Histopathology - Liver Pathology Flashcards
What is the basic structural unit in the liver?
Hepatic lobule
How is the hepatic lobule arranged?
- Centre = terminal branches of hepatic vein (=centrilobular vein)
- Points of hexgon formed by portal tracts containing the portal triad
What components make up the portal triad?
- Branches of bile ducts
- Hepatic artery
- Portal vein
What is Zone 1 of the hepatic lobule
- Closest to portal triad
- Periportal hepatocytes receive more oxygen (best blood supply) + affected first in viral hepatitis
What is Zone 2 of the hepatic lobule?
Mid zone
What is Zone 3 of the hepatic lobule?
- Closest to terminal hepatic vein
- Perivenular hepatocytes are most mature + metabolically active
- Most liver enzymes (most sensitive to metabolic toxins)
What are the functions of the liver?
Metabolism:
- DRUG METABOLISM
- Glycolysis, glycogen storage, glucose synthesis, amino acid synthesis, fatty acid synthesis, lipoprotein metabolism
Protein Synthesis:
- Makes circulating proteins (except gamma globulins)
Storage:
- Glycogen, Vitamins A, D, large amounts of B12 + small amounts of K, folate, iron, copper
Hormone Metabolism:
- Activates Vit D
- Conjugation + excretion of steroid hormones (oestrogen/glucocorticoids)
- Peptide hormone metabolism (insulin, GH, PTH)
Bile Synthesis
Immune Function:
- Antigens from gut reach liver via portal circulation
- Phagocytosed by Kupffer cells
What causes liver injury?
Normal Liver:
- Hepatocytes with microvilli
- Stellate cells lie quiescent in Space of Disse (between hepatocytes + sinusoid)
- Chronic inflammation = loss of microvilli + activation of stellate cells (produce collagen)
- Become myofibroblasts that initiate fibrosis by depletion of collagen in space of Disse
- Myofibroblasts contract, constricting sinusoids + increasing vascular resistance
- Undamaged hepatocytes regnerate in nodules between fibrous septa
What are the causes and histology of acute hepatitis?
Causes:
- Viruses (Hep A-E)
- Drugs
Histology:
- SPOTTY NECROSIS: small foci of inflammation + infiltrates
What are the causes of chronic hepatitis?
- Viruses (more often Hep B/C)
- Drugs
- PBC/PSC
- Wilson’s
- Haemochromatosis
What is the best indicator for portal hypertension (unstable liver disease)?
Splenomegaly
What is the histopathology of chronic hepatitis?
- Portal inflammation
- Interface hepatitis (PIECEMEAL NECROSIS) - can’t see border
- Lobular inflammation
- Bridging fibrosis from portal vein to central vein (critical stage in evolution of hepatitis to cirrhosis) - causes blood to bypass hepatocytes + reduces function of liver (intrahepatic shunting)
What is the stage and grade of chronic hepatitis?
- Grade = Severity of inflammation
- Stage = Severity of fibrosis
What is cirrhosis?
Diffuse abnormality of liver architecture that interferes with blood flow + liver function
What is the histopathology of a cirrhotic liver?
- Hepatocyte necrosis
- Fibrosis
- Nodules of regeneration hepatocytes (micro- + macro-)
- Disturbance of vascular architecture
What are the major causes of cirrhosis?
- ALCOHOLIC LIVER DISEASE
- NON-ALCOHOLIC FATTY LIVER DISEASE
- CHRONIC VIRAL HEPATITIS
- Autoimmune hepatitis
- Biliary causes
- Genetic causes
- Drugs (e.g. methotrexate)
What are some complications of liver cirrhosis?
- Portal hypertension
- Hepatic encephalopathy
- Hepatocellular carcinoma
What is the aetiology of cirrhosis?
- Disruption of liver architecture
- Causes increased blood flow through liver
- Leads to portal hypertension
- FIBROTIC BRIDGES form between portal triad + central vein
- EXTRAHEPATIC SHUNTING occurs due to portal hypertension
- Causes congestion of blood = oesophageal varices, anorectal varices, caput medusae
How can cirrhosis be classified?
According to size of regenerating nodules (micro + macro)
What are features of micronodular cirrhosis?
- Nodules <3mm
- Uniform liver involvement
- Causes: ALCOHOLIC HEPATITIS, Biliary tract disease
What are the features of macronodular cirrhosis?
- Nodules >3mm
- Variable nodule size
- Causes: viral hepatitis, Wilson’s disease, α1-antitrypsin deficiency
What is the purpose of the modified Child’s Pugh Score (ABCDE)?
Indicates prognosis in liver cirrhosis + takes into account albuin, bilirubin, prothrombin times, presence of ascites + encephalopathy
What are the different prognoses from the different Child’s Pugh Scores?
- A = score <7 = 45% 5yr survival
- B = Score 7-9 = 20% 5yr survival
- C = Score 10+ = <20% 5yr survival
What are the three different types of alcoholic liver disease?
- Hepatic Steatosis (Fatty Liver)
- Alcoholic Hepatitis
- Alcoholic Cirrhosis
What are the macro- + microscopic features of hepatic steatosis (fatty liver)?
Macro:
- Large, pale, yellow + greasy liver
Micro:
- Accumulation of fat droplets in hepatocytes (steatosis)
- Chronic exposure leads to fibrosis (late stage)
- Fully reversible if alcohol avoided
What are the macro- and microscropic features of alcoholic hepatitis?
Macro:
- Large, fibrotic liver
Micro:
- Hepatocyte BALLOONING + necrosis (due to accumulation of fat, water + proteins)
- MALLORY DENK BODIES
- Fibrosis
- Mainly zone 3 damage + neutrophil polymorphs
What are the amcro- and microscopic features of alcoholic cirrhosis?
Macro:
- Yellow-tan, fatty, enlarged
- Transforms into shrunken, non-fatty, brown organ
Micro:
- Micronodular cirrhosis (small nodules + bands of fibrous tissue)
What are some basic features of non-alcholic fatty liver disease (NAFLD)?
- Hepatic Steatosis in non-alcoholics
- Histology looks similar to alcoholic hepatitis
- Most common cause of chronic liver disease in West + worldwide
What are some RFs for NAFLD?
- Obese individuals with hyperlipidaemia/metabolic syndrome
- Diabetes
What are the types of NAFLD + their features?
Simple Steatosis:
- Fatty infiltration
- Relatively benign
Non-alcoholic steatohepatitis (NASH):
- Steatosis + hepatitis (fatty infiltration + inflammation)
- Can progress to cirrhosis
What are some features of autoimmune hepatitis?
- Common with other autoimmune diseases
- 78% female = young + postmenopausal
- A/w HLA-DR3
What are the different types of autoimmune hepatitis and how are they different?
Type 1:
- More common in postmenopausal women
- ANA (anti-nuclear Ig)
- Anti-SMA Ig
- Anti-Actin Ig
- Anti-soluble liver Ag Ig
Type 2:
- More common in younger women
- Anti-LKM Ig (anti-liver kidney microsomal Ig)
What is the treatment for autoimmune hepatitis?
Immune suppression until liver transplant
- Disease returns in <40%
What are some biliary causes of cirrhosis?
- Primary Biliary Cholangitis
- Primary Sclerosing Cholangitis
How is primary biliary cholangitis caused and what is its epidemiology?
- Autoimmune inflammatory destruction of small/medium sized intrahepatic bile ducts leads to cholestasis and eventually slow development of cirrhosis (years)
Epi:
- F>M 10:1
- Associated with other AI conditions
- Peak incidence = 40-50yrs
What are some investigative findings of primary biliary cholangitis?
Bloods:
- Increased serum ALP
- Increased cholesterol
- Increased IgM
- Hyperbilirubinaemia (late disease)
- ANTI-MITOCHONDRIAL ABS IN >90%
US Scan:
- No bile duct dilatation
What is the histology of primary biliary cholangitis?
Bile duct loss with granulomas
How does primary biliary cholangitis present?
Initially:
- Fatigue
- Pruritis
- Abdominal discomfort
Secondary:
- Skin pigmentation
- Xanthelasma
- Steatorrhoea
- Vitamin D malabsorption
- Inflammatory arthropathy
What is the treatment + prognosis for primary biliary cholangitis?
- Ursodexoycholic acid in early phase
- Remission in 25%
What is primary sclerosing cholangitis and its epidemiology?
- Inflammation + obliterative fibrosis of extrahepatic + intrahepatic bile ducts leading to multi-focal stricture formation with dilatoin of preserved segments
Epi:
- M > F
- Peak incidence = 40-50yrs
- A/w IBD (especially UC)
What investigative findings are seen for primary sclerosing cholangitis?
Bloods:
- Increased serum ALP
- Several associated auto-Ig
- p-ANCA
US Scan:
- Bile duct dilatation
ERCP:
- Beading of bile ducts (due to strictures)
What is seen on histology for primary sclerosing cholangitis?
ONION SKINNING FIBROSIS (concentric fibrosis)
What are some benign liver tumours and their clinical features?
Hepatic (+bile duct) Adenoma:
- Associated with OCP
- Presents with abdo pain / intraperitoneal bleeding
- Resection IF: symptomatic, >5cm, no shrinkage when OCP stopped
Haemangioma:
- Most common benign lesion (tumour of blood vessels)
- No Tx
What are some malignant liver cancers and which is most common?
- Hepatocellular carcinoma
- Cholangiocarcinoma
- Haemangiosarcoma
- Hepatoblastoma
- Secondary tumours (most common)
What are the causes and investigations for hepatocellular carcinoma?
Causes:
- In pts with chronic liver disease
- Viral hepatitis
- Alcoholic cirrhosis
- Haemochromatosis
- NAFLD
- Aflatoxin (mouldy grain)
- Androgenic steroids
Ix:
- Screening in cirrhotic pts with 6-mthly USS
- Α-FETOPROTEIN (AFP)
- USS
What are the causes, clinical features and histological findings of cholangiocarcinoma?
Causes:
- PRIMARY SCLEROSING CHOLANGITIS
- Parasitic liver disease
- Chronic liver disease
- Congential liver abnormalities
- Lynch syndrome Type II
Features:
- Adenocarcinomas arising from bile ducts
- 10% of liver tumours
- Intra/Extrahepatic
- Poor prognosis
- 90% A/w Gallstones
Histology:
- Capillary ingrowth
What is haemangiosarcoma?
Cancer of the vascular epithelium - highly invasive
What are the clinical features of hepatoblastoma?
- Occurs in children/infants
- Presents with abdominal mass
- Originate from immature liver precursor cells
What are the clinical features of secondary tumours?
- Usually from GI tract, breast or bronchus
- Often multiple
- MOST COMMON
What is the epidemiology and pathophysiology of haemochromatosis?
Epi:
- Caucasian
- Homozygote = 1/400
- Heterozygote = 1 in 10 (carriers)
- Incidence = 40-50yrs
Pathophysiology:
- Autosomal recessive
- Mutation of HFE gene increases gut iron absorption deposits in liver (+ other organs) leading to fibrosis
What is found on histology of haemochromatosis?
- Iron deposits in hepatocytes
- Stain with PRUSSIAN BLUE STAIN
What are the signs and symptoms of haemochromatosis?
- Skin bronzing (melanin deposition)
- Diabetes
- Hepatomegaly with micronodular cirrhosis
- Cardiomyopathy
- Hypogonadism
- Pseudogout
What are the investigations and treatment for haemochromatosis?
Ix:
- Increased Iron
- Increased Ferritin
- Transferrin Saturation >45%
- Decreased TIBC
Tx:
- VENESECTION
- DESFERRIOXAMINE
What is the epidemiology + pathophysiology of Wilson’s Disease?
Epi:
- Rare
- Incidence = 11-14yrs
Patho:
- Autosomal recessive
- Mutated gene ATP7B causes decreased biliary copper excretion, causing deposition and accumulation in liver (+ other organs)
What is seen on histology for Wilson’s Disease?
- Copper stains with RHODAINE STAIN
- Microscopy: Mallory bodies + fibrosis
What are the signs and symptoms of Wilson’s Disease?
- Liver disease: acute hepatitis, fulminant liver failure/cirrhosis
- Neuro disease: parkinsonism, psychosis, dementia
- Kayser Fleischer rings: copper deposits in Descemet’s membrane in cornea
What are the investigations and treatment for Wilson’s disease?
Ix:
- Decreased serum caeruloplasmin
- Decreased serum copper
- Increased urinary copper
Mx:
- Lifelong PENICILLAMINE
- Good Px with early Tx, neurodamage = permanent
- ?liver transplant
What is the pathophysiology of α1-antitrypsin deficiency?
- Autosomal Dominant
- Failure to secrete A1AT in blood causes accumulation in hepatocytes and can lead to hepatitis
- Lack of A1AT in lungs = emphysema
What is seen on histology for α1-antitrypsin deficiency?
Intracytoplasmic globules of A1AT (in hepatocytes) which stain with PERIODIC ACID SCHIFF (periportal red hyaline globules)
What are the signs + symptoms and investigations for α1-antitrypsin deficiency?
Kids:
- Neonatal Jaundice
Adults:
- Emphysema
- Chronic liver disease
Ix:
- Decreased serum A1AT
- Absent α-globulin band on electrophoresis
