Week 4 - Liver Pathology Flashcards
Liver Functions
Metabolism of proteins, carbohydrate and fats
Synthesis of proteins - albumin, alpha1 trypsin, transferrin and coagulation factors
Detoxification of waste products and ingested chemicals
Main digestive function is the production of bile
- bile is a complex substance required for the emulsification, hydrolysis and uptake of fats in the duodenum
Hepatocyte Function
Make up majority of parenchyma
Responsible for:
- secretion of bile
- synthesis of plasma proteins (albumins, fibrinogen e.t.c)
- covert AA into glucose via gluconeogenesis
- breakdown and detoxify ingested toxins including drugs
- AA’s deamination, producing urea removed from the blood in kidneys
- storage of glucose, Vit A
- removal of erythrocytes by Kupffer cells
- storage of iron as ferritin
Liver Blood Supply
Two sources:
1. Arterial blood from the right and left hepatic arteries
2. Venous blood from the hepatic portal vein, which drains much of the alimentary tract, from the stomach to the rectum, and the spleen
Blood leaves the liver through the hepatic veins, which drains into the inferior vena cava
Bile is formed in the liver and drains from it into the right and left hepatic ducts
Liver - Inflammation, Fibrosis and Liver Failure
Injury in the liver depends on the extent of cell death and the duration of the infection and/or virus
Liver architecture will be restored once transient infection is cleared with no residual hepatic damage
Chronic inflammation of the liver can lead to extensive fibrous tissue formation resulting in scarring
- bands of fibrous tissue may entrap regenerating nodules of hepatocytes resulting in cirrhosis
Hepatic Failure Complications
Jaundice
Encephalopathy
- drowsiness, confusion, coma
- coarse hand tremor
Renal impairment secondary to liver failure
Ascites/oedema
Chronic Liver Disease Complications
Bruising
Gynaecomastia
Testicular atrophy
Palmar erythema
Clubbing
Etc.
Viral Hepatitis
Liver inflammation due to viral hepatitis may be caused by specific hepatotropic viruses, as well as EBV
Causes of viral hepatitis incorporate 5 distinct genotypes:
1. Hep A - RNA heptovirus, faecal – oral, acute disease
2. Hep B - DNA orthoheadnavirus, parenteral, acute or chronic
3. Hep C - RNA Flaviviridae, parenteral or sporadic, acute or chronic
4. Hep D - RNA related to plant viroids, pathogenic when combined with HBV, acute or chronic
5. Hep E - RNA virus (unclassified), faecal, oral, epidemic or sporadic, acute
Causative Viruses for Acute Hepatitis - Histology
Acute viral Hep A
- centrolobular bilirubin stasis
- minimal liver damage and inflammation
Acute viral Hep B
- predominance of liver cell damage and inflammation
- presence of lymphocytes
Acute viral Hep C
- cells swelling
- apoptosis
- cholestasis
- lymphocytic intralobular infiltration
- evidence of bile duct damage and portal lymphoid aggregates
Acute viral Hep D
- more severe than other categories
- small lipid droplets in damaged hepatocytes
Acute Viral Hepatitis - Histology
Lobular hepatitis
Ballooning of parenchymal cells
Hepatocytes may shrink, have increase eosinophilia and nuclear pyknosis
Mallory bodies
Steatosis
Parenchyma infiltrated by inflammatory cells
Chronic Viral Hepatitis Histology
Similar to acute hepatitis, with parenchymal necrosis and destruction of the reticulin framework
Severe necrosis is seen with the development of small, glandlike clusters of hepatocytes within inflamed tissue
Portal inflammation in chronic hepatitis may be mild, moderate or dense
Histology of Chronic Viral Hep B
‘Ground glass’ hepatocytes - liver cells demonstrate a finely granular pale appearance of their cytoplasm
- ground glass refers to the cell membrane separated by a clear halo
- due to hypertrophy of the SER which displaces the organelles to the periphery of the cell and which contains excess filamentous structures of Hep B Ag
Sanded nuclei - where hepatocytes with a finely granular, pale eosinophilic appearance of the larger central part of the nucleus, due to accumulation of Hep B Ag
Alcoholic Liver Disease - Hepatic Steatosis
See small lipid droplets accumulating in the hepatocytes
Lipid accumulates to the point of developing large globules, compressing and displacing the nucleus to the periphery of the hepatocyte
Macroscopically - fatty liver of chronic alcoholic is large ~4-6kg, usually yellow and greasy in appearance, with no evidence of fibrosis
Fatty change is completely reversible with abstinence of further alcohol consumption
Alcoholic Liver Disease - Alcoholic Hepatitis
See hepatocyte swelling with/- necrosis
Mallory bodies - eosinophilic inclusions
Neutrophilic reaction - neutrophils are seen in the lobules particularly around degenerating hepatocytes
Fibrosis - activation of sinusoidal stellate cells and portal tract fibroblasts leading to fibrosis
Alcoholic Liver Disease - Alcoholic Cirrhosis
In Cirrhosis, we see diffuse hepatic fibrosis with replacement of normal lobular architecture by parenchymal nodules separated by fibrous tissue
Architectural changes are easily determined on a reticulin stain
Histologically it is characterised by;
- nodular regeneration, destruction of hepatic parenchyma, collapse of hepatic tissues and distortion of hepatic vessels
Irreversible form of liver disease
Symptoms and their Mechanism of Action
Jaundice
- yellow colouration of tissues due to bile pigments
- failure of metabolism or excretion of bile
Bleeding
- failure of hepatic synthesis of clotting factors
Oedema
- swelling of dependent parts owing to extracellular accumulation of H2O
- failure of hepatic synthesis of albumin resulting in reduced plasma pressure
Ascites
- fluid in peritoneal cavity
- low serum albumin and portal hypertension
Gynaecomastia
- enlarged male breasts
- failure to detoxify endogenous oestrogens
Encephalopathy
- altered consciousness, lack of coordination, may lead to coma
- failure to detoxify ammonia and excitatory
Aetiology of Cirrhosis
Chronic Hepatitis secondary to Hep B and C is a major cause of cirrhosis
Alcholic liver disease
NASH - refers to excessive fat accumulation in the liver after excluding alcohol
- obesity
- diabetes
Cholestasis - primary or 2° cholestasis can increase the concentration of bile acids and bilirubin, thereby destroying hepatocytes leading to cirrhosis
Circulation disorders - causes long term liver congestion, hypoxia, leading to necrosis, fibrosis especially in the central lobe of the liver
Primary Biliary Cholangitis - Histology
Similar to chronic non suppurative lymphocytic inflammation, especially around interlobular and septal bile ducts, with/without granuloma formation
Haemochromatosis - Morphology
See deposition of haemosiderin
See cirrhosis and pancreatic fibrosis
In the liver, iron is present as a golden yellow granular appearance or haemosiderin granules in the cytoplasm of hepatocytes - PBR stain
With inc deposition, the liver lobule, bile duct and Kupffer cells may show haemosiderin deposition
Fibrous septa may develop leading to a shrunken liver with a micronodular pattern of cirrhosis
Kayser-Fleischer Rings
Surround eyes
Seen in Wilson’s Disease
