Acid-base Regulation in human body Dr. Noor-ul-ain Waheed Assistant Professor Biochemistry KEMU

Learning objectives By the end of this session you should be able to: Descibe briefly pH of blood Enumerate body buffer systems Explain role of bicarbonate buffer system in human body Discuss Four disorders of acid –base disturbance

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-)

Major Sources of H+ in the body Aerobic respiration of glucose Production of CO2 Anaerobic respiration of glucose: Production of Lactate Fatty Acid Oxidation: Production of ketone bodies Sulfur containing amino acid Production of H2SO4 Hydrolysis of phosphoproteins Production of H3PO4

A Buffer system consists of Buffer pair (weak acid/conjugate base or salt) When Strong acid is added Conjugate base + Strong acid → Salt+ Weak acid When Strong base is added Conjugate Acid + Strong base → Salt + water

BUFFERING CAPACITY When an acid is exactly half-neutralized, [A−] =[HA]. Under these conditions, at half-neutralization, pH = pKa. Equal amount of acid or conjugate base is available for neutralization Therefore buffering capacity depends upon the pKa i.e. nearer to pH

DISTRIBUTION OF BUFFERS Extra-cellular (Bicarbonate, Proteins) Blood Buffers (Bicarbonate, Plasma Proteins, Hemoglobin, Phosphate) Intra-cellular (Phosphate, Proteins, Bicarbonate) Renal (Phosphate, Ammonia, Bicarbonate)

The Most Important Buffer System Bicarbonate buffer system Carbonic Anhydrase CO2 + H2O H2CO3 H+ + HCO3- Sites: RBC, lung epithelium, stomach, renal tissue, intestinal tissue

WORKING IN STOMACH

Bicarbonate buffers maintains alkalinity of blood

Transport of carbon dioxide working with hemoglobin

WORKING WITH RENAL BUFFERS

Chemical Buffer Systems   Combination of weak acid and weak base Binds to H+ as H+ concentration rises Releases H+ as H+ concentration falls Can restore normal pH almost immediately Buffering accomplished by converting: Strong acid  Weak acid Strong base  Weak base

Bicarbonate Buffer System The most powerful extracellular buffer in the body Weak acid - Carbonic acid (H2CO3) Weak base - Bicarbonate ion (HCO3-) CO2 + H20  H2CO3  H+ + HCO3- Works along with respiratory and urinary system (these systems remove CO2 or reabsorb HCO3- )

pH Derangements

Respiratory Acidosis Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg. Hypercapnia – high levels of CO2 in blood Chronic conditions: Depression of respiratory center in brain that controls breathing rate – drugs or head trauma Paralysis of respiratory or chest muscles Emphysema

Respiratory Acidosis Acute conditons: Adult Respiratory Distress Syndrome Pulmonary edema Pneumothorax

Compensation for Respiratory Acidosis Kidneys eliminate hydrogen ion and retain bicarbonate ion

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

Respiratory Alkalosis 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

Compensation of Respiratory Alkalosis Kidneys conserve hydrogen ion Excrete bicarbonate ion

Metabolic Acidosis Bicarbonate deficit - blood concentrations of bicarb drop below 22mEq/L Causes: Loss of bicarbonate through diarrhea or renal dysfunction Accumulation of acids (lactic acid or ketones) Failure of kidneys to excrete H+

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)

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(volume contraction alkalosis) Endocrine disorders(hyperaldosteronism) Heavy ingestion of antacids Severe dehydration

Compensation for Metabolic Alkalosis Respiratory compensation– hypoventilation

Diagnosing Acid Base Disorders

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.

THANKS