Definition

Hypoalbuminemia defined as measured value less than the reference range.

Pathophysiology

• Albumin-constitutive protein exclusively synthesized in the liver.
• Provides 75–80% of plasma colloid oncotic pressure.
• Low oncotic pressure due to serum albumin <1.5 g/dL may permit fluid extravasation into interstitial and potential third-space compartments, causing edema and body cavity effusion.
• Albumin of 1.5–2.5 g/dL does not cause edema or effusion unless other factors (e.g., increased hydrostatic pressure [venous occlusion, vascular bed hypertension, renal water or sodium retention, fluid overload], increased vascular permeability [vasculitis]) are present.

Systems Affected

• Cardiovascular and respiratory-transudative effusions (e.g., pleural effusion, ascites); peripheral edema; pulmonary edema.

Incidence/Prevalence

Accompanies many primary diseases processes: primary necroinflammatory liver disorders, protein losing enteropathy (PLE), protein losing nephropathy (PLN), enteric hemorrhage, negative acute phase response in chronic disease.

Signalment

Signs

Historical Findings

• Varies with the underlying primary disease or syndrome causing hypoalbuminemia.
• May demonstrate increased drug related effects due to reduced protein binding.

Physical Examination Findings

• Varies with the underlying primary disease or syndrome causing hypoalbuminemia.
• Severe hypoalbuminemia (<1.5 g/dL) associated with anasarca and increased propensity for third-space fluid distribution with altered Starling forces.

Causes

Extracorporeal Albumin Loss

• PLN-amyloidosis; glomerulonephritis
• PLE-lymphangiectasia; lymphoma; severe inflammatory bowel disease; histoplasmosis; pythiosis; chronic intussusception
• Severely exudative cutaneous lesions
• Chronic severe blood loss-usually enteric
• Repeated large volume paracentesis-abdominal or pleural effusion

Risk Factors

• Diseases of the liver, kidney, intestines, and blood vessels
• Negative nitrogen balance; poor nutrition

Differential Diagnoses

• Severe hepatic disease-may see jaundice; HE; polyuria-polydipsia; or ascites
• PLE-diarrhea common but inconsistent
• Cutaneous lesions-must be severe and exudative (e.g., burns, TEN, vasculitis, tumors, trauma)
• External blood loss-pallor due to anemia; evidence of extracorporeal blood loss (enteric, urinary, other)
• Malnutrition-causes mild hypoalbuminemia
• Aggressive fluid therapy (especially colloids)-exacerbates low albumin, may cause transient abnormality.

CBC/Biochemistry/Urinalysis

Other Laboratory Tests

• TSBA-usually high with severe hepatic disease; sometimes spurious low values with PLE (fat malabsorption).
• Physicochemical evaluation of effusion-transudate (usually pure) if hypoalbuminemia is a major causal factor.
• Antithrombin (AT)-anticoagulant with molecular weight similar to albumin and synthesized largely in liver; may be low with PLE, PLN, and hepatic synthetic failure.
• Protein C (PC)-anticoagulant; may be low with severe hepatic disease/failure, portosystemic shunting, sepsis.

Imaging

• Thoracic radiography-pleural effusion; pulmonary edema.
• May reveal lymphadenopathy, metastatic disease, cardiac or pulmonary disorders.
• Abdominal radiographs-effusion; altered hepatic size; mass lesions; quadrant signs of pancreatic disease.
• Abdominal ultrasonography-helps identify visceral abnormalities (e.g., small liver, lymphangiectasia in intestinal wall/mucosa), mass lesions, fluid pockets, altered portal blood flow, mesenteric lymphadenopathy, and biliary tree abnormalities.

Diagnostic Procedures

• Hepatic biopsy-after evaluating coagulation (mucosal bleeding time, PIVKA, PT, APTT, platelet count) status; request hepatic staining panel (H&E, rhodanine, Prussian blue, reticulin, Mason's trichrome staining).
• Renal biopsy-differentiates amyloidosis from glomerulonephritis; submit samples for special renal panel staining and ultrastructure studies otherwise biopsy features unlikely to influence treatment.
• Intestinal biopsy-endoscopic or surgical; severe hypoalbuminemia may cause post-laparotomy delay wound healing and seroma formation.

Pathologic Findings

Diverse depending on underlying causal disease.

Appropriate Health Care

• Diverse, depends on cause.
• Pleural effusion restricting ventilation-perform thoracentesis, may require chest tube.

Nursing Care

Provide physical therapy and walk patient to improve mobilization of peripheral edema.

Diet

• Achieve positive energy and nitrogen balance.
• Hepatic encephalopathy-restrict protein intake (see Hepatic Encephalopathy).
• Effusions or edema due to hypoalbuminemia-restrict sodium.
• PLE associated with lymphangiectasia-feed ultra-low-fat diet.

Surgical Considerations

Severe hypoalbuminemia may complicate healing rate, anesthetic drug metabolism, body cavity effusions may complicate drug dosing and dispersal, surgical approach, patient ventilation.

Drug(s) Of Choice

• Depends on underlying disease.
• Glucocorticoids-for some types of chronic hepatitis and some PLE's; prednisolone is preferred if it is effective; dexamethasone lacks mineralocorticoid effects which lessens sodium and water retention, but has greater potential for ulceration/erosion.
• Diuretics-assist in mobilization and excretion of excess body water and sodium; furosemide (1–4 mg/kg IV, IM, or PO q4–12h) in combination with spironolactone (1–4 mg/kg q12h) in patients with hepatic or cardiac disease, use judiciously to avoid intravascular volume contraction. For body cavity effusion mobilization, taper diuretic dose after initial positive response; individualize chronic treatment to response; diuretics may be used intermittently to mobilize recurring ascites.
• Antithrombotic treatment (low AT, PC, evidence of thrombi)-clopidogrel (0.5–1.0 mg/kg PO q24h) especially in PLN.
• Enalapril (0.5 mg/kg PO q12–24h)-for dogs with PLN; alternative is benazepril or telmisartin: angiotensin receptor blocker (ARB), is an alternative diuretic worthy of consideration.

Contraindications

Synthetic colloids-avoid with anuria, renal failure, congestive heart failure, severe coagulopathy, or von Willebrand disease.

Precautions

• Fluid therapy-large doses of synthetic colloids given to patients with severe hypoalbuminemia may cause volume overload with acute worsening of effusions and coagulopathy; avoid over-dosing crystalloid fluids when administered with synthetic colloids as these are rapidly distributed into interstitial spaces (70% volume within 1 hour) aggravating antecedent pulmonary or limb edema, and body cavity effusions; restrict maintenance fluid volume of crystalloids to one-third normal (depending on contemporary losses) when used with colloids.
• Transfusion of canine plasma or human albumin-may be complicated by transfusion or allergic reactions; plasma and albumin transfusions of dubious value if severe contemporary extra-corporeal albumin loss (e.g. PLN, PLE, vasculitis).
• Diuretic therapy-may cause serious volume contraction leading to azotemia, hypotension, and electrolyte and acid-base derangements.
• Unanticipated drug side effects-owing to reduced albumin drug binding.
• Use of DDAVP for bleeding-may aggravate fluid retention and associated complications.
• Glucocorticoids-mineralocorticoid effects of some drugs may worsen fluid accumulation, necessitating use of synthetic glucocorticoids without mineralocorticoid effects.

Possible Interactions

Inadvertent overdosing of drugs with high-protein binding

Patient Monitoring

• Body weight-especially during fluid therapy; monitors fluid retention.
• Vital signs, thoracic auscultation for crackles-monitor for pulmonary edema.
• Sequential serum albumin concentrations.
• Blood pressure-monitors vascular expansion.
• Abdominal girth-monitors ascites.
• Central venous pressure-unreliable; monitors fluid balance; avoid central venous catheters in patients with bleeding or thrombotic tendencies.

Prevention/Avoidance

• Limit glucocorticoid exposure.
• Use alternate-day therapy with prednisolone; titrate to lowest effective dose; use alternative medications to control primary illness.

Possible Complications

• PLN-may be complicated by thromboembolism; minimize IV catheterization and trauma.
• Hypovolemia-in dehydration, Addisonian crisis, blood loss, or diuretic over-dose can predispose to acute renal failure, DIC or HE.

Expected Course and Prognosis

Depends on underlying cause.

Associated Conditions

Numerous diverse diseases or syndromes

Pregnancy/Fertility/Breeding

Condition complicates pregnancy

See Also

• Amyloidosis
• Cirrhosis and Fibrosis of the Liver
• Glomerulonephritis
• Ductal Plate Malformation (Congenital Hepatic Fibrosis)
• Lymphangiectasia
• Portosystemic Shunting, Acquired
• Portosystemic Vascular Anomaly, Congenital
• Protein-Losing Enteropathy

Abbreviations

• ADH = antidiuretic hormone
• APTT = activated partial thromboplastin time
• AT = antithrombin
• DDAVP = 1 desamino-8-d-arginine vasopressin
• H&E = hematoxylin and eosin
• HE = hepatic encephalopathy
• PC = protein C
• PIVKA = proteins invoked by vitamin K absence or antagonism
• PLE = protein-losing enteropathy
• PLN = protein-losing nephropathy
• SLE = systemic lupus erythematosus
• TEN = toxic epidermal necrolysis
• TSBA = total serum bile acids
• UP:UCr = urine protein:urine creatinine ratio