Test 3 - Diuretics (10/7 & 10/14) Flashcards
What is the function of the kidney?
Filter the blood and get rid of waste products (especially ammonia..makes it into urea and is excreted)
How many nephrons does a kidney have?
800,000 to 1,000,000
What are the 3 principle activities of nephrons in producing urine?
- filtration
- reabsorption
- secretion
Where in the nephron is filtration taking place?
Renal corpuscle (Glomerulus)
How much of our urine volume is total filtrate volume
1%
Where in the nephron is reabsorption taking place?
Peritubular capillaries on the proximal tubule
Where in the nephron is secretion taking place?
Distal tubule
List the segments of the nephron
- Renal corpuscle
-glomerulus
-bowmans capsule - renal tubule
-proximal convoluted tubule
-loop of henle
-distal convoluted tubule - collecting ducts (not technically part of the nephron)
What is the blood component of the renal corpuscle?
Glomerulus. afferent arteriole brings blood in, efferent takes blood out
What is the function of the glomerulus. what are the cells called
has a layer of cells called podocytes and they provide the filtration of blood through capillaries. (only found in the cortex)
What is the function of Bowmans capsule?
structure that surrounds the glomerulus, catches the secretions from the glomerulus
Function of the proximal convolutes tubule? What transporter is found here?
reabsorbs about 80% of the glomerular filtrate back into the blood.
NHE3.
Proximal tubule targets for diuretics
Targeting NaCl and NaHCO3 reabsorption
-Carbonic anhydrase inhibitors
-Caffeine
What are the four different parts of the loop of henle
- thick descending limb
- thin descending limb
- thin ascending limb
- thick ascending limb
What part of the nephron goes down into the medula?
The bottom part of the loop of henle
Function of descending loop of henle
water reabsorption due to hypertonic medullary interstitium
Function of ascending loop of henle
driving out NaCl via NKCC2
NaKATPase then pumps Na into interstitum
What happens to Mg and Ca in the ascending loop of henle
if there is extra K in the nephron it will go down its concentration gradient to the lumen, that positive charge will push Mg and Ca to interstitium
what is the osmolality at the bottom of the loop of henle
1200
The ascending loop of henle is _____ to water
impermeable
pump found at distal convoluted tubule
NCC
very little water movement (we are balanced)
low amount of Na absorption via NCC (NaCl goes from lumen to DCT)
active Ca reabsorption (from lumen to DCT) by parathyroid
function of collecting tubule. is it part of nephron?
Na and H2O can be reabsorbed. and K can be secreted
not part of nephron but still target for diuretics
In the collecting tubule the _____ reabsorption is being based on the activity of aldosterone
Na
What happens to the charge in the lumen if we have increased activity of ENaC in the collecting tubule
builds up negative charge because we have more Na in than K out. so Cl will leave through paracellular route
describe ENaC and aldosterone in the collecting tubule if we have hypotension
aldosterone (from adrenal cortex) increases activity of ENaC.
adds more Na into collecting tubule which is then pumped out to interstitum via NaKATP
What is the vasa recta?
Capillary system that is around the ascending and descending loop of henle.
For osmolality changes, reabsorbing ions that will be taken up into the medulla as opposed to the cortex
Location of macula densa and juxtaglomerular apparatus
Located at the end of the distal convoluted tubule by the glomerulus.
What does the macula densa do?
monitors the osmolality and volume of the fluid in the distal tubule. transmits the info to juxtaglomerular cells
Where are the juxtaglomerula located?
They are a thin layer of cells that line the afferent arteriole
what could cause the juxtaglomerular cells to relax
if there isn’t enough fluid or Na coming through the macula densa it can release NO and that will relax the juxtaglomerular
What does the Juxtaglomerular do?
can activate the RAAS system in response to the changes sensed by macula densa. Can also regulate blood flow into the glomerulus by changing size of afferent arteriole.
True/false. We have glomeruli in the medulla
false. only in the cortex
How do the kidneys regulate GFR?
Directly controlled by the juxtaglomerular apparatus.
- Renal Autoregulation (regulated by the kidney itself)
- neural regulation (activation of sympathetic NS..release epi/noreip)
- hormonal regulation (endocrine hormones, epi)
How do the kidneys regulate glomerular filtration rate through neural regulation?
activation of SNS. Release epi and norepi. act at juxtaglomerular cells, increase renin secretion.
How do the kidneys regulate glomerular filtration rate through renal autoregulation?
- Increase BP sensed by macula densa and that info sent to JGA
- JGA will decrease secretion of NO
- arteriole constricts
-some stimulus disrupts homeostasis by increasing GFR (go from sitting to standing that will increase BP)
-The change is sensed by the macula densa cells of JGA
-macula densa sends the input that we have too high of an input
-output from Juxtaglomerular apparatus- decreased secretion of nitric oxide
-afferent arteriole constricts, decreasing blood flow through glomerulus
Function of NHE3 and carbonic anhydrase (only urine side)
NHE3 is the start of the cycle. its is a transporter (Na in; H out)
Once cycled via NHE3, H that was pumped out is combined with HCO3 to form H2CO3.
Carbonic anhydrase will break down H2CO3 to form CO2 and H2O
What happens in the proximal convoluted tubule after NHE3 and carbonic anhydrase made H2O and CO2 in the urine?
CO2 uses simple diffusion back into the proximal convoluted tubule, combines with carbonic anhydrase again to form H2CO3 and then be broken down to H and HCO3.
HCO3 is transported to the blood to buffer
What does NHE3 and carbonic acid have to do with Na and bicarb reabsorption?
The NHE3 pump puts Na into the proximal convoluted tubule from lumen where it is pumped out to the interstitium via Na/K/ATPase.
HCO3 is pumped to the interstitium following a full cycle.
Describe how the osmolality of the kidney medulla affects water movement
Countercurrent mechanism.
In the PCT, water follows Na to keep osmolality constant.
List the 5 major types of diuretics.
- Carbonic anhydrase inhibitors
- Loop diretics
- Thiazides
- Potassium Sparing diuretics
- Osmotic Diuretics
Carbonic Anhydrase Inhibitor: Site of action. med example
Primarily block Na and HCO3 reabsorption in proximal convoluted tubule. (more Na and HCO3 staying in the lumen)
more Na in lumen = more water bc it follows Na.
Acetazolamide.
Carbonic anhydrase inhibitor: urinary electrolytes
Urine: NaCl (+), NaHCO3 (+++), K (+)
Carbonic Anhydrase Inhibitor: main effect.
Major effect is bicarbonate diuresis (Sodium bicarb is excreted in large amounts..nothing for H to bind to) Can lead to metabolic acidosis.
Also K+ depletion, toxicity
When is Acetazolamide used as a diuretic. What kind of diuretic is this?
Only if edema is accompanies by significant metabolic alkalosis. it is a carbonic anhydrase inhibitor
Other uses of acetazolamide
acute mountain sickness
glaucoma, alkalinization of urine, edema with alkalosis
osmolality. what should it be?
the number of dissolved particles in solution. 300mOsm/kg
is osmolality higher in the cortex or medulla?
medulla. bc all the extra Na before it is reabsorbed
in the proximal tubule, water reabsorption must equal _____ to keep osmotic gradient equal
Na
What is the part of the PCT where we have secretion of larger substances into urine? what kind of substances are secreted
Straight segment.
drugs
Effects of mannitol compared to other diuretics. uses. side effects.
osmotic diuretic mainly used to reduce intracranial pressure.
can cause extracellular volume expansion (causing hyponatremia and pulmonary edema).
Toxicity: N/V, headache
Where does mannitol work primarily?
Proximal convoluted tubule
mannitol toxicity
N/V
headache
Mannitos is an ______ solute. as water follows Na, mannitol concentration ______
impermeable.
increases.
If we increase concentrations of mannitol we ______ osmolality
increase
what parts of the nephron will be affected by mannitol?
mainly PCT but works throughout entire nephron
Furosemide is a ___
Loop diuretic
Where do loop diuretics work
thick ascending limb
Loop diuretics: MOA
MOA: Block the NakCC2 pump. Selectively inhibits NaCl reabsorption in the thick ascending limb.
more Na in urine = more water in urine
loop diuretics can cause ______ (alkalosis/acidosis)
alkalosis
what is the most efficacious diuretic
loop diuretic
what happens to Mg and Ca with loop diuretics
we lose it in the urine since we stopped the NACC2 pump the K isnt leaving the nephron to the lumen so its not being driven out.
Loop diuretics: urinary electrolytes
Urine electrolytes: NaCl (++++), K (+), Mg and Ca
Loop diuretics: main side effect
Toxicity: most are sulfonamide, avoid in pt with sulfa allergies.
What loop diuretic would we use in a patient with a sulfa allergy?
ethacrynic acid
Thiazide MOA
Block NCC channel (inhibiting NaCl to come into nephron). keeping more Na in urine = more water
Some inhibition of carbonic anhydrase activity
All thiazides can be given ______
orally
Hydrochlorothiazide is a ___
Thiazide diuretic
Thiazide urine electrolytes
NaCl (++)
NaHCO3 (+)
K (+)
Thiazide side effects
Sulfa allergy. (its a sulfonamide).
What happens if we combine thiazides and loop diuretics
since they have targets at different parts of the nephron we can have greater effects.
shit ton of fluids moved
What do we have in regards to ion movement in the collecting tubule with no diuretics
Na into tubule
K into lumen
more negative charge in lumen will push Cl to interstitum (paracellular route)
ion movement in collecting tubule with K wasting diuretics (Furosemide, thiazides)
Lots of Na into tubule
lots of K to lumen
still net negative, Cl leaving
ion movement in collecting tubule when acetazolamide is given
Huge net negative charge in lumen bc of the bicarb build up.
means LOTs of K out to lumen bc its moving towards the negative.
LOTS of K wasting
Define potassium wasting
diuretics that increase the amount of K lost in the urine
Mechanism of K and HCO3 wasting in the collecting tubule following Acetazolamide administration
Lots of HCO3 in the urine which means negative charge and thats why we have lots of K wasting. (more so)
Spironolactone MOA
Antagonize effects of aldosterone therefore inhibiting ENaC so more Na in lumen.
K sparing diuretic
Amiloride MOA
inhibition of Na flux through ion channels in collecting tubule.
K sparing diuretic
primary clinical indications for K sparing diuretics
Mineralocorticoid excess (something wrong in the adrenal cortex and they are producing extra aldosterone)
Ex.
-Conns syndrome
-Ectopic ACTH production (pituitary gland tumor)
Secondary clinical indication for using K sparing diuretic
-CHF
-nephrotic syndrome
-use of other diuretics that are K wasting
contraindications for K sparing diuretics
-pt taking K
-pt on drugs affecting K
-liver disease impairs metabolism
K sparing diuretic toxicity
hyperkalemia
-increased w renal disease
-most common if k sparing agent is solo diuretic
what is the hormone at the collecting duct
ADH (vasopressin)
what does ADH do at collecting duct
increases blood volume, increasing blood pressure
- binds to receptor
- activates cAMP
- AQP gets migrated to surface of lumen
- causes water to go from lumen to interstitum
water cant move without the AQP.
what happens if there is no production of ADH
urine is very diluted bc there is no movement of water.
when would we give an ADH agonist? what med?
when we want to increase BP. vasopressin
when would we give ADH antagonist? what med?
Hypertension. Conivaptan
2 drugs that reduce K loss during Na diuresis
Conivaptan: ADH antagonist
Spironolactone: block aldosterone receptor
what parts of the nephron are freely permeable to water
PCT and descending loop
Osmotic Diuretic MOA.
Keeps the osmolality high throughout entire nephron so water doesn’t leave
Increase urinary flow by retaining water throughout nephron.
Absorption for mannitol
suppppper poor. Cant ingest it so its injected
when does glomerular filtration occur with osmotic diuretics?
within 30-60 min after administration
Uses for mannitol. what kind of diuretic is this
osmotic diuretic.
- reduce ICP
- promote removal of renal toxins
-acute hemolysis
-after use of radiocontrast agents
pharmacodynamics of osmotic diuretics
counter osmotic force.
result is
-increase urine volume
-reduces Na reabsorption
(lose H2O and Na in urine)
clinical indications for osmotic diuretics
-increases urine output
-reduces ICP
How long does it take to reduce ICP following administration of an osmotic diuretic
60-90 min after administration
Osmotic diuretic toxicity in vasculature system
extracellular volume expansion
nephron isn’t leaky to it but vascular system is so its distributed to extracellular compartments.
can lead to acute pulmonary edema and hyponatremia prior to dieresis
osmotic diuretic toxicity in nephron
High or extended use
1. dehydration
2. hypernatremia
3. hyperkalemia
- in pt with renal failure - hyponatremia
what can happen to mannitol during administration
can crystalize, use in-line filter
most common reason for diuretic use is _____ or _____.
peripheral or pulmonary edema
What would be non edematous states that diuretics are used? (6)
- HTN (decrease by 10-15mmHg)
- renal stones
- rhabdomyolysis (osmotic sweeping out nephron)
- hypercalcemia
- urinary casts
- diabetes insipidus
Why would we use diuretics for neohrogenic diabetes insipidus
These patients have insufficient ADH (pouring out dilute urine)
what diuretic would we use for diabetes insipidus? what are the 6 steps on how this works?
thiazide.
- decrease tubular Na reabsorption
- increase urinary excretion of Na
- overall decrease EC volume
- increase proximal tubule Na and H2O reabsorption
- decrease distal delivery of Na and H2O
- decrease urinary output overall.
