Review of Medical Physiology - William F. Ganong 2002

Respiration
Adaptive changes in respiration in health and disease
Other forms of hypoxia

Anemic Hypoxia

Hypoxia mediated by anemia, characterized by a specific Hemoglobin deficit, is typically not pronounced at rest due to an elevation of 2,3-DPG within erythrocytes. However, under exertion, anemic patients experience difficulties because of a limited capacity to increase O₂ delivery to active Tissues (Fig. 37-10).

Carbon monoxide poisoning

Trace amounts of carbon monoxide (CO) are produced endogenously, serving as a chemical messenger in the Brain and other sites (see Chapters 4 and 27). In large quantities, this gas is toxic. Exogenously, CO is generated by the incomplete combustion of carbon. Ancient Greeks and Romans used it to execute criminals, yet today CO still causes more fatalities than any other gas. CO poisoning is less common in Ukraine, European countries, and the USA since the transition to natural gas—which is free of CO—replacing manufactured gases and coal whose combustion yields high concentrations of CO. Nevertheless, emissions from gasoline engines can raise ambient CO levels to 6% or higher.

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Fig. 37-10. Comparison of the normal oxyhemoglobin dissociation curve (top, hemoglobin concentration 14 g/dL) with the oxyhemoglobin dissociation curve in CO poisoning (50% carboxyhemoglobin) and anemia (hemoglobin concentration 7 g/dL). Note that the curve in CO poisoning is shifted to the left of the anemia curve (reprinted with permission from Leff AR, Schumacker PT: Respiratory Physiology: Basics and Applications. Saunders, 1993).

The toxicity of CO stems from its interaction with hemoglobin to form carboxyhemoglobin (carbon monoxide hemoglobin, COHb), which is incapable of binding O₂ (see Fig. 37-10). Carbon monoxide poisoning is often classified as a form of anemic hypoxia because There is a functional deficiency of O₂-carrying hemoglobin, even though the total Blood hemoglobin concentration remains unaffected by CO. The affinity of hemoglobin for CO is 210 times greater than its affinity for O₂, and COHb releases CO very slowly. An additional complication is that the presence of COHb shifts the dissociation curve of the remaining HbO₂ to the left, which signifies a reduced release of O₂. Consequently, while anemic individuals with 50% of the normal amount of HbO₂ can perform moderate work, individuals with HbO₂ reduced to the same level due to the presence of COHb become severely incapacitated.

Due to the high affinity of CO for hemoglobin, accelerated formation of COHb occurs when the alveolar PCO rises above 0.4 mm Hg. Thus, the extent of COHb formation depends on the duration of CO exposure—namely, the concentration of CO in the inspired air—and alveolar ventilation.

Although CO is toxic to tissue Cytochromes, the concentration of CO required to inhibit cytochromes is 1,000 times greater than the lethal dose. Therefore, tissue-level toxicity plays no significant role in the Clinical presentation of CO poisoning.

The symptoms of CO poisoning resemble those of any hypoxia type: headache and nausea, although respiratory stimulation is minimal since arterial PO₂ remains normal and carotid and aortic chemoreceptors are not stimulated (see Chapter 36). The characteristic cherry-red color of COHb is visible in the Skin, nail beds, and mucous membranes. Death ensues when 70–80% of blood hemoglobin is converted to COHb. Symptoms resulting from chronic exposure to sublethal concentrations of CO are responsible for brain damage, including cognitive changes and occasionally a parkinsonian state (see Chapter 32).

Treatment of CO poisoning begins with the immediate cessation of CO exposure and adequate ventilation, using artificial Respiration if necessary. O₂ ventilation is preferred over fresh air because O₂ accelerates the dissociation of COHb. Hyperbaric Oxygenation is also employed in such cases (see below).

Stagnant Hypoxia

Hypoxia resulting from sluggish blood flow occurs in Organs such as the Kidneys and Heart during Shock (see Chapter 33). Stagnant hypoxia also damages The Liver and potentially the brain in congestive Heart Failure.

Normally, blood flow to the Lungs is robust, and characteristic lesions develop only during prolonged hypotension. Consequently, adult respiratory distress syndrome (see Chapter 33) may develop As a result of prolonged circulatory collapse.

Histotoxic Hypoxia

Hypoxia resulting from the inhibition of tissue oxidative processes is most commonly seen in cyanide poisoning. Cyanides inhibit cytochrome oxidase and possibly Other Enzymes. Methylene blue or nitrites are used to treat cyanide poisoning; they act by generating methemoglobin, which subsequently reacts with cyanides to form cyanomethemoglobin, a non-toxic compound. The therapeutic efficacy of these agents is consequently limited by The amount of methemoglobin that can be safely formed. Hyperbaric oxygenation is also utilized in treatment.