DR. NILESH KATE (M.D.)DR. NILESH KATE (M.D.)ASSOCIATE PROFESSORASSOCIATE PROFESSOR

ESIC MEDICAL COLLEGE, GULBARGA.ESIC MEDICAL COLLEGE, GULBARGA.

ACIDACID BASEBASE BALANCEBALANCE

Objectives. Concept of Acid & base. pH and H ion concentration. Handerson-Hasselbalch equation. Mechanisms to maintain acid base balance. Applied aspects.

Saturday, April 18, 2015

ACIDS Acids are the substances which can donate Acids are the substances which can donate H+ ion (proton).H+ ion (proton).

These are hydrogen containing substances These are hydrogen containing substances which can dissociate in soln. to release H+.which can dissociate in soln. to release H+.

Not all hydrogen containing substances are Not all hydrogen containing substances are acids; e.g. Carbohydrate.acids; e.g. Carbohydrate.

Tightly bound hydrogen; not liberated in Tightly bound hydrogen; not liberated in solution.solution.

HClHCl HH++ ++ ClCl--

ACIDSACIDS Types of acids in the body:Types of acids in the body:1. Volatile Acids: 1. Volatile Acids:

Can leave the solution and enter the environment.H2CO3 is the only volatile acid in the body.

2. Non-Volatile Acids (Fixed Acids/Metabolic 2. Non-Volatile Acids (Fixed Acids/Metabolic

Acids):Acids):Acids that do not leave the solution. All other acids in the body.Ex: Pyruvic acid, Lactic acid, Phosphoric acid etc.

H2CO3H2CO3 H2OH2O ++ CO2CO2

ACIDS Physiologically important acids:Physiologically important acids:

Carbonic acid (HCarbonic acid (H22COCO33))Phosphoric acid (HPhosphoric acid (H33POPO44))Pyruvic acid (CPyruvic acid (C33HH44OO33))Lactic acid (CLactic acid (C33HH66OO33))

These acids are products of various These acids are products of various metabolisms in the body.metabolisms in the body.

Dissolved in body fluids.Dissolved in body fluids.

BASE Base is a substance which can accept H+ ion (proton).,e.g. Hydroxyl ion (OH-).

■Physiologically important bases:➢ Bicarbonate (HCO3

- )➢ Biphosphate (HPO4

-2 )

OHOH-- ++ HH++ H2OH2O

Alkali Used synonymously with base.

Molecule formed by combination of an alkaline metal (Na,K,Li) with a highly basic ion.

Ex- NaOH, KOH, NaHPO4

Base portion of these molecules react quickly with H+ to remove these from solution, i.e. alkalis act as typical bases.

NaOHNaOH NaNa+ + + + OHOH--

+ H+ H++ H2OH2O

Acids & Bases can be classified as strong or weak acid/base

Strong acid/base:Strong acid/base: One that dissociates completely in a solution. Ex: HCl, H2SO4, NaOH

Weak acid/base:Weak acid/base: One that dissociates partially in a solution. Ex: H2CO3,

HClHCl HH++ ++ ClCl--

NaOHNaOH NaNa++ ++ OHOH--

H2CO3H2CO3 HH++ ++ HCO3-HCO3-

PH SCALEPH SCALE HH++ concentration in extracellular fluid (ECF) concentration in extracellular fluid (ECF)

Normal blood pH is 7.35 - 7.457.35 - 7.45 pH range compatible with life is 6.8 - 8.06.8 - 8.0

4 X 10 -8 (0.00000004)

pH = log 1 / HH++ concentration

pH = log 1 / HH++ concentrationpH = log 1/ 4 X 10 -8

pH = 7.2

PH SCALEPH SCALEpH = - log [HpH = - log [H++]]

pH = log 1/ [HpH = log 1/ [H++]]

pH is inversely related to HpH is inversely related to H++ concentration. concentration.low pH – indicates high Hlow pH – indicates high H++ concentration. concentration.high pH – indicates low Hhigh pH – indicates low H++ concentration. concentration.

pH = 4 has 10 times more free HpH = 4 has 10 times more free H++ concentration concentration than pH = 5 and 100 times more free Hthan pH = 5 and 100 times more free H++ concentration than pH = 6concentration than pH = 6

pH range from 1-14.pH range from 1-14.pH < 7 – AcidicpH < 7 – AcidicpH > 7 – BasicpH > 7 – Basic

pH = 7 - NeutralpH = 7 - Neutral

PH of the ECF is regulated very precisely

ACIDOSIS ALKALOSISNORMAL

DEATH DEATH

Venous Blood

Arterial Blood

7.3 7.57.46.8 8.0

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EFFECTS OF pH changeEFFECTS OF pH change pH changes have dramatic effects on normal cell

function 1)1) Changes in excitability of nerve and muscle

cells 2)2) Influences enzyme activity 3)3) Influences KK++ levels

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Changes in cell excitabilityChanges in cell excitability pH decrease (more acidic) depresses the central

nervous system Can lead to loss of consciousness

pH increase (more basic) can cause over-excitability Tingling sensations, nervousness, muscle twitches

pH

pH

Excitability

Excitability

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Influences on enzyme activityInfluences on enzyme activity

pH increases or decreases can alter the shape of the enzyme rendering it non-functional

Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell

INFLUENCES ON KINFLUENCES ON K++ LEVELS LEVELS In kidney Na+ is absorbed

in tubules in exchange of K+ or H+ (K+ > H+).

In acidosis more H+ is secreted thus preserving the K+, causing hyperkalemia.

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ACID BASE BALANCEACID BASE BALANCE Maintenance of the pH of body fluids at a level that

allow optimal function. pH maintenance means maintaining [H[H++].]. This involves two important ions which are regulated by This involves two important ions which are regulated by

various chemical & physiological process:various chemical & physiological process:

H+ HCO3-

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■ Chemical processes:Chemical processes:■ The first line of defence to an acid or base load.■ Include the extracellular and intracellular extracellular and intracellular

buffers.buffers.

■ Physiologic processes:Physiologic processes:■ 1. Changes in cellular metabolism.

2. Excretion of volatile acids by the lungslungs

3. Excretion of fixed acids by the kidneyskidneys

ACID BASE BALANCEACID BASE BALANCE

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■ Maintained by Maintained by threethree mechanisms: mechanisms:➢ 1) 1) Chemical BuffersChemical Buffers

♦ React very rapidlyReact very rapidly(less than a second)(less than a second)

➢ 2) 2) Respiratory RegulationRespiratory Regulation♦ Reacts rapidly (seconds to minutes)Reacts rapidly (seconds to minutes)

➢ 3) 3) Renal RegulationRenal Regulation♦ Reacts slowly (minutes to hours)Reacts slowly (minutes to hours)

ACID BASE BALANCEACID BASE BALANCE

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1)1) Buffer SystemsBuffer Systems2) Respiratory Responses

3) Renal Responses4) Intracellular Shifts of Ions

Buffers. Is a solution of weak acid & its salt with a

strong base that prevent change in pH when H+ ions are added or removed from the solution.

Most effective within 1 pH unit of the pK of the buffer.

Depend on absolute concentration of salt & acid.

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REMEMBER……. Buffer cannot remove H+ ions from the body

temporarily reduce free H+ ions

H+ ions have to be ultimately removed by the renal mechanism.

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Henderson-Hasselbalch equation

HA H+ + A-

When acid is added, --- H+ ion conc increases, reaction forced towards right leads to increase in un dissociated molecules.

When base is added ---- reaction shift towards left, more H+ ion released from buffer to combine with base.

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Most Effective Buffer. Henderson-Hasselbalch equation. HA H+ + A-

By the law of mass action, at equilibrium

K = [H+][A-]/ [HA] ----------- K= Dissociation constant of acid.

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Henderson- Hasselbalch equation.

[H+] = K [HA]/[A-] pH = log 1/ [H+] Log 1/[H+] = log 1/K +log [A-]/[HA] pH = pK + log [A-]/[HA] Thus pH= pK Thus most effective buffers in the body are those with pK

close to the pH in which they operate.from this equation it is seen that buffering capacity of buffer system is greatest when amount of anion[A-] and undissociated acid [HA] is same.

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BICARBONATE BUFFER SYSTEM Predominates in extracellular fluid (ECF)

HCO3- + added H+ H2CO3

H+HCOHCO33-

-

HH22COCO33

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BICARBONATE BUFFER SYSTEMBICARBONATE BUFFER SYSTEM Hydrogen ions generated by metabolism or by

ingestion react with bicarbonate base to form more carbonic acid.

HCO3- + H+ H2CO3

HCOHCO33--

HH22COCO33

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BICARBONATE BUFFER SYSTEM Hydrogen ions that are lost (vomiting) causes

carbonic acid to dissociate yielding replacement H+ and bicarbonate.

HH++ HCOHCO33--

HH22COCO33

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BICARBONATE BUFFER SYSTEMBICARBONATE BUFFER SYSTEM This system is most important because the

concentration of both components can be regulated: Carbonic acidCarbonic acid by the respiratory system BicarbonateBicarbonate by the renal system

Loss of HCl

Addition of lactic acid

HH++ HCOHCO33--HH22COCO33HH22OOCOCO22 + ++

Exercise

Vomiting

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Most important in the intracellular system

Na2HPO4 + H+ NaH2PO4 + Na+

PHOSPHATE BUFFER SYSTEM

H+Na2HPO4+

NaH2PO4 Na++

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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM Most important intracellular buffer.Most important intracellular buffer. The most abundant buffer of the body.The most abundant buffer of the body. Behaves as a buffer in both plasma and cellsBehaves as a buffer in both plasma and cells Hemoglobin is by far the most important Hemoglobin is by far the most important

protein buffer.protein buffer.

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PROTEIN BUFFER SYSTEM

-

-

-- - - -

----

----

----------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++++

++

+ ++

OH-

OH-

OH-

OH-OH-

OH-

OH-

OH-

OH-OH-OH-

OH-H+

H+

H+

H+ H+ H+ H+ H+ H+ H+

H+

H+

H+

H+

H+H+H+H+H+H+H+

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PROTEIN BUFFER SYSTEM H+ generated at the tissue level from the dissociation

of H2CO3 produced by the addition of CO2.

Bound H+ to Hb (Hemoglobin) does not contribute to the acidity of blood.

HbHbO2

O2 O2

O2

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PROTEIN BUFFER SYSTEM As As HH++HbHb picks up picks up OO22 from the lungs the from the lungs the HbHb which has a which has a

higher affinity for higher affinity for OO22 releases releases HH++ and picks up and picks up OO22

Liberated Liberated HH++ from from HH22OO combines with combines with HCOHCO33--

HCOHCO33-- HH22COCO33 COCO22 (exhaled)

HbHbO2

O2 O2

H+

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1) Buffer Systems2) Respiratory Responses2) Respiratory Responses

3) Renal Responses4) Intracellular Shifts of Ions

RESPIRATORY REGULATION CO2 +H2O H2CO3 H+ + HCO3

Respiratory regulation is by increasing or decreasing the exhalation of CO2 from the body.

Hyperventilation in response to increased CO2 or H+ (low pH)

Hypoventilation in response to decreased CO2 or H+ (high pH)

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Respiratory center in brain is able to detect blood concentration levels of CO2 and H+

Increases in CO2 and H+ stimulate the respiratory center RR↑

But the effectdiminishes in1 - 2 minutes

CO2CO2

CO2CO2

CO2

CO2

CO2CO2

CO2

RESPIRATORY REGULATION

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1) Buffer Systems2) Respiratory Responses

3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions

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RENAL RESPONSERENAL RESPONSE The kidney compensates for Acid - Base imbalance

within 24 hours and is responsible for long term control.

The kidney in response:The kidney in response: To AcidosisTo Acidosis

Retains bicarbonate ions and eliminates hydrogen ions. Produce new bicarbonate.

To AlkalosisTo Alkalosis Eliminates bicarbonate ions and retains

hydrogen ions.

RENAL RESPONSERENAL RESPONSE Large amount of HCO3

- filtered & H+ secreted by kidneys.

Almost all (99%) HCO3- is absorbed by

combining it with H+. H+ secreted = H+ needed to absorb all HCO3

- + excess H+ formed in body.

If filtered HCOfiltered HCO33-- > secreted H > secreted H++ net loss of base

from blood.

If filtered HCOfiltered HCO33-- < secreted H < secreted H++ net loss of acid

from blood.

Alkalosis ( H↓Alkalosis ( H↓ ++)) absorption of HCO↓ absorption of HCO↓ 33- - HCO HCO33

- - exc. In exc. In urine.urine.

Acidosis ( H↑Acidosis ( H↑ ++)) all HCOall HCO33- - is absorbed & kidneys produce is absorbed & kidneys produce

new HCOnew HCO33--

So kidneys regulate extracellular fluid H+ concentrationSo kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms: through three fundamental mechanisms: (1) secretion of H+, (1) secretion of H+, (2) reabsorption of filtered HCO3-, and(2) reabsorption of filtered HCO3-, and (3) production of new HCO3-.(3) production of new HCO3-.

RENAL RESPONSERENAL RESPONSE

Secretion of H+ occurs in all segments of nephron.

Secreted H+ is buffered with :Secreted H+ is buffered with : HCO3

- in proximal segments resulting in absorption of HCO3-

Na2HPO4 & NH3 in distal segments resulting in production of new HCO3-

RENAL RESPONSERENAL RESPONSE

HCO3- absorption in proximal segment

Production of new HCO3- by phosphate buffer in distal tubule

Combination of H+ with Ammonia buffer

Combination of H+ with Ammonia in collecting tubules

Disorders of Acid-Base Balance Acidosis:Acidosis:

↓ ↓ pH of ECF.pH of ECF. May be d/t acid / base.↑ ↓May be d/t acid / base.↑ ↓

May be:May be: Respiratory AcidosisRespiratory Acidosis

d/t elimination of CO2 by lungs. ( acid)↓ ↑d/t elimination of CO2 by lungs. ( acid)↓ ↑

Metabolic Acidosis:Metabolic Acidosis: d/t loss of HCO3- by the kidneys. ( base)↑ ↓d/t loss of HCO3- by the kidneys. ( base)↑ ↓

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ACIDOSISdecreasedremoval ofCO2 from

lungs

failure of kidneys to

excreteacids

metabolicacid

productionof keto acids

absorption ofmetabolic acidsfrom GI tract

prolongeddiarrhea

accumulationof CO2 in blood

accumulationof acid in blood

excessive lossof NaHCO3 from blood

metabolicacidosis

deepvomiting

from GI tract

kidneydisease

(uremia)

increase inplasma H+

concentration

depression ofnervous system

accumulationof CO2 in blood

accumulationof acid in blood

excessive lossof NaHCO3 from blood

respiratoryacidosis

Disorders of Acid-Base BalanceDisorders of Acid-Base Balance Alkalosis:

↑ ↑ pH of ECF.pH of ECF. May be d/t base / acid.↑ ↓May be d/t base / acid.↑ ↓

May be:May be: Respiratory AlkalosisRespiratory Alkalosis

d/t elimination of CO2 by lungs. ( acid)↑ ↓d/t elimination of CO2 by lungs. ( acid)↑ ↓

Metabolic Alkalosis:Metabolic Alkalosis: d/t loss of HCO3- by the kidneys. ( base)↓ ↑d/t loss of HCO3- by the kidneys. ( base)↓ ↑

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ALKALOSISALKALOSIS

respiratoryalkalosis

anxiety overdose of certain

drugs

high altitudes

prolongedvomiting

ingestion of excessive

alkaline drugs

excessaldosterone

hyperventilationloss of CO2 and

H2CO2 from blood

loss of acid accumulationof base

metabolicalkalosis

decreasein plasma H+

concentration

overexcitabilityof nervous

system

hyperventilationloss of CO2 and

H2CO2 from blood

loss of acid accumulationof base

Diagnosing Acid-Base imbalanceDiagnosing Acid-Base imbalance Remember 3 important values:Remember 3 important values:

pH = 7.4pH = 7.4

pCO2 = 40 mm HgpCO2 = 40 mm Hg

HCO3- = 24 mmol/lHCO3- = 24 mmol/l

ACID BASE NORMOGRAM

Today's thought.

Saturday, April 18, 2015