Acid-Base Balance PDF

**[Acid-Base Balance: ]** - The **balance** between acids and bases is **delicate with a narrow margin of error**. - **The normal pH of arteriole blood = 7.4 with a normal range of 7.45 to 7.35.** - ECF \[H+\] = 0.00004 mEq/L or 40 nEq/L. - The normal \[H+\] variation = +...

**[Acid-Base Balance: ]** - The **balance** between acids and bases is **delicate with a narrow margin of error**. - **The normal pH of arteriole blood = 7.4 with a normal range of 7.45 to 7.35.** - ECF \[H+\] = 0.00004 mEq/L or 40 nEq/L. - The normal \[H+\] variation = +/- 3-5 nEq/L. - The lethal extremes are \160 nEq/L; but will be very unwell within this range. - **Normal valves:** 1. **Extracellular fluid (arterial, venous, and interstitial fluid):** a. **Arterial blood** **Normal pH = 7.4 (4.0 x 10^-5^).** - Arterial blood is the most important in determining changes in acid-base balance. - Acidosis from the increase in body fluid acidity \[H+\] **Acidaemia (pH \7.45)** b. **Venous blood** **Normal pH = 7.35 (4.5 x 10^-5^).** - Lower pH due to increase PCO~2~ from metabolism. c. **Interstitial fluid** **Normal pH = 7.35 (4.5 x 10^-5^).** 2. **Intracellular fluid** **Range of pH = 6.0 -- 7.4 (1 x 10^-3^ to 4 x 10^-5^).** - Variable range due to different rates of metabolism between cell types and conditions. 3. **Urine** **Range of pH = 4.5 -- 8.0 (3 x 10^-2^ to 1 x 10^-5^).** - Variable range due to different rates of waste excretion during changing conditions/stimuli. - **The homeostatic acid-base balance is important as changes in pH has a number of effects on the body:** 1. **Metabolism** - **Enzymatic activity is dependent on pH** Changes in pH result in reduced rxn efficiency. - See table for consequences in acidaemia and alkalaemia. 2. **Neuromuscular system** - As plasma Ca^2+^ binding to albumin is pH-dependent, changes in pH can **impact free \[Ca^2+^\]**. - **Acidosis** Has an **inhibitory effect** on the neuromuscular system. - **Mechanism: Acidosis increases free \[Ca^2+^\] Decreased bathmotrophy.** - Occurs due to the blocking of the Na~V~ channels Causing a raise in the AP threshold (i.e., harder to stimulate). - This effect is compounded by increase in serum \[K^+^\]. - **Outcome** Headaches, confusion, lethargy, tremors, sleepiness, and cerebral dysfunction that can lead to coma. - **Alkalosis** Has an **excitatory effect** on the neuromuscular system. - **Mechanism: Alkalosis decreases free \[Ca^2+^\] Increased bathmotrophy.** - This effect is compounded by decrease in serum \[K^+^\]. - **Outcome** Muscular weakness, pain, cramping, and spasms of SKM and SM (tetany). 3. **Cardiovascular** - **Acidosis**: a. Impaired cardiac contractility Decreased CO. b. Arteriolar dilation and venoconstriction Hypotension, increased pulmonary vascular resistance, and decreased hepatorenal blood flow. c. Increased risk for cardiac arrhythmias. - **Alkalosis**: a. Arteriolar constriction Reduced coronary blood flow. b. Reduced anginal threshold and increased risk of cardiac arrhythmias. 4. **Respiratory** - **Acidosis** **Hyperventilation** (may result in respiratory failure due to muscle fatigue). - **Alkalosis** **Hypoventilation** (may result in hypercapnia and hypoxemia). - Everyday there is a production of 1 mmol of fixed acid/kg body weight (i.e., 60 kg = 60 mmol/day). - Most acid comes from the metabolism from CHO and fats due to their high energy density. - **Examples of metabolic activities that add \[H^+^\] to the body include:** a. Glycolytic metabolism Production of lactic acid. b. Oxidative metabolism Produces CO~2~ which is converted to carbonic acid. c. FA and AA metabolism Ketoacids. d. Pancreatic HCO~3~^-^ production H^+^ loading in blood. - This is usually balanced with gastric acid production loading HCO~3~^-^ into the blood. - However, vomiting can disrupt this balance Alkalosis. - **Defense mechanism for altered blood pH include:** 1. **Chemical buffering** Immediate but exhaustible response. - Intracellular and extracellular buffers that provide immediate response to acid-base disturbances. - A buffer is a substance that reversibly consumes or release H^+^ to prevent changes in pH. - These buffer systems are made up of a weak acid and its conjugate base (anion). - The conjugate base can accept H+ and the weak acid can donate H+ Minimises changes in free \[H+\]. - The Henderson-Hasselbalch equation describes the relationship between pH of a buffer system and the concentration of its components: - pH = pKa + Log (\[anion\] / \[weak acid\]) - The pKa is the dissociation constant of the weak acid; so, it determines the optimal pH for max buffering capacity That is the system works to minimise pH changes nears its pKa. - The buffer power is determined by the pH appropriateness of the system, and the pKa does not always match the pH. - **Capacity is determined by:** 1. The relative concentrations of the \[anion\] and \[acid\] Determine how much the acid or base can be buffered (i.e., the reaction can be limited by one of these components). 2. Total \[buffer\]. - **There are a number of chemical buffer systems in the body:** 1. **Bicarbonate (HCO~3~^-^)** Most dominant ECF buffer. - The pKa = 6.37 Which is less than blood pH (7.4). - To negate this, carbonic acid is produced in a 1:20 ratio with bicarbonate. - Equation = CO~2~ + H~2~O ↔ H~2~CO~3~ ↔ H^+^ + HCO~3~^-^ - Alkalosis: NaOH Na^+^ + OH^-^ OH^-^ feeds into bicarbonate system. - Acidosis: HCI H^+^ + CI^-^ H+ feeds into the bicarbonate system. 2. **Ammonia (NH~3~)** ECF buffer; important for buffering the renal tubular fluid. - The pKa = 9.25. - NH~4~^+^ ↔ H^+^ + NH~3~ 3. **Phosphate (PO~4~^2-^)** ICF buffer. - The pKa = 7.21. - H~2~PO~4~^-^ ↔ H^+^ + HPO~4~^2-^ 4. **Proteins** ICF buffers (e.g., Hb in the RBCs). - The pKa of proteins is variable but many are close to \~7.4; Hb is \~6.8. - Carboxy: R-COOH ↔ R-COO^-^ + H^+^ - Amino: R-NH~3~^+^ ↔ R-NH~2~ + H^+^ 2. **Pulmonary regulation** Response between minutes to hours; limited capacity. - PCO~2~ is regulated by changes in tidal volume and respiratory rate. - CO~2~ is acidic, so exhalation Increased blood pH (and vice versa). - Central and peripheral chemoreceptors detect changes in pH and \[CO2\] to mediate a compensatory response by modulating RR and TV. - Acidosis Hyperventilation Aim is to 'blow-off' excess CO2. - Doubled V~A~ Increase pH by 0.23 (i.e., 7.4 to 7.63). - Alkalosis Hypoventilation Aim is to retain CO2. - Quartered (1/4) V~A~ Decrease pH by 0.45 (i.e., 7.4 to 6.95). 3. **Renal regulation** Response between hours to days; powerful and infinite capacity. - The kidneys adjust the amount of HCO~3~^-^ and H^+^ that is excreted depending on the state. - Renal excretion of HCO~3~^-^ Decreased blood pH. - Renal excretion of H^+^ Increased blood pH. - Under normal conditions, the kidneys constantly remove HCO~3~^-^ from the blood with some reabsorbed back into the blood to maintain balance (I.e., avoid development of acidaemia). - However, to do this the HCO~3~^-^ must be converted to H~2~O and CO~2~, which involves the secretion of H^+^ (occurs in a 1:1 ratio). - H^+^ is secreted by secondary active transport in the PCT, TAL, and the early DCT. - Apical membrane Na^+^ / H^+^ counter-transport. - Basolateral membrane Powered by Na^+^ / K^+^ ATPase. - HCO~3~^-^ is co-transported with Na^+^ or exchanged with CI^-^ into renal interstitial fluid. - H^+^ is secreted by primary active transport in the late DCT and CD (fine-tuning). - H^+^ ATPase CI^-^ follows. - Carbonic anhydrase is tethered to the glycocalyx of the tubular epithelium to facilitate this process. - \[H^+^\] is the limiting factor in this reaction. - Acid can also be secreted as ammonium Glutamine (AA) can be deaminated in the proximal tubular cells, resulting in 2x NH~4~^+^ and 2x HCO~3~^-^ production. - NH~4~^+^ is countered transported into the tubular lumen in exchange for Na^+^. - HCO~3~^-^ is diffuses into the renal interstitial fluid Increasing blood pH. - In alkalosis, hypokalaemia can develop as it is an obligate cation partner for HCO~3~^-^. - Other mechanisms include: 1. The shift of K^+^ from the plasma ICF via Na^+^ / K^+^ ATPase. 2. In metabolic alkalosis is a common complication of volume depletion, so K^+^ can also be lost via aldosterone-mediated mechanisms. - Acid-base balance is assessed through an arterial blood gas analysis. - The pH establishes the primary process, while PCO~2~ and \[HCO~3~^\_^\] reflect respiratory and metabolic origin. - **Acid-base disorders:** 1. **Metabolic** Occur due to production, ingestion, or loss of acid/bases. - Represented by change in plasma \[HCO~3~^-^\]. - Metabolic disorder Respiratory compensation. - **Respiratory compensation:** a. Acidosis Increased ventilation to 'blow-off' CO~2~. b. Alkalosis Decreased ventilation to retain CO~2~. - Metabolic acidosis can also be determined by the presence of a larger serum anion gap. - The normal serum anion gap is 12 mEq/L, but when this gap is \> 26 mEq/L it implies the existence of an organic acidosis (i.e., poisoning, diabetic/starvation ketoacidosis, methanol, aspirin). - This anion gap essentially represents all the anions that are not tested in the lab (i.e., not CI^-^ or HCO~3~^-^). - UA \~20-24 mEq/L. - UC (i.e., everything but Na^+^) \~11 mEq/L. - Thus, the gap is 23 -- 11 = 12 mEq/L. - A normal anion gap is the presence of metabolic acidosis is more representative of aetiologies such as diarrhoea (loss of bicarbonate), and use of carbonic anhydrase-inhibitors (e.g., acetazolamide, topiramate). 2. **Respiratory** Occur due to hyper- or hypoventilation. - Represented by change in PCO~2~. - Respiratory disorder Metabolic compensation. - **Metabolic compensation:** a. Acidosis Increased HCO~3~^\_^ reabsorption, Increased H^+^ excretion, increased HCO~3~^\_^ production. b. Alkalosis Decreased HCO~3~^\_^ reabsorption (excreted in urine).