Liver disease

Question 1

The hepatic blood supply constitutes______ % of the resting cardiac output ?

Answer 1

25% of the resting cardiac output

Question 2

In anoxia and due to toxic metabolites -(paracetamol EtOH-) which cells are damaged first (in the liver lobule)?

Answer 2

cells around the central vein

Question 3

Damage from direct-acting toxins (phosphorus) begins where?

Answer 3

at periphery, around the portal triad.

Question 4

blood flow in the lobule

Answer 4

From portal triad TO central vein

Question 5

bile composition

Answer 5

• Acids (primary from hepatocytes – cholic acid, chenodeoxycolic acid)
• (secondary – decarboxylated by intestinal bacteria – deoxycholic, lithicolic)
• , cholesterol,
• conjugated acids
• NaHCO3,
• phospholipids,
• bilirubin.

Question 6

bile secretion is___

stimulated by?

inhibited by>?

Answer 6

active process

■continuous

■bile ejected 30min after meal due to CCK produced from duodenum in response to a.as, f. as.

■Secretin →↑bile flow by ↑H2O&HCO3-, not bile salt secretion (opposed by somatostatin)

■vagal stimulation →↑bile flow, splanchnics →↓ flow

Question 7

Enterohepatic circulation?

Answer 7

Enterohepatic circulation:

■bile salts absorbed back into portal circulation in ileum.

Question 8

causes of unconjugated hyperbilirubinemia

Answer 8

As unconjugated bilirubin is water insoluble, it does not enter urine, resulting in unconjugated (acholuric) hyperbilirubinaemia.

Overproduction:
■haemolysis ■ineffective erythropoiesis.
Impaired hepatic uptake:
■drugs: contrast agents, rifampicin ■congestive cardiac failure.
Impaired conjugation:
■glucuronyl transferase deficiency (Gilbert’s & Crigler–Najjar syndromes)

Question 9

conjugated hyperbilirubinemia

causes of..?

Answer 9

Hepatocellular dysfunction:
■Viruses: hepatitis (HAV, HBV, HCV, CMV, EBV) ■drugs ■alcoholic hepatitis ■cirrhosis ■liver metastases/abscess ■haemochromatosis ■autoimmune hepatitis (AIH) ■septicaemia ■leptospirosis ■α1-antitrypsin deficiency ■Budd–Chiari ■Wilson’s disease ■failure to excrete conjugated bilirubin (Dubin–Johnson and Rotor syndromes) ■right heart failure ■toxins:carbon tetrachloride, fungi (Amanita phalloides)

Impaired hepatic excretion:
Obstruction of biliary outflow due to:
• Luminal obstruction: ■gallstones ■Mirrizi’s syndrome
• Wall pathology: ■congenital bile duct abnormalities ■primary biliary cirrhosis ■trauma ■tumour ■choledochal cyst ■primary sclerosing cholangitis ■biliary atresia
• External compression: ■pancreatitis ■lymphadenopathy ■pancreatic tumour ■Ampulla of Vater tumour■lymph nodes at the porta hepatis
■drug-induced cholestasis

Question 10

Pale stools with dark urine ≈ ???

Answer 10

Pale stools with dark urine ≈ cholestatic jaundice.

Question 11

Bilirubin is absent in urine due to what causes of jaundice?

Answer 11

PRE-HEPATIC causes

Question 12

urobilinogen is absent in urine in what jaudice>?

Answer 12

** obstructive jaundice**

Question 13

Courvoisier’s ‘law’

Answer 13

palpable gall bladder in conjunction with painless jaundice suggests a cause other than gallstones

Question 14

Liver cirrhosis definition

Answer 14

implies irreversible liver damage.

Histologically, there is loss of normal hepatic architecture with bridging fibrosis and nodular regeneration.

Question 15

Causes of cirrhosis

Answer 15

• Chronic **alcohol abuse
• Non-alcoholic steatohepatitis
• Chronic HBV or HCV infection**
• Autoimmune disease: AIH, sarcoidosis
• Genetic disorders: haemachromatosis; α1-antitrypsin deficiency, Wilson’s disease
• Others: can be cryptogenic in up to 20%; Budd–Chiari syndrome (hepatic vein thrombosis)
• Drugs: eg amiodarone, methyldopa, methotrexate

Question 16

causes of ascites

Answer 16

1. Sodium and water retention (SNS and the RAAS )
2. Portal hypertension exerts a local hydrostatic pressure
3. Low serum albumin → ↓in plasma oncotic pressure.

Question 17

Liver failure

definition and classifications

Answer 17

Liver failure may occur suddenly in the previously healthy liver: acute hepatic failure.

More commonly it occurs as a result of decompensation of chronic liver disease = acute-on-chronic hepatic failure.

Fulminant hepatic failure is a clinical syndrome resulting from massive necrosis of liver cells leading to severe impairment of liver function: hyperacute = encephalopathy within 7d of onset of jaundice; acute = within 8–28d; subacute = within 5–26 weeks.

There is decreasing risk of cerebral oedema as the onset of encephalopathy is increasingly delayed.

Question 18

causes of liver failure ACUTE

Answer 18

_Infections:_Viral hepatitis (esp B, C, CMV, coxsackie, mumps), yellow fever, leptospirosis.
Drugs: Paracetamol overdose, halothane, isoniazid, sulphonamides, NSAIDs, phenytoin, valproate, penicillins, MAOIs, ecstasy, sulfasalazine, disulfiram, ketoconazole.
Toxins: Alcohol, Amanita phalloides mushroom, carbon tetrachloride.
Vascular:Budd–Chiari synd., veno-occlusive disease, ischaemic injury
Autoimmune: Primary biliary cirrhosis, haemochromatosis, autoimmune hepatitis,
Other: alpha1-antitrypsin deficiency, Wilson’s disease, fatty liver of pregnancy, HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelets; it is usually associated with pre-eclampsia;).
Malignancy: Lymphoma, malignant infiltration.

Question 19

causes of liver cirrhosis

Answer 19

• Chronic alcohol abuse
• Non-alcoholic steatohepatitis
• Chronic HBV or HCV infection
• Autoimmune disease: AIH, sarcoidosis
• Genetic disorders: haemachromatosis; α1-antitrypsin deficiency, Wilson’s disease
• Others: can be cryptogenic in up to 20%; Budd–Chiari syndrome (hepatic vein thrombosis)
• Drugs: eg amiodarone, methyldopa, methotrexate

Question 20

SIGNS of chronic liver disease

Answer 20

1. ■Leuconychia: white nails with lunulae undemarcated, from hypoalbuminaemia;
2. ■Terry’s nails—white proximally but distal ⅓ reddened by telangiectasias;
3. ■clubbing;
4. ■palmar erythema
5. ■hyperdynamic circulation
6. ■Dupuytren’s contracture
7. ■spider naevi
8. ■xanthelasma
9. ■gynaecomastia ■atrophic testes ■loss of body hair
10. ■parotid enlargement;
11. ■hepatomegaly or small liver in late disease.

Question 21

child-pugh-trcotte system

what is it for and what are the criteria?

Answer 21

to classify the severity of liver cirrhosis and determine the prognosis

1. Ascites
2. Encephalopathy
3. Bilirubin (μmol/L)
4. Albumin (g/L)
5. Prothrombin time (sec over normal)

Question 22

causes of portal hypertension

Answer 22

• Prehepatic: ○Portal vein thrombosis

• Intrahepatic
• Presinusoidal
• Schistosomiasis; sarcoidosis
• Primary biliary cirrhosis
• Sinusoidal
• Cirrhosis (e.g. alcoholic)
• Partial nodular transformation

• Post-sinusoidal
• Veno-occlusive disease
• Budd-Chiari syndrome

• Post-hepatic
• Right heart failure (rare)
• Constrictive pericarditis
• IVC obstruction

Question 23

pathogenesis of ascites

Answer 23

• Sodium and water retention results from peripheral arterial vasodilatation and consequent reduction in the effective blood volume. NO and other substances (e.g. ANP and prostaglandins) act as vasodilators. The reduction in effective blood volume activates various neurohumoral pressor systems such as the SNS and the RAAS →salt and water retention
• Portal hypertension exerts a local hydrostatic pressure and → ↑hepatic and splanchnic production of lymph and transudation of fluid into the peritoneal cavity.

• Low serum albumin (a consequence of poor synthetic liver function) → ↓in plasma oncotic pressure.

Question 24

complications of liver cirrhosis

Answer 24

• Portal hypertension
• Coagulopathy
• Gastroesophageal varices
• Factor deficiency
• Portal hypertensive
• gastropathy
• Fibrinolysis
• Splenomegaly, hypersplenism
• Thrombocytopenia
• Ascites
• Bone disease
• Spontaneous bacterial peritonitis
• Osteopenia
• Hepatorenal syndrome
• Osteoporosis
• Osteomalacia
• Hematologic abnormalities
• Hepatic encephalopathy
• Anemia
• Hepatopulmonary syndrome
• Hemolysis
• Portopulmonary hypertension
• Thrombocytopenia
• Malnutrition
• Neutropenia