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Acid and Base Balance

Zhihong Li（李志红）Department of Biochemistry

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The Body and pH

• Homeostasis of pH is tightly controlled

• Extracellular fluid = 7.4

• Blood = 7.35 – 7.45

• < 7.35: Acidosis (acidemia)

• > 7.45: Alkalosis (alkalemia)

• < 6.8 or > 8.0: death occurs

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The body produces more acids than bases

• Acids take in with foods.

• Cellular metabolism produces CO2.

• Acids produced by metabolism of lipids and proteins.

Volatile acid H2CO3 CO2+ H2O

CO2

CO2 CO2

Fixed acidH2SO4 H3PO4

Uric acidLactic acid

Ketone body(H+ < 0.05 –0.10 mol /d)

(H+ 15 –20 mol /d)

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Maintenance of blood pH

• Three lines of defense to regulate the

body’s acid-base balance

– Blood buffers

– Respiratory mechanism

– Renal mechanism

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Buffer systems

• Take up H+ or release H+ as conditions change

• Buffer pairs – weak acid and a base

• Exchange a strong acid or base for a weak one

• Results in a much smaller pH change

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Principal buffers in blood

in Plasma in RBC

H2CO3 / HCO3- 35% 18%

HHb / Hb- 35%

HPro / Pro- 7%

H2PO4- / HPO4

2- 5%

Total 42% 58%

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Bicarbonate buffer• Predominant buffer system

• Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3)

• HCO3- : H2CO3: Maintain a 20:1 ratio

= 6.1+1.3 = 7.4

pH=pKa+lgpH=pKa+lg[HCO[HCO33

－－ ]]

[H[H22COCO33]]

= 6.1+ lg= 6.1+ lg2424

1.21.2

= 6.1+ lg= 6.1+ lg2020

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H2CO3 H+ + HCO3-

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Bicarbonate buffer

• HCl + NaHCO3 ↔ H2CO3 + NaCl

• NaOH + H2CO3 ↔ NaHCO3 + H2O

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Phosphate buffer

• Major intracellular buffer

• NaH2PO4-Na2HPO4

• H+ + HPO42- ↔ H2PO4

-

• OH- + H2PO4- ↔ H2O + HPO4

2-

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Protein Buffers

• Include plasma proteins and hemoglobin

• Carboxyl group gives up H+

• Amino Group accepts H+

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2. Respiratory mechanisms

• Exhalation of CO2

• Rapid, powerful, but only works with volatile acids

• H+ + HCO3- ↔ H2CO3 ↔ CO2 + H20

• Doesn’t affect fixed acids like lactic acid

• Body pH can be adjusted by changing rate and depth of breathing

CO2 CO2

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3. Kidney excretion

• Most effective regulator of pH

• The pH of urine is normally acidic (~6.0)– H+ ions generated in the body are eliminated by

acidified urine.

• Can eliminate large amounts of acid (→H+)

• Reabsorption of bicarbonate (HCO3-) (←HCO3

-)

• Excretion of ammonium ions(NH4+) (→NH4

+)

• If kidneys fail, pH balance fails

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Rates of correction

• Buffers function: almost instantaneously

• Respiratory mechanisms: take several

minutes to hours

• Renal mechanisms: may take several

hours to days

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Acid-Base Imbalances

• pH< 7.35: acidosis

• pH > 7.45: alkalosis

• The body response to acid-base imbalance is

called compensation

– The body gears up its homeostatic mechanism and

makes every attempt to restore the pH to normal level.

– May be complete if brought back within normal limits

– Partial compensation if range is still outside norms.

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Acid-Base Imbalances

• Acidosis- a decline in blood pH ↓– Metabolic acidosis: due to a decrease in

bicarbonate. ↓– Respiratory acidosis: due to an increase in

carbonic acid. ↑

• Alkalosis- a rise in blood pH ↑– Metabolic alkalosis: due to an increase in

bicarbonate.↑– Respiratory alkalosis : due to a decrease in

carbonic acid. ↓

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pH

acidosis alkalosis

respiretory

[HCO3-]↓ [HCO3

-]↑PaCO2↑ PaCO2↓

metabolicmetabolic respiretory

HCOHCO33 －－

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Compensation

• If underlying problem is metabolic,

hyperventilation or hypoventilation can

help: respiratory compensation.

• If problem is respiratory, renal

mechanisms can bring about metabolic

compensation.

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Metabolic Acidosis

• Bicarbonate deficit (↓) - blood concentrations of bicarb drop below 22mEq/L (milliequivalents / liter)

• Causes:– Loss of bicarbonate through diarrhea or renal

dysfunction– Accumulation of acids (lactic acid or ketones)– Failure of kidneys to excrete H+

• Commonly seen in severe uncontrolled DM (ketoacidosis).

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Compensation for Metabolic Acidosis

• Hyperventilation: increased ventilation

• Renal excretion of H+ if possible

• K+ exchanges with excess H+ in ECF

– H+ into cells, K+ out of cells

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Respiratory Acidosis

• Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg.

• Hypercapnia – high levels of CO2 in blood• Causes:

– Depression of respiratory center in brain that controls breathing rate – drugs or head trauma

– Paralysis of respiratory or chest muscles– Emphysema

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Compensation for Respiratory Acidosis

• Kidneys eliminate hydrogen ion (H+ and NH4

+) and retain bicarbonate ion

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Metabolic Alkalosis

• Bicarbonate excess↑ - concentration in blood is greater than 26 mEq/L

• Causes:– Excess vomiting = loss of stomach acid– Excessive use of alkaline drugs– Certain diuretics– Endocrine disorders: aldosterone ↑– Heavy ingestion of antacids

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Compensation for Metabolic Alkalosis

• Hypoventilation to retain CO2 (hence H2CO3↑)

• Renal excretes more HCO3-, retain H+.

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Respiratory Alkalosis

• Carbonic acid deficit↓

• pCO2 less than 35 mm Hg (hypocapnea)

• Most common acid-base imbalance

• Primary cause is hyperventilation– Hysteria, hypoxia, raised intracranial

pressure, excessive artificial ventilation and the action of certain drugs (salicylate) that stimulate respiratory centre.

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Compensation of Respiratory Alkalosis

• Kidneys conserve hydrogen ion

• Excrete bicarbonate ion

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Mixed acid-base disorders

• Sometimes, the patient may have two or

more acid-base disturbances occurring

simultaneously.

• In such instances, both HCO3- and H2CO3

are altered.

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Points• Blood = 7.35 – 7.45; • < 7.35: Acidosis, > 7.45: Alkalosis • Three lines of defense to regulate the body’s acid-base

balance – Blood buffers: Bicarbonate buffer, Phosphate buffer, Protein

Buffers– Respiratory mechanisms: Exhalation of CO2

– Renal mechanism: eliminate acid, Reabsorption of HCO3-

• Acidosis- blood pH ↓(Causes, Compensation)– Metabolic acidosis: bicarbonate ↓– Respiratory acidosis: carbonic acid ↑

• Alkalosis- blood pH ↑ (Causes, Compensation)– Metabolic alkalosis: bicarbonate↑– Respiratory alkalosis : carbonic acid ↓