Transcript Biochemistry of acidobasic regulations

Biochemistry of acidobasic
regulations
Alice Skoumalová
Body water compartments:
Diagram showing chemical
constituents of the three fluid
compartmens:
Derived values:
AG (anion gap)
(Na+ + K+) - (Cl- + HCO3-)
14-18 mmol/l
SID (strong ion difference)
(Na+ + K+) – Cl42 mmol/l
pH
lemon
2,3
orange 3,7
sceletal muscle c. 6,9
prostatic c. 4,5
erythrocytes
7,3
trombocytes 7,0
osteoblasts 8,5
blood 7,36 – 7,44
gastric juice 1,2 – 3
pancreat. juice 7,5 – 8
bile
6,9 – 7,7
urine 4,8 - 8
Acids in the blood:
The Henderson-Hasselbalch equation
Buffer
Titration curve for acetic acid
Equivalents of OH- added
Body buffers:
Blood
ISF
HCO3-
ICF
HCO3-/H2CO3+ CO2
64%
hemoglobin
29%
proteins
6%
proteins
proteins
HPO42-/H2PO4-
1%
phosphates
phosphates
-
HCO3-
Plasma:
 mixed buffer system
Major physiological buffers:
Buffer
pK
concentration
HCO3/CO2
6,1
24 mmol/l
HPO42-/H2PO4-
6,8
1 mmol/l
Proteins
4-12
5,6 – 7,0
histidine
N-term. amino groups 7,6 – 8,4
15 mmol/l
The bicarbonate buffer system:
CO2
+
H2O
in the body – an open system
H2CO3
H+
+
HCO3-
erythrocytes
(carbonic anhydrase)
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
Buffers in an organism
Co-operation of the body buffers:
Carbon dioxide transport:
CO2 in the blood:
1. as HCO3- (ionization of H2CO3)
CO2
+
75-85 %
H2O
H2CO3
H+
+
HCO3-
erythrocytes
(carbonate dehydratase)
2. as carbamino groups (CO2 reacts with amino groups of proteins)
3. dissolved CO2
Partial pressures
air-inspiration
pO2 (kPa)
21
pCO2 (kPa)
0,03
10-15 %
5-12 %
air-expiration
15,3
4,4
arterial blood
12 – 13,3
4,6 – 6
venous blood
4,6 - 6
5,3 – 6,6
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)
The kidney in acid-base balance:
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 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
pCO2 = 5,3 ± 0,5 kPa
Hb, pO2
Calculated:
[HCO3-] = 24 ± 3 mmol/l
[H+] = 40 nmol/l
= 40 torr = 1,2 mmol/l
BE (base excess) = 0 ± 2,5 mmol/l
NBB (buffer base)
(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)
(the concentration of all bases in the blood at the
standard conditions)
plasma 42 ± 3 mmol/l
blood 48 ± 3 mmol/l
AG (anion gap) = 14-18 mmol/l
AG = [Na+] + [K+] - [Cl-] - [HCO3-]
Classification of the acid-base disorders:
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
acute stage
x
compensated
four main disorders x mixed
acidemia x acidosis
alkalemia x alkalosis
The maintenance of pH:
Correction of the acid-base disorders:
Buffer reactions
Compensations Corrections
processes in which one system compensates
the alteration of the other one
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 acidosis
Hypoventilation: - 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