Definitions: acid, base, buffer: An acid a substance that dissociates in water to produce hydrogen ions (H+).

A strong acid almost completely dissociates to produce H+. Hydrochloric acid HCl H+ +ClWhilst a weak acid shows poor dissociation Acetic acid : CH3COOH H+ + CH3COO-

A base is a substance that can yield hydroxyl ions (HO-). A buffer, the combination of a weak acid or weak base and its salt, is the system that resists change in pH.

Hydrogen ion homeostasis: Our body is a continuous producer of H+ (acid) aerobic and anaerobic metabolism. CO2 + H2O H2CO3 H+ +HCO3 Maintenance of a constant normal pH is very vital process, because change in H+ in human body affect functions of the various proteins in the body.

The bodys first line defense against extreme changes in H+ concentration is the buffer systems present in all body fluids. All buffers consists of a weak acid as H2CO3 and its salt conjugate base HCO3- for the bicarbonate carbonic acid buffer system. Another important buffer system is the phosphate buffer system (HPO4-2 H2PO4-) Which play a role in plasma and RBCs.

Maintenance of H+: The normal concentration of H+ in the extracellular body fluid range from 36 44 nmol/L (pH 7.34 to 7.44). Any H+ value outside this range will cause alteration in the rate of chemical reactions and can lead to alterations in consciousness, neuromuscular irritability, tetany, coma, death.

BLOOD PH
Maintained

within narrow limits. pH 7.36 7.44 pH = alkalaemia (alkalosis) pH = acidaemia (acidosis)

ACID BASE BALANCE pH of the extracellular fluid ranges from 7.36 7.44 Plasma is therefore slightly alkaline in comparison with physiochemical neutral solution of pH 7.0
The

 Arterial

blood is slightly more alkaline than venous blood: Arterial blood pH = 7.4 and venous blood pH = 7.37 The pH = negative logarithm of hydrogen ion concentration (H+) i.e. pH = -log (H+)

HENDERSON HASSELBALCH EQUATION

When H+ is produced during metabolic processes it is buffered by the alkali reserve (NaHCO3) to produce H2CO3. The pH = PK + log (HCO3) (H2CO3) where PK = 6.1 At normal pH (7.4) the log (HCO3) (H2CO3) must be 1.3 pH = 6.1+1.3 = 7.4

 At

normal blood pH the ratio between HCO3 TO H2CO3 must be 20:1

fluid such as plasma, H2CO3 is in equilibrium: H2CO3 CO2 + H2O The concentration of H2CO3 is directly proportional to the partial pressure of CO2 (PCO2) and may be related as follows: H2CO3 = PCO2 X 0.03 (mmHg).
In

Where 0.03 = CO2 solubility constant, thus the Henderson Hassel Balch equation may be written as: pH= pK + log HCO3 PCO2 X 0.225 (0.225 = the solubility constant) [Kilopascal]

 When

interpreting acid base studies in patients it can be useful to memorize the equation simply as the relationship: pH HCO3 PCO2

THE BUFFER SYSTEM

In plasma the carbonic acid bicarbonate mechanism is the most important buffering mechanism, although plasma proteins & also phosphate play a part. In the cells, buffering by proteins is more important. Heamoglobin, within the RBDs, plays a major part in the total buffering power of blood.

 Hydrogen

ions can be lost from the body only through the kidney and the intestine. This mechanism is coupled in the kidney with regeneration and reabsorption of bicarbonate ions and is therefore the ideal method for eliminating any excess H+ .

RESPIRATORY REGULATION OF ACID BASE BALANCE increase in H+ concentration is followed by an increase in H2CO3 (H+ + HCO3 H2CO3 This is followed by dissociation of H2CO3 to H2O and CO2 in the lung. Increase in pulmonary ventilation will wash CO2.
Any

ROLE OF KIDNEY IN REGULATION OF ACID BASE BALANCE

Excretion of H+ and reabsorption of bicarbonate: In the cells of proximal and distal convoluted tubules CO2 combines with water to form H2CO3 by carbonic anhyderase enzyme. H2CO3 dissociates to H+ and HCO3-

 H+

is excreted into the lumen of the tubules in exchange with Na+. Na+ enters the tubular cells to combine with HCO3 which is also transported into blood.

AMMONIA FORMATION
Occurs in distal tubular cells where glutamine is splitted by glutaminase to glutamic acid and NH3. NH3 combine with H+ liberated from carbonic acid forming NH4 which excreted in exchange with Na, the later combine with HCO3 which is also transported into blood. NH3 formation is important for elimination of H+.

ACIDAEMIA
Acidaemia

an abnormally raised blood H+ (normal range = 35 45 nmol/L) in the body . Since pH depends on the ratio of HCO3/ PCO2, acidosis can arise in two ways: 1. A fall in HCO3 with normal PCO2 pH metabolic acidosis N

2.

A rise in PCO2 with normal HCO3pH N respiratory acidosis

ALKALAEMIA
Alkalaemia: an abnormal low blood H+ in the body (an elevated pH) Alkalosis can arise in two ways: 1. a rise in HCO3 with normal PCO2 pH metabolic alkalosis. N 2. A fall in PCO2 with a normal HCO3 pH N respiratory alkalosis

COMPENSATION
Plasma

pH would be about 7.4 as long as the ratio of HCO3 / H2CO3 remains at 20/1 If a disease process altered the concentration of one of the components the ratio, and therefore the pH, can be returned to normal if the other component concentration is sufficiently altered in the same direction.

Both component concentrations may be abnormal, but if the pH is restored to normal, then compensation is said to have occurred. Complete compensation if the pH is restored to normal. Partial compensation if the pH has moved towards normal but remains abnormal. pH N

healthy kidney will respond over the next few days (2-3 days) by increasing the plasma level of HCO3- . Compensation has occurred by creating a metabolic alkalosis. pH N In practice a complete compensation rarely occurs, the pH returning 'towards' normal but rarely 'to' normal.

On

the mixed diet the metabolic processes cause an overall production of acid (constant tendency to acidify the extracellular fluid.) So the blood contains efficient buffering mechanisms to prevent the development of acidosis.

After

intermediate buffering in the cells, final compensation of any change in the hydrogen ion concentration of the extracellular fluid is performed by: The lungs. The kidneys.

INVESTIGATION OF ACID BASE BALANCE

According

to Henderson Hassel balch equation, the pH of plasma depends on the ratio of (HCO3) to (H2CO3), normal ratio is 20:1, therefore determination of HCO3 and total CO2 content and pH is important) Any change, even slight in pH will result in marked change in H+

1.

pH determination Normally pH of plasma is 7.36 -7.44. It is determined by a pH meter. It is increased in alkalosis and decreased 1n acidosis When the changes in pH is more than 0.5, death will ensues.

2. 3.

Bicarbonate Normal levels: 23-28 mEq(mmol) per lit. It is increased in alkalosis and decreased in acidosis. Total CO2 contents: It is decreased in metabolic acidosis and respiratory alkalosis and increased in metabolic alkalosis and respiratory acidosis.

NORMAL
7.4
ACIDOSIS ALKALOSIS

7.0

7.8

ACID (CO2)
RESPIRATORY COMPONENT

BASE HCO3
METABOLIC COMPONENT

Acidosis

and alkalosis are conditions which promote an increase or decrease in the hydrogen ion concentration, hence respectively a fall or increase in the pH of the blood. Clinically acidosis itself causes few specific symptoms.

 1. 2.

3. 4.

The symptoms of uncompensated alkalosis are more specific and include: Nausea and anorexia. Neuromuscular irritability with tetany (ionized calcium becomes insoluble and non ionised in alkaline medium) . Potassium depletion and eventual renal failure. In severe alkalosis respiration is depressed and both oxygen intake and the release of' oxygen from haemoglobin to tissues are diminished .

Acidosis

and alkalosis may be respiratory or non-respiratory (metabolic) in origin. Respiratory disturbances are associated primarily with an increase or decrease of the plasma carbonic-acid concentration. Excretion of carbon dioxide is no longer equal to its production .

Metabolic

disturbance are associated primarily with an increase or decrease of the plasma bicarbonate concentration.

is a primary alteration in carbonic acid that result from hyperventilation leading to reduction of plasma carbonic acid. The plasma pH may reach 7.9. The CO2 is decreased .
This

RESPIRATORY ALKALOSIS
7.4

7.0

7.8

ACID (CO2)
RESPIRATORY COMPONENT

BASE (HCO3)
METABOLIC COMPONENT

1. 2. 3. 4. 5.

Hyperventilation which cause excessive wash of CO2 and decreases plasma H2CO3 can result from Fevers. Encephalitis. High altitudes (due to compensation for O2 deficiency). Increased intracranial tension, anaesthesia and automatic ventilation. Hysteria, or overbreathing.

Compensation:

plasma bicarbonate level falls as the kidney excretes excess sodium bicarbonate and an alkaline urine. In chronic respiratory alkalosis the urine eventually becomes acidic when the plasma bicarbonate falls so bicarbonate reabsorption is complete.
The

Treatment: Breathing

air containing increased

CO2 I. V. calcium for tetany.

*It is a primary alteration in carbonic acid that results from depression of ventilation, which causes retention of H2CO3. Plasma pH may reach 7.1 . Rise in the (CO2).

RESPIRATORY ACIDOSIS
7.4

7.0

7.8

ACID (CO2)
RESPIRATORY COMPONENT

BASE (HCO3)
METABOLIC COMPONENT

Diminished respiratory elimination of CO2 can result from: 1. Respiratory obstruction. 2. Chronic lung disease . 3. Drugs which depress respiration e.g. morphine. 4. Certain anaesthetics.

Clinically: Drowsiness,

stupor and coma can occur due to a combination of severe CO2 excess and O2 lack.

Compensation

is poor in acute cases but in chronic cases it is achieved by increased reabsorption of bicarbonate by the kidney increased plasma bicarbonate level. Treatment:of the cause +bronchodilators in chronic lung disease + intermittent O2 inhalation.

in plasma bicarbonate level accompanied by either a decrease of the other anions of the plasma (principally chloride) or an increase of cationic sodium. *The plasma pH may reach 7.9. *There is an increase in the (bicarbonate).
Increase

METABOLIC ALKALOSIS
7.4

7.0

7.8

ACID (CO2)
RESPIRATORY COMPONENT

BASE (HCO3) METABOLIC COMPONENT

 1. 2. 3. 4.

The increase in blood bicarbonate can result from: Excessive intake of sodium bicarbonate (or other alkaline antacids) Loss of hydrogen ions due to vomiting or aspiration Hypochloreamic alkalosis due to loss of HCl as seen in gastric aspiration. Rarely HCO3 administration.

Potassium deficiency often produces alkalosis due to : A- H+ entering the cells to replace lost potassium ions. B- Alteration of renal tubular function (tubular intracellular K+ deficiency enhances bicarbonate reabsorption leading to alkalosis with acid urine) .

 1.

2.

Retention of base: Excess reabsorption of bicarbonate (and sodium) by the renal tubules, usually with loss of potassium. It may be due to mineralocorticoid excess (e.g. primary aldosteronism or to diuretics such as frusemide and the thiazides.

Hypochloremic

alkalosis excessive loss of CI- more than Na+ (e.g. persistent vomiting). It leads to relative decrease in anions which is compensated by an increase in bicarbonate formation and reabsorption by the kidney in order to maintain the anion - cation balance.

I.

V. fluids containing normal saline, potassium chloride and ammonium chloride in order to restore the depleted chloride and the depleted potassium.

decrease of the plasma bicarbonate level, accompanied by a decrease of the plasma sodium. * The plasma pH may reach about 7.1, and the urine pH 4.5. There is a decrease in (bicarbonate).

METABOLIC ACIDOSIS
7.4

7.0

7.8

BBASE (HCO3) ACID (CO2)

RESPIRATORY COMPONENT METABOLIC COMPONENT

1)In

the presence of normal haemostatic mechanisms as In A) Ketoacidosis: Whether the ketosis is due to diabetes, to starvation or to high fat diet. the keto-acids are retained in the plasma and displace bicarbonate. Sodium is lost in urine (from ECF) and potassium (from ICF) with the excreted keto-acids.

B)

Lactic acidosis: In "shock" when poor tissue perfusion causes local hypoxia, and during muscular exercise, lactate is produced as well as hydrogen ions.

2)

Loss of bicarbonate (with sodium): * Losses of pancreatic juice, bile and high small intestinal secretion (all rich in bicarbonate), through a fistula or ileostomy. * in sever diarrhoea (particularly from cholera) .

* During treatment with Diuretics such as acetazolamide ( carbonic anhydrase inhibitors) Sodium and bicarbonate are lost in the urine .

Anion Gap
Major Indicator Anions = cations in the serum Measure anions/cations
Sodium (Na+) Potassium (K+) Chloride (Cl-) Bicarbonate (HCO3-)

Anion Gap = (Na+ and K+) - (Cl + HCO3) Normal Gap = 12