lom acid base_lecture2013-1
TRANSCRIPT
ACID-BASE
Language of Medicine
Chemical Pathology
David Haarburger
BASIC CHEMISTRY
Acid
Base
HA ↔ H+ + A- B + H+ ↔ BH+
HCl ↔ H+ + Cl- NH3 + H+ ↔ NH4+
HOW MANY ACIDS? HOW MANY BASES?
1. H2SO4
2. H2PO4-
3. CH3COOH
4. H2CO3
5. KOH
6. H20
HOW MANY ACIDS? HOW MANY BASES?
1. H2SO4 ↔ H+ + HSO4
-
2. H3PO4 ↔ H2PO4- + H+ ↔ HPO4
2 + 2H+
3. CH3COOH ↔ CH3COO- + H+
4. H2CO3 ↔ H+ + HCO3-
5. KOH + H+ ↔ K+ + H20
6. H20 + H20 ↔ H3O+ + OH-
ACID DISSOCIATION CONSTANTS
Acid Ka
Hydrochloric Acid 108
Sulphuric Acid 103
Acetic Acid 1,8·10-5
Carbonic Acid 2,5∙10-4
Ammonium 5,6∙10-10
][
]][[
HA
AHka
][
]][[
HCl
ClHka
HA ↔ H+ + A-
P FUNCTIONS
pH = - log [H+]
pKa = - log Ka
pH of 1mM HCl = - log (0,001M) = 3
Ka of HCl = 108 → pKa of HCl = - log 108 = -8
BUFFERS
Buffer solutions are solutions consisting of a
weak acid and its conjugate base which resist
changes in pH upon addition of small amounts
of acid or base.
Solution of Sodium Acetate and Acetic Acid
CH3COO- + H+ ↔ CH3COOH
GAS SOLUBILITY
Henry’s Law
C = k x P
C : Concentration of a gas
k : Henry’s constant
P : Partial pressure of a gas
Examples of k (0ºC)
O2 13μmol/l/kPa
N2 6,0μmol/l/kPa
CO2 340μmol/l/kPa
EXAMPLE
A open beaker of water at atmospheric pressure
Gas P
(kPa)
k
(μmol/l/kPa)
C
(μmol/l)
O2 21 13 273
N2 80 6 480
CO2 0,3 340 102
ACID-BASE BALANCE
[H+] is tightly controlled between 35 and 45 nmol/ℓ (pH 7,35 – 7,45)
[H+] too high
Lethargy, neuromuscular irritability, seizures
Cardiac arrhythmias
[H+] too low
Tetany, seizures
Cardiac arrhythmias
ACID PRODUCTION
Where does acid come from?
Metabolism (40 – 80 mmol/l H+ per day)
Metabolism of cysteine and methionine in proteins generates sulphuric acid : H2SO4
Metabolism of DNA and RNA and phospholipids yields phosphoric acid : H3PO4
Incomplete metabolism of fatty acids yields ketones : β-hydroxybutyric acid and acetoacetic acid
Incomplete metabolism of glucose yields lactic acid
Too many of these acids cause a metabolic acidosis
Oxidative respiration (15 mol per day)
Oxidative respiration generates CO2
Carbon dioxide combines with water to yield carbonic acid: H2CO3
Too much CO2 (decreased clearance) causes a respiratory acidosis
PHYSIOLOGICAL BUFFERS
Buffers are only a temporary solution for too much or too little H+, but they work really well in the short term!
Blood pH 7,35-7,45 (35-45 nM)
Buffer pKa Conc
(mmol/l)
Buffering
Capacity
(mmol/l)
Bicarbonate 6,33 25 1
Haemoglobin 7,2 53 40
Phosphate 6,8 1,2 0,3
Protein - - 8
HENDERSON-HASSELBACH EQUATION
H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3-
2225,0
][log1,6
][
][log
][
]][[
3
32
3
32
3
CO
a
a
P
HCOpH
COH
HCOpkpH
COH
HCOHk
HENDERSON-HASSELBACH EQUATION
2
2
225,0
][log1,6
][log
][
][log
][
][loglog]log[
][
][log]log[log
][
][]log[log
][
]][[
][
][
][
]][[
3
3
2
3
2
3
2
3
2
3
2
3
2
32
32
3
CO
CO
a
a
a
a
a
haaha
P
HCOpH
P
HCOpkpH
CO
HCOpkpH
CO
HCOkH
CO
HCOHk
CO
HCOHk
CO
HCOHkkk
CO
COHk
COH
HCOHk
RESPIRATORY CONTROL
Cell
CO2
Hb + H+→
HbH+
H2O+CO2 →
H++HCO3-
HCO3-
HCO3- + H+→
H2O+CO2
HbH+ →
Hb + H+
Alveolus
CO2
RENAL CONTROL
RENAL CONTROL BICARBONATE RE-ABSORBTION
Tubular lumen
Proximal renal tubular cell
ATP Na+
K+
H2O+CO2 →
HCO3-+H+ H+
Na+
H++HCO3- →
CO2+H2O
HCO3-
RENAL CONTROL PROTON SECRETION
Tubular lumen
Distal renal tubular cell
ATP Na+
H+
H2O+CO2 →
HCO3-+H+
H++ NH3 → NH4
+
H+ + HPO32- → H2PO-
CLINICAL ACID-BASE
Acidaemia
A condition of decreased pH of the blood
Alkalaemia
A condition of increased pH of the blood
Acidosis
A pathological condition resulting from accumulation of acid in the body
Alkalosis
A pathological condition resulting from loss of acid from the body
BLOOD GAS MEASUREMENT
Arterial or capillary blood to measure arterial pO2 and pCO2 values
A heparinised sample Most O2 is carried in red cells
Sealed syringe Prevents O2 diffusing in and CO2 diffusing out of the sample
On ice Prevents ongoing red cell metabolism from generating a lactic acidosis
What we measure
pO2 11 – 15 kPa
pCO2 4.5 – 6.0 kPa
pH 7.36 – 7.44
HCO3- 22 – 30 mmol/L (calculated)
2
3
225,0
][log1,6
pCO
HCOpH
RESPIRATORY ACIDOSIS Disorder that interferes with the ability of the lungs to expel CO2.
Examples Depression of respiratory centre
Drugs - morphine, barbiturates, alcohol
Head injury
Physical inability to ventilate Crush injury to chest
Muscle paralysis
Airway obstruction Asthma
Chronic obstructive airways disease
Disease causing decreased CO2 and O2 exchange Severe pneumonia
Severe lung collapse
Laboratory results pH ↓
pCO2 ↑
HCO3- ↑
H2O + CO2 ↔ H+ + HCO3-
RESPIRATORY ALKALOSIS
Disorder that results from an excessive loss of CO2 from the lungs.
Examples
Direct stimulation of respiratory centre
Drugs – salicylates
Anxiety
Mechanical overventilation
Hypoxia
High altitude
Anaemia
Laboratory results
pH ↑
pCO2 ↓
HCO3- ↓
H2O + CO2 ↔ H+ + HCO3-
METABOLIC ACIDOSIS
Disorder that results from an excessive loss of
HCO3-.
Examples
Hypoxia
Diabetic ketoacidosis
Renal failure
Laboratory results
pH ↓
pCO2 ↓
HCO3- ↓
METABOLIC ALKALOSIS
Disorder that results from an excessive accumulation of HCO3
-.
Examples
Vomiting
Anti-acids
Laboratory results
pH ↑
pCO2 ↑
HCO3- ↑
COMPENSATION
Metabolic compensation When lung function is compromised, the kidneys attempt to increase the
excretion of hydrogen ions via the renal route
Metabolic compensation is slow to take effect, coming into effect over 2 - 4 days
Respiratory compensation When there are metabolic disorders, some compensation is possible by the
lungs by altering the rate and depth of respiration, which is affected directly by the blood pH
Respiratory compensation is quick to take effect, coming into effect within 15 - 30 minutes
If compensation is complete, the pH returns to normal, although the bicarbonate and CO2 concentrations are abnormal
Compensation is however often partial, in which case there is a change in both bicarbonate and CO2 concentrations, but the pH is still abnormal.
APPROACH TO ACID-BASE
pH
↑ Alkalosis
↓ Acidosis
pCO2
↑ Respiratory Acidosis
↓ Respiratory Alkalosis
HCO3-
↑ Metabolic Alkalosis
↓ Metabolic Acidosis
Primary / Compensation
Example
pH 7,32 (7,36-7,44)
pCO2 8kPa (4,5-6,0)
HCO3- 31mmol/l (22-30)