clinical pathological correlation Flashcards
AST (aspartate transaminase) elevation
- 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
ALT (alanine transaminase) elevation
- found predominantly in liver
- exclusively cytoplasmic
- most elevations due to liver disease
- used to confirm liver origin of an AST increase
PT (prothrombin time) test
- measure of extrinsic coagulation pathway
- measures factors X, VII, V, II (prothrombin), I (fibrinogen)
- used to monitor coumadin therapy
PTT (partial thromboplastin time) test
- measurement of intrinsic coagulation pathway
- time is prolonged in deficiency of factors of intrinsic pathway
hemostatic dysfunction relevant to PT test can be caused by:
- liver disease
- vitamin K deficiency
- factors deficiency
- disseminated intravascular coagulation
PT test method
- platelet poor plasma is incubated with thromboplastin and calcium, time to clot formation is measured
use of Rumack-Matthew nomogram
- 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
what should we do if time of acetaminophen poisoning is unknown?
- determine serum acetaminophen and AST
- lower than 10 with normal AST, no NAC
- higher than 10, NAC
what is the major toxic effect of acetaminophen overdose?
liver necrosis
normal metabolic pathways for acetaminophen
- 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
acetaminophen overdose pathway
- 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
What is N-acetyl cysteine (NAC)?
- hydrolyzed in body to cystein which is used in formation of glutathione (rate limiting step)
NAC works in 2 ways:
1 - limits the formation of NAPQI
2 - increases capacity to detoxify NAPQI
why does alcohol ingestion exacerbate the overdose?
alcohol induces P450 enzymes which means more NAPQI
cimetidine
- (Tagamet) histamine H2-receptor antagonist for treatment of duodenal ulcer
- inhibits P450, may be helpful in overdose
unconjugated bilirubin
no glucuronide attached to bilirubin, very insoluble
conjugated bilirubin
glucuronide attached to biliruben, soluble
delta bilirubin
bilirubin covalently attached to albumin, soluble
direct bilirubin
- Bc + Bd
- fraction that can react with diazo dye in the absence of detergent or accelerator to form azobilirubin
indirect bilirubin
= total - direct
same as Bu
total bilirubin
= Bc + Bu + Bd
lactulose
- 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
vitamin K
- prothrombogenic properties
- if vitamin K is antagonized it can cause hemorrhage
what does left shift mean?
increase in WBC count due to infection
