Pernicious Anemia

What is Perniciosa anemia?

Pernicious anemia is an anemic form due to vitamin B12 deficiency . Once quite widespread and difficult to treat, this particular anemia has gained the pernicious adjective due to its ability to cause serious damage and important harmful effects. Today, fortunately, pernicious anemia has become rather rare and easily treated.

Causes

Pernicious anemia can develop for various reasons, but most of the time vitamin B12 absorption deficiencies are the cause of the problem. In particular, pernicious anemia is often caused by the absence of the so-called intrinsic factor, a fundamental glycoprotein for a correct absorption of the aforementioned micronutrient. This substance is secreted by the parietal cells of the stomach, which in about 90% of patients with pernicious anemia are attacked and destroyed by abnormal antibodies, which can also directly affect the intrinsic factor, preventing its link with the vitamin or intestinal receptor . In these cases we speak of autoimmune atrophic gastritis or type A gastric inflammatory process that affects the gastric mucosa, reducing its functionality.

Atrophic gastritis can also have non-immune origins, for example due to the perpetuation of chronic gastritis of various nature, including helicobacter pylori (type B atrophic gastritis).

Risk factors for pernicious anemia

Adult and old age, family history of pernicious anemia, Nordic ethnicity, simultaneous presence of endocrine autoimmune disorders, such as Addison's disease, chronic thyroiditis, Graves' disease, hypoparathyroidism, hypopituitarism, myasthenia gravis, secondary amenorrhea, type I diabetes, testicular dysfunction, vitiligo.

Patients with pernicious anemia have been reported to have a three-fold increased risk of gastric cancer.

By-Pass and Gastric Resections

Under normal conditions, thanks to the presence of the intrinsic factor, vitamin B12 is absorbed in the lower part of the small intestine, called the ileum. Surgical resections of this trait can therefore lead, years later, to vitamin B12 deficiencies and to the consequent pernicious anemia.

A similar situation when the stomach or a portion thereof (gastrectomy) is removed, or when a gastric bypass is applied to reduce body weight in severely obese patients; in such circumstances, in fact, the synthesis of intrinsic factor at the gastric level is lacking.

Food Shortages

Pernicious anemia due to reduced food intake has become particularly rare; the individuals most exposed to this risk are the strict vegetarians and the indigent, especially if they are elderly (due to their lower digestive and absorption efficacy).

Vitamin B12 in Foods

Vitamin B12 is present above all in meat foods, while in the human body it is concentrated in the liver, where stocks of a few mg cover its needs for long periods of time (up to three to five years). Not surprisingly, before this vitamin was discovered and isolated, pernicious anemia was treated with large amounts of raw bovine liver. Today, B12 is produced in the laboratory by bacterial fermentation; in the same way, small quantities are produced by some microorganisms residing in the human intestine.

Vitamin B12 absorption

At the gastric level, in the presence of sufficient amounts of hydrochloric acid, the vitamin B12 present in the food is released and readily bound to the salivary R polypeptide. Once it has arrived in the duodenum, this complex is dissolved by pancreatic proteases and vitamin B12 binds to the factor intrinsic of Castle secreted by gastric parietal cells. The absorption of this complex is mediated by a receptor and occurs in the ileum. A very small part is absorbed by simple diffusion (about one or two percent) and this explains the usefulness of oral administrations, provided they are rather high and sufficiently close together.

Other Possible Causes

Pernicious anemia can also result from chronic H. pylori infection or suppression of gastric acid with anti-ulcer drugs (H2-antagonists, proton pump inhibitors).

Finally, enteric infestations from parasites (such as the botriocephalic worm that consumes the vitamin) and the various malabsorption syndromes (resulting from celiac disease, Crohn's disease, etc.), can cause vitamin B12 deficiencies.

Clinical signs and symptoms

Most patients with pernicious anemia have elevated serum levels of gastrin, a hormone secreted by the stomach in order to increase gastric secretion, which is generally absent or deficient in these subjects.

Often, in pernicious anemia, an atrophic glossitis (Hunter's glossitis) can be observed, in which the mucosa of the tongue is smooth and reddened at the edges and at the tip. The patient complains of parageusia, that is an altered perception of flavors.

During pernicious anemia, the skin and sclerae can take on a slight jaundice, caused by the exalted catabolism of red blood cells, with an increase in serum levels of indirect bilirubin. The complexion, however, tends to pale and the patient complains of difficulty concentrating, hypochloridria or achlorhydria, irritability, headache, depression, disturbed balance and diminished mental faculties (difficulty in concentration, memory impairment).

In the most severe and inadequately treated forms, pernicious anemia also affects the nervous system, with paresthesia spread mainly at the extremities and reduced perception of pain.

Pernicious anemia is included in the category of megaloblastic anemias, as it is characterized by the presence of red blood cells, with a considerably increased volume, with a short life and in a number much lower than the norm.