chemical injury case presentation

Question 1

what are the effects of acetominophin on blood?

Answer 1

coagulation factors synthesized in liver - so want CBC, PTT, PT, INR

Question 2

what is ALT?

Answer 2

alanine aminotransferase levels
part of liver enzyme tests for LFT - when injury to liver, cells lysed and enzymes released
10-56 is normal

Question 3

what is AST?

Answer 3

aspartate transaminase
in heart and liver
part of liver enzyme tests for LFT - when injury to liver, cells lysed and enzymes released
normal is 8-45

Question 4

what are the pathways in coagulation?

Answer 4

intrinsic and extrinsic

Question 5

what is PT? what is it used to detect?

Answer 5

prothrombin time
measures intrinsic pathway of coagulation
used to screen for hemostatic dysfunction involving extrinsic pathway due to liver disease, vit K deficiency, factors deficiency, or disseminated intravascular coagulation

Question 6

what is PTT? how is it measured?

Answer 6

partial thromboplastin time
will be prolonged if there’s a deficiency in clotting factors in both intrinsic pathway and common pathway - so measure of all clotting factors except factor 7

platelet-poor plasma is incubated with phospholipid and surface activator - after activation, Ca is added and time to clot formation is measured

Question 7

what are some causes of prolonged PTT?

Answer 7

vit K deficiency
liver disease
DIC
factor deficiency
antifactor antibodies
lupus anticoagulant

Question 8

how long does acetaminophen take to be fully absorbed?

Answer 8

4 hours - so will see a peak at 4 hours and if only took one dose will see drop after that

Question 9

when can you use the rumack-matthew normogram?

Answer 9

only for a single acute ingestion and if the approximate time of ingestion is known

Question 10

how does acetaminophen cause toxicity?

Answer 10

60% of the time, attached to glucouronide and becomes water soluble and can be cleared
35% gets sulfonated, also water soluble so can be cleared
but 5% of the time uses cytochrome P450 to convert it to NAPQI = toxic
normally this will be cleared by conjugating it to glucothione and it can then be conjugated to cysteine or mercaptate and cleared
but if there’s a lot the enzymes needed to add glutathione (CSH) will be overloaded and so the NAPQI will form bonds with AA in proteins and enzymes - these will attack the liver and cause cell death

Question 11

how does NAC prevent liver failure due to acetaminophen?

Answer 11

can be glutathione substitute

Question 12

what is NAC? how does it work?

Answer 12

n-acetyl cysteine
exogenous glutathione does not penetrate hepatocytes unless given in massive doses
thiol-containing compound that is hydrolyzed to cysteine
cysteine is then used intracellularly along with glut and glycine to form glutathione (cysteine is the rate-limiting step in this)
glutathione depletion to cytotoxic damage and cell death
glutathione is a protective molecule against many stressors serving as a conjugant, reducing agent and antioxidant

so NAC is a substitute for glutathione - prevents liver damage because gets around the problem of overloading the system

Question 13

what is direct bilirubin versus indirect bilirubin?

Answer 13

direct = conjugated bilirubin + delta bilirubin

bilirubin that is soluble in plasma

Question 14

what is conjugated bilirubin?

Answer 14

glucuronide attached bilirubin - soluble

Question 14

what is direct bilirubin versus indirect bilirubin?

Answer 14

direct = conjugated bilirubin + delta bilirubin

bilirubin that is soluble in plasma

Question 15

what is conjugated bilirubin?

Answer 15

glucuronide attached bilirubin - soluble

Question 16

what is delta bilirubin?

Answer 16

bilirubin covalently attached to albumin - soluble

Question 16

what is delta bilirubin?

Answer 16

bilirubin covalently attached to albumin - soluble

Question 17

what is unconjugated bilirubin?

Answer 17

no glucuronide attached to bilirubin - very insoluble

Question 19

what is unconjugated bilirubin?

Answer 19

no glucuronide attached to bilirubin - very insoluble

Question 21

what is total billirubin?

Answer 21

conjugated + delta + unconjugated

requires detergent or accelerator so that the unconjugated will react with the diazo dye

Question 22

what is total billirubin?

Answer 22

conjugated + delta + unconjugated

requires detergent or accelerator so that the unconjugated will react with the diazo dye

Question 23

what is the reason to give a patient lactulose? how does it work

Answer 23

high ammonium levels - ammonia can cross BBB and cause encelopathy - can be charged and uncharged - can clear charged molecules in the urine but can’t clear uncharged molecules - these can cross the BBB
lactulose is metabolized by bacteria in the colon and releases lactic, acetic and other organic acids
=> acidfication of colon contents and favors trapping of ammonium ions in the lumen and prevention of absorption

Question 24

what is the reason to give a patient lactulose? how does it work

Answer 24

high ammonium levels - ammonia can cross BBB and cause encelopathy - can be charged and uncharged - can clear charged molecules in the urine but can’t clear uncharged molecules - these can cross the BBB
lactulose is metabolized by bacteria in the colon and releases lactic, acetic and other organic acids
=> acidfication of colon contents and favors trapping of ammonium ions in the lumen and prevention of absorption

Question 25

why would you give a patient vitamin K?

Answer 25

prolonged prothrombin time

vit k will counteract - will cause coagulation to go back to normal

Question 26

why would you give a patient vitamin K?

Answer 26

prolonged prothrombin time

vit k will counteract - will cause coagulation to go back to normal

Question 27

where does alpha-amylase come from?

Answer 27

pancreas or salivary glands
most cleared by kidney by glomerular filtration
in acute pancreatitis, amylase levels will be very high

Question 28

where does alpha-amylase come from?

Answer 28

pancreas or salivary glands
most cleared by kidney by glomerular filtration
in acute pancreatitis, amylase levels will be very high

Question 29

what is disseminated intravascular coagulation (DIC)?

Answer 29

get both bleeding and thrombosis
liver damaged so depletion of platelets and coagulation factors => bleeding
also get intravascular deposition of fibrin in the small vessels => thrombosis of small and midsize vessels and organ failure

Question 30

what is disseminated intravascular coagulation (DIC)?

Answer 30

get both bleeding and thrombosis
liver damaged so depletion of platelets and coagulation factors => bleeding
also get intravascular deposition of fibrin in the small vessels => thrombosis of small and midsize vessels and organ failure

Question 31

what are the mechanisms by which NAPQI causes toxicity?

Answer 31

covalent binding to hepatic proteins => damage to cellular membranes and mitochondrial dysfunction

depletion of FSH => hepatocytes more susceptible to reactive O2 species-induced injury

Question 32

why can acetominophen be more toxic in alcoholics?

Answer 32

alcohol induces CYP2E in liver

Question 33

what is the consequence of aspirin overdose?

Answer 33

alkalosis due to stimulation of respiratory center in medulla => metabolic acidosis => accumulation of pyruvate and lactate due to uncoupling of oxidative phosp and inhibition of krebs
metabolic acidosis enhances formation of nonionized forms of salicylates - diffuse to brain => nausea to coma

Question 34

why can aspirin increase bleeding?

Answer 34

acetylates platelet cyclooxygenase

irreversibly blocks production of thromboxane A2 (activator of platelet aggregation)