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: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 theRATIO between bicarbonate andpCO2

• PCO₂ - ventilatory parameter (40 +/- 4)

• HCO₃⁻ - metabolic parameter (22-26 mmol/L)

ACID

S• VOLATILE ACIDS: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

sFirst 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 DioxideMost 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

SystemCO2 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 withan immediate effect on ECF pH 2

Helps prevent major changes in pH when plasma PCO 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 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 byexcretion of:• Titratable acidity (mainly phosphate)

• Ammonium salts

Renal reabsorption of

bicarbonate• Proximal

tubule: 70-90%

• Loop ofHenle: 10-20%

• Distal tubuleand collectingducts: 4-7%

Factors affecting renal

bicarbonate

reabsorption• Filtered load of bicarbonate

• Prolonged changesin pCO2

• Extracellularfluid volume

• Plasmachloride concentration

• Plasmapotassium concentration

• Hormones (e.g., mineralocorticoids,

• 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

Ammonium

excretion • Occurs when secreted H+

combine with NH3 and aretrapped as NH +

salts4

in tubular fluid

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

• Very adaptable (via glutaminase induction)

Ammonium

excretion• Largeamounts of

H+ can be

excreted

without

extremely

low urine pH

because pKa of NH3/NH +4system 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

DisordersDisorder 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 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

gap)→(Normochloremic)LACTIC

ACIDOSIS

KETOACIDOSIS

Diabetic

Alcoholic

Starvation

RENALFAILURE(acute andchronic)

TOXINS

Ethylene glycol

Methanol

Salicylates

Propylene

glycol

Normal anion

gap(Hyperchloremic)

MET.ACIDOSIS causes Gastrointestinal bicarbonateloss

A.Diarrhea

B.External pancreatic or small-bowel drainage

C.Ureterosigmoidostomy, jejunal loop, ileal loop

D.Drugs

1. Calcium chloride (acidifying

agent)

2. Magnesium sulfate (diarrhea)

3. Cholestyramine (bile acid

diarrhea)

Renal acidosisA. Hypokalemia

1. Proximal RTA (type 2)

Drug-induced hyperkalemia (with renal insufficiency)

A.Potassium-sparing diuretics (amiloride, triamterene,spironolactone)

B.Trimethoprim

C.Pentamidine

D.ACE-Is and ARBs

E.Nonsteroidal anti-inflammatory

drugs

F.Cyclosporine and tacrolimus

OtherA.Acid loads (ammonium chloride,hyperalimentation)

B.Loss of potential bicarbonate: ketosis with ketone excretion

C.Expansion acidosis (rapid saline administration)

URINE NET

CHARGE/UAGDistinguish 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

“DELTA RATIO” / “GAP-GAP”

FIG

• 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 > 1

Compensation for Metabolic

acidosis• H+ buffered by ECF HCO - & Hb in RBC; Plasma Pr and Pi:

3

negligible role (sec-min)

• Hyperventilation – to reduce PCO₂• ↓pH sensed by central and peripheral chemoreceptors

• ↑ in ventilation starts within minutes,well advancedat 2 hours

• Maximal compensation takes 12 – 24 hours

• Expected PCO₂calculatedbyWINTERS’ FORMULA

EXP.PCO₂=1.5 X (ACTUAL HCO₃⁻ )+8 +/- 2 mmHgLimiting value of compensation: PCO₂= 8-10mmHg Quick rule of thumb :PCO₂= last 2 digits of pH

Acid–Base Balance

Disturbances

.

Responses to Metabolic

Acidosis

Metabolic

acidosisSymptoms 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⁻reclamationChloride depletion

Pottasium depletion

ECF volume depletion

Magnesium depletion

CAUSES OF METABOLIC

ALKALOSISI. Exogenous HCO3 −loadsA.Acute alkali administration

B.Milk-alkali syndrome

II. Gastrointestinal origin1. Vomiting

2. Gastric aspiration

3. Congenital chloridorrhea

4. Villous adenoma

III. Renal origin1. Diuretics

2. Posthypercapnic state

3. Hypercalcemia/hypoparathyroidism

4. Recovery from lactic acidosis or ketoacidosis

5. Nonreabsorbable anions including penicillin,

carbenicillin

6. Mg2+ deficiency

7. K+ depletion

Chloride responsive alkalosis

Low urinary chloride concentration(25

meq/L) 1⁰ mineralocorticoidexcess

Severe 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 – 60mmHg

• Hypoventilation not always found due to

Hyperventilation

due to pain

due to pulmonary congestion

due to hypoxemia(PO₂ < 50mmHg)

Acid–Base Balance

Disturbances

.

Metabolic

Alkalosis

Metabolic

AlkalosisDecreased myocardialcontractility

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 -

CAUSESCNS DEPRESSIONDRUGS:Opiates,sedatives,anaesthetics

OBESITY HYPOVENTILATION SYNDROME

STROKE

NEUROMUSCULAR DISORDERS

NEUROLOGIC:MS,POLIO,GBS,TETANUS,BOTULISM, HIGH CORD LESIONS

END PLATE:MG,OP POISONING,AG

TOXICITY

MUSCLE:↓K⁺,↓PO₄,MUSCULARDYSTROPHY

AIRWAY OBSTRUCTION

COPD,ACUTE

CONT

..CHEST WALL RESTRICTION

PLEURAL: Effusions, empyema,pneumothorax,fibrothorax

CHEST WALL: Kyphoscoliosis, scleroderma,ankylosing spondylitis,obesity

SEVERE PULMONARY RESTRICTIVE

DISORDERS

PULMONARY FIBROSIS

PARENCHYMAL INFILTRATION: Pneumonia,

edema

ABNORMAL BLOOD CO₂TRANSPORTDECREASED PERFUSION: HF,cardiac arrest,PE

SEVERE ANEMIA

ACETAZOLAMIDE-CA Inhibition

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 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→↑ICTCO₂NARCOSIS

(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 normalrapidly

• 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. Pain

2. Anxiety, psychosis

3. Fever

4. Cerebrovascular

accident

5. Meningitis,

encephalitis

6. Tumor

7. Trauma

B. Hypoxemia or tissue hypoxia1. High altitude

2. Septicemia

3. Hypotension

4. Severe anemia

C. Drugs or hormones1. Pregnancy, progesterone

2. Salicylates3. Cardiac failure

D. Stimulation of chest

receptors1. Hemothorax

2. Flail chest

3. Cardiac failure4. Pulmonary embolism

E. Miscellaneous1. Septicemia

2. Hepatic failure

3. Mechanical ventilation

4. Heat exposure5. Recovery from metabolicacidosis

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• CN

S: ↑ 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 serumcalcium

Hyponatremia,hypochloremia

Acid Base

DisordersPrimary disorder Compensatory response

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

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 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 andPCO₂

STRONG ION

DIFFERENCE (SID)• STRONG CATIONS – STRONG ANIONS

• Decrease in SID → Acidification ofPLASMA

• Explains – NS induced ACIDOSIS

• ADV: Estimate of H⁺ conc more accuratethan 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

DISORDERDiagnosed by combination of clinicalassessment, 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

YOULIFE IS A

STRUGGLE,

NOT AGAINST

SIN,

NOT AGAINST MONEY

POWER.. BUT AGAINST

HYDROGEN IONS .

H.L.MENCK