KELENJAR ADRENAL

dr Aris Prasetyo,M Kes

 Anatomi
• Kuning
• Berbentuk pyramid
• Kelenjar suprarenal , terletak di sisi atas ginjal
• Banyak vascularisasi
• Berat + 7.5 g
• Kelenjar adrenal dibagi 2 bagian:
– cortex adrenal di permukaan
– medulla adrenal di lapisan dalam
 Cortex Adrenal
• Kekuningan - simpanan lipids, cholesterol dan
asam lemak.
• Memproduksi hormones steroid, oki disebut
adrenocortical steroid, atau disederhanakan
corticosteroid
• Korticosteroid vital
• Hormon steroid, menimbulkan effek dengan
memilih gen dengan ditranskrip ke nukleus sel
target.
3 Zones, dari cortex adrenal :
• (1) zona glomerulosa, diluar
• (2) zona fasciculata,di tengah
• (3) zona reticularis, di dalam
Region/ Hormone(s) Target Hormonal Effects Regulatory Control
Zone
Cortex
Zona Mineralocorticoid Kidney Increase renal reabsorption Stimulated by
glomerulosa s (MC), primarily of Na+ and water (especially angiotensin II;
aldosterone in the presence of ADH) and inhibited by ANP
accelerate urinary loss of K+
Zona Glucocorticoids Most Release of amino acids from Stimulated by ACTH
fasciculata (GC): cortisol cells skeletal muscles, and lipids from anterior
(hydrocortisone), from adipose tissues; pituitary gland
corticosterone, promote liver formation;
cortisone promote peripheral glycogen
utilization of lipids; anti-
inflammatory effects
Zona Androgens Uncertain significance under Stimulated by
reticularis normal conditions ACTH; significance
uncertain
Medulla Epinephrine, Most Increase cardiac activity, Stimulated during
norepinephrine cells blood pressure, glycogen sympathetic
breakdown, blood glucose activation by
levels; release of lipids by sympathetic
adipose tissue preganglionic fibers
 Zona Glomerulosa
• memproduksi mineralocorticoid (MCs),
• hormon steroid
• mempengaruhi komposisi electrolyte cairan
tubuh.
• Aldosteron adalah mineralocorticoid
terpenting
• +15 persen volume cortical
• glomerulus adalah bola-bola kecil
• Bentuk kecil, padat, bergerombol
 Aldosterone
• Merangsang pertambahan ion sodium dan
eliminasi ion potassium yang mengatur
komposisi cairan ekskresi.
• Ini menyebabkan retensi ion sodium di
ginjal, kelenjar keringat,kelenjar saliva dan
pancreas
• mencegah kehilangan Na+ di urine,
keringat, saliva, dan digestive
• Retensi Na+ disertai kehilangan K+
• Sebagai efek samping, reabsorpsi Na+
meningkatkan reabsorpsi osmotik di ginjal,
kelenjar keringat, kelenjar saliva dan
pancreas
• Aldosterone meningkatkan sensitifitas
receptor garam di taste buds di lidah.
Akibatnya peningkatan keinginan
mengkonsumsi asin-asin.
 Gangguan Aldosteron
• hypoaldosteronism
• Gagal memproduksi aldosterone dalam
jumlah cukup.
• Kehilangan sejumlah besar air dan Na+
• Mengubah konsentrasi elektrolit
• transmembrane potentials,
• Gangguan jaringan neural dan otot
 Hyperaldosteronisme
• Ditandai dengan Hipertensi dan Hipokalemi
Macam :
• Primer : Sindroma Conn
• Sekunder
– Stenosis arteri renalis
– Sirosis
– Payah jantung
– Sindrom nefrotik
 Aldosteronisme Primer
• Wanita 30-50 th
• Hiperaldosteron dan kadar renin plasma
rendah
• Etio :
– adenoma adrenalis
– Hiperplasi
– Carcinoma
 Diagnosa
• Hiperaldosteron dan kadar renin yang
rendah dalam plasma
• CT Scan
 Terapi
• Adrenalektomi
• Posterior
• Prabedah : spironolakton 200 – 400 mg/hari
 Zona Fasciculata
• (fasciculus, ikatan kecil)
• memproduksi hormon steroid :
glucocorticoids (GCs)
• Effek : metabolisme glucose
• +78 persen volume kortek
• Sel endocrinenya besar dan
mengandung banyak lipid, tampak
berbusa
 Glucocorticoids
• Dirangsang ACTH dari hipofise anterior
• Produk terpentingnya cortisol, disebut juga
hydrocortisone
• dengan jumlah yang lebih kecil dalam bentuk
corticosterone dan cortisone
• Sekresi Glucocorticoid di regulasi dengan
negative feedback: pelepasan glucocorticoids
mempunyai efek menghambat produksi
corticotropin-releasing hormone (CRH) di
hypothalamus dan ACTH di hipofise anterior
 Efek Glucocorticoid
Meningkatkan synthesis glucose dan
membentuk glycogen
• khususnya dalam liver
• jaringan Adipose merespon dengan melepas
asam lemak dalam sirkulasi
• jaringan lain mulai memecah asam lemak
dan protein disamping glucose
• Proses ini adalah efek glucose- sparing.
 anti-inflammatory effect
• menghambat aktifitas sel leukosit dan
komponen sistem imun lain
• Steroid cream biasa digunakan mengatasi
alergi
• injeksi glucocorticoid mengatasi reaksi
alergi yang lebih berat
• Glucocorticoid memperlambat migrasi sel phagocytic
dan menyebabkan kurang aktif
• mast cells yang terexpos steroid menyebabkan
berkurangnya pelepasan histamine dan bahan lainnya
yang menyebabkan inflamasi. Hasilnya,
pembengkaan dan irritasi dapat dihilangkan
• Kerugiannya, kecepatan penyembuhan luka menurun,
dan kerusakan pertahanannya akan mempermudah
infeksi. Oleh karena itu, steroid topikal digunakan
untuk mengobati kemerahan tapi tidak boleh untuk
luka terbuka.
 Gangguan Produksi
Glucocorticoid
• Addison's disease
– produksi glucocorticoid inadequate
– autoimmune response
– kelemahan dan kehilangan berat badan
– tidak dapat menggunakan cadangan lipid secara
efektif untuk memproduksi ATP
– konsentrasi glucose darah turun sehabis makan
– symptom mirip hypoaldosteronism
• Diagnosa
– Tes lab
– Kadar kalium plasma meningkat
– Kadar natrium dan klorida normal
– ACTH serum meningkat
• Terapi
– Cairan iv
– Kortikosteroid iv po
 Cushing's disease
– Overproduksi glucocorticoids

– Diagnosa banding : Lesi hipofisis menyebabkan

Hypersekresi ACTH

– Metabolism Glucose ditekan

Gejala
• Wanita>>
• Gejala kelebihan sekresi kortisol:
– Atrofi otot, protein perifer dipecah
– Obesitas, cadangan lipid dimobilisasi - "moon-
faced" appearance
– Striae
– hiperpigmentasi
Diagnosa
• Kadar ACTH plasma rendah
• CT Scan untuk menyingkirkan karena lesi
hipofisis
Terapi
• Kemoterapi
• Radiasi
• pembedahan
 Zona Reticularis
• Reticulum = network
• 7 % cortex adrenal
• branching network
• memproduksi androgens
• selain di testis
• juga memproduksi estrogens
• effek pada sexual characteristics
• ACTH merangsang zona reticularis tapi
minimal
 Gangguan pada Zona Reticularis
• Tumor
• androgen meningkat drastis
• adrenogenital syndrome
• pada wanita-maskulin
– postur tubuh
– bulu/rambut
– distribusi tumpukan lemak
– berotot
• pada laki-laki- feminin
– gynecomastia (gynaikos, woman + mastos,
breast).
 Medulla Adrenal

• berwarna coklat kemerahan- kaya pembuluh

darah
• Selnya bulat— mirip ganglion sympathetic
yang diinnervasi oleh preganglionic
sympathetic fibers
• aktifitas sekresi dikontrol oleh divisi
sympathetic dari saraf otonom
• medulla adrenal mengandung dua kelompok
sel sekretory:
– epinephrine (adrenaline)
– norepinephrine (noradrenaline).
• Sekresinya dikemas dalam vesicles
• exocytosis
• Rangsangan sympatis merangsang peningkatan
exocytosis dan pelepasan hormon secara
dramatis
 Epinephrine dan Norepinephrine

• Epinephrine 75-80 percent sekresi medulla

• Sisanya norepinephrine
• Stimulasi reseptor  1 dan ß1, tipe paling
umum
 Ketika medulla adrenal diaktifkan:
• Merangsang mobilisasi cadangan glycogen di otot
skelet dan meningkatkan pemecahan glucose untuk
mendapat ATP. Meningkatkan kekuatan otot dan
ketahanan.
• Di jaringan lemak, simpanan lemak di pecah
menjadi asam lemak, yang dilepas ke sirkulasi untuk
digunakan organ lain.
• Di liver, molekul glycogen dipecah. Molekul glucose
dilepas ke sirkulasi, khususnya untuk jaringan saraf
yang tidak bisa menggunakan asam lemak
• Di jantung, stimulasi reseptor ß1 merangsang
peningkatan kecepatan dan kekuatan kontraksi otot
jantung
 Medulla Adrenal
• Preganglionic fibers masuk ke medulla adrenal
• medulla adrenal adalah modifikasi ganglion
simpatis
• Di dalam medulla, preganglionic fibers melakukan
synapse pada sel neuroendocrine, neurons khusus
yang melepas neurotransmitters epinephrine (E)
dan norepinephrine (NE) ke sirkulasi.
 Ketika aktifasi simpatis :
• Peningkatan kesiagaan, sangat terangsang
• Merasa berenergy dan euphoria, sering
dihubungkan dengan ketakutan akan bahaya
dan rangsangan nyeri
• Peningkatan aktifitas cardiovascular dan pusat
respiratory pons and medulla oblongata,
peningkatan tekanan darah, heart rate, napas
menjadi cepat dan dalam.
• Peningkatan tegangan otot melalui
perangsangan extrapyramidal system
 Membrane Receptors
• Ada 2 kelompok sympathetic receptors:
– alpha receptors
– beta receptors.
 Alpha Receptors
• Stimulasi alpha receptors mengaktifkan enzym di
membran sel.
• Ada 2 tipe alpha receptors:
– alpha-1
– alpha-2
• Hasil alpha receptor 1, pelepasan ion Calsium
intracellular dari tandonnya endoplasmic reticulum
• Respon ini mengikuti second messengers di dalam sel
target
• Pelepasan ion calcium biasanya mempunyai efek
eksitasi pada sel target

• Alpha-2 receptors, perangsangannya menghasilkan

penurunan kadar cyclic-AMP (cAMP) di cytoplasm
• Ini menyebabkan efek inhibisi sel.

• Keberadaan 2 receptors di dalam parasympathetic

menolong koordinasi aktifitas sympatis dan
parasympatis
 Beta Receptors
• Beta (ß) receptors terletak di banyak organs,
termasuk otot skelet, paru, jantung, dan liver
• merangsang perubahan aktifitas metabolik sel
target
• Perubahan ini terjadi secara tidak langsung, ketika
beta receptor menyebabkan pembentukan second
messenger, cAMP, yang menjadi kunci aktif
tidaknya enzym
 Kelainan Medullae Adrenal
• Overproduksi epinephrine oleh medulla
adrenal
• Pheochromocytoma
• Tumor yang memproduksi catecholamin >>
• The most dangerous symptoms are rapid and
irregular heartbeat and high blood pressure;
• Other symptoms include uneasiness, sweating,
blurred vision, and headaches.
• Surgical removal of the tumor is the most
effective treatment.
Pancreas
 pancreatic islets
islets of Langerhans.
 Insulin
• Peptide hormone
• released by beta cells when glucose levels
rise above normal levels (70-110 mg/dl).
• Insulin secretion is also stimulated by
elevated levels of some amino acids,
including arginine and leucine.
• Binds to receptor proteins on the cell
membrane. .
• One of the most important effects is the
enhancement of glucose absorption and utilization
• Insulin receptors are present in most cell
membranes; such cells are called insulin-
dependent.

• Cells in the brain and kidneys, cells in the lining

of the digestive tract, and red blood cells lack
insulin receptors.
• These cells are called insulin-independent,
because they can absorb and utilize glucose
without insulin stimulation.
 The effects of insulin on its target cells
include:
• Acceleration of glucose uptake (all target cells).
• Acceleration of glucose utilization (all target
cells) and enhanced ATP production.
• Stimulation of glycogen formation (skeletal
muscles and liver cells).
• Stimulation of amino acid absorption and protein
synthesis.
• Stimulation of triglyceride formation in adipose
tissues.
• Insulin is secreted when glucose is
abundant, and this hormone stimulates
glucose utilization to support growth and
the establishment of carbohydrate
(glycogen) and lipid (triglyceride) reserves.
• The accelerated use of glucose soon brings
circulating glucose levels within normal
limits.
 Diabetes Mellitus
• Diabetes mellitus (mellitum, honey) is
characterized by glucose concentrations that are
high enough to overwhelm the reabsorption
capabilities of the kidneys.
• Glucose appears in the urine (glycosuria), and
urine production generally becomes excessive
(polyuria).
• Other metabolic products, such as fatty acids and
other lipids, are also present in abnormal
concentrations.
• Caused by genetic abnormalities, and some of the
genes responsible have been identified
– inadequate insulin production
– the synthesis of abnormal insulin molecules
– defective receptor
• Diabetes mellitus may also appear as the result of
other pathological conditions, injuries, immune
disorders, or hormonal imbalances
• There are two major types of diabetes mellitus:
– insulin-dependent (Type I) diabetes and
– non-insulin-dependent (Type II) diabetes.
 Insulin-Dependent Diabetes
Mellitus
• Type I diabetes,
• inadequate insulin production by the beta cells of
the pancreatic islets.
• Glucose transport in most cells cannot occur in the
absence of insulin.
• When insulin concentrations decline, cells can no
longer absorb glucose; tissues remain glucose-
starved despite the presence of adequate or even
excessive amounts of glucose in the circulation.
• After a meal rich in glucose, blood glucose
concentrations may become so elevated that the
kidney cells cannot reclaim all the glucose
molecules that enter the urine.
• The high urinary concentration of glucose limits
the ability of the kidneys to conserve water, so the
individual urinates frequently and may become
dehydrated.
• The chronic dehydration leads to disturbances of
neural function (blurred vision, tingling
sensations, disorientation, fatigue) and muscle
weakness.
• under 40 years of age.
• juvenile-onset diabetes.
 Non-insulin-dependent diabetes
mellitus (NIDDM)
• Type II diabetes, typically affects obese
individuals over 40 year of age.
• Type II diabetes is far more common than
Type I diabetes
• 90 percent of them involve obese
individuals.
 The primary effects of glucagon :

• Stimulation of glycogen breakdown in

skeletal muscle and liver cells.
• Stimulation of triglyceride breakdown in
adipose tissues.
• Stimulation of glucose production at the
liver.
Structu Hormo Primary
re/Cells ne Targets Hormonal Effects Regulatory Control
Mobilizes lipid reserves;
promotes glucose synthesis
Liver, and glycogen breakdown in Stimulated by low blood glucose
Alpha Glucag adipose liver; elevates blood glucose concentrations; inhibited by
cells on tissues concentrations somatostatin from delta cells

Stimulated by high blood glucose

concentrations, parasympathetic
Facilitates uptake of glucose by stimulation, and high levels of
target cells; stimulates lipid and some amino acids; inhibited by
Beta glycogen formation and somatostatin from delta cells and
cells Insulin Most cells storage by sympathetic activation
Inhibits insulin and glucagon
Somat Other islet secretion; slows rates of
ostatin cells, nutrient absorption and
Delta (GH- digestive enzyme secretion along Stimulated by protein-rich meal;
cells IH) epithelium digestive tract mechanism uncertain
Inhibits gallbladder contraction;
Pancre regulates production of
atic pancreatic enzymes; influences Stimulated by protein-rich meal
polype Digestive rate of nutrient absorption by and by parasympathetic
F cells ptide organs digestive tract stimulation