Week 4 Part 2 - Liver Pathology Flashcards
Circulatory Disorders
The livers dual blood supply mitigates against infarction
However, an intrahepatic branch of the hepatic artery by emboli or thrombi can result in localised infarct or haemorrhage with insufficient portal blood
Can be divided into:
- impaired blood flow
- liver impaired due to disease processes
Circulatory Disorders - Impaired Blood Flow Through Liver
Most commonly - cirrhosis
Patient’s with sickle cell disease - obstruction by sickled RBCs
DIC due to small thrombi
Pre eclampsia - in pregnancy
Diffuse intra-sinusoidal metastatic tumour
Hepatic venous obstruction - Budd Chiari syndrome, where obstruction of a single main hepatic vein by thrombosis
Focal Nodular Hyperplasia
A.k.a benign hepatoma, focal or lobar cirrhosis, hepatic hamartoma, cholangiohepatoma
The cells are usually polyclonal, epithelial in type, characterised by nodular hyperplasia of the liver parenchyma in a fibrous meshwork around a central scar
Hepatocellular Adenoma
Benign monoclonal epithelial liver tumour that develops in otherwise normal liver parenchyma
Related to metabolic or hormonal disorders
Usually appear as a solitary lesion of often asymptomatic
>10 HCA in the liver = Liver adenomatosis
The larger HCA are the more risk of haemorrhage, rupture and malignancy transformation
Hepatocellular Adenoma - Aetiology
Linked oral contraceptive pills (OCP)
More risk seen in women on OCP’s with high freq of haemorrhage and rupture
HCA may regress after OCP cessation
Use of anabolic steroids
Increase incidence in obese men, linked to metabolic syndrome
Patients with type I, III and IV glycogen storage disease have an increased incidence of developing HCA
Hepatocellular Adenoma - Pathology
Usually solitary lesions in 70-80% of the cases
Usually soft and well demarcated without evidence of a fibrous capsule
Large blood vessels are present on surface and within the tumour, usually in areas of haemorrhage and necrosis
Hepatocellular Adenoma - Histology
Composed of large plates of benign hepatocytes of normal size or slightly larger
Cytoplasm is normal, with evidence of glycogen or lipid vacuoles
Normal hepatic architecture is lost, with adenomatous cells arranged in normal or thickened trabeculae
Regular septa and portal tracts are absent
Thick walls of blood vessels
Kupffer cells may be present
Reticulin framework intact
Hepatic Abscess - Cystic Liver Lesions
HA is a purulent collection, present singly or as multiple lesions
55% of cases present in the posterior segments of the right hemi liver
- macroabscesses can be complicated by intraperitoneal fissure or peritonitis
- microabscesses represent 35% of cases may be multiple and bilateral
Clinical dx is difficult because of non-specific symptoms
- fever
- fatigue
- nausea
- vomiting
Hepatocellular Carcinoma (HCC) - Pathology
Premalignant foci include dysplastic foci and dysplastic nodules
Small lesions up to 2cm can be early HCC
Dysplastic foci are uniform clusters of hepatocytes <1mm in size showing cellular atypia, with no definite evidence of malignancy
Dysplastic foci are found within the liver parenchyma in chronic liver disease, in particular cirrhotic liver
Dysplastic nodules are >1mm and up to 2cm, typically arise in cirrhotic livers
Low and High Grade HCC
Low grade: share features of non-neoplastic regenerative nodules
High grade: are lesions with degree of architectural atypia, but not sufficient for dx of malignancy
HCC - Histopathology
Architecture is irregular, atypical arteries and distorted portal tracts
Hepatocytes show neoplastic change, inc NC ratio, irreg nuclei, abnormal growth pattern
There may be evidence of steatosis, steatohepatitis, hyaline globules and Mallory bodies
Reticulin framework disrupted
HCC - Grades
Grade 1 - small neoplastic cells, abundant eosinophilic cytoplasm and slightly enlarged nuclei, in thin trabeculae, similar to normal hepatocytes
Grade 2 - moderately differentiated HCC, where neoplastic cells are larger with increased NC ratio, abnormal nuclei, pseudoglandular structures
Grade 3 - poorly differentiated HCC, where neoplastic cells show larger hyperchromatic, clearly irregular nuclei with prominent nucleoli
Grade 4 - marked neoplastic cells with very high NC ratio, presence of anaplastic giant cells and loss of trabecular pattern
HCC - Treatment
Liver resection is the first line of curative tx
Liver transplantation is the best curative tx option for HCC
Local ablation
Multikinase inhibitor tx with sorafenib and levatinib, are being approved for systemic therapy in HCC patients
What is Local Ablation?
Image guided percutaneous ablation therapies include radio frequency ablation, ethanol injection and microwave ablation
All minimally invasive techniques that are increasing in their use especially in small lesions of HCC due to curative aspect
Gall Bladder - Extrahepatic biliary tree
Right and left hepatic ducts
- join to form common hepatic duct (CHD) in the hilum of liver
Common hepatic duct joins the cystic duct to form common bile duct
Gall bladder stores and releases bile
GB empties into cystic duct, which connects it to the extrahepatic biliary tree
Extrahepatic biliary tree serves as a conduit for bile flow
How is Bile Concentrated?
Bile is concentrated 5-10x via active absorption of electrolytes accompanied by passive movement of water
Cholecystokinin
Causes the GB to contract and release stored bile into the gut
Gall Bladder - Cholelithiasis
More than 95% of biliary tract pathology is caused by gall stones
Risk factors:
- being female
- aged >40
- being overweight or obese
- rapid weight loss
- diet high in calories, fat, cholesterol, or refined carbohydrates and low fibre
- excess oestrogen i.e. OCP, or HRT, or Pregnancy
- family hx of gall stones
Gall Bladder - Pathogenesis
Cholesterol is soluble in bile by forming micelles with bile salts and lecthins, both of which act as a detergent
When cholesterol concentration exceed the capacity of bile, cholesterol can no longer remain dispersed and forms into a solid cholesterol monohydrate crystal
Conditions that Contribute to Formation of Cholesterol Gall Stones
Supersaturation of bile with cholesterol
Hypomobility of the gall bladder
Accelerated cholesterol crystal nucleation
Hypersecretion of mucus in the gall bladder, which traps the crystals
Gall Bladder - Cholesterol Stones
Exclusively arise in GB and range from 100% pure white to 50% cholesterol
Pure cholesterol stones are pale yellow, round to oval and have finely granular hard external surface
As proportions of calcium carbonate, phosphates and bilirubin change, the stones may appear grey white to black in colour
Gall Bladder - Pigmented Stones
These are usually brown to black in appearance and usually found in sterile GB bile and in infected larger bile ducts
Black stones contain oxidized polymers of calcium salts and unconjugated bilirubin, small amounts of calcium carbonate, calcium phosphate, mucin glycoprotein and some cholesterol monohydrate crystals
Gall Bladder - Histology
Surface mucosa, muscular wall, perimuscular subserosal CT and serosa
No MM and submucosa
Mucosa - branching folds or simple columnar epithelium on a LP
Muscular wall - shows smooth muscle fibres without well formed distinct layer
Perisubserosal CT or adventitia, contains collagen, elastic tissue, fat, vessels, lymphatics and nerves
Serosa - covers the portion of the GB not connected to liver
Gall Bladder - Chronic Cholecystitis
Inflammation is variable, with lymphocytes, plasma cells and macrophages found in the mucosa and in the subserosal fibrous tissue
Reactive proliferation of the mucosa and fusion of the mucosal folds within the GB wall
Outpouchings of the mucosal epithelium through the wall of the smooth muscle may be prominent (Rokitansky-Aschoff Sinuses**)
Risk Factors for Gall Bladder Cancer
Gallstones
Medical hx of long term inflammation of GB
Hx of first degree relative with GB ca
Inherited genetic conditions or abnormalities of the liver, GB or bile ducts
Overweight/obese
Risk Factors for Biliary Tract Cancer
Medical hx of long term inflammation of bile duct
Pre existing medical conditions, bowel disease, UC, liver disease or PSC
Infection with liver fluke
Inherited genetic conditions of the liver, GB or bile ducts
Toxic exposure to thorotrast a radioactive compound
Older age, diabetes, obesity
Diagnosis of Gall Bladder Cancer or Biliary Tract Cancer
Blood tests include:
- CEA
- CA19-9
Both chemicals are released by normal and cancerous cells, but an abnormal high level of either can indicate disease or cancer
ERCP - endoscopic retrograde cholangiopancreatography (ERCP) creates an image of the GB/bile duct, to investigate if there are any blockages or abnormalities caused by cancer
