Acid-Base Part 2 PDF

CBM 103 Acid-Base Part 2 Tom Kovala Renal causes of Acidosis 2  Renal Failure and Acidosis Progressive renal failure results in the slow loss of nephrons over time Initially, the remaining functional nephrons secret increasing amounts of ammonium When the...

CBM 103 Acid-Base Part 2 Tom Kovala Renal causes of Acidosis 2  Renal Failure and Acidosis Progressive renal failure results in the slow loss of nephrons over time Initially, the remaining functional nephrons secret increasing amounts of ammonium When the GFR falls below 40 ml/min, ammonium secretion begins to fall Part of the acid load is retained, and bicarbonate buffering results in a lower plasma bicarbonate level Much of the H+ is buffered in cells and bone 3 Renal Tubular Acidosis (RTA) A group of disorders where the kidney themselves produce the acidosis RTA is due to defects in renal H+ secretion or in the reabsorption of bicarbonate Two types 1. Impairment of tubular bicarbonate reabsorption causing loss of bicarbonate in the urine 2. Inability of the tubular mechanisms to secret sufficient H+ into the urine – Inadequate amount of titratable acid and ammonium excreted, resulting in a net accumulation of acids in the ECF 4  Type 1 RTA Also called distal RTA A defect in the Type A intercalated cells Decreased H+ excretion and the inability to lower urine pH below 5.6 to 6.0 Can excrete enough ammonium maintain balance The higher urine pH reduces the ability of titratable acids and ammonia to trap H+ in the tubule Associated with hypokalemia 5  Type 1 RTA causes Four different mechanisms 1. Apical H-ATPase not working due to acquired or genetic defects 2. Basolateral Cl-bicarbonate exchange mutations 3. Apical membrane or the tight junctions fail to stop back diffusion of H+ out of the tubules 4. Decreased Na reabsorption by principal cells of cortical collecting duct disrupts the negative potential of the lumen, leading to a disruption of H+ retention in the lumen (also impairs K secretion) 6  Type 2 RTA Also called proximal tubule RTA Impairment of PT bicarbonate reabsorption, leading to bicarbonate loss in the urine Usually, a part of the generalized PT failure in transport seen in Falconi’s syndrome Self-limiting Ability to reabsorb bicarbonate reduced from the normal 26 mEq/L to 17 mEq/L Plasma bicarbonate falls to 17 mEq/L Patient can then excrete the daily acid load New steady state where the plasma bicarbonate remains low Patient has acidemia Acidemia can contribute to bone mineral loss over time 7  Type 3 RTA Extremely rare Is a combination of type 1 and type 2 RTA 8  Type 4 RTA Also called hyperkalemic RTA Due to hypoaldosteronism or pseudohypoaldosteronism (failure to respond to aldosterone) Produces a mild metabolic acidosis Aldosterone normally will directly stimulate distal H+ secretion and K secretion low aldosterone reduces H+ and K secretion, resulting in acidosis and hyperkalemia 9 Determining the Causes of Metabolic Acidosis 10  Anion Gap Plasma anion gap = measured cation – measured anions = [Na+] – [HCO3-] – [Cl-] = 144 -24 -108 = 12 mEq/L (normal range 8-16) Plasma anions and cations must be equal (electrical neutrality) There is no real anion gap Unmeasured anions include albumin, phosphate, sulfate, and other organic anions Unmeasured cations include calcium, magnesium, (and potassium) 11  Anion Gap in Metabolic Acidosis Anion gap used in diagnosis of the causes of metabolic acidosis Plasma HCO3- is reduced If Na+ levels are unchanged, anions must increase (either Cl- or an unmeasured anion) Hyperchloremic metabolic acidosis, Cl- levels increase, anion gap is normal (while HCO3- is reduced) If Cl- levels are unchanged, an unmeasured anion (e.g. lactic acid, ketoacids) has increased, and the anion gap is increased 12  Anion Gap helps determine the cause of metabolic acidosis 0 Netter's Essential Physiology, Fig. 20.4 13 Metabolic Acidosis Associated with Normal or Increased Plasma Anion Gap Guyton Table 31-4 Increased Anion Gap Normal Anion Gap (Normochloremia) (Hyperchloremia) Diabetes mellitus (ketoacidosis) Lactic acidosis Diarrhea Chronic renal failure Renal tubular acidosis Aspirin (acetylsalicylic acid) Carbonic anhydrase inhibitors poisoning Addison's disease (aldosterone Methanol poisoning deficiency) Ethylene glycol poisoning Starvation 14  Urinary Anion Gap Urinary ion gap = (Na+ + K+) – Cl- Measured cations are Na+ and K+ and the anion is Cl- The major unmeasured ions are bicarbonate and NH4+ HCO3- usually negligible, and NH4+ is ~40 mEq/L Normally a positive or near zero gap In metabolic acidosis, the excess H and NH 4+ Cl excretion increases An approximate measure of ammonium excretion as the Cl - increase generates a negative AG Allows differentiation of renal vs non-renal causes of non-anion gap metabolic acidosis An increased urinary anionic gap suggests low NH 4+ (renal tubular acidosis) A decreased urinary anionic gap suggests high NH 4+ (diarrhea) 15  Osmolar Gap Osmolar Gap = measure serum osmolality – calculated osmolarity Calculated osmolarity = 2[Na] + [glucose] + [urea] (all in mmol/L) Normal osmolar Gap