Diuretics, Hemodialysis, and Erythropoietin

Question 1

A ___ is a drug that increases urine output due to their actions on the kidney. They are often called “water pills” (all inhibit water reabsorption), but they can increase excretion of things as well.

Answer 1

diuretic

Question 2

What reasons would one prescribe a diuretic in a patient with CHF or HTN?

Answer 2

CHF: heart weakens → ↓ cardiac output → ↓ GFR → ↑ aldosterone → ↑ Na+ and H2O reabsorption → ↑ ECV and edema

HTN: ↑ ECV → ↑ plasma volume → ↑ blood pressure

Question 3

Match:

1. osmotic diuretics
2. CA inhibitors
3. Loop diuretics
4. Thiazides
5. K+ sparing
6. Aquaretics

A. reduce Na+ reabsorption at the proximal tubule (major site)
B. block Na+/Cl- symporter in early distal tubule
C. retain water by increasing osmotic pressure; act in water-permeable segments of the nephron (PT and descending loop of Henle)
D. ADH receptor antagonists
E. act in late distal tubule and cortical collecting duct to inhibit sodium reabsorption AND potassium secretion
F. act in thick ascending limb to inhibit Na+ reabsorption via the Na+/K+/2Cl- symporter

Answer 3

1 - C
2 - A
3 - F
4 - B
5 - E
6 - D

Question 4

What are the two classes of K+ sparing diuretics?

Answer 4

1. aldosterone

2. ENaC blockers

Question 5

___ diuretics increase the osmotic pressure in the tubular fluid and thus impair Na+ reabsorption. What are some examples.

Answer 5

Osmotic

mannitol and pathologically elevated glucose

Question 6

How do osmotic diurectics work?

Answer 6

1. gain access to tubule by glomerular filtration due to small size
2. are poorly reabsorbed (mannitol - no transporter; glucose - saturates transporter so not all reabsorbed)
3. will have an effect where tubule is freely permeable to water
4. some of what’s not reabsorbed in PT and DL can be reabsorbed downstream, but typically results in excretion of 10% of filtered Na+

note: ↓ water reabsorption → ↓ Ca2+ reabsorption by solvent drag (there is no osmotic gradient established by Na+ so Ca2+ not reabsorbed

Question 7

___ ___ inhibitors reduce Na+ reabsorption by inhibiting CA, thus reducing the H+ available for the Na+/H+ antiporter. Give an example.

Answer 7

Carbonic anhydrase

Acetazolamide

Question 8

CA inhibitors gain access to the proximal tubule via ___.

Answer 8

secretion

most of the effect is in the PT where ~1/3 of Na+ reabsoprtion relies on the Na+/H+ antiporter

Question 9

Why is the effect of CA inhibitors not large?

Answer 9

1. the downstream segments will increase Na+ reabsorption when tubular Na+ increases
2. typically increases Na+ excretion to 5-10% of filtered load

Question 10

___ diuretics are the most powerful of all diuretic. How do thy work? Give an example.

Answer 10

Loop

they inhibit Na+ reabsorption in the ascending limb of the loop of Henle

Furosemide (lasix)

Question 11

T/F. Loop diuretics are filtered not secreted into the proximal tubule.

Answer 11

False, they are secreted NOT filtered

Question 12

Loops inhibit the ___ symporter in the ___ ___ limb which inhibits Na+ reabsorption. What happens as a result?

Answer 12

Na+/K+/2Cl-; thick ascending

1. urine leaving the loop is not dilute
2. no osmotic gradient established in the medulla interstitium so water not reabsorbed along collecting duct → urine is dilute (500 mOsm instead of 1400 mOsm)
3. can increase Na+ excretion to as much as 25% of filtered load, because Na+ reabsorption capacities downstreams of their site of action are limited

Question 13

Thiazide diuretics, like ___, are ___ into the PT, but where do they act?

Answer 13

chlorothiazide; secreted

they act in the distal tubule to block the Na+/Cl- transporter

Question 14

T/F. With thiazides, the kidney’s ability to dilute urine is diminished.

Answer 14

True.

Question 15

With thiazides, reabsorption of water still occurs in the collecting duct, but ___-___% of the filtered Na+ is excreted.

Answer 15

5-20

Question 16

K+-sparing diuretics act where K+ is normally ___ into the tubular fluid by the ___ cells.

Answer 16

secreted; principal

Question 17

How does spironolactone work?

Answer 17

Aldosterone antagonists block aldosterone’s ability to increase Na+ transporters in principal cells

Question 18

How does amiloride work?

Answer 18

ENaC blockers block Na+ reabsorption across the apical membrane. These act on a membrane protein so can gain access by secretion into the PT.

Question 19

T/F. Continued use of diuretics become more effective.

Answer 19

False, continued use of diuretics become LESS effective because volume contraction counteracts the effects of the diuretic.

Question 20

Diuretics decrease ECV so compensatory mechanisms are activated in response to the nervous and endocrine system. Explain this process.

Answer 20

1. ↑ sympathetic activity in response to reduced BP → ↓ GFR → ↑ PT reabsorption and ↑ renin
2. ↓ natriuretic peptides
3. secrete renin from JGA → ↑ angiotensin II and aldosterone ↓ Na+ excretion
4. stimulate ADH release → ↓ water excretion

Question 21

___ removes waste products from the blood when kidney function has been impaired.

Answer 21

Hemodialysis

Question 22

In a kidney-failure patient undergoing dialysis, the blood is briefly removed from the body to be circulated through a ___, which is a cylindrical bundle of hollow fibers. The walls of the fibers are made of a semipermeable membrane with ___ of defined size that allow small molecules to diffuse into the dialysis fluid. The fluid and blood move in ___ directions to remove nitrogenous and other wastes, and adjust osmolarity before the blood is returned to the body.

Answer 22

dialyzer; pores; countercurrent

Question 23

The concentration of ___ in the dialysis fluid is similar to that in plasma. ___, ___, and ___ diffuse from blood into dialysis fluid. ___ is high in the dialysis fluid so it diffuses into blood to correct blood ___.

Answer 23

Na+; Urea; potassium; phosphate; Bicarbonate; acidity

Question 24

Match the following:

1. catheter
2. AV fistula
3. AV graft

A. preferred for long term treatment; creates an anastomosis between artery and vein. Arterial blood is withdrawn, and blood is returned to the vein after dialysis.
B. used to access venous blood for short-term treatment; scarring, vessel narrowing or occlusion can occur
C. uses an artificial/synthetic vessel to join an artery and vein when vascular problems do not permit using a fistula; can become narrowed which can lead to clotting and/or infections.

Answer 24

1 - B
2- A
3 - C

Question 25

T/F. Dialysis treatment requires a prescription and can vary based on type of solution, frequency, and size of dialyzer - typically 3-4 hours per treatment, three times per week.

Answer 25

True.

Question 26

What are the short term side effects of hemodialysis?

Answer 26

fatigue, chest pains, cramps, nausea, headaches

often called “dialysis hangover” due to acute, dramatic changes in blood chemistry

Question 27

What are the long-term side consequences to hemodialysis?

Answer 27

sepsis, endocarditis & osteomyelitis (secondary infections)

Question 28

___ deposits in joints can result from the build up of trace minerals (like copper, zinc, and aluminum) that might be in the dialysis fluid.

Answer 28

Amyloid

Question 29

What are patients with chronic renal failure almost always diagnosed with?

Answer 29

anemia due to inadequate secretion of erythopoietin (EPO) and loss of erythrocytes

Diseased kidneys do not make enough EPO therefore, the bone marrow makes fewer red blood cells.

Question 30

T/F. A healthy kidney produces a hormone called EPO which inhibits bone marrow from making red blood cells.

Answer 30

False, A healthy kidney produces a hormone called EPO which STIMULATES bone marrow to make red blood cells.

Question 31

EPO is produced by ___ ___ in the renal ___ and its production is controlled at the ___ level.

Answer 31

interstitial fibroblasts; cortex; transcriptional

Question 32

How is EPO production stimulated?

Answer 32

when PO2 is low due to activity of transcription factors that regulate EPO synthesis

Question 33

___-___ factors 1 and 2 are continually produced. Under what conditions do they work?

Answer 33

hypoxia-inducible factors 1 and 2 (HIR-1 or HIF-2)

1. targeted for degradation when O2 is normal.
2. When O2 is low, they function as transcription factors to increase EPO synthesis and secretion

Question 34

T/F. EPO stimulates differentiation of erythrocyte progenitor cells in the bone marrow.

Answer 34

True.

Question 35

Treatment of anemia typically uses ___ to stimulate erythropoiesis. What are the side effects of this recombinant drug?

Answer 35

Procrit

SE: flu-like symptoms, headahces, high BP, and cardiovascular problems

Question 36

Anemic women who menstruate and have a hematocrit less than ___% and a hemoglobin level less than ___g/dL should be evaluated for dialysis.

Answer 36

33; 11

Question 37

All anemic men and postmenopausal women with a hematocrit less than ___% and hemoglobin less than ___ g/dL should be evaluated for dialysis.

Answer 37

37; 12