Objectives 3

Question 1

 Where is the majority of body potassium located and why?

Answer 1

98% of total body potassium (K+) is intracellular creating a negative resting potential within the cell

Question 2

What is a normal plasma potassium concentration?

Answer 2

4 mEq/L

Question 3

Why is maintenance of a stable plasma potassium concentration so critical for normal body function?

Answer 3

Changes in potassium concentration effects membrane excitability
o Increase in potassium, hyperkalemia, decreases resting membrane potential increasing membrane excitibility

Question 4

What happens to potassium immediately after ingestion from the GI tract?

Answer 4

Rapidly taken up by Na+-K+-ATPase

Question 5

What hormonal factors are involved in this response?

Answer 5

Epinephrine, insulin, and aldosterone

Question 6

What is the role of the kidneys?

Answer 6

Kidneys excrete potassium when extracellular fluid concentrations are too high

Question 7

Where is the majority of the filtered potassium reabsorbed along the nephron?

Answer 7

Obligatory reabsorption of 90% of the filtered load of K+ in the proximal tubule and ascending limb
o Only 10% of the filtered K+ load is delivered to the distal nephron

Question 8

Is this process regulated to any significant extent?

Answer 8

Physiologic regulation of renal potassium excretion is achieved by controlling the rate of potassium secretion

Question 9

What explains the fact that a greater percentage of the filtered load of potassium is typically excreted than is delivered to the distal nephron?

Answer 9

o Potassium is reabsorbed at the proximal tubule and thick ascending limb
o When the tubular fluid reaches the late distal nephron only 10% of the filtered load of potassium remains
o The amount of potassium excreted in the urine is greater than what initially reaches the late distal nephron because potassium is secreted from the interstitium into the tubular fluid at the late distal tubule and collecting tubule

Question 10

What happens distally in cases of hypokalemia?

Answer 10

The variable secretion of potassium can be decreased resulting in potassium secretion that is less than the 10% of delivered filtered load
o Potassium is conserved and levels rise
o Potassium reabsorption occurs at the luminal membrane through energy dependent K+-H+ anti-porter and efflux across the basolateral membrane via K+ selective channels

Question 11

What are the intracellular mechanisms underlying potassium secretion and reabsorption in the collecting tubule system?

Answer 11

Uptake across the basolateral membrane via Na+-K+-ATPase

o Efflux across the luminal membrane via K+ channels and K+-Cl- cotransporters

Question 12

How can an increase in distal sodium reabsorption increase potassium secretion?

Answer 12

Na+ reabsorption creates lumen negative potential that also promotes K+ secretion

Question 13

The effects of cell lysis and hypertonicity on plasma potassium are pretty obvious, but how can acid-base status affect plasma potassium?

Answer 13

o Metabolic acidosis results in high levels of extracellular H+ that lower the pH of the interstitium.
o H+ ions travel down their concentration gradient from the interstitium into cells in an attempt to achieve homeostasis.
o K+ ions flow out of these cells in an effort to balance intracellular charge
o metabolic acidosis caused by inorgainic acids (HCl, H2SO4) increase plasma levels of K+ to a greater extent than organic acids (lactic acid, keto acids)

Question 14

Is the reverse true; can changes in plasma potassium affect acid-base status?

Answer 14

.

Question 15

How can changes in plasma potassium and tubular fluid flow rate affect potassium secretion?

Answer 15

o Increase in extracellular fluid potassium concentration will result in increased potassium secretion causing increased urine secretion of potassium by
 Directly increasing Na+-K+-ATPase activity on distal nephron cells
 Directly increasing aldosterone secretion which
 Increases Na+-K+-ATPase activity
 Increases luminal membrane permeability to potassium
o Increase in tubular fluid flow increases potassium secretion due to
 Increased flow minimizes the rise in tubular fluid potassium concentration
 Increased flow increases Na+ reabsorption which increases Na+-K+-ATPase activity that increases intracellular K+

Question 16

Why can extended use of loop diuretics lead to hypokalemia?

Answer 16

Extended use of loop diuretics increases K+ excretion leading to hypokalemia by
 Increased distal secretion of K+ through increased distal tubular fluid flow
 Increased distal secretion of K+ through increased distal Na+ reabsorption which increases Na+-K+-ATPase activity that increases intracellular K+

Question 17

What other organ systems, in addition to the kidneys, are involved in maintaining normal plasma calcium levels.

Answer 17

Normal plasma calcium levels are maintained by an integral process involving
 Renal, intestinal, and bone responses
 Mediated by parathyroid hormone (PTH)

Question 18

What are the three roles of the kidney?

Answer 18

Activation of vitamin D
o Renal Ca2+ excretion/reabsorption
o Renal HPO42- excretion/reabsorption (HPO42- is orthophosphate, plasma levels are effected by bone resorption)

Question 19

 How does parathyroid hormone stimulate calcium reabsorption in the distal tubule, and reduce phosphate reabsorption in the proximal tubule?

Answer 19

PTH stimulates Ca2+ reabsorption in the distal tubule through stimulation of Ca2+ ATPase and the Na+-Ca2+ exchanger on the basolateral membrane
o Decreased HPO42- reabsorption in the proximal tubule due to inhibition of the Na+-HPO42- co-transporter on the luminal membrane

Question 20

What is volatile acid?

Answer 20

Volatile acid produces approximately 15-20,000 mmol/day of CO2 through oxidative metabolism

Question 21

Why is it typically not a concern for acid-base balance?

Answer 21

Normally a volatile acid is not problematic since the CO2 generated can be exhaled in the lungs

Question 22

What is “fixed” (non-volatile) acid?

Answer 22

Fixed (non-volatile) acid produces 50 mmol/day of inorganic and organic acid through amino acid metabolism
o Ex 2 C5H11NO2S + 15 O2  4 H+ + 2 SO42- + CO(NH2)2 + 7 H2O + 9 CO2
methionine urea

Question 23

Can fixed acid generation change appreciably?

Answer 23

Fixed acid increases with exercise (lactic acid) or diabetes mellitus (ketoacid)

Question 24

How does the body prevent major shifts in pH when there is a constant generation of metabolic acids?

Answer 24

Physicochemical buffering through substances such as bicarbonate
o Respiratory compensation, exhalation of CO2
o Renal compensation through H+ excretion and generation of HCO3- (bicarbonate)

Question 25

What are buffer systems; where are they located; what is meant by the pK of any given buffer?

Answer 25

A buffer is a molecule that combines with or releases H+ ions
o A buffer system minimizes the change in free H+ concentration
o pKa is the point of maximum buffering capacity

Question 26

Why is the bicarbonate buffer system considered to be the most important extracellular fluid buffer?

Answer 26

This buffer has dual control
o The lungs can regulate CO2 levels
o Kidneys can regulate plasma concentration of HCO3- (bicarbonate)
o H+ + Cl- + Na+ + HCO3-  Na+ + Cl- + H2CO3  H2O + CO2
o (weak acid (H2CO3) conversion to H2O + CO2 catalyzed by carbonic anhydrase; CA)

Question 27

What are typical values for plasma bicarbonate and CO2?

Answer 27

Plasma HCO3- (bicarbonate)- 24 mmol/L
o Plasma CO2 – 1.2 mmol/L
o The ratio of 20:1 in the Henderson-Hasselbalch will result in a pH of 7.4 which is a homeostatic acid/base balance

Question 28

How does the Henderson-Hasselbalch equation help predict pH?

Answer 28

By evaluating the acid base ratio (carbon dioxide/bicarbonate)
o pH = (pK) 6.1 + log [base; HCO3]
[acid; CO2]

Question 29

How is CO2 transported from the tissues to the lungs?

Answer 29

Red blood cells transport CO2 from the tissues to the lungs
o CO2 diffuses from the tissue to the RBC where it is converted to H+ and HCO3- (bicarbonate)
o H+ is buffered by de-oxygenated hemoglobin
o HCO3- (bicarbonate) diffuses out of the RBC in exchange for Cl-
o This process is reversed in the lungs

Question 30

Does H+ preferentially bind to oxygenated or de-oxygenated hemoglobin?

Answer 30

De-oxygenated

Question 31

What are the principal factors that regulate respiration rate?

Answer 31

o CO2 levels (increased CO2 increases respiration)

o Plasma H+ concentration (increased H+ increases respiration)

Question 32

The example worked through in class is clearly a little extreme!! It does however serve to illustrate the role of buffering and respiratory compensation in preventing major changes in body fluid pH. What is the contribution of the kidneys to restoration of normal body fluid pH in this model?

Answer 32

o Generation of new HCO3- (bicarbonate) restoring extracellular fluid levels
o Excretion of H+

Question 33

What is the “indirect” mechanism for bicarbonate reabsorption?

Answer 33

o Intracellular generation of H+ and HCO3- (catalyzed by carbonic anhydrase (CA))
o H+ is secreted into the lumen and combines with filtered HCO3- forming CO2 and H2O
o Intracellularly generated HCO3- transported across the basolateral membrane to ECF
o For every 1 mEq of filtered HCO3- converted, 1 mEq is added to the ECF – “indirect” reabsorption

Question 34

What is the rate-limiting step in this process?

Answer 34

o Presence of H+ATPase

Question 35

How can we generate new bicarbonate?

Answer 35

Occurs predominantly in the distal nephron
o Generation of new HCO3- dependent on the availability of urinary buffers to accept secreted H+
 Rate limiting step
o The kidneys can generate new HCO3- through
 urinary excretion of ammonium (NH4+) salts
 urinary excretion of titratable acids.

Question 36

Why is it essential to have additional tubular fluid buffers (such as titratable acid and NH3)? What is the source of renal NH3?

Answer 36

Bicarbonate stores are quickly depleted
o If buffers are depleted there will be no acceptor for H+ and new bicarbonate cannot be generated
?

Question 37

How can acid-base status affect NH3 synthesis?

Answer 37

Metabolic acidosis increases glutamine metabolism and results in an increased availability of NH3+

Question 38

What are the primary factors that regulate H+ ion secretion?

Answer 38

Intracellular generation of H+ occurs through catalyzation of H2O and CO2 by carbonic anhydrase to form H+ and HCO3-
o H+-Na+ anti-porter (primarily on the luminal membrane of proximal tubule cells)
o H+-ATPase (primarily luminal membrane of intercalated collecting tubule cells)

Question 39

How does aldosterone affect this system; where does it act?

Answer 39

In intercalated (versus principal) collecting tubule cells
o Increase in aldosterone increases H+ ATPase which increases H+ secretion resulting in increased HCO3 reabsorption

Question 40

What are the four simple acid-base disorders?

Answer 40

Respiratory disturbances: A shift in pH caused by a primary change in pCO2
 Respiratory acidosis: increased CO2 concentration decreases pH (e.g. hypoventilation)
 Respiratory alkalosis: decreased CO2 concentration increases pH (e.g. hyperventilation)
o Metabolic disturbances: A shift in pH caused by a primary change in plasma HCO3
 Metabolic acidosis: increased H+ concentration decreases HCO3- (e.g. diabetes mellitus)
 Metabolic alkalosis: decreased H+ causes an increase in bicarbonate concentration HCO3- (e.g. chronic vomiting)

Question 41

How do we compensate for these disorders?

Answer 41

Respiratory disturbances
 Renal compensation for a change in pH due to respiratory change is a change in plasma HCO3- levels to minimize the change in plasma H+ (slow response)
o Metabolic disturbances
 Respiratory compensation for a change in pH due to metabolic disturbance causes a change in respiration rate adjusting pCO2 levels
 Renal compensation for change in pH due to respiratory change is a restoration in plasma bicarbonate through reabsorption of ALL filtered bicarbonate and generation of new bicarbonate

Question 42

In the context of the bicarbonate buffer system and the Henderson-Hasselbalch relationship, what is compensation trying to achieve?

Answer 42

Acid base homeostasis of 7.4

Question 43

In our example of metabolic acidosis, renal compensation involves reabsorption of all filtered bicarbonate and synthesis of new bicarbonate. But if pCO2 is low, the required stimulus for H+ ion secretion is low; how do we resolve this paradox?

Answer 43

Hypoventilation increases pCO2

Question 44

What is an “anion gap”? What is this measurement used for?

Answer 44

A means of identifying the cause of a metabolic acidosis

o Determination if acidosis is from an organic acid (change in gap) or inorganic acid (no change in gap)

Question 45

What are the steps involved in determining a simple acid-base disorder?

Answer 45

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