Wednesday, April 12, 2017

CO2 Transport and Acid/Base Balance

Discuss CO2 transport in blood

See earlier post: Composition of the Blood

Describe the CO2 dissociation curve

CO2, just like O2, can bind to haemoglobin. It binds to a different part of haemoglobin (the amino group as opposed to the haem group), but O2 and CO2 both cause structural conformations such that the two can't bind at the same time. In fact, there's a name for this: the Haldane Effect refers to increased binding of CO2 when less O2 is bound.

The CO2 dissociation curve has a very different shape to the O2 dissociation curve. As you should know, the O2 dissociation curve is sigmoidal: it has a steeper part and a plateau phase. The CO2 curve, however, is just a simple curve, like the slope of a hill. In fact, when you get within the range of CO2 concentrations that you would normally see, the slope is pretty much linear.

Over normal ranges, the CO2 dissociation curve is steeper than that of the O2 dissociation curve. This is because the CO2 dissociation curve lacks a plateau phase.

Discuss the link between CO2 and pH

Increased CO2 causes H+ concentration to increase (which means that pH decreases), due to the buffer system mentioned here. Decreasing CO2 has the opposite effect: the pH will increase.

The pH change can be quantified by using the Henderson-Hasselbalch Equation, which you might remember from CHEM1004 (assuming that you haven't shut the pain out of your mind). As you may (or may not) remember, the Henderson-Hasselbalch equation is pH = pKa + log([A-]/[HA]). We will now apply this equation to the bicarbonate buffer, which I mentioned here and will mention again later on in this post. The pKa of this buffer is 6.1, allowing us to make the following substitution:

pH = 6.1 + log([HCO3-]/[CO2])

The issue with using this formula as it is is that we usually don't measure the concentration of carbon dioxide, but rather the partial pressure of carbon dioxide. Not to worry, however, as Henry's Law tells us that [CO2] = 0.03 * PCO2. We can then make this substitution:

pH = 6.1 + log([HCO3-]/(0.03*PCO2))

Understand the importance of acid-base homeostasis in the body

Acid-base homeostasis is important because if your blood gets too acidic, you die, and if your blood gets too alkaline, you die. So please ignore any quack that tells you to make your blood more alkaline.

Discuss the regulatory systems contributing to acid-base homeostasis

The main regulatory systems are buffers in the blood, the respiratory system and the renal system.

Buffers

The main pH buffering system of the blood is the bicarbonate system, which I mentioned here. Phosphates (HPO42- and H2PO4-) can also serve as buffers. Proteins can also serve as a buffer, as detailed here. Proteins have a high buffering capacity, but are slow to respond.

Respiratory System

The respiratory system controls pH by regulating the concentration of CO2. This can take a few minutes to hours to kick in.

Renal System

The renal system takes longer (hours-days) to regulate pH. It mainly regulates the concentration of HCO3- via affecting its reabsorption or producing more of it in renal tubule cells. The renal system can also increase the secretion of H+. The problem with the latter, however, is that less K+ can be secreted when this happens, causing an increase in serum K+ concentrations, leading to hyperkalemia. This causes a range of problems in the cardiovascular, neuromuscular and gastrointestinal systems. HCO3- reabsorption is described in more detail here.

Discuss the Davenport diagram

Ew, diagrams. Diagrams = drawing, and drawing = effort. Oh well then, if I must...

The Davenport diagram has three main features: pH on the x-axis, plasma bicarbonate on the y-axis and a set of curved lines called isocapnia lines. Each isocapnia line represents a different partial pressure of carbon dioxide. Higher isocapnia lines represent higher partial pressures of carbon dioxide.

I've also drawn a whole bunch of random dots on the diagram. Well, they're not totally random, though now looking at it I've decided that I haven't used the best lettering system. Oh well.

Let's start from point D, which is pretty much in the middle. Let's pretend for now that point D is the normal state of bicarbonate concentration, carbon dioxide pressure and pH.

In respiratory acidosis, represented by point A on the graph, CO2 increases and pH decreases. Respiratory acidosis may be due to hypoventilation (too little breathing), which causes a buildup of CO2. This hypoventilation, in turn, may be due to damage to the respiratory centres or some kind of obstruction. The kidneys can compensate for this by increasing bicarbonate, leading us to point B, where the pH is back to normal.

In respiratory alkalosis, represented by point G on the graph, CO2 decreases and pH increases. This is usually due to hyperventilation, which can occur due to the effects of drugs, CNS disorders and so on. The kidneys can compensate by getting rid of bicarbonate, leading us to point F.

In metabolic acidosis, too little bicarbonate is available, causing pH to drop from point D to point C. This may be due to alcohol abuse, diabetes, lactic acidosis, salicylate (aspirin) poisoning or renal tubular dysfunction. This can be compensated for by blowing off more carbon dioxide, leading us to point F.

In metabolic alkalosis, too much bicarbonate is available, causing pH to rise from point D to point E. This may be due to vomiting, hyperaldosteronism or exogenous steroids. This can be compensated for by blowing off less carbon dioxide, restoring pH to point B.

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