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97 Cards in this Set

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Kidneys filter __1__L of plasma daily to form __2__ L of urine
1. 180

2. 1.5
What does the Nephron consist of?
1. Glomerulus = filtering aparatus; filtration is nonselective

2. Long tubular portion = reabsorbs and conditions glomerular filtrate
What are the 3 basic renal functions?
1. Filtration

2. Reabsorption

3. Secretion
Urine composition is determined mainly by __1__ and modified by __2__
1. Reabsorption

2. Secretion
What are the 3 main goals of Renal Function?
1. Reabsorb substances that the body needs

2. maintain acid-base balance

3. Excrete waste and foreign products that have to be eliminated
Glomerulus:
-all __1__ plasma molecules are filtered while __2__ and __3__ remain in the blood
-the most prominent filtered constituents are __4__ & __5__ with smaller amounts of __6__ & __7__
1. small = electrolytes, aa's, drugs, glucose, metabolic wastes
2. large = lipids, proteins
3. cells
4. Sodium
5. Chloride
6. Bicarbonate
7. Potassium
What does the Proximal Convoluted Tubule absorb? (5)
1. NaCl
2. NaHCO3
3. Glucose
4. Amino Acids
5. Organic solutes

*water is reabsorbed passively to keep osmolarity constant
Reabsorption of NaHCO3 in the Proximal Convoluted Tubule depends on what?
Carbonic Anhydrase activity
Tubular segment between the Proximal and distal convolutions that actively reabsorbs 35% of NaCl but is impermeable to water so that the tubular fluid becomes diluted
thick ascending Loop of Henle
What transport system is contained within the luminal membrane of the Thick Ascending limb of the Loop of Henle?
Na+/K+/2Cl-
Specialized cells in the thick ascending limb of the Loop of Henle that act as chemoreceptors to influence Renin secretion by sensing NaCl influx as tubular fluid leaves the loop
Macula Densa
Tubule segment between the Loop and Collecting Tubule that contains the NaCl transporter which reabsorbs 10% of filtered NaCl
Distal Convoluted Tubule
Part of Nephron that has Principle and Intercalated cells with ion channels for Na+ and K+
-Na+ is reabsorbed in exchange for secreting K+
Collecting Tubule
Nephron part that determines the final Na+ concentration in the urine
Collecting tubule
The coupling of Na+ reabsorption to K+ secretion in the Collecting Tubule is regulated by what?
Aldosterone

*high Aldosterone = high Na+ reabsorption / high K+ secretion
What happens to the concentration of NaCl in the lumen of tubules as you get further away from the Glomerulus?
NaCl will decrease

**important b/c it affects the action of diuretic drugs
Differentiate between 'diuresis' and 'natriuresis"
Diuresis = increase in urine volume

Natriuresis = increase in renal sodium excretion -> causes diuresis
Diuretic drugs increase urine __1__ or __2__ by blocking the __3__ functions of the renal tubules
1. volume

2. flow

3. transport
Explain how diuretic drugs exert their action
Block sodium and choloride reabsorption
-increase intratubular osmotic pressure ➡ prevents passive reabsorption of water ➡ increases urine flow
Which diuretics will have a greater effect, early acting or late acting ones? Why?
Early acting b/c they will block Na+ reabsorption the most (b/c that is where the most Na+ reabsorption occurs)
What clinical conditions are Diuretic drugs used for?
1. HYPERTENSION
2. acute and chronic HEART FAILURE
3. acute and chronic renal failure
4. Nephrotic syndrome
5. Cirrhosis
List the 5 clases of Diuretics
1. Carbonic Anhydrase inhibitors = Acetazoleamide
2. Osmotic agents
3. Loop diuretics
4. Thiazides
5. Potassium sparing
List the 2 groups of Carbonic Anhydrase inhibitors and their respective drugs
1. Oral Preparation
-Acet-azol-amide
-Di-chlor-phenamide
-Meth-azol-amide

2. Ophthalmic preparations
-Brin-zolamide
-Dor-zolamide
Carbonic Anhydrase is located in the luminal membranes of the __1__ cells where it catalyzes dehydration of __2__ for __3__ reabsorption
1. Proximal tubule

2. Carbonic acid (H2CO3)

3. NaHCO3
How do Carbonic Inhibitors produce diuresis?
by blocking the reabsorption of NaHCO3
Why does the diuretic effectiveness of Carbonic Inhibitors diminish after several days?
Bicarbonate depletion eventually enhances NaCl reabsorption
Prototype CA inhibitor used rarely as a diuretic nowadays, but is used instead to inhibit CA at sites other than the kidneys
Acet-azol-amide
CA inhibitors given orally to treat Glacoma

CA inhibitors applied topically for Glaucoma to avoid metabolic effects or Diuresis
Acet-azol-amide
Meth-azol-amide
Di-chlor-phenamide

Brinzol-amide
Dorzol-amide
Explain how CA inhibitors help in treating Glaucoma
CA in the ciliary body normally catalyzes HCO3 secretion into the Aqueous Humor, CA inhibition reduces intraocular pressure by decreasing Aqueous Humor formation
Other than Glaucoma, list 5 other things CA inhibitors are used for
1. Urinary Alkalinization
2. Correction of Metabolic Alkalosis
3. preventtion of acute mountain sickness
4. adjuvant epilepsy treatment
5. increase phosphate excretion during
Explain the mechanism of Carbonic Anhydrase

Explain Acetazolamide's action
1. counter-current across the apical membrane moves Na+ into the cell & H+ into lumen

2. In the lumen, H+ reacts with HCO3- to produce Carbonic Acid (H2CO3)

3. H2CO3 dissociates to form CO2 + H20; this rxn is catalyzed by cytoplasmic CA

Acetazolamide = inhibits CA to reduce reabsorption of Na+ & HCO3-
List 4 Osmotic Diuretics
1. Glycerin
2. Isosorbide
3. Urea
4. MANNITOL
What is the mechanism of action of Mannitol?
1. freely filtered at glomerulus, undergo limited tubular reabsorption, relatively inert

2. Mannitol 5-25% injected IV in large amounts increases osmolarity of plasma and tubular fluid to produce diuresis by causing water retention in the PROXIMAL TUBULE and DESCENDING LIMB of HENLE
What 2 conditions are Osmotic Diuretics used to treat?
1. reduce Intracranial pressure in neurologic conditions

2. reduce Intraocular pressure before opthalmic procedures
What are the adverse side effects of Osmotic Diuretics
1. Severe Dehydration

2. Loss of free water

3. Hypernatremia

4. Headache, nausea, vomiting
What are Osmotic Diuretics contraindicated in? Why?
pts with Congestive Heart Failure

b/c of rapid expansion of EC fluid volume and hyponatremia occuring before diuresis may produce Pulmonary Edema and complicate CHF
List the 4 Loop Diuretics
1. Bumet-anide
2. Furo-semide
3. Tor-semide
4. Ethacrynic acid

**BuFET
Diuretics formerly referred to as 'high-ceiling' b/c they are the most effective diuretics now available
Loop Diuretics
All Loop Diuretics are derivatives of __1__, except __2__
1. Sulfonamide

2. Ethacrynic acid
How can Loop diuretics be administered? Which way produces extremely rapid diuresis?
Orally, IV, IM

IV
What is the mechanism of action of Loop Diuretics?
inhibit Na+/K+/2Cl- cotransporter in the Thick Ascending Limb of Henle = decreased NaCl Reabsorption
List the important effects of Loop Diuretics
1. Increased delivery of Na+ to the Late Distal Tubule & Collecting Tubule = enhances K+ & H+ secretion -> HYPOKALEMIA

2. Reduced NaCl reabsorption -> more Na+ stays in the tubular fluid -> reduced NaCl influx across the Macula Densa chemoreceptors -> INCREASED RENIN SECRETION

3. reduced Ca++ reabsorption in the Loop -> increased Ca++ excretion but hypocalcemia rarely occurs b/c Ca++ is actively reabsorbed downstream in Distal tubule

4. Increase in Mg+ excretion -> HYPOMAGNESEMIA

5. Direct vascular effect due to increased Prostaglandin synthesis may INCREASE RENAL BLOOD FLOW
1. Block the Na+/K+/2Cl- cotransporter to prevent reabsorption of Na+ and Cl- and thereby increase tubular excretion

2. Also decrease potential difference generated by recycling of K+ which normally drives divalent reabsorption

3. The reduced electrical potential thus increases excretion of Ca2+ and Mg2+
Explain the mechanism of Loop Diuretics (List 3 things)
What is the most common use of Loop Diuretics?
relief from EDEMA due to CHF, kidney disease, or hepatic necrosis

** = 1st choice for any kind of Edema
When would you use Loop Diuretics for Hypertension?
only if Thiazides do not work

** = 2nd line choice for HTN
How would you use Loop Diuretics to treat Severe Hyperkalemia?
Use together with NaCl and Water administration to enhance urinary K+ secretion
Diuretic used to treat Acute Renal Failure = converts oliguric to nonoliguric failure; are effective EVEN WHEN GFR IS LOW
Loop Diuretics
What are the side effects of Loop Diuretics?
OH DANG

1. Ototoxicity
2. Hypokalemic metabolic alkalosis = from enhanced K+ & H+ secretion / Hypokalemia leading to cardiac arrhythmias
3. Dehydration & Hyponatremia leading to hypotension, circulatory collapse, reduced GFR, thromboembolic events
4. Allergy = due to Sulfa
5. Nephritis (interstitial)
6. Gout & hyperuricemia = due to increased uric acid reabsorption in the Proximal tubule
Hypokalemia leading to Cardiac Arrhythmias caused by Loop diuretics is more common when patients are taking what other drug?
Digoxin
With what Loop Diuretic are Allergic Rxns less common? Why?
Ethacrynic acid

b/c it is not a Sulfonamide derivative
With what Loop Diuretic is Ototoxicity more common?
Ethacrynic Acid due to inhibition of the Na+/K+/Cl- transport for endolymph production in the cochlea
Loop diuretic that can be used in patients who are either allergic to sulfa drugs or those who have gout
Ethacrynic acid
Most Thiazide diuretics end in -thiazide, but the Sulfonamide Thiazides do not. List 4 of them
1. Chlor-thalidone

2. Indapa-mide

3. Met-ola-zone

4. Quin-etha-zone
What is the mechanism of action of the Thiazide diuretics?
block the NaCl transporter in the Distal Convoluted Tubule = inhibit NaCl reabsorption from lumen
Why are Thiazide diuretics only moderately effective at increasing NaCl excretion?
B/c 90% of the filtered load has been reabsorbed before it reaches the distal tubule
What 2 "-emia's" do Thiazide diuretics produce?
Hypokalemia = due to increased K+ secretion

Hyperuricemia = due to decreased uric acid secretion
What do Thiazide diuretics reduce the excretion of by enhancing the reabsorption in the Distal Convoluted Tubule?
Ca++
Diuretic that is INEFFECTIVE when GFR is low
Thiazide

**unlike Loop Diuretics
Thiazide diuretics
-inhibit NaCl transporter to decrease reabsorption of Na+ and Cl-

-reabsorption of Ca++ is enhanced b/c the increased Na+ concentration gradient across the basolateral membrane stimulates the Na+/Ca++ counter-transport
What Diuretic has its action here? Explain what happens
What are Thiazide's the first choice in treatment of?
Hypertension
What are Thiazides second in line to Loop Diuretics in treatint?
Congestive Heart Failure
Diuretic used to treat Nephrolithiasis due to idiopathic Hypercalciuria = to reduce urinary calcium concentration
Thiazides
Diuretic used to treat Nephrogenic Diabetes Insipidus = to reduce polyuria and polydipsia

What is the paradoxical effect due to?
Thiazides

**the paradoxical effect is due to plasma volume reduction
What are the adverse effects of Thiazides
hyperGLUC

1. hyperGlycemia = due to decreases in pancreatic releace of insulin and tissue glucose utilization

2. hyperLipidemia

3. hyperUricemia

4. hyperCalcemia
---------------------
5. hypokalemic metabolic alkalosis
6. hyponatremia due to elevated ADH
7. Allergic rxns
8. weakness, fatigability, paresthesias
9. Impotence
Diuretic that may induce Hemolytic anemia, thrombocytopenia, and acute necrotizing pancreatitis
Thiazides
Diuretic that causes Impotence 4-times more often than Beta-blockers
Thiazides
-
-
List the 2 classes of Potassium-sparing Diuretics and the drugs within them
Aldosterone antagonists
- Eple-reone
- Spirono-lactone

Na+ channel blockers
- Amilo-ride
- Triam-terene

**the K+ STAys
Diuretics seldomly used alone, but used to counteract Hypokalemia caused by Loop or Thiazide diuretics
K+ sparing diuretics
-Spirinolactone
-Triamterene
-Amiloride
-Eplereone
What is the mechanism of action of Spironolactone and Eplereone?
inhibit K+ secretion by antagonizing the Mineralcorticoid receptors (where Aldosterone binds)

**Aldosterone promotes Na+ reabsorption and K+ secretion in the collecting tubules
What is Aldosterone's mechanism of action?
Promotes Na+ reabsorption & K+ secretion in the Collecting Tubules = water retention effect
What is the mechanism of action of Triamterene and Amiloride? Why is K+ spared?
Block Na+ channels in apical membranes of the Collecting Tubule

b/c its secretion is coupled to Na+ entry
1. The inward diffusion of Na+ creates a negative potential in the lumen to drive efflux of K+

2. Amiloride and triamterene block apical Na+ channels to cause loss of potential (decreases the driving force for K+ secretion) and reduce K+ and H+ secretion

3. Aldosterone receptors (MR) decrease Na+ excretion and increase K+ and H+ secretion; opposite effects are produced when blocked by spironolactone or eplerenone
What Diuretics work here? Explain
What are the clinical uses of the Potassium-sparing diuretics? (3)
1. Primary Mineralcorticoid hypersecretion = such as in Conn's Syndrome or Ectopic ACTH production

2. Secondary Aldosteronism = due to CHF, Hepatic Cirrhosis, Nephrotic Syndrome, and other conditions associated with salt retention & reduced fluid volume

3. used together with Thiazide or Loop Diuretics to minimize potassium depletion
Diuretic than can be used to reduce Digoxin toxicity during treatment of CHF
Spironolactone
List the toxic effects of the Potassium-sparing diuretics
1. Hyperkalemia

2. Hyperchloremic metabolic acidosis = due to inhibition of H+ secretion with the reduced K+ secretion

3. Gynecomastia
Acute renal failure may occur when this diuretic is combined with Indomethacin
Triamterene
Kidney stones may occur with this Potassium-sparing diuretic due to its poor solubility
Triam-terene
What are the 2 most common clinical uses of Diuretics?
1. reducing fluid volume in Edematous states (CHF, Kidney or Hepatic disease

2. HTN
What things increase the risk of Hyperkalemia when using Potassium-sparing diuretics?
1. Renal disease

2. drugs that reduce Renin-angiotensin activity
- Beta-blockers
- ACE inhibitors
- Angiotensin antagonists
Explain how diuretics help in the treatment of CHF
Reduce extracellular fluid volume -> reduce Preload = reduce Cardiac Work
When treating CHF with diuretics, what will concurrent treatment with any Vasodilator cause?
Reduced renal blood flow and inhibit the diuretic effectiveness
Diuretic that has reduced the MORTALITY from CHF
Spironolactone

**but Loop Diuretics are still 1st line treatment
When are Loop diuretics only used for HTN?
1. in presence of Renal Insufficiency

2. in presence of Cardiac Failure
When are Potassium-sparing diuretics used to treat HTN?
only in combination to avoid Hypokalemia
Diuretic of choice for treatment of HTN?
Thiazides
In what groups of people are Thiazides more effective than other anti-HTN agents?
1. Blacks

2. Elderly
1. Acet-azol-amide
2. Osmotic agents
3. Loop agents
4. Thiazides
5. Potassium sparing
6. ADH sparing
Fill in the diuretics
Carbonic Anhydrase Inhibitors
What drug works here?
Diuretics that increase Urine NaCl
All of them
Diuretics that increase Urine K+
All except K+-sparing
Diuretics that lower the blood pH (acidosis)
Carbonic Anhydrase inhibitors

K+-sparing
Diuretics that increase the blood pH (Alkalosis)
Loop diuretics

Thiazides
Diuretics that increase Urine Ca++
Loop diuretics
Diuretic that decreases Urine Ca++
Thiazide
Why do Loop Diuretics have less of an effect on HTN than Thiazides?
Loop Diuretics cause decreased NaCl influx across the Macula Densa chemoreceptors in the Thick Ascending Limb --> Renin secretion --> Angiotensin II formation --> Vasoconstriction & Aldosterone release ( = Na+ reabsorption in Collecting Tubule)
Diuretic whose allergic rxns include cross-reactivity with other Sulfonamides, photosensitivity, and generalized dermatitis
Thiazides