Iron deficiency anemia
Etiology
Liver, spleen, bone marrow and other mononuclear-macrophage systems contain about 1000mg of iron, which can be used by the body to make 1/3 of the blood volume of hemoglobin, and almost all of the iron released from hemoglobin decomposition is reused by the body. Short-term food iron deficiency or iron deficiency increases, and iron deficiency is generally rare. The following various factors will be prone to iron deficiency anemia.
1.Increased iron requirement and insufficient intake. Children need more iron during the birth period and infant lactation, especially premature babies, twins or those whose mothers are anemic. If infants are fed with human milk containing less iron, and if they are not given more iron-containing food such as eggs, vegetables, meat and animal liver in time after teething, iron deficiency anemia can result. During pregnancy and lactation, the amount of iron needed increases, and the gastrointestinal dysfunction and lack of gastric acid during pregnancy affects iron absorption, especially after multiple pregnancies, which can easily cause iron deficiency anemia.
Iron deficiency can also occur in adolescents due to rapid growth and increased iron requirements, especially in young women due to menstrual blood loss, and if the food consumed for a long time does not contain enough iron. The most common causes are insufficient iron content in food, partial diet or malabsorption. Heme iron in food is easily absorbed and is not affected by food composition or stomach acid. Non-heme iron needs to be turned into Fe2 before it can be absorbed. Phosphate, phytic acid and tannic acid in vegetables, cereals and tea can affect the absorption of iron.
The daily requirement of iron for adults is about 1~2mg. 1mg/d is enough for men, but the requirement of iron for women of childbearing age and growing adolescents increases to 1.5~2mg/d. If the diet is rich in iron and the amount of iron stored in the body is sufficient, iron deficiency will rarely occur. Other reasons for insufficient iron intake are drugs or gastrointestinal disorders that affect the absorption of iron, the intake of certain metals such as gallium and magnesium, calcium carbonate and magnesium sulfate in acid preparations, and H2 inhibitors taken in ulcer disease, which can inhibit the absorption of iron.
Atrophic gastritis, reduced gastric acid after gastric and duodenal surgery affect the absorption of iron, etc., are the causes of insufficient iron intake. In addition, an average blood loss of 1300 ml (about 680 mg of iron) during pregnancy requires 2.5 mg of iron supplementation per day, and during the second 6 months of pregnancy, 3-7 mg of iron supplementation per day is required; during lactation, the iron requirement increases by 0.5-1 mg/d. Inadequate supplementation can lead to a negative iron balance. If there are multiple pregnancies, the iron requirement should be increased. About 8% of male donors and 23% of female donors have reduced serum ferritin. The situation will be aggravated if blood is donated several times in a short period of time. Lu Yilong, Department of Hematology, Affiliated Hospital of Jiangsu University
2. Excessive consumption of stored iron. Since 2/3 of the total iron in the body exists in the red blood cells, repeated and excessive blood loss can significantly deplete the body’s iron stores. Chronic small amount of intestinal bleeding caused by hookworm disease, repeated multiple bleeding from upper gastrointestinal ulcers, years of anal bleeding or excessive menstrual flow in women and other long-term losses eventually lead to insufficient body iron stores, resulting in iron deficiency anemia.
In addition, paroxysmal sleep hemoglobinuria, mechanical hemolysis caused by artificial mechanical heart valves, and idiopathic pulmonary iron-containing hemoglobinosis can lead to anemia due to long-term iron loss in the urine. Normal individuals lose about 1 mg of iron per day from the gastrointestinal tract, urinary tract, and skin epithelium, and women lose more iron during menstruation, childbirth, and lactation. Clinically, excessive iron loss is often due to gastrointestinal bleeding in men and excessive menstruation in women.
3, excessive loss of free iron, free iron can be lost with the aging and continuous shedding of epithelial cells in the gastrointestinal tract. In atrophic gastritis, major gastric resection and steatorrhea, the rate of epithelial cell renewal is increased, so the loss of free iron is also increased. Iron deficiency not only causes a decrease in heme synthesis, but also affects the electron transfer system due to a decrease in the activity of iron-containing enzymes (such as cytochrome oxidase) in red blood cells, which can lead to abnormal lipid, protein and sugar metabolism, resulting in abnormal red blood cells that are easily destroyed in the spleen and shorten their life span.
Iron in the human body is in a closed cycle. Under normal circumstances, the absorption and excretion of iron maintain a dynamic balance, and the human body is generally not iron deficient, but only in cases of increased need, insufficient iron intake and chronic blood loss, resulting in a long-term negative balance of iron. The causes of iron deficiency can be divided into two categories: insufficient iron intake and excessive iron loss.
[Classification
In iron deficiency anemia, iron deficiency in the body is a gradual development process. At the beginning of iron deficiency, only the stored iron decreases, i.e., the ferritin and iron-containing hemoglobin stored in bone marrow, liver, spleen and other tissues decrease, the serum iron does not decrease, the number of red blood cells and hemoglobin content also remain in the range of political parties, and the intracellular iron-containing enzymes do not decrease. When the stored iron is depleted and the serum iron decreases, there may still be no anemia performance, and this stage is called the latent period of iron deficiency.
1. Early stage of iron deficiency anemia. When the stored iron and serum iron start to drop, the iron saturation drops below 15%, the bone marrow erythrocyte availability decreases, and the erythropoiesis is restricted, then the anemia is positive cellular orthochromic, and the clinical symptoms of mild anemia start to appear.
2. Severe iron deficiency anemia. When there is a complete lack of iron available in the bone marrow young erythrocytes and a gradual lack of iron-containing enzymes in various cells, the serum iron also decreases or significantly decreases, the iron saturation decreases to 10%, the erythrocyte system in the bone marrow is compensatory hyperplasia, and the clinical manifestation is small-cell hypochromic moderate or severe iron deficiency anemia. The anemia symptoms are significant.
[Pathogenesis].
Iron is an essential trace element that is present in all living cells. In addition to participating in hemoglobin synthesis, iron also participates in a number of biochemical processes in the body, including mitochondrial electron transfer, catecholamine metabolism and DNA synthesis. A variety of enzymes are known to require iron, such as peroxidase, cytochrome C reductase, succinate dehydrogenase, ribonucleic acid reductase and xanthine oxidase, among other proteases and oxidoreductases. If deficient, it will affect the redox function of cells and cause multiple dysfunctions.
The activity of iron-containing enzymes decreases, affecting the oxidative enzymatic cycle of cell mitochondria. It causes keratinization and degeneration of epithelial cells with fast renewal metabolism, atrophy of the mucosa of the digestive system and reduced secretion of gastric acid. In iron deficiency, α-phosphoglycerol dehydrogenase in skeletal muscle is reduced, which tends to cause increased lactic acid accumulation after exercise, resulting in decreased muscle function and stamina. Iron-containing monoamine oxidase plays an important role in the synthesis and decomposition of some neurotransmitters (such as dopamine, norepinephrine and 5-hydroxytryptamine, etc.).
In iron deficiency, the activity of monoamine oxidase is reduced, which can affect neural development and intelligence.
Developing erythrocytes need iron, protoporphyrin and pearl protein to synthesize hemoglobin. Insufficient hemoglobin synthesis causes hypochromic anemia. There are different views on the relationship between iron deficiency and infection. In iron deficiency, macrophage function and spleen natural killer cell activity are significantly impaired; myeloperoxidase and oxygen respiratory burst function of neutrophils are reduced; lymphocyte transformation and mobile inhibitory factor production are impaired, and cellular immune function is decreased. However, others emphasize that iron is also required for bacterial growth and believe that iron deficiency has a protective effect on the organism. Infections are more likely to occur when iron is abundant than when iron is deficient.
What are the early symptoms of iron deficiency anemia?
Clinical manifestations]
The severity of clinical manifestations is mainly determined by the degree of anemia and its speed of occurrence. Acute blood loss is rapid, and even if the degree of anemia is not serious, it will cause obvious clinical symptoms, while chronic anemia, due to its slow onset, the body can gradually adapt to it through regulation without showing symptoms.
1. Symptoms. Yellowish or pale face, tiredness, loss of appetite, nausea and belching, abdominal distension and diarrhea, difficulty in swallowing. Dizziness and tinnitus, or even fainting, shortness of breath and palpitations with slight activity. In patients with coronary arteriosclerosis, angina pectoris may be triggered. Women may have irregular menstruation, amenorrhea, etc.
Special manifestations: Special manifestations of iron deficiency include: stomatitis, tongue papillae atrophy, linguitis, severe iron deficiency may have spatulate nails (anticoronary), loss of appetite, nausea and constipation. European patients often have dysphagia, stomatitis and tongue abnormalities, called Plummer-Vinson or Paterson-Kelly syndrome, which may be related to the environment and genes. Dysphagia is due to the formation of mucosal webs at the junction of the hypopharynx and esophagus, which may occasionally form cuff-like structures around the lumen and bind the opening of the esophagus. Surgery is often required to break these webs or dilate the strictures, and iron supplements alone will not help.
Non-anemic symptoms: Non-anemic symptoms of iron deficiency manifest in children with delayed growth or abnormal behavior, manifested by irritability, irritability, poor concentration in class and decreased academic performance. Heterophagia is a specific manifestation of iron deficiency and may be the cause of iron deficiency, the mechanism of its occurrence is not clear. Patients often eat only one kind of “food”, such as ice, clay, starch, etc., in an uncontrollable manner. It may disappear after iron treatment.
2. Physical signs. In patients with prolonged disease, there may be nail wrinkling, unsmooth, anti nail, pale skin mucosa, dry skin, dry hair loss. Tachycardia, strong pounding of the heart, and systolic murmurs can be heard in the apical or pulmonary valve area. The presence of severe anemia can lead to congestive heart failure, and swelling can also occur. About 10% of patients with iron deficiency anemia have mild splenomegaly, the cause of which is unclear. No specific pathological changes are found in the spleen of patients, which may disappear after correction of iron deficiency. Retinal hemorrhage and exudation can be seen in a few patients with severe anemia.
3. Common complications. Severe and persistent anemia can lead to anemic heart disease and even heart failure.
Diagnostic criteria
1. Blood picture. Mild anemia is orthocytic orthochromic anemia. Severe anemia is typical small cell hypochromic anemia with mean red blood cell volume (MCV) <80fl, mean red blood cell hemoglobin content (MCH) <28pg, and mean red blood cell hemoglobin concentration MCHC <30%. The size of erythrocytes in blood film varies, small ones are more common, irregular morphology, a few oval, target-shaped and irregular-shaped erythrocytes appear, the faintly stained area in the center of erythrocytes is enlarged, or even becomes a narrow ring, reticulocytes are mostly normal, and can be temporarily elevated in acute blood loss.
2. Bone marrow picture. Bone marrow shows active cell proliferation, mainly for young red blood cells, which are small in size and have unbalanced cytoplasmic development.
3.Serum iron. Serum iron is significantly decreased.
4. Erythrocyte protoporphyrin. Hemoglobin synthesis is reduced due to iron deficiency, and erythrocyte free protoporphyrin is 500μg/L in iron deficiency anemia (normal 200-400μg/L).
5. Small cell hypochromic anemia. Hemoglobin (Hb) less than 120g/L in men and less than 110g/L in women; MCV less than 80fl, MCH less than 26pg, MCHC less than 0.31.
6, There is a clear cause and clinical manifestation of iron deficiency.
7, serum iron less than 10.7 μmol/L (60 μg/dl), total iron binding capacity greater than 64.44 μgmol/L (360g/dl).
8.The saturation of ferritin was less than 15%.
9.Bone marrow extracellular iron disappears and intracellular iron is less than 15%.
10, Cytosolic free protoporphyrin (FEB) greater than 0.9 μmol/L (50g/dl).
11.Serum ferritin (SF) less than 14μg/L.
12, Iron therapy is effective.
Differential diagnosis
1, Chronic infectious anemia.
2.Iron granulocytic anemia.
3, Vitamin B6-responsive anemia.
4, Thalassemia.
The diagnosis of iron deficiency anemia can be obtained by careful questioning and analysis of the medical history, together with physical examination, but laboratory confirmation is required to confirm the diagnosis. Clinically, iron deficiency and iron deficiency anemia are classified into 3 stages: iron deficiency, iron deficiency erythropoiesis and iron deficiency anemia. Their diagnostic criteria are respectively as follows.
1. Iron deficiency or potential iron deficiency At this time, there is only depletion of stored iron in the body. The diagnosis can be made by meeting (1) plus any of (2) or (3).
(1) There is a clear cause and clinical manifestation of iron deficiency.
(2) Serum ferritin <14 μg/L.
(3) Bone marrow iron staining shows iron granulocytes <10% or disappearance and extracellular iron deficiency.
2, iron deficiency erythropoiesis Refers to less iron intake by red blood cells than normal, but the reduction of intracellular hemoglobin is not yet obvious. The diagnosis of iron deficiency can be made by meeting the diagnostic criteria and having any of the following
(1) Transferrin saturation <15%.
(2) Erythrocyte free protoporphyrin >0.9µmol/L or >4.5g/gHb.
3. Iron deficiency anemia A significant decrease in intraerythrocytic hemoglobin, presenting as a small cell hypochromic anemia. The diagnosis is based on.
①Compatible with the diagnosis of iron deficiency and iron deficiency erythropoiesis;
②Small cell hypochromic anemia;
③Iron therapy was effective.
Diagnostic evaluation.
(1) Serum iron determination is influenced by many factors: it cannot be a diagnostic indicator of iron deficiency alone, and it should be emphasized that having a total serum iron binding capacity >64.44µmol/L (360µg/L) and transferrin saturation <15% is necessary to diagnose iron deficiency. A decrease in serum iron alone cannot be diagnosed as "iron deficiency" because it is not easily distinguished from a decrease in serum iron caused by other iron utilization disorders (e.g., chronic disease anemia). Similarly, if the total iron binding capacity is <64.44µmol/L (360µg/L) and the transferrin saturation is >15%, it cannot be diagnosed as “iron deficiency”.
(2) In the past, it was thought that bone marrow iron staining showing the disappearance of bone marrow stainable iron was the “gold standard” for the diagnosis of iron deficiency: since the adoption of the immunoassay method for ferritin determination in the 1970s, it was rarely used because the bone marrow iron staining method required high production conditions and was often affected by the inconsistent results of bone marrow sampling from different sites. It is believed that serum ferritin 1µg/L is equal to about 100mg of iron storage.
(3) Clinically, many patients with iron deficiency anemia are often combined with various chronic diseases (including inflammation, tumors and infections): serum ferritin levels are increased by chronic diseases. The criteria for serum ferritin in patients with chronic diseases with iron deficiency have not been standardized (some literature suggests that it should be greater than 60-140 µg/L). In addition to careful analysis of clinical and laboratory findings in such patients, further measurement of transferrin receptors (which should increase in iron deficiency) or erythrocyte ferritin (<5µg/ml cells as iron deficiency) is advisable.
【Treatment】.
Generally speaking, iron deficiency anemia is better treated with Chinese medicine, but when the patient has Hb less than 60g/L and continues to bleed, western iron treatment can be considered when Chinese medicine alone is ineffective, and if necessary, iron can be supplemented by intramuscular injection.
1.Etiological treatment The cause of iron deficiency should be removed as much as possible. Iron supplementation alone can only restore the blood picture. If the primary cause is neglected, the anemia cannot be completely treated.
2.Iron supplementation Iron supplementation therapy should be taken orally, 150~200mg of elemental iron per day is sufficient. Commonly used is ferrous iron preparation (ferrous succinate or ferrous fumarate). It should be taken with or after meals to reduce the stimulation of the gastrointestinal tract. Iron should not be taken with tea, otherwise it is easy to combine with the tannic acid in tea to form insoluble precipitate, which is not easily absorbed. Calcium and magnesium salts can also inhibit the absorption of iron and should be avoided at the same time.
After taking iron, patients can quickly recover from their symptoms. Reticulocytes generally rise in 3-4 days after taking, and reach a peak in about 7 days. Hemoglobin rises significantly after 2 weeks and reaches normal level after 1 to 2 months. After hemoglobin has returned to normal, iron therapy should be continued until serum ferritin returns to 50µg/L before discontinuing the drug. If monitoring with serum ferritin is not possible, iron should be continued for 3 months after hemoglobin has returned to normal to replenish the amount of stored iron that should be in the body.
If the patient cannot tolerate oral iron, cannot be absorbed or has to be replenished in a timely manner due to rapid blood loss, parenteral administration can be used instead. The most commonly used is intramuscular injection of iron dextran or iron sorbitol. The total therapeutic dose is calculated as follows: required supplemental iron (mg) = (150 – patient Hb g/L) × 3.4 (based on 3.4g of iron per 1000g of Hb) × body weight (kg) × 0.065 (normal human blood volume per kg of body weight is about 65m1) × 1.5 (including supplemental stored iron).
The above formula can be simplified as: required supplemental iron (mg) = (150 – patient Hb g/L) × body weight (kg) × 0.33. The first injection should be given at 50 mg, and if there is no adverse reaction, the second injection can be increased to 100 mg, and then 2 to 3 times a week until the total dose is used up. Local muscle pain, lymphadenitis, headache, dizziness, fever, urticaria and arthralgia can occur in about 5% to 13% of patients after iron injection, which are mostly mild and temporary. Occasionally (about 2.6%), anaphylactic shock may occur, which can be life-threatening, so there should be first-aid equipment (epinephrine, oxygen and resuscitation equipment, etc.) at the time of injection.
(i) Oral iron
1.Orally administered iron
(1) Ferrous sulfate Reduced heme synthesis due to iron deficiency, erythrocyte free protoporphyrin 500μg /L in iron deficiency anemia (normal 200-400μg /L).
(2) Iron fumarate 0.2 g/time, 3 times/day. Higher iron content and faster effect.
(3) Ferric ammonium citrate is often prepared as a 10% solution for internal use, 10 ml/time, 3 times/day. It is trivalent iron, not easily absorbed, but can replace tablets.
(4) Ligustrum is an iron ligand complex.
(5) Quicklime is ferrous succinate.
2. Iron for injection. It can be used for those who have gastrointestinal diseases or urgently need to increase iron supply.
(1) Iron dextran.
(2) Iron sorbitol: local pain with intramuscular injection, systemic reaction with iron dextran.
(II) Correction of iron deficiency etiology
1. Prevention and control of parasitic diseases, such as exorcism of hookworms.
2.Treat chronic gastrointestinal disorders.
3.Actively treat chronic blood loss.
4. Give prophylactic iron treatment to susceptible persons.
Prognosis]
The prognosis of iron deficiency anemia depends on whether the primary disease can be treated. After treating the primary disease, correcting dietary habits and stopping bleeding, supplemental iron therapy can make hemoglobin return to normal relatively quickly. If treatment is unsatisfactory, the reasons for failure are often
(i) wrong diagnosis: the anemia is not caused by iron deficiency;
② Combined chronic diseases (such as infection, inflammation, tumor or uremia) interfere with the treatment of iron;
③The cause of iron deficiency is not eliminated, and iron therapy fails to compensate for the lost iron;
(iv) Combination of folic acid or vitamin B12 deficiency affects the recovery of hemoglobin;
⑤ Inappropriate iron treatment (including insufficient daily dose, insufficient treatment course, failure to pay attention to the effect of food or other drugs on iron absorption, etc.).