Megaloblastic Anemia: Causes

Pathogenesis (disease development)

Megaloblastic anemia can be distinguished between vitamin B12 deficiency anemia and folic acid deficiency anemia. In both forms, the very deficiency mentioned above results in a synthesis disorder of hematopoiesis (blood formation) with the formation of megaloblasts (large, nuclear and hemoglobin (blood pigment-containing) precursor cells of erythrocytes (red blood cells) in the bone marrow). Pernicious anemia is the most common subtype of vitamin B12 deficiency anemia. In this form, the intrinsic factor produced by the parietal cells (occupant cells) of the stomach is not produced due to gastric mucosal changes (chronic gastritis type A). This protein complexes with dietary vitamin B12 (cobalamin) to allow absorption (uptake) of the vitamin in the terminal ileum (small intestine).

Etiology (causes)

Etiology of megaloblastic anemia due to vitamin B12 deficiency.

Biographic causes

• Genetic burden – genetic enzyme defects.
• Age – older age

Behavioral causes

• Nutrition
  • Vegan – dietary attitude that implies the absolute avoidance of animal products.
  • Vegetarian
  • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
• Consumption of stimulants
  • Alcohol

Causes related to disease

• Achlorhydria in the stomach – condition caused by lack of or insufficient gastric juice production.
• Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions.
• Chronic atrophic gastritis (gastritis).
• Chronic pancreatitis (inflammation of the pancreas).
• Diabetes mellitus (diabetes)
• Imerslund-Gräsbeck syndrome – selective malabsorption of cobalamin.
• Infection with the fish tapeworm
• Malabsorption syndrome – disorder in the absorption of nutrients.
• Crohn’s disease – chronic inflammatory bowel disease; it usually progresses in relapses and can affect the entire digestive tract; characteristic is the segmental affection of the intestinal mucosa (intestinal mucosa), that is, several intestinal segments may be affected, which are separated by healthy sections from each other
• Whipple’s disease – a chronic recurrent disease caused by the gram-positive rod bacterium Tropheryma whippelii, which can affect the entire body (symptoms: Fever, joint pain, brain dysfunction, weight loss, diarrhea, abdominal pain and more).
• Neoplasms (neoplasms)
• Parasitic infestation of the intestine
• Scleroderma – group of various rare diseases associated with hardening of connective tissue of the skin alone or of the skin and internal organs (especially digestive tract, lungs, heart and kidneys).
• Blind loop syndrome – syndrome that can occur after intestinal surgery; the cause is chronic stasis of intestinal contents in a section of the intestine that ends blindly
• Transcobalamin II deficiency – deficiency of a transport protein for vitamin B12.
• Tropical sprue – chronic intestinal disease associated with fatty stools, vital substance (micronutrient) deficiencies, and emaciation; occurs in the tropics.
• Tuberculosis (consumption)
• Celiac disease (gluten-induced enteropathy) – chronic disease of the mucosa of the small intestine (small intestinal mucosa), which is based on hypersensitivity to the cereal protein gluten.
• Zollinger-Ellison syndrome – usually malignant neoplasm associated with increased gastrin production, leading to increased occurrence of gastric ulcers.

Operations

• Small bowel resection (removal of the small bowel).
• Gastrectomy (removal of the stomach)

Environmental pollution – intoxications (poisoning).

• Nitrous oxide (nitrous oxide)

Etiology of pernicious anemia (subtype of vitamin B12 deficiency anemia)

Biographic causes

• Age
  • Higher age
  • Children (under ten years old)

Causes related to disease

• Agammgaglobulinemia – deficiency or complete absence of immunoglobulins (antibodies) leading to severe immunodeficiencies.
• Hypoparathyroidism (hypothyroidism of the parathyroid gland).
• Idiopathic adrenocortical insufficiency
• Graves’ disease – autoimmune disease leading to hyperthyroidism (overactive thyroid).
• Thyroiditis (inflammation of the thyroid gland).
• Vitiligo (white spot disease)

Etiology of megaloblastic anemia due to folic acid deficiency

Biographic causes

• Genetic burden – genetic enzyme defects.
• Age
  • Children in growth spurt
  • Newborns

Behavioral causes

• Nutrition
  • Unbalanced diet, often in adolescents or the elderly.
  • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
• consumption of food.
  • Alcohol (alcohol dependent)
• Drug addicts

Causes related to disease

• Chronic hemolytic anemia
• Chronic exfoliative (scaling) skin disease.
• Native sprue – chronic intestinal disease associated with fatty stools, vital substance (micronutrient) deficiencies and emaciation.
• Malignant diseases (cancer)
• Tropical sprue – chronic intestinal disease associated with fatty stools, vital substance deficiencies (micronutrients) and emaciation; occurs in the tropics.

Medication

• Barbiturates – drugs such as phenobarbital that are used as antiepileptic drugs, for anesthesia, or as sleep aids.
• Methotrexate – drug, which is one of the cytostatic drugs.
• Pentamidine – drug used for infections with protozoa (protozoa) such as Pneumocystis carinii.
• Phenytoin – an antiepileptic drug; drug used to treat epileptic seizures.
• Pyrimethamine (anti-malarial drug).
• Triamterene – drug belonging to the diuretics (diuretic drugs).
• Trimethoprim – drug, which is one of the antibiotics.

Other causes

• Dialysis (kidney replacement procedure; blood washing).
• Pregnancy

Etiology of megaloblastic anemia without a vitamin B12 or folic acid deficiency

Biographic causes

• Genetic burden – genetic enzyme defects such as Lesch-Nyhan syndrome.

Disease-related causes

• Acute erythroleukemia – blood cancer that affects the red blood cells (erythrocytes).
• Myelodysplastic syndrome (MDS) – acquired clonal disease of the bone marrow associated with a disorder of hematopoiesis (blood formation).

Medication

• Antiepileptic drugs such as phenytoin or phenobarbital – drugs used to treat epileptic seizures.
• Purine antagonists – drugs such as mercaptopurine or azathioprine that are used for immunosuppression
• Pyrimidine antagonists – drugs such as fluorouracil, procarbarin or hydroxyurea, which are used as cytostatics in cancer, among other diseases.
• Virostatics such as aciclovir or zidovudine – drugs that are used for viral infections.