Acid-base/salicylate toxicity Flashcards
Acid/base balance achieved at arterial pH of
7.37-7.42
Which mechs maintain acid/base balance rapidly and which does slowly?
Chemical H+ buffering in ICF and ECF, and respiratory compensation through regulating pCO2 are RAPID; renal compensation occurs SLOWLY
Sources of metabolic acid:
- Volatile acid (CO2 made by aerobic metabolism)
- Nonvolatile acids
a. Sulfuric and phosphoric acid made
b. beta-hydroxybutyric acid and acetoacetic acid (DKA)
c. lactic acid (anaerobic metabolism)
d. excess consumption of acid (aspirin)
Which components of the HH eqn are highly membrane permeable?
B and HA!!! (Hence why protonated form of acetylsalicyclic acid is highly permeable)
The CO2/HCO2 buffer pK is; what is the ratio of bicarb to pCO2 in the equation?
6.1; ideally should be TWENTY!!! Anything greater than 20 would be alkalemia, anything less would be acidemia
Intracellular buffers include:
- Intracellular organic phosphates with their phosphate group: ATP, ADP, AMP
- Large number of weakly acidic and weakly basic groups in IC proteins
- Presence of plasma membrane acid/base transporters like Na/H exchanger and Cl/HCO2 exchanger (former gets acid out, latter gets base out)
The capacity of the proximal tubule to reabsorb HCO3 could be exceeded in
metabolic alkalosis when plasma HCO2 increases to levels above 40 mM (prox tubular HCO2 reabsorption decreased with ECF volume expansion and increased by ECF volume contraction, latter perhaps leading to contraction alkalosis)
Besides bicarb _____, what are two other renal mechs to maintain acid/base balance? When does this latter process decrease?
Excretion of acid to generate bicarb: proton ATPase and H/K exchanger to get proton to titrate dibasic phosphate to monobasic phosphate (bicarb can then be reabsorbed in cases of fixed acid generation that is buffered with bicarb);
Net H secretion stops as pH in urine gets to around 4.4;
Think glutaminase producing ammonia in prox tubule and Na/NH3 exchanger and also same mech in collecting duct as you had with acid titration with NH3 building up in medullary interstitium
In which of the three cases can you not compensate for the production of fixed pH: normal, DKA, chronic renal failure?
Chronic renal failure, leading to metabolic acidosis because of decreased GFR and filtered load of phosphate buffer and decreased synthesis of NH3 from glutamine (they’ll need dialysis)
Causes of metabolic acidosis:
- excess production or ingestion of fixed acid (DKA, lactic acidosis, salicylate poisoning)
- Loss of HCO3 via kidney or GI tract (diarrhea)
- Can’t excrete fixed acid produced from normal metabolism (chronic renal failure);
decrease in pH in ECF, stimulating central chemoreceptors to induce hyperventilation (lung response quicker than renal response)
Causes of metabolic alkalosis:
- Losing fixed acid from GI tract (vomiting) or kidney (hyperaldosteronism); also too high of aldo levels leads to H secretion and more bicarb generated
- Gain of HCO3 (consume it with compromised renal function)
- Volume contraction alkalosis (diuretic therapy): ECF volume contraction increases ECF bicarb concentration; again, compensation occurs faster with respiratory than renal as central chemoreceptors (carotid bodies) are inhibited by increased ECF pH to increase pCO2
Causes of respiratory acidosis:
- Inhibition of the medullary respiratory center by drugs, the late stage of salicylate poisoning, or trauma
- Disorders of respiratory muscles including Guillain-Barre syndrome, ALS, MS
- Airway obstruction resulting from aspiration, sleep apnea
- Disorders of gas exchange including ARDS, COPD, pneumonia, pulmonary edema;
NO RESPIRATORY COMPENSATION and most of the buffering occurs in RBC where H is buffered by Hg and organic phosphates
Causes of respiratory alkalosis:
- Stimulation of medullary respiratory center from hysteria, initial stage of salicylate poisoining, neuro disorders
- Hypoxemia from pneumonia, pulm embolism, severe anemia, or high altitude;
NO RESPIRATORY COMPENSATION and Hg and organic phosphates release H to form CO2 from bicarb
Dose-dependent toxicity of aspirin results from a
progressive decrease in plasma protein bindings and a saturation of salicylate metabolism in the liver which increases tissue exposure due to increased blood levels
Pathogenesis of salicylate toxicity:
- Excess cellular accumulation of salicylate depresses mito respiration by uncoupling oxphos
- Decreased ATP made seen as tissue O2 deficit by medullary respiratory center of the brain, inducing compesatory increase in respiration
- Hyperventilation decreases pCO2, getting respiratory alkalosis (usually ends here for adults)
- In infants and young children, can go from initial respiratory alkalosis with associated compensatory decrease in ECF HCO3 to later respiratory acidosis due to respiratory muscle fatigue and associated hypoventilation; ensuing acidsos compounded by superimposed metabolic acidosis due to organic and inorganic acid accumulation in absence of sufficient bicarb buffering
