lom acid base_lecture2013-1

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)