ACID-BASE BALANCE Acid-base balance means regulation of [H+] in the body fluid. Only slightly changes in [H+] from the normal value can cause marked alteration in the rates of chemical reactions in the cell. For this reason the regulation of [H+] is one of the most important aspects of homeostasis.   1 pH = log -------------- = - log [H+] [H+] For the bicarbonate buffer system the formula may be expressed as Follow: [HCO3-] in mmol/l pH = 6.1 + log -------------------------------- [CO2] in mmol/L  This is called the Henderson— Hasselbalch equation and by using it one can calculate the pH of a solution. Acidosis: low pH -high [H+] Alkalosis: high pH -low [H+]

Defense against change in [H+] To prevent acidosis or alkalosis, several control systems are available: Acid-base buffer system Respiratory system Renal system 1. Acid-base buffer system present in all body fluids combine immediately with any acid or alkali can act within a fraction of a second

2. Respiratory system change rate of breathing ….. change rate of CO2 washing(acid gas) …….. readjust [H+] back to normal within 1 -15 minutes. 3. Renal system Renal excretion of acidic or alkaline urine ….. readjust the [H+] back to normal within hours to several days. The most powerful of all the acid-base regulatory systems.

Acid-base buffer system

[1] The bicarbonate buffer system It consists of mixture of (H2CO3) - (NaHCO3) [carbonic acid- sodium bicarbonate]. When a strong acid such as HCl is added: HCl + NaHCO3 →H2CO3 + NaCl strong HCl is converted into a very weak carbonic acid . When a strong base such as NaOH is added to this buffer, the following takes place; NaOH + H2CO3→ NaHCO3 + H2O The net result is exchange of the strong base NaOH for the weak base NaHCO3.

[2] Phosphate buffer system It is composed of NaH2PO4 and Na2HPO The phosphate buffer is especially important in the tubular fluid of the kidney because of high concentration in the tubules.

[3] The protein buffer system NH2 -Protein-COOH → Undissociated protein(buffer). Behave as weak acids and weak bases. The most plentiful buffer of the body is the plasma and cells proteins.

Hb as a buffer System There are 38 histidine units in the Hb molecules. Histidine is an amino acid which contains additional— NH2 and -COOH groups, thus Hb is a good buffer. Reduced Hb + H+ H-Hb which is a very weak acid.

Respiratory Regulation of Acid-Base Balance Recalling the Henderson-Hasselbalch equation [HCO3-] in mmol/l pH = 6.1 + log -------------------------------- [CO2] in mmol Inverse relationship between CO2 concentration in the body fluids and pH.   The CO2 concentration in the ECF depends on: the rate of metabolic productionof CO2. the rate of pulmonary ventilation(CO2 washing). Since alveolar ventilation can be reduced to zero or increased to about 15 times normal, thus, activity of the respiratory system has marked effects on pH of the body fluids.

On the other hand, a change in blood CO2 concentration or blood [H+] affects the rate of alveolar ventilation by a direct action of H+ on the respiratory center . The overall buffering power of the respiratory system is one to two times as great as that of all the chemical buffers combined.  

Renal regulation of acid-base balance The kidneys regulate H+ conc. principally by increasing or decreasing the HCO3- in the body fluid. Normally H+ secretion = HCO3- filtration, and they titrate each other in the renal tubules the end products being CO2 and water.

The basic mechanism by which the kidney corrects either acidosis or alkalosis is by incomplete titration of H+ against HCO3-, leaving one or the other of these to pass into the urine and therefore to be removed from the extracellular fluid.

Clinical applications 1. Respiratory acidosis(CO2 retention) Alveolar ventilation is not enough to wash CO2 produced by metabolism. increased PCO2 , carbonic acid and fall of pH Pathological causes are: airway obstruction Pneumoinia(infection of alveoli) chest deformities paralysis of respiratory muscles All decrease gas exchange resulting in low PO2 and high PCO2.

2-Respiratory alkalosis (CO2 washout or deficit) Overvbreathing ………. loss of carbonic acid …….occurs in:   Hysteria Mechanical respirator Meningitis or encephalitis(depression of the …..?)

3-Metabolic acidosis Accumulation of acids other than carbonic acid in the body or as a consequence of body depletion of the base bicarbonate. Causes are :   Increased lactic acid (vigorous exercise). Ketoacidosis: accumulation of ketone bodies (uncontrolled diabetes mellitus). Renal diseases(failure of …………?)

4- Metabolic alkalosis Abnormal loss of HCl (prolonged or severs vomiting). newborn children with pyloric obstruction. Excessive ingestion of alkaline drugs such as sodium bicarbonate for the treatment of peptic ulcer.