Acid/Base Physiology Flashcards
Normal acid/base values
Arterial pH: 7.37 - 7.42 (7.4)
pCO2: 38 - 42 (40)
Pco2 x 0.03 = [CO2]
[HCO3-] in venous blood: 20-29
[HCO3-] in arterial blood: 22-26
Volatile acid vs. fixed acid
Volatile acid is CO2, because is converted to H+ (and HCO3-) in RBCs but in lungs, CO2 regenerated and expired so buffering for H+ generated from CO2 is only a temporary problem
Fixed acid are acids that come from catabolism of proteins and phospholipids (sulfuric acid, phosphoric acid), or pathological processes (beta-hydrobutyric acid) or exercise (lactic acid) or consumption (salicylic acid, formic acid) and must be buffered in body before can be excreted
Buffer
Combination of weak acid and its conjugate base (or vice versa).
When you add H+ to a buffered solution, the A- of the buffer combines with H+ to make HA, so you’ve turned a strong acid (H+) into a weak acid (HA) and pH didn’t change as much
Buffers work instantaneously but are only temporary! Have to either blow off CO2 orexcrete via kidney to totally rid body of an H+
What is true when pH = pK?
Concentration of HA = H-
Physiological buffers of ECF
Bicarbonate: A- = HCO3- and HA = CO2
Phosphate A- = HPO4-2 and HA = H2PO4-
(In urine, mostly phosphate, but at lower urine pH, use creatinine, hippurate, acetoacetate, beta-hydroxybutyrate)
Physiological buffers of ICF
Organic phosphates (ATP, ADP, AMP)
Proteins (anything that contains COOH/COO- or NH3+/NH2-, but particularly hemoglobin)
What usually causes metabolic acidosis/alkalosis?
Gain or loss of fixed acid
In general, what are the renal mechanisms of acid/base balance?
1) Increase or decrease reabsorption of HCO3-
2) Production of new HCO3-
3) Excretion of H+ as titratable acid using H2PO4- (one HCO3- is synthesized and reabsorbed)
4) Excretion of H+ as NH4+ (one HCO3- is synthesized and reabsorbed)
Which ingested acids are acidifying and which are not?
Most ingested acids are quickly oxidized and excreted (citric acid just enters citric acid cycle and becomes CO2 and H20)
Acids that are not oxidized are acidifying (benzoic, tartaric, salicylic, formic, glycolic, oxalic, ammonium chloride) because they let off their H+ then go bind to Na+ or something else to be excreted!
What are the types of fixed acid we have to deal with and do they cause acidemia?
1) Protein and phospholipid metabolism produces phosphoric acid but kidney can usually excrete H+ fast enough so it doesn’t produce acidemia
2) Lactic acid from exercise: lactate- is reabsorbed and have extra H+, but as soon as you can resume oxidative metabolism (after exercise) lactate- claims H+ again and is metabolized
3) Ketone bodies (acetoacetic acid and beta-hydroxybutyric acid) as a result of fat metabolism: acetoacetate- and beta-hydroxybutyrate- excreted, leaving behind H+ that causes acidemia
Why can’t respiratory compensation bring pH all the way back to normal?
Drive of [H+] causing increased resipration is opposed because that causes Pco2 to decrease, which decreases respiration
How do you get back to normal pH from a metabolic acidosis?
Must generate more HCO3- to replace the lose HCO3- and get back to normal pH (do this by excreting H+ as titratable acid or excreting H+ as NH4+)
Kidney takes in CO2 from blood and brings it into cell, where it turns into HCO3- and H+ –> the H+ is secreted into the tubule and excreted, but the HCO3- is reabsorbed back into the blood –> got rid of acid (CO2) and made new base (bicarb)
Order of events of response to increased fixed acid (metabolic acidosis)
1) Buffers (minutes)
2) Respiratory compensation (more minutes)
3) Renal correction (days)
Metabolic acidosis
Decreased HCO3-
Decreased Pco2
Decreased pH
Pco2 down 10 for each fall in [HCO3-] 10 mEq/L
Time to completion: 12-24 hours
Causes: Excessive production/ingestion of fixed H+ (diabetic ketoacidosis, lactic acidosis, salicylate poisoning, etc); Loss of HCO3- (diarrhea); inability to excrete fixed H+ (chronic renal failure)
Metabolic alkalosis
Increased HCO3-
Increased Pco2
Increased pH
Pco2 increase 7 for each increase in [HCO3-] 10 mEq/L
Time to completion: 24-36 hours
Causes: Loss of H+ (vomiting, hyperaldosteronism); Gain of HCO3- (ingestion of NaHCO3); Volume contraction alkalosis (loop or thiazide diuretics)
Respiratory acidosis
Increased HCO3-
Increased Pco2
Decreased pH
Acute: [HCO3-] increase 1-2 mEq/L for each Pco2 increase of 10 (Time to completion: 5-10 min)
Chronic: [HCO3-] increase 3.5 mEq/L for each Pco2 increase of 10 (Time to completion: 72-96 hours)
Causes: Inhibition of medullary respiratory center; Disorders of respiratory muscles; Airway obstruction; Disorders of gas exchange
Respiratory alkalosis
Decreased HCO3-
Decreased Pco2
Increased pH
Acute: [HCO3-] decrease 1-2 mEq/L for each Pco2 decrease of 10 (Time to completion: 5-10 min)
Chronic: [HCO3-] decrease 5 mEq/L for each Pco2 decrease of 10 (Time to completion: 72-96 hours)
Causes: Stimulation of medullary respiratory center (hyperventilation); Hypoxemia; Mechanical ventilation
Urinary pH
4.5 - 7.8
What happens for each mmol of H+ excreted in the urine?
One mmol of “new” HCO3- is added to the body
What exactly is “titratable acid”?
H+ secreted with urinary buffers
Why isn’t NH4+ titratable?
If you add NaOH to urine (containing NH4+) up to a pH of 7.4, most of the NH4+ will still be there, and there will be very little of the base
At pH 7.3, [NH3]/[NH4+] = 1/100
So NH4+ is an acid, but is not titratable
Not titratable because cannot estimate the quantity of NH4+ by titrating (like you can for phosphate)
What’s probably going on if it looks like there is complete compensation of an acid/base disorder?
Compensation is NEVER complete, so this means it is a mixed disorder (metabolic alkalosis with respiratory acidosis or something)
Winter’s Formula
Used to confirm that it is metabolic acidosis
expected Pco2 = 1.5 x [HCO3-] + 8
(should be Pco2 within +/- 2)
If NOT within +/- 2, that means it is a mixed disorder, and you have respiratory acidosis/alkalosis too (if expected Pco2 is lower than actual, you have respiratory acidosis too)
Anion gap and gap vs. hyperchloremic acidosis
Anion Gap: Na - HCO3 - Cl = ~12 mEq/L
Unmeasured anions: plasma proteins, phosphate, citrate, sulfate
Gap acidosis: (DKA, lactic acidosis, starving, etc) increase in organic anion such as ketoacid, lactate, formate, salicylate
Hyperchloremic/normal gap/non-gap acidosis: (diarrhea, renal tubular acidosis) decrease in HCO3- concentration is offset by an increase in Cl-
Base Excess
Amount of extra base (HCO3-) in the blood
Distance between where you are on graph and buffer line (if above buffer line you have positive BE and metabolic alkalosis; if below buffer line you have negative BE and metabolic acidosis)
Determines the metabolic component of the acid-base disorder (just like Pco2 determines the respiratory component)
Have real base excess if BE is +/- 2
However, not always accurate because slope of normal buffer line different
How does the RAAS system and angiotensin II relate to acid/base disorders?
Angiotensin II stimulates Na/H exchange in the PCT and stimulates aldosterone secretion –> increased H+ secretion –> increased HCO3- reabsorption –> metabolic alkalosis
(contraction alkalosis)
Saline sensitive vs. saline insensitive metabolic alkalosis
Saline sensitive: alkalosis can be resolved just by giving normal saline and kidneys will do the rest
Saline insensitive: giving normal saline won’t solve the problem (ie lakalosis caused by K+ depletion–you need to replace K+!)
Approach to acid/base disturbances
1) pH acidemic or alkalotic?
2) Bicarb low? Prob metabolic acidosis
3) Calculate anion gap: Na - (Cl + bicarb) and if greater than 12, it is a GAP acidosis
4) Calculate delta gap: Gap - 12 (gives you number of unmeasured acid anions)
5) If metabolic ALKALOSIS, can’t use Winter’s formula, and use rule of thumb to calculate predicted delta PaCO2
6) Winter’s formula: (bicarb x 1.5) + 8 +/- 2 gives you expected value of PCO2 if compensation occurred
7) PaCO2 higher than expected means respiratory acidosis; PaCO2 lower than expected means respiratory alkalosis
Causes of GAP metabolic acidosis
Renal failure (can’t excrete PO4-, SO4-)
Ketoacidosis from DKA or starvation (acetoacetate, b-hydroxybutyrate)
Salicylate poisoning (ie aspirin)
Alcohols (methanol/formic acid, ethylene glycol, ethanol)
Lactic acidosis (anaerobic metabolism)
Causes of NON-GAP metabolic acidosis
GI loss (diarrhea)
Renal tubular acidosis
Carbonic anhydrase inhibitor (acetazolamide/diamox acts on PCT and can’t reabsorb bicarb)
Intake of certain acids (TPN, NH4Cl)
Ureteral diversion
Early renal failure (can’t excrete H+?)
Obstructive uropathy
Pancreatitis
Overall: losing isotonic NaHCO3-, have Cl- left that now accounts for higher concentration of fluid you have left
When you have metabolic alkalosis, how do you get rid of bicarb?
1) You have reduced secretion of H+ –> secrete more bicarb in the tubule because it doesn’t have any H+ to bind to to be reabsorbed
2) Bicarb actively secreted by beta-intercalated cells in collecting tubule
When you have acidosis, how do you use NH4+ to get rid of H+?
Glutamine turned into NH4+ in PCT –> NH4+ secreted into lumen by Na/H transporter (NH4+ acts like H+) –> some NH4+ secreted like that and HCO3- reabsorbed (good!) –> some NH4+ reabsorbed by Na/2Cl/K pump in thick ascending limb –> NH4+ leaves thick ascending limb and goes into interstitum –> in collecting duct, NH3 diffuses into lumen and combines with H+ to secrete NH4+ (now ion-trapped)
Note: during acidosis, PCT increases synthesis of NH3 because this is the major mechanism used to excrete acids during acidosis
