Chapter 4 - Disorders of chloride

Question 1

How do you explain the difference of intracellular chloride concentration between a muscle cell and a red blood cell?

Answer 1

Intracellular concentration of chloride is dependent on the resting membrane potential of the cell.
Muscle cells have a resting membrane potential of approximately -68mV and an average chloride concentration of 2 to 4 mEq/L, whereas red blood cells have a resting membrane potential of approximately -15 mV and an average [Cl?]of 60
mEq/L

Question 2

T/F: Chloride is the most prevalent anion in the intracellular fluid

Answer 2

False, Chloride is the most prevalent anion in the ECF. Polyvalent anions (e.g., DNA, RNA, proteins, organic phosphates) replace chloride ion in ICF

Question 3

In which portion of the intestines is the highest chloride concentration? Lowest?

Answer 3

• Ileum

- Colon (90% of Cl- entering in the colon reabsorbed)

Question 4

In which part of the nephron is chloride transport associated with regulation of acid-base balance?

Answer 4

Cortical collecting tube

Question 5

In pancreatic fluid, is chloride a major anion at a lower or higher rate of pancreatic secretion?

Answer 5

Lower rate of secretion

Question 6

How much of the filtered chloride is reabsorbed in the proximal convoluted and straight tubules?

Answer 6

50-60%

Question 7

What is the mechanisms of loop diuretics?

Answer 7

Loop diuretics such as furosemide and bumetanide act in the loop of Henle by competing for the chloride site on the Naþ-Kþ- 2Cl?carrier.

Question 8

What is the mechanisms of thiazide diuretics?

Answer 8

Thiazide diuretics act by inhibiting the Na+- Cl- carrier in the early distal tubule, apparently at the chloride site

Question 9

What is an important route for reabsorption of chloride in the cortical collecting tubules?

Answer 9

Paracellular pathway by diffusion down an electro- chemical gradient

Question 10

Define strong anion

Answer 10

Strong anions are anions that are completely dissociated at the pH of body fluids (e.g., Cl?, lactate, ketoanions)

Question 11

What happened to the anion gap if chloride (strong anion) is increased?

Answer 11

If the strong anion added is chloride, the sum of the measured anions ([Cl-] + [HCO3-])will remain the same, and the AG will not change (so-called hyperchloremic or normal AG acidosis)

Question 12

At a constant [Na+], how does a decrease in [Cl-] affect SID and blood pH?

Answer 12

At a constant [Na+], a decrease in [Cl-] increases SID causing hypochloremic alkalosis, whereas an increase in [Cl-] decreases SID causing hyperchloremic acidosis.

Question 13

How does volume expansion allows the correction of alkalosis?

Answer 13

Volume expansion suppresses fluid and bicarbonate reabsorption, and more bicarbonate and chloride ions are delivered to distal nephron segments, which possess greater capacity to reabsorb chloride than bicarbonate. Chloride then is retained, bicarbonate is excreted, and alkalosis is corrected

Question 14

Where do the principal mechanisms by which the kidneys correct metabolic alkalosis occur?

Answer 14

The principal mechanisms by which the kidneys correct metabolic alkalosis probably operate in the collecting ducts, especially in the cortical segment, where HCO3- can either be secreted or reabsorbed

Question 15

How may hypokalemia cause hypochloremia?

Answer 15

Hypokalemia may cause hypochloremia by impairing recycling of potassium at the luminal membrane in the thick ascending limb ofHenle’s loop. This, in turn, impairs the effectiveness of the Naþ-Kþ-2 Cl? carrier, decreasing net chloride reabsorption

Question 16

How do the kidneys participate to metabolic acidosis correction?

Answer 16

Kidneys increase net acid excretion (primarily by enhanced NH4Cl excretion) beginning on day 1 and reaching a maximum after 5 to 6 days. The loss of chloride ions in the urine decreases urinary SID, because Cl- is accompanied by NH4+ (a weak
cation) rather than Na+.

Question 17

How does chronic respiratory alkalosis affect renal chloride handling?

Answer 17

Renal H+ ion excretion is decreased in chronic respiratory alkalosis. This effect probably is mediated by a decrease in intracellular [H+]. In this setting, there is a decrease in NH4Cl excretion in urine and an increase in renal reabsorption of Cl-. The increase in Cl- reabsorption decreases plasma SID and consequently [HCO3-]is
responsible for the hyperchloremia observed in dogs with chronic hypocapnia

Question 18

What is associated acid-base disorder related to corrected hyperchloremia and corrected hypochloremia, respectively?

Answer 18

Corrected hyperchloremia- decreased SID- hyperchloremic acidosis

Corrected hypochloremia- increased SID- hypochloremic alkalosis

Question 19

What are 2 conditions associated with high chloride concentration with normal corrected chloride concentration?

Answer 19

Pure water loss (DI, essential hypernatrmiea) or hypotonic fluid loss (osmotic diuresis)

Question 20

Which one mediates hypochloremia-induced renin release?

Answer 20

Macula densa

Question 21

GI causes of corrected hypochloremia

Answer 21

vomiting of stomach contents
GI disease associated with hyperkalemia and hyponatremia in dogs without hypoadrenocorticism (whipworm, duodenal ulcer, salmonellosis)

Question 22

Renal causes of corrected hypochloremia

Answer 22

Diuretics (thiazide, loop diuretics)

Chronic respiratory alkalosis

Question 23

True/false: Dogs with hypoadrenocorticism have corrected hyperchloremia

Answer 23

True (corrected hypochloremia with GI disease associated with hyperkalemia and hyponatremia in dogs without hypoadrenocorticism (whipworm, duodenal ulcer, salmonellosis)

Question 24

Which drug can cause pseudohyperchloremia?

Answer 24

Potassium bromide

Question 25

Mechanism of hyperchloremic acidosis in distal renal tubular acidosis

Answer 25

1. decrease in ammonia excretion

2. chloride replaces bicarbonate in the plasma

Question 26

3 mechanisms of hyperchloremia during the resolving phase of DKA

Answer 26

1. administration of large amount of NaCl
2. KCL is often infused in large doses
3. ketones are excreted in urine in exchange for NaCl

Question 27

What are two diuretics retaining chloride and cause hyperchloremia?

Answer 27

1. Potassium sparing diuretics (spironolactone, compete aldosterone)
2. Acetazolamine inhibitor carbonic anhydrase in proximal tubule

Question 28

When bicarbonate is recommended as the treatment of choice for hyperchloremic metabolic acidosis?

Answer 28

If plasma pH is less than 7.2 or bicarbonate concentration is less than 12 mEq/L in patients with hyperchloremic metabolic acidosis.