Acid-Base Physiology Flashcards
Normal values for pH, PCO2, HCO3
.pH: 7.35-7.45
. PCO2:35-45 mmHg
. HCO3: 22-26 mEq/L
Acute respiratory disorder PCO2 and HCO3 conc.
. Inc. PCO2 of 10 mmHg and inc. of HCO3 by 1 mEg/L
. Dec. PCO2 of 10 mmHg and dec. HCO3 by 2
Compensated respiratory disorder PCO2 and HCO3
. Inc. PCO2 of 10 mmHg causes inc. in HCO3 by 4 mRq/L
. Dec. PCO2 by 10 mmHg causes dec. HCO3 by 5 mEq/L
Normal, increased,and decreased base excess
. Normal: 0 =/- 2 mEq/L
. Inc: >+ 2mEq/L
. Dec:
Normal anion gap range
8-16 mEq/L
HCO3 and PCO2 for metabolic acidosis vs. respiratory acidosis
. Metabolic: Dec. HCO3
. Respiratory: inc. PCO2
Metabolic vs respiratory alkalosis
. Metabolic: inc. HCO3
. Resp: dec. PCO2
T/F pH is a function of ratio of plasma bicarbonate to dissolved CO2
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pH is maintained by _____
. Kidney’s ability to regulate plasma bicarbonate conc.
. Lung’s ability to regulate plasma CO2 conc.
Bicarbonate buffer system
. Most important buffer in the blood
. Accounts for 53% buffering capacity despite having pKa of 6.1 bc of high HCO3 conc., kidney and lung regulation
Hb as buffer
. Accounts for 35% total buffering capacity
. Buffering action is greater in venous blood (pK is 7.85 when de-oxygenated vs 6.6 when oxygenated)
T/F buffers reversible bind and release H as the concentrations change
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Bone buffers
. Bone has Ca, Na, and K salts of carbonate (CO3)
. In response to inc. H conc., the excess ions are exchanged w/ Ca, Na, and K ions assoc. w/ carbonate on the bone surface
. During chronic metabolic acidosis, osteoclasts in bone are also activated which release CaCO3 and CaPO4 into ECF
. Buffering of H by bone can contribute up to 40% of total buffering capacity during chronic acidosis
Intracellular buffers
. Besides RBCs, proteins, organic and inorganic phosphates are buffers due to their high intracellular conc.
. Intracellular HCO3 is bad buffer bc it has a low intracellular conc.
Buffering for metabolic acidosis
. Poop shoots cause loss of HCO3
. Half of excess H will be buffered by remaining bicarbonate
. Remaining H will enter cells or exchange cations on bone
. Buffering by bicarbonate takes minutes
. Entry and neutralization of H in cells/bone takes 2-4 hrs
. Respiratory system compensate by inc. ventilation
Buffering for respiratory acidosis
. COPD leads to acidosis
. Excess H will be buffered by intracellular buffered since bicarbonate is so low
. Process takes 2-4 hrs
. Renal system will compensate by creating new bicarbonate
Ion exchange due to different H concentrations
. Inc. in extracellular H: H ions will enter cells down conc. Gradient and a cation must leave to keep neutrality (normally K)
. Transcellular ion exchange during acidosis leads to K efflux that can lead to fatal elevation in plasma K
. Reverse exchange causes alkalosis
. Renal cells respond to changes in intracellular H conc. By changing expression of carbonic anhydrase and activity of glutaminase
. In acidosis the rate of bicarbonate recovery and production of new bicarbonate inc.
Law of mass action
. Only applies to respiratory disturbances
. CO2 conc. Will change the HCO3 conc.
. Metabolic issue won’t change won’t change PCO2 bc the extra CO2 would be quickly eliminated
How much acid is produced in an adult per day
. 50-70 mEq/L of acid/day
Acids that contribute to daily acid load
carbonic acid and non-carbonic acids
Carbonic acid
. Metabolism of carbs and fats produces CO2 which combines w/ H2O in RBCs to form carbonic acid
. Reaction facilitated by carbonic anhydrase
.
Non-carbonic acids
. Metabolism of proteins and intake of foods w/ phosphate and sulphates lead to daily acid production
. Metabolism of Cys and Met generate sulfuric acid while metabolism of Lys produces HCl
. Metabolism of Glu generates base
. Net effect is acid production
T/F bicarbonate can be reabsorbed
F, it is not reabsorbed
. There are only mechanisms for bicarbonate recovery and creation of new bicarbonate exist
H in proximal tubule
. CO2 and H2O converted into bicarbonate and H via CA
. H is secreted into lumen and bicarbonate is revered by circulation
. H secreted is neutralized by filtered bicarbonate in early nephron portions
. Bicarbonate is revered by its production and loss (1:1) in prox. Tubule
Mechanisms for new bicarbonate
. Prox tubule: Glu is metabolized to form new bicarbonate and ammonium, new bicarbonate is added back into circulation
. Medullary collecting duct: CA produces new bicarbonate and secreted H is neutralized by non-bicarb buffers so there is no bicarbonate loss
Bicarbonate recovery amounts throughout nephron
. 80% bicarbonate recovered in prox. Tubule . 10% in thick ascending limb . 6% distal tubule . 4% collecting duct . Almost none present in urine
H secretion in prox. Tubule
. 2/3 H secretion into tubular lumen mediated by Na-H exchanger
. High Na conc. In prox. Tubule contributes to high capacity
. 1/3 H transported w/ ATP dependent pump
Buffering in prox. Tubule
. Secreted H buffered by filtered bicarbonate and resulting carbonic acid is converted into CO2 and H2O via luminal CA
. Luminal CA keeps H conc. Low optimizing gradient or H secretion
Bicarbonate recovery in prox. Tubule
. Bicarbonate is transported across basolateral membrane and into the interstitial fluid by a 3HCO3: 1Na co-transporter
. Co-transported assisted by electronegative potential generated by Na/K ATPase
. Bicarbonate also transported into interstitial fluid by Cl ion exchange
New bicarbonate via Gln metabolism
. Prox. Tubular cells transport Gln (basolateral) and co-transport Na and Gln (apical) into cells
. Gln broken down by glutaminase, delaminates, and oxidized to produce 2HCO3 and 2NH4
. Retention of new carb is dependent upon ammonium excretion by Na exchange
Ammonium handling in prox. Tubule
. Pos. Charge on NH4 prevents reabsorption in prox. Tubule
. Ammonia (NH3) is filtered and can buffer H secreted into tubular lumen to produce NH4
. NH4 is then trapped in tubular lumen and allows for excretion of large quantities of H w/ little change in tubular fluid pH
Ammonium handling in thick ascending limb
. Apical membrane is permeable to NH4
. Substitutes for K on the K-Na-2Cl cotransporter and to lesser extent via K channels
. NH4 then exits the cell into the interstitium by diffusing through K channels on basolateral side of membrane
. In interstitium, NH4 disassociates into NH3 and H
. Reabsorption and movement of NH4 into interstitium contributes to counter current mechanism
Ammonium handling in collecting duct
. Basolateral and apical membranes are permeable to NH3 and allow it to diffuse across these cells and into the lumen of collecting duct
. H secreted into lumen of collecting duct via H-ATPase binds w/ NH3 to form NH4
. Apical membrane is impermeable to NH4 so it is trapped again and excreted in the urine
. Buffering of H ion w/ NH3 minimizes acidification of lumen which facilitates additional H ions secretion in the collecting duct
Why does ammonium secretion i prox. Tubule increase in chronic acidosis?
. Glutaminase is activated by acidosis
. NH4 excretion can inc. from 30-40 to over 300 mEq/day
Type A cells
. New HCO3 is transported into interstitial fluid by Cl ion exchange
. H secretion dependent upon active transport by H-ATPase
New bicarbonate via non-bicarbonate buffer
. Scented H buffered by non-bicarbonate buffers in distal nephrons
. Primary buffer here is Na2hPO4, creatinine, and uric acid
. Production of new bicarbonate via CA and neutralization of H via non-bicarbonate buffer(1:0) results in net gain of new bicarbonate
. Dependent on availability of Na2HPO4 regulated to maintain phosphate balance bs acid-base balance
.aldosterone inc. H-ATPase activity which inc. formation of new bicarbonate
Renal H secretion increased when ___
. Inc. partial pressure of CO2
. Dec. extracellular HCO3
. Inc. activity of CA
. Dec. lumen. H conc./inc. lumen pH
Renal H secretion decreased when _____
. Dec. partial pressure CO2
. Inc. extracellular HCO3
. Dec. CA activity
. Inc. lumen H conc./dec lumen pH
Respiratory acidosis will ____ H excretion
. Increase
Relationship between plasma K and HCO3
. Reciprocal relationship
. Hyperkalemia leads to K einflux and H efflux, inc. pH reduces CA activity and bicarbonate recovery dec.
. Inc. in plasma K dec. HCO3 recovery
. Opposite occurs w/ hypokalemia
Limitations to H secretion
. As the conc. Of a buffer is reduced, tubular fluid becomes more acidic
. As pH approaches 4.4 the H conc. Gradient exceeds capacity of H-ATPase to transport H ions into lumen
Type B cells
. During periods of chronic metabolic alkalosis, these cells in cortical collecting duct transport HCO3 into tubular fluid and transport H ion into interstitial fluid
. Once bicarbonate is in tubular lumen it will assoc. w/ available cation (Na)
. NaHCO3 is excreted in urine eliminated bicarbonate from body
. Cells are like type A in medullary collecting duct
Pure acid/base disturbance
. Uncompensated changes
. Pure metabolic disruption follows PCO2 line of 40 mmHg and pH will change accordingly w/ no change in PCO2
. Pure respiratory disruption will follow the mass action line
Metabolic acidosis
. Induced by dec. in extracellular HCO3 which leads to dec. in cerebral spinal fluid HCO3
. Shift in conc. Leads to inc. H conc.
. Extra H diffuses into extracellular fluid surrounding chemosensitive neurons, activate them, and inc. signaling to pre-Botzinger complex
. Stimulates inc. in ventilation to dec. PCO2 and bring pH closer to normal at expense of further dec. in HCO3
Metabolic alkalosis
. Induced by HCO3 inc. that inc. cerebral HCO3
. Reduces H conc.
. Dec. H diffusion will reduce chemoreceptor signaling for ventilation which will inc. PCO2
Compensation for metabolic acidosis
. Directed toward dec. in PCO2 to return HCO3: CO2 ratio to 20:1
. Direction of compensation is in same direction as causative factor
. CO2 reduced which further dec. bicarbonate conc.
Compensation for metabolic alkalosis
. Directed toward inc. PCO2 to return HCO3: CO2
. CO2 will be inc. by slowing the respiratory rate
Limitation of renal compensation
. Only achieve partial compensation
. Limited by respiratory workload, reduction in signaling mechanism for sustained ventilation at central chemoreceptors, lower limit of PCO2 (10-15 mmHg)
. Dec. in ventilation limited by hypoxemia
Winter’s formula
PCO2 = ((1.5 x HCO3) +8) +/- 2
. Normal respiratory compensation: measured PCO2 = wintered’s calc.
. Secondary respiratory acidosis: measured PCO2 > winter’s calc.
. Secondary respiratory alkalosis: measured PCO2 < winter’s calc.
Causes of secondary respiratory acidosis
. Respiratory fatigue
. Meds (opiates, ethanol, barbiturates, benzos)
. COPD
Secondary respiratory alkalosis causes
. Psychological . Meds . Hypoxic hypoxia/high altitude . Pregnancy . Head injury
Respiratory acidosis
. Inc. in extracellular CO2
. Inc. in CO2 conc. In renal tubular cells will inc. expression and activity of CA
. Inc. production and secretion of H into tubular lumen and production and transport of HCO3 into circulation
. Gln metabolism in prox. Tubule stimulated to promote new HCO3 formation and loss of H via NH4 excretion
. Medullary collecting duct the secretion of H and buffering by non-bicarbonate buffers forms new bicarbonate
. Mechanism try to inc. plasma HCO3 to compensate for inc. in plasma CO2
Compensation for respiratory alkalosis
. Caused by dec. in CO2
. Directed toward dec. in HCO3 to return the causative factor
. When CO2 dec., plasma HCO3 will dec. as result of mass action
. Compensation occurs when kidneys dec. HCO3 beyond effect of mass action
T/F renal compensation can lead to complete compensation
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Compensation vs correction of acid-base imbalance
. Compensation: return pH to normal levels at the expense of further deviation from normal bicarbonate or CO2 values
. Correction: cause of imbalance is corrected and pH, HCO3, and CO2 return to normal
Respiratory acidosis and alkalosis correction
. Acidosis: Inc. ventilation rate to return CO2 to normal values
. Alkalosis: dec. ventilation rate to retain CO2 and return CO2 levels to normal
Metabolic acidosis and alkalosis correction
. Acidosis: kidney’s make additional HCO3 and return HCO3 to normal value
. Alkalosis: kidneys inc. HCO3 excretion and dec. H secretion to return HCO3 to normal
Metabolic acidosis types
. Pure: low HCO3, normal PCO2
. Partially compensated: dec. HCO3, dec. PCO2, pH under 7.35
. Completely compensated: rarely occurs
Respiratory acidosis types
. Pure: inc. PCO2, normal HCO3
. Partially compensated: inc. PCO2, inc. HCO3, pH under 7.35
. Complete compensation: inc. PCO2, inc. HCO3, pH normal
Mixed acidosis
. PH under 7.35
. Inc. PCO2
. Variable but usually dec. HCO3
Metabolic alkalosis types
. Pure: inc. HCO3, normal PCO2
. Partially compensated: inc. HCO3, inc. PCO2, pH over 7.45
. Complete rarely occurs
Respiratory alkalosis types
. Pure: dec. PCO2, normal HCO3
. Partially compensated: dec. PCO2, dec. HCO3, pH over 7.45
. Complete compensation: dec. PCO2, dec. HCO3, pH normal
Mixed alkalosis
PH over 7.45
. Dec. PCO2
. Variable but usually inc. HCO3
What ion is measured but not factored into anion gap?
K
. Calculation is [Na - (Cl+ HCO3)]
Metabolic acidosis w/ normal anion gap
. Exzcess H is assoc. w/ equivalent inc. in anions
. If acid is HCl then a proportional inc. in Cl ion conc. Will occur
. H wil be buffered by bicarbonate dec. that conc.
. Called hyperchloremic acidosis
. Causes: GI loss of HCO3 from diarrhea, renal failure leasing to dec. bicarbonate recovery or dec. H excretion (renal tubular acidosis)
Metabolic acidosis w/ wide anion gap
. Production of pathologic acid (non-HCl) leads to similar loss of HCO3 dur to buffering
. Conc. Of unmeasured anions will cause wide anion gap
. Causes: diabetic ketoacidosis, lactic acidosis, injection of methanol, ethylene glycol, inhalation of toluene(sniffing glue), renal failure (inadequate excretion of sulfates and phosphates)
Role of proteins in anions gap
. Neg. charged proteins account for majority of unmeasured anions
. Hypoalbuminemia causes retention in other neg. charged ions (Cl and HCO3) resulting in false narrowing of anion gap due to low plasma protein levels and not acid/base disturbances
. Causes: excess K, Ca, Mg, and Li, bromide ingestion (via instrument error)
Changes in anion gap from compensatory changes in ion conc.
. If unmeasured anions (H2PO4) inc., measured cations (Na) inc. and measured anions (CL/HCO3) dec. resulting in wide anion gap
. Causes: hyperalbuminemia
. Hyperphosphatemia from low PTH or renal failure
Urinary anion gap
. (Na + K)-Cl
. Normally positive but close to zero
. NH4 is major UNmeasured cation w/ conc. Of 20-40 mEq/L
. Acidosis stimulates new bicarbonate and will narrowe urinary gap or make it neg.
. If patient has acidosis and urinary anion gap remains positive it may suggest kidney function is impaired
. Urinary Cl is indirect measure of new bicarbonate and NH4 production and renal function
Base excess
. Important in determination of metabolic acid-base imbalance
. Can calculate thoretical amt of replacement HCO3 needed to correct metabolic acidosis
. Base excess is different btw expected total buffer pool (48 mEq/L) and the patient’s total buffer pool
. If patient has excess base the value will by over 50
. If less. Than normal it will be under 46
. Inc. or dec. base excess may result from cause of metabolic imbalance as well as compensation for a respiratory imbalance
Base excess in respiratory acidosis
. Inc. PCO2 inc. HCO3 but HCO3 in blood can’t act as buffer so other buffers in blood are consumed (dec. BUF)
. Total buffer pool does not change, no effect on base excess
Respiratory alkalosis base excess
. Dec. PCO2 dec. HCO3
. PCO2 dec. keep H conc. Low sparing blood buffers (inc. BUF)
. Total buffer pool and base excess is unchanged
Contraction alkalosis
. In response to volume contraction, conc. Of AII and aldosterone inc.
. stimulates Na-H exchange in prox. Tubule and H-ATPase in collecting duct
. While returning volume to normal, the mechanisms inc. H ion secretion, bicarbonate recovery, and formation of new bicarbonate promoting metabolic alkalosis
Effect of Cl deficiency in metabolic alkalosis
. When there is a Cl deficiency, less Cl is available for NKCC cotranspoer in ascending limb
. Inc. Na excretion which stimulates RAAS
. Bicarbonate secretion in collecting duct relies on Cl ion
. Deficiency dec. conc. Gradient and dec. bicarbonate secretion
. Reduction of Cl diffusion out of tubule makes lumen more neg. which promotes H secretion
. All of these things together promote metabolic alkalosis
Hypokalemia effect on metabolic alkalosis
. Promotes movement of K out of cells in exchange for H ion
. Inc. H ion in renal tubular cells stimulates CA and production of new bicarbonate
. Promotes metabolic alkalosis
Chloride responsive metabolic alkalosis
. addition of Cl reduces H secretion, inc. NKCC transporter in thick ascending limb
. Promotes retention of Na and water and facilitates bicarbonate excretion in the collecting duct via apical Cl/HCO3 exchanger
How can a saline infusion correct a metabolic alkalosis
. W/ volume depletion RAAS is activated
. Enhanced Na reabsorption contributes to bicarbonate recovery and H excretion
. Saline inc. volume which inactivates RAAS to dec. H secretion and dec. bicarbonate recovery
Chloride resistant metabolic alkalosis
. Can’t be reversed w/ saline infusion
. Caused by mineralcorticoid excess accompanied w/ severe hypokalemia
. Hypokalemia leads to K efflux and H influx
. Transcellular exchange of ions inc. intracellular H which enhances bicarbonate recovery and addition of new bicarbonate
. Treatment: correct hypokalemia and administer aldosterone antagonist
Renal tubular acidosis
. Disorder in H ion secretion, bicarbonate recovery, or new bicarbonate
. 4 types: H-ATPase in collecting ducts (I), Na-H transporter in prox tubule (II), glutaminase deficiency in prox. Tubule (III), prox. Tubule (IV)
Type I RTA
. Distal RTA
. Type I for dysfunction in collecting duct
. Result of impaired H secretion by H-ATPase in cortical and medullary collecting tubules
. Dec. in H secretion contributes to urinary loss of Na
. Loss of Na is small but it can stimulate the RAAS w/ aldosterone acting to inc. K secretion
. Hypokalemia normally asoc. W/ it
. Loss of ATPase pump attenuates new bicarbonate formation and NH3 excretion as lack of H prevents the formation of NH4 and diffusion trapping so NH3 returns to circulation where liver converts it to urea and H
Chronic acidosis on bone breakdown
. Promotes bone breakdown and release of bone Ca phosphate and carbonate
. Can slow one growth in children
. Inc. risk for precipitation of Ca salts in alkaline tubular fluid of nephron leading to bi-lateral kidney stones
. Most patients have chronic mild metabolic acidosis requires intermittent therapy w/ NaHCO3
Type II RTA
. Caused by defect in Na-H exchanger in prox. Tubule and early portions of distal convoluted tubule
. Impairment in H secretion prevents bicarbonate recovery and leads to bicarbonate excretion
. Due to prox. H secretion, large fraction of filtered HCO3 is delivered to distal nephron which exceeds the capacity for complete HCO3 recovery
. Bicarbonate is lost in urine
. When mild, the filtered load of HCO3 declines until steady state is reached
. Severe assoc. w/ hypokalemia from excessive Na loss stimulating RAAS , inc. aldosterone and HCO3 delivery stimulating K secretion
Type I RTA causes
. Autoimmune destruction of H-ATPase pump, drug (anti-fungal drug, amphotercin B) and defects in Ca metabolism leading to kidney stone formation and tubule damage
Type II-RTA causes
. Fanconi syndrome (Wilson’s disease)
. Lead and aminoglycosides (toxic to prox. Tubule)
. CA inhibitors
. Anti-cancer drugs
. Accompanied defects in other prox. Tubular transport functions
How are type I and II RTA differentiated?
. By their response to NaHCO3 infusion
. Type II: urine pH and fractional excretion of HCO3 will inc. as recovery mechanisms for HCO3 and already working at max capacity
. Type I: urine pH and fractional excretion of HCO3 will remain constant as mechanisms in prox. Tubule for HCO3 recovery are intact
type IV RTA
. Impair Glu metabolism and new bicarbonate formation in prox. Tubule
. Urinary bicarbonate loss not prominent feature bc Na/H transporter in prox. Tubule is function and bicarbonate recovery mechanisms inntact
. Metabolic acidosis is usually not severe
. Causes: hypoaldosteronism, aldosterone resistance, and K sparing diuretics
. Associated w/ hyperkalemia
. Correct hyperkalemia corrects metabolic acidosis
Mechanisms for how aldosterone deficiency leads to hyperkalemia and contributes to metabolic acidosis
. Hyperkalemia leads to H efflux from renal cells, loss of H slow glutaminase activity and dec. new bicarbonate formation in prox. Tubule
. Dec. glutaminase and inc. K disrupts NH3/4 recycling in diffusion trapping and K competition w/ NH4 for NKCC transporters
. Alsodterone deficicency leads to dec. Na reabsorption that diminishes driving force for H secretion and dec. H-ATPase activity to dec. H secretion
