Renal Flashcards
Describe the 60-40-20 rule
How are intravascular and interstitial fluid determined?
60% of total body weight is water
40% of total body weight is intracellular
20% of total body weight is extracellular
The interstitial and intravascular make of the ECF- 1/4 of ECF is intravascular and 3/4 is interstital
What compartment do diuretics work on? How do they work?
Intravascular of the ECF
They force Na and water elimination in the urine
How do diuretics work to decrease blood pressure (use the equations to explain)?
Diuretics decrease the intravascular volume
The intravascular volume determines stroke volume
CO= HR x SV
BP= TPR x CO
How much of the CO does the kidney take? How much of this is renal plasma flow? How much of the renal plasma flow is actually filtered?
Kidney is greedy and takes 20% of CO
50% of the blood reaching the kidney makes up the renal plasma flow
20% of the renal plasma flow is actually filtered
How does the kidney regulate blood volume and osmolarity? Which is more important in regulation?
By changing the urine composition
It’s more important to maintain blood volume
What is the most important determinant of blood volume?
The amount (moles) of sodium in the ECF
An increase in the amount of sodium in the ECF causes volume contraction of expansion? A increase or decrease in the urine output? An increase or decrease in kidney reabsorption?
Volume contraction
Increase in urine output
Decrease reabsorption in the kidney
What does it mean to be in sodium balance?
Dietary intake matches urinary output
How does the kidney respond to a decrease in sodium intake?
A decrease in sodium intake causes a decrease in ECF volume, causes an increase in sodium reabsorption and a decrease in the sodium urinary output
The regulation of sodium balance is mainly associated with regulating volume or osmolarity?
Volume
What is the definition of edema? What are some causes?
Excess fluid in the interstitial place due to an imbalance in the hydrostatic and oncotic pressure in the capillaries
Can be due to cardiac (increased hydrostatic), nephrotic (decreased oncotic), hepatic (decreased oncotic), endocrine (hyperaldosteronism)
Describe the parts of the nephron, defining features of each part, and where it’s located: glomerulus, proximal convoluted tubule, tAL, TAL, distal convoluted tubule, collecting duct
Glomerulus: in the cortex, site of filtration that has the same osm as plasma minus proteins- this is the raw material for urine- GFR= 125 mL/min
Proximal convoluted tubule: in the cortex, passive diffusion done isotonically; major site of reabsorption (66% of filtered filtrate is reabsorbed and returned to the circulation via the renal vein here)
tAL: in medulla- impermeable to water, but permeable to ions
TAL: extends from the medulla into the cortex- impermeable to water, uses active transport for a Na/K/Cl cotransporter (dilutes the tubular fluid and maintains the counter current multiplier)
Distal tubule: cortex- early is impermeable to water, late is permeable to water but only on the presence of ADH; sensitive to aldosterone
Collecting duct: begins in cortex and extends into the medulla; permeable to water in the presence of ADH
What is the equation for the fractional filtration? How would you put this in words?
FF= GFR/RPF
The fraction of plasma flowing through the glomeruli that is ultrafiltered to form tubular fluid
What is the equation for the fractional excretion of water? How would you put this in words?
What’s another way of calculating GFR?
FE= V/ GFR
This is the fraction of the glomerular filtrate that is not reabsorbed in the nephron
Can also calculate GFR by the clearance of inulin since inulin is neither reabsorbed nor secreted the clearance equals the GFR
C=UV/P
FE= P/U
What is the equation for the fractional excretion of solute X?
FE= C(x)/GFR FE= [U(x) P(creat)]/ [P(x) U(creat)]
What is the fractional excretion of water and sodium when water and sodium are in balance?
1%
When the patient is dehydrated, they are said to be in positive or negative water balance? What is the fractional excretion relative to 1?
Negative water balance
FE of water is less than 1
The patient is volume contracted so is going to need to absorb more water from the filtrate
When the patient is volume expanded, they are said to be in positive or negative water balance? What is the fractional excretion relative to 1?
Positive water balance
FE is greater than 1
The patient has more water to get rid of
What is the formula for fractional reabsorption? How would you put this in words?
Fractional Reabsorption= 1- FE
This is the fraction of filtered solute/water that is reabsorbed and not in the urine
In which parts of the tubule are potassium reabsorption constant? Which parts of the tubule are sensitive to the dietary potassium and can change from reabsorption to secretion?
Constant: proximal tubule and TAL
Fluctuating: distal tubule and collecting duct
A low potassium diet, causes positive or negative potassium balance? This causes what change in secretion and reabsorption and what change in the fractional excretion of potassium?
Negative potassium balance
Decreased secretion, increased reabsorption
Decrease in the FE
What parts of the nephron does aldosterone work on and how does this effect potassium?
Late distal tubule and collecting duct
Aldosterone causes an increase in the secretion of potassium (aldosterone adds Na/K ATPase to increase the reabsorption of sodium)
How is potassium secretion related to acidosis/ alkalosis?
Potassium is coupled to a proton transporter in the distal tubule
In acidosis will try and get rid of the proton and will exchange the potassium for the proton and decrease the secretion of potassium
In alkalosis will try and reabsorb more protons which will cause an increase in potassium secretion
How do diuretics increase the secretion of potassium? (there are two different ways)
Diuretics prevent the reabsorption of sodium in the earlier segments of the nephron. This allows more sodium to reach the late distal tubule and the collecting duct, where sodium reabsorption is coupled to potassium secretion
Diuretics also increase the flow rate- whenever the tubular flow rate is increased, there is a greater gradient for the potassium to flow down
Briefly describe the movement of solute in the TAL?
The basolateral membrane has a Na/K ATPase that sets up the Na gradient. On the lumenal side there are Na/Cl/K cotransporters, that are coupled as Na moves down the gradient to enter the cell. K returns into the filtrate. The removal of Na and Cl creates a positive charge in the lumen, which pushes Mg and Ca to passive diffuse through the interstitial space into the blood
The TAL is ALWAYS impermeable to water
What is the definition of free water?
Water that is not obligated to stay in tubular fluid due to the presence of solutes- the gain or loss of free water serves to normalize ECF volume and osmolarity
What is the equation for free water clearance? How would you put this in words? What is meant by a free water clearance less than 0? A free water clearance greater than 0?
C (water) = V- C (osm)
C (water)= V- (UV/P)
The free water clearance is the rate at which the kidney can eliminate or retain water that is free of solute
A free water clearance less than zero (negative free water clearance) has a more concentrated or hypertonic urine. The kidney is retaining water and the free water clearance would be the volume of water that would have to be added to the hypertonic urine to make it isotonic with plasma
A free water clearance greater than zero (positive) has a dilute or hypotonic urine. This is the water that would have to be removed from the urine to make it isotonic with water
Briefly describe the solute movement in the early distal tubule
The basolateral membrane has a Na/K ATPase that sets up the gradient. Na is then able to move down it’s concentration gradient into the cell via the Na/Cl cotransporter on the lumenal membrane. The Cl then passively diffuses down it’s gradient and into the interstitium
The early distal tubule is ALWAYS impermeable to water
What drugs act on the early distal tubule? Where do they act specifically?
Thiazide diuretics
Act on the Na/Cl cotransporter by competing with Cl for the binding site
Briefly describe the solute movement in the late distal tubule and the collecting duct
The basolateral membrane has a Na/K ATPase that sets up the gradient. Na then flows down its concentration gradient through a Na epithelial channel. K flows down it’s gradient back into the tubular fluid.
What diuretics act in the late distal tubule and the collecting duct?
Potassium sparing diuretics
including both aldosterone dependent and independent
How does aldosterone get into the cell? Where does it work?
Aldosterone passively diffuses into the cell from the blood, and then binds to a receptor in the cytoplasm forming a aldosterone-receptor complex. This complex then enters the nucleus which increases the transcription of Na/K pumps that get placed in the basolateral membrane and the number of K channels in the lumenal membrane
What are the three different major classes of diuretics?
- Aquaretics- decrease the ability of ADH to increase water permeability in the late distal tubule and collecting duct– (lithium, fluroride- methoxy flurane, demeoclocycline)
- Saluretics- decrease the solute reabsorption (loop diuretics, thiazide diuretics, potassium sparing diuretics)
- Osmotic diuretics- enter filtrate via the glomerulus and then neither reabsorbed nor secreted, but draw water in by increasing osmotic pressure (mannitol, excess glucose, urea, isosorbide)
What is the definition of a diuretic?
A drug that increases the volume and rate of urine output by decreasing the active reabsorption of solutes (saluretics) or water (aquaretics) in one or more segments of the nephron
What are some uses of diuretics?
- HTN- decrease blood volume, decreases stroke volume, decreases cardiac output, decreases BP
- Edema - can mobilize fluid from extravascular into the intravascular, decrease CSF pressure, decrease intraocular pressure
- Calcemia/ kalemia
Which part of the nephron do the carbonic anhydrase inhibitors work?
Proximal tubule
How do carbonic anhydrase inhibitors work?
Work by inhibiting carbonic anhydrase in the lumen. By inhibiting carbonic anhydrase then can’t convert into water and carbon dioxide which normally passively diffuse into the cell. When in the cell these get converted into H+ and bicarb and the H+ has a countertransport with sodium
Where does aminophylline work in the nephron? How does it work?
Proximal tubule
A phosphodiesterase inhibitor that increases cAMP which causes P of the Na/H exchanger preventing influx of Na
What are the carbonic anhydrase inhibitors? (There are 3)
Acetazolamide
Methazolamide
Dichlorphenamide
Where does Grassl classify the osmotic diuretics in the nephon?
Proximal tubule
What are the loop diuretics (high ceiling diuretics)? (there are 4)
Furosemide
Bumetanide
Torsemide
Ethcrynic acid (dichlorophenoxyaetic acid)
What part of the nephron do thiazide diuretics work in?
Early distal tubule
What are the thiazide diuretics? (there are 2)
What are the thiazide-like diuretics? (there are 4)
Thiazide: chlorothiazide, hydrochlorothiazide
Thiazide-like: chlorthalidone, quinethazone, metolazone, indapamide
What effect do carbonic anhydrase inhibitors have on urine volume and composition? What are the complications? Toxicities? What patients are these contraindicated in and why?
Slight increase in urine volume and the concentration of sodium, potassium, and bicarb
Complications: metabolic acidosis (because reabsorbing less bicarb), hypokalemia (from compensation downstream),
Toxicities: accumulation of ammonia, BM suppression, skin tox
Contraindicated in patients with cirrhosis - increased risk of hepatic encephalopathy due to increased ammonia
The ability of the kidney to dilute urine depends on what segment of the nephron?
The TAL
The diluting segment
The ability of the kidney to concentrate urine depends on what segment of the nephron?
The TAL
Sets up the counter current multiplier which then effectively reabsorbs water and concentrates urine
What type of free water clearance do loop diuretics affect? Why?
Both positive and negative water clearance are affected
Loop diuretics work by inhibiting the Na/K/Cl cotransporter- this decreases the ability of the TAL to dilute the filtrate AND decreases the concentration of the interstitium
The inability to make the filtrate more dilute decreases the positive free water clearance (can’t make the urine as dilute)
The inability to generate the counter current multiplier decreases the ability to make a more negative free water clearance (can’t make the urine as concentrated)
What type of free water clearance do thiazide diuretics affect? Why?
Positive free water clearance
Thiazide diuretics work by inhibiting the Na/Cl cotransporter in the early distal tubule. This decreases the ability to create a more dilute urine (a more positive free water clearance). The distal tubule is in the cortex and has nothing to do with the counter current multiplier and therefore doesn’t affect the negative free water clearance
Due to only positive free water clearance being affecting, these patients are more susceptible to hyponatremia (because not diluting the urine as well if have an excess of water)
What are the major uses of aminophylline?
Decrease inflammation and bronchospasm in asthmatics
What are some clinical uses of mannitol?
Increase drug clearance, minimize renal failure during shock/injury (forces the kidneys to make urine), decrease intraoccular and intracranial pressure, Dx oligouria (low urine output)
What are the uses of thiazide diuretics?
Exacerbation with pulm edema, and edema from CHF and cirrhosis, hypercalcemia, and drug toxicity
What are the complications from using thiazide diuretics?
Hypokalemia (can onset DM or exacerbate existing), hypomagnesemia, hyperuricemia, increased BUN/creatinine, contraction alkalosis, hyponatremia, ototoxicity when used with aminoglycoside antibiotics
What is the mechanism of loop diuretics?
Inhibit the Na/Cl/K cotransporter in TAL
What is the mechanism of thiazide diuretics?
Compete with Cl receptor on the Na/Cl cotransporter in the early distal convoluted tubule
What are the effects of ECF volume contraction seen with both thiazide diuretics and loop diuretics?
Hyperbicarbonatremia (alkalosis), hyperuricemia, increased BUN/creatinine, hyponatremia
What are the main uses of thiazide diuretics?
Primarily controlling HTN
Other uses include chronic edema 2/2 cardiac insufficiency, idiopathic hypercalciuria, nephrogenic diabetes insipidus and in conjunction with lithium therapy
What are the complications associated with thiazide diuretics?
Hypokalemia (DM), hyponatremia, contraction alkalosis, hyperuricemia, increased BUN/creat, hypercalcemia
Which do you use for DI? Loop diuretics or thiazide diuretics? Why?
Thiazide
DI are already volume contracted so don’t want to decrease the negative free water balance
Thiazide only affect positive free water balance (ability to respond to volume expanded), while loop diuretics affect both positive and negative free water balance
What is the aldosterone dependent potassium sparing diuretic?
Spironolactone
What are the aldosterone independent potassium sparing diuretics?
Triamterene and amiloride
What are the main determinants of diuretic activity? Which is the exception?
- Plasma concentration
- Renal blood flow
- Glomerular filtration
- Tubular secretion
- Tubular fluid concentration
Sprinolactone- only depends on plasma concentration and renal blood flow
