Duan > Diuretics I Flashcards
1
Q
what are the 5 major fxns of the kidney?
A
- filtration & reabsorption
- regulation
- secretion
- excretion
- gluconeogenesis
2
Q
what does the kidney regulate?
A
body fluid volume & osmolarity
electrolyte balance
acid-base balance
BP
3
Q
what does the kidney secrete?
A
EPO
1,25-dihydroxy vitamin D3
renin-angiotensin-aldosterone
prostaglandin
4
Q
what does the kidney excrete?
A
metabolic pdts
foreign substances
XS stuff (water, etc)
5
Q
what is the functional unit of the kidney?
A
nephron
6
Q
what are the 2 major components of a nephron?
A
glomerulus
tubule system
7
Q
what is the glomerulus?
A
a compact cluster of convoluted capillaries
8
Q
what does the glomerulus do?
A
filtration > remove substances from blood before it flows into the convoluted tubule
9
Q
what is the tubule system the site of?
A
reabsorption
secretion
excretion
10
Q
where does filtration occur?
A
glomerulus
11
Q
where does reabsorption occur?
A
desc & asc limb of the loop of Henle
12
Q
where does secretion occur?
A
desc & asc limb of the loop of Henle
13
Q
where does excretion occur?
A
distal convoluted tubule
14
Q
what is the 1st step in urine formation?
A
bulk transport of fluid (usu passive) from blood to kidney tubule
15
Q
what triggers the 1st step of urine formation?
A
“push” of blood flow + hydraulic pressure thruout the whole nephron (esp in the glomerulus & Bowman’s capsule)
16
Q
why do things go thru the pores in the endothelium of the glomerulus?
A
extremely high BP in the structure
17
Q
what 2 things do NOT filter thru the glomerulus?
A
blood cells & proteins
18
Q
what is the mechanism of filtration?
A
bulk flow (passive) by starling forces of filtration
19
Q
what is the driving force behind filtration?
A
pressure gradient (NFP > net filtration pressure)
20
Q
NFP = ?
A
(favoring force) - (opposing force)
21
Q
what is the favoring force?
A
capillary BP
22
Q
what is the opposing force? (2 things)
A
blood colloid osmotic pressure (COP) capsule pressure (CP)
23
Q
what direction does the favoring force go?
A
OUT of the capillary
INTO the tubule
24
Q
what direction does the opposing force go?
A
INTO the capillary
25
what is GFR?
volume of fluid filtered from the glomerular capillaries into Bowman's capsule per unit time
26
GFR = ?
(urine conc x urine flow) / plasma conc
27
what do you use for creatinine?
creatinine clearance based on serum creatine level
28
Ccr = ?
(Ucr x V) / Pcr
29
what 5 factors alter filtration pressure & change GFR?
```
increased renal blood flow
decreased plasma protein
hemorrhage
molecular weight
molecular charge
```
30
what causes increased renal blood flow?
vasodilators
31
what does increased renal blood flow do to GFR?
increase
32
what does decreased plasma protein do to GFR?
increase
| causes edema
33
what does hemorrhage do to GFR?
decrease
| via decreased capillary BP
34
what 3 things regulate GFR?
renal autoregulation
neural regulation
hormonal regulation
35
the 3 things that regulate GFR also regulate 2 more things:
renal BP
| resulting blood flow
36
T/F: blood flow through the cortex is slow
FALSE
| it's rapid!
37
what is a cortical nephron?
nephron w/ glomeruli in the outer cortex & short loops of Henle that extend a short distance into the medulla
38
the majority of nephrons are (cortical/juxtamedullary)
cortical (70-80%)
39
is cortical interstitial fluid hyperosmotic?
nope
| it's isosmotic at 300mOsm
40
what is a juxtamedullary nephron?
glomeruli in inner part of cortex & long loops of Henle that extend deep into the medulla
41
T/F: blood flow through the vasa recta in the medulla is slow
TRUE
42
is medullary interstitial fluid hyperosmotic?
YES
43
what do juxtamedullary nephrons do?
maintain osmolality
filter blood
maintain acid-base balance
concentrate urine
44
reabsorption has how many steps?
2
45
what is the 1st step of reabsorption?
active or passive extraction of substances from the tubular fluid into the renal interstitium
46
what is the 2nd step of reabsorption?
transport substances from interstitium into bloodstream
47
what drives the transport processes in reabsorption?
Starling forces
passive diffusion
active transport
48
where is the concentration of interstitial fluid HIGHEST?
inner medulla (1200)
49
where is the concentration of interstitial fluid the LOWEST?
cortex (300)
50
when does reabsorption happen in the PCT?
when pH needs to be maintained
51
what ions are reabsorbed back into the bloodstream in the PCT?
bicarb
52
what things are ACTIVELY TRANSPORTED into the blood in the PCT?
glucose
amino acids
K+
53
what does sodium get absorbed with?
HCO3 mostly
| Cl in late PCT
54
what % of organic solutes are reabsorbed?
70-80%
55
what substances are actively secreted from the blood into the PCT?
H+
| toxins
56
what is NHE3?
a Na+/H+ exchanger (Na from urine to cell, H from cell to urine)
57
what is CA?
carbonic anhydrase
| converts CO2 + H2O > bicarb
58
the descending limb of the loop of henle is permeable to what?
highly permeable to H2O!
| allows for reabsorption of H2O thru osmosis
59
the ascending limb is not very permeable to what?
H2O
| aka the diluting segment
60
which limb of the loop of Henle is responsible for 15% of reabsorption but can increase to 50%?
ascending
61
what is actively transported OUT of the ascending limb into the interstitium?
NaCl
62
what happens in the thick ascending limb?
passive & active transport of salts OUT of the tubules to be reabsorbed
63
what supplies the energy for the Na/K/2Cl transporter?
Na/K ATPase
64
what direction does the Na/K/2Cl transporter move things?
Lumen > cell
65
how does Cl move out of the cell into the interstitium/blood?
Cl channels
AND
K-Cl symport
66
what happens to most of the K in the tubules?
cycles back into the lumen thru K channels
67
how are Mg & Ca reabsorbed?
passively
| via paracellular shunt pathway (go btwn cells from lumen to interstitium/blood)
68
what is the fxn of the loop of Henle?
to create a conc gradient in the medulla of the kidney
69
how does the loop of Henle create a conc gradient?
countercurrent multiplier system (electrolyte pumps)
70
what is the loop of Henle concentrating?
urea
| creates an area of high urea conc deep in the medulla near the collecting duct
71
what are the 3 countercurrent mechanisms?
1. loss of H2O (filtrate entering desc limb becomes more conc)
2. blood in vasa recta removes water leaving the loop
3. asc limb pumps out Na, K, Cl > filtrate becomes hypo-osmotic
72
is the DCT permeable to water?
NO
| "relatively impermeable"
73
what happens to the urine in the DCT?
DCT creates more DILUTE urine
74
how does the DCT create dilute urine?
absorb NaCl
75
how are Na and Cl transported in the DCT?
Na & Cl cotransporter (NCC)
76
how is Ca reabsorbed in the DCT?
actively
77
what regulates Ca reabsorption in the DCT?
PTH > parathyroid hormone
78
what are the 2 cell types in the collecting tubule?
principal cells
| intercalated cells
79
what do intercalated cells do?
acid-base homeostasis
80
what are the 2 types of intercalated cells?
alpha & beta
81
what 2 hormones act on the principal cells?
aldosterone
| vasopressin/ADH
82
what does aldosterone do at the collecting tubule (principal cells)?
affects expession of Na channels (ENaC) & Na/K ATPase pumps > regulates Na permeability & final level of K+ in urine
83
what does vasopressin/ADH do to the principal cells of the collecting tubule?
determines expression of aquaporin channels (for water) so it controls water permeability
84
how does aldosterone affect the electrical potential in principal cells?
increase
85
how does aldosterone affect Na reabsorption & K secretion?
increases both
86
what drives the reabsorption of Cl & efflux of K in the principal cells?
inward diffusion of Na via ENaC > leaves lumen + potential
87
how does aldosterone affect the channels of the principal cells?
increases activity of both apical Na+ channels & Na/K ATPase
88
what channel does ADH regulate?
aquaporin-2 (AQP2) into apical membrane of principal cells
89
what effect does LOW ADH have on principal cells & urine?
low H2O permeability
dilute hypotonic urine
(getting rid of water)
90
what effect does HIGH ADH have on principal cells & urine?
high H2O permeability
Concentrated hypertonic urine
(you're holding onto all your water)
91
which way does water move through aquaporins?
into the cell
92
what do alpha intercalated cells secrete?
acid in the form of H+ ions
93
how do apha intercalated cells secrete H+?
apical H+ ATPase & H+/K+ exchanger
94
what do alpha intercalated cells reabsorb?
bicarb
95
how do alpha intercalated cells reabsorb bicarb?
band 3 > a basolateral Cl-/bicarb exchanger
96
what do beta intercalated cells secrete?
bicarb
97
how do beta intercalated cells secrete bicarb?
pendrin > specialized apical Cl/bicarb exchanger
98
what do beta intercalated cells reabsorb?
acid
99
how do beta intercalated cells reabsorb acid?
basal H+ ATPase
100
what is the general trend for secretion & reabsorption at alpha & beta intercalated cells?
```
secrete apical (c-c)
reabsorb basal (b-b)
```
101
what is excretion?
loss of fluid from body in the form of urine
102
amount of solute excreted = ?
amt filtered + amt secreted - amt reabsorbed
103
how is osmolarity affected when there is XS water in the body?
lower
104
how is osmolarity affected when there is a deficit of water & extracellular fluids in the body?
HIGH
105
what are the 2 basic requirements for forming concentrated or dilute urine?
1. ADH secretion
| 2. high osmolarity of renal medullary interstitial fluid (osmotic gradient for water reabsorption)
106
if there is no ADH, what does the urine look like?
large volume, dilute urine
107
in the presence of ADH, what does the urine look like?
small volume, concentrated urine
108
where do ALL diuretics act (except aldosterone agonists)?
luminal surface
109
where are osmotic diuretics filtered?
at the glomerulus
110
What happens to diuretics not filtered at the glomerulus?
transported into nephron by organic acid or organic base transported in the proximal tubule
111
what decreases diuretic access to the tubule lumen?
decreased renal blood flow
decreased GFR
increased levels of drugs also transported by the organic acid & base transporters
112
what drugs are also transported by the organic acid & base transporters?
```
alpha-ketoglutarate
uric acid
histamine
cimetidine
catecholamines
choline
abx
probenecid
```
113
what 4 things affect diuretic effectiveness?
1. where the diuretic acts in the nephron
2. transport mechanism affected
3. osmolarity
4. reabsorption of Na+ w/o H2O
114
diuretics that act PROXIMALLY are strong or weak?
WEAK
this is despite the fact that 70-80% of the filtered load is handled there
BUT their actions are counteracted by distal reabsorption mechanisms!
115
diuretcs that act DISTALLY are weak or strong?
WEAK
| only 5-10% of filtered load is involved
116
are loop diuretics weak or strong?
STRONG
117
why are loop diuretics strong?
1. Na/K/2Cl cotransporter is inhibited
2. Affected site handles large fraction of filtered load
3. more distal mechanisms cannot compensate
118
what does the interstitium need to be like to create CONCENTRATED urine?
hypertonic medullary interstitium
119
how do you create a hypertonic medullary interstitium?
lose H2O & gain Na in descending limb
| reabsorb Na w/o H2O in ascending limb
120
how do you create a hypotonic filtrate?
reabsorb Na w/o H2O in ascending limb & DCT
121
what does dilute urine require?
hypotonic filtrate
122
what do loop diuretics do?
block reabsorption of Na w/o H2O in the ascending limb
| impairs BOTH concentration & dilution of urine
123
what do you need to make ANY urine, concentrated or dilute?
reabsorption of Na w/o H2O in the ascending limb
124
how do diuretics that act DISTAL to the loop of Henle affect concentrated or dilute urine production?
influence dilution but NOT concentration of the urine
125
why are diuretics used?
reduce extracellular fluid volume
126
how do diuretics reduce ECF volume?
```
decrease total Na+ content
via
reabsorption back into the plasma
OR
secretion in the urine
```
127
what are the 7 types of diuretics?
1. carbonic anhydrase inhibitors
2. osmotic diuretics
3. adenosine A1 receptor antagonists
4. loop/high ceiling diuretics
5. thiazide & related
6. K+ sparing
7. anti-diuretics & ADH antagonists
128
which classes of diuretics are NON K+ sparing?
CA inhibitors
Thiazide & related
Loop/high ceiling
osmotic
129
what class is mannitol?
osmotic diuretic
130
how does hypokalemia result from diuretic use?
K & H are exchanged for Na in the distal nephron
131
what are the sx of hypokalemia?
ECG abnormalities, cardiac arrhythmias, muscular weakness, drowsiness, confusion, loss of sensation, increased binding of cardiac glycosides
132
what drugs should you use for CHF?
thiazides
loop diuretics
aldosterone antagonists
133
what drugs should you use for hepatic cirrhosis & ascites?
thiazide
loop
K sparing diuretics
134
what drugs should you use for pulmonary edema?
loop diuretics
135
what drugs should you use for cerebral edema?
osmotic diuretics
136
what is the goal w/ renal edema?
maintain kidney fxn
137
what drugs should you use to treat nephrotic syndrome?
```
thiazide diuretics
(and decrease salt intake)
```
138
what drugs should you use for acute renal failure?
osmotic
| loop
139
what drugs should you use for chronic renal failure?
aggressive RX w/ loop
140
what are the 4 non-edematous conditions you can treat w/ diuretics?
HTN
nephrolithiasis
hypercalcemia
nephrogenic diabetes insipidus
141
how should you treat HTN?
decrease salt intake
| add thiazides, +/- K sparing or loop
142
how should you treat nephrolithiasis?
decrease salt intake
| thiazides to increase Ca reabsorption
143
how should you treat hypercalcemia?
loop to inc Ca excretion
normal saline to prevent contraction of extracellular space
+/- K sparing as needed
144
how should you treat nephrogenic diabetes insipidus?
thiazide or loop to reduce plasma volume & contract extracellular space
145
what is diabetes insipidus?
polyuria d/t decreased ADH
146
why can you treat diabetes insipidus w/ thiazides or loop?
salt depletion & contraction of ECF > inc proximal tubule reabsorption of Na > dec volume of fluid reaching distal tubule
147
what are the 2 types of diabetes insipidus?
central
| nephrogenic
148
what is central DI?
dec ADH d/t injury, tumor, infection
149
how do you treat central DI?
arginine vasopression
vasopressin analogs
chlorpropamide
150
what are the vasopressin analogs?
desmopressin & lypressin
151
how do you give the vasopressin analogs?
IM, SC, or intranasal
152
what is chlorpropamide & what does it do?
a sulfonylurea
| increases the actions of ADH
153
what is nephrogenic DI?
decreased ADH RESPONSIVENESS d/t hypercalcemia, hypokalemia, post-obstructive renal failure, lithium
154
what is the treatment for nephrogenic DI?
ADD THIAZIDES
| DELETE LOOPS
155
what drugs do you give to pts w/ nephrogenic DI?
```
amiloride
NSAIDS (indomethacin)
```
156
what does amiloride do w/ DI?
blocks Li uptake
157
why do you treat DI w/ NSAIDs?
decrease prostaglandin synthesis > increased response to ADH
158
what is SIADH?
syndrome of inappropriate secretion of ADH
159
how do you treat SIADH?
loop diuretics
demeclocycline
vaptans
lithium
160
what do loop diuretics do for SIADH pts?
decrease the ability to conc the urine
161
what does Demeclocycline do in SIADH pts?
decrease ADH actions (but cannot use if pt has liver dysfxn)
162
what are vaptans?
nonpeptide V2 receptor antagonist for use in SIADH pts
163
what does lithium do for SIADH pts?
decrease ADH actions
| not used clinically, can be ineffective, can damage kidney
