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Pathology Lecture 7 - Liver
Pathology Lecture 7 - Liver
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
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
- Central obesity
- Impaired glucose tolerance (T2DM)
- Dyslipidaemia
- Hypertension
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
Outcomes
Complete recovery
Chronic hepatitis
Cirrhosis
Massive liver necrosis +/- HCC
Hep A
Hep B
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
Autoimmune hepatitis
Cachexia/Caput medusa
Dermatogenic symptoms
Edema/encephalopathy
Fetor hepaticus
Hepato-renal/-pulmonary syndrome/hepatomegaly
Icterus
Spider naevi
Types of cirrhosis
i. Macronodular (nodules >3mm diameter)
- Chronic active viral hepatitis B&C
- Drugs
Alcohol Infection
Tyrosinosis Coagulopathy
Hypopituitarism/hypogonadism
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
NB: Often associated with concurrent non-organ specific AI diseases e.g. autoimmune thyroiditis
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
Histological features:
Causes of granulomas
8. Hepatic neoplasm
Benign
Malignant
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)