Protein & Protein Disorders Flashcards
What are the 2 types of plasma proteins? What are their 4 overall functions?
albumin and globulins
- exert colloid osmotic pressure
- participate in immune/inflammatory responses and clotting processes
- nutritive functions
- aid in the maintenance of acid-base balance
What 2 systems synthesize plasma proteins?
- liver
- immune system - cytokines, immunoglobulins
In what animals do age-related changes in plasma and serum protein concentrations occur? How does this change occur?
mammals and birds
- plasma and serum protein concentrations are low at birth and increase after the absorption of colostrum
- declines over 1-5 weeks as colostrum is metabolized
- increases to adult levels within 6 months
How does the concentration of proteins compare in plasma and serum?
PLASMA —> anticoagulation frees clotting factors and fibrinogens, making proteins levels higher
SERUM —> coagulation means that clotting factors and fibrinogen are no longer free, making protein levels low
What 2 values are in the total protein?
- albumin
- globulins
(not separate —> one value)
How much of the serum protein concentration does albumin make up? Where is it synthesized?
35-50%
synthesized in the liver, regulated by IL-1 and other cytokines
What is the half-life of albumin in dogs, horses, and cattle?
- DOG = 8 days
- HORSE = 19 days
- CATLLE = 2-3 weeks
What are the 2 major functions of albumin?
- transport proteins
- maintains oncotic pressure in about 75% of colloidal osmotic activity of plasma by affecting the concentration of other plasma constituents
How are globulins categorized? What are the 3 types?
based on electrophoretic motility from serum samples (no fibrinogen to alter results)
- α-globulins
- β-globulins
- γ-globulins
Where are α-globulins produced? What is their primary function?
liver
transport proteins and inactivate proteases, making them anti-inflammatory proteins
Where are β-globulins produced? What are their primary functions? What are 3 examples of proteins in this category that are not present in serum protein fractions?
- LIVER by transferrin (transport proteins, complement C3)
- B-LYMPHOCYTES/PLASMA CELLS in response to antigenic stimulation (IgM, IgA)
fibrinogen, prothrombin, plasminogen
What is te most common type of γ-globulins? Where are they produced?
IgG antibodies produced by B-lymphocytes and plasma cells
What are the 3 major methods of measuring proteins?
- refractometry
- biuret method by colorimetric automated chemistry analyzers
- turbidometric method by precipitation or dye-binding methods
What is the most common method of measuring total solid concentrations in plasma, serum, and other fluids? What causes a difference in the protein concentration in plasma and serum?
refractometry
coagulation = serum lacks fibrinogen = less protein
What 4 things cause falsely elevated levels of proteins in refractometry readings? What also has a possibility?
- CHolesterol/lipemia
- Hemoglobin
- Urea
- GLucose
(CHUGL)
sodium chloride
How does bilirubin affect refractometry?
alters color, but does not affect the reading
What 3 analytes are reported in protein measurements from chemistry analyzers? Which one is calculated?
- TP measured by spectrophotometry (more accurate than refractometry)
- albumin measured by spectrophotometry
- globulin calculation (TP - albumin)
How is globulin calculated? How are the different globulin fractions separated?
total protein - albumin = globulin
serum protein electrophoresis (SPE)
How does serum protein electrophoresis (SPE) separate globulin fractions? Why is this commonly done?
separates proteins into multiple bands of the same size, charge, and shape of the protein and uses a densitometer to translate them into a tracing
distinguishes between hyperglobulinemia caused by innate/acquire immune response from that caused by neoplastic lymphoid proliferation
How do albumin and globulin levels compare in electrograms?
albumin is the smallest protein with the highest net negative charge, making it first on the x-axis because it migrates the fastest and furthest
globulins are larger, so they do not migrate as far - γ-globulin has the weakest negative charge and migrates the shortest distance, so it is the furthest to the right
What is the most common cause of hyperproteinemia? What are 2 causes of artifactual increase?
increased total protein concentration, most commonly caused by increased globulin production
- hemolysis
- lipemia
What causes relative hyperproteinemia?
dehydration - less water makes proteins seem more concentrated
When can hyperproteinemia be considered due to dehydration?
when albumin is increased, regardless of globulin levels
What are 4 common causes of hypoproteinemia?
- burns
- GI disease (protein-losing nephropathy)
- exudative dermatopathies (loss through inflammatory processes)
- whole blood loss
What causes relative hypoproteinemia? How can it be identified?
dilution of plasma proteins by excess fluids —> excess fluid therapy
look at PCV
What is hyperalbuminemia almost always associated with? What are 2 causes of artifactual increase?
dehydration
- hemolysis
- lipemia
When is it common to find mild increases in albumin in dogs?
those undergoing glucocorticoid therapy, likely due to an increased synthesis or lifespan
What are 6 causes of decreased production of albumin?
- maldigestion - EPI
- malabsorption - small intestinal disease
- malnutrition - dietary deficiency in amino acids, chronic parasitism
- catabolic states - pregnancy, lactation, malignant neoplasia
- advanced hepatic disease
- hyperglobulinemia - cytokines decreased albumin synthesis, compensation to maintain colloid osmotic pressure
How much hepatic functional mass must be lost to affect its protein metabolism? What animals do not show this?
> 80% loss of mass will lead to a decreased synthesis of all plasma proteins, except immunoglobulins
horses with liver disease will not have hypoalbuminemia
What are 4 common causes of increased loss or catabolism of albumin?
- renal disease with chronic proteinuria - protein-losing nephropathies, glomerular damage
- severe exudative skin disease
- ascites
- hypoadrenocorticism
What are 3 causes of increased loss or catabolism of albumin and globulins?
- acute and chronic hemorrhage
- protein-losing enteropathies
- severe loss of plasma by burns or severe exudative inflammatory disorders
What are 3 characteristics of nephrotic syndrome?
- hypoalbuminemia —> severe drop is colloid pressure causes ascites, hydrothorax, hydropericardium, pulmonary edema
- azotemia
- hypercholesterolemia
What is a common iatrogenic cause of hypoalbuminemia?
fluid therapy —> dilutional
How does calcium typically travel through the blood?
bound to albumin —> total serum/plasma calcium concentration will be decreased in animals with hypoalbuminemia
What is the most common cause of hyperglobulinemia? What causes an increase in the concentration of globulin fractions?
hemoconcentration due to dehydration
infection, inflammation, or neoplasia releases cytokines, like IL-1, IL-6, IFN-γ, and TNF-α increases the production of globulins by hepatocytes and immunoglobulins by lymphocytes (acute phase of the innate immune system)
When is protein electrophoresis indicated?
increased serum golbulins
What does an increase in acute phase proteins lead to?
hyperglobulinemia and hyperproteinemia depending on the magnitude of disease
What kind of globulins are acute phase proteins? What are 2 functions?
most are α-globulins, but some are β-globulins
- plays a role in the immune system to protect against oxidative stress with anti-infective properties
- produced in response to physical stress and corticoisteroid administration
What 3 cytokines stimulate acute phase protein synthesis? When does hepatic synthesis begin?
- IL-1 β
- IL-6
- TNF
24 hours after acute tissue injury
What is the difference between major and moderate acute phase proteins?
MAJOR - increase in concentration by 100-1000x after stimulation and reach peak in 24-48 hours, falling rapidly on recovery
MODERATE - increase by 5-10x, reach a peak at 2-3 days and decrease more slowly
What are the major and moderate acute phase proteins produced by cats, dogs, horses, cows, and pigs?
CATS: serum amyloid A, α1-acid glycoprotein - AGP, haptoglobin
DOGS: C-reactive protein, SAA - SAA, AGP, Hp, fibrinogen
HORSES: SAA - Hp, CRP, Fb
COWS: Hp, SAA - Fb, AGP, CRP
PIGS: pig major acute phase protein, CRP - AGP, Hp, SAA, CRP
Where is fibrinogen produced? What kind of acute phase protein is it? What causes an increase?
liver
moderate —> late responder to acute and chronic inflammation, tissue damage, and neoplasia
In what species is fibrinogen an important inflammatory indicator?
cattle —> more sensitive than total WBC count
- can be useful in horses and dogs
What are the 2 most common causes of hypofibrinogenemia?
- liver failure causes decreased production
- DIC increases consumption
What kind of acute phase protein is serum amyloid A? When does it reach peak levels? Normal levels?
major acute phase protein, considered a rapid reactive APP
2 days after injury and returns to normal within 5-7 days
How are serum amyloid levels used for diagnosis in horses and cattle/dogs?
HORSE - inflammation, monitoring therapy and post-operative recovery, prognosis
CATTLE/DOGS - severity of inflammation
What is C-reactive protein? How do levels fluctuate?
major acute phase protein in the dog produced by the liver
concentrations in healthy dogs are low, marked increase occurs rapidly in response to acute inflammation, then decrease rapidly with resolution of inflammation
How does the type of inflammation affect serum globulin levels?
- in acute phase reactions, an initial increased concentrations of α and β-globulins are observed
- as inflammation becomes chronic, albumin may decrease, α and β-globulins increase, and a broad-based peak of γ-globulin is seen (polyclonal gammopathy)
What is polyclonal gammopathy characterized by? What 3 conditions is it most commonly seen in? Specifically in cats?
increased globulin fraction with a broad-based electrophoretic peak composed of a heterogeneous mixture of immunoglobulins
- chronic inflammatory diseases
- immune-mediated diseases
- liver disease
profound polyclonal peak occurs in cats with feline infectious peritonitis
What characterizes monoclonal gammopathies? What is the most common cause?
increased globulin fraction with a narrow-based electrophoretic peak that is not wider than the albumin peak
single clone of neoplastic lymphoid cells produce immunoglobulins with identical structure - lymphoid neoplasia (lymphoma, plasma cell myeloma)
How can the albumin peak be altered in monoclonal gammopathies?
peak may be decreased due to hyperviscosity syndrome in order to reduce colloid osmotic pressure
What are 3 causes of hypoglobulinemia?
- decreased production - SCIDS (Arabians, Appaloosas), acquired immunodeficiency diseases
- abnormal loss - hemorrhage, protein-losing enteropathy
- failure of passive transfer in neonates
What is characteristic of failure of passive globulin transfer at birth? What can cause this in neonates?
very low γ-globulin levels at birth
hypoglobulinemia reflecting inadequate absorption of colostral antibodies
