Glandula adreanal

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    GLANDULA ADRENAL

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     ADRENAL GLAND

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     ADRENAL GLAND

    Terletak di superior polus superior masing2 ginjal

    (retroperitoneal)

    Dibungkus oleh capsula glandula adrenal (jaringan

    ikat) yg kaya vascularisasi

    Berbentuk pyramidal, dibagi menjadi: Adrenal cortex 80–90% masa

    Medulla adrenalis (ditengah)

    Cortex Adrenal menghasilkan hormon steroid yang

    penting untuk kehidupan

     kehilangan hormon2korteks menyebabkan kematian

    Medulla Adrenal menghasilkan 3 Hormon

    catecholamine: norepinephrine, epinephrine, dan

    sejumlah kecil dopamine

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    Lapisan-Lapisan Glandula Adrenal

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    HORMON STEROIDOGENIC

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    Organ2 steroidogenic:Korteks adrenal

    Testis

    Ovarium

    Menghasilkan hormon

    steroid yang berbeda2

    karena tidak memiliki

    semua enzim konversi

    Jaringan lain:

     jaringan lemak, hepar,

    kulit

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    ZONA GLOMERULOSA

    Sel-sel tersusun membulat seperti bola (glomerulosa

    = bola kecil)

    Mensekresikan hormon Mineralocorticoid,karena

    berfungsi dlm homeostasis mineral tubuh

    Mineralocorticoid utama dan paling penting adalah Aldosteron Contoh lain apa?

    Fungsi:

    1. Regulasi ion (Na+) dan (K+): tubular reabsorpsi Na dan

    sekresi K pd Ginjal, Glandula Salivaria, Glandula

    sudorifera, dan colon

    2. Mengatur volum darah dan tekanan darah (akibat point

    1)

    3. Mengatur kesetimbangan asam basa darah (eksresi ion

    H+)

    NB: Klinis terkait dg Patofisiologi Hipertensi (HT) dan

    Tx

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    RENIN–ANGIOTENSIN–

     ALDOSTERONE SYSTEM (RAAS)

    Sel epitel

    tubulus

    kolektivus

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    REGULASI SEKRESI ALDOSTERON

    1. Increased potassium ion concentration in the

    extracellular fluid greatlyincreases aldosterone

    secretion.

    2. Increased activity of the renin-angiotensin

    system (increased levels of angiotensin II) also

    greatlyincreases aldosterone secretion.

    3. Increased sodium ion concentration in the

    extracellular fluidvery slightly decreases

    aldosterone secretion.

    4. Regulation of aldosterone secretion is largely

    independent of ACTH

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    KORELASI KLINIS

    Bagaimana hubungan Aldosteron dengan

    patofisiologi dan terapi HT?

    Bagaimana kerja obat golongan ACE Inhibitor,

     ARB, renin inhibitor, dll dalam terapi HT?

    Bagaimana kerja golongan Diuretika?

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    ZONA FASCICULATA

    Tersusun oleh sel yang membentuk kolom

    panjang dan lurus (zona paling lebar);

    Hormon yg dihasilkan disebut “Glucocorticoid”

    karena memiliki efek terutama dalam

    homeostatis glukosa darah, contoh lain apa?

    Fungsi? Banyak sekali! Memiliki banyak sel

    target dengan fungsi yang sangat bervariasi

    diantara sel target

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    REGULASI

    GLUKOKORTIKOID

    1. Control melalui Negative

    feedback pada CRH

    2. Rendahnya Kortisol darahmenstimulasi neusecretory di

    Hypothalamus CRH

    3. CRH Hpituitary Ant ACTH

    4. ACTH cotex Adrenal 

    cortisol

    5. Cortisol menuju organ target

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    KERJA CRH DAN ACTH

    CRH cAMP ke sel penghasil ACTH

     ACTH cAMP ke sel di zona reticularis dan

    fasciculata ACTH enhances many steps in the synthesis of

    cortisol:

    Memobilisasi kolesterol

    Meningkatkan produksi pregnenolon

    Meningkat produksi enzim konverter kortisol dan

    DHEACRH dan ACTH dihambat oleh kortisol umpan

    balik (-)

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             R                                                                                                                                                                                                                                                                                                                                                                                                                                                        E                                                                                                                                                                                                                                                                                                                                                                                                                                                                 G                                                                                                                                                                                                                                                                                                                                                                                                                                                                          U                                                                                                                                                                                                                                                                                                                                                                                                                                                        L                                                                                                                                                                                                                                                                                                                                                                                                                                                       A                                                                                                                                                                                                                                                                                                                                                                                                                                                                          S                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

    I                                                                                                                                                                                                                                                                                                                                                                                                                                                                G                                                                                                                                                                                                                                                                                                                                                                                                                                                                 L                                                                                                                                                                                                                                                                                                                                                                                                                                                        U                                                                                                                                                                                                                                                                                                                                                                                                                                                        

    K                                                                                                                                                                                                                                                                                                                                                                                                                                                                 O                                                                                                                                                                                                                                                                                                                                                                                                                                                                 K                                                                                                                                                                                                                                                                                                                                                                                                                                                                 O                                                                                                                                                                                                                                                                                                                                                                                                                                                                          R                                                                                                                                                                                                                                                                                                                                                                                                                                                        

    T                                                                                                                                                                                                                                                                                                                                                                                                                                                        I                                                                                                                                                                                                                                                                                                                                                                                                                                                       K                                                                                                                                                                                                                                                                                                                                                                                                                                                        

     O                                                                                                                                                                                                                                                                                                                                                                                                                                                                 I                                                                                                                                                                                                                                                                                                                                                                                                                                                       D                                                                                                                                                                                                                                                                                                                                                                                                                                                        

    • STRESS

    • RITME DIURNAL

    Efek Metabolik:

    1.Glukoneogenesis

    2.inhibits glucose uptake and use

    by many tissues, but not thebrain

    3.protein degradation

    4.facilitates lipolysis

    PERMISSIVE ACTIONS

    ROLE IN ADAPTATION TO

    STRESS

     ANTI-INFLAMMATORY &

    IMMUNOSUPPRESSIVE

    EFFECTS• Memilki banyak manfaat

    dalam terapi obat

    kortikosteroid

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    EFEK TERAPI KORTIKOSTEROID

    Lebih rentan terhadap infeksi

    development of gastric ulcers, high blood

    pressure, atherosclerosis, menstrual

    irregularities, and bone thinning

    Irreversible atrophy of the cortisol-secreting cells

    of the adrenal gland

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    Memacu

    Menghambat

    stressor

    InternalExternal

    STRESmengaktiva

    si aksis HPA

    • Axis Hypothalamus-Pituitary-Adrenal (HPA)

    Mekanisme

    Survivalitas

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    HIPOTALAMUS

    (inisiasi GAS melalui 2 jalur)

    1. STIMULASI

    (1) SS SIMPATIS (2) MEDULA

     ADREAL

     ALARM REA!TIO

    ("IGHT OR "LIGHT REA!TIO)

    (res#$n2 %an& 'imul sea&ai

    reasi 'er*a+a# a*a%a)

    2. STIMULASI

    (1) PITUITARIA

      (2) ,ORTE,S ADREAL

    RESISTE!E REA!TIO

    (reasi resis'ensi)

    Si-a' / #r$sesn%a lama'

      / e-en%a erlan&sun& lama

     AKTIVASI SS SIMPATIS

     AKTIVASI AKSIS HPA

    STRES

    S

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     Effect

    Glucocortic

    oid

     Resistanceto stress

     Anti-inflammatory effects

    Depression of

    immuneresponses

     Proteinbreakdown

    Glucose

     formation

     Lipolysis

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    KORELASI KLINISChusing’s Syndrom

    Penggunaan obat-obatan steroid = golongan kortison,

    dexamethason, prednison, metil prednisolon “Obat Dewa”

    Penyakit Addison

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    ZONA RETICULARIS

    Mensekresikan Androgen pada pria dan wanita

    Dalam bentuk utama Dehydroepiandrosterone (DHEA) 

    androgen lemah

     Androgen pada wanita: Untuk Libido, sumber Estrogen

    setelah Post-MenopauseMenstimulasi tanda-tanda seks sekunder pada anak lelaki

    dan perempuan (rambut ketiak, rambut pubis, dan

     prepubertal growth spurt)

    Regulasinya bukan melalui ACTH diduga CHAS

    (Cortical Androgen Stimulatin Hormon)DHEA menghambat GnRH

    Level DHEA seajalan dg kortisol kec pada pubertas

    wanita (DHEA meningkat >< Kortisol tetap)

    Puncak Sekresi: 25-30 th menurun

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    DHEA SEBAGAI ANTI-AGING

    Pada pria DHEA tidak terlalu berperan 

    testosteron > 100 x dari DHEA

    Pada wanita menjadi sangat penting 

    menimbulkan efek androgen androgen-dependent

    processesDHEA replacement therapy fountain of youth 

    tidak terbukti

    FDA melarang penrdagangan DHEA sbg obat

    anti-agingEfek samping: ↑risiko serangan jantung (↓↓ HDL)Rambut muka pd wanita

    ↑ risiko kanker payudara & ovarium (wanita), kanker

    prostat pada pria

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    MEDULLA ADRENAL

     A modified sympathetic ganglion of the

    autonomic nervous system (ANS)

    The hormone-producing cells, calledchromaffin

    cells

    These cells are innervated by sympathetic

    preganglionic neurons of the ANS

    Hormon:epinephrine and norepinephrine

    (NE)

    Fungsi: Terkait dg Mekanisme Survivalitas

    terhadap stress (Lih. Axis HPA)

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    HIPERSEKRESI ADRENAL

     ALDOSTERONE HYPERSECRETIONPrimary hyperaldosteronism (Conn’s

    syndrome) tumor

    Secondary hyperaldosteronism RAAS

    CORTISOL HYPERSECRETIONCushing’s syndrome

    excessive amounts of CRHadrenal tumorscortisol independent of ACTH

     ACTH-secreting tumors

     paruMenyebabkan asadrenal diabetes

    Penimbunan lemak a “buff alo hump” and a “moon face,”muscle weakness and fatigue

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     ADRENAL ANDROGEN HYPERSECRETIONa masculinizing condition

     In adult females:Hirsutism,deepening of the voice, more muscular arms and

    legs, breasts become smallermenstruation may cease

     In newborn femalesmale-type external genitalia female pseudohermaphroditism

     In prepubertal males

    precocious pseudopuberty:deep voice, beard, enlargedpenis, and sex drive

    adrenogenital syndrome defek enzim turunanSterilglucocorticoid therapy

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     ADRENOCORTICAL

    INSUFFICIENCY

    Primary adrenocortical insuffi ciency

    (Addison’s disease) Autoimmune destruction

    ↓Aldosteron & Cortisol

    Hyperpigmentation αMSH’s receptors

    Secondary adrenocorticalHypothalamic abnormality

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    TESTOSTERON

    Disekresikan oleh??Sebagain besar ke darah sel target, dmn saja?

    Ke tubulus seminiferus spermatogenesis

    Sel target: Testosteron berikatan dg androgen-receptor complex di

    sitoplasama inti sel transkripsi

    Efek dikelompokkan dlm 5 hal:

    1. effects on thereproductive system before birth

    2. effects on sex-specific tissues after birth3. other reproduction-related eff ects;

    4. Effects on secondary sexual characteristics

    5. Nonreproductive actions

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    TESTOSTERON

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    REGULASI

    Gonadotropin-releasing hormone

    activity

    increases at puberty

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    DHT METABOLIT AKTIF

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    ESTROGEN

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