C10 Laboratory Evaluation of Lipids & Proteins Flashcards
Micelles contain:
Long chain fatty acids
Triglycerides
Cholesterol
Vitamins AEDK
Lipid digestion overview
- come in through digestive tract, where lipids are emulsified by bile salts into micelles
> pancreatic lipase interacts with micelles and tears them apart into different types of fatty acids
> these products pass into mucosal cells
what causes lipemic samples?
- triglycerides contained into chylomicrons
- post-prandially, chylomicrons come into the body through the intestine and travel into various tissues
> the triglycerides in them are stripped out and used for other purposes
> most commonly a lipemic sample is caused by triglyceride-containing chylomicrons
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- nonpost-pranidal, we can can have hyperlipidemia involving VLDL, which also contain triglycerides
Post-Prandial (Physiologic) Hyperlipidemia
- when does this occur? what does this mean for blood collection?
- when triglycerides in the chylomicrons are high
- increased chylomicrons starting 1-2h after a meal, peaks at 6 hours, tapers off at 16h
<><> - Lipemia > interferes with many commonly analyzed components of serum
- Fast 12 h before collecting blood
- If still lipemic – additional tests > some disease causing pathologic hyperlipidemia
Lipemic Blood Sample = Interference!
- how does it interfere with light and mess up our samples?
- The line on the refractometer – false ↑ TP
- Biochemical analyzer > spectrophotometric techniques
Lipemic Blood Sample = Interference!
- how does this interfere with cell membranes and mess up our samples?
- RBCs – enhances hemolysis
Clinically Important Lipids in Blood
- Triglycerides
* Nonesterified fatty acids (NEFAs, aka free fatty acids, LCFA) - Cholesterol
- Ketones (as fat-related compounds)
Hypocholesterolemia:
- seen when, most commonly?
- Liver failure / portosystemic shunt
* Often results in hypocholesterolemia
> not enough liver available to make cholesterol, or nothing is going to the liver so it can’t do anything
* NB: Animals with concurrent cholestasis
> no bile or cholesterol is leaving, backs up into blood - Hypoadrenocorticism (Addison’s disease)
> unknown etiology, perhaps immune mediated
Hypocholesterolemia and hypotriglyceridemia concurrently:
- seen when?
- Maldigestion / malabsorption
> maldigestion = no pancreatic lipase to break down micelles. Malabsorption = its just not getting in.
> steatorrhea - Protein losing enteropathy
> lymphoma, lymphangectasia… - Cachexia/starvation
Hyperlipidemia - categories
- Primary hyperlipidemia – inherited
> schnauzers - Secondary hyperlipidemia – everything else
> more common
Secondary Hyperlipidemia – Pathologic Altered Clearance or Cellular Uptake
- what is this associated with in cats, dogs, and horses, usually? (very generally)
- some sort of endocrinopathy
Secondary Hyperlipidemia – Pathologic Altered Clearance or Cellular Uptake
- specific causes in the dog
Dog
* Hyperadrenocorticism, hypothyroidism, diabetes mellitus (DM), cholestasis, pancreatitis, obesity
* Protein-losing nephropathy (PLN), glucocorticoids, phenobarbital
* Idiopathic hyperlipidemia of miniature schnauzers with pancreatitis < mechanism not determined
Secondary Hyperlipidemia – Pathologic Altered Clearance or Cellular Uptake
- specific causes in the cat
- Negative energy balance (NEB), cholestasis, hyperthyroidism, DM
- Protein-losing nephropathy (PLN), obesity, glucocorticoids
- pancreatitis < mechanism not determined
Secondary Hyperlipidemia – Pathologic Altered Clearance or Cellular Uptake
- specific causes in the ruminant, pony, miniature horses, donkeys, sheep, llamas
- Negative energy balance
- Pituitary Pars Intermedia Dysfunction & Equine Metabolic Syndrome – horses & ponies (obesity)
- Pregnancy toxemia of sheep
Lipid Metabolism in Ruminants Assessment in the Transition Period
- what do we measure? what do we see?
↑NEFAs – pre-calving
* = negative energy balance / stress conditions
* Mobilization of fat from reserves
* ↑ risk:
> LDA, subclinical ketosis, RFM, 1- 1.5 kg/d ↓ milk production, early culling
* If prolonged – fatty liver
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Beta-hydroxybutyrate (β-OHB) – post-calving
* NEB
* Ketosis, fatty liver
* Pregnancy toxemia in sheep
Protein Measurement (g/L)
- what and where?
- Plasma protein =
a. Albumin
b. Globulins
c. Fibrinogen – inflammation – LA - Serum total protein (TP)
a. Albumin
b. Total Protein - albumin = globulins
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- Serum protein electrophoresis quantitates & separates
* Albumin and the 5 fractions of globulins in serum
Hyperfibrinogenemia causes
- Inflammation in LA
- Dehydration (hemoconcentration)
Hypofibrinogenemia causes
- Consumptive coagulopathies – DIC
- Decreased production
> Liver failure; liver is what produces fibrinogen
Hyperproteinemia – The Patterns
- what might we see?
↑ albumin ± ↑ globulins
* Dehydration (hemoconcentration)
>Skin tent / PCV / urea / creatinine / USG…
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↑ globulins and ↓ albumin
* Increased protein synthesis
> Infectious & non-infectious inflammatory disease
> B-cell neoplasia (lymphoma / multiple myeloma)
> in this case alnbumin decreases to make sure plasma oncotic pressure is balanced
how can we tell normal values in an electrophoresis measurement from a chronic inflammatory response from a monoclonal gammopathy
NORMAL:
-tons of albumin, everything else pretty low
CHRONIC INFLAMMATORY:
- lower albumin
- increased alpha-1 and -2 peaks (pro-inflammatory cytokines)
- decrease in beta region (negative acute phase reactant here)
- broad-based increase in gamma globulins due to stimulation of B cells and plasma cells
MONOCLONAL GAMMOPATHY
- spike in gamma region
> One clone of a single type of neoplastic plasma cell, making a single type of immunoglobulin
- As tall or taller & as narrow or narrower than the albumin spike
Monoclonal Gammopathy – Multiple Myeloma
- required findings to diagnose?
Need 2 of the following 4:
1. Monoclonal gammopathy
2. Increased plasma cells in bone marrow
* >20%
* unusual to see plasma cells in peripheral blood
3. Bence-Jones proteinuria (light chains)
4. Lytic lesions in bones (rare in cats)
Common Causes of Hypoproteinemia
- Increased loss
- Dilution
- Inadequate production
- Inadequate intake
Hypoproteinemia – The Patterns of Loss
↓ albumin and ↓ globulins
- why?
↓ albumin and ↓ globulins
* Hemorrhage / blood suckers
* Protein Losing Enteropathy > gut becomes ‘holey’ and we lose very large globulins and smaller albumin out the back end (lymphangectasia, lymphoma… can cause)
* Malabsorption/maldigestion
* Cachectic states
> inadequate plane of nutrition
* Exudative skin disease (burns / large wounds - plasma oozes out, can’t be recaptured)
“Panhypoproteinemia”
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– Dilution
* Hemodilution (eg. LRS)
* Repeated effusion draining
what does panhypoproteinemia look like on the electophorogram?
- decreased albumins
- decreased gamma globulins
- decreased beta and alpha-2 region
when do we see hypoalbuminemia
↓ albumin
* PLN > only place we will see decreased albumin but not globulins is through the kidney
* Hallmarks are low albumin and high cholesterol
* Hypercoagulable
Hypoproteinemia – Inadequate Production
- what will we see?
↓ albumin and ↑ globulins
- Advanced liver disease <20% functional tissue - not filtering antigens, they end up in lymph nodes, antigenic stimulation of B / plasma cells
> not enough liver to make albumin - Cirrhosis, neoplasia, necrosis, inflammation
- PSS leading to hepatic atrophy
> no materials to make albumin
Hypoproteinemia
- when do we see just ↓ globulins
- Failure of passive transfer (FPT)
Which of the following causes a falsely increased reading in total solids protein (i.e., plasma protein measurement estimate using the refractometer)?
- Hyperbilirubinemia (icteric plasma)
- Lipemia
- Hemolysis
- Lipemia
- yes - Hemolysis
- moderate to severe hymolysis is associated with a false increase as well
Which of the following are causes of hypolipidemia? Select all that apply.
A. Hyperadrenocorticism
B. Malabsorption/maldigestion
C. Hypothyroidism
D.Protein losing enteropathy
B. Malabsorption/maldigestion
D.Protein losing enteropathy
Which of the following are causes of hyperlipidemia? Select all that apply.
A. Hypoadrenocorticism
B. Hyperadrenocorticism
C. Hypothyroidism
D. Hyperthyroidism
E. Protein losing Nephropathy
F. Negative energy balance
B. Hyperadrenocorticism
C. Hypothyroidism
- Yes, in dogs
D. Hyperthyroidism
- Yes, in cats
E. Protein losing Nephropathy
F. Negative energy balance
- Yes, often in overconditioned animals that experience a sudden decrease in food intake – decreased beta-oxidation of fats
While species differences exist at the fine detail level, what is the general sequence of events in the development of fatty liver?
A. Overconditioning > acutely off food > lipid mobilization > hepatocellular lipid accumulation
B. Acutely off food > lipid mobilization > overconditioning > hepatocellular lipid accumulation
C. Lipid mobilization > hepatocellular lipid accumulation > acutely off food > overconditioning
D. Hepatocellular lipid accumulation > lipid mobilization > overconditioning > acutely off food
A. Overconditioning > acutely off food > lipid mobilization > hepatocellular lipid accumulation
