(61) Diseases of the Liver and Pancreas Flashcards Preview

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

Flashcards in (61) Diseases of the Liver and Pancreas Deck (71)
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1

Describe the basic structure of the liver

- hepatocytes constitute 60% of liver mass
- each hepatocyte is in contact with sinusoid, bile canaliculus and neighbouring hepatocyte

2

Describe the hepatocyte organelles

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

3

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

SER

4

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

- glycogen storage and synthesis
- glycolysis and gluconeogenesis

5

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

- synthesis and catabolism
- clotting factors, amino acid metabolism, urea synthesis

6

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

- lipoprotein and cholesterol synthesis
- fatty acid metabolism
- bile acid synthesis

7

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

- bile acid and bilirubin excretion
- drug detoxification and excretion
- steroid hormone inactivation and excretion

8

What are the miscellaneous functions of the liver?

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

9

Describe the functional capacity of the liver

- excess of hepatic capacity for normal anabolic and catabolic processes
- hepatic repair and regeneration following damage is a dynamic process

10

What is measured in LFTs?

- alkaline phosphate
- ALT (alanine aminotransferase)
- bilirubin
- albumin

- total protein
- GGT (y glutamyl transferase)

11

Name 4 general types of liver function tests

- production of metabolites
- clearance of endogenous substances
- clearance of exogenous substances
- imaging, biopsy

12

What are 3 general tests for liver damage?

- hepatocellular damage
- biliary tract damage
- imaging, biopsy

13

What sorts of things can cause liver disease?

- poisoning
- drugs
- infection
- alcohol
- fatty liver
- autoimmune
- metabolic
- tumours and metastases

14

What are markers of hepatocyte damage?

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

- tumour markers = a-fetoprotein (primary HCC)

15

Which 2 types of aminotransferases are measured for hepatocyte damage?

- alanine transaminase = ALT
- aspartate transaminase = AST

16

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

ALT

(AST is also found in muscle and red blood cells)

17

What is a tumour marker for primary hepatocellular carcinoma?

a-fetoprotien

18

What is there increased levels of in biliary tract damage?

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

19

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

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

20

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

- liver
- bone
- intestine
- placenta

21

Liver and bone ALP isoenzymes can be separated by what?

Electrophoresis

22

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

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

23

Elevated gamma glutamyltransferase can be induced by...

- 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)

24

Describe the biochemical markers of fibrosis

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

25

Bilirubin is measured as...

- total
- unconjugated (pre-hepatic and hepatic)
- conjugated (hepatic and post-hepatic = obstructive)

26

What do bilirubin levels indicate?

Excretory capacity of the liver and free flow of bile

27

Jaundice occurs at serum bilirubin levels of what?

More than 40-50umol/L

28

Describe the pre-hepatic aetiology of hyperbilirubinaemia/jaundice

- haemolysis eg. rhesus incompatibility
- ineffective erythropoieis eg. spherocytosis

29

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

- gallstones
- biliary stricture
- cancer ie. cholangiocarcinoma, head of pancreas
- cholangitis

30

Describe the hepatic causes of hyperbilirubinaemia - unconjugated

- pre-microsomal
- microsomal
- inherited disorders of conjugation eg. Gilbert's syndrome, Crigler-Najjar syndrome

31

Describe the hepatic causes of hyperbilirubinaemia - conjugated

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

32

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

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

33

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

Decreased activity of UDP glucuronyl transferase (disorders of conjugation)

34

Dubin-Johnson and Rotor are syndromes of what?

Reduced ability to excrete bilirubin glucuronide (conjugated bilirubin)

35

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

Approx 90% will have hepatitis

36

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

Approx 90% will have obstructive jaundice

37

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

No urinary bilirubin

38

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

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

39

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

Dark urine (and pale stools)

40

What are the specific tests for viral hepatitis?

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

41

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

- anti-smooth muscle antibodies
- anti-liver/kidney antibodies
- anti-microsomal antibodies
- anti-nuclear antibodies

42

What are the specific tests for primary biliary cirrhosis?

Anti-mitochondrial antibodies

43

What are the specific tests for hereditary haemachromatosis?

Ferritin, transferrin saturation, liver biopsy, genetic testing

44

What are the specific tests for Wilson's disease?

- caeruloplasmin
- urine copper
- plasma copper
- liver biopsy

45

What are the specific tests for a1-antitrypsin deficiency?

- a1-antitrypsin
- genetic testing

46

What are the specific tests for hepatocellular carcinoma?

AFP (alpha feto-protein)

47

List the systemic effects of liver disease

- jaundice
- oestrogen symptoms
- bruising
- pigmentation
- clubbing
- dependent oedema
- ascites
- encephalopathy
- osteomalacia/osteoporosis

48

What are the oestrogen symptoms due to liver disease?

- gynaecomastia
- spider nevi
- liver palms (palmar erythema)
- testicular atrophy

49

How useful are routine LFTs?

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

50

Which signs and symptoms would encourage measurement of LFTs?

- pain
- itchy
- jaundice
- TATT
- bruising

51

Which lifestyle factors would encourage measurement of LFTs?

- alcohol
- obesity
- diabetes
- recent travel
- drug use

52

LFTs would be measured in the case of which diseases?

- hepatits
- haemochromatosis
- liver cancer
- drugs

53

Describe the pancreas

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

Where do pancreatic endocrine secretions come from?

Islets of Langerhans

55

Where do pancreatic exocrine secretions come from?

Ductal and acinar cells

56

What are the endocrine secretions of the pancreas?

- insulin, glucagon
- pancreatic polypeptide

57

What are the exocrine secretions of the pancreas?

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

58

What is pancreatic polypeptide?

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

Name 5 disorders of the pancreas

- acute pancreatitis
- chronic pancreatitis
- pancreatic insufficiency
- cystic fibrosis
- carcinoma of the pancreas

60

What are the features of acute pancreatitis?

- acute necrotising liquefaction
- inflammatory

61

What is the aetiology of acute pancreatitis

- gallstones
- alcohol
- drugs
- hypertriglycerideaemia
- trauma
- infectious
- rare tumours
- autoimmune
- scorpion toxins

62

What are the symptoms of acute pancreatitis?

- severe epigastric pain
- sudden onset
- radiating to back

63

What are the potential biochemical features of acute pancreatitis?

- uraemia
- hypoalbuminaemia
- hypocalcaemia
- hyperglycaemia
- metabolic acidosis
- abnormal LFTs

64

How is acute pancreatitis diagnosed?

- amylase or lipase
- imaging
- clinical history

65

How does chronic pancreatitis present?

Progressive loss of both islet cells and acinar tissue
- abdominal pain
- malabsorption
- impaired glucose tolerance
- alcohol often an important factor

66

What is often the presenting feature of chronic pancreatitis?

Malabsorption

67

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

NO, of no value except for during acute exacerbations

68

How is chronic pancreatitis diagnosed?

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

69

What do direct (invasive) pancreatic function tests involve?

Intubation to collect aspirated in the duodenum
- secretin, CCK, Lundh tests

70

What is the Lundh test?

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

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

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