MEDICAL LIVER DISEASES

Question 1

Jaundice

Answer 1

Visible when bilirubin >40umol/l. Commonest sign of liver disease
blood test biochemistry of liver enzymes: ALT AST leak from hepatocytes and Alk phos. Leaks from bile ducts. Bilirubin, albumin and clotting factors tested too.
ultrasound scan check or dilated ducts for obstruction. Bile in liver parenchyma is first sign

Question 2

Pre-hepatic

Answer 2

– too much bilirubin produced e.g. Haemolytic anaemia, (Gilbert’s syndrome – enzyme deficiency)
unconjugated – bound to albumin, insoluble, not excreted = patient notices yellow eyes/skin only

Question 3

Hepatic

Answer 3

– too few functioning liver cells e.g. Acute diffuse liver cell injury e.g. End stage chronic liver disease or Inborn errors. Mainly conjugated, Soluble = patient notices yellow eyes and dark urine

Question 4

Post hepatic

Answer 4

– bile duct obstruction, conjugated = stone, stricture, tumour – bile duct, pancreas conjugated – soluble, excreted, but can’t get into gut = patient notices yellow eyes, pale stool and dark urine

Question 5

Hepatitis

Answer 5

inflammation in the liver. Clinically liver enzymes raised.
use of liver biopsy in diagnosis to determine the cause of the damage / specific features, if present and to assess the stage of disease e.g. how much scarring, spectrum from normal to cirrhosis

Question 6

ACUTE hep

Answer 6

Acute liver injury caused by something that goes away  Inflammatory injury: viral, drugs, autoimmune. Or  toxic metabolite injury: alcohol, drugs (paracetamol)

Question 7

CHRONIC HEPATITIS

Answer 7

Caused by something that doesn’t go away
Immunological injury – virus, autoimmune, drugs
Toxic/metabolic injury – fatty liver disease, alcohol, non-alcoholic fatty liver disease (NAFLD) drugs
Genetic inborn errors – iron, copper, alpha1antitrypsin
Biliary disease – autoimmune, duct obstruction, drugs, Vascular disease – clotting disorders, drugs.
Pathology: Injury to liver cells, inflammation, formation of scar tissue and regeneration of hepatocytes. Non-specific features of injury. Specific pathological features depend on the cause of injury.
Aetiology: During any chronic liver disease, scarring gradually increases and starts to link vascular structures (bridging) eventually transforming the liver tissue into separate nodules – end stage = cirrhosis

Question 8

Viral hepatits

Answer 8

Hepatotrophic viruses: A, B, C, D = delta, only in people with B. E waterborne, increasingly recognised in UK in last few years, zoonosis, pigs.
Other viruses cause hepatitis, as part of systemic disease. EBV, CMV, HSV – usually immunocompromised host
Clinical features, pathology and complications – as for acute and chronic hepatitis

Question 9

Alchohol

Answer 9

Spectrum of fatty change in the liver.

1) fatty change
2) inflammation –> alchoholic steatohepatitis
3) cirrhosis

Question 10

Obesity: Non-alcoholic fatty liver disease

Answer 10

commonest cause of liver disease now

Same pathological spectrum as alcoholic liver disease.
Steatosis, steatohepatitis, cirrhosis, HCC.
Aetiology: Associated with Metabolic syndrome – obesity, type 2 diabetes, hyperlipidaemia, also some drugs.
Now recognised to be the commonest cause of liver disease.
Treat by lifestyle. increases chances of hepatocellular carcinoma.

Question 11

Drugs

Answer 11

Iatrogenic: induced by doctor/medical treatment/diagnostic procedures  Drug induced liver injury
Hepatotoxicity: Intrinsic e.g. paracetamol every time, predictable.
Idiosyncratic – - rare, unpredictable, metabolic, immunological
Clinical: Acute liver injury  Hepatocellular, Cholestatic/ Mixed.
Clinico-pathological diagnosis role of biopsy?
Raised liver enzymes: severe, persistent, diagnostic uncertainty. Exclude other causes: Alcohol, NAFLD, Acute presentation of underlying chronic liver disease, Autoimmune, Biliary, vascular.

Question 12

INHERITED: Haemachromotosis

Answer 12

Inborn error of iron metabolism: ‘bronzed diabetes’
Iron accumulates in: Liver – cirrhosis, Pancreas – diabetes, Skin – pigmented. Joints – arthritis. Heart – cardiomyopathy. Rx venesection: to deplete iron stores to normal

Question 13

INHERITED: Alpha-1-antitrypsin deficiency

Answer 13

Abnormal anti-protease which cannot be exported from hepatocyte:See PAS+ve globules in hepatocytes
Accumulates in liver cells and injures them – cirrhosis. Insufficient in blood, failure to inactivate neutrophil enzymes: emphysema.

Question 14

Autoimmune hep

Answer 14

Diagnosis: Auto-antibodies (anti-nuclear, smooth muscle, etc.), raised IgG, ALT, other autoimmune diseases.
Liver biopsy – plasma cells, interface hepatitis.
Primary biliary cholangitis (PBC, previously primary biliary cirrhosis)
Anti-mitochondrial antibodies, IgM, alkaline phosphatase, Bile duct granulomas at early stage, Then ductopenia and cirrhosis.
Primary sclerosing cholangitis (PSC)
Associated with ulcerative colitis, high alk phos, ‘pruned tree’ on biliary imaging. Periductal onion skin fibrosis then ductopenia and cirrhosis.

Question 15

CIRRHOSIS = end point of chronic liver disease

Answer 15

Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Liver cells still present, but portal vein blood bypasses the sinusoids so the liver cells cannot perform their functions.
Pressure inside the liver increases, portal hypertension.
Cirrhosis develops over months-decades.

Question 16

structural changes in cirrhosis

Answer 16

fibrosis, Portal hypertension, Increased blood flow, stiff liver Pressure rises in portal vein
Oesophageal varices.