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- 1. 1 Purpose: formation knowledge on etiology and pathogenesis of hypoxia D. P. Bilibin, V. A. Frolov
- 2. Questions 1. Definition of hypoxia and its classification 2. Exogenous hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, oxygen blood capacity, PaCO2 and pH in the given type of hypoxia 3. Respiratory hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, oxygen blood capacity, PaCO2 and pH in the given type of hypoxia 4. Anemic hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, oxygen blood capacity, PaCO2 and pH in the given type of hypoxia
- 3. Questions 5. Circulatory hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, oxygen blood capacity, PaCO2 and pH in the given type of hypoxia 6. Histotoxic and substrate types of hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, blood oxygencapacity, PaCO2 and pH in the given type of hypoxia 7. Overutilization hypoxia: causes, types and typical changes of PaO2, PvO2, Pa-vO2, oxygen blood capacity, PaCO2 and pH in the given type of hypoxia 8. Conditions that determine the susceptibility of cells to hypoxia. 9. Signs of acute hypoxia. 10. Adaptive reactions in acute hypoxia. 11. Mechanisms of long-term adaptation to hypoxia.
- 4. Hypoxia is a typical pathologic process characterized by a decrease in biological oxidation leading to depletion of ATP. Definition 2
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- 9. Fulminant hypoxia usually develops within several seconds after a decrease in oxygen arterial tension (PaO2) up to 20 mm Hg or less. manifests in dizziness, blurred vision, loss of consciousness or collapse. Pulmonary and arterial hypertension in the first few seconds can be observed. Elimination of causative factors leads to rapid restoration of consciousness and all the disturbed functions.
- 10. ACUTE HYPOXIA lasts from several minutes to several hours appears when oxygen arterial pressure ranges from 25 to 40 mm Hg The symptoms are similar to those of alcohol intoxication and include ataxia, slowed reflexes, slurred speech, overconfidence, and, eventually, unconsciousness. Coma and death can occur in minutes to hours if the compensatory mechanisms of the body are not adequate
- 11. CHRONIC HYPOXIA develops in the setting of PaO2 ranging from 40 to 60 mm Hg. Symptoms of chronic hypoxia are similar to those of severe fatigue, and include dyspnea and shortness of breath. Dyspnea, Cheyne-Stokes breathing, can occur in patients with chronic hypoxia, especially during sleep.
- 12. Oxygen balance indicators • Arterial Partial pressure of oxygen (рaО2) – 80 – 100 mm Hg. (0,3 ml О2 in 100 ml of blood) • Venous Partial pressure of oxygen 35-45 mm Hg • Oxygen carrying capacity of arterial blood 16,5 - 20,5vol.%, ~20 ml О2 in 100 ml of blood; • Oxygen carrying capacity of venous blood 15 vol.% • Arteriovenous oxygen difference 4-5 vol.% (oxygen utilization) • Hemoglobin saturation: - SаО2 arterial blood 95 – 98 % - SvО2 venous blood 70 - 77 %
- 13. • The oxyhemoglobin dissociation curve describes the relation between the partial pressure of oxygen (x axis) and the oxygen saturation (y axis). The curve has a sigmoidal or S-shape. At pressures above about 60 mmHg, the standard dissociation curve is relatively flat, which means that the oxygen content of the blood does not change significantly even with large increases in the oxygen partial pressure.
- 14. Joseph Barcroft
- 15. Exogenous hypoxia рО2 in the air Examples: unventilated rooms, submarines hypoventilation during mechanical ventilation Mountain sickness High altitude sickness Decompression syndrome NORMOBARIC: рО2, normal Patm HYPOBARIC: Patm, рО2 © П.Ф.Литвицкий, 2004 © ГЭОТАР-МЕД, 2004
- 16. • Exogenous hypobaric hypoxia results from the inhalation of air containing oxygen at subnormal pressure. For example, on ascent to high altitude, the percentage composition of the air does not change, but the oxygen partial pressure decreases.
- 17. Patm, рО2 HYPOXEMIA EXITATION OF THE RESPIRATORY CENTER HYPERPNEA HYPOCAPNIA, GASEOUS ALKALOSIS HYPOBARIC HYPOXIA Redused blood supply to heart and brain Shift of oxyhemoglobin dissociation curve to left
- 18. • Exogenous normobaric hypoxia can occur when oxygen is displaced by the inert or anesthetic gases such as nitrous oxide and ethylene, or oxygen is consumed by combustion in closed space. • рО2 in inhaled air • hypoxemia • hypercapnia • Gaseous and metabolic acidosis • Dilation of cardiac and brain vessels • Shift oxyhemoglobin dissociation curve to the right
- 19. Respiratory hypoxia • alveolar hypoventilation (can be induced by diverse causes which interfere in the respiratory mechanics, the neural control of depth and rate of respiration and the passage of air through the airways). • lungs diffusion capacity disorder (occurs when pathologic process destroys a large portion of alveolar membrane reducing the surface area or when significantly increases the diffusion distance across the alveolar-capillary membrane • Lungs perfusion disorders hypoxemia hypercapnia gaseous and metabolic acidosis
- 20. Type of hypoxia OCC (vol. %) Arterial blood Venous blood О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg А/V О2 differe nce О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg exogeno us + respirato ry N or N or Indicators of different types of hypoxia
- 21. Circulatory hypoxia • Generalized (diseases of cardiovascular system) • Local (regional circulation disorders) Ischemic Congestion )
- 22. Type of hypoxia OCC (vol. %) Arterial blood Venous blood О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg А/V О2 differe nce О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg Circulato ry N or N N N Indicators of different types of hypoxia
- 23. HEMIC (ANEMIC) HYPOXIA • Anemia (decrease in blood Hb content) • abnormal hemoglobin affinity to oxygen (CO, nitrites poisoning ) • Shifting of oxyhemoglobin dissociation curve
- 24. СО poisoning Incomplete combustion of organic matter due to insufficient oxygen supply (cigarette smoke, house fires, heaters, wood burning stoves, internal combustion vehicle exhaust СО Formation of carboxyhemoglobin (HbСО) The affinity between hemoglobin and carbon monoxide is approximately 230 times stronger than the affinity between hemoglobin and oxygen (Blood is unnatural crimson (as raspberry), skin is bright red) raspberry
- 25. • Methemoglobin is formed when hemoglobin iron is oxidized from the ferrous (F++) to the ferric (Fe+++) state. Methemoglobin is incapable of carrying oxygen. Some drugs and foods, such as nitrites, phenacetin and fava beans can produce methemoglobin, especially in people with genetic deficiency of glucose-6-phosphate dehydrogenase. • MetHb is brown; the color of blood is brown. Skin surfaces are dirty grey.
- 26. Type of hypoxia OCC (vol. %) Arterial blood Venous blood О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg А/V О2 differe nce О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg Hemic (anemia) N N N or Hemic (СО poisonin g) N
- 27. Histotoxic (tissue) hypoxia • Histotoxic hypoxia is due to interference with the ability of the tissue to use oxygen even though the supply is normal or greater than normal. Any factor that leads to mitochondrial disfunction may be a cause of tissue histotoxic hypoxia. In histotoxic hypoxia, the oxygen delivery remains normal, but the venous oxygen tension and content are high because the oxygen is not consumed by the tissue
- 28. Type of hypoxia OCC (vol. %) Arterial blood Venous blood О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg А/V О2 differe nce О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg Tissue N N N N
- 29. • Substrate hypoxia takes place at starvation, hypoglycemia • Overutilization hypoxia is due to an increase in the demand of tissues for oxygen to a level which exceeds the available oxygen supply. An example of overutilization hypoxia is seizures.
- 30. Type of hypoxia OCC (vol. %) Arterial blood Venous blood О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg А/V О2 differe nce О2 в con- tent in vol.% Нв saturat ion with О2 рО2 Mm Hg egogeno us + respirato ry N or N or circulato ry overutiliz ation N or N N N hemic N N N Tissue, substrate N N N N
- 31. Adaptation to hypoxia • Immediate compensatory reactions include: • Increased alveolar ventilation. The hypoxic stimulation of the chemoreceptors increases alveolar ventilation to a maximum of about 65%. • Increased diffusing capacity as much as threefold. • Cardiac output often increases as much as 30% • An increase in numbers of capillaries in the tissues, which is called, increased capillarity. • An increase of blood flow rate • Centralization of blood flow • Increased Hb content • Erythrocytosis • Activation of oxidative enzymes • Glycolysis activation
- 32. Formation of mitochondrial net at hypoxia
- 34. Prolonged adaptation to hypoxia • Hyperplasia and hypertrophy in organs and systems needed for oxygen transport and oxygen utilization by tissues • Increased tissue myoglobin, cellular mitochondria, brain neuroglobin • Hyperplasia of erythropoietic tissue • Neuroglobin reversibly binds oxygen with an affinity higher than that of Hb. It also increases oxygen availability to brain tissue and provides protection under hypoxic conditions, potentially limiting brain damage. It binds to cytochrome C and prevents apoptosis
- 37. Remodelling of vascular system Activation of Oxidative enzymes Proliferative processes and survival Erythropoiesis activation HIF-1a >200 Target genes
- 38. • Metabolic disorders • ↓O2 → energy deficiency → activation of glycolysis, glycogenolysis, lipolysis, ketogenesis, proteolysis → exhaustion of energetic depot, ketosis, negative nitrogen balance, azotemia.
- 39. • Disorders of organism’s functions • CNS. Neurons are highly susceptible to hypoxia. Firstly there are disorders of inhibition processes in brain cortex. That leads to euphoria. Then there is inhibition processes prevalence. One of the most important effects of hypoxia is decreased mental proficiency, which decreases judgment, memory and the performance of discrete motor movements. Neurons suffer irreversible injury in 3-5 min.
- 40. Consequences of ATP deficiency ATP cellular functions glycolysis Lactic acid acidosis Lysosomal enzymes activation autolysis ionic imbalance calcium hydrolases activation reduction in protein synthesis
- 42. • Respiratory system. Firstly hyperpnea occurs then it is changed by bradypnea and periodic breathing. • Cardio-vascular system. Cardiac muscle and kidney take 30 minutes to 2 hours to develop irreversible cell injury in response to hypoxia. At the beginning there is tachycardia, increased cardiac output and centralization of blood flow. Then there are different disorders of cardiac functions: arrhythmia, low contractile ability. • Alimentary tract. Hypoxia inhibits secretion of gastrointestinal juices, impairs absorption of meals.