Acid-Base Balance PDF

ACID-BASE BALANCE An acid is a substance that can yield a hydrogen Ion (H) or hydronium ion when dissolved in water. Abase is a substance that can yield hydroxyl ions (OH( The relative strengths of acids and bases, their ability to dissociate in water, are described by their dissociation co...

ACID-BASE BALANCE An acid is a substance that can yield a hydrogen Ion (H) or hydronium ion when dissolved in water. Abase is a substance that can yield hydroxyl ions (OH( The relative strengths of acids and bases, their ability to dissociate in water, are described by their dissociation constant (also ionization constant K value). The pK, defined as the negative log of the ionization constant, is also the pH in which the protonated and unprotonated forms are present in equal concentrations. Strong acids have pK values of less than 3. , strong bases have pK values greater than 9.0. For acids, raising the pH above the pK will cause the acid to dissociate and yield an H. For bases, lowering the pH below the pK will cause the base to release OH. Many species have more than one pK, meaning they can accept or donate more than one H. To change 100 mL of normal blood from a pH of 7.35 to a pH of 7.00, approximately 25 mL of 0.05 mol/L HCl is needed. With 5.5 L of blood in the average body, more than 1300 mL of HCl would be required to make this same change in pH. The normal concentration of H in the extracellular body fluid ranges from 36–44 nmol/L (pH, 7.34–7.44); however, through metabolism, the body produces much greater quantities of H. Through mechanisms that involve the lungs and kidneys, the body controls and excretes H in order to maintain pH homeostasis Any H value outside this range will cause alterations in the rates of chemical reactions within the cell and affect the many metabolic processes of the body and can lead to alterations in consciousness, neuromuscular irritability, tetany, coma, and death. The logarithmic pH scale expresses H concentration (c is concentration) :pH = log1/cH = -- log cH The reference value for arterial blood pH is 7.40 and is equivalent to an H concentration of 40 nmol/L. Because pH is the negative log of the cH, an increase in H concentration decreases the pH, whereas a decrease in H concentration increases the pH. A pH below the reference range (7.34) is referred to as acidosis, whereas a pH above the reference range (7.44) is referred to as alkalosis. Technically, the suffix -osis refers to a process in the body; the suffix -emia refers to the corresponding state in blood (-osis is the cause of the -emia). bicarbonate–carbonic acid buffer system. H2CO3 is a weak acid because it does not completely dissociate into H and HCO3. (In contrast, a strong acid, such as HCl, completely dissociates into H and Cl in solution.) When an acid is added to the bicarbonate– carbonic acid system, the HCO3 will combine with the H from the acid to form H2CO3. When a base is added, H2CO3 will combine with the OH group to form H2O and HCO3. In both cases, there is a smaller change in pH than would result from adding the acid or base to an unbuffered solution. Although the bicarbonate–carbonic acid system has low buffering capacity, it still is an important buffer for three reasons: (1) H2CO3 dissociates into CO2 and H2O allowing CO2 to be eliminated by the lungs and as water; (2) changes in CO2 modify the ventilation (respiratory) rate; and (3) HCO3 concentration can be altered by the kidneys. this buffering system immediately counters the effects of fixed nonvolatile acids (HA) by binding the dissociated hydrogen ion (HA HCO3 H2CO3 A). The resultant H2CO3 then dissociates, and the H is neutralized by the buffering capacity of hemoglobin. shows the interrelationship of hemoglobin in the red blood cells and the H from the bicarbonate buffering system Other buffers also are important. Phosphate buffer system (HPO4 2 H2PO4 ) plays a role in plasma and red blood cells and is involved in the exchange of sodium ion in the urine H filtrate. Plasma protein, especially the imidazole groups of histidine, also forms an important buffer system in plasma. Most circulating proteins have a net negative charge and are capable of binding H. The lungs and kidneys play important roles in regulating blood pH. The interrelationship of the lungs and kidneys in maintaining pH is depicted by the Henderson- Hasselbalch equation The numerator (HCO3 ) denotes kidney function, whereas the denominator (pCO2, which represents H2CO3) denotes lung function. The lungs regulate pH through or elimination of CO2 by changing the rate and volume of ventilation. The kidneys regulate pH by excreting acid, primarily in the ammonium ion, and by reclaiming HCO3 from the glomerular filtrate.  Regulation of Acid-Base Balance: Lungs and Kidney Carbon dioxide, the end product of most aerobic metabolic processes, easily diffuses out of the tissue where it is produced and into the plasma and red cells in the surrounding capillaries. In plasma, a small amount of CO2 is physically dissolved or combined with s.proteins to form carbamino compounds. In the lungs, the process is reversed. Inspired O2 diffuses from the alveoli into the blood and is bound to hemoglobin, forming oxyhemoglobin (O2Hb). The H that was carried on the (reduced) hemoglobin in the venous blood is released to recombine with HCO3 to form H2CO3, which dissociates into H2O and CO2. The CO2 diffuses into the alveoli and is eliminated through ventilation. The net effect of the interaction of these two buffering systems is a minimal change in H concentration between the venous and arterial circulation. When the lungs do not remove CO2 at the rate of its production (as a result of decreased ventilation or disease), it accumulates in the blood, causing an increase in H concentration. If, however, CO2 removal is faster than production (hyperventilation), the H concentration will be decreased. Consequently, ventilation affects the pH of the blood. A change in the H concentration of blood that results from non respiratory disturbances causes the respiratory center to respond by altering the rate of ventilation n an effort to restore the blood pH to normal. The lungs, by responding within seconds, together with the buffer systems, provide the first line of defense to changes in acid-base status. The kidney’s main role in maintaining acid-base homeostasis is to reclaim HCO3 from the glomerular filtrate. Without this reclamation, the loss of HCO3 in the urine would result in an excessive acid gain in the blood. sodium (Na) in the glomerular filtrate is exchanged for H in the tubular cell. The H combines with HCO3 in the filtrate to form H2CO3, which is converted into H2O and CO2 by carbonic anhydrase. The CO2 easily diffuses into the tubule and reacts with H2O to reform H2CO3 and then HCO3 which is reabsorbed into the blood along with sodium.With alkalotic conditions, the kidney excretes HCO3 to compensate for the elevated blood pH. Under normal conditions, the body produces a net excess (50–100 mmol/L) of acid (H) each day that must be excreted by the kidney. Because the minimum urine pH is approximately 4.5, the kidney excretes little non buffered H. The remainder of the urinary H combines with dibasic phosphate (HPO4) and ammonia (NH3) and is excreted as dihydrogen phosphate (H2PO4 ) and ammonium (NH4 It is unlikely that the plasma will exceed an HCO3 value of 30 mmol/L unless the excretory capabilities fail (e.g., kidney failure occurs). However, a frequent exception to this is compensatory retention of HCO3 for chronic hypercarbia as seen with chronic lung disease. The HCO3 level may increase if an excessive amount of lactate, acetate, or HCO3 is intravenously infused. It also may increase if there is an excessive loss of chloride with sweating, vomiting, or prolonged nasogastric suction) because the HCO3 will be retained by the tubule to preserve electroneutrality replacement (as occurs with Several factors may result in decreased HCO3 levels. Most diuretics, regardless of mechanism of action, favor the excretion of HCO3 Reduced HCO3 reabsorption also occurs in conditions in which there is an excessive loss of cations. In kidney dysfunction (such as chronic nephritis or infections), HCO3 reabsorption may be impaired. ASSESSMENT OF ACID-BASE HOMEOSTASIS The Bicarbonate Buffering System and the Henderson-Hasselbalch Equation pH = pK + log cA / cHA where A is proton acceptor, or base (e.g., ,)HCO3). HA is proton donor, or weak acid (e.g., H2CO3), and pK’ is pH at pH pK log (Eq. 16-3) where A is proton acceptor, or base (e.g., HCO3) HA is proton donor, or weak acid (e.g., H2CO3), and pK’ is pH at which there is an equal concentration of protonated and unprotonated species. Knowing any of the three variables allows for the calculation of the fourth. There are many factors that can influence the amount of O2 that moves through the alveoli into the blood and then to the tissue. Among the more common are: Destruction of the alveoli. The normal surface area of the alveoli is as big as a tennis court. When the surface area is destroyed to a critically low value by diseases such as emphysema, an inadequate amount of O2 will move into the blood.  Pulmonary edema. Gas diffuses from the alveoli to the capillary through a small space. With pulmonary edema, fluid “leaks” into this space, increasing the distance between the alveoli and capillary walls and causing a barrier to diffusion Airway blockage. Airways can be blocked, preventing the air from the atmosphere from reaching the alveoli. Asthma and bronchitis are more common causes of this type of problem  Inadequate blood supply. When the blood supply to the lung is inadequate, O2 enters the blood in the lungs, but not enough blood is being carried away to the tissue where it is needed. This may be the consequence of a blockage in a pulmonary blood vessel (pulmonary embolism), pulmonary hypertension, or a failing heart. Diffusion of CO2 and O2. Because O2 diffuses 20 times slower than CO2, it is more sensitive to problems with diffusion. Structural or physiologic alterations to the alveolar-capillary bed impair O2 uptake with minimal alteration of CO2 excretion. This type of hypoxemia is generally treated with supplemental O2. The percentage of O2 can be increased temporarily when needed; however, 60% or higher O2 concentrations must be used with caution because it can be toxic to the lungs  Acid-Base Balance The pH of blood plasma should be within the narrow range 7.35-7.45. The pH of plasma is stable by different buffers: A-CO2 excretion via lung & excretion of nonvolatile acids through kidney  B-Buffers: 1. HCO3-/H2CO3: Most important in plasma, glomerular filtrate & RBCs HCO𝟑−𝟏 +𝑯+ →H2CO3→CO2+H2O 2. HPO𝟒−𝟐 /H2PO4-: Most important in urine 3. Plasma Proteins as buffers: the imidazole ring of histidene acts as buffer. It is important in plasma 4. Hb as buffer: important in RBCs Alkalosis: ↑ in blood alkalinity due to an accumulation of alkaline substances or reduction of acids Acidosis:↑in the acidity of blood due to an accumulation of acids or an excessive loss of HCO3-  Anion Gap: cation - an ion carrying a positive charge, anion - an ion carrying a negative charge The anion gap is a calculation of the difference between anions and cations in blood. The gap represents chemical anions other than those used in the formulas (sodium, potassium, chloride, and bicarbonate) that might be present in blood. The gap is used to estimate acid-base and electrolyte disturbances. The most commonly used formula is Anion Gap (AG)=([Na+]+[K+])-([HCO3-]+[Cl-]) The reference range is (10 to 20 mmol/L).  Its AG adjusted to albumin & phosphate: AG=([Na+ + K+] – [HCO3– + Cl–]) – 2 [Alb g/dl] – 0.5 [PO4 mg/dl] – lactate or AG=([Na+ + K+] – [HCO3– + Cl–]) – 2 [Alb g/dl] – 1.5 [PO4 mmol/l] – lactate AG > 20 mmol/l: 1) ↓unmeasured cations: i. Hypocalcemia ii. Hypomagnesemia. 2)↑ unmeasured anions: i. Hyperalbuminemia (e.g. due to volume depletion) ii. ↑organic anions ↓AG < 7 mmol/l: 1) ↑ unmeasured cations: i. Hyperkalemia. ii. Hypermagnesemia. iii. Lithium intoxication. iv. Paraproteinemias. 2) ↓unmeasured anions: Hyperalbuminemia Note: commonly, a decreased anion gap is an indication of technical problems.  RENAL COMPENSATORY MECHANISM Kidney is the final defense mechanism against any changes in body pH. o PH of the unmodified glomerular filtrate is ~ 7.4 & urinary pH of a fasting person is ~ 6. This drop in pH is due to excretion of the nonvolatile acids produced by metabolic processes by the kidneys. o Renal excretion of acid and conservation of HCO3 occur through: (1) Reclamation of HCO3, (2) Production of ammonia and excretion of NH4+. Excretion of acids o Strong acids such as sulfuric, hydrochloric, and phosphoric acids are fully ionized at the pH of urine and are excreted only after the H+ derived from these acids reacts with a buffer base (e.g. HPO4= or NH3).  o Some acids (e.g. acetoacetate and β- hydroxybutyrate) are present in blood in ionized form but are partially non-dissociated urine pH & can be excreted as such. o To provide electrochemical balance, H+ from the tubular cells can be exchanged for Na+ from the tubular fluid (an energy- dependent). This process is enhanced in acidosis and decreased in alkalosis. o K+ competes with H+ in the Na+-H+ exchange. i. If the IC K+ level of renal tubular cells is ↑, more K+ and fewer H+ are exchanged for Na+ the urine becomes less acid and the acidity of body fluids increases. ii. If there is K+ depletion, more H+ are exchanged for Na+, and the urine becomes more acid and the body fluids become more alkaline (metabolic alkalosis). the body fluids become more alkaline (metabolic alkalosis). Notes: 1. Ammonia, being a gas, diffuses readily across the cell membrane into the tubular lumen, where it combines with H+ to form NH4+ ions that cannot cross cell membranes and is excreted with anions such as phosphate, chloride, or sulfate. 2. In normal persons, NH4+ production in the tubular lumen accounts for the excretion of ~ 60% (30-60 mmol) of the H+ associated with nonvolatile acids.  In fact, NH4+ excretion accounts for the greatest net excretion of H+ by the kidneys. 4. K+ depletion ↑NH4+ production while K+ overload↓it. 5. High protein diet↑ phosphate production & filtration; vice versa. 6. ↓GFR↓ H2PO4-. 7. More H+ is excreted more Na+ is reabsorbed Reclamation of HCO3 e.  Notes: The process of reclamation is enhanced in the acidosis (and decreased in alkalosis) as a result of increased Na+ - H+ exchange. Metabolic acidosis– acidosis resulting from increase in acids other than carbonic acid Causes and Clinical Signs of Metabolic Acidosis: Clinical signs: pH47 mm/Hg (H2CO3)  Causes: A- Loss of H+: 1-Severe vomiting & nasogastric suction (loss of HCl) 2-Renal loss of H+ due to a-certain diuretics (frusemide) ↓ H+, K+, Na+ b-↑Aldosterone B- Excess bicarbonate: Treatment with sodium bicarbonate, sodium lactate, citrate, or acetate C- Ingestion of Antacids Reference ranges: whole blood arterial pH, 7.35–7.45; whole blood arterial PCO2, 35–48 mm Hg; bicarbonate, 22–28 mmol/L.  Respiratory acidosis (Failure to ventilate)– acidosis caused by retention of carbon dioxide due to pulmonary insufficiency leading to increase carbonic acid levels. ↓pH, ↑HCO3-, ↑PCO2 (H2CO3) Causes: A- Acute respiratory failure: 1-Depression of respiratory 2-Pulmonary cardiac arrest B- Chronic respiratory failure: 1-Advanced chronic bronchitis 2-Emphysema Respiratory alkalosis Respiratory alkalosis (Hyperventilation): alkalosis with an acute reduction of plasma HCO3- and a proportionate reduction in plasma CO2 is caused by a deficit of carbonic acid and hyperventilation of CO2 gas. Causes:  Causes: A- Hypoxia: due to 1-CHF 2-Severe hypertension 3-Severe anemia (↓Hb ↓O2) 4-Pumonary diseases e.g. pneumonia & Pulmonary embolism 5-High altitude residents. B- Direct stimulation of respiratory center in brain: due to 1-psychogenic (hysteria) 2- hepatic failure 3-salicylate intoxification. C- Mechanical ventilation. A 7-year-old boy was admitted unconscious to a casualty department. On examination he was found to be hyperventilating. He had inadvertently consumed ethylene glycol antifreeze, which he had found in his parents’ garage stored in a lemonade bottle. Blood results were as follows: Plasma Sodium 134 mmol/L (135–145) Potassium 6.0 mmol/L (3.5– 5.0) Bicarbonate 10 mmol/L (24–32) Chloride 93 mmol/L (95–105) Glucose 5.3 mmol/L (3.5–6.0) Arterial blood gases pH 7.2 (7.35–7.45) PaCO2 3.18 kPa (4.6–6.0) PaO2 13.1 kPa (9.3–13.3).  DISCUSSION The results show a high anion gap, normally about 15–20 mmol/L, but in this case 37 mmol/L, with metabolic acidosis, i.e. (134 + 6) – (10 + 93). Hyperkalaemia is present due to the movement of intracellular K+ out of cells because of the acidosis. The compensatory mechanism of hyperventilation ‘blows off’ volatile acid in the form of CO2, hence the low PCO2 A 52-year-old woman with type I renal tubular acidosis attended a renal out-patient clinic. Her blood results were as follows: Plasma Sodium 144 mmol/L (135–145) Potassium 3.0 mmol/L (3.5–5.0) Bicarbonate 13 mmol/L (24–32) Chloride 118 mmol/L (95– 105)  DISCUSSION The results are suggestive of a normal anion gap metabolic acidosis or hyperchloraemic acidosis. Hypokalaemia is unusual in the face of an acidosis, one of the exceptions being renal tubular acidosis type I or II. Note that the anion gap here is (144 + 3) – (13 + 118) = 16 mmol/L, which is a normal gap although with high plasma [Cl–] and low [HCO3–]. A 67-year-old retired printer presented to casualty because of increasing breathlessness. He had smoked 20 cigarettes a day for 50 years. On examination he was found to be centrally cyanosed and coughing copious green phlegm. His arterial blood results were as follows: pH 7.31 (7.35–7.45) PaCO2 9.3 kPa (4.6–6.0) PaO2 6.9 kPa (9.3– 13.3) Bicarbonate 37 mmol/L (24–32)  DISCUSSION The patient had chronic obstructive pulmonary disease, and the blood gases show a respiratory acidosis with hypercapnia and hypoxia. The latter has resulted in central cyanosis. Compensation is via the kidneys, with increased acid excretion and HCO3– reclamation. Chronic cases of respiratory acidosis are usually almost totally compensated as there is time for the kidneys and buffer systems to adapt. This is unlike an acute respiratory acidosis due to bilateral pneumothorax, in which the rapid acute changes do not give sufficient time for the compensatory mechanisms to take place. This patient had an acute exacerbation of his lung disease and the CO2 retention exceeded the compensatory mechanisms.  A baby girl a few days old had had projectile vomiting since birth due to pyloric stenosis. Her blood results were as follows: Plasma Sodium 137 mmol/L (135–145) Potassium 3.0 mmol/L (3.5– 5.0) Bicarbonate 40 mmol/L (24–32) Chloride 82 mmol/L (95–105) Arterial blood gases pH 7.52 (7.35–7.45) PaCO2 6.2 kPa (4.6–6.0) PaO2 12.9 kPa (9.3– 13.3) DISCUSSION The results are suggestive of a metabolic alkalosis due to the severe vomiting. Note also the low plasma [Cl–] due to loss of hydrochloric acid in vomit, and hypokalaemia resulting from K+ movement into cells due to the alkalosis. Compensation is by hypoventilation and retention of CO2.  Tight homeostatic control of acid–base balance is essential, otherwise cell malfunction and death can occur. The kidneys excrete non- volatile acid via the renal tubules into the urine, while the lungs excrete volatile acid as CO2. The major extracellular buffer system involves HCO3–. Blood pH is inversely proportional to the PCO2 and directly proportional to the [HCO3–]. This can be determined on a blood gas analyser. Respiratory acidosis results from disorders of the respiratory system and is caused by CO2 retention. Conversely, respiratory alkalosis is due to excess CO2 loss, as in hyperventilation. In the case of the former, compensation is by the renal excretion of non-volatile acid and reclamation of HCO3–. In the latter, the kidneys compensate by losing HCO3–.  Metabolic (non-respiratory) acidosis results from increased non-volatile acid such as lactic acid or certain ketones. Compensation is by the lungs, which increase CO2 excretion by hyperventilation. Metabolic (non- respiratory) alkalosis is caused by HCO3– excess and acid loss, such as in prolonged vomiting, and its compensation is via the lungs, which hypoventilate, thereby retaining volatile acid as CO2.