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Acid-base Regulation in human body
Dr. Noor-ul-ain Waheed Assistant Professor Biochemistry KEMU
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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
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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
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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-)
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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
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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
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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
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DISTRIBUTION OF BUFFERS
Extra-cellular (Bicarbonate, Proteins) Blood Buffers (Bicarbonate, Plasma Proteins, Hemoglobin, Phosphate) Intra-cellular (Phosphate, Proteins, Bicarbonate) Renal (Phosphate, Ammonia, Bicarbonate)
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The Most Important Buffer System
Bicarbonate buffer system Carbonic Anhydrase CO2 + H2O H2CO3 H+ + HCO3- Sites: RBC, lung epithelium, stomach, renal tissue, intestinal tissue
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WORKING IN STOMACH
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Bicarbonate buffers maintains alkalinity of blood
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Transport of carbon dioxide working with hemoglobin
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WORKING WITH RENAL BUFFERS
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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
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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- )
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pH Derangements
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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
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Respiratory Acidosis Acute conditons:
Adult Respiratory Distress Syndrome Pulmonary edema Pneumothorax
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Compensation for Respiratory Acidosis
Kidneys eliminate hydrogen ion and retain bicarbonate ion
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Respiratory Alkalosis
Carbonic acid deficit pCO2 less than 35 mm Hg (hypocapnea) Most common acid-base imbalance Primary cause is hyperventilation
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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
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Compensation of Respiratory Alkalosis
Kidneys conserve hydrogen ion Excrete bicarbonate ion
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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+
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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)
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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
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Compensation for Metabolic Alkalosis
Respiratory compensation– hypoventilation
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Diagnosing Acid Base Disorders
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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.
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THANKS
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