Endocrine Physiology

Front 1

Factors that affect hormone binding protein synthesis

Back 1

Estrogen increases binding proteins; androgens decrease binding proteins. In pregnancy there's increased total hormones with normal levels of free hormone.

Front 2

Site of synthesis of CRH

Back 2

Paraventricular nucleus

Front 3

Site of synthesis of TRH

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Paraventricular nucleus

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Site of synthesis of PIF

Back 4

Arcuate nucleus

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Site of synthesis of GHRH

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Arcuate nucleus

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Site of synthesis of GnRH

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Preoptic region

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Site of synthesis of ADH

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Supraoptic and paraventricular nuclei

Front 8

How do hypothalamic hormones reach the anterior pituitary?

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Hormones are released in the hypophyseal-portal system

Front 9

Hypothalamic hormones

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GHRH, GnRH, PIF (dopamine), TRH, CRH, Somatostatin, ADH, prolactin

Front 10

Anterior pituitary hormones

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ACTH, TSH, LH, FSH, GH, prolactin

Front 11

Sheehan syndrome

Back 11

Ischemic necrosis of the pituitary due to severe blood loss during delivery. Causes hypopituitarism.

Front 12

Obstruction of pituitary stalk

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Adenoma compresses pituitary stalk and decreases secretion of anterior pituitary hormones except prolactin.

Front 13

What prevents downregulation of pituitary receptors?

Back 13

Pulsatile release of hypothalamic hormones.

Front 14

Hyperprolactinemia

Back 14

Results from dopamine antagonists or pituitary adenomas that compress the pituitary stalk. Amenorrhea, galactorrhea, decreased libido, impotence, hypogonadism

Front 15

What hormone controls release of cortisol and adrenal androgens?

Back 15

ACTH

Front 16

What hormone regulates release of aldosterone?

Back 16

Angiotensin II and also potassium in hyperkalemia

Front 17

Layers of the adrenal cortex

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From external to internal: glomerulosa (aldosterone), fasciculata (cortisol), reticularis (androgens)

Front 18

Consequences of loss of zona glomerulosa

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No aldosterone: loss of Na, ↓ECF, ↓blood pressure, circulatory shock, death

Front 19

Consequences of loss of zona fasciculata

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No cortisol: circulatory failure (cortisol is permissive for cathecolamine vasoconstriction), can't mobilize energy stores during exercise or cold (hypoglycemia)

Front 20

Consequences of loss of adrenal medulla

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No epinephrine: decreased capacity to mobilize fat and glycogen during stress. Not necessary for survival.

Front 21

What are the 17-OH steroids?

Back 21

17OHpregnenolone, 17OHprogesterone, 11-deoxycortisol, cortisol. Urinary 17OH steroids are an index of cortisol secretion.

Front 22

What is the rate-limiting enzyme for steroid hormone synthesis?

Back 22

Desmolase - converts cholesterol into pregnenolone

Front 23

What are the 17-ketosteroids?

Back 23

DHEA and androstenidione

Front 24

DHEA

Back 24

Weak androgen 17-ketosteroid conjugated with sulfateto make it water-soluble

Front 25

What is measured as an index of androgen production?

Back 25

Urinary 17-ketosteroids. In females and prepubertal males is an index of adrenal 17-ketosteroids. In postpubertal males is an index of 2/3 adrenal androgens and 1/3 testicular androgens.

Front 26

Stimulus for the zona glomerulosa

Back 26

Angiotensin II and potassium in hyperkalemia stimulate production of aldosterone

Front 27

Hormone responsible for negative feedback for ACTH release

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Cortisol

Front 28

Enzyme deficiencies that produce congenital adrenal hyperplasia and low cortisol levels

Back 28

21β-OH, 11β-OH and 17α-OH all result in low cortisol levels.

Front 29

21β-OH deficiency

Back 29

No aldosterone: loss of Na, ↓ECF, ↓blood pressure in spite of high renin and angiotensin II, circulatory shock, death. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, hypotension (persmissive for catecholamines), fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism

Front 30

11β-OH deficiency

Back 30

Excess 11-deoxycorticosterone: Na and water retention, low-renin hypertension. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism

Front 31

17α-OH deficiency

Back 31

Excess 11-deoxycorticosterone and low aldosterone (no AII): Na and water retention, low-renin hypertension. No cortisol: skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia; corticosterone partially compensates low cortisol levels. No 17-ketosteroids: male pseudohermaphrodite, no testosterone, no estrogen.

Front 32

↓17OH-steroids ↑ACTH, ↓blood pressure, ↓mineralocorticoids, ↑17-ketosteroids

Back 32

21β-OH deficiency

Front 33

↓17OH-steroids ↑ACTH, ↑blood pressure, ↓aldosterone, ↑11-deoxycorticosterone, ↑17-ketosteroids

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11β-OH deficiency

Front 34

↓17OH-steroids ↑ACTH, ↑blood pressure, ↓aldosterone, ↑11-deoxycorticosterone, ↓17-ketosteroids

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17α-OH deficiency

Front 35

Stress hormones

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GH, Glucagon, cortisol, epinephrine

Front 36

Actions of GH in stress situations

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Mobilizes fatty acids by increasing lipolysis in adipose tissue

Front 37

Actions of glucagon in stress situations

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Mobilizes glucose by increasing liver glycogenolysis

Front 38

Actions of cortisol in stress situations

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Mobilizes fat, carbs and proteins

Front 39

Actions of epinephrine in stress

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Mobilizes glucose via glycogenolysis and fat via lipolysis.

Front 40

Metabolic actions of cortisol

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1) Protein catabolism and delivery of amino acids; 2) lipolysis and delivery of fatty acids and glycerol 3) gluconeogenesis raises glycemia; also inhibits glucose uptake.

Front 41

Permissive actions of cortisol

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Enhances glucagon (without cortisol --> fasting hypoglycemia); enhances epinephrine (without cortisol -->hypotension)

Front 42

α-MSH

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Stimulates melanocytes and causes darkening of skin. Synthesized along with ACTH from pro-opiomelanocortin.

Front 43

↑cortisol, ↓CRH, ↓ACTH, no hyperpigmentation

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Primary hypercortisolism

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↓cortisol, ↑CRH, ↑ACTH, hyperpigmentation

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Addison disease - primary hypocortisolism

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↑cortisol, ↓CRH, ↑ACTH, hyperpigmentation

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Secondary hypercortisolism

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↓cortisol, ↑CRH, ↓ACTH, no hyperpigmentation

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Secondary hypocortisolism

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↓cortisol, ↓CRH, ↓ACTH, no hyperpigmentation, symptoms of excess cortisol

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Steroid administration

Front 48

Cushing syndrome

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Protein depletion, weak inflammatory response, poor wound healing, hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, osteoporosis, purple striae, hirsutism, hypertension, hypokalemic alkalosis, buffalo hump

Front 49

Actions of aldosterone

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↑Na channels in lumen of principal cells, ↑activity of Na/K ATPase of principal cells --> increases Na reabsorption. Also ↑ secretion of K and H leading to hypokalemic metabolic alkalosis.

Front 50

Addison disease

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↑ ACTH, hyperpigmentation, hypotension (no aldosterone, no cortisol), hyperkalemic metabolic acidosis (no aldosterone), loss of body hair (no androgens), hypoglycemia, ↑ ADH secretion

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Causes of secondary hyperaldosteronism

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CHF, vena cava constriction, cirrhosis, renal artery stenosis

Front 52

Primary hyperaldosteronism

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Na and water retention, hypertension, hypokalemic metabolic alkalosis, ↓ renin and angiotensin, no edema due to pressure diuresis and natriuresis.

Front 53

Primary hypoaldosteronism

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Na and water loss, hypotension, hyperkalemic metabolic acidosis, ↑ renin and angiotensin II, no edema

Front 54

Secondary hyperaldosteronism

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↑ renin and angiotensin II, ↑ Na and water retention in venous circulation, edema

Front 55

Factors that influence ADH secretion

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↑ osmolarity --> ↑ ADH secretion; ↓ blood volume --> baroreceptors --> medulla --> ↑ ADH secretion

Front 56

Actions of ADH

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Inserts water channels in luminal membrane of collecting ducts, increases reabsorption of water.

Front 57

Central diabetes insipidus

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Not enough ADH secreted. Dilute urine is formed in spite of water deprivation. Responds to injected ADH.

Front 58

Nephrogenic diabetes insipidus

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ADH is secreted but ducts are unresponsive to it. Dilute urine is formed in spite of water deprivation or injected ADH.

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SIADH

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Excessive secretion of ADH in spite of low osmolarity. Concentrated urine is formed.

Front 60

↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↓ ECF, ↑ osmolarity

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Diabetes insipidus

Front 61

↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↓ ECF, ↑ osmolarity

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Dehydration

Front 62

↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↑ ECF, ↓ osmolarity

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SIADH

Front 63

↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↑ ECF, ↓ osmolarity

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Primary polydipsia

Front 64

Actions of ANP

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Atrial stretch or ↑ osmolarity --> ANP secretion --> dilation of afferent, constriction of efferent --> ↑ GFR --> natriuresis; also decreases permeability of collecting ducts to water.

Front 65

Delta cells of the pancreas

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Between alpha and beta cells, represent 5% of islets. Secrete somatostatin.

Front 66

Alpha cells of the pancreas

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Near the periphery of the islets, represent 20%. Secrete glucagon.

Front 67

Beta cells of the pancreas

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In the center of the islets, represent 60-75%. Secrete insulin and C peptide.

Front 68

Insulin receptor

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Has intrinsic tyrosine kinasae activity. Insulin receptor substrate binds tyrosine kinase, activates SH2 domain proteins: PI-3 kinase (translocation of GLUT-4), p21RAS.

Front 69

Tissues that require insulin for glucose uptake

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Resting skeletal muscle and adipose tissue

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Tissues independent of insulin for glucose uptake

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Brain, kidneys, intestinal mucosa, red blood cells, beta cells of the pancreas.

Front 71

Anabolic hormones

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Insulin, GH/IGF-1, androgens, T3/T4, IGF-1 (somatomedin C)

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Effects of insulin on potassium

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Increases Na/K ATPase uptake of K. Insulin + glucose used to treat hyperkalemia.

Front 73

Mechanism of insulin release

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Glucose enters β cells and is metabolized --> ↑ ATP --> closes K channels --> ↑ depolarization --> ↑ Ca influx --> exocytosis of insulin.

Front 74

Factors that stimulate secretion of insulin

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Glucose, arginine, GIP, glucagon

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Factors that inhibit insulin release

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Somatostatin, norepinephrine via α1 receptors

Front 76

↑ glucose, ↑ insulin, ↑ C peptide

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Type 2 diabetes

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↑ glucose, ↓ insulin, ↓ C peptide

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Type 1 diabetes

Front 78

↓ glucose, ↑ insulin, ↑ C peptide

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Insulinoma

Front 79

↓ glucose, ↑ insulin, ↓ C peptide

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Factitious hypoglycemia (insulin injection)

Front 80

Actions of somatomedin C

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Increases cartilage synthesis at epiphyseal plates (↑ bone length). Also ↑ lean body mass. Protein-bound and long half-life correlates with GH secretion. Also called IGF-1.

Front 81

Secretion of GH

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Pulsatile during non-REM sleep; more frequent in puberty due to increased androgens; requires thyroid hormones; decreases in the elderly.

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Factors that stimulate GH secretion

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Deep sleep, hypoglycemia, exercise, arginine, GHRH, low somatostatin

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Factors that inhibit GH secretion

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Negative feedback by GH on GHRH; positive feedback on somatostatin by IGF-1

Front 84

Dwarfism

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Due to GH insensitivity during prepuberty

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Acromegaly

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Due to excess GH in postpuberty. Enlargement of hands, feet and lower jaw, increased proteins, decreased fat, visceromegaly, cardiac insuficiency.

Front 86

Composition of bone

Back 86

Phosphate and calcium precipitate forming hydroxyapatite in osteoid matrix.

Front 87

Actions of PTH

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Rapid actions: increases Ca reabsorption in distal tubules and decreases phosphate reabsorption in proximal tubules, thus lowering blood phosphate and lowering solubility product which leads to bone resorption and raises plasma Ca. Slow actions: increases number and activity of osteoclasts (via osteoclast activating factor released by osteoblasts), increases activity of alpha-1 hydroxylase in the proximal tubules which increases active vitamin D and absorption of Ca and phosphate in the instetines.

Front 88

Clinical features of primary hyperparathyroidism

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↑ plasma Ca and ↓ plasma phosphate, phosphaturia, polyuria, calciuria (filtered load of Ca exceeds Tm), ↑ serum alkaline phosphatase, ↑ urinary hydroxyproline, muscle weakness, easy fatigability.

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Clinical features of primary hypoparathyroidism

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↓ plasma Ca and ↑ plasma phosphate, hypocalcemic tetany due to increased excitability of motor neurons.

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↑ PTH, ↑ Ca, ↓ phosphate

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Primary hyperparathyroidism. Causes: parathyroid adenoma (MEN I and II), ectopic PTH tumor (lung squamous CA)

Front 91

↓ PTH, ↓ Ca, ↑ phosphate

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Primary hypoparathyroidism. Cause: surgical removal of parathyroid.

Front 92

↑ PTH, ↓ Ca, ↑ phosphate

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Secondary hyperparathyroidism due to renal failure (no active vitamin D, decreased GFR)

Front 93

↑ PTH, ↓ Ca, ↓ phosphate

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Secondary hyperparathyroidism. Causes: deficiency of vitamin D due to bad diet or fat malabsorption.

Front 94

↓ PTH, ↑ Ca, ↑ phosphate

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Secondary hypoparathyroidism due to excess vitamin D.

Front 95

Vitamin D synthesis

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Dietary and skin cholecalciferol is hydroxylated by 25-hydroxylase in the liver and activated to 1,25 di-OH cholecalciferol by 1-alpha hydroxylase in the proximal tubules.

Front 96

Actions of 1,25 di-OH cholecalciferol

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Increases Ca binding proteins by intestinal cells which increases intestinal reabsorption of Ca and phosphate. Also increases reabsorption of Ca in the distal tubules. Increased serum Ca promotes bone deposition.

Front 97

Osteomalacia

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Underminerilized bone in adults due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.

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Rickets

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Underminerilized bone in children due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.

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Excess vitamin D

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Leads to bone reosprtion and demineralization

Front 100

Synthesis of thyroid hormones

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1) Iodine is actively transported into follicle cell; 2) thyroglobulin is synthesized in the RER, glycosylated in the SER and packaged in the GA; 3) Peroxidase is found in the luminal membrane and catalizes oxidation of I-, iodination of thyroglobulin and coupling to form MITs and DITs; 4) iodinated thyroglobulin is stored in the follicle lumen.

Front 101

Structure of thyroid hormones

Back 101

T4 has iodine attached to carbons 3 and 5 of both fenol rings; T3 has iodide attached to carbons 3 and 5 of the amino terminal fenol ring and the 3 prime carbon of the hydroxyl end fenol ring; reverse T3 has iodide in carbon 3 of the amino terminal fenol ring but not carbon 5.

Front 102

Secretion of thyroid hormones

Back 102

Iodinated thyroglobulin is endocytosed from the lumen of the follicles into lysosomes. Thyroglobulin is degraded into amino acids, T3, T4, DITs and MITs. T4 and T3 are secreted in a 20:1 ratio. DITs and MITs are deiodinated and iodine is recycled.

Front 103

Transport of thyroid hormones

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99% is bound to TBG, 1% is free. T4 has greater affinity for TBG and a half-life of 6 days. T3 has greater affinity for nuclear receptor and is the active form with a 1 day half-life. 50:1 T4/T3 ratio in periphery.

Front 104

Activation and degradation of thyroid hormones

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5' monodeiodinase activates T4 into T3. 5-monodeiodinase inactivates T4 into reverse T3.

Front 105

Actions of thyroid hormones

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↑ metabolic rate by ↑ Na/K ATPase except in brain, uterus and testes; essential for brain maturation and menstrual cycle; permissive for bone growth; permissive for GH synthesis and secretion; ↑ clearance of cholesterol; required for activation of carotene; ↑ intestinal glucose absorption; ↑ affinity and number of β1 receptros in the heart.

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Effects of hypothyroidism in newborns

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↓ dendritic branching and myelination lead to mental retardation.

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Effects of hypothyroidism in juveniles

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Cretinism results in ↓ bone growth and ossification --> dwarfism. Due to lack of permissive action on GH.

Front 108

Control of thyroid hormone secretion

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Circulating T4 is responsible for negative feedback of TSH by decreasing sensitivity to TRH. T4 is converted to T3 in the thyrotroph to induce negative feedback.

Front 109

Effects of TSH

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Rapid actions: ↑ iodide trapping, ↑ synthesis of thyroglobulin, ↑ reuptake of iodinated thyroglobulin, ↑ secretion of T4; late effects: ↑ blood flow to thyroid gland, ↑ hypertrophy of follicles and goiter.

Front 110

↓ T4, ↑ TSH, ↑ TRH

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Primary hypothyroidism; ↑ TSH is the more sensible index

Front 111

↓ T4, ↓ TSH, ↑ TRH

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Pituitary (secondary) hypothyroidism

Front 112

↓ T4, ↓ TSH, ↓ TRH

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Hypothalamic (tertiary) hypothyroidism

Front 113

↑ T4, ↑ TSH, ↓ TRH

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Pituitary (secondary) hyperthyroidism

Front 114

↑ T4, ↓ TSH, ↓ TRH

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Graves disease

Front 115

Pathophysiology of iodine deficiency

Back 115

Thyroid makes less T4 and more T3 so actions of T3 may be normal but low levels of T4 stimulate TSH secretion with development of goiter. Thus euthyroid with goiter.

Front 116

Clinical features of hypothyroidism

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↓ basal metabolic rate with cold intolerance, ↓ cognition, hyperlipidemia, nonpitting myxedema (mucopolysacchride accumulation around eyes retains water), physiologic jaundice (↑ carotene), hoarse voice, constipation, anemia, lethargy

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Clinical features of hyperthyroidism

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↑ metabolic rate with heat intolerance and sweating, ↑ apetite with weight loss, muscle weakness, tremor, irritability, tachycardia, exophthalmos.

Front 118

Leydig cells

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Stimulated by LH; produce testosterone for peripheral tissues and Sertoli cells. Testosterone provides negative feedback for LH secretion by pituitary.

Front 119

Sertoli cells

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Stimulated by FSH; produce inhibins (inhibits secretion of FSH), estradiol (testosterone is converted by aromatase), androgen binding proteins and growth factors for sperm. Responsible for development of sperm in males. Also MIH in male fetus.

Front 120

↓ sex steroids, ↑ LH, ↑ FSH

Back 120

Primary hypogonadism or postmenopause.

Front 121

↓ sex steroids, ↓ LH, ↓ FSH

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Pituitary hypogonadism or constant GnRH infusion (downregulates GnRH receptors of pituitary.

Front 122

↑ sex steroids, ↓ LH, ↓ FSH

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Anabolic steroid therapy. LH supression causes Leydig cell atrophy with decreased Leydig testosterone which suppresses spermatogenesis.

Front 123

↑ sex steroids, ↑ LH, ↑ FSH

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Pulsatile infusion of GnRH

Front 124

Fetal development of male structures

Back 124

LH --> Leydig cells --> testosterone --> Wolffian ducts (internal male structures: epididymis, vasa deferentia and seminal vesicles). Testosterone + 5-alpha reductase --> dihydrotestosterone --> urogenital sinus and external organs. MIH by Sertoli cells --> regression of Mullerian ducts and female structures.