3/27 Liver Disease - Forester

Question 1

transaminases

Answer 1

preformed active enzymes present in normal hepatocytes → when hepatocellular necrosis occurs, they are released into plasma

• marker of disease process (necroinfl disease)

transaminase levels

• upper limit of normal = 40
• 40-60 = min elev
• 60-100 = mild elev
• 100-250 = moderate elev
• over 250 = marked elev

up into 1000s in acute hep/necr

ALT: alanine aminotransferase

• aka SGPT
• highest specificity for liver

AST: aspartate aminotransferase

• aka SGOT
• intermed specificity for liver

LDH: lactate dehydrogenase

• less specific

Question 2

cholestasis

definition

types

Answer 2

deficient bile transit

1. microscopic aka intrahepatic cholestasis: ductal system is unobstructed, but there is impairment of transport of some/all bile constituents from hepatocytes into bile ductules
2. macroscopic aka extrahepatic cholestasis: partial/complete obstruction of bile duct

Question 3

components of bile

Answer 3

water

electrolytes

enterohepatic circulatin pdts

excretory pdts

phospholipid

cholesterol

bile salts

bilirubin

work together to solubilize cholesterol ester in bile

Question 4

biochem consequences of cholestasis

Answer 4

1. biochem abnormalities are IDENTICAL no matter what type of cholestasis - macro/extrahepatic or micro/intrahepatic)
2. all types of cholestasis can be partial or complete
3. abnormalities reflect components of bile AND rxn of biliary epithelium to injury
   * incr synthesis and release of alkaline phosphatase into plasma

Question 5

alkaline phosphatase

Answer 5

AP is not a component of bile → not excreted with it

• rise due to irritative increase in synthesis
• released secondary to cholestasis
• elevation develops stepwise over a period of days as synthesis rises

elevated AP is a biochemical hallmark of cholestasis

normal approx 140

Question 6

GGTP

Answer 6

gamma-glutamyl transpeptidase

• often rises with alk phos
• elevation helps confirm hepatic issue

normal ~60

Question 7

normal bilirubin metabolism

Answer 7

senescent or prematurely destroyed RBCs → Fe + hemoglobin

• Fe goes to RES
• Hb is metabolized
  
  • Hb → biliverdin → bilirubin, avidly taken up by hepatocytes
  • in hepatocytes, bilirubin conjugated to bilirubin diglucuronide (conjugated bilirubin, “direct” bilirubin)
  • conjugated bilirubin excreted in bile

Question 8

jaundice

Answer 8

yellowish discoloration secondary to elevated bilirubin

• skin? → CB and UCB affect skin, sclerae, mucous membranes
• urine → only CB

total cholestasis will always/eventually produce high enough bilirubin levels to cause jaundice

Question 9

5 mechs of jaundice

diff between noncholestatic and cholestatic?

Answer 9

1. prehepatic aka hemolytic
   
   • incr bilirubin load
   • hepatocytes and bile flow normal
2. hepatocellular infl
   
   • ​infl liver cell injury → preserved bile flow, no fxal liver failure
3. hepatocellular failure
   
   • ​​fxal failure (“parenchymal wipeout”)
4. intrahepatic cholestasis
   
   • ​​​impaired bile flow without mechanical obstruction
5. obstructive cholestasis

non-cholestatic (1-3) and cholestatic (4-5) differ in presence/absence of:

• incr AP, GGTP, cholesterol
• clinical pruritis

Question 10

what about bilirubin fractionation?

Answer 10

pure prehepatic jaundice?

• pl bilirubin is all UC → seldom rises above 5, never above 8

other mechanisms?

• pl bilirubin is both C and UC
• when both are elevated, distribution between the two have no ddx value

*“rule” for UC bilirubin level implies that bilirubin > 8 will be some combo of C + UC

SO, only fractionate bilirubin if below 8!

Question 11

LDH comes from liver and RBCs

AST also in liver and RBCs

Question 12

hepatic infiltration

Answer 12

unique pattern of liver enzymes seen in infiltration of liver by TUMOR, GRANULOMA, ABSCESS

• NOT seen in “infiltration” with Fe, Cu, amyloid, glycogen

elevated alk phos and GGTP

normal or low transaminases

normal bilirubin

• similar to cholestatic pattern, but lacking 4 features of cholestasis
  
  • elevated bilirubin
  • elevated bile salts
  • elevated chol
  • pruritis

exception: bilirubin can rise in infiltration if liver replaced by abnl tissue or if associated hepatitis

Question 13

liver functions

Answer 13

1. synthesis

• proteins: albumin, clotting factors, etc
• lipoproteins

2. metabolic regulation

• energy metabolism (carbs, lipids)
• hormonal metabolism
• protein metabolism
• salt/water metabolism

3. detox/excretion

• N (urea synthesis from NH3)
• bilirubin
• endog and exog compounds
• reticuloendothelial fx

Question 14

what do liver enzymes help assess?

Answer 14

AST, ALT, AP, GGTP

DO reflect active disease processes within hepatobiliary system

DON’T help assess functional status of liver!

• for function, try albumin, protime, glucose, BUN, chol, bilirubin, ammonia

Question 15

insensitivity

vs

nonspecificity

Answer 15

insensitivity - finding absent bc impairment too subtle (false negative)

nonspecificity - abnormal bc of non-liver cause (false positive)

• examples:
  
  • purpura - thrombocytopenia
  • jaundice - hemolysis
  • low albumin - renal loss