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Hypoxia regulated molecules Proteins

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Hypoxia regulated molecules Proteins

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Hypoxia regulated molecules Proteins Background

Hypoxia refers to a pathological process that causes abnormal changes in the metabolism, function, and morphology of a tissue due to insufficient oxygen supply or impaired oxygen use. Hypoxia is a very common pathological process in various clinical diseases. Hypoxia of vital organs such as the brain and heart are also an important cause of death. In addition, due to the marked decrease in arterial blood oxygen content, the tissue is insufficiently supplied with oxygen, which is also called hypoxemia. Hypoxia refers to the lack of endogenous oxygen. Endogenous oxygen refers to the oxygen bound to the cells.


Common causes of hypotonic hypoxia are low oxygen partial pressure of inhaled gas, pulmonary dysfunction, and increased venous blood adulteration into arterial blood.

(1) The oxygen partial pressure of the inhaled gas is too low: Hypoxia caused by inhaling the gas with a low oxygen partial pressure is also called atmospheric hypoxia.

(2) External respiratory dysfunction: caused by pulmonary ventilation or ventilation dysfunction, called respiratory hypoxia. Common in various respiratory diseases, respiratory central depression or respiratory muscle paralysis.

(3) Venous blood flows into arteries: more common in congenital heart disease.

Physiological change

Characteristics of blood oxygen changes

① PaO2 is reduced due to the low oxygen pressure diffused into the arterial blood. Too low PaO2 can directly cause the decrease of CaO2 and SaO2;

② If there is no abnormal change in quality and quantity of Hb, CO2 max is normal;

③ As PaO2 decreases, 2,3-DPG in red blood cells increases, so blood SaO2 decreases;

④In hypotonic hypoxia, the decrease of PaO2 and blood SaO2 reduces CaO2;

⑤ Arterial-venous oxygen difference decreases or changes little. Usually about 5ml of oxygen is used when 100ml of blood flows through the tissue, that is, A-V d O2 is about 2.23mmol/L (5ml/dl). The motive force for the diffusion of oxygen from the blood to the tissue is the oxygen partial pressure difference between the two. When hypotonic hypoxia, PaO2 is significantly reduced and CaO2 is significantly reduced, which slows down the diffusion rate of oxygen and diffuses the same amount of blood to the tissue. Reduced oxygen levels eventually lead to reduced AV d O2 and tissue hypoxia. In the case of chronic hypoxia, the change in A-Vd O2 may be insignificant when the tissue's ability to use oxygen is increased.

Changes in skin and mucous membrane color

The average concentration of deoxygenated Hb in normal capillaries was 26 g/L. During hypotonic hypoxia, the oxygenated Hb concentration in both arterial and venous blood is reduced, the oxygenated Hb in capillaries is necessarily reduced, and the deoxygenated Hb concentration is increased. When the average concentration of deoxygenated Hb in capillaries is increased to more than 50g/L (5g/dl) (SaO2 ≤ 80% to 85%), the skin and mucous membranes can appear blue and purple, which is called cyanosis. It is easy to appear in chronic hypotonic hypoxia. Aster is a manifestation of hypoxia, but patients with hypoxia do not necessarily all have cyanosis. For example, blood hypoxia caused by anemia may be without cyanosis. Similarly, patients with cyanosis may also be free of hypoxia. For example, patients with polycythemia vera, due to the abnormal increase in Hb, the deoxygenated Hb content in capillaries can easily exceed 50g/L, so cyanosis is prone to occur without hypoxia symptoms. Hemic hypoxia Hemic hypoxia refers to changes in the quantity or quality of Hb that cause CaO2 to decrease or at the same time the oxygen associated with oxygenated Hb is not easy to release the tissue caused by hypoxia. Hemorrhagic hypoxia caused by a decrease in the amount of Hb, CaO2 decreases due to its normal PaO2, also known as isotonic hypoxemia.

Hypoxia regulated molecules Proteins

1. HIF-1 sensory regulation

Research suggests that HIF-1 (hypoxia induced factor-1) is a vital transcription factor controlled by changes in oxygen concentration. HIF-1 in the nucleus, as a promoter of hypoxia-sensitive genes, binds to the hypoxia-responsive element (HRE, 5-RCGTG-3) of the target gene to initiate gene transcription and protein translation.

Hypoxia regulated molecules Proteins Figure 1. Protein structure of HIF.

2. Increased red blood cell adaptability

People living on the plateau and people with chronic chronic hypoxia can increase red blood cells to 6 × 106 /mm 3 and Hb up to 21g/dl. The increase mechanism is that when hypoxia, hypoxic blood can stimulate mesangial cells to increase the production of erythropoiesis-stimulating factor (EPO). EPO can stimulate RBC-based unidirectional stem cells to differentiate into proto-RBC and proliferate and mature. EPO can also promote the synthesis of Hb and reticulocytes into the blood, increase the red blood cells and Hb in the blood, and increase the oxygen capacity in the blood. Eventually, the blood's ability to carry oxygen is increased to increase the oxygen content, thereby increasing the O2 supply to tissues and organs.

Hypoxia regulated molecules Proteins Figure 2. Red blood cell.

3. Increased Myoglobin (Mb)

Because Mb has a greater affinity for oxygen than Hb, for example, when the oxygen partial pressure drop is 10mmHg, the oxygen saturation of Hb is about 10%, and the oxygen saturation of Mb can reach 70%. Therefore, when athletes perform vigorous exercise to make muscles When the tissue oxygen partial pressure is further reduced, Mb can release a large amount of oxygen for use by tissues and cells. Increased Mb may have the effect of storing oxygen.

Hypoxia regulated molecules Proteins Figure 3. Protein structure of Myoglobin.

4. Cell membrane changes

The decrease in cell membrane potential precedes the decrease in intracellular ATP content. The reason for the decrease in membrane potential is the increased permeability of the cell membrane to ions, resulting in poor ion concentration through the cell membrane, followed by sodium influx, potassium outflow, calcium inflow, and cells A series of changes such as edema.

Hypoxia regulated molecules Proteins Figure 4. Illustration of a Eukaryotic cell membrane.


  1. Gore CJ, et al.; Nonhematological mechanisms of improved sea-level performance after hypoxic exposure. Med Sci Sports Exerc.2007,39 (9): 1600–09.

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