CHAPTER 15 DIURETICS Flashcards
What are the three main functions of the nephron?
Glomerular Filtration
Tubular Reabsorption
Tubular Secretion
What is filtration?
Movement of fluids from the Glomerulus into the Bowman’s Capsule.
Where is 100% of the filtrate produced?
Bowman’s Capsule
What is Reabsorption?
Selective transfer of Solutes and Water back into the blood.
Where is 80% of the filtrate reabsorbed?
Proximal convoluted tubules.
Reabsorbs HCO3-, Na+, and H2O
What percentage of the urine volume is filtrate volume?
1%
What is secretion?
Movement of waste from the blood into the nephron.
What is the only capillary network both fed and drained by arterioles?
Glomerulus
What area of the nephron has a lot of transporters for waste products?
S2 segment of the proximal convoluted tubule.
What determines how much blood can get into the glomerulus?
The tone of the afferent arteriole.
What does the Juxtaglomerular Apparatus do?
Quality control mechanism to ensure proper GFR
Controls the patency of the afferent arteriole
What makes up the Juxtaglomerular Apparataus?
Macula Densa (will sense how much urine is going through the nephron)
Juxtaglomerular Cells
Extraglomerular Mesanginal Cells (smooth muscle cells).
What is the function of the Macula Densa cells?
They monitor the osmolality and volume of fluid in the distal tubule and transmit info to the Juxtaglomerular Cells.
What is the function of the Juxtaglomerular Cells?
Makes Renin for RAAS
Modify Smooth Muscle in the Afferent Arterioles.
How is GFR regulated?
-Adjustment of blood flow
-Alter capillary surface area through the mesangial cells
-Controlling arteriole diameter
Renal auto-regulation
Neural regulation- direct activation of the SNS response
Hormonal regulation- release of epinephrine
Describe Mechanism of how GFR is returned to homeostasis if there is a stimulus that causes an increase in GFR.
- Macula Densa Cells of the JGA detects an increase delivery of Na+, Cl-, and water (TOO MUCH)
- The input into the JGA will produce the output to decrease secretion of nitric oxide
- The decrease in NO will cause afferent arteriole constriction, which decreases blood flow through the glomerulus and overall decrease in GFR
Describe the process of how bicarb is reabsorbed into our body through the proximal convoluted tubule? Essay question
- NHE3 starts the cycle in the PCT cell. Na+ in for a H+ out into the lumen urine.
- The H+ in the lumen/urine will bind to HCO3- and form H2CO3 (carbonic acid)
- On the luminal surface there is an enzyme called carbonic anhydrase (CA) which will get rid of an H2O
- CA will break down H2CO3 to H2O and CO2
- CO2 is a gas and will freely diffuse into the cell.
- Once inside the cell, it also has H2O. The CA works in both directions and convert H2O and CO2 to carbonic acid.
- Carbonic acid can exist in an equilibrium as H+ and HCO3-
- HCO3- can now be reabsorbed into blood, maintaining bicarb buffering system
What are clinical uses for using a CA Inhibitor?
What drug is a CA Inhibitor?
Glaucoma,
Alkalinizing the Urine,
Metabolic Alkalosis
Acute Mountain Sickness.
CA Inhibitor: Acetazolamide
What ions are loss if CA is blocked?
Huge loss of HCO3-
Na+/Cl-/K+ will also be loss.
Overall decrease in BP
How does mannitol get rid of excess fluid and lowers BP?
- Mannitol is an impermeable solute that is filtered and not reabsorbed throughout the nephron.
- Mannitol will have increased levels throughout the nephron, because it is not reabsorbed.
- Water will rush into the nephron to decrease osmolality, mannitol concentration increases.
- Mannitol will keep water in the nephron, through the collecting ducts and out into the urine.
Where is H2O reabsorbed in the Loop of Henle?
Thin Descending Limp of the Loop of Henle
How does the hypertonic medullary interstitium play a role with water?
Osmolality increases as you go down the medulla (300/600/900/1200). As Osmolality increases water leaves the nephron and enters the medulla.
Where does movement of ions in the Loop of Henle?
Thick Ascending Limb (TAL). Ions will move out of the nephron to balance the low osmolality as you move up the TAL.
What does the NKCC2 symporter do?
Where is it located?
Does it use ATP?
This is a transporter on the luminal surface of the Thick Ascending Limp of the Loop of Henle where Na+, K+, and 2Cl- are transported.
No ATP required, as we go up the loop of Henle the Osmolality inside the nephron is higher than the medulla. Since water can not leave, ions are driven out to the medulla in order to balance the concentration.
How does Potassium come into the TAL and go into the urine?What does the high positive charge of K+ in the urine do to Mg2+ and Ca2+?
NKCC2 and Na/K+ pump will bring potassium into the TAL. Excess K+ will leave through an open K+ channel into the urine.
Positive charge of K+ will push Mg2+ and Ca2+ into the interstitium through the paracellular route.
How does Cl- get back into the body from the TAL?
NKCC2 will bring two Cl- in along with Na+ and K+. K+ and Cl- will use a symporter and bring Cl- and K+ back in the body.
What ions are reabsorbed in the Thick Ascending Limb?
Sodium
Potassium
Chloride
Magnesium
Calcium
Which Diuretic will Target the Thick Ascending Limb?
What does it do?
Loop Diuretics (furosemide)
Blocks the NKCC Transporter
As you go down the medulla what happens to it’s osmolality? How does water move to balance out gradient?
Medulla increases osmolality as you go down. In order to balance concentration water leaves the nephron into the medulla.
What area is impermeable to water in the Loop of Henle?
Thick Ascending Limb
What causes the high 1200 osmolality in the medulla.
All the ions being driven out in the TAL.
What happens to osmolality of nephron as you reach the top of the TAL?
The medullas has absorbed so much ions that the osmolality is now 100. As we enter the distal tubule, where nephron can now be soluble to water and rebalance itself to be 300 mOsm
What happens to water as the nephron goes into the collecting duct?
Water is reabsorbed into the medulla. Urine becoming more concentrated.
What does a loop diuretic target?
How does it work?
Name most efficacious loop diuretic used?
Blocks the NKCC2 of the Thick Ascending Limb in the Loop of Henle.
With the NKCC2 blocked, water will follow all the ions out into the urine.
Ex: Furosemide (sulfanamide)
Furosemide: strongest diuretics out there (most efficacious)
What is the only loop diuretic that is not a sulfonamide?
Ethacrynic Acid
Where is the Distal Convoluted Tubule located in regards of the kidney and what does it do?
The DCT is located in the renal cortex.
The DCT has very littler water movement
Low amount of Na+ absorption
Active Ca2+ reabsorption by PTH.
How does the PTH work when we are low on serum Ca2+?
- When Ca2+ in the blood is low, PTH is release the pituitary gland.
- PTH binds to a receptor on the DCT and induces an increase uptake of Ca2+ in the DCT.
- Ca2+ is then transported into the interstitium through two routes.
Route 1: Ca2+ Na2+ exchanger (NO ATP)
Route 2: Ca2+/H+ ATPase pump. (need ATP)
What is the main target in the DCT?
What can target this?
The NCC transporter (Sodium/Chloride Transporter).
Thiazides
What are the toxicities of carbonic anhydrase inhibitors (Acetazolamide)?
Decrease Plasma K+
Potassium Wasting
Metabolic Acidosis
What are the toxicities of Loop Diuretics (Furosemide)?
Decrease Plasma K+
Potassium Wasting
Metabolic Alkalosis
Decrease Plasma Mg2+ and Ca2+
Polyuria
Allergy
What are the toxicities of Thiazides?
Decrease Plasma K+
Potassium Wasting
Metabolic Alkalosis
Allergy
Where is the final site of sodium reabsorption and most important site for potassium secretion?
Collecting Tubule
What are the principle cells in the collecting duct?
They are the main site for water, Na+, and Potassium transport.
What is the ENaC in the collecting duct?
What does it do?
Epithelial Sodium Channel in the Collecting Tubule
Transport sodium into the principle cell.
How does Na+ get back into the interstitium/blood from the collecting duct?
Na/K ATPase pump.
How does Aldosterone work in the collecting duct
What does this do to Blood Pressure?
Aldosterone will increase activity of the ENaC and the Sodium potassium ATPase pump. Increasing the reabsorption of sodium.
Water follows Na+, increases BP.
How does Na+ movement into the interstitium affect the K+ movement?
As more Na+ is reabsorbed in the body, K+ has to move out into the collecting duct where it will be excreted.
Direct correlation
How does is chloride driven to the interstitium from the collecting tubules/ collecting ducts?
Through the paracellular route, it wants to follow sodium.
Diuretics upstream result in excess sodium in the _________.
Collecting tubules.
Excess bicarb ban be in the collecting duct from upstream diuretics (thiazides/acetazolamide).
If Acetazolamide is given how does it affect potassium level?
HCO3- won’t be able to leave the nephron, increase amount of HCO3- in the lumen.
In order to balance negative charge of the bicarb, greater amount of K+ will enter the collecting tubule.
Further driving K+ depletion.
Acetazolamide is greater wasting K+ diuretic than furosemide and thiazides.
What will antagonize the effects of aldosterone?
Spironolactone blocks the aldosterone receptors.
What will inhibit the ENaC?
Amiloride. More Na in the urine, more water in the urine.
When are potassium sparing diuretics most useful?
Most useful in states of mineralcorticoid excess.
Conn’s syndrome (moon face, buffalo hump)
Ectopic ACTH production
Secondary Uses: CHF, Nephrotic syndrome
Describe the pathway of ADH in the Collecting Duct.
- ADH is produced in the pituitary gland and binds to the ADH Receptors.
- ADH activates cAMP that moves water channels initially in vesicles, merge into the other membrane making more water channels presents (aquaporins) allowing water to come in and into the blood stream.
What can block ADH?
Conivaptan (Potassium Sparring)
What is the primary use of mannitol?
To decrease ICP
Other uses: promote removal of renal toxins, great to use after radio contrast agents, acute hemolysis
What are symptoms of Diabetes Insipidous?
Insufficient ADH
Excessive Thirst (polydipsia)
Excessive Urination (polyuria)
What would you give to someone with DI?
Thiazide Diuretics
Thiazide will decrease plasma volume and decrease GFR.
Whenever GFR decreases there is Water and NaCl reabsorption in the PCT.
What area of the nephron does Acetazolamide target?
What does it target?
PCT
Inhibits the Carbonic Anhydrase Enzyme
What area of the nephron does osmotic diuretic agents (mannitol) target?
PCT and Thin Descending Limb are freely permeable to water
Move water into the nephrons
What area of the nephron does loop agents (furosemide) target?
What does it taraget?
Thick Ascending Limb of the Loop of Henle
NKCC2
What area of the nephron and target does Thiazides work on?
PCT and DCT
NCC
What area of the nephron and target does spironolactone work on?
Collecting tubule
Targets the aldosterone receptor
What area of the nephron and target does Conivaptan work on?
Collecting tubule
Blocks ADH receptor
What two diuretics are only used in conjunction in clinical only?
Loop Diuretics and Thiazides (Massive amount of Water Loss)
Can result in significant kidney damage if not monitored closely
What drug besides Acetazolamide can inhibit the Carbonic Anhydrase Enzyme?
Thiazides
Where area of the nephron does amiloride work on?
What does it target?
Collecting tubule
Targets ENaC
