Pathology

Question 1

Thiamine is a key enzyme for pyruvate dehydrogenase, which is involved in glucose metabolism. Thiamine deficiency results in the brain’s inability to properly metabolize glucose and turn it into energy. The structure most affected is the mamillary body

Answer 1

Maple Syrip Urine disease is an AR disorder marked by defective breakdown of branched-chain AAs (leucine, isoleucine, and valine) due to defects in branched-chain A-ketoacid dehydrogenase complex (BCKDC) resulting in accumulation of the AAs in serum and peripheral tissues, resulting in neurotoxicity that includes seizures, irritability, lethergy, and poor feeding.

Urine has sweet odor due to a metabolite of isoleucine

Tx: thiamine and lifelong dietary restrictions

Question 2

Branched-chain a-ketoacid dehydrogenase (in addition to pyruvate dehydrogenase and a-ketoglutarate dehydrogenase) need what 5 cofactors?

Answer 2

Thiamine, lipoate, CoA, FAD, and NAD

Question 3

The main findings after an ischemic stroke include:

12-24 hrs: Red neurons (eosinophilic cytoplasm, pyknotic nuclei, and loss of Nissl substance)

24-72 hrs: Neutrophilic infiltration

3-7 days: Macrophage/microglia infiltration and phaogcytosis begin

1-2 weeks: Reactive glisosis and vascular proliferation around the necrotic area as well as formation of liquefactive necrosis

2+ weeks: Glial scar formation

Question 4

SCD- Sickling promoted by low oxygen levels, increased acidity, or low blood volume (dehydration)

Organs with high oxygen demand like the brain, muscles and placenta cause sickling by extrcting more oxygen from blood, while the liver and spleen due so via increased acidity

Question 5

Normally, the terminal ileum is needed for recycling bile acids for fat absorption. When the mucosa is inflammated in Crohn disease, bile acids cannot be reabsorbed and are lost in feces. As a result, lesser bile acids are present in bile, and ratio of the cholesterol to bile acids increase, promoting the formation of gallstones

Answer 5

Gallbladder hypomotility may contibute to cholesterol gallstone formation in pts with spinal cord injury or those receiving parenteral nutrition

Question 6

An elevated creatinine is highly suggestive of underlying myopathy, due to direct damage and leakage of enzymes into circulation. Common causes of myoapthy with elevated CK include hypothyroidism, muscular dystrophies, inflammatory muscle diseases, and meds such asHMG-cOA reductase inhibitors

Question 7

Glucocorticoid induced myopathy- progressive proximal muscle weakness and atrophy WITHOUT pain (CK normal)

PMR- Muscle pain and stiffness in shoulder, neck, and pelvic girdle. Worse in morning and with activity.(CK normal)

Answer 7

Inflammatory myopathies (e.g. polymyositis)- Proximal muscle weakness, skin rash and inflammatory arthritis may be present (CK elevateed)

Statin-induce myopathy- proximal muscle pain and weakness usually within weeks-months (CK elevated)

Hypothyroid myopathy- muscle pain, cramps, weakness, delayed tendon reflexes, features of hypothyroidism)

Question 8

Homocystinuria- presents in children, 3-10 yo, with seeing difficulty (ectopia lentis), and possibly intellectual disability, Marfanoid habitus

Pts are at risk for death via thromboembolic occlusion

AR disease of deficiency of cystathionine bet-synthase, an enzyme that regulates pyridoxine (VitB6)

Answer 8

Tx with high doses of vitB6 and restriction of methionine

Question 9

Chronic renal allograft rejection is marked by worsening HTN, a progressive rise in serum CK at 3+ months from transplant

Fibrous itimal thickening seen with scattered PMN infiltrates

Question 10

Gallstone ileus- unommon complication of longstanding cholelithiasis that usually occurs in ELDERLY women in which a gallstone forms a cholecystenteric fistula between the gallbladder and adjoining gut, allowing passage of the stone into the small bowel, where it travels freely intul it becomes trapped in the ILEUM, the narrowest part of the small bowel.

Answer 10

Pts present with signs of bowel obstruction, including high-pitched bowel sounds, and tenderness to palpation

Abdominal x-ray may show air-fluid levels trapping

Communicaton between the intestine and gallbladder may also allow gas to enter the biliary trree (pneumobilia)

Question 11

An increase in estrogen activity (e.g. pregnancy, OCP, post-menopausal therapy) raises circulating TBG levels (binding thyroid hormone), causing a reduction in free T4 and T3 levels. This causes a compensatory increase in total T4 and total T3 levels, while the free hormone levels reamin normal, euthyroid

Question 12

Adenomysosi is the presence of endometrial glandular tissue within the myometrium, common in middle-aged parous females. Symptoms include heavy menstrual bleeding, due to an increased endometrial surface, and dysmenorrhea.

Phsyical exam classically shows a uniformly enlarged uterus

Question 13

Optic tract lesions- contralateral homonymous hemianopia, positive swinging light test

Meyer’s loop lesions- contralateral upper quadrantanopia (“pie in the sky” defect)

Latera genticulate nucleus or optic radiation lesion- contralateral homonymous hemianopia, but no swinging light positive

Question 14

Hypocalcemia can present with muscle cramps, perioral paresthesias, hypotension, and possibly laryngospasm (e.g. thyroid surgery with damage to PTH, autoimmune hypoPTHism, sepsis, TLS, acute pancreatitis, and vitD deficiency)

Positive Chvostek sign- facial muscle contraction by tapping on the facial nerve anterior to the ear

Positive Trossau sign- carpopedal spasm triggerred by prolonged inflation of a blood pressure cuff

Question 15

Graves disease is tx with ablating doses of radioactive iodine. The sodium-iodide symporter at the follicle BM also transports perchlorate into follicles with iodine.. thus tx with potassium perchlorate can be used prophylatically to decrease the effects of radiotherapy (competitive transport)

Question 16

Uric acid stones are diamond or rhomboid shaped crystals. Radiolucent and thus cannot be seen on plain radiography.

Risk factors include low urinary pH and low urine volume with high uric acid conc. (gout, high cell turnover states, metabolic syndrome, chronic diarrhea)

Answer 16

Pts with chronic diarrhea or those who have had a colectomy have reduced bicarb reabsorption from th gut, leadint o a chronic metabolic acidosis state.

Question 17

Colitis-associated CRC (compared to sporadic):

Affects younger pts

Progress from flat and non-polypoid dysplasia

Develop early p53 and late APC gene mutations, opposite of sporadic disease

Be multifocal in nature

Answer 17

Usually develops after 10 yrs of colitis (highest risk with pancolitis)

Question 18

Chronic glucocorticoid use is marked by low CRH, ACTH, and cortisol levels that cannot rise in response to stressful situations (e.g. infections, surgery), resulting in a relative deficiency (even when meds are maintained)

Question 19

Graft vs. Host disease usually occurs after allogenic bone amrrow transplant (but can occur in other situations) and occurs when donor T cells react against host MHC antigens. Presents as a diffuse maculopapular rash that has a predisposition for the palms and soles and may desquamate. GI involvement causes diarrhea, intestinal bleeding, and abdominal pain

Question 20

Hindgut structures of the bowel and colon drain via the inferior mesenteric vein, which drains into the splenic vein, and then into the portal vein

Question 21

The kidneys try to correct metabolic acidosis via:

Increased HCO3- reabsorption

Increased H+ secretion

Increased acid buffer excretion: pH changes rapidly with relaively small amounts of H+ excretion, so buffers are used to maximize the amount of hydrogen loss without drastically lowering urine pH (2 most important: HPO42- and NH3)

Question 22

Survival motor neuron (SMN1) gene in spinal muscular atrophy encodes a protein involved in assembly of snRNPs in LMNs. Defective snRNP assembly results in impaired splicesome function and degeneration of anterior horn cells in the spinal cord