Hypoproteinemia

Hypoalbuminemia

Albumin is the most abundant of the plasma proteins. It accounts for approximately 75% of plasma colloidal oncotic pressure (COP), and its synthesis is primarily regulated by COP.

Albumin production can decrease with chronic insufficient intake of amino acids. In particular, protein-energy malnutrition can lead to hypoalbuminemia more quickly than total starva­tion.⁷⁶ Hypoalbuminemia is an indicator of chronic malnutrition given albumin's relatively long half-life, and clinical signs relating to hypoalbuminemia develop over a prolonged period. GI disorders that disrupt normal protein digestion and absorp­tion can lead to decreased protein synthesis and are discussed below under protein-losing enteropathy (PLE).

Although albumin is produced by the liver, synthesis gener­ally does not decrease in acute liver disease. Chronic, diffuse liver diseases such as chronic hepatitis, fibrosis, and hepatic neoplasia may cause hypoalbuminemia. Because the half-life of albumin is longer in horses and cattle than in dogs and humans, hypoalbuminemia is uncommon in large animal hepatic disease but can occur in conditions such as chronic hepatic lipidosis or chronic pyrrolizidine alkaloid toxicosis. In one study 6% of horses with acute liver disease and 18% of those with chronic liver disease were hypoalbuminemic; increased globulins were found in 64% of all horses with liver disease.⁷⁷ Decreased albumin and increased globulins can indicate a poorer prognosis in horses with liver disease.⁷⁸ A potentially more useful indicator of liver disease in horses than hypoal- buminemia is a postalbumin shoulder (a small hump on the right [cathodal] side of the albumin peak) on SPE; this shoulder can also appear with acute inflammatory disease or severe 25 79

hypoalbuminemia.,

Excessive albumin loss usually occurs through the urinary and/or GI tracts.

Renal proteinuria arises due to diseases of the glomeruli and/ or proximal tubules; hemorrhage or inflammation within the kidney is another cause but is often categorized under “postre- nal” proteinuria. Albumin is readily filtered through defects in the glomerular basement membrane due to its low molecular weight. Proteinuria due to glomerular lesions consists largely

■ BOX 26.5

Causes of Hypoproteinemia in Horses Hypoalbuminemia

Common Causes

Parasitism Glomerulonephritis Pyelonephritis

Idiopathic granulomatous enteritis

Intestinal lymphoma (lymphosarcoma) Parasitism

Salmonellosis

Equine ehrlichial enterocolitis (Potomac horse fever) Colitis

Clostridiosis

Nonsteroidal antiinflammatory drug toxicosis

Less Common Causes

Chronic hepatic fibrosis (pyrrolizidine alkaloid toxicity and other causes)

Hepatic neoplasia

Chronic hepatitis Amyloidosis

Tuberculosis

Histoplasmosis

Chronic eosinophilic gastroenteritis Starvation, malnutrition

Panhypoproteinemia

Common Causes

Excessive fluid therapy or water intake Acute blood loss

Gastrointestinal ulceration

Strangulating gastrointestinal obstruction, infarction

Protein-losing enteropathy (chronic granulomatous bowel disease)

Acute severe peritonitis

Nonsteroidal antiinflammatory drug toxicity Glomerulonephritis

Less Common Causes

Blood-sucking gastrointestinal or external parasites Intestinal lymphoma (lymphosarcoma)

Urinary tract blood loss

Congenital vascular disorders: renal trauma Renal calculi

Pyelonephritis Neoplasia Cystic calculi

Disseminated intravascular coagulation Immune-mediated thrombocytopenia Congestive heart failure

of albumin and can result in hypoalbuminemia and overall hypoproteinemia, whereas tubular proteinurias do not produce hypoalbuminemia.⁸⁰ Glomerulonephritis, amyloidosis, and less commonly pyelonephritis are top differentials for glomerular disease leading to proteinuria and hypoalbuminemia.⁸¹

PLE is a GI condition resulting in net loss of protein from the body, due to abnormal loss of protein from the GI tract and/or inability of the GI tract to absorb proteins.

■ BOX 26.6

Causes of Hypoproteinemia in Ruminants Hypoalbuminemia

Common Causes

Protein malnutrition, starvation

Amyloidosis

Pyelonephritis

Glomerulonephritis

Salmonellosis

Johne's disease

Trichostrongylus infection

Less Common Causes

Chronic liver failure

Intestinal lymphangiectasia

Intestinal lymphoma

Panhypoproteinemia

Common Causes

Excessive intravenous fluid therapy or water intake

Acute blood loss

Abomasal ulceration

Blood-sucking gastrointestinal or external parasites Gastrointestinal ulceration

Less Common Causes

Ingestion of caustic chemicals

Strangulation, infarction of intestine

Congestive heart failure

Pyelonephritis

Urinary tract blood loss

horses with diarrhea, albumin was lower in horses that died than in those that survived, likely reflecting albumin leakage across inflamed intestinal mucosa.²⁰

In horses the most common cause of PLE is idiopathic granulomatous enteritis, one of the chronic inflammatory bowel diseases of the horse.¹⁴ Other causes of equine PLE are acute enterocolitis, including bacteria-associated disease; GI lym­phoma and other GI neoplasia; nonsteroidal antiinflammatory drug (NSAID) toxicity, including phenylbutazone toxicity; GI parasitism; and other conditions in the chronic inflammatory bowel disease group, including intestinal tuberculosis, histoplas­mosis, and eosinophilic gastroenteritis. Proliferative enteritis of foals or yearlings due to Lawsonia intracellularis infection often 82 83 presents with hypoalbuminemia or panhypoproteinemia.^82,83

The most common cause of chronic PLE in ruminants is infection with Mycobacterium avium subsp.

In addition to the above causes of decreased albumin production and increased albumin loss from the body, hypoalbuminemia can arise from dilution within the body. Redistribution of albumin into subcutaneous tissues and higher- protein body cavity effusions can result in hypoalbumemia. Edema and peritoneal effusions may contribute to the severe acute hypoalbuminemia described in fescue toxicity in horses.⁸⁵ Some edematous and effusive disorders such as congestive heart failure (see the Panhypoproteinemia section later) can cause either hypoalbuminemia or panhypoproteinemia.

The clinical sequelae of hypoalbuminemia relate to the decrease in COP and subsequent fluid shift. Severe hypoal­buminemia (e.g., from protein-losing nephropathy or chronic liver disease) can cause a very low-protein effusion called a pure transudate. Other clinical signs of hypoalbuminemia include edema of the limbs, head, and ventrum. The albumin level generally must be below 1.5 g/dL in horses and below 1 g/dL in ruminants before clinical signs occur. A correlate of the longer albumin half-life in large animals is that albumin replacement by synthesis is also slower, resulting in more clinically significant edema due to hypoalbuminemia.⁷⁹

Panhypoproteinemia

Vigorous fluid therapy or excess water intake can cause dilution of plasma proteins and subsequent relative panhypoproteinemia. Panhypoproteinemia due to both dilution and increased GI protein loss occurs frequently in patients with acute GI disease receiving intravenous fluid therapy.

Acute blood loss with subsequent interstitial fluid shift into the vasculature, and volume expansion during pregnancy, can also cause relative panhypoproteinemia.

GI disorders can lead to panhypoproteinemia via loss of either blood or protein alone. Differentials for GI blood loss include abomasal or gastric ulcers, blood-sucking parasites (e.g., Haemonchus contortus in ruminants), viral or bacterial infection, azotemia, neoplastic invasion, or exposure to caustic chemicals. NSAID toxicosis and strangulating GI obstructions or infarctions can result in mucosal necrosis and leakage of plasma proteins into the gut lumen. Although protein-losing enteropathy usually initially causes hypoalbuminemia, panhypoproteinemia often develops over time. Proliferative enteropathy of young horses (described above) often results in panhypoproteinemia. Acute severe peritonitis with massive protein exudation due to GI rupture can also quickly lead to hypoproteinemia.

Other conditions resulting in clinically significant blood loss include urinary tract disorders due to congenital vascular disorders, renal trauma, renal or cystic calculi, pyelonephritis, and renal neoplasia. Coagulopathies, including disseminated intravascular coagulation (DIC) or immune-mediated throm­bocytopenia, may cause either external blood loss via the GI or urinary tract or internal bleeding into body cavities.

Congestive heart failure may cause either hypoalbuminemia or panhypoproteinemia via several mechanisms, including dilutional effects from plasma volume expansion, protein loss into ascitic fluid and the interstitium, and decreased albumin synthesis due to hepatic congestion and/or concurrent inflammation.⁸⁶