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Abdul Salam M. Sofro Faculty of Medicine YARSI University

Teaching aims

By the end of lecture session, the students are expected to:

Understand the underlying concept of acid-base balance in human body Be able to identify various conditions caused by acid-base imbalance Understand compensation mechanism in acid- base imbalance


pH Review

pH = - log [H+] H+ is really a proton Range is from 0 - 14 If [H+] is high, the solution is acidic; pH < 7 If [H+] is low, the solution is basic or alkaline ; pH > 7

Plasma ion concentrations Ion* H+ K+ Ca++ nmoles/L 40 4,000,000 2,500,000 mEq/L 40 x 105 4 5




*K+, Potassium ion; Ca++, calcium ion; Mg++, magnesium ion; Na+, sodium ion.

pH and hydrogen ion concentration

Blood pH Acidemia [H+] (nmoles/L)

7.10 7.30 Normal

80 50

7.4 Alkalemia
7.52 7.70 8.00


30 20 10

Acids: An acid is defined as any compound, which forms hydrogen ions in solution. For this reason acids are sometimes referred to as "proton donors (H+ donors)

Bases: A base is a compound that combines with hydrogen ions in solution. Therefore, bases can be referred to as "proton acceptors (H+ acceptors, or give up OH- in solution).

Acids and bases can be: Strong dissociate completely in solution HCl, NaOH Weak dissociate only partially in solution Lactic acid, carbonic acid

Strong Acids: A strong acid is a compound that ionizes completely in solution to form hydrogen ions and a base. Example 2 illustrates a strong acid in solution, where this dissociation is complete. Weak Acids and Bases: these are compounds that are only partially ionised in solution. Example 3 shows a weak acid in solution with incomplete dissociation.

Figure 3 shows how as hydrogen ions are added to a buffer solution they combine with A- (the conjugate base) and the reaction is pushed to the left. This creates more HA whilst removing the excess H+ from the solution. Similarly, as hydrogen ions are removed from solution by addition of a strong base the reaction moves to the right restoring the hydrogen ion concentration and reducing the quantity of HA.

The Body and pH

Homeostasis of pH is tightly controlled Extracellular fluid = 7.4 Blood = 7.35 7.45 < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45

Small changes in pH can produce major disturbances

Most enzymes function only with narrow pH ranges Acid-base balance can also affect electrolytes (Na+, K+, Cl-) Can also affect hormones

The body produces more acids than bases

Acids take in with foods Acids produced by metabolism of lipids and proteins Cellular metabolism produces CO2. CO2 + H20 H2CO3 H+ + HCO3-

The acids which can cause changes in blood pH are:

Metabolic or non-respiratory acids Organic Lactic Acid Hypoxia Drug Induced Idiopathic Diabetes Starvation Inorganic acids, increase in renal failure Might be called "true" metabolic acidosis

Keto Acids Inorganic Sulphuric Acid Phosphoric Acid Hydrochloric Acid

Respiratory acids

Organic only

Carbonic Acid

Acid-base balance

Body fluid pH is significant because proteins are sensitive to pH, both in terms of their conformation and optimal range of function. pH affects membrane structure, enzyme activity, & structural proteins.
H+ concentration in body fluids is the major factor contributing to pH. + Most H is result of cellular metabolism & digestive intake pH of ECF ranges between 7.35 - 7.45

Control of Acids
1. Buffer systems 2. Respiratory mechanisms 3. Kidney excretion

1. Buffer systems

Buffer systems - substances that have the ability to bind or release H+ in solution

Weak acids that donate H+ & weak bases that absorb H+ Keeps pH of a solution relatively constant despite addition of considerable quantities of H+ or OH-. Act quickly but are temporary, do not remove H+ from body.

Take up H+ or release H+ as conditions change Buffer pairs weak acid and a base Exchange a strong acid or base for a weak one Results in a much smaller pH change

A buffer solution

A buffer solution is one in which the pH changes less when an acid or base is added than would have occurred in a non-buffer solution Such a solution contains both acidic and basic groups. A mixture of a weak acid or a weak base and a salt of that acid or base in solution is a buffer solution.

Bicarbonate buffer

Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 H2CO3 + NaCl NaOH + H2CO3 NaHCO3 + H2O

HendersonHasselbalch equation

The HendersonHasselbalch equation relates blood pH to the components of the bicarbonate buffer system:

where pK is the negative log of the dissociation constant of carbonic acid and has the value 6.1

Phosphate buffer

Major intracellular buffer H+ + HPO42- H2PO4OH- + H2PO4- H2O + H2PO42-

Phosphate buffer system When pH decreases, monohydrogen phosphate ion acts as H+ acceptor When pH increases, dihydrogen phosphate ion donates H+ Phosphates are major ions in intracellular fluid and in collecting tubules of kidneys where they buffer urine

Protein Buffers

Protein Buffer system - proteins have carboxyl & amino groups

When pH increases, the carboxyl group can dissociate & release H+ (gives up H+ ). Histidine in Hb & cysteine are effective buffers. They donate H+ When pH decreases, amino group acts as a H+ acceptor. Limited to free amino acids & the terminal amino acid of protein. Side chains that can buffer H+ are present on 27 amino acids. Affects both ICF & ECF. Only intracellular Hb buffer system rapidly affects ECF pH

2. Respiratory mechanisms

Exhalation of carbon dioxide Powerful, but only works with volatile acids Doesnt affect fixed acids like lactic acid CO2 + H20 H2CO3 H+ + HCO3Body pH can be adjusted by changing rate and depth of breathing

3. Kidney excretion

Can eliminate large amounts of acid Can also excrete base Can conserve and produce bicarb ions Most effective regulator of pH If kidneys fail, pH balance fails

Rates of correction

Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days

CO2 & Acid from Muscle

The chloride shift

Bicarbonate and chloride ions are transported across the red blood cell membrane in opposite directions by the bicarbonate-chloride carrier protein. The chloride shift is extremely rapid, occurring within 1 second. The chloride shift results in the chloride content of venous blood being greater than that of arterial blood.

Acid-Base Imbalances

pH< 7.35 acidosis pH > 7.45 alkalosis The body response to acid-base imbalance is called compensation May be complete if brought back within normal limits Partial compensation if range is still outside norms.


If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation. If problem is respiratory, renal mechanisms can bring about metabolic compensation.


Principal effect of acidosis is depression of the CNS through in synaptic transmission. Generalized weakness Deranged CNS function the greatest threat Severe acidosis causes Disorientation coma death


Alkalosis causes over excitability of the central and peripheral nervous systems. Numbness Lightheadedness It can cause : Nervousness muscle spasms or tetany Convulsions Loss of consciousness Death

Clinical classification of causes of changes in blood ph

Clinical states of pH disturbance (acid-base imbalance) can conveniently be divided into two groups, i.e.
(a) respiratory and (b) metabolic or non-respiratory.

The reasons for this division into respiratory and non-respiratory are that: i) the compensatory mechanisms and treatments of the two types are different.; ii) the recognition of non-respiratory disturbances is masked by compensatory alterations in PCO2 and the recognition of changes in pH caused by PCO2 changes are masked by renal compensation.

Types of acid-base imbalance

Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

Respiratory Acidosis

Any condition that increases blood pCO2 (above 45 mmHg, pH <7.35). ex. emphysema, pneumonia, pulmonary edema This is synonymous with CO2 retention and is usually a sign of hypoventilation. Compensation is renal. There is renal loss HCl in the form of buffer or as NH4Cl. During recovery chloride has to be supplied and retained.


Central nervous system Peripheral nervous system Neuromuscular transmission Muscle disorders Chest wall abnormalities Lung and airway disorders.

Inhalation of CO2 Increased production of CO2

Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg. Hypercapnia high levels of CO2 in blood

Acute conditions: Adult Respiratory Distress Syndrome Pulmonary edema Pneumothorax

Chronic conditions: Depression of respiratory center in brain that controls breathing rate drugs or head trauma Paralysis of respiratory or chest muscles Emphysema

Compensation for Respiratory Acidosis

Kidneys eliminate hydrogen ion and retain bicarbonate ion

Signs and Symptoms of Respiratory Acidosis

Breathlessness Restlessness Lethargy and disorientation Tremors, convulsions, coma Respiratory rate rapid, then gradually depressed Skin warm and flushed due to vasodilation caused by excess CO2

Treatment of Respiratory Acidosis

Restore ventilation IV lactate solution Treat underlying dysfunction or disease

Respiratory Alkalosis

Respiratory alkalosis - any condition that decreases blood pCO2 (below 35 mmHg, pH >7.45). This is associated with hyperventilation. Usually these are acute so there is no time for renal compensation, but if prolonged, such as in acclimatization to high altitudes, there would probably be renal compensation.

Carbonic acid deficit pCO2 less than 35 mm Hg (hypocapnea) Most common acid-base imbalance Primary cause is hyperventilation

Respiratory alkalosis (cont.) Causes:

Deliberate induced hyperventilation during anaesthesia Some causes of hypoxia associated with hyperventilation Fever Some types of C.N.S. damage Hysterical hyperventilation

Conditions that stimulate respiratory center:

Oxygen deficiency at high altitudes Pulmonary disease and Congestive heart failure caused by hypoxia Acute anxiety Fever, anemia Early salicylate intoxication Cirrhosis Gram-negative sepsis

Compensation of Respiratory Alkalosis

Kidneys conserve hydrogen ion Excrete bicarbonate ion

Treatment of Respiratory Alkalosis

Treat underlying cause Breathe into a paper bag IV Chloride containing solution Cl- ions replace lost bicarbonate ions

Metabolic Acidosis (non-respiratory


This (non-respiratory acidosis) is due to increase in acids (i.e. H+ donating substances) other than H2CO2 or decrease in base (i.e. H+ acceptors) in the blood. Compensation is by hyperventilation. This lowers the PaCO2 thus deducing the any pH change

Metabolic acidosis (cont.)

Bicarbonate deficit - blood concentrations of bicarb drop below 22mEq/L Causes:

Increased alimentary or parenteral intake of acid or alimentary loss of base (Loss of bicarbonate through diarrhea) Accumulation of acids (lactic acid or ketones) Failure of excretion of acid (excrete H+) or loss of base by the renal system (or renal dysfunction)

Symptoms of Metabolic Acidosis

Headache, lethargy Nausea, vomiting, diarrhea Coma Death

Compensation for Metabolic Acidosis

Increased ventilation Renal excretion of hydrogen ions if possible K+ exchanges with excess H+ in ECF ( H+ into cells, K+ out of cells)

Treatment of Metabolic Acidosis

IV lactate solution

Metabolic Alkalosis

Bicarbonate excess - concentration in blood is greater than 26 mEq/L Causes:

Excess vomiting = loss of stomach acid Excessive use of alkaline drugs Certain diuretics Endocrine disorders Heavy ingestion of antacids Severe dehydration

Compensation for Metabolic Alkalosis

Alkalosis most commonly occurs with renal dysfunction, so cant count on kidneys Respiratory compensation difficult hypoventilation limited by hypoxia

Symptoms of Metabolic Alkalosis

Respiration slow and shallow Hyperactive reflexes ; tetany Often related to depletion of electrolytes Atrial tachycardia Dysrhythmias

Treatment of Metabolic Alkalosis

Electrolytes to replace those lost IV chloride containing solution Treat underlying disorder

Diagnosis of Acid-Base Imbalances



Note whether the pH is low (acidosis) or high (alkalosis) Decide which value, pCO2 or HCO3- , is outside the normal range and could be the cause of the problem. If the cause is a change in pCO2, the problem is respiratory. If the cause is HCO3- the problem is metabolic.

3. Look at the value that doesnt correspond to the observed pH change. If it is inside the normal range, there is no compensation occurring. If it is outside the normal range, the body is partially compensating for the problem.


A patient is in intensive care because he suffered a severe myocardial infarction 3 days ago. The lab reports the following values from an arterial blood sample:
pH 7.3 HCO3- = 20 mEq / L ( 22 - 26) pCO2 = 32 mm Hg (35 - 45)

Metabolic acidosis With compensation