Gastric secretions, pernicious anemia

Pernicious anemia Anemia resulting from lack of secretions by the gastric mucosa of the intrinsic fador essential to the formation of RBCS and the absorption of vitamin B ... 

Castle then showed (1929) that beef muscle was as effective as liver in preventing pernicious anemia, provided it was administered with normal gastric juice. He therefore concluded two factors were involved—an extrinsic one which was a component in liver or muscle and an intrinsic factor which was secreted by the stomach. Major efforts were therefore directed at identifying the extrinsic factor in liver or other meats. 

Cobalamine can only be resorbed in the small intestine when the gastric mucosa secretes what is known as intrinsic factor—a glycoprotein that binds cobalamine (the extrinsic factor) and thereby protects it from degradation. In the blood, the vitamin is bound to a special protein known as trans-cobalamin. The liver is able to store vitamin Bi2 in amounts suf cient to last for several months. Vitamin B12 deficiency is usually due to an absence of intrinsic factor and the resulting resorption disturbance. This leads to a disturbance in blood formation known as pernicious anemia. 

Histamine has only minor uses in clinical medicine. In the past it was used to diagnose pernicious anemia, in which histamine fails to evoke the usual secretion of gastric acid. Histamine has been used to assess bronchial hyperreactivity, although this test may be quite hazardous for asthmatics. Today the main clinical use of histamine is as a positive control injection for allergy skin testing. 

Pernicious anemia results from defective secretion of intrinsic factor by the gastric mucosal cells. Patients with pernicious anemia have gastric atrophy and fail to secrete intrinsic factor (as well as hydrochloric acid). The Schilling test shows diminished absorption of radioactively labeled vitamin B12, which is corrected when intrinsic factor is administered with radioactive B12, since the vitamin can then be normally absorbed. 

The story of vitamin B12 began with pernicious anemia, a disease that usually affects only persons of age 60 or more but which occasionally strikes children.3 Before 1926 the disease was incurable and usually fatal. Abnormally large, immature, and fragile red blood cells are produced but the total number of erythrocytes is much reduced from 4-6 x 106 mm-3 to 1- 3 x 106 mm-3. Within the bone marrow mitosis appears to be blocked and DNA synthesis is suppressed. The disease also affects other rapidly growing tissues such as the gastric mucous membranes (which stop secreting HC1) and nervous tissues. Demyelination of the central nervous system with loss of muscular coordination (ataxia) and psychotic symptoms is often observed. 

This condition has often been referred to in the past as juvenile pernicious anemia but it appears to be a quite separate entity. Confusion probably arose because there is a deficiency of intrinsic factor resulting in vitamin B12 malabsorption in both conditions. However, it differs from the disease in adults in that free acid is present in the gastric secretion (A8,L3,M5), the gastric mucosa is usually normal, and antibodies to intrinsic factor are not a feature. Megaloblastic anemia usually develops during the first 2 years of life but this depends on the amount of residual intrinsic factor available, and... 

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

The mucoprotein fraction concentration in gastric juice correlated with HCl and pepsin (G27, G52, G53) secretion, increased on vagal stimulation (G25, G27-G29, G35, G48, G52), and was absent or appeared in traces in juices of patients with pernicious anemia (Gll, G38) and those with advanced atrophic gastritis (Gll, G22, G28). 

Others confirmed (K18) that achlorhydric gastric juice from patients with pernicious anemia had inhibitory activity on gastric secretion. They... 

C7. Castle, W. B., Heath, C. W., and Strauss, M. B., Observations on the etiologic relationship of achylia gastrica to pernicious anemia. IV. A biologic assay of the gastric secretion of patients with pernicious anemia having free hydrochloric acid and that of patients without anemia or with hypochromic anemia having no free hydrochloric acid, and of the role of intestinal impermeability to hematopoietic substances in pernicious anemia. Am. J. Med. Sri. 182, 741-764 931). 

The intragastrically neutralized juices resembled those of pernicious anemia and showed many more lines than gastric juices neutralized in vitro. Since salivary contamination was avoided, both saliva and gastric juice apparently contained immunologically common components, which undergo rapid destruction in the presence of acid and pepsin, even if only a few minutes have elapsed between the secretion of the acid and its neutralization in vitro. 

Vitamin B] deficiency is commonly caused by pernicious anemia (PA). TA is an autoimmune disease resulting from the body s production of antibodies that recognize inlrinsic factor or other proteins of the parietal cell. The binding of antibodies to these proteins results in loss of their function. The parietal cells may be destroyed and be undetectable in patients with PA. The major defect in PA is gastric atrophy. 1 here may be a lack of all gastric secretions, including intrinsic factor, gastric acid, and pepsin. 

A large number of disorders are associated with cobalamin deficiency in infancy or childhood. Of these, the most commonly encountered is the Imerslund-Graesbeck syndrome, a condition that is characterized by inability to absorb vitamin B,2, with or without IF, and proteinuria. It appears to be due to an inability of intestinal mucosa to absorb the vitamin B,2 IF complex. The second most common of these is congenital deficiency of gastric secretion of IF. Very rarely, congenital deficiency of vitamin B12 in a breast-fed infant is due to deficiency of vitamin B12 in maternal breast milk as a result of unrecognized pernicious anemia in the mother. This is rare because most women with undiagnosed and untreated pernicious anemia are infertile. Additionally, there are some rare methylmalonic acidemias (acidurias) caused by inborn errors in homocysteine and methionine metabolism that are responsible for disorders in vitamin B status. ... 

Vitamin Bn can be deficient due to a lack of intrinsic factor, which is a glycoprotein secreted by gastric parietal cells. A lack of intrinsic factor or a dietary deficiency of cobalamin can cause pernicious anemia and neuropsychiatric symptoms. The only known treatment lor intrinsic factor deficiency (vitamin Bn deficiency) is intramuscular injection of cyanocobalamin throughout the patient s life. 

Pernicious anemia arises from a B12 deficiency. Gastric tissue secretes a glycoprotein called intrinsic factor, which complexes with ingested B12 in the digestive tract and promotes its absorption through the small intestine into the blood stream. Pernicious anemia results from insufficient secretion of intrinsic factor. Figure 20.22 outlines a probable explanation for why failure to absorb B12 leads to the deficiency of red blood cells that define anemias. 

V.B12 is also known as antipemicious anemia factor. Pernicious anemia is characterized by a severely reduced production of red blood cells, deficient gastric secretion and disturbances of the nervous system. It is not usually caused by dietary deficiency of V.B]2, but by the absence of intrirrsic factor, which is required for V.B[2 absorption. Intrinsic factor is a neuraminic acid-containing glycoprotein, normally present in the gastric mucosa, which forms a pepsin-resistant complex with V.B,2, and enables V.B,2 absorption in the lower part of the intestinal traet. 

Castle knew that the acid- and pepsin-secreting part of the stomach in patients with pernicious anemia had atrophied. In the year Thomas Addison published his distinction between idiopathic anemia and the anemia of adrenal insufficiency, Charles Handheld Jones of St. Mary s Hospital wrote that no trace of the gastric tubules was to be seen in the stomach of a patient who had died of profound ane-mia. " Five years later, Samuel Fenwick of London Hospital cited Handheld Jones when he reported the results of an autopsy he performed on a patient who had died of what Fenwick clearly understood was the unremitting form of anemia described by Addison. Fenwick made certain that the patient did not have the characteristic pigmentation of adrenal insufficiency, and at autopsy he found the adrenal glands unaffected. In the same year, Arnold Cahn and Joseph von Mering, working in... 

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