Diagnostic Evaluation of the Liver

Question 1

List the major functions of the liver

Answer 1

1. immunoregulation
2. Storage
   
   • Trace minerals
   • Vitamins
   • Glycogen
   • Trigycerides
   • Blood
3. Detoxification and excretion of toxins
4. Digestive functions (bile secretion)
5. Metabolism
   
   • Carbohydrates
   • Proteins
   • Lipids
   • Vitamins
   • Endocrine hormones

Question 2

List the common known breed predispositions to specific liver diseases

Answer 2

1. Copper Storage diseases:
   
   • Bedlington Terriers, Labrador, Dobermans, Dalmation, Skye Terrier, WHWT
2. Chronic hepatitis - with excessive copper
   
   • Labrador, Dobermans
3. Hepatic amyloidosis
   
   • Abyssinian, Oriental and siamese cats
   • Chinese Shar-pei
4. Portosystemic shunts
   
   • EHPSVA - small and toy breeds: maltese, yorkshir terrier, pugs, miniature schnauzer
   • IHPSVA - large breed dogs: Irish wolfhound, labrador, golden retriever, ACD, Aust. Shepherd
5. Portal vein hypoplasia
   
   • Toy breeds: Maltese, Yorkshire terrier, Cairn terrier
6. Progressive vacuolar hepatopathy
   
   • Scottish Terriers

Question 3

What clinical signs can be specific to liver disease?

Answer 3

• The majority of clinical signs seen in dogs or cats with liver disease are NOT SPECIFIC

1. Icterus
   
   • can also be seen with rapid RBC destruction and post-hepatic bile duct obstruction
2. Ascites
   
   • Multiple causes with the hepatic specific causes of either portal hypertension (PH) or hypoalbuminaemia
   • Must therefore exclude other more common causes of low albumin such as PLE and pre- and post-hepatic causes of PH including right heart failure or PV thrombosis.
3. Hepatic encephalopathy
   
   • While pathognomonic for hepatic insufficiency - either acute fulminant hepatic failure or chronic collateral circulation causing hepatic bypass, the clinical signs are not definitive and intracranial and other toxic causes for the signs should be excluded
4. Hepatocutaneous Syndrome
   
   • Fairly typical dermatological signs (superficial necrolytic dermatitis) occur with this uncommon syndrome

Question 4

List the potential causes of elevated liver enzymes originating outside of the liver - ie. reactive hepatopathy

Answer 4

1. Medications
   
   • Phenobarbitone
   • Glucocorticoids
2. Hypoxia
   
   • Status epilepticus
   • Acute anaemia / hypotension / shock
   • CHF
3. Inflammation / infection
   
   • Pancreatitis
   • Peritonitis and other systemic infections
   • Sepsis
   • Muscle injury
   • GIT disease
4. Endocrine disease
   
   • Diabetes
   • Hyperadrenocorticism
   • Hyper- or hypothyroidism
5. Other
   
   • OSA / bone disease
   • Post-caval syndrome
   • Mammary tumours
   • Growing young animals
   • Laboratory error

Question 5

Discuss the sensitivity and specificity of the cytosolic liver enzymes in both cats and dogs.

Answer 5

• ALT and AST are the two routinely assessed cytosolic liver enzymes
• Both ALT and AST are elevated with hepatocyte damage. As ~20% of AST is retained within the mitochondria, AST is slightly less sensitive that ALT in the detection of liver cell damage.
• Furthermore, AST is also found in muscle and red blood cells, whereas the vast majority of ALT is located within the hepatocytes, so an increase in AST is less specific for primary liver disease
• Both enzmes are sensitive in the detection of primary hepatic insults, but do not differentiate the inciting cause.
• Both enzymes can be affected and increased with secondary hepatic insults from hypoxia, GIT or pancreatic disease, thus reducing their specificity for primary liver disease
• ALT has a short half-life in cats of ~ 6 hours, so increases tend to suggest a current / ongoing hepatic insult

Question 6

Discuss the sensitivity and specificity of the membrane bound enzymes in both cats and dogs.

Answer 6

• ALKP and GGT are the two routinely assessed membrane bound hepatic enzymes
• Increases in ALP occur either via increasedde novo synthesis or in the presence of bile acids
• In dogs, the sensitivity and specificity of an elevated ALKP are 80% and 51% respectively
• ALP is present as 5 isoenzymes - bone, renal, intestinal, liver and corticosteroid-induced (dogs only).
  
  • Renal and intestinal isoenzymes have very short half-lives and do not contribute significantly to increases
• ALP half life in cats is 6 hours, making changes in ALKP more specific (93%) but less sensitive (50%) for primary liver disease.
• GGT has a sensitivity of 50% and specificity of 87% in dogs
• GGT sensitivity and specificity in cats is 86% and 67% respectively
  
  • GGT activity is generally increased further in necro-inflammatory conditions in cats

Question 7

List the routine biochemisty tests that can be of relevance to the functional capacity of the liver.

How may liver disease alter the results of these tests?

Answer 7

1. Glucose
   
   • functional mass needs to be less than 25%
   • low glucose can be seen with PSS, cirrhosis and acute fulminant failure
   • More commonly low for reasons other than primary hepatic insufficiency. eg. insulinoma, paraneoplasic, hypoadrenocorticism, starvation (especially in young dogs)
2. BUN
   
   • Can be low, primarily with shunting
   • Reduced ammonia presentation to the liver for conversion to urea is more common compared to reduced functional reserve.
   • Can also be low with fasting/starvation or a strict low-protein diet
3. Bilirubin
   
   • pre-hepatic, hepatic and post-hepatic causes
   • hepatic jaundice is due to inadequate uptake, conjugation or excretion of bilirubin
   • Only elevated in ~ 10% of patients with primary liver disease
4. Cholesterol
   
   • Variable findings
   • Increased with cholestatic liver disease
   • Decreased with severely reduced functional mass and starvation/fasting
5. Albumin / globulin
   
   • Low albumin only occurs after loss of ~ 70% of functional mass
   • While globulins are produced in the liver, these are primarily produced by B lymphocytes
   • Reduced globulins is more often seen with GIT loss as opposed to hepatic dysfunction
6. Bile Acids
   
   • Produced exclusively in the liver from cholesterol
   • Effective and efficient enterohepatic circulation means bile acids reduce to low levels quickly with normal hepatic function
   • Increases seen with PSVAs or reduced hepatic function
   • Spuriously normal results may be seen with severe ileal disease or with failure of gallbladder contraction

Question 8

Discuss the changes that may be seen on the CBC with hepatic disease?

Where relevant, note the mechanisms that contribute to development of the noted abnormalities

Answer 8

1. Microcytosis
   
   • Primarily due to impaired iron transport with PSS
2. Target cells
   
   • Due to reduced cytosolic Hb (relative membrane excess)
3. Poikiliocytes
4. Heinz body formation (cats)
5. Anaemia
   
   • Haemorrhage from GIT ulceration
   • Chronic disease
6. Mild thrombocytopenia may be present