Cobalamin Deficiency in Cats

Cobalamin Deficiency in Cats

Kenneth W. Simpson, Ithaca, New York

Paul A. Worhunsky, Ithaca, New York

Gastrointestinal disease may decrease the availability of a number of micronutrients, such as vitamins and minerals, with important consequences for the pathogenesis, diagnosis, and treatment of gastrointestinal disease. Measuring the serum concentration of cobalamin (CBL) aids in the detection of gastrointestinal disease, guides therapeutic intervention, and informs prognosis in cats.

Cobalamin Absorption

Metabolism of CBL in cats is very different from that in people. CBL homeostasis is a complex, multistep process that involves participation of the stomach, pancreas, intestines, and liver (Figure 127-1).

Figure 127-1 The pathway of cobalamin absorption involving the gastrointestinal tract, pancreas, and liver. Cbl, Cobalamin; Cbl-R, cobalamin bound to haptocorrin; Cbl-IF, cobalamin bound to intrinsic factor; Cbl-TCII, cobalamin bound to transcobalamin 2; IF, intrinsic factor.

After ingestion, CBL is released from food in the stomach. It then is bound to a nonspecific CBL-binding protein of salivary and gastric origin called haptocorrin. Intrinsic factor (IF), a CBL-binding protein that promotes CBL absorption in the ileum, is produced by the pancreas, not the stomach, in cats. In contrast, humans produce only gastric IF, and deficiency usually is associated with atrophic gastritis and the resultant lack of gastric IF production. The affinity of CBL for haptocorrin is high at acid pH, so most CBL is bound to haptocorrin in the stomach. Upon entering the duodenum, haptocorrin is degraded by pancreatic proteases, and CBL is transferred from haptocorrin to IF, a process facilitated by the high affinity of IF for CBL at neutral pH. Cobalamin-IF complexes traverse the intestine until they bind to specific receptors (previously called intrinsic factor cobalamin receptor [IFCR] but recently dubbed cubilin) located in the microvillus pits of the apical brush-border membrane of ileal enterocytes. CBL then is transcytosed to the portal bloodstream bound to a protein called transcobalamin 2 (TC II), which mediates CBL absorption by target cells. A portion of CBL taken up by hepatocytes is thought to be reexcreted rapidly in bile bound to haptocorrin. CBL of hepatobiliary origin, in common with dietary-derived CBL, is thought to undergo transfer to IF and receptor-mediated absorption, thus establishing enterohepatic recirculation of the vitamin. This situation of rapid turnover means that cats with CBL malabsorption can deplete totally their body CBL stores within 1 to 2 months. The half-life of exogenous parenteral CBL was 13 days in healthy cats as compared with 5 days in cats with GI disease. This is completely different from people, in whom CBL depletion may take several years, possibly because of the presence of long-term storage enabled by the CBL-binding protein TCI, which is absent in cats.

Serum concentrations of CBL are labile and reflect the balance between dietary intake, bacterial use and production, intestinal absorption, and body losses. Factors influencing serum CBL in cats are summarized in Table 127-1.

TABLE 127-1

Factors Influencing Serum Concentrations of Cobalamin in Cats

Increase	Decrease
High dietary content	Dietary deficiency
Parenteral supplementation	Inflammatory bowel disease
*Cholestatic liver disease	Alimentary lymphoma (multicentric lymphoma†)
	Exocrine pancreatic insufficiency
	Pancreatitis*
	Cholangitis*
	Hyperthyroidism*
	Intestinal bacterial utilization†
	Receptor abnormality†

^*Recognized disease association, pathomechanism unclear.

^†Theoretic cause not adequately documented in cats.

Measurement of Serum Cobalamin

CBL can be measured using a bioassay, radioimmunoassay (RIA), or an Immulite assay. The bioassay was the original method used and has been shown to correlate with RIA. In the RIA method an assay must be used that denatures endogenous CBL-binding proteins, usually by boiling the sample. The Immulite assay also has been shown to correlate with the RIA. Hemolyzed blood samples also affect test performance.

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Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off

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