Pernicious anaemia patients with

Failure of intrinsic factor secretion is commonly due to autoimmune disease 90% of patients with pernicious anaemia have antibodies to the gastric parietal cells. Similar autoantibodies are found in 30% of the relatives of pernicious anaemia patients, suggesting that there is a genetic basis for the condition. 

Cl. Castle, W. B., Observations on the etiologic relationship of achylia gastrica to pernicious anaemia. I. The effect of the administration to patients with pernicious anaemia of the contents of normal human stomach recovered after the ingestion of beef muscle. Am. J. Med. Sci. 178, 748-764 (1929). 

C9. Cooper, B. A., and Whitehead, V. M., Evidence that some patients with pernicious anaemia are not recognized by radiodilution assay for cobalamin in serum. N. Engl. J. Med. 299, 816-818 (1978). 

Schwartz, M., Intrinsic factor antibody in serum from patients with pernicious anaemia. Lancet 2, 1263-1267 (1960). 

Schilling s test assesses the oral absorption of vitamin B12 and is used to diagnose pernicious anaemia. The patient is injected intramuscularly with non-labelled vitamin B12, to saturate body stores. An oral dose of vitamin B12 labelled with cobalt-58 is administered, followed by a second dose labelled with cobalt-57 bound to intrinsic factor. Prior saturation of body stores ensures any absorbed radiolabelled vitamin B12 is rapidly excreted in the urine. Urinary excretion of orally administered vitamin B12 is low in patients with pernicious anaemia due to poor absorption. Absorption is increased when it is administered with intrinsic factor. The ratio of cobalt-57 to cobalt-58 is thus raised in patients with pernicious anaemia. Intrinsic factor antibody testing is now generally used to diagnose pernicious anaemia, though the Schilling s test may occasionally be used. 

T18. Taylor, W. H., Gastric proteolysis in disease. 1. The proteolytic activity of gastric juice from patients with pernicious anaemia. J. Clin. Pathol. 12, 210-214 (1959). 

The serum concentration of vitamin Bj is low (normal 170-925 nanogram/1). In severe deficiency there is pancytopenia, the blood film shows anisopoikilocytosis with oval macrocytes and hyper-segmented neutrophils the marrow is megaloblastic. In many patients with pernicious anaemia antibodies to intrinsic factor can be identified in the serum. 

First the patient is given a small dose of radioactive vitamin Bj2 orally, with a simultaneous large dose of nonradioactive vitamin B intramuscularly. The large injected dose saturates binding sites so that any of the oral radioactive dose that is absorbed cannot bind and will be eliminated in the urine where it can easily be measured (normally > 10% of the administered dose appears in urine collected for 24 h, if renal function is normal). In pernicious anaemia and in malabsorption, gut absorption and therefore subsequent appearance of radioactivity in the plasma (measured 8-12 h later) and urine are negligible. 

Haemoglobin estimations are necessary at least every 6 months to check adequacy of therapy and for early detection of iron deficiency anaemia due to achlorhydria (common in patients with pernicious anaemia > 60 years) or carcinoma of the stomach, which occurs in about 5% of patients with pernicious anaemia. 

Fears have been voiced that vitamin C will destroy vitamin B,2 and that a person taking megado.se.s of vitamin C (about 5-10 g per day) could possibly be in danger of destruction of the body stores of vitamin B 2 and hence be liable to pernicious anaemia. In fact it has been found that addition of vitamin C in large quantities to food and incubation at 37 C had no effect upon the vitamin B,2 content. Similarly, experiments with rats have. shown that feeding with vitamin C did not deplete the vitamin B,2 contents of the plasma or liver. No vitamin B,2 depletion was observed in male patients suffering from spinal cord injury, when 4 g of vitamin C per day was given over eleven months. 

A patient with pernicious anaemia is being treated with parenteral vitamin B,. Bccau.se she has recently been feeling tired and mn down . her physician sends a sample to the clinical biochemistry lab requesting a. serum B,] level. 

Measuring the serum vitamin B j concentration is inappropriate in patients on parenteral treatment. A routine blood count is much more appropriate. In a patient with pernicious anaemia feeling run down , hypothyroidism should also be suspected and thyroid function assessed. The incidence of carcinoma of the stomach is increased among patients with pernicious anaemia and this diagnosis should also be borne in mind. 

Cyanocobalamin (vitamin B12), injected into a muscle, travels to the bone-marrow and is accumulated there after a dilution of 10 -fold in the body fluids. Even a microgram, injected in this way, is enough to cause new reticulocytes to form in the marrow of a patient suffering from pernicious anaemia. The process of distribution has been followed with Co. 

Orotic acid at high doses (3-6 g per day) was used with moderate success in adult patients with pernicious anaemia [444]. Kelley and co-workers [445] investigated the use of orotic acid in the treatment of hyperuricaemia. There was a 20-30% inhibition of purine biosynthesis and an increase in renal clearance of uric acid, but orotic acid offered no advantages over other available agents. Orotic acid in combination with vitamin was used in children with disturbed memory [446], and in combination with Kanaform in patients with cerebral trauma and vascular affections [447]. 

The other clinical feature of vitamin B deficiency, which is very rarely seen in folic acid deficiency, is degeneration of the spinal cord - hence the name pernicious for the anaemia of vitamin B deficiency. The spinal cord degeneration is due to a failure of the methylation of one arginine residue on myelin basic protein and occurs in about one-third of patients with megaloblastic anaemia due to vitamin B deficiency and in about one-third of patients who do not show signs of anaemia. 

About 70% of patients also have anti-intrinsic factor antibodies in plasma, saliva and gastric juice. Although the oral administration of partially purified preparations of intrinsic factor will restore the absorption of vitamin B in many patients with pernicious anaemia, this can result eventually in the production of anti-intrinsic factor antibodies, so parenteral administration of vitamin B is the preferred means of treatment. For patients who secrete anti-intrinsic factor antibodies in the saliva or gastric juice, oral intrinsic factor will be useless. 

Most estimates of vitamin B requirements are based on the amounts given parenterally to maintain normal health in patients with pernicious anaemia due to a failure of vitamin B absorption. This overestimates normal requirements because of the enterohepatic circulation of vitamin B (section 11.10.1) in people with defective absorption, the vitamin that is excreted in the bile will be lost in the faeces, whereas normally it is almost completely reabsorbed. 

Stomach to produce adequate amounts of intrinsic factor. Intrinsic factor antibodies and/or gastric parietal cell antibodies can be demonstrated in many patients with pernicious anaemia. 

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