Liver pathology Flashcards
Why is vascular pathology rare in liver disease?
Dual blood supply - hepatic artery (oxygenated blood) + portal vein (deoxygenated blood drained from intestine)
Liver anatomy
Cells are arranged into hepatic lobules, which are hexagonal structures with portal triads (hepatic artery branch, bile duct branch, hepatic portal vein branch) at each vertice and a central vein. Hepatic arteries supply oxygenated blood into the sinusoid (and form metabolic zones (1, 2 and 3) with increasing distance from the hepatic artery); hepatic portal vein supplies deoxygenated blood, which travel along hepatic sinusoids to the central vein; bile duct forms bile canaliculi that radiate into the centre. Blood mixes within the sinusoid – oxygenated blood from artery and deoxygenated blood from vein. It is lined with discontinuous, fenestrated endothelium. Hepatocytes are separated from the endothelium of sinusoids by the space of DIsse, which contains Kupffer cells (hepatic macrophages). Hepatic stellate cells are also present here and are involved in scar formation in response to liver damage. Bile released from hepatocytes flows into the bile canaliculi and travels in the opposite direction back to the portal triad biliary duct branch.
REALLY IMPORTANT
Cellular change in liver injury
- Healthy liver - endothelial cells discontinuous with spaces between them - blood easily passes between endothelial cells to get to hepatocytes
- Liver injury - Kupffer cells in sinusoids activate - endothelial cells stick together - blood passes less easily to get to hepatocytes
Basically liver injury = harder for blood to get from capillaries to hepatocytes
4 features of cirrhosis
- Whole liver involved
- Fibrosis (collagen deposition)
- Nodules of regenerating hepatocytes
- Distorted vasculature (intra-hepatic and extra-hepatic shunting)
End-point of liver injury
Acute hepatitis –> Chronic hepatitis –> Cirrhosis
How is cirrhosis classified?
Alcohol/insulin resistance - fatty changes - micronodular (smaller) regenerating nodules Viral hepatitis (BCD) - macronodular (bigger) regenerating nodules
Micronodular (small) regnerating nodules
Fatty changes
Alcohol / insulin resistance causing cirrhosis
Macronodular (large) regenerating nodules
Virus (chronic only - BCD) causing cirrhosis
3 key complications of cirrhosis
Portal hypertension (extra-hepatic shunting = varices, splenomegaly)
Hepatic encephalopathy
Liver cell cancer
Spotty necrosis w/ small inflammatory foci
2 main causes: Hepatitis (A + E), drugs
Acute hepatitis
Chronic inflammation + fibrosis (blue strands of collagen)
3 main causes: Hepatitis (BCD), AI, Drugs
Chronic hepatitis
Grade of chronic hepatitis = ?
Stage of chronic hepatitis = ?
Grade = degree of inflammation (i.e. hepatocyte damage) Stage = Degree of fibrosis
Active chronic hepatitis
ASMA antibodies in serum
Responds well to steroids
Flooding with plasma cells + big Golgi
AI hepatitis
Pale yellow liver
Alcoholic liver disease
Fat = yellow
3 patterns of alcoholic liver disease
- Fatty liver
- Alcoholic hepatitis
- Cirrhosis
(Increasing inflammation + fibrosis down list)
Reversible fat infiltration
Drinking excess alcohol
Fatty liver
Balloon cells containing Mallory Denk bodies
Apoptosis
Pericellular fibrosis
Zone 3 - most metabolically active cells (alcohol breakdown happens here)
Alcoholic hepatitis
Micronodular regenerating
nodules containing fat
Alcohol related cirrhosis
Alcoholic liver disease type picture without alcohol drinking
Insulin resistance - raised BMI, DM
NASH
Females
AMA diagnostic
Risk of cirrhosis
Granulomatous bile duct destruction
Primary biliary cholangitis (PBC)
Previously primary biliary cirrhosis
Males, UC
ERCP / MRCP diagnostic ‘Beaded appearance’
Risk of cirrhosis, cholangiocarcinoma
Fibrotic bile duct destruction (onion skinning around duct)
Primary sclerosing cholangitis (PSC)
GENETIC - HFe gene on chromosome 6
Iron deposition in HEPATOCYTES, pancreas, heart
Cirrhosis, HF, bronzed diabetes
Prussian blue stain
Elevated serum iron + ferritin, redued TIBC
Hereditary haemochromatosis
Iron accumulation in MACROPHAGES (Kupffer cells)
Blood transfusion
NOT GENETIC - blood transfusion
Haemosiderosis
Cu accumulation in basal ganglia (LN) + eye
Kayser-Fleischer Rings
Parkinsonism
Rhodanine stain
Wilson’s disease
Pink alpha1-antitrypsin globules in hepatocytes
Low alpha1-antitrypsin in blood
Alpha1-antitrypsin deficiency
Commonest liver cancer
Metastastic
Collection of macrophages in chronic inflammation
Granuloma
Causes of hepatic granuloma
Liver specific - PBC, drugs
General - TB, sarcoid
3 types of benign liver tumour
Liver cell adenoma (hepatocytes)
Bile duct adenoma (bile duct cells)
Hemangioma (endothelial cells)
Commonest benign liver tumour
Hemangioma
Multiple malignant lesions
Secondary (metastatic) cancer
Single malignant lesion
Primary
Malignancy associated with:
Chronic HepB/HepC infection
Cirrhosis
HCC
Malignancy associated with:
PSC
Worm infections
Cirrhosis
Cholangiocarcinoma
Abdo pain, nausea + vomiting
Tender hepatomegaly + ascites
CT = hepatic vein occlusion, diffuse abnormal parenchyma
Hepatic vein thrombosis
Budd-Chiari syndrome
‘After a fall’
Alcohol
