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Clinical Pathology > Diseases of the liver and pancreas > Flashcards

Diseases of the liver and pancreas Flashcards

1
Q

Which organelle conjugates bilirubin?

A

Smooth endoplasmic reticulum

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2
Q

What are the functions of the liver?

A

Carbohydrates

  • Glycogen storage & synthesis
  • Glycolysis & gluconeogenesis

Proteins

  • Synthesis & catabolism
  • Clotting factors
  • Amino acid metabolism &urea synthesis

Lipids

  • Lipoprotein & cholesterol synthesis
  • Fatty acid metabolism
  • Bile acid synthesis

Excretion & detoxification

  • Bile acid & bilirubin excretion
  • Drug detoxification & excretion
  • Steroid hormone inactivation & excretion

Miscellaneous

  • Iron storage
  • Vitamin A, D, E & B12 storage & metabolism
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3
Q

What is measured by LFTs?

A

Alkaline phosphatase

ALT (alanine aminotransferase)

AST (aspartate transaminase)

Bilirubin

Albumin

Total protein

GGT (glutamyl transferase)

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4
Q

What tests might be used for specific liver functions?

A

Carbohydrate metabolism
- glucose

Protein metabolism

  • albumin
  • urea
  • prothrombin (clotting factors)

Lipid metabolism

  • cholesterol
  • triglycerides
  • bile acids

Excretion and detoxification

  • bilirubin
  • drugs
  • steroid hormones

Misc

  • Ferritin (iron storage)
  • Prothrombin time (Vit K)
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5
Q

What tests give an indication of hepatocyte damage?

A

Aminotransferases

  • Alanine/ALT
  • Aspartate/AST
  • Found in the cell and only released by cellular damage.

ALT is more specific for liver than AST

AST also found in muscle and red blood cells

Tumour markers – α-fetoprotein (primary hepatocellular carcinoma)

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6
Q

What tests give an indication of biliary tract damage?

A

Impaired excretory function
- Increased Conjugated bilirubin

Increased synthesis of enzymes by cells lining the bile canaliculi

  • ALP
  • γGT
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7
Q

What might be the causes of increased ALP in biliary tract damage?

A

Cholestasis (intra- or extrahepatic)

Infiltrative diseases

Space-occupying lesions (tumours)

Cirrhosis

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8
Q

Which organs also secrete ALP isoenzymes?

A

Liver

Bone

Intestine

Placenta

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9
Q

If γGT and ALP are raised, what might this mean?

A

A raised γGT supports a liver source of ALP (as opposed to any other isoenzyme).

Elevated due to structural damage

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10
Q

What can cause biliary tract damage?

A

alcohol

enzyme inducing agents
- e.g. anti-epileptics

fatty liver
- e.g. due to alcohol, diabetes or obesity

heart failure

prostatic disease

pancreatic disease
- acute & chronic pancreatitis, cancer

kidney damage
- ARF, nephrotic syndrome, rejection

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11
Q

What are the biochemical markers of fibrosis?

A

ELF score

  • PIIINP
  • TIMP-1
  • Hyaluronic acid
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12
Q

What is bilibrubin a measure of?

A

Excretory capacity of the liver and free flow of bile.

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13
Q

What is bilirubin measured as?

A

Total

Unconjugated
- Pre-hepatic & Hepatic

Conjugated
- Post-hepatic (Obstructive) & Hepatic

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14
Q

What serum level of bilirubin is considered to be jaundice?

A

> 40-50 μmol/L

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15
Q

What happens to bilirubin in the liver?

A

It is conjugated to bilirubin glucuronide by glucuronyl transferase.

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16
Q

What protein is bilirubin bound to in the blood?

A

Albumin

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17
Q

What are the pre-hepatic causes of jaundice?

A

Haemolysis
- e.g. Rhesus incompatibility

Ineffective erythropoiesis
- e.g. spherocytosis

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18
Q

What are the post-hepatic (obstructive) causes of jaundice?

A

Gallstones

Biliary Stricture

Cancer
- i.e. cholangiocarcinoma, head of pancreas

Cholangitis

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19
Q

What are the hepatic causes of jaundice?

A

Unconjugated

  • Pre-microsomal
  • Microsomal
  • Inherited disorders of conjugation e.g. Gilberts, Crigler-Najjar

Conjugated

  • Post-microsomal/impaired excretion
  • Intrahepatic obstruction
  • Inherited disorders of excretion e.g. Dubin-Johnson, Rotor.
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20
Q

What are the inborn errors of bilirubin metabolism?

A

Decreased activity of UDP glucuronyl transferase

  • Gilbert’s
  • Crigler-Najjar

Reduced ability to excrete bilirubin glucuronide

  • Dubin-Johnson
  • ROTOR
21
Q

What is the pathway from haemoglobin to bilirubin glucuronide?

A

Haemoglobin -> bilirubin albumin-bound bilirubin -> bilirubin -> bilirubin glucuronide -> bile duct

22
Q

The patient is jaundiced, their AST/ALT is elevated and their ALP is normal. What will are they likely to have?

A

Approx 90% of these patients will have hepatitis

23
Q

The patient is jaundiced, their AST/ALT is normal and their ALP is elevated. What will are they likely to have?

A

Approx 90% will have obstructive jaundice

24
Q

What will urine tests show in prehepatic jaundice?

A

Unconjugated bilirubin - no urinary bilirubin

25
Q

What will urine tests show in hepatic jaundice?

A

Variable depending on degree of obstruction due to either disease or inflammatory oedema

26
Q

What will urine tests show in post-hepatic jaundice?

A

Dark urine (&pale stools)

27
Q

What are the systemic effects of liver disease?

A

jaundice

oestrogen XS

  • gynaecomastia
  • spider naevi
  • liver palms
  • testicular atrophy

bruising

pigmentation

clubbing

dependent oedema

ascites

encephalopathy

osteomalacia / osteoporosis

28
Q

What specific tests can be used in chronic active and autoimmune hepatitis?

A

Anti smooth muscle, anti liver/kidney, anti microsomal and anti nuclear antibodies

29
Q

What test can be used for primary biliary cirrhosis?

A

Anti mitochondrial antibodies

30
Q

What test can be used for hereditary haemachromatosis?

A

Ferritin

transferrin saturation

liver biopsy

genetic testing

31
Q

What tests can be used to detect Wilson’s disease?

A

Caeruloplasmin

urine copper

plasma copper

liver biopsy

32
Q

Are routine LFTs useful?

A

No - only 1% of people with abnormal LFTs have liver disease

33
Q

What should LFTs be measured?

A

Signs and symptoms ?

  • Pain
  • itchy
  • jaundice
  • TATT
  • bruising

Lifestyle ?

  • Alcohol
  • obesity
  • diabetes
  • recent travel
  • drug use

Is liver disease present ?

  • hepatitis
  • haemochromatosis
  • liver cancer,
  • drugs

What is the severity ?
- chronic hepatitis vs acute onset

34
Q

How does the pancreas drain?

A

Drains via main pancreatic duct joined to the common bile duct.

Opens into duodenum via Sphincter of Oddi.

35
Q

What part of the pancreas produces endocrine secretions?

A

Islets of Langerhans

36
Q

What are the endocrine secretions of the pancreas?

A

Insulin

Glucagon

Pancreatic Polypeptide

37
Q

What part of the pancreas produces exocrine secretions?

A

Ductal and acinar cells

38
Q

What are the exocrine secretions of the pancreas?

A

Bicarbonate

Digestive enzymes

  • Trypsin, Chymotrypsin & Elastase
  • Carboxypeptidases
  • Amylase
  • Lipase
39
Q

What is acute pancreatitis?

A

Acute necrotising liquefaction

Inflammatory

40
Q

What is the aetiology of acute pancreatitis?

A

Gallstones

Alcohol

Drugs

Hypertiglyceridaemia

Trauma, infectious

Rare tumours, autoimmune, Scorpion Toxins!

41
Q

What are the symptoms of acute pancreatitis?

A

Severe epigastric pain

Sudden onset

Radiating to the back

42
Q

What are the potential biochemical features of acute pancreatitis?

A

Uraemia

Hypoalbuminaemia

Hypocalcaemia

Hyperglycaemia

Metabolic acidosis

Abnormal LFTs

43
Q

What tests might be used in the diagnosis of acute pancreatitis?

A

Amylase or Lipase

Imaging

Clinical History

44
Q

What is chronic pancreatitis?

A

Progressive loss of both islet cells and acinar tissue.

45
Q

What is the presentation of chronic pancreatitis?

A

Abdominal pain

Malabsorption
- often presenting feature

Impaired glucose tolerance

Alcohol often an important factor

46
Q

Are tests of exocrine function of any use in chronic pancreatitis?

A

No - only in acute exacerbations

47
Q

How does one perform the diagnosis and management of chronic pancreatitis?

A

Imaging

Pancreatic Function test for investigating insufficiency

  • Direct
  • Indirect

Miscellaneous

  • Vitamin D
  • calcium
  • FBC
  • LFTs
  • glucose
  • lipids
48
Q

What are direct (invasive) tests of pancreatic function?

A

Intubation to collect aspirates in the duodenum.

Secretin, CCK, Lundh Tests

49
Q

What are indirect (non-invasive) tests of pancreatic function?

A

Pancreatic enzyme analysis in stools (Elastase)

Trypsinogen (IRT) measured in blood in CF screening

Pancreolauryl & NBT-PABA tests

Clinical Pathology (65 decks)

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