ACID BASE BALANCE DISCUSSION HEADINGS • BASICS • NORMAL PHYSIOLOGY • ABNORMALITIES • METABOLIC ACID BASE DISORDERS • RESPIRATORY ACID BASE DISORDERS • ALTERNATIVE CONCEPTS • Acid Any compound which forms H⁺ ions in solution (proton donors) eg: Carbonic acid releases H⁺ ions • Base Any compound which combines with H⁺ ions in solution (proton acceptors) eg:(HCO3⁻) accepts H+ ions Acid–Base Normal pHBalance : 7.35-7.45 Acidosis Physiological state resulting from abnormally low plasma pH Alkalosis Physiological state resulting from abnormally high plasma pH Acidemia: plasma pH < 7.35  Alkalemia: plasma pH > 7.45 Henderson-Hasselbach equation (clinically relevant form) - • pH = pKa + log([HCO3 ]/.03xpCO2) - • pH = 6.1 + log([HCO3 ]/.03xpCO2) • Shows that pH is a function of the RATIO between bicarbonate and pCO2 • PCO₂ - ventilatory parameter (40 +/- 4) • HCO₃⁻ - metabolic parameter (22-26 mmol/L) ACID • VOLATILE ACIDS: S  Produced by oxidative metabolism of CHO,Fat,Protein  Average 15000-20000 mmol of CO₂per day  Excreted through LUNGS as CO₂ gas • FIXED ACIDS (1 mEq/kg/day)  Acids that do not leave solution ,once produced they remain in body fluids Until eliminated by KIDNEYS Eg: Sulfuric acid ,phosphoric acid , Organic acids Are most important fixed acids in the body Are generated during catabolism of: amino acids(oxidation of sulfhydryl gps of cystine,methionine) Phospholipids(hydrolysis) Response to ACID BASE challenge

1.Buffering 2. Compensati on Buffer s First line of defence (> 50 – 100 mEq/day) Two most common chemical buffer groups – Bicarbonate – Non bicarbonate (Hb,protein,phosphate) Blood buffer systems act instantaneously Regulate pH by binding or releasing H⁺ Carbonic Acid–Bicarbonate Buffer SystemCarbon Dioxide Most body cells constantly generate carbon dioxide Most carbon dioxide is converted to carbonic acid, which dissociates into H+ and a bicarbonate ion Prevents changes in pH caused by organic acids and fixed acids in ECF  Cannot protect ECF from changes in pH that result from elevated or depressed levels of

CO2  Functions only when respiratory system and respiratory control centers are working normally Acid–Base Balance

The Carbonic Acid–Bicarbonate Buffer System The Hemoglobin Buffer System

CO2 diffuses across RBC membrane No transport mechanism required As carbonic acid dissociates Bicarbonate ions diffuse into plasma In exchange for chloride ions (chloride shift) • Hydrogen ions are buffered by hemoglobin molecules HelpsIs the onlyprevent intracellular major changes buffer systemin pH when with 2 plasmaan immediate PCO is risingeffect oron fallingECF pH Phosphate Buffer System

- Consists of anion H2PO4 (a weak Worksacid)(pKa like- 6.8)the carbonic acid–bicarbonate buffer system Is important in buffering pH of ICF Limitations of Buffer Systems  Provide only temporary solution to acid– base imbalance  Do not eliminate H+ ions  Supply of buffer molecules is limited Respiratory Acid-Base Control • When chemicalMechanisms buffers alone cannot prevent changes in blood pH, the respiratory system is the second line of defence against changes. Eliminate or Retain CO₂ Change in pH are RAPID Occuring within minutes PCO₂∞ VCO₂/VA Renal Acid-Base Control Mechanisms • The kidneys are the third line of defence against wide changes in body fluid pH. – movement of bicarbonate – Retention/Excretion of acids – Generating additional buffers Long term regulator of ACID – BASE balance May take hours to days for correction Renal regulation of acid base balance • Role of kidneys is preservation of body’s bicarbonate stores. • Accomplished by: – Reabsorption of 99.9% of filtered bicarbonate – Regeneration of titrated bicarbonate by excretion of: • Titratable acidity (mainly phosphate) • Ammonium salts Renal reabsorption of bicarbonate • Proximal tubule: 70- 90% • Loop of Henle: 10- 20% • Distal tubule and collecting ducts: 4-7% Factors affecting renal bicarbonate reabsorption• Filtered load of bicarbonate • Prolonged changes in pCO2 • volume • Plasma chloride concentration • Plasma potassium concentration • Hormones (e.g., mineralocorticoid s, • If secreted H+ ions combine with filtered bicarbonate, bicarbonate is reabsorbed • If secreted H+ ions combine with phosphate or ammonia, net acid excretion and generation of new bicarbonate occur NET ACID EXCRETION • Hydrogen Ions Are secreted into tubular fluid along • Proximal convoluted tubule (PCT) • Distal convoluted tubule (DCT) • Collecting system Titratable acidity

• Occurs when secreted H+ encounter & titrate phosphate in tubular fluid • Refers to amount of strong base needed to titrate back to pH 7.4 • 40% (15-30 mEq) of daily fixed acid load • Relatively constant (not highly Ammonium excretion • Occurs when secreted H+ combine with NH3 + andtrappedare as NH4 insalts tubular fluid • 60% (25-50 mEq) of daily fixed acid load • Very adaptable (via glutaminase induction) Ammonium • Large amounts ofexcretion H+ can be excreted without extremely low urine pH because pKa + of NH3/NH4 system is very high (9.2) Acid–Base Balance Disturbances

Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. Acid–Base Balance Disturbances decreased

Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. Four Basic Types of Imbalance • • • • Acid Base Disorders Disorder pH [H+] Primary Secondary disturbance response

Metabolic -    [HCO3 ]  pCO2 acidosis

Metabolic -    [HCO3 ]  pCO2 alkalosis

Respiratory -    pCO2  [HCO3 ] acidosis

Respiratory -    pCO2  [HCO3 ] alkalosis Metabolic Acidosis • Primary AB disorder • ↓HCO₃⁻ → ↓ pH • Gain of strong acid • Loss of base(HCO₃⁻) CONCEPT • To know if Metabolic Acidosis due to Loss of bicarbonate Accumulation of non-volatile acids • Provides an index of the relative conc of plasma anions other than chloride,bicarbonate • *serum Na⁺ - (serum Cl⁻ + serumHCO₃⁻)+ • Unmeasured anions – unmeasured cations • 8 – 16 mEq/L (5 – 11,with newer techniques) • Mostly represent ALBUMIN Concept of Anion Gap Bac k CAUSES OF METABOLIC ACIDOSIS (High anion

LACTICgap)→(Normochloremic)TOXINS ACIDOSIS Ethylene glycol KETOACIDOSIS Methanol Diabetic Salicylates Alcoholic Propylene Starvation glycol RENAL FAILURE (acute and chronic) Normal anion gap(Hyperchloremic)  Gastrointesti  Drug-induced nal MET.ACIDOSIShyperkalemiacauses (with bicarbonate renal insufficiency) loss A.Potassium-sparing diuretics (amiloride, triamterene, A.Diarrhea spironolactone) B.External pancreatic or small- B.Trimethoprim bowel drainage C.Pentamidine C.Ureterosigmoidostomy, D.ACE-Is and ARBs jejunal loop, ileal loop E.Nonsteroidal anti-inflammatory D.Drugs drugs 1. Calcium chloride (acidifying F.Cyclosporine and tacrolimus agent)  Other 2. Magnesium sulfate (diarrhea) A.Acid loads (ammonium chloride, 3. Cholestyramine (bile acid hyperalimentation) diarrhea) B.Loss of potential bicarbonate: Renal acidosis ketosis with ketone excretion C.Expansion acidosis (rapid A. Hypokalemia saline administration) 1. Proximal RTA (type 2) URINE NET CHARGE/UAG Distinguish between hyperchloremic acidosis due to DIARRHEA RTA UNC= Na⁺+ K⁺- Cl⁻ • Provides an estimate of urinary NH₄⁺production • Normal UAG = -25 to -50 Negative UAG – DIARRHEA(hyperchloremic acidosis) Positive UAG – RTA “” / “GAP-GAP” FIG • Ratio between ↑ i n AG and ↓inbicarbonate • (Measured AG – 12):(24 – measured HCO₃⁻) • To detect another metabolic ACID BASE disorder along with HAGMA (nagma/met.alkalosis) • HAGMA(NORMOCHLOREMIC ACIDOSIS) :- RATIO = 1 HYPERCHLOREMIC ACIDOSIS (NAGMA):- RATIO < 1 In DKA pts,after therapy with NS • Met.acidosis with Met.alkalosis :- RATIO > 1 Compensation for Metabolic

• Hacidosis+ buffered by ECF HCO3 - & Hb in RBC; Plasma Pr negligibleand Pi: role (sec-min) • Hyperventilation – to reduce PCO₂ • ↓pH sensed by central and peripheral chemoreceptors • ↑ in ventilation starts within minutes,well advanced at 2 hours • Maximal compensation takes 12 – 24 hours • Expected PCO₂calculatedby WINTERS’ FORMULA EXP.PCO₂=1.5 X (ACTUAL HCO₃⁻ )+8 +/- 2 mmHg Limiting value of compensation: PCO₂= 8- 10mmHg Quick rule of thumb :PCO₂= last 2 digits of pH Acid–Base Balance Disturbances

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Responses to Metabolic Acidosis Metabolic

Symptoms areacidosis specific and a result of the underlying pathology • Respiratory effects:  Hyperventilation • CVS:  ↓ myocardial contractility  Sympathetic over activity  Resistant to catecholamines • CNS:  Lethargy,disorientation,stupor,muscle twitching,COMA, CN palsies • Others : hyperkalemia Metabolic

↑ pH due to ↑HCOAlkalosis₃⁻ or ↓acid • Initiation process :  ↑in serum HCO₃⁻  Excessive secretion of net daily production of fixed acids • Maintenance:  ↓HCO₃⁻ excretion or ↑ HCO₃⁻ reclamation  Chloride depletion  Pottasium depletion  ECF volume depletion  Magnesium depletion CAUSES OF METABOLIC I. ExogenousALKALOSIS HCO3 −loads A. Acute alkali administration B.Milk-alkali syndrome II. Gastrointestinal origin 1. Vomiting 2. Gastric aspiration 3. Congenital chloridorrhea 4. Villous adenoma III. Renal origin 1. Diuretics 2. Posthypercapnic state 3. Hypercalcemia/hypoparathyroidism 4. Recovery from or ketoacidosis 5. Nonreabsorbable anions including penicillin, carbenicillin 6. Mg2+ deficiency 7. K+ depletion Chloride responsive alkalosis Low urinary chloride concentration(<15 meq/L) Gastric acid loss Diuretic therapy Volume depletion for hypercapnea

Chloride resistant alkalosis Elevated urinary chloride (>25 meq/L) 1⁰ mineralocorticoidexcess Severe pottasium depletion A/W volume expansion Compensation for Metabolic Alkalosis • : HYPOVENTILATION - ↑PCO₂=0.6 mm  pCO2 per 1.0 mEq/L ↑HCO3 • Maximal compensation: PCO₂ 55 – 60 mmHg • Hypoventilation not always found due to Hyperventilation due to pain due to pulmonary congestion due to hypoxemia(PO₂ < 50mmHg) Acid–Base Balance Disturbances

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Metabolic Alkalosis Metabolic DecreasedAlkalosis myocardial contractility Arrythmias

↓ cerebral blood flow Confusion Mental obtundation Neuromuscular excitability

• Hypoventilation pulmonary micro atelectasis V/Q mismatch(alkalosis inhibits HPV) Contraction Alkalosis • Loss of HCO₃⁻ poor, chloride rich ECF • Contraction of ECF volume • Original HCO₃⁻ dissolved in smaller volume • ↑HCO₃⁻ concentration • Eg : Loop diuretics/Thiazides in a generalised edematous pt. Respiratory Acidosis • ↑ PCO₂→ ↓pH • Acute(< 24 hours) • Chronic(>24 hours) RESPIRATORY ACIDOSIS - CNSCAUSESDEPRESSION DRUGS:Opiates,sedatives,anaesthetics OBESITY HYPOVENTILATION SYNDROME STROKE NEUROMUSCULAR DISORDERS NEUROLOGIC:MS,POLIO,GBS,TETANUS,B OTULISM, HIGH CORD LESIONS END PLATE:MG,OP POISONING,AG TOXICITY MUSCLE:↓K⁺,↓PO₄,MUSCULAR DYSTROPHY AIRWAY OBSTRUCTION COPD,ACUTE CONT CHEST WALL RESTRICTION PLEURAL: Effusions, .. empyema,pneumothorax,fibrothor ax CHEST WALL: Kyphoscoliosis, scleroderma,ankylosing spondylitis,obesity SEVERE PULMONARY RESTRICTIVE DISORDERS PULMONARY FIBROSIS PARENCHYMAL INFILTRATION: Pneumonia, edema ABNORMAL BLOOD CO₂TRANSPORT DECREASED PERFUSION: HF,cardiac arrest,PE SEVERE ANEMIA ACETAZOLAMIDE-CA Inhibition Compensation in Respiratory AcuteAcidosisresp.acidosis: Mainly due to intracellular buffering(Hb,Pr,PO₄) HCO₃⁻ ↑ = 1mmol for every 10 mmHg↑ PCO₂ Minimal increase in HCO₃⁻ pH change = 0.008 x (40 - PaCO₂)

Chronic resp.acidosis Renal compensation (acidification of urine & bicarbonate retention) comes into action HCO₃⁻ ↑ = 3.5 mmol for every 10 mmHg ↑PCO₂ pH change = 0.003 x (40 - PaCO₂) Acid–Base Balance Disturbances

Respiratory Acid–Base Regulation. • RS: Stimulation of ventilation ( tachypnea) dyspnea • CNS: ↑cerebral blood flow→↑ICT CO₂NARCOSIS (Disorientation,confusion,headache,lethargy) COMA(arterial hypoxemia,↑ICT,anaesthetic effect of ↑ PCO₂> 100mmHg) • CVS: tachycardia,bounding pulse • Others: peripheral vasodilatation(warm,flushed,sweaty) Post hypercapnic alkalosis • In chronic resp.acidosis • Renal compensation → ↑HCO₃⁻ • If the pt intubated and mechanical ventilated • PCO₂ rapidly corrected • Plasma HCO₃⁻ doesn’t return to normal rapidly • HCO₃⁻ remains high Respiratory Alkalosis • Most common AB abnormality in critically ill • ↓PCO₂ →↑pH • 1⁰ process : hyperventilation • Acute: PaCO₂ ↓,pH-alkalemic • Chronic: PaCO₂↓,pH normal / near normal CAUSES OF RESPIRATORY A. CentralALKALOSIS nervous C. Drugs or hormones system stimulation 1. Pregnancy, progesterone 1. Pain 2. Salicylates 2. Anxiety, psychosis 3. Cardiac failure 3. Fever D. Stimulation of chest 4. Cerebrovascular receptors accident 1. Hemothorax 5. Meningitis, 2. Flail chest encephalitis 3. Cardiac failure 4. Pulmonary embolism 6. Tumor E. Miscellaneous 7. Trauma 1. Septicemia B. Hypoxemia or tissue hypoxia 2. Hepatic failure 3. Mechanical ventilation 1. High altitude 4. Heat exposure 2. Septicemia 5. Recovery from metabolic 3. Hypotension acidosis 4. Severe anemia Compensation for respiratory AcuteAlkalosis resp.alkalosis:  Intracellular buffering response-slight decrease in HCO₃⁻  Start within 10 mins ,maximal response 6 hrs  Magnitude:2 mmol/L↓HCO₃⁻ for 10 mmHg↓PCO₂  LIMIT: 12-20 mmol/L (avg=18)

Chronic resp.alkalosis:  Renal compensation (acid retention,HCO₃⁻ loss)  Starts after 6 hours, maximal response 2- 3 days  Magnitude : 5mmol/L ↓HCO₃⁻ for 10mmHg↓PCO₂  LIMIT: 12-15 mmol/L HCO₃⁻ Acid–Base Balance Disturbances

Respiratory Acid–Base Regulation. Respiratory • CN  ↑S: neuromuscularalkalosis irritability(tingling,circumoral numbness)  Tetany  ↓ ICT(cerebral VC)  ↓CBF(4% ↓ CBF per mmHg ↓PCO₂)  Light headedness,confusion • CVS:  CO& SBP ↑ ( ↑ SVR,HR)  Arrythmias  ↓ myocardial contractility • Others:  Hypokalemia,hypophosphatemia  ↓Free serumcalcium  Hyponatremia,hypochloremia Acid Base Primary disorderDisordersCompensatory response

Metabolic acidosis PCO₂=1.5 X (HCO₃⁻) + 8 +/₋ 2*Winter’s formula+

- Metabolic alkalosis 0.6 mm  pCO2 per 1.0 mEq/L  HCO3

- Acute respiratory acidosis 1 mEq/L  HCO3 per 10 mm  pCO2

- Chronic respiratory acidosis 3.5 mEq/L  HCO3 per 10 mm  pCO2

- Acute respiratory alkalosis 2 mEq/L  HCO3 per 10 mm  pCO2

- Chronic respiratory alkalosis 5 mEq/L  HCO3 per 10 mm  pCO2 STRONG ION • Metabolic parameter divided into 2 components “STRONG”APPROACH acids and bases  Electrolytes, lactate,acetoacetate,sulfate “WEAK” buffer molecules  Serum proteins and phosphate • pH calculated on the basis of 3 simple assumptions  Total concentrations of each of the ions and acid base pairs is known and remains unchanged  Solution remains electroneutral  Dissociation constants of each of the buffers are known • Both pH and bicarbonate are dependent variables that can be calculated from the concentrations of “STRONG” and “WEAK” electrolytes and PCO₂ STRONG ION • STRONGDIFFERENCE CATIONS – STRONG(SID) ANIONS • Decrease in SID → Acidification ofPLASMA • Explains – NS induced ACIDOSIS • ADV: Estimate of H⁺ conc more accurate than Henderson Hasselbalch equation. • DIS ADV:Complex nature of equations,increased parameters limit clinical application BASE

• Base excessEXCESS/DEFICIT and base deficit are terms applied to an analytical method for determination of the appropriateness of responses to disorders of acid- base metabolism • by measuring blood pH against ambient PCO2 and against a PCO2 of 40 mmHg

• deficit is expressed as the number of mEq of bicarbonate needed to restore the serum bicarbonate to 25 mEq/L at a PCO₂ of 40 mmHg compared with that at the ambient PCO₂ • misleading in chronic respiratory alkalosis or acidosis • physiological evaluation of the patient be the mode of analysis of acid-base disorders rather than an emphasis on derived formulae ACID BASE NORMOGRAM MIXED ACID BASE DISORDER Diagnosed by combination of clinical assessment, application of expected compensatory responses , assessment of the anion gap, and application of principles of physiology. Respiratory acidosis and alkalosis never coexist Metabolic disorders can coexist Eg: lactic acidosis/DKA with vomiting Metabolic and respiratory AB disorders can coexist Eg: salicylate poisoning (met.acidosis + resp.alkalosis) THANK YOU LIFE IS A STRUGGLE, NOT AGAINST SIN, NOT AGAINST MONEY POWER.. BUT AGAINST HYDROGEN IONS . H.L.MENCK