1. Respiratory adjustments in health and disease [Part 2]
High altitude physiology and drowning

2. Learning outcomes
At the end of this lecture, the students would be able to –
Explain the relation between altitude, barometric pressure and maximum oxygen tension of arterial blood
Describe the immediate and delayed effects of high altitude on the body
Describe the effects of carbon monoxide on O2 transport
Describe the pathophysiology of drowning

3. Main Gases of the Atmosphere
Gas Symbol Approximate %
Nitrogen N
Oxygen O
Carbon Dioxide CO
Water Vapor H2O

4. Definition of Partial Pressure
Partial pressure refers to the pressure that is exerted by a single gas in some given system (atmosphere, blood, tissue, lung or experimental mixture).
The sum of the individual partial pressures produces the total pressure -is called barometric pressure
Barometric pressure of the atmosphere is 760 mmHg at sea level.

5. Calculation of Partial Pressure
Partial pressure is directly proportional to the percentage of a gas in a mixture.
For calculating the partial pressure of a gas, multiply the percentage of a given gas by the total pressure of the system.
The general formula is;
partial pressure (P) = % of gas X total pressure

6. Calculation of Partial Pressure Continued
If the percentage of oxygen in the atmosphere is 20.9% and the total barometric pressure of the atmosphere is 760 mmHg, then:
PO2 = X 760 mmHg.
This gives an oxygen partial pressure (PO2) of (159 rounded) mm Hg.

7. Barometric pressure
Barometric pressure decreases with increase in altitude because total pressure at any altitude is proportion to the weight air at that altitude.
Altitude closer to sea level show much more change in barometric pressure as compared to very high altitude because air at altitude closer to sea level is compressible due to effect of gravity.

8. Altitude, Barometric pressure PO2
atmospheric oxygen partial pressure decreases proportionately with decrease in Barometric pressure.
Maintaining at all times slightly less than 21 per cent of the total barometric pressure.

9. Alveolar Oxygen at high altitude
At sea level, the alveolar Po2 is 104 mm Hg
at 20,000 feet altitude, it falls to about 40 mm Hg in the unacclimatized person but only to 53 mm Hg in the acclimatized.
The difference between these two is that alveolar ventilation increases much more in the acclimatized person than in the unacclimatized person.

10. Altitude, Barometric pressure PO2

11. Alveolar Carbon di oxide at high altitude
Alveolar Pco2 falls from the sea-level value of 40 mm Hg to lower values.
In the acclimatized individual, the Pco2 falls to about 7 mm Hg because of increased five fold ventilation.
Water vapor pressure in the alveoli remains 47 mm Hg regardless of altitude under normal body temperature.
Dilute the oxygen in alveoli.

12. Determination of Alveolar PO2
Where R is the respiratory exchange ratio (Vco2/Vo2) and F is correction factor, PB is barometric pressure, PH2O water vapor pressure, PAco2 , Alveolar CO2 , PAo2 Alveolar O2 . (correction factor is normally ignored)

13. Immediate effects of high altitude
On Central Nervous system-drowsiness, mental and muscle fatigue, sometimes headache, occasionally nausea, and sometimes euphoria.
These effects progress to a stage of seizures above 18,000 feet and end in coma at above 23,000 feet in the unacclimatized person,
followed shortly thereafter by death

14. Immediate effects of high altitude
On Respiratory System-Increased Pulmonary Ventilation due to stimulation of Arterial Chemoreceptors by exposure to low Po2
increases alveolar ventilation to a maximum of about 1.65 times normal.
This increase in ventilation lasts for short duration due to increased wash out of CO2,thus causes respiratory alkalosis and depresses the respiratory centers.

15. Immediate effects of high altitude
On blood- increases the 2,3 DPG of red blood cells due to immediate exposure and reduces the affinity of Hb for oxygen.
Favors the dissociation of oxygen at tissue level
But limits the oxygen diffusion at lung level.

16. Immediate effects of high altitude
On Circulatory system- cardiac output often increases as much as 30 per cent immediately

17. Immediate effects of high altitude
Cerebral edema-local vasodilation of the cerebral blood vessels, caused by the hypoxia. Leading to increased blood flow into the capillaries, thus increasing capillary pressure, which in turn causes fluid to leak into the cerebral tissues. Finally results in Acute cerebral edema.
can lead to severe disorientation and other effects related to cerebral dysfunction.
Acute pulmonary edema. Some of the arterioles of the lungs constricts leading to increased capillary pressures locally leading to leak of fluid causing edema, which progressively spreads to other areas of lung.

18. Delayed effects of high altitude
On Respiratory system-
Pulmonary ventilation increase up to about five times normal
Inhibition of respiratory center due to alkalosis is removed due to reduction of bicarbonate ion concentration in the cerebrospinal fluid as well as in the brain tissues.
decreases the pH in the fluids surrounding the chemosensitive neurons of the respiratory center, thus increase activity of the center

19. Delayed effects of high altitude
Increased Diffusing Capacity to three fold from normal value of 21 ml/mm Hg/min
Due to increased pulmonary capillary blood volume to lung which expands the capillaries and increases the surface area for diffusion of oxygen into the blood
increase in lung air volume, expands the surface area of the alveolar-capillary interface
increase in pulmonary arterial blood pressure; this forces blood into greater numbers of alveolar capillaries than normally

20. Delayed effects of high altitude
On Circulatory system-
Decrease after some time due to increased blood viscosity.
growth of increased numbers of systemic circulatory capillaries in the non-pulmonary tissues, which is called increased tissue capillarity (angiogenesis)
Hypertrophy of the heart due to increased capillary density and work load.
Pulmonary hypertension

21. Delayed effects of high altitude
Increased production of Red blood Cells
Increased hematocrit to about 60%.
Increase in whole blood hemoglobin concentration from normal of 15 g/dl to about 20 g/dl.
blood volume also increases, often by 20 to 30 per cent,
blood viscosity increases several fold.

22. Delayed effects of high altitude
On Renal system-
Compensate for the alkalosis respiratory
kidneys reduce hydrogen ion secretion by increased bicarbonate excretion leading to metabolic compensation for the respiratory alkalosis gradually reduces plasma and cerebrospinal fluid bicarbonate concentration and pH toward normal and removes part of the inhibitory effect on respiration.

23. Delayed effects of high altitude
Increased ability of the tissue to use oxygen due to-
Cell mitochondria and cellular oxidative enzyme systems are slightly more plentiful than in sea-level inhabitants
Facilitate increased cellular utilization of oxygen

24. Delayed effects of high altitude
work capacity is reduced in direct proportion to the decrease in maximum rate of oxygen uptake that the body can achieve

25. effects of carbon monoxide on O2 transport
The lethal effect of carbon monoxide (CO) is well known. This colorless, odorless gas occurs in cigarette smoke, engine exhaust, and fumes from furnaces and space heaters.
It binds to the ferrous ion of hemoglobin to form carboxyhemoglobin (HbCO).Thus, it competes with oxygen for the same binding site.
Not only that, but it binds 210 times as tightly as oxygen.
Persons with a 50% CO-block of a normal haemoglobin concentration have a leftward shift of the oxy-CO-haemoglobin dissociation curve.
All the binding sites that are bound to CO do not respond to falling oxygen tension.
The remaining oxygen molecules on the haemoglobin molecules are much more avidly bound and unload slower than normal.

26. effects of carbon monoxide on O2 transport
Patients with CO poisoning and anemia and with the same arterial oxygen concentration can be compared
At an oxygen tension of 10 mm Hg feeding the peripheral tissues, the CO blood keep most of its oxygen bound, whereas the anemia blood unload almost all its oxygen.
This is why the anemia patient can go to work and the carbon monoxide poisoned person is dying. 

27. Downing

28. Pathophysiology of drowning
Most important contributory factors to morbidity and mortality from drowning are hypoxia and acidosis and the multi-organ effects of these processes.
prolonged tissue hypoxia causes damage of Central nervous system (CNS) during the drowning episode (primary injury) or
may result from arrhythmias, ongoing pulmonary injury, reperfusion injury, or multiorgan dysfunction (secondary injury)

29. Mechanism of hypoxia in Downing

30. Pulmonary effects Target organ of injury is the lung
Aspiration of as little as 1-3 mL/kg of fluid leads to significantly impaired gas exchange. Effects on other systems is largely secondary to hypoxia and ischemic acidosis.
Aspiration in the lungs produces vagally mediated pulmonary vasoconstriction and hypertension
Water in the lung causes disruption of alveolar surfactant. Destruction of surfactant produces alveolar instability, atelectasis, and decreased compliance, with marked ventilation/perfusion (V/Q) mismatching.
Fluid-induced bronchospasm also may contribute to hypoxia

31. Cardiovascular effects
Hypovolemia is primarily due to fluid losses from increased capillary permeability. Profound hypotension may occur during and after the initial resuscitation period, especially when rewarming is accompanied by vasodilatation
hypoxia may directly damage the myocardium, decreasing cardiac output
Myocardial dysfunction may result from ventricular dysrhythmias, pulseless electrical activity (PEA), and asystole due to hypoxemia, hypothermia, acidosis, or electrolyte abnormalities

32. Central nervous system effects
Primary CNS injury is initially associated with tissue hypoxia and ischemia
cerebral edema is a common consequence
Autonomic instability has also been found present with signs and symptoms of hyper stimulation of the sympathetic nervous system, including the following:
Tachycardia
Hypertension
Tachypnea
Diaphoresis
Agitation
Muscle rigidity