Acid & Base
What are acids?
An acid is any substance which can produce protons (H+ ions) in solution. Acidity is measured in terms of the concentration of H+ ions found in solution.
Strong acids, such as hydrochloric acid (HCl) split apart almost completely in water, producing H+ and Cl- ions. Although these ions could recombine to form HCL, very few actually do. The balance point of the equation
HCl H+ + Cl-
Lies well over to the right. Because there are lots of H+ ions in solution, HCL is a strong acid.
In physiological systems, strong acids are not encountered very often. Most ‘physiological’ acids are quite weak – they do not break up completely as HCl does. An example of this would be acetate (one of the molecules involved in glucose metabolism). Acetate can split to form acetic acid – it has a COOH group which can generate H+.
CH3COOH CH3COO- + H+
In contrast to HCl, the balance point of the reaction for acetate is much further to the left. Much of the acetate will not split to produce any H+ ions, and so acetate is a weak acid in solution.
Measuring the actual concentration of H+ ions in, say, water is rather awkward. The number (0.0000001 M) is fiddly, and the range between strong acids and strong alkali solutions can vary from 0.1 – 0.00000000000001 M.
Because of this huge range, it is usual to take the negative base10 logarithm of the H+ concentration instead – this disposes of all the zeros and gives a number known as the pH
Eg. Water: -log [0.0000001] = 7
Strong acid: -log [0.1] = 1
Strong alkali: -log [0.00000000000001] = 14
There is therefore a range, centred around pH 7 (neutral) with pH values less than 7 being acidic, and higher values alkaline.
The body must regulate the acidity of the plasma within very fine limits, with ‘normal’ lying between 7.35 and 7.45. Acidity affects cells dramatically, changing the shape of proteins and affecting the activity of enzymes. Remember that a change of 1 unit in the pH scale represents a 10 fold change in the actual concentration of H+ ions.
What processes upset the body’s pH balance?
- Respiration (CO2 production).
When glucose is metabolysed via glycolysis and the krebs cycle, oxygen is used up and carbon dioxide (CO2) is produced. The CO2 is in solution, and combines with water to form a weak acid (carbonic acid):
CO2 + H20 H2CO3 HCO3- + H+
The acid load produced by CO2 production would accumulate very quickly if it were not for the lungs, where the reverse of the above reaction occurs. CO2 is reformed and passes across the alvaeolar membrane down a concentration gradient. By controlling the depth and frequency of respiration, the CO2 level in the blood can be acurately controlled.
TissuesBloodLungsAir
CO2 is always moving down a concentration gradient, from tissues where it is produced to the atmosphere.
If CO2 build up in the blood, we say there is a respiratory acidosis (eg. Patients with chronic bronchitis).
If there is too little CO2 in the blood, we say there is a respiratory alkalosis (eg. Patient hyperventilating during a panic attack)
- Metabolism
Under strenuous exercise, muscles can break down glucose or glycogen without using oxygen (anaerobic metabolism). This is not as energy efficient as using oxygen, but can occur quickly and allows extra muscular effort for short periods. The result of anaerobic metabolism is lactate (produces lactic acid in solution).
The other important situation in which lactic acid is produced is shock. Shock is defined as inadequate perfusion of the tissues, and as a result, anaerobic metabolism takes place. Most ‘bad’ physiological processes lead to a lactic acidosis – hypotension, hypoxia, hypovolaemia, sepsis etc.
During protein breakdown, phosphorus and sulphur containing compounds are liberated, producing phosphoric and sulphuric acid. The higher the protein level in the diet, the greater this load.
Metabolic acids are excreted by the kidneys (cf. lungs for respiratory acid)
If lactic acid or other acidic metabolic products build up, we say there is a metabolic acidosis (cf. respiratory acidosis from CO2). Eg. A patient in shock
If levels of lactic acid are unusually low, we say there is a metabolic alkalosis. Eg. Some types of poisoning.
Buffers
Between the production of H+ ions, and their excretion either by the lungs or the kidneys, shifts in pH are avoided by the process of buffering. Buffers are all negatively charged and bind to the H+ ions, forming neutral compounds. The primary buffering systems within the body are bicarbonate / CO2, proteins and intracellular phosphate.
We have already seen that reactions to produce acids can go in both directions (see acetate above). The reaction:
CO2 + H20 HCO3- + H+
Can be driven in reverse by high H+ concentrations, generating CO2. In fact, HCO3- is in plentiful supply in the extracellular fluid.
If an acidosis occurs, some of the H+ can be ‘mopped up’ by combination with HCO3-, generating CO2 in solution. The build up of CO2 would quickly limit the usefulness of this reaction were it not for the fact that acidosis also stimulates the carotid body chemorecepters leading to an increase in respiratory depth and rate. Thus more CO2 is excreted, allowing further combination of HCO3- and H+.
Proteins have many COO- groups within their complex structure. These groups can accept H+ ions, allowing further buffering of an acid load.
Buffering offers a short term solution to acid/base problems, but before long a final solution must be found. We have already seen how a rise in CO2 stimulates extra ventilatory effort to reduce levels towards normal. For metabolic acids, the final excretion takes place in the kidneys, where hydrogen ions are secreted into the urine and not reabsorbed.
Urine acidity would quickly increase and limit excretion, were it not for buffers also found in the tubular fluid. The primary buffers are HPO4— and ammonia (NH3).
HPO4-- + H+ H2PO4-
NH3 + H+ NH4+
HPO4— is filtered and not reabsorbed, whereas ammonia is produced within tubular cells and diffuses into the tubular lumen. The tubular membrane is quite permeable to ammonia, but not to NH4+. Therefore once the H+ ion has combined with ammonia in the tubular lumen to produce NH4+, it is trapped there.
Buffering thus allows a large acid load to be excreted in a smaller volume of urine, with obvious advantages for survival in hot or dry environments etc.
Blood Gases
Clinically, we use blood gas monitoring to investigate both oxygenation and acid/base disturbances. Here are a few simple rules for interpreting blood gases.
The information we usually get from a blood gas machine (with normal values) is as follows:
PaO210 – 13 KPa
PaCO24 – 4.5 KPa
pH7.35 – 7.45 (no units)
BE-2 - +2 mmol/l
The ‘Pa’ abbreviation before the oxygen and carbon dioxide values is shorthand for ‘Arterial partial pressure’. Partial pressure is measured in the same units as atmospheric pressure – mmHg or KPa. Confusingly, some hospitals use one set of units, other the other! Most places use KPa, and so will we.
Normal atmospheric pressure is about 101 KPa, with oxygen making up 21% of the gases present. The contribution of oxygen to atmospheric pressure is therefore 101 x .21 = 21.2 KPa. This is known as the partial pressure of oxygen. Why is the normal partial pressure of oxygen in the blood so much lower than the 21 KPa in atmospheric air? When air enters the trachea it becomes humidified, and the water vapour exerts its own partial pressure – about 6KPa, then there is a dilution effect from alvaelor gas which has already given up oxygen to the blood. Finally there is a concentration gradient across the alvaeolar membrane, of around 0.5 KPa.
Oxygen is always flowing down a concentration gradient from atmosphere to cell.
There are two separate parts to blood gas analysis – oxygenation and acid/base.
Oxygenation first!
The oxygenation side of things rarely causes problems. Just compare the PaO2 result with the normal values. However, you must know what oxygen concentration the patient is breathing in to be able to make sense of the numbers. This is usually expressed as either the %age itself, or by the fractional inspired (Fi) concentration – this is just %age expressed as a fraction (eg 50% oxygen = FiO2 0.5, 100% oxygen = FiO2 1.0)
A PaO2 of 9 (below normal) might mean your patient is only slightly affected by a pneumonia if they are breathing room air (O2 21%), but the same PaO2 whilst on 100% oxygen means their lung function is terrible! The only way to tell is to know what concentration of oxygen the patient is breathing.
Now Acid/Base…
pH
We have already looked at pH as a measure of acidity. The pH should be your first stop when trying to work out what is happening regarding acid and base. It tells you what the overall problem is – too acid or too alkaline. Once you know this, you can work out why.
Sometimes the body tried to correct or compensate for acid/base problems. Even with compensatory mechanisms running full tilt, these NEVER overshoot. That means whichever way the pH is pointing, that must be the primary problem.
PaCO2
Next look at the PaCO2. We know that the PaCO2 is regulated by the depth and rate of respiration, and the PaCO2 tells us about the respiratory side of acid/base.
Remember CO2 is acid in solution, so if the PaCO2 is high, there is a respiratory acidosis. If the PaCO2 is low, there is a respiratory alkalosis.
BE
Finally we look at the base excess (BE).
What IS the BE? The blood gas machine takes your sample and corrects the CO2 to normal values. It then works out the amount of acid or base which would have to be added to titrate the pH back to normal (7.4) at body temperature. By correcting the CO2, the machine takes away all the respiratory component of acid/base variation. What is left must come from a metabolic change in acid/base balance.
So BE tells us about a metabolic shifts in acid. The normal range varies between plus two and minus two. Anything below zero reflects a metabolic acidosis, any value above zero reflects a metabolic alkalosis. I remember this by thinking that anything ‘bad’ happening to the body (hypoxia, hypotension, sepsis etc. generates a metabolic acidosis. Bad things happening to you are negative, and so a negative BE represents acidosis!
So, the Base Excess tells us just what is going on in terms of metabolic acid/base.
A negative base excess is technically also know as a positive base deficit. This gets very confusing with double negatives abounding, so it is best to refer only to a positive or negative base excess.
So now we know the overall acid/base problem (from the pH) and we know what the respiratory and metabolic systems are up to (from the PaCO2 and BE).
Compensation
The body has two ways of compensating for acid/base problems. One is fast, the other slow.
- Respiratory compensation - FAST
Lets assume the body has a problem with a metabolic acidosis. A good example might be a patient developing diabetic ketoacidosis. Their plasma glucose levels are very high but none can enter the cells in the absence of insulin. Because of this, cells begin to undergo anaerobic respiration producing lactic acid, which rapidly overwhelms the body’s buffering systems and produces a metabolic acidosis.
As the pH falls, the body responds by increasing the depth and rate of breathing. This reduces the pCO2 causing a respiratory alkalosis. This respiratory alkalosis partially cancels out the metabolic acidosis, so the pH is not as low as might be expected. It will NEVER cancel out the metabolic acidosis completely, so the pH will never show an overall alkalosis. This sort of compensation mechanism can occur within minutes.
- Metabolic compensation - SLOW
Some patients with chronic bronchitis develop CO2 retention. The normal triggers to respiratory rate and depth are blunted by chronic high CO2 levels. However, the high levels of CO2 still cause a respiratory acidosis.
Over time, the kidneys increase the amount of acid secreted generating a metabolic alkalosis. This can correct the pH to near-normal (but will NOT over correct). This takes weeks and months to occur.
It is important to remember that although metabolic compensation takes months to occur, a metabolic acidosis can build up very rapidly when bad things happen. Take, for example the patient in cardiac arrest. Even with CPR happening, there is very poor perfusion of most tissues and lactic acid build up quickly generates a metabolic acidosis.
Examples
- Diabetic Ketoacidosis:
FiO20.3 (30%)
pH6.857.35 – 7.45
PaCO21.48 kPa4 – 4.5 kPa
PaO217.0 kPa10-13 kPa on air
BE-29.2 mmol/l+/- 2 mmol/l
This patient has no problems with oxygenation – their PaO2 is above normal on just 30% oxygen.
pH – This patient’s pH is very acidic. Remember that a change of 1 unit in pH reflects a 10 fold change in H+ ion concentration. Below 7 = extremely unwell!
BE – A BE of -29 shows there is a huge metabolic acidosis
PaCO2 – A value of 1.48 is very low, and shows a respiratory alkalosis
So the overall acidosis is being caused by the metabolic problem, with respiratory compensation trying to improve things towards normal. Clinically these patients have a very high respiratory rate & volume – know as Kussmaul breathing.