4. Essentials of Renal Physiology Pt. II Flashcards
Amount of Filtered Na is Huge
• Kidney is filter and throws everything away an takes back what it needs ○ Throws out: 25,500 mmol of sodium ○ And vast majority reabsorbed ○ 200x what you're taking in in a normal diet ○ 10x amount what you have in ECF ○ Preserve this: excrete more or less the same amount you take in to keep your \_\_\_\_ controlled
ECF
Reabsorption Very Tightly Regulated
* Reabsorption has to be very \_\_\_\_ regulated * \_\_\_\_% resorption
tightly
99.6
What if Reabsorption Drops to 95%?
• Go to 24,225 mmol/day • Increase urine A loss 100 to 1200 ○ Half of total EC fluid volume in a day and die of \_\_\_\_ • Inconsistent of life • Cannot make the kidney do this
hypovolemia
What if It Increases to 99.9%?
* Dropped urine excretion to 25 mmol/day and taking in the same amount * In course of a month > would double EC content of Na > \_\_\_\_ and \_\_\_\_ * Increased urine sodium reabsorption > also problems
hypertensive
edematous
- One nephron
- Glomerulus with arteriole in > tuft of capillaries > out
- High enough pressure > squeezing fluid > captured by BC > proto-urine travels along long tube > vast majority of stuff that’s filtered gets resorbed, and poisons secreted > net result is excretion
- ____ is where majority of absorption occurs (65-70%)
- LH dives in the medulla of the kidney > ____% of absorption occurs here
- DCT resorbs another ____%
- Fine tuning > ____
- Diuretic class acts on each four segment separately
PCT
25
5-10
cortical collecting duct
Proximal Tubule
• Source of energy for Na absorption > \_\_\_\_ ○ Ubiquitous ○ Major source of energy for maintain cell gradients in life ○ Only thing where you see \_\_\_\_ getting used throughout the whole process § Everything else are \_\_\_\_, but energy comes from this pump • Lumen is the urine side (apical side) • Interstitium is the blood side • Many transporters on the apical side ○ Co-transporters that take back stuff you need ○ Glucose gets into the urine, and needs to be taken back § If peeing out glucose > lots of calories lost § Major site where \_\_\_\_ is reclaimed • Major mechanism here is \_\_\_\_ absorption thorugh the Na-H+ exchanger ○ Na+ going in, and \_\_\_\_ going out § If all that happened is this > buildup an acidic pH > stop being able to have protons travel up cxn gradient > little \_\_\_\_ absorption ○ H+ combines with \_\_\_\_ in the urine > facilitated by CA > yields \_\_\_\_ > can percolate through cell membranes without facilitations with channels > split back into a H+ and \_\_\_\_ > H+ can be recycled into the urine, and bicarb can leave cell via \_\_\_\_ transporter § Two CA > lumenal one, and a cytosolic one
NaK ATPase ATP transporters glucose Na-bicarb H+ Na bicarb CO2 bicarb Na-bicarb
Proximal Tubule
• Inhibited by \_\_\_\_ ○ Diuretic • So much Na absorption occurs here > but, not a powerful diuretic > impossible to completely \_\_\_\_ this process without killing these cells ○ Still lose some sodium § But not powerful: □ Don't completely inhibit it □ A lot of tubule left after this can \_\_\_\_ and catch up and reabsorb the sodium • Used rarely ○ Not that strong ○ Makes you lose a lot of bicarb § Clinical circumstances > do not want to do that • One diuretic taken by young healthy people > \_\_\_\_ ○ Purposely make bicarb low in high altitude
acetazolamide
inhibit
compensate
altitude sickness
Thin Limbs of the Loop of Henle
- Thin descending limb has ____ NaCl permeability
- But high ____ permeability
- Medullary interstitium has high ____ concentration
- NaCl concentration in the lumen increases along its ____
- NaCl is ____ reabsorbed from the thin ascending limb due to its high concentration in the lumen
- This segment is water ____• Doesn’t take part in Na reabsorption
○ Low permeability
○ Permeable to water though
○ Pssive action
• Dives into hypertonic nephrone > bc of actions of thick ascending limb
○ Water gets sucked out of thin descending, but NaCl trapped into it
• Thin ascending limb
○ Small segemnt - permeable to Na
○ Little passive Na absorption bc of how conc the urine is
• Major action in thick ascending
low water NaCl length passively impermeable
Thick Ascending Limb of the Loop of Henle
• Impermeable to \_\_\_\_, unlike thin descending • Reabsorbs \_\_\_\_ ○ Transporter that has Na, 2 Cl, and K that all have to go together § \_\_\_\_ transporter ○ In order to work, all the ions have to be in this proportion ○ Can resorb a lot of Na as long as Cl and K is present § A lot of Cl in urine at this point, but not a lot of K at this point; if tried to have this transporter work on its own > depelte K in urine; need to recycle K > second channel allows K to leak out □ \_\_\_\_ transporter □ \_\_\_\_ □ Creates a net \_\_\_\_ charge in urine here > allows for absorption of other things ® A lot of transporters that facilitate things being absorbed > live in cell-cell junctions; net positive charge by back leak of K, drives through cell positive ions (\_\_\_\_) > clinically important where if you inhibit K you waste more \_\_\_\_ in your urine!
water salt NKCC ROMK unidirectional positive Ca++ Ca++
• NKCC2 inhibited by ____
○ Used a lot
○ Very potent
○ Severe heart failure > retain a lot of fluid in body
loop diuretics
Distal Convoluted Tubule
• \_\_\_\_ cotransporter • \_\_\_\_r impermeable, but pumps Na out > further \_\_\_\_ the urine • Inhibited by \_\_\_\_ diuretics ○ Most frequently used in general; not just severely volume overloaded, but also an \_\_\_\_ ○ The \_\_\_\_ medicine you're put on should be this
NaCl water dilutes thiazide antihypertensive first
Question:
• What if you wanted to reabsorb Na+, but the anion it was paired with was not reabsorbable?
• Needed to get Na back, want to be able to resorb if you need to ○ Causes a problem, if resorb the sodium > rapidly develop \_\_\_\_ charge that prvenets from resorbing \_\_\_\_ ions
negatieve
positive
How to reabsorb Na without anion:
Cation Exchanger
• Build a \_\_\_\_ exchanger, trade it for another cation > \_\_\_\_ ○ Not a problem that the anion is not resorbable
cation
K+
Cortical Collecting Duct: Principal Cells
• ENaC ○ Epithelial sodium channel ○ Allows Na to come in by \_\_\_\_> generates net \_\_\_\_ charge in urine; separate \_\_\_\_ channel that allows it to leak out ○ Actual energy comes from \_\_\_\_ on the basolateral side § Also the same for the prior 3 slides ○ Major method of Na reabsorption that occurs in the CCD • Inhibited by another class: \_\_\_\_ ○ \_\_\_\_-sparing diuretics • Water permeability varies with \_\_\_\_ (hormone)
itself negative K+ NaK ATPase amiloride K AVP
Regulation of Renal Sodium Excretion
• Vary the input of Na in a subject, and measuring the output • Solid = represents how Na is taken in a day • Dotted = output of Na from the urine • Start with Na being low > and two lines are superimposed ○ Taking in little Na a day, and putting out a little a day • Put a ton of Na in the diet ○ 10 mequiv to 150 mequiv - ACUTELY ○ Transiently taking in more Na than peeing out § Retaining \_\_\_\_ § Weight \_\_\_\_ § Then subject detects > amount of Na in the urine goes up each day > until it reaches a point where amount of Na peed out is the same as the \_\_\_\_ taken in § Body does in \_\_\_\_ curve, not a stepwise way □ Measuring the sodium on a daily basis here, so looks like steps □ If every 5 mins > curve ○ Leave person at this Na intake > won't change > will pee out as much as take in § Difference: weight has \_\_\_\_; NOT THE SAME! • Acutely drop the amount of Na in the diet ○ 150 to 10 ○ Taking in less than peeing out ○ First day: pee out \_\_\_\_ than take in; weight \_\_\_\_ ○ Next day: continue to pee out more, but not as much; and weight doesn’t drop as much; until the amount you excrete \_\_\_\_ the amount you're taking in
fluid increases amount continuous increased more drops equals
• Stretch sensors in multiple vascular structures:
○ Kidney
○ Small arterial heading in the glomerulus
○ Multiple vital organs on arterial side
○ Cardiac atria
• Send signals via multiple pathways
○ In kidney
§ Direct impact on ____ release and RAT
§ Tells it to hang onto ____+ (lose less)
○ In vascular
§ Feedback through ANS back to brain, integrated and sent out thorugh the symp NS and impacts ____ release (high symp tone); and vascular ton/stiffness
§ Tells it to hang onto ____ (lose less)
○ In cardiac atria
§ Release a signal that causes natriuesis > casues Na ____
§ Stretch these structures > ANP > inhibits ____ from the kidney
§ Decrease ____ > decreased ANP bc decrease stretch > removing a negative signal > causes increase absorption and decreased excretion of Na+
§ ANP
Normally tells to lose Na, but have less of it > so then resorb more ____
renin Na+ renin Na+ reabsorption Na absorption eff circulating volume Na
• Stretch receptors
○ Body isn’t detecting fluid in the EC space > knows how stretched BV are > knows you have plenty of fluid and stretched > decreased ____ tone
If BV aren’t stretched and collapsed > not enough fluid in BV > upregulate ____ retention > increased sympathetic tone and twill lead to increased Na ____, and bc symp tone acts directly on kidney (hang onto salt), and innervating the JG apparatus tells it to synthesize ____
sympathetic
Na
absorption
renin
- Inc Na intake > inc ____ > inc plasma volume > increase ____ > inc ANP > inc Na+ ____ > inc stretch of JG apparatus > inhibit ____ > inhibit reabsorpiton of ____ (lose more of it)
- All stretch receptors throughout the vascular > feedback to CNS > dec ____ > dec signaling for Na reabsorption > excrete more ____
ECF volume stretch receptors excretion RAT Na symp tone Na+
Neurohormonal Regulation of Proximal Tubule Sodium Reabsorption • Antinatriuretic factors – \_\_\_\_ – \_\_\_\_ • Natriuretic factors – \_\_\_\_
* A lot of ANP > pee out more Na * If it drops > resorb more Na
angiotensin II
sympathetic nervous system
atrial natruretic peptide (ANP)
Little Evidence of Neurohormonal Regulation in ____
Also Little Evidence of Neurohormonal Regulation in ____
loop of henle
distal convuluted tubule
Also Little Evidence of Neurohormonal Regulation in Distal Convoluted Tubule
• Function of this segment does get ____ locally with high Na delivery
• That means that when patient is on a ____ (which blocks reabsorption proximal to this), the DCT’s function is ____
• Important clinically > block the LH (loop diuretics) > deliver a lot of Na+ to the DCT > amount fo Na+ reabsorption does \_\_\_\_ for it over time
up-regulated
loop diuretic
up-regulated
increase
Cortical Collection Tubule VERY Tightly Regulated
• Cortical collecting duct
– ____
– Vasopressin and Angiotensin II stimulate ____ transport
– Prostaglandins reduce ____ activity and antagonize effects of ____
• Almost all the time you have to resorb 97% > important control is in last fine tuning • Major way: Na reabsorption regulated with aldosterone ○ Stimulated by AT II acting on the adrenal gland ○ And vasopressin can stimulate ○ Prostagladins > inhibited by \_\_\_\_ and NSAID § Reduce Na+ absorption at this site § NSAIDs if taken chronically > Na \_\_\_\_ ○ [???]
aldosterone epithelial sodium channel (ENaC) ENaC AVP aspirin retention
Cellular Actions of Aldosterone
• Substance that is \_\_\_\_ ○ Only one today that is! • Aldo binds mineralocorticoid receptor is inside the cell > impacts \_\_\_\_ > increased ENAC channels \_\_\_\_ to apical membrane ○ Can block it! ○ Has an inhibitor > \_\_\_\_ § Commonly used § Helps out with disease states
cytosolic
transcription
delivered
spiranolactone
Hypovolemia
• decreased TB Na+ and water with decreased ”effective” circulating blood volume
• Causes – Renal: > \_\_\_\_—by far the most common > Osmotic diuretic (hyperglycemia) > \_\_\_\_ – Extrarenal: > \_\_\_\_: Vomiting/GI losses, diarrhea > Skin > Lungs > “\_\_\_\_” accumulations: ascites, edema, pancreatitis
• Implies too low TB Na+ and decreased eff circulating BV • Decreased EC volume > too little \_\_\_\_ in the body > where did you lose it? ○ Pee hole § Common in diuretics □ Hospitalized § Somebody has high \_\_\_\_ > cannot resorb all of it > once so much is there, it traps water, Na and Cl in the urine > osmotic diuresys § Missing hormone that resorbs Na > high Na in the urine □ Most frequent: aldosterone ® \_\_\_\_ attack on adrenal gland ® Damage to kidney from diabetes > decreases \_\_\_\_ and ultimately adolsterone ○ Most common source of volume depletion is via GI § Diarrhea (GI) □ More frequent than hypovolemia due to losses from kidney § Skin barrier □ \_\_\_\_ victims lose a lot of salt and water through skin § Hard to lose fluid through your \_\_\_\_ § "Third-space" accumulations □ Space that's not usually there, but is filled with fluid ® Abdomen isn't usually filled, but ascites ◊ Liver disease ◊ Cancer that coated intestines can cause this ® Severe \_\_\_\_ ◊ Pancreas is so inlfamed it becomes a sponge full of fluid
diuretics hypoaldosteronism GI third-space Na sugar autoimmune RAT burn lungs pancreatitis
Hypovolemia
• Clinical findings:
– ____, hypotension
– decreased Tissue turgor
– Organ ____ and shock
• Treatment:
– ____ and volume
> Salt-rich foods and water
> IV ____l
> Blood replacement for substantial hemorrhage
– Address underlying ____
> Stop diuretics, treat hyperglycemia, etc
• \_\_\_\_ > frequent way to assess volume status ○ Change position from lying to standing ○ The act of standing creates huge changes for circulatory system > veins and heart are on same level as far as gravity; then part of body goes below heart ○ If hypovolemic, cannot handle this \_\_\_\_ § Take vitals flat, and stand them up and look to see how they change □ What happens to the HR and BP (HR up or BP down) ® Changes in \_\_\_\_ is more sensitive than BP, but we measure both • Decreased skin turgor ○ Pince someone's forhead ○ Normal hydration > goes back to where it's before; but if dehydrated > stays \_\_\_\_ • Blood tests to injury to vital organs ○ Hyperperfused organs • Changes in HR when standing are signs of hypovolemia • Treatment ○ Na is the key to volume ○ Give NaCl with H2O; if resources limited > just give \_\_\_\_ rich foods and oral rehydration solutions ○ In hospital > IV > saline into the body ○ Hemorrhaging > you'll give them blood
orthostatic tachycardia hypoperfusion NaCl NaCl cause vital signs adjustment HR tented salt
