Metabolic AcidosisDr.Samir Jha

• Acidosis : is a process that increases [H+]• Acidemia: When blood pH <7.35• Metabolic acidosis: When an acid other than

carbonic acid accumnulates in the body resulting in fall in HCO3- .

• Mechanism:• gain of H+

• loss of HCO3-

• Results in:• ↓pH (7.35)• ↓HCO3- (<22mEq/L)• pCO2 depends on compensation

Anion gap

• ([Na+] + [K+]) − ([Cl−] + [HCO3−])

• Anion gap (AG) = [Na+] − ([Cl-] + [HCO3−])

unmeasured anions subtracted by unmeasured cations (in ECF)

• Omission of potassium has become widely accepted, as potassium concentrations, being very low, usually have little effect on the calculated gap.

• Normal value: 3–11 mEq/L

• ↑AG = ↑ unmeasured anions such as organic acids, phosphates, sulfates

• ↓AG = ↓ alb or ↑ unmeasured cations (Ca, Mg, K, Li, bromine, immunoglobulin)

Low anion gap

• A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease in the gap.

• In hypoalbuminaemia the anion gap is decreased from between 2.5 to 3 mmol/L per 1 g/dL decrease in serum albumin. Common conditions that reduce serum albumin in the clinical setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis.

• The anion gap is sometimes reduced in multiple myeloma, where there is an increase in plasma IgG (paraproteinaemia).

• expected AG is [albumin] X2.5 (ie, 10 if albumin is 4 g/dL)

Causes

• Renal Tubular Acidosis• Gastrointestinal Base Loss(loss of HC03-)• Inorganic acid poisoning(addn of anions)• Ureteral diversion

• Ketoacidosis: Diabetic, Starvation• Lactic Acidosis• Renal Failure• Poisoning: Ethanol Glycol, Methanol, Aspirin,

Acetaminophen

Renal Failure

• Accumulation of organic anions such as phosphates, sulphates, urate, etc

Lactic Acidosis

• Type A: impairment in tissue oxygenation, eg, circulatory or

• acidosis respiratory failure, sepsis, ischemic bowel, carbon monoxide, cyanide

• Type B: no impairment in tissue oxygenation, eg, malignancy, alcoholism, meds (metformin, NRTIs, salicylates, propylene glycol)

• Methanol (windshield fluid, antifreeze, solvents, fuel): metab to formic acid

• Ethylene glycol (antifreeze): metab to glycolic and oxalic acids

• Propylene glycol (pharmaceutical solvent, eg, IV diazepam & lorazepam antifreeze): lactic acidosis

• Salicylates: metabolic acidosis (from lactate, ketones) respiratory alkalosis due to stimulation of CNS respiratory center

• Acetaminophen: glutathione depletion -> inc endogenous organic acid 5-oxoproline in susceptible host (malnourished, female, renal failure)

Consequence of Acidemia on various Organ System

Organ System Effect

Cardiovascular System Dec contractility, Arterial vasodilatation, Dec MAP, Dec CO, Dec response to Catecholamine, Inc risk of arrhythmias

Respiratory System Hyperventilation(compensatory), Dec Respiratory Muscle Strength

Metabolic Inc Potassium(Due to H+/K+ pump exchanging excess H+ with Intracellular K+)

Neurological Altered Mental Status

Investigation• Evaluate history for causes(diarrhea, ingestion

of mineral acids/drugs, kidney diseases, diabetes, any diversional surgery, starvation)

• For suspected ketonuria (dipstick acetoacetate) or plasma hydroxybutyrate [as urine aceto-acetate often not present in early ketoacidosis due to shunting to ᵝOH butyrate, aceto-acetate may later turn +ve]

If Ketones negative

• renal function, lactate(inc by about 10 fold in lactic acidosis), toxin screen, and osmolal gap

• Osmolal gap (OG)=measured osmoles -calculated Osmoles

• calculated osmoles(2 XNa)+(glucose/18)+(BUN/2.8)

• OG>10 suggests ingestion

• In case of hyperchloraemic (normal anion gap) acidosis with no evidence of gastrointestinal disturbance and Urine pH is inappropriately high>5.5 in +nce of systemic acidosis points toward Renal Tubular Acidosis.

Proximal RTA (Type 2)

↓ proximal re-absorption of HCO3E.g: Fanconi Syndrome, Multiple Myeloma,

Amyloidosis, Myeloma, Carbonic Anhydrase inhibitor

Urinary pH <5.3, moderate acidosis, serum K+ normal or low

Classical Distal RTA (Type 1)

defective distal H+ secretionE.g.: Congenital, Autoimmune(RA, Sjogren’s), SLE, Drugs (Lithium, Amphotericin)

pH of a fresh sample of urine is > 5.5. Serum potassium level is normal or low. Urine anion gap is positive because of inadequate hydrogen ion secretion

Hyperkalaemic distal RTA (type 4)

HypoaldosteronismObstructive NephropathyDrugs: Amiloride, Spironolactone, ACEI, ARB, NSAIDsDiseases: Sickle cell, SLE, Amyloidosis

urine pH is < 5.5. Serum potassium level is elevated. Urine anion gap is positive because of defective NH3 generation.

Compensation

• Early compensation by repsiratory sytem by hyperventilation wish washes out Co2 to restore the pH level

• Late compensation is by kidneys which causes excretion of H+ and retention of HCO3-

• Initially resuscitation with IV fluids is often needed.

• DKA: insulin & IVF; dextrose, IVF, replete K, Mg, PO4 as needed

• Lactic acidosis: treat underlying condition, avoid vasoconstrictors

• Renal failure: hemodialysis• Methanol & ethylene glycol: early fomepizole,

vit. B6 (ethylene glycol), folate(methanol), hemodialysis (especially if late presentation)

• Alkali therapy: NaHCO3

• Use of IV bicarbonate is controversial• Rapid correction causes hypokalemia or

reduced plasma ionised calcium• To be used in critical acidosis (pH <7.00)• In RTA type 1 & 2 supplements of Na & K

bicarbonate are necessary• In RTA type 4 diuretics of loop or thiazide class

may be effective in increasing acid secretion.

Thank you