Liver Pathology Flashcards by Zoe Doak

What shape are the lobules of the liver? Which cells in these lobules are most vulnerable to injury?

hexagonal lobules
portal triad at each corner (artery, vein and bile duct)
central draining vein
cell types - periportal (most peripheral), mid acinar, pericentral
pericentral cells most likely to be affected by pathology

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Describe the 4 pathological stages of liver disease

Insult to hepatocytes (e.g. virus, drug, toxin, antibody)
inflammation
fibrosis
Cirrhosis

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What symptom is commonly associated with acute liver failure?

acute onset of jaundice

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What can cause acute liver failure?

viruses
alcohol
drugs
bile duct obstruction

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Describe how a paracetamol overdose causes acute liver failure

Confluent necrosis (necrosis and assoc. inflammation)

- This produces massive acute necrosis and liver failure

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What are the 3 potential outcomes of acute liver failure?

complete recovery
chronic liver disease
death from liver failure

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How can jaundice be classified?

By site:

Pre-hepatic
Hepatic
Post-hepatic

By Type:

Conjugated
Unconjugated

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What causes jaundice to be PRE-HEPATIC?

Too much haem to break down
=> Haemolytic conditions e.g. anaemias can cause this
=> Unconjugated bilirubin

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What can cause HEPATIC jaundice?

the Liver cells are injured/ dead

=> Causes:

Acute liver failure (virus,drugs,alcohol)
Alcoholic hepatitis
Cirrhosis
Bile duct loss (atresia, PBC, PSC)
Pregnancy

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What causes POST HEPATIC jaundice?

Bile cannot escape into the bowel
=> bilirubin is CONJUGATED as liver is working

=> Causes:

Congenital biliary atresia
Gallstones blocking Duct
Strictures of Common bile Duct
Tumours (Ca head of pancreas)

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Cirrhosis is irreversible. TRUE/FALSE?

TRUE

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How does cirrhosis appear on histology?

Bands of fibrosis separating regenerative nodules of hepatocytes
Can be Macronodular or micronodular (alcoholic)
Changes hepatic microvasculature

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What can cause cirrhosis of the liver?

Alcohol
Hep B/C infection
Iron overload (Fe3+)
Gallstones
autoimmune liver disease

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What complications can arise elsewhere in the body, after a patient develops cirrhosis of the liver?

Portal hypertension
=> oesophageal varices
=> caput medusa
=> haemorrhoids
Ascites

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Why may patients with cirrhosis/liver failure have bruising or excessive bleeding?

May struggle to make clotting factors in the liver

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How does alcohol cause direct damage to the cells of the liver?

Acetaldeyhde (a product of alcohol metabolism) causes injury to the cells
neutrophils then are attracted to the inflammation and cause necrosis

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If a patient has been drinking alcohol excessively, how long does it take for the damage to their liver to become irreversible?

Drinking for 2-3 days = Fatty liver => Reversible
Drinking for 4-6 weeks = Hepatitis => Reversible

Drinking for Months-Years = Fibrosis => Irreversible
Drinking for Years = Cirrhosis => Irreversible

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What medical term describes “fatty liver” disease?

Steatohepatitis

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How do fat molecules appear on liver histology?

Fat vacuoles appear clear in hepatocytes

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Other than alcohol excess, what can cause steatohepatitis in liver?

Non-Alcoholic Liver disease
Pregnancy
Drugs
Nutritional
Diabetes
Hep C virus (type 3)

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Describe how the histological appearance of alcoholic hepatitis is different from just steatohepatitis?

Hepatocyte necrosis
Neutrophils
Mallory Bodies
Pericellular fibrosis

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Describe how collagen appears on histology if a patient has liver fibrosis?

it is laid down around cells

- appears blue due to the stain

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Describe how cirrhosis appears on liver histology and how this is different from fibrosis.

Bands of collagen laid down during fibrosis are larger

- They now separate regenerative nodules

What groups of patients usually get non-alcoholic steatohepatitis?

diabetes
obesity
hyperlipidaemia

What viruses commonly cause hepatitis?

Hep A, B, C, D (less common), E

What viruses can rarely cause hepatitis?

- Epstein Barr (EBV) - Yellow Fever - Herpes Simplex (HSV) - Cytomegalovirus (CMV)

How is Hep A spread and how long does it normally last?

- Faecal-oral spread - Short incubation period - acute illness, no carrier/ chronic state - Mild illness, usually full recovery

How is Hep B transmitted and how long does infection last?

- Spread by blood products, sexually, vertically (in utero) - Long incubation period - Carriers exist - Liver damage from antiviral immune response

How is Hep C transmitted and how long does infection persist?

- Spread by blood products, sexually - Has short incubation period, but can become chronic - Often asymptomatic

How does chronic viral hepatitis appear on histology?

- Portal inflammation (lots of lymphocytes) - Interface Hepatitis (piecemeal necrosis) - Lobular inflammation - Fibrosis (collagen)

What autoimmune causes are there for chronic hepatitis?

- Autoimmune hepatitis - Primary Biliary Cirrhosis - Primary Sclerosing Cholangitis

Primary Biliary Cirrhosis is caused by autoantibodies to what?

- mitochondria

Is it mainly males or females who get PBC?

Females (90%)

What can be seen on histology of PBC if a biopsy is taken?

Granulomas and bile duct loss | - portal inflammation and bile duct inflammation common

If PBC is left untreated, what can occur as a result?

- bile duct loss leads to cholestasis => liver injury => inflammation, fibrosis and cirrhosis

Are males or females more likely to get autoimmune hepatitis?

Commoner in females

What causes autoimmune hepatitis?

- Numerous plasma cells - Autoantibodies to smooth muscle, raised IgG - May have triggers, including some drugs

What problems occur if patients develop Primary Sclerosing Cholangitis?

- Chronic inflammatory process affects intra- and extra-hepatic bile ducts => Periductal fibrosis, duct destruction, jaundice and fibrosis

Are males or females more likely to develop PSC?

- Males

PSC is associated to which autoimmune disease of the bowel?

- Associated with Ulcerative Colitis

PSC causes an increased cancer risk. TRUE/FALSE?

TRUE - Increased risk of malignancy in bile ducts - AND COLON (due to UC link)

What histological feature is typical of PSC?

- Periductal onion-skinning fibrosis

What is Haemochromatosis and what is the difference between Primary and Secondary types of this disease?

Iron overload Primary = Genetic => increased absorption of iron Secondary = Iron overload from diet, transfusions, iron therapy

How is haemochromatosis inherited?

Autosomal recessive | - Worse in male homozygotes

What problems can haemochromatosis eventually cause?

- Asymptomatic for years - deposits in portal connective tissue and stimulates fibrosis - Cirrhosis if not treated - Predisposes to carcinoma - Causes diabetes, cardiac failure and impotence

HOw is haemochromatosis confirmed on histology?

Using Perl's stain highlights the iron in blue

How can Haemochromatosis be treated in early stages in an attempt to prevent liver damage?

- regular venesection

What is Wilson's disease?

- Autosomal recessive disorder of copper metabolism | - Copper accumulates in liver and brain (basal ganglia)

How do patient's present with Wilson's disease?

- Kayser-Fleischer rings in eye at corneal limbus - Low serum caeruloplasmin - Chronic hepatitis and neurological deterioration

What is Alpha-1-Antitrypsin deficiency and what does it cause?

- Autosomal Recessive disorder - Patients don;t produce enough Alpha-1-antitrypsin - A1AT normally protects the lungs against neutrophil elastase (which disrupts connective tissue) - if deficient, the A1AT that is produced stays in the liver and clogs it up causing cirrhosis

What primary tumours can occur in the liver?

- Hepatocellular adenoma (BENIGN) | - Hepatocellular carcinoma (Hepatoma)

What secondary tumours commonly occur in the liver

- metastases are usually multiple | - From colon, pancreas, stomach, breast, lung etc

Hepatocellular adenomas are more common in females. TRUE/FALSE?

TRUE

What symptoms can benign hepatocellular adenomas cause?

- become large and can rupture or bleed | - Most remain asymptomatic

HCC is associated with which other conditions?

- Hep B and C | - Cirrhosis

HOw does HCC normally present?

- Usually presents as a mass, pain, obstruction - Presents advanced unless discovered incidentally => Poor prognosis

When are liver metastases potentially curable?

If it is a single solid metastases, then it may be able to be operated on