Clinical Pathology Chapter 8
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Clinical Chemistry (or serum chemistry)
Refers to chemical assays which measure the level of a dissolved substance normally carried in the blood (plasma and/or serum) or the amount of a substance not normally found in blood which has been released into the blood from damaged of destroyed cells.
Results of chemical chemistry can be affected by a number of factors including
sample collection, anticoagulant used, and improper sample handling.
Different factors can influence the results of chemical chemistryies
- Chemical contamination
- Improper labeling
- Patient influences ie. fasting, postprandial (after eating) lipemia
Much of clinical chemistry involves
the measurement of blood enzyme levels and their correlation to organ dysfunction.
proteins inside cells. They induce chemical changes in other substances (called Substrates) to produce a new product, but are not themselves changed. Enzymes often increase the rate of a biochemical reaction by acting as a catalyst tot the reaction.
Most enzymes are formed and function intracellulary
so they are found in the highest concentrations within cells. for this reason the blood level of enzymes is low in a healthy animal. The blood level for an enzyme may be elevated if the enzyme has leaked out of damaged cells, or if the cells have increase production of that enzyme and the excess has leaked out of the cells into the blood.
Since many exnzymes are relatively specific to certain organs,
the increased blood level of a certain enzyme may indicate a problem in the organ that produces it.
Diagrammatically, enzyme reaction can be as defined as
- S + E --> P + E
- E= enzymes
- P= product
- The substrat is converted by the enzyme into the product, leaving the enzyme unchanged.
Most enzyme assay methods are classified as either an endpoint or a kinetic assay.
The product from enzymatic action interacts with a reagent to produce a color complex present, which indirectly refelects the concentration of enzyme present in the sample.
Measures the rate of the enzymatic reaction while it is in progress and usually involves serial measurements of the product concentration per unit of time. The rate of the product formation, and hence the rate of the reaction, is proportional to the amount of enzyme present.
Enzyme activity can be affected by a number of factors
Enzyme activity is often inhibited by los temperature and accelerated by high temperature
- Each Enzyme works at a certain optial temperature which must be maintained throughout the test.
- Enzyme, which are porteins, can be denatured by temperature and pH extremes or by organic sovents
assays are given the name of the developer In an attempt to standarize units
The international Unit (IU) was developed by
the international union of biochemistry.
Enzymes are usually named for the substrte on which they act. Teh name of most enzymes end with the suffix
- Lipase is an enzyme that hydrolyzes lipids
- Lactate dehydrogenase oxidizes lactate to pyruvate
An isoenzyme is one of a group of enzymes with similar catalytic activities but different physical properties.
Alkaline phosphotase occurs in
- the cells of hepatocytes and bones.
- Then enzymes in the different tissues are similar, but not identical, and are called isoenzymes.
- The total serum alkaline phosphates level reflects all of the isoenzymes.
- The total serum alkaline phosphotase level reflects all of the isoenzymes.
Liver enzyme Assay associated with hepatocellular damage
Alanine aminotransferase (ALT)
- Previous name was serum glutamic pyruvic transferece (SGPT)
- In dogs, cats, and primates, that major source of ALT is hepatocytes: it is considered a liver-specific enzyme in these species
What is ALT used to test for
- uses as a screening test for liver damage but does not diagnose any specific liver disease.
- There is often no correclation between the blood level and the severity of the hepatic damage.
- Not liver slecific in other species; other sources of ALT include renal cells, cardiac muscle, skeltal muscle, and the pancreas Sample collection is plasma or serum
- Hemolysis and lipemia can artifically increase the enzyme concentration
Sorbital dehydrogenase (SD)
- Primary sources of SD is hepatocytes, especially i large animals
- Since ALT is non specific in large animals, SD is usefully in specifically diagnosing hepatic damage in large animals
- Sample collection is plasma or serum. SD is unstable. It's activity deteriorates rapidly so the assay must be done within 12 hours of collection.
- Hemolysis does not appear to affect the results
Previous name was serum glutamic oxaloacetic transaminase (SGOT)
- Source of AST include hepatocytes, erythrocytes, cardiac muscle, kidney cells, and pancreatic cells.
- AST is non specfic. However the most common cause of AST elevation is hepatic disease, muscle inflammation or necrosis, and hemolysis.
- Sample collection is plasma or serum
- Lipemia can artifically increase the enzyme concentration.
Liver Enzyme Assays Associated with Choloestasis
- Bile, which is produced by liver cells, is stored in the gallbladder for release into the intestine on demand.
- When bile is blocked from completing this cycle (biliary obstruction), it is called chloestasis.
- Blood levels of certain enzymes become elevated with cholestasis.
Alkaline Phosphatase (AP)
- AP occurs as an isoenzyme in many tissues including the liver, bone cells, and cartilage cells.
- In young animals, most AP comes from osteoblasts (bone cells) because of active bone development. In older animals, most AP comes from the liver as bone development stablizes.
A hepatocyte is a cell of the main tissue of the liver
- Hepatocytes increase production of AP in response to
- intrability pressure.
- Hemolysis does not appear to affect the results.
Gamma Glutamyltransferase (GGT) - Equine
- Primary sours of GGT is the liver.
- Other sources of GGT include kidneys, pancreas, intestine, and muscle.
- Relative specific of obstructive liver disease
- Hemolysis does not appear to affect the results
Other liver assays (non enzymes)
Bile acids are synthesized
from cholesterol in liver cells. After synthesis they are secreted into the bile canaliculi and stored in the gall bladder until they are carried in the bile to the intestine.
In the intestine bile acids aid in
- fat digestion. Most of the bile acids 90-95% are reabsorbed back into the bloodstream to be used from the terminal part of the small intestine and returned to the liver and to restart the same cycle.
- If the liver is damaged, it cannot take in all of the returning bile acids so the blood bile acid levels rise.
Readings of the bile acids are read after a
- 12 hour fast, then 2 hours after eating (postprandial) for consumption.
- Normal 12 hours after fasting:
- < 10umol/L
- Normal 2 hours after eating (postprandial)
Bilirubin Assay- Liver
Bilirubin is a
- breakdown of the heme portion of hemoglobin
- Icterus (jaundice) is the yellow staining of tissue caused by increased amounts of bilirubin in the blood (hyperbilirubinemia)
- Interpreting the amounts of a bilirubin assay requires understanding of normal hemoglobin metabolism, and the mechanisms which can cause hyperbilirubinemia.
Normal Heme Metabolism
- When hemoglobin is broken down, the globulin and the iron portions are recycled.
- The heme portion cannot be recycled and needs to be discarded
- Heme is broken down fast by macrophages, then by the liver, then excreted through the intestine.
Hemoglobin from the old RBC, and free hemoglobin from hemolysis, is taken up by
- Macrophages separate the iron, the globulin, and the heme (waste portion)
- the heme portion is converted to bilirubin
- The bilirubin is released into the bloodstream where it quickly binds to the plasma protein albumin.
- The bilirubin-albumin complex (unconjugated bilirubin or indirect bilirubin is transported to the liver.
- In the liver, the albumin is removed and the bilirubin is conjugated with glucoronic acid (conjugated bilirubin) or direct bilirubin)
- This conjugated is excreted in the bile where it goes to the intestine
Unconjugated bilirubin (bilirubin bound to albumin) is delivered to the liver for processing.
Bilirubin is processed in the liver and conjugated to glucoronic acid to form conjugated bilirubin
- Conjugated bilirubin is excreted in the bile via the bile canaliculi.
- Anything which interferes with this cycle of bilirubin excretion will result in hyperbilirubinemia. Bilirubin, both conjugated and unconjugated will stain tissues yellow (yellow/jaundice)
Ictrus (jaundice) occurs whenever the
- levels of bilirubin rise in the blood (hyperbilirubinemia)
- Bilirubin stains all tissues a yellowish color, however it is usually evident only on pale or shitish tissues.
- In animals icterus is best observed in the sclera of the eyes and on the gums. It is also evident in the tissues during postmortem examination.
Causes of Hyperbilirubinemia
- Increased bilirubin production
- Decreased uptake into the lover cells - liver damage
- Genetically impaired liver conjugation
- Obstruction of the biliary system
Increased Bilirubin Production
- Results in increased production of bilirubin
- More bilirubin is conjugated and excreated than normally, but the cinjugation mechanism is overwhelmed, and an abnormally large amount of unconjugated bilirubin is found in the blood.
Unconjugated bilirubin is not water soluble and cannot appear in the urine because it is
- bound to albumin.
- If bilirubin becomes unbound to albumin (due to hypoalbuminemia) it is particular toxic to the brain (Hemolysis)- AIHA
- Auto Immune Hemotyltic anemia
Decreased uptake by liver cells
- When hepatocytes are sick or damaged, then may be incapable of handling the normal load of bilirubin presented to them.
- As a result, unconjugated bilirubin accumulates in the bloodstream
Genetically Impaired liver conjugation
- Some animals are born with a genetic enzyme difiency which prevents conjugation of bilirubin in the liver cells.
- Unconjugated bilirubin is retained by the body.
Obstruction of the Biliary system
- Biliary calculi (stones) can cause backup and reabsorption of conjugated bilirubin,
- Consequently, conjugated bilirubin returns to the blood and accumulates
- Conjugated bilirubin is water soluble and increased amounts on the blood often pass into the urine leading to bilirubinuria.
Other Liver Assays (non-enzyme)
- Icterus is accompanied by (and often precede by) an increased in the total serum bilirubin
- Total serum bilirubin is combination of
- Indirect reacting bilirubin (unconjugated bilirubin)
- direct reacting bilirubin (conjugated bilirubin)
- Total serum bilirubin and conjugated bilirubin can be directly measured; unconjugated bilirubin is calculated by subtracting the conjugated valve from the total bilirubin valve.
- ExampleTotal Bilirubin-direct bilirubin = indirect
- 15mg/dl - 2mg/dl = 13mg/dl
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