Table of Contents

This form of renal tubular acidosis is a failure of the cortical collecting duct to decrease chloride resorption in response to acidosis. The defect seems to be in the activity of alpha-intercalated cells of the collecting duct.

Hypoaldosteronism and hypoadrenalism cause a metabolic acidosis by causing a renal loss of sodium by interfering with the ENaC channel, as well as by impairing renal ammoniagenesis and decreasing chloride secretion. Type 4 renal tubular acidosis is an entity which can result from an interruption of the actions of aldosterone at any stage, as well as from mutations in the regulatory proteins  which regulate the function of sodium potassium and chloride resorption (and which manifest as a series of rare Mendelian disorders).

This page graphically describes the behaviour of bicarbonate in the face of a decreasing strong ion difference. Generally speaking, the "classical" explanation of normal anion gap metabolic acidosis has always been somewhat unsatisfying. The textbooks have called it "hyperchloraemic" acidosis, and have discussed it in terms of bicarbonate loss as the chief problem. In this fashion, the acidosis which accompanied normal saline administration was described as "dilutional". The main disturbance was thought to be the consequence of a stable amount of bicarbonate becoming dispersed in a larger amount of fluid, this process giving rise to a lower bicarbonate concentration and thus acidosis. In terms of the quantitative approach, the change in pH occurs due to the change in the "strong ion difference", the potential bicarbonate space generated by the difference in sodium and chloride concentration in the body fluids.

The normal anion gap metabolic acidosis associated with ureteric diversion results from the resorption of urinary chloride by the gut mucosa, and the excretion of bicarbonate in exchange.  When the ureter empties into the ileum, metabolic acidosis is seen in 80% of patients. This is the consequence of using a piece of gut as a container and conduit for urine, a task it was never meant to perform.

The overzealous administration of sodium chloride causes a normal anion gap metabolic acidosis by decreasing the strong ion difference. This is the archetypal normal anion gap acidosis. Previously discussed calculations suggest that every bag of saline increases the serum chloride by 3mmol/L. In Stewarts terms, normal saline has a strong ion difference of 0mmol/L (given how equal the concentrations of sodium and chloride are), and thus adding it to a body fluid will decrease the strong ion difference. The strong ion difference of Hartmanns, on the other hand, is 28mmol/L, and so it has a much gentler acidifying effect.

The normal anion gap metabolic acidosis associated with ureteric diversion results from the resorption of urinary chloride by the gut mucosa, and the excretion of bicarbonate in exchange.  When the ureter empties into the ileum, metabolic acidosis is seen in 80% of patients. This is the consequence of using a piece of gut as a container and conduit for urine, a task it was never meant to perform.

Diarrhoea can result in a metabolic acidosis by causing a disproportionate loss of sodium, and thus decreasing the strong ion difference. However, precisely what sort of acid-base disturbance will occur depends entirely on what is being lost, and how. The content of the gastrointestinal fluid losses is likely to vary from patient to patient, depend strongly on the diet, and be dependent on whether there are any attempts at reclamation (i.e. if the colon is still making an effort to retain electrolytes).

A small bowel fistula causes a metabolic acidosis by increasing the strong ion difference, due to the loss of a large amount of strong cations (sodium and potassium) with a relatively small loss of chloride. The reason for this is the relatively large amount of bicarbonate (and thus small amount of chloride) in the fluid at this part of the gut.

Uncontrollable leakage of pancreatic secretion causes a metabolic acidosis due to the loss of strong cations.  Pancreatic secretions are dechlorinated by the chloride-bicarbonate anion exchanger, which enriches the lumen with bicarbonate. In other ways, the pancreatic fluid remains similar to the rest of the extracellular fluid, i.e. rich in sodium.  Thus, with uncontrolled loss of pancreatic secretions (eg. with a pancreatic fistula) there is a loss of sodium without an equivalent loss of chloride.

If chloride is not a product of metabolism, how can you call its excess a "metabolic" acidosis? While trying to bravely ignore certain crippling epistemological problems,  this chapter focuses on the mechanisms of non-respiratory acid-base disturbances, and how one might attempt to pidgeonhole them into a sensible taxonomy. Several possible alternatives present themselves, and while Stewart's quantitative approach to acid-base interpretation offers a comprehensive framework, it remains clearly unfamiliar, and its application in clinical medicine remains clearly non-superior. Thus, the framework used to organise subsequent chapters uses the more "traditional" anion gap method of classification.

This chapter focuses on the ways in which a changing CO2 concentration might alter the pH of a solution, particularly that of your precious bodily fluids. The physiological consequences of acidaemia and alkalaemia are discussed in dedicated chapters, as are the various effects of having an excessively high or precipitously low blood CO2 level (independent of pH changes). A chapter which summarises the bedside rules and equations used in the interpretation of blood gases is also available as a brief overview of the empirically derived formulae which describe acute and chronic compensation for acidosis and alkalosis.

This chapter focuses on the transport of CO₂ in the bloodstream, which is an issue at least as important as the transport of oxygen.  CO₂ is transported by three major mechanisms: as bicarbonate, as carbamates, the conjugate bases of carbamino acids and as dissolved CO₂ gas.

Lets face it, we don't really care about venous oxygenation (or arterial, for that matter). The real issue is how much oxygen is in the cells? How are those cells using it? The intracellular environment is a place of massively heterogenous oxygen demands. Some organelles are involved in enzymatic metabolism of drugs or maintenance of electrolyte gradients - these areas require a higher oxygen tension than, for example, mitochondrial ATP synthesis.

Since Arrhenius started being taught in schools, and since most people started going to school, the concentration of hydrogen ions became a household term, synonymous with pH. Even as Sørensen revised his definition in terms of activity rather than concentration, people were taking up the notion that in every glass of water, some 10⁷ protons and hydroxyl ions were lurking, free and naked, ready to tear molecules to shreds. Plainly, this is insane.