general patho

Question 1

what are the 7 functions of liver

Answer 1

1) blood storage
2) nutrient metabolism
3) protein synthesis
4) bile formation & excretion
5) detoxification & excretion
6) storage of fat soluble vitamins & minerals (fe)
7) immune function

Question 2

functions of liver -> blood storage

Answer 2

. crucial in response to increase (expand and absorb blood) or decrease (release blood) in bloow flow
. portal vein and hepatic artery important

Question 3

functions of liver -> nutrient metabolism

Answer 3

. synthesise, metabolise, interconvert
. remove/release from blood stream when required

. carbohydrate metabolism
- store large excess of glycogen for glucose buffer function (store more glucose to release when low glucose)
- convert galactose to fructose and glucose
- gluconeogenesis: convert AA and glycerides to glucose
- intermediate compounds converted to chemical compounds

. lipid metabolism
- oxidation of fatty acids for energy when low glucose
- synthesis of cholesterol, phospholipids, lipoproteins
- synthesis of vitamin K

. protein metabolism
- oxidative deamination & transamination (recycle AA to make new AA or for carbs metabolism)
- urea cycle: only at liver, excrete N in form of urea in urine, ammonia toxic to CNS cuz freely permeable across BBB

Question 4

function of liver -> protein synthesis

Answer 4

. synthesis of albumin and plasma protein: maintain oncotic pressure
. synthesis of coagulation factors: prothrombin, fibrinogen, factor VII (produced by liver sinusoidal endothelial cells & endothelial cells outside liver throughout body)
. synthesis of vitamin K for coagulation

Question 5

function of liver -> bile formation and excretion

Answer 5

. primary bile acid produced by hepatocytes formed from cholesterol & conjugated to form taurine & glycine
. haemoglobin broken down by macrophage -> heme & globin -> bilirubin
. bilirubin secreted -> reabsorbed -> recycled
- mechanism of action: 1) passive diffusion 2) carrier mediated active transport (most important) 3) deconjugation to pri bile salts to before reabsorption 4) subsequent absorption: pri convert to secondary bile salts

Question 6

function of liver -> detoxification & excretion (biotransformation)

Answer 6

. drugs, hormones, bilirubin

. phase I
- add/expose to more polar functional group
- oxidation most common, p450

. phase II
- add highly polar functional group
- conjugate more hydrophilic, less likely to be absorbed
- excreted in bile/transport to bloodstream to be transported to urine for excretion

Question 7

function of liver -> immune function

Answer 7

. hepatic macrophage system
- clear antigen and bacteria from portal circulation
- Kupffer cells: line sinusoidal lining, clear blood as it flows through sinusoids

Question 8

what is jaundice

Answer 8

yellow discolouration of skin, scelera, mucous membranes due to excess accumulation of bilirubin

Question 9

clinical markers for bilirubin

Answer 9

. serum bilirubin > 1.2mg/dL
. clinically significant if > 2.5 - 3.0 mg/dL

Question 10

probable causes of bilirubin (pre/intra/post)

Answer 10

1) pre-hepatic: excessive RBC haemolysis, reduced hepatic uptake
2) intra-hepatic: cirrhosis, fibrosis, liver cancer
3) obstructive (post): obstruction of bile outflow, gall stones, tumours

Question 11

bilirubin metabolism

Answer 11

1) RBC broken down in spleen -> haemoglobin
2) haemoglobin broken down into heme and globin
3) globin converted into unconjugated bilirubin by heme oxidase & biliverdin transferase
4) conjugated in liver
5) secreted unchanged into bile and secreted into small intestine
6) some reabsorbed & recycled, the rest excreted in urine

Question 12

conjugated vs unconjugated bilirubin

Answer 12

. unconjugated bilirubin
- water insoluble, tight complex with iron, not many exist as albumin free anion, not secreted even though high blood concentration, toxic to new born’s brain in excess
. conjugated bilirubin
- water soluble, non toxic, bind loosely to serum albumin, excreted in urine, not passively reabsorbed from intestinal lumen

Question 13

types of jaundice

Answer 13

. differentiated by type of bilirubin to determine post/pre
. pre: unconjugated, post: conjugated
. common causes:
- unconjugated: drug induced immune haemolytic anaemia
- conjugated: viral hepatitis, ALD, nonalcoholic steatohepatitis, liver, drug induced liver injury

Question 14

alcoholic liver disease

Answer 14

. chronic alcohol consumption
. spectrum of diseases (alcoholic fatty liver, alcoholic hepatitis, fibrosis, cirrhosis, HCC)

Question 15

pathogenesis of alcoholic liver disease

Answer 15

1) ethanol & metabolites, acetyldehyde, NADP hepatoxic
2) induced CYP450 oxidation stimulates ROS and cytokine pathway (TNF-alpha)
3) initiate & perpetuate hepatic injury -> fibrosis through stellate cell devision

Question 16

types of alcoholic liver disease

Answer 16

1) fatty liver (steatosis)
- possible cause: fatty change, perivenular fibrosis
- elevated ALT/AST +/- hepatomegaly
- disappear after 3 months of abstinence

2) alcohol hepatitis
- possible cause: liver cell necrosis, inflammation, mallory body, fatty change, complications of portal HTN
- jaundice + hepatomegaly
- possible complications of portal HTN

3) cirrhosis
- possible causes: fibrosis, hyperplastic nodules, portal HTN
- serious complications
- abstinence is the important start

Question 17

What is non alcoholic fatty liver disease (NAFLD)

Answer 17

. chronic liver disease associated w metabolic syndrome
. hepatic steatosis w/wo inflammation & fibrosis + no other secondary cause of fat accumulation

Question 18

severity of NAFLD

Answer 18

1) NAFLD
2) nonalcoholic fatty liver (NFL)
3) cirrhosis

Question 19

pathogenesis of NAFLD

Answer 19

• insulin resistance
• fat accumulation -> change in cell signalling that regulates response to stress that potentiates liver damage and death -> lipotoxicity