Acid/Base & Aspirin Toxicity Flashcards
What’s the pK of the HCO3-/CO2 system? SO, what is the H-H for this system? What should the ration of HCO3- to CO2 be n order to achieve normal pH? If it is less, what does this impy and v.v.?
pK = 6.1. H-H – pH = 6.1 + log[HCO3-]/[(0.03 x pCO2)]. The ratio of HCO3- to CO2 should be 20. Acidemia 20.
How is Ca2+ related to pH?
Acidemia: Increase Ca2+. Alkalemia: Decrease Ca2+.
In the proximal tubule, what are the kinetics of Na, HCO3 and H+? WHen is plasma HCO3 saturated?
Net reabsorption of Na & HCO3. No net secretion of H+. Saturation of HCO3- above 40 mM. However, if H+ is excreted via a H+-ATPase and titrated off HPO4- to H2PO4-, then a NEW HCO3- is reabsorbed.
In the proximal tubule, how is NH4+ excreted? Where does this NH4+ come from? Is any HCO3- formed? Where does this come from? What about in the collecting duct? So, all in all, H+ are excreted as ____ & ____, which produces NEW ____, which is needed to _____.
NH4+ secretion in the proximal tubule arises from the generation of NH3 from glutamine and the addition of a proton. NH4+ then moves across the luminal membrane via a Na/NH4+ exchanger. a-ketoglutarate is derived from glutamine, and this gives off a NEW HCO3- that is added to circulation to replenish stores. In the collecting duct, H+ is pumped via an H+-ATPase and added to NH3 to form NH4+, which is trapped and excreted. The proton is derived from H2CO3, so the process forms a NEW HCO3- to be added to circulation. Titrateable Acid & NH4+, HCO3-, buffer fixed H+ in circulation.
What is the therapeutic plasma concentration of aspirin? What is fatal ranges in adults, children? Is this dose-dependent toxicity? What does that mean in terms of increasing doses?
Therapeutic: 1-2 mM. 10-30 gm in adults, 3 gm in children can be fatal. It is dose-dependent, meaning that at increasing doses, less plasma protein binding occurs and the liver metabolism becomes overwhelmed, leading ot progressive tissue exposure and increased blood levels.
What is mxn of salicylate toxicity in adults?
Uncoupling of ox phosph, decreased ATP, perceived as O2 deficit, increased respiration –> respiratory alkalosis with renal compensation (in adults, toxicity usually does not proceed further).
What is the mxn of salicylate toxicity in children? Besides the primary disorder, what else occurs in toxicity?
In children, a respiratory alkalosis occurs as it does in adults due to hyperventilation, but respiratory failure due to muscle fatigue occurs. This leads to hypoventilation and respiratory acidosis, which is compounded for by decreases in HCO3- which leads to a superimposed metabolic acidosis due to organic and inorganic acid accumulation without sufficient buffering. Due to the acidosis, the unionized (protonated) form of salicylate forms, which freely moves into cells; within the cell, salicylate deprotonates, trapping the ionized form in the cell and leading to accumulation, ultimately in the brain, which causes the toxicity. Also: dehydration due to sweating, hyperventilation, decreased water reabsorption from the kidney + increased aldosterone in response, with subsequent hypernatremia and hypokalemia.
What are the therapeutic interventions to reverse salicylate toxicity?
In severe cases: hemodialysis and stomach pumping to rid the ECF of salicylate. Also: Increase blood pH via IV infusion of HCO3-, which promotes efflux of saicylate from cells to blood. This also corrects the low blood pH and corrects the ECF volume contraction. In addition (and very importantly), this will alkalinize the tubular fluid, which increases the concentration of the membrane impermeable ionized form of salicylate, which will trap salicylate in the tubular fluid and increase renal excretion (the reverse is also true – in acidosis, the decreased pH promotes the formation of the ionized form of salicylate, which is membrane permeable and thus can be reabosrbed – so in acidosis, salicylate excretion is low, as is clearance).
