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Renal: Fluid and Electrolyte Balance (2) - (Talbot) - JCN
Talbot, part 2/2 TEST = Important
Terms in this set (71)
What are the 3 main mechanisms that act on the renal tubules themselves to alter Na reabsorption?
1) Hormones (aldosterone, ADH, ANP)
2) Sympathetic NS
3) Blood pressure and/or composition of blood flowing to kidneys
TEST: The blood pressure flowing to the kidneys dictates the ______ _____ of Na.
What is the equation that calculates this?
FILTERED LOAD = GFR x Plasma [Na]
TEST: What is the mechanism that balances out the amount of Na filtered and the amount of Na reabsorbed in the PCT when GFR is changing?
Glomerulotubular (GT) balance,
which refers to the ability of the PCT to reabsorb a CONSTANT FRACTION (%) of the filtered load (regardless of GFR)
GT balance says that as the amount of Na filtered increases due to a(n) (increased/decreased) GFR, the quantity of Na reabsorbed in the PCT (increases/decreases) proportionally.
What is this called?
What is the normal value of this?
As the amount of Na filtered increases due to an
INCREASED GFR, the quantity of Na reabsorbed in the PCT INCREASES proportionally
This is called the PCT REABSORPTION FRACTION.
- Normal = 67%
The GT balance prevents ___ ____ from being overloaded with Na+
TRUE or FALSE: The PCT reabsorption fraction of Na is always 67% (of the filtered load)
it can vary based on neural and hormonal influences
TEST: Na reabsorption in the late proximal tubule is limited by the quantity of ______ _______ remaining in the tubular fluid at that point
(Na reabsorption in the PCT is coupled with organic
nutrients like glucose, amino acids, phosphates, etc...
TEST/TEST: Normally, the flow through the PCT is (fast/slow) so that most of the organic nutrients is (reabsorbed in early PCT/left over in late PCT). Therefore, (more/less) Na is reabsorbed in the late PCT.
This is why as GFR increases, the amount of Na reabsorbed in the late PCT is (higher/lower). Explain.
the flow through the PCT is SLOW
so that most of the organic nutrients are
REABSORBED IN THE EARLY PCT. = LESS Na reabsorbed in the late PCT
(since Na reabsorption is coupled to organic nutrients).
This is why
as GFR increases, the amount of Na reabsorbed in the late PCT is HIGHER.
higher the GFR, the GREATER the FILTERED LOAD of nutrients and the LESS TIME for early PCT reabsorption.
Thus, there will be more organic nutrients at the late PCT --> more Na-coupled reabsorption!!
Besides the GFR, pressure in the ______ capillaries can also influence reabsorption of solutes in the PCT.
Since the blood in these capillaries came from the _______, it has (high/low) hydrostatic pressure and (high/low) oncotic pressure.
This promotes fluid (absorption/secretion) (from/to) the interstitial space.
Pressure in the PERITUBULAR capillaries can also influence reabsorption of solutes in the PCT.
Since the blood came from the
GLOMERULUS, it has LOW hydrostatic pressure and HIGH oncotic pressure.
This promotes fluid ABSORPTION FROM the interstitial space (after it has been reabsorbed from the tubule transcelullarly)
The rate of flow of the tubular fluid is dependent on ____.
The greater the___ the more ____ in the tubule and the faster the rate of flow past epithelial transporters....
What effect does the GFR have on GLUCOSE in the late PT?
Depends on GFR
↑ GFR →↑ volume in tubule and faster rate of flow
↑ GFR = More glucose left in late PT
TEST: Fluid from the tubule gets reabsorbed (actively/passively) into the cell via a (transcellular/paracellular) pathway.
From here, it goes into the _______ ______ spaces, where it can either flow into the ______ space and into the peritubular _______, or leak back to the tubules through the ______ ______.
Fluid from the tubule gets reabsorbed ACTIVELY into the cell via a TRANSCELLULAR pathway.
From here, it goes into the
spaces, where it can either flow:
1) into the
INTERSTITIAL space and into the peritubular
2) Leak back to the tubules through the TIGHT JUNCTIONS
At the level of the tubule, the net Na reabsorption is the difference between active ________ reabsorption and passive _________ backleak
Net Na reabsorption at tubule = Difference between active TRANSCELLULAR transport (reabsorption) and passive PARACELLULAR backleak.
TEST: The greater the GFR, the (greater/lesser) the blood volume and the (higher/lower) the oncotic pressure.
Both of these (increase/decrease) the net reabsorption of solutes from the LIS towards the capillary.
Greater the GFR →
LESS blood volume, HIGHER oncotic pressure →
INCREASE the net reabsorption of solutes from the LIS towards the capillary
TRUE or FALSE: An increase in GFR increases the filtered fraction, which subsequently increases the net reabsorption
TEST: What are the FIVE extrarenal effectors that directly affect tubular Na reabsorption?
List whether each increases or decreases the REABSORPTION of Na.
1) Insulin (INCREASE)
2) Sympathetic innervation of kidneys (INCREASE)
3) Antidiuretic hormone (INCREASE)
4) RAAS (INCREASE)
5) Atrial natiuretic peptide (DECREASE)
RECALL: Besides Na reabsorption coupled to organic nutrients, what other apical transporter at the PCT contributes to a large amount of the Na reabsorption?
Na/H exchanger (Na into the cell for hydrogen ions into the urine)
TEST: In terms of sympathetic effects on tubular Na reabsorption, the NT _______ acts on (alpha/beta) adrenergic receptors on the ______ (part of nephron) which stimulates apical _____ (transporter) and basolateral _______ activity
NorE acts on ALPHA adrenergic receptors on the PCT, which stimulates apical Na/H EXCHANGERS and basolateral Na/K ATPase activity (both of which, when stimulated, PROMOTES Na reabsorption)
TEST: What are the two MAJOR players of the RAAS that contributes directly to increased Na reabsorption? Briefly list the mechanism of each.
1) Angiotensin II
- Stimulates apical Na/H exchanger activity in the PCT, just like sympathetic stimulation
- Promotes Na/K ATPase and Na channels for Na reabsorption in the PRINCIPAL CELLS, as well as K channels for K excretion
About ___-___% of the filtered Na load is reabsorbed and regulated by _______ acting on the distal collecting duct
2-3% of filtered Na load is REABSORBED and REGULATED by ALDOSTERONE acting on the distal collecting duct
TRUE or FALSE: Angiotensin II receptors are found only on the apical membrane of the early PCT
it is found on BOTH apical AND basolateral membranes of the early PCT
Apical angiotensin II acts on the ____ transporter to promote Na reabsorption, while basolateral angiotensin II stimulates Na reabsorption by acting on _____ transporters.
Acts on Na/H exchanger on PCT
Basolateral ATII: Acts on NCC symporter on DISTAL tubule
The early PCT has a _______ response to ATII, so that at lower angiotensin II concentrations the Na/H exchanger is (inhibited/stimulated), while at higher concentrations the Na/H exchanger is (inhibited/stimulated)
BIPHASIC response to ATII:
- Low conc, STIMULATES Na/H exchanger
- High conc, INHIBITS Na/H exchanger
RECALL: Aldosterone acts by binding to a _________ receptor.
Where are these receptors found in the kidneys?
Found in the PRINCIPAL CELLS of the collecting duct system
AGAIN: List at least 2 major effects of aldosterone on the principal cells of the collecting duct system
1) Increase activity of basolateral Na/K ATPase
2) Increase activity of apical ENaC
Both of these PROMOTE Na reabsorption
_______ is in much higher concentrations in the blood than aldosterone, but it can also bind to the ______ receptor and mimic the effects of aldosterone
TEST: In aldosterone (responsive/non-responsive) cells, what enzyme can convert cortisol to a different form? What is the significance of this?
In aldosterone RESPONSIVE cells, there is 11-beta hydroxysteroid dehydrogenase (11-beta-HSD) that converts cortisol to CORTISONE.
Purpose: Since these are ALDOSTERONE-responsive cells,
cortisone can no longer bind to the MR
that aldosterone can bind to and this is one way the cell ensures a response to aldosterone (and not the overwhelming cortisol)
- Keeps MR activity SPECIFIC to aldosterone!!
What candy can cause symptoms that mimic hyperaldosteronism? Briefly explain the mechanism.
BLACK LICORICE! (contains glycyrrhizic acid)
- This blocks the action of beta-HSD,
→ too much aldosterone activity
(now both aldosterone AND cortisol is binding to MR receptors) →
excess Na retention and HTN
AGAIN: Inhibition of 11beta-HSD leads to symptoms similar to what syndrome?
TRUE or FALSE: ADH promotes both water AND Na reabsorption
How does ADH stimulate Na reabsorption? (two possible mechanisms)
ADH acts on:
1) Thick ascending limb, stimulating the APICAL NKCC transporter
2) Principal cells, stimulating ENaC channels
TEST: ADH is secreted primarily in response to what?
An increase in ECF OSMOLALITY
In addition to affecting the GFR, ___ directly affects Na+ reabsorption...this stimulates?
NHE in proximal tubule
NKCC in TALH
ENaC (phosphorylates SGK)
Na/K ATPase activity
TRUE or FALSE: Atrial Natriuretic Peptide (ANP) acts on the early (proximal/distal) tubule and the ______ to (stimulate/inhibit) Na reabsorption
Acts on the early DISTAL tubule and the INNER MEDULLARY COLLECTING DUCT (IMCD) to INHIBIT Na reabsorption
A decreased effective circulating volume will cause (more/less) ANP to be secreted. Explain.
because you want more Na reabsorption to try and retain more water
(so you don't want ANP exhibiting its effects)
TEST: What are the two main control systems that regulate the volume and osmolality of the ECF? In each system, what is the major regulator?
1) Effective circulating volume (regulating the total body content of Na) - ECV
2) Extracellular osmolality (monitoring and adjusting total body content of WATER)
Effective circulating volume is important to maintain because it is the part of the ECF that is where?
What can this impact if it isn't balanced?
Effective circulating volume (ECV) refers to the volume of the ECF that is in the ARTERIAL system
- If this isn't balance, it can affect the BLOOD PRESSURE!
TEST: ECV and ECF are typically proportional to total body content of (water/sodium)
So as sodium levels increase, ECV increases
TRUE or FALSE:
The kidneys increase Na excretion in response to an increase in Na concentrations in the ECF
The kidneys increase Na excretion in response to an increase in ECF VOLUME!!
As more fluid builds up extracellularly, the kidneys get rid of Na to drive more fluid excretion.
It wouldn't make sense for the kidneys to increase Na excretion in response to an increase in Na in the ECF because that would just draw more fluid out of the ECF, which will keep the osmolarity high (doesn't solve the problem)
AGAIN: The regulation of ECF (volume/Na concentration) is done by renal Na excretion
The regulation of ECF osmolality is done by what?
ECF VOLUME --> Maintained by Na excretion
ECF osmolality --> Maintained by WATER excretion
TEST: List whether the following will INCREASE or DECREASE in response to a DECREASE in ECF:
1) Renin levels
2) Aldosterone levels
3) ADH secretion
4) Sympathetic NS activity
5) ANP secretion
1) Renin INCREASES (for more vasoconstriction and Na retention)
2) Aldosterone INCREASES (more Na retention)
3) ADH INCREASES (retains water/Na)
4) Sym NS activity INCREASES (retains Na)
5) ANP secretion DECREASES (more Na retention)
TRUE or FALSE: Angiotensinogen is constitutively secreated from the liver and circulates in the blood as an active form
FALSE, it is circulating as the INACTIVE form
Where is renin released from?
Granular cells of the JGA
TEST: In response to a
ECV, _____ is released from the kidney that cleaves off a part of _________ to make ________ __. This has little/no physiologic activity, until it encounters _______ _____ enzyme which converts it to _______ __. This physiologically active form acts on many sites, one of which is the ______ cortex to stimulate aldosterone secretion.
DECREASED ECV -->
RENIN is released -->
cleaves part of ANGIOTENSINOGEN -->
ANGIOTENSIN I (no physiological activity) -->
ANGIOTENSIN CONVERTING ENZYME -(ACE) -->
ANGIOTENSIN II (physiologically active) -->
ADRENAL cortex to stimulate aldosterone secretion
List three stimulating factors of renin secretion.
1) Decreased systemic blood pressure
2) Decreased renal perfusion
3) Decreased NaCl in the filtrate
TEST: What cells of the kidney actually sense the decrease in systemic blood pressure?
Would you expect an increase or decrease in [NaCl] in the tubular fluid with a decrease in systemic BP, and what senses this?
Decrease in blood pressure sensed by JGA GRANULAR CELLS (baroreceptors)
DECREASE in [NaCl] with a decreased systemic BP, sensed by the MACULA DENSA of the JGA
TEST: List at least 4 actions of angiotensin II
1) Induce aldosterone secretion
2) Stimulates Na reabsorption by increasing activity of the Na/H exchanger from the PCT
3) Stimulates THIRST and ADH secretion
Angiotensin II has stronger constriction effects on the (afferent/efferent) arteriole, as well as the ______ artery
EFFERENT arteriole, as well as the RENAL artery
TEST: What is the impact of preferential efferent vasoconstriction at the glomerulus on GFR?
What about overall Na reabsorption and the total filtered load of Na?
The effect on GFR depends on the CONCENTRATON of ATII
- At high conc, GFR increases
- At low conc, GFR decreases
OVERALL: ATII increases GFR -->
increases filtered load of Na -->
increased Na reabsorption (even though more Na filtered means more Na in the filtrate, there are multiple sites of reabsorption so there is still a NET reabsorption of Na)
Besides increasing the GFR and filtered load, how else does angiotensin II enhance salt and water reabsorption?
By VASOCONSTRICTION of the VASA RECTA, which SLOWS down flow to enhance reabsorption along the nephron
When does sympathetic NS activity become more of a main player in maintaining ECV?
When there are LARGE changes in the volume or Na content (such as in traumatic bleeding)
AGAIN: List 3 effects of the sympathetic NS on ECV
1) Decreases renal blood flow and GFR
2) Increases Na/H exchanger in PCT
3) Stimulate renin secretion
When does ADH become more of a main player in maintaining ECV?
When there is an excessive volume loss (by 5-10%)
TEST: As ECV changes, so does the _______ of the posterior pituitary to stimuli inducing ____ secretion. When there is volume depletion, there is a (lesser/greater) amount of ADH secretion with (small/large) increases in plasma osmolality
SENSITIVITY of the posterior pituitary to stimuli inducing ADH secretion
- During volume depletion, there is a GREATER amount of ADH secretion with SMALL increases in plasma osmolality!!
TEST: Increasing GFR and filtered load of Na will cause (more/less) ANP to be secreted. Explain.
MORE ANP, because increased filtered load leads to not only increased Na reabsorption, but also MORE Na REMAINING in the filtrate.
You want ANP to excrete this EXTRA Na in the urine (or at least those that couldn't be reabsorbed)
AGAIN/TEST: A decreased ECV will (stimulate/inhibit) ANP secretion. Explain.
INHIBIT ANP, because this allows more Na retention and more fluid retention.
Also, ANP normally INHIBITS aldosterone, and with a depletion of ECV you want MORE aldosterone to retain more Na!!
AGAIN/TEST: List what the "sensor" is for regulating:
1) ECF volume
2) ECF osmolality
What is each one maintained by?
1) ECF volume sensor = BARORECEPTORS (sensing changes in BP) --> maintained by SODIUM excretion
2) ECF osmolality sensor - HYPOTHALAMIC OSMORECEPTORS -->
maintained by WATER excretion (AVP secretion)
Where are the major hypothalamic osmoreceptors?
In the OVLT and SFO in the hypothalamus
OVLT = Organum Vasculosum of the lamina terminalis
SFO = Subfornical organ
TEST: ADH secretion is ultimately dependent on what?
Under normal conditions, when does the hypothalamus secrete ADH/AVP?
Under normal conditions, only when the plasma osmolality exceeds 280 mOsm does AVP get secreted.
TEST: An increase in plasma osmolality will result in (more/less) AVP secretion from the posterior pituitary
MORE AVP secretion!
TRUE or FALSE: Osmoreceptors in the hypothalamus all induce ADH/AVP secretion when stimulated
FALSE, some osmoreceptors do that but others induce THIRST and SODIUM APPETITE
TEST: How is potassium balanced in acute versus chronic changes of ECF potassium levels?
ACUTE: Shifting K into and out of the cellular compartment
CHRONIC: Reabsorbing and secreting K from the kidney
RECALL: Whether potassium is reabsorbed or secreted in the DISTAL nephron is dependent on what?
TEST/TEST: With a low potassium diet, there is net (secretion/reabsorption) in the ICT/CCT mediated by _____ transporter in the (principal/intercalated) cells
LOW K diet =
net REABSORPTION in the ICT/CCT mediated by the H/K exchanger in the INTERCALATED cells
TEST/TEST: What channels in the collecting duct are responsible for secreting K in a high potassium diet, and in what cells are these channels found?
RomK channels (apical K channels)
- Found in PRINCIPAL cells
Besides the RomK channels, what is another transporter that helps potassium SECRETION in the principal cells?
KCC co-transporter (K and Cl)
TEST: Besides the levels of potassium in the filtrate, what is another major factor that can influence the H/K exchanger on the principal cell membranes?
- As ECF pH DECREASES, → ↑ H in the blood,
the H/K exchanger will be STIMULATED to drive more H efflux in exchange for K influx (to the cell)
Epinephrine stimulates K+ (secretion/uptake) while aldosterone stimulates K+ (secretion/uptake)
Epinephrine: K+ UPTAKE
Aldosterone: K+ SECRETION
TRUE or FALSE: An increase in the activity of the Na/K ATPase in the principal cell basolateral membrane can lead to an INCREASED K+ SECRETION
As the Na/K ATPase pumps K into the cell, it will travel back out of the cell and into the tubule via RomK apical channels!
RECALL: Amiloride (increases/decreases) secretion of K into the tubule. Explain.
DECREASES secretion of K into the tubule, because Amiloride inhibits the ENaC which keeps Na in the tubule (K-sparing diuretic). This prevents the negative lumenal potential, which is what normally drives K and H secretion!
TEST: As the flow rate past the principal cells is INCREASED, it (inhibits/promotes) secretion of potassium into the tubule. Why?
PROMOTES secretion, because fast flow rate keeps the potassium INSIDE the cell,
which will maintain a HIGH APICAL GRADIENT (high inside, low in tubule) which PROMOTES SECRETION!!
TEST: As the [Na] increases in the tubular fluid adjacent to the principal cells, there will be (more/less) potassium secretion into the tubule. Why?
MORE potassium secretion, because more Na in the lumen means more REABSORPTION which keeps the lumenal potential NEGATIVE, driving MORE potassium SECRETION
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