Pathology of the liver Flashcards
What is important about the blood supply to the liver?
Hepatic artery (30%)
Portal vein (70%)
What is the pattern of venous drainage within the liver?
Terminal hepatic venules/central venules
Segmental hepatic veins
Lobar hepatic veins
Hepatic vein
IVC
What is the acinus within the liver?
Functional unit with a portal tract in centre and terminal hepatic venules at the periphery.
How does blood flow influence the zones of the liver?
Zone 1 = periportal
Zone 3 = pericentral
Blood flows from portal vasculature to terminal hepatic venules (central vein) decreasing nutrients and oxygen closer to the central vein (zone 3)
Identify the different structures of the portal triad
Dilated - vein - large lumen and thin wall with an irregular shape
Bottom left - pink wall - smooth muscle - artery
Duct is the remain structure - tend to have cuboidal/culmnar epithelium
What are the key arrangement of hepatocytes relevant to their physiology?
Hepatocytes arranged in one cell thick plates separated by sinusoids (fenestrated endothelium)
Free exchange of molecules at the cell surface
Bile drains into canaliculi between hepatocytes
What is the space od disse?
What is found there?
Space between hepatocytes and the sinusoids.
Kupfer cell - macrophages
Stellate cells (Ito cells) - store vitamin A
What is the pattern of LFTs shown in hepatitis?
Hepatocellular
Disproportionate rise in aminotransferases (ALT and AST) compared to ALP
In severe cases bilirubin may be elevated
Test of synthetic function may be abnormal - if severe hepatocytes undergo necrosis.
What are the key histological features of hepatitis?
Portal and lobular inflammation +/- necrosis
Typically lots of immune cells cluster round portal triad and start to infiltrate
Necorsis - has a pink shiny or haline appreance
What are the time lines for hepatitis disease progression?
Acute hepatitis <6months
May then resolve, develop into chronic hepatitis >6m or hepatic failure
Chronic hepatitis may later develop into hepatic failure
What are the three key causes of hepatitis?
Infections - Hep A?B?C?D, HIV, EBV< CMV, HSV
Autoimmune - type 1, type 2, SLE
Drug induced - antibiotics (isoniazid, NSAIDs, herbal
What are the different causes of hepatotropic viral hepatitis?
These cause inflammation to the liver only
Acute = HAV, HEV (oral route)
Chronic = HBV, HCV, HDV (blood)
What are the causes of non-hepatotropic viral hepatitis?
Systemic infections with liver involvement
Acute = CMV, EBV, HSV
What are the key pathogenic features of Hepatitis A?
RNA virus
Foecal oral route
Life long immunity once infected
Only causes acute disease, typically self limited with <1% hepatic failure
What are the key symptoms of hepatitis A infection?
Nausea
Anorexia
Fever
Malaise
Abdo pain
Dark urine
Pale stools
Jaundice
What are the key diagnostic tests for hepatitis A?
Serum IgM anti-HAV antibodies
What are the key pathogen features of hepatitis B virus?
DNA virus with 8 genotypes
High in Asia, Sub-saharan afric
Transimission - horizontal or vertical by bodily fluids
Can be acute or chronic infection
What is the link between hepatitis B virus and cancer?
Integration of HBV into human genome
Pro-carcinogenic pathways
Strong risk factor for hepatocellular carcinoma
What are the key symptoms of a hepatitis B infection?
Acute - maj asymptomatic, milkf flu-like NV and jaundice
Chronic - risk less than 5%
What are the diagnostic tests for hepatitis B?
Serum markers - Hep B surface antigen
What is the treatment for hepatitis B?
Acute = supportive
Chronic - antiviral agents - pegylated interferon = Entacavir, Tenofovir
What are the key histological features of hepatitis B virus in hepatocytes?
Ground glass hepatocytes
Clearly defined borders, pale pink cytoplasm
These are the signs of a chronic hepatocyte infection
What are the features of hepatitis B in this histological image?
Cytoplasmic inclusions
Perl Iron stain
Shows iron storage in hepatocytes and kupfer cells -> sign of hepatocellular injury
What are the typical outcomes of an acute Hepatitis B infection?
> 90% recover
0.5% fulminant
10% chronic -> of which 30% are healthy carriers, 20% develop cirrhosis of which 15% develop HCC.
What are the key pathogen features of a Hepatitis D virus?
Delta virus
RNA virus
Dependent on hepatitis B for life cycle - may be coinfection or superinfection
Infects 5% hepatisis B hosts
Exacerbates HepB liver disease increasing mortality
Highest fatality rates of all he hepatitis
What are the pathological features of the Hepatitis C virus?
RNA virus
Transmission - blood (IVDU etc) or STI
Up to 90% infections become chronic - remains symptomatic with mild non-specific symptoms such as fatigue
Cirrhosis in 30%, hepatocellular carcinoma risk.
What is the typical treatment for a hepatitis C virus?
Commonest cause for liver transplantation worldwide but the virus will recur
90% cure with antiviral sufosbuvir.
What are the key pathogenic features of hepatisis E virus?
Single stranded RNA virus
Transmission - foeco-oral
Animal reservoir - monkey, cats, pigs, dogs
High mortality in pregnant women up to 20%
Symptoms range from mild to fatal
What factors are considered triggers for autoimmune hepatitis?
Viral infections
Drugs - statins, minocycline, nitrofurantoin.
What are the key epidemiology of an autoimmune hepatitis?
Female predominance - young and perimenopausal
May have other autoimmune disorder - SLE and RA
What are the two different types of autoimmune hepatitis?
Type 1 - positive ANA, anti-SMA, anti-soluble liver antigen. Predominantly in adults
Type 2 - anti-liver kidney microsomal antibodies (LKM), predominantly in children.
What are the different types of drug induced hepatitis?
Intrinsic -> predictable e,g paracetamol, CCL4 and alcohol
What is meant by idiosyncratic causes of drug induced hepatitis?
Unpredictable causes
Reflect individual genetic differences in the hepatic metabolism of drugs.
What are the three main morphological features of liver cirrhosis?
Bridging fibrous septa
Parenchymal nodule formation
Disruption of the architecture of the entire liver - diffuse changes
What are the different histological stages in the development of cirrhosis?
Stage 1/2 - fibrosis around central veins and portal tracts
Stage 3 - Bridging fibrosis
Stage 4 - cirrhosis - nodule formation, diffuse fibrosis, loss of architecture
How is the reticulin stain useful in cirrhosis histology?
Stains fibrosis - dark
hepatocytes - light
Allows for clearer identification of areas of fibrosis for bridging and nodule formation
What are the main causes of cirrhosis in developed countries?
Alcoholic liver disease
Metabolic associated steatotic liver disease
Chronic viral hepatitis (hepatitis C)
What are some biliary causes of hepatitis?
Primary and secondary biliary cirrhosis
Primary sclerosing cholangitis
What are the genetic and metabolic causes of liver disease?
Haemochromatosis
Wilson disease
Alpha 1 antitrypsin deficienc cy
What are the features of metabolic syndrome that contribute to steatotic liver disease?
Obesity
Type 2 diabetes mellitus
Hypertension
Hypercholesterolemia
What is the key histology of steatotic liver disease?
Bubbly appearance
Hepatocytes have vacuoles as fatty acids (white like adipocytes) that push the nucleus to the periphery.
Ballooned hepatocytes - microtubular disruption - contain Mallory Denk bodies
Fibrosis
Necroinflammation - immune cells
What is the key histological feature of steatohepatitis seen in this image?
Ballooning hepatocytes
Mallory dense bodies - note enlarged but not clear, contain cytoplasmic inclusion called Mallory Denk bodies.
What special stain can be used to highlight Mallory-denk bodies seen in steatohepatitis?
p62 immunohistochemistry
What is the key histological features of PSC?
Periductal onion-skin fibrosis around the bild duct - can affect intrahepatic and extrahepatic
Note typically young men
What are the key features of primary biliary cholangitis?
Granulomatous bile duct lesions
Typically middle aged women
What is the key pathological features of hereditary hemochromatosis?
Autosomal recessive - HFE C282Y
Iron deposition in liver - hepatomegaly
Pancreas and skin - bronze diabetes
heart - cardiomyopathy
joints - arthritis
How can hereditary haemochromatosis be diagnosed?
Biochem = raised transferrin saturations
MRI = estimation of iron overload
Liver biopsy.
What is shown in this image of the liver?
Using perl stain
Shows iron granules
Indicates hereditary haemochromatosis
What are the key pathological features of an alpha-1 antitrypsin deficiency?
Autosomal recessive disorder
A1A = Glycoprotein synthesised by hepatocytes = protease inhibitor
Mutant peptide accumulates in ER of hepatocytes
Clinically -> pulmonary emphysema and liver disease
What are the different genotypes of alpha 1 antitrypsin?
Three possible alleles = PiM, PiZ and PiS
PiMM - 90% - homozygous normal
PiS = moderate reduction
PiZ most common clinically sig deficiency
PiZZ - homozygous very low deficiency
What disease is this liver biospy indicative of?
Alpha 1 antitrypsin deficiency
Shown by diastase resistance globules = accumulation of A1A in cytoplasm
Must use DPAS stain
What are the pathological features of Wilsons disease?
Autosomal recessive inheritance
Copper overload in the liver, eye and brain
Key features - Kayser-Fleischer ring, tremors, gait disturbance, neuropsychiatric manifestations
What are the histological features of Wilsons disease in the liver?
Must use Orcein stain
Shows copper associated protein granules
