Hypoxia – Classification, Pathogenesis, Mechanism, Types, Risk Factors

Hypoxia is a typical pathological process in which aerobic metabolism weakens due to a decrease in the partial pressure of oxygen in the mitochondria, i.e. in the cell, the number of high-energy compounds decreases and the products of anaerobic metabolism accumulate (Nunn, 1969).

Hypoxia is a condition observed in the body with an inadequate supply of oxygen to tissues and organs or with a violation of the utilization of oxygen in them in the process of biological oxidation (AM Charny, 1961).

Hypoxia (oxygen deficiency) is a discrepancy between metabolic demand and its energy supply, which is accompanied by a temporary release of any indicators of oxygen homeostasis from the oscillation limits outlined by the boundaries of the physiological zone. (V.A. Berezovsky, 1978).

Hypoxemia – insufficient oxygen saturation of the blood.

Asphyxia (translated from Greek – no pulse) is a state of hypoxia, combined with an increase in the tension of carbon dioxide in the blood and tissues.

CLASSIFICATION

  1. Hypoxia due to a decrease in the partial pressure of oxygen in the inhaled air (exogenous type of hypoxia or hypoxic hypoxia).
  2. Hypoxia in pathological processes that disrupt the supply of oxygen to tissues at normal levels in the environment or utilization of oxygen from the blood at normal oxygen saturation with O 2 :
    1. respiratory (respiratory);
    2. cardiovascular (circulatory);
    3. blood (hemic);
    4. tissue (histotoxic);
    5. mixed.


PATHOGENETIC VARIANTS OF VARIOUS HYPOXIA

EXOGENIC TYPE OF HYPOXIA OR HYPOXIC HYPOXIA

  1. Hypobaric form – occurs when the total barometric pressure decreases (rise to altitude).
  2. Normobaric form – occurs when the oxygen content selectively decreases at normal total pressure (being in confined or poorly ventilated spaces).

RESPIRATORY (RESPIRATORY) TYPE OF HYPOXIA

It occurs when there is insufficient oxygen transport from normal atmospheric air to the blood plasma flowing through the lungs due to a violation of the external respiration system.

DEVELOPMENT MECHANISMS

  1. Alveolar hypoventilation.
  2. Violation of general pulmonary perfusion.
  3. Local violations of ventilation-perfusion relations.
  4. Excessive shunting of venous blood in the lungs.
  5. Difficulty diffusion of oxygen through the alveolar-capillary membrane.

CARDIOVASCULAR (CIRCULATORY) TYPE OF HYPOXIA

It arises as a result of hemodynamic disturbances, leading to an insufficient supply of organs and tissues with oxygen for normal life, with a normal saturation of arterial blood with it.

The main hemodynamic indicator characterizing circulatory hypoxia is a decrease in comparison with the proper values ​​of the blood flow velocity (Q), i.e. the amount of blood flowing through the total lumen of microvessels per unit time.

Q depends on several factors:

Q = f (V, P, W, R),

where V is the volume of blood circulating in a tissue site, organ or organism as a whole; P = Pa-P in – pressure gradient between the arterial part of the bed (Pa) and the venous (Pv); W is the total vascular tone of the given pool; R – rheological properties of blood.

Thus, the development of this type of hypoxia can be caused by any of the listed hemodynamic factors and changes in blood flow. There is often a combination of two or more factors.

BLOOD (HEMIC) TYPE OF HYPOXIA

It arises as a result of the inability of blood, in the presence of normal oxygen tension in the pulmonary capillaries, to bind, transfer to tissues and give off a normal amount of oxygen, i.e. the pathogenetic basis of this type of hypoxia is a decrease in the real oxygen capacity of the blood.

This can be when:

  1. a decrease in the amount of hemoglobin;
  2. qualitative changes in hemoglobin of hereditary and acquired genesis;
  3. violations of the physicochemical conditions necessary for the normal absorption of oxygen by hemoglobin from the blood plasma of the pulmonary capillaries and the release of oxygen in the tissue capillaries.

TISSUE (HISTOTOXIC) TYPE OF HYPOXIA

It arises as a result of disruption of the processes of biological oxidation in cells during the normal functioning of all links of the oxygen transport system to the place of its utilization.

Oxygen utilization by tissues can be difficult in the following cases.

  1. The action of various inhibitors of biological oxidation enzymes:
    1. 1st type of inhibition – cyanides (compound with Fe 3+ , which prevents the reduction of iron of respiratory enzymes and the transfer of oxygen to cytochrome);
    2. the second type of inhibition – reversible or irreversible binding with functional groups of the protein part of the enzyme, which play an important role in the catalytic activity of the enzyme (heavy metals, alkylating agents, etc.);
    3. the third type of inhibition – competitive inhibition: interaction of enzymes with substances that have a structural similarity to natural oxidation substrates (many dicarboxylic acids).
  2. Changes in the physical and chemical conditions of the environment, significantly affecting the activity of enzymes (pH, temperature, concentration of some electrolytes, etc.).
  3. Violation of the synthesis of enzymes.
  4. Disorganization of cell membrane structures:
    1. lipid peroxidation (LPO);
    2. activation of phospholipases;
    3. osmotic stretching of membranes;
    4. binding of proteins to the membrane surface and changes in protein conformation;
    5. the effect of excess calcium ions.


MIXED TYPE OF HYPOXIA

  1. The same factor causes a combination of two or more types of hypoxia.
  2. Initially, one type of hypoxia occurs, and then, as the disease progresses, other types join.

PROTECTIVE-ADAPTIVE REACTIONS IN HYPOXIA

1. URGENT ADAPTATION TO HYPOXIA

  1. Adaptive reactions of the external respiration system:
    1. an increase in alveolar ventilation due to deepening and increased respiration and mobilization of reserve alveoli;
    2. an increase in pulmonary blood flow and an increase in perfusion pressure in the capillaries of the lungs;
    3. an increase in the permeability of the alveolar-capillary membranes for gases.
  2. Adaptive reactions in the circulatory system:
    1. the development of tachycardia, an increase in stroke and cardiac output;
    2. an increase in the mass of circulating blood due to the release from the blood depot;
    3. an increase in systemic blood pressure and blood flow velocity;
    4. centralization of blood circulation.
  3. Adaptive reactions of the blood system:
    1. increased dissociation of oxyhemoglobin due to acidosis and an increase in the content of 2,3-diphosphoglycerate in erythrocytes;
    2. increasing the oxygen capacity of the blood by increasing the leaching of erythrocytes from the bone marrow;
    3. activation of erythropoiesis by increasing the formation of erythropoietins in the kidneys and, possibly, other organs.
  4. Tissue adaptive reactions:
    1. limitation of the functional activity of organs and tissues that are not directly involved in the provision of oxygen transport;
    2. an increase in the conjugation of oxidation and phosphorylation and the activity of enzymes of the respiratory chain;
    3. enhancement of anaerobic ATP synthesis due to the activation of glycolysis.

Stage 1 – urgent adaptation – can develop in two directions.

  1. If the action of the hypoxic factor stops, then adaptation does not develop and the functional system responsible for adaptation to hypoxia is not fixed.
  2. If the action of the hypoxic factor continues or is periodically repeated for a sufficiently long time, then the third stage of long-term adaptation begins .

2nd stage – transitional.

With it, there is a gradual decrease in the activity of systems that ensure the adaptation of the body to hypoxia, and a weakening of stress responses to the repeated action of the hypoxic factor.

3rd stage – the stage of sustainable long-term adaptation.

It is characterized by a high resistance of the organism to the hypoxic factor.

4th stage.

  1. If the action of the hypoxic factor ceases, then gradually maladjustment of the organism occurs.
  2. If the action of the hypoxic factor increases, then the failure of the functional system, the breakdown of adaptation and the complete depletion of the organism are likely.