Clinical Chemistry Flashcards
What are Reference ranges
normal values
reference ranges established by measuring the laboratory parameters in a group of normal animals
Describe the anatomy of the liver
receives nutrient blood hepatic artery- (20%) blood supply
80%-hepatic portal vein from- stomach, intestines, pancreas, spleen
blood leaves the liver- HEPATIC VEIN –> Caudal VENA CAVA
Describe the portal triad
hepatic a., portal v. –> blood flow toward central v
bile duct–> bile flows in opposite direction
What is the function of the liver
metabolism of fats, carbohydrates, and protein
Stores Glucose as glycogen
Production of albumin and other plasma proteins
Detoxification ( drugs, ammonia)– urea
Bile Metabolism –excretion of bilirubin
Produces Coagulation Factors
Why would an animal be jaundice if his liver wasn’t working
His body cannot reabsorb the bilirubin
Why wound an animal have hypoalbuminemia if his liver wasn’t working
Because the liver isn’t producing albumin
Why would the animal have problems with hemostasis if his liver wasn’t working
The liver isn’t producing the clotting factors
Why would the animal have hypoglycemia if his liver wasn’t working
There are glucose stores in the liver
Why would the animal have Hyperlipoproteinemia if his liver wasn’t working
Due to the lack of metabolism of proteins and fats
Why would the animal have hepatoencephalopathy if his liver wasn’t working
Because the ammonia isn’t being filtered out
At what point in liver damage does clinical signs occur
Usually liver disease is greatly progressed before clinical signs appear ( 80%)
What are the 3 types of tests used to evaluate the liver for damage
Enzymes released by damaged hepatocytes = leakage enzymes
Enzymes Associated with Cholestasis
Hepatic function tests
What are the Enzymes released by damaged hepatocytes
Alanine Aminotransferase ALT (SGPT)
Aspatate Aminotransferase AST (SGOT)
What tests are used to find enzymes released by damaged hepatocytes
Sorbitol (Iditol) Dehydrogenase SDH
Glutamate Dehydrogenase GLDH
What is Cholestasis
obstruction of flow of bile
What are the enzymes associated with cholestasis
Alkaline Phosphatase ALK
Gamma glutamyl transpeptidase GGT
What are the four hepatocyte function tests
Bilirubin
Bile Acids
Dye excretion
Bile Acids
What is the significance of ALT in cats and dogs
In Dogs Cats, primates, hepatocyte is major source Considered liver specific in these species
It is considered a screening test for liver disease
What can cause a false positive increase in ALT in cats and dogs
There will be a Mild increase in feline hyperthyroidism + steroid therapy + anticonvulsant tx
What is specific about ALT in horse, ruminant, pig, bird
it is not clinically significant as a marker for liver function
When are elevations seen in ALT
elevations seen w/n 12 hours of liver hepatocyte damage
When do elevations of ALT return to normal
in 2 weeks
Describe the significance of elevated AST in cats and dogs
Enzyme is in the mitochondria thus more severe liver damage required to elevate it
AST also found in muscle tissue- cardiac+ skeletal + RBCs- rise after strenuous exercise, or muscle damage as well as hemolysis will cause an elevation
When do AST levels return to normal
Rise more slowly and return to normal w/n a day (short half life)
How do you distinguish if AST levels are from muscle or liver damage
Increase in AST but normal ALT = muscle damage
CK will rise only with muscle damage
What is CK
Creatinine Kinase is an enzyme that is in muscle tissue, but not in liver. skeletal muscle, and cardiac muscle damage
CK is frequently assayed if an animal has an elevated blood AST level but shows no clinical signs of liver disease
What causes CK elevations
from intramuscular injections,
persistent recumbency, surgery,
vigorous exercise, electric shock, laceration, bruising, and hypothermia. Myositis and other myopathies
When is CK included on a biochem profile
In horses or Cows to screen for liver damage
What is Sorbitol (Iditol) Dehydrogenase
Primarily found in hepatocyte
Shows liver damage in large animals ( ALT NOT USEFUL)
Can be use in all species
What is special about testing Sorbitol Dehydrogenase
Unstable in serum- samples have to be frozen
What is AP/ALK
Found In Liver, osteoblast (BONE)
corticosteroid induces an isoenzyme of AP
Young animals - elevated AP due to - bone development
What is AP/ALK used to determine
Used to detect cholestasis in dog and cat
Will see elevations with cushings b/c of x/s cortisol
Very significant in cat
Not useful in large animals
How do you determine Indirect Bilirubin amount
Usu 2/3 of the Total Bilirubin
see ↑ liver problem
What happens to direct bilirubin in cholestasis
↑ with actual biliary obstruction
What are bile acids
Synthesized in the hepatocyte from cholesterol and glycine or taurine
Secreted in the bile duct for fat digestion
95% actively reabsorbed from the ileum back into the liver
What do you do if you see elevated SBA
—> serum BA are usually very low.
Elevated SBA- screen for liver function
How do you test for elevated bile acids
Need 2 blood samples 1- fasting + 2 hour post prandial
What is a portosystemic shunt
Often congenital
ductus venosus fails to collapse at birth this allows blood to bypass or shunt around the liver.
What are the clinical signs of a portosystemic shunt
clinical signs include “stunted” growth
May have mild microcytic anemia- ammonium biurate crystals and will have increase Bile Acids
What are liver function tests used in research settings
Indocynine Clearance
Ammonia Tolerance
Caffeine Clearance
Bromsulfophthalein Excretion
What is cholesterol
Plasma lipoprotein produced by liver
What are cholesterol levels a screening test for
Screening test for hypothyroidism
T4 controls synthesis and destruction of cholesterol
Also elevations seen with other endocrine diseases
What is elevated cholesterol usually associated with
Elevated CHOL is often associated w Hyperlipemia
What are the functions of the kidneys
Filter waste and other products Water and electrolyte Balance Acid-base balance Activate Vit D Renin-angiotesin ( blood pressure control) EPO
What is the BUN
Urea is an end product of amino acid metabolism
The more protein in diet- the more urea is formed in the liver
What happens to UREA in the body
All urea passes through the glomerulous – about ½ gets reabsorbed by the renal tubules and ½ will get excreted
In what situations do you see elevated BUN
Dehydration
High protein diet
+strenuous exercise -
Loss of kidney function (75%)
What is creatinine
Formed from creatine from the msl
Remains constant with constant physical activity
Total amount of Creatinine is related to msl mass
All creatinine is filtered through the kidney
None is reabsorbed
Not influenced by a high protein diet
How much of the kidney must be destroyed to see elevated creatinine
Must have >75% kidney destruction to see elevation
What is GFR
Glomerular Filtrate Rate
How is GFR and Creatinine related
Any condition that alters GRF alters creatinine since all is excreted and none is reabsorbed
What does the BUN/Creatinine ratio show
75% kidney destroyed b/f inc in Bun/CREAT
Not that sensitive for early detection of renal dse
GFR has to be decrease 4 fold b/f there is an increase
What is micro albuminuria used for
Can be useful To detect early onset kidney disease
what do you look for in UA for evidence of kidney disease?
Low Spec. Gravity, protein loss
Why is the UPC used to detect early renal disease
Based on the concept that the tubular concentration of urine increases both the urinary protein and creatinine concentrations equally
How do you evaluate UPC
Cystocentesis is preferred method
5- renal dse
What is SDMA
SDMA is a methylated form of the amino acid arginine, which is produced in every cell and released into the body’s circulation during protein degradation. SDMA is excreted almost exclusively by the kidneys, making it a good marker for estimating kidney function
What is uric acid produced
By product of protein metabolism
Transported to kidney by albumin- passes thru the glomerulous and gets reabsorbed by the tubule cell- gets converted to allantoin and then excreted in the urine
Describe the defect of the dalmation
Uric acid is excreted into urine to create urate urolith
In avian and reptile, describe uric acid significance
Uric acid is major end product of nitrogen metabolism
Uric acid is used to measure renal function in Avian and Reptile species
What is Gout
uric acid crystals deposit in joints, tendons, and surrounding tissues and cause inflammation.
Birds and reptiles on a too high of a protein diet or with Kidney disease will get gout
What is a water deprivation test used for
Is done to see if the Kidney can concentrate urine
What are differential diagnoses if you have PUPD
Cushing’s dse
Diabetes mellitus
Diabetes insipidus
Psychogenic polydipsia
What is the goal of the water deprivation test
GOAL: Dehydrate the patient safely until endogenous ADH is produced
This happens at 5% body weight loss
What must you monitor if you’re doing a water deprivation test
When doing a water deprivation test you must monitor body weight and C.S. of dehydration
Monitor urine specific gravity
When is the water deprivation test contraindicated
Test is contraindicated if animal is already dehydrated or azotemic
What is the vasopressin response test used for
to see if you have Diabetes Insipidus
What are common endocrine pancreas problems
Endocrine — Diabetes mellitus, insulinoma
What are common exocrine pancreas problems
Excocrine – EPI- pancreatitis– cancer
What are the exocrine pancreas function tests
Exocrine Pancreas – Lipase, amylase, trypsin…..
What are the endocrine pancreas function tests
Endocrine Pancreas– Insulin + glucagon
What happens when there is inflammation of the pancreas
trypsin, amylase, lipase- when there is inflamation these enzymes leak into the serum
What is EPI
Low level enzymes in pancreas
What does EPI cause
MALDIGESTION– secondary to malabsorption
Causes- Pancreatic Acinar Atrophy (German Shepard)
or loss of pancreatic tissue from chronic pancreatitis
How do you test for trypsin levels
Can test feces for its presence
Test tube method, x-ray film method
Why do you test for trypsin
To rule out pancreatic exocrine insufficiency
What is Serum Trypsinlike immunoreactivity TLI
Radioimmunoassay that uses antibodies to trypsin
Detects both trypsin+trypsinogen
TLI is increased in pancreatitis but not that useful a test for pancreatitis
What is the TLI good for
Specific and sensitive test for pancreatic exocrine insufficiency when decreased
What type of blood sample do you need for TLI
Use fasting blood sample
What is Malabsorption
Nutrients are not being absorbed through the microvilli
What are tests for malabsorption
Tests for Malbsorption
serum Cobalamin + Folate
Why do you test for amylase levels
Amylase: acute/chronic pancreatitis or obstruction of pancreatic duct will result in elevations
If GFR decreased- rise in amylase
What is an insulinoma
Tumor of beta cells- produces hypoglycemia with seizures- common in ferrets
What does increased fructosamine indicate
Increase fructosamine indicates a persistent hyperglycemia
What is the half life of albumin
Half life of albumin is 1-2 weeks
So gives an indication of glucose control over the last 2 weeks
How long do glycosylated Hb last
2-4 months
What hormone lowers blood glucose
Insulin
What hormones raise blood glucose
glucagon, adrenaline, cortisol, growth hormone
What is type 1 diabetes
insulin dependant diabetes
pancreas is not producing enough insulin usually because of immune destruction of the beta cells
What is type 2 diabetes
Type II diabetes- non insulin dependant diabetes – insulin resistance
cats more common – associated with obesity-(fat cells hide receptors)
What are the predisposing factors to type 2 diabetes
About 1 in 200 animals affected Obesity esp in cats causes type 2 Middle age Genetics Other hormones-- cortisone, progesterone More in Neutered male cats or middle age intact bitches
What does insulin do in the body
it allows the cells to use glucose- Even though the blood glucose is high – the cells can not use the glucose- so they breakdown fat and use protein from the lean body mass
What are the clinical signs of diabetes
Polyphagia, PUPD, weight loss Cataracts (dogs) Polyneuropathy, Plantigrade posture(cats) Prone to bacterial infections Hyperglycemia Glucosuria
How do you diagnose diabetes
Glucosuria
Hyperglycemia
Fructosasmine elevated ( 2-4 weeks)
Glycosylated hemaglobin increased (2-4 months)
What si the goal of treatment of the diabetic
Stabilize– glucose levels-
Insulin injection
Minimize post prandial hyperglycemia
Provide optimum amount of nutrients
Minimize clinical signs (PUPD, neuropathy…
Avoid hypoglycemia- fatal
What are the 3 steps to dietary treatment of diabetes
1-Consistent amounts, consistent timing, consistent ingredients, consistent proportion of CHO, protein, fat – fixed ingredient profile
2-Slow absorption of glucose from intestine
Low in simple sugars, High in Complex carbohydrates—barley, sorghum- to slow glucose absorption( low in simple sugars)
3-Fiber- some slow gastrointestinal transit time- hemicellulose, carboxymethylcellulose
Fibers slows absorption of nutrients – ie glucose
Describe nutrition goals of a diabetic
Protein- good quantity and quality- to protect lean body mass– also will provide amino acids for gluconeogenesis
Antioxidants– Vit E
FAT content will depend on BCS
What are the important macros for diabetic animals
For Dog Diet
60% CHO
20% Protein
20% FAT
CAT REQUIRE HIGHER Protein, less CHO–
What nutraceuticals should you give if an animal is diabetic
Chromium- potentiate insulin
Carnithine – help with fat metabolism
Antioxidants-
When is a glucose curve done after an animal is diagnosed with diabetic
Glucose curve is usually done 4-6 weeks post start of injections
How do you perform a glucose curve
Hospitalize the animal ( can train owners to do at home)
Follow the pet owner’s normal regime. This includes insulin injections, size, type and timing of meals and exercise routine. – ALSO good to watch Owner give the Insulin
Take a blood sample prior to insulin injection.
Feed the animal ( 1/3 daily ration). Administer the insulin
Take a blood sample every two (to four) hours, if possible for 24 hours but at least until the concentration has crossed back above the renal threshold.
Blood glucose concentrations are measured and plotted against time to produce a blood glucose curve.
What is the aim of treatment of diabetes mellitus
You want blood glucose concentrations to be below the renal threshold and to avoid hypoglycemia
Thus the goal is to maintain blood glucose concentrations roughly between:
5 and 10-12 mmol/l (90 and 180-216 mg/dl) in dogs
5 and14-16 mmol/l (90 and 252-288 mg/dl) in cats
How do you measure the duration of insulin action
The duration of insulin action is measured from the time of insulin injection, followed by a fall in blood glucose concentration, to the time that blood glucose exceeds the renal threshold.
How is once daily caninsulin treatment to be considered effective in dogs
For once daily Caninsulin treatment to be considered effective in dogs the duration of the insulin action needs to be at least 20 hours.
How is twice daily caninsulin treatment to be considered effective in dogs
For twice daily Caninsulin treatment to be considered effective, the duration of the insulin action has to be around 8-12 hours following each insulin injection.
What is the ideal blood glucose curve
Normal blood glucose in non-diabetic cats ranges from 2.6 - 8.4 mmol/l.
The renal threshold is 14mmol/l.
The goal is produce a blood glucose curve that approaches the reference range but avoids potentially fatal hypoglycaemia, for example 5 - 14 mmol/l for most of each 24 hour period.
What is the Somogyi effect
An insulin dose that is too high may bring about the Somogyi effect or rebound hyperglycaemia.
This can also be produced if blood glucose concentrations fall too rapidly. The moment that the Somogyi effect is triggered is very individual – it is a life-saving response.
What do long-acting insulins do
Long-acting insulins and insulin analogs
Ultralente insulins - 100% crystalline insulin
PZI insulins - contain protamine and zinc
Insulin glargine is an insulin analog that is released slowly over a period of up to 24 hours (in humans) and intended to supply a basal level of insulin.
What are intermediate acting insulins
Lente insulins (e.g. Caninsulin) - mixtures of 30% amorphous (semilente) and 70% crystalline (ultralente) insulin in an aqueous suspension. NPH insulins - contain protamine
What are rapid acting insulins
Soluble insulin and semilente insulin: intravenous administration possible
Insulin lispro, insulin aspart and insulin glulisine are insulin analogs that readily absorbed from the injection site which are used to provide a bolus of insulin for after a meal (in humans)
What is 40 IU mean
40 units per ml
How do you do an insulin tolerance test
Give .1IU/kg regular- short acting insulin
Insulin resistance if BSL fails to drop50% of the pre fasting level
Insulin receptors are unresponsive to insulin
How do you treat hypoglycemia
Always be ready to tx hypoglycemia – with IV glucose