CO6 1. Quality Assurance 2. Clinical Enzymology Flashcards

1
Q

Laboratory Quality Assurance Program
- whats this?

A
  • Procedures and strategies to ensure that a
    laboratory reports trustworthy results
  • Quality assurance programs assure both precision
    and accuracy of test results
    – e.g., run control samples
  • CRITICAL that your laboratory has a quality control
    program
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2
Q

Pre-Analytical Considerations – Part of QA, too!

A
  • Careful test selection
  • +/- Fasting
  • Correct tube
  • Order of fill
  • Adequate volume
  • Collection technique
  • Label tube correctly
  • Fill out requisition form
  • PROVIDE HISTORY
  • Correct storage /
    transportation To
  • Time lapse before analysis
  • Always check with the laboratory prior to sending special samples
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3
Q

You Can Help! Post-Analytical Variables - Interpretation If something doesn’t fit:

A
  • Be sure you’ve ordered the correct test for the case
  • Understand reference intervals and cut-points
  • Consult with colleagues / pathologists
    <><>
  • Always interpret results in light of clinical picture
    – EDTA contamination of serum tube
    – Significant laboratory vs clinical changes
    – Amylase increases with decreased GFR
    – Platelet clumps, band neutrophils
    > always look at a blood smear
    <><>
    Treat the patient, not the lab results
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4
Q

get a bunch of errors on a biochem printout, what to do?

A
  • Look for an error message on the printout
  • if there are errors, how long has this been going on?
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5
Q

should we use a lab or in house lab that does not maintain quality control?

A

A laboratory that does not maintain a Quality Assurance Program cannot ensure its test results are valid, and should not be used
Same goes for in-house laboratory equipment!

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6
Q

Disadvantages of In-House Tests

A
  • Records are legally required
  • Reference intervals?
  • The in-house test result will be different than the reference laboratory result!
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7
Q

Advantages of Commercial Veterinary Laboratories

A
  • Gold Standard
    – Properly validated reference intervals
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8
Q

should each lab generate its own reference intervals? how many animal samples required?

A
  • Should be generated by each lab
  • Ideally >100 animals, minimum 40
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9
Q

Isoenzymes definition

A
  • differ in animo acid sequence but catalyze the same reaction
    – Occur in one or multiple tissues
    <><>
  • Most are present in several tissues = isoenzymes
    – Catalyze same reaction but originate from different tissues
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10
Q

Increased enzymes enter plasma by:

A
  1. Injury
  2. Decreased excretion
  3. Increased production
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11
Q

“Ideal” Diagnostic Enzyme qualities

A

Measured in serum
Assay simple to perform
Single cell type or tissue source
Increase = clinical disease process

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12
Q

how do we measure enzyme activity? decreases with what?

A
  • have substrate in solution
  • add enzyme
  • measure product
    <><>
    Decreases with time / temperature
  • critical for some enzymes
  • consider if a remote or ambulatory practice
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13
Q

what does it mean if we see increased enzyme activity in a lab result?

A
  1. Tissue injury & leakage of enzyme
  2. Increased production (induction)
  3. Decreased excretion
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14
Q

what does it mean if we see decreased enzyme activity in a lab result?

A

rarely significant

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15
Q

Tissue specificity of enzymes allows localization of

A

– Injury
– Increased production

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16
Q

Patterns of enzyme increase help us

A

– Understand disease processes
– Make diagnoses

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17
Q

how can we differentiate isoenzymes?

A
  • by half life
    > eg. ALP half-life in dogs is different depending on tissue source: 3d from liver, only 6 min from intestine, placenta, kidney
    > Less commonly, ALP can be increased from intestinal inflammation, or bone sources
  • other tissue specific enzymes
    > eg. ALP and ALT are found in liver
    > ALT also found in muscle
    > damaged liver: increased ALT (and sometimes ALP)
    > ALT also occurs in skeletal muscle, but so is CK
    > if we have eg. a broken femur, we see that evidence of catastrophic damage, as well as elevated CK, so we can be more confident that ALT is from muscle
  • route of excretion
    > kidney origin GGT gets peed out; even if we have damage to renal tubular epithelial cells, GGT will not be increased
    > however, if we have induction of GGT in the liver, we see increased GGT in biochem profile
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18
Q

Leakage Enzymes
- where are they found? when are they increased?

A
  • Cytosol, organelles or both
    > Injury
    a) Sublethal / reversible
    b) Necrosis
    > ↑ activity detected within hours of injury on biochem profile
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19
Q

Most important liver leakage enzymes

A

ALT
AST
GLDH - used more for large animal
SDH - used in large animal

20
Q

Most important muscle leakage enzymes

A

CK
AST
(ALT) - requires massive damage

21
Q

Most important RBC leakage enzymes

A

AST - hemolysis
(CK)

22
Q

amylase is a leakage enzyme from where?

A

pancreatic acinar cells

23
Q

lipase is a leakage enzyme from where?

A
  • pancreatic acinar cells
  • hepatic tumours
24
Q

Induced Enzymes
- usually found where? when do we see them?

A
  • usually attached to cellular membranes; plasma membrane, or organelle membrane
  • stimulus zaps the cell and tells it to increase production
    > days rather than hours to increase
    > when increased, the enzyme falls off the membrane, enters blood, increased activity can be measured
  • sometimes, if we have massive damage, these will also be released
    <><>
    Only two induction enzymes:
  • ALP
  • GGT
25
Q

two induction enzymes? where are they from?

A

Liver
- ALP, GGT

Bone
- ALP

26
Q

administration of prednisone will induce what enzymes in the liver, in dogs? when else can we see these enzymes?

A

ALP, GGT
- also see with cholestasis, or when we have hyperbilirubinemia
> induction enzymes associated with the irritation that occurs from bile sitting between hepatocytes in the canaliculi

27
Q

What enzyme is induced in hypothyroid cats? when else can we see it?

A

bone origin ALP
- also from lytic lesions involving bone, like multiple myeloma (holes on radiographs), bone tumor

28
Q

Leakage vs Induced Enzymes
- why is the difference not clear cut?
- interpretation depends on what?

A

– Loss of leakage enzymes may lead to increased production
– Acute injury may cause a rapid increase in induced enzymes
<><>
Interpretation
* Depends on:
– Sources of enzyme & half-life
– Excretory route
– Assay method
– Clinical history

29
Q

half life of CK compared to AST? how can we use that to our advantage?

A
  • CK has shorter half-life than AST
    > CK peaks early and decreases early
    > AST takes longer to increase. Never goes as high as CK, then takes longer to decrease
  • if there is ongoing muscle damage, CK will remain high upon a second measurement!
    > if first measurement has high CK and lower AST, and second has lowering CK and higher AST, we know we are winning
30
Q

amylase can be increased with pancreatitis. how is it excreted? how can we use this info to help rule out pancreatitis?

A
  • excreted renally
    > any reason for a decrease in GFR, eg. dehydration, cardiac disease, shock, kidney disease, can also lead to increased amylase
  • if we see increased amylase, look at urea and creatinine (garbage products that are excreted renally)
    > are they high? then we likely have a decreased GFR due to kidney disease
    > use U/S, rest of clinical picture to rule out pancreatitis
31
Q

does it matter if we use different assays and get different numerical results, but they are trending in the same direction?

A

no this is fine, the assays just use different methods. Don’t get stuck on it.

32
Q

if we see elevated AST in an animal with hemolytic anemia, should we be worried about liver and/or muscle?

A
  • not really, we know it has hemolytic anemia which can increase AST from RBCs
  • resolve hemolytic anemia and check that AST trends down
33
Q

what should we remember about the big picture when looking at enzyme values? 3 important considerations

A
  • Biological variation
    – Age, sex, species, breed, physiological status
  • Effects of drugs
    – Steroids, anticonvulsants
  • Artifacts
    – Collection, storage, transit time, assay type
34
Q

Serum Enzymes Summary
- synthesized where?
- recognized how?
- increased enzyme activity meaning?

A
  • Synthesized by various cell types – some serum activity normally present
  • Recognized by increased activity in serum
  • If enzyme activity ↑ there must be cellular damage or
  • Production of enzyme increased due to a stimulus or
  • Elimination of enzyme from body is decreased
    – e.g., amylase & lipase are excreted renally
    – In dogs and cats they can be increased with decreased glomerular filtration rate
35
Q

why is DGGR lipase better than regular lipase for measuring?

A

Lipase - Pancreatic acinar cells, hepatic tumours
> DGGR lipase (AHL and Antech) is less affected by decreased renal excretion–more trustworthy!

36
Q

ALP is found in which organs / situations?

A
  • liver
  • bone
  • sometimes intestine
  • prednisone administration in dogs
37
Q

GGT is found in what organs / situations

A
  • liver
  • prednisone administration in dogs
38
Q

ALT is found in what organs / situations

A
  • liver
  • muscle if damage is extreme
39
Q

AST is found in what organs / situations?

A
  • liver
  • muscle
  • hemolysed sample
40
Q

CK is found in what organs / situations?

A
  • muscle
  • hemolysed sample
41
Q

GLDH is found in what organs / situations?

A

liver

42
Q

regular lipase is found in what organs / situations?

A
  • pancreas
  • Decreased GFR
43
Q

DGGR lipase is found in what organs / situations?

A

pancreas

44
Q

amylase is found in what organs / situations?

A
  • pancreas
  • decreased GFR
45
Q

which enzymes are only used in large animal? small animal? both?

A

LA only: GLDH

SA only: ALP, ALT, lipase, amylase

Both: GGT, AST, CK