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Y4 SA - Clinical pathology > Tests for hepatic and pancreatic function and integrity 1 + 2 > Flashcards

Tests for hepatic and pancreatic function and integrity 1 + 2 Flashcards

1
Q

Name 4 factors that can be tested to assess liver function/integrity

A
  • Hepatocellular injury
  • Cholestasis
  • Hepatocellular function
  • Hepatic portal circulation
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2
Q

What is hepatocellular injury?

A

Damage to hepatocytes leading to leakage of enzymes

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3
Q

How can cholestasis be used to assess liver function?

A

Reduced/blocked bile excretion
Release of enzymes induced by retained bile

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4
Q

How can hepatocellular function be used to assess liver function?

A

Decreased production or catabolism of substances

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5
Q

How can hepatic portal circulation be used to assess liver function?

A

Decreased extraction of substances absorbed from the GI

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6
Q

How are liver enzymes assessed?

A
  • Very difficult to measure in amount directly, so expressed as activity rather than concentration
  • Different localisation within the cell
  • Not usually present in blood
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7
Q

What are liver ‘leakage’ enzymes?

A

Found in the blood when the cells are damaged

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8
Q

Name and describe the liver enzymes

A
  • ALT: largely liver specific, but also from muscles. SA only.
  • AST: liver and muscle so not liver specific
  • LDH: liver and muscle so not liver specific
  • SDH: liver specific in all species. unstable
  • GLDH: liver specific in all species
  • ALP and GGT: indicative of liver damage in horses and ruminants
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9
Q

What is the significance of increased liver ‘leakage’ enzymes?

A
  • Indicative of hepatocellular damage
  • Magnitude of increase correlates with degree of hepatocellular damage but NOT with reversibility of injury, prognosis or hepatic function
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10
Q

Myocyte damage can lead to a mild increase in which liver enzymes?

A

AST, LDH +/- ALT

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11
Q

How can myocyte damage be differentiated from liver damage?

A

Check creatine kinase when liver enzymes are increased

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12
Q

Other than liver and muscles damage, why else might liver enzymes be increased?

A

Artefact (haemolysis) can increase AST and LDH

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13
Q

How can you differentiate an artefact from liver damage?

A

Check serum/plasma quality

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14
Q

Give two examples of when the increase in liver enzymes doesn’t correlate with the reversibility of injury, prognosis or hepatic function

A
  • Chronic hepatopathies
  • When there is a reduction of the overall hepatocellular mass (cirrhosis, PSS)
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15
Q

Describe the half life of liver enzymes in small animal species

A

Short half-life: days in dogs, hours in cats, thus even small increases may be significant in cats

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16
Q

Name the 2 cholestatic enzymes

A

ALP
GGT

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17
Q

Which liver enzyme has a good sensitivity for canine liver-disease, poor sensitivity for feline liver-disease?

A

ALP

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18
Q

List the components of bile

A

Bilirubin
Bile acids
Cholesterol

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19
Q

Describe the isoenzymes and isoforms of ALP

A

Two isoenzymes (intestinal and non-tissue specific)
Several isoforms (produced from post-translational modification of isoenyzmes)

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20
Q

Describe the major measurable isoforms of ALP

A

Liver-ALP (L-ALP) and bone-ALP (B-ALP)
B-ALP causes usually only mild increases
- Negative prognostic marker in osteosarcoma
- Partially responsible for the increased ALP in cats with hyperthyroidism

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21
Q

Describe C-ALP

A

Unique to dogs and is induced by corticosteroids (endogenous or exogenous).
Product of the I-ALP gene, but produced in hepatocytes

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22
Q

Describe I-ALP

A

Intestinal-ALP (I-ALP) produced by intestinal ALP gene
- Short half-life (minutes) and lost in GI tract
- Not generally detected in plasma

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23
Q

Name the three types of hyperbilirubinaemia

A

Prehepatic
Hepatic
Post-hepatic

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24
Q

Describe the cause of prehepatic hyperbilirubinaemia

A

Secondary to haemolysis
Check for anaemia!

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25
Describe the causes of hepatic hyperbilirubinaemia
Can be due to decreased bilirubin uptake, conjugation, and excretion (so hepatocyte dysfunction and intrahepatic cholestasis) - Viral hepatitis - Drugs - Cirrhosis - Tumours
26
Describe the cause of post-hepatic hyperbilirubinaemia
Secondary to obstruction of the extrahepatic bile duct. - Gallstones - Cancer of the bile duct
27
How is post-hepatic hyperbilirubinaemia diagnosed?
- Often cholestatic enzymes (ALP and GGT) much higher than leakage enzymes (ALT and AST) - Serum cholesterol often high - Ultrasound very helpful
28
Describe measuring bilirubin levels
Total and conjugated can be measured directly
29
Conjugated bilirubin is also called ..?
Direct bilirubin
30
Unconjugated bilirubin is also called ...?
Indirect bilirubin
31
Determination of relative amounts of conjugated and unconjugated bile is not very useful to classify ... ?
Hyperbilirubinaemia
32
Determination of relative amounts of conjugated and unconjugated bile is not very useful to classify hyperbilirubinaemia except in?
Horses fasting hyperbilirubinaemia is mostly due to unconjugated bilirubin
33
What are the clinical signs of hyperbilirubinaemia?
- Jaundice persists long after liver function has returned to normal due to delta-bilirubin, bound to albumin - If jaundice is due to delta-bilirubin, there will be no bilirubinuria
34
List the functions of the liver (8)
- Detoxification of body wastes and drugs - Synthesis of cholesterol and bile acids - Synthesis of plasma proteins - Breakdown of RBCs - Carbohydrate, lipid and amino acids metabolism - Removal of bacteria - Production of clotting factors - Storage of glycogen, iron, copper and vitamins
35
List the factors that can be used to test hepatocellular function
- Decreased uptake and excretion of bilirubin and bile acids increased (unconjugated) bilirubin and bile acids - Decreased conversion of ammonia to urea: increased ammonia, decreased urea - Decreased synthesis of metabolites, decreased albumin, cholesterol, coagulation factors and inhibitors, glucose - Decreased synthesis of coagulation proteins decreased fibrinogen, increased PT, PTT - Decreased immunologic function decreased clearance of toxins and antigens -> systemic stimulation -> increased immunoglobulins
36
What are the consequences of altered hepatic blood flow?
1. Decreased uptake and excretion of bile acids 2. Decreased conversion of ammonia to urea 3. Decreased immunologic function
37
Describe ammonia metabolism in the body
- Produced in the GIT by protein digestion or bacteria metabolism - Enters the liver via portal vein - Uptake by hepatocytes to synthesise urea, amino acids, proteins - Urea diffuses to sinusoidal blood or bile canaliculi and is excreted through kidneys or intestine, respectively
38
When are the levels of ammonia significant?
When raised - hepatic encephalopathy?
39
When are the levels of ammonia raised?
Congenital and acquired portosystemic shunts Liver failure
40
Describe bile acid metabolism in the body
- Bile salts are produced by hepatocytes - Released into biliary system and then intestine: allow fat absorption and digestion - More than 90% of BAs then reabsorbed from the ileum, enter portal vein, return to liver, re-circulate - Small amounts lost in faeces; replaced by liver
41
List the causes of increased bile acids
- Reduced uptake/excretion by hepatocytes due to: reduced hepatocellular mass or impaired hepatocyte function - Disruption of enterohepatic circulation due to: portosystemic shunts or cholestasis/bile obstruction
42
If bilirubin levels are already increased why do you not need to measure bile acid levels?
Bile acid test if more sensitive than bilirubin
43
Describe how you would interpret fasting serum bile acid results
- Values > 25-30 mmol/L are abnormal and indicate hepatobiliary pathology: many underlying causes possible and cannot differentiate between cholestasis and liver failure - Values < 25-30 mmol/L: cannot completely exclude portosystemic shunt, perform a bile acid stimulation test (BAST) if still suspecting hepatic pathology
44
What is a post prandial serum bile acid test?
- BA stimulation test/dynamic BA - Take resting sample - Fatty meal - Post-prandial sample 2 hours after feeding
45
List some extrahepatic diseases that can cause an elevation in liver enzymes
- Hypoxia - GI and pancreatic disease - Endocrine diseases (fat or glycogen accumulation) - Sepsis (can also cause functional cholestasis)
46
What are reactive hepatopathies?
- Most reactive hepatopathies have normal (or mildly elevated) bile acids - Other markers of liver function will be normal
47
Describe what may be seen on haematology of patients with liver disease
Often unremarkable, but we may see: - Microcytosis (portosystemic shunts or severe liver insufficiency, likely due to altered iron transport or metabolism) - Ovalocytes (elliptocytes) are frequently seen in cats with hepatic lipidosis - Acanthocytes: lipid disease, disruption of normal vasculature
48
Describe what may be seen on urinalysis of patients with liver disease
Often unremarkable, but we may see: - Isosthenuria or inappropriately low USG - Bilirubinuria (more than 2+ in dogs, any in cats) - Ammonium biurate crystals or uroliths (40-70% of patients with portosystemic shunts)
49
Describe the microscopic anatomy of the pancreas
Each pancreatic lobule is composed primarily of acinar cells (that synthesize digestive enzymes) and smaller cells of the branching duct system. The pancreas also contains islets of Langerhans (1-2% of the glands), that carry out endocrine functions
50
List the functions of the pancreas
Alpha cells produce glucagon Beta cells produce insulin Delta cells produce somatostatin
51
List the functions of the exocrine pancreas
- Secrete digestive enzymes, zymogens produced by pancreatic acinar cells - Enzymes: proteases (trypsin, chymotrypsin, elastase), lipases, amylase - Also high concentration of bicarbonate in secretions - Aids B12 and zinc absorption - Antibacterial activity - Intestinal mucosal modulation
52
Specific enzymes assay for ... and ... are used to identify injury to pancreatic cells
Amylase Lipase
53
Injury to pancreatic cells is most commonly due to?
Inflammation (pancreatitis)
54
How is pancreatitis diagnosed?
- Specific enzyme assays - Imaging
55
Describe the main features of amylase
- Catalyses hydrolysis of complex starches - Short half-life (hours) - Salivary and intestinal not found in serum - More useful in dogs than other species - Can increase due to decreased GFR
56
Describe the main features of lipase
- Catalyses hydrolysis of triglycerides - Very short half-life (2 hours) - Mostly from pancreas - Can increase (mildly) due to decreased GFR - Different tests have different positive and negative predictive value
57
Is lipase useful in diagnosing pancreatitis?
Elevation in lipase is suggestive but: - Other causes possible - Higher the increase higher the likelihood - Degree of increase doesn't equal severity of disease
58
How can pancreatitis be diagnosed?
- Clinical signs - PLI (specific pancreatic lipase): not to be used on isolation! - Imaging (ultrasound), fluid analysis, biopsy
59
Describe the possible haematology changes seen in a patient with pancreatitis
Often leucocytosis, neutrophilia and left shift, due to the presence of inflammation
60
Describe the possible biochemistry profile changes seen in a patient with pancreatitis
- Hyperglycaemia due to transient or true diabetes mellitus - Hyperlipidaemia due to primary, or secondary to pancreatitis, Cushing's etc - Hypocalcaemia due to saponification of fat, glucagon release -> increased release of calcitonin
61
Name 2 tests used to assess exocrine pancreas function
TLI = trypsin-like immunoreactivity Exocrine pancreatic insufficiency test
62
The TLI (trypsin-like immunoreactivity) test can be used in which spp?
Dogs Cats Horses - species specific assays needed
63
Describe the features of the TLI (trypsin-like immunoreactivity) test
- Detects trypsinogen, trypsin, and trypsin bound to protease inhibitors (most TLI in blood is trypsinogen; do not want free trypsin in the blood) - Pancreas normally leaks some trypsinogen into blood - In animals with clinical signs of maldigestion/malabsorption, (decreased activity) high sensitivity and specificity for exocrine pancreatic insufficiency - Less useful for pancreatitis (increased activity)
64
Describe the exocrine pancreatic insufficency test
Serum TLI < 2.5 ug/L in dogs (< 5 ug/L equivocal/subclinical) TLI < 8 mg/L in cats
65
Exocrine pancreatic insufficency can be excluded if?
TLI is normal

Y4 SA - Clinical pathology (1 decks)

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