Pathology Lecture 7 Liver pathology
CCL07 Conditions of the liver
1. Alcoholic liver disease
Pathological changes to the liver occur progressively through the spectrum of ALD
Alcoholic fatty liver disease
Soft, pale yellow liver
Spongy appearance due to fat-filled vacuoles
Hepatomegaly
Alcoholic steatohepatitis
Hepatocyte necrosis with focal reticulin collapse
Mallorys hyaline bodies (intracellular eosinophilic i.e. red aggregates of cytokeratines)
Focal neutrophil infiltrate
Alcoholic fibrosis
Chicken-wire fibrosis (network of intra-lobular connective tissue surrounding cells & venules)
Result of cytokines/chemokines from Kuppfer cells stimulating collagen production via hepatic stellate
cells
Alcoholic cirrhosis
Attempted hepatocyte regeneration
Formation of non-functioning regenerative micronodules
Interrupted bile flow
Deranged blood flow with abnormal anastomoses
Portal hypertension
Causes of hepatic decompensation mnemonic: HEPATICUS
Haemorrhage/hypoglycaemia/HCC
Electrolyte imbalance
Protein load/Paracetamol OD
Alcohol
Trauma
Infection/ischaemia (portal vein thrombosis; Budd-Chiari syndrome)
Constipation
Uraemia
Sedatives/shunts/surgery
Complications of decompensation
Hepatic encephalopathy
o Drowsy coma
o Confusion
o Constructional apraxia
Portal hypertension
o Ascites
o Bleeding (haemorrhage, haemorrhoids)
o Caput medusae
o Diminished liver
o Enlarged spleen
Hyperoestrogenaemia
Portal hypertension complications
1. Enlargement of collateral veins
- Gastro-oesophageal junction with varices & haematemesis
- Periumbilical region with prominent subcutaneous veins (caput medusa)
- Splanchnic vascular congestion with ascites
2. Splenomegaly +/- hypersplenism
o Hypersplenism = rate of RBC, leukocyte +/- platelet destruction
3. Non-alcoholic fatty liver disease (NAFLD)
Primary NAFLD
Identical histological findings to ALD (inc Mallory hyaline bodies), but not associated with alcohol use.
More associated with micro-vesicular steatosis & nuclear vacuolisation
Considered part of metabolic (insulin resistance) syndrome
Metabolic syndrome diagnostic criteria
- Central obesity
- Impaired glucose tolerance (T2DM)
- Dyslipidaemia
- Hypertension
Metabolic syndrome NAFLD NASH Cryptogenic cirrhosis (with no steatosis)
Secondary NAFLD
- Drugs e.g. amiodarone, steroids, tamoxifen
- Surgical procedures e.g. extensive bowel resection, gastroplasty
- TPN
4. Acute hepatitis
Acute-onset inflammation of hepatocytes with associated necrosis.
Causes
1. Infectious agents e.g. HAV, HBV, HCV, delta HV
2. Autoimmune hepatitis due to T-cell mediated autoimmunity
3. Drug-induced due to direct drug-toxicity, immune-mediated injury
4. Idiopathic
Clinical sequence
i. Pre-icteric phase
- Fever, nausea, vomiting, epigastric pain, myalgia, hepatic tenderness
ii. Icteric phase
a. Jaundice, dark urine + pale stools, peripheral blood lymphocytosis
Outcomes
Complete recovery
Chronic hepatitis
Cirrhosis
Massive liver necrosis +/- HCC
Hep A
Acute, benign & self-limiting
Hep B
Can lead to rapid death due to fulminant/massive liver cell necrosis
Generally chronic, associated with cirrhosis, HCC
Endemic in SE Asia
Presence of lymphocytes
Ground glass-like cytoplasm
Hep C
Less likely to cause death short-term; more associated with chronic deaths
High incidence of progression to chronic hepatitis (80%)
Associated with carrier status & drug abuse
Hep D
Incomplete virus requires Hep B surface antigens for proliferation
Always occurs in tandem with Hep B
Autoimmune hepatitis
Most common demographic young women
Classified under type I, IIa, IIB and III according to presence/absence of specific autoantibodies
Large numbers of lymphocytes present T-cell mediated autoimmune reaction
o Focal lymphocytic infiltrate
o Absence of neutrophils/macrophages
NB: anti-smooth muscle antibody + antinuclear antibody = hallmark diagnostic
Sequence from hepatitis to cirrhosis
5. Cirrhosis
Liver damage characterised by diffuse distortion of hepatocyte architecture, bridging fibrosis (subdividing
parenchyma) and regenerative nodules.
Clinical features of cirrhosis Mnemonic: ABCDEFGHI PS
Asterixis/ascites
Bruit/bruising (purpura, epistaxis)
Cachexia/Caput medusa
Dermatogenic symptoms
Edema/encephalopathy
Fetor hepaticus
Gynaecomastia/testicular atrophy/impotence/irregular menses/amenorhoea
Hepato-renal/-pulmonary syndrome/hepatomegaly
Icterus
Palmar erythema/portal hypertension
Spider naevi
Types of cirrhosis
i. Macronodular (nodules >3mm diameter)
- Chronic active viral hepatitis B&C
- Drugs
ii. Micronodular (nodules <3mm diameter)
- Chronic alcoholism
Causes of cirrhosis Mnemonic: HEPATIC Complications of cirrhosis Mnemonic: VARICES
Haemochromatosis Varices
Enzyme deficiency (-1 antitrypsin) Anaemia
PBC/Post-hepatic (infection/drug-induced) Renal failure
Alcohol Infection
Tyrosinosis Coagulopathy
Indian childhood (galactosemia) Encephalopathy
Cardiac/cholestatic (biliary)/cancer/copper (Wilsons) Sepsis
Haemochromatosis
Genetic disease due to abnormal accumulation of iron in the liver may lead to HCC
How to distinguish b/w haemochromatosis and chronic haemolysis
Peripheral blood smear
Reticulocyte count
Serum LDH
Liver biopsy
Complications of haemochromatosis Mnemonic: HaemoChromatosis Can Cause Deposits Anywhere
Hypopituitarism/hypogonadism
Cancer (HCC)/colouring (skin pigmentation)
Cirrhosis
Cardiomyopathy/cardiac failure
Diabetes
Arthropathy
-1 antitrypsin deficiency
Caused by the absence of inactivation protein for -1 antitrypsin. Patients develop:
Panlobular emphysema
Chronic hepatitis
Micronodular cirrhosis
Abnormal accumulation of -1 antitrypsin in hepatocytes
NB: PAS stain used for diagnosis
Primary Biliary Cirrhosis (PBC)
Affects middle aged elderly women (90%)
Characterised by chronic autoimmune destruction of intrahepatic bile ducts
Patients present with:
o Pruritis
o Skin hyperpigmentation
o Xanthoma
o Xanthelesma (inappropriate lipid breakdown)
Diagnosed using anti-mitochondrial antibody (detectable in ~90% of affected patients)
NB: Often associated with concurrent non-organ specific AI diseases e.g. autoimmune thyroiditis
6. Cholestasis (bile stasis)
Obstruction within the biliary tract which prevents entry of bile into the duodenum. There are 2 types:
i. Intrahepatic/hepatocellular cholestasis
Cholestatic drugs Mnemonic: CHOLESTATIC
Chlorpromazine/contraceptive (OCP)
Ofloxacin
Largactil (i.e. chlorpromazine)
Erythromycin/Gentamicin
Sulfamethoxazole
Trimethroprim
Augmentin
Tetracycline
Ibuprofen
Cimetidine
ii. Extrahepatic
cholestasis/obstructive jaundice
Dark brown mucous plugging in dilated biliary tree
7. Hepatic granulomas
Granuloma = organised compact <2mm ball-like clusters of cells caused by prolonged inflammatory response to
foreign organism/antigen in the liver.
Histological features:
Epithelioid macrophages w elongated & enlarged nuclei (slipper/shoe-like
nuclei)
Pink, more eosinophilic cytoplasm
Poorly defined individual cell-borders
Can have lymphocytes/neutrophils/eosinophils/multinucleated giant
cells/fibroblasts/collagen
Causes of granulomas
8. Hepatic neoplasm
Benign
Hepatocellular adenoma (tumour of hepatocytes)
Cavernous haemangioma (tumour of blood vessels)
Malignant
Hepatocellular carcinoma (HCC) (malignancy of hepatocytes)
Cholangiocarcinoma (malignancy of bile duct epithelium)
Metastatic carcinoma e.g. from GIT, lung, breast, leukaemia
Hepatocellular carcinoma
Most common kind of hepatic malignancy
Can present as solitary intrahepatic mass or multiple masses (metastasis)
Primary HCC tumours are generally well-defined and arises in setting of cirrhosis
Will show mosaic arrangement of atypical hepatocyte-like cells
Cholangiocarcinoma
Most common in pt between 50 70y.o.
Carcinoma of biliary duct epithelium with white scar-like appearance
Have prominent fibrosis surrounding carcinoma cells
Histology
o Glandular tumour cells
o NB: histological features may be identical to gallbladder or pancreatic cancer
Hepatic metastases
Common in patients with disseminated carcinoma or arising in areas drained by the portal venous system
Metastases tend to have multinodular, well-defined appearance
Can have umbilication i.e. central depression in liver due to necrosis/fibrosis
From the TORG
LO1 Recognise the role of liver biopsy in persistently abnormal LFTs
LO2 Discuss normal fat metabolism by the liver and list the causes of fatty liver
Causes of fatty liver
Alcohol
Erythromycin + pregnancy (acute fatty liver of pregnancy)
LO3 Interpret Fe2+ studies
LO4 Recognise Fe2+ overload in the liver
See matrix on Haemochromatosis
LO5 Active and chronic hepatitis
LO6 Clinical symptoms, signs and causes of cirrhosis
