Clinical Pathology, Biochem

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Steven Kopp

Albumin

Most abundant protein, Major contributor to plasma oncotic pressure and transporter for many substances including Ca, Mg, fatty acids, hormones and unconjugated bilirubin.

Globulin

Important transporters and anti-inflammatory proteins, iron and lipid transport. Gamma globulins are the Immunoglobulins

Total Protein

Measured as Albumin plus globulins.

Hypoproteinanaemia

Could be relative- due to over-hydration
Could be due to hypoalbuminaemia or hypoglobulinaemia

Hypoalbuminaemia

Could be due to decreased production
-liver disease,
-intestinal malabsorption,
-malnutrition,
-neoplasia,
-exocrine pancreatic insufficiency
Accelerated loss
-haemorrhage,
-protein losing nephropathy or enteropathy,
-burns,
-parasites,
-high-protein effusions)
Mild decrease in
-acute tissue injury
-inflammation

Hypoglobulinaemia

failure of passive transfer of antibodies. SCID, Loss (haemorrhage, exudation, protein losing enteropathy) decreased production (malnutrition, digestion and absorption), or increased use of fibrinogen

Hyperproteinaemia

May be due to dehydration, hyperfibrinogenaemia, hyperglobulinaemia (happens with neoplastic or inflammatory disease)

Calcium

Derangment can occur with renal failure, neoplasia, endocrine and nutritional disorders. Majority bound to albumin- so can get skewed results in hypoalbuminaemic patients. Intimate relationship with P and vitamin D

Phosphorus

Absorbed gastrointestinally and is excreted by the kidney. Use Ca:P ratio

Magnesium

Useful in identifying hypo and hypermagnesemic states. Absorbed through the GIT and excreted in urine and feces

Causes of physiologic hyperglycaemia

Excitement - circulating catecholamines suppress insulin release and promote the conversion of glycogen to glucose.
Stress - high levels of circulating glucocorticoids result in insulin resistance
Post-prandial - after eating

hypoglycaemia

starvation, hepatic dysfunction, insulin producing tumors, sepsis and physical exertion

hyperlipoproteinaemia

Elevation of Cholesterol and/or triglyceride- Generally stem from either liver dysfunction or interference with lipase enzymes.

Bilirubin

Hyperbilirubinaemia - consider accelerated breakdown of heme containing substances and be mindful that bilirubin excretion requires a functional liver and biliary tree.

BUN

Blood urea nitrogen- excreted by the kidney and used as a measure of GFR. Elevated BUN with or without Creatinine is termed azotemia

Creatinine

Product of normal muscle metabolism. Excreted by the kidney and a good measure of GFR

Azotemia

Elevation of either BUN or creatinine. Can be pre-renal (dehydration) renal (primary renal disease) or post renal (urinary obstruction)

Amylase

Produced and stored in pancreatic acinar cells. Leaked during damage. Dogs with pancreatitis should have levels 3-4 times the normal limit, but affected dogs may not always have increased levels. May also increase with renal failure, GI, hepatobiliary or neoplastic disease, corticosteriods, morphine, or
stress. Interpret with Lipase

Alanine Aminotransaminase (ALT)

Reasonably liver specific enzyme but can be elevated with muscle damage (CK to differentiate) Significant at 2-3 X increase. Increased levels due to cellular damage or leakage. Half life 60 hours in dog and 4-6 hours in cat. Increases with corticosteriods and anticonvulsants

Aspartate Aminotransferase (AST)

High activity in liver, muscle, kidney, pancreas, and RBC. Sensitive but not specific for liver disease and may be elevated for haemolysis. Elevated AST indicated more severe liver damage than elevated ALT. Half life 12 hours in dogs, less in cats

Iditol dehydrogenase (ID)

Indicate hepatocellular disease in horses and production animals. Increases in horses with obstructive bowel lesions and acute enterocoloitis and portal toxins. Half life of less than 12 hours

Alkaline Phosphatase (ALP)

Bound to plasma mem of bile canaliculi and hepatocytes. Increase due to obstruction of bile flow. Not specific for cholostatis but it is elevated from this. May be elevated in growing animals, those with destructive bone disease, carcinomas, and mammary gland tumors, corticosteriods. 2x elevation significant in the dog, any elevation significant in the cat. May be elevated in hyperthyroidism in the cat. Half life 72 hours in dog and 6 hours in the cat.

Gamma- Glutamyltransferase (GGT)

More specific for cholostasis than ALP. Used in dogs, horses and farm animals. Increased levels in urine may indicate tubular damage. Half life 3 days in dogs.

Creatine-Kinase (CK)

Highly expressed in tissues that consume lots of energy- muscle and brain. Indicates insult to skeletal, cardiac and smooth muscle. Levels rise quickly with damage and fall quickly following resolution. Half like less than 2 hours

Accuracy

Quality of being near to the true value

precision

Quality of reproducibility

Polychromasia

Describes the bluish color of immature, non-nucleated red blood cells

macrocytosis

increased red blood cell size, may indicate regeneration

microcytosis

decreased red blood cell size.

Anicytosis

variability in red blood cell size

hypochromasia

due to decreased cytoplasmic staining. Appears as increased central pallor and is caused by insufficient haemoglobin concentration. Immature RBC may also appear hypochromatic

poikilocyte

misshapen RBC usually due to cell fragmentation

howell jolly bodies

basophilic nuclear remnants of RBCs that are common in regenerative anemia

Crenation

Evenly spaced projections from the RBC, usually due to drying artefact, glass artefact, or slow drying of the smear

changes seen with a stress leucogram

increase in neutrophils and monocytes and decrease in eosinophils and lymphocytes

What causes a stress leucogram

corticosteriods (either exogenous or endogenous)

BMBT

Tests primary haemostasis (platelet and vessel wall function) A prolonged time in an animal with a normal platelet count indicated platelet dysfunction (vWD) or vessel was defects

ACT

Assesses secondary haemostasis, intrinsic and common pathways. Test will be prolonged once only 5% of clotting factors remain. ALso will be prolonged with very low numbers of platelets. If clot forms then liquifies again it indicated fibrinolysis or hypofibrinogenaemia

PT

Assesses extrinsic and common pathways of secondary haemostasis. For test to be affected less than 30% of factors remian. Test does not take platelets into account. Very sensitive to warfrin toxicity

APTT

Assesses the intrinsic and common pathways. Prolonged in haemophiliacs, XII def, vitamin K def

FDP

Fibrin degredation products. Present in thrombosis, severe haemorrhage, and DIC. Their absence does not rule out DIC

TT

Thrombin clotting time. Quantifies fibrinogen. Prolonged with the presence of FDPs, in DIC and liver disease

Toxic Change in Neutrophils

Dohle bodies present (small blue-grey cytoplasmic inclusions), foamy blue cytoplasm and pink-purple granules. Indicate bacteremia, toxemia, and generalized infection.

echinocyte

crenated red blood cell. Has evenly spaced protrusions. Drying or EDTA artefact

Puncuate reticulocytes

In cats circulate for 1-2 weeks. Have dense dark staining large clumps of reticulum. Can be seen on NMB stain. Not diagnostic of regeneration because they have a long life in circulation

Aggregate reticulocytes

In cats, become punctuate after one day. Diagnostic of regeneration.

Spherocyte

spherical red blood cell with no central pallor. Created from partial removal of the membrane without disturbing the cytoplasmic volume

Function of the Neutophils

Phagocytose bacteria, destroy or inactivate bacteria, some fungi viruses and other pathogens. Generate inflammatory mediators

Functions on monocyte

phagocytose and kill bacteria, viruses, fungi and protozoa. Phagocytose foreign material and dead cells. Involved in acute and chronic inflammation, immune recognition, and antibody dependent cytotoxicity

Functions of eosinophils

killing helminths, involvement in hypersensitivity reactions, promote inflammatory response and anti tumour response

Functions of Basophils

Immediate and delayed hypersensitivity reactions, prevention and promotion of haemostasis, parasite rejection, and tumor cell cytotoxicity

Stress Leucogram

Brought about by corticosertiods- exogenous or endogenous. Increase in neutrophils and monocytes and decrease in lymphocytes and eosinophils. Neutrophilis due to increase release from marginal pool and increased release from marrow and decreased uptake into tissue

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