Liver pathology Flashcards
(33 cards)
Anatomy of the liver
Basic structural unit is the hepatic lobule – thought of as a hexagon. At the centre are the terminal
branches of the hepatic vein (= centrilobular vein). The points of the hexagon are formed by the
portal tracts, which contain 3 structures (portal triad): branches of the bile ducts, hepatic artery
and portal vein.
The liver cells can be split into three zones.
• Zone 1 (closest to the portal triad) – periportal hepatocytes receive more oxygen and
• Zone 2 – mid zone
• Zone 3 (close to terminal hepatic vein) – perivenular hepatocytes are the most mature
and metabolically active. Zone 3 has most liver enzymes
Functions of the liver
- Metabolism – involved in glycolysis, glycogen storage, glucose synthesis, amino acid
synthesis, fatty acid synthesis and lipoprotein metabolism. Drug metabolism. - Protein synthesis – makes all circulating proteins (except gamma globulins) including
albumin, fibrinogen, and coagulation factors. - Storage – glycogen, vitamins A, D and B12 in large amounts, small amounts of vitamin K,
folate, iron and copper - Hormone metabolism – Activates vitamin D. Conjugation and excretion of steroid
hormones (oestrogen/glucocorticoids). Peptide hormone metabolism (insulin, GH, PTH) - Bile synthesis – 600-1000ml daily
- Immune function – antigens from gut reach liver via portal circulation. Phagocytosed by
Kupffer cells.
Histopathology of liver injury
- A normal liver has hepatocytes with microvilli and stellate cells which lie quiescent in the space of Disse (space between hepatocytes and sinusoid)
- Chronic inflammation causes the loss of microvilli and activation of stellate cells, which produce collagen.
- They become myofibroblasts that initiate fibrosis by deposition of collagen in the space of Disse.
- Myofibroblasts contract constricting sinusoids and increasing vascular resistance.
- Undamaged hepatocytes regenerate in nodules between fibrous septa
Features of acute hepatitis
Can either be caused by viruses (A to E) or by drugs.
Histopathology - SPOTTY NECROSIS (small foci of inflammation and infiltrates)
Features of chronic hepatitis
The severity of inflammation = grade The severity of fibrosis = stage Histopathology: 1. Portal Inflammation 2. Interface hepatitis (PEICEMEAL NECROSIS) – cannot see the border between the portal tract and parenchyma 3. Lobular inflammation 4. Bridging from the portal vein to central vein (critical stage in the evolution of hepatitis to cirrhosis)
Definition and features of cirrhosis
Diffuse abnormality of liver architecture that interferes with blood flow and liver function.
There is a disruption of liver architecture - ↑resistance to blood flow through liver portal
hypertension. Fibrotic bridges form between the portal triad and central vein – extra hepatic
shunting results in anastomoses.
Histopathology of a cirrhotic liver
Hepatocyte necrosis
Fibrosis
Nodules of regenerating hepatocytes
Disturbance of vascular architecture
List major causes of cirrhosis
- Alcoholic liver disease
- Non-alcoholic fatty liver disease
- Chronic viral hepatitis (hep B+/-D and C)
- Autoimmune hepatitis
- Biliary causes: Primary biliary cirrhosis & Primary sclerosing cholangitis
- Genetic causes:
a) Haemochromatosis- HFE gene Chr 6
b) Wilson’s disease- ATP7B gene Chr 13
c) Alpha 1 antitrypsin deficiency (A1AT)
d) Galactosaemia
e) Glycogen storage disease - Drugs e.g. methotrexate
Classification of cirrhosis
MICRONODULAR (nodules < 3mm). Uniform liver involvement.
• Caused by: alcoholic hepatitis, biliary tract disease
MACRONODULAR (nodules > 3mm). Variable nodule size.
• Caused by: viral hepatitis, Wilson’s disease, alpha1 antitrypsin deficiency
Scoring system of cirrhosis
Modified Child’s Pugh score (ABCDE)
Albumin Bilirubin Clotting - PT Distention - ascites Encephalopathy
- Total Score <7 = Child’s Pugh A (45% 5yr survival)
- Total Score 7-9 = Child’s Pugh B (20% 5yr survival)
- Total Score 10+ = Child’s Pugh C (<20% 5yr survival)
Describe progression of alcoholic liver disease
Hepatic steatosis (fatty liver)
Alcoholic hepatitis
Alcoholic cirrhosis
Features of hepatic steatosis
Macroscopic
Large, pale, yellow and greasy liver
Microscopic
Accumulation of fat droplets in hepatocytes (=steatosis)
Chronic exposure -> fibrosis (late stage)
Fully reversible if alcohol avoided
Features of alcoholic hepatitis
Macroscopic
Large, fibrotic liver
Microscopic
Hepatocyte ballooning and necrosis due to accumulation
of fat, water and proteins
Mallory Denk Bodies
Fibrosis
Seen acutely after night of heavy drinking. Ranges from
asymptomatic to fulminant liver failure. Each episode has
10-20% mortality
Features of alcoholic cirrhosis
Macroscopic Yellow-tan, fatty, enlarged. Transforms into shrunken, non-fatty, brown organ.
Microscopic
Micronodular cirrhosis – i.e. small nodules + bands of
fibrous tissue
Features of non-alcoholic fatty liver disease
● = hepatic steatosis in non-alcoholics – histologically looks very similar to alcoholic hepatitis
● Most common cause of chronic liver disease in West
● Mainly in obese individuals with hyperlipidaemia/metabolic syndrome. Diabetes is also a risk
factor.
● NAFLD includes:
o Simple steatosis: fatty infiltration, relatively benign
o Non-alcoholic steatohepatitis (NASH)
▪ Steatosis + hepatitis (fatty infiltration + inflammation)
▪ Can progress to cirrhosis
Features of autoimmune hepatitis
● Common with other autoimmune diseases e.g. coeliac, SLE, RA, thyroiditis, Sjögren’s, UC
● 78% female– young and postmenopausal.
● Associated with HLA-DR3
● Type 1: ANA (antinuclear Ig), anti-SMA (anti-smooth muscle Ig), anti-actin Ig, anti- soluble
liver antigen Ig
● Type 2: Anti-LKM Ig (anti liver-kidney-microsomal Ig)
● Treatment: Immune suppression until transplant, BUT disease returns in up to 40%
What are the biliary causes of cirrhosis
Primary biliary cirrhosis (PBC)
Primary sclerosing cholangitis
Features of primary biliary cirrhosis
● Autoimmune inflammatory destruction of medium sized intrahepatic bile ducts à
cholestasis à SLOW development of cirrhosis over many years
● F > M 10:1
● Peak incidence at 40-50yrs
● ↑serum ALP, ↑cholesterol, ↑IgM, hyperbilirubinaemia (late)
● Anti-mitochondrial antibodies in > 90%
● US scan shows no bile duct dilatation
● Histology: bile duct loss with granulomas
● Presents with fatigue, pruritus and abdominal discomfort
● Secondary symptoms incl: skin pigmentation, xanthelasma (part. eyelid),
steatorrhoea, vitamin D malabsorption, inflammatory arthropathy.
● Can treat with ursodeoxycholic acid in early phase à remission in 25%
Features of primary sclerosing cholangitis
● Inflammation and obliterative fibrosis of extrahepatic and intrahepatic bile ducts
à multi-focal stricture formation with dilation of preserved segments
● M > F
● Peak incidence at 40-50yrs
● Associated with IBD (especially UC)
● ↑ serum ALP, several associated auto-Ig, particularly p-ANCA
● US scan: bile duct dilatation
● ERCP: shows beading of bile ducts (due to multifocal strictures)
● Histology: onion skinning fibrosis – concentric fibrosis
● ↑ incidence of cholangiocarcinoma
Genetic causes of cirrhosis?
Haemochromatosis
Wilson’s disease
Alpha 1 antitrypsin deficiency
Pathophysiology, histology of haemochromatosis
P - Autosomal recessive
Mutated HFE gene at 6p21.3 ↑Fe gut
absorption which deposits in liver, heart,
pancreas, adrenals, pituitary, joints, skin
fibrosis
H - Fe deposits in liver – stains with Prussian blue
stain
Clinical features, investigations, treatment of haemochromatosis
CF - ● Skin bronzing (melanin deposition) ● Diabetes ● Hepatomegaly with micronodular cirrhosis ● Cardiomyopathy ● Hypogonadism ● Pseudogout I - ● ↑ Fe, ↑ Ferritin ● Transferrin saturation > 45% ● ↓ TIBC T - Venesection Desferrioxamine 30% with cirrhosis → HCC
Pathophysiology, histology of Wilson’s disease
Autosomal recessive
Mutated gene ATP7B (Chr 13): Encodes copper
transporting ATPase expressed on canalicular
membrane therefore à ↓biliary Cu excretion and
deposition in liver, CNS, iris.
Cu stains with Rhodanine stain
Mallory bodies and fibrosis on microscopy
Clinical features, investigations, treatment of Wilson’s disease
CF - ● Liver disease: acute hepatitis, fulminant liver
failure or cirrhosis
● Neuro disease: parkinsonism, psychosis,
dementia (basal ganglia involvement)
● Kayser Fleischer rings: copper deposits in
Descemet’s membrane in cornea
I - ● ↓ serum caeruloplasmin
● ↓ serum copper
● ↑ urinary copper
T - Lifelong penicillamine.
Good prognosis with early treatment but any neuro
damage is permanent and may require liver
transplant
