week 1, lecture 1

Question 1

NAFLD pathologic findings

Answer 1

hepatocyte ballooning, lobular inflammation, steatosis

progress to fibrosis and cirrhosis

Question 2

2 hit model of NAFLD

Answer 2

1. hepatic fat accumulation
2. increased oxidative stress

Question 3

cirrhosis

Answer 3

liver scarring remodels into nodules

Question 4

pathogenesis of cirrhosis

Answer 4

activate stellate cells and differentiate into fibrogenic myofibroblasts
–>activated by cytokines, ROS, toxins,
–>TGF beta, IL17 signalling

Question 5

what % of hepatic steatosis to diagnose NAFLD

Answer 5

5%

Question 6

MAFLD criteria (1 of 3)

Answer 6

T2D
overweight/obese
metabolic risk abnormalities (i.e. BP, HDL, CRP)

Question 7

MAFLD increases risk of… (over NAFLD)

Answer 7

diabetes, chronic kidney disease, worsened lung function

Question 8

why do insulin resistance and fatty liver cluster together?

Answer 8

Insulin resistance –> increased FFA liberation from adipocytes –> conversion into triglycerides and storage in hepatocytes

Elevated glucose and insulin levels –> hepatic triglyceride synthesis

Question 9

what happens to adiponectin levels when abdominal fat increases

Answer 9

decreases

Question 10

what is adiponectin

Answer 10

adipokine released by visceral fat

it increases glucose utilization and fatty acid oxidation

(helps remove glucose)

Question 11

what vitamin reduces oxidative stress in hepatocytes and can educe inflmmation in steatohepatits

Answer 11

vitamin E

Question 12

3 tests to measure function of liver

Answer 12

1. serum albumin (oncotic pressure)
2. bilirubin (breakdown product of heme)
3. PT/INR (coagulation/ time to clot)

Question 13

what happens to serum albumin in liver damage?

Answer 13

decreases

Question 14

what happens to bilirubin in liver damage?

Answer 14

increases

Question 15

what happens to PT/INR in liver damage?

Answer 15

increases

Question 16

what are the 2 types of patterns of damage

Answer 16

1. hepatocellular pattern
2. cholestatic pattern

Question 16

what is the hepatocellular pattern?

Answer 16

hepatocytes damaged, but biliary tree fine

Question 17

what is cholestatic pattern?

Answer 17

obstructer or inflamed biliary tree (intra or extra hepatic bile ducts or wall of gallbladder)

Question 18

what happens to AST, ALT, ALP and GGT in the hepatocellular pattern?

Answer 18

major increase in AST and ALT
normal or mild elevation in ALP and GGT

Question 19

what happens to AST, ALT, ALP and GGT in the cholestatic pattern?

Answer 19

major increase in ALP and GGT
normal or mild elevation in AST and ALT

Question 20

what does ALT stand for and where is it found?

Answer 20

alanine aminotransferase
found in cytosol of hepatocytes mainly

Question 21

what pattern is ALT relatively specific for

Answer 21

hepatocellular pattern

bc mainly found in hepatocytes and for hepatocyte damage

Question 22

what are the liver enzymes tests looking at

Answer 22

serum levels of enzymes increase with damage

damage to hepatocytes or biliary tree cause enzymes to leak into bloodstream

Question 23

what does AST stand for and where is it found

Answer 23

aspartate aminotransferase

found in cytosol and mitochondria of hepatocytes
and many other cells… skeletal myocyte, cardiomyocsyte, renal, pancreatic

Question 24

what is more specific for hepatocyte damage, AST or ALT?

Answer 24

ALT -ALT only found in cytosol of hepatocytes -AST found in cytosol and mitochondria and many other cells (skeletal myocyte, cardiomyocsyte, renal, pancreatic)

Question 25

what does ALP stand for and where is it found? when does it increase?

Answer 25

alkaline phosphatase found at canalicular membrane of hepatocytes and bone and by placenta damage to biliary apparatus - i.e. cholestasis, cholecystitis

Question 26

what does GGT stand for and where is it found

Answer 26

gamma-glutamyl transpeptidase found in cell membranes of wide variety of cells (hepatocytes & cholangiocytes, kidney, pancreas, spleen, heart...)

Question 27

what is 5' nucleotidase (5-NT) found and increase in what disease

Answer 27

many cells types increases in hepatobiliary disease

Question 28

what is the purpose of testing GGT and 5-NT

Answer 28

to double check if elevated ALP means hepatobiliary disease

Question 29

what is bilirubin

Answer 29

heme portion when hemoglobin is broken down

Question 30

how does bilirubin get broken down

Answer 30

in macrophage : heme --> biliverdin (unconjugated bilirubin) --> goes through serum --> into hepatocyte its conjugated into bilirubin glucuorinde

Question 31

what are the 2 forms of bilirubin

Answer 31

1. unconjugated bilirubin (indirect) 2. conjugated bilirubin (direct)

Question 32

unconjugated bilirubin (indirect) is found where?

Answer 32

in serum, not yet complexed to bilirubin glucuronide

Question 33

unconjugated bilirubin (indirect) is due to what?

Answer 33

hematomas (RBC damage) and disorders affecting bilirubin conjugation

Question 34

conjugated bilirubin (direct) is found where

Answer 34

it was in hepatocyte but leaked back into blood stream

Question 35

conjugated bilirubin (direct) is due to what?

Answer 35

blocked biliary system inability to transport conjugated bilirubin into canaliculi damage to hepatocytes

Question 36

main preseason for elevation in serum bilirubin

Answer 36

hepatocyte damage or impaired bile flow ... could be deficit in liver function though

Question 37

when a hepatocyte is damaged what happens to bilirubin and which form is affected

Answer 37

when a hepatocyte is damaged, conjugated bilirubin increases in the serum more than unconjugated bilirubin

Question 38

what does an elevation in unconjugated bilirubin indicate?

Answer 38

Elevations in only unconjugated bilirubin is almost always an RBC problem or an enzyme deficit in conjugation

Question 39

what is albumin?

Answer 39

protein synthesized by the liver carry hydrophobic molecules (i.e. bilirubin) and established oncotic pressure in capillary

Question 40

what causes a decrease in serum albumin

Answer 40

deficiency in production from chronic liver disease (or serious protein malnutrition)

Question 41

PT/ INR (prothrombin time/ international normalized ratio); what happens in liver damage?

Answer 41

increased (ratio >1) ; take longer to form blood clot

Question 42

what vitamin is needed for coagulation in the liver

Answer 42

vitamin K

Question 43

acute vs chronic for assessing liver function;;; PT/INR vs albumin

Answer 43

acute= PT/INR chronic= albumin

Question 44

in acute haptocyte injury what happens to ALT, AST and GGT and ALP, albumin and bilirubin

Answer 44

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

Question 45

in chronic haptocyte injury what happens to ALT, AST and GGT and ALP, albumin and bilirubin , PT/INR

Answer 45

ALT and AST slight increase (ALT > AST) ALP and GGT normal or slight increase albumin decreased PT/INR increase unconjugated and conjugated bilirubin increase

Question 46

liver function tests (albumin, bilirubin, PT/INR) in chronic vs short term

Answer 46

Decreased liver function is often a result of late-stage disease – early disease often exhibits normal bilirubin, PT/ INR, and albumin

Question 47

in hepatocellular injury what happens to ALT and AST and which one is more impacts

Answer 47

ALT and AST increase (ALT>AST)

Question 48

cholestasis (bile duct slow)- what happens to AST, ALT, ALP, GGT, bilirubin, PT/INR, albumin

Answer 48

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

Question 49

when is ALP and GGT very elevated

Answer 49

cholestasis

Question 50

SEE SLIDE 32 for diagram of liver lab patterns

Answer 50

xx

Question 51

eating disorder psychological factors

Answer 51

OCD traits, cognitive rigidity, emotion sensitivity and impulsivity as well as history of developmental stressors/ trauma and challenging interpersonal relationships, body dissatisfaction, sports

Question 52

eating disorder biological factors

Answer 52

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

Question 53

sociocultural factors of eating disorders

Answer 53

idealization of thinness

Question 54

eating disorder complications

Answer 54

death, vitamin deficiencies, stunted growth, reduced gastric motility, osteopenia, myopathies, metabolic alkalosis, bradycardia, hypotension, hypothermia, purging: hematemesis, metabolic acidosis, hypokalemia, cardiomyopathies