H: Acid Base

Question 1

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Answer 1

A:Normally Kidneys Excrete [50-100 mEq of H+] equal to production of nonvolatile acids, and then replenish HCO3 loss by neutralization of nonvolatile acids. Kidneys prevent HCO3 loss in urine via ReAbsorption AND Excretion of acids via [H+ secretion].

B: Purpose of most [H+ secretion] is to ReAbsorb [filtered HCO3]. Because of [H+ secretion]–>Urine is Acidic BUT NOT BELOW [pH 4.0-4.5]. In order to excrete urine that isn’t too acidic Kidneys use [urinary buffer phosphate or creatinine]
B2: Urinary buffers = [Titratable Acids]

C: [H+ EXCRETION] as a [Titratable Acid] is insufficient to balance daily nonvolatile acid load.

D: Normally 100% of [Filtered HCO3] is ReAbsorbed and adjusted to stay that way by [GT balance mechanism]

• 80% ReAbsorbed in PCT
• 10% TAL
• 6% DCT
• 4% [Cortex Collecting Duct]

E: Synthesis & EXCRETION of [NH4 ammonium] also is HUGE in [acid-base balance].

Question 2

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Answer 2

A: In PCT although there is an [apical H+-ATPase] and [apical Na/H ANTIporter] the net [H+ SeCretion] is LOW due to neutralization rxn with HCO3 during [HCO3 ion ReAbsorption/H+ recycling]. Also in PCT CO2 hydration rxn predominates becuz of [Carbonic Anhydrase]

A2: During [HCO3 ion ReAbsorption/H+ recycling] HCO3 in proximal tubule combines with [recycled H+] –> H2CO3 and this disassembles to H20 and CO2. CO2 is ReAbsorbed into actual PCT cell where it combines with Water AGAIN to make H2CO3–>HCO3 (ReAbsorbed mostly via [basolateral Cl-HCO3 ANTIporter]) and H+ (recycled to tubular lumen)

B: [DCT and CCD] have predominately phosphate & NH4 rxns occurring due to little [carbonic anhydrase] and little amounts of HCO3.
ºNet [H+ SeCretion] in [DCT and CD] is HIGH due to
1) strong H+ pumping
2) phosphate buffering
3) [Ion Trapping] as NH4

B2: [DCT and CCD] have an [apical H-ATPase] / [apical K-H ATPase] and [basolateral Cl-HCO3 ANTIporter]

Question 3

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Answer 3

A: º[Type 1 Distal Renal Tubular Acidosis] = failure of distal nephron to SeCrete H+ –>[back-leaking] of H+ or pump failure–> DEC plasma pH

vs.

[Type 2 proximal renal tubular acidosis]= failure of proximal nephron to Recycle H+ due to low [carbonic anhydrase]—> [DEC HCO3] ReAbsorption and [DEC plasma pH]

Question 4

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Answer 4

A: Plasma HCO3 is regulated near the [Renal Plasma Threshold] of HCO3

B: There are some HCO3 SECRETING pumps in the [Collecting Duct] activated during [metabolic AlKalosis]

1. [basolateral H-ATPase]
2. [apical Cl-HCO3 ANTIporter]

Question 5

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Answer 5

7 Factors Regulate HCO3 ReAbsorption

1. GFR
2. [Na+ balance]
3. [systemic acid-base balance]
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume]
   - ————————————————————————————-
8. GFR: HCO3 ReAbsorption rates are matched to filtered loads by [GT balance mechanisms]

Question 6

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Answer 6

7 Factors Regulate HCO3 ReAbsorption

1. GFR
2. Na+ balance
3. [systemic acid-base balance]
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume]
   - ————————————————————————————-

B: Lose Na+—> [volume contraction & negative Na+ balance]—-> INC HCO3 ReAbsorption

Question 7

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Answer 7

7 Factors Regulate HCO3 ReAbsorption

1. GFR
2. [Na+ balance]
3. systemic acid-base balance
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume]
   - ————————————————————————————-

respiratory/metabolic alkalosis will do the exact opposite

Question 8

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Answer 8

A: 7 Factors Regulate HCO3 ReAbsorption
1. GFR
2. [Na+ balance]
3. [systemic acid-base balance]
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume] 
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4. Aldosterone (when INC)
A: DIRECTLY [INC H+ SeCretion] in [Collecting Duct intercalated cells] 

B: [INC CD Na+ ReAbsorption]—> DEC negativity of lumen
—> [indirect H+ SeCretion]

C: DECREASING Aldosterone actually [DEC H+ SeCretion]

Question 9

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Answer 9

A: 7 Factors Regulate HCO3 ReAbsorption

1. GFR
2. [Na+ balance]
3. [systemic acid-base balance]
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume]
   - ————————————————————————————-
8. [INC Arterial K+]–> [INC basolateral K-H exchanger]
   - –>EXTRACELLular acidosis with an [alkaline urine] = [Hyperkalemic metabolic acidosis]

DECREASING Arterial K+ causes the exact opposite

Question 10

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Answer 10

A: 7 Factors Regulate HCO3 ReAbsorption

1. GFR
2. [Na+ balance]
3. [systemic acid-base balance]
4. Aldosterone
5. [Arterial K+]
6. [Arterial Cl-]
7. [EXTRAcellular fluid volume]
   - ————————————————————————————-
8. INC [Arterial Cl-] —> [DEC HCO3 ReAbsorption] by competing for the same Cations in tubular fluid HCO3 binds to

• *exact opposite occurs with [DEC Arterial Cl-]**
• 7. [EXTRAcellular fluid volume] = HCO3 ReAbsorption is STOPPED during ECF Expansion due to the dilution of [Plasma HCO3]

Question 11

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Answer 11

A: [Urinary pH= 4.4 - 7] and is higher for vegetarians since plant proteins lack sulfur. Urinary pH DEC to 5-6 with diets containing [sulfur-containing Amino Acids] because it forms H2SO4

B: Minimal Urine pH is around 4.4 due to [distal nephron] ability to SeCrete H+ against [strong tubular acid gradient] BEFORE [back-leaking] occurs

C: [Urinary FREE H+] can come from

1) Fixed acids like [Strong sulfuric acid]
2) Titratable acids like [weak phosphoric acid]

**and CAN NOT COME FROM CARBONIC ACID because CO2 readily diffuses back into blood

Question 12

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Answer 12

A: [Titratable Acids]
ºSeCreted H+ can combine with HPO4 –> H2PO4 and pKa for phosphoric acid is 6.8. HPO4 is Negatively charged Anion that’s lipid insoluble so there is NO BACK DIFFUSION.

B: Since [weak ammonium acid] lies to the left to the [urinary pH] and [STRONG SULFURIC ACID] lies to RIGHT of [urinary pH]… [Phosphate Acid] is the most predominant [titratable acid] because it lies within [Urinary pH]

Question 13

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Answer 13

A: [Diffusion-Trapped ions] occurs when [SeCreted H+] reacts with NH3—> [NH4(pKa=9.3}] .

B: NH3 is made from metabolizing [Amino Acids], is uncharged and freely permeable across tubular cells.
vs.
NH4 which is CHARGED and LIPID IMPERMEABLE–>[H+ Diffusion Trapping!]. NH4 formation keeps NH3 concentration low

C: During enhanced NH4 formation (Chronic Acidosis) there is an [INC in renal NH3 production]. SeCretion of H+ load into tubular fluid at pH levels equivalent to normal

[Chronic Acidosis]—> [INC renal NH3 production]—> Adaptive [INC SeCretion of extra H+ into tubular fluid]

Question 14

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Answer 14

transport & excretion of NH4
1st: [PCT Glutamine] is metabolized—> NH4 and HCO3
(NH4 can also come from [NH4 AND NH3] diffusing from blood —> [Collecting Duct Lumen])

2nd: [PCT NH4] is SeCreted into tubular lumen [via Na-NH4 ANTIporter] and HCO3 enters the blood
3rd: [Tubular NH4] is ReAbsorbed in [THICK aLOH] and accumulates in [medullary interstitium]

4th:NH4 is then SeCreted into collecting duct via
º [nonionic diffusion]
º[diffusion trapping (used for NH3 diffusing into CD)]
º[NH4-H+ ANTIporters used for NH3 diffusing into CD)] which all require [H+ SeCretion] into CD as well

5th:For every NH4 SeCreted into [Collecting Duct] a HCO3 is returned to the ECF

Question 15

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Answer 15

A: Balancing H+ and CO2 is somewhat difficult since they are continually being produced in metabolism

• Volatile acid production= CO2
• NONvolatile acid production= H+

B: [normal arterial pH= 7.4] H+ are highly reactive cations which change [charge distribution on proteins]—> conformational changes and modified rxn rates

C: Protein enzymes are mostly intracellular and so regulating [intracellular H+] is important! [EXTRACELLular H+] in Plasma is regulated by Kidneys & Lungs

D: [H+ transfer] from [intracell–(slow)–>Interstitial space] BUT from [Interstitial space—(FAST)–>Plasma] and [H+ transfer] from [Plasma—(slow again)—>Tubular space]

E: HCO3 ReAbsorption from [Tubular space] to Plasma is slow

F: [H+ transfer as CO2] from Plasma–(FAST)—>[Alveolar air]

Question 16

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Answer 16

A: STRONG shifts in K+ are induced by mineral acids (HCL and KCL)

B: weak shifts in K+ are induced by organic acids ([lactic metabolic acidosis] / [hypercarbia respiratory acidosis] / [hypOcarbia respiratory alkalosis] )

C: [Renal [H-K-ATPase] secretes H+ and recycles K+ via apical K+ channels during K+ REpletion(plenty to spare). [Basolateral K+ channels] ReAbsorbs K+ basolaterally during K+ DEPELETION

Question 17

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Answer 17

There are 3 systems that maintain [Arterial Plasma H+]

1) Chemical Buffering
2) [slow responding Renal system]
3) [RAPID Respiratory system]

1) Chemical Buffering=
º phosphate buffer system effective in kidney
º protein buffers system (hgb / intracellular proteins)
º HCO3 buffer system

Question 18

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Answer 18

There are 3 systems that maintain [Arterial Plasma H+]

1) Chemical Buffering
2) [slow responding Renal system]
3) [RAPID Respiratory system]

2) [slow responding Renal system]
ºKidney excretes 50 mmol H+/day as H+, NH4 and H2PO4 = makes urine acidic

ºKidney ReAbsorbs [5500 mmol HCO3]/day and [Concentrated HCO3 is at Renal Plasma threshold]

Question 19

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Answer 19

There are 3 systems that maintain [Arterial Plasma H+]

1) Chemical Buffering
2) [slow responding Renal system]
3) [RAPID Respiratory system]

3) [RAPID Respiratory system]
º Lung ventilates off a lot of CO2 per day which could help
ºLung has 150 x capacity of kidney

Question 20

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Answer 20

A: BAPD = Bronsted Acid is Proton Donor and [small Kd = weak acid]
B: pKd= - log(Kd)

C: pH= pKd + log([base]/[acid]) and [INC base] can be balanced by corresponding [DEC in Acid] but the ([Base]/[acid] ratio) is what’s important and NOT absolute concentrations of acid or base individually

D: [Dissociation of K]= { [H+][A-] / [HA] }

Question 21

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Answer 21

A: [Principles of Titration]
ºTitration of 10 mol acetic acid in 1L water = pH of 4.7
and
acetic acid is a weak acid

ºpH= pKd (Acetic acid) is half [undissociated acid] and [Half Dissociated Base]

º2 mmol H+ added = pH DEC to 4.33

Question 22

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Answer 22

A: [Principles of Buffer Action]

1) Buffering Power= resistance to [H+ changes] is greatest when operating pH matches pKd
* *Buffering power for combined Buffering systems has constant power over a wide pH range where as single system would only work within specific pH

2) Buffer Range= buffering ability still persists within 1 pH
3) Buffer Capacity= strength of buffering is directly related to concentration of [buffer components]

Question 23

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Answer 23

A:There is a balance between [Acid HA] and [Base A] forms when operating at pH= pKd. BUT if..
ºpH > pKd the molecule will enjoy staying as a [dissociated Base A]

ºpH HgB + H ] pKd values of different imidazole groups vary from 5.3 - 8.3 and many groups have [pKd values within physiological range = 6.4-8.4]

Question 24

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Answer 24

A: Phosphate Buffer system is weak! HPO4 acts as the proton acceptor and grabs H–> H2PO3 which is then the proton donor

2. This system has a low buffer capacity = weak buffer system but is stronger in the Kidney because renal environment is more [acidic pH less than 7.4] and there is higher concentration HPO4
3. [Phosphate Buffer system] is a CLOSED system within the body

Question 25

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Answer 25

BICARBONATE BUFFER SYSTEMS (interaction of CO2 and water)

1. [CO2 Hydration Rxn] has 3 variables (analogous to Henderson-Hasselbalch derivation)
   - CO2= the [BAPD]
   - HCO3= [BBProton Acceptor]
   - H+ = free proton responsible for setting pH
2. Two constants:
   º0.03 constant converts PCO2 from (mmHg) to (mM) CO2 –this should NOT be confused with CO2 has solubility of 0.06 mL CO2 /dL blood per mmHg
   ºpKd = 6.1 (Out of physiological range)
3. pH= 6.1 + log(kidney/lung)
4. {[ H+] = 24•(PaCO2) / [HCO3] }}

Question 26

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Answer 26

• *IMPORTANCE of the Bicarbonate Buffer System**
  1) bicarbonate system is an OPEN system with CO2 directly linked to environment via lungs (ventilation) and H+ directly linked to environment via kidneys (Excretion/urination)

2) In an OPEN system mass action shifts can continue throughout life in 1 direction. CO2 and H+ are removed just as fast as produced = [Steady State balance]–> No build up in body fluids of either but pathologically they can build up (acidosis/alkalosis)
3) Open nature of this system compensates for its low pKd

Question 27

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Answer 27

A: [isohydric principle]= Hydrogen ions equilibrate multiple [Acid-Base pairs] in solution

B: [isohydric principle]: Conditions which change [1 buffer system] will change ALL OTHERS because they all buffer one another by trading H+ back and forth between them.
ºThis means only 1 buffer system needs to be examined to understand [Plasma H+]

C: pK of each buffer dictates ratio of concentrations of its base and weak acid forms at a given pH (in accordance with Henderson-Hasselbalch equation)

D: Multiple weak acids are coupled through individual Ka values

F: Biomedical

1st: Bicarbonate buffer system is MOST IMPT
2nd: HgB buffer = 2nd IMPT
3rd: phosphate buffer= 3rd IMPT

G: Origin of acid-base disturbances and presence of compensations are determined by

• Measuring [Bicarbonate buffer system] and pH= simple
• Interpreting plasma electrolyte concentration= COMPLICATED

Question 28

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Answer 28

A: [Bicarbonate buffer system values] = [PaCO2 / HCO3 / pH] and can all be calculated from at least 2 of each.
ex. pH can be calculated from HCO3 & PaCO2
and PaCO2 can be calculated from HCO3 & pH

B: Anion Gap accounts for [random unmeasured anions] present in PLASMA to neutralize the charge of [Na+ cations] that weren’t neutralized by [HCO3 or Cl] = maintains [plasma electroneutrality]. = normally [15 mEq/L]. If [35 mEq/L then it is likely [pancreatic DKA].

renal/GI problems have NORMAL ANION GAP

Question 29

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Answer 29

A: Uncompensated [Acid-base] disturbance exist if pH is out of its normal range. Normal [Acid-base status] exist if [bicarbonate system Variables ] and [Anion Gap] variables are within normal limits:
[º pH = 7.35 - 7.45]

[ºPaCO2= 35-45 mmHg = RESPIRATORY]

[ºHCO3= 22-28 mM = metabolic]

[ºH+ = 35mM - 45NM]*

[ºAnion Gap = 10 - 15 mEq/L]

B: If Both RESPIRATORY and metabolic problems occurred at the same time—> SEVERE ACIDOSIS/ALKALOSIS

C: pH of 7.4 is the assumed reference point but just remember that each pt has their own unique pH

Question 30

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Answer 30

A: [MIXED Acid-base disturbances] exist if [plasma pH] is within NORMAL range (due to compensatory situation) but both RESPIRATORY and metabolic [Bicarbonate System Variables] are NOT normal

ex: *ex: low pH/Acidosis with (HCO3 less than 22) but (PaCO2 LOWER than 35 mmHg) = suspect MIXED ABD because remember: pH is normal

A2: LARGE ANION GAPS (Greater than 15) ARE MIXED ORDERS

Question 31

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Answer 31

A: [DOUBLE Acid-base disturbances] exist if [plasma pH] is ABNORMAL and BOTH RESPIRATORY and metabolic [Bicarbonate System Variables] are ABNORMAL on SAME SIDE of the abnormal pH

*ex: low pH/Acidosis with (HCO3 less than 22) AND (PaCO2 higher than 45 mmHg)

Question 32

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Answer 32

A: When Compensatory situations exist, the cause of that situation can be determined by examining which side of normal the pH value resides

B: Secondary compensations can never be complete and control systems state [error signal] must exceed 0

C: 4 Primary Disturbances =
ºMetabolic Acidosis *
ºMetabolic Alkalosis
ºRespiratory Acidosis *
ºRespiratory Alkalosis
————————————————————————————–
D: ACIDOTIC disturbances are more common but more easily regulated (than alkalotic)
————————————————————————————-
E: METABOLIC DISORDERS ARE MORE COMPLICATED (than respiratory)

Question 33

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Answer 33

A: Primary Metabolic ACIDOSIS (more common) can be caused by

High Dose ASA as well as DM, DKA, [severe shock] and heart failure

Question 34

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Answer 34

Primary Metabolic alkalosis can be caused by

• [chronic K+ depletion] from aggressive diuretic tx or hyperaldosteronism
• [Gastric Acid Loss from vomiting / pyloric obstruction / gastric ulcers]

B: in [Primary Metabolic alkalosis] urine pH will be acidic if there is chronic depletion of K+

C: 2º Renal compensation of retaining CO2–>DEC Acid drive on ventilation = hypOventilation–> DEC PaO2 which limits compensation —> [hypoxic drive on breathing]