As part of my fundamentals of Anesthesiology and Critical Care Series I have posted 3 tutorials on the Role of CO2 /HCO3 in Acid Base Balance. These are entirely new tutorials (not part of the previous acid base series – that I have not finished yet! There is some overlap and updated facts and figures) and I have put a lot of work into getting the message of why the respiratory system is so important in acid base. Tutorial 1 is the basics of acid base. Tutorial 2 discusses respiratory acidosis, acute and chronic, and respiratory alkalosis. Tutorial 3 discusses respiratory compensation for acute metabolic acidosis. Although I cover the respiratory component in great depth, I also explain what metabolic acidosis is, what causes it and briefly discuss the anion gap, expected bicarbonate, base deficit and base deficit gap. I guarantee that you will learn something.
Hyperchloremic Acidosis is a common problem. It is usually an iatrogenic problem. Unfortunately, the majority of doctors who cause a patient to have Hyperchloremic Acidosis (HCA) are either unaware of the problem or ambivalent to it. For the most part, HCA is caused by the intravenous administration of isotonic saline solution (NS – “normal saline – NaCl 0.9%). This problem has been known about for more than 100 years and led Alexis Hartmann, a pediatrician from St Louis, to construct a balanced intravenous fluids, that he called “Lactated Ringers” solution. Ironically, in clinical practice, HCA is induced as part of the local hospital “protocol” for management of Diabetic Ketoacidosis. Inevitably, as the ketones fall, the Chloride rises, and the acidosis persists.
HCA is the only cause of “normal” anion gap metabolic acidosis and is almost always caused, . In the tutorial I explain that HCA is caused by a reduction in the Na-Cl strong ion difference (SID). The acidosis associated with NaCl 0.9% is more complex that merely a rise in plasma Chloride. Other serum electrolytes, Albumin and Hemoglobin are diluted – and this has an alkalinizing effect. Other resuscitation fluids have different impacts on acid base. Hyperchloremia is also a feature of Renal Tubular Acidosis (RTA), various other nephropathies, the administration of acetazolamide and other drugs, and following surgical transplantation of the ureters into the small bowel, If renal function is normal, and the Chloride level is lower than 125mmol/L, then the patient’s kidneys will resolve the problem over 36 to 48 hours. If the Chloride is very high, acidosis will persist, particularly in patients with poor renal function, and Sodium Bicarbonate infusions may be warranted.
Lactic acidosis is one of the best biomarkers of acute critical illness, its presence should alert the clinician to a major stress response, where medical and surgical and iatrogenic sources should be considered.
The magnitude and duration of hyperlactatemia (in the acute phase) is predictive of patient prognosis in critical illness. A sustained high lactate reflects a prolonged stress response. The lactate is not the cause or the problem. It is merely a biomarker.
If I were to pick one topic over which I have sweated tear during the past 2 decades, it is lactic acidosis. The problem is that every time I try to explain lactic acidosis, many of those around me become hostile, as if I was committing some atrocity against their religion. And that is because, for the past 100 years, every high school, science, nursing and medical student has been taught that lactate is a waste product that is only made in anerobic conditions. This is 100% ABSOLUTELY completely verifiably WRONG. Lactate, or lactic acid is produced all the time, continuously, in all tissues and is likely the major endpoint of glycolysis. Once produced, it is then either used for oxidative phosphorylation, shuttled to other tissues as a partially metabolized energy source (e.g. the heart and the brain – they love lactate) or metabolized in the liver, principally (the “Cori Cylcle”) – where gluconeogenesis takes place leading to subsequent glycogen storage, fat production or oxidative phosphorylation. As such, glucose is a universal substrate and lactate is a universal fuel.
Lactic acidosis occurs when the production of lactate exceeds the capacity of the liver to clear it. As we produce at least 1250mmol of lactate per day and it is barely measurable in the blood, hepatic clearance capacity is vast. Hyperadrenergic states promote the production of lactate, increase blood glucose and reduce hepatosplanchnic blood flow. The consequence is sometimes called “stress hyperlactatemia” or “aerobic glycolysis.” This is the form of hyperlactatemic seen in sepsis, for example. As such it is an acute phase reactant biomarker – lactate concentration mirrors adrenaline/epinephrine, and should be seen in the same light as CRP, IL-6 and Procalcitonin.
Hyperlactatemia results in metabolic acidosis as a consequence of water dissociation. The strong ion difference (SID) falls. The surplus “hydrogen ions” are mopped up by bicarbonate resulting in a modest fall in pH, but a mEq/L for mEq/L fall in bicarbonate and base excess. Lacate, like Chloride and Ketones, always functions as an acid surrogate and chronic hyperlactatemia is compensated for, usually, by increasing urinary Chloride loss, manifest as hypochloremia.
The terms “Type A” and “Type B” lactic acidosis were introduced by Huckabee in 1961. I believe that these monikers are still useful today. “Type A” represents lactic acidosis associated with blood loss and hypovolemia, intense systemic and splanchnic vasoconstriction, high ejection fraction, low stroke volume and cardiac output and low mixed venous oxygen saturation. Production of lactate increases (and this is multifactorial – not just anerobic), and production falls – due to hepatic hypoperfusion. The treatment is resuscitation, preferably with blood products.
For lactic acidosis, what is not Type A must be Type B – and this represents medley causes (toxic – alcohols), metabolic (end stage liver disease), inflammatory (sepsis), drug induced (metformin and particularly intravenous or inhaled catecholamines).
The term “Clearance” has been used to describe the removal of lactate from the circulation. It is a pharmacological rather than biochemical term, and that has led to some abuse in clinical practice: the belief that “Clearance” can be hurried along with aggressive fluid resuscitation. However, like any particle that is metabolized by the liver, clearance of lactate is determined by the quantity delivered, hepatic blood flow and hepatic clearance capacity. If there is a sustained surge in lactate production, then it may take a while for the liver to clear the surplus from the system while simultaneously dealing with the continued production of lactate by the tissues. In critical illness, we like to see the plasma lactate level falling, but 10-20% is sufficient to be reassuring. A rising lactate is ominous and may indicated inadequate source control or a secondary problem, such as bowel ischemia.
Lactic acidosis may or may not be a marker of tissue perfusion. It is a poor endpoint of resuscitation – and if used as such (the “drive by saline assault”), the result is fluid overload, mutiiorgan dysfunction and prolonged ICU stay.
Sodium Lactate Solutions do not cause lactic acidosis, as they are fully balanced. Most formulations contain a racemic mixture of L-Lactate (which is what the body produces) and D-Lactate (produced by fermentation by bacteria). Blood gas machines do not measure D-Lactate.
To truly understand acid base chemistry, it is imperative that you have a grasp of ionization theory. Although this might appear a little nerdy, it is quite straightforward and will also provide you with a basis for understanding the basic pharmacology of local anesthetics and opioids. Particles that disintegrate into component parts that carry charge are known as ions. If that charge is positive they are cations and if it is negative they are anions. Measurement of charge is known as valency, Most electrolytes in the body are univalent – Na, Cl, K, HCO3 – and their valency is quantifiably identical to their molarity (i.e. 140 mmol/L of Na+ = 1mEq/L). Some, however, are divalent – Calcium and Magnesium and Phosphorous. Ionized particles are a major component of acid base chemistry. They may be derived from mineral salts – Na, Cl, K, PO4, Mg, Ca or organic molecules – Lactate, Ketones, Metabolic Junk Products – manufactured in the body. Weak anionic acids are also manufactured – Bicarbonate and Albumin.
The relative quantities of different particles is governed by MASS CONSERVATION. Regardless of the source and quantity of anions and cations ELECTRICAL NEUTRALITY must always hold. Where there is imbalance between anions and cations the electrochemical void is filled by hydrogen or hydroxyl (derived from water dissociation) and acid base abnormalities ensue.
What makes ionized particles “strong” or “weak” acids or bases is determined by the pKa – the Ion Dissociation constant. This is the pH at which the particle is 50% dissociated or associated. As all electrochemical activity in the body occurs withing the physiological range of pH – 6.8 to about 7.65 – whether a ionic particle’s pKa is below or above, essentially 7.4, determines whether it is an acid or a base. For example – Lactic Acid has a pKa of 3.1 – at that point is is 50% associated (LA-H) and 50% dissociated (La-). At the environmental pH falls, for example towards 1, for example in the stomach, the chemical associates more (Lactic Acid). As the pH rises towards 7.4 it dissociates more (Lactate). At all physiologic ranges of pH Lactate is fully dissociated. Likewise, chemicals that have a pKa above the physiologic range pH (i.e greater than 7.6) are bases – and they become more associated at higher pH ranges. Sodium Hydroxide has a pKa of greater than12, which means that at pH 12 it is 50% associated, at pH 15 it is close to 100% associated. At physiologic range pH it is fully dissociated. Particles that are fully dissociated at all physiologic ranges of pH – cations such as Na+, K+, Mg2+ and Ca2+ and anions such as Cl-, Lactate- and Beta-Hydroxybutyrate, are known as STRONG IONS – they never bind to other ions (to create salts), hydroxyl or hydrogen in the body. Particles that are partially dissociated, whose pKa is closer to 7.4 – Bicarbonate, Albumin, Phosphate, Hemoglobin, are WEAK ACIDS and as they pick up more hydrogen ions at lower pH levels, they act as buffers.
Metabolic acid base balance is governed by the relative charge distribution (mEq/L) of STRONG IONS – known as the STRONG ION DIFFERENCE (SID) and the availability of weak acid buffers (ATOT). If the SID reduces, there is excess anion and metabolic acidosis. If the SID increases, there is excess cation or deficient anion and metabolic alkalosis.
ORtoICU 