METABOLIC ACIDOSIS AND METABOLIC ALKALOSIS

MODERATOR: PROF.DINESH.K

INTRODUCTION

Why pH 7.35-7.45 is necessary ?

FOR OPTIMAL FUNCTIONING OF CELLULAR ENZYMES & METABOLIC PROCESSES

NORMAL ACID-BASE HOMEOSTASISAcid - Base balance is primarily concerned with two ions:Hydrogen (H+) Bicarbonate (HCO3

- )

Henderson-Hasselbalch equation

6.1 = the pKa of carbonic acid 0.03 is the solubility coefficient in blood of carbon

dioxide (CO2)

pH is the dependent variable while the bicarbonate concentration [HCO3

-] and Paco2 are independent variables;

Systemic arterial pH is maintained between 7.35 and 7.45

extracellular and intracellular chemical buffering mechanism

Respiratory renal regulatory mechanisms.

Chemical Buffers: (First system within minutes)

Bicarbonate-buffer-system

Phosphate buffer-system Protein-buffer-system

BICARBONATE BUFFER H++ HCO3ˉ == H2O+ CO2 ( pK 6.1 ) NON-BICARBONATE BUFFERS 1. ALBUMIN ( PK 6.5) 2. Hb

3. phosphate[H2PO4ˉ == H+ + HPO4ˉˉ ( pK6.8)] 4. Bone

Chemoreceptors in the medulla of brain sense pH changes and vary the rate and depth of breathing to compensate for pH changes.

The lungs combine CO2 with water to form carbonic acid. carbonic acid leads to a in pH.

The kidneys regulate plasma [HCO3

–] through three main processes:

(1) reabsorption of filtered HCO3

–,

(2) formation of titratable acid, and

(3) excretion of NH4+ in

the urine

Renal compensation begins 12-24 hr after, hyperventilation starts.

It takes 3-4 days to complete appropriate metabolic compensation.

METOBOLIC ACIDOSIS

Metabolic acidosis can be defined as primary decrease in [HCO3]

i) Consumption of HCO3 by a strong nonvolatile acid

ii) Renal or gastrointestinal wasting of bicarbonate

iii) Rapid dilution of ECF compartment with a bicarbonate free fluid.

Cardiovascular Impairment of cardiac contractility Arteriolar dilatation, venoconstriction, and

centralization of blood volume Increased pulmonary vascular resistance Reduction in cardiac output, arterial blood pressure,

and hepatic and renal blood flow Sensitization to reentrant arrhythmias and reduction

in threshold of ventricular fibrillation Attenuation of cardiovascular responsiveness to

catecholamines

Respiratory Hyperventilation-Kussmaul breathing is the very deep

and labored breathing  Decreased strength of respiratory muscles and

promotion of muscle fatigue

LUNG

C.T ZONECATOTID BODY

VASOCONSTRICTION/PPHN

ACIDOSIS

TACHYPNOEA

HYPERPNOEA

LUNG

O2 SENSITIVE K+CHANNEL

MEDULLA

Metabolic Increased metabolic demands Insulin resistance Inhibition of anaerobic glycolysis Reduction in ATP synthesis Hyperkalemia Increased protein degradation

CNS Cerebral

Inhibition of metabolism and cell-volume regulation

Headache Lethargy Confusion and coma

CNS EFFECTSACIDOSIS

LETHARGY

ATP dependent K+ CHANNEL

CONFUSIONHEADACHE

HYPOXIA

CEREBRAL VASODILATION—ICP Incr.

ANION GAP

Most commonly defined as the difference between major measured cations and major measured anions.

Anion Gap = [Na+] - ([Cl-] + [HCO3-]) Normal range: 10-12mmol/L

Increase Anion Gap Acidosis: Methanol Uraemia Diabetic ketoacidosis Salicylate poisoning Lactic ketoacidosis Ethylene glycol Ethanol overdose Paraldehyde

Normal Anion Gap: (HYPER CHLORAEMIC)

Increased GIT Losses of HCO3: Diarrhea Anion exchange resins (cholestyramine) Ingestion of CaCl2; MgCl2, Fistulae (pancreatic; biliary; small bowel) Ureterosigmoidostomy

Increased renal losses of HCO3: Renal tubular acidosis Carbonic anhydrase inhibitors Hypoaldosteronism

Dilutional

Large amount of bicarbonate free fluids Total parentral nutrition. Increased intake of chloride-containing acids :

· Ammonium chloride

· Lysine hydrochloride

· Arginine hydrochloride

Evaluation of a Patient with Metabolic Acidosis  Is acidosis being caused by measured or

unmeasured anions (i.e., chloride)?  Look at blood chemistry  

 Calculate anion gap( normal  10-12mmol/L)  If gap is normal, there is too much chloride

present, owing to excessive administration, excess loss of sodium (diarrhea, ileostomy), or renal tubular acidosis  

 If gap is wide (>16), there are other unmeasured anions present, causing acidosis  

Check serum lactate—if >2, probably lactic acidosis  

 If high lactate is explained by circulatory insufficiency (shock, hypovolemia, oliguria, under-resuscitation, anemia, carbon monoxide poisoning, seizures), then “type A” lactic acidosis

If not think about “type B (rare)” causes—biguanides, fructose, sorbitol, nitroprusside, ethylene glycol, cancer, liver disease

 Look at creatinine and urine output  If patient is in acute renal failure, these may be

renal acids.

 Look at blood glucose and urinary ketones    If patient is hyperglycemic and ketotic, this is

diabetic ketoacidosis    If patient is ketotic (unmeasured anion) and

normoglycemic, this is either alcoholic (check blood alcohol) or starvation ketosis

 Check for presence of chronic alcohol abuse—high mean corpuscular volume, increased γ-glutamyl transferase on liver panel

 If all of these tests are negative, think of intoxication  Send toxicology laboratory tests (particularly

salicylates) and serum osmolality, and calculate osmolality using the formula: 2(Na + K) + Glucose/18 + BUN/2.8

 Look for unmeasured source of osmoles: if gap between measured and calculated serum osmolality >12, think of alcohol, particularly ethylene glycol, isopropyl alcohol, and methanol

TREATMENTGeneral measures Any respiratory component of acidemia should be

corrected. A PaCO2 in the low 30s may be desirable to partially

return pH to normal. If arterial pH remains below 7.20; alkali therapy usually

in the form of NaHCO3(usually a 7.5% solution) may be necessary. The amount of NaHCO3 given is decided emperically as a fixed dose (1mEq/kg) or is derived from the base excess and the calculated bicarbonate space

(NaHCO3 = 30% x Body wt x base deficit)

Half of the calculated deficit should be administered within the first 3–4 hours to avoid overcorrection.

Large amounts of HCO3– may have deleterious

effects.

- hypernatremia

- hyperosmolality

- volume overload

- worsening of intracellular acidosis.

Specific therapy

Diabetic ketoacidosis: replacement of existing fluid deficit(as a result of

hyperglycemic osmotic diuresis) Insulin Potassium,phosphate and magnesium

In alcoholic ketoacidosis, Thiamine should be given with glucose to avoid

Wernicke encephalopathy DOSE – 10-25 mg IM/IV

Salicylate-Induced Acidosis: Vigorous gastric lavage with isotonic saline (not

NaHCO3) Alkalinization of urine with NaHCO3 to a pH >7.5

increases elimination of salicylate.

Ethanol infusions (an iv loading dose; 8-10ml/kg of a 10% ethanol in D5 solution over 30 min with the concomitant administration of a continous infusion at 0.15 ml/kg/hr to achieve a blood ethanol level of 100-130mg/dL) are indicated following methanol/ehtylene glycol intoxication.

Ethylene Glycol—Induced Acidosis:

saline or osmotic diuresis,

thiamine and pyridoxine supplements. Fomepizole-alcohol dehydrogenase inhibitor(15mg/kg).

Ethanol

Hemodialysis

Anaesthetic considerations in patients with acidosis Preoperative assessment should emphasize volume status

and renal function. Acidemia can potentiate the depressant effects of most

sedatives and anaesthetic agents on the CNS and circulatory systems.

As most OPIOIDS are weak bases; acidosis can increase the fraction of the drug in the nonionized form and facilitate penetration of opiod into the brain.

Increased sedation and depression of airway reflexes may predispose to pulmonary aspiration.

Circulatory depressant effects of both volatile and intravenous anaesthetics can be exaggerated.

Any agent that rapidly depresses sympathetic tone can potentially allow unopposed circulatory depression in the setting of acidosis.

Halothane is more arrythmogenic in the presence of acidosis.

Succinylcholine avoided in acidotic patient with hyperkalaemia to prevent further increase in K+.

METABOLIC ALKALOSISMetabolic alkalosis Manifested by an elevated arterial pH Increase in the serum [HCO3

–]

Increase in Paco2 as a result of compensatory alveolar hypoventilation.It is often accompanied by hypochloremia and hypokalemia.

PATHOGENESIS Metabolic alkalosis occurs as a result of net gain

of [HCO3–] or loss of nonvolatile acid (usually

HCl by vomiting) from the extracellular fluid. metabolic alkalosis represents a failure of the

kidneys to eliminate HCO3– in the usual manner.

The kidneys will retain, rather than excrete, the excess alkali and maintain the alkalosis if (1) volume deficiency, chloride deficiency, and K+ deficiency exist in combination with a reduced GFR, which augments distal tubule H+ secretion.

(2) hypokalemia exists because of autonomous hyperaldosteronism.

Physiologic Effects of Alkalosis

Alkalosis increases affinity of Hb for O2 and shifts the ODC to the left,making it more difficult for Hb to give up O2 to tissues.

Movement of H+ out of the cells in exchange of extracellar K+ into cells,can produce hypokalaemia.

Alkalosis increases the number of anionic binding sites for Ca2+ on plasma proteins and can therefore decrease ionized plasma [Ca2+] leading to circulatory depression and neuromuscular irritability.

SYMPTOMS Mental confusion Obtundation Predisposition to seizures Paresthesia, muscular cramping, tetany,

aggravation of arrhythmias, and hypoxemia in chronic obstructive pulmonary disease.

Related electrolyte abnormalities include hypokalemia and hypophosphatemia.

TREATMENT Primary treatment is correcting the underlying

stimulus for HCO3– generation.

[H+] loss by the stomach or kidneys can be mitigated by the use of proton pump inhibitors or the discontinuation of diuretics.

Isotonic saline-reverse the alkalosis if ECFV contraction is present.

Acetazolamide-a carbonic anhydrase inhibitor,accelerate renal loss of HCO3 which is usually effective in patients with adequate renal function.

Dilute hydrochloric acid (0.1 N HCl) is also effective but can cause hemolysis, and must be delivered centrally and slowly.

Hemodialysis against a dialysate low in [HCO3–]

and high in [Cl–] can be effective when renal function is impaired

ANAESTHETIC CONSIDERATIONS Combination of alkalemia and hypokalemia can

precipitate severe atrial and ventricular dysrhythmia.

Potentiation of non-depolarizing neuromuscular blockade is reported with alkalemia but more directly related to concomitant hypokalemia.

REFERENCES1)Miller’s Anesthesia 7th edn

2)Barash Clinical anesthesia 4th edn.

3)Clinical Anesthesiology,Morgan 4th edn.

4) Harrison's Principles of Internal Medicine 18th edn.