Biochemistry of acidobasic regulations Alice Skoumalová.

Biochemistry of acidobasic regulations

Alice Skoumalová

Body water compartments:

Derived values:

AG (anion gap)

(Na+ + K+) - (Cl- + HCO3-)

14-18 mmol/l

SID (strong ion difference)

(Na+ + K+) – Cl-

42 mmol/l

Diagram showing chemical constituents of the three fluid compartmens:

pHlemon 2,3orange 3,7

sceletal muscle c. 6,9 prostatic c. 4,5erythrocytes 7,3trombocytes 7,0osteoblasts 8,5

blood 7,36 – 7,44gastric juice 1,2 – 3pancreat. juice 7,5 – 8bile 6,9 – 7,7

urine 4,8 - 8

Acids in the blood:

Buffer The Henderson-Hasselbalch equation

Titration curve for acetic acid

Equivalents of OH- added

Body buffers:

Blood ISF ICF

HCO3-/H2CO3+ CO2 64% HCO3

- HCO3-

hemoglobin 29% - -

proteins 6%

proteins proteins

HPO42-/H2PO4

- 1% phosphates phosphates

Plasma:

mixed buffer system

Buffer pK concentration

HCO3/CO2 6,1 24 mmol/l

HPO42-/H2PO4

- 6,8 1 mmol/l

Proteins

histidine

N-term. amino groups

4-12

5,6 – 7,0

7,6 – 8,4

15 mmol/l

Major physiological buffers:

The bicarbonate buffer system:

CO2 + H2O H2CO3 H+ + HCO3-

erythrocytes (carbonic anhydrase)

in the body – an open system

The Henderson-Hasselbalch equation for the bicarbonate buffer system:

The pKa of carbonic acid – 3,8

But: carbonic acid is replenished from CO2 in body fluids and air (the concentration of dissolved CO2 is 400 times greater than that of carbonic acid)

dissolved CO2 is in equilibrium with the CO2 in the alveoli (the availability of CO2 - breathing)

the pKa combines the hydratation constant of CO2 with the chemical pKa

- a modified version of the H.-H. equation:

s - a conversion factor (0,23 in kPa

0,03 in Torr)

Phosphate buffer:

intracellular fluids (0,1M)

Protein buffer:

intracellular fluids (and also extracellular)

Hemoglobin buffer:

in erythrocytes

+ Bohr effect

Co-operation of the body buffers:

Buffers in an organism

Carbon dioxide transport:

CO2 in the blood:

1. as HCO3- (ionization of H2CO3) 75-85 %

2. as carbamino groups (CO2 reacts with amino groups of proteins) 10-15 %

3. dissolved CO2 5-12 %

Partial pressures air-inspiration air-expiration arterial blood venous blood

pO2 (kPa) 21 15,3 12 – 13,3 4,6 - 6pCO2 (kPa) 0,03 4,4 4,6 – 6 5,3 – 6,6

CO2 + H2O H2CO3 H+ + HCO3-

erythrocytes (carbonate dehydratase)

O2 and CO2 transport:

Bohr effect (the increase in acidity of hemoglobin as it binds O2, releases H+)

Isohydric carriage of CO2 (Hb‘s ability to take up H+ with no change in pH through Bohr effect)

Chloride shift (the exchange of Cl- and HCO3- between the plasma and the erythrocyte)

Structure of a nephron:

Urine pH 4,8 – 8

(most acids must be in some form other than H+)

60 mmol H+ / day

Urine buffers: phoshate

NH3

The physiological levels of the metab. acids:

lactate – 0,6-2,4 mmol/l

ketone bodies – 3-20 mg/l (0,2mmol/l)

Possibilities of H+ excretion: 1. Reaction with HCO3- (reabsorption of NaHCO3)

2. Reaction with HPO42- (titratable acidity of the urine)

3. Reaction with NH3

The kidney in acid-base balance:

The liver in acid-base balance:

In acidosis: induction of the glutamine synthesis and renal glutaminase (increased excretion of NH4

+)

In alkalosis: induction of the urea synthesis, excretion of HCO3-

The major indicators of acid-base imbalance (arterial blood):

Measured: pH = 7,4 ± 0,04 [H+] = 40 nmol/l

pCO2 = 5,3 ± 0,5 kPa = 40 torr = 1,2 mmol/l

Hb, pO2

Calculated: [HCO3-] = 24 ± 3 mmol/l

BE (base excess) = 0 ± 2,5 mmol/l (the amount of acid that would have to be added

to the blood to titrate it to pH 7,4 at a pCO2 of 5,3 kPa at 37 °C)

NBB (buffer base) (the concentration of all bases in the blood at the

standard conditions)

plasma 42 ± 3 mmol/lblood 48 ± 3 mmol/l

AG (anion gap) = 14-18 mmol/l AG = [Na+] + [K+] - [Cl-] - [HCO3-]

acute stage x compensated

four main disorders x mixed

Classification of the acid-base disorders:

acidemia x acidosis

alkalemia x alkalosis

Acidosis: a process leading to the accumulation of H+ in the body

Alkalosis: a process leading to a decrease in H+ concentration in the body

Two components of acid-base balance: respiratory, metabolic

Correction of the acid-base disorders:

Buffer reactions

Compensations - processes in which one system compensates the alteration of the other one

Corrections

The maintenance of pH:

Diagram of Henderson-Hasselbalch equation showing compensations for acid-base disorders:

Metabolic acidosis (MAc):

1. Increased production of H+: -lactasidosis (hypoxia, intensive muscular work, ethanol)

-ketoacidosis (starvation, diabetes)

-acid retention (renal failure)

2. Exogenous intake of H+: - methanol, ethylene glycol intoxication, salicylate poisoning

3. Loss of HCO3-: -diarrhoea, burns, renal tubular disorders, diuretics

4. Relative dilution of HCO3-: -excessive infusion of isotonic solutions !

physiological acute compensation

-lungs

-hyperventilation

[HCO3-] 24 mmol/l ↓

pCO2 5,3 kPa N ↓

[HCO3-]/[H2CO3+CO2] 20 : 1 < 20 : 1 ≤ 20 : 1

pH 7,34 – 7,44 < 7,34 ≤ 7,4

Metabolic alkalosis

1. Loss of H+: - vomiting, gastric lavage

2. Input of HCO3-: - bicarbonate overdosing

3. Loss of Cl- and K+: - diuretics

physiological acute compensation

-lungs

-hypoventilation

[HCO3-] 24 mmol/l

pCO2 5,3 kPa N

[HCO3-]/[H2CO3+CO2] 20 : 1 > 20 : 1 ≥ 20 : 1

pH 7,34 – 7,44 > 7,44 ≥ 7,4

Respiratory acidosisHypoventilation: - depression of the respiratory center (opiates, sedatives, narcotics, CO2)

- failures -ventilation, diffusion, perfusion (respiratory diseases)

-gass transport (anemia, circulatory failure, CO intoxication)

-gass exchange between the blood and tissues (cyanide intoxication)

-neuromuscular junction (pharmaceuticals, nikotine, botulin intoxication)

-neural transmission (spinal cord injuries)

physiological acute compensation

-kidney

- excretion of H2PO4- and NH4

+

- resorption of HCO3-

[HCO3-] 24 mmol/l N,

pCO2 5,3 kPa

[HCO3-]/[H2CO3+CO2] 20 : 1 < 20 : 1 ≤ 20 : 1

pH 7,34 – 7,44 < 7,34 ≤ 7,4

Respiratory alkalosis

Hyperventilation: - mechanical ventilation

- respiratory center stimulation: from CNS (hysteria, anxiety, infection), drugs (salicylates), from thermoregulation center (fever, physical effort)

physiological acute compensation

-kidney

- excretion of HCO3-

[HCO3-] 24 mmol/l N, ↓ ↓

pCO2 5,3 kPa ↓

[HCO3-]/[H2CO3+CO2] 20 : 1 > 20 : 1 ≥ 20 : 1

pH 7,34 – 7,44 > 7,44 ≥ 7,4

Mixed acid-base disorders

1. Antagonistic – metabolic acidosis + metabolic alkalosis acid-base indicators are often physiological (hypochloremia discovers MAlk)

2. Synergic – e.g. metabolic acidosis + respiratory acidosis

Diagnosis: electrolytes, proteins, lactate, calculation from the iontogram, symptoms

Study material:

Liebrman and Marks, Mark‘s Basic Medical Biochemistry a Clinical Approach, 2009