Sriramula Flashcards
1
Q
Major sites of Sodium Reabsorption
A
- Proximal Tubule
- 65-70%
- Ascending limb of loop of Henle
- 20-25%
- Distal Tubule
- 5%
- Collecting duct
- 1-5%
- Where sodium goes, water goes
- Less than 1% of the filtered sodium load is excreted per day
2
Q
Na+
A
- Kidneys always want to preserve at the expense of other electrolytes
- even K+
- Water follows
- <1% of filtered sodium load exreted per day
3
Q
What controls renal function
A
- Renin Angiotensin Aldosterone System
- Renal Nerves/catecholamines
- Renal pressure gradient
- perfusion pressure
- Interstitial pressure
- Vasopressin (ADH)
- Autocoids
- prostaglandins
- Nitric Oxide
- Bradykinin
4
Q
What is the function of the kidneys
A
- Fluid and electrolyte homeostasis
- BP control
- Detoxification
5
Q
What electrolyte is preferentially absorbed by the kidneys?
A
Sodium at the expense of other electrolyes
even K+
6
Q
What is the role of the afferent and efferent arteriole
A
- Differential resistance buiilt in these 2 vascular beds
- blood will be forced to stay in the capsule
- glomerular filtration
- changes in GFR=constriction/dilation of afferent/efferent
7
Q
What regulate afferent and efferent arteirole tone
A
x
8
Q
Why is renin important with renal artery stenosis
A
- Upregulation of intra-renal renin-angiotensin system maintains GFR in renal artery stenosis patients
- vasoconstricts efferent arterioles
9
Q
What drugs would lead to renal failure with renal arter stenosis
A
- ACEIs or ARBs leads to kidney failure.
10
Q
Diuretics
A
- Inhibit electrolyte reabsorption in the kidney
- increase rate of urine flow
11
Q
What are the primary and secondary effects of diuretics
A
- Primary
- increase solute excretion
- mainly Na+
- increase solute excretion
- Secondary effect
- increase urine flow
- response to the osmotic force of solutes within the renal tubule lumen
- increase urine flow
12
Q
Different types of Diuretics and major site of action
A
13
Q
Epithelial Transporters
A
- Channels
- Na, K, Cl
- Antiporter/Countertransport
- Na-K ATPase
- Na-H Exchanger
- Sympoter/Cotransport
- Na-Cl
- Na-K-2Cl
14
Q
Osmotic DIuretics
A
- Prototype=Mannitol
- no molecular target
- interfer directly with osmosis
- Major site of action=Proximal tubule
15
Q
Osmotic Diuretic Characteristics
A
- Free Glomerular Filtration
- Limited or no tubular reabsorption
- Pharmacologically inert
- minor side effects/DDI
16
Q
What is the prototypical osmotic drug
A
Mannitol
17
Q
How do osmotic diuretics work?
A
interfere directly with osmosis
18
Q
What is the major site of action of osmotic diuretics
A
- Proximal tubule
19
Q
What is the MOA of mannitol
A
- Water moves across the membrane from low osmolarity (dilute side) to higher osmoloarity (Concentrated side)
- Mannitol:
- Loss of water
- Reduced intracellular volume
- Hypernatremic risk
20
Q
Osmotic Diuretics: Therapeutic uses
A
- acute renal failure (hypovolemic shock/trauma)
- Prophylactic diuresis
- maintains urine flow
- Cerebral edema (Mannitol I/V infusion
- raises osmotic pressure
- water moves from brain to general circulation)
- raises osmotic pressure
- Glaucoma
- preoperatively
- reduce intraocular pressure before surgery
21
Q
Adverse effects/Contraindications of osmotic diuretics
A
- evidence of renal epithelial cell or BBB injury
- Heart Failure patients
- may develop pulmonary edema
- Electrolyte imbalances
- dry mouth
- thirst
- blurred vision
22
Q
How does bicarbonate ion regulate Sodium Absorption
A
- Na+-H+ exchanger on luminal border allows Na+ to enter the cell in exchange for H+ ion.
- Next reabsorbed Na+ is pumped out of the cell by Na+-K+-ATPase, whereas, secreted H ion combines with luminal bicarbonate to form carbonic acid.
- This carbonic acid is dissociated by Carbonic Anhydrase enzyme into water and CO2. CO2 diffuses into the cell and is rehydrated to form carbonic acid. Because the concentration of cellular H+ ion is low, carbonic acid dissociates into H+ and bicarbonate.
- Thus the constant supply of H+ is furnished for countertransport of Na+ and absorption of bicarbonate.
23
Q
What is the prototypical carbonic anhydrase inhibitor?
A
Acetazolamide
24
Q
Acetozolamide: MOA
A
- As a result:
- bicarbonate gets retained in the lumen
- No H+ ion is produced for NHE
- results in inhibition of Na+ absorption
25
Carbonic Anhydrase Inhibitors: Therapeutic Uses
* **edema** of congestive heart failure (self limiting diuretic)
* **weak diuretic effect**
* max activity at proximal tubule
* but Na+ and Bicaronate can be still reabsorbed at distal parts of nephron
* Other Pharmacological uses:
* Glaucoma
* **to reduce intraocular pressure**
* **Mountain sickness**
* prophylactic meausre, metabolic acidosis implicated
* Alkalization of urine
* enhance excretion of weak acids (uric acid, aspirin)
26
Carbonic Anhydrase Inhibitors: Adverse effects
* **Metabolic acidosis**
* ****loss of bicarb buffering
* Sulfonamide derivative
* allergic rxn
27
What are the Na-K-2Cl Symport Inhibitors
* Prototype=Furosemide
* Sulfa-based (-ide)
* furosemide
* Bumetanide
* Torsemide
* Non-sulfa
* Ethacrynic acid
28
What is another name for Na-K-2Cl Symport Inhibitors
* Loop diuretics
* High Ceiling diuretics
* greater effect than other diuretics
29
illustrate the high ceiling effect of loop diuretics
* high ceiling-greater effect than other diuretics
30
What is the MOA of loop diuretics
* F=Furosemide
* binds to symporter
* loss of potassium
31
what are the Extra-renal effects contribute to the diuretic activity and beneficial cardiac effects of loop diuretics
32
Loop Diuretic: Therapeutic Uses
* **Edema** control in Heart Failure
* Hypertension
* toresmide=approved
* Adjunctive therapy w/digoxin (in heart failure)
* Treat Hypercalcemia
* Furosemide
33
Adverse Effects of Loop Diuretics
34
Which one of the following increases the efferent arteriole tone to restore kidney function in presence of renal artery stenosis?
A.ACE inhibitors
B.ARBs (Angiotensin Receptor Blockers)
C.Angiotensin II
D.Renin
C. Angiotensin II
35
Which arteriole, afferent (arriving) or efferent (egressing) has the wider diameter?
afferent
36
Which one of the following loop diuretics is the best choice for individuals who are allergic to drugs that contain the sulfonamide moiety?
A.Furosemide
B.Ethacrynic Acid
C.Torsemide
D.All of the above
B. Ethacrynic Acid
37
Intravenous administration of which one of the following diuretics can reduce cerebral edema due to extraction of water from the intracranial space?
A.Acetazolamide
B.Amiloride
C.Hydrochlorothiazide
D.Mannitol
E.Torsemide
D. Mannitol
