  pH,  HCO 3  hours for complete activation of respiratory compensation   PCO 2 by 1.2mmHg for every 1 mEq/L  HCO 3  The degree of compensation is assessed via the Winter’s Formula  PCO 2 = 1.5(HCO 3 ) +8  2

 Metabolic Gap Acidosis ◦ M - Methanol ◦ U - Uremia ◦ D - DKA ◦ P - Paraldehyde ◦ I - Infection ◦ L - Lactic Acidosis ◦ E - Ehylene Glycol ◦ S - Salicylate  Non Gap Metabolic Acidosis ◦ Hyperalimentation ◦ Acetazolamide ◦ RTA (Calculate urine anion gap) ◦ Diarrhea ◦ Pancreatic Fistula

The Anion Gap:  In the body cations = anions  Not all of the anions are measured in routine laboratory analysis  [K + Na + ] – ( [Cl - ] + [HCO3 - ] ) = 12

There are more measurable cations compared to measurable anions in the serum; therefore, the anion gap is usually positive. Because we know that plasma is electro-neutral we can conclude that the anion gap calculation represents the concentration of unmeasured anions. The anion gap varies in response to changes in the concentrations of the above-mentioned serum components that contribute to the acid-base balance. Calculating the anion gap is clinically useful, as it helps in the differential diagnosis of a number of disease states.

 Anion gap can be classified as either high, normal or low. Laboratory errors need to be ruled out whenever anion gap calculations lead to results that do not fit the clinical picture. Methods used to determine the concentrations of some of the ions used to calculate the anion gap may be susceptible to very specific errors. For example, if the blood sample is not processed immediately after it is collected, continued leukocyte cellular metabolism may result in an increase in the HCO 3 − concentration, and result in a corresponding mild reduction in the anion gap. In many situations, alterations in renal function (even if mild, e.g., as that caused by dehydration in a patient with diarrhea) may modify the anion gap that may be expected to arise in a particular pathological condition.

The Anion Gap:  In the body cations > anions  Not all of the anions are measured in routine laboratory analysis  [Na + ] – ( [Cl - ] + [HCO3 - ] ) = 8-16

The Anion Gap:  The usual unmeasured anions that account for the “gap” are: ◦ Albumin ◦ Phosphates ◦ Sulphates

A high anion gap indicates that there is loss of HCO 3 − without a concurrent increase in Cl −. Electroneutrality is maintained by the elevated levels of anions like lactate, beta- hydroxybutyrate and acetoacetate, PO 4 −, and SO 4 −. These anions are not part of the anion-gap calculation and therefore a high anion gap results. Thus, the presence of a high anion gap should result in a search for conditions that lead to an excess of these substances.

 A high anion gap indicates acidosis. e.g. In uncontrolled diabetes, there is an increase in ketoacids (i.e. an increase in unmeasured anions) and a resulting increase in the anion gap.

 Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β- hydroxybutyrate.  Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased. In extreme cases ketoacidosis can be fatal

 Ketoacidosis is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis.  Ketoacidosis can be smelled on a person's breath. This is due to acetone, a direct byproduct of the spontaneous decomposition of acetoacetic acid  It is often described as smelling like fruit or nail polish remover.

High Anion Gap Acidosis: TypeAnion:  Lactic lactate  Diabeticketones  Uremiasulphate/phosphate  ASAsalicylate  Methanolformate  E. Glycoloxalate

 Uremia is a term used to loosely describe the illness accompanying kidney failure, in particular the nitrogenous waste products associated with the failure of this organ.  In kidney failure, urea and other waste products, which are normally excreted into the urine, are retained in the blood. Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures. It is usually diagnosed in kidney dialysis patients when the glomerular filtration rate, a measure of kidney function, is below 50% of normal

 Increases from: antifreeze, solvent, fuel, and as a denaturant for ethanol. Methanol is also produced naturally in the anaerobic metabolism of many varieties of bacteria

Why do we need oxygen?  For oxidative phosphorylation What is oxidative phosphorylation?  ADP + P i = ATP (requires energy)  The formation of ATP What does the oxygen do?

Lactic Acidosis Glycolysis: Glucose  Pyruvate  Acetyl CoA Kreb’s: Acetyl CoA  NADH & FADH Electron transport chain (ETC) NADH & FADH  ATP

 The bulk of ATP is generated in the electron transport chain (ETC) in the mitochondrion  The energy for creating the high-energy phosphate bond is generated at several points in the ETC. So are hydrogen ions

High - Oxygen allows for ATP formation in an electrically-neutral biologically safe manner

Lactic Acidosis  Type A:failure of oxidative phosphorylation ( Pyruvate  Lactate )  Type B:lactate production overwhelms lactate metabolism

Failure of ETC: Decreased Oxygen delivery ◦ Shock of any type ◦ Severe hypoxemia/hypoxia ◦ Severe Anemia ◦ Inhibitors (CO, CN); left shifts

Lactate production overwhelms lactate metabolism (not anaerobic)  Malignancies (after chemotherapy)  Hepatic failure  Drugs (biguanides, AZT, INH) Lactate production overwhelms lactate metabolism (not anaerobic)  Malignancies (after chemotherapy)  Hepatic failure  Drugs (biguanides, AZT, INH)

 Treat the underlying cause  Lower the H + concentration

Ex: Profound rapid blood loss Normal Saline boluses 1-2 Liters, maintain systolic BP of 90 or more Transfusion of blood and products Circulatory support

Lower the H + concentration H + + HCO 3 -  H 2 CO 3  H 2 O + CO 2 Lower the p a CO 2 by increasing minute ventilation

Lower the p a CO 2 by increasing minute ventilation

For every 1meq/l drop in HCO 3 - from 25, p a CO 2 should decrease by ~ 1 torr “Normal” p a CO 2 in the face of HCO is 25 (40 subtracted by 15)

Intravenous bicarbonate administration: Pro:lowers H + concentration (  pH) improves pressor response improves myocardial function Con:worsens intracellular acidosis may worsen outcome hypertonic

Bottom line: If there is adequate circulation and if minute ventilation is appropriate, some bicarbonate administration is warranted. Don’t aim for full correction, continue arterial blood analysis

With hemodynamic instability: Severe acute bleed Sepsis Trauma Increase minute ventilation Analyze arterial blood Judicious intravenous NaHCO 3 -