Lecture 2

Question 1

Cardiac output depends on:

Answer 1

1. myocardial contractility

2. ventricular filling pressure

Question 2

Vascular resistance depends on:

Answer 2

1. state of smooth muscle cells

2. activity of systems (sympathetic NS, RAAS, etc)

Question 3

Normal filtration rate

Answer 3

approx 120 mL/min

99% of the filtered fluid is reabsorbed

Question 4

Nephron

Answer 4

basic urine-forming unit

Question 5

glomerulus

Answer 5

filtration

Question 6

tubule

Answer 6

reabsorption and conditioning

conditioning= general term which stands for final adjustment of urine composition or secretion/ urine formation

Question 7

Reabsorption (of water, salt, and other nutrients) is the greatest in the ___

Answer 7

proximal tubule

and it declines distally towards the collecting duct!

Question 8

Bowman’s capsule

Answer 8

holds the glomerulus/ filtrated blood

Question 9

proximal tubule

Answer 9

65% of Na+ reabsorption

also highly permeable to H2O

Question 10

loop of Henle

Answer 10

25% of Na+ reabsorption
Thick ascending limb= main part for Na+ reabsorption
Thin descending limb= only part that does H2O

Question 11

early distal tubule & distal convoluted tubule

Answer 11

5% of Na+ reabsorption

Urea is IMPERMEABLE

Question 12

late distal tubule & collecting tubule (duct)

Answer 12

FINE CONTROL of ultrafiltrate composition and volume

Urea is IMPERMEABLE

Question 13

Na+ reabsorption is controlled by:

Answer 13

aldosterone

Question 14

H2O reabsorption is controlled by:

Answer 14

ADH (anti-diuretic hormone)

Question 15

___ is a major determinant of extracellular fluid volume in the body

Answer 15

NaCl

Question 16

Diuretics

Answer 16

increase the rate of urine flow and Na+ and Cl- excretion (and water follows sodium)

Question 17

Initial effects of diuretics

Answer 17

inc Na/Cl excretion –> dec extracellular fluid vol –> dec venous return –> dec cardiac output –> dec BP

Question 18

Chronic effects of diuretics

Answer 18

stimulation of compensatory mechanisms –> inc Na/Cl excretion; ex.cell. fluid vol returns to normal –> dec peripheral resistance –> BP remains lowered (mechanisms are not fully understood)

Question 19

Loop (high ceiling) diuretics

Answer 19

High ceiling= very potent drugs (Can cause really good diuresis)
MOA: inhibit Na/K/2Cl symporter (inhibit reabsorption/ trap the positive ions in the renal fluid/ filtrate)
Indirect effect: disrupted reabsorption of Ca and Mg

Question 20

Main urinary and hemodynamic effects of loop diuretics

Answer 20

1. great increase in urine flow (inc excretion of Na, K, Cl, Ca, Mg, [and uric acid if used acutely])
2. volume depletion & decrease in BP (initially) –> stimulation of renin release and SNS activity

Question 21

Adverse effects for loop diuretics

Answer 21

1. Fluid and electrolyte balance abnormalities
   - hypoNaemia
   - hypochloremic alkalosis
   - hypokalemia
   - hypomagnesemia and hypocalcemia
2. ototoxicity
3. hyperuricemia & hyperglycemia
4. increase in LDL and decrease in HDL

Question 22

What is the most potent loop diuretic?

Answer 22

bumetanide (Bumex)

Question 23

Site of action for thiazide diuretics

Answer 23

distal convoluted tubule (5% of Na+ reabsorption in this segment!)

Question 24

Site of action of loop diuretics

Answer 24

thick ascending limb of loop of Henle (25% of Na+ reabsorption in this segment!)

Question 25

Thiazide diuretics

Answer 25

MOA: inhibit Na/Cl symporter (inhibit reabsorption of Na, Cl)

Question 26

Main urinary and hemodynamic effects of thiazide diuretics

Answer 26

1. moderate inc in urine flow
   - inc excretion of Na, Cl, H2O
   - inc excretion of K (indirectly)
   - chronic use: dec excretion of Ca
   - chronic use: dec excretion of uric acid
2. lower BP in the result of inc Na excretion

Question 27

Caution with thiazides

Answer 27

diuretic (not BP lowering) effect is altered when GFR is <35 mL/min
exception: metolazone & indapamide

Question 28

Adverse effects of thiazides

Answer 28

1. Extracellular volume depletion, hypotension
   - hypoNaemia, hypoClemia, hypokalemia (high risk for arrhythmias)
   - hypercalcemia
   - hyperuricemia (high risk for gout)
2. reduction in glucose tolerance
3. increase risk for sexual impotency
4. increase levels of LDL, total cholesterol, and TG

Question 29

HCTZ vs chlorthalidone

Answer 29

Chlor is 50X more potent and has much longer half life

Question 30

Most potent thiazide

Answer 30

indapamide

Question 31

Site of action for K+-sparing diuretics – Na channel inhibitors

Answer 31

late distal tubule & collecting duct (fine adjustment of urine composition, 2% Na reabsorption!)

Question 32

Potassium-sparing diuretics – Na channel inhibitors

Answer 32

MOA: inhibit renal epithelial Na+ channels –> dec reabsorp of Na –> K+ (and H+) is NOT excreted into the lumen!
act on principal cells which normally capture Na from the filtrate and release K

Question 33

Main effects of K-sparing diuretics – Na channel inhibitors

Answer 33

slight increase in urine flow

• slight inc in excretion of Na, Cl
• inc excretion of K+ (and H+ indirectly)

Question 34

Adverse effects of K-sparing diuretics – Na channel inhibitors

Answer 34

hyperkalemia
N/V, diarrhea, HA
triamterene can reduce glucose tolerance and cause photosensitization

Question 35

Site of action for K+-sparing diuretics – Aldosterone antagonists

Answer 35

late distal tubule & collecting duct

Question 36

K+-sparing diuretics – Aldosterone antagonists

Answer 36

MOA: inhibit aldosterone binding to its (mineralocorticoid) receptors –> effects of aldosterone are blocked –> reabsorption of Na decreases –> K+ (and H+) are NOT excreted!
act on intercalated cell on the mineralocorticoid receptors

Question 37

Adverse effects of K+-sparing diuretics – Aldosterone antagonists

Answer 37

• hyperkalemia
• spironolactone may cause gynecomastia, sexual impotency, decreased libido, etc/ can alter clearance of digitalis glycosides