Clinical Pathology: Tests for Hepatic, Intestinal and Pancreatic Function Flashcards
Describe basically what markers show for:
1. Hepatocellular injury
2. Cholestasis
3. Hepatocellular function
4. Hepatic portal circulation
- Damage to hepatocytes leading to leakage of enzymes
- Reduced/blocked bile excretion- release of enzymes induced by retained bile
- Decreased production or catabolism of substances
- Decreased extraction of substances absorbed from the GI
What ‘leaky’ liver enzymes?
- ALT- alanine aminotransferase (largely liver-specific)
- AST- aspartate aminotransferase (liver and muscle)
- LDH- Lactic dehydrogenase (liver and muscle)
- ALP- alkaline phosphotase (horses and ruminants)
- GGT- gamma glutamyl transferase (horses and ruminants)
What is the significance of increased leakage enzymed?
Indicative of hepatocellular damage
* Myocyte can cause mild increase in AST, LDH or artefact
Magnitude of increase correlates with degree of hepatocellular damage but not with reversibility of injury
Increases may only be mild in chronic or reduction of hepatocellulas mass
Relatively how long are ‘leaky’ liver enzymes half-life
What is the significance?
Short half-life
* Days in dogs
* Hours in cats
Small increases significant in cats
What enzymes show cholestasis?
ALP- alkaline phosphate
GGT- gamma glutamyltransferase
What are the different forms of ALP?
Isoenzymes- intestinal and non-specific
Isoforms
Liver and Bone
(B-ALP, L-ALP)
What is C-ALP?
Unique to dogs
Induced by corticosteroids
(endogenous and exogenous)
Describe the mechanism for normal bilirubin breakdown
- Sensecent (old) RBC are a source of heme
- Breakdown of heme to bilirubin in macrophages
- Unconjugated bilirubin is transported through the blood to the liver
- Facilitated diffusion by the liver and conjugated with glucuronic acid
- Conjugated bilirubin is actively secreted into the bile and then the intestine
- Intestinal bacteria remove glucuronic acid producing urobillinogen
- Some reabsorbed into portal blood
- Some enterd urobillinogen cycle
- Remainder is transported to the kidney
- Converted to urobilin and excreted giving urine its charactersitic colour
What causes hyperbilirubinaemia?
What are the three types and causes?
Haemolysis
- Pre-hepatic- secondary to haemolysis- anaemia
- Hepatic- cirrhosis, viral hepatitis, drugs, tumours (decreased bilirubin uptake, conjugation and excretion)
- Post hepatic- carcinoma, gall stones
Obstruction of extrahepatic bile duct, often cholestatic enzymes much higher then leakage
How is bilirubin measured?
- Total and conjugated (direct)
- Unconjugated- total- direct
What are the clinical signs of hyperbilirubinaemia?
- Jaundice persists a long time after liver function has returned to normal
What shows low hepatocellular function?
- Decreased uptake and excretion of bilirubin and bile acids- increased unconjugated bilirubin
- Decreased conversion of ammonia to urea- increased ammonia, decreased urea
- Decreased synthesis of metabolites- albumin, cholestrol, glucose
- Decreased synthesis of coagulation proteins- fibrin, platelets
- Decreased immunologic function- increase immunoglobulina, decreased clearance of toxins
How can alterations of hepatic blood flow be identified?
- Decreased uptake and excretion of bile acids (increased)
- Decreased conversion of ammonia to urea (increased)
- Decreased immunologic function
Describe ammonia metabolism
- Produced in the GIT by protein digestion or bacteria metabolism
- Enters liver (portal vein)
- Uptaken by hepatocytes to synthesis urea, aminoacids
- Urea diffuses to sinusoidal blood or bile canaliculi
- Excreted through kidneys or intestine
When is ammonia significantly raised?
Hepatic encephalopathy
Elevated in congenital/acquired portosystemic shunts and liver failure
Describe bile acid metabolism
- Bile salts produced by hepatocytes
- Released into biliary system then intestine (fat absorption/digestion)
- Over 90% reabsorbed from the ileum, enter portal vein, return to liver, re-circulate
- Small ammounts lost in faeces
What can cause increased bile acids?
Reduced uptale/excretion by hepatocytes
* Reduced hepatocellular mass
* Impaired hepatocyte function
Disruption of enterohepatic circulation
* Portosystemic shunts
* Cholestasis/bile obstruction
When is there little to no point in measuring bile acids?
If bilirubin is already increased
BA more sensitive
What is fasting SBA?
Fasting (a dog that has not eaten recenlty)
Serum bile acid
What is the interpretation of fasting SBA?
Values over 25-30 mmol/l indicated hepatobiliary pathology
Values under 25-30 mmol/l- cannot exdluse PSS perform a bile acid stimulation test if suspecting of hepatic pathology
How is a post prandial SBA done?
BA stimulation test
Initial
Fatty meal- sample 2 hours later
over 25-30 mmol/l abnormal
What extrahepatic disease can cause elevation of liver enzymes?
- Hypoxia
- GI and pancreatic disease
- Endocrine disease
- Sepsis
- Reactive hepatopathies
How can reactive hepatopathies be identified?
- Most reactive hepatopathies have normal bile acids
- Other markers of liver function will be normal- unless affected by primary disease
- Bile acids may be markedly elevated in sepsis/endotoxaemic shock/SIRS
What may be seen on haematology with lvier disease?
- Microcytosis- PSS or severe liver insuffiency
- Ovalocytes- cats with hepatic lipidosis
- Acanthocytes- lipid disorders, disruption of normal vasculture
What may be seeon on urinalysis with liver disease?
Often unremarkable but we may see:
* Isothenuria or inappropriately low USG
* Bilirubinuria
* Ammonium biurate crystals or uroliths
What are the functions of the pancreas?
Exocrine
* Acinar cells 98%
* Secrete enzymes for food digestion
Endocrine
* Islets secrete insulin 2% pancreas
* Insulin and glucagon
What exocrine hormones does the pancreas release?
Proteases
* trypsin, chymotrypsin, elastase
Lipases
Amylase
Also high concentration of bicarb
Aids in B12 and Zinc absorption
How are proteases stored in the pancreas
Inactive zymogens
What are the tests for exocrine pancreas
- Specific enzyme assay for amylase and lipase are used to identify injury to pancreatic cells
- Diagnosis should be tests with imaging signs
- What is the function of amylase
- How long is its half life?
- What species is is most useful in?
- What can cause an increase? (other then pancreatic damage)
- Catalyses hydrolysis of complex starches
- Short (hours)
- Dog
- Decreased GFR
- What is the function of triglycerides?
- What is its half life?
- What can cause an increase?
- Catalyses hydrolysis of triglycerides
- Very short- 2 hours
- Pancreas or mildly from decreased GFR
What is the advantage of DGGR lipase test?
Higher specificity
How can exocrine pancreas integrity be tested?
Specific canine pancreatic lipase
Snap tests
How should pancreatitis be diagnosed?
- Elevation in DGGR is suggestive
- Clinical signs
- PLI
- Imaging
What haematology and non-pancreatic enzymes may show pancreatitis?
Haematology:
* Leucocytosis
* Neutrophilia
* Left shift
Biochemistry
* Hyperglycaemia
* Hyperlipidaemia
* Hypocalcaemia
How is exocrine pancreas function tested?
TLI- trypsin-like immunoreactivity
* Used in dogs, cats and horses
* Detects trypsinogen, trypsin, tryptin bound to protease inhibitors
How can exocrine pancreatic insuffieincy be diagnosed in dogs and cats?
Dogs:
Clinical signs:
* Maldigestion
* Malabsorption
With high TLI Serum < 2.5 ug/l
Cats:
* Decreased VitB12
