week 1, lecture 1 Flashcards
NAFLD pathologic findings
hepatocyte ballooning, lobular inflammation, steatosis
progress to fibrosis and cirrhosis
2 hit model of NAFLD
- hepatic fat accumulation
- increased oxidative stress
cirrhosis
liver scarring remodels into nodules
pathogenesis of cirrhosis
activate stellate cells and differentiate into fibrogenic myofibroblasts
–>activated by cytokines, ROS, toxins,
–>TGF beta, IL17 signalling
what % of hepatic steatosis to diagnose NAFLD
5%
MAFLD criteria (1 of 3)
T2D
overweight/obese
metabolic risk abnormalities (i.e. BP, HDL, CRP)
MAFLD increases risk of… (over NAFLD)
diabetes, chronic kidney disease, worsened lung function
why do insulin resistance and fatty liver cluster together?
Insulin resistance –> increased FFA liberation from adipocytes –> conversion into triglycerides and storage in hepatocytes
Elevated glucose and insulin levels –> hepatic triglyceride synthesis
what happens to adiponectin levels when abdominal fat increases
decreases
what is adiponectin
adipokine released by visceral fat
it increases glucose utilization and fatty acid oxidation
(helps remove glucose)
what vitamin reduces oxidative stress in hepatocytes and can educe inflmmation in steatohepatits
vitamin E
3 tests to measure function of liver
- serum albumin (oncotic pressure)
- bilirubin (breakdown product of heme)
- PT/INR (coagulation/ time to clot)
what happens to serum albumin in liver damage?
decreases
what happens to bilirubin in liver damage?
increases
what happens to PT/INR in liver damage?
increases
what are the 2 types of patterns of damage
- hepatocellular pattern
- cholestatic pattern
what is the hepatocellular pattern?
hepatocytes damaged, but biliary tree fine
what is cholestatic pattern?
obstructer or inflamed biliary tree (intra or extra hepatic bile ducts or wall of gallbladder)
what happens to AST, ALT, ALP and GGT in the hepatocellular pattern?
major increase in AST and ALT
normal or mild elevation in ALP and GGT
what happens to AST, ALT, ALP and GGT in the cholestatic pattern?
major increase in ALP and GGT
normal or mild elevation in AST and ALT
what does ALT stand for and where is it found?
alanine aminotransferase
found in cytosol of hepatocytes mainly
what pattern is ALT relatively specific for
hepatocellular pattern
bc mainly found in hepatocytes and for hepatocyte damage
what are the liver enzymes tests looking at
serum levels of enzymes increase with damage
damage to hepatocytes or biliary tree cause enzymes to leak into bloodstream
what does AST stand for and where is it found
aspartate aminotransferase
found in cytosol and mitochondria of hepatocytes
and many other cells… skeletal myocyte, cardiomyocsyte, renal, pancreatic
what is more specific for hepatocyte damage, AST or ALT?
ALT
-ALT only found in cytosol of hepatocytes
-AST found in cytosol and mitochondria and many other cells (skeletal myocyte, cardiomyocsyte, renal, pancreatic)
what does ALP stand for and where is it found? when does it increase?
alkaline phosphatase
found at canalicular membrane of hepatocytes
and bone and by placenta
damage to biliary apparatus - i.e. cholestasis, cholecystitis
what does GGT stand for and where is it found
gamma-glutamyl transpeptidase
found in cell membranes of wide variety of cells (hepatocytes & cholangiocytes, kidney, pancreas, spleen, heart…)
what is 5’ nucleotidase (5-NT) found and increase in what disease
many cells types
increases in hepatobiliary disease
what is the purpose of testing GGT and 5-NT
to double check if elevated ALP means hepatobiliary disease
what is bilirubin
heme portion when hemoglobin is broken down
how does bilirubin get broken down
in macrophage : heme –> biliverdin (unconjugated bilirubin) –> goes through serum –> into hepatocyte its conjugated into bilirubin glucuorinde
what are the 2 forms of bilirubin
- unconjugated bilirubin (indirect)
- conjugated bilirubin (direct)
unconjugated bilirubin (indirect) is found where?
in serum, not yet complexed to bilirubin glucuronide
unconjugated bilirubin (indirect) is due to what?
hematomas (RBC damage) and disorders affecting bilirubin conjugation
conjugated bilirubin (direct) is found where
it was in hepatocyte but leaked back into blood stream
conjugated bilirubin (direct) is due to what?
blocked biliary system
inability to transport conjugated bilirubin into canaliculi
damage to hepatocytes
main preseason for elevation in serum bilirubin
hepatocyte damage or impaired bile flow
… could be deficit in liver function though
when a hepatocyte is damaged what happens to bilirubin and which form is affected
when a hepatocyte is damaged, conjugated bilirubin increases in the serum more than unconjugated bilirubin
what does an elevation in unconjugated bilirubin indicate?
Elevations in only unconjugated bilirubin is almost always an RBC problem or an enzyme deficit in conjugation
what is albumin?
protein synthesized by the liver
carry hydrophobic molecules (i.e. bilirubin) and established oncotic pressure in capillary
what causes a decrease in serum albumin
deficiency in production from chronic liver disease (or serious protein malnutrition)
PT/ INR (prothrombin time/ international normalized ratio); what happens in liver damage?
increased (ratio >1) ; take longer to form blood clot
what vitamin is needed for coagulation in the liver
vitamin K
acute vs chronic for assessing liver function;;; PT/INR vs albumin
acute= PT/INR
chronic= albumin
in acute haptocyte injury what happens to ALT, AST and GGT and ALP, albumin and bilirubin
ALT and AST very elevated (ALT more than AST)
GGT and ALP maybe elevated or normal
not enough time for albumin to change
direct and indirect bilirubin increase
in chronic haptocyte injury what happens to ALT, AST and GGT and ALP, albumin and bilirubin , PT/INR
ALT and AST slight increase (ALT > AST)
ALP and GGT normal or slight increase
albumin decreased
PT/INR increase
unconjugated and conjugated bilirubin increase
liver function tests (albumin, bilirubin, PT/INR) in chronic vs short term
Decreased liver function is often a result of late-stage disease – early disease often exhibits normal bilirubin, PT/ INR, and albumin
in hepatocellular injury what happens to ALT and AST and which one is more impacts
ALT and AST increase (ALT>AST)
cholestasis (bile duct slow)- what happens to AST, ALT, ALP, GGT, bilirubin, PT/INR, albumin
ALP and GGT very elevated
AST and ALT normal or moderate elevation
Usually large increase in serum bilirubin, especially conjugated, but PT/INR and albumin are normal
when is ALP and GGT very elevated
cholestasis
SEE SLIDE 32 for diagram of liver lab patterns
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eating disorder psychological factors
OCD traits, cognitive rigidity, emotion sensitivity and impulsivity as well as history of developmental stressors/ trauma and challenging interpersonal relationships, body dissatisfaction, sports
eating disorder biological factors
50% due to multiple genetic effects
Dysfunction in serotonin, dopamine, norepinephrine, opioid and cholecystokinin systems
Hypothalamic regulation (amenorrhea can precede weight loss!)
Some research suggests changes within peripheral satiety network
Vicious cycle as malnourishment can exacerbate the comorbid psychiatric conditions and further the behaviours
sociocultural factors of eating disorders
idealization of thinness
eating disorder complications
death, vitamin deficiencies, stunted growth, reduced gastric motility, osteopenia, myopathies, metabolic alkalosis, bradycardia, hypotension, hypothermia,
purging: hematemesis, metabolic acidosis, hypokalemia, cardiomyopathies
