Acid-base disturbances: Pathology review

Definitions & Key takeaways

Acid-base disturbances are a type of electrolyte imbalance that occurs when the body's pH balance is disturbed. The blood pH is maintained in a narrow delicate range of 7.35 to 7.45, which is optimal for many biological processes taking place in our body. Below that range, the blood is too acidic, and above it, it's too alkalic, which is not ideal.

The acid-base disturbances are divided into two major groups due to their causes and the clinical picture of the patient. First, there are metabolic disturbances that can either be metabolic acidosis or alkalosis, which are reflected by disturbances in the serum HCO3 ��. The second group consists of respiratory disturbances, which can be either respiratory acidosis or alkalosis, depending on the blood's Pco2. There are a variety of causes for acid-base disturbances, including dehydration, hypoventilation, kidney failure, and diabetic ketoacidosis.

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Case Study0:00–0:56

Two people came into the Emergency Department one day. The first one is 33 year old Muriel who came in with abdominal pain, a severe headache and hyperventilation.
One of Muriel’s friends said that she caught her drinking antifreeze. The other one is 35 year old Eustace who came in with confusion and hypoventilation.
Eustace also has duodenal ulcers, for which he has been taking antacids. Among other tests, an ABG was done for both individuals.
The results showed that Muriel had low pH, along with low levels of bicarbonate and low levels of pCO2, while Eustace had high pH, along with high levels of bicarbonate and high levels of pCO2.
Okay, based on lab results, both individuals seem to have acid-base disturbances. Now, let’s go back to the basics for a bit.

Physiopathology0:56–3:51

So, in plasma you can find carbon dioxide or CO2 and water or H2O. They are constantly mixing together in order to make bicarbonate ion or HCO3− and hydrogen ion or H+.
Similarly, HCO3− and H+ can form CO2 and H2O. Now, HCO3 − is mostly regulated by the kidneys and metabolism, while CO2 is regulated by the lungs.
The blood pH which corresponds to the hydrogen ion concentration needs to stay in a very narrow range, between 7.37 and 7.42.
Basically, the more hydrogen ions, the more acidic the blood is and the lower the pH. Less hydrogen ions means the blood is more alkaline, and the higher the pH.
So, let’s say that HCO3− levels decrease for some reason. In this case, the equation shifts to the right and more HCO3− and H+ will be produced and as a result the blood becomes more acidic, so pH levels decrease.
On the other hand, if HCO3− levels rise, less H+ will be produced and the pH rises. Now, if CO2 increases, then the equation shifts to the right and the pH drops.
If CO2 decreases, then the equation shifts to the left and the pH rises. Stay with us here.
In practice, the Henderson-Hasselbalch equation is used to calculate the pH based on HCO3 and pCO2 values, where pCO2 represents the partial pressure of carbon dioxide.
Now, In order not to overcomplicate things here, just remember, If HCO3 goes up or if pCO2 goes down, then pH increases and if HCO3 goes down or if pCO2 goes up, then pH decreases.
Now, let’s start talking about acid-base disturbances, which are divided into four types: metabolic acidosis, respiratory acidosis, metabolic alkalosis and respiratory alkalosis.
In order to determine which is which, the 4 high yield parameters are: pH, pCO2, bicarbonate levels and compensatory response.
Okay, so, metabolic acidosis can happen either from the buildup of acid in our blood, which could be due to increased production or ingestion.

Metabolic Acidosis3:51–5:38

It can also happen because the body can’t get rid of it, or from excessive bicarbonate loss from the kidneys or gastrointestinal tract.
The main problem with all of this is that they lead to a decrease in the concentration of bicarbonate in the blood, so HCO3 levels will be low, usually less than 20mEq/L.
Remember this as it’s very high yield. As a result, the pH is lower than 7.35 and as a compensatory response, there’s immediate hyperventilation in order to eliminate more CO2.
By eliminating more CO2, pCO2 lowers and less hydrogen ions are produced.Now, with metabolic acidosis, in order to determine the cause, we need to check the anion gap.
which equals sodium minus chloride plus bicarbonate. Normally it ranges between 3 and 11 mEq/L.
The reason that it’s not 0, is that there are some unmeasured anions like organic acids and negatively charged plasma proteins, like albumin.
Now, based on the anion gap, there are causes of high anion gap metabolic acidosis which happens when the anion gap is above 12 mEq/L and normal anion gap metabolic acidosis, which happens when the anion gap is between 8 and 12 mEq/L.
Let’s begin with high anion gap metabolic acidosis. In this case, HCO3 − decreases when it binds to excess H+, which results in the formation of H2CO3 carbonic acid, which subsequently breaks down into CO2 and H2O.

High anion GMA5:38–8:18

These H+ can come from increased organic acid production in our body. One such example is lactic acidosis, which is where decreased oxygen delivery to the tissues leads to increased anaerobic metabolism and the buildup of lactic acid.
Another high yield example is diabetic ketoacidosis, which can occurs in uncontrolled diabetes mellitus, where the lack of insulin forces cells to use fats as primary energy fuel instead of glucose.
Fats are then converted to ketoacids, such as acetoacetic acid and β-hydroxybutyric acid. Another way acids can build up in our blood is due to an inability of the kidneys to excrete them.
This can happen in cases of chronic renal failure in the uremic phase.In other cases, H+ don’t come from inside our bodies at all, but, instead, they are accidentally ingested.
These include oxalic acid which can build up after an accidental ingestion of ethylene glycol, which is used in antifreeze, and formic acid, which is a metabolite of methanol, a highly toxic alcohol.
Salicylates overdose can also lead to high gap metabolic acidosis in the later phases, due to the buildup of H+ in the blood.
Finally, there are certain substances can lead to metabolic acidosis by promoting anaerobic metabolism and in turn, lactic acid production.
These are propylene glycol, iron overdose and isoniazid overdose, which you have to know for your exams.To sum up, you can remember the causes of metabolic acidosis using the mnemonic MUDPILES, where M is for methanol, U is for uremia, D is for diabetic ketoacidosis, P is for propylene glycol, I is for iron tablets and isoniazid, L is for lactic acidosis, E is for ethylene glycol and finally, S is for salicylates.
In contrast, in normal gap metabolic acidosis, the decrease in bicarbonate HCO3− ions is offset by the buildup of Cl- ions which are part of the anion gap equation, so the anion gap remains normal.

Non-Anion GMA8:18–13:02

The most common cause is severe diarrhea, where bicarbonate rich intestinal and pancreatic secretions rush through the gastrointestinal tract before they can be reabsorbed.
Another cause is type 2 renal tubular acidosis where acidosis develops because the proximal convoluted tubule is unable to reabsorb bicarbonate HCO3− so it’s lost in the urine.
Other types of renal tubular acidosis also result in normal anion gap metabolic acidosis, but the underlying mechanism is an inability to excrete protons H+ in the urine.
The excessive loss of HCO3− results a lower pH.Another cause is Addison disease, where the adrenal glands don’t produce enough steroid hormones, including aldosterone.
Normally, aldosterone tells the kidneys to reabsorb more sodium in the distal tubule and this is linked to hydrogen ion secretion, meaning as sodium is reabsorbed, hydrogen is secreted.
Since there’s not enough aldosterone, less sodium is reabsorbed and more hydrogen will remain in the blood, leading to metabolic acidosis.
Similarly, spironolactone can lead to metabolic acidosis by blocking aldosterone receptors. Another cause is the use of acetazolamide, which lowers bicarbonate reabsorption in the proximal tubule, leading to bicarbonate wasting and metabolic acidosis.
Now, in some cases, saline infusion can lead to metabolic acidosis and that’s because the standard 0.9% saline solution has a pH around 5.5.
Finally, total parenteral nutrition can lead to metabolic acidosis because it leads to the accumulation of H+. Finally, in cases of chronic metabolic acidosis, the kidneys will try to compensate for the low HCO3- with renal ammoniagenesis.
This is when the renal tubular epithelial cells convert glutamine to glutamate and create ammonia and HCO3- as byproducts.
The HCO3- can then be reabsorbed into the blood while the ammonia is lost through urine. To sum up, causes of normal gap acidosis can be remembered using the mnemonic HARDASS, where H stands for hyperalimentation, A for Addison disease, R for renal tubular acidosis, D for diarrhea, A for acetazolamide, S for spironolactone and the other S is for saline infusion.
Now, hang in there for one last fun fact about metabolic acidosis. You can actually calculate if the respiratory compensation is adequate in metabolic acidosis by using Winters formula.So, for example, let’s say that our HCO3− is 15, then the calculated arterial pCO2 is: 1.5 times 15 plus 8 plus or minus 2.
So 1.5 times 15 is 22.5, and 22.5 plus 8 is 30.5, so it’s 30.5 plus or minus 2, so the range is 28.5 to 32.5. So if the measured pCO2 is between 28.5 and 32.5, then there’s an appropriate respiratory compensation for the metabolic acidosis.
If the measured pCO2 comes back greater than calculated, then there’s a metabolic acidosis and an associated respiratory acidosis.
And if the measured pCO2 is lower than calculated, then there’s a metabolic acidosis and an associated respiratory alkalosis and remember this for your tests.
Let’s now move on to respiratory acidosis, where the normal mechanism of ventilation is disturbed and is inadequate to balance the pH.
The high yield concept here is that this is a result of hypoventilation, which leads to the accumulation of CO2, so the main problem here is the rise in pCO2, usually above 44 mm Hg.

Respiratory Acidosis13:02–15:57

As a result, more H+ is produced and pH levels decrease. In order to compensate for the acidosis, bicarbonate levels increase and the kidneys will eventually increase the absorption of HCO3− .
Now unlike the respiratory response for metabolic acidosis, which happens immediately, the kidneys take time to increase bicarbonate levels.
This can take around 24 hours of persistent respiratory acidosis before the delayed compensation take effect. This is why in acute respiratory acidosis, the pH is very low while the HCO3- is only slightly elevated or normal.
In Chronic respiratory acidosis, the kidneys can often compensate enough to bring the pH closer to the normal range and there will be very elevated HCO3-, typically over 30.
Now, to remember the causes of respiratory acidosis, we must think about causes of hypoventilation. One reason is airway obstruction, which might happen if a child aspirates an object like a peanut and it lodges in the right mainstem bronchus, preventing that lung from ventilating.
Sometimes the diaphragm or chest wall muscles don’t work properly, which can happen after severe trauma, or due to obesity when the chest wall is too heavy for the muscles to lift.
There might also be impaired gas exchange between the alveoli and the capillaries. That might happen if alveoli are damaged from chronic obstructive pulmonary disease, or in acute conditions, like pulmonary edema.
Sometimes, the problem is not in the lungs themselves, but in the respiratory centers of the brainstem. After a stroke or a medication overdose, like with opioids or sedatives, the respiratory centers can slow their rate of firing, so breathing becomes extremely slow or stops entirely.
Now, to easily remember the causes of respiratory acidosis, let’s imagine a cow that’s breathing slowly: AS A COW, A for airway obstruction, S for sedative use, A for acute lung disease, C for chronic lung disease, O for opioids and W for weakening of the respiratory muscles.
Now, let’s move on to metabolic alkalosis and the high yield concept here is that this can typically arise in two ways; loss of H+ ions and gaining HCO3 - or, most often, a combination of these two.

Metabolic Alkalosis15:57–18:32

Whatever the cause, there’s an increase in bicarbonate levels, usually above 28 mEq/L which will cause the pH to rise. As a compensatory response, there will be immediate hypoventilation, which will retain more CO2 and in turn, increase levels of pCO2.
Now, loss of H+ can occur either from the gastrointestinal tract or from the kidneys. The first case most commonly happens during vomiting, because the gastric secretions are very acidic, meaning that they contain lots of H+.
So during vomiting, not only is the stomach acid lost, but in addition the pancreas doesn’t secrete bicarbonate into the intestines, and it builds up in the blood instead.
Another way that hydrogen H+ ions can be lost is through the urine, in the context of having too much aldosterone hormone and this is called hyperaldosteronism.
Remember aldosterone causes the kidneys to reabsorb sodium, excrete H+ and reabsorb HCO3 − . The result is that the urine becomes more acidic and the blood becomes more alkaline.
Moving on, increased HCO3 - is usually caused by an increased reabsorption from the kidneys. One way this can happen is volume contraction or excessive loss of extracellular fluids.
When a lot of fluid is lost but not as much HCO3 -, we get alkalosis and this can occur with the use of loop diuretics. The resulting alkalosis is called a contraction alkalosis.
Now, in other cases, excess HCO3 − don’t come from within our bodies at all, but are ingested in large amounts, usually in the form of antacids, like NaHCO3 - .Now, to easily remember the causes of metabolic alkalosis, think LAVA-UP, where L stands for loop diuretics, A stands for antacid use, V for vomiting and A-up is for aldosterone increase.
Finally, with respiratory alkalosis, the normal mechanism of ventilation is also disturbed, but this time, there’s hyperventilation and more CO2 is eliminated through the lungs and as a result, and there’s decreased levels of pCO2, usually lower than 36 mm Hg, In turn, pH levels increase and in order to compensate,HCO3 - levels decrease when the kidneys decrease HCO3- reabsorption.

Respiratory Alkalosis18:32–20:26

Now, for ventilation to increase, the respiratory centers have to start firing more than usual. This increased firing can be a normal compensatory response, or an abnormal response to a situation that doesn’t really call for hyperventilation.
Hyperventilation is a normal response to things like hypoxia which can happen with pulmonary embolism. Another way this can happen is when a person climbs a high mountain, like Mount Everest.
This is because as we climb, levels of oxygen decrease, causing hypoxemia, which triggers hyperventilation. But, increased ventilation can be an abnormal response that sometimes happens in situations like anxiety and panic attacks or in overdoses with salicylates in the early phases.
Sometimes, a tumor in the brain can stimulate respiratory centers, leading to hyperventilation. Now, to remember the causes of respiratory alkalosis, let’s think PAST PH.
Okay, so P is for panic attacks, A is for anxiety attacks, S is for salicylates, T is for tumor and P for pulmonary embolism.
H is for hypoxemia- think about high altitudes here. Alright, as a quick recap.
With metabolic acidosis, there’s a decrease in HCO3 − which results in a low pH and low pCO2 values and there’s immediate hyperventilation as a compensatory response.
With metabolic alkalosis, there’s an increase in HCO3 − which results in a high pH and high pCO2 values and there’s immediate hypoventilation as a compensatory response.

Review20:26–21:29

With respiratory acidosis, there’s an increase in pCO2, which results in a low pH and high HCO3 − levels and to compensate, there’s an increased renal HCO3 − reabsorption, but this usually takes longer to take effect, so it’s delayed.
Finally, with respiratory alkalosis, there’s a decrease in pCO2 which results in a high pH and a decrease in HCO3 − levels and there’s delayed decreased renal HCO3 − reabsorption.
Back to our cases. As we can recall, Muriel came in with hyperventilation and her ABG showed low pH, along with low bicarbonate and low pCO2.
Now, her history showed that Muriel drank antifreeze, which we know contains ethylene glycol, which is an organic acid that cause symptoms like abdominal pain and severe headaches.

Summary21:29–22:34

Now, given the history and the ABG results, Muriel most likely has metabolic acidosis with a high anion gap. This can be confirmed by calculating the anion gap, where we will need an electrolyte panel in order to see what the values of sodium and chloride.
Moving on to Eustace, he came in with hypoventilation and the ABG showed high pH, along with high bicarbonate and high pCO2.
Now, his history is positive for duodenal ulcer being treated with antacids, which we know are a cause of metabolic alkalosis.
Now, given the history and the ABG results, we can say that Eustace has metabolic alkalosis, and he’s compensating through hypoventilation.
Pco2 know, his history is positive for duodenal ulcers, being treated with an acids, which we know are a cause of metabolic alkalosis.
So given his history and a BG results. We can say that Eustace has metabolic alkalosis,