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YEAR 5: Chemical Pathology > ChemPath: LFTs and cases > Flashcards

ChemPath: LFTs and cases Flashcards

1
Q

List some functions of the liver.

A
  • Intermediary metabolism
  • Protein synthesis
  • Xenobiotic metabolism
  • Hormone metabolism
  • Bile synthesis
  • Reticulo-endothelial system
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2
Q

Define intermediary metabolism.

A

Enzyme-catalysed processes within cells that extract energy from nutrient molecules and use that energy to construct cellular components.

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3
Q

List some examples of processes that count as intermediary metabolism.

A
  • Glycolysis
  • Glycogen storage
  • Gluconeogenesis
  • Amino acid synthesis
  • Fatty acid synthesis
  • Lipoprotein metabolism
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4
Q

List some metabolic consequences of liver failure.

A
  • Reduction in blood sugar due to a lack of glycogen / metabolism
  • Lactic acidosis (reduced ability to metabolise lactic acid)
  • Increased ammonia (no longer able to process amino acids)
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5
Q

What are the main stages of xenobiotic metabolism in the liver?

A

Glucuronidation increases the solubility of

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6
Q

Outlie the roles of the liver regarding hormone metabolism.

A
  • Vitamin D (25-hydroxylation)
  • Steroid hormones (conjugation and excretion)
  • Peptide hormones (catabolism)
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7
Q

What are the constituents of bile?

A
  • Water
  • Bile acids/salts
  • Bilirubin
  • Phospholipids
  • Cholesterol
  • Proteins
  • Drugs and metabolites
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8
Q

What are the functions of bile?

A
  • Excretion
  • Micelle formation
  • Digestion
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9
Q

Describe the metabolism and excretion of bilirubin.

A
  • Red cells are broken down to produce haem, iron and globin
  • Heme breaks down to form unconjugated bilirubin
  • Unconjugated bilirubin is bound to albumin in plasma
  • This unconjugated bilirubin travels to the liver where it becomes glucuronidated
  • The conjugated bilirubin is released into the bile
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10
Q

What are the main cells of the reticuloendothelial system found in the liver?

A

Kupffer cells

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11
Q

What are the roles of Kupffer cells?

A
  • Clearance of infection and lipopolysaccharides (LPS)
  • Antigen presentation
  • Immune modulation (e.g. cytokine production)
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12
Q

What is another key reticuloendothethial function of the liver besides the role of Kuppfer cells?

A

Erythropoesis

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13
Q

What are the main serum markers of liver cell damage?

A
  • ALT
  • AST
  • ALP
  • GGT
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14
Q

What are the main markers of liver synthetic function?

A
  • Albumin
  • Pro-thrombin time/INR (important in acute setting)
  • Bilirubin
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15
Q

What is the tumour marker of primary liver malignancy?

A

AFP

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16
Q

What cells are ALT and AST found in?

A

Within the cytoplasm of hepatocytes

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17
Q

What is the function of ALT and AST?

A

ALT - catalyzes the transfer of an amino group from L-alanine to α-ketoglutarate to form pyruvate and L-glutamate

AST - catalyzes the interconversion of aspartate and α-ketoglutarate to oxaloacetate and glutamate.

Both these reactions catalysed are reversible

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18
Q

Other than the liver, where else is ALT and AST found?

A

Muscle, kidney, bone, pancreas

eg. can be released in rhabdomyolysis

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19
Q

Describe the rise in ALT and AST seen in alcoholic liver disease.

A

AST: ALT > 2:1 in alcoholic liver disease

In the absence of alchol AST:ALT ratio >1 indicated advanced fibrosis or cirrhosis

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20
Q

Describe typical ALT and AST levels in cirrhosis.

A
  • May be raised
  • May be normal in long-standing chronic liver disease
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21
Q

What is the role of gamma-glutamyl transferase?

A

Catalyses the transfer of gamma-glutamyl groups between peptides

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22
Q

Where is GGT found?

A

Hepatocytes and epithelium of small bile ducts

NOTE: also found in kidney, pancreas, spleen, heart, brain and seminal vesicles

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23
Q

List some causes of raised GGT.

A
  • Chronic alcohol abuse
  • Bile duct disease (e.g. gallstones)
  • Hepatic metastases
24
Q

What is the likely function of ALP?

A

Precise function unknown
Catalyse the hydrolysis of a large number of organic phosphate esters at an alkaline pH.

25
Q

Where is ALP found?

A

Liver isoenzyme is found in the sinusoidal and canalicular membranes (bile ducts)

Other sources: bone, small intestine, kidneys, placenta, white blood cells

26
Q

List some hepatobiliary causes of raised ALP.

A
  • Obstructive jaundice
  • Bile duct damage (e.g. PSC, PBC)

Elevated to a lesser degree in viral and alcoholic hepatitis

27
Q

List some non-hepatobiliary causes of raised ALP.

A
  • Bone disease (e.g. Paget’s, bone tumours)
  • Pregnancy
28
Q

How much albumin is produced by the liver per day?
What is the half-life of albumin?

A
  • 8-14 g/day produced by liver
  • Half-life of 20 days
29
Q

What are the main roles of albumin?

A
  • Major contributor to plasma oncotic pressure
  • Binds to steroids, drugs, bilirubin, calcium
30
Q

List some causes of low albumin.

A
  • Low production - chronic liver disease, malnutrition
  • Increased loss - gut, kidney (nephrotic syndrome)
  • Sepsis - third spacing (endothelium becomes leaky and albumin leaks into the tissues)
31
Q

Why is PT a better acute marker of liver function than albumin?

A

Most clotting factors have half-lives that are a matter of hours as opposed to 20 days with albumin

32
Q

What are the main roles of alpha-fetoprotein?

A
  • In the foetus, it plays a role in foetal transport and immune regulation
  • No known function in adults
33
Q

Which tissues produce alpha-fetoprotein in the foetus?

A
  • Yolk sac
  • GI epithelium
  • Liver
34
Q

What causes a high alpha-fetoprotein?

A
  • Hepatocellular carcinoma
  • Pregnancy
  • Testicular cancer
35
Q

List how the cause of jaundice may be classified and give examples?

A
36
Q

How might the cause of jaundice be identified?

A
37
Q

Which investigation is crucial for differentiating between causes of jaundice with raised ALP?

A

Biliary ultrasound scan

  • Dilated ducts - obstruction (gallstones, cancer)
  • Non-dilated ducts - drugs, PSC/PBC, pregnancy
38
Q

Under what circumstances may bilirubin be detected in the urine?

A
  • There should be NO bilirubin in the urine.
  • Only conjugated bilirubin can be seen in the urine as it is soluble.
  • This would only occur when the bile duct is blocked leading to backflow of conjugated bilirubin into the circulation.
39
Q

How is urobilinogen produced?

A

It is a breakdown product of bilirubin in the intestines by bacteria

40
Q

What is the significance of absent urobilinogen in the urine?

A
  • Suggests obstructive jaundice
  • Urobilinogen is soluble so some of it should enter the enterohepatic circulation and be excreted in the urine
  • Its absence in the urine suggests that bilirubin is not entering the intestines
41
Q

List some causes of increased urobilinogen in the urine.

A
  • Haemolysis
  • Hepatitis (due to reduced intrahepatic urobilinogen cycling)
42
Q

List some other investigations that may be used as part of a liver panel.

A
  • Fasting lipids (for fatty liver)
  • Fasting glucose
  • Coeliac serology
  • Hepatitis serology (HBV surface antigen, HCV antibody)
  • Alpha-1 antitrypsin
  • Caeruloplasmin (Wilsons = low)
  • Immunoglobulins (anti-LKM, anti-SM, AMA)
  • Ferritin
  • ANCA screen (PSC)
43
Q

List some more specialised investigatons for the liver

A
44
Q

Name a dye test used to assess liver function.

A

Indocyanine green/bromsulphalein
- Measures excretory function of the liver
- Measures hepatic blood flow

45
Q

Name a breath test used to assess liver function.

A

Aminopyrine - measures residual functioning of liver cell mass

  • Can be used to predict survival in alcoholic hepatitis
  • Can be used to distinguish cirrhosis without biopsy (70-80% sensitivity)
46
Q

List some causes of elevated serum bile acids.

A
  • Obstetrics cholestasis (10-100x)
  • PBC/PSC (25x)
47
Q

What is the gold-standard investigation for liver pathology?

A

Liver biopsy

48
Q

What are non-invasive alternatives to liver biopsy?

A
  • Fibroscan - measures liver elasticity as a marker of fibrosis
  • Serum markers of fibrosis
49
Q

What is an additional cause of jaundice with LFT changes consistent with biliary obstruction?

A

Drug-induced cholestasis

NOTE: biliary USS will be normal (i.e. undilated ducts whereas dilated suggests an obstruction). It usually resolves over 3 weeks.

50
Q

What are common causes of drug-induced cholestasis?

A
  • Penicillin antibiotics
  • Anabolic steroids
51
Q

What is Courvoisier’s law.

A

Painless jaundice in the presence of a palpable non-tender gallbladder is unlikely to be caused by gallstones (i.e. it is more likely to be cancer)

52
Q

State three causes of ALT >1000.

A
  • Toxins (paracetamol)
  • Viruses
  • Ischaemia
53
Q

How often should patients with cirrhosis be followed up to check for hepatocellular carcinoma?

A

Every 6 months with liver ultrasound

54
Q

How is paracetamol overdose treated?

A
  • N-acetylcysteine (within 24 hours, ideally within 8 hours)
  • Liver transplant - if in acute liver failure
55
Q

Label this diagram.

A

YEAR 5: Chemical Pathology (27 decks)

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