Acid Base Integration Flashcards
What is the largest soruce of acid in the body?
the CO2 produced from metabolism of CHO, amino acids, and fat
What are the processes involved that prevent large changes in blood pH in response to an acute load?
extra cellular and intracellular buffers that act to neutralize excess H+ and thus prevent changes in pH induced acid load
alveolar ventilation increases to eliminate CO2 rapidly and more efficiently
the plasma HCO3- concentration is held within narrow limits by regulation of renal H+ excretion
What are some of the reactions that produce metabolic sources of acids and bases?
reactions producing CO2 - complete oxidation of neutral carbohydrates and fat
reactions producing nonvolatile acids - oxidation of sulfur-containing amino acids
reactions producing bases - oxidation of anionic amino acids
What is the Henderson-Hasselbach equation for predicting acid/base balance in the body?
pH = 6.1 + log([HCO3-]/(0.03 x pCO2))
What is the immediate compensation for changes in HCl load?
extracellular buffering of the excess H+ by HCO3- present in the blood
What is the response after several minutes to HCl changes in the blood?
respiratory compensation begins, resulting in hyperventilation, a decrease in the PCO2, and therefore an increase in the pH toward normal
What is the defense against an acid load after 2 to 4 hours?
intracellular buffers (primarily proteins and organic phosphates) and bone provide further buffering, as H+ ions enter the cells in exchange for intracellular K+ and Na+
What is the body’s response to an acid load after a day and lasts up to 4 to 6 days?
renal excretion of the acid load
returns plasma HCO3- towards normal levels
What are some of the mechanisms that cells use to maintain intracellular pH?
most important are the Na+/H+ exchanger and a Cl-/HCO3- exchanger (Na+ dependent and independent)
How does a cell respond to metabolic acidosis?
addition of hydrogen ions stimulates the Na+/H+ exchanger to extrude H+
at the same time, the decrease in pH inhibits the HCO3- and the Cl- exchanger
How does a cell respond to metabolic alkalosis?
increased OH- stimulates the export of HCO3- by combining OH- with CO2 and activating the HCO3-/Cl- exchanger
higher pH inhibits the activity of the Na+/H+ exchanger
How does the kidney respond to acidemia?
increased H+ secretion
increaed HCO3- reabsorption
happens primarily in the proximal tubule and the collecting duct
How does the kidney respond to alkalemia?
decreased H+ secretion
decreased HCO3- reabsorption
How does ECF volume affect HCO3- reabsoprtion in the kidney?
ECF expansion inhibits HCO3- reabsorption
ECF contraction augments HCO3- reabsorption
How does aldosterone affect H+ secretion?
directly stimulates H+ secretion by intercalated cells by stimulating synthesis and insertion of ATPase pumps in the apical cell membrane
indirectly stimuates H+ secretion via stimulating sodium reabsorption by principal cells
Na+ reabsoprtion produces a lumen-negative transepithelial voltage, which favors alpha-intercalated cell H+ secretion
What facilitates the major fraction of proximal tubular HCO3- reabsorption?
H+ secretion via the Na+/H+ antiporter located in the apical membrane of the cells
factors that increase kidney H+ secretion
low blood pH
high blood pCO2
endothelin (proximal tubule)
ECF volume contraction (proximal tubule)
angiotensin II (PCT and DCT)
aldosterone (DCT and CCD)
hypokalemia (proximal tubule)
PTH (chronic, TAL and DCT)
factors that decrease kidney H+ secretion
high blood pH
low blood pCO2
ECF volume expansion (proxmial tubule)
low aldosterone level (DCT and CCD)
hyperkalemia (proximal tubule)
PTH (acute, proximal tubule)
How does parathyroid hormone, angiotensin II, and hypokalemia affect HCO3 reabsorption?
inhibits
How should bicarb behave in pure anion gap acidosis?
it should decrease the same amount that the anion increases above normal value
defense mechanisms for metabolic alkalosis
hypoventilation (increased pCO2)
decreased renal net acid excretion which leads to decrease in blood HCO3-
defense mechanisms for metabolic acidosis
hyperventilation (increased pCO2)
increased renal net acid excretion, which leads to an increase in blood HCO3-
defense mechanisms for respiratory acidosis
increased renal net acid excretion which leads to increased blood HCO3-
defense mechanisms for respiratory alkalosis
decreased renal net acid excretion which leads to a decrease in blood HCO3-
causes of hyperchloremic (normal anion gap) metabolic acidosis
bicarbonate wastage - diarrhea, urnary tract diversions to intestine
impaired renal H+ secretion and reduced NH4+ excretion - distal renal tubular acidosis and aldosterone deficiency
impaired NH3 formation and reduced NH4+ excretion - advanced chronic kidney disease (GFR < 20 mL/min) and hyperkalemia
administration of chloride containing acid (rare)
expected compensatory chang ein pCO2 or HCO3 in metabolic acidosis
decrease in pCO2 = 1.2 x (delta HCO3-)
delta HCO3- = (24-observed HCO3-)
expected compensatory chang ein pCO2 or HCO3 in metabolic alkalosis
increase in pCO2 = 0.6 x (delta HCO3-)
delta HCO3 = (measured HCO3- - 24)
expected compensatory chang ein pCO2 or HCO3 in chronic respiratory acidosis
increase in HCO3- = 0.4 x (delta pCO2)
delta pCO2 = (measured pCO2 - 40)
expected compensatory chang ein pCO2 or HCO3 in chronic respiratory alkalosis
decrease in HCO3 = 0.5 x (delta pCO2)
delta pCO2 = (40 - measured pCO2)
What are two ways that H+ can build up in the circulation?
as inorganic acid - HCL
as organic acid - lactic acid
pathogenesis of lactic acidosis
increased lactic acid generation - tissue hypoxia
decreased utilization of lactic acid - liver failure
general types of acidosis of primary renal origin
renal insufficiency
distal RTA (classic or type I)
proximal RTA (bicarbonate wastage or type II)
distal RTA with bicarbonate wastage (type III)
hyperkalemic RTA associated with aldosterone deficiency (type IV)
hyperkalemic forms of distal RTA not primarily caused by aldosterone deficiency
features of urinary acidification in proximal tubular acidosis
bicarbonate wastage at normal or high plasma HCO3- concentrations
reduced renal HCO3 threshold (15-20 mEq/L)
intact ability to lower urine pH < 5.5 during acidosis
How does type I RTA differ from type II RTA in terms of NH4+ secretion and urine pH?
type I pH > 5.5 and NH4+ excretion is reduced
type II pH <5.5 and NH4+ excretion is normal
clinical features of proximal RTA
bicarbonaturia which increases K+ excretion (hypokalemia)
glycosuria
phsphaturia
hyperuricosuria
aminoaciduria
no nephrocalcinosis or kidney stones
rickets
clinical symptoms of distal RTA syndrome
hyperchloremic metabolic acidosis
hypokalemia
nephrocalcinosis
kidney stones
inability to lower urinary pH below 5.5 despite acidemia
fractional bicarbonate excretion less than 5-10%
What does a large negative urine anion gap mean?
NH4 is abundant in the urine
appropriate in the presence of metabolic acidosis
What does a positive urine anion gap reflect?
NH4 is low in the urine, which is an abnormal finding in the presence of acidosis and therefore a clue that the patient has distal RTA, a disease with metabolic acidosis because NH4+ is excreted in the urine in low amounts
common causes of metabolic acidosis with increased plasma anion gap
ketoacidosis
renal failure
methanol
ethylene glycol
salicylates
What is the limiting factor in the response to metabolic alkalosis?
the development of hypoxemia
pCO2 rarely exceeds 55 mmHg
What is the renal compensatory response to metabolic alkalosis?
excretion of HCO3- by reducing its reabsorption along the nephron
What is the renal response in the setting of decreased ECV?
HCO3- does not occur due to the low volume
if the underlying cause is corected, pH is eventually returned to normal by increased excretion
causes of metabolic alkalosis
loss of hydrogen ions - gastrointestinal loss through vomiting or renal loss through loop or thiazide-type diuretics, minaralocorticoid excess, and tubular disorders
administration of NaHCO3
What is the urine chloride in chloride responsive mtabolic alkalosis?
less than 15 mEq/L
caused by fluid H+ ion losses
urine chloride in chloride-resistant metabolic alkalosis
>30 mEq/L
caused by diuretics, primary hyperaldosteronism, or Barter’s syndrome
How much does pCO2 change with a 1.0 mEq/L increase in HCO3-?
0.6 mmHg
What is the pathophysiological process following metabolic alkalosis (maintenance phase)?
decreased GFR
enhanced proximal bicarbonate reabsorption, which leads to volume and potassium depletion
increased distal tubular bicarbonate reabsorption leads to mineralocorticoid excess and hypokalemia
What is the pathophysiological process following metabolic alkalosis (recovery phase)?
Cl- administratino (usually 0.9% NaCl) to reexpand volume and corect chloride deficit
Kcl administration if hypokalemia is present
What is the expected compensation for a 1 mmHg rise in blood Pco2?
0.4 mEq/L increase in blood HCO3-
How much does pCO2 decrease for each mmEq/L decrease in HCO3-?
1.2 mmHg
