Pathology of the liver Flashcards by Elizabeth McCabe

What is important about the blood supply to the liver?

Hepatic artery (30%)
Portal vein (70%)

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What is the pattern of venous drainage within the liver?

Terminal hepatic venules/central venules
Segmental hepatic veins
Lobar hepatic veins
Hepatic vein
IVC

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What is the acinus within the liver?

Functional unit with a portal tract in centre and terminal hepatic venules at the periphery.

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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)

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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

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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

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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

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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.

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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

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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

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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

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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)

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What are the causes of non-hepatotropic viral hepatitis?

Systemic infections with liver involvement
Acute = CMV, EBV, HSV

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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

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What are the key symptoms of hepatitis A infection?

Nausea
Anorexia
Fever
Malaise
Abdo pain
Dark urine
Pale stools
Jaundice

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What are the key diagnostic tests for hepatitis A?

Serum IgM anti-HAV antibodies

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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

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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

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What are the key symptoms of a hepatitis B infection?

Acute - maj asymptomatic, milkf flu-like NV and jaundice
Chronic - risk less than 5%

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What are the diagnostic tests for hepatitis B?

Serum markers - Hep B surface antigen

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What is the treatment for hepatitis B?

Acute = supportive
Chronic - antiviral agents - pegylated interferon = Entacavir, Tenofovir

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What are the key histological features of hepatitis B virus in hepatocytes?

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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?

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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?

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> 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

Pathology of the liver Flashcards

(53 cards)