endocrine wk5

  1. cortisol
    • Released from zona fasciculata of the adrenal cortex
    • Stimulated by ACTH from anterior pituitary
    • inhibits tissues (muscle, fat) from absorbing glucose
    • promotes glyconeogenesis from amino acids and lipids, especially in the liver
    • promotes muscle breakdown and release of fats from adipose tissue (theorized to provide raw materials for wound healing).

    • inhibitory effect over several proinflammatory cytokines, thus exerting an inhibitory influence over the immune system. This is believed to be a manner in which pain and inflammation are reduced during an emergency situation.
    • net effect: increases glucose in bloodstream
  2. gonadocorticoids (DHEA and androstenedione)
    • adrenal cortex, zona reticularis
    • converted to estrogen or testosterone in gonadal tissues
  3. EPI, NE
    • released from adrenal medulla chromaffin cells
    • Dilated pupils

    Elevated heart rate

    Elevated blood pressure

    Dilated respiratory tract

    • Shunting of blood from skin to skeletal muscle
    • Increased metabolic rate

    Elevated blood sugar
  4. Somatostatin
    • inhibits TSH and ACTH release from the pituitary gland
    • inhibits Alpha and Beta islet cells secretion.
  5. Thyroid hormones
    Tri-iodothyronine (T3) Tetra-iodothyronine (T4, also known as thyroxine
  6. Anterior pituitary
    classes of cells
    • Most numerous in adenohypophysis
    • Protein-based hormonal products inside vesicles
    • Brownish-red color
    • GH, prolactin

    • Glycoprotein-coated secretory products
    • Stain brightly basophilic or purplish with PAS
    • POMC (cleaved into ACTH), TSH, FSH, LH
  7. Posterior pituitary
    • Derived from nervous tissue and behaves like it
    • Cells here don't synthesize hormones
    • Neurosecretory cells within hypothalamic nuclei synthesize vasopressin and oxytocin
    • Send those products down axons that terminate on fenestrated capillaries in the post pit
    • Vasopressin: maintains blood pressure, kidney fluid resorption, arteriole smooth muscle tone
    • Oxytocin: response to infant nursing, milk to be secreted by mammary glands, social/emotional behaviors
    • Herring bodies: Basophilic-staining, non-cellular objects, Elaborated axons from the neurosecretory cells
    • Pituicytes: Specialized glial cells, Cytoplasmic extensions surround axon termianls of neurosecretory cells from hypothalamus
  8. Zona glomerulosa
    • outermost layer of adrenal cortex
    • Mineralocorticoids: aldosterone
    • Stimulates resorption of Na and K by kidneys
    • Release regulated by renin-angiotensin system
    • Thin layer relative to middle layer
    • Spherical arrangement of cells
  9. Zona reticularis (innermost layer)
    • Gonadocorticoids: DHEA, androstenedione
    • Hormones taken up by gonadal tissues and converted to testost/estrogen
    • Small minority of the sex hormones for an individual
    • Stains darker than other layers with H&E
    • Cells contain lots of pigment called lipofuscin, breakdown product of lipid metabolism
  10. Endocrine pancreas
    • Alpha cells: glucagon
    • Signals liver to undergo glycolysis to raise blood glucose
    • Beta cells: insulin
    • Signals muscle/liver/adipose to take up glucose
    • Signals muscle to take up AAs
    • Delta cells: somatostatin
    • Inhibits TSH and ACTH release from the pituitary
    • Inhibits alpha/beta islet cells
  11. Hyperthyroidism
    • Fatigue
    • Weight gain
    • Dry brittle hair
    • Decreased HR
    • Joint pain
    • Decreased sweating
    • Constipation
  12. Histology of thyroid
    • Large spherical thyroid follicles surrounded by follicular cells
    • Filled with substance called colloid in lumen
    • Colloid is reservoir for iodine (bound by protein called thyroglobulin) cells
    • Secrete calcitonin, promotes calcium absorption in bone
    • Stain lightly with H&E, but darkly with lead hematoxylin
  13. Parathyroid histology
    • Principal cells
    • Lightly staining, numerous
    • Synthesize PTH
    • Oxyphil cells
    • Highly eosinophilic cytoplasm
    • Unknown function
    • Large number of capillaries
  14. Parathyroid glands
    • Four small bean shaped glands, deep surface of the thyroid gland
    • Secrete parathyroid hormone PTH
    • Elevate serum calcium
    • Stimulates osteoblasts which stimulate osteoclasts to catabolize bone, liberating sequestered calcium from the bone matrix
    • Acts on kidneys to increase calcium reabsorption
    • Small intestine to increase calcium uptake
  15. parathroid hormone actions
    • Kidneys - increase Ca2+ reabsorption, decrease PO4 reabsorption
    • stimulate osteoblasts in bone -> M-CSF released + RANK ligand binds to osteoclast precursor
    • Osteoclasts break down bone
    • increase plasma Ca2+, PO4 -> neg feedback on PTH glands
    • increase urine PO4 -> Vit D, incr. plasma Ca2+ and PO4
  16. Amts and distribution of Ca2+, phosphate, Mg2+ in body
    • Ca2+: 1kg, almost all in bone (65% mineral phase, 35% organic matrix) - about 50% ionized. When total [Ca2+] goes down, the percentage adjusts so that the same amt of [Ca2+] is free
    • PO4-: 600g, almost all in bone, <20% intracellular, 80% ionized
    • Mg2+: 10g
  17. Hormones regulating phosphorus and Ca2+ metabolism
    • PTH: kidney, bone. PTH changes greatly with change in [Ca2+]
    • 5-10% of Ca2+ reabsorption occurs in DCT, regulated by PTH
    • Vit D: intestine, bone, kidney. Activated in skin, liver, kidney
  18. 1-alpha hydroxylase
    • Stimulated by: incr. PTH, decr Ca2+, decr PO4
    • Inhibited by: decr PTH, incr Ca2+, incr PO4
  19. clinical measurement of vit D
    • 25-(OH)D, calcidiol is used
    • 1,25(OH)2D, calcitriol, has a shorter half life
  20. Symptoms of hypercalcemia
    • 80% have no symptoms (primary hyperparathyroidism)
    • GI: dry mouth, thirst, polydipsia, vomiting, nausea, constipation
    • Genitourinary: polyuria, nocturia, renal stones, renal failure
  21. Causes of hypercalcemia
    • Malignancy - bone metastasis, humoral hypercalcemia
    • Viatmin D intoxication
    • Sarcoidosis (1,25(OH)2-vit D)
    • Renal reabsorption: Familial hypocalciuric hypercalcemia, thiazide diuretics, lithium
  22. Parathyroid hormone-related peptide
    • promotes proliferation and apoptosis of chondrocytes
    • required for normal bone development
    • malignancy marker
  23. Causes of hypocalcemia
    • Low serum albumin (apparent)
    • Chronic renal failure
    • Magnesium deficiency
    • Hypoparathyroidism
    • Pseudohypoparathyroidism
    • Osteomalacia due to Vitamin D deficiency
    • “Hungry bone” syndrome-after parathyroidectomy
    • Acute hemorrhagic/edematous pancreatitis
    • Hyperphosphatemia
  24. Hyperphosphatemia
    • renal failure
    • cell lysis
    • excessive PO4 administration
    • hypoparathyroidism/pseudohypoparathyroidism
  25. Renal failure
    • hypocalcemia - secondary hyperparathyroidism
    • hyperphosphatemia
    • decreased production of active vit D
    • elevated BUN, creatinine
    • usually elevated PTH
  26. acromegaly v. gigantism
    • Caused by tumor of pituitary or hypothalamus/ectopic tumors
    • acromegaly: excess of GH, adult onset
    • thickening of skin on face, hands, feet
    • lethargy, sweating, headaches
    • incr. incidence of HTN, diabetes
    • gigantism: onset before fusion of epiphyseal plates
  27. diagnosis and treatment of acromegaly
    • diagnosis: incr. IGF-1, failure to suppress GH levels with glucose
    • treatment: surgery, octreotide (somatostatin analog), B-adrenergic agonists
  28. Dwarfism
    • GH deficiency caused by congenital defect in GH, GHRH, GH receptor, IGF-1, IGFR, abnormality of pituitary or hypothalamus; or acquired (tumors, pituitary trauma, psychosocial deprivation)
    • Clinically: short, plump, retarded bone age
    • Injection of GH or IGF-1
  29. GH indications
    • Turner's syndrome
    • renal failure
    • dwarfism
  30. adult onset GH deficiency
    low mood, reduced E, obesity, reduced bone density
  31. How is GH released?
    • Pulsatile/nocturnal
    • Stimulated by: hyppoglycemia, stress, sleep, aa's, sex steroids, ACh, fasting, alpha-adrenergic
    • Inhibited by: obesity, B-adrenergic, glucocorticoids, high FFA, hyperglycemia, hypothyroidism, IGF-1
  32. GH regulation
    • GH stimulates production of somatostatin, inhibits more GH release
    • Thyroid hormones stimulate GH release and activity
    • GHRH stim by sleep, stress
    • Can have insulin-like and anti-insulin like effects based on binding to JAK2->IRS (insulin receptor substrate) and interfering w/insulin's actions
  33. IGF-1
    • synthesis induced by GH, prenatal and postnatal growth
    • produced by liver and other tissues
    • binds insulin receptor or IGFR
    • regulation by soluble IGF-binding proteins to extend half-life (GH has similar reg)
  34. placental lactogen
    • homology to GH
    • GH-like anti-insulin activity
    • contributes to gestational diabetes
  35. cortisol in the kidney
    • cortisol can bind and activate the mineralcorticoid receptor (aldosterone), but is normally inactivated by 11beta-OH DH
    • people w/mutated 11beta-OH DH have high blood pressure
  36. causes of HTN
    • Essential hypertension: effects 25% adult population.
    • Primary aldosteronism: Adrenal tumor. Overproduction of aldosterone leads to hypertension.
    • Malignant hypertension: Renal damage leads to loss of control of renin secretion and increased plasma renin
    • levels.
    • Liver disease: aldosterone is not degraded normally.
    • Addisons disease: destruction of adrenals (source of aldosterone)
    • Congenital Adrenal Hypertension Type II: mutation in 11 hydroxylase
  37. treatment for HTN
    • ACE inhibitors
    • Antagonists of MR (in kidney tubules)
    • Antagonists of AT1 angiotensin II receptor (smooth muscle cells and adrenal cells)
  38. SE of testosterone/androgen abuse
    • increased muscle mass
    • increase blood pressure
    • increased cholesterol (LDL) and lower HDL
    • increased risk of liver and heart damage
    • gynecomastia (enlarged male breast tissue)
    • increased risk of prostate cancer
    • acne on the face and body
    • shrunken testicles
    • reduced sperm count
    • mood swings and increased aggressive behavior
Card Set
endocrine wk5
week 5 block 3