W20 72 jaundice and liver failure

Question 1

Page693 image of liver anatomy

Answer 1

View image plez

Question 2

What are the critical functions of the liver?

Answer 2

Immunity - Kupffer cells (like macrophages) destroy pathogens entering the gut
Blood - synthesis of clotting factors and filtration of toxins
Metabolism - bile synthesis, breakdown of fats and protein, regulation of blood glucose
Storage - fat, proteins, glycogen, vitamins, copper, iron

Question 3

How is the liver tissue organised? - PG693 IMAGE!

Answer 3

The functional units of the liver = hepatocytes
Hepatocytes are organised into liver lobules - hexagons with a central vein (part of hepatic vein), with a portal triad on each 6 corners
Portal triad = bile duct, portal vein and hepatic artery

Question 4

How does the liver detoxify blood/blood flow to the liver? (Pg694 img)

Answer 4

Hepatic artery carries oxygen-rich blood to supply the liver
The hepatic portal vein brings blood from the gut to the liver, carrying the nutrients that the liver needs. Drugs are absorbed in the gut and metabolites will travel to the liver and shave enzymatic reactions before being released into the bloodstream.
Blood enters hepatic sinusoids (capillaries)
Blood rains via central veins to hepatic veins to the vena cava

Question 5

How does the liver produce bile?

Answer 5

Bile produced by liver cells (hepatocytes) drains via canaliculi into bile ducts (opposite direction to blood flow)
Bile ducts eventually merge into the common hepatic duct, through which the bile can pass into the duodenum or be stored and concentrated in the gallbladder.

Question 6

What does bile contain?

Answer 6

Bile acids
Cholesterol
Phospholipids
Bile pigments (including bilirubin)

Question 7

What are the stages of liver failure/disease?

Answer 7

Healthy liver
Fibrotic liver - liver starts to thicken up and healthy tissue is replaced with scar tissue
Cirrhotic liver - as fibrosis progresses, liver getters nodular, harder, distorted
Liver cancer

Question 8

Upto what point is liver damage reversible?

Answer 8

Liver has regenerative capacities. Cirrhotic liver and further is irreversible.

Question 9

What is liver failure?

Answer 9

Occurs when large parts of the liver become damaged beyond repair. Usually gradual (chronic) but can be acute.

Question 10

What are the causes of chronic liver failure?

Answer 10

Alcohol related liver disease
Non-alcoholic fatty liver disease
Hepatitis B and C
Metabolic diseases eg haemachromatosis
Immune mediated diseases eg primary biliary cirrhosis, primary sclerosing cholangitis
Drugs - eg paracetamol overdose, antibiotics eg penicillin

Question 11

When is liver failure classed as acute?

Answer 11

1. Occurring within 8 weeks of symptom onset
2. In patients without pre-existing liver disease
   (Poor outcome)

Question 12

What are some causes of acute liver failure?

Answer 12

Drugs eg paracetamol
Acute viral hepatitis (A B E)
Seronegative hepatitis

Question 13

What are some common clinical signs of liver disease?

Answer 13

Yellow - jaundice
Ascites - fluid in belly or legs
Appear confused - difficult to work out the cause of confusion but can be part of liver encelopathy
Bleeding tendencies - platelet levels and INR

Question 14

What are som complications of (chronic) liver failure?

Answer 14

Loss of hepatic synthetic function causing - protein malnutrition, coagulopathy, hypoglycaemia, cardiovascular instability
Failure of hepatic clearance causing - testicular atrophy, encephalopathy, failure to clear drugs (important for dose adjustment of drugs), renal failure, jaundice

Question 15

How does liver failure cause protein malnutrition and coagulopathy?

Answer 15

Protein malnutrition - because protein metabolism is involved in the liver
Coagulopathy - clotting factors produced by the liver are stopped, so INR (marker of blood thinness) will go up as platelets start to go down, so bleeding tendency in liver failure

Question 16

What is ascites?

Answer 16

Pressure is so high within the vessels that the fluid starts to squeeze out of them and starts collecting in empty spaces, usually seen in belly or ankles (oedematous)

Question 17

What is varices?

Answer 17

Increased pressure in the venous system causes vessels on the inner lining of oesophagus or spleen to blow up - if the pt present with GI bleeds or haematemasis (vomiting blood), or black stools, one of the varices has popped.

Question 18

How does liver cirrhosis cause portal hypertension?

Answer 18

Irregular hardened liver means architectural distortion causes irregular blood flow through the liver. Eg hepatic portal vein has distorted flow, increasing blood pressure = portal hypertension. Also increases the pressure in the spleen and gut (collaterals). Causes ascites and varices.

Question 19

What is the treatment for liver failure?

Answer 19

Treat underlying cause if possible - eg no alcohol, antivirals for hepatitis, corticosteroids for autoimmune hepatitis
Nutritional support - malnourished since absorption is not as good, sarcopenia (sill loss a lot of muscle mass)
Prevention of bleeding from varices, management of ascites
Liver transplant

Question 20

What is jaundice?

Answer 20

Yellowing of the skin/sclera due to hyperbilirubinanemia (also icterus)

Question 21

Why might there be excess bilirubin?

Answer 21

Because it is being produced a lot, or liver is not taking it up/mopping it from circulation, or liver failing to excrete it.

Question 22

What is the difference between conjugated and unconjugated hyperbilirubinaemia?

Answer 22

Conjugated hyperbilirubinaemia = within the liver, either the enzymes responsible for conjugating the bilirubin are not working properly; or the pathways responsible for excretion of bilirubin are not working properly.
Unconjugated hyperbilirubinaemia = lots of production outside of the liver - so problem is not within the liver, eg sickle cell disease or disorders of metabolism

Question 23

How is bilirubin formed?

Answer 23

RBCs break down and release haem
Haem is combined with albumin - how bilirubin travels around
This bilirubin albumin combination travels into the liver
Within the liver, the bilirubin and albumin get separated and the bilirubin gets conjugated to form conjugated bilirubin which enters the gut and comes out in stools
10% of that re-enters the liver = interhepatic circulation

Question 24

Don’t need to learn but give an overview of what might be high in different liver function tests (LFTs) to help determine the cause. PG699 IMAGE

Answer 24

Acute hepatitis - very high AST and ALT, normal ALP, high bilirubin
Chronic hepatitis - slightly elevated AST and ALT, normal ALP and bilirubin
Biliary disease (cholestasis) - normal or slight elevation of AST and ALT, high ALT and bilirubin

Question 25

What can chronic hepatitis cause?

Answer 25

Cirrhosis and liver cancer

Question 26

How do different cases of acute hepatitis occur and what is their treatment?

Answer 26

Hep A and E: ingestion of contaminated food and water. Usually heals itself, conservative treatment.
Hep B: exposure to contaminated blood/needles/bodily fluids. Treat with antivirals. Hep D only occurs in patients with hep B.
Hep C: exposure to contaminated blood. Treat with antivirals.

Question 27

What is alcoholic hepatitis?

Answer 27

Inflammatory response of the liver when binge drinking. Tends to settle down quite quickly.

Question 28

What is the treatment for end stage liver disease?

Answer 28

Liver transplantation

Question 29

What is the clinical manifestation for hyperbilirubinaemia?

Answer 29

Jaundice