Clinical Biochemistry 2 Flashcards
Total proteins in diagnostics.
Comprises albumin and globulin fractions.
Measure globulins by subtracting albumin from total protein.
Ratio between albumin and globulin can narrow down the differentials list.
Estimated by ‘total solids’ (TS) on refractometer.
- TS also incorporates other solids – cholesterol, glucose, urea, (but not electrolytes – hence raised baseline). (Rough estimate).
Specific other proteins to consider.
Acute phase proteins – that increase and decrease in inflammation. E.g. CRP.
Can be used as worry-metres.
Clotting factors.
- Albumin size, charge and activity.
- Where is albumin synthesised?
- Albumin protein type?
- Albumin function?
- What analytes are albumin-bound?
- Why does relative hyperalbuminemia occur?
- Large (65kDa), negatively charged (Repelled from glomerular surface so does not cross glomerulus very well), osmotically-active.
- Liver.
- Negative acute phase protein.
- Maintaining colloid oncotic pressure – so a decrease in inflammatory state will cause a loss of water from the blood.
- Calcium – changes in albumin affect total calcium readings (as ~1/2 circulating calcium stuck to albumin).
Thyroid hormones.
Steroids and fatty acids. - Haemoconcentration often as a result of dehydration (also increased total protein).
What can cause hypoalbuminemia?
Reduced absorption so malnutrition; GI disease.
Reduced production
- Hepatic dysfunction
- APP (acute phase protein) response
Increased loss
- Protein losing enteropathy (PLE). E.g. parvo. (albumin and globulins lost at same time so + and - charge).
- Protein losing nephropathy (PLN). Albumin-selective.
- Haemorrhage. E.g. RTA, fleas, ticks, GI, renal.
- Severe exudative disease incl. third-spacing e.g. ascites (+/- losses via drainage). E.g. burns.
Hypoproteinaemia differentials.
Hypoproteinaemia.
Distinguish whether pan-hypoproteinaemia or isolated hypoalbuminemia.
If pan-hypoproteinaemia, consider:
- haemorrhage.
- Severe exudative disease.
- protein losing enteropathy.
- third spacing.
If isolated hypoalbuminemia, consider:
- mild-moderate.
- mild-marked.
If mild-moderate:
- (negative) APP response.
If moderate-marked:
- liver failure.
- protein losing nephropathy.
- protein losing enteropathy (w/ inflammatory component).
How can the differentials for hypoproteinaemia be worked through?
With haematology, serum biochemistry, liver function testing, urinalysis, advanced imaging.
- What are globulins?
- What type of globulin contributes most to globulin fraction? – Where are these synthesised?
- Causes of hypoglobulinaemia?
- Every other protein other than albumin in serum/plasma. They are mostly very large proteins.
There are alpha, beta and gamma globulins. - Gamma globulins, which are antibodies (aka immunoglobulins) – synthesised by B-lymphoid (plasma) cells.
- Immunological incompetency e.g. failure of passive transfer (colostrum ingestion).
Protein loss (w/ concurrent hypoalbuminemia).
– Caused by haemorrhage, exudative disease, and PLE (NB. not in PLN or liver disease).
- What causes hyperglobulinaemia?
- Differentiation between types?
- Mild-moderate commonly accompanies inflammatory / infectious diseases.
- APP response.
- Polyclonal gammopathy (diverse antigen stimulation).
Marked (less commonly mild-moderate) secondary to B-cell neoplasia (e.g. multiple myeloma; lymphoma). - Serum protein electrophoresis (SPE).
Hyperglobulinaemia investigative pathway.
Distinguish if mild-moderate or moderate-marked.
If mild-moderate, consider whether:
- Other features of inflammation present and evaluate for inflammatory / infectious disease e.g. immune-mediated, severe skin / dental disease.
- No other evidence of inflammation so consider moderate-marked differentials.
If moderate-marked:
- Run serum protein electrophoresis:
– If monoclonal, evaluate for B-cell neoplasia (most likely). Very rarely chronic inflammatory disease causes monoclonal (or restricted oligoclonal) gammopathies.
– If polyclonal, review for inflammatory / infectious disease e.g. leishmaniosis, ehrlichiosis, FIP.
- What happens to negative APPs in inflammation?
- Give examples of negative APPs.
- What happens to positive APPs in inflammation?
- Give examples of positive APPs.
- Decrease.
- Albumin and transferrin (iron sequestered –> inhibits RBC production).
- Increase.
- C-RP (dogs)
serum amyloid A (SAA) in horses (pre-racing inflammation).
a1-acid glycoprotein (A1-AGP) – cats.
Haptoglobin – ruminants.
- How is glucose acquired?
- What if inadequately supplied?
- Use?
- Normal glucose range for dogs and cats?
- How glucose glucose controlled in the body?
- What happens when glucose levels drop too low?
- ” “ increase to too high?
- Ingestion in diet and end product of carbohydrate breakdown.
- Synthesised in the liver.
- Utilised by all cells (incl. bacteria) for energy.
- 3.5-5.0 mmol/L.
- Under hormone control.
Insulin is released in response to hyperglycaemia.
Various hormones (importantly glucagon and catecholamines e.g. adrenaline) released in response to hypoglycaemia or rapidly decreasing glucose concentrations. - Ultimately coma, seizure, death.
- Osmotic impact on blood.
Cuts and abrasions more likely to become infected with bacteria.
- Glucose measurement.
- Mild postprandial hyperglycaemia.
- Point of care (in-house) glucometers.
Lab via biochemistry machine (external).
Where there is a delay between sampling and testing, ideally use OxF tubes. So the cells in the sample do not get a chance to use up the glucose that is in that sample. - Fasted samples from cats and dogs.
Consider stress as well e.g. urine samples to be taken from felines days after vet appts and not straight away.
Avoid fasting equine spp.
Fasted samples not possible in ruminants.
– in lactating cows, mammary vein glucose lower than jugular vein glucose.
- In what breeds is hypoglycaemia commonly seen? – Why?
- Hypoglycaemia differentials?
- Toy breeds – Low fat (and therefore glycogen) reserves so if stop eating for reasons such as GI disease, likely to become hypoglycaemic, often to the point of loss of consciousness.
- Inadequate synthesis due to:
- hepatic dysfunction / portosystemic shunting.
- hypoadrenocorticism (Addisons).
Excessive consumption e.g. sepsis.
Excess hypoglycaemic agents.
- insulin (syringes, persons).
- Xylitol (toxicity). – sweet taste kick starts insulin where it is not needed.
- Oral hypoglycaemics e.g. w/ diabetic owner or newer diabetic drugs.
Paraneoplastic e.g. insulinoma, hepatomas, IGF-2 producing tumours. OR massive cancer using up a lot of glucose for energy.
Investigating hypoglycaemia.
Consider signalment.
Liver dysfunction / portovascular anomaly e.g. shunt.
- Routine blood analysis –> ammonia, BAST –> advanced imaging.
Hypoadrenocorticism.
- Basal cortisol (screen) –> ACTH stim (diagnostic).
Sepsis
- T-FAST / A-FAST / other imaging.
Neoplasia
- imaging – hepatoma; IGF-2 producing tumours (typically smooth muscle); insulinoma (pancreas and metastasis).
- glucose WITH insulin (NB: during hypoglycaemia as insulin release may be episodic). –> insulin conc. appropriate?
Hyperglycaemia causes?
Transient (i.e. physiological)
- Stress-associated hyperglycaemia common in cats.
- Post-prandial (monogastrics).
Persistent (i.e. pathological)
- Diabetes mellitus = insulin insufficiency.
– glucosuria; =/- ketonaemia / ketonuria; usually increase serum fructosamine.
- Pre-diabetes mellitus (w/ potential to progress).
– obesity
– steroids –> exogenous vs endogenous (hyperadrenocorticism; pars pituitary intermedia dysfunction).
– Hypersomatotropism (i.e. acromegaly) – overproduction of GH due to brain tumour.
