High altitude polycythemia

Introduction to high altitude polycythemia Highaltitude polycythemia (highlytitude polycythemia) refers to excessive red blood cell hyperplasia caused by people who have lived in the high altitude for a long time. It is the most common clinical type of chronic high altitude disease, most people Occurred in the area above 3200m above sea level, but there are also a few people with low oxygen susceptibility that can occur in areas below 3200m above sea level. Compared with healthy people at the same altitude, the red blood cells, hemoglobin, and red blood cell volume of patients with high redness are significantly increased. The blood oxygen saturation is reduced, accompanied by clinical symptoms and signs of plethora; pathological changes are congestion of various organs and tissues, stasis of blood flow and hypoxia damage. basic knowledge The proportion of illness: 25% (more common in the plains to go to the plateau) Susceptible people: good for people living in the plateau Mode of infection: non-infectious Complications: cerebral hemorrhage

Causes of high altitude polycythemia

Environmental factors (55%):

Chronic hypobaric hypoxia is the root cause of high altitude polycythemia. Long-term smoking in the plateau will hinder the transmission of oxygen, reduce the oxygen uptake of tissues, and aggravate hypoxemia, leading to the occurrence of hyperbilirubinemia.

Other factors (35%):

Although this disease is a systemic multi-system disease, other factors such as high altitude obesity, nighttime sleep-disordered breathing, etc. are also likely to induce excessive red blood cell hyperplasia, which leads to the occurrence of high altitude polycythemia.

Pathogenesis

Chronic hypobaric hypoxia is the root cause of this disease. It is caused by many ways and mechanisms to cause erythrocytosis. Although many theories and hypotheses have been put forward, the more concentrated views are:

1. Respiratory drive weakened

Previous studies have suggested that plateau inhabitants and long-time residents have reduced hypoxic ventilatory response (HVR), which is considered to be the best adaptation of the human body to the plateau environment (accommodation), the passivation of ventilation response and the time of living plateau. Related to the length, Weil et al found that when the plain people lived on the plateau for 25 to 30 years, their HVR is similar to that of the plateau, but some people have doubts about this. However, a few plain people have reached the plateau for several months. A few years later, HVR showed a weakening, and there was excessive red blood cell hyperplasia, hypoxemia and elevated partial pressure of carbon dioxide. Cruz found that at the same altitude, the PaCO2 of high redness was significantly higher than that of non-hypertensive, which was 38.1mmHg. And 32.5mmHg (P<0.01); the scholars studied the blood gas and lung function of 21 cases of high red syndrome in 4300m area, and found that the resting lung ventilation of patients is about 70%-80% of healthy people, and the tidal volume is 60%. ~75%, and mild small airway obstruction; blood gas analysis patients' pH is lower than normal, and PaCO2 increased, suggesting that hyperosmolar has insufficient alveolar ventilation, Severinghaus suggested that in the case of normal lung function, resulting in Alveolar hypoventilation The reason may be related to the weakening of respiratory drive, that is, the surrounding or (and) central chemoreceptors are weakened by hypoxia. Sun et al. studied the HVR of plateau people in Lhasa (3685m), and the results were high red and normal human HVR. The slopes were A=17±8mmHg/(L·min) and 114±22mmHg/(L·min) (P<0.05), and the end-tidal PCO2 was 36.6±1.0mmHg and 31.5±0.5 mmHg (P<0.05), respectively. This further suggests that hyperventilation of the lungs may be associated with inactivation of HVR.

However, Kryger et al (3100m) compared the HVR of patients with high red syndrome and plateau inhabitants, and found no significant difference in HVR between the two groups, that is, the HVR of both groups showed passivation, but the tidal volume of the patient group decreased, invalid. The ratio of cavity to tidal volume is increased. What is more interesting is that when inhaling pure oxygen (100%), the patient's lung ventilation increases, and the end-tidal PCO2 decreases, while the normal person has no significant change, so the HVR passivation does not lead to high redness. The only reason may be other factors, thus leading to the hypoxia hypothesis of hypoxic ventilatory depression, the current study shows that respiratory drive is weakened (regardless of peripheral or central) Is the main cause of significant hypoxemia and relative hypercapnia in patients, but the causal relationship between them is still unclear. Is it the same as high altitude redness in patients with high altitude edema? That is to say, it is related to heredity. It is a new topic worthy of further discussion. Some people think that this disease is not a single factor. In addition to respiratory-driven factors, a large number of smoking, chronic respiratory tract Dyeing, nocturnal sleep-disordered breathing and obesity hypoventilation syndrome, can induce arterial oxygen saturation decreased.

2. The role of erythropoietin

Erythropoietin (EPO) is a glycoprotein hormone with a molecular weight of approximately 39,000. It acts mainly on the erythropoietin receptor on the erythroid committed progenitor cell membrane, promoting the proliferative differentiation of these committed progenitor cells and accelerating red blood cell maturation. Prevention of apoptosis (Apoptosis), fetal and neonatal EPO is secreted by hepatocytes, adulthood is mainly secreted by tubulointerstitial fibroblasts, but the liver still retains the ability to produce EPO, in addition to the brain, lung and thymus of mice A small amount of EPO is also found in the tissue. Regarding the regulation of EPO, the recognized factor is tissue hypoxia, but there may be other factors. Hypoxia, whether low-pressure (plateau) or blood-borne (anemia) can stimulate EPO. Generated, when the animal was exposed to 7% hypoxic environment, the mRNA of erythropoietin increased 150 times, and when it was severe anemia increased 300 times. Klause measured serum EPO for 9 climbers, with an average sea level of 6 units. It entered 4350m above sea level, increased to 58 units at 42h, and decreased to 31 units after 88h, but still higher than the plain value, and the concentration of EPO was significantly negatively correlated with SaO2 (r=-0.6), and the animals were at low pressure. After exposure to hypoxia for 30 minutes, EPO began to rise, reached a peak at 48h, and then gradually decreased. These data suggest that EPO will initially increase regardless of simulated hypoxia or high altitude, after 2 to 4 days of hypoxic induction. Decline, but does not fall to the plain value, indicating that the kidney has a feed-back regulation effect on the EPO.

However, how the kidney regulates EPO and how EPO regulates the production of red blood cells is still controversial. In general, when the renal oxygen receptor is stimulated by hypoxia, the tubulointerstitial fibroblasts secrete EPO and stimulate the original cells of the bone marrow. The division of nucleated red blood cells accelerates the maturation of red blood cells, thus increasing the number of red blood cells in the blood. As a result, on the one hand, it increases the oxygen carrying capacity of hemoglobin, increases oxygen transmission, and improves tissue hypoxia; on the other hand, if the hematocrit exceeds 60%, It significantly increases blood viscosity, slow blood flow, blood stasis in the microcirculation, and even thrombosis, which hinders the transmission of oxygen, thus aggravating the hypoxia of the tissue, so winslow proposed that in the absence of oxygen, the secretion of EPO may be excessive It is an important factor in the formation of high red disease, but some researchers have found that EPO in patients with high redness is not significantly higher than normal. Leon-Velarde studied EPO in the high altitude and high red syndrome in Peru (4300m). And compared with normal people in the plains, it was found that the EPO of the plateau group (regardless of normal or high redness) was significantly higher than that of the plain group, while the normal people of the plateau No significant difference between the high red disease, therefore, is the primary regulator of erythropoiesis EPO although the rate factor, but it is difficult to explain the EPO by changing mechanism are all formed of high red disease.

Modern EPO molecular biology research, EPO gene expression is related to hypoxia-inducible factor (HIF), HIF is a heterodimeric protein, composed of HIF-1 and HIF-1. It is believed that HIF-1 is an oxygen receptor that activates transcription of proteins (or enzymes) associated with hypoxia, such as EPO, vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and Glycolytic enzymes, etc., but the current study is more about the relationship between EPO and HIF, HIF-1, also known as EPO gene expression induction or potentiation factor, acts on the 3' side of the EPO gene, when the cells are cultured At 1% hypoxia, the RNA level of HIF-1 was significantly increased, while the culture was decreased at 20% oxygen, indicating that the production of HIF is closely related to the oxygen tension of the cells. The increase of HIF-1 can promote EPO. Gene transcription, accelerates EPO secretion and erythrocyte formation. Recently, Yu (1999) exposed 10% of oxygen to congenital partial defects HIF-1 (HIF1±) and non-defective HIF-1 (HIF1±) mice. After 1 to 6 weeks, a control was found and HIF1± mice developed erythrocytosis, right ventricular hypertrophy, pulmonary hypertension and lung The occurrence of tube myogenesis was significantly later than that of the control group, suggesting that HIF-1 not only acts on the formation of EPO, but also on other tissues such as pulmonary artery pressure and cardiac hypertrophy, which will provide new research on the pathogenesis of chronic high altitude disease. The idea.

3. Hemoglobin-oxygen affinity reduction

About 97% of oxygen transported by blood is combined with Hb and exists in red blood cells. The binding and dissociation of oxygen and Hb is a reversible reaction, that is, Hb O2óHbO2. In the process of oxygenation or oxygenation, a sigmoid curve can be formed due to the different conformations of Hb. The oxygen separation curve has important physiological significance. It is affected by pH, PCO2, temperature and 2,3-diphosphoglycerate (2,3-DPG), of which 2,3-DPG is especially important. 2,3-DPG is the product of the red blood cell glycolysis branch. The increase of 2,3-DPG in the blood can be combined with Hb, thus reducing the affinity of Hb and oxygen, the oxygen ion curve shifts to the right, the oxygen release increases, and the human body advances rapidly. After the plateau, the concentration of 2,3-DPG was significantly increased, which is the compensatory performance of the body for hypoxic acclimatization. However, the relationship between the change of 2,3-DPG and hyperbilirubation is not very clear, Eaton It was found that the 2,3-DPG of patients with high redness was 23% higher than that of normal people at the same altitude. The author found that in the 4300m area, the patient's whole blood and red blood cell 2,3-DPG were significantly higher than the local healthy people, and PaO2 is negatively correlated and positively correlated with P50 (PO2 when SaO2 is equal to 50%). Therefore, the increase in 2,3-DPG concentration in the plateau is increased. Oxygen transmission increases the oxygen uptake of the tissue, but its abnormal elevation can cause a decrease in free hemoglobin in the lungs, a significant decrease in blood oxygen affinity, and difficulty in the process of oxygen uptake from the alveoli, thereby reducing SaO2; the result is 2,3 - The synthesis of DPG causes SaO2 to be further reduced, thereby forming a vicious circle and developing a more serious erythrocytosis. Therefore, the excessive concentration of 2,3-DPG is one of the manifestations of the human body's maladaptive adaptation to the plateau.

Although the disease is a systemic multi-system disease, there are very few cases of direct death from hyper-redness. Arias-Stellar reports 3 autopsy, and Wrinkle reports 12 cases. The pathological damage of hyper-redness is extensive and multi-systemic, Heart, brain and lung involvement are most common, and the degree of damage is also serious. The brain manifests itself in the shallow curvature of the brain parenchyma, the vasodilatation of the brain and pia mater, or the rupture of blood vessels, and the presence of spots or slices in the brain. Hemorrhage; brain cell swelling, interstitial edema, necrosis of nerve cells, localized or extensive softening, simple hyperactivity of the heart does not occur, such as the heart has obvious pathological changes, it is considered high altitude heart disease The surface of the lung is dark red and the texture is relatively solid; the alveolar wall is thickened, the cavity is enlarged or the interstitial edema is enlarged, the pulmonary capillaries are highly dilated and congested, the pulmonary arterioles are thickened, the thrombus is formed in the lumen, and other organs such as Hemorrhage, thrombosis and tissue necrosis occur in the adrenal gland, digestive tract, kidney and spleen.

Plateau polycythemia prevention

1, pay attention to proper rest, cold and warm, avoid alcohol and tobacco, low-salt diet, with some sedatives, blood pressure can be reduced. Eat three meals on the plateau and have an experience; eat early, eat at noon, eat less at night.

2, the plateau pressure is low, the boiling point of water is also low, use the pressure cooker to cook, so that employees eat hot meals, cooked rice. Pay attention to improving the pattern of main and non-staple foods, and make good use of seasonings to make the dishes taste delicious and stimulate appetite.

3. People who enter the plateau should be educated against cold and frost, equipped with cold-proof articles such as cotton coats, leather caps, cotton shoes and gloves. Marching or traveling in the plateau should wash your feet frequently, change underwear, bake insoles, handle sweat, apply grease to hands and feet, and reduce direct contact with metal and ice. Pay attention to the rest activities in the march, such as rubbing your hands and feet, and stepping on the ground to avoid standing for a long time.

4, for the hematology 3 indicators are particularly high, and patients with comorbidities, or each time the disease returns to the plateau gradually worsening, should leave the hypoxic environment as soon as possible, transfer to the plain or lower altitude areas.

Plateau polycythemia complications Complications

Plateau polycythemia can be complicated by cerebral hemorrhage and high altitude heart disease.

Symptoms of high altitude polycythemia common symptoms fatigue shortness shortness chest tightness heart palpitations plateau bloody face thin anorexia insomnia tinnitus dizziness

Symptom

The disease is mostly chronic, and there is no clear onset time. It usually occurs when you move to the plateau for one year, or the original acute high altitude disease is delayed. The high red syndrome is caused by the increase of blood viscosity and slow blood flow. The anaerobic injury of various organs of the whole body; the severity of each organ is different, the clinical symptoms are different, the changes are very complicated, the most common symptoms are headache, dizziness, shortness of breath, fatigue, memory loss.

The severity of clinical symptoms is related to the degree of hypoxia caused by changes in hematology. After returning to the plains from a hypoxic environment, the hemoglobin and hematocrit return to normal, and the symptoms gradually disappear, but they can recur when they return to the plateau.

Peruvian scholars summarized the common symptoms and signs of high red syndrome: headache, shortness of breath, fatigue, mental dysfunction, palpitations, sleep disorders, tinnitus, poor appetite, cyanosis, conjunctival capillary congestion, muscle and/or joint pain, Finger (toe), finger toe numbness, abnormal feeling; domestic scholars counted 360 cases, the common symptoms are: dizziness, headache, shortness of breath, chest tightness, fatigue, joint pain, anorexia, weight loss, memory loss, insomnia. In addition, women's irregular menstruation, male impotence, loss of libido, etc. have also been reported.

2. Signs

Hair blemishes are the main signs of this disease. More than 95% of patients have different degrees of cyanosis, lips, cheeks, auricle edges, nails and other parts of the nail bed are blue-purple, and facial telangiectasia is purple-red stripes. The unique face of this disease, that is, "high-level blood surface", the eye-bound membrane is highly congested, the tongue purple tongue is thick and dry, the glossopharynx mucosa is black or blue-purple, about 17.7% of patients have clubbing, 12.8% There are nail depressions, some patients have facial and lower extremity edema, liver and spleen can be swollen, general rhythm rules, a few people with bradycardia, or with sinus arrhythmia, about 20% of cases in the apical region and pulmonary valve area can be heard I-II grade murmur, pulmonary artery II sound hyperthyroidism or division, blood pressure can be high or low, pulse pressure difference is small.

Examination of high altitude polycythemia

1. Blood examination <br /> The number of red blood cells in the blood increased abnormally, and the hemoglobin concentration also increased abnormally. Velarde reported 72 cases of high redness in Peru (3850m), with an average hemoglobin of 235g/L and a hematocrit of 71%. The diagnostic criteria for high redness in China are: erythroprotein > 200g / L, hematocrit > 65% and red blood cell count > 6.5 × 1012 / L, the total number of white blood cells and classification are normal, platelets are the same as healthy people at the same altitude. The main feature of the myeloid granulocyte system is that the red system proliferates vigorously, and the erythroid cells account for 33.3% of the nucleated cells. Among them, the late red blood cells are obvious, and the granulocyte and megakaryocyte systems have no obvious changes.

2. Blood gas analysis

The blood pH of patients with high red syndrome decreased, blood gas analysis showed significant hypoxemia, PaO2 decreased, PaCO2 increased, A-aDO2 increased, relative hypercapnia, lung function was mild except for small airway function, other no obvious Changes, small airway function in the patient's closed volume increased, forced exhalation in the middle of the flow decreased.

3. Gastroscopic examination

Due to the increased blood viscosity and slow blood flow, it not only directly affects the gastric mucosal microcirculation, but also causes capillary thrombosis due to hypercoagulable state of the blood. The gastric mucosa is severely hypoxic and hypoxic, prone to mucosal bleeding, erosion and necrosis. He has reported changes in gastroscope and pathology in 21 cases of hyperosmolar disease. The main manifestations are chronic erosive gastritis, chronic superficial gastritis and linear ulcer of gastric antrum. About 90% of the tumors show gastric mucosal hemorrhage or bleeding spots. It is edematous, about 81% have mucosal erosion and necrosis, and a few people have mild intestinal metaplasia and hyperplastic changes in histology.

4. ECG examination

Simple hyperactivity usually does not cause changes in ECG, or mild changes, such as QRS low voltage, incomplete right bundle branch block or localized right block.

5. X-ray inspection

Patients with high red syndrome often have a history of smoking, so the lung texture is generally increased and thickened, and some have a reticular change. If the heart and blood pressure are not combined, the heart shadow can be normal. If pulmonary hypertension and high altitude heart disease occur, the right ventricle appears. Increased, the pulmonary artery segment protruded and the right lower pulmonary artery tube diameter increased.

Diagnosis and differentiation of high altitude polycythemia

Diagnostic criteria

1. Migrants living in the plateau above 3000m above sea level, or a few inhabitants.

2. Have headache, dizziness, shortness of breath, fatigue, sleep disorders, cyanosis, eyeball combined with membrane congestion.

3. Hemoglobin > 200 g / L, hematocrit > 65% and red blood cell count > 6.5 × 1012 / L.

4. After leaving the hypoxic environment, the symptoms and signs disappeared, and then relapsed when returning to the plateau.

5. Exclude erythrocytosis caused by other diseases.

Differential diagnosis

Secondary erythrocytosis

Mainly caused by chronic bronchitis, emphysema, cyanotic congenital heart disease, thoracic deformity and other polycythemia, these diseases have typical symptoms and signs, such as chronic cough, heart murmur, etc., it is not difficult to identify.

2. Polycythemia vera

Most of the disease is in people over 50 years old. There is no primary disease and cause. The immigration plain can't be recovered, the blood oxygen saturation is normal, there is no blood surface, and the bone marrow changes to full hematopoietic hyperplasia and spleen enlargement.

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