Anemia of chronic disease

Introduction to chronic disease anemia Anemia of chronic disease (ACD) refers to a group of anemia secondary to chronic infections, inflammation and malignant tumors, characterized by shortened red blood cell life, iron metabolism disorders, increased inflammatory cytokines leading to a decrease in erythropoietin, and bone marrow to anemia. Compensatory hyperplasia inhibition. basic knowledge Sickness ratio: 35% Susceptible people: no special people Mode of infection: non-infectious Complications: heart disease, chronic heart failure

Chronic disease anemia cause

The role of cytokines (20%):

ACD is stimulated by the cellular immune system to cause a complex and extensive cytokine-mediated response, resulting in increased inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interferon. (IFN), etc., leading to erythroid hematopoietic inhibition, manifested by decreased production of erythropoietin (EPO) and slow response of bone marrow to EPO. Decreased EPO production is also associated with increased NO production. Patients with rheumatoid arthritis still have IL-6 liters. High, the latter can increase blood volume leading to blood thinning.

Red blood cell life is shortened (15%):

Factors such as enhanced phagocytic activity, bacterial toxins, hemolysin of tumors, vascular damage, and damage to erythrocyte membranes caused by fever in patients cause shortening of red blood cell life.

Abnormal iron metabolism (10%):

ACD has hypocalcemia, which is characterized by decreased serum iron, bone marrow iron utilization disorder, but excessive iron in macrophages. The mechanism may be excessive iron uptake after macrophage activation. IL-1 stimulates neutrophil release of milk during inflammation. Ferritin, which is easy to combine with iron, causes a decrease in the saturation of transferrin. The transferrin receptor on the erythrocyte membrane is also reduced in ACD, which makes iron utilization disorder. Recent studies have shown that iron metabolism abnormalities and iron stability in chronic disease anemia Iron homeostasis is regulated by heparic bactericidal protein. In the inflammatory disease, heparin is produced and secreted by the liver. Duodenal crypt cells and macrophages express 2M-HFE-TfR1 (2 microglobulin). - Hereditary hemochromatosis gene product HFE protein-transferrin receptor 1) complex, heparine acts on the 2M-HFE-TfR1 complex of crypt cells and macrophages through blood flow, promoting crypt cells and macrophages As the intake of iron increases, the duodenal crypt cells receive too much information about iron, which reduces the iron absorption of duodenal epithelial cells, resulting in hypocalcemia, while macrophages exhibit excessive iron.

Chronic infection (5%):

Lung abscess, tuberculosis, subacute infective endocarditis, osteomyelitis, chronic urinary tract infection, pelvic inflammatory disease, meningitis, chronic deep mycosis and AIDS.

Chronic non-infectious inflammatory disease (5%):

Connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, rheumatic fever, vasculitis, etc., as well as severe trauma, burns, etc.

Malignant tumors, lymphoma, leukemia, myeloma, etc.

Chronic disease anemia prevention

First, lose weight. Obese people have a much higher proportion of heart disease than normal weight, especially those with "apple-shaped" body (waist-hip obesity). As long as the elderly lose 3-5 kilograms, the heart condition will be greatly improved. At the same time, experts warn the fatter old man, do not expect to become a super model at once, to gradually achieve the purpose of weight loss through balanced diet and exercise.

Second, eat less egg yolk. A normal-sized egg yolk contains about 200 mg of cholesterol. If the elderly have higher cholesterol, they can only eat up to two egg yolks a week.

Third, more exercise. A moderate exercise for 20 minutes a day can reduce the risk of heart disease by 30%, and the quickest effect is best.

Fourth, quit smoking. Smokers are twice as likely to suffer from heart disease as non-smokers. The study found that after 2-3 years of smoking cessation, the risk of heart disease fell to the same level as non-smokers.

Fifth, pay attention to diet. In normal life, insist on eating low-fat foods, such as lean meat and low-fat dairy products.

Sixth, moderate drinking. Drinking 3-9 glasses of wine a week is appropriate for the heart. But be careful not to be greedy, because excessive drinking can cause heart disease.

Chronic disease anemia complications Complications, heart disease, chronic heart failure

Long-term chronic anemia can be complicated by anemia. Anemia in heart disease is mainly caused by severe anemia, which causes a significant decrease in blood oxygen carrying capacity, and insufficient oxygen supply to various systems of the body, thus increasing cardiac output. The heart load is aggravated. Although the increase in cardiac output is associated with decreased blood viscosity, accelerated blood flow, and increased cardiac contractility, it is primarily an increase in heart rate and stroke volume. The increase in stroke volume is closely related to the expansion of peripheral arterioles and the decrease in peripheral circulation resistance, so the surrounding circulation resistance is reduced, which is the main factor of high cardiac output. As the cardiac output increases, the systemic systolic blood pressure remains normal, so the left and right ventricles work significantly increase, the left and right ventricles expand and hypertrophy. A sustained increase in cardiac output inevitably leads to cardiac insufficiency.

Chronic disease anemia symptoms Common symptoms Cold conjunctiva becomes shallow or pale bone marrow damage white hair feces or rectum s... Abdominal "gas-like" mass

ACD often has the above chronic infection, inflammation or tumor history, lasting for more than 1 to 2 months, anemia is mild and moderate, non-progressive, often masked by underlying diseases.

1. Domestic diagnostic criteria

(1) Mostly mild to moderate anemia, often accompanied by chronic infection, inflammation or tumor and other basic diseases: the symptoms of anemia are often covered by the symptoms of the underlying disease, usually 1 to 2 months after the onset of the underlying disease After ACD, the severity of ACD is related to the underlying disease. For example, infectious diseases are associated with significant chills. The severity of anemia in fever is heavier than that without obvious systemic symptoms. The activity of rheumatoid arthritis and anemia are also Correlation; when the severity of anemia is more serious than the tumor limitation, the aggravation of the anemia does not require the tumor to involve the bone marrow. The ACD patient has no characteristic findings, and the diagnosis is generally dependent on laboratory tests. In most cases, The hematocrit is between 0.25 and 0.40, but 20% to 30% of patients are significantly lower than this level. The level of hemoglobin is generally 70-110 g/L, mostly positive cell anemia, 30% to 50%. The ACD manifests as small cell hypochromic anemia, which is seen in 50% to 100% of patients with rheumatoid arthritis and 44% to 64% of cancer patients, but the MCV is rarely lower than 72fl, and the red blood cell morphology is normal. Center was slightly lightly stained reticulocyte count in the normal range or slightly elevated.

(2) Serum iron and total iron binding capacity are lower than normal, and transferrin saturation is normal or slightly lower: these serum iron parameters have certain value for the diagnosis of ACD, serum iron often occurs after injury or infection It can be reduced in a short time, but the clinical value of serum iron alone is not significant, because the level of serum iron fluctuates greatly in normal people every day, and the transferrin is moderately reduced, which is slower than the rate of decline of serum iron. It may be because the half-life of transferrin (8-12 days) is longer than the half-life (90min) of serum iron. In patients with infectious diseases, serum iron is generally reduced within 24 hours of onset. If the disease improves in the short term, serum iron It returns to normal and there is no anemia. The decline in serum iron is related to the severity of the underlying disease.

(3) Iron staining of bone marrow cells showed a decrease in iron in red blood cells, and increased iron particles in macrophages: bone marrow, red ratio of 3:1 or 4:1, uncompensated bone marrow hyperplasia, bone marrow examination is the most important The value is to understand the iron storage in the bone marrow, the increase of iron storage in macrophages, the reduction of iron red blood cells accounted for 5% to 20% of the young red blood cells (normally 30% to 50%), therefore, serum iron levels and The decrease of iron granule count and the increase of bone reserve iron are characteristic features of ACD, and in combination with iron deficiency, the hemosiderin in macrophages can be reduced.

(4) Increased free protoporphyrin in red blood cells.

(5) Serum ferritin (SF) levels are higher than normal: Serum ferritin levels are a good indicator of iron storage in patients with no underlying chronic disease. However, for patients with ACD, serum ferritin is used to determine iron storage in vivo. The standard should be improved.

In addition to SF, serum copper is elevated in patients with ACD, which is largely due to increased levels of serum copper-binding protein (plasmin ceruloplasmin), an acute phase-reactive protein other than ceruloplasmin. Many serum proteins are elevated, such as C-reactive protein, haptoglobin, etc., and the level of certain plasma proteins is decreased, such as transferrin, which is due to its reduced synthesis in the liver or shortened life in circulation. Some studies have found that serum albumin levels in ACD patients decreased, serum albumin and transferrin levels and anemia degree were well correlated.

2. Foreign diagnostic criteria

Clinical manifestations and laboratory tests are the same as domestic diagnostic criteria. In addition, erythropoietin (EPO) levels are lower than those of iron deficiency anemia, which is equivalent to anemia. Serum EPO levels are low, probably due to cytokines and some unknowns. Factors inhibited the production of EPO. The level of serum EPO in ACD patients did not increase with the increase of anemia. Compared with hematocrit, the level of serum erythropoietin was particularly low.

Chronic anemia check

1. Peripheral blood: Anemia is normal cell, normal pigmentation, but also small cells and hypochromic anemia.

2. Serum iron (SI) is reduced and total iron binding capacity (TIBC) is also reduced.

3. Serum ferritin (SF) increased, serum soluble transferrin receptor (sFfR) did not increase, but ACD with iron deficiency can also increase.

4. Erythrocyte free protoporphyrin (FEP) and zinc protoporphyrin (ZPP) were only slightly elevated.

5. Bone marrow iron staining can increase the number of iron, but the number of iron granules is reduced and serum EPO levels are decreased.

According to the condition, clinical manifestations, symptoms, signs can choose ECG, X-ray, B-ultrasound and biochemical examination.

Diagnosis and diagnosis of chronic disease anemia

Diagnostic criteria

The basis of chronic infection, inflammation or malignant disease meets the following conditions: mild to moderate anemia, normal cell or small cell hypochromic anemia, normal bone marrow cell proliferation level and granular red ratio, serum iron and total iron binding capacity At the same time, the serum ferritin is increased, the iron in the bone marrow macrophages is normal or increased, the number of iron granule cells is decreased, and there is an iron utilization disorder, and ACD diagnosis can be considered.

Differential diagnosis

Iron deficiency anemia

Chronic disease anemia (ACD) is the second highest incidence of anemia following iron deficiency anemia (IDA). Both are easily misdiagnosed. The identification of simple IDA and ACD is relatively easy, but in patients with chronic diseases. It is very difficult to identify IDA and ACD. The statistics of rheumatoid arthritis (RA) anemia combined with iron deficiency can reach 27%, and Shanghai Huashan Hospital also accounts for 25%. Because the treatment methods are completely different, the differential diagnosis is important. Clinical significance, the following contribute to the identification of ACD and IDA.

(1) History: ACD is often associated with chronic infection, inflammation or tumor (sustained for more than 1 to 2 months), but the blood loss caused by these diseases itself, renal failure, drug-induced myelosuppression and tumor invasion of bone marrow must be ruled out. Anemia, while IDA often has a history of malnutrition or a history of chronic blood loss.

(2) degree of anemia: ACD is mild to moderate anemia, non-progressive, with components of dilute anemia, and is related to the severity of the underlying disease, but 20% to 30% ACD hematocrit (Hct) can be significantly reduced.

(3) Red blood cell morphology: ACD patients are normal cell, normal pigmentation, small cell cytoplasm accounts for 2% to 8%, up to 20% to 40%, and erythrocyte hypochromic changes of 23% to 50% (chronic infection) ), 44% to 64% (cancer), even 50% to 100% (RA), ACD MCHC decrease before MCV decrease, IDA MCV decrease before MCHC decrease, red blood cell size is different and profile is significant in IDA, ACD Not significant, the differential value of MCV is higher than serum iron/total iron binding, MCV <72fL is rare in ACD, and IDA is very common [average 74 (53-93) fL].

(4) Serum iron/total iron binding capacity (SI/TIBC): typical ACD: SI decreased, TIBC decreased, transferrin saturation (TS) was normal or decreased; typical IDA: SI decreased, TIBC increased, TS decreased, Information from Shanghai Huashan Hospital: There was no statistically significant difference in TIBC levels between IDA, ACD and chronic disease with iron deficiency (CDID).

(5) Bone marrow iron staining: It is the gold standard for identifying IDA and ACD. IDA and CDID bone marrow can be stained with iron deficiency, while ACD bone marrow can increase iron staining, but iron granule cells are reduced (5% to 20%).

(6) serum ferritin (SF): SF is elevated in ACD, IDA is decreased, SF can be reduced in CDID, but how low is helpful for diagnosis? Some people think that SF 30 ~ 200g / L can be used as an overlapping standard, <60g/L was used as the diagnostic criteria for RA anemia combined with iron deficiency. Shanghai Huashan Hospital applied SF<60g/L+erythroferrin<5g/cell as the diagnostic criteria for the diagnosis of RA anemia with iron deficiency, with an accuracy of 0.94. The positive likelihood ratio of iron deficiency and non-iron deficiency in chronic anemia is the highest at SF of 25-44 g/L.

(7) Serum soluble transferrin receptor (sTIR): Calculate the area under the receiver operating characteristic (ROC) curve (AUCROC) to evaluate the diagnostic efficiency of various iron parameters for identifying ACD and IDA.

(8) Erythrocyte free protoporphyrin (FEP) and zinc protoporphyrin (ZPP): The degree of ACD elevation is inferior to that of IDA, which is of little value for differential diagnosis.

(9) Serum erythropoietin (sEPO) level and O/P (1ogEPO) ratio: The measured value of ACD patient is lower than the EPO level of the anemia Hb level.

2. Dilute anemia

Dilute anemia can occur in patients with chronic diseases, especially in highly advanced malignant tumors, but the chronic diseases that can be seen clinically with dilute anemia are mainly myeloma or macroglobulinemia, and attention should be paid to the diagnosis of ACD. Identification of diluted anemia.

3. Other types of anemia

In addition to chronic disease anemia, malignant tumor anemia can also cause bone marrow disease due to malignant tumor cell bone marrow metastasis, anti-tumor chemotherapy caused by drug-induced megaloblastic anemia and aplastic anemia, malignant tumor and connective tissue disease can merge themselves Immune hemolytic anemia, renal damage caused by kidney damage caused by connective tissue disease can cause renal anemia, etc. Therefore, it is necessary to pay attention to the identification of anemia of the above type when diagnosing ACD.

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