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707 Cards in this Set

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The 60-40-20 rule is?
Body Weight x
60% is total body water
40% is intracellular fluid
20% is extracellular fluid
what happens to osmolarity of ECF if person is infused with isotonic saline solution?
stays the same
Describe the isotonic water transport at the proximal tubule.
- high Lp
- only need small osmotic gradient: Na+ uptake leads to slight decrease in hypo-osmolarity of luminal fluid.
- fluid uptake by peritubular capillaries driven by Starling forces
Markers used to measure TBW?
tritiated water
D20
antipyrene
Clearance equation
C = (urinary conc x urinary flow) / plasma conc
Why is Na+ delivery to distal tuble more or less constant?
- tubuloglomerular feedback mechanism:
constriction of afferent arteriole in response
to high tubular [Na+] sensed by macula densa.

- glomerulotubular balance:
ability of proximal tubule to absorb
more Na+ when GFR is increased
What are the three hormones that the kidneys synthesize and secrete?
Renin
Erythropoietin
1,25-dihydroxycholecalciferol
What happens to the following with isotonic NaCl infusion?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
- ECF volume: up
- ICF volume: no change
- ECF osmolarity: no change
- Hct: down
- serum [Na+]: no change

Because osmolarity is unchanged, there is no water shift between ECF and ICF.
major cations/anions of ICF?
cations--K+, Mg2+; anions--protein, organic phosphates (eg ATP)
Total body water (TBW) is highest in?
____ is highest in newborns and adult males.
what happens to osmolarity of ECF if person has loss of isotonic fluid? (example)
diarrhea
stays the same
Where is glucose absorbed in the nephron?
proximal tubule (100%)
- early part: apical SGLT2 (Na+/Glu) and basalateral GLUT transporter
- late part: apical SGLT1 and SGLT2 (Na+/Glu) and basalateral GLUT transporter.
- Tmax = 1.9mMol/min
Markers used to measure ECF?
sulfate
inulin
mannitol
How much of the CO is the RBF?
20%
What % of Na+ is excreted with max aldolsterone?
0.1%
What is the difference between superficial cortical nephrons and juxtamedullary nephrons?
The two types of nephrons are distinguished by the location of their glomeruli.

The superficial cortical nephrons
have their glomeruli in the outer cortex, have relatively short loops of Henle, and descend only into the outer medulla. Juxtamedullary nephrons have their glomeruli near the corticomedullary border.


The glomeruli
are also larger, have higher glomerular filtration rates, have longer loops of Henle that descend deep into the inner medulla and papilla, and are essential for the concentration of urine.

The vasa recta are found following the juxtamedullary nephrons.
What happens to the following with diarrhea (isotonic volume loss)?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
- ECF volume: down
- ICF volume: no change
- ECF osmolarity: no change
- Hct: up
- serum [Na+]: unchanged

BP decreases because ECF volume decreases.
markers for measuring TBW
D2O, tritiated H2O
markers for measuring ECF?
mannitol, sulfate, inulin
Major intracellular fluid (ICF) cations are?
__________________ cations are K+ and Mg2+.
what happens to osmolarity of ECF if person has high NaCl intake?
incresaes
What is the Tm and threshold for plasma [glucose]?

What explains the splay?
- Tm = 350 mg/dl
- threshold = 250 mg/dl
- difference is called splay which is explained by heterogeneity of nephrons and the relatively low affinity of the Na/Glu transporter.
markers used to measure plasma?
RISA
evan's blue
What are some things that vasodilate the renal arterioles?
PGE2
PGI2
Bradykinin
NO
Dopamine
What % of Na+ is excreted with no aldolsterone?
5%
What does the renal artery branch into?
Interlobar arteries
Arcuate arteries
Cortical radial arteries
What happens to the following with high NaCl intake?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
Hyperosmotic volume expansion
- ECF volume: up
- ICF volume: down
- ECF osmolarity: up
- Hct: down
- serum [Na+]: up

Water shifts from ICF to ECF because of increased ECF osmolarity.
markers for measuring plasma?
RISA, Evan's blue
Major intracellular fluid (ICF) anions are?
___________________ anions are protein, and organic phosphates (ATP, ADP, AMP).
what happens to ECF osmolarity if person is sweating in the desert?
increases (sweat is hyposmotic... more water than salt is lost)
What type of diabetes is this?

- glucosuria
- normal plasma [glucose]
- diuresis
- thirst
renal diabetes mellitus
- reduced Tmax, reduced threshold, increased splay
measuring interstitial fluid?
ISF = ECF - plasma
Over what range of arterial pressures does autoregulation occur?
80-200 mmHg
Where is the receptor for aldolsterone located?
on the nucleus of principal cells and type A intercalated cells
Who has the highest percentage of water? Who has the lowest percentage of water?
Thin men have the highest percentage of body weight as water (~70%).
Obese women have the lowest percentage of body weight as water (~50%).
What happens to the following when sweat or with fever or diabetes insipidus?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
Hyperosmotic volume contraction
- ECF volume: down
- ICF volume: down
- ECF osmolarity: up
- Hct: no change
- serum [Na+]: up

Because RBC shrink due to high plasma osmolarity, it offsets the volume loss so Hct stays the same.
markers for measuring interstitial fluid?
indirect: ECF - plasma (mannitol - Evan's blue)
Major ECF cation is?
__________ cation is Na+.
what happens to ECF osmolarity in SIADH?
decreases
Where is PAH absorbed/secreted?
- PAH is secreted in the proximal tubule
- at low [PAH], secretion rate increases
- at high [PAH] above Tmax, scretion rate is constant
measuring ICF
ICF = TBW - ECF
What are the mechanisms for autoregulation of RBF?
Myogenic mechanism: afferent arteriole constricts in response to stretch
TGF mechanism: increased flow across the macula densa constricts the afferent arteriole
Mechanism of aldolsterone.
bind to receptors on nuclear membrane of principal cell and type A intercalated cells.
- stimulate Na+/K+ channels on principal cells
- stimulate H+/K+ channels on type A intercalated cells
- increase oxidative metabolism of taget cells
How much water is in the ICF? In the ECF?
About two-thirds of total body water is in the ICF. About one-third is in the ECF.
What happens to the following with SIADH (excess ADH)?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
Hyposmotic volume expansion
- ECF volume: up
- ICF volume: up
- ECF osmolarity: down
- Hct: no change
- serum [Na+]: down

Hct is expected to decrease, but remains unchanged because water shifts into RBC, increasing their volume and offsetting the diluting effect.
markers for measuring ICF?
do indirectly: TBW - ECF (D2O - mannitol)
Major ECF anions are?
_________ anions are Cl- and HCO3-.
what happens to ECF osmolarity in adrenocortical insufficiency (NaCl loss)?
decreases (lack of aldosterone), kidneys excrete more NaCl than water
PAH can be used to measure the size of which fluid compartment?
RPF
Volume of body compartment calculation
Volume = Amt injected - Amt excreted / concentration
What substance is used to calculate RPF?
PAH, because it is filtered and secreted
What some stimulators of aldolsterone?
- high plasma [K+]
- angiotensin II
What is the 60-40-20 rule?
60% of body weight is water, 40% is ICF, 20% is ECF.
What happens to the following with adrenal insufficiency (less aldolsterone)?

- ECF volume
- ICF volume
- ECF osmolarity
- Hct
- serum [Na+]
Hyposmotic volume contraction - loss of NaCl
- ECF volume: down
- ICF volume: up
- ECF osmolarity: down
- Hct: up
- serum [Na+]: down

BP decreases because of the decrease in ECF volume.
What happens if isotonic NaCl is infused?
isosmotic volume expansion
The dilution method to measure TBW uses?
__________ is measured with tritiated water, or D20.
what happens to plasma protein [] and hematocrit in infusion of isotonic NaCl?
decreases (overall increase in fluid)
How to calculate the fraction of H2O reabsorbed using inulin method?
1 - 1/(U/P)inulin
infusion of isotonic NaCl

aka. iso-osmotic volume expansion
- ECF volume increases
- no change in osmolarity
- no change in ICF volume
- plasma protein/ Hct decrease
- arterial BP increases
How close is calculated RPF to actual RPF?
It underestimates actual RPF by 10%
Where is aldolsterone produced?
produced and released by zona glomerulosa cells of adrenal cortex.
How much of the ECF water is found in the interstitial fluid? In the plasma?
About three-fourths of the ECF is found in the interstitial compartment, and the remaining one-fourth is found in the plasma.
What is this fluid compartment?

- volume: 3.5L
- [Na+] = 146 mM
- [Cl-] = 105mM
- [K+] = 4.2 mM
- osmolarity = 285
Plasma
- can be measured by Evan's Blue
What happens to fluid volumes if you have diarrhea?
loss of isotonic fluid-->isometric volume contraction
The dilution method to measure ECF uses?
__________ is measured with mannitol, inulin, or sulfate.
what happens to plasma protein [] and hct in diarrhea?
increases (from volume contraction)
What % filtered K+ remains in the tubular fluid given that U/P(K+) / U/P (inulin) is 0.3?
30%
diarrhea

aka. isoosmotic volume contraction
- ECF volume decreases
- no change in osmolarity
- no change in ICF volume
- plasma protein/Hct increase
- arterial BP decreases
What is the formula for RBF?
RBF = RPF / (1-hematocrit)
Size of ECF volume is determined by ___.

A. Na+
B. HCO3-
C. Glucose
D. K+
A.
How much of the blood is plasma?
On a volume basis, plasma constitutes 55% of blood volume, and blood cells constitute the remaining 45% of blood volume.
What is this fluid compartment?

- volume: 10.5L
- [Na+] = 142 mM
- [Cl-] = 107mM
- [K+] = 4 mM
- osmolarity = 283
ISF
- ECF - P
what happens to fluid volumes if excessive NaCl intake?
hyperosmotic vol expansion
The dilution method to measure plasma volume uses?
____________ is measured with Evans blue, or radiolabled albumin (RISA).
what happens to plasma protein [] and hct in high NaCl consumption?
decrease (ICF shrinks to accomodate the increased osmolarity in ECF, this dilutes out the plasma protein)
Where are Na+ reabsorbed? by what transporters?
1) 67% at proximal tubule

- Na+/glu cotransporter
- Na+/H+ exchanger
- Na+/HCO3- cotransporter
- Na+/AA cotransporter
- Na+/phosphate cotransporter
- Na+/lactate cotransporter
- Na+/Cl- cotransporter in late proximal tubule

2) 25% at thick ascending limb of loops of Henle:

- Na+/K+/2Cl- transporter

3) 8% at distal tubule and collecting duct

- early distal tubule: Na+/Cl- transporter
- late distal tuble and collecting duct: Na+/K+ channels which are stimulated by aldolsterone
excessive NaCl intake

aka. hyperosmotic volume expansion
- ECF osmolarity increases
- volume shifts from ICF to ECF
- ECF volume increases
- ICF volume decreases
- plasma protein/Hct decrease
What substances are used to calculate GFR?
Inulin or creatinine, because they are filtered but are not secreted or reabsorbed
Factors that regulate Na+ balance.
1) renin-angiotensin-aldolsterone system:
- low ECF -> renin released from JG cells -> Ang converted to AngI -> AngI converted to AngII(vasoconstriction) by ACE in the lungs -> aldolsterone release -> increased Na+ reabsorption -> normal ECF restored
2) GFR regulation: high ECF -> increased GFR and decreased proximal fluid resorption
3) third factor
- increased venous filling pressure -> ANP release -> decreased sympathetic tone -> decrease Na+ reabsorption
- ourabain-like factor (hypothalamus/adrenal cortex) -> inhibit Na+/K+ pumps of collecting duct
What is the average hematocrit? Is it higher in males or in females?
The average hematocrit is 0.45 or 45%. It is higher in males (0.48) than in females (0.42).
What is this fluid compartment?

- volume: 28L
- 40% body weight
- [Na+] = 10 mM
- [Cl-] = 6mM
- [K+] = 160 mM
- osmolarity = 283
ICF
- TBF - ECF
what happens to fluid volumes if you get lost in a desert? (dehydration)
hyperosmotic vol contractino
The TBW of a 70 kg man is?
The TBW of a ___ man is 42 L.
what happens to plasma protein [] and hct when swaeting in desert?
protein increases
hct stays same b/c fluid leaves rbcs to offset fuid loss
What is the action of ouabain?
block Na+/K+ ATPase that set up the diffusion gradient
sweating in a desert - loss of water

aka. hyperosmotic volume contraction
- ECF osmolarity increases
- water shifts from ICF to ECF until osmolarity has equilibriated
- ICF volume increases
- plasma protein conc. increases
- Hct remains the same
What happens to the BUN/creatinine ratio during azotemia (hypovolemia)?
It increases (greater than 20:1)
What happens when kidney is unable to maintain normal ECF as in severe blood loss and excessive sweating?
>15% volume contraction -> creaving for Na+ -> ingestion of salt -> Na+ balance
What is the Gibbs-Donnan effect?
The Gibbs-Donnan effect predicts that plasma will have a slightly higher concentration of small cations than interstitial fluid and a slightly lower concentration of small anions.
What is this fluid compartment?

- volume: 14L
- 20% body weight
- [Na+] = 144 mM
- [Cl-] = 106mM
- [K+] = 4.3 mM
- osmolarity = 284
ECF
- can be measured by inulin
what happens to fluid volumes in SIADH?
hyposmotic volume expansion
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
isoosmotic volume expansion?
ECF increases
ICF unchanged
ECF osm unchanged
Hct decreases
[Na+] unchanged
what happens to plasma protein [ ] and hct in siadh
decreases
stays same
What is the action of phlorizin?
Block SGLT2 (Na+/Glu) in proximal tubule
syndrome of inappropriate ADH

aka. hypoosomotic volume expansion
- water retention = decreased ECF osmolarity, increased ECF volume
- water shifts from ECF to ICF --> ICF volume increases, osmolarity decreases
- plasma protein decreases
- hct unchanged
What happens to GFR as we age?
Decreases
How does kidney react to volume depletion?
volume depletion -> increase AngII and aldolsterone, release of NE -> increase in Na+ reabsorption -> increased osmolarity -> ADH release -> water reabsorption -> volume returns to normal
What is special about mannitol? Where is it distributed?
Mannitol is a large molecular weight sugar that cannot cross cell membranes. It will be distributed in ECF but not ICF.
Mannitol is a marker for ECF volume.
What is this fluid compartment?

- volume: 42L
- 60% body weight
TBF
- can be measured by D2O, THO, antipyrine
what happens to fluid volumes if adrenocortical insufficiency?
hyposmotic volume contraction
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
isoosmotic volume contraction?
ECF decrease
ICF no change
ECF osm no change
Hct increase
[Na+] no change
what happens to plasma protein [] and hct in adrenal insuff?
plasma protein increases
hct increases (from decreased ECF volume and rbc swelling from water entry)
What is the action of acetazolamide?
carbonic anhydrase inhibitor
- diuretics that act in proximal tubule by inhibiting reabsorption of HCO3-.
adrenocortical insufficiency - loss of NaCl

aka. hypoosmotic volume contraction
- osmolarity of ECF decreases
- volume of ECF decreases, shifts to ICF
-ICF osmolarity decreases, volume increases
- plasma protein conc. increases
- Hct increases
What is the equation for filtration fraction?
FF = GFR / RPF
What is the strongest stimulator of aldolsterone release?
high [K+] > 5mM
What substances are distributed wherever water is found?
The markers for total body water include isotopic water (D2O and tritiated water) and antipyrine.
Why is [Na+] higher in plasma than in ISF, but [Cl-] lower in plasma than ISF?
Donnan effect
- negative charges on plasma proteins attract positively charged ions and repell negatively charged ones.
treatment of SIADH?
demeclocyclene, water restriction
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
hyperosmotic volume expansion?
ECF increase
ICF no change
ECF osm increase
Hct decrease
[Na+] increase
how does vasoconstriction of renal arterioles affect RBF? how is this achieved?
decreases RBF
SNS
What is the action of furosemide?
Loop diuretics
- block Na+/K+/2Cl- cotransporter in the thick ascending limb of the Loop of Henle
clearance
- definition (1)
- equation (2)
1 = amount of plasma cleared of a substance per unit time
2 - C = UV/P
What is the normal value for the filtration fraction?
20% (that is, 20% of RPF is filtered)
Mechanisms of aldolsterone causing K+ wasting (kaliuretic)
- electrical coupling with Na+ influx
- insertion of additional Na+/K+ channels
- intracellular alkalosis
What are some markers for plasma volume?
Substances that distribute in plasma but not in interstitial fluid, because they are too large to cross capillary walls. These substances include radioactive albumin and Evans blue (dye that binds to albumin).
What part of nephron is this?

- apical brush border microvilli
- basal infoldings with lots of mitochondria
- function: absorption of fluid
proximal tubule
renal blood flow is what % of CO?
~25%
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
hyperosmotic volume contraction?
ECF decrease
ICF decrease
ECF osm increase
Hct no change (brs pys p.155)
[Na+] increase
how does AII affect renal arterioles
preferentially constricts efferent arterioles unless it is a situation where there is a massive hemorrhage. then, so much AII is released that it constricts both efferent and afferent arterioles
What stimulates Na+/K+/2Cl- cotransporter in the thick ascending limb of the Loop of Henle? what inhibits it?
- ADH stimulates it
- Loop diuretics (furosemide) inhibits it
renal blood flow (RBF)
- (1) % of CO
- proportional to pressure diff. between (2) and (3)
- inversely proportional to resistance of (4)
1 = 25$
2 = renal artery and renal vein
4 = renal vasculature
If the FF is increased, what effect does this have on reabsorption in the proximal tubule? What if it is decreased?
Increases and decreases proximal tubule reabsorption, respectively
Increase in UFR ___ (stimulates/inhibits) K+ secretion.
stimulate
- increase flow rate -> decrease tubular [K+] -> favor secretion
- increase flow rate -> larger Na+ delivery to distal tubule -> increased Na+ absorption and K+ secretion by Na+/K+ transporters
How do you calculate ICF volume? Interstitial fluid volume?
Since there are no unique markers, ICF volume is calculated as the difference between total body water and ECF volume. Interstitial fluid volume is the difference between ECF volume and plasma volume.
What part of nephron is this?

- simple squamous epithelium
- function: selective salt absorption
thin part of Loop of Henle (diluting segement)
at low [ang II], what effect on renal arterioles?
preferential dilation of efferent arteriole--> protects GFR
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
hypoosmotic volume expansion?
ECF increase
ICF increase
ECF osm decrease
Hct no change
[Na+] decrease
how does ACE affect renal arterioles
preferentially constricts efferent arterioles
What is the action of thiazide?
diuretics
- block Na+/Cl- cotransporter at the cortical diluting segment (early distal tubule)
angiotensin II preferentially constricts (1) arteriole causing an (2) in GFR
1 = efferent arteriole
2 = increaes
What is the formula for GFR?
GFR = Kf [(Pgc - Pbs) - (PIgc - PIbs)]
Note that PIbs is typically 0 because there should be no protein in Bowman's space
What type of cell is most active during K+ depletion?
type A intercalated cell
- active uptake of K+ by H+/K+ pump
What is the ECF volume determined by?
The volume of a body fluid compartment depends on the amount of solute it contains. Since the major cation of ECF is Na+ (with accompanying anions Cl- and HCO3-), ECF volume is determined by the amount of NaCl and NaHCO3 (sodium bicarbonate) it contains.
What part of nephron is this?

- simple cuboidal epithelium
- basal infoldings with mitochondria
- function: selective salt absorption
thick ascending limb of Loop of Henle (diluting segement)
over what range of pressures does renal blood flow remain constant (autoregulation)
80-200mmHg (thanks to myogenic mech and tubuloglomerular feedback)
How are ECF, ICF, ECF osm, Hct, and [Na+] affected by:
hypoosmotic volume contraction?
ECF decrease
ICF increase
ECF osm decrease
Hct increase (brs pys p155)
[Na+] decrease
what effects does AII have on GFR?
increases it
What is the action of spironolactone and amiloride?
K+ sparing diuretics
- inhibits Na+ transporter in the principle cells of the collecting duct
- inhibit K+ secretion in the principle cells of collecting duct
vasodilation of renal arterioles causes an (1) in RBF and is caused by: (2), (3), (4) and (5)
1 = increase
2 = PGE2, PGI2
3 = bradykinin
4 = NO
5 = dopamine
How does the glomerular barrier contribute to Kf?
Kf is the filtration coefficient, and it is maintained by the size barrier and the charge barrier (anionic glycoproteins inhibit the passage of negatively charged plasma proteins)
What causes water diuresis?
What causes osmotic diuresis?
- water diuresis: absence of ADH
- osmotic diuresis: increased excretion of a solute
What is the normal value for osmolarity of the body fluids?
290 mOsm/L (~300 mOsm/L for simplicity)
What part of nephron is this?

- small apical brush border
- basal infoldings and mitochondria
- function: selective water/salt absorption
distal tubule
How measure renal plasma flow?
use PAH, which is both filtered and secreted by renal tubules (so that~none in renal veins); this is the effective RPF
The equation to calculate clearance is?
The equation to calculate ______ is = UV/P.
what effect do ACE-I have on GFR
decreass it by dilating efferent arterioles
What are some actions of aldolsterone on distal tubules and collecting duct?
1) on principle cells:
- increases Na+ reabsorption
- increase K+ secretion
2) on intercalated cells
- increases H+ secretion
autoregulation of RBF
maintains a constant range of arterial pressure between 80 -200 mmHg
What happens to Kf in glomerular disease?
It decreases because the anionic charges on the barrier are lost, resulting in proteinuria
Drugs that cause natriuresis.
- acetazolamide (weak): inhibition of carbonic anhydrase
- loop diuretics
- thiazide
- K+ sparing diuretics
What is the equation to estimate plasma osmolarity?
Plasma Osmolarity (mOsm/L) =

2 x Plasma Na + Glucose/18 + BUN/2.8
Type A or B intercalated cell of the collecting duct?

- acid secreting
type A
filtration fraction?
GFR/RPF (normal~0.20)
Renal blood flow is decreased by?
___________ is decreased by sympathetic activation and angiotension II.
what does afferent arteriole constriction do to RPF?
decreases
List some drugs that act directly on Na+ reabsorption.
- loop diuretics: block Na+/K+/2Cl- on thick ascending loops of Henle
- thiazide diuretics: block Na+/Cl[ on early distal tubule
- K+ sparing diuretics: block Na+ absorption and K+ secretion on principle cells
myogenic mechanism of autoregulation of RBF
renal afferent arterioles contract in response to stretch
What is the principal determinant of Pbs (hydrostatic pressure of Bowman's space)?
Constriction of the ureters
Why do loop diuretics cause stronger natriuresis than acetazolamide(carbonic anhydrase inhibitor)?
- loop diuretics inhibit tubuloglomerular feedback
- loop diuretics disrupt the corticopapillary gradient
Why is the Na+ concentration multiplied by 2 in the equation?
Na+ must be balanced by an equal concentration of anions (Cl- and HCO3-).
Type A or B intercalated cell of the collecting duct?

- HCO3- secreting
type B
where does acetozolamide work in kidney?
(carbonic anhydrase inhibitor) works in PCT to inhibit resorption of HCO3- (w/o bicarb, don't have H+ needed for Na-H antiport) (N.B. can also tx acute mountain sickness)
None
GFR is protected by low doses of?
_________ is _______ by low doses of angiotension II (via selective efferent vasoconstriction).
what does efferent artiorole constriction do to GFR?
increases (by increasing Pgc)
ECF volume contraction ___ (increase/decrease) reabsorption in proximal tubules.
increase
- volume contraction -> increase peritubular capillary osmolarity and decrease Pcap -> reabsorption
tubuloglomerular feedback
increased renal arterial pressure leads to increased delivery of fluid to macula densa; macula densa causes constriction of nearby afferent arteriole
What happens to the glomerular capillary oncotic pressure as we go along the length of the capillary?
It increases because as water is filtered out, the protein concentration is increased
How do loop diuretics, thiazide cause K+ wasting?
natriuresis -> more Na+ delivered to distal tubule and collecting duct -> stimulation of Na+/K+ exchanger -> more K+ secreted -> hypokalemia
What does volume contraction and volume expansion mean?
Volume contraction means a DECREASE in ECF volume.

Volume expansion means an INCREASE in ECF volume.
Name the two capillary bed in the kidney and what are the main function of each capillary bed?
- glomerulus: filtration
- peritubular capillary: absorption
middle/late PCT vs. early PCT?
early PCT--Na resorb.coupled with glucose, aa, phosphate, etc.; mid/late PCT--Na resorb.w/ Cl-
The kidney receives how much CO?
25%
what does increased plasma protein do to GFR?
decreases it by increasing osmotic pressure in GC
ECF volume expansion ___ (increase/decrease) reabsorption in proximal tubules.
decrease
- volume expansion -> decrease peritubular capillary osmolarity and increase Pcap -> less reabsorption
para-aminohippuric acid (PAH) is used to measure (1); PAH is both (2) and (3) by renal tubules
1 = effective renal plasma flow
2 = filtered
3 = secreted
What is the equation for filtered load?
Filtered load = GFR x plasma conc
What is a good drug of choice for treating life-threatening edema of the lung and brain?
loop diuretics and thiazide
- high ceiling level

also good in treating congestive heart failure and hypertension
What does a hyperosmotic disturbance mean?
There has been an increase in ECF osmolarity.
Equation for filtration pressure Pfil.
Pfil = (P(cap) - P(bs)) - (O(cap) - O(bs))

because O(bs) = 0, so
Pfil = (P(cap) - P(bs)) - O(cap)
where do K+sparing diuretics work?
in CCD
Renal arterioles are vasodilated by stimulation with?
Renal arterioles are _______ by stimulation with PGE1, PGI2, bradykinin. nitric oxide, and dopamine.
what does decreased plasma protein do to GFR?
increases it by decreasing osmotic pressure in GC
Cell types on late distal and collecting duct and their specialzed transporters.
1) principle cells:
- Na+ reabsorption
- K+ secretion
- H2O reabsorption in the presence of ADH
2) Type A intercalated cells
- apical: H+ pump, K+ reabsorption during K+ depletion
- basalateral HCO3-/Cl- exchanger
3) Type B intercalated cells
- apical HCO3-/Cl- exchanger
- basalateral H+ pump
Formula for RPF
RPF = C pah = U(pah)V(pah) / Ppah
What is the equation for excretion rate?
Excretion rate = urine flow rate x urine conc
What is the compatible blood pH range?
7-7.8
What does a hyposmotic disturbance mean?
There has been a decrease in ECF osmolarity.
Equation for GFR using Pfil.
GFR = Kfil x Pfil
- Kfil = Lp x A
- Pfil = (P(cap) - P(bs)) - (O(cap)
role of alpha intercalated cells?
secrete H+ and resorb. K+ if hypokalemic (or acidic?)
The myogenic mechanism for renal autoregulation is?
changes in renal artery pressure as sensed as changes in stretch, and the afferent arteriole contracts to maintain RBF.
what does increased plasma protein do to RBF?
nothing
What is this disease?

- impaired reabsorption of di-basic AA such as lysine, arginine, ornithine, cystein
cysinuria (AR)
- see cystein stones (calculi)
Formula for RBF
RPF / (1 - Hct)
What is the equation for reabsorption rate?
Reabsorption rate = filtered load - excretion rate
What is the most abundant acid in the body?
CO2
What are some examples of Isosmotic Volume Contraction?
Diarrhea, burn.
What are the two mechanism of autoregulation of GFR?
1. myogenic: decreased systemic BP -> stretch reflex -> vasoconstriction -> maintain constant renal pressure. RBF remains constant over the range of arterial pressures from 80 to 200.
2. tubuloglomerular response: increased [Na+] sensed by macula densa -> constriction of afferent arteriole -> decrease GFR
what cell is responsible for excreting K+ in hyperkalemia?
principal cell (via Na-K ATPase and K channels)
The tubuloglomerular feedback mechanism for renal autoregulation is?
increased renal artery pressure increase fluid flow to macula densa, which signals afferent vasoconstriction to maintain RBF.
what does decreased plasma protein [] do to RBF?
nothing
What is this disease?

- defective AA transport resulting in Tryptophan deficiency
Hartnup's disease (AR)
What substance can you use to measure GFR? Why?
inulin
-bc it is filtered but it is NOT secreted or reabsorbed
What is the equation for secretion rate?
Secretion rate = excretion rate - filtered load
What are the sources of each of the following acid?

- phosphoric acid
- sulfuric acid
- uric acid
- carboxylic acid
- phosphoric acid: lipid, nucleic acid
- sulfuric acid: AA. low pKa, minimal excretion
- uric acid: purines. low pKa, minimal excretion
- carboxylic acid:ketoacidosis, lactic acidosis
What are other consequences of diarrhea?
Increased hematocrit and increased plasma protein concentration, which are explained by the loss of isosmotic fluid from the ECF compartment.
Equation for excretion.
excretion = filtration + secretion - absorption
where is phosphate resorbed?
only in PCT. ~15% of filtered phosphate excreted (imp for buffering later on)
Renal plasma flow (RPF) is measured with?
_______ is measured with para-aminohippuric acid (PAH).
what does efferent arteriole constriction do to RBF?
decreases it
Describe K+ reabsorption/secretion along the nephron and the specific transporters.
1) proximal tubule: 67% reabsorption
2) thick ascending limb of the loop of Henle: 20%
- Na+/K+/2Cl- cotransport
3) distal tubule and collecting duct
- reabsorption by type A intercalated cell:
- secretion by principle cells: determined by concentration gradient
blood urea nitrogen and serum creatinine (1) when GFR (2)
1 = increase
2 = decreases
How can you tell if a substance is reabsorbed? Excreted?
If it is reabsorbed, excretion rate is lower than filtered load. If it is secreted, excretion is higher than filtered load
On normal western diet, how much fixed acids are excreted by the kidney?
50-70 mmol
What are some examples of Hyperosmotic Volume Contraction?
Sweating, fever, diabetes insipidus.
Equation for GFR using UFR.
GFR = (U/P) x UFR
effect of PTH on phosphate in kidney?
PTH inhibits phosphate resorb. in PCt via inc'd AC-->cAMP. (get phosphaturia and inc'd urinary cAMP)
Renal blood flow is calculated?
____ = RPF/(1-Hct)

(1-Hct) is the fraction of blood volume occupied by plasma.
what happens to the filtration fraction in afferent arteriole constriction?
(GFR/RBF)
GFR decreases, RBF decreases
FF no change
Factors that increase K+ secretion by the principal cells.
- high K+ diet: high intracellular [K+] -> high driving force
- aldolsterone: stimulate Na+, K+ channels on principal cells
- alkalosis: too little H+ in blood -> H+ leaves the cells and K+ enters the cell from basalateral membrane -> increased driving force
- thiazide and loop diuretics: increase flow rate in distal tubule -> dilution of luminal [K+] -> increased driving force
- luminal anions: negativity of the lumen drives K+ out
formula for filtration fraction

normal value for filtration fraction
filtration fraction = GFR / RPF

normal = 0.20
What is the conversion factor between ml and dl?
100 ml = 1 dl
Where are HCO3- absorption in the nephron?
- 90% in proximal tubule: Na+/H+ exchanger, brushborder carbonic anhydrase. Luminal pH = 6.7
- rest is absorned in distal tubule and collecting duct (intercalated cells: absorption in typeA, secretion in typeB cells). Final pH 4.5
What occurs during water deprivation?
Hyperosmotic Volume Contraction:

Sweat is hyposmotic relative to ECF. Since a hyposmotic fluid is lost from ECF, ECF volume decreases and ECF osmolarity increases. The difference in osmolarity between ECF and ICF causes water to shift from ICF to ECF until the osmolarities are equal. In the new steady state, both ECF and ICF volumes will be decreased, and both osmolarities will be increased and equal to each other.
What is the normal serum creatinine level? what about normal urine content?
Ccr = 90 uM
urine content = U x UFR = 11 uM/min
which diuretics can be used to treat hypercalcemia?
loop diuretics
In prerenal azotemia the change in the BUN:Cr is ___ because?
The change in _______ is >20 because BUN increases more than Cr (as BUN is partially reabsorbed).
what happens to FF in efferent arteriole constriction
GFR/RBF
GFR increases, RBF decreases
FF increases
Factors that decrease K+ secretion by the principal cells.
- low K+ intake: low intracellular [K+] -> small driving force
- hypoaldolsterone: no stimulation of Na+, K+ channels on principal cells
- acidosis: excess H+ in blood -> H+ enters cell and K+ leaves through basalateral membrane -> low intracellular [K+] -> small driving force
- K+ sparing diuretics: decrease K+ secretion by blocking K+ channel on principal cells
increase in filtration fraction produces an (1) in protein conc. of peritubular capillary blood, which causes (2)
1 = increased
2 = increased reabsorption in proximal tubule
How is glucose reabsorbed?
Na-glucose cotransport in the proximal tubule reabsorbs Na and glucose from the lumen. Note that the number of these cotransporters is limited
What is the max [HCO3-] before you see it in the urine?
30mM
What happens to the plasma protein concentration and hematocrit during hyperosmotic volume contraction? Why?
Plasma protein concentration is increased, but the hematocrit is unchanged.

The hematocrit remains the same because even though ECF loses volume, the blood cells ALSO lose volume (ICF volume shift). The two effects offset each other.
PAH clearance is close to what value?
PAH is filtered and secreted
Clearance close to RPF
which diuretics can be used to treat hypercalciURIA
thiazides (increase Ca resorb.)
Filtration fraction is calculated as ________ and is normally?
___ = GFR/RPF

Normally is 0.20
what happens to FF in increased plasma protein concentraton
GFR/RBF
GFR decreases, RBF no change
FF decreases
Specialized transporters on type B intercalated cells in the late distal tubule and collecting duct.
- apical: Cl-/HCO3- exchanger
- basalateral: H+(out) and Cl(out) transporter.
glomerular barrier
- components (1)
- lined with? (2)
1 = capillary endothelium
basement membrane
filtration slits of podocytes

2 = anionic glycoproteins (prevent proteins from passing through)
What is the transport maximum?
The reabsorptive rate at which all available transporters are saturated and no further reabsorption can occur, so excess solute will be excreted in the urine
What can cause a left shift of HCO3- curve?
- alkalosis
- volume expansion
What are some examples of Hyposmotic Volume Contraction?
Adrenal insufficiency
Glucose clearance is close to what value?
zero
- glucose is filtered and absorbed
Rank the following in decreasing clearance.

- PAH
- inulin
- Na+
- K+
- glucose/AA/HCO3-
- urea
PAH
K+
inulin
urea
Na+
glucose/AA/HCO3-
relationship of K+ and NH3?
hyperkalemia inhibits NH3 synthesis (RTA type 4), dec'd H+ excretion; hyPOkalemia--stim NH3 synthesis
If the filtration fraction increases, you will see what in the peritubular capillary network?
The protein concentration will increase in the peritubular capillaries and there will be increased PT reabsoption.
what happens to FF in decreased plasma protein []
GFR/RBF
GFR increases, RBF no change
FF increases
T/F: There is no active transport in thin loop of Loops of Henle.
T.
glomerular capillary hydrostatic pressure
- increased by dilation of (1) and constriction of (2)
1 = afferent arteriole
2 = efferent arteriole
What is the Tm for glucose?
Under 250 mg/dl, all filtered glucose is reabsorbed because there are plenty of carriers. Over 350 mg/dl, the carriers are entirely saturated, so increased plasma concentration doesn't result in increased reabsorption. The threshold (where glucose first begins to appear in the urine) is about 250 mg/dl
What can cause a right shift of HCO3- curve?
- acidosis
- volume depletion
What occurs during adrenal insufficiency?
Hyposmotic Volume Contraction:

Adrenal insufficiency results in aldosterone deficiency, which leads to excess NaCl excretion in the urine. NaCl is an ECF solute, so ECF osmolarity decreases. This causes water to shift from ECF to ICF until both osmolarities are decreased and equal. In the new steady state, both ECF and ICF osmolarities will be lower than normal and equal to each other. ECF volume will be decreased and ICF volume will be increased.
How does aging affect the following?

- GFR
decreases
ECF volume contraction and acid/base balance?
ECF volume contraction-->HCO3- resorb. , contraction alkalosis (N.B. in vomiting, met alk made worse if ECF vol contracts!)
None
Decreases in the filtration fraction result in?
decreases in protein concentration (ie oncotic pressure) or peritubular capillarys, and less PT reabsorption.
what happens to FF when ureter is constricted?
GFR/RBF
GFR decreases, RBF no change
FF decreases
How does PTH affect phosphate transport in proximal tubule?
PTH lowers Tmax for phosphate thus increases excretion and leads to low level of phosphate in the body.
bowman's space hydrostatic pressure
- increased by constriction of (1)
1 = ureters
What is "splay?"
The region of the solute titration curve (Tm curve) between threshold and Tm. It represents the excretion of solute in the urine before saturation of reabsorption occurs
What can cause volume depletion alkalosis? Is it easy to correct?
volume depletion alkalosis
- constant vomit: loss of acid and volume at the same time
- alkalosis hard to correct because volume depletion shifts HCO3- excetion to the right.
What happens to the plasma protein concentration and hematocrit during hyposmotic volume contraction? Why?
Both plasma protein concentration and hematocrit will be increased because of the decrease in ECF volume. Hematocrit increases also because of the shift of water into red blood cells, increasing cell volume.
How does aging affect the following?

- plasma [creatinine]
no change
- decreased GFR -> increased [creatinine]
- decreased muscle mass -> decreased [creatinine]
- so overall no change in [creatinine]
why might you get tingling, numbness, muscle spasms in respiratory alkalosis?
signs/symptoms of hypocalcemia, b/c H+ and Ca2+ compete for protein binding sites and dec'd H+ means more bound Ca and less free Ca (~hypocalc.)
The GFR formula?
____ = Kf [(Pgc - Pbs) - (ONCgc-ONCbs)]

K x (hydrostatic p - oncotic p)
what things are reabsorbed in the PCT?
glucose
AA's
most of the HCO3
What can you do to treat barbituates poisoning?
HCO3- infusion to make the tubular fluid more alkaine
- barbituric acid in charged form -> absorption of barbituric acid blocked
glomerular capillary oncotic pressure
- increases along (1) due to increased (2)
1 = length of glomerular capillary bed
2 = increased protein conc.
How can you promote excretion of weak acids?
Alkalinization of the urine will deprotonate the acid (that is, you'll have the A- form instead of the HA form), which is less able to diffuse from the urine to the blood
Name the two mechanisms that fixed acids are excreted.
- titratable acid: di-basic phosphate
- ammonium: glutamine -> NH3 -> NH4+ -> Na+/NH4+ exchanger
What are some examples of Isosmotic Volume Expansion?
Infusion of isotonic NaCl.
Equation for filtration fraction FF.
FF = GFR/RPF
effect of insulin on K+?
insulin deficiency--> shift of K+ out of cells, hyperkalemia; insulin-->shift of K+ into cells, hypokalemia
What are the breakdowns of RPF, GFR, and RBF?
RPF is about 600 mL entering afferent aa. GFR is about 20% of that, or 125 mL filtered across glomeruli. RBF is the remainder that perfusses the kidney, about 475 mL.
describe how HCO3 is handled in PCT
HCO3 is in the lumen and combines with H that is secreted into the lumen --> H2CO3
Carbonic anhydrase --> H20 + CO2
which re-enters the tubule and reforms as H2CO3 with CA
the H is then secreted into the lumen and the HCO3 is reabsorbed
How are weak organic acids secreted in the late proximal tubules?
- basalateral side: transporter takes up the acid
- apical: anion transporter to secrete the acid (site where different drug may compete)
constriction of afferent arteriole:
- (1) GFR
- (2) RPF
- (3) filtration fraction
1 = decreases
2 = decreases
3 = no change
What does it mean if TF/P > 1?
There has been secretion, so the concentration in the tubular fluid is higher than that in the plasma
pKa of phosphate and NH4+.
- pKa (phosphate) = 6.8
- pKa (NH4+) = 9.3
What occurs during an infusion of isotonic NaCl?
Isosmotic Volume Expansion:

Since NaCl is an extracellular solute, all of the isotonic NaCl solution is added to the ECF, causing an increase in ECF volume, but no change in ECF osmolarity. There will be no shift of water between ICF and ECF.
What is the FF under normal condition?
20%
- 20% of RPF is filtered
What are the effects on GFR, RPF, and FF when changing Starling Forces by: afferent constriction (ie sympathetics)?
GFR decrease
RPF decrease
FF no change
what happens in the TAL?
NKCC pump (blocked by furosemide): aids in reabsorbing Na, Cl, K
K flows back out into lumen and the gradient drives the absorption of Mg and Ca
also aids in the running of the NKCC pump
How are weak organic bases secreted in the late proximal tubule?
- basalateral: transporter taken up the base
- apical: organic cation/H+ exchanger

ex. creatinine, EPI, NE, atropine, amiloride
constriction of efferent arteriole:
- (1) GFR
- (2) RPF
- (3) filtration fraction
1 = increases
2 = decreases RPF
3 = increases
What is the significance of TF/Pinulin, and what is the equation?
Marker for water absorption
% of filtered water that is reabsorbed = 1 - [1 / (TF/Pinulin)]
Where is ammonium reabsorbed?
- thick ascending limb
- medullary collecting duct
What happens to the plasma protein concentration and hematocrit during isosmotic volume expansion? Why?
Both plasma protein concentration and hematocrit will decrease (i.e., be diluted) because of the increase in ECF volume.
Effect of decreased GFR on the following.

- Pgc
- O(gc)
higher Pgc
lower Ogc
What are the effects on GFR, RPF, and FF when changing Starling Forces by: efferent constriction (angiotension II)?
GFR increase
RPF decrease
FF increase
is the TAL permeable to water
no
Where is urea reabsorbed?
- proximal tubule: passively
- inner medullary collecting duct: in the presence of ADH, contributes to corticopapillary osmotic gradient.
increased plasma protein causes:
- (1) GFR
- (2) RPF
- (3) filtration fraction
1 = decreased
2 = no change on RPF
3 = decreased FF
How much filtered Na is reabsorbed?
Over 99% (less than 1% of filtered load is in the urine)
What happens to acid excretion during acidosis?
- stimulate enzyme in deamination of glutamine
- increase amount of titratable acid
What are some examples of Hyperosmotic Volume Expansion?
High NaCl intake.
Kfil is ____ (increased/decreased) in glomerulonephritis, diabetic nephropathy, and glomerulosclerosis.
decreased
What are the effects on GFR, RPF, and FF when changing Starling Forces by: increased plasma protein?
GFR decrease
RPF no change
FF decrease
what is the thin descending loop permeable to?
water, but not Na
Where is phosphate reabsorbed?
- 85% in proximal tubule by Na+/PO4- cotransporter
- 15% excreted

* PTH decreases Tmax thus decreases reabsorption and increase excretion (phosphaturia and urinary cAMP)
ureteral stone causes:
- (1) GFR
- (2) RPF
- (3) filtration fraction
1 = decreased GFR
2 = no change RPF
3 = decreased FF
How much Na is reabsorbed in the proximal convoluted tubule?
67%
What happens to acid excretion during diabetic ketoacidosis?
- stimulate enzyme in deamination of glutamine
- increase amount of titratable acid
- additional proton acceptor in the urine (beta-hydroxybutyrate, acetoacetate)
What occurs during high NaCl intake?
Hyperosmotic Volume Expansion:

After ingesting a lot of NaCl (i.e., eating a bag of potato chips), there will be an increase in the amount of solute in the ECF, which increases the ECF osmolarity. ECF osmolarity is higher than ICF osmolarity, which causes water to shift from ICF to ECF, decreasing ICF volume. Both ECF and ICF osmolarities are higher than normal and equal.
How does ADH affect Kfil?
ADH -> mesangial cell contract -> decreases A(surface area) -> lower Kfil -> lower GFR
What are the effects on GFR, RPF, and FF when changing Starling Forces by: a ureteral stone?
GFR decrease
RPF no change
FF decrease
what is happens in the early distal convaluted tubule
actively reabsorbs Na, Cl
Ca absorption is controlled by PTH receptors found here
Mechanism of action of PTH on phosphate reabsorption.
PTH decreases Tmax thus decreases reabsorption and increase excretion (phosphaturia and urinary cAMP)
- activate adenylate cyclase -> increase cAMP -> inhibit Na+/PO4- cotransport.
formula for filtered load
filtered load = GFR x plasma conc.
How much Na is reabsorbed in the thick ascending limb of the loop of Henle?
25%
Henderson-Hasselbach equation for calculating pH in bicarbonate buffer system.
pH = 6.1 + log ([HCO3]/(0.3xPCO2))
What happens to the plasma protein concentration and hematocrit during hyperosmotic volume expansion? Why?
Both plasma protein concentration and hematocrit will be decreased due to the increase in ECF volume. Also, hematocrit will decrease because of the water shift out of the red blood cells into plasma.
What is the change in the following with constriction of afferent arteriole?

- GFR
- RPF
- FF
- GFR: down
- RPF: down
- FF: no change

Caused by decreased Pgc
what happens in the collecting tubules
Na is reabsorbed in exchange for K/H (regulated by ALDOSTERONE!!!)
reabsorption of water regulated by ADH (aquaporins)
Mechanism that contributes to corticopapillary osmotic gradient.
- countercurrent multiplication in loops of Henle: Na+/K+/2Cl- cotransport(augmented by ADH) in thick ascending loop with no H2O permeability.
- increased urea concentration in inner medulla: ADH increase urea absorption in inner medullary collecting duct
- countercurrent system of vasa recta in medulla: minimize washout of osmolytes from medullary interstitium
excretion rate
excretion rate = V x urine conc.
How much Na is reabsorbed in the distal convoluted tubule?
5%
Equation for anion gap calculation.
anion gap = [Na+] - [Cl-] - [HCO3] = 12mM (8-16mM)
What are some examples of Hyposmotic Volume Expansion?
Syndrome of inappropriate antidiuretic hormone (SIADH)
What is the change in the following with constriction of efferent arteriole?

- GFR
- RPF
- FF
- GFR: increase then decrease (due to tubuloglomerular regulation)
- RPF: decrease
- FF: increase

Caused by increased Pgc
which part of the nephron is impermeable to water?
TAL (and collecting tubule if there is no ADH)
Where does ADH act on the nephron?
- thick ascending limb: stimulate Na+/K+/2Cl- cotranport
- distal tubule and collecting duct: stimulate V2 receptor on basalateral membrane -> adenylate cyclase -> increase cAMP -> PKA -> insertion of aquaporins
- inner medullary collecting duct: increase urea absorption thus aid in corticopapillary osmotic gradient

* also stimulate V1 receptor in vasculature: vasoconstriction
reabsorption rate
reabsorption rate = filtered load - excretion rate
How much Na is reabsorbed in the collecting duct?
3%
What can cause this?

- increased anion gap
diabetic acidosis
- anion gap = [Na+] - [Cl-] - [HCO3]
What occurs during syndrome of inappropriate antidiuretic hormone (SIADH)?
Hyposmotic Volume Expansion:

Too much ADH leads to too much water reabsorption, and the excess water is retained and distributed throughout the total body water. The volume of water that is added to the ECF and ICF is in direct proportion to their original volumes. ECF and ICF volumes will be increased, and ECF and ICF osmolarities will be decreased.
What is the change in the following with increased plasma protein?

- GFR
- RPF
- FF
- GFR: decrease
- RPF: no change
- FF: decrease

Caused by increased Ogc
where in kidney is EPO released from
endo cells of peritubular capillaries
What stimulate ADH release from posterior pituitary gland? what inhibits it?
Stimulate ADH:
- stimulation of osmoreceptors in the wall of 3rd ventricle

Inhibition of ADH:
- stimulation of volume receptors in atria
- caffeine
- alcohol
secretion rate
secretion rate = excretion rate - filtered load
How much filtered water is reabsorbed in the proximal tubule?
67%
What can cause this?

- normal anion gap
HCL ingestion
- anion gap = [Na+] - [Cl-] - [HCO3]
What happens to the plasma protein concentration and hematocrit during hyposmotic volume expansion? Why?
Plasma protein concentration is decreased by dilution. However, the hematocrit is unchanged as a result of two offsetting effects: the concentration of RBCs decreases due to dilation, but RBC volume increases because water shifts into the cells.
What is the change in the following with uretral stone?

- GFR
- RPF
- FF
- GFR: decrease
- RPF: no change
- FF: decrease

Caused by increased Pps
what enzyme converts 25-OH vitamin D to its active form?
1-alpha hydroxylase
Where is ADH released?
posterior pituitary gland
- neucleus supraopticus
- nucleus paraventricularis
where is glucose reabsorbed in nephron? what kind of transporter?
proximal tubula

Na+ glucose cotransport
What is glomerulotubular balance?
The same FRACTION of solute is reabsorbed at all times, for all concentrations (that is, for any concentration, X% is always reabsorbed)
How does kidney compensate for respiratory acidosis?
- increase in HCO3 absorption: type A intercalated cell
- increase in H+ excretion: titratable acid, ammonium
What is the definition of renal clearance?
Renal clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time.
What is the change in the following with ACE inhibitors?

- GFR
- RPF
- FF
ACE inhibitors dilate efferent arteriole
- GFR: increase then decrease
- RPF: no change
- FF: increase
what do JG cells do?
secrete renin in response to low renal blood pressure
What happens when there is 1% reduction in plasma osmolarity?
complete ADH block
Tm for a carrier (1)

Tm of glucose = (2)
1 =reabsorptive rate at which carriers are saturated
2 = 350 mg/dL
What part of the nephron is the site of glomerulotubular balance?
The proximal tubule
How does kidney compensate for respiratory alkalosis?
- spill over HCO3-: type B intercalated cell
What is the equation for renal clearance?
Cx = [U]xV/Px

Cx = clearance of X. Units are mL/min
[U]x = urine concentration of X
Px = plasma concentration of X
what does the macula densa do?
senses the amt of Na
What happens when there is 1-2% increase in plasma osmolarity?
maximum antidiuresis
threshold (1)

threshold of glucose (2)
1 = plasma conc. at which substance first appears in urine
2 = 250 mg/dL
What does it mean for proximal tubule Na and water reabsorption to be isosmotic?
The reabsorption of both Na and water in this region are exactly proportional, so osmolarity is maintained (both Na and water have TF/P ratios of 1.0 here)
Name some etiology of metabolic acidosis.
- diabetic ketoacidosis: increased production of acids
- aspirin overdose: ingestion of acids
- secretory diarrhea: loss of alkaline fluid
- renal failure: inability to excrete fixed acids
Renal clearance is the ratio of ___________ to ____________.
Renal clearance is the ratio of urinary excretion ([U]x*V) to plasma concentration.
where is the macula densa
part of the DCT
What happens when plasma osmolarity is > 294 mOsM?
exceeded thirst threshold, drink water
splay
region between threshold and Tm
--> represents excretion of glucose in urine before saturation of reabsorption (Tm) is full achieved

for glucose = between 250 and 350
How is Na reabsorbed in the early proximal tubule?
Na-Glucose cotransporter
Na-solute cotransport with various solutes
Na-H symporter
Name some etiology of metabolic alkalosis.
- lye poisoning: ingestion of alkali
- vomiting: loss of gastric juice
- volume depletion: retention of HCO3-.
Which substance is freely filtered across the glomerular capillaries, but not reabsorbed or secreted?
Inulin, which is used to determine the glomerular filtration rate (GFR).
what do PGs do to the kidney
vasodilate the afferent arterioles (that's why NSAIDS can --> ARF by inhibiting PG)
Equation for osmotic clearance.
Cosm = UFR x (U/P)osm
where does secretion of PAH occur?
proximal tubule
How and where do carbonic anhydrase inhibitors work?
By inhibiting CA, the reabsorption of HCO3 is decreased. These inhibitors (like acetazolamide) act in the proximal tubule, where H is secreted via Na-H antiport
What can cause this?

- respiratory acidosis
- lactic acidosis
severe asthma

- respiratory acidosis: insufficient expiration of CO2
- lactic acidosis: hypoxia
What is the formula for Clearance Ratio?
Clearance ratio = Cx/Cinulin
what effect does aldosterone have on H
more H is secreted
Equation for free H2O clearance.
C(H2O) = UFR - Cosm = UFR x (1 - (U/P)osm)
which form of weak acid can back diffuse from urine to blood?
HA - lipid soluble, uncharged
How is Na reabsorbed in the late proximal tubule?
Na-Cl symport
What happens in acid/base balance when in altitude region?
lack of O2 -> hyperventilate -> hypocapnea -> respiratory alkalosis -> decrease HCO3 absorption (kidney response) -> metabolic acidosis
What does Cx/Cinulin = 1.0 mean?
The clearance of substance x equals the clearance of inulin, and is neither reabsorbed or secreted.
where does aldosterone work in kidney?
DCT
Compare H2O clearance during diuresis and antidiuresis.

- % reabsorption
- urine osmolarity
- UFR
- Cosm
- C(H2O))
Diuresis (absence of ADH)
- 1% reabsorption in distal tubule
- 4% reabsorption in collecting duct
- urine osmolarity: 50-60 mOsM
- UFR: 12mL/min
- Cosm: 2.4 mL/min
- C(H2O)): 9.6 mL/min

Antidiuresis (presence of ADH)
- 10% reabsorption in distal tubule
- 4.6% reabsorption in collecting duct
- urine osmolarity: 1200 mOsM
- UFR: 0.5mL/min
- Cosm: 12 mL/min
- C(H2O)): -1.5 mL/min
which form of weak base can back-diffuse from urine to blood?
B form - uncharged, lipid soluble
How does extracellular fluid volume influence Na reabsorption?
If ECFV decreases, reabsorption is increased
If ECFV increases, reabsorption is decreased
T/F: Metabolic acidosis may persist 1-2 days after descending from a high altitude region.
T.
What does Cx/Cinulin < 1.0 mean?

What substances show this property?
The clearance of x is lower than inulin. It is either not filtered, or it is reabsorbed.

Albumin, Na+, Cl-, HCO3-, phosphate, urea, glucose, and amino acids.
where does PTH work?
PCT to decrease PO4 reabsorption
DCT to increase Ca reabsorption
stimulates 1-alpha hydroxylase in PCT
When is C(H2O) zero?
under treatment with loop diuretics
- no diluting effect
- no role in setting up corticopapillary gradient.
TF/ P ratio = 1.0
no reabsorption of substance (or reabsorption exactly proportional to water)
How is Na reabsorbed in the thick ascending limb of the loop of Henle?
Na-K-2Cl cotransporter
What does Cx/Cinulin > 1.0 mean?

What substances show this property?
The clearance of x is higher than inulin. It must be secreted.

Organic acids and bases, and sometimes K+.
where is ACE released from?
lung
where does TF/P = 1,0?
Bowman's space
What inhibits the Na-K-2Cl cotransporter?
Loop diuretics such as furosemide, ethacrynic acid, and bumetanide
What percentage of cardiac output do the kidneys receive?
25% of cardiac output.
if TF/ P is less than 1.0
reabsorption of substance has been greater than reabsorption of water

--> conc. in tubular fluid is less than plasma
Is the thick ascending limb of the loop of Henle permeable or impermeable to water?
Impermeable, so in this region, NaCl is reabsorbed without water. Therefore, this segment is known as the diluting segment.
What effect do the sympathetic nervous system and circulating catecholamines have on RBF and GFR? Why?
There is a decrease in both RBF and GFR.
Sympathetic nervous system produces vasoconstriction by activation of α1 receptors. α1 receptors are found on both afferent and efferent arterioles, but are much more prevalent on afferent arterioles.
if TF/P is greater than 1.0
either reabsorption has been less than water OR there has been secretion of substance
What sort of potential difference is observed in the thick ascending limb of the loop of Henle?
Lumen-positive
What effect does Angiotensin II have on RBF and GFR?
Angiotensin II vasoconstricts both arterioles. This causes a decrease in RBF.
However, efferent arterioles are more sensitive to angiotensin II. Thus, at low levels of angiotensin II, there is an increase in GFR. A high level of angiotensin II produces a decrease in GFR.
Na+ reabsorption in PCT
- percent?
- along with?
1 = 67%
2 = H20 - isosmotic
How is Na reabsorbed in the early distal tubule?
Na-Cl cotransporter
What effect do prostaglandins have?
Prostaglandins, produced locally in the kidneys, cause vasodilation of both afferent and efferent arterioles. This increases RBF, and opposes the effects of the sympathetic NS and angiotensin II.
Na+ reabsorption in early PCT
- transporters? (2)
1 = Na+ cotransport with glucose, amino acids, phosphate and lactate
2 = Na+ and H+ exchanger
What inhibits the Na-Cl cotransporter of the early distal tubule?
Thiazide diuretics
What effect does dopamine have on renal arterioles?
At low levels, Dopamine dilates renal arterioles, and has a protective (vasodilatory) effect on blood flow.
Na+ reabsorption in late PCT
Na+ reabsorbed with Cl-
Is the early distal tubule permeable or impermeable to water?
Impermeable
How can renal plasma flow (RPF) be estimated?
RPF can be estimated from the clearance of an organic acid para-aminohippuric acid (PAH).
carbonic anhydrase inhibitors
ex. acetazolaminde
- diuretics
- act on early PT
- inhibit reabsorption of filtered HCO3-
What do the principal cells of the late distal tubule and collecting duct do?
Reabsorb Na and water
Secrete K
What is the formula for Effective RPF?
Effective RPF = [U]PAH x V/[P]PAH = Clearance of PAH

Effective RPF is in ml/min
ECF volume contraction (1) reabsorption; ECF volume expansion (2) proximal tubular reabsorption
1 = increases reabsorption
2 = decreases reabsorption
What effect does aldosterone have upon Na and K transport?
Increases Na reabsorption and K secretion in the late distal tubule and collecting duct
What is the difference between effective RPF and true RPF?
Effective RPF underestimates true RPF by ~10%. This is because we assume the concentration of PAH in the renal vein is zero, when in reality it is nearly zero.
Na+ reabsorption in Thick Ascending Loop of Henle
- percent? (1)
- transporter? (2)
1 = 25%
2 = Na+ K+ 2Cl- transporter
What effect does ADH have upon water permeability?
It increases water permeability in the collecting duct by inducing the insertion of aquaporin 2 into the apical membrane. In the absence of ADH, the principal cells of the collecting duct are virtually impermeable to water.
What is the formula for RBF?
RBF = RPF/(1-Hematocrit)
loop diuretics inhibit?
Na+/K+/2Cl- cotransporter in TAL

ex. furosemide
ethacrynic acid
bumetanide
What are K-sparing diuretics?
Spironolactone, tiramterene, amiloride -- these decrease K secretion
What constitutes the most significant barrier of the glomerular capillary?
The basement membrane and its three layers: lamina rara interna, lamina densa, and lamina rara externa. The basement membrane does not permit filtration of plasma proteins, unlike the endothelial cell layer.
What part of nephron is impermeable to water?
thick ascending limb of loop of henle
How is Na reabsorbed in the late distal tubule and collecting duct?
Amiloride-sensitive Na channels
What is the Starling Equation?
GFR = Kf [(Pgc - Pbs) - πgc]

Kf = Hydraulic conductance or filtration coefficient

Pgc = Hydrostatic pressure in glomerular capillary

Pbs = Hydrostatic pressure in Bowman's space

πgc = Oncotic pressure in glomerular capillary
What is Kf (filtration coefficient)? What are the two factors that contribute to Kf?
The filtration coefficient is the water permeability or hydraulic conductance of the glomerular capillary wall.

The two factors that contribute to Kf are the water permeability per unit of surface area and the total surface area.
Na+ reabsorption in distal tubule and collecting duct
- percent? (1)
- transporters? (2)
1 = 8%
2 - Na+ Cl- co transport
What do the intercalated cells of the late distal tubule and collecting duct do?
Secrete H via an H-ATPase that is induced by aldosterone
Reabsorb K via an H-K-ATPase
What other substances, besides inulin, can estimate GFR?
Creatinine is the closest substance. It is freely filtered, but is also secreted to a small extent. The clearance of creatinine slightly overestimates the GFR.

Blood urea nitrogen (BUN) and serum creatinine concentration are also used to estimate GFR.
thiazide diuretics inhibit?
Na+ Cl- cotransporter in distal tubule/collecting duct
What body compartment is the majority of K found in?
The intracellular fluid
What is the filtration fraction? What is the normal value?
Filtration fraction = GFR/RPF

The normal value is about 0.20 or 20%.
principal cells of late distal tubule/CD
- reabsorb? (1)
- secrete? (2)
- function increased by what hormone? (3)
1 = Na+ and H20
2 = secrete K+
3 = aldosterone
How do K shifts contribute to hypo/hyperkalemia?
A shift of K OUT of the cells causes hyperkalemia
A shift of K INTO the cells causes hypokalemia
What is the formula for filtered load?
Filtered Load = GFR* [P]x
ADH acts on (1) cells in (2) nephron segment to increase (3)
1 = principal cells
2 = late DT and CD
3 = water permeability
Is K filtered by the nephron? Secreted? Reabsorbed?
Yes to all three
What is the formula for excretion rate?
Excretion rate = V x [U]x
K+ sparing diuretics
ex. (1)
- function? (2)
1 = spironolactone, triamterene, amiloride
2 = decrease K+ secretion in principal cells of late DT and CD
How do we achieve K balance?
When urinary excretion is exactly equal to dietary intake
What is the formula for Reabsorption of Secretion rate?
Reabsorption or Secretion Rate = Filtered load - Excretion Rate
alpha-intercalated cells
- location? (1)
- function? (2)
1 = late DT and CD
2 = secreted H+ and reabsorb K+ by an H+/K+ ATPase
What are some causes of hyperkalemia (K shift out of cells)?
Insulin deficiency
B-adrenergic antagonists
Acidosis
Hyperosmolarity
Na-K ATPase inhibitors
Exercise
Cell lysis
At what plasma glucose concentrations does glucose start to be excreted in the urine?
What is this point called?
At plasma glucose concentrations above 200 mg/dL.

This is called threshold.
Causes of Hyperkalemia?
insulin deficiency
B-adrenergic antagonists
acidosis
hyperosmolarity
inhibitors of Na+/K+ pump
exercise
cell lysis
What are some causes of hypokalemia (K shift into cells)?
Insulin
B-adrenergic agonists
Alkalosis
Hyposmolarity
What is Tm?
Tm (transport maximum) is the plasma glucose concentration when all glucose carriers are saturated and cannot reabsorb any more. This occurs at plasma concentrations above 350 mg/dL.
Causes of Hypokalemia?
insulin
B-adrenergic agonists
alkalosis
hypoosmolarity
How much can K excretion vary?
A lot! 1-110% of filtered load, depending upon dietary intake, aldosterone levels, and acid-base status
What is splay?
Splay is the difference between threshold and transport maximum (Tm).
Causes of Hypokalemia?
insulin
B-adrenergic agonists
alkalosis
hypoosmolarity
K+ reabsorption
- PCT (1)
- TAL of henle (2)
- a-intercalated cells (3)
1 = 67%
2 = 20% (Na+ K+ 2Cl- cotransporter)
3 = H+K+ ATPase
How much K is reabsorbed in the proximal tubule?
67%
What are some causes of glucosuria?
- In diabetes mellitus, the filtered load of glucose exceeds the reabsorptive capacity (plasma [glucose] is above Tm)

- During pregnancy, GFR is increased, which increases the filtered load of glucose to the extent that it may exceed the reabsorptive capacity.

- Congenital abnormalities of the Na+-glucose cotransporter lead to decreases in Tm.
K+ reabsorption
- PCT (1)
- TAL of henle (2)
- a-intercalated cells (3)
1 = 67%
2 = 20% (Na+ K+ 2Cl- cotransporter)
3 = H+K+ ATPase
K+ secretion occurs in (1) and is mediated by what transporter? (2)
1 = principal cells of distal tubule
2 = passively secreted down electrochemical gradient
How much K is reabsorbed in the thick ascending limb of the loop of Henle?
20%
How is urea reabsorbed?
Urea is reabsorbed by simple diffusion, in most segments of the nephron.
Causes of Increased Distal K+ secretion? (6)
high K+ diet
hyperaldosteronism
alkalosis
thiazide diuretics
loop diuretics
luminal anions
K+ secretion occurs in (1) and is mediated by what transporter? (2)
1 = principal cells of distal tubule
2 = passively secreted down electrochemical gradient
How is K reabsorbed in the thick ascending limb of the loop of Henle?
The Na-K-2Cl cotransporter
What percentage of PAH is filtered across the glomerular capillaries?
<10%. Ninety percent of the PAH in blood is bound to plasma proteins. Only the unbound portion is filterable. The filtered load increases linearly as the unbound concentration of PAH increases.
Causes of Decreased Distal K+ secretion? (4)
low K+ diet
acidosis
hypoaldosteronism
K+ sparing diuretics
How do the distal tubule and collecting duct handle K transport?
They either reabsorb OR secrete it, depending upon dietary intake
Causes of Increased Distal K+ secretion? (6)
high K+ diet
hyperaldosteronism
alkalosis
thiazide diuretics
loop diuretics
luminal anions
What happens when PAH carriers reach Tm?
When Tm is reached, there can be no further increase in the secretion rate of PAH.
How is K reabsorbed in the distal tubule and collecting duct?
H-K ATPase in the apical membrane of alpha intercalated cells
Causes of Decreased Distal K+ secretion? (4)
low K+ diet
acidosis
hypoaldosteronism
K+ sparing diuretics
What drug uses the PAH transporter for secretion?
Penicillin.
Under what conditions is K reabsorbed in the distal tubule and collecting duct?
Low K diet (K depletion). It is under these conditions that K excretion is 1% of filtered load
Where and what percent is urea absorbed?
50% of urea is reabsorbed in the proximal tubule
At what urine pH does the HA form of a weak acid predominate?
Why is there more "back-diffusion" from urine into blood at this ph?
At acidic urine pH.

There is more "back-diffusion" from urine into blood because the uncharged HA form can diffuse across the cells. The A- form of a weak acid cannot diffuse.
How is K secreted in the distal tubule?
The Na-K ATPase imports K into the cell across the basolateral membrane
K channels export K across the apical membrane into the lumen
ADH increases the permeability to urea in (1)
inner medullary collecting ducts
At what urine pH does the A- form of a weak acid predominate?
At alkaline urine pH.

There is less "back-diffusion" from urine to blood, and excretion of the acid is increased.
What drives K transport in the distal tubule?
Chemical and electrical driving forces
Things that increase intracellular K (or decrease luminal K) will increase the driving force for K secretion
low urine flow rate, (1) urea reabsorption and (2) urea excretion; high urine flow rate, (3) urea reabsorption and (4) urea excretion
1 = greater
2 = decreased
3 = decreased
4 = increased
What does [TF/P]x = 1.0 indicate?
The [TF/P]x ratio compares the concentration of a substance in tubular fluid to its concentration in systemic plasma.

When [TF/P]x = 1.0, it means that the concentrations are equal. This can mean a few things:
- The ratio was measured in Bowman's space for a freely filtered substance (and no reabsorption or secretion occurred yet)
- Reabsorption of the solute has occurred, but reabsorption of water has occurred in exactly the same proportion.
What specific things increase distal K secretion?
High dietary K (increases intracellular K)
Aldosterone (stimulation of the Na-K ATPase)
Alkalosis
Thiazide and loop diuretics
Luminal anions
where is phosphate reabsorbed? (1)
- how much of it is reabsorbed? (2)
- transporter? (3)
1 = proximal tubule
2 = 85%
3 = Na+ phosphate cotransport
What does [TF/P]x < 1.0 indicate?
The reabsorption of the solute must have been greater than reabsorption of water.
What affect does hyperaldosteronism have upon K secretion?
It increases K secretion and causes hypokalemia
What hormone inhibits phosphate reabsorption?
PTH
- causes phosphaturia and increased urinary cAMP
What does [TF/P]x > 1.0 indicate?
There are two possible meanings:
- There has been a net reabsorption of the solute, but solute reabsorption has been less than water reabsorption.
- There has been a net secretion of the solute into tubular fluid.
What affect does hypoaldosteronism have upon K secretion?
It decreases K secretion and causes hyperkalemia. The Na-K ATPase is no longer stimulated to remove K from the interstitium.
Which diuretics increase Ca2+ excretion (1) and which decrease Ca2+ excretion (2)?
1 = loop diuretics (furosemide)
2 = thiazide diuretics
How can water reabsorption be calculated?
Water reabsorption can be calculated from the value of [TF/P]inulin.
What effect does pH have upon K secretion?
Alkalosis increases K secretion
Acidosis decreases K secretion
H and K are effectively exchanged for each other across the basolateral membrane, so if the blood has excess H (acidosis), that H displaces K inside the cell such that K is no longer available for secretion
Mg2+ and Ca2+ compete for reabsorption in the (1)
1 = thick ascending limb
What equation corrects for water reabsorption?
What would a value of 0.3 mean?
[TF/P]x/[TF/P]inulin is a double ratio that corrects for water reabsorption.
A value of 0.3 means that 30% of the filtered load of the solute remains in the tubular fluid, or 70% has been reabsorbed.
How do thiazide and loop diuretics affect K secretion?
They increase flow rate through the distal tubule, which dilutes the K concentration within the lumen and creates a driving force for K secretion
presence of ADH (1) the size of corticopapillary osmotic gradient by stimulating reabsorption of (2) in (3)
1 = increases
2 = NaCl
3 = thick ascending limb
presence of ADH (1) the size of corticopapillary osmotic gradient by stimulating reabsorption of (2) in (3)
1 = increases
2 = NaCl
3 = thick ascending limb
The reabsorption of which ion is the most important? Why?
The reabsorption of sodium (Na+) is the most importnat function the kidney has. Sodium is the major cation of the ECF compartment. The amount of Na+ in ECF determines the ECF volume, which in turn determines plasma volume, blood volume, and blood pressure.
How do K-sparing diuretics affect K secretion?
They decrease K secretion, and can cause hyperkalemia if not used in conjunction with thiazide or loop diuretics (which would reduce urinary K loss)
osmolarity of final urine = (1)
1200 mOsm/L
osmolarity of final urine = (1)
1200 mOsm/L
What percentage of Na+ reabsorption occurs in the proximal convoluted tubule?
67% (two-thirds) of the filtered load is reabsorbed. It is isosmotic reabsorption.
How do luminal anions affect K secretion?
Excess anions in the lumen increase the negativity of the lumen, which favors K secretion
What area of nephron does urine get concentrated? (1)
- due to presence of (2) and (3)
1 = collecting ducts
2 = ADH which increases H20 permeability AND corticopapillary gradient
What area of nephron does urine get concentrated? (1)
- due to presence of (2) and (3)
1 = collecting ducts
2 = ADH which increases H20 permeability AND corticopapillary gradient
Which part of the nephron reabsorbs 25% of the filtered load of Na+?
Thick ascending limb of the loop of Henle. This region is impermeable to water.
Where in the nephron is urea reabsorbed?
50% is passively reabsorbed in the proximal tubule
The rest is reabsorbed in the inner medullary collecting duct upon ADH stimulation
corticopapillary osmotic gradient is (1) without ADH
decreased
corticopapillary osmotic gradient is (1) without ADH
decreased
Which portion of the nephron is responsible for Na+ balance?
The late distal convoluted tubule and collecting ducts, which also reabsorb the final 3% of the filtered load.
How does ADH affect urea reabsorption?
It increases the permeability of the inner medullary collecting duct
free water clearance
estimates the ability to concentrate or dilute urine
free water clearance
estimates the ability to concentrate or dilute urine
Which portion of the nephron does aldosterone act on?
The late distal convoluted tubule and collecting ducts.
How does urea contribute to the corticomedullary osmotic gradient?
ADH causes urea to be reabsorbed from the collecting duct to the interstitium, which creates an osmotic gradient that increases as you go deeper into the medulla
Positive C H20 (free water clearance)
- low ADH (no ADH)
- urine is hypoosmotic to plasma
- high water intake, central diabetes insipidus, nephrogenic diabetes insipidus
In the early proximal tubule, what is Na+ reabsorbed with?
In the late proximal tubule?
In the early proximal tubule, Na+ is reabsorbed primarily with HCO3- and organic solutes such as glucose and amino acids.
In the late proximal tubule, Na+ is reabsorbed primarily with Cl-.
How does urine flow rate affect urea excretion?
At low flow rates, more urea is reabsorbed and less is excreted, whereas at high flow rates, urea tends to be excreted
Negative C H20 (free water clearance)
high ADH
- urine is hyperosmotic to plasma
- water deprivation or SIADH
What are the cotransport mechanisms in the luminal membrane of the early proximal tubule?
Na+-glucose (SGLT), Na+-amino acid, Na+-phosphate, Na+-lactate, and Na+-citrate.
Where is phosphate reabsorbed (and how much)?
Proximal tubule; 85%
The remaining 15% is excreted in the urine
Ch20 = ZERO
produced with loop diuretics
-> inhibit both dilution in TAL and production of corticopapillary osmotic gradient which prevents concentration in CD
What is the countertransport or exchange mechanism in the luminal membrane of the early proximal tubule?
Na+-H+ exchanger.
How is phosphate reabsorbed in the proximal tubule?
Na-phosphate cotransport
volatile acid
CO2
--> produced by aerobic metabolism of cells
What two exchangers exist in the late proximal tubule?
Na+-H+ exchanger and Cl-formate anion exchanger, driven by the high tubular fluid Cl- concentration.
How does PTH affect phosphate reabsorption?
It inhibits it by generating cAMP and inhibiting Na-phosphate cotransport. Since phosphate reabsorption is decreased, PTH causes phosphaturia
non volatile acid
aka. fixed acids
- sulfuric acid
- phosphoric acid
- ketoacids
- lactic acid
- salicylic acid
If there is an increase in GFR (and therefore an increase in filtered load of Na+), how does the nephron maintain glomerulotubular balance?
Glomerulotubular balance ensures that a constant fraction of the filtered load is reabsorbed by the proximal tubule. When the GFR is increased, there is more fluid filtered. This leads to an increase in πc (oncotic pressure of peritubular capillary), which leads to increased reabsorption.
Where is Ca reabsorbed (and how much)?
Proximal tubule and thick ascending limb of the loop of Henle (90%)
major extracellular buffer
HCO3-
During infusion of isotonic NaCl (ECF volume expansion), what is the mechanism that maintains glomerulotubular balance?
An increase in ECF volume decreases the plasma protein concentration, and increases the capillary hydrostatic pressure. Both of the changes in these forces lead to a decrease in fractional reabsorption of isosmotic fluid in the proximal tubule.
How much of the plasma Ca is filtered across the glomerular membrane?
60%
minor extracellular buffer
phosphate
During diarrhea or vomiting (ECF volume contraction), what are two mechanisms that maintain glomerulotubular balance?
- A decrease in ECF volume increases plasma protein concentration, and decreases the capillary hydrostatic pressure. This leads to an increase in fractional reabsorption of isosmotic fluid.
- Decrease in blood volume and arterial pressure activates the renin-angiotensin-aldosterone system. Angiotensin II stimulates Na+-H+ exchange in the proximal tubule, and thereby stimulates reabsorption of Na+, HCO3-, and water.
How do loop diuretics (eg furosemide) affect Ca excretion?
They increase urinary Ca excretion because Na and Ca reabsorption in the loop of Henle are linked. Therefore, if the volume lost by the diuretic is replaced, loop diuretics can be used to treat hypercalcemia
most important urinary buffer
phosphate
What is the result of activation of renin-angiotensin system during ECF volume contraction?
Because angiotensin II mechanism specifically stimulates HCO3- reabsorption (along with Na+ and water), ECF volume contraction causes contraction alkalosis (metabolic alkalosis secondary to volume contraction).
How does PTH affect Ca transport?
It increases reabsorption in the distal tubule
intracellular buffers (2)
organic phosphates
proteins
What is the thin descending limb permeable to?
The thin descending limb is permeable to water and small solutes such as NaCl and urea.
How do thiazide diuretics affect Ca transport?
They increase reabsorption in the distal tubule, so they can be used to treat hypercalciuria
major intracellular buffer
hemoglobin (deoxy is better than oxy)
What is the thin ascending limb permeable/impermeable to?
The thin ascending limb is permeable to NaCl and impermeable to water.
Where in the nephron is Mg reabsorbed?
Hahaha! Pretty much everywhere -- proximal tubule, thick ascending limb, distal tubule
Where does reabsorption of filtered HCO3- occur?
proximal tubule
What percentage of filtered Na+ is reabsorbed by the thick ascending limb?
25%, although the thick ascending limb (and distal tubule) are load-dependent (the more Na+ delivered, the more it reabsorbs).
How do calcium imbalance disorders affect Mg transport?
In the thick ascending limb, Mg and Ca compete for reabsorption, so if you are hypercalcemic, Mg reabsorption is inhibited and Mg is excreted (likewise, hypermagnesemia increases Ca excretion by inhibiting Ca reabsorption)
increases in filtered load for HCO3- result in (1) rates of HCO3- reabsorption until person develops (2) and then HCO3- is (3)
1 = increased
2 = metabolic alkalosis
3 = excreted
What is the mechanism for reabsorption of Na+ in the thick ascending limb?
The luminal membrane contains a Na+-K+-2Cl- cotransporter.
What hormone is responsible for the production of concentrated urine?
ADH
increased PCO2 = (1) HCO3- reabsorption

- basis for renal compensation of (2)
1 = increased
2 = respiratory acidosis
Why is the Na-K-2Cl cotransporter considered electrogenic? What happens because of this?
The cotransporter transports all three ions (Na, K, and Cl) into the cell of the thick ascending limb; Na is extruded from the cell by the Na-K ATPase, and Cl and K diffuse through channels in the basolateral membrane.

A portion of the K, however, diffuses back into the lumen. Thus, the cotransporter brings slightly more negative than positive charge into the cell. This results in a lumen-positive potential difference across the cells of the thick ascending limb. This is the driving force for the reabsorption of divalent cations such as Ca and Mg.
When is ADH produced?
Water deprivation
Hemorrhage (depleted ECFV)
Increased plasma osmolarity
ECF volume expansion = (1) HCO3- reabsorption
ECF volume contraction = (2) HCO3- reabsorption
1 = decreased
2 = increased
How do the loop diuretics work?
Look diuretics are organic acids that are related to PAH. At physiologic pH, the loop diuretics are anions that attach to the Cl- binding site of the Na-K-2Cl cotransporter.
What hormone is responsible for the generation of the corticomedullary osmotic gradient?
ADH
angiotensin II stimulates (1) and thus (2) HCO3- reabsorption which contributes to (3) seen with ECF volume contraction
1 = Na+ H+ exchange
2 = increases
3 = contraction alkalosis
What is the [TF/P]na and [TF/P]osm for the fluid that leaves the thick ascending limb?
[TF/P]na < 1.0
[TF/P]osm < 1.0
What is the corticomedullary osmotic gradient?
As you go from the cortex to the medulla, the osmolarity increases from 300 mOsm/L to 1200 mOsm/L. It is established by countercurrent multiplication and urea recycling, and is maintained by countercurrent exchange in the vasa recta
aldosterone increases (1) on PT luminal mb which increases (2) of H+ and reabsorption of (3)
1 = H+ ATPase
2 = secretion
3 = reabsorption of HCO3-
What is the mechanism of reabsorption of filtered Na in the early distal tubule?
The mechanism is an Na-Cl cotransporter in the luminal membrane.
What compounds create the corticomedullary osmotic gradient?
NaCl and urea
amount of H+ excreted as NH4+ depends on (1) and (2)
1 = amount of NH3 synthesized by renal cells
2 = urine pH
How do thiazide diuretics work?
The thiazides are organic acids, which are anions at physiologic pH. They bind to the Cl site of the Na-Cl cotransporter and prevent it from cycling.
How does ADH affect NaCl reabsorption?
It increases reabsorption in the thick ascending limb of the loop of Henle, which augments the corticomedullary osmotic gradient
hyperkalemia (1) NH3 synthesis resulting in (2) H+ excretion as NH4+
1 = inhibits
2 = decreased
What are the two major cell types of the late distal tubule and collecting duct? What do they do?
Principal cells are involved in Na reabsorption, K secretion, and water reabsorption.
α-Intercalated cells are involved in K reabsorption and H secretion.
What role do the vasa recta play in the corticomedullary osmotic gradient?
They act as osmotic exchangers, meaning they osmotically equilibrate with the interstitial fluid of the medulla
metabolic acidosis
- increase in arterial (1)
- decrease in arterial (2) (buffer)
- respiratory compensation is (3)
1 = H+ conc.
2 = HCO3- conc.
3 = hyperventilation
What is the mechanism of Na reabsorption in the principal cells?
The luminal membrane of the principal cells contain Na channels, through which Na diffuses down its electrochemical gradient.
How does ADH rectify water deprivation?
Water deprivation
Increased plasma osmolarity
Stimulation of hypothalamus osmoreceptors
Secretion of ADH from anterior pituitary
Increased water permeability of late distal tubule and collecting duct
Increased water reabsorption
Increased urine concentration
Decreased plasma osmolarity
compensation of metabolic acidosis
- increased excretion of (1)
- increased reabsorption of (2)
- adaptive increase in (3)
1 = H+ as titratable acid and NH4+
2 = HCO3-
3 = NH3 synthesis
What does aldosterone do to increase the reabsorption of Na?
The steroid hormone, which is able to diffuse into the cell and is transferred to the nucleus, directs the synthesis of specific mRNAs. These mRNAs then direct the synthesis of new proteins that are involved in Na reabsorption by the principal cells, which include the Na channel itself, Na-K ATPase, and enzymes of the citric acid cycle.
How does the osmolarity of glomerular filtrate compare to that of plasma?
They are equal (300 mOsm/L)
serum anion gap
[Na+] - ( [Cl-] + [HCO3-] )

represents unmeasured anions in serum including phosphate, citrate, sulfate and protein
What are the renal mechanisms that regulate Na excretion?
Sympathetic nerve activity
Atriopeptin (ANP)
Starling forces in peritubular capillaries
Renin-angiotensin-aldosterone system
What is the TF/Posm along the length of the nephron?
Proximal tubule: 1
Thick ascending limb: < 1 (because of dilution)
Late distal tubule: 1
Collecting duct: > 1 in the presence of ADH (because of water reabsorption), < 1 in the absence of ADH
normal value of serum anion gap
12mEq/L
How does Sympathetic nerve activity regulate Na balance/excretion?
Sympathetic activity is activated by the baroreceptor mechanism in response to a decrease in arterial pressure. It causes vasoconstriction of afferent arterioles and increased proximal tubule Na reabsorption.
What is the water permeability in the various segments of the nephron?
Proximal tubule: permeable
Thick ascending limb: impermeable
Early distal tubule: impermeable
Late distal tubule: permeable in response to ADH
Collecting duct: permeable in response to ADH
serum anion gap is (1) if the conc. of an unmeasured anion is (2) to replace HCO3-
1 = increased
2 = increased
How does atriopeptin (ANP) regulate Na excretion?
ANP is secreted by the atria in response to an increase in ECF volume. It causes vasodilation of afferent arterioles, vasoconstriction of efferent arterioles, increased GFR, and decreased Na reabsorption in the late distal tubule and collecting ducts.
How does ADH alter the magnitude of the corticomedullary osmotic gradient?
Increases it
serum anion gap is (1) if the conc. of Cl- is (2) to replace HCO3-
1 = normal
2 = increased

aka. hyperchloremic metabolic acidosis
How does the renin-angiotensin-aldosterone system regulate Na excretion?
The system is activated in response to decreased arterial pressure. Angiotensin II stimulates Na reabsorption in the proximal tubule, and aldosterone stimulates Na reabsorption in the late distal tubule and collecting ducts.
What is free-water clearance (Ch2o)?
It is used to estimate the kidney's ability to concentrate or dilute the urine. Free water is the solute-free water produced in the diluting segments where NaCl is reabsorbed and water is left behind in the lumen
metabolic alkalosis
- decrease in arterial (1)
- increase in arterial (2)
- respiratory compensation with (3)
1 = H+ conc.
2 = HCO3- conc.
3 = hypoventilation
What are 5 things that cause K to shift into cells, and cause hypokalemia?
Insulin
α-Adrenergic antagonists
β2-Adrenergic agonists
Alkalosis
Hyposmolarity
How does ADH affect the sign of Ch2o?
In the absence of ADH, Ch2o is POSITIVE (solute-free water is excreted)
In the presence of ADH, Ch2o is NEGATIVE (solute-free water is reabsorbed in the late distal tubule and collecting duct)
What happens when metabolic alkalosis is accompanied by ECF volume contraction?
reabsorption of HCO3- increases, worsening the metabolic alkalosis (contraction alkalosis)
What are 7 things that cause K to shift out of cells, and cause hyperkalemia?
Insulin deficiency
α-Adrenergic agonists
β2-Adrenergic antagonists
Acidosis
Hyperosmolarity
Cell lysis
Exercise
What is the formula for Ch2o?
Ch2o = urine flow rate x osmolar clearance
respiratory acidosis
- caused by (1)
- increased arterial (2)
- increased arterial (3) and (4)
1 = decrease in respiratory rate and retention of CO2
2 = PCO2
3 = H+ and HCO3-
How does insulin stimulate K uptake into cells?
Insulin increases the activity of Na-K ATPase.
What does it mean when Ch2o is equal to 0?
Urine is isosmotic (isosthenuric) to plasma
compensation for respiratory acidosis
- respiratory comp (1)?
- renal comp (2)
1 = no respiratory compensation
2 = increased excretion of H+ and increased reabsorption of HCO3-
What happens to the K balance during alkalemia? Acidemia?
In alkalemia, the H+ concentration is decreased: H+ leaves the cells and K+ enters the cells, producing hypokalemia.
In acidemia, H+ concentration in blood is increased: H+ enters the cells and K+ leaves the cells, producing hyperkalemia.
How do loop diuretics contribute to a Ch2o of 0?
They inhibit NaCl reabsorption in the thick ascending limb and abolish the corticomedullary osmotic gradient. Therefore, urine cannot be diluted (because the diluting segment is inhibited) or concentrated (because there is no longer an osmotic gradient)
respiratory alkalosis
- caused by (1)
- decreased arterial (2)
- decreased arterial (3) and (4)
1 = increase in respiratory rate and loss of CO2
2 = PCO2
3 = H+ and HCO3-
Why is there generally no K+ shift during respiratory acidosis or respiratory alkalosis?
Because these conditions are caused by a primary disturbance of CO2. CO2 is lipid soluble, so it freely crosses cell membranes and needs no exchange with K+ to preserve electroneutrality.
What does it mean when Ch2o is positive?
Urine is hyposmotic to plasma (low ADH conditions)
This occurs during high water intake (supressed ADH release) and during central and nephrogenic diabetes insipidus (inadequate response to ADH)
compensation for respiratory alkalosis
- respiratory comp?
- renal comp?
1 = no respiratory compensation
2 = decreased excretion of H+ and decreased reabsorption of HCO3-
When would metabolic acidosis not cause a K+ shift?
When the metabolic acidosis is caused by an excess of an organic acid (i.e. lactic acid, ketoacids, or salicylic acid).
What does it mean when Ch2o is negative?
Urine is hyperosmotic to plasma (high ADH conditions)
This happens when you are water-deprived (stimulates ADH release) or overproduce ADH (SIADH)
What are the effects of activating adrenergic receptors?
Activation of β2-adrenergic receptors by β2-agonists (i.e. albuterol) increases the activity of the Na-K ATPase, causing a shift of K into the cells, and possibly producing hypokalemia.

α-Adrenergic receptor activation causes a shift out of cells, and may produce hyperkalemia.
What stimulates PTH secretion?
Decreased plasma Ca
Which cells reabsorb K in the distal tubule and collecting ducts? Which cells secrete K?
What are the mechanisms of the reabsorption and secretion?
α-Intercalated cells reabsorb K through H-K ATPases in the luminal membrane.
Principal cells secrete K via Na-K ATPase and K channels.
What effect does PTH have upon the kidney?
Decreases phosphate reabsorption in the proximal tubule
Increases Ca reabsorption in the distal tubule
What are the three effects that aldosterone has on the secretion of K+?
1. Aldosterone induces the synthesis of more luminal membrane Na channels.
2. Aldosterone increases the quantity of Na-K ATPase
3. Aldosterone increases the number of K+ channels in the luminal membrane.
What stimulates ADH secretion?
Increased plasma osmolarity
Decreased blood volume
How and where is phosphate reabsorbed?
70% of the filtered load is reabsorbed in the proximal convoluted tubule. 15% is reabsorbed in the proximal straight tubule (right before loop of henle). 15% of the filtered load of phosphate is excreted.

Phosphate reabsorption is accomplished by an Na-phosphate cotransporter in the luminal membrane of the proximal tubule cells.
What effect does ADH have upon the kidney?
Increases water permeability of the late distal tubule and collecting duct
How does PTH regulate phosphate excretion?
PTH inhibits the Na-phosphate cotransporter.
What stimulates aldosterone secretion?
Decreased blood volume (via the RAS)
Increased plasma K
How is Ca reabsorbed in the thick ascending limb?
Like Na, 25% of the filtered load of Ca is reabsorbed in the thick ascending limb. Due to the lumen-positive potential difference, Ca is reabsorbed in a paracellular route (between cells).
What effect does aldosterone have upon the kidney?
Increased Na reabsorption in the distal tubule principal cells
Increased K secretion in the distal tubule principal cells
Increased H secretion in the alpha intercalated cells
Where is magnesium reabsorbed the most in the nephron?
Mg2+ is reabsorbed most in the thick ascending limb, where 60% of the filtered load is reabsorbed, in comparison to the proximal tubule, which only reabsorbs 30%.
What stimulates ANP release?
Increased atrial pressure
What is the two step process of countercurrent multiplication?
The single effect, the first step, refers to the function of the thick ascending limb. In the TAL, NaCl is reabsorbed via the Na-K-2Cl cotransporter. Due to the permeabilities of the loop of Henle, the result of the single effect is to decrease the osmolarity of the ascending limb, and increase the osmolarities of the interstitial fluid and descending limb.

The second step is the flow of tubular fluid. Fluid continuously flows through the nephron, and the new fluid that enters the descending limb will have an osmolarity of 300 mOsm/L. The high osmolarity fluid in the descending limb (created by the single effect) is pushed down toward the bend of the loop of Henle.
What effect does ANP have upon the kidneys?
Increases GFR
Decreases Na reabsorption
What are the steps of urea recycling? Where does it occur?
Urea recycling occurs in the inner medulla.
1. In the cortical and outer medullary collecting ducts, ADH increases water permeability, but not for urea. Water is reabsorbed, urea remains behind.

2. Urea concentration increases.

3. In the inner medullary collecting ducts, ADH increases both water and urea permeability.

4. Urea diffuses down its concentration gradient into the interstitial fluid in the inner medulla, where it is added to the corticopapillary osmotic gradient.