Chemistry

Question 1

Where in the cell do AST/ALT reside? And what are they markers of?

Answer 1

Liver injury; AST in mitochondria and ALT in cytoplasm

Question 2

Which tissue express AST? (6)

Answer 2

Cardiac muscle, liver, skeletal muscle, kidney, brain, lungs, pancreas (in decreasing order)

Question 3

Which tissues express ALT? (3) what relation does it have to BMI and hep C?

Answer 3

Liver, kidney, muscle

Increases with BMI, levels higher in males

Fluctuates in chronic Hep C and can be normal in spite of increased AST

Question 4

In what instances is the DeRitis ratio increased (flipped)?

Answer 4

AST/ALT, alcoholic steatohepatitis, Wilson disease and cirrhosis

Question 5

Examples of instances where LD is increased

Answer 5

Increased hemolysis, megaloblastic anemia, disorders of the muscle, liver, kidney and lung

Also neoplastic; lymphoma, leukemia, germ cell tumors, carcinomas

Question 6

Fastest LD (2)
LD of liver and skeletal muscle (2)
Where is L3 found?
Order of LD concentration

Answer 6

LD1 and LD2 are fastest, found in heart, rbc and kidney

LD4 and LD5 (high in liver and skeletal muscle injury)

Lung, spleen, lymphocytes and pancreas have L3

LD2>LD1>LD3>LD4>LD5

Question 7

Flipped LD ratio, ie LD1>LD2 (3)

Answer 7

Acute MI - rise in 10 h, peak 24-48 h, high for 14 days

Hemolysis
Acute kidney infarct

Question 8

How do we tell AlK phos apart?

Answer 8

Bone burns (90%)
50% inactivation of biliary alk phos through heat
Intestinal
0% inactivation of placental

Urea incubation parallels heating

Question 9

In which populations does intestinal alk phos cause factitious elevation?

Answer 9

Non fasting Lewis+ blood group B or O secreters
Their alk phos can go up 30% for up to 12 h by just eating a meal

Question 10

Low alk phos (4)

Answer 10

Hypophosphatasia (malnutrition)
Hemolysis
Wilson dz
Theophylline therapy
Estrogen therapy

Question 11

Situations with elevated GGT, gamma glutamyl transferase

Answer 11

Hepatobiliary injury (from epithelial cells)
Warfarin, barbiturates, Dilantin, valproate, methotrexate and alcohol (2-3x ULN in heavy drinkers)

Question 12

Unconjugated hyperbilirubinemia (3 categories)

Answer 12

Gilbert- AD, CN1 (bad), CN2 - AR; UGT1 A1 gene mutation

Excess conversion of Heme: Extravasc hemolysis, ineffective hematopoiesis (intramedullary hemolysis), large hematoma;

Excess delivery of unconj bili: blood shunting (cirrhosis), RHF

Poor uptake to hepatocyte: Gilbert, drugs like rifampin, probenecid

Impaired conjugation in hepatocyte: CN 1 and 2, hypothyroid

Question 13

Conjugated hyperbili

Answer 13

Impaired transmembrane secretion of conj bili into canaliculus (hepatocellular jaundice): hepatitis, hep injury, endotoxin (sepsis), pregnancy (estrogen), drugs (estrogen, cyclosporine) DJ and Rotor

Impaired flow of conj bili through canaliculi and bile ducts (cholestatic jaundice) : intrahepatic- PBC, meds, alcohol, pregnancy, sepsis

Extrahepatic: PSC, tumor, stricture, stone, AIDS cholodochopathy

Question 14

Neonatal jaundice (unconj bili)

Answer 14

Physiologic
Breast milk
Polycythemia
Hemolysis (HDFN, hemoglobinopathy, inherited membrane or enzyme defects)
Increased enterohepatic circulation (Hirchsprung, CF, ileal atresia)

Inherited disorders of bili metab (Gilbert, CN)

Question 15

Neonatal jaundice (conj bili)

Answer 15

Biliary obstruction (extrahepatic biliary atresia)
Sepsis (TORCH)
Neonatal hepatitis (idiopathic, Wilson, alpha1 antitrypsin def)
Metabolic disorders (galactosemia, hereditary fructose intolerance, glycogen storage dz)
Inherited disorder of bili transport: DJ, Rotor
Parenteral alimentation