pathophysiology and aspects of liver disease W4

Question 1

functions of the liver cells?

Answer 1

hepatocytes - metabolism
kupffer cells - inflammatory response
stellate cells - responsible for fibrosis

Question 2

drug metabolism (xenobiotic metabolism)?

Answer 2

process of transforming less polar compounds into more polar compounds (water soluble) that can be excreted more easily.
typically occurs via enzymatic reactions involving cytochrome P450 system

Question 3

liver toxins?

Answer 3

metabolic end products
micro-organisms
contaminants/pollutants
insecticides/pesticides
food additives
drugs/alcohol

Question 4

phase 1 and 2 of drug metabolism?

Answer 4

phase 1 = oxidation/hydrolysis
phase 2 = glutathione conjugation or sulphation/acetylation/glucuronidation

Question 5

paracetamol chemical name?

Answer 5

acetaminophen

Question 6

normal paracetamol metabolism?

Answer 6

metabolised by liver through process of conjugation with glucuronide/sulphate (non-toxic)

Question 7

paracetamol metabolism during overdose?

Answer 7

P450 converts paracetamol to NAPQI (toxic)
this uses glutathione which is also needed by hepatocytes, therefore hepatocytes die.

NAPQI + glutathione -> cysteine and mercapturic acid conjugates (non-toxic)

Question 8

acute liver failure definition?

Answer 8

loss of liver function that occurs quickly in days or weeks in a person with NO pre-existing liver disease

Question 9

late acute liver failure features?

Answer 9

acidosis, profound hypoglycaemia, coagulopathy and encephalopathy leading to coma. renal failure, multi-organ failure

Question 9

what is the leading cause of acute liver failure?

Answer 9

paracetamol overdose

Question 9

early acute liver failure features?

Answer 9

malaise, nausea, vomiting, abdominal pains, dehydration

Question 10

malaise meaning

Answer 10

general feeling of discomfort and illness

Question 11

acute liver failure spectrum of clinical features?

Answer 11

elevated transaminases (asymptomatic)
-> progressive jaundice, elevated transaminases, coagulopathy
-> hepatic encephalopathy
-> multi-system failure
-> death

Question 12

unconjugated bilirubin features

Answer 12

hydrophobic
strongly albumin-bound
not excreted in urine

Question 13

conjugated bilirubin features

Answer 13

conjugated in liver
makes it water soluble and can then be excreted in bile/urine

Question 14

what causes brown coloured urine

Answer 14

conjugated bilirubin

Question 15

pathophysiology of cirrhosis?

Answer 15

fibrotic tissue disrupts hepatic architecture. venous inflow dammed back leading to portal hypertension and disruption of hepatocyte function.
disorganised hepatocyte regeneration. hepatocyte function deregulated. constant stimulation to regenerate.
leads to cirrhosis - nodules of hepatocytes surrounded by fibrosis

Question 16

liver cirrhosis - first event?

Answer 16

sustained inflammation within liver activates Kupffer cells, inflammatory mediators destroy hepatocytes, stellate cells activated.

Question 17

liver cirrhosis - once stellate cells are activated?

Answer 17

stellate cells produce collagen, replacing dead hepatocytes. fenestrations of epithelial cells (in front of space of Disse) close up.

Question 18

effect of closed fenestrations of epithelial cells in liver cirrhosis?

Answer 18

increased pressure in sinusoids, pressure gradient transmitted into main portal vein system causing increased pressure here -> portal hypertension.

Question 19

portal hypertension clinical effects?

Answer 19

bleeding from varices
encephalopathy
ascites

Question 20

liver biochemistry in cirrhosis?

Answer 20

low albumin
prolonged PT
low urea high ammonia

Question 21

how do varices form?

Answer 21

portal hypertension leads to blood from mesenteric system having to bypass the liver via the coronary vein. this creates collaterals (small new veins) that shouldn’t exist around the stomach and the oesophagus. these are called varices

Question 22

variceal bleeding?

Answer 22

varices can burst in the oesophagus and stomach