Ch.5,6-Distal Nephron, Hormones Flashcards
What % of the filtered load of WATER and SALT makes it all the way to the Distal Nephron (both Distal Tubule and Collt Tubule)
10% of both
What does ADH regulate in the Distal Nephron?
WATER!!! more ADH=more H2O reabsorption
What does Aldosterone regulate in the Distal Nephron?
SALT!!!! more Aldosterone=more NaCl reabsorption
HOW does ADH do its job in the collecting tubule?
ADH makes the collecting duct permeable to H20. KICK it out of the Kidney to KEEP it in the body!! ANTIDIURESIS
What happens to the collecting duct when ADH is NOT present??
Collecting duct is IMPERMEABLE to H20…MORE water peed out…DIURESIS
Which Apq type does ADH move to the ______ membrane of the collecting duct? WHAT G-protein messenger is used??
Aqp-2….luminal….uses cAMP (more cAMP=more Aqp-2)
Which channels are “super-glued” to the BL membrane in the Collecting duct?
Aqp-3
Is the ADH/Aqp-2 process reversible??
YES! less ADH=less Aqp-2’s
Which Aqp’s do we see in the Proximal Tubule?
Aqp-1’s
Which region of the nephron DOES NOT have Aqp’s?
The Ascending Limb (luminal portion)
Review: Which region is most active in the reabsorption of Na+?? What is used on the Luminal and BL membranes to make this happen?
Cortical Collecting Duct….Selective Na+ transporters used on the membrane,
What does the Cortical Collecting Duct secrete?
K+
What are the 3 things Aldosterone is doing to promote Na reabsorption? (think aldosterSLOWone)
1.make more Na+ channels 2.make more Na+/K+ pumps 3.Boost ATP production (via Krebs cycle)
Aldosterone and ______ have similar affinity for the mineralocorticoid receptor.
cortisol (a GLUCOcorticoid!)
What is used to combat the Cortisol/Aldosterone dilemma?
11-Beta-HydroxySteroid Dehydrogenase Type 2 (hahaha our longest name yet!!!)
Mutations in 11-Beta-HydroxySteroid Dehydrogenase Type 2 can lead to ______ and _______.
NaCl retention and hypertension (cause Cortisol is frontin’ on Aldosterone’s receptors, yo)
What does PTH do to the Distal Tubule? (2 methods) (which membrane)
promotes more Ca2+ reabsorption…1. Make more Ca2+ATPase’s and 2. More Na+/Ca2+ exchangers (BOTH on BL membrane)
What mechanism do we use to create the medullary hypertonic intersitium? What magical fluid does it use?
CounterCurrent Multiplication…pre-[ ] tubular fluid
What are the 3 steps to CounterCurrent Multiplication?
1.Reabsorption and retention of NaCl in the ascending limb 2.Reabsorption of H2O in the descending limb (remove w/ vasa recta) 3.Proximal tubule sends Isotonic fluid into the Lof H, now the fluid is hypertonic in the ascending limb
After the countercurrent multiplication, which has more of an osmotic gradient: vertical or horizontal?
Vertical has a 275 gradient > horizontal 200 gradient
Urea Recycling: The _____/_____ ______ collecting tubule cannot reabsorb urea.
Cortical/outer medullary collecting tubule
What happens to [Urea] in the presence of ADH? (2 things)
- [Urea] increases in the collecting tubule (you are reabsorbing H2O)….2.FARTHER down the collecting tubule ADH makes Urea more permeable so it moves to the interstium (then back into the ascending limb (REDUCE–>REUSE–>RECYCLE, learn it, live it, love it)
What happens to Urea in the ABSENCE of ADH?
No ADH=low [Urea]=low urea reabsorption=high urea excretion
What does HIGH ADH do to Urea excretion?
High ADH=High Urea Reabsorption=Low Urea Excretion
What does Low ADH to to Urea excretion?
Low ADH=Low Urea Reabsorption=High Urea Excretion
What does low ADH do to Medullary Osmolarity?
Low ADH=Low Medullary Osmolarity
What are the 3 main functions of the Vasa Recta during ‘CounterCurrent Exchange”?
1.Nutrient supply 2.Remove the reabsorbed H2O and NaCl 3.NET-preserve the hypertonic gradient of the medullary interstitium
In countercurrent exchange, how does the osmolarity of the plasma flowing in compare to the osmolarity of the plasma leaving the medulla?
in isotonic 300mOsm….vs….out more hypertonic 320 mOsm
Main idea of urea and protein: how do cells survive in the denaturing environment of urea?
By expanding and contracting (Aqp’s)
Since water in MUST EQUAL water out, what is the ONLY output that we can TIGHTLY control?
Urine output!
What is max diuresis (low ADH)? (in L/day AND mOsm/kg)
20-25 L/day & 50-75 mOsm/kg
What is max antidiuresis? (high ADH) (in L/day AND mOsm/kg)
0.5 L/day & 1200-1400 mOsm/kg
What is another name for ADH?
AVP-Argenine VasoPressin
ADH/AVP is synthesized in neural cell bodies located in _______ and _______ nucleii of hypothalamus.
SupraOptic & Paraventricular
Wait, which general part of the brain is ADH/AVP synthesized again?
the Hypothalamus :)
Where is ADH/AVP stored once synthesized?
the PURSE! posterior pituitary (not the flat peg/anterior pituitary)
What is ADH secretion regulated by?
Hypothalamic OsmoReceptors
Which has a more SENSATIVE effect on ADH release…plasma osmolarity OR plasma volume?
Plasma Osmolarity….Osmoreceptors are MUCH more sensitive then the Volume Receptors
What is the set point when looking at plasma [ADH] vs plasma osmolarity graphed? What does DECREASING volume or pressure do to the set point and the slope?
Plasma mOsm/kg when ADH is NOT secreted (about 278 mOsm/kg)….Decreasing vol/pressure decreases the set point and Increases the slope (sensitivity of ADH release)
What does INCREASING plasma volume or pressure do to the set point and slope of the ADH/mOsm graph?
Increasing vol/pressure increases the set point (osmotic point at which ADH is released) and decreases the sensitivity of ADH release
Relatively _____ changes in ADH elicit _____ changes in urine osmolality.
small…..large
Increase in urine osmolality = ______ in urine volume
Increase in Urine osmolality = decrease in urine volume
Stimuli that regulate ADH release also regulate the ______ ______.
THIRST DRIVE!
What is SIADH? What are the three causes?
Syndrome of Inappropriate ADH secretion (SIADH)…1.Head Trauma 2.ADH secreting tumor 3.Drugs
What can be the 2 MAIN effects of SIADH?
HypoNatremia–>COMA (water moving IN to brain cells)
What are the 2 causes for D.I.?
Diabetes Insipidus is caused by 1. Decreased production of ADH in the Hypothalamus (HYPOTHALAMIC DI) or 2.Renal Unresponsiveness to ADH (NEPHROGENIC DI)
What are the 2 MAIN effects of D.I.?
1.HyperNatremia 2.Coma (water moving OUT of brain cells)
What is the rate limiting factor for free water clearance?
Ability to reabsorb NaCl from the acending limb
What happens if we are excreting LESS then 2L H20/day?
Our ability to reabsorb NaCl in the ascending limb is diminished
When is free water clearance 0?
When exerting ISOTONIC urine
xtracellular fluid (ECF) volume _____ related to total body sodium (chloride)
directly….increase total body Na+ = increase ECF volume
What % of Na+ reabsorption happens: Proximal tubule? Ascending limb? Collecting duct?…END RESULT?
Prox: 67%…..Ascending 23%….Collecting Duct: 9%…End result: excretion = 1% of filtered Na+
Na+ excretion primarily regulated by the action of aldosterone on the ________.
Cortical Collecting Tubule (duct)
Aldosterone regulates the excretion of approximately __% of the filtered load of sodium
5%
Consider that 0.056% of the filtered load = 140 mEq of NaCl (25,200 mEq/d x 0.0056)…..If this small percentage was inappropriately retained, it would obligate the retention of ____ L of H2O
1L of H20!!!!
he cortical collecting tubule i. reabsorbs _______ and ii. secretes _______.
sodium….potassium
Absolute dependence on Na+-K+-ATPase located ONLY on the ________ membrane to maintain _____ intracellular Na+ concentration.
BasoLateral membrane..low
Will a change in total body Na+ content be reflected in a Na+ concentration change in the ECF?
No
Does 1) infusion of isotonic saline or 2) hemorrhage affect Na+ concentration change in the ECF?
No
Aldoserone stimulation: Total body Na+ changes sensed as changes in _______ _______ ______ (___). Which is monitored by _________!
Effective Circulating Volume (ECV)….BARORECEPTORS!
What is the RATE-LIMITING STEP in aldosterone release from the adrenal cortex?
Renin (ENZYME, not hormone!!!) release by the KIDNEY!
What are the 4 pharmacological methods of blocking the renin-Angiotensin-Aldosterone system?
1.Renin Inhibitor 2.ACE inhibitor 3.A-II receptor agonist 4.Aldosterone receptor agonist
Renin secreted by ______ cells of the _______ arteriole;
granular cells….afferent
What are the 3 mechanisms to promote Renin release? (nothing new here)
1.Baroreceptor 2.Sympatheic sys 3.Macula Densa
Not only will A-II promote renin release it also does these 2 IMMEDIATE actions…
POTENT vasoCONSTRICTOR and Increases Heart Rate
What are the 4 LONG TERM actions of A-II on the kidney?
……….1…….Constrict Afferent Arteriole–>Lower GFR—>Lower H2O and NaCl excretion–>increase BP……..2……… Increase H2O and NaCl Reabsorption!–>(again) lowers H2O & NaCl exertion–>increases BP……..3……..Directly stimulate cortical collecting ducts to reabsorb Na+…..4…..ADH stimulation for H2O reabsorption
What is the 7th function of A-II not discussed yet?
Thirst
Increase in aldosterone = ______ in BP…this leads to Aldosterone “______”
Increase…“escape” (at high BP, Na+ and H2O get pushed out of the body)
Renal adjustments for changes in H2O intake are rapid (_______) but renal compensation for a sudden alteration in NaCl intake can take several ____. WHY?
(minutes)….days..c/o ADH and Aldosterone action
What hormone takes over with increased ExtraCellularVolume? Where is it secreted?
ANP…secreted from atrial myocytes
ANP works by VasoDilation of the ______ arteriole.
afferent
ANP works by inhibition of the enzyme ______.
Renin (and therefore Aldosterone)
ANP works by inhibition of NaCl resorption in the _________ and _______.
Proximal tubule….collecting tubule
ANP works by inhibition the releases of the hormone _____ and its effect on the _______.
ADH…collecting tubule
Bartter’s syndrome is a genetic abnormality leading to altered ______ transport. WHICH gene?
Na+….ENCC-Electro Neutral sodiumChloride Cotransporter
ENCC1’s are found…
in the distal tubule
ENCC2’s are found…
in the ascending limb
ENCC3’s are found…
in the collecting tubule
Bartter’s Syndrome: Mutations in the gene expressing the __________ (ENCC2) and/or luminal ___ (ROMK) ______ in the _________.
Na+-K+-Cl- cotransporter……K+ channel…thick ascending limb
What is the main effect of Bartter’s Syndrome? Due to this what happens with the Pt handling of Salt and ECV?
Cannot reabsorb NaCl!…Salt Wasting (increased excretion) and therefore volume depletion
What happens to renin/aldosterone levels in Bartter’s syndrome?
Hyperreninemic hyperaldosteronism
What is the effect of Bartter’s syndrome on plasma Calcium?
HyperCalciuria (decrease in lumen + potential
Bartter’s syndrome: What happens to potassium plasma levels and therefore acid/base plasma effects?
HypoKalemia and therefore Metabolic Alkalosis
Polycystic Kidney Disease (PKD); Cysts are fluid-filled sacs that develop from renal _________ cells.
tubular EPITHELIAL
Polycystic Kidney Disease (PKD); which genetic link is more common: the Autosomal dominant or the autosomal recessive?
The autosomal dominant is 85% of the cases
Autosomal Dominant Polycystic Kidney Disease often associated with ________; leads to end-stage renal disease in ___% of patients
hypertension..50%
Which Polycystic Kidney Disease is associated with high infant mortality: autosomal dominant or autosomal recessive?
Autosomal Recessive
Diuretics: Inhibit specific enzymes, transport proteins, hormone receptors or ion channels that are involved in transepithelial ____ _________.
Na+ reabsorption
What is the NET effect of diuretics?
Increased NaCl & water excretion
What ENZYMES do diuretics inhibit?
Proximal Tubule Carbonic Anhydrase inhibitors (no Na+HCO3- reabsorption…typically not Rx’d
Which diuretics inhibit transport proteins and WHERE do they work? (what specific transport proteins?)
LOOP DIURETICS of the ascending limb (inhibit the Na+K+2Cl- transporters
Which diuretics inhibit transport proteins on the distal tubule luminal side? How do they compare to Loop Diuretics?
Thi-a-zides…much milder then Loop Diuretics
What is the nickname for the diuretics that act on K+ ion channels?
“K+ sparing” diuretics (inhibit liminal Na+ channels) (amiloride)
What is the Aldosterone receptor agonist that also is a “K+ sparing” diuretic?
Spir-on-ol-act-one
EDEMA: normally in times of low plasma proteins, it will eventually equal out, BUT WHAT does the kidney do to PERPETUATE generalized edema?
sees the low ECV–>and INCREASES ALDOSERONE which then keeps plasma protein [ ] low and then boosts interstitial fluid
