Transcript CO 2 CO 2

Acid and Base Balance
Zhihong Li（李志红）
Department of Biochemistry
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The Body and pH
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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
CO2
proteins.
Volatile acid
H2CO3
CO2+ H2O
CO2
CO2
(H+ 15 –20 mol /d)
Fixed acid
H2SO4 H3PO4
Uric acid
Lactic acid
Ketone body
(H+ < 0.05 –0.10 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
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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
H2CO3 / HCO3-
in Plasma
in RBC
35%
18%
HHb / HbHPro / Pro-
35%
7%
H2PO4- / HPO42Total
5%
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
pH=pKa+lg
H2CO3
H+ + HCO3-
[HCO3－]
[H2CO3]
= 6.1+ lg
= 6.1+ lg
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1.2
20
1
= 6.1+1.3 = 7.4
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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 + HPO4210
Protein Buffers
• Include plasma proteins and hemoglobin
• Carboxyl group gives up H+
• Amino Group accepts H+
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2. Respiratory mechanisms
CO2
CO2
• 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
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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
HCO3－
alkalosis
metabolic respiretory metabolic respiretory
[HCO3-]↓
PaCO2↑
[HCO3-]↑
PaCO2↓
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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
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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 ↓
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