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Y2 Clinical Pathology > Investigation of Liver & Pancreatic Disease > Flashcards

Investigation of Liver & Pancreatic Disease Flashcards

1
Q

What is involved in investigation of the liver?

A
  • structure & function of the liver
  • effects of liver disease
  • tests of liver function
  • tests of liver damage
  • specific diagnostic tests
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2
Q

What is investigated when looking at the structure & function of the liver?

A

the hepatocellular component and the biliary tract

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3
Q

What is the function of the liver with regards to carbohydrates and proteins?

A

carbohydrates:

  • glycogen storage & synthesis
  • glycolysis & gluconeogenesis

proteins:

  • synthesis & catabolism
  • clotting factors, amino acid metabolism & urea synthesis
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4
Q

What are the functions of the liver with regards to lipids, excretion and miscellaneous?

A

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 and B12 storage and metabolism
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5
Q

What is meant by the functional capacity of the liver?

A
  • excess of hepatic capacity for normal anabolic & catabolic processes
  • hepatic repair & regeneration following damage is a dynamic process
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6
Q

What are the different causes of liver disease?

A
  • poisoning
  • drugs
  • infection (viral and non-viral)
  • alcohol
  • inadequate perfusion
  • fatty liver
  • autoimmune
  • metabolic
  • tumours & metastases
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7
Q

What are the systemic effects of liver disease?

A
  • jaundice
  • excess of oestrogen
  • bruising
  • pigmentation
  • clubbing
  • dependent oedema
  • ascites
  • encephalopathy
  • osteomalacia / osteoporosis
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8
Q

What does excess oestrogen as a result of liver disease cause?

A
  • gynaecomastia
  • spider naevi
  • liver palms
  • testicular atrophy
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9
Q

What is meant by spider naevi?

A

a spider naevus is a type of telangiectasis (swollen blood vessels) found slightly beneath the skin surface

they often contain a central red spot and reddish extensions which radiate outwards like a spider’s web

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10
Q

What is gynaecomastia?

A

an enlargement of the male breast tissue due to a hormone imbalance

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11
Q

Do all patients have symptoms of liver disease?

A

NO!

sometimes there may be no physical signs of liver disease

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12
Q

What are LFTs?

What would you test for when looking at the carbohydrate function of the liver?

A

tests of liver function

you would test for glucose

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13
Q

What LFTs would you perform for the protein and lipid functions of the liver?

A

proteins:

  • synthesis & catabolism - albumin
  • clotting factors - prothrombin time
  • amino acid metabolism & urea synthesis - urea

lipids:

  • lipoprotein & cholesterol synthesis - cholesterol
  • fatty acid metabolism - triglycerides
  • bile acid synthesis - bile acids
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14
Q

What LFTs would you use when looking at the excretion and miscellaneous functions of the liver?

A

excretion & detoxification:

  • bile acid & bilirubin excretion - bilirubin
  • drug detoxification & excretion - drugs, steroid hormones

miscellaneous:

  • iron storage - ferritin
  • vitamin K - prothrombin time
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15
Q

What are the 4 categories of available liver function tests?

A
  • production of metabolites
  • clearance of endogenous substances
  • clearance of exogenous substances
  • imaging, biopsy
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16
Q

What is looked for in tests of liver damage?

A
  • hepatocellular damage
  • biliary tract damage
  • using imaging / biopsy
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17
Q

What are the 6 routine LFTs?

A
  • alkaline phosphatase
  • alanine aminotransferase (ALT)
  • bilirubin
  • albumin
  • total protein
  • GGT (gamma-glutamyl transferase)
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18
Q

What is the specific test for viral hepatitis?

A

serology to look for:

  • hepatitis A, B, C, D & EB
  • HIV
  • CMV
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19
Q

What is the specific test to look for chronic active & autoimmune hepatitis?

A

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

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20
Q

What is the specific test for primary biliary cirrhosis?

A

anti-mitochondrial antibodies

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21
Q

What is the specific test for hereditary haemachromatosis?

A
  • ferritin
  • transferrin saturation
  • liver biopsy
  • genetic testing
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22
Q

What is the specific test for Wilson’s disease?

A
  • caeruloplasmin
  • urine copper
  • plasma copper
  • liver biopsy
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23
Q

What is the specific test for a1-antitrypsin deficiency?

A
  • a1 antitrypsin
  • genetic testing
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24
Q

What is the specific test for hepatocellular cancer?

A

AFP

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25
Q

What tests are used to look for hepatocyte damage?

Are they sensitive and specific?

A

aminotransferases - ALT (alanine) & AST (aspartate)

ALT is more specific for the liver than AST

they are only released by cellular damage

  • viral hepatitis
  • toxic insults
  • infiltrative

tests are sensitive but not specific

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26
Q

What are common causes of acute and chronic hepatitis?

A

acute:

  • paracetamol
  • viral hepatitis B & E

chronic:

  • viral hepatitis B & C
  • alcohol
  • Wilsons disease
  • alpha-1-antitrypsin deficiency
  • autoimmune hepatitis
27
Q

What is the difference in development of acute and chronic hepatitis?

A

acute:

  • severe hepatic dysfunction developing within 6 months of the first onset of liver disease
  • and in the absence of pre-existing liver disease

chronic:

  • clinial or biochemical features of liver disease persisting for more than 6 months
  • graded according to necroinflammatory activity and degree of fibrosis
28
Q

What are the characteristic features of acute and chronic hepatitis?

A

acute:

  • hepatic encephalopathy
  • prolonged and persistent PT/INR
  • grossly hepatic picture
  • deep jaundice
  • possible hypoglycaemia

chronic:

  • abnormal transferases 2-10 x ULN
  • AP & bilirubin usually normal unless cirrhosis has developed
  • PT/INR mildly abnormal
  • low albumin
29
Q

What are the 3 stages associated with alcoholic liver disease?

A

there are 3 stages relating to the patterns of histological change in liver tissue associated with ethanol ingestion

  • fatty liver (steatosis)
  • alcoholic hepatitis
  • cirrhosis
30
Q
A
31
Q

What is steatosis (fatty liver)?

What changes are present?

A

a response to excess alcohol in all individuals which is reversible with abstinence

biochemical changes:

  • minimal biochemical changes
  • very mild increased ALT
  • occasionally cholestatic picture
  • raised GGT
32
Q

What is alcoholic hepatitis?

What are the biochemical changes present?

A
  • appearances of steatosis and creeping fibrosis with potential for progression to cirrhosis
  • often occurs after a heavy bout of drinking on the back of heavy chronic drinking

biochemical features:

  • very wide spectrum of results
  • anaemia
  • raised ALT and AST
  • can progress to prolonged jaundice, fever & hepatic failure
33
Q

What is cirrhosis in alcoholic liver disease?

How is it diagnosed?

A
  • final stage of alcoholic liver disease
  • disturbance of normal hepatic architecture following recurrent episodes of necrosis, cell death and attempts to regenerate
  • requires a histological diagnosis with a wide spectrum of results
34
Q

What tests are used in biliary tract damage and why?

A
  • impaired excretory function
    • increased conjugated bilirubin
  • increased synthesis of enzymes by cells lining the bile canaliculi
    • ​ALP and GGT
35
Q

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

A

elevated due to increased production by cells lining the bile canaliculi and overflow into the blood

this is due to:

  • cholestasis (intra- or extrahepatic)
  • infiltrative diseases
  • space-occupying lesions (tumours)
  • cirrhosis

multiple sites of production - liver, bone, intestine, placenta

36
Q

How can ALP isoenzymes be identified?

A

liver and bone ALP isoenzymes are separated by electrophoresis

37
Q

Why is gamma glutamyltransferase (GGT) elevated in biliary tract damage?

A
  • can support a liver source of raised ALP
  • elevated due to structural damage
  • can be induced by:
    • 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)
38
Q

What is primary biliary cirrhosis?

What are the symptoms?

A

a chronic cholestatic condition with destruction of bile ducts

it has a strong female predilection

symptoms are pruritus, jaundice and non-specific tiredness

39
Q

What tests are used in primary bilary cirrhosis?

A
  • it is often an incidental finding with an isolated raised ALP
  • raised IgM and specifically raised anti-mitochondrial antibodies (AMA)
40
Q

What is primary sclerosing cholangitis?

A

a progressive disease characterised by diffuse inflammation and fibrosis of the biliary system

men are affected more than women

it is autoimmune and often related to IBD

41
Q

What are the tests for primary sclerosing cholangitis?

A

progression over years from minor elevations of ALP to a very severe cholestatic condition with deep jaundice

42
Q

What are the biochemical markers of fibrosis?

A

historically only imaging, biopsy & predictive scores

novel biochemical markers:

  • ELF score
    • PIIINP
    • TIMP-1
    • hyaluronic acid
43
Q

How is bilirubin measured?

What does it show?

A

it shows the excretory capacity of the liver and free flow of bile

it is measured as:

  • total
  • unconjugated - pre-hepatic & hepatic
  • conjugated - post-hepatic (obstruction) & hepatic
44
Q

What is serum bilirubin when there is jaundice?

A

jaundice at serum bilirubin > 40-50 umol/L

45
Q

What are the pre-hepatic and post-hepatic (obstructive) causes of hyperbilirubinaemia producing jaundice?

A

pre-hepatic aetiology:

  • haemolysis e.g. Rhesus incompatibility
  • ineffective erythropoiesis e.g. spherocytosis

post-hepatic (obstructive) causes:

  • gallstones
  • biliary stricture
  • cancer i.e. choloangiocarcinoma, head of pancreas
  • cholangitis
46
Q

What are the hepatic causes of hyperbilirubinaemia leading to 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
47
Q

What are examples of 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
48
Q

What blood tests are performed in the presence of jaundice and what do they show?

A
  • AST / ALT elevated and normal ALP
    • approx 90% have hepatitis
  • AST / ALT normal and elevated ALP
    • ​approx 90% have obstructive jaundice
49
Q

What are the results of urine tests in the presence of jaundice?

A

prehepatic - unconjugated bilirubin:

  • no urinary bilirubin

hepatic - hepatocellular:

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

post-hepatic - obstruction:

  • dark urine & pale stools
50
Q

How useful are routine LFTs?

A

only 3-4% of subjects with abnormal LFTs have liver disease

  • alcohol-related
  • Gilbert’s syndrome
  • obesity
  • diabetes
  • side effects of medication
51
Q

When 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
52
Q

What is the pancreas?

Where is the head located?

A

an elongated, flattened gland lying on the posterior abdominal wall

the head lies within the duodenal loop

it has an essential endocrine & exocrine function

53
Q

How does the pancreas drain?

What does it open into?

A

the pancreas drains via main pancreatic duct joined to the common bile duct

it opens into the duodenum via the sphincter of Oddi

54
Q

What are the endocrine secretions of the pancreas?

A

secreted from islets of Langerhans

  • insulin, glucagon
  • pancreatic polypeptide
55
Q

What are the exocrine secretions of the pancreas?

A

secreted from the ductal & acinar cells

  • bicarbonate
  • digestive enzymes
    • trypsin, chymotrypsin & elastase
    • carboxypeptidases
    • amylase
    • lipase
56
Q

What are the 5 main disorders of the pancreas?

A
  • acute pancreatitis
  • chronic pancreatitis
  • pancreatic insufficiency
  • cystic fibrosis
  • carcinoma of the pancreas
57
Q

What is the I GET SMASHED mnemonic for causes of pancreatitis?

A

I - idiopathic

G - gall stones

E - ethanol (alcohol)

T - trauma

S - steroids

M - mumps / malignancy

A - autoimmune

S - scorpion stings

H - hypercalcaemia / hypertriglyceridemia

E - ERCP

D - drugs

58
Q

What are the symptoms of acute pancreatitis?

How is it diagnosed?

A

symptoms:

  • severe epigastric pain
  • sudden onset
  • radiating to the back

diagnosis:

  • amylase or lipase
  • imaging
  • clinical history
59
Q

What are the potential biochemical features in acute pancreatitis?

A
  • uraemia
  • hypoalbuminaemia
  • hypocalcaemia
  • hyperglycaemia
  • metabolic acidosis
  • abnormal LFTs
60
Q

What is chronic pancreatitis?

A

progressive loss of both islet cells and acinar tissue

61
Q

What is the presentation of chronic pancreatitis like?

A
  • abdominal pain
  • malabsorption
  • impaired glucose tolerance
  • alcohol is often an important factor

malabsorption is often the presenting feature

62
Q

What tests are performed for chronic pancreatitis?

What is involved in diagnosis and management?

A

tests of exocrine function (i.e. amylase / lipase) are of NO value except during acute exacerbations

diagnosis & management:

  • imaging
  • pancreatic function test for investigating insufficiency (direct or indirect)
  • miscellaneous - vitamin D, calcium, FBC, LFTs, glucose, lipids
63
Q

What are direct (invasive) tests of pancreatic function?

A
  • intubation to collect aspirates in the duodenum
  • secretin, CCK, Lundh tests
64
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

Y2 Clinical Pathology (76 decks)

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