Jackson 8

Question 1

Diuresis =

Answer 1

excessive urine ouput

Question 2

Reasons for use of diuretics

Answer 2

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

hypertension
↑ ECV → ↑ plasma volume → ↑ blood pressure

Question 3

Different diuretics act on different segments of the nephron. They gain access to tubules either by

Answer 3

filtration or secretion.

Question 4

Osmotic diuretics - retain water by

Answer 4

increasing osmotic pressure; act in water-permeable segments of the nephron (PT & descending loop of Henle)

Question 5

CA inhibitors – reduce

Answer 5

Na+ reabsorption; proximal tubule is major site of action

Question 6

Loop diuretics – act in

Answer 6

thick ascending limb to inhibit Na+ reabsorption via the Na+ K+ 2Cl- symporter

Question 7

Thiazides – block

Answer 7

Na+Cl- symporter in early distal tubule

Question 8

K+ - sparing – two classes that both act in

Answer 8

late distal tubule and cortical collecting duct to inhibit sodium reabsorption AND potassium secretion

1. aldosterone antagonists
2. ENaC blockers

Question 9

Aquaretics –

Answer 9

ADH receptor antagonists

Question 10

Osmotic diuretics increase the osmotic pressure in the

Answer 10

tubular fluid, and, thus, impair Na+ reabsorption.

Question 11

Osmotic diuretics

Examples include

Answer 11

mannitol and pathologically elevated glucose.

Question 12

Osmotic diuretics

Answer 12

gain access to tubule by glomerular filtration

are poorly reabsorbed

will have an effect where tubule is freely permeable to water

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

Question 13

Carbonic anhydrase inhibitors reduce

Answer 13

Na+ reabsorption by inhibiting CA, thus reducing the H+ available for the Na+/H+ antiporter.

Question 14

Acetazolamide is an example of a

Answer 14

CA inhibitor.

Question 15

CA inhibitors gain access to the

Answer 15

proximal tubule via secretion

Question 16

CA inhibitors

Most of the diuretic effect is in the

Answer 16

proximal tubule where ~1/3 of Na+ reabsorption relies on the Na+/H+ antiporter

Question 17

CA inhibitors

Diuretic effect is

Answer 17

not large
downstream segments will increase Na+ reabsorption when tubular Na+ increases

typically increases Na+ excretion to 5-10% of filtered load

Question 18

Loop diuretics are the most

Answer 18

powerful of all diuretics; they inhibit Na+ reabsorption in the ascending limb of the loop of Henle.

Question 19

Furosemide (lasix) is an example of a

Answer 19

loop diuretic.

Question 20

Loop diuretics are secreted into the

Answer 20

proximal tubule (not filtered)

Question 21

LOOP DIURETICS:

Inhibit

Answer 21

Na+K+2Cl- symporter in the thick ascending limb which inhibits Na+ reabsorption

Question 22

Loop diuretics

urine leaving loop is not

Answer 22

dilute

Question 23

Loop diuretics

no osmotic gradient established in the

Answer 23

medulla interstitium so water is not reabsorbed along collecting duct → urine is dilute (500 mOsm instead of 1400 mOsm)

Question 24

Loop diuretics

Can increase

Answer 24

Na+ excretion to as much as 25% of filtered load, because Na+ reabsorption capacities downstream of their site of action are limited.

Question 25

Thiazide diuretics | Thiazide diuretics like

Answer 25

chlorothiazide are secreted into the proximal tubules, and they act in the early distal tubule to block the Na+Cl- transporter

Question 26

Thiazide diuretics kidney’s ability to dilute urine is

Answer 26

diminished

Question 27

Thiazide diuretics | reabsorption of water in the collecting duct still occurs, but

Answer 27

5-20% of the filtered Na+ is excreted

Question 28

K+-sparing diuretics | K+ - sparing diuretics act where

Answer 28

K+ is normally secreted into the tubular fluid by the principal cells. There are two types of K+- sparing diuretics

Question 29

K+-sparing diuretics 1. aldosterone antagonists, e.g. spironolactone block

Answer 29

aldosterone’s ability to increase Na+ transporters in principal cells must get inside tubular cells to block aldosterone receptors

Question 30

K+-sparing diuretics 2. ENaC blockers, e.g. amiloride block

Answer 30

Na+ reabsorption across the apical membrane these act on a membrane protein so can gain access by secretion into the proximal tubule

Question 31

Aquaretics | Aquaretics, e.g. tolvaptan, increase excretion of water by blocking the action of

Answer 31

ADH in the late distal tubules and collecting duct. Water is eliminated without the loss of solutes.

Question 32

Secondary effects of diuretics Diuretic braking phenomenon Continued use of diuretics becomes

Answer 32

less effective because volume contraction counteracts the effects of the diuretic, i.e. diuretics decrease ECV so compensatory mechanisms activated

Question 33

diuretic braking | 1. increased sympathetic activity in response to reduced BP --->

Answer 33

decrease GFR à increase PT reabsorption & increase renin

Question 34

diuretic braking | 2. decrease

Answer 34

natriuretic peptides

Question 35

diuretic braking | 3. secrete renin from

Answer 35

juxtaglomerular apparatus à increase angiotensin II and aldosterone à decrease Na+ excretion

Question 36

diuretic braking | 4. stimulate ADH release ---->

Answer 36

decrease water excretion

Question 37

Side effects of Procrit ® treatment include

Answer 37

flu-like symptoms, headaches, high BP, and cardiovascular problems

Question 38

Using EPO to treat anemia in dialysis patients | Treatment of anemia typically uses

Answer 38

Procrit ® to stimulate erythropoiesis (rather than rely on transfusions).

Question 39

Increased excretion of K+ | Diuretics increase Na+ reabsorption, so they secondarily influence

Answer 39

renal processing of other solutes (and water)

Question 40

K+ excretion increases because……

Answer 40

diurectics increase the flow of tubular fluid which stimulates K+ secretion diuretics reduce ECV à increase aldosterone à stimulate K+ secretion K+ -sparing diuretics are used to prevent an increase in K+ secretion

Question 41

Disruption of acid-base balance Acid-base balance is affected by all diuretics CA inhibitors --->

Answer 41

metabolic acidosis

Question 42

Loop and thiazide diuretics --->

Answer 42

reduced ECV à metabolic alkalosis

Question 43

potassium-sparing diuretics ---->

Answer 43

metabolic acidosis because H+ secretion in distal tubule and cortical collecting duct is inhibited

Question 44

Except for the K+ sparing diuretics, all other diuretics

Answer 44

alter calcium excretion.

Question 45

Osmotic and CA inhibitors both act in

Answer 45

proximal tubule and reduce reabsorption of calcium in this segment (so excretion is increased).

Question 46

Loop diuretics increase calcium excretion by affecting the

Answer 46

transepithelial voltage that normally provides the driving force for paracellular transport of calcium.

Question 47

Thiazide diuretics stimulate calcium reabsorption in the distal tubule and thus reduce

Answer 47

excretion. | Normally, distal tubule reabsorbs 9% of filtered calcium via active transport.

Question 48

The concentration of NaCl in the dialysis fluid is similar to that in

Answer 48

plasma. Urea, potassium, phosphate diffuse from blood into dialysis fluid.

Question 49

Bicarbonate is high in the dialysis fluid so it

Answer 49

diffuses into blood to correct blood acidity

Question 50

Methods of accessing the blood for dialysis: pros & cons catheter –

Answer 50

used to access venous blood for short-term treatment; scarring, vessel narrowing or occlusion can occur

Question 51

Methods of accessing the blood for dialysis: pros & cons AV fistula –

Answer 51

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.

Question 52

Methods of accessing the blood for dialysis: pros & cons | AV graft –

Answer 52

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.

Question 53

Dialysis treatment requires a prescription and can vary based on

Answer 53

type of solution, frequency, and size of dialyzer – typically 3-4 hours per treatment, three times per week

Question 54

Side effects and complications of hemodialysis Short-term side effects:

Answer 54

fatigue, chest pains, cramps, nausea, headaches often called “dialysis hangover” due to acute, dramatic changes in blood chemistry.

Question 55

Long-term consequences of hemodialysis

Answer 55

sepsis, endocarditis & osteomyelitis (secondary infections)

Question 56

amyloid deposits in joints (like amyloid plaques that form in neural tissue) can result from the

Answer 56

build-up of trace minerals (e.g. copper, zinc, and aluminum) that might be in the dialysis fluid.

Question 57

Patients with chronic renal failure are almost always diagnosed with anemia due

Answer 57

inadequate secretion of erythropoietin (EPO) and loss of erythrocytes.

Question 58

EPO is produced by

Answer 58

interstitial fibroblasts in the renal cortex, and its production is controlled at the transcriptional level.

Question 59

EPO production is stimulated when

Answer 59

PO2 is low due to activity of transcription factors that regulate EPO synthesis (hypoxia-inducible factors 1 and 2 or HIF-1 and HIF-2)

Question 60

HIFs are continually produced, but are targeted for degradation when

Answer 60

O2 is normal.

Question 61

When O2 is low, they function as

Answer 61

transcription factors to increase EPO synthesis and secretion.

Question 62

EPO stimulates differentiation of

Answer 62

erythrocyte progenitor cells in the bone marrow