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:
12500 mEq/d CO2 from metabolism 50 - 100 mEq/d H+ load from AA metabolism

H+ ion

Ingestion of NH4Cl, CaCl2 Strenuous Exercise Lactic Acid

Failure of Kidneys to Excrete PO 4--, SO 4--

Diabetic KA

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 Neutrality 2. Mass conservation 3. 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 Normogram To 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+ + ApH = 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 Plasma (35%) Erythrocyte(18%) Hemoglobin Plasma Proteins Organic & Inorganic Phosphates
53%

35% 7% 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- + H O 2 .NH OH + H+ <====> NH + H O 3 3 2 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 bicarbonate 3. Formation of titrable acid (1mEq/Kg/d) 4. Excretion of NH4+ in urine

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

PERITUBULAR BLOOD
RENAL TUBULAR CELL

GLOMULAR FILTRATE
Glutamine

HCO3- Na+ HPO42- Na+ NH3 Na+

HCO3- + H+ 1. NaHCO3 CO2 H2CO3 CO2 + H2 O CO2

2.

NaHCO3

HCO3- + H+
CA

H2PO4-

3.

NaHCO3

HCO3- + H+

NH4+

H2O

H2PO4-

NH4+

CO2 can be obtained from blood or the tubular fluid

 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 disorders

Disorder Respiratory Acidosis Alkalosis Metabolic Acidosis Alkalosis Primary change Compensatory response HCO3 HCO3

PaCO2 PaCO2

HCO3 HCO3

PaCO2 PaCO2

Normal reference range

pH
HCO3PaCO2 PaO2 Base excess/Deficit Anion gap A-aO2 SaO2

7.35-7.45
22-26meq/l 35-45mmHg 80-100mmHg -2 to +2meq/l 8 to 12 meq/l 5-25mmHg 96-100%

Prediction of Compensatory Responses on Simple Acid Base Disorders

Disorder
Metabolic Acidosis

Prediction of Compensation
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 Respiratory Alkalosis Acute Chronic Respiratory Acidosis Acute Chronic

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

[HCO3- ] will 2mmol/L per 10 mmHg in PaCO2 [HCO3- ] will 4mmol/L per 10 mmHg in PaCO2 [HCO3- ] will 1mmol/L per 10 mmHg in PaCO2 [HCO3- ] will 4mmol/L per 10 mmHg in PaCO2

General approach to acid-base disorder

pH

Acidemia pH <7.35

Normal pH7.35-7.45

Alkalemia pH> 7.45

HCO3

PaCO2

Normal or mixed disorder

HCO3

PaCO2

Metabolic acidosis

Respiratory acidosis

Metabolic alkalosis

Respiratory alkalosis

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 1. Loss of HCO3 Diarrhoea, CA inhibitors, Ureterosigmoidostomy,Proximal RTA 2. Failure to excrete H+ Distal RTA 3. Addition H+ NH4CL infusion Increased Anion Gap 1. Metabolic disorders: Lactic acidosis, DKA, Alcoholic ketoacidosis 2. Addition of exogenous acids Salicylate/ methanol poisoning 3. Failure to excrete acid Acute/chronic renal failure

 Clinical manifestations: Pulmonary changes- Kussmauls 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 frusemide pH 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 disorder So 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

Chloride sensitive (urine CL- <20meq/l) Chloride resistant (urine CL- > 40meq/L)

GI Losses Nasogastric suction, vomiting, Rectal adenoma

Renal acid losses Penicillins , post-diuretic, Post-hypercapneic

Hypertensive Renovascular hypertension, hyperaldosteronism

Normotensive Diuretics, administration of alkali

Diagnosis: HCO3 ,pH, compensatory PaCO2 Serum potassium & chloride low Urinary chloride estimation useful for diagnosis

 Treatment: Chloride sensitiveIV normal saline volume expansion Discontinue diuretics if possible H2 blockers & PPI in case of nasogastric suction & vomiting Chloride resistantRemove 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 centre 3. Rate of correction PaCO2 should be gradual & target is usually patients 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 its various deleterious effects.

References
Millers Anesthesia, 7th Edition Civetta, Taylor, Kirby; Critical care 4th Edition Wylie And Churchill Davidsons A Practice of Anaesthsia, 5th Edition Morgan Michael , 4th Edition Clinical Application of Blood Gases, Shapiro, 5th Edition Harrisons Principles of Internal Medicine, 16th Edition

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