JH renal final index cards exam I(1) Flashcards
1
Q
What is the osmotic coefficient?
A
function of particle interactions in solutions, which decreases the effective #s of osmoles
2
Q
What are effective osmoles?
A
impermeable solutes that can sustain osmosis
3
Q
What are ineffective osmoles?
A
permeable solutes that cannot sustain osmosis
4
Q
reflection coefficient = 100%
A
particle is reflected back 100% of the time; IMPERMEABLE
5
Q
reflection coefficient = 0
A
particle is as permeable as water
6
Q
Describe the Donnan Effect
A
behavior of charged particles near a semi-permeable membrane that sometimes fail to distribute evenly across the two sides of the membrane. The usual cause is the presence of a different charged substance that is unable to pass through the membrane and thus creates an uneven electrical charge. Ex: the large anionic proteins in blood plasma are not permeable to capillary walls. Because small cations are attracted, but are not bound to the proteins, small anions will cross capillary walls away from the anionic proteins more readily than small cations.
7
Q
What is the 60-40-20 rule?
A
Total Body Water (TBW) = 60% of body weight
ICFV = 40% of body weight
ECFV = 20% of body weight
ISFV = 15% of body weight (or 3/4 of ECFV)
PV = 5% of body weight (or 1/4 of ECFV)
8
Q
Two reasons that account for the high water permeability of cell membranes
A
1) lipid bilayer has a small, but not negligible water permeability. Since whole cell surface is available for the transport, there is significant water transport
2) presence of aquaporins, which increase the inherent water property of the cells
9
Q
What increases the driving force for water entry via Donnan effect in the cell?
A
1) presence of high intracellular concentrations of macromolecules and metabolic intermediates
2) membrane is impermeable to these molecules, but permeable to water –> results in a significant driving force for osmotic water entry
10
Q
What is the active process that counters the tendency of cells to swell? What is the net result on ICF and ECF?
A
Na/K ATPase - net efflux of Na from the cell in order to maintain cell volume; net result: effective osmolality in ICF becomes equal to that in ECF
11
Q
T/F @ steady state ICF osmolality = ECF osmolality
A
True.
12
Q
T/F @ steady state Plasma osmolality = ISF osmolality
A
False. Plasma is slightly > than ISF due to the presence of plasma proteins
13
Q
What is the main determinant of plasma osmolality
A
Na
14
Q
What are the effective osmoles maintained in the ECF and ICF?
A
ECF: Na and associated anions
ICF: K and associated anions
15
Q
T/F Plasma proteins exert a Donnan Effect
A
True. They’re negatively charged and can attract counterions.
16
Q
Why is the concentrations of Cl- and HCO3- higher in the ISF?
A
Donnan Effect. Plasma proteins attract small cations, therefore the concentration of the small cations is 5% higher in the aqueous phase than in the interstitial fluid, and the concentration of small Anions is 5% lower.
17
Q
How do you figure out the effective osmolality?
A
2 * [Na]
18
Q
How do you figure out total plasma osmolality?
A
2[Na] + [Glucose]/18 + [BUN]/2.8
19
Q
What is the osmolar gap? What does it mean if it’s increased?
A
Osmolar gap = measured osmolality - calculated osmolality. An increased osmolar gap indicates the presence of a toxin that contributes to the osmolality
20
Q
What determines the size of any given compartment (ie ECFV, ICFV, etc)
A
of osmotically active particles present
21
Q
What accounts for the decrease in Hct after eating a salt-laden meal?
A
1) Since Na is restricted to the ECF, this draws fluid out of the cells until ECF=ICF osmolality (but the total number of osmoles is higher in the ECF)
2) ECFV is increased, and this extra fluid is redistributed between the ISFV and plasma in a 3:1 ratio since the endothelium is freely permeable to Na.
3) Hct decreases because a) plasma volume is increased and 2) increased osmolality of the plasma (due to ingestion of Na) results in cell shrinkage
22
Q
What are the effective osmoles (main determinant of oncotic pressure) in the plasma?
A
albumin
23
Q
What are the two opposing forces on fluid movement in the capillaries?
A
hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in)
24
Q
What is the effective oncotic pressure dependent on?
A
reflection coefficient of the capillary membrane for protein.
25
What is the net ultrafiltration pressure (PUF)?
Sum of all hydrostatic and effective oncotic pressures
26
If PUF is +, this means
fluid moves out of the capillary (ultrafiltration)
27
if PUF is -, this means
fluid moves into the capillary (absorption)
28
What is the filtration coefficient (Kf) a measure of?
measure of water permeability
29
What is the reflection coefficient (s) a measure of?
measure of protein permeability
30
What modifies Kf and s?
vasoactive hormones and cytokines
31
How does PUF change throughout the length of a capillary? How does this affect fluid movement?
It goes from + --> - such that most of the ultrafiltrate produced in the initial portion of the capillary gets reabsorbed at the venous end.
32
What two forces contribute to the autoregulation of plasma (and thus blood) volume?
hydrostatic pressure (promotes fluid exit) and oncotic pressure (draws fluid in): increases/decreases in capillary hydrostatic pressures will cause fluid to be drawn in or seep out from the capillaries
33
What are 4 things that can contribute to edema?
increase in venous pressure
reduced oncotic pressure (fluids seeps out of capillary)
changes in capillary wall permeability (endothelial injury/inflammation)
obstruction of lymphatics (tumors/parasites)
34
What happens to patients with hypoalbuminemia?
Edema, since there is reduced oncotic pressure, fluid will seep out of the capillary and into the interstitum
35
How does inflammation/endothelial cell injury change Kf and s?
Increase Kf (increase water permeability)
decrease s (capillary becomes more permeable to proteins)
36
What are crystalloids? Examples?
Na and glucose
37
What is the effect of administering a hypertonic saline solution?
expand ECFV, reduce ICFV
38
What is the effect of administering a hypotonic saline solution?
expand ECFV and ICFV
39
What is the effect of administering a normal saline solution?
ECFV increases, but no change in ICFV (since isotonic saline was used, there was no change in osmolality and therefore no water shift between ICFV and ECFV)
40
What is the effect of administering glucose?
hemolysis
41
What is the effect of administering pure water?
hemolysis
42
What are colloids? Examples?
plasma expanders (ie albumin, gelatins, dextrans, starches)
43
What is ORT? What is it made of?
oral rehydration therapy: Na w. glucose in a slightly hypotonic solution (net: expand ECFV and ICFV)
44
What is the main energy consumer in the kidney?
active reabsorption of the ultrafiltrate, specifically Na (via Na/K ATPase)
45
T/F O2 consumption determines renal blood flow
False. In the kindey, blood flow drives O2 consumption (because more blood flow = more active reabsorption = more O2 consumption)
46
Why is the kidney an ideal site to monitor changes in arterial O2 content?
Unlike other organs, renal tissue pO2 is independent of blood flow and is thus proportional to arterial pO2 content. Therefore, RBC production is regulated by the kidneys
47
How is the renal vasculature arranged in terms of capillary beds and arterioles?
afferent arteriole --> glomeruli --> efferent arteriole --> peritubular capillaries
48
Where is blood flow the highest in the kidneys? Lowest? Why is this important?
Blood flow is highest in the superficial cortex. The medulla has no direct arterial blood supply, but it does receive blood from juxtamedullary glomeruli thrrough the peritubular network in the outer medulla and vasa recta in the inner medulla. Blood flow in outer medulla is 6-10% of cortical flow, and only 1/10 of that is transmitted to the vasa recta. The low blood flow in medulla and the coutnercurrent arrangement of flow in the vasa recta is critical for conserving the medullary hyperosmolality required for concentration of urine.
49
What are the forces that govern ultrafiltration?
ultrafiltration is drive by hydrostatic pressure in glomerular capillary (PGC), opposed by hydrostatic pressure in bowman's space (PBS), and the oncotic pressure in the glomerular capillary (pGC)
50
What determines GFR?
hydrostatic pressure in glomerular capillary (PGC)
hydrostatic pressure in bowman's space (PBS)
oncotic pressure in the glomerular capillary (pGC)
permeability of the membrane for small molecules (filtration coefficient Kf)
51
What is the equation for GFR?
GFR = Kf [(PGC-PBS)-pGC]
pBS is not included because the reflection coefficient for glomerular filtration barrier for protein is ~1 and thus fluid in BS under physiological conditions is practically protein free
52
Why is GFR so high in the kidneys?
It has a high Kf (filtration coefficient)
53
Why is Kf so high in the kidneys?
Because glomerular capillaries have large fenestrations that allow the passage of small molecules (and therefore a much larger fraction of the total surface area is available for the passage of H2O/small molecules)
54
How does one calculate filtration fraction (FF)?
FF = GFR/RPF (renal plasma flow)
55
How does RBF and GFR change with changes in afferent tone?
Since PGC is the main determinant of GFR: RBF, GFR, and FF changes in parallel with changes in afferent tone (ie afferent constriction --> decrease RBF, GFR, and FF)
56
How does RBF and GFR change with changes in efferent tone?
Since PGC is the main determinant of GFR, GFR and FF changes in opposite directions with changes in efferent tone (ie efferent constriction --> increase GFR and FF), but RBF will change in parallel (efferent constriction --> decrease RBF)
57
How does constriction of the efferent arteriole affect RBF/GFR/fluid reabsorption?
Increase GFR, decrease RBF, increase fluid reabsorption from the tubules by decreasing hydrostatic pressure and increasing oncotic pressure in the peritubular capillaries
58
What about the glomerulus prevents albumin and Igs from being filtered?
Filtration barrier rejects Igs based on their large size. Albumin is rejected based on charge (the filtration barrier carries a significant negative surface charge, which restricts the passage of negatively charged proteins)
59
How does proteinuria occur?
damage to the filtration barrier
60
What is minimal change nephropathy?
kidney disease --> proteinuria
61
What is renal clearance?
virtual volume of plasma completely cleared from a substance (s) per unit time
62
How do you calculate renal clearance?
Clearance = (Us x V)/(PaS)
Us = conc. of urine in substance
V = urine flow rate
PaS = concentration of substance in arterial plasma
63
How do you calculate GFR using inulin?
GFR = (Uinulin x V)/PaInulin
U = conc. of inulin in urine
V = urine flow rate
Pa = concentration of inulin in arterial plasma
64
What is PAH and what is it used to measure?
PAH is used to measure RPF. It is actively secreted into tubular fluid from the peritubular capillaries and is almost completely cleared from the blood after a single passage (renal concentration ~0)
65
What is Inulin and what is it used to measure?
Inulin is used to measure GFR. It is freely filtered by the glomerulus and is neither reabsorbed nor secreted by the tubules.
66
What is the endogenous marker of GFR?
creatinine, because it is produced in the body at a relatively constant rate and is eliminated primarily by glomerular filtration
67
What does a high plasma creatinine level indicate?
low GFR (they're inversely related)
68
At what point does autoregulation of RBF and GFR breakdown?
180mmHg
69
How does autoregulation affect RBF in the kidneys?
RBF remains relatively constant over a wide range of mean arterial pressure (~80-180)
70
Where does autoregulation in the kidneys occur?
afferent arteriole, which stabilizes glomerular capillary pressure (the main determinant of GFR)
71
How is autoregulation achieved? (2 mxns)
1) myogenic response
2) tubuloglomerular feedback (TGF)
72
What is the myogenic response?
when the afferent arteriole contracts in response to an increase in blood pressure (stretching of the vessel)
73
What is TGF?
tubuloglomerular feedback (TGF) - an increase in arterial pressure temporarily increases GFR, and thus more salt and water is delivered to the tubules. In response to an increased NaCl load, the macula densa sends a humoral signal to the neighboring afferent arteriole to contract and thus decrease GFR.
74
What is the signal that activates TGF?
increased NaCl load detected by the macula densa
75
What is the TGF response?
macula densa sends a humoral signal to the neighboring afferent arteriole to CONTRACT, thereby decreasing GFR
76
What is the effect of a vasoconstrictive hormone?
reabsorption
77
What is the effect of a vasocondilator hormone?
inhibit reabsorption
78
What are the 4 things that induce renin RELEASE?
1) decreased stretch of granular cells in afferent arteriole
2) decreased Na load to macula densa
3) increased sympathetic tone in response to reduced systemic BP
4) AII
79
What is the negative feedback loop on renin release?
Angiotensin II
80
What is the action of AII?
preserve GFR by counteracting the direct effects of reduced perfusion
81
What are some vasoconstrictors that act on the afferent arteriole?
sympathetic nervous system, adenosine
82
What is the effect of a vasoconstrictor acting on the afferent arteriole?
decrease RBF, GFR, and FF
83
What are some vasoconstrictors that act on the efferent arteriole?
angiotensin II, endothelin, ADH
84
What is the effect of a vasoconstrictor acting on the efferent arteriole?
decrease RBF, but increase GFR and FF (filtering more, but since protein doesn't get filtered, oncotic pressure is increased in the blood vessels, which pulls water out of the tubules)
85
What are some vasodilators that act on the afferent arteriole?
dopamine, ANP
86
What is the effect of a vasodilator on the afferent arteriole?
Increase RBF, GFR, FF
87
What are some global vasodilators?
prostaglandins, NOs, kinins
88
What are unique about Kinins?
they are degraded by the same enzyme (ACE) that generates Angiotensin II. Thus, AII and kinins have opposing effects
89
What is the effect of NSAIDs in a person with congestive heart failure?
NSAIDs block prostglandins production (which is a normal vasodilator). NSAIDs normally have no significant effects on GFR in healthy patients, but in a person with congestive heart failure (which is already hypertensive), this can cause renal insufficiency.
90
What is renal insufficiency?
Renal failure - condition in which the kidneys fail to adequately filter waste products from the blood
91
What is the effect on ACE inhibitors on blood pressure?
It is a hypertensive drug (ACE normally breaks down Kinins, which are vasodilators. If ACE is blocked, then you get unapposed effects of AII, which is an efferent constrictor)
92
What are the two mediators of TGF?
endothelin and NO.
Endothelin is potent vasoconstrictor on the efferent arteriole.
NO is a vasodilator
think "TEN"
93
What is the effect of ANP on RBF and GFR?
ANP is a vasodilator and acts on the afferent arteriole. Therefore RBF and GFR will increase
94
What is the effect of Sympathetic Nervous System on RBF and GFR?
SNS is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease
95
What is the effect of Angiotensin II on RBF and GFR?
Angiotensin II is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase
96
What is the effect of dopamine on RBF and GFR?
Adenosine is a vasodilator of the afferent arteriole. Therefore RBF and GFR will increase
97
What is the effect of endothelin on RBF and GFR?
Endothelin is a vasoconstrictor of the efferent arteriole. Therefore RBF will decrease, but GFR will increase
98
What is the effect of Adenosine on RBF and GFR?
Adenosine is a vasoconstrictor of the afferent arteriole. Therefore RBF and GFR will decrease
99
Give an example of a vasoconstrictor that is buffered by the simultaneous release of vasodilators.
Increase in AII/NE (vasoconstrictors) promote the release of prostaglandins (vasodilators)
100
What is the effect of ADH on RBF and GFR?
ADH is a vasoconstrictor of the efferent arteriole. But because it selectively targets a tiny population of nephrons, it has no significant effects on total RBF and GFR
101
How does RBF and GFR change with pregnancy?
they both increase
102
How does RBF and GFR change with a (chronic) protein diet?
they both increase, but due to certain a.a. that serve as substrates for NO production. Increased NO --> vasodilation --> increased glomerular hypertension and acceleration of renal disease
103
What are the two main purposes of the kidney?
1) Eliminate metabolic end products (urea, creatinine) via ultrafiltration
2) keep volume/electrolyte composition of ECF/ICF constant
104
What is the main energy consumer in the kidney?
reabsorption of Na by the tubules (Na/K ATPase, ENaC)
105
Why is the macula densa stragetically placed at the beginning of the DCT?
the DCT has limited reabsorption capacity, and therefore the MD is located at the beginning of the DCT to ensure a constant Na load via the tubuloglomerular feedback mechanism
106
How is the PCT/LOH different than the DCT in terms of function?
the PCT/LOH function more along the lines of Na reabsoprtion (energetically favorable) whereas the DCT has limited reabsorption capacity and functions to establish the steep concentration gradients (energetically demanding)
107
What are the two main transport mechanisms that occur in the proximal tubules?
1) reabsorption of 2/3 of the filtered water and Na, 80% of bicarbonate and phopshate, and all nutrients.
2) Secretion of xenobiotics
108
Where and how is HCO3 primarily reabsorbed?
HCO3 is primarily reabsorbed in the PT, and this process is indirect.
1) PT secretes H+, which combines with filtered HCO3- to form carbonic acid (catalyzed by carbonic anhydrase), which dissociates into CO2 and H2O and is reabsorbed into the PCT cells
2) In the cell, CO2 and H2O are converted back to carbonic acid by an intracellular carbonic anhydrase and H2CO3 spontaenously dissociates into H+ and HCO3-.
3) HCO3- is exported to the blood by an Na/HCO3 on the basolateral side, while the H+ is secreted into the tubular fluid by the Na/H exchanger for another round
109
What is acetazolamide?
It is a carbonic anhydrase inhibitor, and therefore it increases Na excretion (and is therefore, a potent diuretic)
110
What influences the solvent drag in the PCT?
1) reabsorption of Na, glucose, lactate, and inorganic phosphates increases the osmolality of the interstitial fluid (while reducing the osmolality of the tubular fluid).
2) Due to preferential reabsorption of Na with HCO3-, phosphates, and other ions, the concentration of Cl- in the tubular fluid gradually increases towards the later segments of Cl-, and this differene allows Cl- to diffuse through the paracellular pathway, which creates a luminal (+) voltage
111
What is non-ionic diffusion?
passive movement of lipid soluble weak acid and bases in their undissociated forms through the cell membrane.
112
How are is Cl- reabsorbed in the PCT?
Transport of Cl- is mediated by the Cl-/A- and Na/H exchangers.
1) Uphill movement of Cl- into the cell is driven by the higher concentrations of organic anions (formate) inside the cell than in the tubular fluid.
2) Secretion of H+ neutralizes the secreted organic anions, the neutralized organic acid becomes lipophilic and diffuses into the cell
3) resulting cellular alkalination (due to the H+ secretion) aids the dissociation of organic acid into an anion and H+ inside the cell.
4) Na is then transported into the blood via basolateral Na/K ATPase, while Cl- exits via basolateral K/Cl cotransporter.
113
What is the purpose of the Na/K ATPase?
to keep the intracellular concentrations of Na low so that Na can be reabsorbed (energetically favorable movement of ions down its concentration gradient)
114
What are the advantages/disadvantages of the transport events in the PCT?
Pro: the PCT is relatively leaky and therefore large amounts of Na/H2O are reabsorbed with relatively little energy expenditure
Cons: since the PCT is so permeable, it is prone to back-leak
Net: since the PCT is so leaky, its rate of transport is so high that the rate of uptake into the peritubular capillary can become limiting
115
What are two ways that salt/water transport is regulated in the PT?
1) glomerulotubular balance
2) Hormonal and neural regulation (AII, dopamine, ANP)
116
What is glomerulotubular balance?
balance between reabsorption of solutes in the proximal renal tubules and glomerular filtration, which must be as constant as possible. The PT always reabsorbs a constant fraction of the filtered load. The purpose is to stabilize the rate at which Na and water is delivered to the LOH and ultimately to the distal nephron, which has limited transport capacity. Balance is maintained by neural, hormonal, and other mechanisms
117
What is the net effect of the GT feedback under the influence of AII or endothelin?
AII/endothelin is present during low ECFV, and they act to constrict the efferent arteriole. This results in
1) increased hydrostatic pressure in the glomerulus bed, which enhances filtration of a protein-free filtrate and thus leads to increased oncotic pressure entering the peritubular capillaries.
2) increased oncotic pressure + decreased hydrostatic pressure in the peritubular bed results in an enhanced reabsorption of fluid from the tubular fluid/interstitium, thereby reducing the likelihood of backflow in the PCT
118
Since the PCT is so leaky, how is backflow minimized?
AII/endothelin constricts the efferent arteriole under low ECFV. This results in
1) increased hydrostatic pressure in the glomerulus bed, which enhances filtration of a protein-free filtrate and thus leads to increased oncotic pressure entering the peritubular capillaries.
2) increased oncotic pressure + decreased hydrostatic pressure in the peritubular bed (due to constriction of efferent arteriole) results in an enhanced reabsorption of fluid from the tubular fluid/interstitium, thereby reducing the likelihood of backflow in the PCT
119
What are the main hormones that stimulate Na reabsorption in the PCT? What transporter do they act on?
Angiotensin II (but also catecholamines/sympathetic) via the Na/H exchanger
120
Which receptors sense and respond to ECFV depletion?
low-pressure receptors in the atria/large veins
121
What happens under severe ECFV depletion?
increased renal sympathetic activity -> increased secretion of catecholamines -> increased Na/H activity to stimulate water and salt reabsorption
122
What are the two main inhibitors of Na reabsorption in the PCT?
dopamine and ANP
123
How are xenobiotics normally eliminated?
they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF.
124
How are xenobiotics related to PAH?
they are actively taken up through the PCT basolateral membrane via high affinity transporters and then secreted into the tubular fluid. Thus, they are cleared at a rate comparable to RBF. This is the basis of PAH clearance and is used to measure RBF
125
How are filtered proteins eliminated from the tubular fluid?
1) oligopeptides are degraded by ectopeptidases in the brush border
2) larger proteins are taken up by the cell via receptor mediated endocytosis and degraded intracellularly.
--> amino acids are returned to blood through the basolateral membrane
126
Where is water reabsorbed in the LOH?
descending limb
127
Where is Na reabsorbed in the LOH?
thick ascending limb (TALH)
128
T/F the acending limb of LOH is water permeable
False. It is water impermeable
129
Why does the tubular fluid become hypoosmotic as it moves through the LOH?
The descending limb is where most water is absorbed, but the TALH is where it is water impermeable, and therefore water cannot follow the reabsorbed salt in the TALH. Thus:
-> tubular fluid becomes hypo-osmotic
-> the medullary interstitium becomes hyperosmotic due to accumulation of reabsorbed salt)
130
What is the effect of a hyperosmotic medullary environment?
drives the reabsorption of water from the thin ascending limb and from the collecting ducts if ADH is present
131
What is the main route of entry for Na in the TALH?
Na/K/2Cl cotransporter
132
How are cations (Na/Mg/Ca) reabsorbed in the TALH? What facilitates this?
Na/K/2Cl cotransporter is an electroneutral transporter, but it facilitates reabsorption of Na. K is returned to the tubular lumen, which generates a lumen (+) voltage. This drives the reabsorption of cations through the paracellular pathway.
133
What do loop diuretics act on?
Na/K/2Cl cotransporter; prevents the reabsorption of Na, resulting in an ablation of the countercurrent multiplier gradient, and can result in isoosmotic urine production (because there is no concentration capability of the kidneys)
134
What happens with chronic use of loop diuretics?
Chronic use prevents the reabsorption of Na, resulting
1) increases Na load arriving to the DT, which results in an upregulation of the NaCl cotransporters in the DT.
2) an ablation of the countercurrent multiplier gradient, and can result in isoosmotic urine production (because there is no concentration capability of the kidneys)
135
How is the TAL auto-regulated? Whats the purpose this autoregulation?
TAL increases the rate of Na reabsorption with an increase in salt delivery, and its purpose is to buffer changes in salt load arriving to the distal tubule (which has limited transport capacity)
136
What is the purpose of the Ca sensor in the TAL?
The TAL reabsorbs significant amounts of Ca and Mg without water into the medullary interstitium. These cations have limited solubility and are prone to precipitate at high concentrations. When activated, this sensor inhibits the apical K channels in the TAL, which eliminates the (+) luminal voltage that drives the paracellular reabsorption of Ca.
137
What does the Ca sensor in the TAL act on?
K channels (allows K to leave the cell into the lumen)
138
What type of feedback is the MD involved in?
Tubuloglomerular feedback. The MD senses the increased NaCl load arriving to the distal tubule, and inihits the TGF to ensure that the downstream segments are not overwhelmed by a Na load
139
What are two process that the MD is involved in?
TGF and Renin secretion
140
Which two parts of the nephron is impermeable to water?
TALH and DCT
141
How is Na reabsorbed in the DCT?
through a NaCl cotransporter
142
What do thiazides do? What happens with chronic thiazide use?
They block the NaCl cotransporter in the DCT, which results in decreased Na reabsorption; chronic use leads to salt wasting.
143
What transporter is responsible for Na transport in the CD?
ENaC - highly selective for Na
144
What drives the ENaC?
low intracellular Na concentration (due to basolateral Na/K/ATPase) and negative potential inside of cell
145
Which two ions are coupled in the CD?
Na reabsorption (via ENaC) and K secretion (via K channels)
146
What are K sparing diuretics? What do they act on?
blocks ENaC or blocks the effects of aldosterone, therefore K excretion is reduced due to the coupling of Na reabsorption to K secretion in the CD
147
What are the effects of aldosterone?
Increases Na reabsorption by:
1) upregulates ENaC in CD
2) upregulating NaCl cotransporter in the DT
148
What is the effect of ADH?
It caues the insertion of AQP2 water channels in the apical side of the priniciple cells, which allows water to be reabsorbed.
149
What antagonizes ADH?
ANP, prostaglandins, divalent cations (Ca/Mg)
150
Under normal conditions, how much of filtered urea is excreted?
~70%
151
Under water deprivation, how much of filtered urea is excreted?
~15%
152
What happens to urea transport in the nephron under severe ECFV depletion? What hormone regulates this?
ADH increases urea permeability of the inner medullary CD (which is normally impermeable to urea), which allows urea to be reabsorbed. This is to maximize water conservation during dehydration (since water follows urea reabsorption): if the CD is impermeable to urea but permeable to water, urea excretion would require the excretion of additional water.
153
Under normal conditions, how is urea transported in the nephron?
50% is reabosrbed in the PCT by paracellular diffusion and solvent drag, and about 20% is reabsorbed in the thin limb of LOH. The rest of the nephron has low urea permeability.
154
Why is acute cell volume regulation limited to a few organs?
Extrusion or uptake of electrolytes in every tissue would dramatically change the electrolyte composition of the ECF
155
Which two organs can regulate their cell volume during osmotic challenge?
brain and intestines
156
What limits the brain from responding to an osmotic challenge? What does it do in response?
It's limited by changes in excitability that result from transmembrane ion fluxes. The brain cells eventually adapt to an abnormal osmolality by regulating the conc. of small organic molecules that do not disturb cell function (ie taurine, sorbitol, etc)
157
What is the solute that significantly affects tonicity?
Na
158
What is principle ion in osmoregulation? How is it regulated?
Na, by regulating the Na concentration (via adjusting the amount of water)
159
How is an abnormal Na plasma corrected?
by adjusting the amount of water (because it changes much more readily than the amount of Na)
160
What is hyponatremia an indication of?
water excess/overhydration (NOT a Na problem)
161
What is hypernatremia an indication of?
water deficit/dehydration (NOT a Na problem)
162
Why is hyponatremia associated with oligoura, even though the expected response would be polyuria?
because the kidneys ability to excrete H2O is compromised. Therefore oligouria is the cause, not consequence, of hyponatremia
163
What is the expected urine output in response to hypernatremia due to dehydration?
oligouria
164
What is the expected urine output in response to hypernatremia that's caused by a renal concentrating defect?
polyuria
165
Oligouria
low urine volume
166
Polyuria
high urine volume
167
What is insensible water loss?
water loss that you can't measure (water lost via evaporation from the lungs and skin)
168
Which receptors sense and response to changes in osmolality? Where are they located?
osmoreceptors - located in the CNS in an area where it is "leaky. This allows neurons to sense a change in plasma Na concentration (since these neurons are sensitive to changes in cell volume)
169
Under normal conditions, what governs water balance?
ADH secretion and consequently water secretion
170
Under conditions of excessive water loss (ie hot weather, exercise), what governs water balance?
The kidneys ability to conserve water becomes exhausted (it can only conserve up to 1L/day via ADH) and therefore water balance depends almost exclusively on the thirst mechanism
171
Is the threshold for ADH secretion lower or higher than the threshold for thirst response?
lower. Thus, under normal conditions, water balance is maintained by regulating ADH secretion and consequently water secretion
172
How is water balance regulated?
behavioral response of thirst determines water intake
ADH regulates renal water excretion by altering permeability of the collecting duct
173
What role do cold receptors in the mouth and stretch receptors in the esophagus and stomch play in water regulation?
they temporarily inhibit the sensation of thirst to prevent overhydration. This is because the osmoreceptors regulation of water intake is insufficient.
174
What is the primary function of ADH and thirst?
prevent changes in plasma osmolality, and therefore cell volume
175
Under normal conditions, what is the #1 priority of volumetric control?
under normal conditions, regulation of cell volume takes precedence over regulation of ECFV. But with extreme disturbances of ECFV (ie hypovolemic/hemorrhagic shock, the body tolerates changes in plasma osmolality to prevent circulatory collapse.
176
What is a potent inducer of thirst?
AII
177
How can diluted urine be produced? How does this affect the medulla? Where is this normally occuring? What is this process called?
reabsorbing solute without H2O generates dilute urine, but generates a hyperosmotic medulla. This occurs in the TALH, and this is called the "single effect" of urinary concentration
178
In what parts of the nephron contributes to the formation of dilute urine?
ascending limb of LOH, DT, and in the absence of ADH, the CD (since all of these areas are water-impermeable)
180
What is the "single effect" of urinary concentration?
deposition of Na into the interstitium (without water)
181
What does the countercurrent multiplier result in?
at any one level in the medulla, there is only a modest difference in the salt concentration of the tubular fluid in the ascending limb of LH and the interstitium, but the counterflow arrangement generates a large axial (corticopapillary) salt gradient
182
How does the medullary maintain its hyperosmotic environment?
blood flow through the vasa recta in the medulla at a sluggish rate and in opposite directions.
183
What is "medullary washout"?
an increased medullary blood flow results in an incomplete equilibration between the ascending and descending blood, and thus the vasa recta carries away more salt from the medulla than what the TAL can produce
184
What are some things that can reduce the kidney's concentrating ability?
1) increased medullary blood flow
2) increased luminal flow
3) loop diuretics (block salt reabsorption in TALH, thereby abolishing the corticopapillary salt gradient)
all three reduces the time available for equilibration with the interstitium, which increase tubular flow, and consequently diminishes renal concentrating ability
185
In the presence of ADH, the bulk of water reabsorption occurs in the cortical CD. Why is that?
to maintain the medullary osmotic gradient
186
What is the effect of ADH on the nephron?
1) increase H2O permeability along the entire length of the CD.
2) increase urea permeability in the terminal portion of the CD. NET: corticopapillary urea gradient established
187
What is the rapid vs chronic effect of ADH?
rapid: increase AQP2 transcription
chronic: increase AQP2 transcription
188
Where is the bulk of water reabsorption in the CD occur?
cortical collecting duct
189
How is urea permeability changed under the influence of ADH? Whats the purpose of the change?
ADH increases urea permeability of the inner medullary CD (which is normally impermeable to urea), which allows urea to be reabsorbed. Urea deposited into the medullary interstitium is taken up by the thin limbs of LH, which has constitutively high urea permeability. During anti-diuresis, tubular fluid exiting the LH contains more urea than what was filtered. The subsequent segments up to the point of the terminally medullary CD are impermeable to urea, and due to water reabsorption under the influence of ADH, urea concentration increases in the cortical and outer medullary.
190
What two compounds undergo the counter-current multiplier process?
Na and urea
191
What happens to urea under chronically high levels of ADH?
rate of urea excretion is reduced, and therefore urea concentration in the blood increases. Since urea is not an effective osmole, the increased blood urea does not change ICFV, and the accumulated urea can be excreted upon rehydration?
192
Is urea an effective or ineffective osmole?
ineffective osmole - increased blood urea does not change ICFV
193
How would you expect BUN and creatinine to change during renal plasma failure?
In renal failure plasma creatinine and BUN increase in parallel (because the problem lies within the ability of the urine to filter/reabsorb stuff)
194
How would you expect BUN and creatinine to change during dehydration?
During dehydration (as long as GFR is maintained) creatinine excretion and thus plasma creatinine remain constant whereas BUN increases. (because ADH causes increased urea permeability, whereas creatinine is not affected by ADH)
195
What is the effect of ANP on water permeability?
ANP inhibits Na reabsorption in the CD and antagonizes the effect of ADH. This results in rapid reduction of the ECFV.
196
What is the effect of prostaglandins on water permeability?
it antagonizes the effect of ADH.
197
What is the effect of NSAIDs on water permeability?
ADH-like effects (because they inhibit prostaglandins, which normally antagonize ADH). As a result, ADH can act on the CDs, resulting in increased urine osmolality
198
What is the purpose of the Ca sensor in the CD?
The CD monitors urinary [Ca] via luminal Ca++ receptors. If the urine Ca concentration is too high (which increases risk of precipitation, these receptors are activated to inhibit the effect of ADH on the CD, thus generating more dilute urine.
199
Where are two places in the kidneys were Ca sensors are placed?
TALH and cortical CD
200
Hyperosmotic urine results in ___________ plasma osmolality (increase or decrease)
decreased (more water is retained)
