 348

organ of corti 370skin 316smell 346touch 316vibration 316warm 316

Sensory aphasia 376impression 314input, central processing 324modality 314physiology 314ff.receptors sensors

SERCA (sarcoplasmic endo-plasmic reticulum Ca2-trans-porting ATPase) 16, 64

Serotonin 102, 160, 232, 276, 278,332, 334cerebral cortex 334neurons 332platelets 102, 103 Areceptor types 55 F, 276, 278second messenger 55 F, 276,

278tubular tranport 160

Sertoli cells 308Serum 88

disease 100electrolytes, ECG 200sickness 100

Servocontrol 6Servomechanism 6Set point, variation 6

value 4Sex characteristics, female 304

male 308chromosomes 308genetic 308hormones, binding globulin

270, 304, 308female 296, 300, 302male 296, 306, 308synthesis 296

Sexual arousal 310behavior 332development 308

delayed 290differentiation 308maturation 300reflexes 310response 310

SFO (= Subfornical organ) 170SGLT1 (sodium glucose trans-

porter, type 1) 158SGLT2 26, 158SH2 (src[sarcoma]-homology)

domains 280, 284, 286SHBG (sex hormone-binding

globulin) 270, 304, 308Shear force 92Shivering, thermoregulation

224 f.Shock 100, 188, 208, 220

anaphylactic 100, 220causes 220compensation mechanisms

220hypoglycemic 220, 286index 220irreversibel 220lung 122manifest (progressive) 220

Shunt 120alveolar 120arteriovenous 122


435

Shunt (cont.)blood flow 122, 222extra-alveolar 120left-to-right 222right-to-left 222

SI units 378f.Sickle cell anemia 92Siemens (S), unit 381Sieving coefficient 24

glomerular (GSC) 154Siggaard–Andersen nomogram

146, 147 CSignal recognition particle (SRP)

12Signal sequence 12

transduction 276Sildenafilcitrate (Viagra) 280Silibants, voice 376SIH somatostatinSilicon (Si) 228Simultaneous contrast 360Singing 376Single-unit, muscle typ 70Sinoatrial (SA) node 192, 194,

202Sinus arrhythmia 202

bradycardia 202rhythm 194tachycardia 202

Skeletal growth, STH 282Skeletal muscle 56 ff., 326 ff.

actin–myosin interaction 68action potential 56, 59 Aall-or-none response 66blood flow 74

regulation 216Ca2 concentration, cytosolic

66contracture 66difference cardiac/smooth

muscle 68fibers

extrafusal 318intrafusal 318stimulation 62types 58

glycogen concentration 58glycogenesis 284gradation of contraction

force 66lactate production 76length–force curve 68mechanical features 66mitochondria 63 Amotor units 58, 66myoglobin function 72, 128persistant local depolariza-

tion 66reflex tone 66rigor 66

complex 64summation 66

Skeletal muscle (cont.)superposition 66tetanus 58, 66

Skin 74, 224, 226α1 -adrenoceptors 216blood flow 188, 224

physical work 74regulation 216

formation of cholecalciferol294

mechanosensors 316nocisensors 320sensibility 316sensory functions 224ff., 316,

324temperature 224, 226thermosensors 224ff.

Sleep 334, 336deprivation 336disorders 340functions 340phases 336regulation 338stages 336

Sleep–wake cycle 336Sliding filament hypothesis 62,

64Slit membrane, glomerular 148SMA (suplementary motor area)

326Small intestine 234, 242

Ca2 absorption 292cell replacement 246function 246motility 246stucture 246

Smell 346Smooth muscle 70

intestine 246M3 -receptors 82

SNAP-25 (synaptosome-associated protein 25) 50

SNARE (synaptosome-associatedprotein receptor) 30

Sneezing 132, 322Snorkel diving 134SO2 (O2 saturation) 126Sodium Na

Softening effect, ATP 64Solubility coefficient, CO2 126

O2 128Solubility product, calcium

phosphate 292Solutes, activity 24, 382Solutions 382Solvent drag 24, 156, 162Soma, nerve cell 42Somatic sensory functions 316Somatoliberin 232, 236, 270, 271,

282Somatomedins 282, 286Somatosensory centers 316, 324

Somatostatin (SIH) 84 ff., 232,236, 242, 270ff., 282 ff., 286 f.actions 286cotransmitter 84effects 286influence on glucagon secre-

tion 274, 286on insulin release 274, 284,

286pancreas 284receptors 55 Fsecond messenger 55 F, 276secretion 286stomach 236, 244

Somatotopic representation 324,326

Somatotropin (= STH = growthhormone = GH) 271, 280, 282,286, 290, 305influence on insulin release

286receptor 280release-inhibiting hormone

somatostatinreleasing hormone soma-

toliberinSomatovisceral senses 316Sone 368Sorbitol 264Sorting 12, 13 FSound 368

analysis 374central processing 374conduction 370, 372

air 370deafness 370

direction 374distance 374frequencies 368, 374intensity 368, 374loudness 368perception 368physics of 368pressure 368, 372, 374

level 368sensors 370, 372speech 376stimulus 368

Space travel 136Spatial orientation 348, 374Spatial summation 52, 322, 358,

360, 364Specific dynamic action diet-

induced thermogenesisSpectrum, visible 362Speech 238, 368, 376

fundamental frequencies 376Sperm 30, 304, 308

capacitation 304, 310emmision 310estrogens 304fertilization 310


436

Sperm (cont.)maturation 308motility 30, 58testosterone 308uterus 304f.

Spermatids 308Spermatocytes 308Spermatogonia 308Spermatogenesis 308Spermatozoa 308Spherical aberration 352Sphincter, esophagus 240

precapillar 190pupil 350

Spines, cerebral cortex 334Spinal cord 78, 312, 322, 324,

326, 328anterior roots 312dorsal roots 312grey matter 312hemisection 324ipsilateral paralysis 324reflexes 322segments 312transection 330white matter 312

ganglion 312, 320nerves 312shock 330

Spinocerebellum 328Sphingomyelin 14Spinnbarkeit of cervix mucus 300Spiral ganglion 374Spirometer 112, 116Spironolactone 174SPL (sound pressure level) 368Spleen 234

blood cell formation 88Spliceosome 10Splicing 8

variable 270Split-brain patient 342Spot, blind 354, 364Squalene 296Src (sarcoma) protein 280SRF somatoliberinSRH somatoliberinSRP (signal recognition particle)

12Standard bicarbonate concentra-

tion 142measurement 146

Standard temperature pressuredry (STPD) 112

Stapedius muscle 370Stapes 370Starch, digestion 248, 260Starling relationship 210Start codon 10Starvation 142Static (postural) work 74Statoliths 348

Steady state 41Stellate cells 330Stem cells 88, 308Step test, Margaria 76Stercobilin 252Stercobilinogen 252Stereocilia 348Stereognosis 316Steroid diabetes 298Steroid hormones steroidsSteroids 250, 252, 270, 306

biosynthesis 296degradation 296metabolism 296placenta 306producing glands 296receptors 280secretion 250, 252, 296sex, male 308

STH somatotropinStimulus 42

adequate 314contrast 360transduction 314transformation 314

Stokes–Einstein equation 20Stomach ( also gastric) 242,

244, 254, 260, 266anatomy 242chief cells 242digestive activity 260distal 234, 242emptying time 234

rate 242function 242gastric acid 244gastrin production 236glands 244juice 244motility 242mucus neck cells 242parietal cells 242, 244protein digestion 260proximal 234, 242secretion 244size 242ulcer 244

Stool 264, 266color 252

Stop codon 10Storage in memory 340

of energy 284STPD (standard temperature

pressure dry) 112Strabismus 366

amblyopia 366Strength, ionic 382

training 76Streptokinase 104Stress, CRH secretion 298

cortisol secretion 298hyperprolactinemia 305

Stretch sensors 216rectum 266

reflex 318, 330Stria vascularis372Striatum 328Stroke volume (SV), heart 76,

106, 188, 192, 204, 206increased afterload 206

preload 206physical work 74

Strophantin 196Struma 288STS somatostatinST segment (ECG) 198

elevation 200Stuart–Prower factor 102Subfornical organ 282Sublingual gland 238Submandibular gland 238Substance P 52, 86, 250, 320, 326,

328gallbladder 250

Substantia nigra 326, 328Subsynaptic Potential 50Successive contrast 358

color 360Succinate, tubular transport 160Suckling 238, 282, 305

reflex 322, 332Sucrose, digestion 260Sugar hormones glucocorti-

coids and cortisolSulci, brain 312Sulfate 156, 158, 160, 252, 264,

296conjugates 160, 252

carrier 252tubular secretion 156, 160steroids 296transcellular secretion 156,

160intestinal absorption 264

Sulfuric acid ( also sulfate) 142,176

Summation 322skeletal muscle 66spatial 322, 360, 364

neuron 52vision 358

temporal 322neuron 52vision 358

Superoxide dismutase 96Superposition, skeletal muscle

66Suppository 266Suppression, saccadic 366

T helper cells 98Supraventricular arrhythmias

202Surface sensitivity 316

tension 118


437

Surfactant (surface-active agent)118, 122hyperoxia 136

Suxamethonium 46, 56SV (stroke volume), heart 76, 106,

188, 192, 204, 206Swallowing 132, 238, 240, 242,

322S wave (ECG) 198Sweat 224, 226

glands 216, 224innervation 78, 79ff., 226

secretion 226SWS (slow-wave sleep) 336Symbiosis hypothesis, mitochon-

dria 12Sympathetic also adrenergic

and autonomicSympathetic nervous system,

activation 74constriction, veins 220flight or fight behavior 332gallbladder 250gastrointestinal tract 236heart 196physical work 74regulation of circulation 216saliva secretion 238

Symport, definition 26Synapse 42, 50ff., 268

axoaxonic 322electrical 18, 50latency 52postsynaptic receptors 50,

55 Ffunctions 42reciprocal 346valve-like function 48

Synaptic cleft 42, 50delay 52facilitation 50inhibition 322knobs 42pontentiation 50transmission 42

termination 52, 56Synapsin 50Synaptobrevin 50Synaptosome-associated protein

25 (SNAP-25) 50Synaptosome-associated protein

receptor (SNARE) 30Synaptotagmin 50Synchronization to day-night

cycle 336Syncytium 16, 18Synovial A-cells 96System, closed 40

conicellular 364endocrine 268ff.limbic 312, 332magnocellular 364

T

t (ton), unit 380T (multiple of a unit) 379T wave, ECG 198T3 triiodothyronine and thy-

roid hormonesT4 thyroxine and thyroid hor-

monesTachycardia 202, 220

atrial 202in shock 220sinus 202ventricular 202

Tachykinin 55 Fsecond messenger 278

Tachypnea 108Tactile motor function 316TAL (thick ascending limb) 162Tanning lamps, calcitriol synthe-

sis 294Target value (control circuit) 4Taste 344Taurine 250Tawara’s bundle branches 194TBG (thyroxine-binding globulin)

290TBPA (thyroxine-binding preal-

bumin) 290TCT (thyrocalcitonin) calci-

toninTears 350Tectorial membrane 370Tectum 328TEE (total energy expenditure)

228Telencephalon 312Temperature 381

body 132, 224, 226circadian variation 226,

387 Cregulation 224ff.skin 224unit 381

Temporal lobe system 340Temporal summation, visual

receptors 358Tendon, Golgi organs 318Tension time index, heart muscle

212Tensor tympani muscle 370Terminal button 42Testis 256, 270, 296, 308

FSH effect 308HDL receptors 256

Testosteron, 5-α-dihydro 308

Testosterone 270, 302, 308receptor 308synthesis 296

Tetanus 56skeletal muscle 66smooth muscle 70

Tetany 46, 292, 294Tetrahydrofolate 262Tetraiodothyronine (T4) 288Tetrodotoxin (TTX) 47 BTF (= Tissue factor) 104TFPI (= Tissue factor pathway

inhibitor) 104TGF(tubuloglomerular feedback)

174, 186TGF(transforming growth factor)-

receptor 280Thalamus 312, 320, 324, 344,

346, 374auditory pathway 374disinhibition 328visual pathway 364

Theca cells 302Theophylline 278Thermal balance 224

neural factors in 227 DThermodynamics, laws 38ff.Thermogenin 224, 232, 290Thermogenesis, non-shivering

226Thermoneutral zone 226Thermoregulation 224, 226

TRH release 288Thermosensors 226, 316

hypothalamus 332central 226

Thiamine, intestinal absorption262

Thiazide 162, 174Thick ascending limb (TAL)

162Thiocyanate 288Thiouracil 288Thirst 170, 226, 238

shock 220Thorax 108ff.Three-dimensional vision 366Threonin 228Threshold(s) 314, 346

aerobic 76anaerobic 72, 76audiogram 372auditory 368ff.potential 46, 48, 194recognition, smell 346

taste 344visual 358

Thrombin 102, 104Thrombocyte ( also platelet)

88, 102f.aggregation 102

inhibition 85, 104

System, closed (cont.)opened 40parvicellular 364

Systole 192


438

Thrombocytopathia 104Thrombocytopenia 100, 104Thrombopoietin 88, 148Thromboprotection 104Thrombosis 104Thromboxane A2 102, 216, 271,

278second messenger 278

Thrombus 102, 104Thymine 8Thymosin 268Thymus 88, 94Thyreotropic hormone-releasing

hormone (TRH) thyroliberinThyrocalcitonin calcitoninThyroglobulin 288Thyroid gland 36, 288

hormones 288nuclear receptors 280, 290actions 290control of release 290

parafollicular C cells 36, 288,294

peroxidase (TPO) 288Thyroid-stimulating hormone

thyrotropinThyroliberin 270, 271, 282, 288,

305second messenger 276, 278

Thyrotropic hormone (TSH) thyrotropin

Thyrotropin (TSH) 271, 282, 288receptor, autoantibody 290releasing hormone

thyroliberinsecond messenger 276, 278

Thyroxine (T4) 270, 288Thyroxine-binding globulin

(TBG) 290prealbumin (TBPA) 290

Tidal volume 106, 112, 114, 118,120

alveolar part (VA) 114, 120exercise 74maximum 77 Cphysical work 74training 76

Tiffeneau test 118Tight junction, function 18

renal tubule 154Timbre 368Tin (Sn) 228Tip links 348, 372Tissue factor (TF) 104Tissue factor pathway inhibitor

(= TFPI) 104Tissue, hormones 270

injury, blood clotting 103 B1plasminogen activator (tPA)

104respiration 106, 130thrombokinase 104

Tissue, hormones (cont.)thromboplastin 102

inhibitor 104Titin 60, 66Titratable acid 176Titration curve 386T-killer cells 94, 98, 234TLC (total lung capacity) 112,

113 ATNF(tumor necrosis factor)α,

effect on CRH secretion 298Tocopherol 262Tolerance, immunologic, periph-

eral 98central 94

Ton, unit 380Tone (sound) 368Tongue 344Tonicity 383f.Tonotopicity, auditory pathway

374Tonus, skeletal muscle 330

smooth muscle 70myogenic 70neurogenic 70

Tonus fibers 66neurogenic 70

Torr, conversion into SI unit 380Touch sensor 316tPA (tissue plasminogen activa-

tor) 104TPO (thyroid peroxidase) 288TPR (total peripheral resistance)

188 f.Trace elements 228Trachea 376Tractus, corticospinalis lateralis

326olfactoius 346opticus 364reticulospinalis lateralis 330

medialis 330retinohypothalamic 336rubrospinalis 330spinocerebellaris anterior 330spinoreticular 320spinothalamicus ventralis 320,

324vestibulospinalis 330

Training 76Tranexamic acid 104, 105 CTranscellular transport 18, 154Transcobalamine 92, 262Transcortin 92, 298Transcription factor, hormon-

activated 280, 290Transcytosis 18, 28Transducin 278, 354, 356, 358Transduction 314, 354

channels, hair cells 372photoelectric 354signal 276stimulus 314

Transfer ribonucleic acid tRNATransferrin 90Transformation 314Transforming growth factor

(TGF)- 280Transfusion, placental 222Translation 10Translocation, hormone-receptor

protein complex 280Translocator protein 12Transmembrane proteins 12Transmission, hereditary 8f.Transmitter neurotransmitterTransplant rejection, primary 100

immunosuppression 98Transport, active 26

axoplasmic 42, 58, 282convection 24electrogenic 26, 28electroneutral 28energy-dependent 26non-ionic 176paracellular 18, 154passive 20primary active 26rate, maximal (Jmax) 389f.rheogenic 26, 28saturable 28secondary active 26specific 28tertiary active 29 Btranscellular 18, 154transmembrane 16

all-trans-retinal 354Treadmill ergometry 76Trehalase 260Trehalose 260Tremor, intention 330

of resting 328TRF thyroliberinTRH thyroliberinTriacylglycerol 254, 256

absorption 254, 256chemical structure 229 Bdigestion 248, 256hydrolase 254lipoproteins 256source 259 Dfate 259 Dsynthesis, from free fatty ecids

258Triads 60, 62Trigger effect, Ca2, heart 62, 196Trigger zone, chemosensory 240Triglycerides TriacylglycerolTriiodothyronine (T3) 270, 280,

288Trimetaphan 82Tripalmitin 230Tripeptides, intestinal absorption

260Tricuspid valve 192Tritanomaly 362


439

Tritanopia 362tRNA (transfer ribonucleic acid) 8Tropomyosin 60Troponin 60, 62Troponin-tropomyosin complex

64Trypsin 248, 254, 260, 262

activation 249 DCCK secretion 248colipase activation 254phospholipase A2 activation

254effects 249 D

Trypsinogen 248Tryptophan 228TSC (thiazide sensitive co-trans-

porter) 162TSH thyrotropinT(ransversal tubules) system,

skeletal muscle 60TTX (Tetrodotoxin) 47 BTube, uterine 310, 311 ATuberculum olfactorium 346Tubocurarine 56, 82Tubular excretion 154

reabsorption 154, 158secretion 154

Tubule ( also Kidney), distal148

convoluted (DCT) 148driving forces for resorption

162epithelium, structure 154proximal 148, 162, 166, 176

convoluted (PCT) 164Tubules, longitudinal, skeletal

muscle 60seminiferous 308transverse, skeletal muscle 60

Tubulin 30, 58Tubuloglomerular feedback (TGF)

174, 186Tumor cells, immune defense 96Tumor necrosis factor (TNF)α

298Tuning, hearing 374T wave, ECG 198, 200Two-point discrimination 316,

324TXA2 (thromboxane A2) 102, 271Tympanic cavity 370Tyrosine 84

derivates, hormonal 270Tyrosine kinase-associated

receptors 280

U

UCP (uncoupling protein) 232UDP(uridindinucleotid)-glu-

curonic acid 252Ulcer, gastric 244

Ultrafiltrate 154Ultrafiltration coefficient 152Umami 344Umbilical artery 222

vein 222Unconsciousness, anoxia 130Uncoupling protein (UCP) 232Uniporter 28Units, basic 378

derived from SI units 378information 314multiples 379SI 378submultiples 379

Unmyelinated nerve fibers 48Uracil 8Urate uric acidUrea 158, 166, 178

carrier 166excretion 166production 178reabsorption, renal 156, 158recirculation 166urine concentration 166

Ureter 148innervation 79ff.

Urethra 310Uric acid 158, 178

excretion, renal 176reabsorption 156, 158secretion 156,

Urinary bladder 70, 148, 310innervation 79ff.

calculi 158, 180Urine 148ff., 186

Ca2 292concentration mechanism 164,

166disorders 166

flow rate 15217-ketosteroids 296NH

4 178osmolality 166pH 156, 176, 178primary 164titratable acid 176volume 152

Urobilinogen 252Urokinase 104UT1 (urea transporter Typ 1) 166UT2 166Uterine tube 310, 311 AUterus 70, 305, 306

α1-adrenoceptor 306contractions 282erection 310estrogens 304gap junctions 306menstrual cycle 300muscle 305oxytocin 305progesteron 305prostaglandins 306, 310

UTP (uridine triphosphate) 252Utricle 348UV light, exposure 294

formation of vitamin D 294deficiency 294

Uvula, cerebellum 328

V

V.

O2 O2 utilizationVA (alveolar part of tidal volume)

114VD (dead space volume) 114VE (expiratory volume) 114VT (tidal Volume) 114Vaccination 94Vagina 304, 310

estrogens 304pH 304

Vagus nerve ( also cholinergic)244, 250, 376

val, unit 381Valence, ion 381Valine 228Valsalva’s maneuver 116Vanadium (V) 228Vanilloid receptor Typ 1 (VR1)

316Van’t Hoff’s law 24, 389, 394

Staverman 24Vas afferens, glomerulus 148, 186

deferens 310efferens, glomerulus 148, 186

Vasa recta, renal medulla 150,164

Vasoactive intestinal peptide(VIP) 52, 86, 234, 236, 238,264, 276, 282

cerebral cortex 334neurons 242rectum 266second messenger 276

substances 214Vasoconstriction 122, 214, 215 B,

216, 222cortisol 298hypoxic 122, 214, 222

fetus 223 Cshock 220thermoregulation 226veins 220

Vasodilatation 214, 215 B, 216,280NO 280thermoregulation 226

Vasomotion 210Vasopressin ( also adiuretin)

166, 276, 278Vegetarian diet 142Vectorcardiogram 198Vein(s) 190, 206


440

Vein(s) (cont.)pulmonary 188umbilical 222valves 206

Velocity, blood flow 190of conduction, in nerve fibres

48detectors 316, 318linear, unitvolume 380

Venae cavae 190Venoles 189 A

postcapillary 190Venous central pressure 188, 192,

206, 220circulation 206flow 206pressure 206

curve 193 Aindifference point 206influence on capillary fluid

exchange 210shock 220

return 110, 206artificial respiration 110Bainbridge reflex 218driving forces 206respiration 206

artificial 110Ventilation ( also lung) 74, 106,

108, 120, 130alveolar 106, 120

high altitude 136peak expiratory pressure 116

inspiratory pressure 116pressure differences 108

dead space 106, 114diving 134driving force for 108exercise 74high altitude 136mechanical 110muscle 108, 132/perfusion ratio 122regulation 126

chemosensors 126rhythm generator 132total 106

acidosis 142hypoxia 136maximum 77 C

endurance athletes 77physical work 74hypoxia 136

venous return 206Ventilation–perfusion ratio 122Ventricles, cerebrospinal fluid

312Ventricular ( also heart)

arrhythmias 202fibrillation 202pressure 192, 204

Ventricular arrhythmias (cont.)tachycardia 202volume 204work diagram 204

Veratridine 47 BVerbalization 340Vergence, eye movement 366Vermis 328Vertical type (heart) 200Vertigo 330, 348Very low density lipoproteins

(VLDL) 256, 258, 262Vesicles 28

chromaffin 84secretory 12, 30

Vessels, capacitance 190wall tension 190

Vestibular ganglia 348nuclei 330, 348organ 348reflex 348

Vestibulocerebellum 328Viagra (sildenafilcitrate)

280Vibration, sensors 316Vieth–Müller horopter 366Villi, intestinal 246Vimentin 14VIP vasoactive intestinal pep-

tideVirilization 308Virus, immune defense 94, 96,

98Visceral afferents 78, 236Viscosity, blood 92, 190Viscous-isotropic phase, lipid

digestion 254Visible spectrum 362Vision ( also eye and retina)

352binocular 364, 366color 362day 354

threshold 358depth 366dim-light 354movement 364night 354photopic 354scotopic 354three dimensional 366

Visual ( also eye and retina)acuity 354, 360, 364cortex 364field 364

binocular 366pathways 364pigment 350, 354, 356

role in adaptation 356sensors, spatial summation

358temporal summation 358

Visual acuity (cont.)thresholds 358

absolute 358Vital capacity (VC) 112

forced (FVC) 118Vitamin A 228, 254, 262, 356

deficiency 356intestinal absorption 262

B1 (thiamin) 228, 262B2 (riboflavin) 228, 262B6 (pyridoxin) 228, 262B12 (cobalamines) 90, 228

absorption 262C 90, 228, 262

intestinal absorption 262renal reabsorption 156

D 228, 254, 294daily intake 294deficiency 264, 294

optimal 392binding protein (DBP) 158,

294D2 (= ergocalciferol) 228, 294D3 (= cholecalciferol = calciol)

228, 262, 294E (D-α-tocopherol) 228, 254,

262H (biotin) 228, 262K (Phytonadion) 102, 104, 228,

254, 266antagonists 104deficiency 104

K1 228, 262K2 228, 262

Vitamins 228absorption 262deficiencies 228fat-soluble 228, 254, 262,

304toxiciticy 228water-soluble 262

Vitrous body 350opacification 136

VLA-4 (adhesion molecule) 98VLDL (very low density lipo-

proteins) 256, 258, 262estrogen effect 304remnants 256

Vocal cord 376paralysis 118

Voice 376change 308

Volume clearance, esophagus240deficit 170, 175 E

compensation 220shock 220

excess 170, 175 Eextracellular ECF 168hypertension 218interstitial 168intracellular ICF 168


441

Volume clearance, esophagus(cont.)ratio 382regulation 170unit 378velocity 380

Voluntary motor function 326inhibition 328

Voltage clamp 34Vomiting 78, 142, 240

center 240salt and water homeostasis

175 Evon Willebrand factor 102, 103 AVowels 376V1 receptor (ADH), second mes-

senger 278V2 receptor (ADH) 24

second messenger 278VR1 receptor (vanilloid receptor

type 1) 316Vulnerable phase (myocard) 202

W

W (watt), unit 380f.Wakefulness 324, 334Warfarin 104Warm sensors 224ff., 316Water H2OWatt second, unit 380f.

Waves, EEG 334paroxysmal 334slow, intestine 246stomach motiltity 242

W cells, retina 364Weber’s rule 358Weber’s test 370Weight, unit 380Wernicke’s area 376Whispering 376White matter, spinal cord 312Wilson leads (ECG) 198Window, oval/round 370, 372Wind space 376Windkessel 190, 204Withdrawal reflex 322Work, muscle 74

negative dynamic 74physical 74, 142positive dynamic 74pressure/volume, heart 204static postural 74unit 380

Writing 332, 340Ws, unit 380

X

X cells, retina 364X-chromosome 8, 309 B,CXenobiotics 160

Y

Yard, conversion into SI unit 378Yawning 132Y cells, retina 364Y-chromosome 8, 309 B,CYohimbin 87 B

Z

Zeitgeber, external 336Zero-current potential 34Z-plates, muscle 60Zona fasciculata adrenal cor-

texglomerulosa adrenal cortexpellucida 310

reaction 310reticularis adrenal cortex

Zone, comfort 226, 228thermoneutral 226

Zonulae occludentes Tightjunctions 18

Zonular fibers 350


287 11 Hormone s and R eproduc tion Plate 11.10 ... - ENPAB

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Transcript of 287 11 Hormone s and R eproduc tion Plate 11.10 ... - ENPAB