Acid-Base Physiology Flashcards

1
Q

Normal values for pH, PCO2, HCO3

A

.pH: 7.35-7.45
. PCO2:35-45 mmHg
. HCO3: 22-26 mEq/L

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2
Q

Acute respiratory disorder PCO2 and HCO3 conc.

A

. Inc. PCO2 of 10 mmHg and inc. of HCO3 by 1 mEg/L

. Dec. PCO2 of 10 mmHg and dec. HCO3 by 2

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3
Q

Compensated respiratory disorder PCO2 and HCO3

A

. 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

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4
Q

Normal, increased,and decreased base excess

A

. Normal: 0 =/- 2 mEq/L
. Inc: >+ 2mEq/L
. Dec:

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5
Q

Normal anion gap range

A

8-16 mEq/L

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6
Q

HCO3 and PCO2 for metabolic acidosis vs. respiratory acidosis

A

. Metabolic: Dec. HCO3

. Respiratory: inc. PCO2

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7
Q

Metabolic vs respiratory alkalosis

A

. Metabolic: inc. HCO3

. Resp: dec. PCO2

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8
Q

T/F pH is a function of ratio of plasma bicarbonate to dissolved CO2

A

T

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9
Q

pH is maintained by _____

A

. Kidney’s ability to regulate plasma bicarbonate conc.

. Lung’s ability to regulate plasma CO2 conc.

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10
Q

Bicarbonate buffer system

A

. 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

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11
Q

Hb as buffer

A

. 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)

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12
Q

T/F buffers reversible bind and release H as the concentrations change

A

T

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13
Q

Bone buffers

A

. 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

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14
Q

Intracellular buffers

A

. 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.

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15
Q

Buffering for metabolic acidosis

A

. 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

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16
Q

Buffering for respiratory acidosis

A

. 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

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17
Q

Ion exchange due to different H concentrations

A

. 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.

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18
Q

Law of mass action

A

. 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

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19
Q

How much acid is produced in an adult per day

A

. 50-70 mEq/L of acid/day

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20
Q

Acids that contribute to daily acid load

A

carbonic acid and non-carbonic acids

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21
Q

Carbonic acid

A

. Metabolism of carbs and fats produces CO2 which combines w/ H2O in RBCs to form carbonic acid
. Reaction facilitated by carbonic anhydrase
.

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22
Q

Non-carbonic acids

A

. 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

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23
Q

T/F bicarbonate can be reabsorbed

A

F, it is not reabsorbed

. There are only mechanisms for bicarbonate recovery and creation of new bicarbonate exist

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24
Q

H in proximal tubule

A

. 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

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25
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
26
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 ```
27
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
28
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
29
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
30
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
31
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
32
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
33
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
34
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
35
Type A cells
. New HCO3 is transported into interstitial fluid by Cl ion exchange . H secretion dependent upon active transport by H-ATPase
36
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
37
Renal H secretion increased when ___
. Inc. partial pressure of CO2 . Dec. extracellular HCO3 . Inc. activity of CA . Dec. lumen. H conc./inc. lumen pH
38
Renal H secretion decreased when _____
. Dec. partial pressure CO2 . Inc. extracellular HCO3 . Dec. CA activity . Inc. lumen H conc./dec lumen pH
39
Respiratory acidosis will ____ H excretion
. Increase
40
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
41
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
42
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
43
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
44
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
45
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
46
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.
47
Compensation for metabolic alkalosis
. Directed toward inc. PCO2 to return HCO3: CO2 | . CO2 will be inc. by slowing the respiratory rate
48
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
49
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.
50
Causes of secondary respiratory acidosis
. Respiratory fatigue . Meds (opiates, ethanol, barbiturates, benzos) . COPD
51
Secondary respiratory alkalosis causes
``` . Psychological . Meds . Hypoxic hypoxia/high altitude . Pregnancy . Head injury ```
52
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
53
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
54
T/F renal compensation can lead to complete compensation
T
55
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
56
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
57
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
58
Metabolic acidosis types
. Pure: low HCO3, normal PCO2 . Partially compensated: dec. HCO3, dec. PCO2, pH under 7.35 . Completely compensated: rarely occurs
59
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
60
Mixed acidosis
. PH under 7.35 . Inc. PCO2 . Variable but usually dec. HCO3
61
Metabolic alkalosis types
. Pure: inc. HCO3, normal PCO2 . Partially compensated: inc. HCO3, inc. PCO2, pH over 7.45 . Complete rarely occurs
62
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
63
Mixed alkalosis
PH over 7.45 . Dec. PCO2 . Variable but usually inc. HCO3
64
What ion is measured but not factored into anion gap?
K | . Calculation is [Na - (Cl+ HCO3)]
65
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)
66
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)
67
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)
68
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
69
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
70
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
71
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
72
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
73
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
74
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
75
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
76
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
77
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
78
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
79
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)
80
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
81
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
82
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
83
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
84
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
85
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
86
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
87
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