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Pathophysiology(endocrine)*

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Combination of hyperthyroidism, nodular goiter & abscence of exopthalmus
Plummer Dse
-"hot nodules" can be adenomas or non-neoplastic
Ovarian teratoma made of thyroid tissue
Struma Ovarri
Assoc. w/ various autoantibodies (Antithyroglobulin,Antithyroid Peroxidase,Anti-TSH receptor,Anti iodine receptor antibodies)
Hashimoto Thyroiditis
Focal destruction of thyroid tissue & granuloma inflammation due to viral infxn.(mumps,coxsackie virus)
Subacute(de Quervain,granulomatous)thyroiditis
1 molecule of DIT & Monoiodotyrosine (MIT) combine to form
T3(triiodothyronine)
-3 to 4 times more active than T4, down regulates TRH receptors & inhibits TSH secretion
Antibodies to TSH receptors w/c incr. T3,T4 secretion & stimulate glandular hyperplasia in Graves Dse.
Thyroid-stimulating immunoglobulin(TSI) & Thyroid growth immunoglobulin(TGI)respectedly
Autonomic effects of T3 & T4
B-andrenergic stimulation
-B-blockers(propranolol) are used in therapy for hyperthyroidism
Metabolic effect of T3 & T4
Inc. glucose absorption in GIT, Glycogenolysis, Gluconeogenesis, glucose oxidation, lipolysis, & incr. catabolism
Inversely proportional to the # of unbound thyroid hormone binding sites on TBG
T3 resin uptake(Thyroid Hormone-binding ratio)
Benign child tumor of Post. Pituitary charact. by nests & cords of squamous or columnar cells in loose stroma resembling appearance of the embryonic tooth bud enamel organ
Craniopharyngioma(adamantinoma)
Prognathism, enlargement of the face, vicera, feet, & hands(sausage-like fingers)
Acromegaly
-growth hormone hypersecretion caused by somatotroph cell adenoma
Epigastric pain radiating to the back w/ an incr. in serum amylase & lipase
Acute Pancreatitis
-major assoc. w/ alcoholism and gallstones
Migratory thrombophlebitis(Trousseau Syndrome)
Carcinoma of the pancreas
Severe retardation, short stature, coarse facies, protruding tongue, and umbilical hernia
Cretinism(Hypothyroidism in children)
Moon facies, hypertention, & accumulation of truncal fat
Cuching syndrome
-caused by the action of cortisol
Most commonly caused by iatrogenic corticosteroid therapy
Cushing synd.
Marked incr. in free water clearance
Diabetes Isipidus
-caused by lack of ADH
Increased Hemoglobin A1c(HbA1c)
Diabtetes Mellitus
-HbA1c=serum marker for nonenzymatic glycosylation of proteins
Loss of pain sensation in extremities
Diabetic neuropathy
Retinal microaneurysms and cotton-wool spots
Diabetic retinopathy
Female w/ staring gaze & exopthalamos
Graves' disease
-characterized by anti-TSH receptor antibodies in serum
Hypoglycemia & CNS impairment, w/c are reversed upon glucose administration, & increased serum C-peptide
Insulinoma
-px. surreptitiously administering insulin do not have inc. C-peptide levels in serum
Most common thyroid carcinoma assoc. w/ exposure to ionizing radiation
Papillary carcinoma of the thyroid
-histologically charact. by papillae lined by "Orphan Annie" nuclei or empty-looking nuclei
Paroxysmal hypertention, tachycardia, sweating, tremor, & hyperglycemia
Pheochromocytoma
Causes compression of the optic chiasm resulting in bitemporal hemianopsia
Pituitary adenoma
-often visualized as radiographic enlargement of the sella turcica
Hypotension, hyperpigmentation, & dec.
heart rate
Primary adrenal cortical insufficiency(Addisons disease)
Osteitis Fibrosis Cyctica
Primary hyperparathyroidism
-cysts, fibrinous accumulation, & focal hemorrhage in bone; also called brown tumor of bone
Premenopausal woman w/ amenorrhea, galactorrhea, loss of libido, & infertility
Prolactinoma
-most common hyperfunctioning pituitary adenoma
Peripartal hypotension resulting in necrosis & destruction of the ant. pituitary
Sheehan Synd
Excessive resorption of free water w/ hyponatremia & cerebral edema, but no peripheral edema
SIADH(syndrome of inappropriate antidiuretic hormone secretion)
Tremor, tachycardia,increase in appetite w/ dec. in weight
Thyrotoxicosis(hyperthyroidism)
-most commonly caused by Graves' dse.
Hypergastrinemia, hyperchlorhydria, & recurrent peptic ulcer dse.
Zollinger-Ellison Synd.
Inhibits secretion of Prolactin from ant. pituitary
Dopamine(PIF),Bromocriptine(dopamine agonist),Somatostatin,Prolactin(neg. feedback)
Salt-losing hyponatremia leading to hypotension and virilization of female infants
21-hydroxylase def.
-most common enzymatic defect in congenital adrenal hyperplasia
Ant. pituitary tumor w/c causes galactorrhea, decreased libido, failure to ovulate
Prolactinoma(excess prolactin)
Inhibits the iodide(I-)pump
Thiocyanate & Perchlorate Anions
Used to reduce thyroid hormone synthesis in tx. of hyperthyroidism by inhibiting "peroxidase"
Propylthiouracil
2 molecules of Diiodotyrosine(DIT) combine to form
T4(thyroxine)
-synthesized more than T3
Most common thyroid anomaly
Thyroglossal duct cyst
-does not lead to alteration in thyroid fxn.
Most common cause of secondary hyperparathyroidism
Renal failure
Malignant catecholamine producing tumor of early childhood charact. by amplification of the N-myc oncogene w/ thousands of gene copies per cell(Karyotypic changes)
Neuroblastoma
-malignant cells may differentiate into benign cells reflective of reduction of gene amplification
Factors w/c stimulate insulin release(tyrosine kinase receptor)
Inc. bld. glucose, inc. A.A, inc. F.A, glucagon, GIP, GH, cortisol
Factors w/c stimulate glucagon release(cAMP mechanism)
Dec. bld.glucose, inc. A.A, CCK(cholecystokinin), norepinephrine, epinephrine, acetylcholine
Adrenogenital synd. showing inc. aldosterone levels w/ dec. androgen & glucocorticoid levels
17 alpha-Hydroxylase Def.
General apathy, cold intolerance, obesity, & constipation
Myxedema(hypothyroidism)
Adrenal insufficiency & vascular collapse due to hemorrhagic necrosis of the adrenal cortex
Waterhouse-Frederichsen Synd.
-assoc. w/ DIC;due to Meningococcemia in assoc. w/ Meningococcal meningitis
Drug used to inhibit steroid hormone synthesis in tx. of Cushing's Dse.
Ketoconazole
Endocrine disorder presenting w/ hypertension, hypokalemia, metabolic alkalosis & inc. serum renin
Secondary Aldosteronism
-as compared to Conn's Synd(Primary Aldosteronism)in w/c serum renin is low
Malignant tumor of the thyroid w/c originates from C cells & produces calcitonin
Medullary Carcinoma
-assoc. w/ Multiple Endocrine Neoplasia(MEN)Synd. IIa & IIb(III)
Enzyme stimulated by ACTH to inc. steroid hormone synthesis by inc. conversion of cholesterol to pregnelone
Cholesterol Desmolase
Procedure use to test the neg. feedback control of cortisol in the hypothalmic-pituitary-adrenocortical axis
Dexamethasome Suppression Test
-based on the ability of Dexamethasome(potent synthetic glucocorticoid) to inhibit ACTH secretion
Factors w/c regulate aldosterone secretion
ACTH, Renin-Angiotensin System(Angiootensin II) & potassium
Actions of glucocorticoid(cortisol)
Gluconeogenesis, Anti-inflamatory effects, suppression of immune response, maintenance of vascular responsiveness to catecholamines
Enzyme synthesized by glucocorticoid w/c inhibits Phospholipase A2, an enzyme w/c provides arachidonate, a precursor for prostaglandin & leukotriene synthesis
Lipocortin
Anti-inflammatory effects of glucocorticoids
Inhibit formation of arachidonate, production of interleukin-2(IL-2) & release of histamine & serotonin
In determinng the origin of cause for Cushing Synd.,an inc. in ACTH secretion would come from these origin
Pituitary & Ectopic ACTH production
-as compared to adrenal where ACTH levels are low
Endocrine disorders caused by deficient ACTH, no hyperpigmentation, no volume contracion, no hyperkalemia or metabolic acidosis
Secondary Adrenocortical insufficiency
Actions of insulin on liver, adipose tissue & muscle
Inc. glucose,K,A.A uptake; promote glycogen form. & fat deposition; inhibit glycogenolysis,ketoacid form,lipolysis,protein degradation, gluconeogenesis
Actions of Somatostatin released from the hypothalmus & delta cells(pancreas)
Inhibit secretion of GH(hypothalmus) & inhibit secretion of insulin, glucagon, gastrin(pancreas)
Causes of Cushing's Synd.
Exogenous corticosteroid medication(most common),hyperproduction of ACTH(by pituitary),adrenal cortical adenoma,adrenal carcinoma,ectopic prod. of ACTH(small cell carcinoma)
Ca+ resorption of the organic matrix of bone due to PTH is reflected in increased
Hydroxyproline excretion
PTH inc. intestinal Ca+ reabsorption by stimulating production of this enzyme in the kidney
1,25-dihydroxycholacalciferol
Pathophysiology of inc. PTH(most commonly caused by Parathyroid Adenoma)
Hypercalcemia,hypophosphatemia,phosphaturia effect of PTH, inc. filtered load of Ca+, inc. urinary cAMP, inc. bone resorption
Pathophysio. of chronic renal failure in causing renal osteodystrophy
Dec. GFR~inc. serum phosphate~dec. ionized Ca+ due to phosphate-Ca complexes;dec. production of 1,25-dihydroxychole. by dse. kidney;inc. PTH due ti dec. serum Ca+ leads to inc. bone resorption & osteomalacia
Active form of Vit.D
1,25-dihydroxycolecalciferol
-catalyzed by 1alpha-hydroxylase
Factors w/c inc. 1alpha-hydroxylase activity in the production of Vit. D
Dec. (Ca+,phosphate,PTH)
Hormone secreted from the parafollicular cells of the thyroid; stimulated by high serum Ca+; inhibitsbone resorption; used to tx. hypercalcemia
Calcitonin
Hormones secreted from the testes(sertoli cells)w/c cause atrophy of the mullerian ducts(become the female internal genital tract)
Antimullerian Hormone
Hormones secreted from the testes(leydig cells)w/c stimulate growth & differentiation of the Wolffian ducts(become the male internal genital tract)
Testosterone
Hormone found in the accessory sex organs(ex.Prostate) used to convert testosterone to its active form(dihydrotestosterone)
5 alpha-reductase
-inhibited by Finasteride w/c is used in tx. of BPH
Hormone produced by Sertoli cells in the testes w/c inhibits release of FSH from the ant. pituitary
Inhibin
Actions of testosterone
Differentiation of Wolffian ducts, pubertal growth, spermatogenesis in Sertoli cells, inc. libido
Effects of FSH & LH on Sertoli cells & Leydig cells in the testes, respectedly
Maintain spermatogenesis & promote testosterone synthesis
Effects of FSH & LH on the ovaries
Steroidogenesis in the ovarian follicle & corpus luteum, follicular involvement beyond the antral stage, ovulation, luteinization
Actions of estrogen
Neg.&post. feedback effect(FSH,LH)secretion;maturation & maitenance of(fallopian tubes,uterus,cervix, vagina);develop. female secondary sex charact.at puberty;develop. of breast; upregulates(estrogen,LH,progesterone) receptors;proliferation & devel. of ovarian granulosa cells;maintains preg.;lowers uterine threshold to contractile stimuli during preg,;stimulate prolactin secretion
Actions of Progesterone
Neg. feedback effect on(FSH,LH)during luteal phase; maintains secretory activity of uterus during luteal phase; maintaince preg.; raises uterine threshold to contractile stimuli; develop. of breast
Hormone produced by Theca cells w/c later diffuses granulosa cells
Testosterone
Enzyme found in Granulosa cells w/c convert testosterone to 17B-estradiol
Aromatase
Benign tumor of the adrenal medulla (chromaffin cells) resulting in inc. renal excretion of catecholamines & their metabolites(metanephrine,normetanephrine,vanillylmandelic acid)
Pheochromocytoma
-if derived from extra adrenal chromaffin cells, called Paraganglioma
Hormone level of FSH compared to LH during senescence
FSH>LH
-as compared to childhood(FSH>LH) & puberty(LH>FSH)
In Cushing Synd., a neg. Dexamethasome Suppression Test, signifies the origin of excess production of ACTH comes from
Adrenal Neoplasm
-if Pituitary in origin, the test would be positive
Adrenogenital Synd. w/c show dec. cortisol & aldosterone levels w/ inc. 17-hydroxyprogesterone & progesterone levels resulting in inc. androstenedione
21 Beta-Hydroxylase def.
Most common cause of hypothyroidism in iodine sufficient areas
Hashimoto Thyroiditis
-histologically charact. by dense lymphocytic infiltrate & germinal centers in the thyroid
Parathyroid dse. resulting in end-organ resistance to PTH due to a defective Gs protein in the kidney & bone
Pseudohypoparathyroidism type Ia- Albright's hereditary osteodystrophy
-not correctable by exogenous adm. of PTH; inc. PTH levels, hypocalcemia, hyperphosphatemia

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