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FISIOLOGI GINJAL
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Fisiologi GINJAL
1. Regulation of body fluid osmolality and volume
2. Regulation of electrolyte balance
3. Regulation of acid-base balance
4. Excretion of metabolic product and foreignsubstance
5. Production and secretion of hormones
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PHYSIOLOGY OF
BODY FLUID
1.PHYSICOCHEMICAL PROPERTIES
OF ELECTROLYTE SOLUTION
2.VOLUME OF BODY FLUID
COMPARTMENTS
3.MESASUREMENT OF BODY FLUID
VOLUME
4.COMPOSITION OF BODY FLUID
COMPARTMENT
5.FLUID EXCHANE
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VOLUMES OF BODY FLUID
COMPARTMENT
Total body water(TBW)=0,6BW=42 L
ECF=1/3 TBW=14LICF=2/3 TBW=28L
Interstial fluid
ECF =10,5L
Plasma=1/4ecf
3.5L
Cell mbr
Cap. endotel
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FLUID EXCHANG BETWEEN BODY
FLUID COMPARTMEN
Capillary fluid exchange :
Fluid movement=Kf[(Pc +Oi)- (Pt=Oc)]
Kf=filtration coeff of the cap. Wall
Pc=hydrostatic pressure within the cap. Lumen.
Oc= oncotic pressue of the plasma.Pt = hydrostatic pressure of the interstitium
Oi = oncotic pressure of the interstitial fluid.
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Celluler fluid exchange :
osmotic pressure differencebetween ECF and ICF are
responsible for fluid movement
between these compartment
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ALTERATION IN STARLING FORCE
. Increasing in capillary hydrostatic (Pc) Decrease in plasma oncotic pressure(Oc)
Lymphatic obstruction.
Increase in capillary permiabelity.
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THE ROLE OF THE KIDNEY
VENOUS PRESSURE
CAPILLARY HYDROS
PRESSURE
MOVE OF FLUID INTO
INTERSTITIUM
PLASMA VOLUME
VOL RECEPTORS
DETECT ECF
NaCl and H2O
Reabsorption by
The kidney
Restore plasma
volume
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STRUCTURE AND FUNCTION OF
THE KIDNEYS AND THE LOWER
URINARY TRACT
OBYECTIVES
1.Describe the location of the kidneys and their gross anatomicalfeature.
2.Describe the defferent parts of the nephron and their location
within the cortex and medulla.
3.Identify the components of the glomerulus and the cell types
located in each component.
4.Describe the structur of glomerular capillaries and identify
which structures are filtration barriers to plasma proteins.
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OBYECTIVE
5.Describe the components of the yuxtaglomerular
apparatus and the cells located in each component
6.Describe the bood supply to the kidneys.
7.Describe the innervation of the kidneys.
8.Describe the anatomy and physiology of thelower urinary tract.
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STRUCTURE OF THE KIDNEYS
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Yuxtaglom: is one component of an important feedback mechanism
that is involved in the autoregulation of RBF and GFR
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GLOMERULAR FILTRATION
AND RENAL BLOOD FLOW
OBJECTIVES1. Describe the concepts of mass balance and clearence
and explain how they are used to analyze renal trnsport
2. Define the three general process by which substances arehandled by the kidneys:glom. Filtration, tub.reabsorb and
tub. Secretion.
3. Explain the use of inulin and creatinine clearence to mea-
sure the GFR.
4. Explain the use of p-aminohippuric acid (PAH) clearence
to measure renal plasma flow(RPF)
5. Describe the composition of theglom.ultrafiltrate, and
identify which molecule are not filtered by the glomerulus.
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OBJECTIVES (cont.)
6. Explain how the los of negative charges on the glom.
capillaries results in proteinuri.7.Describe starling forces involved in the formation of
the glom. Ultrafiltrate , and explain how charges in each
force affect the glom.filtration rate.
8.Explain how the starling force change along the length
of the glom. Capillaries.
9.Describe how changes in the renal plasma flow rate
influence the GFR.
10.Explain autoregulation pf renal blood flow and the GFR
and identify the factors responsible for autoregulation11.Identify the major hormones that influence RBF.
12.Explain how and why hormones influence RBF despite
autoregulation.
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RENAL CLEARENCE
GLOMERULAR FILTRATION
REABSORBTION
SECRETION
C x= Ux X V
Px
Cx=clearence x
Ux=conc. x in
urine
V= urine flowrate/minute
P= conc. x in
plasma
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MEASUREMENT OF GFR
CLEARENCE OF INULIN
Amount filtered = amount excreted
GFR X Pin = Uin X V
GFR = Uin X V
Pin
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MEASUREMENT OF RENAL PLASMA FLOW
AND RENAL BLOOD FLOW.
RPF= CLEARENCE OF PAH PAH LOW 0,12mg/ml
RPF = Upah X V
P pah
RBF = RPF
1 - HCT
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REQUIREMENTS FOR USE OF A SUBSTANCE
TO MEASURE GFR
1. The substance must be freely filtered by the
glomerulus.
2. The substance must not be reabsorbed or
secreted by the nephron .
3. The substance must not be metabolized or
produce by the kidney.4. The substance must not alter GFR
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RENAL BLOOD FLOW
RBF = 25% CARDIAC OUT PUT (1.25 L/min)
THE IMPORTANT FUCTION OF RBF INCLUDING :
1. Determining the GFR
2. Modifying the rate of solute and water reabsorption by
the proximal tubule.
3. Participating in the concentration and dilution of urine.
4. Delivering oxygen, nutrients and hormones to the nephroncell and returning CO2 and reabsorbed fluid and solute to
general circulation.
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REGULATION OF RENAL BLOOD FLOW
hemorrhage
Arterial blood pressure
Intra renal receptors
Renin secretion
Plasma renin
Plasma angiotensin
Constriction of
Renal arterioles
RBF and GFR
Activity of renal
Symphatic nerves
Carotic sinus andAortic arch reflexs
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RENAL TRANSPORT MECHANISM
NaCL AND WATER REABSORPTION ALONG THE NEPHRON
OBJECTIVE
1.Explain the three processes involved in the production of urine
a. filtration b. reabsorption c. secretion..
2.Describe the magnitude of the processes of filtration and reab-sorption by the nephron.
3.Describe the composition of normal urine.
4.explain the basic transport mechanisms present in each nephron
segment.5.Describe how water reabsorption is coupled to Na+ reabsorp
tion in the proximal tubule.
6.Explain how solutes, but not water , are reabsorbed by the thick
ascending limb of Henles loop.
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OBJECTIVE - COUNT.
7. Describe how Starling forces regulate solute and
water reabsorption across the proximal tubule.
8. Explain glomerulotubular balance and its phy-siological significance .
9. Identify the major hormones that regulate NaCl
and water reabsorption by its nephron segment
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COMPOSITION OF URINE
SUBSTANCE CONCENTRATION
Na+ 50 - 150 meq/l
K+ 20 - 70 meq/l
NH4- 30 - 50 meq/l
Ca++ 5 - 12 meq/lMg++ 2 - 18 meq/l
Cl - 50 - 130 meq/l
PO4 20 - 40 meq/l
Urea 200400 mM
Kreatinin 6 - 20 mM
pH 5 - 7
Osmolality 500 - 800 mOsm/Kg H2O
others 0
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Tubuler fluid
Paracelluler
pathway
Transcelluler
pathway
Tight
junction
Apical cell
membrane
Lateral intercellular space
blood
Na+
K+
Na+
Na+
Basolateral
membrane
Capillary
Basement
membrane
ATP
ATP
ATP
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Tubular fluidblood
Na+
X
Na+H+
HCO3
K+
Na+ATP
X
CO2 + H2O
CA
First half of proximal tubule
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Tubular fluid
blood
NaCl
H2O
Na+
Cl-
orga
nics
H2O
0rganics Na+ Cl-
org
anic Na+ Cl-
organics Na+ Cl-
H2O
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Tubular fluid
CL-
Na+
Na+ Na+ Na+
H+
Hbase
Base
Cl-
Cl-
Na+
Cl-
H base
K+ATP
K+
Cl-
blood
Second half of proximal tubule
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Some organic secreted by the proximal tubule
Endogenous anions Drug
cAMP acetazolamideBile salts chlorothiazide
Hippurate(PAH) furosemide
Oxalate penicillin
Prostaglandins probenecid
Urate salicylate(aspirin)
hidrochlorthiazide
bumetanide
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Some organic cations secreted by the
proximal tubule
Endogenous cations Drugs
Creatinine atropineDopamine isoproterenol
Epinephrine cimetidine
Norepinephrine morphine
quinineamiloride
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Tubular
fluid
A-
PAH
(OA-)
Na+
K+
Na+
Di/tri carboxylaseDi/tri carboxylase
PAH(OA-)
ATP
BLOOD
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REGULATION OF ECF
OBJECTIVE
1. Recognize the vital role Na plays in determining the
volume of the ECF compartment.
2. Explain the concept of effective circulating volume
and its role in the regulation of renal Na+ excretion.
3. Describe the mechanisms by which the body monitors
the effective circulating volume ( volume receptors)
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OBJECTIVE cont.
4. Identify the major signals acting on the kidney to alter
their excretion of Na+.
5. Describe the regulation of Na+ reabsorption in each of
the various portion of the nephron and how changes in
effective circulating volume affect these regulatory
mechanisms.
6. Explain the pathophysiology of edema formation and the
role of Na+ retention by the kidneys
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CONCEPT OF EFFECTIVE CIRCULATING VOLUME
Effective circulating
volume
Volume sensors
Kidney
Alteration in
NaCl excretion
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ECF VOLUME RECEPTORS
Vasculer
low pressure
cardiac atria
pulmonary vasculature
high pressure
carotid sinus
aortic arch
yuxtaglomeruler apparatus
of the kidney (afferent arteriole)Central nervous system
Hepatic
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SIGNALS INVOLVED IN THE
CONTROL OF RENAL NaCl AND
WATER EXCRETION
Renal sympathetic nerves ( activity
NaCl excretion )
1. Glomerular filtration rate
2. Renin secretion
3. Prox, tubule and thick ascending limb
of Henles loop NaCl reabsorption
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SIGNALS INVOLVED IN THE
CONTROL OF RENAL NaCl AND
WATER EXCRETION cont
ReninAngiotensinaldosteron
( secretion : NaCl axcretion )
1. Angiotensin II levels stimulate prox.
tubule NaCl reabsorption.
2. Aldosteron levels stimulate thick
ascend limb of Henles loop andcollect.Duct NaCl reabsorption.
3. ADH secretion
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SIGNAL INVOLVED IN THE
CONTROL OF RENAL NaCl
AND WATER EXCRETION
cont
Atrial Natriuretic Peptide ( Secretion : NaCl
excretion)
1. GFR
2. Renin secretion.3. Aldosteron secretion
4. NaCl reabsorption by the collecting duct.
5. ADH scretion
ADH ( secretion : H2O and NaCl excretion )
1. H2O reabsorption by the collecting duct.
2. NaCl reabsorption by the thick asc,of Henles loop
3. NaCl reabsorption by the collecting duct.
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Brain ADH
Angiotensin II
Lung Ang II
Adrenal
Aldosteron
Kidney
Na+ excretion
H2O excretion
Angiotensin I
Angiotensinogen
Hepar
Renin
RAAS
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RENIN
Three factors play an important role in stimulatingrenin secretion :
1. Perfussion presure
2. Sympathetic nerve activity
3. Delivery of NaCl to the macula densa
ANP antagonize those of RAAS
1. Vasodelation of aff and eff ---GFR
2. Inhibition of renin secretion3. Inhibition of aldosteron secretion
4. Inhibition of NaCl reabsorption
5. Inhibition of secretion and activity of ADH
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CONTROL OF Na+ EXCRETION WITH
NORMAL ECF
EUVOLEMIA: NaCl ingested and axcreted--- balance
1.Na+ reabsorption by the proximal tubule, Henles
loop , and the distal tubule is regulate so that a re-latively constan portion of the filtered load of Na+
is diliveredto the collecting duct..
2.Reabsorption of Na+ by the collecting duct is regu
lated such that the amount of Na+ excreted in theurine matches the amount ingested in the diet.
------------ maintain the euvolemic state.
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CONTROL OF Na+ EXCRETION WITH
INCREASE ECV
The signal acting on the kidneys include:
1. Activity of the renal sympathetic
2. Release of ANP.
3. Inhibition of ADH secretion.
4. Renin secretion
Three general responses to an increases in ECV :
1. GFR increases
2. Reabsorption of Na+ decreases in the prox.tubule.
3. Reabsorption of Na+ decreases in the collec.
duct.
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CONTROL OF Na+ EXCRETION WITH
DECREASES ECV
The signal acting on kidneys include :
1. Increases renal sympathetic activity.
2. Increases secretion of renin.
3. Inhibition of ANP secretion.
4. Stimulation of ADH secretion.
Three general respons to decreases ECV:
1. GFR decreases.
2. Increases of Na+ reabsorption in the prox.tubule.
3. Increases of Na+ reabsorption in the
collecting duct.
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REGULATION OF ACID-BASE
BALANCE
Objective1. Explain the chemistry of the CO2/HCO3 buffer system
and its role as the primary physiological buffer of ECF.
2. Describe the metabolic process that produce acid and al
kali and their net effect on systemic acid-base balance.Distinguish between volatile and non volatile acids.
3. Explain the concept of net acid excretion by the kidneys
and the importance of urinary buffers in this process.
4. Describe the mechanisms of H+ secretion in the various
segment s of the nephron and how these mechanisms
are regulated.
5. Distinguish between the reabsorption of filtered HCO3
and the formation of new HCO3.
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REGULATION OF ACID-BASE
BALANCE objective cont
6. Describe the mechanisms of ammonia production and
excretion by the kidneys, and explain their importance
in renal acid exfretion and thus systemic A-B balance.
7. Describe the three general mechanisms used by the bo-
dyto defend against acid-base disturbances:
a. intra and extracelluler buffering.
b. respiratory compensation
c. renal compensation.
8. Distinguish between simple metabolic and respiratoryacid-base disorders and the bodys response to them.
9. Analyze acid-base disorders and distinguis between
simple and mixed disorders.
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HENDERSON-HASSELBALCH
pH = 6,1 + log HCO3
pCO2
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Metabolic production of non volatile
Acid and alkali from the diet.
Food source acid/alkali quantity
produced (mEq/day)
carbohydrates normally (none) 0
fats normally (none) 0
amino acidsa.sulfur containing
(cysteine,methionine) H2SO4
b.cationic (lysine, argi
nine, histidine) HCL 100
c.anionic (aspartate,glutamate) HCO3-
Organic anions HCO3- -60
Phosphate H3PO4 30
TOTAL 70
PROXIMAL TUBULE
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Tubular fluidblood
Na
HCO3 + H+
H2CO3
CA
H2O+CO2 CO2 + H2O
CA
H+
ATP
Na+
K+ ATP
3Na+
HCO3
Cl-
PROXIMAL TUBULE85%
COLLECTING DUCT
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HCO3 + H+
H2CO3
CO2 + H2O
CO2 + H2O
CAH+ HCO3
Cl-
COLLECTING DUCT
5%
THICK ASC. LIMB 10%
F t l ti H+ ti
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Factors regulating H+ secretion
(HCO3 reabsorption) by the nephron
Factors nephron site of action
Increasing H+ secretion
increase in filtered load of HCO3 proximal tubule
Decrease in ECF volume proximal tubule
Decrease in plasma HCO3 ( pH ) prox.,tub.collect.Increase in blood Pco2 idem
Aldosteron collecting duct.
Decreasing H+ secretionDecrease in filtered load of HCO3 proximal tubule
Increase in ECF volume proximal tubule
Incraese in plasma HCO3 ( pH ) prox, tub collect.
Decrease in blood Pco2 idem
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RESPONSE TO ACID-BASE DISORDERS
1. ECF AND ICF BUFFERING
2. VENTILATORY RATE OF THE LUNGS
3. RENAL ACID EXCRETION
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SIMPLE ACID-BASE DISORDERS
Characteristics of simple acid-base disorders.
Diorders plasma pH primary defense
alteration mechanism
Metab.acidosis plasma HCO3 ICF and ECF
buffer, Pco2
Metab.alkalosis plasma HCO3 idem. Pco2
Respir. Acidosis Pco2 ICF buffers,
renal H excr.
Respir. Alkalosis Pco2 ICF buffers ,
renal H excr.
Approach for analysis of simple acid base disorders
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Approach for analysis of simple acid-base disorders
Arterial blood sample
pH 7,40
Alkalosis
HCO3 > 24mEq/L Pco2 < 40 mmHg
Metabolic .alkalosis respiratory alkalosis
Pco2 < 40 mmHg HCO3 > 24 mEq/L Pco2 > 40 mmHg HCO3 < 24 mEq/L
Respiratory compensation renal compensation respiratory compensation renal compensation
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REGULATION OF POTASSIUM BALANCE
OBJECTIVES
1.Explain how the body maintains K+ homeostasis
2.Describe the distribution of K+ within the body compart.
3.Identify the hormon and factors that regulate plaqsma K+levels.
4.Describe the transport pattern of K+ along the nephron.
5.Describe the cellular mechanism of K+ secretion by
distal tubule and collecting duct, and how secretion is
regulated.
6.Explain how plasma K+ levels ,aldosteron, ADH, tubular
fluid flow rate , acid-base balance , and Na+ concentra-
tion in tubular fluid influence K+ secretion.