Hepatology 1 Flashcards
- Non-specific clinical signs of liver disease.
- Specific clinical signs of liver disease.
- Inappetence.
Weight loss.
V+/D+.
PU/PD. - Jaundice (icterus).
Ascites.
Hepatic encephalopathy.
Coagulopathy.
Others - rare.
Jaundice (icterus).
Yellow discolouration of a patient.
Initially seen on the sclera.
Normal ref range for bilirubin is 10-15 microM/L. Start to see jaundice at around 35 microM/L on sclera.
See jaundice on skin and MMs with bilirubin at around 50 microM/L.
Differentials of jaundice:
- could be pre/hepatic/post.
— pre = accelerated breakdown of RBCs due to pathological haemolytic process producing too much bilirubin for the liver to process.
— hepatic = liver cells not functioning properly, cannot convert bilirubin into form it needs to be in to be excreted from the gall bladder, so accumulation of bilirubin.
— post = obstructive process anywhere in the biliary trees e.g. fall bladder, common bile duct, duodenal obstruction where common bile duct enters duodenum, compression of the common bile duct e.g. pancreas, LN
- bilirubin is from RBCs that reach end of life.
- normally, RBCs at end of life are sequestered by macrophages in liver, spleen or bone marrow — remove them from circulation.
— RBCs get broken down from haemoglobin to bilirubin > transported bound to albumin to liver > further processing in liver > storage in gall bladder which contracts when eat a meal > excretion into bile duct into intestines > excretion from the body.
Ascites.
Fluid in the abdomen
Liver disease = Modified transudate or transudate (low protein and low cellularity fluid).
Governed by capillary haemodynamics.
Albumin produced in liver, of liver dysfunction, low albumin > reduced oncotic pressure in vessels > fluid seeps out of vessels into surrounding tissues > transudate.
Increase hydrostatic pressure:
- increased resistance to venous blood flow through liver due to cirrhosis
> increased venous pressure and capillary pressure > fluid leaks out of capillaries > high protein and cellularity > modified transudate.
Hepatic encephalopathy.
Seen with extreme hepatic dysfunction or portosystemic shunting.
Toxins accumulate in blood stream as a result of liver disease and affect the brain and brain function.
Most recognised toxin is ammonia as is measurable on clinical practice.
Others are not as measurable.
Clinical signs:
- lethargy, dullness, obtunded, pacing aimlessly, difficulty to settle, circling, head pressing, seizure, coma, death.
Confirmation by demonstrating a high ammonia in blood or other evidence of liver disease.
Coagulopathy.
In presence of marked hepatic dysfunction.
Vast majority of clotting factors produced in the liver.
Liver dysfunction - may not produce sufficient clotting factor and eventually see clinical bleeding in the patient:
— typically GI haemorrhage, cutaneous bleeding.
Other rare signs - hepatocutaneous syndrome.
Hyperkeratotic foot pads - thickened, cracked, fissured.
Diagnosis on skin biopsy.
Liver looks like Swiss cheese on U/S.
Using clinical progression to facilitate prioritisation of differential lists.
Most peracute disease seen are either vascular - bleed or thrombus, trauma - RTA, toxin. (Within 2-6hrs).
Next most acute disease seen is inflammatory disease (infectious or sterile). (Hours to a few days).
Little more chronically is metabolic
- insidious onset, gradual, wax and wane, progressively worsening. (Months).
Neoplastic disease often chronic but can be acute - insidious and gradual, tends to happen with age so owners associate initial mild signs with aging.
- Exception = splenic haemangiosarcomas that suddenly rupture — but is on list of differentials for peracute.
Most chronic disease is degenerative:
- occur over months to years.
- vague, poorly specific signs that happen over a very long time.
Using hepatic enzyme elevations to determine whether predominantly hepatocellular or cholestatic.
Predominant hepatocellular enzymes are ALT and AST.
Predominant cholestatic enzymes are ALP and GGT.
Helps establish most likely differentials
Cholestatic elevations can show as elevation in ALP and/or GGT, and sometimes show other features of cholestasis with increased severity:
- hupercholesterolaemia, hyperbilirubinaemia, overt jaundice.
Need to look at the X-fold elevation above the reference range.
- with mixed disease processes, elevations. May be comparable.
Be aware of limitations, especially in cats due to short half-life.
Common causes of hepatobiliarh diseases, primarily causing a hepatocellular pattern.
Toxic:
- Acute — drugs —> antimicrobials (TMPS, doxycycline), immunosuppressives (e.g. azathioprine), anti-thyroidals (methimazole).
— toxins —> e.g. blue-green algae, Alfatoxins, Amanita spp. (mushrooms), xylitol.
- Chronic — chronic and low-level exposure e.g. phenobarbitone.
Traumatic:
- Acute — blunt trauma —> hepatic contusions.
Inflammatory:
- Acute — infectious e.g. neutrophilic cholangitis (cats) / cholangiohepatitis (dogs), lepto (dogs), CAV-1 (unvaccinated dogs).
- Chronic — sterile e.g. lymphocytic cholangitis (cats), chronic hepatitis (dogs).
Metabolic:
- chronic — reactive hepatopathies.
Neoplastic:
- chronic — hepatocellular adeno/carcinoma, lymphoma, mets to the liver.
Common causes of hepatobiliary disease, primarily causing a cholestatic pattern.
Toxic:
- Acute — drugs/toxins —> some can cause an idiosyncratic cholestatic pattern.
- chronic — chronic, low-level exposure e.g. phenobarbitone.
Traumatic:
- Acute — biliary rupture, typically secondary to underlying disease.
Inflammatory:
- Acute — infectious —> neutrophilic cholangitis (cats) / cholangiohepatitis (dogs), colecystitis, FIP (cats), toxoplasma.
— sterile —> acute pancreatitis (not hepatobiliary but critical differential).
- chronic — sterile —> e.g. lymphocytic cholangitis (cats), chronic hepatitis (dogs), chronic pancreatitis.
Metabolic:
- Acute — hepatic lipidosis, gall bladder mucocoele, obstructive choleliths.
- chronic — vacuolar hepatopathies (incl. steroid/metabolic), gall bladder mucocoele.
Neoplastic:
- chronic — hepatocellular adeno/carcinoma (sometimes just cause isolated ALP elevation), primarily biliary neoplasia.
Other reasons hepatic enzymes will elevate apart from liver disease (as these enzymes are not specific to liver).
ALP: - steroid (dogs) and bone (growth) isoenzymes.
- commonly induced by some drugs e.g. steroids (dog), phenobarbitone.
GGT: - steroid isoenzyme.
AST: - so found in muscle.
- concurrent crayons kinase (CK) will help evaluate for myopathy.
ALT: - also found in muscle (needs to be severe myopathy to increase ALT).
Considering whether hepatic enzyme elevations may be secondary/reactive rather than primary hepatic.
Primary: Disease specifically targeting, and of, the liver.
- inflammatory — infectious vs sterile.
- neoplastic — primary vs metastatic vs multisystemic.
- metabolic — e.g. feline hepatic lipidosis.
- toxic — environmental vs neutraceuticals/pharmaceutical.
- traumatic — e.g. hepatic contusions (bruises).
Secondary :
- liver as an immune organ — any systemic inflammatory disease (esp. dental or GI).
- drugs causing enzyme induction — e.g. glucocorticoids, phenobarbitone.
- metabolic diseases — causing vacuolar hepatic change (e.g. hyperadrenocorticism, DM) or a toxic hepatopathy e.g. hyperthyroidism.
- hepatic hypoxaemia, anaemia, hypovolaemia, heart failure.
Considering the magnitude of enzyme elevations.
Most useful to monitor trends rather than telling you about cause of underlying disease.
May be low with end-stage liver disease (or in cats).
Often low-moderate with secondary/reactive - can be markedly increased with steroid induction.
Can be anything (low-high) with primary liver disease.
May fluctuate so re-assess if not sure of significance (and animal clinically well).
Magnitude NOT prognostic.
Evaluating for evidence of hepatic dysfunction.
Hypoalbuminaemia, hypocholesterolaemia, low urea, hypoglycaemia.
Hyperbilirubinaemai (pre/hepatic/post causes) (a waste of time to measure bile acids in a jaundice patient).
Elevated bile acids, elevated ammonia.
Coagulation derangements.
Measure clotting times before sampling liver.
Evaluating for evidence of multisystemic disease.
I.e. liver AND other organs.
E.g. renal — lepto, toxins.
E.g. lymphadenomegaly/ multiple organs — lymphoma.
E.g. ocular — CAV1.
