clinical pathological correlation

Question 1

AST (aspartate transaminase) elevation

Answer 1

• enzyme found in several organs

- elevation originating from liver is due to some degree of acute injury in which enzyme is released from damaged cells

Question 2

ALT (alanine transaminase) elevation

Answer 2

• found predominantly in liver
• exclusively cytoplasmic
• most elevations due to liver disease
• used to confirm liver origin of an AST increase

Question 3

PT (prothrombin time) test

Answer 3

• measure of extrinsic coagulation pathway
• measures factors X, VII, V, II (prothrombin), I (fibrinogen)
• used to monitor coumadin therapy

Question 4

PTT (partial thromboplastin time) test

Answer 4

• measurement of intrinsic coagulation pathway

- time is prolonged in deficiency of factors of intrinsic pathway

Question 5

hemostatic dysfunction relevant to PT test can be caused by:

Answer 5

• liver disease
• vitamin K deficiency
• factors deficiency
• disseminated intravascular coagulation

Question 6

PT test method

Answer 6

• platelet poor plasma is incubated with thromboplastin and calcium, time to clot formation is measured

Question 7

use of Rumack-Matthew nomogram

Answer 7

• greater than 200 ug/mL at 4 hours or 50 at 12 hours

- only used for single acute ingestion and if approximate time of ingestion is known

Question 8

what should we do if time of acetaminophen poisoning is unknown?

Answer 8

• determine serum acetaminophen and AST
• lower than 10 with normal AST, no NAC
• higher than 10, NAC

Question 9

what is the major toxic effect of acetaminophen overdose?

Answer 9

liver necrosis

Question 10

normal metabolic pathways for acetaminophen

Answer 10

• 90% - absorbed from stomach and UGI - hepatic glucuronide and sulfate conjugation to form harmless metabolites
• 5% - oxidized by CYP2E1, CYP1A2, CYP3A4 subfamilies of cytochrome P450 to NAPQI. NAPQI reacts with glutathione to form nontoxic cysteine or mercaptates conjugates, leave in urine

Question 11

acetaminophen overdose pathway

Answer 11

• major pathways are saturated
• more NAPQI, glutathione (GSH) can’t be made fast enough
• hepatic toxicity when GSH is less than 30% normal
• NAPQI binds arylate critical cell proteins leading to cell death

Question 12

What is N-acetyl cysteine (NAC)?

Answer 12

• hydrolyzed in body to cystein which is used in formation of glutathione (rate limiting step)

Question 13

NAC works in 2 ways:

Answer 13

1 - limits the formation of NAPQI

2 - increases capacity to detoxify NAPQI

Question 14

why does alcohol ingestion exacerbate the overdose?

Answer 14

alcohol induces P450 enzymes which means more NAPQI

Question 15

cimetidine

Answer 15

• (Tagamet) histamine H2-receptor antagonist for treatment of duodenal ulcer
• inhibits P450, may be helpful in overdose

Question 16

unconjugated bilirubin

Answer 16

no glucuronide attached to bilirubin, very insoluble

Question 17

conjugated bilirubin

Answer 17

glucuronide attached to biliruben, soluble

Question 18

delta bilirubin

Answer 18

bilirubin covalently attached to albumin, soluble

Question 19

direct bilirubin

Answer 19

• Bc + Bd

- fraction that can react with diazo dye in the absence of detergent or accelerator to form azobilirubin

Question 20

indirect bilirubin

Answer 20

= total - direct

same as Bu

Question 21

total bilirubin

Answer 21

= Bc + Bu + Bd

Question 22

lactulose

Answer 22

• treatment for nitrogenous hepatic enchephalopathy
• metabolized by bacteria in colon to release lactic, acetic, and other acids, decreasing stool pH to 5.5
• decreases serum ammonia levels

Question 23

vitamin K

Answer 23

• prothrombogenic properties

- if vitamin K is antagonized it can cause hemorrhage

Question 24

what does left shift mean?

Answer 24

increase in WBC count due to infection

Question 25

what does amylase elevation mean?

Answer 25

acute pancreatitis? order lipase as well.

Question 26

what is DIC (disseminated intravascular coagulation)?

Answer 26

- characterized by bleeding...... | - consumption of clotting factors due to liver failure

Question 27

DIC mechanism

Answer 27

- widespread activation of coagulation - fibrin deposited causing thrombotic occlusion of small and midsize vessels - use and depletion of platelets and coag factors induce bleeding - septicemia

Question 28

NAPQI toxicity

Answer 28

- damages kidneys

Question 29

APAP poisoning phase 1 (.5-24hrs)

Answer 29

- anorexia, nausea, vomiting, diaphoresis | - may appear normal

Question 30

APAP poisoning phase 2 (24-72hrs)

Answer 30

- RUQ pain - elevation of liver enzymes and bilirubin - PT time prolonged - renal function deterioration - BUN stays low

Question 31

APAP poisoning phase 3 (72-96hrs)

Answer 31

- hepatic necrosis - coagulation defects, jaundice, renal failure, hepatic encephalopathy - centrilobular necrosis in liver

Question 32

APAP poisoning phase 4 (4d-2w)

Answer 32

- if damage is not irreversible, resolution of dysfunction may occur