Postassium, Calcium, & Hydrogen Ion Balance

Front 1

____% of total body K⁺ is intracellular

Back 1

98

Front 2

What is the normal plasma [K⁺]?

Back 2

4 mEq/L

Front 3

Define hyperkalemia

Back 3

Plasma [K⁺] > 5.5 mEq/L

Front 4

Define hypokalemia

Back 4

Plasma [K⁺] < 3.5 mEq/L

Front 5

Changes in extracellular K⁺ can change...

Back 5

Resting membrane potential (e.g., ↑ K⁺ → ↓ resting membrane potential → ↑ excitability)

Front 6

How are dietary intake-induced changes in plasma [K⁺] prevented?

Back 6

• Rapid cellular uptake of K⁺ (epinephrine, insulin, aldosterone → ↑ Na⁺-K⁺-ATPase)

• Renal excretion (much slower)

Front 7

~____% of the filtered load of K⁺ is reabsorbed by the proximal tubule and the thick ascending limb

Back 7

90

Front 8

How is the rate of K⁺ excretion primarily regulated?

Back 8

By controlling the rate of K⁺ secretion into the late distal nephron and collecting tubule

Front 9

How is K⁺ secreted into the distal nephron and collecting tubule?

Back 9

1. Uptake of K⁺ across the basolateral membrane via Na⁺-K⁺-ATPase

2. Efflux of K⁺ across the luminal membrane via K⁺ channels & K⁺-Cl⁻ cotransporters

3. Lumen negative potential created by Na⁺ reabsorption promotes K⁺ secretion

Front 10

In cases of hypokalemia, how is K⁺ secretion prevented in the distal nephron & collecting tubule?

Back 10

1. Uptake of K⁺ across the luminal membrane via energy-dependent K⁺-H⁺ anti-porter
2. Efflux of K⁺ across the basolateral membrane via K⁺-selective channels

Front 11

List two potential causes of hyperkalemia

Back 11

1. Hypertonic ECF - causes cells to shrink, increasing intracellular [K⁺] and thus increasing K⁺ efflux
2. Cell lysis - releases K⁺ into the ECF → (local) hyperkalemia (e.g., exercise-induced muscle breakdown)

Front 12

Changes in ECF ____ concentration can cause parallel changes in ECF [K⁺]

Back 12

H⁺

Front 13

Describe the effects of changes in ECF [H⁺] on ECF [K⁺]

Back 13

Metabolic alkalosis (↓ ECF H⁺) → ↓ plasma [K⁺] (K⁺ moves from ECF to ICF)

Metabolic acidosis (↑ ECF H⁺) → ↑ plasma [K⁺] (K⁺ moves from ICF to ECF)

Front 14

Which has the greater effect on plasma [K⁺], metabolic acidosis due to inorganic acids (HCl, H₂SO₄) or a similar acidosis due to organic acids (lactic acid, keto acids)?

Back 14

Metabolic acidosis due to inorganic acids

Front 15

What effect do respiratory acid-base disorders have on plasma [K⁺]?

Back 15

Little or no effect

Front 16

How do increases in ECF [K⁺] affect K⁺ secretion and excretion in the urine?

Back 16

K⁺ secretion and thus excretion are increased by:

1. Direct ↑ Na⁺-K⁺-ATPase activity on distal nephron cells
2. Direct ↑ aldosterone secretion → ↑ Na⁺-K⁺-ATPase activity & ↑ luminal membrane K⁺ permeability

Front 17

What effect does tubular fluid flow have on K⁺ secretion?

Back 17

↑ Flow → ↑ K⁺ secretion due to:

1. ↑ Flow minimizes the rise in tubular fluid K⁺ concentration (↑ cell-to-lumen K⁺ gradient)
   
2. ↑ Flow → ↑ Na⁺ reabsorption → ↑ Na⁺-K⁺-ATPase activity → ↑ intracellular K⁺

Front 18

What effect do loop diuretics have on plasma [K⁺]?

Back 18

May increase K⁺ excretion and lead to hypokalemia due to:

1. ↓ K⁺ reabsorption in the thick ASC
   
2. ↑ Distal K⁺ secretion due to ↑ tubular fluid flow & ↑ distal Na⁺ reabsorption
   

Front 19

Maintenance of normal plasma [Ca²⁺] is dependent upon PTH-mediated effects on...

Back 19

• Kidney (↓ [Ca²⁺] → ↑ PTH secretion → ↑ renal Ca²⁺ reabsorption)
• GI tract (↓ [Ca²⁺] → ↑ PTH secretion → ↑ calcitriol → ↑ intestinal Ca²⁺ absorption)
• Bone (↓ [Ca²⁺] → ↑ PTH secretion → ↑ bone resorption)

Front 20

How is Ca²⁺ reabsorbed in the distal tubule?

Back 20

1. Luminal Ca²⁺ channels
2. Ca²⁺ ATPase & Na⁺-Ca²⁺ exchanger on the basolateral membrane
   

Front 21

How is bone resorption-induced hyperphosphatemia prevented?

Back 21

Inhibitory effect of PTH on renal HPO₄²⁻ reabsorption

Front 22

How does PTH reduce HPO₄²⁻ reabsorption by the proximal tubule?

Back 22

Inhibition of luminal Na⁺-HPO₄²⁻ co-transporter

Front 23

How does the distal convoluted tubule reabsorb NaCl?

Back 23

1. Luminal NCC (Na⁺-Cl⁻ co-transporter)
2. Basolateral KCC4 (K⁺-Cl⁻ co-transporter) & CIC-Kb (Cl⁻ channel)

Front 24

____ diuretics target the NCC (Na⁺-Cl⁻ co-transporter)

Back 24

Thiazide

Front 25

How does the distal convoluted tubule reabsorb Ca²⁺?

Back 25

Luminal TRPV5 channel (Transient Receptor Potential Vanilloid type 5)

Front 26

How does the distal convoluted tubule reabsorb Mg²⁺?

Back 26

Luminal TRPM6 channel (Transient Receptor Potential Melastatin type 6)

Front 27

How do you calculate pH?

Back 27

pH = -log[H⁺]

Front 28

What is the normal plasma pH?

Back 28

7.37-7.42

Front 29

What are the survival limits of plasma pH?

Back 29

6.80-8.00

Front 30

What are the two principal metabolic sources of H⁺?

Back 30

Volatile acid (~15-20,000 mmol/day of CO₂ generated by oxidative metabolism)

Fixed (non-volatile) acid (~50 mmol/day of inorganic and organic acid generated (for example) by amino acid metabolism; increases with exercise (lactic acid) and diabetes mellitus (ketoacid)

Front 31

Does volatile acid typically cause any problems?

Back 31

No, because it is efficiently eliminated by the lungs

Front 32

What are the three "lines of defense" that help prevent fixed acid-induced acidification of body fluids?

Back 32

1. Physicochemical buffering
2. Respiratory compensation (CO₂ elimination)
3. Renal compensation (H⁺ excretion & generation of HCO₃⁻)

Front 33

Define buffer

Back 33

A molecule that combines with or releases H⁺ ions

Front 34

Describe the dibasic-monobasic phosphate buffer system

Back 34

H⁺ + HPO₄²⁻ ↔ H₂PO₄⁻

↑ H⁺ + HPO₄²⁻ → H₂PO₄⁻

↓ H⁺ + HPO₄²⁻ ← H₂PO₄⁻

Front 35

Define pK

Back 35

pH at which buffer component concentrations equal (represents the point of greatest buffering capacity)

Front 36

What is the pK of the PO₄⁻ buffering system?

Back 36

6.8

Front 37

What is the isohydric principle?

Back 37

The free H⁺ concentration (pH) is determined by the combined effect of all buffers in a given compartment

Front 38

What buffering system is present in both plasma and urine?

Back 38

Phosphate buffering system

Front 39

What buffering systems are present intracellularly?

Back 39

Protein buffering

Organic phosphate buffering

Front 40

What buffering system is present within RBCs?

Back 40

Hemoglobin buffering

Front 41

What buffering system is present within bone?

Back 41

Hydroxyapatite

Front 42

What is the most important extracellular buffering system?

Back 42

Carbon dioxide-bicarbonate buffering system

Front 43

What enzyme catalyzes the conversion of water and carbon dioxide to carbonic acid (and vice versa)?

Back 43

Carbonic anhydrase (CA)

Front 44

What is the Henderson-Hasselbalch equation?

Back 44

pH = pK + log [base; HCO₃]/[acid; CO²]

Front 45

How do you convert pCO₂ to mmol/L of dissolved CO₂?

Back 45

pCO₂ × 0.03 (CO₂ solubility coefficient)

Front 46

How is CO₂ transported for tissues to the lungs?

Back 46

RBCs

Front 47

Describe the process of CO₂ elimination from the tissues

Back 47

1. CO₂ diffuses from tissue → RBCs where it is converted to H⁺ + HCO₃⁻ (by carbonic anhydrase)
2. H⁺ buffered by de-oxygenated hemoglobin
3. HCO₃⁻ diffuses out of the RBC in exchange for Cl⁻ (the "chloride shift")
4. Process reversed at the lungs

Front 48

Under normal conditions, what controls arterial pCO₂?

Back 48

Alveolar ventilation

Front 49

Alveolar ventilation is regulated by...

Back 49

• Arterial pCO₂

• Plasma H⁺ concentration

Front 50

Describe the relationship between arterial pCO₂ and alveolar ventilation

Back 50

↑ Arterial pCO₂ → ↑ alveolar ventilation

Front 51

Describe the relationship between plasma H⁺ concentration and alveolar ventilation

Back 51

↑ Plasma [H⁺] → ↑ alveolar ventilation

Front 52

How would the body respond to an IV infusion of HCl?

Back 52

1. Physiochemical buffering (all acid buffered by HCO₃⁻)
2. Respiration eliminates the CO₂ generated in the buffering process
3. Continued low pH will stimulate respiration & further decreases in pCO₂
4. Kidneys generate new HCO₃⁻ and excrete excess H⁺ that was retained with other buffers

Front 53

>____% of filtered HCO₃⁻ is reabsorbed by the proximal tubule

Back 53

99

Front 54

How is HCO₃⁻ reabsorbed in the proximal tubule?

Back 54

1. Intracellular generation of H⁺ and HCO₃⁻ from CO₂ and H₂O (catalyzed by CA)
2. H⁺ secreted into the lumen (via H⁺-Na⁺ anti-porter) where it combines with filtered HCO₃⁻ forming CO₂ & H₂O (catalyzed by CA)
3. HCO₃- transported across basolateral membrane to ECF (via Cl⁻-HCO₃⁻ anti-porter)

Front 55

____ inhibits carbonic anhydrase and can cause acidosis

Back 55

Acetazolamide (a diuretic)

Front 56

Proximal tubule HCO₃⁻ reabsorption is regulated by...

Back 56

• Arterial blood pCO₂ (↑ pCO₂ → ↑ H⁺ secretion → ↑ HCO₃⁻ reabsorption)

• Na⁺ reabsorption (↑ Na⁺ reabsorption → ↑ Na⁺-H⁺ antiport → ↑ H⁺ secretion → ↑ HCO₃⁻ reabsorption)

Front 57

What segment of the nephron is responsible for the majority of new HCO₃⁻ production?

Back 57

Distal nephron intercalated collecting tubule cells

Front 58

Generation of new HCO₃⁻ depends on...

Back 58

The availability of urinary buffers to accept secreted H⁺ (HPO₄²⁻/H₂PO₄⁻)

Front 59

How is HCO₃⁻ generated in the proximal tubule?

Back 59

From glutamine metabolism

Front 60

Proximal tubule HCO₃⁻ generation also produces...

Back 60

Ammonium (NH₄⁺)

Front 61

What happens to the NH₄⁺ generated in the proximal tubule?

Back 61

1. NH₄⁺ is secreted into the tubular lumen
2. NH₄⁺ is reabsorbed in the thick ASC (substitutes for K⁺ on the Na⁺-K⁺-2Cl⁻ co-transporter)
3. NH₄⁺ transported across intercalated cells into the lumen and excreted
4. NH₃ transported into lumen and interacts with secreted H⁺ forming new HCO₃⁻

Front 62

How does metabolic acidosis affect renal HCO₃⁻ synthesis?

Back 62

It increases glutamine metabolism and thus HCO₃ synthesis/NH₃ availability

Front 63

How does aldosterone affect HCO₃ synthesis?

Back 63

↑ Aldosterone → ↑ H⁺ ATPase → ↑ H⁺ excretion → ↑ HCO₃⁻ reabsorption/synthesis

Front 64

Define acidemia

Back 64

Blood pH < 7.35

Front 65

Define alkalemia

Back 65

Blood pH > 7.45

Front 66

Define respiratory acidosis

Back 66

↑ pCO₂ → ↓ pH (e.g. hypoventilation)

Front 67

Define respiratory alkalosis

Back 67

↓ pCO₂ → ↑ pH (e.g., hyperventilation)

Front 68

Define metabolic acidosis

Back 68

↑ H⁺ → ↓ HCO₃⁻ (e.g., ketoacidosis)

Front 69

Define metabolic alkalosis

Back 69

↓ H⁺ → ↑ HCO₃⁻ (e.g, chronic vomiting)

Front 70

How does the body respond to respiratory acidosis?

Back 70

Renal production of HCO₃⁻ (relatively slow)

Front 71

Why should you avoid immediate removal of a respiratory obstruction in a patient with respiratory acidosis?

Back 71

pCO₂ will normalize quickly, but excess HCO₃⁻ will cause metabolic alkalosis

Front 72

How does the body respond to metabolic acidosis?

Back 72

Increased respiration (very fast response)

Front 73

After respiratory compensation, how is there enough H⁺ to reabsorb/synthesize the necessary HCO₃⁻?

Back 73

Low plasma HCO₃⁻ resultes in a greatly reduced filtered load of HCO₃⁻, thus H⁺ is still sufficient to reabsorb all filtered HCO₃⁻and generate new HCO₃⁻ (1 meq H⁺ secreted = 1 meq HCO₃- reabsorbed/synthesized)

Front 74

How do you calculate the anion gap?

Back 74

Anion gap = [Na⁺] - ([Cl⁻] + [HCO₃⁻])

Front 75

What is a normal anion gap?

Back 75

8-16 mEq/L

Front 76

How is the anion gap used clinically?

Back 76

To identify the cause of metabolic acidosis

Front 77

List some causes of metabolic acidosis that present with a high anion gap

Back 77

• Diabetic ketoacidosis
  
• Lactic acidosis

Front 78

List some causes of metabolic acidosis that present with a normal anion gap

Back 78

• HCl-induced acidosis (↓ HCO₃⁻ but ↑ Cl⁻)
• Diarrhea (loss of HCO₃⁻ in the stool but retention of Cl⁻)