Pathophysiology & Management of Acid Base and Common Electrolyte Imbalance

in Critically ill

Dr. Shalini Saini

University College of Medical Sciences & GTB Hospital, Delhi

Acid Base Equilibrium

What is Acid Base Equilibrium About?

?Buffers?

Fixed Cation?

Base Excess/ Deficit?

Anion Gap?

Acid Base Equilibrium

Acid Base Equilibrium is all about Maintenance of H+ ion concentration of the ECF.

Source of H+ ion in Body:

CO2 from metabolism

H+ load from AA metabolism

Strenuous Exercise Lactic AcidDiabetic KA

Ingestion of NH4Cl, CaCl2

Failure of Kidneys to Excrete PO 4

--, SO 4--

12500 mEq/d50 - 100 mEq/d

Some Basic Chemistry

Definitions:

Arrhenius(1903):– Acid: H+ Donor in Solution– Base: OH- Donor in Solution

Browsted and Lowry(1923):– Acid: Proton Donor– Base: Proton Acceptor

Some Basic Chemistry

pH (Potenz or Power of Hydrogen): Sorenson

Negative logarithm of H+ ion concentration to the base of 10

Why pH?• Normal H+ ion conc: 0.00004meq/L or 40nEq/L or 4x10-9 mol/L• pH converts decimal numbers & takes away negative sign.• Normal pH: 7.35-7.45• Normal H+ Conc: 0.00002mEq/L – 0.0001 mEq/L

Acid Base Equilibrium:

Solutions:

When substances are added to water, 3 simple rules have to be satisfied at all time:1. Electrical Neutrality2. Mass conservation3. Dissociation Equilibrium

Clinical Concepts:Base Excess: Amount of Acid or Alkali required to return plasma in vitro

to normal pH under standard conditions( pH 7.4, PCO2 40 , temp 37 C)

Standard BE: BE calculated for Anemic Blood (Hb = 6gm%).– Since Hb effectively buffers plasma & ECF to a large extent.

• Quantity of Acid or Alkali required to return plasma in-vivo to a normal pH under standard conditions

Siggard Anderson NormogramTo calculate Base Excess

Acid Base Equilibrium:The Henderson-Hasselbalch Equation:

H2 CO3 <====> H+ + HCO3-

=> Ka = [H+ ][HCO3 ]/ H2 CO3

Taking Logarithm on both sides & Rearranging: pH= pKa + log10[HCO3

-]/SX*PCO2

pKa = 6.1, S = 0.03(solubility coefficient), PCO2 = 40, HCO3 =25

On putting values & solving, pH = 7.4 Significance:• Includes components of both Metabolic & Respiratory Acid base disorders• Value of any one variable can be determined if other two known. Mostly HCO3

- is calculated

• pH determined by ratio of [HCO3-]/PCO2

• Increase=> alkalosis, Decrease => Acidosis

Anion Gap:• Estimate of relative abundance of unmeasured anions• Footprint of metabolic acidosis • UC & UA in electrochemical balance equation: Na + UC = (Cl + HCO 3 ) + UA

Rearranging equation : UA-UC (AG) = [Na+] - {[HCO3-] + [Cl-]}

• Normal Value: 8-12mEq/L• ↑ AG reflects ↑ Unmeasured Anion• Unmeasured Anions- Albumin,Phosphate, Sulphate, Organic acid.• 1mg/dl fall in Albumin, AG↓ by 3meq/l • High AG acidosis- Ketones, Lactate, Methanol.• Normal AG acidosis- Diarrhea.

Clinical Concepts:

Acid Base Equilibrium:• Elimination of Acid• Recovery/Regeneration of Base

Mechanisms that keep pH stable Buffering Compensation Correction

Clinical Concepts:

Buffers:

Definition: A substance that can bind or release H+ ions in solution, thus keeping the pH of the solution relatively constant despite addition of large amounts of acid or base.

For Buffer HA,HA <====>H+ + A-

pH = pKa + log [A-]/[HA]

– When [A-] = [HA], pH= pK, buffering capacity is maximum.

Clinical Concepts:

Most buffers are weak acids (H+ buffer) & their Na+ Salts (Na+ buffer)• Strong Acids Buffered by Na+ Buffer

• HCl + Na Buffer <====> H+ + Cl- +Na+ + Buffer <====> H Buffer + NaCl• Strong Bases Buffered by H+ buffer

• NaOH + H Buffer <====> Na+ + OH- + H+ + Buffer <====> Na Buffer + H2O

Buffer Effectiveness Depends on:• Quanitity

– H2CO3 /HCO3

- - Most important Extracellular Buffer– Protein Buffers – Most important Intracellular Buffer

• pKa

– Buffering capacity maximum when pH=pKa

Clinical Concepts:Buffers in ECF:• Carbonate-Bicarbonate Buffer 53%

– Plasma (35%)– Erythrocyte(18%)

• Hemoglobin 35%• Plasma Proteins 7%• Organic & Inorganic Phosphates 5%

Buffers in ICF:• Intracellular Proteins• H2PO4-HPO4

- system

Intracellular buffers are responsible for ~85% buffering in Met. Acidosis and ~35% in Met Alkalosis and almost complete buffering in Respiratory Acidosis and Alkalosis.

Clinical Concepts:

Bicarbonate Buffer:

• HCl + NaHCO3- <==>NaCl + H2CO3<==>NaCl + H2O + CO2

• Useful only for Metabolic Acidosis

Hb System:

• Both Respiratory & Metabolic Acidosis in ECF

Hemoglobin buffer

• Chloride Shift • Buffers H+ directly• HCO3 - diffuses out

• Cl diffuses in

Clinical Concepts:

Protein Buffer:• Predominant Intracellular Buffer – Large total concentration• pK = 7.4• AA have Acidic & Basic Free radicals

.COOH + OH- <====> COO- + H2O

.NH3OH + H+ <====> NH3 + H2O

Phosphate Buffer:• pK = 6.8• Predominantly Intracellular• Also in renal tubular

HCl + Na2HPO4 <====> NaH2PO4 + NaCl

NaOH + NaH2PO4 <====> Na2HPO4 + H2O

Clinical Concepts:

Compensation:Pulmonary Compensation

H+ + HCO3-<====> H2CO3 <====>CO2 + H2O

• H+ acts on medullary centres. – Metabolic Acidosis – Increased Ventilation– Metabolic Alkalosis – Depression of Ventilation• Minute ventilation increases 1-4l/min for every 1mmHg increase in

PaCO2

Clinical Concepts:

Renal Compensation:

Mechanisms:1. Reabsorption of filtered HCO 3

- (4000-5000 mEq/d)

2. Generation of fresh bicarbonate3. Formation of titrable acid – (1mEq/Kg/d)4. Excretion of NH4

+ in urine

PERITUBULAR BLOODPERITUBULAR BLOOD RENAL TUBULAR CELLRENAL TUBULAR CELL

GLOMULAR FILTRATEGLOMULAR FILTRATE

HCO3- + H+

CO2

HCO3- + H+

HCO3- + H+

HCO3- Na+ HPO4

2- Na+ NH3 Na+

H2CO3

CO2 + H2 O

H2O

H2PO4-

H2PO4-

NH4+

NH4+

1. NaHCO3

2. NaHCO3

3. NaHCO3

MAJOR RENAL MECHANISMS RESPONSIBLE FOR H+ EXCRETION/HCO3- RETENTIONMAJOR RENAL MECHANISMS RESPONSIBLE FOR H+ EXCRETION/HCO3- RETENTION

CO2 can be obtained from blood or the tubular fluidCO2 can be obtained from blood or the tubular fluid

Glutamine

CO2

CA

Acidemia or Acidosis? Alkalemia or Alkalosis?

Any condition that disturbs acid -base balance by increasing H+ through endogenous production,↓ buffering capaity, ↓ excretion, or exogenous addition is termed as ACIDOSIS Any condition that ↓ H+ is termed as ALKALOSIS

Acidemia or Alkalemia refer to net imbalance of H+ in blood.

Defining acid base disordersDisorder Primary change Compensatory

responseRespiratory AcidosisAlkalosis

↑PaCO2

↓PaCO2

↑HCO3

↓HCO3

MetabolicAcidosis Alkalosis

↓HCO3

↑HCO3

↓PaCO2

↑PaCO2

Normal reference range

pH 7.35-7.45

HCO3- 22-26meq/l

PaCO2 35-45mmHg

PaO2 80-100mmHg

Base excess/Deficit -2 to +2meq/l

Anion gap 8 to 12 meq/l

A-aO2 5-25mmHg

SaO2 96-100%

Prediction of Compensatory Responses on Simple Acid Base DisordersPrediction of Compensatory Responses on Simple Acid Base Disorders

Disorder Prediction of CompensationMetabolic Acidosis • For every 1mmol/l ↓ in HCO3

- → 1mm Hg ↓ in PaCO2

• Expected PaCO2 = 1.5 (HCO3- ) + 8

• PaCO2 should approach last two digits of pH

Metabolic Alkalosis For every 1 mmol/l ↑ in HCO3- ,↑ PaCO2 By 0.7mmHg

Respiratory Alkalosis

Acute [HCO3- ] will ↓ 2mmol/L per 10 mmHg ↓ in PaCO2

Chronic [HCO3- ] will ↓ 4mmol/L per 10 mmHg ↓ in PaCO2

Respiratory Acidosis

Acute [HCO3- ] will ↑ 1mmol/L per 10 mmHg ↑ in PaCO2

Chronic [HCO3- ] will ↑ 4mmol/L per 10 mmHg ↑ in PaCO2

General approach to acid-base disorder

pH

AcidemiapH <7.35

NormalpH7.35-7.45

AlkalemiapH> 7.45

Normal or mixed disorder↓HCO3 ↑PaCO2

Metabolic acidosis

Respiratory acidosis

↑HCO3 ↓PaCO2

Metabolic alkalosis

Respiratoryalkalosis

Diagnosis of acid base disturbance

Step -1: Is there an acid – base disturbance? look at PaCO 2 & HCO3 , whether in normal range. If normal range,

no acid-base disturbance or rule out mixed disorder. If abnormal, proceed to step 2. Step-2: Is there acidemia or alkalemia? Step-3: What is primary acid base disorder? Step-4: Calculate the expected compensation? Determine whether actual value matches with the expected compensation. Matching of both confirms diagnosis of primary disorder.

Step 5: Determine the presence of mixed acid-base • Check the direction of changes- As per ‘Rule of same direction’, in simple acid-base disorder PaCO2 & HCO3 changes from normal in same

direction. If changes occur in opposite direction; mixed disorder.• If expected compensation > or < than calculated compensation; mixed.• Check for anion gap :

i. If high AG , High AG metabolic acidosis.

ii. If normal AG , Non-AG metabolic acidosis.

• Case scenario: A 66 year old man seen in emergency room. He has had 8 days of severe diarrhea, abdominal pain, & decreased intake, but adequate intake of liquids. His medical history is significant for diabetes & hypertension. Presently on enalapril, aspirin, atenolol, metformin. Physical examination: B.P 105/70, Pulse 72/min, R.R 32. Lab report: Na 136, K 3.9, Cl 114, HCO3 13, creatinine 1.2, glucose 128

Urine: pH 6, Na 32, K 21, Cl 80 ABG: pH 7.27, PO2 90, PCO2 30

Which acid base disorder is present?

• pH low & ↓ HCO3 Metabolic acidosis.

• Respiratory compensation :

Expected PCO2 = 1.5 X 13 + 8 = 27.5 (Adequate)

• Anion Gap = 136– (114 + 13) = 9 (Normal)

Non-AG Metabolic Acidosis

Metabolic acidosis

Characterized by fall in plasma HCO3 & fall in pH Causes:

Normal Anion Gap Increased Anion Gap

1. Loss of HCO3

Diarrhoea, CA inhibitors, Ureterosigmoidostomy,Proximal

RTA

1. Metabolic disorders: Lactic acidosis, DKA, Alcoholic

ketoacidosis

2. Failure to excrete H+ Distal RTA

2. Addition of exogenous acids Salicylate/ methanol poisoning

3. Addition H+

NH4CL infusion3. Failure to excrete acid Acute/chronic renal failure

Clinical manifestations:• Pulmonary changes- Kussmaul’s breathing( deep,regular,sighing respiration)• Cardiovascular changes- if severe (pH<7.2), ↑ susceptibility for cardiac arryhthmias, ↓ response to ionotropes & secondary hypotension.• Neurological changes- headache, confusion to coma.• Other- Renal failure

Diagnosis:• ABG values - ↓ HCO3 , ↓ pH, compensatory ↓ PaCO2

Treatment of Metabolic Acidosis:1. Specific management of underlying disorder

As a rule treat underlying disorder meticulously. It may be the only required treatment for mild to moderate acidosis & Non-AG acidosis.

2. Alkali therapy

Reserved only for selective patients with Severe Acidemia (controversial) & for Non-AG Acidosis Indications: pH<7.2 with sign of shock or myocardial irritability. HCO3 < 4meq/l

Severe Hyperchloremic acidemia Goal: To return pH to about 7.2 & HCO3 ↑ by 8-10meq/l.

Amount of HCO3 required= (Desired HCO3 – Actual HCO3 ) X0.3 X Bodywt.

Half of the correction is given f/b repeat ABG after sometime.

Case scenario: ABG of a patient with CHF on frusemidepH 7.48, HCO3 34 mEq/l, PaCO2 48 mmHg

• pH = alkalosis• HCO3 = s/o metabolic alkalosis

• PaCO2 = s/o compensation

• Rise in PaCO2 = 0.75 x rise in HCO3 = 0.75 x (34-24) = 7.5

Expected compensation = 40+7.5= 47.5 mmHg ~ actual PaCO2 s/o simple acid base disorderSo patient has primary metabolic alkalosis due to diuretics

Metabolic alkalosis

Characterized by ↑ HCO3 , ↑ pH,& compensatory ↑ in PaCO2

Occurs when there is excess of buffers present, raising systemic pH. Clinical features:• CNS- ↑ neuromuscular excitability leading to paresthesia, headache.• CVS- hypotension & arrythmias• Others- weakness, muscle cramps

• Causes: Metabolic alkalosis by chloride handling

Diagnosis:• ↑ HCO3 ,pH, compensatory ↑ PaCO2

• Serum potassium & chloride low• Urinary chloride estimation useful for diagnosis

Chloride sensitive(urine CL- <20meq/l)

Chloride resistant(urine CL- > 40meq/L)

GI LossesNasogastric suction, vomiting,Rectal adenoma

Hypertensive Renovascular hypertension, hyperaldosteronism

Renal acid lossesPenicillins , post-diuretic,Post-hypercapneic

Normotensive Diuretics, administration of alkali

Treatment:• Chloride sensitive-

IV normal saline volume expansion Discontinue diuretics if possible H2 blockers & PPI in case of nasogastric suction & vomiting

• Chloride resistant-

Remove offending agent Replace potassium if deficit• Extreme Alkalosis

Hemodialysis HCl can also be used(Dose = ∆ HCO3 X wt. X 0.5)

( infused at 0.1mmol/kg/hr)

Case scenario: Following sleeping pill ingestion, patient presented in drowsy state with sluggish respiration with rate of 4/min

pH 7.1, HCO3 28 mEq/l, PaCO2 80 mmHg, PaO2 42 mmHg

• pH = acidosis

• PaCO2 = s/o respiratory acidosis

• PaO2 = moderate hypoxemia

• HCO3 = s/o compensation

• Rise in HCO3 = 0.1 x rise in PaCO2 = 0.1 x (80-40) = 4 mEq/l

Expected compensation = 28 mEq/l ~ actual PaCO2 s/o simple acid base disorder

So patient has primary respiratory acidosis due to respiratory failure, due to sleeping pills

Respiratory Acidosis

Characterised by ↑ PaCO2 , ↓ pH, & compensatory ↑ HCO3

Causes:• Airway obstruction- Foreign body,Aspiration, Obstructive sleep apnea, Laryngospasm or Brochospasm.• Neuromuscular disorders of respiration- Myasthenia gravis, Guillain-Barre syndrome, Tetanus, Botulism, Hypokalemia, Cervical spine injury, Obesity• Central respiratiory depression- Drugs(Opiates, sedatives),Brain trauma• Respiratory disorder- Severe Pulmonary edema, Asthma, ARDS, COPD, Pulmonary fibrosis.

Clinical presentation: Headache, confusion, irritability, delirium Severity relates with the rapidity of development of disturbance. Treatment:A. General measures 1. Major goal is to identify & treat underlying cause. 2. Establish patent airway & restore oxygenation. 3. If patient with chronic hypercapnia develops sudden ↑ PaCO2 , search for aggravating factor, vigrous treatment of pulmonary infection, brochodilator therapy, removal of secretions. B. Oxygen therapy 1. In Acute , major threat is hypoxia, so oxygen is supplemented. 2. In Chronic hypercapnia, oxygen therapy instituted carefully & in lowest possible concentration.

C. Mechanical Ventilatory Support 1. Patient selection: In acute acidosis, early use of ventilatory assistance advised. In chronic, a more conservative approach is advisable because of great difficulty in weaning. 2. Indications: • Unstable,symptomatic or progressively hypercapneic.• If signs of muscle fatigue• Refractory severe hypoxemia• Depression of respiratory centre3. Rate of correction PaCO2 should be gradual & target is usually patient’s prior stable level & in acute should be normal level.D. Alkali Therapy Avoid except in severe acidemia or severe bronchospasm.

CASE SCENARIO A 15 year old boy brought from examination hall in apprehensive state

with complain of tightness in chest. pH 7.54, PCO 2 21, HCO 3 21

• pH ↑ = s/o alkalosis• ↓ PCO 2 = s/o respiratory alkalosis• ↓ HCO 3 = s/o compensation• expected compensation = 0.2 X (40- 21) = 3.8 • expected HCO 3 = 24-3.8= 20.2 meq/l ~ actual HCO 3 s/o simple acid-base disorder. so, the patient has primary respiratory alkalosis due to anxiety.

Respiratory Alkalosis

Characterised by ↓ PaCO2 due to hyperventilation & leads to ↑ pH.

Diagnosis: ↓ PaCO2 (<35mmHg), ↑ pH , compensatory ↓ HCO3

serum HCO3 does not fall below 15meq/l unless metabolic

acidosis is present. Causes:

1. Hypoxemia- Pulmonary disease( Pneumonia, Fibrosis, Edema,Emboli), CHF, Hypotension, Severe anemia, High altitude. 2. Direct stimulation of respiratory centre- Psychogenic or voluntray hyperventilation, Pain, Hepatic failure, Neurological disorder. Clinical features: Headache, arrythmias, tetany, seizures. Severity of hypocapnia constitutes grave prognosis.

Treatment• Vigrous treatment of the underlying cause• Mild alkalosis with few symptoms needs no treatment.• As hypoxemia is common cause, oxygen supplememtation is essential.

Case scenario

Known case of COPD develops severe vomiting pH 7.4, HCO3 36meq/l, PCO2 60mmHg

• pH normal = s/o either no acid –base disorder or mixed• ↑ PCO2 = s/o respiratory acidosis ( due to COPD)

• ↑ HCO3 = s/o metabolc alkalosis ( due to vomiting)

the patient has mixed disorder , respiratory acidosis & metabolic alkalosis.

Normal pH can be due to end result of opposite changes caused by primary disorder.

Mixed Acid Base Disorders

• Difficult to diagnose• Suspected whenever pH is normal or if apparent compensation is not adequate in a patient with known primary acid-base disorder.• Mixed metabolic & respiratory acidosis occurs when respiratory compensation is insufficient .• Gram- negative sepsis is a common cause of respiratory alkalosis & metabolic acidosis .

Summary:• Acid Base Homeostasis is all about maintenance of normal H+

concentration.• Changes in acid base status of ECF have profound and often

unpredicatable clinical and laboratory effects, more so during anaesthesia.

• pH scale is a negative logarithmic scale.• Anion gap must always be calculated to decipher more accurately the

complex acid-base disorders in critically ill patients.• Bicarbonate therapy must be used with caution in view of it’s various

deleterious effects.

References

• Miller’s Anesthesia, 7th Edition• Civetta, Taylor, Kirby; Critical care 4th Edition• Wylie And Churchill Davidson’s A Practice of

Anaesthsia, 5th Edition• Morgan Michael , 4th Edition• Clinical Application of Blood Gases, Shapiro, 5th

Edition • Harrison’s Principles of Internal Medicine, 16th

Edition

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