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Year 2 > Liver Pathology > Flashcards

Liver Pathology Flashcards

1
Q

What are the major lifestyle contributors to liver disease?

A

Alcohol and obesity.

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2
Q

How is alcohol broken down in the liver?

A

Alcohol -> Acetaldehyde by alcohol dehydrogenase
Acetaldehyde is toxic -> Acetate by acetate dehydrogenase.

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3
Q

How does alcohol affect the liver?

A

Insufficient breakdown of alcohol into acetate results in accumulation of the toxic metabolic product Acetaldehyde. This causes increased levels of LDL in the liver, inflammation of the liver that causes damage and scar tissue to form and portal hypertension to occur.

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4
Q

What are the common causes of hepatic pathology?

A

Alcohol
Fatty liver disease
Hepatitis C and B
Biliary cirrhosis

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5
Q

What are the stages of alcohol damage in the liver?

A

Stage 1 is fatty alcoholic where increased accumulation of LDL causes the liver to be enlarged; this is reversible.

Stage 2 is chronic hepatitis where Acetaldehyde causes recruitment of macrophages and generation of radical oxygen species. This leads to hepatic jaundice, fever and an enlarged liver.

Stage 3 is Cirrhosis, which is irreversible damage that causes scar tissue formation.

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6
Q

What are the effects of portal hypertension?

A

Toxic products of metabolism aren’t cleared by the liver, and travel to the brain and cause neurological damage, leading to confusion, drowsiness and tremor.

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7
Q

What are the risk factors for alcoholic liver disease?

A

Women
Daily drinking > Binge drinking
Genetics
Lifestyle, with spirits being worst.

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8
Q

How does obesity affect the liver?

A

Insulin resistance causes high levels of circulating blood glucose which is taken up by the liver for storage into fat. Hypertension and hyper lipidaeimia contribute to accumulation of fat cells in the liver which impair function and result in liver cirrhosis. It begins with:

Non-alcoholic fatty liver with pain in the upper right abdomen which progresses to
Non-alcoholic steatohepatitis which is when fat cells accumulate enough to cause inflammation and jaundice.
Liver cirrhosis is the final irreversible stage.

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9
Q

What is the composition of the liver?

A

Liver is composed of cuboidal hepatocytes that have bile canaliculi between them, with blood supply from the hepatic artery and hepatic portal vein, where blood supply from the digestive system enters. This enters through the sinusoid which is lined with endothelial cells containing Kuppfer cells.

Large molecules such as protein move out through the porous gaps and gases move out into the Space of Disse, allowing nutrients to be taken up by hepatocytes.

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10
Q

What are Kuppfer cells?

A

Liver macrophages found on endothelial cells which line the sinusoids.

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11
Q

What are the hepatic stellate cells (HSC)?

A

Present in the sinusoid which activated when liver injury occurs, induce collagen production from hepatocytes that leads to liver fibrosis. When quiescent, they store vitamin A.

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12
Q

What are sinusoids?

A

Blood vessel which receives supply from branches of the hepatic artery and hepatic portal vein. It is lined with endothelial cells that contain Kuppfer macrophages for immune defences. Hepatocytes lie in close contact for uptake of nutrients.

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13
Q

What are the features of endothelial cells in the liver?

A

Highly leaky and porous, which lack a basement membrane and contribute to maintaining low pressure in the liver during digestion.

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14
Q

What is the Space of disse?

A

Area for the reversible flow of nutrients between the sinusoids and the hepatocytes.

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15
Q

What is the portal tract?

A

AKA portal triad hoc contains the hepatic artery, hepatic vein and bile duct.

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16
Q

What is the acinus?

A

Functional unit for blood flow in the liver.

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17
Q

What is the structure of a liver lobule?

A

Consists of a central vein with hepatocytes in rows, separated by sinusoids which receive blood from the portal tract.

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18
Q

Where does the central vein drain?

A

Inferior vena cava.

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19
Q

What is the exocrine function of the liver?

A

Produces bile, Along with bile acids and bile salts and albumin.

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20
Q

What are the endocrine function of the liver?

A

IGF-1
Plasma proteins and clotting factors like Angiotensinogen and Thrombopoetin
C

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21
Q

What separates the left and right lobes of the liver?

A

Falciform ligament, located anteriorly. It splits into the coronary ligaments.

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22
Q

What is the bare area?

A

Region in the liver not covered by peritoneum, where it is in contact with the diaphragm.

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23
Q

Which ligaments demarcate the bare area?

A

Coronary ligaments which posteriorly, form the left and right triangular ligaments.

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24
Q

Where do the ligaments connecting the liver to the organs originate?

A

From the porta hepatis. These include:
Hepatoduodenal ligmaent
Hepatogastric ligament: to lesser stomach curvature
Hepatorenal ligament

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25
Q

What connects the liver to the anterior abdominal wall?

A

Falciform ligament.

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26
Q

What is the major blood supply to the liver?

A

Hepatic portal vein, which is nutrient rich and contains drugs, but is oxygen poor.

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27
Q

What provides oxygenated blood to the liver?

A

Hepatic artery, a branch of the aorta. Majority is from the right hepatic artery

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28
Q

What is the round ligament?

A

Embryological remnant of the umbilical vein on the free edge of the Falciform ligament that develops 2 months post birth.

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29
Q

What are the hepatic veins of the liver?

A

They drain the liver into the inferior vena cava.
Upper group arise from the posterior aspect of liver to drain the caudate and left lobe.
Lower group arise from the right and quadrate lobe.

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30
Q

Where dot eh quadrate and caudate lobes arise?

A

From the right lobe of the liver.

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31
Q

How does liver damage affect glucose levels?

A

Causes hypoglycaemia because the liver stores glycogen, performs gluconeogenesis and releases glucose stores.

32
Q

How does liver damage affect fluid levels?

A

Liver synthesises albumin and catabolises amino acids, produces urea. Impaired function causes hypoalbuminemia and ascites.

33
Q

What are the common causes of hepatitis?

A

Alcohol
Virus
Obesity
Drug
Autoimmunity

34
Q

What is Hepatitis A?

A

Single-stranded RNA virus that causes acute infection, with 99% recovery. It is transmitted by faeces-oral route typically through seafood like shellfish and oysters or contaminated water supply. It enters the oropharyngeal mucosa and infiltrate the small intestine to replicate in the liver and be released into the bile and then stool.

35
Q

Which groups are at risk of Hepatitis A infection?

A

Travellers and daycare workers.

Travellers are recommended Hepatitis A vaccines for overseas travel

36
Q

What is the recovery for Hepatitis A?

A

6 weeks period of recovery, which is accompanied with vomiting, diarrhoea and appear yellow due to hepatitis jaundice. Patients are infectious in this stage, even when asymptomatic. Small proportion progress onto fulminant hepatitis.

37
Q

What is fulminant hepatitis?

A

Rapidly progressive liver failure.

38
Q

What are the antibody investigations for hepatitis A?

A

IgM for initial infection
IgG for chronic hepatitis

39
Q

What is Hepatitis B?

A

Double stranded DNA virus which is transmitted through fluids or blood and can lead to either acute or chronic hepatitis. Uses reverse transcription.

40
Q

Which group is more likely to experience chronic Hep B infection?

A

Babies and young children. Risk decreases with age because interaction with naive immune system through maternal transmission increases the tolerance of T cells to virus.
Sub Saharan Africa, China and Korea have the greatest prevalence of Hep B.

41
Q

How can Hepatitis B be transmitted?

A

Sexual transmission
IV drug use
Mother to Baby
Toothbrushes
Piercings.

42
Q

What are the antibody investigations for Hep B?

A

HbEAg antibody in chronic phase, which has a high infectivity and fluctuates.
Fluctuating levels of ALT

43
Q

What are the phases of chronic Hepatitis B infection?

A

Immune tolerance
Immune clearance
Inactive carrier
Reactivation

Liver inflammation is measured by ALT.

44
Q

What is the immune tolerance stage?

A

Occurs due to neonatal exposure to Hepatitis B, where even at a high antigen load, there is little inflammation of the liver which is indicated by ALT levels.

45
Q

What is the immune clearance stage?

A

High levels of liver inflammation and fibrosis, which has intermittent active and chronic phases. Treatment is optimal here.

46
Q

What is the inactive carrier stage?

A

There is mild hepatitis and minimal fibrosis.

47
Q

What is Hepatitis C?

A

Single stranded RNA infection that is transmitted parenterally through blood and fluids and enters hepatocytes via clarithrin mediated endocytosis. Majority will develop chronic hepatitis and liver cirrhosis, that is more common in Asians than Caucasians.

48
Q

What are the diagnostic tests for Hepatitis C?

A

Anti HCV antibody which indicates immune response and HCV RNA, indicating viral particles
Both are present in chronic infection.
Only HCV antibody is present in resolved HCV infection.

49
Q

What is hepatitis D?

A

Negative sense RNA which occurs after Hep B infection, identified through IgM and IgG.

50
Q

What is Hepatitis E?

A

Single stranded RNA virus which is transmitted by faeco-oral route from contaminated water or food. It is the most common type of hepatitis which is majorly acute. It rarely progresses to chronic liver disease.

51
Q

What is the primary host of hepatitis E?

A

Pigs.

52
Q

Which type of Hepatitis has a high mortality rate in pregnant women?

A

Hepatitis E, which causes fulminant hepatitis.

53
Q

Which antibodies indicate active hepatitis infection?

A

IgM.

54
Q

Which antibodies indicate resolved hepatitis infection?

A

IgG.

55
Q

How does liver cirrhosis form?

A

Damage to hepatocytes triggers the activation of hepatic stellate cells which produce TGF-beta that induces collagen production from hepatocytes to creates scar tissue that grows in the perisinusoidal space and increases pressure.

Sinusoid develops a basement membrane to form a capillary and endothelial cells lose fenestrations. Hepatocytes become nodules and this creates portal hypertension which prevents nutrients and toxic byproducts from being detoxified in the liver, leading to cognitive impairment, oedema and jaundice.

56
Q

What are the consequences of liver cirrhosis?

A

Varicella haemorrhage: A consequence of portal hypertension in liver cirrhosis where there is backflow of blood into the varices (veins) that causes leakage and haemorrhage. These vessels are typically the oesophagus and rectum and lead to haematoemesis and bloody/black stools

57
Q

What are the cognitive impairments with liver cirrhosis?

A

Bizarre behaviour, altered sleep pattern, coma and asterixis (inability to maintain posture).

58
Q

How does liver cirrhosis affect the sex hormones?

A

Liver metabolises oestrogen, therefore cirrhosis causes high circulating oestrogen leading to gynaecomastia
Palmar erythema: oestrogen increases blood volume
Spider angioma: dilated blood vessels creating red marks on skin, due to increased BV from oestrogen.

59
Q

What is the risk of ascites with liver disease?

A

Bacterial peritonitis, due to accumulation of abdominal fluid.

60
Q

How is liver cirrhosis diagnosed?

A

Liver biopsy
Serum bilirubin levels
Liver enzyme levels

61
Q

What is the gold standard for diagnosis of liver cirrhosis?

A

Biopsy.

62
Q

Which liver enzymes indicate cirrhosis?

A

AST, AAT, ALT, GGLP and ALP.

ALT and AST are most important.

63
Q

When is AST higher than ALT?

A

Alcoholic liver disease.

64
Q

What is hepatorenal syndrome?

A

Liver damage causes the release of the vasodilator NO which acts on the heart and reduces BP, casing hypotension. This leads to the kidney activating the RAAS system to cause more fluid retention, leading to ascites.

65
Q

What is the most common liver cancer?

A

Hepatocellular carcinoma which typically occurs following liver cirrhosis due to hepatitis or alcoholic use.

66
Q

How is hepatocellular carcinoma diagnosed?

A

Sudden increase of AFP (alpha-feto protein)
Liver ultrasound or CT

67
Q

How is liver cirrhosis treated?

A

CHemostabilsation
Radio frequency ablation
Advanced liver cirrhosis is treated via liver transplantation, ideally with a fresh or living donor.

68
Q

What is portal circulation?

A

Connection between two capillary beds via veins to prevent loss of nutrients and substances. In the liver, it receives venous blood supply from the digestive organs of the lower oesophagus to the upper anal canal, spleen and pancreas via the hepatic portal vein. These drain into the hepatic sinusoids to be screened by Kuppfer cells.

69
Q

What is the venous drainage of the foregut?

A

Lower oesophagus, stomach, spleen, gall bladder, pancreas to proximal duodenum.
Drainage is via the:
left and right gastric veins
Splenic vein which gives off pancreatic vein, short gastric vein and inferior mesenteric vein.
Cystic vein

70
Q

What does the superior mesenteric vein drain?

A

Mid organs such as the distal duodenum, jejunum, ileum, caecum, ascending colon and proximal transverse 2/5 colon.

71
Q

What does the inferior mesenteric vein drain?

A

Branch of the splenic vein which drains the Hindgut organs such as:
Distal transverse colon, descending colon, sigmoid colon, rectum and upper anal canal.

72
Q

How is the liver involved in metabolism?

A

First pass effect, carried out by Cytochrome p450 enzyme in phase I and phase II reaction.

73
Q

What is phase I reaction?

A

Cytochrome p450 acts on drugs to cause oxidation and make them more polarised, so it is easier to excrete in the urine.

74
Q

What is phase II?

A

Conjugation of drug with glucoronic acid, sulphanomide or methyl group to make them less toxic and more easily excretable.

75
Q

Which drugs cause hepatitis?

A

NSAIDs
Anabolic steroids
Acetaminophen
Birth control pills

76
Q

What is haemachromatosis?

A

Genetic condition where there is excess iron absorption from food which slowly builds over time and causes liver disease.

77
Q

Which type of hepatitis never progresses to chronic?

A

Hepatitis A.

Year 2 (247 decks)

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