Test 2 (Dr. Karius DSA) Flashcards
Hypoxic Hypoxia
- In this form of hypoxia, the PaO2 is below normal because either the alveolar PO2 is reduced (e.g environmental reasons such as altitude)
- Or the blood is unable to equilibrate fully with the alveolar air (e.g. as would occur in lung diseases with diffusion impairments such as emphysema or fibrosis)
Anemic Hypoxia
- In this form of hypoxia, the lungs are in perfect working condition, but the oxygen carrying capacity of the blood has been reduced.
- As the name implies, anemia is a very effective way of producing anemic hypoxia.
- Carbon Monoxide produces anemic hypoxia - because it binds to the Hb with such high affinity, preventing oxygen from binding, it reduces the oxygen carrying-capacity of the blood.
- The tissues do not get sufficient oxygen to maintain their metabolic needs because the blood is not carrying it.
Circulatory Hypoxia
- In this form of hypoxia the lungs are working just fine and the blood can carry sufficient oxygen.
- However, the tissue is not receiving sufficient oxygen because the heart cannot pump the blood to the tissue (or the arteries leading to the tissue have been blocked by clots etc…).
- Sickle cell anemia can lead to circulatory hypoxia as the cells sickle in the blood vessels and block them. (Yes - It also produces an anemic hypoxia as the sickled blood cells are removed from circulation.)
Histotoxic Hypoxia
- Histotoxic literally means that the cells have been poisoned.
- In this form of hypoxia, there is no problem getting the oxygen to the tissue - the lungs, blood and circulatory system are all working just fine.
- However, the tissue is unable to use the oxygen. CYANIDE leads to histotoxic hypoxia by poisoning the systems that utilize oxygen to create energy and preventing them from using the oxygen.
- Even though there is plenty of oxygen there, the cells experience a lack of oxygen and are affected as if there was too little/no oxygen available.
Chronic Disease
- Early in lung disease, we may see an low or normal PaO2 with a low PaCO2.
- This decreases the surface area available for diffusion in his lungs and decreases the net volume of gas that can cross the alveolar membrane.
- Because of the diffusion coefficients for O2 and CO2 (remember that CO2 has a diffusion coefficient about 20x that of O2), John will start having problems with oxygen before he has problems with CO2. In other words, John will develop hypoxia before he develops hypercapnia.
About the CSF
- The composition of the CSF is very much like extracellular fluid or plasma, with two exceptions - there is much, MUCH less protein in the CSF (20 mg/dl in CSF vs. 6000.0 mg/dl in plasma) and almost no cholesterol.
- In general, there is also slightly more HCO3 in the CSF than in plasma (without the protein, the CSF has considerably reduced ability to buffer changes in pH).
Modifying of CSF in response to changes in PaCO2
- The cells of the choroid plexus are also capable of creating hydrogen ion and bocarbonate from the CO2 in the blood.
- Unlike the situation near the central chemoreceptors (where the carbonic anhydrase is located in the CSF), the cells of the choroid plexus contain the carbonic anhydrase and can then selectively pump either the hydrogen ion or the bicarbonate into the CSF.
- Although the mechanism of control is not understood at this time, the end result is that under conditions of chronic hypocapnia (as we see with John), the CSF pH will be adjusted back to normal by the addition of more H+ or less HCO3- by the cells of the choroid plexus.
- Bicarbonate is moved to the blood (you have to get it out of the cells of the plexus to prevent the process from stopping). The kidneys will get rid of it from there.
Chronic Hypercapnia
- Let’s assume that John’s lung disease has now progressed to the point that he is now retaining CO2 (hypercapnia) in addition to his hypoxia.
- This, predictably, leads to a respiratory acidosis as well as acidifying the CSF
- From one standpoint, this acidification of the CSF will stimulate breathing, something that is good at this point. However, there is a flip side - neurons are very sensitive to acidic pH’s and do not function as well in an acidic environment.
- Once again, we are going to have to rely on the choroid plexus to adjust the CSF pH back towards normal, even though this means that the central chemoreceptors now “accept” the higher PaCO2 as normal.
- To correct the CSF pH back to normal, the cells of the choroid plexus will add MORE bicarbonate to the CSF. The H+ ion created is moved back to the blood for elimination by the kidney.
Acute Response to Altitude
1) Step One IMMEDIATE Responses to HYPOXIA: Not surprisingly, the immediate response to hypoxia is mediated through the peripheral chemoreceptors. These begin to increase their firing rate at about a PaO2 of 70 mm Hg and will increase ventilation in response to the hypoxia.
2) Step Two: An increase in alveolar ventilation will INCREASE the PaO2. The flip side is that, unless metabolic production of CO2 were to change (and we are going to assume it does NOT), this increase in ventilation will lead to a DECREASE in the PaCO2.
3) Step Three: The decreased PaCO2 causes a DECREASE in the FIRING of the PERIPHERAL and CENTRAL chemoreceptors. This modifies the increase in ventilation we saw initially - the person at altitude has a greater alveolar ventilation than we would if they were at sea level, but it is not as great as the initial increase had produced. Once again, we are in a precarious position.
Acclimatization
1) The cells of the CHOROID PLEXUS are confronted with a CSF pH that is more basic than normal. They then pump more H+ or less HCO3- than under normal conditions into the CSF. This brings the CSF pH back to the normal range, allowing the peripheral chemoreceptors to drive ventilation in response to the hypoxia. It also means that the central chemoreceptors maintain a PaCO2 that is lower than normal. This accommodation is complete within a couple of weeks.
2) The hypoxia causes INCREASED release of the hormone ERYTHROPOIETIN from the kidney. If you’ll recall from earlier in the cardiopulmonary section, erythropoietin stimulates the production of red blood cells by the bone marrow. This increase in hematocrit increases the Hb content of the blood, increasing the oxygen carrying capacity of the blood.
3) The cells of the body also adjust by INCREASING THE NUMBER AND SIZE OF THE MITOCHONDRIA, as well as (if possible) expressing more of the enzymes required for anaerobic glycolysis. These changes allow the cells of the body to make more efficient use of the oxygen that is delivered to them.
Altitude Sickness
- In response to the hypoxia, the cerebral vasculature will dilate. This produces an increase in the perfusion pressure and therefore INCREASED FILTRATION.
- The increase in net filtration from the cerebral capillaries leads to mild CEREBRAL EDEMA, particularly if the autoregulatory mechanisms do not cause vasoconstriction.
- Reminder: autoregulation is the effect of perfusion pressure on the vasculature - an increase in perfusion pressure produces vasoconstriction to protect the tissue downstream of the increased pressure.
- In some cases, the cerebral edema that results is severe, and can be life threatening.
Pulmonary edema is another severe side-effect of altitude
- It is particularly likely to develop in individuals who rapidly ascend to elevations greater than 2500 m and then do heavy physical labor within the first few days of arriving
- The edema is the result of an increase in pulmonary vascular permeability.
- There is pulmonary hypertension, but the left atrial pressure is normal (so blood isn’t backing up from the left ventricle - it is a direct effect on the pulmonary capillaries).
Quantifying the increase in barometric pressure
- The important fact to know: For every 10 m below the water surface (sea water) you go, the barometric pressure increases by 1 atm.
- Remember: Always add on the 1 atm of pressure produced by the atmosphere on top of the water! (Hint - forgetting to add on that 1 atm. is a common way to get a test question wrong!)
Effects of hyperbaric pressure 1: Oxygen
- Oxygen toxicity results in irritation of the tracheobronchial tree, nasal congestion, sore throat, coughing, muscle twitching, tinnitus (ringing in the ears), dizziness, convulsions, and death.
- These effects are due to the formation of large amounts of the superoxide anion (O2-) and peroxide (H2O2).
- Both of these are highly reactive species (especially the superoxide anion, which is a free radical) and are toxic to cells (in fact, we have multiple enzymes to protect ourselves from these species).
Examples:
1) If given 100% oxygen at 4 atm of pressure, half the people exposed will develop serious symptoms of oxygen toxicity within 30 minute.
2) At 6 atm of pressure, convulsions develop within minutes.
3) At 1 atm pressure (sea level) 80 - 100% oxygen produces respiratory tract irritation within 8 - 10 hours (but the more severe side effects are limited).
Treatment:
- HYPERBARIC OXYGEN treatment is useful in treating certain conditions (CARBON MONOXIDE POISONING, injuries resulting in or related to decreased perfusion etc…). Exposure to 100% oxygen at 2 - 3 atm for less than 5 hours can greatly increase the PaO2 (~ 2000 mm Hg) and increase tissue PO2 without toxic side effects (or minimal side effects).
Pulmonary Effects of Oxygen Toxicity
- If given for prolonged periods, supplemental oxygen at 1 atm of pressure can have severe side-effects, particularly in infants. These include the development of bronchopulmonary dysplasia (abnormal lung growth, particularly the presence of lung cysts and densities)
