Acid-Base Balance PDF

# Acid-Base Balance ## What is acid-base balance? Refers to the precise regulation of free (that is unbound) hydrogen ion (H+) concentration in the body fluids. ## Why acid-base balance is important? 1. Changes in excitability of nerve & muscle cells 2. Influence on enzyme activity 3. Influence...

# Acid-Base Balance ## What is acid-base balance? Refers to the precise regulation of free (that is unbound) hydrogen ion (H+) concentration in the body fluids. ## Why acid-base balance is important? 1. Changes in excitability of nerve & muscle cells 2. Influence on enzyme activity 3. Influence on K+ levels in body (e.g. acidosis causes decreased K+ secretion whereas alkalosis causes increased K+ secretion) 4. Changes in excitability of nerve & muscle cells ## Sources of H+ ion in body 1. Carbonic acid formation by metabolic process 2. Organic acids from intermediary metabolism, the body has elaborate mechanisms that maintain blood H+ concentration within a narrow range pH of 7.45 to 7.35, where pH = -log [H+]. Ideally, H+ is 40 nEq/L (40 nmol/L) and pH = 7.40. Disturbances of these mechanisms can have serious clinical consequences. Metabolism of carbohydrates and fats generates of carbon dioxide (CO2)daily. CO2 is not an acid itself, but CO2 combines with water (H2O) in the blood to create carbonic acid (H2CO3), which dissociates into hydrogen ion (H+) and bicarbonate (HCO3-). amounts of organic acid derive from the following: - Incomplete metabolism of glucose and fatty acids into lactic acid and ketoacids - Hydrolysis of dietary phosphate - "Fixed" or "metabolic" acid load cannot be exhaled and therefore must be neutralized or excreted by the kidneys. ## Types of Acid-Base Disorders There are two abnormalities of acid-base balance: * **Acidosis:** The blood has too much acid (or too little base), resulting in a decrease in blood pH. * **Alkalosis:** The blood has too much base (or too little acid), resulting in an increase in blood pH. Acidosis and alkalosis are not diseases but rather are the result of a wide variety of disorders. The presence of acidosis or alkalosis provides an important clue to doctors that a serious problem exists. ## Types of acidosis and alkalosis Acidosis and alkalosis are categorized depending on their primary cause as * **Metabolic** * **Respiratory** ## Henderson-Hasselbalch equation [A-] pH = pK + log [HA] where - pH = -log10[H+] (pH units) - PK = -log10 K (pH units) - [A-] = Concentration of base form of buffer (mEq/L) - [HA] = Concentration of acid form of buffer (mEq/L) ## What is Buffer? buffer is a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid | Weak Acid | Conjugate Base | |:--:|:--:| | *H₂CO₃* (carbonic acid) | *HCO₃-* (bicarbonate) | | *H₂PO₄* (dihydrogen phosphate) | *HPO₄²-* (monohydrogen phosphate) | | *NH₄+* (ammonium ion) | *NH₃* (ammonia) | # Classes of Acids - **Fixed Acids:** Fixed acids are acids that do not leave solution. Once produced, they remain in body fluids until they are eliminated by the kidneys. Sulfuric acid and phosphoric acid are the most important fixed acids in the body. They are generated in small amounts during the catabolism of amino acids and compounds that contain phosphate groups, including phospholipids and nucleic acids. - **Organic Acids:** Organic acids are acid participants in, or byproducts of, cellular metabolism. Important organic acids include lactic acid (produced by the anaerobic metabolism of pyruvate) and ketone bodies (synthesized from acetyl-CoA). Under normal conditions, most organic acids are metabolized rapidly, so significant accumulations do not occur. - **Volatile Acids:** Volatile acids can leave the body by entering the atmosphere at the lungs. Carbonic acid (H₂CO) is a volatile acid that forms through the interaction of water and carbon dioxide. CO₂ + H2O → H2CO3 → H+ + HCO3- Carbon Water Carbonic Bicarbonate dioxide acid ion # pH is regulated by | TYPE | RESPONSE TIME | EXAMPLE | |---|---|---| | Chemical buffer systems | Immediate | Bicarbonate buffer system, Phosphate buffer system, Protein buffer system | | Physiological buffer systems | Minutes, Hours | Respiratory response system, Renal response system | # Buffer Systems - **Intracellular fluid (ICF)** - *Phosphate Buffer System:* The phosphate buffer system has an important role in buffering the pH of the ICF and of urine. - _Protein Buffer Systems:_ Protein buffer systems contribute to the regulation of pH in the ECF and ICF. These buffer systems interact extensively with the other two buffer systems. - _Hemoglobin buffer system (RBCs only)_, _Amino acid buffers (All proteins)_, _Plasma protein buffers_ - **Extracellular fluid (ECF)** - *Carbonic Acid-Bicarbonate Buffer System:* The carbonic acid-bicarbonate buffer system is most significant in the ECF ## Regulation of pH by buffers ### Bicarbonate Buffer System - The bicarbonate buffer system is a mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3, a weak base), in the same solution. - When a strong acid such as HCl is added to this buffer system: HCl + NaHCO₃ → H₂CO₃ + NaCl strong acid weak base weak acid salt - When a strong base such as sodium hydroxide (NaOH) is added: ### Phosphate Buffer System - The operation of the phosphate buffer system is nearly identical to that of the bicarbonate buffer. The components of the phosphate system are the sodium salts of dihydrogen phosphate (H2PO4¯) and monohydrogen phosphate (HPO4²¯). NaH2PO4 acts as a weak acid. Na2HPO4 with one less hydrogen atom, acts as a weak base. Again, H+ released by strong acids is tied up in weak acids: HCI + Na2HPO4 → NaH2PO4 + NaCl strong acid weak base weak acid salt - And strong bases are converted to weak bases: NaOH + NaH2PO4 → Na2HPO4 + H2O strong base weak acid weak base water ## The main buffers in the human body | Buffer | Acid | Conjugate base | Site of main buffering action | |:--:|:--:|:--:|:--:| | Hemoglobin | HHb | Hb- | Erythrocytes | | Proteins | HProt | Prot- | Intracellular fluid | | Phosphate buffer | H2PO4 | HPO4² | Intracellular fluid | | Bicarbonate | CO2 → H2CO3 | HCO3- | Extracellular fluid | ## pH regulation by respiration A rising plasma H+ concentration resulting from any metabolic process excites the respiratory center indirectly (via peripheral chemoreceptors) to | Respiratory Compensations (pH 7.4) | Acid-Base Status | Nonrespiratory (metabolic) Alkaliosis (pH 7.7) | Nonrespiratory (metabolic) Acidosis (pH 7.1) | |:--:|:--:|:--:|:--:| | Normal | ↑ | ↓ | ↑ | | Normal | ↑ | ↓ | ↑ | | Normal | ↓ | ↑ | ↓ | | Normal | ↓ | ↑ | ↓ | When blood pH rises, the respiratory center is depressed. As respiratory rate drops and respiration becomes shallower, CO2 accumulates, pushing the equilibrium to the right and causing the H+ concentration to increase. ## Role of the lungs | Condition and Hallmark | Possible Causes; Comments | |:--:|:--:| | Respiratory Acidosis (Hypoventilation) | Impaired lung function (e.g., chronic bronchitis, cystic fibrosis, emphysema): impaired gas exchange or alveolar ventilation, Impaired ventilatory movement: paralyzed respiratory muscles, chest injury, extreme obesity, Narcotic or barbiturate overdose or injury to brain stem: depression of respiratory centers, resulting in hypoventilation and respiratory arrest | | Respiratory Alkalosis (Hyperventilation) | Strong emotions: pain, anxiety, fear, panic attack, Hypoexemia: asthma, pneumonia, high altitude, represents effort to raise Po2 at the expense of excessive CO2 excretion, Brain tumor or injury: abnormal respiratory controls | ## Renal mechanism for regulation of acid base balance by 1. Conservation/ reabsorption of HCO3- 2. Generation of new HCO3- via * a-excretion of buffered H+ / excretion of H+ as titratable acid and * b-NH4+ excretion 3. Excretion of HCO3 ## Table 26.3 Causes and Consequences of Acid-Base Imbalances | Condition and Hallmark | Possible Causes; Comments | |:--:|:--:| | Metabolic Acidosis | Severe diarrhea: bicarbonate-rich intestinal (and pancreatic) secretions rushed through digestive tract before their solutes can be reabsorbed; bicarbonate ions are replaced by renal mechanisms that generate new bicarbonate ions, Renal disease: failure of kidneys to rid body of acids formed by normal metabolic processes, Untreated diabetes mellitus: lack of insulin or inability of tissue cells to respond to insulin, resulting in inability to use glucose; fats are used as primary energy fuel, and ketoacidosis occurs, Starvation: lack of dietary nutrients for cellular fuels; body proteins and fat reserves are used for energy-both yield acidic metabolites as they are broken down for energy, Excess alcohol ingestion: results in excess acids in blood | ## Role of the kidneys - The kidneys are able to affect blood pH by excreting excess acids or bases. The kidneys have some ability to alter the amount of acid or base that is excreted, but because the kidneys make these adjustments more slowly than the lungs do, this compensation generally takes several days. - Bicarbonate ion levels below or above the normal range of 22-28 mEq/L indicate a metabolic acid-base imbalance. The second most common cause of acid-base imbalance, metabolic acidosis, is recognized by low blood pH and HCO3- levels ## Summary of Acid-Base Disorders | Disorder | CO₂ + H2O → H+ + HCO3- | Respiratory Compensation | Renal Compensation or Correction | |:--:|:--:|:--:|:--:| | Metabolic Acidosis | ↓ ↑ ↓ | Hyperventilation | ↑ HCO reabsorption (correction) | | Metabolic Alkalosis | ↑ ↓ ↑ | Hypoventilation | ↑ HCO, excretion (correction) | | Respiratory Acidosis | ↑ ↑ ↑ | None | ↑HCO, reabsorption (compensation) | | Respiratory Alkalosis | ↓ ↓ ↓ | None | ↓HCO, reabsorption (compensation) | Bold arrows indicate initial disturbance. ## Summary of defense lines To prevent acidosis or alkalosis, several control systems are available: 1. **Acid-base buffer system:** Which are present in all body fluids that immediately combine with any acid or alkali and thereby prevent excessive change in [H + ] this system can act within a fraction of a second to prevent excessive changes in [H + ]. 2. **Respiratory center:** Upon the changes in [H+] the respiratory center is immediately stimulated to alter the rate of breathing .As a result, the rate of CO2 removal from the body fluids is automatically changed and this causes the [H + ] to return toward normal. This mechanism takes 1 to 15 minutes to readjust the [H+] after sudden changes have occurred. 3. Kidneys: when the [H + ] changes from normal the kidneys excrete either an acid or alkaline urine thereby also helping readjust the [H + ] of the body fluids back to normal. The kidneys provide the most powerful of all the acid-base regulatory systems but requires many minutes to several days to readjust the [H + ]. ## The buffer system of the body fluids The three major buffer systems of the body fluids are the bicarbonate buffer, the phosphate buffer, and the protein buffer. [1] The bicarbonate buffer system: It consist of mixture of carbonic acid (H2CO3) and sodium bicarbonate (NaHCO3) [2] Phosphate buffer system: It constitutes about 2% of buffering capacity of whole blood. It is composed of NaH2PO4 and Na2HPO4. HCl + Na2HPO4 → NaH2PO4 + NaCL The net result of this reaction is that the HCl is removed and in its place an additional quantity of NaH2 PO4 is formed which is weak acid and the pH changes relatively slight. NaOH + NaH2PO4 Na 2 HPO4 + H2O [3] The protein buffer system: It constitutes about 42% of buffering capacity of whole blood (Hb 35% and plasma proteins 7%). ## Respiratory regulation of acid-base balance [1] The CO2 concentration in the extracellular fluid can be increased or decreased if the rate of metabolic formation of CO2 becomes increased or decreased respectively. ## Renal regulation of acid-base balance The kidneys regulate H+ concentration principally by increasing or decreasing the HCO3 - concentration in the body fluid. [1] Increase H + secretion to the urine and HCO3 - reabsorption to the interstitial fluids: