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12. CP - Diseases of the Hepatobiliary system and Pancreas > (61) Diseases of the Liver and Pancreas > Flashcards

(61) Diseases of the Liver and Pancreas Flashcards

1
Q

Describe the basic structure of the liver

A
  • hepatocytes constitute 60% of liver mass

- each hepatocyte is in contact with sinusoid, bile canaliculus and neighbouring hepatocyte

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2
Q

Describe the hepatocyte organelles

A
  • nucleus
  • mitochondria (oxidative phosphorylation, TCA cycle, fatty acid oxidation)
  • RER (protein, lipid, enzyme synthesis)
  • SER (bilirubin conjugation, drug detoxification)
  • lysosomes (intracellular scavengers - copper, ferritin)
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3
Q

Where in the hepatocyte does bilirubin conjugation and drug detoxification occur?

A

SER

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4
Q

What are the functions of the liver in terms of carbohydrates?

A
  • glycogen storage and synthesis

- glycolysis and gluconeogenesis

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5
Q

What are the functions of the liver in terms of proteins?

A
  • synthesis and catabolism

- clotting factors, amino acid metabolism, urea synthesis

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6
Q

What are the functions of the liver in terms of lipids?

A
  • lipoprotein and cholesterol synthesis
  • fatty acid metabolism
  • bile acid synthesis
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7
Q

What are the functions of the liver in terms of excretion and detoxification?

A
  • bile acid and bilirubin excretion
  • drug detoxification and excretion
  • steroid hormone inactivation and excretion
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8
Q

What are the miscellaneous functions of the liver?

A
  • iron storage

- vitamin A, D, E and B12 storage and metabolism

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9
Q

Describe the functional capacity of the liver

A
  • excess of hepatic capacity for normal anabolic and catabolic processes
  • hepatic repair and regeneration following damage is a dynamic process
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10
Q

What is measured in LFTs?

A
  • alkaline phosphate
  • ALT (alanine aminotransferase)
  • bilirubin
  • albumin
  • total protein
  • GGT (y glutamyl transferase)
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11
Q

Name 4 general types of liver function tests

A
  • production of metabolites
  • clearance of endogenous substances
  • clearance of exogenous substances
  • imaging, biopsy
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12
Q

What are 3 general tests for liver damage?

A
  • hepatocellular damage
  • biliary tract damage
  • imaging, biopsy
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13
Q

What sorts of things can cause liver disease?

A
  • poisoning
  • drugs
  • infection
  • alcohol
  • fatty liver
  • autoimmune
  • metabolic
  • tumours and metastases
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14
Q

What are markers of hepatocyte damage?

A

Aminotransferases (ALT and AST) - found in the cell and only released by cellular damage

  • tumour markers = a-fetoprotein (primary HCC)
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15
Q

Which 2 types of aminotransferases are measured for hepatocyte damage?

A
  • alanine transaminase = ALT

- aspartate transaminase = AST

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16
Q

Out of ALT and AST, which is more specific for liver damage?

A

ALT

AST is also found in muscle and red blood cells

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17
Q

What is a tumour marker for primary hepatocellular carcinoma?

A

a-fetoprotien

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18
Q

What is there increased levels of in biliary tract damage?

A
  • increased conjugated bilirubin (due to impaired excretory function)
  • increased synthesis of enzymes by cells lining bile canaliculi (ALP, yGT)
  • alkaline phosphatase (ALP)
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19
Q

Why is alkaline phosphatase (ALP) elevated in biliary tract damage?

A

Due to increased production by cells lining bile canaliculi and overflow into blood, due to:

  • cholestasis (intra- or extra-hepatic)
  • infiltrative disease
  • space-occupying lesions (tumours)
  • cirrhosis
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20
Q

Alkaline phosphatase (ALP) has multiple sites of production including…

A
  • liver
  • bone
  • intestine
  • placenta
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21
Q

Liver and bone ALP isoenzymes can be separated by what?

A

Electrophoresis

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22
Q

Why is gamma glutamyltransferase (yGT) measured as part of LFTs?

A

Elevated due to structural damage (biliary tract damage) - can support a liver source of raised ALP

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23
Q

Elevated gamma glutamyltransferase can be induced by…

A
  • alcohol
  • enzyme inducing agents eg. anti-epileptics
  • fatty liver eg. due to alcohol, diabetes or obesity
  • heart failure
  • prostatic disease
  • pancreatic disease (acute and chronic pancreatitis, cancer)
  • kidney damage (ARF, nephrotic syndrome, rejection)
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24
Q

Describe the biochemical markers of fibrosis

A 
Historically only imaging, biopsy and predictive score, but now novel biochemical markers:
ELF score
- PIIINP
- TIMP-1
- hyaluronic acid
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25
Q

Bilirubin is measured as…

A
  • total
  • unconjugated (pre-hepatic and hepatic)
  • conjugated (hepatic and post-hepatic = obstructive)
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26
Q

What do bilirubin levels indicate?

A

Excretory capacity of the liver and free flow of bile

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27
Q

Jaundice occurs at serum bilirubin levels of what?

A

More than 40-50umol/L

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28
Q

Describe the pre-hepatic aetiology of hyperbilirubinaemia/jaundice

A
  • haemolysis eg. rhesus incompatibility

- ineffective erythropoieis eg. spherocytosis

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29
Q

Describe the post-hepatic (obstructive) causes of hyperbilirubinaemia/jaundice

A
  • gallstones
  • biliary stricture
  • cancer ie. cholangiocarcinoma, head of pancreas
  • cholangitis
30
Q

Describe the hepatic causes of hyperbilirubinaemia - unconjugated

A
  • pre-microsomal
  • microsomal
  • inherited disorders of conjugation eg. Gilbert’s syndrome, Crigler-Najjar syndrome
31
Q

Describe the hepatic causes of hyperbilirubinaemia - conjugated

A
  • post-microsomal/impaired excretion
  • intrahepatic obstruction
  • inherited disorders of excretion eg. Dubin-Johnson syndrome, Rotor sydrome
32
Q

Haemoglobin break down produced bilirubin which becomes bound to albumin, what happens next?

A

Bilirubin is converted to bilirubin glucuronide by the enzyme UDP glucuronyl transferase

33
Q

Gilbert’s and Crigler-Najjar are syndromes of what?

A

Decreased activity of UDP glucuronyl transferase (disorders of conjugation)

34
Q

Dubin-Johnson and Rotor are syndromes of what?

A

Reduced ability to excrete bilirubin glucuronide (conjugated bilirubin)

35
Q

Blood test - What is the diagnosis if AST/ALT are elevated and ALP is normal? (in the case of jaundice)

A

Approx 90% will have hepatitis

36
Q

Blood tests - What is the diagnosis is AST/ALT are normal but ALP is elevated? (in the case of jaundice)

A

Approx 90% will have obstructive jaundice

37
Q

What would a urine test show in prehaptic causes of jaundice?

A

No urinary bilirubin

38
Q

What would a urine test show in hepatic causes of jaundice?

A

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

39
Q

What would a urine test show in post-hepatic causes of jaundice?

A

Dark urine (and pale stools)

40
Q

What are the specific tests for viral hepatitis?

A

Serology (Hep, A, B, C, D and EB, CMV, HIV)

41
Q

What are the specific tests for chronic active and autoimmune hepatitis?

A
  • anti-smooth muscle antibodies
  • anti-liver/kidney antibodies
  • anti-microsomal antibodies
  • anti-nuclear antibodies
42
Q

What are the specific tests for primary biliary cirrhosis?

A

Anti-mitochondrial antibodies

43
Q

What are the specific tests for hereditary haemachromatosis?

A

Ferritin, transferrin saturation, liver biopsy, genetic testing

44
Q

What are the specific tests for Wilson’s disease?

A
  • caeruloplasmin
  • urine copper
  • plasma copper
  • liver biopsy
45
Q

What are the specific tests for a1-antitrypsin deficiency?

A
  • a1-antitrypsin

- genetic testing

46
Q

What are the specific tests for hepatocellular carcinoma?

A

AFP (alpha feto-protein)

47
Q

List the systemic effects of liver disease

A
  • jaundice
  • oestrogen symptoms
  • bruising
  • pigmentation
  • clubbing
  • dependent oedema
  • ascites
  • encephalopathy
  • osteomalacia/osteoporosis
48
Q

What are the oestrogen symptoms due to liver disease?

A
  • gynaecomastia
  • spider nevi
  • liver palms (palmar erythema)
  • testicular atrophy
49
Q

How useful are routine LFTs?

A

1% of subjects with abnormal LFTs have liver disease (alcohol-related, Gilbert’s syndrome, obesity, diabetes, side effects of medication)

50
Q

Which signs and symptoms would encourage measurement of LFTs?

A
  • pain
  • itchy
  • jaundice
  • TATT
  • bruising
51
Q

Which lifestyle factors would encourage measurement of LFTs?

A
  • alcohol
  • obesity
  • diabetes
  • recent travel
  • drug use
52
Q

LFTs would be measured in the case of which diseases?

A
  • hepatits
  • haemochromatosis
  • liver cancer
  • drugs
53
Q

Describe the pancreas

A

Elongated, flatted gland lying on posterior abdominal wall

  • head lies within duodenal loop
  • drains via main pancreatic duct joined to common bile duct
  • opens into duodenum via sphincter of Oddi
  • essential endocrine and exocrine function
54
Q

Where do pancreatic endocrine secretions come from?

A

Islets of Langerhans

55
Q

Where do pancreatic exocrine secretions come from?

A

Ductal and acinar cells

56
Q

What are the endocrine secretions of the pancreas?

A
  • insulin, glucagon

- pancreatic polypeptide

57
Q

What are the exocrine secretions of the pancreas?

A
  • bicarbonate

- digestive enzymes (trypsin, chymotrypsin, elastase, carboxypeptidases, amylase, lipase)

58
Q

What is pancreatic polypeptide?

A

PP, a 36 amino acid peptide produced and secreted by PP cells (originally termed F cells) of the pancreas which are primarily located in the Islets of Langerhans. It is part of a family of peptides that also includes Peptide YY (PYY) and Neuropeptide Y (NPY)

59
Q

Name 5 disorders of the pancreas

A
  • acute pancreatitis
  • chronic pancreatitis
  • pancreatic insufficiency
  • cystic fibrosis
  • carcinoma of the pancreas
60
Q

What are the features of acute pancreatitis?

A
  • acute necrotising liquefaction

- inflammatory

61
Q

What is the aetiology of acute pancreatitis

A
  • gallstones
  • alcohol
  • drugs
  • hypertriglycerideaemia
  • trauma
  • infectious
  • rare tumours
  • autoimmune
  • scorpion toxins
62
Q

What are the symptoms of acute pancreatitis?

A
  • severe epigastric pain
  • sudden onset
  • radiating to back
63
Q

What are the potential biochemical features of acute pancreatitis?

A
  • uraemia
  • hypoalbuminaemia
  • hypocalcaemia
  • hyperglycaemia
  • metabolic acidosis
  • abnormal LFTs
64
Q

How is acute pancreatitis diagnosed?

A
  • amylase or lipase
  • imaging
  • clinical history
65
Q

How does chronic pancreatitis present?

A

Progressive loss of both islet cells and acinar tissue

  • abdominal pain
  • malabsorption
  • impaired glucose tolerance
  • alcohol often an important factor
66
Q

What is often the presenting feature of chronic pancreatitis?

A

Malabsorption

67
Q

Are tests of exocrine function eg. amylase/lipase of value in chronic pancreatitis?

A

NO, of no value except for during acute exacerbations

68
Q

How is chronic pancreatitis diagnosed?

A
  • imaging
  • pancreatic function test for investigating insufficiency (direct and indirect)
  • miscellaneous: vitamin D, calcium, LFTs, glucose, lipids, FBC
69
Q

What do direct (invasive) pancreatic function tests involve?

A

Intubation to collect aspirated in the duodenum

- secretin, CCK, Lundh tests

70
Q

What is the Lundh test?

A

Direct test of pancreatic function in which duodenal contents are collected for two hours following a meal containing carbohydrate, protein and fat.

Low enzymic activity - amylase, trypsin or lipase - indicates pancreatic insufficiency

It is less informative than the secretin / CCK-PZ test

71
Q

What do indirect (non-invasive) pancreatic function tests involve?

A
  • pancreatic enzyme analysis in stools (elastase)
  • trypsinogen (IRT) measured in blood in CF screening
  • pancreolauryl and NBT-PABA tests

12. CP - Diseases of the Hepatobiliary system and Pancreas (5 decks)

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