Acid-Base Balance PDF
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This document provides detailed explanation of Acid-Base Balance, a crucial aspect of human physiology. It covers various aspects including the concept of maintaining the delicate balance between acids and bases in the body, exploring the clinical implications, and offering detailed insights on the subject of acid-base balance.
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**[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).