- Definition
- Pathophysiology
- Systems Affected
- Genetics
- Incidence/Prevalence
- Geographic Distribution
- Signalment
- Signs
- Causes
- Risk Factors
BASICS
- Occurs when plasma TP concentration <5.2 g/dL (<52 g/L)
- Decrease can be nonselective or selective
- Specific deficiencies can result in immune deficiency/defective hemostasis
- Plasma contains numerous proteins that perform nutritive functions, maintain oncotic pressure, regulate immune function, aid acid–base balance, and affect hemostasis/fibrinolysis
- All albumin and fibrinogen and ~80% of globulins synthesized in the liver. Remaining globulins formed in lymphoid tissue
- TP is determined by filtration between the intravascular/extravascular spaces, metabolic demands, hormonal and water balance, nutritional status
- TP in neonates is influenced by passive transfer. In adults, TP remains relatively stable unless there is pathology
- Hypoproteinemia can:
- Be nonselective—panhypoproteinemia
- Be selective, i.e. hypoalbuminemia/hypoglobulinemia
- Have normal TP with hypoalbuminemia and hyperglobulinemia
- Have normal TP with hyperalbuminemia and hypoglobulinemia (rare)
- Panhypoproteinemia—relative or absolute
- Relative panhypoproteinemia occurs when TP is decreased but absolute content of protein in vascular space is normal, e.g. dilution by excessive fluid therapy
- Absolute panhypoproteinemia occurs when there is a reduction in TP with a normal plasma volume due to impaired production/accelerated loss:
- Reduced production—primarily as a result of malnutrition/starvation, possibly in the face of increased metabolic demand, e.g. growth, pregnancy, lactation. Liver disease—rare cause
- Accelerated loss more common. Loss can be from the vascular into the extravascular compartment (increased capillary permeability) or from the body. These may cause panhypoproteinemia/selective protein loss. Hypoalbuminemia occurs first (small size and low molecular weight). If disease is severe/chronic, globulins also may be decreased
- Severe/acute hemorrhage results in hypoproteinemia through direct loss of protein followed by dilution effect via movement of fluid from the extravascular to vascular space
- Persistent, low-grade hemorrhage causes normovolemic anemia/hypoproteinemia
- Albumin—produced in liver; has the lowest molecular weight of plasma proteins; contributes 75% of osmotic pressure. Albumin binds/transports components lacking specific transport proteins
- Hypoalbuminemia may be accompanied by decreased/normal TP and normal/increased/decreased globulin concentrations. Hypoalbuminemia usually precedes hypoglobulinemia owing to preferential loss of albumin or synthesis of globulins
- Hypoalbuminemia usually the result of increased loss; decreased production and increased catabolism may occur
- Increased loss of albumin occurs with:
- PLE—causes include ulceration, defective lymphatic drainage, increased mucosal permeability, and exudation. Most common
- PLN—albumin is readily filtered through glomerular basement membrane defects. Glomerulopathies cause albuminuria/hypoalbuminemia
- Congestive heart failure—retention of sodium and water forces fluid into the extravascular spaces with concomitant protein loss. Reduced food intake, inadequate protein absorption, and inadequate hepatic synthesis also contribute
- Chronic inflammation—albumin lost via exudation, e.g. into thoracic/abdominal cavities
- Decreased production rarely due to liver disease; can occur with starvation, malnutrition, and chronic GI disorders. Inflammatory processes—albumin: decreased production; globulins: increased production. The half-life for albumin is ≈18 days; therefore, when decreased synthesis causes hypoalbuminemia, the underlying disease is usually chronic with increased globulins; results in normal/increased TP
- Albumin—catabolism may occur with increased metabolic demands/negative nitrogen balance. Chronic antigenic stimulation also increases albumin catabolism to provide amino acids for immunoglobulin production. Resulting hypoalbuminemia usually offset by hyperglobulinemia resulting in normal TP
- Hypoalbuminemia causes low plasma colloid oncotic pressure, allowing fluid movement from vascular to extravascular space, reducing plasma volume. May manifest as tissue edema and hypoperfusion and consequent organ dysfunction. Hypoalbuminemia also reduces transportation of molecules (and drugs) within plasma
- Hypoglobulinemia with normal albumin is rare. Exception—FTPI
- Hypoglobulinemia with immunodeficiencies results in decreased gammaglobulins (lymphoid hypoplasia/aplasia). Compensatory increase in albumin
- Specific immunodeficiencies
- Fell Ponies
- Purebred Arabs
Neonates with hypoproteinemia, particularly hypoglobulinemia—FTPI and/or specific immunodeficiencies.
Fever, lethargy, ventral edema, weight loss, GI dysfunction, dysuria, hemorrhage, or history of prolonged NSAID administration.
- Relative dilution, i.e. excessive fluid therapy/water intake
- Reduced production:
- Malnutrition, starvation
- Chronic liver disease, e.g. pyrrolizidine alkaloid toxicity
- Increased loss:
- Endotoxemia/vasculitis, e.g. purpura haemorrhagica, African horse sickness
- Acute/chronic hemorrhage, e.g. trauma, epistaxis, internal vascular rupture, coagulopathies; chronic blood loss
- PLN, e.g. glomerulonephritis, amyloidosis, pyelonephritis
- PLE, e.g. intestinal parasitism, salmonellosis, clostridiosis, Potomac horse fever, Lawsonia intracellularis infection, inflammatory bowel disease, lymphosarcoma, NSAID toxicosis, exposure to caustic chemicals, strangulating GI obstructions/infarction
- Peritonitis/pleural effusion, e.g. bacterial pleuropneumonia
- Chronic heart failure
- May occur in initial stages of diseases causing panhypoproteinemia
- Chronic antigenic stimulation/infections—increased catabolism, e.g. fever, trauma, surgery, neoplasia
- Chronic, diffuse/severe liver disease—decreased production, e.g. chronic hepatitis/fibrosis/neoplasia
- FTPI
- Immunodeficiencies, e.g. SCID, selective immunoglobulin M deficiency, agammaglobulinemia, Fell Pony immunodeficiency syndrome
- Adult acquired immunodeficiency
DIAGNOSIS
TREATMENT
MEDICATIONS
FOLLOW-UP
MISCELLANEOUS