Terjadi pada dinding lambung / duodenum dimana diproduksi asam dan pepsin Bisa juga terjadi pada oesophagus dan diverticulum Meckel dimana adanya ectopic gastric mucosa
ETIOLOGI AKUT 1. Terjadi kerusakan / kelemahan gastric mucosa barrier 2. Bertahun dianggap akibat kelebihan asam lambung 3. 1982 Dr. Barry Marshal di Perth Australia → penyebabnya adalah infeksi kuman helicobacter pylorii → melalui makanan / minuman
3. Penyebab lain - iritasi mukosa lambung oleh obat – obatan: aspirin, NSAID PATOLOGI - multiple - terjadi di semua bagian gaster dan first part duodenum - oval 1 – 2 mm - jarang menembus muscular
TANDA KLINIS - tidak khas : dyspepsia hematemesis Pengobatan konservatif dengan obat – obatan berhasil baik
STRESS ULCER Suatu special group dari ulcus akut → terjadi pada pasien yang baru mengalami : - operasi besar - cardiac infarct - septic shock - trauma cerebral - operasi bedah syaraf
CURLING ULCER - akibat luka bakar > 35% - terjadi multiple erosi pada corpus + fundus dalam 48 jam pertama luka bakar - hematemesis hebat
KRONIK a.Duodenal Ulcer Etiologi 1. Infeksi H. Pylorii 2. Genetic : - familier - gol. Darah O 3X 3. Neurogenic Stress dan anxiety merangsang vagus → gastric hypersecretion + hypermotility
4. Endocrine Stress / physical stress → sarana hormonal merangsang pituitary adrenal axis → hypersekresi asam lambung 5. Accesory - perokok - makan tak teratur - alkohol - deff. Vitamin - mastikasi tak sempurna
incidence ♂ : ♀ = 2 : 1 mikroskopis : kerusakan muskular > mukosa
b. Gastric Ulcer - Normal acidity / lyposekresi - atrophic gastritis - perokok Incidence : - 1 – 2 % - ♂ : ♀ = 1 : 1
Patologi : - ulcus > duodenal ulcer - dasar ulcer sampai ke muscularis - tergantung lokasi → bisa menembus liver atau pancreas - bisa mengalami degenerasi maligna : ADENOCARCINOMA → kronik duodenal ulcer tidak
TANDA KLINIK A. KRONIK GASTRIC ULCER 1. nyeri epigastric t.u 2 jam setelah makan menjalar ke belakang yang hilang bila berbaring tidak pernah ada serangan pada malam hari 2. nyeri periodicity : 2 – 6 bulan 3. vomitting : 50 % relief the pain
4. hematemesis : melena = 60 : 40 5. nafsu makan baik tapi takut makan 6. BB b. CHRONIC DUODENAL ULCER - umur 25 – 50 tahun - periodicity jelas → timbul bila di- presipitasi : work,worry,weather
1. pain : severe, 1 - 2½ jam after meal → hunger pain, relief by food ( carry biscuit ) 2. vomitting : jarang 3. hematemesis : melena = 40 : 60 4. nafsu makan baik 5. BB tidak
INVESTIGASI 1. Ba Meal : ada daerah yang melekuk 2. Blood studies : - Hb → chronic blood loss 3. Gastric function test 4. Gastro duodenoscopic
TREATMENT Tujuan : menghilangkan symptom - control gastric acid - H. Pylorii → Amoxicillin - H2 receptor blockade / antagonist - cimetidin, ranitidin - stop obat – obatan irritant - salicylat, NSAID - stop alkohol, rokok
Evaluasi 6 minggu bila gagal → operasi Pemeriksaan endoscopy dilakukan tiap bulan untuk mengetahui kemajuan terapi.
OPERASI Tindakan operasi dilakukan bila : 1. Gangguan nyeri hebat dan berulang-ulang dimana respon terhadap obat-obatan kecil. 2. Komplikasi - Pyloric stenosis - Bleeding hebat - Deformity hour glass - Perforasi dengan keganasan
JENIS OPERASI 1. Billroth I : Partial gastrectomy →Pemotongan bagian distal dari gaster →Gastroduodenostomy 2. Billroth II : Gastrectomy - Pemotongan gaster diatas ulcer → Gastrojejunostomy
3. Vagotomy + Pyloroplasty pada Benigna Gastric Ulcer. 4. Utk Duodenal Ulcer - Vagotomy+Pyloroplasty - Vagotomy+Gastrojejunostomy - Lesser Curve Seromyotomy
5. Untuk perdarahan - Laparatomy → Lambung dibuka, pembuluh darah dijahit. 6. Untuk perforasi - Laparatomy → daerah yang bocor di excisi →dijahit + omental patch.
Sabtu, 24 Januari 2009
KANKER PROSTAT
KANKER PROSTAT
Kanker prostat sering terjadi pada laki-laki
.Kanker prostat merupakan masalah yang sering dialami kaum laki-laki
Penyebaran sel kanker (metastase),bisa langsung ke organ sekitar prostat seperti tulang panggul dan kandung kencing.Selain itu ,bisa juga melalui pembuluh darah ke organ yang jauh dari prostat seperti otak,hati dan tulang anggota,atau melalui pembuluh limfe ke organ-organ yang jauh dari prostat.
Kebanyakan penderita yang kelak didiagnosa sebagai kanker prostat,ternyata tidak menunjukkan gejala klinik yang mencurigakan sebelumnya hingga diagnosa sering ditegakkan setelah melakukan otopsi (setelah penderita meninggal karena dicurugai mengidap kanker prostat)ya itu sekitar 1/3 kasus
1. FAKTOR RESIKO
Laki-laki usia >55 tahun yang mempunyai riwayat famili menderita kanker prostat
Makanan terbiasa mengandung asam lemak jenuh.
Kontak dengan logam berat seperti cadmium.
Ras Afrika yang tinggal di Amerika.
Kebiasaan hidup kurang melakukan gerakan fisik atau olah raga
Kebiasan merokok
2. GEJALA
Masalah kelenjar prostat,baik karena membesar atau karena mengalami peradangan,boleh dikatakanmenimbulkan gejala yang serupa,yaitu :
Mengalami kesulitan dalam buang air kecil
Buang air kecil lebih sering ,terutama kalau pada malam hari.
Mengalami kesulitan memulai pancaran air seni .
Mengalami kesulitan juga dalam mengakhiri aliran air seni
Pancaran aliran air seni lemah
Merasa kandung kencing tidak kosong sempurna
Jika disertai infeksi timbul keluhan nyeri waktu buang air kecil,atau waktu mengeluarkan air mani selesai bersetubuh.
Kadang-kadang,aliran air seni berhenti sendiri.
Makin ada darah di dalam air seni atau air mani
Pada kanker prostat,selain keluhan tersebut diatas juga disertai :
Perasaan nyeri pada daerah bawah pinggang.
Mengalami kesulitan memulai dan mempertahankan ereksi penis.
Keluhan nyeri pada pangkal paha dan daerah tulang pinggul.
Mungkin air seni berdarah.
3. DIAGNOSA
Berikut ini dapat dicermati diagnosa kanker prostat,antara lain :
a. Pada permulaan,kanker prostat biasanya muncul tanpa gejala.Pada pemeriksaan prostat melalui anus,ukuran prosta normal sebesar kemiri dengan kekenyalan seperti tulang ujung hidung.Pada kanker konsistensi keras dengan benjolan-benjolan tersebar.Bila ada perlekatan dengan jaringan sekitar,kanker sulit digerakkan pada pemeriksaan.
Pada 25 % penderita,bendungan air seni biasanya tiba-tiba (akut)
Kadang-kadang terjadi hematuria (air seni berdarah)
Gejala metastase keorgan lain yang jauh dari prostat :
Berat badan turun
Kurang darah (anemi)
Napas sesak bila sudah metastase kejaringan paru.
Sembab bila ada bendungan pembulu limfe.
Gejala saraf bila sudah metastase kejaringan saraf atau otak .
Pemeriksaan cairan prostat,secara histopatologi ditemukan sel kanker.
Biopsi prostat melalui saluran kencing (transurethral biopsi) untuk pemeriksaan patologi anatomi.
Pemeriksaan foto kandung kencing (sitoskopi) terlihat penonjolan dibagian bawah kandung kencing.Dan kekakuan saluran kencing yang berada di daerah jaringan prostat.
Pemeriksaan asam pospatase,yang meningkat sampai 500-1000 kali dari lipat dari kadar normal di darah.
Pemeriksaan kadar alkalin pospatase didalam darah juga mengikat pada penderita kanker prostat.
Scanning tulang untuk mengetahui metastase kanker prostat.Meskipun pada foto rontgen tidak ditemukan kelainan tetapi dari pemeriksaan scanning bisa terlihat kelainan.
b. Pemeriksaan prostata spesifik anti gen (PSA)
PSA sejenis enzym protease yang dihasilkan sel epitel baik yang tumor jinak maupun yang mengalami keganasan.Di dalam darah beredar dalam bentuk komfleks tidak aktif dalam dua bentuk yaitu a1 anticymotrypsin dan makroglobulin.
4. PENYEBAB
a. Faktor predisposisi genetik (turunan).
b. Pengaruh hormon
c. Pengaruh zat yang bersifat menimbulkan kanker (karsinogenik).
d. Akibat Infeksi
e. Pengaruh lingkungan
Beberapa teori penyebab kanker prostat :
f. Staus perkawinan
5. PENCEGAHAN
Selain mengurangi dan menghindari faktor-faktor resiko penyebabnya,didalam literatur disebuitkan bahwa sebaiknya mengkonsumsi :
Buah aprikot yang mengandung vit.B17 sebanyak 7 buah sehari atau setar dengan 50-75 mg vit.B17 di Amerika sudah disebar luaskan pemasaran buah afrikot serta petunjuk penggunaannya sebagai pencegahan dan pengobatan kanker.Aprikot sejenis buah berbentuk bulat berwarna kuning keemasan kalau sudah matang,dengan daging buah yang lunak dan biji yang keras seperi batu.
Vit.B17 juga disebut juga sebagi laetril atau amygdalin
Buah cabai merah
6. PENGOBATAN KANKER PROSTAT
Dasar pengobatan kanker prostat,antara lain :
Operasi
Penyinaran
Pengobatan menggunakan hormon
Pengobatan dengan menggunakan obat-obatan kimiawi
Konserfatif,menunggu sambil mewaspadai gejala yang mengancam
Gambar sel ca.prostat
expression in Ca prostate Gr.IV 384 x 274 - 45k - jpg www.icmr.nic.in
www.e-radiography.netCa prostate (BM metastasis) 500 x 328 - 102k - jpg www.cc.uoa.gr
Kanker prostat sering terjadi pada laki-laki
.Kanker prostat merupakan masalah yang sering dialami kaum laki-laki
Penyebaran sel kanker (metastase),bisa langsung ke organ sekitar prostat seperti tulang panggul dan kandung kencing.Selain itu ,bisa juga melalui pembuluh darah ke organ yang jauh dari prostat seperti otak,hati dan tulang anggota,atau melalui pembuluh limfe ke organ-organ yang jauh dari prostat.
Kebanyakan penderita yang kelak didiagnosa sebagai kanker prostat,ternyata tidak menunjukkan gejala klinik yang mencurigakan sebelumnya hingga diagnosa sering ditegakkan setelah melakukan otopsi (setelah penderita meninggal karena dicurugai mengidap kanker prostat)ya itu sekitar 1/3 kasus
1. FAKTOR RESIKO
Laki-laki usia >55 tahun yang mempunyai riwayat famili menderita kanker prostat
Makanan terbiasa mengandung asam lemak jenuh.
Kontak dengan logam berat seperti cadmium.
Ras Afrika yang tinggal di Amerika.
Kebiasaan hidup kurang melakukan gerakan fisik atau olah raga
Kebiasan merokok
2. GEJALA
Masalah kelenjar prostat,baik karena membesar atau karena mengalami peradangan,boleh dikatakanmenimbulkan gejala yang serupa,yaitu :
Mengalami kesulitan dalam buang air kecil
Buang air kecil lebih sering ,terutama kalau pada malam hari.
Mengalami kesulitan memulai pancaran air seni .
Mengalami kesulitan juga dalam mengakhiri aliran air seni
Pancaran aliran air seni lemah
Merasa kandung kencing tidak kosong sempurna
Jika disertai infeksi timbul keluhan nyeri waktu buang air kecil,atau waktu mengeluarkan air mani selesai bersetubuh.
Kadang-kadang,aliran air seni berhenti sendiri.
Makin ada darah di dalam air seni atau air mani
Pada kanker prostat,selain keluhan tersebut diatas juga disertai :
Perasaan nyeri pada daerah bawah pinggang.
Mengalami kesulitan memulai dan mempertahankan ereksi penis.
Keluhan nyeri pada pangkal paha dan daerah tulang pinggul.
Mungkin air seni berdarah.
3. DIAGNOSA
Berikut ini dapat dicermati diagnosa kanker prostat,antara lain :
a. Pada permulaan,kanker prostat biasanya muncul tanpa gejala.Pada pemeriksaan prostat melalui anus,ukuran prosta normal sebesar kemiri dengan kekenyalan seperti tulang ujung hidung.Pada kanker konsistensi keras dengan benjolan-benjolan tersebar.Bila ada perlekatan dengan jaringan sekitar,kanker sulit digerakkan pada pemeriksaan.
Pada 25 % penderita,bendungan air seni biasanya tiba-tiba (akut)
Kadang-kadang terjadi hematuria (air seni berdarah)
Gejala metastase keorgan lain yang jauh dari prostat :
Berat badan turun
Kurang darah (anemi)
Napas sesak bila sudah metastase kejaringan paru.
Sembab bila ada bendungan pembulu limfe.
Gejala saraf bila sudah metastase kejaringan saraf atau otak .
Pemeriksaan cairan prostat,secara histopatologi ditemukan sel kanker.
Biopsi prostat melalui saluran kencing (transurethral biopsi) untuk pemeriksaan patologi anatomi.
Pemeriksaan foto kandung kencing (sitoskopi) terlihat penonjolan dibagian bawah kandung kencing.Dan kekakuan saluran kencing yang berada di daerah jaringan prostat.
Pemeriksaan asam pospatase,yang meningkat sampai 500-1000 kali dari lipat dari kadar normal di darah.
Pemeriksaan kadar alkalin pospatase didalam darah juga mengikat pada penderita kanker prostat.
Scanning tulang untuk mengetahui metastase kanker prostat.Meskipun pada foto rontgen tidak ditemukan kelainan tetapi dari pemeriksaan scanning bisa terlihat kelainan.
b. Pemeriksaan prostata spesifik anti gen (PSA)
PSA sejenis enzym protease yang dihasilkan sel epitel baik yang tumor jinak maupun yang mengalami keganasan.Di dalam darah beredar dalam bentuk komfleks tidak aktif dalam dua bentuk yaitu a1 anticymotrypsin dan makroglobulin.
4. PENYEBAB
a. Faktor predisposisi genetik (turunan).
b. Pengaruh hormon
c. Pengaruh zat yang bersifat menimbulkan kanker (karsinogenik).
d. Akibat Infeksi
e. Pengaruh lingkungan
Beberapa teori penyebab kanker prostat :
f. Staus perkawinan
5. PENCEGAHAN
Selain mengurangi dan menghindari faktor-faktor resiko penyebabnya,didalam literatur disebuitkan bahwa sebaiknya mengkonsumsi :
Buah aprikot yang mengandung vit.B17 sebanyak 7 buah sehari atau setar dengan 50-75 mg vit.B17 di Amerika sudah disebar luaskan pemasaran buah afrikot serta petunjuk penggunaannya sebagai pencegahan dan pengobatan kanker.Aprikot sejenis buah berbentuk bulat berwarna kuning keemasan kalau sudah matang,dengan daging buah yang lunak dan biji yang keras seperi batu.
Vit.B17 juga disebut juga sebagi laetril atau amygdalin
Buah cabai merah
6. PENGOBATAN KANKER PROSTAT
Dasar pengobatan kanker prostat,antara lain :
Operasi
Penyinaran
Pengobatan menggunakan hormon
Pengobatan dengan menggunakan obat-obatan kimiawi
Konserfatif,menunggu sambil mewaspadai gejala yang mengancam
Gambar sel ca.prostat
expression in Ca prostate Gr.IV 384 x 274 - 45k - jpg www.icmr.nic.in
www.e-radiography.netCa prostate (BM metastasis) 500 x 328 - 102k - jpg www.cc.uoa.gr
ENDOCRINE SYSTEM
Comparison of Nervous and Endocrine Systems
Functions of Endocrine System
1. Reproduction
2. Growth and development
3. Response to stress
4. Maintenance of fluid (water), electrolyte and nutrient balance
5. Regulation of cellular metabolism and energy
Organs of the Endocrine System
1. Pituitary gland
2. Hypothalamus (neuroendocrine)
3. Pineal gland
4. Thyroid gland
5. Parathyroid gland
6. Thymus gland
7. Adrenal gland
8. Pancreas (also has exocrine function)
9. Gonads (testes or ovaries - also have exocrine functions)
Topics
Hormone
Types
Modes of Action
Target cell activation
Control
Specific glands, their hormones, and disorders
Pituitary
Thyroid
Parathyroid
Adrenal
Pancreas
Thymus
Gonads (testes and ovaries)
General Adaptation Syndrome
Hormones
chemicals
secreted by endocrine gland cells into blood (by way of interstitial fluid)
regulate metabolic functions of other cells (called target cells)
carried to all cells, but action is specific to cells that have receptors for the hormone
specificity of body’s response to hormone depends on how many cells have the receptor (highly specific if few cells respond [e.g., ACTH]; diffuse action if many respond [e.g., thyroxine])
Chemical Types of Hormones
Amino-acid based (amino acids, short or long peptides, proteins)
e.g., insulin, growth hormone, prolactin
Steroids - lipid derivatives of cholesterol
e.g., hormones from gonads (testosterone, estrogen)
e.g., hormones from adrenal cortex (adrenocortical hormones)
Eicosanoids - locally-secreted, locally-acting hormones secreted by all cell membranes (e.g., prostaglandins, which increase blood pressure and contribute to uterine contraction)
Types of Changes in Target Cells
plasma membrane permeability changes (opening of protein channels; may change membrane potential)
activation of genes for increased protein synthesis, including enzymes
activation or deactivation of enzymes already present
secretion of cellular products
stimulation of cell division (mitosis)
Mechanisms of Action
action in target cell depends on receptor
receptor may be:
in plasma membrane
second messenger mechanisms
used by most amino acid-based hormones (water soluble)
intracellular (in cytoplasm or nucleus)
direct gene activation
used by steroids and thyroid hormones (lipid soluble)
Mechanisms of Action: Steroids
bind to intracellular receptors
hormone diffuses through plasma membrane and makes its way to nucleus
> where it binds with intracellular receptor to form hormone-receptor complex
> hormone-receptor complex interacts with chromatin (DNA) to affect gene activity (turn genes on or off)
> synthesis of mRNA
> synthesis of protein
Steroid Signaling
Mechanism of Action: Thyroid Hormone
similar to mechanism for steroid hormones
diffuses across plasma membrane
diffuses into nucleus where it interacts with intracellular receptors to activate genes for proteins (enzymes) involved in cellular respiration (glycolysis)
also, binds to receptors at mitochondria to activate genes for proteins involved in cellular respiration (Krebs cycle and electron transport chain)
Mechanisms of Action: Other Hormones
plasma membrane receptor
used by most amino acid-based hormones
interaction of hormone with plasma membrane receptor results in activation of second messenger systems (cyclic AMP or PIP-calcium)
activation of second messenger has cascade effect resulting in:
enzyme activation, or
membrane permeability changes or secretion
Membrane Receptor Mechanisms: 1. Cyclic AMP (cAMP) Signaling
interaction of hormone with receptor
> activates G protein (cleaves phosphate from GTP)-> excitation
> G protein activates adenylate cyclase
> adenylate cyclase forms cAMP from ATP
> cAMP activates protein kinases
> protein kinases activate (or inhibit) other proteins by phosphorylation
> cAMP degraded by enzyme
slightly different G protein inactivates adenylate cyclase - associated with different hormone receptor
Link to animation: http://student.ccbc.cc.md.us/c_anatomy/animat/cAMP.htm
cAMP Signaling Mechanism
Membrane Receptor Mechanisms: 2. PIP-Calcium Signaling
interaction of hormone with receptor --> activates membrane-bound enzyme phospholipase
> phospholipase cleaves PIP2 (phosphatidyl inositol diphosphate) into diacylglycerol (DAG) and IP3 -- each of which acts as a second messenger
diacylglycerol (DAG) activates protein kinases
IP3 (inositol triphosphate) causes release of Ca2+ into cytoplasm (from endoplasmic reticulum or other storage areas) --> Ca2+ acts as third messenger
PIP-Calcium Mechanism (con’t)
-> Ca2+ (third messenger)
changes enzyme activity and plasma membrane channels, or
binds to calmodulin (intracellular regulatory protein) --> activates enzymes
PIP-Calcium Signaling Mechanism
Factors Affecting Target Cell Activation
a. blood levels of hormone, which depend on:
rate of hormone release
rate of deactivation (by target cell or liver)
b. affinity of hormone for receptor
greater affinity means greater association --> greater effect
c. number of receptors available
Factors Affecting Target Cell Activation (con’t)
c. number of receptors available
up-regulation: increase in blood level of specific hormone (normally present at low levels) causes cells to make more receptors
down-regulation: prolonged exposure to high level of specific hormone --> cells remove some receptors
-->return to normal response level
cross-regulation: influence of one hormone on number of receptors for another hormone; e.g., progesterone causes uterus to make fewer estrogen receptors; estrogen causes uterus to make more progesterone receptors
Hormone Removal
hormones may be:
degraded by specific enzymes within target cells;
removed from blood by kidneys (excreted in urine)
degraded by liver (excreted in urine and feces)
half-life - time for 1/2 of hormone to be removed (from a fraction of a minute to 30 minutes)
onset - time from release to action (minutes [amino acid-based] to days [steroids])
duration of action - how long the effects last (~20 minutes to several hours)
Control of Hormone Release
Humoral control
Neural control
Hormonal control
Control of Hormone Release: Humoral
Hormone released in response to changing blood levels of ion or nutrient (negative feedback)
Control of Hormone Release: Humoral
Other examples:
pancreas:
beta cells detect high blood glucose insulin decreases blood glucose
alpha cells detect low blood glucose glucagon raises blood glucose
zona glomerulosa (of adrenal cortex) detects low blood Na+ or high blood K+ aldosteronetthy, K+
Control of Hormone Release: Neural
Hormone released in response to nerve impulse
Control of Hormone Release: Hormonal
Hormone produced by one endocrine gland (or hypothalamus) affects secretion of hormone by another endocrine gland
hypothalamus acts as overall coordinator releases regulatory hormones (releasing hormones or inhibitory hormones) affects anterior pituitary
anterior pituitary, when stimulated, secretes hormones that affect other glands (e.g., TSH [thyroid stimulating hormone] stimulates release of thyroid hormones from thyroid gland)
Hormonal Control: Role of Hypothalamus
Releasing hormones from hypothalamus stimulate secretion from anterior pituitary
Inhibitory hormones from hypothalamus inhibit secretion by anterior pituitary
Impulses from hypothalamus cause release of hormones from posterior pituitary
Hormone Control - Misc.
nervous system can override normal endocrine control
e.g., in “fight-or-flight” response, sympathetic impulses result in release of epinephrine and norepinephrine from adrenal medulla --> increases blood glucose levels to maintain fuel supply during stress or exertion (overrules effect of insulin on blood glucose level)
Organs of the Endocrine System and Their Products
The following major glands will be covered one at a time with their products:
1. Pituitary gland / Hypothalamus
2. Thyroid gland
3. Parathyroid gland
4. Adrenal gland
5. Pancreas (also has exocrine function)
6. Gonadal hormones (ovaries and testes)
7. Thymus
1. Pituitary Gland (Hypophysis)
located in sella turcica of sphenoid bone (in cranial cavity), inferior to hypothalamus
consists of two lobes:
A. neurohypophysis (~ posterior pituitary)
attached to hypothalamus by infundibulum
contains axons and axon terminals of neurosecretory cells whose cell bodies are in hypothalamic nuclei
B. adenohypophysis (~ anterior pituitary)
consists of glandular epithelium
Pituitary Development
A. Neurohypophysis (Posterior Pituitary)
consists of nerve fibers (axons of neurosecretory cells with cell bodies in hypothalamus) and pituicytes (glial cells that support nerve fibers)
acts primarily as a storage and releasing area for hormones actually made in hypothalamic nuclei
hormones released in response to impulses from hypothalamus (neural control)
hormones are short amino acid chains (peptides)
oxytocin
antidiuretic hormone (ADH or “vasopressin”)
A. Neurohypophysis : Oxytocin (OT)
action, in pregnant or nursing women:
stimulates contraction of smooth muscle of uterine wall during labor and delivery
stimulates ejection of milk in lactating mothers
action, in men and non-pregnant women, may be involved in sexual arousal and orgasm
A. Neurohypophysis : Oxytocin (OT)
control:
during labor/delivery, positive feedback: stretching of uterus/cervix --> sensory impulses to hypothalamus --> increased secretion of OT --> increased contraction
suckling: sucking of infant on breast --> sensory to hypothalamus --> oxytocin release --> release of milk
A. Neurohypophysis: Antidiuretic Hormone (ADH)
action: antidiuretic hormone (ADH) directly affects blood pressure - acts as powerful vasoconstrictor --> increases blood pressure (hence name “vasopressin”)
action: affects water balance (indirect affect on blood pressure) - acts on tubules of kidney to increase reabsorption of water less water lost in urine
A. Neurohypophysis: ADH
disorders:
hyposecretion due to damage of hypothalamic nucleus or neurohypophysis--> diabetes insipidus - excessive urine production (polyuria) and thirst
hypersecretion --> SIADH (syndrome of inappropriate ADH secretion) - water retention, headache, cerebral edema, weight gain, hypoosmolarity
Antidiuretic Hormone (ADH): Control
neural control: increased electrolyte (NaCl) concentration --> affects (supraoptic) nucleus in hypothalamus --> impulse to neurohypophysis --> release of ADH --> increased water reabsorption --> decrease in electrolyte concentration
other stimuli: pain, low BP, morphine, barbiturates, nicotine, aldosterone (hormone from adrenal cortex - hormonal control)
inhibition: alcohol (results in more urine production and, potentially, dehydration)
diuretic drugs - some act to supress ADH secretion; used to treat hypertension and congestive heart failure
B. Adenohypophysis (Anterior Pituitary)
linked to hypothalamus via hypophyseal portal system (capillary networks and small veins)
carries regulatory hormones from hypothalamus to pituitary
releasing hormones stimulate secretion of pituitary hormones
inhibitory hormones inhibit secretion
consists of epithelial cells
all hormones produced are proteins
tropic hormones - affect some endocrine glands or provide maintenance oversight for other organs
B. Adenohypophysis : Growth Hormone (GH)
highest levels during evening and sleep
action: stimulates increased rate of protein synthesis leading to cell growth and division
bones and skeletal muscle respond more than other body cells
action: stimulates use of fat as energy source and decreases rate of glucose uptake and glucose metabolism (diabetogenic effect – “spares” glucose)
control:
release stimulated by GHRH (growth hormone releasing hormone) from hypothalamus
inhibited by GHIH (from hypothalamus) and somatomedins (produced by liver under GH stimulation)
Growth Hormone (GH): Disorders
Disorders:
hypersecretion
gigantism (in children)
up to 8’ tall, normal body proportions
acromegaly (after epiphyseal plates close)
enlargement of extremities and face, thickening of soft tissue
hyposecretion
pituitary dwarfism - in children, up to 4’ tall
progeria - premature aging, atrophy of body tissues
B. Adenohypophysis: Prolactin (PRL)
action:
stimulates milk production in mammary glands;
helps stimulate development of mammary glands (along with other hormones);
in males, may help regulate testosterone production
control:
stimulation: PRH (prolactin-releasing hormone from hypothalamus), high estrogens, breast-feeding
inhibition: PIH (hypothalamus), stimulated by rising PRL levels, low estrogen
B. Adenohypophysis : Prolactin (PRL)
Disorders
hyperprolactinemia = hypersecretion due to adenohypophyseal tumors; results in galactorrhea, lack of menses and infertility in women, impotence in men
B. Adenohypophysis: Thyroid-Stimulating Hormone (TSH)
TSH = thyrotropin
action:
stimulates secretion of hormones from thyroid gland (T4 and T3); also stimulates development of thyroid in youth
control:
release stimulated by TRH (thyroid releasing hormone from hypothalamus)
inhibited by rising levels of thyroid hormones and by GHIH
B. Adenohypophysis: Adrenocorticotropic hormone (ACTH)
ACTH=corticotropin
action: stimulates release of hormones from adrenal cortex
control:
release stimulated by CRH (corticotropin-releasing hormone from hypothalamus)
release inhibited by rising levels of glucocorticoids from adrenal cortex
B. Adenohypophysis: Gonadotropins
regulate activity and secretion by gonads (testes in males; ovaries in females)
control:
stimulated by GnRH (gonadotropin-releasing hormone from hypothalamus)
release of GnRH is inhibited by rising levels of estrogens, progestins and androgens (testosterone)
two important hormones
FSH
LH
Gonadotropins: Follicle-Stimulating Hormone (FSH)
action:
females (ovaries) - stimulates development of ovarian follicles and estrogen production
males (testes) - stimulates sperm production and development
inhibited by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary) and estrogen, progesterone and inhibin from ovaries (feedback to anterior pituitary)
Gonadotropins: Luteinizing Hormone (LH)
LH=lutropin
action:
females (ovaries) - induces ovulation; stimulates secretion of estrogens and progestins (e.g., progesterone)
males (testes) - stimulates production of androgens (e.g., testosterone )
inhibited by estrogen, progesterone and inhibin form ovaries (feedback to anterior pituitary) and by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary)
2. Thyroid Gland
located anteriorly in cervical region, just inferior to thyroid cartilage; two lobes connected by thin isthmus
largest purely endocrine gland in body
consists of follicles (cuboidal or simple squamous epithelium) filled with colloid (combination of protein [thyroglobulin] containing amino acid tyrosine [building block of thyroid hormones])
parafollicular cells produce calcitonin
2. Thyroid Gland: T4 and T3
hormones based on amino acid tyrosine (differ in number of iodine ions)
thyroxine (tetraiodothyronine [T4]) and
triiodothyronine (T3)
T3 is 10x more active, but less common (T4 accounts for about 90% of all thyroid hormone)
much T4 converted to T3 by liver, kidneys, some other tissues
2. Thyroid Gland: T4 and T3
affect metabolic rate of every cell in the body, except brain, spleen, testes, uterus and thyroid gland
affect other activities within these organs and glands
readily cross membranes (diffuse through plasma membrane to bind to mitochondrial receptors and receptors in nucleus)
2. Thyroid Gland
T4 and T3: Actions
increase synthesis of enzymes involved in cellular respiration --> increase basal metabolic rate
increases glucose oxidation --> ATP synthesis
increases ATP synthesis in cytoplasm and by mitochondria
results in increased heat production (calorigenic effect)
work with GH to promote normal tissue growth and development, especially important to growth/development of CNS, skeletal and reproductive systems
T4 and T3: Control
release stimulated by TSH (thyroid-stimulating hormone from adenohypophysis)
release of TSH stimulated by TRH from hypothalamus
release of TRH is stimulated by cold, pregnancy, low thyroxine
release inhibited by GHIH, high glucocorticoid levels, high sex hormone levels, high iodine
Hypothyroidism
too little thyroid hormone (thyroid gland defect, inadequate TSH, TRH, or iodine)
Hashimoto’s thyroid – autoimmune disorder in which thyroid is attacked and function decreases
myxedema - low BMR, constipation, puffy eyes, edema, lethargy, mental sluggishness
endemic goiter - enlargement of thyroid gland usually due to lack of sufficient iodine
cretinism - genetic deficiency of thyroid gland or lack of dietary iodine during development resulting in mental retardation, disproportionate growth, short body with thick tongue and neck
treatment - reversed by iodine supplements or hormone replacement therapy
Hyperthyroidism
too much thyroid hormone (thyrotoxicosis)
Grave’s disease - autoimmune disease in which abnormal antibodies similar to TSH mimic its function and continuously stimulate release of thyroid hormones; results in high BMR, sweating, rapid heart rate, weight loss, restlessness, mood shifts, fatigues easily, limited energy; also toxic goiter
exophthalmos - protrusion of eyeballs, fibrous tissue become edematous (swollen)
treatments - removal of thyroid gland or irradiation
patient must be on synthetic thyroid hormone the rest of his/her life
2. Thyroid Gland: Calcitonin (CT)
polypeptide produced by parafollicular cells
actions: decreases blood calcium levels by:
stimulating osteoblasts (Ca2+ uptake and incorporation into bone)
inhibiting osteoclast activities (osteoclasts break down bone matrix releasing calcium)
control: responds directly to blood calcium levels
very rapid effect
probably more important during childhood when it stimulates bone growth
important because at high blood Ca2+, membranes become less permeable to Na+
3. Parathyroid Glands
2 paired structures on posterior of thyroid gland
oxyphyil cells - function unknown
chief cells secrete parathyroid hormone (PTH; protein)
actions: increases blood Ca2+ by:
stimulating osteoclast activity (which break down bone matrix) while inhibiting osteoblasts (which form bone matrix)
stimulating increased reabsorption of Ca2+ by kidney
indirectly stimulating increased absorption of Ca2+ by small intestine by causing secretion of calcitrol form kidneys
3. Parathyroid Glands
Hyperparathyroidism
rare; caused by parathyroid gland tumor
results in hypercalcemia (excess Ca2+ levels in blood) --> depression of nervous system (because of effect on sodium permeability), abnormal reflexes, skeletal muscle weakness, nausea, vomiting, kidney stones, calcium deposits in soft tissues; bones become soft
Hypoparathyroidism
trauma to or removal of parathyroid gland
results in hypocalcemia (low blood Ca2+) --> neurons become too excitable --> muscle tetany --> spasms/cramps --> respiratory paralysis --> death
4. Adrenal Glands
located in abdominal cavity against back wall (retroperitoneal), superior to kidney
surrounded by connective tissue capsule
two regions:
cortex - outer region, “glandular”, three zones
zona glomerulosa - outer zone
zona fasciculata - middle zone
zona reticularis - inner zone
4. Adrenal Gland Development
4. Adrenal Gland: Regions and Zones
Adrenal Cortex: Zona Glomerulosa
produces steroid hormones based on cholesterol
mineralocorticoids - ion (and water) balance
main hormone is aldosterone
action:
stimulates reabsorption of Na+ and secretion of K+ from kidney, sweat glands, salivary glands, pancreas
secondarily, increases water reabsorption in kidney (water follows Na+)
Adrenal Cortex: Zona Glomerulosa
control:
aldosterone release stimulated by:
high K+, low Na+
angiotensin II (result of renin-angiotensin pathway stimulated by low blood pressure),
ACTH (when under severe stress)
inhibited by low K+, high Na+
Adrenal Cortex: Zona Glomerulosa
Disorders:
aldosteronism = hypersecretion (adrenal tumor)
increased water and Na+ reabsorption --> hypertension, edema;
loss of K+ --> disruption of neural and muscle function
Adrenal Cortex: Zona Glomerulosa
Disorders:
Addison’s Disease = hyposecretion glucocorticoids and mineralocorticoids
results in decreased Na+ and water reabsorption, increased blood K+ --> low blood volume --> hypotension, dehydration;
changes in membrane potentials --> disruption in neural and muscular function
also decreased cortisol secretion by zona fasciculata --> decreased blood glucose levels (especially during prolonged stress)
Adrenal Cortex: Zona Fasciculata
glucocorticoids - effects on glucose metabolism
main hormone is cortisol (hydrocortisone)
actions:
maintains blood glucose levels, especially in times of stress, by:
promoting gluconeogenesis (making new glucose in liver) and use of alternative fuels by other cells (saves glucose for the brain)
anti-inflammatory decrease immune response
can be used clinically to treat allergic reactions (e.g., poison ivy), rheumatoid arthritis
Adrenal Cortex: Zona Fasciculata
Control
stimulated by ACTH
inhibited by cortisol (inhibits secretion of CRH from hypothalamus)
blood levels peak in the morning
Disorders:
Addison’s Disease
- hyposecretion of glucocorticoids and mineralocorticoids
Zona Fasciculata: Cushing’s Disease
hypersecretion of glucocorticoids
caused by hypersecretion of ACTH due to tumor in ZF, pituitary, lungs, kidneys, or pancreas
suppresses glucose metabolism resulting in
hyperglycemia (elevated glucose= steroid diabetes),
stimulates lipid metabolism (weight loss),
loss of muscle and bone mass,
“buffalo neck” and “moon face” (fat redistribution),
anti-inflammatory effects (mask infection)
water and salt retention (effect of aldosterone hypersecretion --> water retention --> hypertension)
Adrenal Cortex: Zona Reticularis
gonadocorticoids
most are androgens (“male” sex hormones) - converted to testosterone; small amounts of estrogens
actions: may contribute to onset of puberty (levels rise between 7 and 13 years of age; exact function compared to hormones from ovaries or testes unclear)
control: stimulated by ACTH
Adrenal Cortex: Zona Reticularis
hypersecretion results in:
masculinization and masculine pattern of hair distribution in females
in males - rapid maturation of reproductive organs, secondary sex characteristics; hypersecretion of estrogens causes feminization and gynecomastia (enlarged breasts)
Adrenal Medulla
chromaffin cells (modified neurons - arise from same embryonic tissue as postganglionic neurons of sympathetic division)
catecholamines - epinephrine (~80%), norepi (NE)
control: secretion stimulated by preganglionic fibers of sympathetic nerves during flight-or-fight response
Adrenal Medulla
actions:
epinephrine (more potent) - increases HR (beta receptors), bronchodilation (in lungs), increased blood glucose (breakdown of glycogen in liver and skeletal muscle, and breakdown of adipose tissue)
NE - peripheral vasoconstriction --> increased BP
5. Pancreas
has both exocrine (acini secrete digestive enzymes) and endocrine function (islets of Langerhans)
control: responds to blood glucose levels (humoral)
hormones are polypeptides (proteins)
5. Pancreas
major cell types
alpha cells secrete glucagon
beta cells secrete insulin
delta cells secrete somatostatin (which inhibits insulin and glucagon secretion, and decrease fat absorption in intestines)
F cells regulate exocrine function of pancreas (secrete pancreatic polypeptide)
5. Pancreas: Glucagon
actions: hyperglycemic (increases blood glucose)
stimulates formation and release of glucose from liver (main target)
glycogenolysis - breakdown of glycogen (storage form of glucose)
gluconeogenesis - formation of glucose from noncarbohydrate molecules (e.g., amino acids, glycerol, lactic acid)
stimulates glycogenolysis in skeletal muscle
stimulates triglyceride breakdown in adipose tissue (fat mobilization)
5. Pancreas: Glucagon
control:
secreted in response to low blood sugar, rising amino acid levels in blood
inhibited by increased blood glucose and by somatostatin
5. Pancreas: Insulin
actions: hypoglycemic (lowers blood glucose)
increases transport of glucose into muscle and fat cells (NOTE: does not increase uptake by brain, liver, or kidney)
inhibits breakdown of glycogen and formation of glucose from amino acids or fatty acids (inhibits glycogenolysis and gluconeogenesis)
promotes formation of glycogen (liver, skeletal muscles), protein synthesis (muscle), and fat synthesis and storage (adipose)
5. Pancreas: Insulin (Control)
stimulated by:
increased blood glucose
increased blood amino acid and fatty acid levels
parasympathetic impulses
hyperglycemic hormones (GH, glucagon, epinephrine, thyroxine, glucocorticoids) indirectly result in insulin secretion by increasing blood glucose levels
inhibited by:
low blood glucose and by somatostatin
sympathetic impulses
5. Pancreas: Insulin - Disorders: Diabetes Mellitus (DM)
hyposecretion (or hypoactivity) of insulin
body cells not stimulated to take up glucose
hyperglycemia (excess blood glucose)
very high glucose --> nausea --> fight-or-flight response --> secretion of hyperglycemic hormones (epi, NE [adrenal medulla], glucocorticoids [adrenal cortex]) --> stimulates gluconeogenesis, lipolysis, glycogenolysis --> adds to already high glucose
not all sugar reabsorbed from urine --> glucose lost in urine (glucosuria) --> increased water loss --> excessive urine production (polyuria) and excessive thirst (polydipsia)
5. Pancreas: Insulin - Diabetes Mellitus
cells use fats as energy source (due to poor glucose uptake)
hyperglycemic hormones stimulate fat mobilization --> fats in blood (lipidemia) --> increase in lipid metabolites in blood (ketone bodies, which are strong organic acids) --> decrease blood pH (ketoacidosis) and ketone bodies in urine (ketonuria)
decreased blood pH --> severe depression of nervous system --> deep breathing --> diabetic coma --> death
polyphagia (excessive hunger) - final sign, due to use of fats and proteins as energy sources
Type I Diabetes mellitus
also called insulin-dependent diabetes (IDDM; formerly juvenile onset diabetes)
onset is sudden, usually before age 15
may be due to autoimmune attack of proteins in beta cells (see “A Closer Look”, p. 640-641)
result is lack of insulin activity
lipidemia (high blood lipid content) and increased cholesterol lead to long-term vascular problems (arteriosclerosis, strokes, heart attacks, renal shutdown, gangrene, blindness)
treated with insulin injections or pancreatic islet transplant (newer technique)
Type II Diabetes Mellitus
non-insulin-dependent (NIDDM; formerly mature-onset diabetes)
usually starts after age 40
insulin levels are normal or elevated, but peripheral tissue become less sensitive to it
25-30% of Americans carry gene that predisposes them to NIDDM, more likely in over-weight people (~90% of cases)
adipose cells secrete tumor necrosis factor alpha that depresses production of protein needed for glucose uptake
often controllable with diet and exercise
Hyperinsulinism
excess of insulin (usually from injection of excess)
causes hypoglycemia --> secretion of hyperglycemic hormones (to raise blood glucose) - low glucose to brain --> anxiety, nervousness, tremors, weakness --> eventually, disorientation, convulsions, death due to “insulin shock”
treated by providing sugar source
6. Gonadal Hormones
Female - ovaries
produce/secrete estrogens and progesterone
estrogens alone --> development and maintenance of ovaries, uterus, secondary sex characteristics
estrogens with progesterone --> breast development, uterine cycle
6. Gonadal Hormones
Male - testes
produce androgens (testosterone) --> development and maintenance of male reproductive system and secondary sex characteristics; sperm production, protein synthesis
inhibin - inhibits release of FSH and LH
7. Thymus
located in mediastinum
function:
active during childhood and before puberty,
after puberty gradually decreases in size and becomes fibrous (involution)
secretes thymosin (thymic extract containing several complementary hormones)
action: promotes development and maturation of lymphocytes
gradual decrease in size and secretory abilities make the elderly more susceptible to disease
General Adaptation Syndrome (GAS)
stress response
stress = any condition that threatens to alter homeostasis
same general response to a variety of stress
major endocrine player is adrenal gland (medulla and cortex)
three phases:
alarm
resistance
exhaustion
GAS: Alarm Phase
immediate response to stress
mobilization of energy sources
sympathetic division activated results in release of epinephrine, NE from adrenal medulla
GAS: Alarm Phase
direct neural and epinephrine effects:
increased heart rate
dilation of pupils
changes in circulation (more to skeletal & cardiac muscle, less to gut)
increased respiration
increased energy use by cells
increased blood glucose
decreased digestion and urine production
increased perspiration
GAS: Resistance Phase
when stress is present more than a few hours, able to cope for weeks to a few months
secretion of renin from kidney --> renin-angiotensin pathway --> aldosterone secretion --> increased Na+ reabsorption --> increased water retention
secretion of ACTH from pituitary
increased aldosterone secretion
increased glucocorticoid secretion --> increased blood glucose, conservation of glucose by muscle, lipids and proteins mobilized as alternative energy sources
secretion of glucose conservation hormones (growth hormone, thyroid hormone, epi) --> conservation of glucose and use of alternatives
GAS: Exhaustion Phase
prolonged stress (more than a few months)
homeostatic breakdown due to:
mineral (electrolyte) imbalances
depletion of glucocorticoids
exhaustion of lipid reserves (especially with starvation)
structural or functional damage to organs
Adrenal Gland Role in GAS
Functions of Endocrine System
1. Reproduction
2. Growth and development
3. Response to stress
4. Maintenance of fluid (water), electrolyte and nutrient balance
5. Regulation of cellular metabolism and energy
Organs of the Endocrine System
1. Pituitary gland
2. Hypothalamus (neuroendocrine)
3. Pineal gland
4. Thyroid gland
5. Parathyroid gland
6. Thymus gland
7. Adrenal gland
8. Pancreas (also has exocrine function)
9. Gonads (testes or ovaries - also have exocrine functions)
Topics
Hormone
Types
Modes of Action
Target cell activation
Control
Specific glands, their hormones, and disorders
Pituitary
Thyroid
Parathyroid
Adrenal
Pancreas
Thymus
Gonads (testes and ovaries)
General Adaptation Syndrome
Hormones
chemicals
secreted by endocrine gland cells into blood (by way of interstitial fluid)
regulate metabolic functions of other cells (called target cells)
carried to all cells, but action is specific to cells that have receptors for the hormone
specificity of body’s response to hormone depends on how many cells have the receptor (highly specific if few cells respond [e.g., ACTH]; diffuse action if many respond [e.g., thyroxine])
Chemical Types of Hormones
Amino-acid based (amino acids, short or long peptides, proteins)
e.g., insulin, growth hormone, prolactin
Steroids - lipid derivatives of cholesterol
e.g., hormones from gonads (testosterone, estrogen)
e.g., hormones from adrenal cortex (adrenocortical hormones)
Eicosanoids - locally-secreted, locally-acting hormones secreted by all cell membranes (e.g., prostaglandins, which increase blood pressure and contribute to uterine contraction)
Types of Changes in Target Cells
plasma membrane permeability changes (opening of protein channels; may change membrane potential)
activation of genes for increased protein synthesis, including enzymes
activation or deactivation of enzymes already present
secretion of cellular products
stimulation of cell division (mitosis)
Mechanisms of Action
action in target cell depends on receptor
receptor may be:
in plasma membrane
second messenger mechanisms
used by most amino acid-based hormones (water soluble)
intracellular (in cytoplasm or nucleus)
direct gene activation
used by steroids and thyroid hormones (lipid soluble)
Mechanisms of Action: Steroids
bind to intracellular receptors
hormone diffuses through plasma membrane and makes its way to nucleus
> where it binds with intracellular receptor to form hormone-receptor complex
> hormone-receptor complex interacts with chromatin (DNA) to affect gene activity (turn genes on or off)
> synthesis of mRNA
> synthesis of protein
Steroid Signaling
Mechanism of Action: Thyroid Hormone
similar to mechanism for steroid hormones
diffuses across plasma membrane
diffuses into nucleus where it interacts with intracellular receptors to activate genes for proteins (enzymes) involved in cellular respiration (glycolysis)
also, binds to receptors at mitochondria to activate genes for proteins involved in cellular respiration (Krebs cycle and electron transport chain)
Mechanisms of Action: Other Hormones
plasma membrane receptor
used by most amino acid-based hormones
interaction of hormone with plasma membrane receptor results in activation of second messenger systems (cyclic AMP or PIP-calcium)
activation of second messenger has cascade effect resulting in:
enzyme activation, or
membrane permeability changes or secretion
Membrane Receptor Mechanisms: 1. Cyclic AMP (cAMP) Signaling
interaction of hormone with receptor
> activates G protein (cleaves phosphate from GTP)-> excitation
> G protein activates adenylate cyclase
> adenylate cyclase forms cAMP from ATP
> cAMP activates protein kinases
> protein kinases activate (or inhibit) other proteins by phosphorylation
> cAMP degraded by enzyme
slightly different G protein inactivates adenylate cyclase - associated with different hormone receptor
Link to animation: http://student.ccbc.cc.md.us/c_anatomy/animat/cAMP.htm
cAMP Signaling Mechanism
Membrane Receptor Mechanisms: 2. PIP-Calcium Signaling
interaction of hormone with receptor --> activates membrane-bound enzyme phospholipase
> phospholipase cleaves PIP2 (phosphatidyl inositol diphosphate) into diacylglycerol (DAG) and IP3 -- each of which acts as a second messenger
diacylglycerol (DAG) activates protein kinases
IP3 (inositol triphosphate) causes release of Ca2+ into cytoplasm (from endoplasmic reticulum or other storage areas) --> Ca2+ acts as third messenger
PIP-Calcium Mechanism (con’t)
-> Ca2+ (third messenger)
changes enzyme activity and plasma membrane channels, or
binds to calmodulin (intracellular regulatory protein) --> activates enzymes
PIP-Calcium Signaling Mechanism
Factors Affecting Target Cell Activation
a. blood levels of hormone, which depend on:
rate of hormone release
rate of deactivation (by target cell or liver)
b. affinity of hormone for receptor
greater affinity means greater association --> greater effect
c. number of receptors available
Factors Affecting Target Cell Activation (con’t)
c. number of receptors available
up-regulation: increase in blood level of specific hormone (normally present at low levels) causes cells to make more receptors
down-regulation: prolonged exposure to high level of specific hormone --> cells remove some receptors
-->return to normal response level
cross-regulation: influence of one hormone on number of receptors for another hormone; e.g., progesterone causes uterus to make fewer estrogen receptors; estrogen causes uterus to make more progesterone receptors
Hormone Removal
hormones may be:
degraded by specific enzymes within target cells;
removed from blood by kidneys (excreted in urine)
degraded by liver (excreted in urine and feces)
half-life - time for 1/2 of hormone to be removed (from a fraction of a minute to 30 minutes)
onset - time from release to action (minutes [amino acid-based] to days [steroids])
duration of action - how long the effects last (~20 minutes to several hours)
Control of Hormone Release
Humoral control
Neural control
Hormonal control
Control of Hormone Release: Humoral
Hormone released in response to changing blood levels of ion or nutrient (negative feedback)
Control of Hormone Release: Humoral
Other examples:
pancreas:
beta cells detect high blood glucose insulin decreases blood glucose
alpha cells detect low blood glucose glucagon raises blood glucose
zona glomerulosa (of adrenal cortex) detects low blood Na+ or high blood K+ aldosteronetthy, K+
Control of Hormone Release: Neural
Hormone released in response to nerve impulse
Control of Hormone Release: Hormonal
Hormone produced by one endocrine gland (or hypothalamus) affects secretion of hormone by another endocrine gland
hypothalamus acts as overall coordinator releases regulatory hormones (releasing hormones or inhibitory hormones) affects anterior pituitary
anterior pituitary, when stimulated, secretes hormones that affect other glands (e.g., TSH [thyroid stimulating hormone] stimulates release of thyroid hormones from thyroid gland)
Hormonal Control: Role of Hypothalamus
Releasing hormones from hypothalamus stimulate secretion from anterior pituitary
Inhibitory hormones from hypothalamus inhibit secretion by anterior pituitary
Impulses from hypothalamus cause release of hormones from posterior pituitary
Hormone Control - Misc.
nervous system can override normal endocrine control
e.g., in “fight-or-flight” response, sympathetic impulses result in release of epinephrine and norepinephrine from adrenal medulla --> increases blood glucose levels to maintain fuel supply during stress or exertion (overrules effect of insulin on blood glucose level)
Organs of the Endocrine System and Their Products
The following major glands will be covered one at a time with their products:
1. Pituitary gland / Hypothalamus
2. Thyroid gland
3. Parathyroid gland
4. Adrenal gland
5. Pancreas (also has exocrine function)
6. Gonadal hormones (ovaries and testes)
7. Thymus
1. Pituitary Gland (Hypophysis)
located in sella turcica of sphenoid bone (in cranial cavity), inferior to hypothalamus
consists of two lobes:
A. neurohypophysis (~ posterior pituitary)
attached to hypothalamus by infundibulum
contains axons and axon terminals of neurosecretory cells whose cell bodies are in hypothalamic nuclei
B. adenohypophysis (~ anterior pituitary)
consists of glandular epithelium
Pituitary Development
A. Neurohypophysis (Posterior Pituitary)
consists of nerve fibers (axons of neurosecretory cells with cell bodies in hypothalamus) and pituicytes (glial cells that support nerve fibers)
acts primarily as a storage and releasing area for hormones actually made in hypothalamic nuclei
hormones released in response to impulses from hypothalamus (neural control)
hormones are short amino acid chains (peptides)
oxytocin
antidiuretic hormone (ADH or “vasopressin”)
A. Neurohypophysis : Oxytocin (OT)
action, in pregnant or nursing women:
stimulates contraction of smooth muscle of uterine wall during labor and delivery
stimulates ejection of milk in lactating mothers
action, in men and non-pregnant women, may be involved in sexual arousal and orgasm
A. Neurohypophysis : Oxytocin (OT)
control:
during labor/delivery, positive feedback: stretching of uterus/cervix --> sensory impulses to hypothalamus --> increased secretion of OT --> increased contraction
suckling: sucking of infant on breast --> sensory to hypothalamus --> oxytocin release --> release of milk
A. Neurohypophysis: Antidiuretic Hormone (ADH)
action: antidiuretic hormone (ADH) directly affects blood pressure - acts as powerful vasoconstrictor --> increases blood pressure (hence name “vasopressin”)
action: affects water balance (indirect affect on blood pressure) - acts on tubules of kidney to increase reabsorption of water less water lost in urine
A. Neurohypophysis: ADH
disorders:
hyposecretion due to damage of hypothalamic nucleus or neurohypophysis--> diabetes insipidus - excessive urine production (polyuria) and thirst
hypersecretion --> SIADH (syndrome of inappropriate ADH secretion) - water retention, headache, cerebral edema, weight gain, hypoosmolarity
Antidiuretic Hormone (ADH): Control
neural control: increased electrolyte (NaCl) concentration --> affects (supraoptic) nucleus in hypothalamus --> impulse to neurohypophysis --> release of ADH --> increased water reabsorption --> decrease in electrolyte concentration
other stimuli: pain, low BP, morphine, barbiturates, nicotine, aldosterone (hormone from adrenal cortex - hormonal control)
inhibition: alcohol (results in more urine production and, potentially, dehydration)
diuretic drugs - some act to supress ADH secretion; used to treat hypertension and congestive heart failure
B. Adenohypophysis (Anterior Pituitary)
linked to hypothalamus via hypophyseal portal system (capillary networks and small veins)
carries regulatory hormones from hypothalamus to pituitary
releasing hormones stimulate secretion of pituitary hormones
inhibitory hormones inhibit secretion
consists of epithelial cells
all hormones produced are proteins
tropic hormones - affect some endocrine glands or provide maintenance oversight for other organs
B. Adenohypophysis : Growth Hormone (GH)
highest levels during evening and sleep
action: stimulates increased rate of protein synthesis leading to cell growth and division
bones and skeletal muscle respond more than other body cells
action: stimulates use of fat as energy source and decreases rate of glucose uptake and glucose metabolism (diabetogenic effect – “spares” glucose)
control:
release stimulated by GHRH (growth hormone releasing hormone) from hypothalamus
inhibited by GHIH (from hypothalamus) and somatomedins (produced by liver under GH stimulation)
Growth Hormone (GH): Disorders
Disorders:
hypersecretion
gigantism (in children)
up to 8’ tall, normal body proportions
acromegaly (after epiphyseal plates close)
enlargement of extremities and face, thickening of soft tissue
hyposecretion
pituitary dwarfism - in children, up to 4’ tall
progeria - premature aging, atrophy of body tissues
B. Adenohypophysis: Prolactin (PRL)
action:
stimulates milk production in mammary glands;
helps stimulate development of mammary glands (along with other hormones);
in males, may help regulate testosterone production
control:
stimulation: PRH (prolactin-releasing hormone from hypothalamus), high estrogens, breast-feeding
inhibition: PIH (hypothalamus), stimulated by rising PRL levels, low estrogen
B. Adenohypophysis : Prolactin (PRL)
Disorders
hyperprolactinemia = hypersecretion due to adenohypophyseal tumors; results in galactorrhea, lack of menses and infertility in women, impotence in men
B. Adenohypophysis: Thyroid-Stimulating Hormone (TSH)
TSH = thyrotropin
action:
stimulates secretion of hormones from thyroid gland (T4 and T3); also stimulates development of thyroid in youth
control:
release stimulated by TRH (thyroid releasing hormone from hypothalamus)
inhibited by rising levels of thyroid hormones and by GHIH
B. Adenohypophysis: Adrenocorticotropic hormone (ACTH)
ACTH=corticotropin
action: stimulates release of hormones from adrenal cortex
control:
release stimulated by CRH (corticotropin-releasing hormone from hypothalamus)
release inhibited by rising levels of glucocorticoids from adrenal cortex
B. Adenohypophysis: Gonadotropins
regulate activity and secretion by gonads (testes in males; ovaries in females)
control:
stimulated by GnRH (gonadotropin-releasing hormone from hypothalamus)
release of GnRH is inhibited by rising levels of estrogens, progestins and androgens (testosterone)
two important hormones
FSH
LH
Gonadotropins: Follicle-Stimulating Hormone (FSH)
action:
females (ovaries) - stimulates development of ovarian follicles and estrogen production
males (testes) - stimulates sperm production and development
inhibited by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary) and estrogen, progesterone and inhibin from ovaries (feedback to anterior pituitary)
Gonadotropins: Luteinizing Hormone (LH)
LH=lutropin
action:
females (ovaries) - induces ovulation; stimulates secretion of estrogens and progestins (e.g., progesterone)
males (testes) - stimulates production of androgens (e.g., testosterone )
inhibited by estrogen, progesterone and inhibin form ovaries (feedback to anterior pituitary) and by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary)
2. Thyroid Gland
located anteriorly in cervical region, just inferior to thyroid cartilage; two lobes connected by thin isthmus
largest purely endocrine gland in body
consists of follicles (cuboidal or simple squamous epithelium) filled with colloid (combination of protein [thyroglobulin] containing amino acid tyrosine [building block of thyroid hormones])
parafollicular cells produce calcitonin
2. Thyroid Gland: T4 and T3
hormones based on amino acid tyrosine (differ in number of iodine ions)
thyroxine (tetraiodothyronine [T4]) and
triiodothyronine (T3)
T3 is 10x more active, but less common (T4 accounts for about 90% of all thyroid hormone)
much T4 converted to T3 by liver, kidneys, some other tissues
2. Thyroid Gland: T4 and T3
affect metabolic rate of every cell in the body, except brain, spleen, testes, uterus and thyroid gland
affect other activities within these organs and glands
readily cross membranes (diffuse through plasma membrane to bind to mitochondrial receptors and receptors in nucleus)
2. Thyroid Gland
T4 and T3: Actions
increase synthesis of enzymes involved in cellular respiration --> increase basal metabolic rate
increases glucose oxidation --> ATP synthesis
increases ATP synthesis in cytoplasm and by mitochondria
results in increased heat production (calorigenic effect)
work with GH to promote normal tissue growth and development, especially important to growth/development of CNS, skeletal and reproductive systems
T4 and T3: Control
release stimulated by TSH (thyroid-stimulating hormone from adenohypophysis)
release of TSH stimulated by TRH from hypothalamus
release of TRH is stimulated by cold, pregnancy, low thyroxine
release inhibited by GHIH, high glucocorticoid levels, high sex hormone levels, high iodine
Hypothyroidism
too little thyroid hormone (thyroid gland defect, inadequate TSH, TRH, or iodine)
Hashimoto’s thyroid – autoimmune disorder in which thyroid is attacked and function decreases
myxedema - low BMR, constipation, puffy eyes, edema, lethargy, mental sluggishness
endemic goiter - enlargement of thyroid gland usually due to lack of sufficient iodine
cretinism - genetic deficiency of thyroid gland or lack of dietary iodine during development resulting in mental retardation, disproportionate growth, short body with thick tongue and neck
treatment - reversed by iodine supplements or hormone replacement therapy
Hyperthyroidism
too much thyroid hormone (thyrotoxicosis)
Grave’s disease - autoimmune disease in which abnormal antibodies similar to TSH mimic its function and continuously stimulate release of thyroid hormones; results in high BMR, sweating, rapid heart rate, weight loss, restlessness, mood shifts, fatigues easily, limited energy; also toxic goiter
exophthalmos - protrusion of eyeballs, fibrous tissue become edematous (swollen)
treatments - removal of thyroid gland or irradiation
patient must be on synthetic thyroid hormone the rest of his/her life
2. Thyroid Gland: Calcitonin (CT)
polypeptide produced by parafollicular cells
actions: decreases blood calcium levels by:
stimulating osteoblasts (Ca2+ uptake and incorporation into bone)
inhibiting osteoclast activities (osteoclasts break down bone matrix releasing calcium)
control: responds directly to blood calcium levels
very rapid effect
probably more important during childhood when it stimulates bone growth
important because at high blood Ca2+, membranes become less permeable to Na+
3. Parathyroid Glands
2 paired structures on posterior of thyroid gland
oxyphyil cells - function unknown
chief cells secrete parathyroid hormone (PTH; protein)
actions: increases blood Ca2+ by:
stimulating osteoclast activity (which break down bone matrix) while inhibiting osteoblasts (which form bone matrix)
stimulating increased reabsorption of Ca2+ by kidney
indirectly stimulating increased absorption of Ca2+ by small intestine by causing secretion of calcitrol form kidneys
3. Parathyroid Glands
Hyperparathyroidism
rare; caused by parathyroid gland tumor
results in hypercalcemia (excess Ca2+ levels in blood) --> depression of nervous system (because of effect on sodium permeability), abnormal reflexes, skeletal muscle weakness, nausea, vomiting, kidney stones, calcium deposits in soft tissues; bones become soft
Hypoparathyroidism
trauma to or removal of parathyroid gland
results in hypocalcemia (low blood Ca2+) --> neurons become too excitable --> muscle tetany --> spasms/cramps --> respiratory paralysis --> death
4. Adrenal Glands
located in abdominal cavity against back wall (retroperitoneal), superior to kidney
surrounded by connective tissue capsule
two regions:
cortex - outer region, “glandular”, three zones
zona glomerulosa - outer zone
zona fasciculata - middle zone
zona reticularis - inner zone
4. Adrenal Gland Development
4. Adrenal Gland: Regions and Zones
Adrenal Cortex: Zona Glomerulosa
produces steroid hormones based on cholesterol
mineralocorticoids - ion (and water) balance
main hormone is aldosterone
action:
stimulates reabsorption of Na+ and secretion of K+ from kidney, sweat glands, salivary glands, pancreas
secondarily, increases water reabsorption in kidney (water follows Na+)
Adrenal Cortex: Zona Glomerulosa
control:
aldosterone release stimulated by:
high K+, low Na+
angiotensin II (result of renin-angiotensin pathway stimulated by low blood pressure),
ACTH (when under severe stress)
inhibited by low K+, high Na+
Adrenal Cortex: Zona Glomerulosa
Disorders:
aldosteronism = hypersecretion (adrenal tumor)
increased water and Na+ reabsorption --> hypertension, edema;
loss of K+ --> disruption of neural and muscle function
Adrenal Cortex: Zona Glomerulosa
Disorders:
Addison’s Disease = hyposecretion glucocorticoids and mineralocorticoids
results in decreased Na+ and water reabsorption, increased blood K+ --> low blood volume --> hypotension, dehydration;
changes in membrane potentials --> disruption in neural and muscular function
also decreased cortisol secretion by zona fasciculata --> decreased blood glucose levels (especially during prolonged stress)
Adrenal Cortex: Zona Fasciculata
glucocorticoids - effects on glucose metabolism
main hormone is cortisol (hydrocortisone)
actions:
maintains blood glucose levels, especially in times of stress, by:
promoting gluconeogenesis (making new glucose in liver) and use of alternative fuels by other cells (saves glucose for the brain)
anti-inflammatory decrease immune response
can be used clinically to treat allergic reactions (e.g., poison ivy), rheumatoid arthritis
Adrenal Cortex: Zona Fasciculata
Control
stimulated by ACTH
inhibited by cortisol (inhibits secretion of CRH from hypothalamus)
blood levels peak in the morning
Disorders:
Addison’s Disease
- hyposecretion of glucocorticoids and mineralocorticoids
Zona Fasciculata: Cushing’s Disease
hypersecretion of glucocorticoids
caused by hypersecretion of ACTH due to tumor in ZF, pituitary, lungs, kidneys, or pancreas
suppresses glucose metabolism resulting in
hyperglycemia (elevated glucose= steroid diabetes),
stimulates lipid metabolism (weight loss),
loss of muscle and bone mass,
“buffalo neck” and “moon face” (fat redistribution),
anti-inflammatory effects (mask infection)
water and salt retention (effect of aldosterone hypersecretion --> water retention --> hypertension)
Adrenal Cortex: Zona Reticularis
gonadocorticoids
most are androgens (“male” sex hormones) - converted to testosterone; small amounts of estrogens
actions: may contribute to onset of puberty (levels rise between 7 and 13 years of age; exact function compared to hormones from ovaries or testes unclear)
control: stimulated by ACTH
Adrenal Cortex: Zona Reticularis
hypersecretion results in:
masculinization and masculine pattern of hair distribution in females
in males - rapid maturation of reproductive organs, secondary sex characteristics; hypersecretion of estrogens causes feminization and gynecomastia (enlarged breasts)
Adrenal Medulla
chromaffin cells (modified neurons - arise from same embryonic tissue as postganglionic neurons of sympathetic division)
catecholamines - epinephrine (~80%), norepi (NE)
control: secretion stimulated by preganglionic fibers of sympathetic nerves during flight-or-fight response
Adrenal Medulla
actions:
epinephrine (more potent) - increases HR (beta receptors), bronchodilation (in lungs), increased blood glucose (breakdown of glycogen in liver and skeletal muscle, and breakdown of adipose tissue)
NE - peripheral vasoconstriction --> increased BP
5. Pancreas
has both exocrine (acini secrete digestive enzymes) and endocrine function (islets of Langerhans)
control: responds to blood glucose levels (humoral)
hormones are polypeptides (proteins)
5. Pancreas
major cell types
alpha cells secrete glucagon
beta cells secrete insulin
delta cells secrete somatostatin (which inhibits insulin and glucagon secretion, and decrease fat absorption in intestines)
F cells regulate exocrine function of pancreas (secrete pancreatic polypeptide)
5. Pancreas: Glucagon
actions: hyperglycemic (increases blood glucose)
stimulates formation and release of glucose from liver (main target)
glycogenolysis - breakdown of glycogen (storage form of glucose)
gluconeogenesis - formation of glucose from noncarbohydrate molecules (e.g., amino acids, glycerol, lactic acid)
stimulates glycogenolysis in skeletal muscle
stimulates triglyceride breakdown in adipose tissue (fat mobilization)
5. Pancreas: Glucagon
control:
secreted in response to low blood sugar, rising amino acid levels in blood
inhibited by increased blood glucose and by somatostatin
5. Pancreas: Insulin
actions: hypoglycemic (lowers blood glucose)
increases transport of glucose into muscle and fat cells (NOTE: does not increase uptake by brain, liver, or kidney)
inhibits breakdown of glycogen and formation of glucose from amino acids or fatty acids (inhibits glycogenolysis and gluconeogenesis)
promotes formation of glycogen (liver, skeletal muscles), protein synthesis (muscle), and fat synthesis and storage (adipose)
5. Pancreas: Insulin (Control)
stimulated by:
increased blood glucose
increased blood amino acid and fatty acid levels
parasympathetic impulses
hyperglycemic hormones (GH, glucagon, epinephrine, thyroxine, glucocorticoids) indirectly result in insulin secretion by increasing blood glucose levels
inhibited by:
low blood glucose and by somatostatin
sympathetic impulses
5. Pancreas: Insulin - Disorders: Diabetes Mellitus (DM)
hyposecretion (or hypoactivity) of insulin
body cells not stimulated to take up glucose
hyperglycemia (excess blood glucose)
very high glucose --> nausea --> fight-or-flight response --> secretion of hyperglycemic hormones (epi, NE [adrenal medulla], glucocorticoids [adrenal cortex]) --> stimulates gluconeogenesis, lipolysis, glycogenolysis --> adds to already high glucose
not all sugar reabsorbed from urine --> glucose lost in urine (glucosuria) --> increased water loss --> excessive urine production (polyuria) and excessive thirst (polydipsia)
5. Pancreas: Insulin - Diabetes Mellitus
cells use fats as energy source (due to poor glucose uptake)
hyperglycemic hormones stimulate fat mobilization --> fats in blood (lipidemia) --> increase in lipid metabolites in blood (ketone bodies, which are strong organic acids) --> decrease blood pH (ketoacidosis) and ketone bodies in urine (ketonuria)
decreased blood pH --> severe depression of nervous system --> deep breathing --> diabetic coma --> death
polyphagia (excessive hunger) - final sign, due to use of fats and proteins as energy sources
Type I Diabetes mellitus
also called insulin-dependent diabetes (IDDM; formerly juvenile onset diabetes)
onset is sudden, usually before age 15
may be due to autoimmune attack of proteins in beta cells (see “A Closer Look”, p. 640-641)
result is lack of insulin activity
lipidemia (high blood lipid content) and increased cholesterol lead to long-term vascular problems (arteriosclerosis, strokes, heart attacks, renal shutdown, gangrene, blindness)
treated with insulin injections or pancreatic islet transplant (newer technique)
Type II Diabetes Mellitus
non-insulin-dependent (NIDDM; formerly mature-onset diabetes)
usually starts after age 40
insulin levels are normal or elevated, but peripheral tissue become less sensitive to it
25-30% of Americans carry gene that predisposes them to NIDDM, more likely in over-weight people (~90% of cases)
adipose cells secrete tumor necrosis factor alpha that depresses production of protein needed for glucose uptake
often controllable with diet and exercise
Hyperinsulinism
excess of insulin (usually from injection of excess)
causes hypoglycemia --> secretion of hyperglycemic hormones (to raise blood glucose) - low glucose to brain --> anxiety, nervousness, tremors, weakness --> eventually, disorientation, convulsions, death due to “insulin shock”
treated by providing sugar source
6. Gonadal Hormones
Female - ovaries
produce/secrete estrogens and progesterone
estrogens alone --> development and maintenance of ovaries, uterus, secondary sex characteristics
estrogens with progesterone --> breast development, uterine cycle
6. Gonadal Hormones
Male - testes
produce androgens (testosterone) --> development and maintenance of male reproductive system and secondary sex characteristics; sperm production, protein synthesis
inhibin - inhibits release of FSH and LH
7. Thymus
located in mediastinum
function:
active during childhood and before puberty,
after puberty gradually decreases in size and becomes fibrous (involution)
secretes thymosin (thymic extract containing several complementary hormones)
action: promotes development and maturation of lymphocytes
gradual decrease in size and secretory abilities make the elderly more susceptible to disease
General Adaptation Syndrome (GAS)
stress response
stress = any condition that threatens to alter homeostasis
same general response to a variety of stress
major endocrine player is adrenal gland (medulla and cortex)
three phases:
alarm
resistance
exhaustion
GAS: Alarm Phase
immediate response to stress
mobilization of energy sources
sympathetic division activated results in release of epinephrine, NE from adrenal medulla
GAS: Alarm Phase
direct neural and epinephrine effects:
increased heart rate
dilation of pupils
changes in circulation (more to skeletal & cardiac muscle, less to gut)
increased respiration
increased energy use by cells
increased blood glucose
decreased digestion and urine production
increased perspiration
GAS: Resistance Phase
when stress is present more than a few hours, able to cope for weeks to a few months
secretion of renin from kidney --> renin-angiotensin pathway --> aldosterone secretion --> increased Na+ reabsorption --> increased water retention
secretion of ACTH from pituitary
increased aldosterone secretion
increased glucocorticoid secretion --> increased blood glucose, conservation of glucose by muscle, lipids and proteins mobilized as alternative energy sources
secretion of glucose conservation hormones (growth hormone, thyroid hormone, epi) --> conservation of glucose and use of alternatives
GAS: Exhaustion Phase
prolonged stress (more than a few months)
homeostatic breakdown due to:
mineral (electrolyte) imbalances
depletion of glucocorticoids
exhaustion of lipid reserves (especially with starvation)
structural or functional damage to organs
Adrenal Gland Role in GAS
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