BALANCE

By: Dr. MITESH SINHA

ACID

BASE

ACIDS AND Bases

H⁺ : Single free proton released from H atom

3

C C C C C C

H H H H H H

HHHHHH

What is an Acid?Particle or molecule that can release

H+ in solution.

HCl H⁺+ Cl⁻H₂CO₃ H⁺+ HCO₃⁻

What is base? Ion or molecule that can accept a H⁺.

HCO3⁻ + H⁺ H2CO3HPO4⁻⁻ + H⁺ H2PO4⁻

What is alkali?It is often used synonymously with base,

It is formed by combination of one or more Alkaline metals Na, K, Li…with highly basic ion such as OH⁻

Base part of these molecule reacts quickly with H⁺ to remove them from solution , so they are typical bases.

What is Alkalosis?It refers to excess removal of H⁺ from

body fluids.

What is Acidosis?It is excess addition of H⁺ into body

fluids.

Acids Bases

HCl very very Cl⁻H3O⁺ strong weak H2OH2CO3 rather rather HCO3⁻H2 PO4⁻ weak strong HPO4⁻HPr (n-1)⁻ Protinate n⁻NH4⁺ very very NH3H2O weak strong OH⁻

STRONG AND WEAK ACIDS AND BASES

H+ CONCENTRATION IS PRECICELY REGULATEDH⁺ is essential because activities of

almost all enzyme systems in body are influenced by H⁺ concentration, so changes in H⁺ concentration alter virtually all cell and body functions.

H⁺ concentration of body fluids kept at low level compared with other ions.

Example:

Na⁺ → 142 mEq/L in ECF H⁺ → 0.00004 mEq/L in ECFWhich is 3.5 million times as great as H⁺.Thus precision with which H⁺ is regulated ,

emphasizes its importance to various cell function.

Why pH?Because H⁺ number is low and because these

small number are cumbersome, it is customary to express H⁺ concentration on a logarithm scale using pH units.

From this formula,

pH = log 1 = -log[H⁺] [H⁺]

pH inversely related to H⁺ concentration,

Low pH High H⁺ concentrationHigh pH Low H⁺ concentration

pH and H⁺ concentration of Body fluids

H⁺ conc.(mEq/L) pH

ECF

Arterial blood 4.0 x 10⁻⁵ 7.40

Venous blood 4.5 x 10⁻⁵ 7.35

Interstitial blood 4.5 x 10⁻⁵ 7.35

ICF 1 x 10⁻³ to 4.0 x 10⁻⁵ 6.0 to 7.4

Urine 3 x 10¯² to 1.0 x 10⁻⁵ 4.5 to 8.0

Gastric HCl 160 0.8

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pH SCALE

Mechanisms of regulation of pH(a) Front line defenses

1) Chemical Buffers React very rapidly

(less than a second)2) Respiratory Regulation

Reacts rapidly (seconds to minutes)

(b) Second line defense

3) Renal Regulation Reacts slowly (minutes to hours)

1)Buffer Systems2) Respiratory Responses3) Renal Responses

BUFFERSA buffer is a combination of

chemicals in solution that resists any significant change in pH

Able to bind or release free H+ ionsBuffering systems provide an

immediate response to fluctuations in pH

TYPES OF chemical BUFFERS Mainly three types of buffers are active in the body:

1) Bicarbonate Buffer System2) Phosphate Buffer System3) Protein Buffer System

Bicarbonate buffer systemIt consist of two ingredients1)H2CO3 (weak acid)2)NaHCO3 (bicarbonate salt)

H₂CO₃ CO2 + H2O H2CO3 (Lung alveoli) H2CO3 H⁺ + HCO3⁻ (kidney

tubules)

NaHCO3 NaHCO3 Na⁺ + HCO3⁻When put together H2O + CO2 H2CO3 H⁺ + HCO3¯ + Na⁺

CA

CA

When strong acid like HCl is added to bicarbonate buffer solution, H+ released from HCl

(HCl H⁺ + Cl¯) buffered by H₂CO₃

H⁺ + HCO₃⁻ H₂CO₃ CO₂ + H₂O

Excess of CO₂ stimulate respiration, which eliminate CO₂ from ECF.

Opposite when strong base (NaOH) added to Bicarbonate buffer solution

NaOH + H₂CO₃ NaHCO₃ + H2O (strong base) (weak base) Here, H₂CO₃ is decreased and so more CO2 combine

with H₂O to form H₂CO₃

CO2 + H₂O H₂CO₃ HCO₃⁻ + H+ + NaOH +Na⁺Thus, 1) strong base replaced by weak base 2) CO2, inhibit respiration and CO2 expiration 3) HCO₃¯ excreted by kidney

Quantitative Dynamics Of Bicarbonate Buffer SystemAll acids including H2CO3, are ionised to some

extent .From mass balance consideration conc. of H⁺ and

HCO3¯ are proportional to conc. Of H2CO3.H2CO3 H⁺ + HCO3¯For any acid, conc. Of acid relative to its

dissociation ions is defined by Dissociation Constant K’

K’ = H⁺ x HCO3⁻ H2CO3 ______________________(1) H⁺ = K’ x H2CO3 HCO3⁻ ________________________(2)

The conc. of H2CO3 cant be measured because it rapidly dissociated into CO2 and H2O or H⁺ and HCO3⁻,

However CO2 dissolved in blood is directly proportional to amount of undissociated H2CO3,

So equation 2 rewritten as H⁺ = K x CO2 HCO3⁻

______________________(3)

Here CO2 is total amount dissolved in solution while in most laboratory blood CO2 tension is measured

But amount of CO2 is linear function of solubility and solubility of CO2 in blood is 0.03 mmols /mmHg at body temperature, so 0.03 mmols ofH2CO3 is present in blood for each millimeter of mercury PCO2 measured. Now

H⁺ = K x (0.03 x PCO2) HCO3⁻

_____________________(4)

Handerson-Hasselbalch Equation-log H⁺ = -log pK – log (0.03 x Pco2)

HCO3⁻ ______(5)

Therefore, pH=pK - log (0.03 x Pco2)

HCO3⁻ _____(6)pH = pK + log HCO3⁻ (0.03 x Pco2) ______________(7)For bicarbonate buffer system pK is 6.1, so pH = 6.1 + log HCO3⁻ (0.03 x Pco2)

_______________(8)

Bicarbonate titration curve

2.Phosphate buffer system The main elements of the phosphate buffer system are

H2PO4⁻and HPO4²⁻. Na2HPO4 + H+ NaH2PO4

+ Na+

The phosphate buffer system has a pK of 6.8, whichis not far from the normal pH of 7.4 in the body fluids;this allows the system to operate near its maximumbuffering power. However, its concentration in theextracellular fluid is low, only about 8 per cent of theconcentration of the bicarbonate buffer.

In contrast to its rather insignificant role as an extracellular

buffer, the phosphate buffer is especiallyimportant in the tubular fluids of the kidneys, for

tworeasons: (1) phosphate usually becomes greatly

concentrated in the tubules, thereby increasing the buffering power of the phosphate system, (2) the tubular fluid usually has a considerably

lower pH than the extracellular fluid does, bringing the operating range of the phosphate buffer closer to the pK (6.8) of the system.

And most imp. Intra cellular buffer system..

3. Protein Buffer System

They are most plentiful buffers as maximum intra cellular

concentration .In acidic medium: Protein acts as a base, NH2 group takes up H⁺ ions from medium forming NH3 ⁺, and protein becomes +vely charged.In alkaline medium: Protein acts as an acid,Acidic COOH group dissociates giving H⁺ and COO⁻ , H⁺ combines OH ⁻ to produce a molecule of water , proteins become –vely charged.

Major protein are 1)Plasma proteins 2)Haemoglobin and other intra cellular

proteinsBut Haemoglobin is far better buffer compared

withother proteins, 1gram of plasma protein binds 0.110 mEq of

H⁺ while 1 gram of Hb binds 0.183 mEq of H⁺

Hb as buffering agent With the range of 7.0 to 7.8 most of the

physiological buffering action of Hb is due to “imidazole” group of amino acid “histidine”, which remain dissociated in acidic medium and conjugate in base forms. Oxygenated Hb is a stronger acid than deoxygenated Hb and it donates H⁺ ions into the medium.

Deoxygenated Hb acts as base and it take H⁺ ions from the medium.

H⁺ + Hb HbH

Respiratory Mechanisms in Regulation of Acid-Base Operates through regulation of ECF CO2

concentration by lungsIt is 1-2 times as great as the buffering power

of all other chemical buffers in ECF.

CO2 : ↑PCO2 → ↑Ventilation →Eliminates CO2 →

Reduces [H⁺] & ↑pH

↓PCO2 → ↓Ventilation → ↑CO2 → ↑ [H⁺] & ↓ pH

Doubling the ventilation → ↑pH(about 0.23 units) i.e 7.4 → 7.63

¼ of normal ventilation → ↓ pH(about 0.45 units) i.e 7.4 → 6.95

Reason: ↑pH→↓PO2 (by decrease vent.)→Stimulate Vent. Therefore, respiratory compensation is not effective!

So Respiratory Mechanism has effectiveness between 50-75% & is 1-2 times as great as the buffering power of all other chemical buffers in ECF.

Renal Mechanisms in Regulation of Acid-BaseKidneys operate through;

i. Active secretion of H⁺ ions ii. H⁺ ion buffering within tubular lumen: a. buffering with HCO3¯;

Result in only reabsorption of filtered HCO3¯ ions b. buffering with HPO4¯ orNH3 ; Result in net H⁺ ion excretion & generation of

new HCO3¯ ionsOutcome: by excreting acidic or basic urine

Process is achieved by three buffer systems;1. Carbonic Acid buffer system2. Ammonia buffer system3. Phosphate buffer system• Kidney’s acid-base regulatory potency is that it has ability to return the pH almost exactly to normal.

Reabsorption of bicarbonate ionsDaily Reabsorption of HCO3 ¯ : 85% HCO3¯ reabsorption (H⁺ Secretion)

occurs in PCT 10% HCO3¯ reabsorption (H⁺ secretion)

occurs in thick ascending LOH 4.9% (approx 5%) reabsorption (H⁺ secretion)

occurs in DCT & CT.

For each HCO3¯ reabsorbed, there must be one H+ ion secreted.• Secretion of H+ : by two mechanisms;1) Via Na⁺-H ⁺ antiporter (major) in proximal tubule2)Via H ⁺ -ATPase (proton pump) in distal tubule

The net effect is the reabsorption of one HCO3¯ and one Na⁺ for each H⁺ secretion in tubules.

However, this secreted H⁺ is consumed in reaction with filtered HCO3¯

H⁺ secretiona) Secondary active transport in Early Tubular segment( H⁺ –Na⁺ ATPase)

b) Primary active transport in intercalated cell of distal tubule(H⁺ ATPase)

Phosphate Buffer System in Renal Tubules •Consists of HPO4⁻² & H2PO4 ⁻ (Both are

poorly reabsorbed in renal tubules, get concentrated by reabsorption of H2O)

• Under normal conditions 30-40 mEq/day filtered phosphate is available for buffering H⁺.

• Operates when secreted [H+] is in excess than filtered [HCO-3]

Ammonia Buffer System Special Buffer System in kidney

• Consists of NH3 & NH4⁺• More important ‘quantitatively’ than phosphate buffer system.

Excess H⁺ excretion induce Glutamine metabolism and produce new Bicarbonate ions

Ammonia Buffer System in Renal Tubules

• Under normal conditions: Ammonia buffer system accounts for50% elimination of excess H⁺ ions & 50% new HCO3⁻ are generated by kidneys.• In Chronic Acidosis: Rate of NH4⁺ excretion increases as muchas 500 mEq/day by enhancing glutamine metabolism in kidneys

Acid Base Imbalance Can arise due to:

1. Respiratory Dysfunction2. Metabolic DysfunctionChanges in [H⁺] are reflected by changes in Ratio of [HCO3⁻] to [CO2]• Normal Ratio = 20/1  [HCO3⁻] = 24 mM/L,

[CO2]= 1.2 ml/LRatio < 20/1 = Acidosis : ↓ pH less than 7.35

Ratio > 20/1 = Alkalosis: ↑ pH more than 7.45

• Change in blood pH (Acidosis or Alkalosis) are counteracted by physiological responses of Buffer Systems (Lungs + kidneys) called compensation.

• Altered blood pH of ‘metabolic origin’ is helped by ‘respiratory compensation’ (Change in PCO2)

• Altered blood pH of ‘respiratory origin’ is helped by ‘renal compensation’ (change in [HCO-3])

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Acidosis and alkalosis are not diseases but rather are the results of a wide variety of disorders

The presence of acidosis or alkalosis provides

an important clue to physicians that a seriousmetabolic problem exists.

Difference between metabolic and respiratory acidosisMETABOLIC ACIDOSIS

RESPIRATORY ACIDOSIS

1. Primary HCO3- deficit2.HCO3⁻ = 20 = pH H2CO3 1

1.Primary carbonic acid excess

2.HCO3⁻ = 20 = pH H2CO3 1 .

3. Compensatory Mechanisms:(a)I˙-- Respiratory – low pH

stimulates respi centre(b)II˙-- Renal –• H⁺ -Na⁺ exchange

increase• HCO3⁻ reabsorption

increase• NH3 formation increase(c) Urinary findings: pH-acidic increased Excretion of NH4Cl and

NaH2PO4 in titrable acidity

3. Compensatory Mechanisms:(a) I˙-- Renal: Most important increase in H+:Na+ exchangeMore HCO3- reabsorptionIncrease NH3 formation(b) II˙ -- respiratory Low pH and high CO2 induces

ventilation But CO2 elimination is partial

due to lung pathology or resp. centre disorder

(c)Urinary findings: pH-acidic increased Excretion of NH4Cl and

NaH2PO4 in titrable acidity

4. (a) In uncompensated phase:

Disproportionate decrease in HCO3-

[H2CO3] pCO2 Total CO2Ratio (b) In fully compensated

phase:Total CO2 low , but

decrease in [HCO3-] and [ H2CO3] is proportionate and ratio 20:1 and pH is maintained.

4. (a) In uncompensated phase:

Disproportionate increase in [H2CO3]

HCO3- pCO2 Total CO2 Ratio (b) In fully compensated

phase:Total CO2 high but

increase in [HCO3-] and [ H2CO3] is proportionate and ratio 20:1 and pH is maintained

5. Causes: 1.Abnormal increase in

anions other than HCO3⁻(acid gain )

Endogenous production• Diabetic acidosis• Starvation• High fever• Violent exercise(L.A)• Lactic acidosis due to

shock and hemorrhageIngestion of acidifying

saltsRenal insufficiency:

retention of acids2. Abnormal loss of

HCO3⁻ e.g. severe diarrhoea, fistulas

5. Causes1.Conditions in which there isdepression/suppression of Respiration Damage to C.N.S Brain damage(trauma,

inflammation , compression) Drug poisoning like morphine or

barbiturates Excessive anesthesia Bulbar palsy Loss of ventilatory functions due to

tension cyst, tension pneumothrax, pulmonary tumours , emphysema

Effects of pain- pleurisy2.Impaired diffusion of CO2 across

alveolar MembraneEmphysema, pneumonia, pulmonary

fibrosis ,etc.3. Obstruction to escape of CO2

from alveoli: 4.pulmonary blood flow

insufficiency- congenital heart disease

Metabolic alkalosis and respiratory alkalosisMetabolic alkalosis Respiratory alkalosis

1. Primary HCO3- excess2.B.HCO3- = 20 = pH H2CO3 1

1. Primary H2CO3 deficit2.HCO3- = 20 = pH H2CO3 1

3.Compensatory mechanisms(a) Primary: Respiratory

depression of RC and hypoventilation leading to retention of CO2.

(b) Secondary: Renal H⁺-Na⁺ exchange NH3 formation HCO3⁻ reabsorption K ⁺ excretion Cl⁻ retention(c) Urinary findings: pH of urine- alkaline NH3 decreased Titrabile acidity decresed

3. Compensatory mechanisms(a) Primary: Renal Decreased H⁺-Na⁺ exchange Decresed excretion of acid

decreased Increased excretion of

HCO3⁻ Decreased NH3⁻ K⁺ excretion Cl⁻ retention(b) secondary: respiratory High pH and low pCO2

produces hypoventilation and increase in H2CO3.

(c) Urinary findings: pH of urine: alkaline decreased NH3 Decresed titrable acids

4. (a) In uncompensated phase:

Disproportionate increase in HCO3⁻

[H2CO3] or N pCO2 Total CO2 Ratio (b) In fully compensated

phase:Total CO2 high, but

increase in [HCO3⁻] and [ H2CO3] is proportionate and ratio 20:1 and pH is maintained.

4. (a) In uncompensated phase:

Disproportionate decrease in H2CO3

[HCO3⁻] or N pCO2 Total CO2Ratio (b) In fully compensated

phase:Total CO2 low , but

decrease in [HCO3⁻] and [ H2CO3] is proportionate and ratio 20:1 and pH is maintained.

5. Other findings:Low ionic Ca⁺

leading to tetany.K⁺ depletion:

hypokalemiaKetosis and

ketonuria may develop

Kidney damage, degenerative changes in tubules leading to N2 retention and oliguria.

5. Other findings:Low ionic Ca⁺

leading to tetany.K⁺ depletion:

hypokalemiaKetosis and

ketonuria may develop

Kidney damage, degenerative changes in tubules leading to N2 retention and oliguria

6. Excessive loss of HCl -Protracted gastric

lavage -Pyloric obstruction -High intestinal

obstruction -PylorospasmAlkali ingestion Excessive loss of K+X-ray therapy, UV

radiation

6.Stimulation of

respiratory centre -CNS disease:

meningitis, encephalitis etc.

-Salicylate poisoning -HyperpyrexiaOther causes -Hysteria -Apprehensive blood

donors -High altitude ascending -Judicious use of

respirator

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pH changes have dramatic effects on

normal cell function1) Changes in excitability of nerve and

muscle cells2) Influences enzyme activity3) Influences K+ levels

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Changes in nerve cell exitabilitypH decrease (more acidic)

depresses the central nervous systemCan lead to loss of consciousness

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

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Influence on enzyme activitypH 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

Effect on K⁺ ionsNormally for reabsorption of Na⁺ takes place

in exchange of H⁺ or K⁺ in renal tubules.Acidosis causes excess H⁺ compared to K⁺ so

less K⁺ is secreted in exchange of Na⁺, leads to hyper kaelemia, causes cardiac arrhythmias and other dysfunction.

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ACID – BASE DISORDERSClinical State Acid-Base

Disorder Pulmonary Embolus Respiratory Alkalosis

Cirrhosis Respiratory Alkalosis

Pregnancy Respiratory Alkalosis

Diuretic Use Metabolic Alkalosis

Vomiting Metabolic Alkalosis

Chronic Obstructive Pulmonary Disease Respiratory Acidosis

Shock Metabolic Acidosis

Severe Diarrhea Metabolic Acidosis

Renal Failure Metabolic Acidosis

Sepsis (Bloodstream Infection) Respiratory Alkalosis,Metabolic Acidosis

Anion GapThe “anion gap” (which is only a diagnosticconcept) is the difference between unmeasured

anionsand unmeasured cations, and is estimated as

Plasma anion gap = [Na⁺] – [HCO3⁻] – [Cl⁻] = 144 – 24 – 108 = 10 mEq/L

The plasma anion gap is used mainly in diagnosing

different causes of metabolic acidosis. In metabolic acidosis,the plasma HCO3– is

reduced,if it is compensated by increase in Cl¯ there is no anion gap called Hyperchloremic acidosis, and

If not, other unmeasured anions increase to maintain elecrical neutrality leads to Normochloremic acidosis.

Increased Anion Gap Normal Anion Gap Acidosis Acidosis(Normochloremic) (Hyperchloremic) Diabetes mellitus Diarrhea Lactic acidosis Renal tubular

acidosis Chronic renal failure Carbonic anhydrase

inhibitor

Aspirin (acetylsalicylic acid) Addison’s disease poisoning Methanol poisoning Ethylene glycol poisoning Starvation

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Normo gram

Normal

TREATMENT OF ACIDOSIS AND ALKALOSISThe best treatment of acid base imbalance is

correction of underlying condition caused abnormality.

But in case of impaired lung function or chronic kidney failure various agents used to neutralise excess acid or base in ECF.

For acidosis, sod. Bicarbonate, sod. Lactate, sod gluconate is used, as they metabolise in body to give bicarbonate ions.

For alkalosis, ammonium chloride administered by mouth and metabolised to urea, and during this process it gives HCl.

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