LO 1

LO 1AnatomiAnatomi Kelenjar AdrenalLetaknya di superomedial ginjalDibungkus oleh fascia renalis, tetapi dipisahkan dari ginjal oleh jaringan lemak perirenal.Sisi kanan bentuk piramidSisi kiri bentuk bulan sabit

Korteks AdrenalBagian luar kelenjar adrenalDari mesodermMenghasilkan steroid hormon (glucocorticoid, mineralocorticoid, sex steroids)

Medula AdrenalBagian dalam kelenjar adrenalDari sel krista neuralMenghasilkan hormon epinephrine dan norepinephrine

Vaskularisasi dan InervasiPerdarahan:arteri suprarenalis superior dari arteri phrenica inferiorarteri suprarenalis media dari aorta abdominalisarteri suprarenalis inferior dari arteri renalisVena:V.suprarenalis dextra V.cava inferiorV.suprarenalis sinistra + V.phrenica inferior V.renalis sinistraPersarafan:Plexus coeliacus & abdominopelvic

LO 2Histologi

Histologi Kelenjar AdrenalKorteks AdrenalMedula AdrenalTerdiri atas deretan sel kromafin, dengan sinusoid venosa lebar diantaranya.Terdapat sekelompok kecil sel sarafMenghasilkan adrenalin & nor adrenalin Sitoplasma mengandung banyak vesikel berisikan sekret ini.Sel tersusun dalam deretan setebal satu sel pada tepi sinusoid venosa.

LO 3Faal

Hormon Korteks AdrenalHormon hormon adrenokorteks steroid lipofilik; diangkut oleh protein plasma dalam darah

60% aldosteron dalam darah terikat ke protein (terutama albumin nonspesifik)90% kortisol terikat ke protein plasma spesifik corticosteroid-binding globulin / transcortin98% DHEA terikat albuminPada keadaan normal, androgen & estrogen adrenal tdk cukup banyak / kuat utk menimbulkan efek maskulinisasi / feminiasiDHEA (dehidroepiandrosteron) efek bermakna pada wanita pertumbuhan rambut pubis & ketiak, peningkatan lonjakan pertumbuhan pubertas, perkembangan & pemeliharaan dorongan seks wanita

Sintesis Hormon AdrenokorteksPengaruh Mineralokortikoid~aldosteronAktivitas utama tubulus distal ginjal retensi Na+ & eliminasi K+Retensi Na+ memicu retensi osmotik H2O volume CES>> tekanan darah >>

Sangat esensial tanpa aldosteron meninggal akibat syok sirkulasi

Stimulasi aldosteronSRAA (o/ krn penurunan Na+ & tekanan darah)Peningkatan konsentrasi K+ plasmaPengaruh Glukokortikoid ~kortisol

Efek metabolikMerangsang glukoneogenesis hatiMenghambat penyerapan glukosa o/ banyak jaringan kecuali otakMerangsang penguraian protein di banyak jaringan terutama otot asam amino bebas > glukoneogenesis Meningkatkan lipolisis asam lemak bebas > sumber bahan bakar pengganti glukosaEfek permisifKortisol hrs adekuat agar katekolamin dapat memicu vasokonstriksi

Peran dalam adaptasi thdp stresStresor >Fisik (trauma, pembedahan, panas, dingin hebat)Kimia (penurunan pasokan O2, ketidakseimbangan asam basa)Fisiologis (olahraga berat, syok perdarahan, nyeri)Psikologis / emosi (cemas, ketakutan, kesedihan)Sosial (konflik pribadi, perubahan gaya hidup)Pengaruh fisiologis lainMengubah suasana hati & prilaku

Efek anti-inflamasi & imunosupresifMenghambat hamir semua respon peradanganMenekan sistem imunitas normal tubuh, efek inhibitorik pada sistem imun tubuh keseluruhan anti alergi, rentan infeksi

Agar sekresi kortisol relatif konstan letupan letupan sekresi tingkat sedang & dipisahkan oleh periode hening (sekresi minimal/tidak ada)Jumlah total kortisol dapat diubah dgn mengubah frekuensi letupan sekretorik

Faktor tambahan yg mempengaruhi sekresi irama diurnal & stres

Kelainan sekresi hormon adrenokorteksHipersekresi aldosteronHiperaldosteronisme primer ~ sindrom ConnHiperaldosteronisme sekunder

Gejala hipernatremia & hipokalemiaHipersekresi kortisol (sindrom cushing)Stimulasi berlebihan korteks adrenal oleh CRH dan atau ACTHTumor adrenal yg secara tdk terkontrol menghasilkan kortisol yg tdk tergantung ACTHTumor penghasil ACTH terutama di paru

Gejala moon face, buffalo hump, striae, lebam & ekimosis, mudah fraktur

Hipersekresi androgen adrenalPseudohermafroditisme wanitaPseudopubertas prekoks

Insufisiensi adrenokorteksPrimer (Addison disease)Destruksi autoimun atrofi idiopatik kelenjar adrenal sekresi hormon adrenal asam lemak bebas >Laju metabolisme >Efek lainKeadaan terjaga & kewaspadaan SSPKeringat > pengeluaran panasMembesarkan pupil, mendatarkan lensa mataStimulasi katekolamin Dikontrol o/ masukan simpatis; peningkatan impuls simpatis ke kelenjarFaktor2 utama yg mengontrolKondisi stresTrauma fisik atau psikologis, perdarahan, penyakit, olahraga, hipoksia (O2 arteri rendah), pajanan dingin, hipoglikemiaRespons terhadap stress

LO 4Biokimia

CATECHOLAMINESFamily of bioamines and are secretory products of the sympathoadrenal systemEpinephrine (8085% of stored catecholamines) is synthesized primarily in the cells of the adrenal medullaNorepinephrine (1520% of stored catecholamines) is synthesized and stored not only in the adrenal medulla but also in various areas of the central nervous systemBiosynthesis of cathecolamines

Secretion of cathecolaminesStimulators pain, hemorrhage, exercise, hypoglycemia, and hypoxiaHormon releaseStress nerve impulses emanating from adrenergic nuclei in the hypothalamus release of the neurotransmitter acetylcholine from preganglionic neurons that innervate the adrenomedullary cells rapid entry of extracellular calcium (Ca2) into the cytosol synthesis and release of epinephrine and norepinephrine from the chromaffin granulesEmanating = keluar39Physiological effects

Inactivation of cathecolamines

Renin-angiotensin-aldosteron system

GLUCOCORTICOIDSCortisol (hydrocortisone) is the major physiologic glucocorticoid (GC) in humans, although corticosterone also has some glucocorticoid activityBiosynthesis of glucocorticoids , adrenal androgen & mineralocorticoids

Regulation of glucocorticoids secretion

Physiological effects of glucocorticoids

Fuel metabolism effect of GCLO 5Kelainan kelenjar adrenalHyperfunction of adrenal cortexCushings syndromeAldosteronism Syndrome of adrenal androgen excessCushings syndromeEtiologyAdrenal hyperplasiaSecondary to pituitary ACTH overproductionPituitary-hypothalamic dysfunctionPituitary ACTH-producing micro- or macroadenomasSecondary to ACTH or CRH-producing nonendocrine tumors (bronchogenic carcinoma, carcinoid of the thymus, pancreatic carcinoma, bronchial adenoma)Adrenal macronodular hyperplasia (including ectopic expression of GIP receptors in the adrenal cortex)Adrenal micronodular dysplasiaSporadicFamilial (Carney's syndrome)Adrenal neoplasiaAdenomaCarcinomaExogenous, iatrogenic causes Prolonged use of glucocorticoidsProlonged use of ACTH Clinical signs

Diagnostic tests

Pituitary cushing syndrome ACTH >; cant be suppressed with low dose dexamethasone Ectopic ACTH secretion ACTH >; completely insensitive to low or high doses of exogenous dexamethasoneAdrenal tumor cushing syndrome ACTH < (feedback mechanism

Screening overnight dexamethasone suppression test; measurement of a 24-h urine free cortisol can also be used as a screening test (>140 nmol/d (50 g/d) is suggestive of Cushing's syndrome)Radiologic test CT scan of the abdomen adrenal tumors and for diagnosing bilateral hyperplasia

Pituitary MRI hypersecretion of pituitary ACTH

Diagnosis

DDPseudo-cushings syndromeobesity, chronic alcoholism, depression, and acute illness of any type abnormalities in steroid output:elevated urine cortisolblunted circadian rhythm of cortisol levelsresistance to suppression using the overnight dexamethasone test

TreatmentAdrenal neoplasm resected using laparoscopic techniquesmitotane (o,p'-DDD), an isomer of the insecticide DDT Mitotane suppresses cortisol production and decreases plasma and urine steroid levelsreceive long-term glucocorticoid maintenance therapy, and, in some, mineralocorticoid replacement is appropriateBilateral hyperplasia surgical removal ACTH- or CRH-producing tumors

Aldosteronism Primary Aldosteronism with an Adrenal TumorPrimary Aldosteronism without an Adrenal TumorSecondary AldosteronismPrimary Aldosteronism with an Adrenal Tumoraldosterone-producing adrenal adenoma excessive and inappropriate aldosterone production (Conns syndrome)Unilateral adenoma; usually small and may occur on either side

twice as common in women as in menusually occurs between the ages of 30 and 50, and is present in ~1% of unselected hypertensive patientsPrimary Aldosteronism Without an Adrenal Tumor~idiopathic hyperaldosteronism, and/or nodular hyperplasiae/ bilateral cortical nodular hyperplasia; a solitary adenoma is not found at surgery

Signs & symptomsdiastolic hypertension severe, headachePotassium depletion muscle weakness and fatigue Polyuria, polydipsiastructural damage to the cerebral circulation, retinal vasculature, and kidney Proteinuria (50%), renal failure (5%)

Pathophysiology

Laboratory findingsHypokalemia may be severe ( virilization

Type"pure" syndromes of virilization "mixed" syndromes associated with excessive glucocorticoids and Cushing's syndromePathophysiology

Most etiology Congenital adrenal hyperplasia (21-Hydroxylase Deficiency) ->Neonate with ambiguous genitaliaHypofunction of the Adrenal CortexPrimary Adrenal InsuffiencySecondary Adrenal InsufficiencyHypoaldosteronism Primary Adrenocortical Deficiency (Addison's Disease)Incidence relatively rare, may occur at any age, and affect both sexes equally

Etiology

Signs & symptoms

Laboratory findingsserum sodium, chloride, and bicarbonate levels are reduced, and the serum potassium level is elevatedextravascular sodium loss depletes ECFV and accentuates hypotensionElevated plasma vasopressin and angiotensin II levels may contribute to the hyponatremia by impairing free water clearanceDiagnosis

Treatment Hydrocortisone (cortisol) is the mainstay of treatment (2030 mg/d)maintain an ample intake of sodium (34 g/d)mineralocorticoid supplementation administration of 0.050.1 mg fludrocortisone per day POfemale patients with adrenal insufficiency, androgen levels are also low 2550 mg of DHEA PO Secondary Adrenocortical Insufficiencye/ ACTH deficiency

Signs & symptomsprimary disease but are not hyperpigmentednear-normal level of aldosterone secretion

Tests low-dose (1 g) ACTH test for suspected secondary ACTH deficiency

laboratory findingslow blood cortisol and ACTH levels

Treatment Glucocorticoid Adrenal crisis rapid and overwhelming intensification of chronic adrenal insufficiency, usually precipitated by sepsis (Pseudomonas or meningococcemia (Waterhouse-Friderichsen syndrome)) or surgical stress

Signs & symptomsNausea, vomiting, and abdominal pain may become intractableFever may be severe or absentLethargy deepens into somnolence, and hypovolemic vascular collapse ensuesmineralocorticoid secretion is usually preservedTreatmentIV infusion of 5% glucose in normal saline solution should be started with a bolus IV infusion of 100 mg hydrocortisone followed by a continuous infusion of hydrocortisone at a rate of 10 mg/hVasoconstrictive agents (such as dopamine) may be indicated in extreme conditions as adjuncts to volume replacement

Hypoaldosteronism Isolated aldosterone deficiency accompanied by normal cortisol production occurs in association with hyporeninism

Features unexplained hyperkalemia, which is often exacerbated by restriction of dietary sodium intakedeficiency in renin production Tests Low renin and aldosterone levels hyporeninemic hypoaldosteronismhigh renin levels and low aldosterone levels biosynthetic defect or a selective unresponsiveness to angiotensin II

Treatment administration of 0.050.15 mg fludrocortisone PO daily should restore electrolyte balance if salt intake is adequate (e.g., 150200 mmol/d)Hyperenimic hypoaldosteronims higher doses of mineralocorticoid to correct hyperkalemia

Kelainan padaMedula ADRENALLO3.Definisi, epidemiologi, etiologi, patofisiologi, tanda dan gejala, diagnosis, pemeriksaan fisik, pemeriksaan penunjang, tatalaksana, komplikasi, prognosis.Pheochromocytoma catecholamine-producing tumors derived from the sympathetic (pheochromocytomas) or parasympathetic nervous system (paragangliomas)

Epidemiology 28 out of 1 million persons per year, and about 0.1% of hypertensive patients harbor a pheochromocytoma"rule of tens 10% are bilateral, 10% are extraadrenal, and 10% are malignant

Etiology of most sporadic pheocromocytoma unknown; mutations in the RET, VHL, NF1, SDHB, SDHC, or SDHD genes Clinical features

Macro & microscopic appearance

zellbalen appearance in microscopicDiagnosis

Treatment Complete tumor removal is the ultimate therapeutic goal-Adrenergic blockers (phenoxybenzamine) should be initiated at relatively low doses (e.g., 510 mg orally three times per day)Oral prazosin or intravenous phentolamine can be used to manage paroxysms while awaiting adequate alpha blockadeBefore surgery blood pressure should be consistently below 160/90 mmHgBeta blockers (e.g., 10 mg propranolol three to four times per day)Other antihypertensives, such as calcium-channel blockers or angiotensin-converting enzyme inhibitorslaparoscopy, using either a transperitoneal or retroperitoneal (for bilateral adrenalectomy)