acid base balance

ACID BASE BALANCE

Dr Amith Sreedharan

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

• BaseAny compound which combines with

H⁺ ions in solution (proton acceptors) eg:Bicarbonate(HCO3⁻) accepts H+ ions

Acid–Base BalanceNormal pH : 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)

ACIDS• VOLATILE ACIDS: Produced by oxidative metabolism of CHO,Fat,Protein Average 15000-20000 mmol of CO₂ per 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 acidsAre most important fixed acids in the bodyAre generated during catabolism of:

amino acids(oxidation of sulfhydryl gps of cystine,methionine)

Phospholipids(hydrolysis)

nucleic acids

Response to ACID BASE challenge

1.Buffering2. Compensation

Buffers

First line of defence (> 50 – 100 mEq/day)Two most common chemical buffer groups– Bicarbonate– Non bicarbonate (Hb,protein,phosphate)Blood buffer systems act instantaneouslyRegulate 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 Ability to buffer acids is limited by availability of

bicarbonate ions

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

Is the only intracellular buffer system with an immediate effect on ECF pH

Helps prevent major changes in pH when plasma PCO2 is

rising or falling

Phosphate Buffer System

Consists of anion H2PO4- (a weak acid)(pKa-6.8)

Works like 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 Mechanisms

• When chemical buffers alone cannot prevent changes in blood pH, the respiratory system is the second line of defence against changes.Eliminate or Retain CO₂Change in pH are RAPIDOccuring within minutesPCO₂ ∞ 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 buffersLong term regulator of ACID – BASE balanceMay 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

• Extracellular fluid volume

• Plasma chloride concentration

• Plasma potassium concentration

• Hormones (e.g., mineralocorticoids, glucocorticoids)

• 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 urine back to pH 7.4

• 40% (15-30 mEq) of daily fixed acid load

• Relatively constant (not highly adaptable)

Ammonium excretion• Occurs when

secreted H+ combine with NH3 and are trapped as NH4

+ salts in tubular fluid

• 60% (25-50 mEq) of daily fixed acid load

• Very adaptable (via glutaminase induction)

Ammonium excretion• Large amounts

of 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

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

decreased

Four Basic Types of Imbalance

• Metabolic Acidosis• Metabolic Alkalosis• Respiratory Acidosis• Respiratory Alkalosis

Acid Base Disorders

Disorder pH [H+] Primary disturbance

Secondary response

Metabolic acidosis

[HCO3-] pCO2

Metabolic alkalosis

[HCO3-] pCO2

Respiratory acidosis

pCO2 [HCO3-]

Respiratory alkalosis

pCO2 [HCO3-]

Metabolic Acidosis

• Primary AB disorder• ↓HCO₃⁻ → ↓ pH • Gain of strong acid• Loss of base(HCO₃⁻)

ANION GAP CONCEPT

• To know if Metabolic Acidosis due toLoss of bicarbonateAccumulation of non-volatile acids• Provides an index of the relative conc of plasma anions

other than chloride,bicarbonate• [serum Na⁺ - (serum Cl⁻ + serum HCO₃⁻)]• Unmeasured anions – unmeasured cations• 8 – 16 mEq/L (5 – 11,with newer techniques)• Mostly represent ALBUMIN

Concept ofAnion Gap

Back

CAUSES OF METABOLIC ACIDOSIS(High anion gap)→(Normochloremic)

LACTIC ACIDOSISKETOACIDOSISDiabeticAlcoholic Starvation RENAL FAILURE

(acute and chronic)

TOXINSEthylene glycolMethanolSalicylatesPropylene glycol

Normal anion gap(Hyperchloremic) MET.ACIDOSIS causes

Gastrointestinal bicarbonate loss

A. DiarrheaB. External pancreatic or small-bowel drainageC. Ureterosigmoidostomy, jejunal loop, ileal loopD. Drugs1. Calcium chloride (acidifying agent)2. Magnesium sulfate (diarrhea)3. Cholestyramine (bile acid diarrhea)Renal acidosisA. Hypokalemia1. Proximal RTA (type 2)2. Distal (classic) RTA (type 1)B. Hyperkalemia

Drug-induced hyperkalemia (with renal insufficiency)

A. Potassium-sparing diuretics (amiloride, triamterene, spironolactone)B. TrimethoprimC. PentamidineD. ACE-Is and ARBsE. Nonsteroidal anti-inflammatory drugsF. Cyclosporine and tacrolimus

OtherA. Acid loads (ammonium chloride, hyperalimentation)B. Loss of potential bicarbonate: ketosis with ketone excretionC. Expansion acidosis (rapid saline administration)

URINE NET CHARGE/UAG

Distinguish between hyperchloremic acidosis due toDIARRHEA RTAUNC= Na⁺+ K⁺- Cl⁻• Provides an estimate of urinary NH₄⁺ production• Normal UAG = -25 to -50Negative UAG – DIARRHEA(hyperchloremic acidosis)Positive UAG – RTA

“DELTA RATIO” / “GAP-GAP”

• Ratio between ↑in AG and ↓in bicarbonate • (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 > 1Use of NG suction and DIURETICS in met.acidosis pt

FIG

Compensation for Metabolic acidosis• H+ buffered by ECF HCO3

- & Hb in RBC; Plasma Pr and Pi: negligible 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 PCO₂ calculated by WINTERS’ FORMULAEXP.PCO₂ =1.5 X (ACTUAL HCO₃⁻ )+8 +/- 2 mmHgLimiting value of compensation: PCO₂ = 8-10mmHgQuick rule of thumb :PCO₂ = last 2 digits of pH

Acid–Base Balance Disturbances

.

Responses to Metabolic Acidosis

Metabolic acidosis

Symptoms are 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 Alkalosis

↑ pH due to ↑HCO₃⁻ 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 ALKALOSISI. Exogenous HCO3 − loadsA. Acute alkali administrationB. Milk-alkali syndrome

II. Gastrointestinal origin1. Vomiting2. Gastric aspiration3. Congenital chloridorrhea4. Villous adenoma

III. Renal origin1. Diuretics2. Posthypercapnic state3. Hypercalcemia/hypoparathyroidism4. Recovery from lactic acidosis or ketoacidosis5. Nonreabsorbable anions including penicillin, carbenicillin6. Mg2+ deficiency7. K+ depletion

Chloride responsive alkalosisLow urinary chloride concentration(<15 meq/L)

Gastric acid lossDiuretic therapyVolume depletionRenal compensation for hypercapnea

Chloride resistant alkalosisElevated urinary chloride (>25 meq/L)

1⁰ mineralocorticoid excessSevere pottasium depletion

A/W volume expansion

Compensation for Metabolic Alkalosis

• Respiratory compensation: HYPOVENTILATION↑PCO₂=0.6 mm pCO2 per 1.0 mEq/L ↑HCO3

-

• Maximal compensation: PCO₂ 55 – 60 mmHg• Hypoventilation not always found due toHyperventilation due to paindue to pulmonary congestiondue to hypoxemia(PO₂ < 50mmHg)

Acid–Base Balance Disturbances

.

Metabolic Alkalosis

Metabolic AlkalosisDecreased myocardial contractilityArrythmias

↓ cerebral blood flowConfusionMental obtundationNeuromuscular excitability

• Hypoventilationpulmonary micro atelectasisV/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 - CAUSESCNS DEPRESSIONDRUGS:Opiates,sedatives,anaestheticsOBESITY HYPOVENTILATION SYNDROMESTROKENEUROMUSCULAR DISORDERSNEUROLOGIC:MS,POLIO,GBS,TETANUS,BOTULISM,HIG

H CORD LESIONSEND PLATE:MG,OP POISONING,AG TOXICITYMUSCLE:↓K⁺,↓PO₄,MUSCULAR DYSTROPHYAIRWAY OBSTRUCTIONCOPD,ACUTE ASPIRATION,LARYNGOSPASM

CONT..CHEST WALL RESTRICTIONPLEURAL: Effusions, empyema,pneumothorax,fibrothoraxCHEST WALL: Kyphoscoliosis, scleroderma,ankylosing

spondylitis,obesitySEVERE PULMONARY RESTRICTIVE DISORDERSPULMONARY FIBROSISPARENCHYMAL INFILTRATION: Pneumonia, edemaABNORMAL BLOOD CO₂ TRANSPORTDECREASED PERFUSION: HF,cardiac arrest,PESEVERE ANEMIAACETAZOLAMIDE-CA InhibitionRED CELL ANION EXCHANGE: Loop diuretics, salicylates,

NSAID

Compensation in Respiratory AcidosisAcute resp.acidosis:Mainly due to intracellular buffering(Hb,Pr,PO₄)HCO₃⁻ ↑ = 1mmol for every 10 mmHg ↑ PCO₂Minimal increase in HCO₃⁻pH change = 0.008 x (40 - PaCO₂)

Chronic resp.acidosisRenal compensation (acidification of urine & bicarbonate

retention) comes into actionHCO₃⁻ ↑= 3.5 mmol for every 10 mm Hg ↑PCO₂pH change = 0.003 x (40 - PaCO₂)Maximal response : 3 - 4 days

Acid–Base Balance Disturbances

Respiratory Acid–Base Regulation.

• RS:Stimulation of ventilation ( tachypnea)dyspnea• CNS:↑cerebral blood flow→ ↑ICTCO₂ NARCOSIS

(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 ALKALOSISA. Central nervous system stimulation1. Pain2. Anxiety, psychosis3. Fever4. Cerebrovascular accident5. Meningitis, encephalitis6. Tumor7. Trauma

B. Hypoxemia or tissue hypoxia1. High altitude2. Septicemia3. Hypotension 4. Severe anemia

C. Drugs or hormones1. Pregnancy, progesterone2. Salicylates3. Cardiac failureD. Stimulation of chest receptors1. Hemothorax2. Flail chest3. Cardiac failure4. Pulmonary embolismE. Miscellaneous1. Septicemia2. Hepatic failure3. Mechanical ventilation4. Heat exposure5. Recovery from metabolic acidosis

Compensation for respiratory AlkalosisAcute 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 alkalosis• CNS: ↑ neuromuscular 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 serum calcium Hyponatremia,hypochloremia

Acid Base DisordersPrimary disorder Compensatory 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 APPROACH• Metabolic parameter divided into 2 components“STRONG” acids and bases Electrolytes, lactate,acetoacetate,sulfate“WEAK” buffer molecules Serum proteins and phosphate• pH calculated on the basis of 3 simple assumptionsTotal concentrations of each of the ions and acid base pairs

is known and remains unchangedSolution remains electroneutralDissociation 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 DIFFERENCE (SID)• STRONG CATIONS – STRONG ANIONS• Decrease in SID → Acidification of PLASMA• 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 EXCESS/DEFICIT

• Base excess 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 coexistMetabolic disorders can coexistEg: lactic acidosis/DKA with vomitingMetabolic and respiratory AB disorders can coexistEg: salicylate poisoning (met.acidosis + resp.alkalosis)

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