Week 1 Pathology

Front 1

Differentiate the autoimmune mechanisms involved in Hashimoto's and Graves Dx

Back 1

Graves: antibodies to thyroid stimulating receptors. there are autoantibodies that block the TSHR as well.
Hashimotos: antibodies to thyroid peroxidase, which causes hypothyroidism

Front 2

Describe the use of the antimocrisomal antithyroid peroxidase ab test in the dx of hashimotos

Back 2

this is a serum collection with a normal negative for the test. its increased greater than 99% in hashimotos

Front 3

Describe the causes of acute adrenal insufficiency and list associated features

Back 3

THe most frequent cause: idiopathic atrophy of autoimmune origin.
Drugs that can increase steroid metabolism can cause acute adrenal insufficiency.
Features: weakness, pigmentation of the skin, weight loss, abdominal pain, salt craving, diarrhea, constipation, syncope, vitiligo.

Front 4

Explain the MOA of the following drugs and their use in tx of adrenal dx:
Aminoglutethimide
Metyrapone
ketoconazole
Spironolactone

Back 4

Aminoglutethimide: Inhibiting the conversion of cholesterol to pregnenolone. used in tx malignancies of the adrenal cortex b/c of reduction of steroid secretion
Metyrapone: blocks the 11hydroxylation in glucocorticoid synthesis, leading to an increase in adrenal androgens and 11 eoxycorticosterone. used to tx cushings and to test adrenal fxn.
Ketoconazole: blocks adrenal steroid synthesis by blocking 11bhydroxylase, blocking testosterone to cortisol
spironolactone: K sparing diuretic. Tx hyperaldosteroneism, also good for hirsuitism

Front 5

Describe the causes of addison's disease with mechanisms

Back 5

may be primary adrenal, or secondary low acth pituitary.

Front 6

Understand the various endocrine disorders linked in a common autoimmune etiology:

Back 6

PAS1: due to defects in T cell immunity. can present with hypoparathyroidism and addison's disease, and mucocutaneouscandidiasis.
PAS2: Schmidt's syndrome. Addison's disease/adrenal insufficiency, autoimmune thyroid disease, and Type 1 DM. Autosomal Dominant.

Front 7

Describe the autoimmune mechanisms involved in Addison's Disease:

Back 7

Progressive desctruction of the adrenals which involves 90% before insufficiency ensues. Circulating adrenal antibodies, but probably T lymphocyte mediated. Complement is fixed on surface of adrenal cells.

Front 8

ID clinical dx associated w/ADH excess

Back 8

Can be a primary defect in AVP secretion or can be 2dary to a non osmotic stimulus such as hypovolemia. Neoplasms of lung, duodenum, pancreas. Head trauma. Infections like Pneumonia, vascular causes like occlusions, Guillan barre syndrome, Congenital, Metabolic, and drugs.

Can also be deficiency: DI, granulomas, infections, toxins, sheehan's syndrome, pregnancy, idiopathic.

Front 9

List the symptoms of DI and describe a workup

Back 9

Excessive thirst, High fluid intake, High urine output, Plasma Osm High or normal, Urine osmolality is low.
TESTS: Plasma/Urine osmolality. Water Deprivation test

Front 10

Explain how to distinguish DI from Hypernatremia and polydypsia

Back 10

With water deprivation, Pts with DI will become increasingly hypertonic and dehydrated while urine still is submaximally concentrated.

Front 11

Describe the genetic and biochemical basis for nephrogenic DI

Back 11

Xlinked: causes lesions in the V2 receptor for ADH on principle cells in the late distal Collecting tubule and collecting duct. Result is increased ADH secretion, but kidney does not register it.
Autosomal NDI: Mutations in aquaporin 2 gene, ADH binds to V2 receptor, but no relay to form aquaporins is made.

Front 12

Describe the causes, MOA, clinical, and tx of SIADH

Back 12

Causes: Malignant lung dx, tumors, drugs that stimulate ADH, Adrenal insufficiency, HIV, surgery.
MOA: Dysfunctional osmoreceptors in the hypothalamus.
Clinical: Cerebral edema, cellular swelling, hyponatremia, headaches, blurred vision, muscle cramps.
TX: Bring osmolality back to normal. use Loop diuretis and give lytes.

Front 13

Describe the various ADH receptor subtypes

Back 13

V1 receptor: mediates vasoactive effects PLC-IP3+DAG = PKC and Ca which yields contraction
V2 receptor: renal effects. activates adenylyl cyclase, cAMP, protein kinase A, and fusion of water channels with cell membrane

Front 14

explain how pancreatic injury leads to exocrine and endocrine pancreatic deficiences with digestive and metabolic consequences:

Back 14

without necessary digestive enzymes and bicarb to neutrolize acidic chyme, proper digestion cannot take place. tissue destruction occurs b/c of release of toxic enzymes, cytokines, and mediators into the circulation leadint to explosive systemic inflammatory response. Can have Secondary DM.

Front 15

Define pressure natureisis and how it relates to SIADH

Back 15

PN is increase in sodium excretion with an increase in arterial pressure. in SIADH, the ECF expansion suppresses the RAA system, because of an increase in ANP. this leads to an increase in Na excretion. this leads to hyponatremia associated with the hypervolemia.