STUDY - Technical - New Dacian's Medicine
Hypoxia,
Polycythemia and Cyanosis (1)
Translation Draft
I can't believe that, in such a short space of time, I repeat the impossibility of posting daily (so, clearly, these delays will get stuck). But I won't repeat it again, I'll recover. Offf, my problems are less interesting... Get to work!
Let's start with hypoxia! The main role of the cardiorespiratory system is to provide oxygen (and nutrients) to cells and remove carbon dioxide (and other metabolism products) from their level.
Proper maintenance of this function depends on an intact cardiovascular and respiratory system and an inspired gas supply containing oxygen to an adequate extent. Changes in oxygen and carbon dioxide pressure, as well as changes in intraeritrocytic concentration of organic compounds with phosphate groups, in particular 2,3 diphosphoglyceric acid (2,3-DPG), cause alterations in the oxygen dissociation curve.
When hypoxia is a consequence of respiratory failure the pressure of alveolar dioxide (PaCO2) usually increases and the oxygen dissociation curve is diverted. Under these conditions, or when the concentration of 2.3-DPG increases, the proportion of saturated hemoglobin in the arterial blood at a given level of alveolar oxygen pressure (PaO2) decreases.
Both arterial hypoxia and cyanosis are more influenced by the degree of reduction of PaO2 when it results from lung disease than when the reduction occurs by lowering the partial oxygen pressure in the inspired air, in which case PaCO2 decreases consecutively to anoxia-induced hyperventilation, and the oxygen dissociation curve is diverted to the left, thus limiting the reduction of oxygen saturation of hemoglobin.
From the point of view of differential diagnosis we have several landmarks. We'll start with anemic hypoxia. Any decrease in haemoglobin concentration is accompanied by an appropriate decrease in the blood's oxygen transport capacity. PaO2 remains normal, but the absolute amount of oxygen carried by the blood volume unit is diminished. As anemic blood passes through the capillaries and the usual amount of oxygen is extracted from it, PO2 from the venous blood decreases to a greater extent than would normally be the case.
Another milestone would be carbon monoxide poisoning. Hemoglobin combined with carbon monoxide (carboxyhemoglobin) is not available for oxygen transport. In addition, the presence of carboxyhemoglobin moves the dissociation curve of hemoglobin to the left, so that oxygen can only be discharged at low pressures.
Through this formation of carboxyhemoglobin, a given level of reduced oxygen carrying capacity produces a higher degree of tissue hypoxia than the equivalent reduction of hemoglobin due to simple anemia. In the case of respiratory hypoxia, lack of arterial saturation is a common finding in advanced lung diseases. The most common cause of respiratory hypoxia is the non-correlation of ventilation with infusion, resulting from the infusion of poorly ventilated alveoli.
It can also be caused by hypoventilation when associated with increases in PaCO2. These two forms of respiratory hypoxia are usually easily corrected by the inspiration of O2. A third cause is the shunt of blood circulation from right to left by infused unventilated portions of the lung, as in pulmonary atelectasis or in vascular abnormalities of the lung with arteriovenous connections. In this situation the low PaO2 is not correctable by O2 ventilation.
Low PaO2 is usually correctable by the inspiration of O2. Secondary hypoxia of right-left extrapulmonary shunts is physiologically similar to intrapulmonary right-left shunts, but is determined by congenital heart defects, such as Fallot tetralogy, transposition of large vessels, The Eisenmenger complex. Like right-left lung shostile, PaO2 cannot be brought back to normal by taking O2.
In the case of circulatory hypoxia, as in hypoxia due to anaemia, PaO2 is normal, but venous and tissue PO2 are reduced as a consequence of reduced tissue infusion, under conditions of normal tissue consumption of O2. Generalized circulatory hypoxia occurs in heart failure and in most forms of shock.
It's the turn of specific organ hypoxia. Low circulation to a particular organ, which causes localized circulatory hypoxia, may be due to organic arterial obstruction or may occur as a consequence of vasoconstriction. The latter is observed at the upper extremities in the Raynaud phenomenon. Insufficient circulation may occur in all limbs, in patients with heart failure or hypovolemic shock, in an attempt to maintain adequate infusion of vital organs.
Hypoxic ischemia associated with pallor occurs in organic arterial obliterating diseases. Localized hypoxia can also result from venous obstructions with consecutive congestion and reduced arterial flow. Edema, which increases the distance that airs oxygen until it reaches the cells, can also cause localized hypoxia.
In the case of increased oxygen needs, if the oxygen consumption of tissues is increased without a corresponding increase in the volume of flow per unit of time, PO2 of venous blood (and hence capillary and tissue PO2) can be reduced. This will occur even if the oxygen diffusion in the blood that infuses the pulmonary capillary bed is normal and hemoglobin is normal quantitatively and qualitatively.
Such a situation can be encountered when fever or thyrotoxicosis occurs in patients where the heart rate is fixed and cannot increase normally. Under such conditions, circulation can be considered deficient in relation to metabolic requirements.
Typically, the clinical picture of the patient with hypoxia due to the increased rate of metabolism is completely different from that of other types of hypoxia, the skin being warm and colored, due to the increased skin blood flow that dissipates excessive heat produced, and cyanosis is usually absent. Physical exertion is a classic example of increased oxygen tissue needs.
These increased demands are normally met due to several simultaneous mechanisms: 1. increased heart rate and ventilation and thus tissue oxygenation, 2. preferential blood targeting to muscles that support effort and away from resting muscles, skin and viscera (by altering vascular resistance in different vascular beds, directly and/ or reflex), 3. increase in the extraction of oxygen from the supplied blood and increase in the arteriovenous gradient in oxygen and 4. reducing the pH of tissue and capillary blood, thus increasing the discharge of oxygen from hemoglobin.
When the capacity of these mechanisms is exceeded, hypoxia will occur, especially that of the muscles that perform the effort. Let me introduce a few things about improper oxygen use. Cyanide and other poisons of similar action produce a paradoxical state in which tissues are unable to use oxygen and consequently venous blood tends to have an increased oxygen pressure.
This condition has been called histotoxic hypoxia. Cyanides produce cellular hypoxia by paralyzing the electron transfer function of cytochromoxidase, so that it cannot transfer electrons to oxygen, while diphtheria toxin is supposed to inhibit the synthesis of one of the cytochromes, thus interfering with the oxygen consumption and energy production of the cells involved.
I will complete this post, dedicated to hypoxia, with the presentation of some elements about the effects of hypoxia. Changes in the central nervous system, especially in the upper centers, are extremely important. Acute hypoxia produces disorders of judgment, motor coordination and a clinical picture close to that of acute alcoholism.
When hypoxia is longer lasting, fatigue, apathy, drowsiness, inattention, delayed reaction time and reduced working capacity occur. When hypoxia becomes more severe, the centers in the brain stem are affected and death usually occurs through respiratory failure.
With the reduction of PaO2 also decreases cerebrovascular resistance and increases cerebral blood flow, tending to reduce cerebral hypoxia. On the other hand, when PaO2 reduction is accompanied by hyperventilation and PaCO2 decrease, cerebrovascular resistance increases, blood flow decreases and hypoxia is increased.
Compared to the brain, spinal cord and peripheral nerves, which are philogenetically older, they are relatively insensitive to hypoxia. Hypoxia also produces pulmonary arterioconstriction, which serves useful blood directing from poorly ventilated portions to the best ventilated portions of the lung. However, it has the disadvantage of increasing pulmonary vascular resistance and post-pregnancy of the right ventricle.
A complex disruption of cellular functions results from the metabolic effects of severe acute hypoxia. In liver and muscle, carbohydrate metabolism normally flows anaerobic (i.e. without oxidation) to the stage of pyruvic acid formation. The metabolism of pyruvate requires oxygen and, when insufficient, an increasing proportion of pyruvate is reduced to lactic acid, which cannot be catabolized further.
For this reason there is an increase in lactacidemia with decreased bicarbonate and subsequent metabolic acidosis. In this circumstances, the total energy obtained from the catabolization of the nutritional material is greatly reduced and the amount of energy available for the continuation of the resynthesis of phosphate-macroergic components becomes inadequate, leading to complex disturbances of cellular function.
Most of the respiratory response to hypoxia occurs in special chemoreceptors in the carotid and aorta, although the respiratory center in the brain stem is also directly stimulated by lack of oxygen. Consecutive increase in ventilation, with loss of carbon dioxide, leads to respiratory alkalosis. On the other hand, the diffusion of additional amounts of lactic acid from tissues in the blood tends to produce metabolic acidosis.
In both cases, the total amount of bicarbonate and, by implication, the combination power of carbon dioxide, tends to decrease. Low oxygen pressure in any tissue causes local vasodilation, and diffuse vasodilation occurring in generalized hypoxia causes increases in cardiac output.
In patients with pre-existing heart disease, the development of hypoxia and the needs of peripheral tissues for increased heart rate may precipitate congestive heart failure. In patients with ischemic cardiopathy, a reduction in PaO2 may intensify ischemia and consequently affect left ventricular function. Prolonged or severe hypoxia may also affect liver and kidney functions.
One of the most important compensating mechanisms for prolonged hypoxia is the increase in the concentration of hemoglobin. This is not due to the direct stimulation of the bone marrow but to the effect of erythropoietin. The level of erythropoietin is increased by hypoxia and it has been found that its production is regulated by the balance between the supply and demand of oxygen at the tissue level.
I can't believe that, in such a short space of time, I repeat the impossibility of posting daily (so, clearly, these delays will get stuck). But I won't repeat it again, I'll recover. Offf, my problems are less interesting... Get to work!
Let's start with hypoxia! The main role of the cardiorespiratory system is to provide oxygen (and nutrients) to cells and remove carbon dioxide (and other metabolism products) from their level.
Proper maintenance of this function depends on an intact cardiovascular and respiratory system and an inspired gas supply containing oxygen to an adequate extent. Changes in oxygen and carbon dioxide pressure, as well as changes in intraeritrocytic concentration of organic compounds with phosphate groups, in particular 2,3 diphosphoglyceric acid (2,3-DPG), cause alterations in the oxygen dissociation curve.
When hypoxia is a consequence of respiratory failure the pressure of alveolar dioxide (PaCO2) usually increases and the oxygen dissociation curve is diverted. Under these conditions, or when the concentration of 2.3-DPG increases, the proportion of saturated hemoglobin in the arterial blood at a given level of alveolar oxygen pressure (PaO2) decreases.
Both arterial hypoxia and cyanosis are more influenced by the degree of reduction of PaO2 when it results from lung disease than when the reduction occurs by lowering the partial oxygen pressure in the inspired air, in which case PaCO2 decreases consecutively to anoxia-induced hyperventilation, and the oxygen dissociation curve is diverted to the left, thus limiting the reduction of oxygen saturation of hemoglobin.
From the point of view of differential diagnosis we have several landmarks. We'll start with anemic hypoxia. Any decrease in haemoglobin concentration is accompanied by an appropriate decrease in the blood's oxygen transport capacity. PaO2 remains normal, but the absolute amount of oxygen carried by the blood volume unit is diminished. As anemic blood passes through the capillaries and the usual amount of oxygen is extracted from it, PO2 from the venous blood decreases to a greater extent than would normally be the case.
Another milestone would be carbon monoxide poisoning. Hemoglobin combined with carbon monoxide (carboxyhemoglobin) is not available for oxygen transport. In addition, the presence of carboxyhemoglobin moves the dissociation curve of hemoglobin to the left, so that oxygen can only be discharged at low pressures.
Through this formation of carboxyhemoglobin, a given level of reduced oxygen carrying capacity produces a higher degree of tissue hypoxia than the equivalent reduction of hemoglobin due to simple anemia. In the case of respiratory hypoxia, lack of arterial saturation is a common finding in advanced lung diseases. The most common cause of respiratory hypoxia is the non-correlation of ventilation with infusion, resulting from the infusion of poorly ventilated alveoli.
It can also be caused by hypoventilation when associated with increases in PaCO2. These two forms of respiratory hypoxia are usually easily corrected by the inspiration of O2. A third cause is the shunt of blood circulation from right to left by infused unventilated portions of the lung, as in pulmonary atelectasis or in vascular abnormalities of the lung with arteriovenous connections. In this situation the low PaO2 is not correctable by O2 ventilation.
Low PaO2 is usually correctable by the inspiration of O2. Secondary hypoxia of right-left extrapulmonary shunts is physiologically similar to intrapulmonary right-left shunts, but is determined by congenital heart defects, such as Fallot tetralogy, transposition of large vessels, The Eisenmenger complex. Like right-left lung shostile, PaO2 cannot be brought back to normal by taking O2.
In the case of circulatory hypoxia, as in hypoxia due to anaemia, PaO2 is normal, but venous and tissue PO2 are reduced as a consequence of reduced tissue infusion, under conditions of normal tissue consumption of O2. Generalized circulatory hypoxia occurs in heart failure and in most forms of shock.
It's the turn of specific organ hypoxia. Low circulation to a particular organ, which causes localized circulatory hypoxia, may be due to organic arterial obstruction or may occur as a consequence of vasoconstriction. The latter is observed at the upper extremities in the Raynaud phenomenon. Insufficient circulation may occur in all limbs, in patients with heart failure or hypovolemic shock, in an attempt to maintain adequate infusion of vital organs.
Hypoxic ischemia associated with pallor occurs in organic arterial obliterating diseases. Localized hypoxia can also result from venous obstructions with consecutive congestion and reduced arterial flow. Edema, which increases the distance that airs oxygen until it reaches the cells, can also cause localized hypoxia.
In the case of increased oxygen needs, if the oxygen consumption of tissues is increased without a corresponding increase in the volume of flow per unit of time, PO2 of venous blood (and hence capillary and tissue PO2) can be reduced. This will occur even if the oxygen diffusion in the blood that infuses the pulmonary capillary bed is normal and hemoglobin is normal quantitatively and qualitatively.
Such a situation can be encountered when fever or thyrotoxicosis occurs in patients where the heart rate is fixed and cannot increase normally. Under such conditions, circulation can be considered deficient in relation to metabolic requirements.
Typically, the clinical picture of the patient with hypoxia due to the increased rate of metabolism is completely different from that of other types of hypoxia, the skin being warm and colored, due to the increased skin blood flow that dissipates excessive heat produced, and cyanosis is usually absent. Physical exertion is a classic example of increased oxygen tissue needs.
These increased demands are normally met due to several simultaneous mechanisms: 1. increased heart rate and ventilation and thus tissue oxygenation, 2. preferential blood targeting to muscles that support effort and away from resting muscles, skin and viscera (by altering vascular resistance in different vascular beds, directly and/ or reflex), 3. increase in the extraction of oxygen from the supplied blood and increase in the arteriovenous gradient in oxygen and 4. reducing the pH of tissue and capillary blood, thus increasing the discharge of oxygen from hemoglobin.
When the capacity of these mechanisms is exceeded, hypoxia will occur, especially that of the muscles that perform the effort. Let me introduce a few things about improper oxygen use. Cyanide and other poisons of similar action produce a paradoxical state in which tissues are unable to use oxygen and consequently venous blood tends to have an increased oxygen pressure.
This condition has been called histotoxic hypoxia. Cyanides produce cellular hypoxia by paralyzing the electron transfer function of cytochromoxidase, so that it cannot transfer electrons to oxygen, while diphtheria toxin is supposed to inhibit the synthesis of one of the cytochromes, thus interfering with the oxygen consumption and energy production of the cells involved.
I will complete this post, dedicated to hypoxia, with the presentation of some elements about the effects of hypoxia. Changes in the central nervous system, especially in the upper centers, are extremely important. Acute hypoxia produces disorders of judgment, motor coordination and a clinical picture close to that of acute alcoholism.
When hypoxia is longer lasting, fatigue, apathy, drowsiness, inattention, delayed reaction time and reduced working capacity occur. When hypoxia becomes more severe, the centers in the brain stem are affected and death usually occurs through respiratory failure.
With the reduction of PaO2 also decreases cerebrovascular resistance and increases cerebral blood flow, tending to reduce cerebral hypoxia. On the other hand, when PaO2 reduction is accompanied by hyperventilation and PaCO2 decrease, cerebrovascular resistance increases, blood flow decreases and hypoxia is increased.
Compared to the brain, spinal cord and peripheral nerves, which are philogenetically older, they are relatively insensitive to hypoxia. Hypoxia also produces pulmonary arterioconstriction, which serves useful blood directing from poorly ventilated portions to the best ventilated portions of the lung. However, it has the disadvantage of increasing pulmonary vascular resistance and post-pregnancy of the right ventricle.
A complex disruption of cellular functions results from the metabolic effects of severe acute hypoxia. In liver and muscle, carbohydrate metabolism normally flows anaerobic (i.e. without oxidation) to the stage of pyruvic acid formation. The metabolism of pyruvate requires oxygen and, when insufficient, an increasing proportion of pyruvate is reduced to lactic acid, which cannot be catabolized further.
For this reason there is an increase in lactacidemia with decreased bicarbonate and subsequent metabolic acidosis. In this circumstances, the total energy obtained from the catabolization of the nutritional material is greatly reduced and the amount of energy available for the continuation of the resynthesis of phosphate-macroergic components becomes inadequate, leading to complex disturbances of cellular function.
Most of the respiratory response to hypoxia occurs in special chemoreceptors in the carotid and aorta, although the respiratory center in the brain stem is also directly stimulated by lack of oxygen. Consecutive increase in ventilation, with loss of carbon dioxide, leads to respiratory alkalosis. On the other hand, the diffusion of additional amounts of lactic acid from tissues in the blood tends to produce metabolic acidosis.
In both cases, the total amount of bicarbonate and, by implication, the combination power of carbon dioxide, tends to decrease. Low oxygen pressure in any tissue causes local vasodilation, and diffuse vasodilation occurring in generalized hypoxia causes increases in cardiac output.
In patients with pre-existing heart disease, the development of hypoxia and the needs of peripheral tissues for increased heart rate may precipitate congestive heart failure. In patients with ischemic cardiopathy, a reduction in PaO2 may intensify ischemia and consequently affect left ventricular function. Prolonged or severe hypoxia may also affect liver and kidney functions.
One of the most important compensating mechanisms for prolonged hypoxia is the increase in the concentration of hemoglobin. This is not due to the direct stimulation of the bone marrow but to the effect of erythropoietin. The level of erythropoietin is increased by hypoxia and it has been found that its production is regulated by the balance between the supply and demand of oxygen at the tissue level.
Have a good day!
Dorin, Merticaru