liver Flashcards
(38 cards)
Pathologies that are associated with
significant hepatocellular injury- Primary hepatic disorders
- Necrosis
- Inflammation due to infectious or non-
infectious background - Toxic insult (drugs, chemicals plants)
- Neoplasia (hepatocellular, biliary)- level of increase can be variable; absence
of increase does not excluded neoplasia. - Biliary obstruction
- Extensive trauma
Pathologies that are associated with
significant hepatocellular injury- Secondary hepatic effec
Ischaemic injury (circulatory, severe anaemia,
cardiovascular)
* Metabolic (endocrine disease, often as a result
of lipidosis or steatosis, negative energy
balance – same mechanism of lipidosis)
* Toxic effect of thyroid hormones in
hyperthyroidism
* Neoplasia, metastatic cancer
* Acute severe injury can be reversable and
hence would not necessarily result in impaired
function.
Main tool for evaluation of hepatocellular
damage is
measuring of leakage enzymes
Leakage enzymes : Enzymes which are present in high concentration within hepatocytes
and leak to serum when cells are damage
Most specific to Liver
Alanine Aminotransferase (ALT)- Small animal only
Less specific to the liver, present in liver
and muscle
* Aspartate Aminotransferase (AST)
* Lactate Dehydrogenase. (LDH )
lare animal-
Sorbitol Dehydrogenase (SDH)
Glutamate Dehydrogenase (GLDH)
Correlation with muscle specific
enzyme: CK can help assess
significance in terms of
hepatocellular injury
ALT
Most specific parameter for hepatocellular damage
* Main tool in small animals
* Acute stage: severity of increase is proportionate to no. cells affected – but not whether lethal/sub
lethaL
In a repeatable injury, concurrent increased levels from regeneration
* ALT half-life is 17-60 hours but may not return to normal level as quickly as expected based on
its serum half-life
* Persistent high levels imply ongoing damage and/or concurrent regeneration
In advanced severe liver disease, there is decrease in no. functional hepatocytes – may be minimal
ALT inc.
* There are several toxins (aflatoxin, microcystin) which interfere with transaminase production;
massive acute hepatic necrosis may occur with minimal increases in ALT (or AST).
* Steroid hepatopathy – ALT will go up (endocrinopathy, GC tx or severe sustained metabolic stress)
- Rapid elevation (no synthesis de novo but release of accumulating enzymes)
- Mild (2-3 folds)
- Moderate (4-5 folds)
- Marked, higher, up to 10 and over is considered marked
- Severity does not correlate with reversibility
- Acute severe injury can be reversable and hence would not necessarily result in impaired function.
- End stage liver disease may have only slight increase in leakage or induction enzymes, or none at all.
AST
Not organ specific
* Skeletal muscle»_space; Liver & Cardiac muscle
* Can be useful when confirmed as liver only in absence of elevation of CK
* Erythrocytes contain enough to raise activity in serum when intravascular or invitro hemolysis occurs
AST has cytosolic and mitochondrial isoenzymes. Reflected in two-tiered pattern of elevation.
* Mild elevation, mild reversable injury
* Marked elevation, severe irreversible injury
The expectation is for the elevation to lag behind the elevation in ALT and recovery to be slower.
* AST is more sensitive marker for liver injury in cats, particularly with granulomatous hepatitis in FIP where you can
see mild AST elevation with normal ALT
Hepatic torsion in rabbit clinical indications
Presentation: Anorexia, lethargy, jaundice and
abdominal pain
.
Lab results: Anaemia elevated liver enzymes
ALT, AST and GGT should prompt US where
diagnosis is established.
Cholestasis
Any pathology, hepatic or extra
hepatic which decrease bile flow
result in the following
Increase in induction and/or
release of enzymes
ALP (induction)
GGT (induction and/or release)
Increase in bilirubin concentration,
specifically conjugated bilirubin- functionality of liver ramins intact however this is an obstructive issue
- Hyperbilirubinemia (conjugated higher then unconjugated )
- Bilirubinuria - low renal threshold of the conjugated (soluble bilirubin)
- Disproportionate increase of cholestatic/inducible enzymes
- Increase in bile acid concentration (clearance function vs cholestasis)
Additional relating changes: - Abnormal Vitamin K absorption resulting in coagulopathy
- Hyper cholesterolemia reflecting decrease clearance of cholesterol in bile
- Impact on lipoproteins and lipid metabolism
Pathologies resulting in cholestasis
structural cholestasis-
Intra hepatic obstruction
* Hepatocellular swelling
* Severe cellular infiltrate
* Solid hepatic biliary or metastatic tumours
* Fibrosis around biliary tree
* Parasites
*
Extra hepatic obstruction
* Tumours adjacent to the liver
* Pancreatitis
* Fibrosis
Functional cholestasis-
Defects in the transporters needed for
active transport of bile acids into the
canaliculi
* Endotoxins
* Inflammatory cytokines
γ-glutamyl transferase (GGT)
Transmembrane protein ,expressed on the cell membrane, with expression
being restricted to the luminal surface
* Solubilization of the membrane with bile acids and increased synthesis
result in increased activity in serum
* NOT liver specific BUT elevation in serum activity is almost always of
hepatobiliary origin
- Present in high concentration in kidney, mammary tissue, pancreases BUT typically secreted to
luminal surface of these organs and hence do not result in elevated serum levels
Interpretation of increased GGT activity in dogs and cats
Hepatobiliary Disease Detection:
* Cholestasis, cholangiohepatitis, hepatitis, and liver necrosis.
* GGT activity can often increase before other liver enzymes, valuable for early detection.
Biliary Hyperplasia:
* Biliary hyperplasia, a response to increased biliary pressure (e.g.) extrahepatic bile duct obstruction and
structural cholestasis.
Sensitive marker with differentiating value in cats
* May increase before alkaline phosphatase (ALP) and can be a more sensitive indicator of various liver
disease; minimal and/or or delayed increase is expected in hepatic lipidosis.
Drug-Induced Changes:
* Certain medications, like corticosteroids and phenobarbitone, can lead to increased GGT activity in
dogs.
* Understanding the potential drug-induced effects on GGT levels is important for accurate diagnosis and
treatment.
Hyperadrenocorticism:
* Dogs with Cushing’s often exhibit elevated GGT levels - useful marker for both diagnosis and monitoring
of treatment response.
interpreting GGT results in large animals
Neonates will have high levels from colostrum ingestion
Significant in liver complications of gastrointestinal diseases-
Colonic Displacement:
* GGT elevation observed in horses with right and left colonic
displacement and direct compression of bile duct
Proximal Enteritis:
* GGT increase linked to hepatic cell swelling from ascending
bacterial infections or toxin absorption.
* Histologic evidence of biliary hyperplasia or cholestasis.
Parvovirus-induced Hepatitis:
* increases in horses with parvovirus-induced hepatitis. Lag in
peak GGT activity compared to other liver enzymes
Plant Toxicity:
* Pyrrolizidine Alkaloids: marker for pyrrolizidine alkaloid toxicity in
ruminants.
Alkaline Phosphatase (ALP)
Tissue Sources
Liver:
* Hepatocytes & biliary tract epithelium.
* L-ALP isoform (all species) & C-ALP (corticosteroid induced isoform) in dogs
* Induced by cholestasis or corticosteroids
Bone:
* Produced by osteoblasts.
* Increases with osteoblastic activity.
* Elevated in osteosarcoma.
Others (Intestinal, Renal, Mammary, Placental):
* Usually not major sources.
* Exceptions in late pregnant queens, mares, and dogs with mammary tumours
dogs-
Cholestatic diseases can result in
marked increases in serum ALP
activity in dogs (greater than 10-fold
URL)
* Diff. cholestatic ALP from
stress/steroid – bilirubin…. may not be
increased if only partial biliary tree
obstruction
* Steroid hepatopathy does not
normally affect hepatic function
(bilirubin) although can if severe
* ALP and neoplasia – liver, bone and
mammary
cats-
* Shorter half-life & lower concentration- smaller increase more significant
* Smaller magnitude of serum ALP
activity increases compared to dogs
* ALP is less sensitive but more clinically
specific for feline cholestatic liver
disease (2–3× URL) can be significant
* Pancreatic + intestinal lesions can
sometimes be the primary cause of
cholestasis due to extrahepatic bile
duct obstruction.
Pre-hepatic Bilirubin/icterus
Immune-mediated hemolytic
anemia
Infectious (e.g., Mycoplasma spp.)
Toxins (e.g., paracetamol)
Hypophosphatemia
Hereditary defects (PK deficiency)
Hepatic Bilirubin/icterus
Inflammatory hepatopathies
Hepatotoxicity (e.g., diazepam)
Neoplastic
Cirrhosis/hepatic fibrosis
Hepatic lipidosis
Amyloidosis
Bacterial (cholangiohepatitis)
Protozoal (toxoplasmosis)
FI{
Post-hepatic Bilirubin/icterus
Bile duct obstruction (cholelithiasis,
biliary tree neoplasia,
inflammation)
Bile duct extraluminal compression
(pancreatitis, neoplasia, duodenal
disease)
Cholangitis/cholangiohepatitis
icterus and urinalysis
Renal threshold for bilirubin is low ,
bilirubinuria will proceed bilirubinemia
and/or icterus
Additional findings in urine :
* SG can be low, hyposthenuria ( low tonicity of
renal medulla due to low urea )
* Assess sediment
Hyperthyroidism liver markers
ALP, AST, ALT elevated.
GGT, bilirubin normal.
Hepatic lipidosis liver markers
ALP elevation early
Bilirubin increase follows
GGT elevation in later stages
Necro inflammatory Disorders liver markers
very very high ALT
GGT > ALP increase when there is
biliary structures or pancreas
involvement.
Healing Phase after Necrosis:
*Sustained ALT ALP, GGT increase.
Biliary proliferative
Diseases liver markers
GGT > ALP without
cholestasis
*e.g., biliary
carcinoma & biliary
hyperplasia
Cushing’s Disease
ALP significant increase
GGT variable increase,
ALT/ bilirubin variable
Parameters
of Liver synthetic
function
- Albumin
- Glucose
- Urea
- Cholesterol
- Coagulation factors
- Coagulation inhibitors
- Lipoprotein – impact lipid metabolism
- Iron/hem metabolism
Parameters
of liver clearance capacity
Endogenous
* Bile acids
* Ammonia
* Bilirubin
Exogenous
* Caffeine
causesof liver dysfunction
low albumin, urea, cholesterol (or high)
low coagulation factoe and coagulation inhibitoes
llipoproteans
heamoglobin synthesis
clearance capacity-
Endogenous
* Bile acids
* Ammonia
* Bilirubin (non-conjugated)
all elevated
Resulting in hyper lipidaemia
Elevated triglycerides and/or
cholestero
Coagulopathies
intrinsic & extrinsic
pathways (PT &PTT
impacted)
* Different from
coagulopathies of
cholestasis which is
impacting the extrinsic
pathways only (PT) as a
result of decreased
vitamin K absorption
May be reflected by microcytosis
Between 70-75 of liver
parenchyma need to be
lost before there is
notable compromise to
liver function
Different conditions with hepatic insufficiency
Chronic hepatitis
* infectious background: Leptospirosis, bacillus piliformis, helicobacter, bartonella spices, etc
Toxic injury
* Hepatic copper excess
* Any breed, but particularly those overrepresented (Bedlington Terrier , Dalmatian, Labrador
Retriever, Doberman Pinscher, and West Highland White Terrier)
Metabolic conditions
* Alpha-1 antitrypsin deficiency, American and British Cocker Spaniels
Immune mediated
* Immunological diagnostic tool, enzymology, IgG, and autoantibodies including antinuclear
antibodies, anti-mitochondrial antibodies, and anti-liver and kidney microsomal antibodies
