3 - plasma proteins and dysproteinemias Flashcards
what are the sites of plasma protein synthesis
liver: most plasma proteins
lymphoid organs: immunoglobulins
what are the functions of plasma proteins
- transport of nutrients, small hormones, waste, drugs
- colloid osmotic effects
- acid- base
- regulatory proteins (cell production and inflammation)
- immune defense
- hemostasis
what is the difference between the total PP concentrations or neonates and adults
neonate 4-6 g/dL
adults 6-8 g/dL
- neonates lacks immunoglobulin until colostrum ingestion and absorption
- immunoglobulins continue to increase as young animals are exposed to a wide variety of antigens
what does a microhematocrit tube measure
packed cell volume (PCV) or Hct
- buffy coat appearance
- plasma appearance
Plasma protein determination
fibrinogen determination
what does a refractometer measure
measure total solids in plasma or urine
- it is a quick screen of total plasma proteins (also used for urine specific gravity)
- based upon the fluid’s refractive index
What causes erroneously increased plasma protein concentrations
- hemolysis in the sample (hemoglobin is not a plasma protein)
- lipemia - interference with light transmission
- marked increases in nonprotein solids (ex high glucose in diabetics or urea nitrogen in kidney dz)
Normal HCT with low, normal, and high TPP
low TPP : GI protein loss, proteinuria, liver dz
normal TPP: normal
High TPP: increased globulin synthesis, dehydration masked anemia
high HCT with low, normal, and high TPP
low TPP: protein loss combined with relative or absolute erythrocytosis
normal TPP: splenic contraction, absolute erythrocytosis, dehydration masked hypoproteinemia
high TPP: dehydration
Low HCT with low, normal, high TPP
Low TPP: substantial ongoing or recent blood loss, overhydration
normal TPP: increased erythrocyte destruction, decreased erythrocyte production, chronic hemorrhage
high TPP: anemia of inflammatory dz, multiple myeloma or other lymphoproliferative dz
how are serum proteins measured
total protein and albumin concentrations in serum (or plasma) are measured separately using 2 different spectrophotometric assays
- total globulin concentration is calculated by subtracting albumin concentrations from total protein concentrations
what migrated the farthest in serum protein electrophoresis
albumin
- stained with coomassie blue
when is serum protein electrophoresis preformed
**- unexplained hyperglobulinemia is present
- immunoglobulin deficiency is suspected **
SPE abnormalities are seldom specific for a given dz
what is albumin
a single homogenous protein
- with a small molecular weight and contains minimal carbohydrates
negative acute phase protein
what can hypoalbuminemia result in for osmotic pressure
edema
what are the transport functions or albumin
- organic and inorganic substances
- cations (mostly Ca++) metabolites, certain hormones, poorly soluble drugs, toxic substances
**hypoalbuminemia = low total Ca++ in blood **
what are acute phase proteins
acute phase proteins (APPs) are proteins with more than 25% change in serum concentrations in response to inflammatory cytokines (IL-1, TNFa, IL-6)
how are APPs categorized
positive = increasing serum concentration
negative = decreasing serum concentration
what does an increased production of positive APPs mean
it is a sensitive indicator of inflammation which can occur prior to the development of an inflammatory leukogram
- this is helpful in some species like cattle and manatees, bc they often do not exhibit prominent leukogram changes in response to inflammation
what is serum amyloid A
a major acute phase protein in all common domestic mammals
- a family of apolipoproteins associated with high density lipoproteins (HDLs)
- a very low conc in normal animals
what is C-reactive protein
major acute phase protein in dogs and humans
- normally present in very low concentrations
what is haptoglobin
**major acute-phase protein in ruminants **
- it binds free plasma Hb irreversibly
- glycoprotein (20% CHO) that migrates in a-2 region
- prevents initial loss of free Hb in urine
-**protects against bacterial infections ** - antioxidant activity
what is fibrinogen
- optimal platelet aggregation
- classified as coagulation factor I
- precursor to fibrin in coagulation
- scaffolding for inflammatory cells, fibroblasts, and endothelial cells when deposited in tissues
- moderate acute-phase protein (APP) that increases in inflammation (most prominent in horses, cattle and goats)
how is fibrinogen estimated
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when is fibrinogen increased
With active inflammation
- cattle and goats
- horses
dehydration (all plasma proteins)
when is fibrinogen decreased
- disseminated intravascular coagulation (DIC) sometimes
- other causes: liver failure, some snake venoms
- heat precipitation estimation method is too insensitive to clearly detect low values
what is ceruloplasmin
- copper transport
- ferroxidase activity facilitates iron mobilization from tissue stores
- plasma antioxidant
- a-2 protein
what is transferrin
- iron binding metalloprotein
- correlates with total iron binding capacity (TIBC)
- iron transport throughout the body
-** negative acute phase protein **
what is ferritin
- lron containing protein, primarily found inside cells
- low concentrations in plasma
- **plasma ferritin correlates with total body iron stores **
- acute- phase protein also so high values might reflect inflammation
explain hormone binding proteins
they bind with small MW hormones, preventing them form being rapidly filtered by the kidney
- corticosteroid-binding protein
- thyroxine-binding globulin
- sex hormone binding globulin
what does antithrombin do
- protease inhibitor
- inhibits thrombin and certain other coagulation factors
- requires GAGs (ex heparin) for optimal activity
what are the negative acute phase proteins
albumin
- reduction in conc is more noticeable in chronic inflammation Dz. conc falls gradually
- reduced production of albumin allows greater increase in AAs available for positive APP production
transferrin
- decreased is not marked. may help limit iron availability for microbes
what does hyperproteinemia cause (a change in plasma conc)
dehydration and hyperglobulinemia
what does hypoproteinemia case (a change in plasma conc.)
- dilution = overhydration
- decreased production
- increased loss
- sequestration in body cavities
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what happens to the fluid balance during dehydration
only the fluid component of blood is lost. proteins and erythrocytes are not lost
- **causes relative hyperproteinemia and erythrocytosis **
what happens to the fluid balance during external hemorrhage
all components of blood are lost equally
- fluid is replaced more rapidly than protein and cells
- causes hypoproteinemia and anemia
what can cause hypoalbuminemia
excessive fluid therapy
- globulins should also be decreased
decreased synthesis
- chronic liver failure (synthesizes albumin)
- inflammation (negative acute phase protein)
- marked hyperglobulinemia (compensatory for osmotic balance?)
loss from the body
-** protein losing glomerulopathy (globulins may be normal bc albumin is a much smaller protein and more easily lost) **
- hemorrhage (also low total globulins)
- protein- losing enteropathy (globulins usually low also)
- severe exudative dermatopathies (globulins may also be low unless increase in response to inflammation)
sequestration
- accumulation of protein rich fluids in body cavities (ex peritonitis)
what can cause hyperalbuminemia
dehydration - globulins should also be increased with normal AG ratio
—– can be seen as an artifact in the assay
what are the causes of hypoglobulinemia
Increased loss (albumin also low)
- hemorrhage
- protein-losing enteropathy
failure of passive transfer of immunoglobulins via colostrum
over hydration (albumin also low)
decreased production of immunoglobulins
– humoral immunodeficiency (rare)
what immunoglobulin dominates in domestic animals colostrum and milk
IgG
how can we diagnose failure of passive transfer in foals and cattle
rapid immunoturbidimetric IgG assays
what are the causes of hyperglobulinemia
hemoconcentration - dehydration
increased immunoglobulins
– immune mediated response
– neoplastic lymphoid cells (usually plasma cells)
increased acute-phase protein concentrations may contribute when inflammation is present
– haptoglobin
–fibrinogen (if plasma is used)
most acute phase protein do not occur in sufficiently high concentration to appreciably increase the total globulin concentration
what does polyclonal hyperglobulinemia mean on an serum protein electrophoresis
polyclonal
- blunt broad peak
Ig from many lymphoid cones
antigenic stimulation
- infections
- immune-mediated
- immune response to neoplasia
what does monoclonal hyperglobulinemia mean on a serum protein electrophoresis
monoclonal
-narrow sharp peak
**Ig (or bence jones protein) from a single lymphoid cone **
neoplasia
- multiple myeloma
- lymphoma/leukemia
rarely non-neoplastic
rarely biclonal
what are Bence jones proteins
immunoglobulin light chains are referred to as Bence jones proteins
explain the production and function of lipoproteins
-synthesis of lipoproteins occurs in GI and liver
- transport of water insoluble lipids in blood
what is the composition of lipoproteins
high MW water-miscible complexes of lipids (triglycerides, cholesterol, phospholipids) and proteins called apolipoproteins
- pseudo micellar particles with hydrophilic apolipoproteins and *charged phospholipids on the surface *
- hydrophobic triglycerides and cholesterol esters inside
what are chylomicrons
very large lipoproteins of low density that remain at the origin when electrophoresis is performed
- formed in the *mucosal cells of the duodenum and jejunum *following digestion of fat in the diet
secreted into lacteals which merge with larger lymphatic vessels and enter the circulation via the thoracic duct
- their core triglycerides are** rapidly hydrolyzed by the action of lipoprotein lipase** in capillary beds (primarily muscle and adipose tissue) where resultant fatty acids and glycerol are metabolized
what is postprandial lipemia
white cloudy plasma because of chylomicronemia after eating a meal containing fat (carnivores and omnivores not herbivores)
- chylomicrons have a short half life in circulation so they are not normally measured in fasted samples
what is the chylomicron refrigerator test
In plasma
- chylomicrons have a density less than water. Therefore they form a “cream layer” in plasma samples allowed to stand overnight in the refrigerator
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what are very low density lipoproteins and what is their function
VLDLs are primarily synthesized by the liver although some intestinal formation can occur
They transport the bulk of the *endogenous triglycerides *
– triglycerides in VLDVs are hydrolyzed by lipase in tissues and residual VLDS are transformed into LDLs
plasma remains “cloudy/milky” after standing overnight in a fridge, but a cream layer is NOT present
what are low density lipoproteins
LDLs arise as metabolic products from VLDLs
- LDLs are the major mechanism by which cholesterol is transported to peripheral tissues
cholesterol is needed as a component of cell membranes and for the formation of steroid hormones
what high density lipoproteins
HDLs are the densest lipoproteins
- HDL precursors are formed in the liver and complete molecules are formed in the plasma by addition of remnants form other lipoproteins
HDLs transport cholesterol from tissues back to the liver in a process termed reverse cholesterol transport
what is the cause of lipemia in plasma or serum
caused by hypertriglyceridemia, but NOT hypercholesterolemia
Increased chylomicrons and/or VLDL
Primary causes
- hyperchylomicronemia in cats with lipoprotein lipase deficiency
- hereditary hypertriglyceridemia in miniature schnauzer dogs (unknown etiology)
Secondary causes
- postprandial hyperchylomicronemia
- diabetes mellitus
- acute pancreatitis
- hyperadrenocorticism
- hypothyroidism
explain the differences in lipoproteins in humans and domestic animals
Humans
- LDLs account for 50% or more of the lipoprotein content present in plasma of fasting humans
- cholesterol contained within LDLs contributes to the prevalence of atherosclerosis in people
Domestic animals
- HDLs account for about 50% to 75% if the lipoprotein content present in the plasma of most fasting domestic animals
- High HDLs likely account for the rare occurrence of atherosclerosis in domestic animals
Atherosclerosis is a condition that occurs when plaque builds up and hardens in the inner lining of your arteries, causing them to thicken and narrow.
