Homeostasis B - Regulation of Acid-Base Balance PDF

Homeostasis – B Regulation of Acid-Base Balance Year 2, Unit I Problem 3 Academic Year 2023 - 2024 9/19/2024 1 Acid-Base Balance (Homeostasis) Acid-base balance is concerne...

Homeostasis – B Regulation of Acid-Base Balance Year 2, Unit I Problem 3 Academic Year 2023 - 2024 9/19/2024 1 Acid-Base Balance (Homeostasis) Acid-base balance is concerned with maintaining a normal hydrogen ion concentration in the body fluids. trying to keep hydrogen in the body in a normal range [H+] is precisely regulated so that H+ is in the range of 35 - 45 nEq/L. Normal H+ concentration in body fluids = 0.00000004 Eq/L (40 nEq/L) between 35-45 range fluids normal H in body pH is inversely related to the H+ concentration. pH = log 1 / [H+] = - log [H+] = −log (0.00000004) pH = 7.4. Normal range of pH venous blood and Arterial pH is 7.35 - 7.45 (Average = 7.4) interstitial fluid is more Venous blood and interstitial fluids have an average pH of 7.35. acidic because they have more CO2 When arterial pH is less than 7.35 it is called pH range compatible with life is 6.8 to 8.0. acidemia. above or lower than that When arterial pH is greater than 7.45, it is called the compensatory mechanisms alkalemia. can't work  Acids in the body Acid Production in the Body 1 CO2 that's produced from foods react with water and form carbonk. Sulfuric 2 acid phosphoric acid (from catabolism). 3 organic acids (metabolic byproduct) ex ketone bodies 1. CO2, produced by oxidation of foods, reacts with water to form carbonic acid (Volatile acid). Carbonic acid (H2CO3 ) is the most important factor affecting the pH of ECF. About 70 - 80 mEq H+ ingested or Inverse relationship between pH and concentration of CO2 produced each day by metabolism. 2. Sulfuric acid and phosphoric acid (non-volatile or fixed acids) Generated during catabolism of amino acids 3. Organic acids Metabolic byproducts such as lactic acid, and ketone bodies 9/19/2024 3 Mechanisms of pH Regulation Mechanisms of pH Regulation- Body Fluid Buffer Systems Bicarbonate- Carbonic Acid Buffer System Most important ECF buffer. A buffer is any substance that can reversibly bind H+. H2O + CO2 H2CO3 H+ + HCO3 - Buffer + H+ HBuffer HCl + NaHCO3 → H2CO3+ NaCl NaOH + H2CO3 → NaHCO3 + H2O ↓ CO2(Expired)+ H2O The buffer systems of the body fluids react within seconds to minimize these changes. Buffer systems do not Phosphate: important renal tubular and ICF buffer (Weak acid eliminate H+ from or add H+ to the body, but only keep them tied up until balance can be re-established. H2PO4 and weak Base Na2HPO4) HCl + Na2HPO4 → NaH2PO4+ NaCl (strong acid) (weak acid) Buffers NaOH + NaH2PO4 → Na2HPO4+ H2O bicarbonate-carbonic (ecf buffer) (strong base) (weak base) Phosphate (renal tubulars, if buffer) Ammonia: important renal tubular buffer ammonia (renal tubular buffer) Proteins (1 Cf NH3 + H+ NH4+ buffer) Proteins: important intracellular buffers (Hemoglobin: Hb) buffer system do not H+ + Hb HHb Especially in RBC removeoraddH teis 9/19/2024 (60-70% of buffering of body fluids is inside the cells.) 5 Respiratory Regulation of Acid-Base Balance Respiratory regulate It by ventilation Respiratory regulation refers to changes in pH due - changing breathing rate to pCO2 changes (which affect carbonic acid levels) from alterations in rate of ventilation. dysfunction Impairment of lung function can cause respiratory acidosis. because they cannot ventilate properly Reminders (Luminal)  Renal Regulation of Acid-Base Balance at the same time Is being absorbed being secreted , bicarb His Handling of HCO3- Secretion of H+ (~4400 mEq /day) Filtration De Novo synthesis: Excretion in urine (4320 mEq /day) (80 mEq/day) to (~4320 mEq /day) Production of new rid the body from (1 mEq /day) non-volatile acids HCO3- (~80 mEq /day) Reabsorption (~4319 mEq /day) almost all is absorbed Much of the secretion of hydrogen ions is coupled to: 1. reabsorption of HCO3- 2. de Novo synthesis of HCO3- Reabsorption of HCO3- (and H+ secretion) in different segments of the renal tubule  Bicarbonate ions do not readily permeate the luminal membranes of the renal tubular cells; therefore, HCO3− that is filtered cannot be directly reabsorbed. HCO3− must react with a secreted H+ to form H2CO3 before it can be reabsorbed. bicarbonate has to react with secreted hydrogen , so it can be reabsorbed Secondary Active Transport Secretion of H+ Primary Active Transport Secretion of H+ HCO3- reabsorption and Na+- H+ counter- HCO3- reabsorption and H+ secretion by transport H+-ATPase and H+-K+ -ATPase Key point: For each HCO3- reabsorbed, an H+ must be secreted. This mechanism is important in forming maximally 9/19/2024 acidic urine (pH of tubular fluid=4.5). 9  Urinary Buffer Mechanism of Phosphate - forming new bicarbonate It will - bicarbonate buffers the blood absorbed only be - Buffering of secreted H+ by filtered phosphate (NaHPO4-) and generation of “new” HCO3- Occurs when H+ is secreted in excess of the HCO3− filtered into the tubular fluid. Phosphate buffer system carries excess H+ into the urine and generates new HCO3-. New” HCO3- Whenever an H+ secreted into the tubular lumen combines with a buffer other than HCO3-, the net effect is the addition of a new HCO3-. Under normal conditions, much of the filtered phosphate is reabsorbed, and only 30 to 40 mEq/day is available for buffering H+. Therefore, much of the buffering of excess H+ in the tubular fluid in acidosis occurs through the ammonia buffer system. There is a net gain of HCO3- by the blood, rather than Whenever hydrogen secreted into the tubular lumen combines with merely a replacement of filtered HCO3-. any buffer other than bicarbonate , net effect In the Is the new bicarbonate absorbed 9/19/2024 blood 10  Mechanism of NH4+ / NH3 Buffering System Production and secretion of NH4+ and HCO3- Buffering of hydrogen ion secretion by by proximal tubules ammonia (NH3) in the collecting tubules With chronic acidosis, the dominant mechanism for New HCO3- New HCO3- acid elimination is excretion of NH4+(titratable acid). Glutamine comes mainly from metabolism of amino acids in the liver. Chronic Acidosis: An increase in extracellular fluid H+ concentration stimulates renal glutamine metabolism and, therefore, increases formation of NH4+ and new HCO3- to be used in H+ buffering in the ECF. 11 9/19/2024 Acid-Base Disturbance/Disorders Renal Compensations for Acid-Base Disorders Acidosis: Secrete hydrogen Increased H+ secretion and excretion in urine Increase bicarbonate absorption Increased HCO3- reabsorption Produce new bicarbonate Production of new HCO3- Alkalosis: decreasehydrogensecreto a Decreased H+ secretion option Decreased HCO3 reabsorption- excretion of HCO3 in Vrine Excretion of HCO3- in urine Diagnosis of Acid-Base Disorders know this Acid-Base Nomogram The shaded areas in the nomogram show the approximate limits for the normal compensations caused by simple metabolic and respiratory disorders. 14 Classification of Acid-Base Disturbances CLUE: In respiratory causes, the changes in pH and PCO2 are in opposite directions. Henderson-Hasselbalch equation In metabolic causes, pH and PCO2 change in the same direction. Compensation Addition of new HCO3− to the ECF by the kidneys. A reduction in plasma HCO3− concentration, caused by increased renal excretion of HCO3−. Increased ventilation rate, which reduces PCO2 & addition of new HCO3− to the ECF by the kidneys. Decreased ventilation, which raises PCO2, & increases in renal HCO3− excretion. If PH and PCO2 in opposite direction its a respiratory cause metabolic cause If same direction , Causes of the 4 Primary Acid-Base Disorders Respiratory Acidosis (Low pH, High PCO2) Metabolic Acidosis (Low pH, Low HCO3- ) Brain damage Diarrhea Pneumonia Vomiting intestinal content Emphysema Drinking ethylene glycol our Problem Other lung disorders Ketoacidosis (Diabetes mellitus) Lactic acid accumulation Respiratory Alkalosis (High pH, Low PCO2) Uric acid (kidney disease) High altitude Psychic (fear, pain, etc) Metabolic Alkalosis (High pH, High HCO3- ) Increased base intake (e.g., NaHCO3)- antiacid ingestion Vomiting gastric acid Mineralocorticoid (aldosterone) excess Overuse of some diuretics  Hyperaldosteronism and Acid-Base Disturbance H+ secretion hydrogen Urine alot secreted in the because of high hydrogen Secretion , bicarbonate will be highly absorbed HCO3 reabsorption So it'll cause bicarbonate alkalosis Metabolic Alkalosis high aldosterone causes add base disturbance , because aldosterone AtFase activity Increase hydrogen Acid-Base Disturbances Caused By Overuse of Diuretics Overuse of Diuretics ECF volume angiotensin II K+ depletion Aldosterone secretion tubular H+ secretion HCO3 reabsorption Metabolic Alkalosis 9/19/2024 18  Clinical Evaluation Of Disturbances In Acid-base Status – The Anion Gap tool to evaluate ada-base disturbance The simplest reports may only give the [Na+], [Cl-], and the [HCO3-] (Measured parameters). However, the "real" ionic balance is given by the equation: [Na+]+ [Unmeasured Cations] = [Cl-] + [HCO3-] + [Unmeasured Anions] The unmeasured anions are phosphate, sulphate, proteins in anionic form such as albumin, and other organic anions like lactate. The unmeasured cations are potassium, calcium and magnesium. Rearranging the equation: [Na+] – ([Cl-] + [HCO3-]) = [Unmeasured Anions] - [Unmeasured Cations] = “Anion Gap" The anion gap measures the difference—or gap—between the negatively charged and positively charged electrolytes in the blood. An increased anion gap can result from an increase Normal values for the anion gap (AG) are 10-14 mEq/L (Average = 12 in the unmeasured anions (hyperalbuminemia, mEq/L). lactic acidosis, ketoacidosis) or a decrease in the The anion gap is a useful shorthand measure, particularly in the differential unmeasured cations (hypocalcemia, hypokalemia, diagnosis of acid/base disturbances. hypomagnesemia). - AG >20 mEq/L indicates metabolic acidosis. increase anyon gap means : - 19/09/2024 AG is also useful in differentiating the causes of metabolic acidosis. - increased unmeasured anion - decreased unmeasured cation Causes of Anion Gap Changes  Indicate the Acid-Base Disorders in Each of the Following Patients CLUE: In respiratory causes, the changes in pH and PCO2 are in opposite directions. (20-28) (35 - 45) In metabolic causes, pH and PCO2 change in the same direction. acidic low ~ low alkalosis night high acidic high night low v alkalosis audic 100 high 9/19/2024 21