DIAGNOSIS AND TREATMENT OF ACID BASE DISORDERS

Why pH is important ?• Precise regulation of the pH in a narrow range of 7.35-7.45

is essential.• pH is vital for normal cellular enzymatic reactions and for

normal ionic concentration.• Extreme ranges of pH (<7.2 or >7.5) are potentially life

threatening (for eg cardiac arrhythmias )as can cause disruption of many vital cellular enzymatic reactions and physiological processes.

Buffering: the concentration of free hydrogen is controlled by buffers which acts as hydrogen sponge.When H conc is low (high pH) , hydrogen sponges release hydrogen and increase the free H conc.When H conc is high (low pH), hydrogen sponges engulf the free hydrogen and decrease the free H conc.The major Hydrogen buffers are Bicarbonate, phosphate ,hemoglobin and bone.

Acid base terminology 1/3Clinical terminology CriteriaNormal pH 7.4 (7.35-7.45)Acidemia pH < 7.35Alkalemia pH > 7.45Normal PaCO2 40 (35- 45 ) mm of HgRespiratory acidosis (failure) PaCO2 > 45 mm Hg and

low pHRespiratory alkalosis (hyperventilation)

PaCO2 < 35 mm Hg and high pH

Normal HCO3 24 (22- 26 ) mEq/LMetabolic Acidosis HCO3 < 22 mEq/L and

low pHMetabolic Alkalosis HCO3 > 26 mEq/L and

high pH

Acid base terminology 2/3

pH: pH signifies free hydrogen ion concentration. pH is inversely related to H ion concentration.• Increase in pH means H ion is decreasing.• Decrease in pH means H ion is Increasing.Acid: A substance that can “donate” H ion or when added to solution raises H ion (ie. Lowers pH)Base: A substance that can accept H ion or when added to solution lowers H ion (ie. Raises pH)Anion: An ion with negative charge is anion (ie. Cl, HCO3)Cation: An ion with positive charge is cation (ie. Na, K, Mg)If cation and anion is confusingAnion “n” –negative charge.Cation “t” – Positive (+) charge.

Acid base terminology 3/3

• Acidemia and alkalemia : The “-aemia” is the same suffix found in anemia . It means “blood”.

• Acidemia : means “acid blood” refers to a blood pH below normal (pH < 7.35) and increased H ion concentration.

• Alkalemia : means “alkaline blood” refers to a blood pH above normal (pH > 7.35) and decrease H ion concentration.

• Acidosis : Abnormal process or disease which reduce pH due to increase in acid or decrease in alkali is called acidosis.

• Alkalosis : Abnormal process or disease which increases pH due to decrease in acid or increase in alkali is called alkalosis.

Basic Concepts : Hydrogen Ion Concentration and pH

• The hydrogen ion concentration [H1] in extracellular fluid is determined by the balance between the partial pressure of carbon dioxide (PCO2) and the concentration of bicarbonate (HCO3) in the fluid. This relationship is expressed as follows(The Henderson Equation)

• Using a normal arterial PCO2 of 40 mm Hg and a normal serum HCO3 concentration of 24 mEq/L, the normal [H+] in arterial blood is 24 × (40/24) = 40 nEq/L.

3

224HCOPaCO

H

Respiratory regulation

• By excreting volatile acids, lung regulates PaCO2.

• Normally CO2 production and excretion are balanced which maintain CO2 at 40 mm hg.

• When rate of CO2 production increases it will stimulate PaCO2 sensitive chemoreceptors at central medulla with resultant rise in rate and depth of breathing. This hyperventilation will maintain PaCO2 at normal range.

When the respiratory regulation falls what will be the consequences ?

1. If the underlying disorder (respiratory or CNS) causes hypoventilation, CO2 excretion is reduced. Retained PaCO2 (hypercapnia) causes fall in pH leading to respiratory acidosis.

2. If the underlying disorder causes inappropriately high hyperventilation, CO2 is washed out. Low PaCO2 (hypocapnia) causes rise in pH leading to respiratory alkalosis.

Hypoventilation= Hypercapnia= Respiratory AcidosisHyperventilation= Hypocapnia= Respiratory Alkalosis

Renal regulation

• The role of kidney is to maintain plasma HCO3 concentration and there by pH regulation.

• The kidneys regulate HCO3 by:1. Excretion of H ions by tubular secretion.2. Reabsorption of filtered bicarbonate ions.3. Production of new HCO3 ions.

How kidney responds to metabolic ABD and regulate HCO3 ?

1. In response to acid load, normal kidneys are able to increase net acid excretion greatly. Increased excretion of H ions along with regeneration of HCO3 will correct plasma HCO3 to normal range.

2. When there is primary increase in plasma HCO3 ,there will be increase renal excretion of HCO3 in urine.

When does metabolic regulation falls ?

• Metabolic acidosis occurs when excess HCO3 is lost (diarrhea), acids are added (DKA/lactic acidosis)/Salicyclate overdose or bicarbonate is not generated (renal failure ).

• Metabolic alkalosis occurs when excess H ion is lost (vomiting), or renal bicarbonate excretion fails (hypovolemia).

one feature of metabolic disorders with respiratory is that the pH, bicarbonate and PCO2 all changes in the same

direction.

In respiratory acid-base disorders, the pH changes in the opposite direction as the change in bicarbonate

and PCO2.

• THOUGH SECONDARY RESPONSES SHOULD NOT BE CALLED “COMPENSATORY RESPONSES” BECAUSE THEY DO NOT COMPLETELY CORRECT THE CHANGE PRODUCED BY PRIMARY ACID BASE DISORDER.

Compensation

Disorder Expected compensationMetabolic Acidosis Expected PaCO2= HCO3 X 1.5 +

8Metabolic Alkalosis Rise in PaCO2 = Rise in HCO3 X

0.75Respiratory Acidosis

Rise in HCO3 = Rise in Paco2 X 0.1

Respiratory Alkalosis

Fall in HCO3 = Fall in PaCo2 X 0.2

Characteristics of Primary acid-base disorders

Basic disorder pH Primary change

2nd change

Metabolic Acidosis

Low HCO3 Low

PaCO2 decreased

Metabolic Alkalosis

High

HCO3 High

PaCO2 Increased

Respi Acidosis Low PaCO2 High

HCO3 Increased

Respi Alkalosis High

PaCO2 Low

HCO3 decreased

High

Clinical conditions

Clues to possible ABD Type

CNS

Coma (hypo/hyperventilation Respiratory Acidosis/alkalosis

CVS

Congestive heart failureShock (decrease perfusion/lactic acid production)

Respiratory AlkalosisMetabolic Acidosis/ Respiratory Alkalosis

Respiratory

Tachypnea (Co2 washout)Bradypnea (CO2 retention)

Respiratory AlkalosisRespiratory Acidosis

GIVomiting (loss of H)Diarrhea (Loss of HCO3)Abdominal pain

Metabolic alkalosisMetabolic AcidosisRespiratory Alkalosis

Clinical conditions

Clues to possible ABD TypeRenalOliguria/ anuriaPolyuria

Metabolic AcidosisMetabolic Alkalosis

EndocrineMyxedema (bradypnea)Hypertension (Na gain and H loss)

Respiratory acidosisMetabolic alkalosis

Common mixed Acid base disorderDisorders Common causesMetabolic Acidosis

Respi Acidosis

↓ pH, ↓ HCO3, ↑PCO2

Cardiac arrest (hypoventilation + lactic acidosis)

Respi Alkalosis

↔pH, ↓HCO3, ↓ PCO2

Salicyclate intoxicationLiver failure with hyperventilation

Metabolic Alkalosis

Respi Acidosis

↔ pH, ↑ HCO3, ↑ PCO2

COPD with diuretics

Respi Alkalosis

↑pH, ↑ HCO3, ↓PCO2

Pneumonia with vomiting

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Evaluation and investigations

History and examination : Careful history and examination can provide clue for underlying clinical disorders.

• Diarrhea or ketoacidosis metabolic acidosis

• Presence of Kussmaul’s breathing Metabolic acidosis.

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• Basic investigations are essential as they may provide clue for underlying disorders.

• Most useful investigations are serum sodium, potassium, chloride, Hco3 and anion gap.

• Other relevant investigations are CBC, urine examination, urine electrolytes, blood sugar, renal function test etc.

Primary investigations

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Indications for ABG

1.Critical and unstable patients where significant acid base disorder is suspected.

2.If history, examination and serum electrolytes suggest severe progressive acid base disorders.

3.Sick patient with significant respiratory distress, secondary to acute respiratory diseases or exacerbation of chronic respiratory diseases

• If pH and PaCO2 changes in same direction, the primary disorder is metabolic and if they change in opposite direction ,the primary disorder is respiratory.

Step II: determine the primary disorder

Chemical change

Primary disorder

Compensation pH

Low HCO3- Metabolic acidosis

Respiratory alkalosis

low pH

High HCO3- Metabolic alkalosis

Respiratory acidosis

High pH

High PaCO2 Respiratory acidosis

Metabolic alkalosis

Low pH

Low PaCO2 Respiratory alkalosis

Metabolic acidosis

High pH

• Normal pH is 7.4• Calculate the change in pH (from 7.4)

A. in acute respiratory disorder (acidosis / alkalosis)change in pH = 0.008 X [PaCO2 -40]expected pH = 7.4 +/-change in pHB. in chronic respiratory disorder (acidosis/alkalosis)change in pH = 0.003 X [PaCO2 -40 ]expected pH = 7.4 +/- change in pH

Compare the pH on ABGif pH on ABG is close to A, it is acute disorderif pH on ABG is close to B, it is chronic disorder

Step III: if primary disorder is respiratory, determine acute / chronic disorder

Unmeasured Anions Unmeasured Cation

Albumin: 15 mEq/L Calcium: 5 mEq/L

Organic Acids: 5 mEq/L Potassium: 4.5 mEq/L

Phosphate: 2 mEq/L Magnesium: 1.5 mEq/L

Sulfate: 1 mEq/L

Total UA: 23 mEq/L Total UC: 11 mEq/L

Anion AG = UA – UC = 12 mEq/L

Determination of anion gap

Adjusted AG = calculated AG + 2.5 X [4 – S.albumin gm%]

Pneumonic Causes

M Methanol

U Uremia

D Diabetic ketoacidosis

P Paraldehyde

I Isoniazid / iron

L Lactate

E Ethanol, ethylene glycol

R Rhabdomyolysis / renal failure

S Salicylate / sepsis

Causes of a raised AG metabolic acidosis

Pneumonic Causes

H Hyper alimentation

A Acetazolamide

R Renal tubular acidosis

D Diarrhea

U Uremia (acute)

P Post ventilation hypocapnia

Causes of a non – AG metabolic acidosis

• Check urinary AG in non-AG metabolic acidosis• U Na + U K – U Cl• Normal : negative

• Non-renal loss of bicarbonate [diarrhea] : negative

• Renal loss of bicarbonate[ RTA / H+ excretion] : positive

Urinary AG

• In less obvious cases, the coexistence of two metabolic acid-base disorders may be apparent by calculating the difference between the change in AG [delta AG] and the change in serum HCO3- [delta HCO3-].

• e.g. Diabetic ketoacidosis

• This is called the Delta gap or gap –gap.

Step VII: for an increased anion gap metabolic acidosis; are there other disorders

• Delta gap = delta AG – delta HCO3-• Where delta AG = patient’s AG – 12 mEq/L• Delta HCO3- = 24 mEq/L – patient’s HCO3-• Normally the delta gap is zero :

– AG acidosis • A positive delta gap of more than 6 mEq/L :

– metabolic alkalosis and/or HCO3- retention.• The delta gap of less than 6 mEq/L :

– Hypercholremic acidosis and/or HCO3- excretion.

Delta Gap

GENERATION OF M.AKL

FACTORS EX

I. LOSS OF ACID FROM ECS

A. LOSS OF GASTRIC ACID VOMITING

B. LOSS OF ACID IN URINE PRIMARY ALDOSTERONISM+DIURETIC

C. SHIFT OF ACID INTO THE CELL POTASSIUM DEFICIENCY

D. LOSS OF ACID INTO THE STOOL CONGENITAL CHLORIDE LOSING DIARRHEA

II. EXCESSIVE BICARBONATE LOAD

A. ABSOLUTE

ORAL /PARENTRAL HCO3 MILK ALKALI SYNDROME

CONVERSION OF SALTS OF ORGANIC ACIDS INTO HCO3

LACTATE/CITRATE/ACETATE ADMINSTRATION

B. RELATIVE NaCO3 DIALYSIS

III.POST HYPERCAPNEIC STATES Correction (e.g., by mechanical ventilatory support) of chronic hypercapnia

• Metabolic alkalosis is associated with 1. hypokalemia, 2. ionized hypocalcemia,3. secondary ventricular arrhythmias, 4. increased digoxin toxicity,5. and compensatory hypoventilation (hypercarbia),

although compensation rarely results in Paco2 >55 mm Hg

6. Alkalemia may reduce tissue oxygen availability by shifting the oxyhemoglobin dissociation curve to the left and by decreasing cardiac output.

• In patients in whom arterial blood gases have not yet been obtained, serum electrolytes and a history of major risk factors, such as vomiting, nasogastric suction, or chronic diuretic use, can suggest metabolic alkalosis.

• Total CO2 -should be about 1.0 mEq/L greater than [HCO3

-] on simultaneously obtained arterial blood gases. If either calculated [HCO3

-] on the arterial blood gases or “CO2” on the serum electrolytes exceeds normal (24 and 25 mEq/L, respectively) by >4.0 mEq/L, either the patient has a primary metabolic alkalosis or has conserved bicarbonate in response to chronic hypercarbia.

Classification of metabolic alkalosis

TREATMENT

• Etiologic therapy- expansion of intravascular volume or the administration of

potassium. Infusion of 0.9% saline will dose-dependently increase serum [Cl-]

and decrease serum [HCO3-].

• Nonetiologic therapy - acetazol-amide (a carbonic anhydrase inhibitor that causes renal

bicarbonate wasting), (5-10mg/kg iv/po) infusion of [H+] in the form of ammonium chloride, arginine

hydrochloride, or 0.1 N hydrochloric acid (100 mmol/L), or dialysis against a high-chloride/low bicarbonate dialysate. 0.1 N hydrochloric acid most rapidly corrects life-threatening

metabolic alkalosis but must be infused into a central vein; peripheral infusion will cause severe tissue damage.

Infusion rate 0.2mEq/l/hr

METABOLIC ACIDOSIS

• hypobicarbonatemia (<21 mEq/L) • an acidemic pH (<7.35)• Metabolic acidosis occurs as a consequence of-1. endogenous or exogenous acid loads2. abnormal external loss of bicarbonate.

• Approximately 70 mmol of acid metabolites are produced, buffered, and excreted daily; -

1. 25 mmol of sulfuric acid from amino acid metabolism, 2. 40 mmol of organic acids, and phosphoric and other acids. • Extracellular volume in a 70-kg adult contains 336 mmol of

bicarbonate buffer (24 mEq/L × 14 L of extracellular volume). Glomerular filtration of plasma volume necessitates reabsorption of 4,500 mmol of bicarbonate daily, of which 85% is reabsorbed in the proximal tubule, 10% in the thick ascending limb, and the remainder is titrated by proton secretion in the collecting duct

• Calculation of the anion gap • [(Na+ - ([Cl-] + [HCO3

-])] distinguishes between two types of metabolic acidosis

• The anion gap - normal (<13 mEq/L.)• In metabolic acidosis associated with a high anion gap,

bicarbonate ions are consumed in buffering hydrogen ions, while the associated anion replaces bicarbonate in serum.

• Because three quarters of the normal anion gap consists of albumin, the calculated anion gap should be corrected for hypoalbuminemia

• Corrected AG = AG+2.5x(4.5-albumin in g/dl)

DIFFERENTIAL DIAGNOSIS OF M.AC

ELEVATED A.G NORMAL A.G

THREE DISEASES RENAL TUBULAR ACIDOSIS

UREMIA DIARRHEA

KETOACISOSIS CARBONIC ANHYDRASE INHIBITOR

LACTIC ACIDOSIS URETERAL DIVERSION

TOXINS EARLY RENAL FAILURE

METHANOL HYDRONEPHROSIS

ETHYLENE GLYCOL HCL ADMINISTRATION

SALISYLATES CHLORIDE ADMINISTRATION

PARALDEHYDE

METABOLIC ACIDOSIS CAUSES

• Decrease myocardial contractility,• increase pulmonary vascular resistance,• and decrease systemic vascular resistance.

ANESTHETIC IMPLICATION

• A patient with hyperchloremic metabolic acidosis may be relatively healthy, those with lactic acidosis, ketoacidosis, uremia, or toxic ingestions will be chronically or acutely ill.

Preoperative assessment should emphasize volume status and renal function.

• If shock has caused metabolic acidosis,-1. direct arterial pressure monitoring 2. preload may require assessment via echocardiography or pulmonary

arterial catheterization. Intraoperatively, one should be concerned about the possibility of

exaggerated hypotensive responses to drugs and positive pressure ventilation.

In planning intravenous fluid therapy, consider that balanced salt solutions tend to increase [HCO3

-] (e.g., by metabolism of lactate to bicarbonate) and pH and 0.9% saline tends to decrease [HCO3

-] and pH

TREATMENT

• The treatment of metabolic acidosis consists of the treatment of the primary pathophysiologic process, that is, hypo-perfusion, hypoxia, and if pH is severely decreased, administration of NaHCO3

-. • Hyperventilation, although an important

compensatory response to metabolic acidosis, is not definitive therapy for metabolic acidosis.

• The initial dose of NaHCO3 can be calculated as: NaHCO3 (mEq/L)= WT(kgs)x 0.3(24mEq/L-actual HCO3) / 2• 0.3 = the assumed distribution space for

bicarbonate and 24 mEq/L is the normal value for [HCO3

-] on arterial blood gas determination. • The calculation markedly underestimates dosage

in severe metabolic acidosis. In infants and children, a customary initial dose is 1.0 to 2.0 mEq/kg of body weight.

DILUTIONAL ACIDOSIS

• It occurs when the plasma bicarbonate concentration is decreased due to extracellular volume expansion with solutions(NS, albumin) that contain neither acid nor alkali.

• A hyperchloremic metabolic acidosis may accompany large volume infusion of isotonic saline I/O complicated with blood loss and extensive tissue dissection.

RESPIRATORY ALKALOSIS

• hypocarbia (Paco2 ≤35 mm Hg) • alkalemic pH (>7.45), • results from an increase in minute ventilation that is greater than that required

to excrete metabolic CO2 production. • respiratory alkalosis may be a sign of pain, anxiety, hypoxemia, central nervous

system disease, or systemic sepsis, the development of spontaneous respiratory alkalosis in a previously normocarbic patient requires prompt evaluation.

• Respiratory alkalosis, like metabolic alkalosis, may produce1. hypokalemia, 2. hypocalcemia, 3. cardiac dysrhythmias, 4. bronchoconstriction, 5. and hypotension,6. and may potentiate the toxicity of digoxin. 7. In addition, both brain pH and cerebral blood flow are tightly regulated and

respond rapidly to changes in systemic pH.Doubling minute ventilation reduces Paco2 to 20 mm Hg and halves cerebral blood flow; conversely, halving minute ventilation doubles Paco2 and doubles cerebral blood

TREATMENT

• Treatment of respiratory alkalosis per se is often not required.

• The most important steps are recognition and treatment of the underlying cause.

• For instance, correction of hypoxemia or hypoperfusion-induced lactic acidosis should result in resolution of the associated increases in respiratory drive.

• Preoperative recognition of chronic hyperventilation necessitates intraoperative maintenance of a similar Paco2.

RESPIRATORY ACIDOSIS

• hypercarbia (Paco2 ≤45 mm Hg) • low pH (<7.35),• occurs because of a decrease in minute alveolar ventilation

(VA), an increase in production of carbon dioxide (VCO2) or both, from the equation:

• PaCO2=k x VCO2 / VA where• K = constant • Respiratory acidosis - acute, without compensation by renal [HCO3

-] retention chronic, with [HCO3

-] retention offsetting the decrease in Ph.

CAUSES

• A reduction in VA may be due to an overall decrease in minute ventilation (VE) or to an increase in the amount of wasted ventilation (VD), according to the equation;

• VA= VE-VD• Decreases in VE –1. central ventilatory depression by drugs or2. central nervous system injury.3. airway obstruction 4. neuromuscular dysfunction. • Increases in VD –1. with chronic obstructive pulmonary disease, 2. pulmonary embolism, and most acute forms of respiratory

failure.3. VCO2 may be increased by sepsis, high-glucose parenteral

feeding, or fever

ANESTHETIC IMPLICATION

• Patients with chronic hypercarbia due to intrinsic pulmonary disease require careful preoperative evaluation.

• The ventilatory restriction imposed by upper abdominal or thoracic surgery may aggravate ventilatory insufficiency after surgery.

• Administration of narcotics and sedatives, even in small doses, may cause hazardous ventilatory depression.

• Preoperative evaluation should consider direct arterial pressure monitoring and frequent intraoperative blood gas determinations, as well as strategies to manage postoperative pain with minimal doses of systemic opioids.

• Intraoperatively, a patient with chronically compensated hypercapnia should be ventilated to maintain a normal pH.

• Inadvertent restoration of normal VA may result in profound alkalemia.

• Postoperatively, prophylactic ventilatory support may be required for selected patients with chronic hypercarbia

• Epidural narcotic administration may provide adequate postoperative analgesia while limiting depression of ventilatory drive.

TREATMENT• The treatment of respiratory acidosis depends on whether

the process is acute or chronic.• Acute respiratory acidosis – require mechanical ventilation unless a simple etiologic

factor (i.e., narcotic overdosage or residual muscular blockade) can be treated quickly.

Bicarbonate administration rarely is indicated unless severe metabolic acidosis is also present or unless mechanical ventilation is ineffective in reducing acute hypercarbia.

• chronic respiratory acidosis is rarely managed with ventilation but rather with efforts to improve pulmonary function.

Changes of [HCO3-] and pH in Response to Acute

and Chronic Changes in Paco2

• Decreased PaCO2

pH increases 0.10 per 10 mm Hg decrease in PaCO2 • [HCO3

-] decreases 2 mEq/L per 10 mm Hg decrease in PaCO2 • pH will nearly normalize if hypocarbia is sustained • [HCO3

-] will decrease 5 to 6 mEq/L per 10 mm Hg chronic ↓ in PaCO2a

• Increased PaCO2

pH will decrease 0.05 per acute 10 mm Hg increase PaCO2 • [HCO3

-] will increase 1.0 mEq/L per 10 mm Hg increase PaCO2 • pH will return toward normal if hypercarbia is sustained • [HCO3

-] will increase 4–5 mEq/L per chronic 10 mm Hg increase in PaCO2

Consequences of acidosis

Consequences of alkalosis