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291 Cards in this Set

  • Front
  • Back
how much is total body water (TBW)?
~60% of body weight
what is the diff in TBW in newborns, males, and females?
- highest in newborns and adult males
- lowest in adult females and fatty people
intracellular fluid (ICF)
- 2/3 of TBW
- main cations: K+ and Mg2+
- main anions: Protein and organic phosphates (ATP, ADP, AMP)
extracellular fluid (ECF)
- 1/3 of TBW
- made of interstitial fluid and plasma
- main cation: Na
- main anions: Cl- and HCO3-
Plasma, in relation to ECF
- 1/4 of the ECF --> 1/12 of TBW (1/4 x 1/3)
- main proteins: albumin and globulins
interstitial fluid, in relation to ECF
-3/4 of ECF --> 1/4 of TBW (3/4 x 1/3)
- composition is the same as plasma, except there is little protein (ultrafiltrate of plasma)
60-40-20 rule
- TBW is 60% of body weight
- ICF is 40% of body weight
- ECF is 20% of body weight
what is a marker for TBW
- tritiated water
- D2O
what is a marker for ECF
- mannitol. A large molecule that cannot cross cell membranes --> excluded from ICF
- sulfate
- inulin
what is a marker for plasma volume?
- Evans blue- a dye that binds to serum albumin
- Radioiodinated serum albumin (RISA)
how do you calculate volume of distribution?
Volume = amount / concentration

Volume - volume of distribution, or volume of the body fluid compartment (L)
Amount = amount of substance present (e.g. manitol, tritated water) mg.
concentration = concentration in plasma (mg/L)
what is a marker for insterstitial fluid?
measure indirectly (ECF volume-plasma volume
what is a marker for ICF
measure indirectly (TWB-ECF volume)
at steady state, what is the difference between ECF osmolarity and ICf osmolarity?
equal. water shifts between the 2 compartments
what happens with addition of isotonic fluid (e.g. isotonic NaCl)
- ECF volume increases
- osmolarity of ECF and ICF stays the same
- no water shift
- plasma protein and hemotocrit concentrations decrease
- arteiral blood pressure increases b/c of ECF volume increase
define isotonic
same concetration as blood
aka isosmotic
what happens with loss of isotonic fluid (e.g diarrhea)
- ECF volume decrease
- no change in somolarity of ECF or ICF
- plasma protein concentrations and hematocrit increase
- arterial blood pressure decreases
what happens with excessive NaCl intake?
(aka hyperosmotic volume expansion)
- osmolarity of ECF increases --> water shift until ICF osmolarity is equal to ECF
- ECF volume expansion; ICF volume contraction
- plasma protein concetration and hematocrit decrease
what happens with excessive sweating?
(aka hyperosmotic volume contraction)
- osmolarity of ECF increases b/c sweat is hypoosmotic
- ECF volume decreases. Water shift from ICF
- ICF osmolarity increases until equal to ECF
- ICF volume contraction
- plasma protein concentration increases b/f of decrease in ECF volume
define hematocrit
The proportion of the blood that consists of packed red blood cells. The hematocrit is expressed as a percentage by VOLUME. The red cells are packed by centrifugation.
syndrome of inappropriate antidiuretic hormone (SIADH)
aka hyposmotic volume expansion
- osmolarity of ECF decreases b/c of retained water
- ECF volume increases b/c of retension --> water shift into ICF
- ICF osmolarity decrease and volume increase
- plasma protein concentration decreases
adrenocortical insufficiency
aka hyposmotic volume contraction
- osmolarity of ECF decreases
- lack of Aldosterone --> kidneys secrete more NaCl than water
- ECF volume decreases -> water shift -> ICF osmolarity decreases; volume increases
- plasma protein conecntration increases; hematocrit increases b/c of decreased ECF and b/c RBCs swell
- arterial blood pressure decreases
define clearance
volume of plasma cleared of substance per unit time

C = UV / P

Clearance = ml/min or ml/24 hr
U = urine concentration (mg/ml)
V = urine volume/time (ml/min)
P = plasma concentration (mg/ml)
Renal blood flow (RBF)
25% of CO
- proportional to the pressure diff btw renal artery and vein
- inversely proportional to resistance of vasculature
what happens during vasoconstriction of the renal arterioles?
decrease in RBF
- the vasoconstriction is caused by activating the sympathetic nervous system and angiotensin II
what does angiotensin II do at low concentrations?
- constricts efferent arterials --> maintaining RBF and protecting the GFR
what do ACE inhibitors do?
- dilate efferent arterioles and cause a decrease in GFR
- reduce hyperfiltration and occurrence of diabetic neuropathy
what causes vasodiation of renal arterioles?
- prostaglandins E2 and I2
- bradykinin
- Nitric oxide
- and dopamine
causes increase in RBF
autoregulation of RBF
- accomplished by changing renal vascular resistance to keep pressures between 80-200 mmHg
1. myogenic mechanism
2. tubuloglomerular feedback
myogenic mechanism
- form of autoregulation
- renal afferent arterioles contract in response to stretch
- increased renal arterial pressure causes stretch. arterioles contract to increase resistance and maintain blood flow
tubuloglomerular feedback
- autoregulatory mech
- increase renal arterial presure causes increased fluid delivery to the macula densa
- macula densa senses increased load --> causes constrction of afferent arterioles --> increase resistance to maintain blood flow
para-aminohippuric acid (PAH)
measure of renal plasma flow
- PAH is filtered and secreted by renal tubules
- clearance of PAH is used to measure RPF. However, this underestimates true RPF by 10% since it does nto measure RPF to retions of the kidney that do not filter and secrete PAH
Renal Plasma Flow (RPF)
RPF = C_PAH = [U]_PAH x V/ ([P]_PAH)
- U_PAH: urine concentration of PAH
- V: urine flow rate
- P_PAH: plasma concentration of PAH
Renal Blood Flow (RBF)
RBF = RPF / (1-hematocrit)
Glomerular Filtration rate (GFR)
- volume of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time
- calculated via the clearance of inulin

GFR = [U]_inulin x V/ [P]_inulin
what happens to BUN and serum [creatinine] when GFR decreases?
BUN increases
serum [creatinine] increases
what happens in prerenal azotemia?
BUN increases more than serum creatinine --> increase in BUN/Creatinine ratio (>20:1)
define: azotemia
Abnormally high concentrations of urea and other nitrogenous substances in the blood.
what is prerenal azotemia?
blood supply to the kidneys is inadequate
what is postrenal azotemia?
the urinary outflow tract is obstructed
what happens to GFR with age?
decreases. Serum [creatinine] stays constant b/c of decreased muscle mass
filtration fraction
- fraction of RPF filtered across the glomerular capillaries


- measures the efficacy of reabsorption
- normal: 20% of RBF is filtered. 80% leaves the glomerular capillaries vai the efferent arterioles and becomes the peritubular capillary circulation
what are peritubular capillaries?
tiny blood vessels that travel along side nephrons allowing reabsorbtion and secretion between blood and the inner lumen of the nephron.
- come from efferent arterioles
what happens with increased filtration fraction?
increases the protein concentration of the peritubular capillary blooe --> increase reabsorption in the proximal tubule
what happens with decreased filtration fraction?
- decreases protein concentration in peritubular capillary and decreases reabsorption in the proximal tubule
what drives glomerular filtration?
net ultrafiltration pressure across the glomerular capillaries
GFR expressed via the starling equation
GFR = K_f[(P_GC - P_BS) - (pi_GC - pi_BS)]

- GFR is the filtration across the glomerular capillaries
what is K_f?
the filtration coefficient of the glomerular capillaries
- increased by inflammation
what constitutes the glomerular barrier?
1. capillary endothelium
2. basement membrane
3. filtration slits of the podocytes
what restricts filtration of plasma proteins?
the anionic glycoprotein lining at the filtration barrier.
what happens during glomerular disease?
anionic charge barrier may be destroyed, leading to proteinuria
what is P_GC
the glomerular capillary hydrostatic pressure
- usually constant along the length of the capillary
- is increased by dilation fo the afferent arteriole or constriction of the efferent arteriole
- increases in P_GC -> increase in net ultrafiltration pressure and in GFR
what is P_BS?
- bowman's space hydrostatic pressure (like P_i in systemic capillaries)
- increased by constriction of the ureters --> causes decreases in net ultrafiltration pressure and in GFR
what is pi_GC
glomerular capillary oncotic pressure
- normally INCREASES along the length of the capillary b/c water leaving causes increasing protein concentration
what is pi_BS
- the Bowman's space oncotic pressure
- usualy zero
eqn for filtered load
filtered load = GFR x [plasma]

e.g. filtered load = GFR x [plasma]_glucose
eqn for excretion rate
excretion rate = V x [urine]
eqn for reabsorption rate
reabsorption rate = filtered load - excretion rate
eqn for secretion rate
secretion rate = excretion rate - filtered load
what does it mean when the filtered load is greater than the excretion rate?
net reabsorption of the substance has occured.
filtered load of glucose
increases in direct proportion to the plasma glocuse concentration
filtered load = GFR x [plasma]_glucose
what is T_m?
the transport maximum
- we go over it for glucose and for PAH
Reabsorption of glucose
- Na-glucose cotransport is found in the proximal tubule
- at plasma [glucose] < 250mg/dL, all of the filtered glucose can be reabsorbed b/c there are enough Na-glucose carriers.
- at concentrations >350mg/dl, the carriers are saturated --> increasing plasma concentration of glucose does nto increase rates or reabsorption --> T_m
Excretion of glucose
- at plasma [glucose] < 250mg/dl, all of the filtered glucose is reabsorbed, and excretion is 0
- at plasma [glucose] > 350mg/dl, reabsoprtion is saturated (T_m) --> all excess glucose is excreted
what is the threshold for glucose?
the plasma concentration at which glucose first appears in the urine (350mg/dl)
- region of the glucose curves between threshold and T_m
- occurs between plasma [glucose] of 250-350mg/ml
- represents the excretion of glucose before saturation of reabsorption is fully achieved
Filtered load of PAH
- increases proportionally to plasma [PAH]
Secretion of PAH
- secretion occus from peritubular capillayr blood into tubular fluid (urine) via carriers in the proximal tubule
- at low plasma [PAH], secretaion rate increass as plasma concentrations increase
- once carriers are saturated, further increase in [PAH] does not cause further secretion --> Tm
Excretion of PAH
- sum of filtration across the glomerular capillaries and the secretion from peritubular capillaries
- once all the carriers for secretion are saturated, the excretion curve becomes parallel to the filtration curve
- RPF is measured by clearance of PAH at plasma [PAH] < Tm
which substances have the highest clearances?
those that are both filtered adn secreted (e.g. PAH)
which substances have the lowest clearances?
- those that are entier not filtered (e.g. protein), or filtered but then reabsorbed:
- Na
- glucose
- amino acids
- HCO3-
- Cl-
which substances have clearances equal to that of GFR?
- susbtances that are freely filtered, but not reabsorbed or secreted (e.g. inulin)
give the list of relative clearances
PAH > K > inulin > urea > Na > glucose > amino acids > HCO3-
Weak acids and diffusion
- the HA form (uncharged) can back-diffuse from urine to blood (the A- form cannot)
- at acidic urine pH, the HA form predominates --> more back diffusion, and less excretion of the acid
- at alkaline urine pH, the A- form predominates --> less back-diffusion, and more excretion
Weak bases and diffusion
- have BH+ and B- form
- at acidic urine pH, the BH+ form predominates. There is less back diffusion, and more excretion
- at alkaline urine pH, the B form predominates. There is more back diffusion, and less excretion
what is tubular fluid (TF)?
urine- at anay point along the nephron
what is plasma (P)?
systemic plasma. considered as constant
TF/P_x ratio
- compares the concentration of a substance in tubular fluid with the concentration of plasma
what does it mean if TF/P = 1.0?
- if TF/P = 1: there has been no reabsorption, or that the reabsorption of the substance is exactly proportional to the reabsorption of water
- e.g. if TF/P_Na, then the [Na] in tubular fluid is the same as that in plasma
what is the TF/P for any freely filtered substance in the Bowman's space
1.0 in bowman's space- before any reabsorption or secretion has modified the TF
what does it mean if TF/P < 1.0?
reabsorption of the substance is creater than the reabsorption of water
e.g. if TF/P_Na = 0.8, then the [Na] in tubular fluid is 80% of [Na] in plasma
what does it mean if TF/P > 1.0
1. reabsorption of substance has been less than the reabsorption of water, or
2. there has been secretion of the substance
- used as a marker for water reabsorption along the neprhon
- increases as water is reabsorbed
how do you calculate the fraction of filtered water that has been reabsorbed?
fraction of filtered H2O reabsorbed = 1 - 1/[TF/P_inulin]
[TF/P]_x/[TF/P]_inulin ratio
- corrects the TF/P_x ratio for water reabsorption.
- gives the fraction of the filtered load remaining at any point along the nephron
- e..g if the ratio = 0.3 at the end of the proximal tubule, then 30% of the filtered K reamins in the tubular fluid and 70% has been reabsorbed in blood
is Na freely filtered across the glomerular capillaries?
[Na] in tubular fluid of Bowman's space equals that in plasma (TF/P_Na = 1.0)
where is Na reabsorbed?
along the entire nephron, very little is excreted (<1% of filtered load)
Na reabsorption along the proximal tubule
- proximal tubule reabsorbs 2/3 of the filtered Na and H2O (isosmotic process)
where is the site of glomerulotubular balance?
proximal tubule
what does the early proximal tubule reabsorb?
Na and H2O WITH HCO3-, glucose, amino acids, phosphate, and lactate
what is Na cotransported with in the early proximal tubule?
- glucose, amino acids, phosphate, and lactate
- this cotransport accounts for all of the reabsorption of the filtered glucose and amino acids
what is Na countertransported with in the early proximal tubule?
Na-H exchange- linked directly to the reabsorption of HCO3-
how do carbonic anhydrase inhibitors act as diuretics?
acetazolamide inhibits the reabsorption of filtered HCO3-, and thereby inhibits the Na-H countertransport
- acts at the early proximal tubule
what does the late rpoximal tubule filter?
Na is reabsorbed with Cl
where is all of the HCO3- reabsorbed?
early proximal tubule
what is glomerulotubular balance?
- It refers to the finding that the proximal tubule tends to reabsorb a constant proportion of the glomerular filtrate rather than a constant amount. The effect of this is to minimise the effect of changes in GFR on sodium and water excretion.
- maintains constant fractional reabsorption (2.3) of the filtered Na and H2O
what is the mechanism of glomerulotubular balance?
- based on Starling forces in the peritubular capillaries
- fluid resorption is increased by increases in pi_c and decreased by decreases in pi_c
- so, when you get an increase in GFR, pi_c of the peritubular capillaries will naturally increase
effect of ECF volume on proximal tubular reabsorption
- ECF volume contraction promotes reabsorption
- volume contraction --> increases in peritubular pi_c and decrease in P_c
What does the thick ascending loop of Henle absorb?
- reabsorbs 25% of filtered Na (but not water!)
- contains the Na-K-2Cl cotransporter on the luminal membrane
where is the Na-K-2Cl cotransporter found?
on the luminal membrane of the thick ascending limb of the loop of Henle
where do loop diuretics act?
on the Na-K-2Cl cotransporter on the luminal side of the thick ascending loop of Henle
what happens to the TF/P_Na and TF/P_osm in the TAL?
the both become less than 1, or basically, the tubular fluid [Na] and osmolarity decrease to less their concentration in plasma
- that is why the TAL is called the diluting segment
tell me about the charge in the TAL
- has a lumen-positive potential differnece.
- although the Na- K- 2Cl cotransporter seems to be electroneutral, some K diffuses back into the lumen, making it postive
what does the distal tubule and collecting duct reabsorb?
- together, they reabsorb 8% of the filtered Na
features of the early distal tubule
- reabsorb NaCl by a Na-Cl cotransporter
- site of action of thiazide diuretics
where do thiazide diuretics act?
at the early distal tubule
what is the permeability of the early distal tubule to water?
impermeable (like the TAL) --> further dilution of the tubular fluid
what is another name for the early distal tubule?
cortical diluting segment
features of the late distal tubule
- have two cell types:
1. Principal cells
2. Intercalated cells
what do principal cells do?
- reabsorb Na nad H2O
- secrete K
- affected by aldosterone to increase Na reabsorption and increase K secretion
- affected by ADH to increase H2O permeability
what do alpha- intercalated cells do?
- secrete H by H-ATPase, which is stimulated by aldosterone
- reabsorb K by H, K, ATPase
where do K sparing diuretics act?
- at the last distal tubule and collecting duct, principal cells
- spironolactone, triamterene, amiloride
- decrease K secretion
Name some K sparing diuretics
- spironolactone
- triamperene
- amiloride
- acts on principal cells in the distal tubule and CD
- increases Na reabsorption
- increases K secretion
- like the other steroid hormones, takes several hours to develop b/c of new protein synthesis requirement.
how much of Na reabsorption is affected by aldosterone?
2% of overall Na reabsorption
how does antidiuretic hormone (ADH) increase H2O permeability?
- increases insertion of H2O (aquaporin) channels into the luminal membrane.
what is the permeability of principal cells to water in the absence of ADH?
where is most of the body's K located?
in the ICF
what are the adjustments made to K by the nephron?
- filtered
- reabsorbed
- secreted
how is K balance achieved?
urinary excretion exactly equals K intake
what influcnes K excretion?
- K excretion can vary from 1-110% of the filtered load, depending on the:
1. dietary K intage
2. aldosterone levels
3. acid-base status
K filtration
- occurs freely across the glomerular capillaries
- TF/P_K in the Bowman's space = 1.0
causes for Hyperkalemia
- insulin deficiency
- B-adrenergic antagonists
- acidosis (exchange of extracellular H for intracellular K)
- hyperosmolarity (H2O flows out of cell, K diffuses out with H2O)
- Inhibitors of Na-K pump (digitalis)
- exercise
- cell lysis
how do inibitors of the Na-K pump affect K levels?
e.g. digitalis
- K is no longer taken up by cells --> may cause hyperkalemia
causes for Hypokalemia
- insulin
- B-adrenergic agonists
- Alkalosis
- Hyposmolarity
K+ reabsorption in the Proximal Tubule (PT)
- 67% of filtered K is reabsorbed, along with Na and H2O
K+ reabsorption in the TAL
- 20% of filtered K is reabsorbed
- invovles the Na-K-2Cl cotransporter in the luminal membrane
K+ reabsorption in the distal tubule and CD
- either reabsorb or secrete K, depending on dietary intake
- reabsorption of K: H,K-ATPase in the luminal membrane of the intercalated cells
- secretion of K: principal cells
describe K reabsorption in the DT and CD
- involves the H,K-ATPase in the luminal membrane of the a-intercalated cells
- only occus during K depletion
describe K secretion in the DT and CD
- occurs in principal cells
- is variable (depends on diet, aldosterone levles, pH, and urinary flow)
- mech: at the basolateral membrane, K is actively transported into cell by Na-K pump
- at luminal membrane, K is passively secreted into the lumen via K channels
which factors change distal K secretion?
- secretion by principal cells is increased when the electrochemical driving force of K across the membrane is increased
1. Dietary K: high K diet- increases K secretion
2. Aldosterone: increases K secretion
3. Acid-Base (acidosis decreases K secretion)
4. Thiazide and loop diuretics increase K secretion
5. K-sparing diuretics decrease K secretion
6. Luminal anions increase K secretion
what is the mechanism of aldosterone on K secretion?
- increased Na entry into cells across teh luminal membrane --> increase pumping of Na out of the cells by the Na-K pump.
- Stimulation of this pump also stimulates K uptake into the principal cells --> changes the electrochemical driving force so that more K is secreted.
how does the acid-base status change K secretion?
- H and K exchange across the basolateral membrane
- acidosis causes excess H to enter via the basolateral memrbane --> K leaves the cell --> intracellular [K] decreases and there is less driving force for K secretion
how do thiazide and loop diuretics change K secretion?
- increase K secretion
- diuretics that increase the FLOW RATE through the DT (eg thiazide and loop diuretics) cause dilution of the luminal K concentration --> increase driving force for secretion.
what is a side effect of loop and thiazide diuretics?
how do K-sparing diuretics change K secretion?
- decrease K secretion
- can cause hyperkalemia
- most important role is to use in conjunction with thiazide or loop diuretics to reduce K loss
- K sparing diuretic
- aldosterone antagonist
Triamterene and amiloride
- K sparing diuretics
- act directly on principal cells
who do luminal anions change K secretion?
- increase K secretion
- excess anions (e.g. HCO3-) increase negativity of lumen and increase K secretion driving force
where is urea reabsorbed?
- 50% is reabsorbed passively in the PT
- the DT and CD are impermeable to urea
what does ADH do to urea?
increases urea permeability in the inner medullary collecting ducts --> contributes to the corticopapillary osmotic gradient
what does urea excretion vary with?
urine flow rate. At high levels of water resorption (low urine flow rate), there is greater urea reabsorption -> less urea excretion
where is phosphate reabsorbed?
- 85% of filtered phosphate is reabsorbed in the PT by Na-phosphate cotransport.
- the remaining 15% is excreted in urine since no other place absorbs phosphate
what does PTH do to phosphate reabsorption?
- inhibits reabsorption in the PT by activating adenylate cyclase --> generating cAMP, and inhibiting the Na-phosphate cotransport
- causes phosphaturia, and increased urinary cAMP
what can cause phosphaturia and increased urinary cAMP?
name a urinary buffer for H+
- excretion of H2PO4- is called a titratable acid
how much of Ca is filtered across the glomerular capillaries?
60% of plasma Ca
where is Ca reabsorbed?
- 90% of filtered Ca is reabsorbed in the PT and TAL by passive processes coupled to Na reabsorption
- 8% is reabsorpted in the DT and CD by an active process
what do loop diuretics do to Ca excretion?
e.g. furosemide
- increases Ca excretion
- Since Ca reabsorption is coupled to Na reabsorption in the loop of Henle, inhibiting Na reabsorption also inhibits Ca reabsorption.
what can be used to treat hypercalcemia?
loop diuretics, provided that volume is replaced
what is the effect of PTH on calcium reabsorption?
- increases reabsorption by activating adenylate cyclase in the DT
what is the effect of thiazide diuretics on calcium reabsorption?
- increases reabsorption in the DT
- used to treat idiopathic hypercalciurea
what can be used to treat hypercalciurea?
thiazide diuretics
where is Mg reabsorbed?
- PT, TAL, and DT
- in the TAL, Mg and Ca compete for reabsorption
- hypercalcemia causes increase in Mg excretion
- hypermagnesemia cuases increase in Ca excretion
what is the effect of hypermagnesemia on Ca excretion?
- increases Ca excretion by inhibitng Ca resorption, since Mg and Ca compete for resorption in the TAL
how do you regulate plasma osmolarity?
- vary the amount of water exreted relative to the amoutn of solute excreted
what happens during water deprivation?
- increase in plasma osmolarity -> osmoreceptors in ant. hypothalamus are stimulated -> increase ADH secretion from post. pituitary -> increase water permeability of DT and CD -> increase water reabsorption -> increase urine osmolarity and decrease urine volume -> decrease plasma osmolarity towards normal
what happens during water intake?
- decrease in plasma osmolarity -> osmoreceptors in ant. hypothalamus are inhibited -> decrease ADH secretion from post. pituitary -> decrease water permeability of DT and CD -> decrease water reabsorption -> decrease urine osmolarity and increase urine volume -> increase plasma osmolarity towards normal
how do you make concentrated urine?
- hyperosmotic urine (urine osmolarity > blood osmolarity) is caused by high ADH levels
- seend during water deprivation, hemorrhage, and SIADH
corticopapillary osmotic gradient- at high ADH (hyperosmotic urine)
- the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L)
- maintained by urea and NaCl
- established by countercurrent multiplication and urea recycling
- maintained by countercurrent exchange in the vasa recta
describe countercurrent multiplication in the loope of Henle
- depends on NaCl reabsorption in the TAL, and countercurrent flow in the dscending and ascending limbs of the loop of Henle
- increased by ADH
what is the effect of ADH on the countercurrent multiplication in the loop of Henle?
- ADH increases the countercurrent multiplication by stimulating NaCl reabsortion in the TAL -> increase the size of the corticopapillary osmotic gradient
what is the effect of ADH on urea recycling?
- urea recycling from the inner medullary collecting ducts into the medullary interstitial fluid is INCREASED
what are the vasa recta?
capillaries that supply the loop of Henle. They branch off of the efferent arterioles of juxtamedullary nephrons
- they maintain the corticopapillary gradient by serving as Osmotic exchanges
- Vasa recta blood equilibrates osmotically wiht the interstitial fluid of the medulla and papilla
what are juxtamedullary nephrons?
- Most human nephrons are termed cortical nephrons because their corpuscles are located in the mid to outer cortex and their loops of Henle are very short and pass only into the outer medulla. But a small portion are called juxtamedullary nephrons and their loops travel deep into the inner medulla. These nephrons are important in concentrating the urine by increasing the amount of water reabsorbed.
what is the difference between vasa recta and peritubular capillaries?
The efferent arterioles of the juxtamedullary nephrons give rise to two different capillary beds.
1. One branch gives rise to a peritubular capillary network which envelops the proximal and distal convoluted tubules.
2. A second branch parallels the long loops of Henle extending deep into the medulla where they divide repeatedly into vascular bundles which form the vasa recta. The vasa recta are composed of the descending (arterial) limbs which gives rise to a capillary network that envelopes the loops of Henle and the collecting ducts.
Proximal Tubule- at high ADH (hyperosmotic urine)
- osolarity of the filtrate is the same as plamsa (300 mOsm/L)
- 2/3 of filtered H2O is reabsorbed isosmotically (with Na, Cl, HCO3-, glucose, aas, etc) in the PT -> TF/P_osm 1.0 throughout the PT
TAL- at high ADH (hyperosmotic urine)
- called the diluting segment
- reabsorbes NaCl by the Na-K-2Cl cotransporter
- impermeable to H2O
- tubular fluid that leaves the TAL has an osmolarity of 100mOsm/L (TF/P_osm <1.0)
Early distal tubule- at high ADH (hyperosmotic urine)
- cortical diluting segment
- like the TAL, reabsorbs NACl, but is impermeable to water
Late DT - high ADH (hyperosmotic urine)
- ADH increases H2O permeability of the principal cells in the late DT
- osmolarity of DT = that of the surroudning interstitial fluid (300mOsm/L)
- TF/P_osm = 1.0 b.c osmotic equilibration occurs in the presence of ADH
Collecting ducts - high ADH (hyperosmotic urine)
- ADH increase H2O permeability in principal cells of the CDs
- as TF flows through the CDs, it passes through the corticopapillary gradient (est. by countercurrent multiplication and urea recycling)
- H2O is reabsorbed until the osmolarity of the final urine = the bend of the loop of Henle (1200mOsm/L)
- TF/P_osm > 1.0 b/c of osmotic equilibration
what cuases hyposmotic urine?
- low levels of ADH
- insensitivity to ADH
what causes low circulating levels of ADH?
- water intake
- central diabetes insipidus
what causes insensitivity to ADH?
- nephrogenic diabetes insipidus
what is diabetes insipidus?
excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced.
- kidney cannot concentrate urine
- caused by a deficiency or insensitivity to ADH)
- Symptoms of DI are quite similar to those of untreated DM, with the distinction that the urine is not sweet and there is no hyperglycemia
what is central diabetes insipidus?
- damage to the hypothalamus or pituitary due:
- tumor, stroke, neurosurgery - If the hypothalamus is damaged, the feeling of thirst may be completely absent.
what is nephrogenic diabetes insipidus?
inability of the kidney to respond normally to ADH. There are hereditary causes (90% are due to mutations of the ADH V2 receptor, and 10% mutations of the aquaporin 2 water channel), but these are rare
- Most are male, because V2 receptor mutations are x-linked recessive defects.
- More common are acquired forms of NDI, which occur as a side-effect to some medications (such as lithium citrate and amphotericin B), as well as in polycystic kidney disease (PKD) and sickle-cell disease, and electrolyte disturbances such as hypokalaemia and hypercalcaemia.
what is dipsogenic Diabetes insipidus?
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
what is gestational Diabetes Insipidus?
Gestational DI only occurs during pregnancy. While all pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI. Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.
Corticopapillary osmotic gradient- no ADH (hyposmotic urine)
- smaller than in the presence of ADH b/c ADH stimulates:
1. countercurrent multiplication and
2. urea recycling
proximal tubule- no ADH (hyposmotic urine)
- as in the presence of ADH, 2/3 of filtered water is reabsorbed isosmotically
- TF/P_osm - 1.0 throughout the PT
TAL- no ADH (hyposmotic urine)
- as in the presence of ADH, NaCl is reabsorbed without water.
- TF becomes dilute (although nto as dilute as in the presence of ADH)
- TF/P_osm < 1.0
- TF/P_osm = 1.0 throughout
Early DT- no ADH (hyposmotic urine)
- as in the presence of ADH, NaCl is reabsorbed without H2O and tubular fluid is futher diluted
- TF/P_osm < 1.0
Late DT and CDs- no ADH (hyposmotic urine)
- impermeable to H20
- osmotic equilibration does not occur
- osmolarity of final urine will be dilute (~50 mOsm/L)
- TF/P_osm < 1.0
Free water clearance (C_H20)
- used to estimate the ability to concentrate urine
- free water is made in the diluting segments (TAL and early DT)
what happens to the C_H2O in the absence of ADH?
- solute-free water is excreted and C_H2O is positive
what happens to the C_H2O in the presence of ADH?
- solute-free water is not excreted, and C_H2O is negative
eqn for C_H20
- C_H20 = V-C_osm

C_H20: free-water clearance
V: urine flow rate
C_osm: osmolar clearance
urine that is isosmotic to plasma
what is the C_H2O of isothenuric urine?
C_H2O = 0
- is produced during treatment with a loop diuretic, which inhibits NaCl reabsorption in the TAL -> urine cannot be diluted during high water intake or concetrated eduring water deprivation respectively b/c:
- diluting seg is inhibited
- corticopapillary gradient is abolished
Urine that is hyposmotic to plasma (low ADH)
- C_H2O is positive
- produced with:
- high water intake (suppressed ADH release from post. pit)
- central diabetes insipidus (pit ADH is insufficient)
- nephrogenic diabetes insipidus (collecting ducts are unresponsive to ADH)
urine that is hyperosmotic to plasma (high ADH)
- C_H2O is neg
- produced during:
- water deprivation (ADH release from post. pit is stimulated
Renal hormones (list)
1. PTH
2. ADH
3. Aldosterone
4. ANP
5. Angiotensin II
PTH on kidneys
- decrease phoshate reabsorption in PT
- increase Ca reabsorption in DT
- stimulates 1a-hydroxylase in PT
- Basolat recepotr Adenylate cyclase increase [cAMP]
what stimulates PTH secretion?
low plasma [Ca]
what is the time course for PTH?
ADH on the kidneys
- increase H2O permeability in DT and CD principal cells
- basolateral V2 receptor --> cAMP
where are V1 receptors found?
on blood vessels
Mech: Ca -IP3
what stimulates ADH secretion?
- high plasma osmolarity
- low blood volume
what is the time course for ADH?
Aldosterone on the kidneys
- Increase Na reabsortion in DT principal cells
- increase K secretion in DT principal cells
- increase H secretion in DT a-intercalated cells
- new protein synthesis
what stimulates aldosterone secretion?
- low blood volume (via the renin-angiotensin II system)
- increase plasma [K]
what is the time course for aldosterone
slow (needs new protein synthesis)
ANP on the kidneys
- increases GFR
- decreases Na reabsorption
- Guanylate cyclase -> cGMP
what stimulates ANP secretion?
- increased atrial pressure
what is the time course of ANP?
angiotensin II on the kidneys
- increase GFR
- decrease Na reabsorption
- increase Na-H exxchange and HCO3- reabsorption in the PT
- not listed
what stimulates Angiotensin II secretion?
- decrease in blood volume (via renin)
what is the time course of angiotensin II?
what are the two types of acids made by the body?
1. volatile
2. non-volatile
Volatile acid
- CO2
- made from aerobic metabolism
- CO2 + H2O <-> H2CO3 <-> H + HCO3-
- depends on CA to catalyze the reversible rxn between CO2 and H2O
Nonvolatile acids
- aka fixed acids
- sulfuric acid & phosphoric acid
- made at the rate of 40-60 mmoles/day
what makes sulfuric acid?
- protein catabolism
what makes phosphoric acid?
phospholipid catabolism
what are some fixed acids that may be overproduced during disease or ingestion?
- ketoacids
- lactic acid
- salicylic acid
where are buffers most effective?
- within 1 pH unit of the pK (aka, within the linear portion of the titration curve)
what is the main extracellular buffer?
- HCO3(main)
- pK of CO2/HCO3 is 6.1
what is the minor extracellular buffer?
- pK of H2PO4/HPO4-2 = 6.8
- most important as a urinary buffer
- excretion of H+ as H2PO4- is called a 'titratable acid'
Name two extracellular buffers
1. HCO3-
2. phosphate
List the intracellular buffers
- Organic phosphates (AMP, ADP, ATP, 2,3-DPG)
- Proteins
what are the protein intracellular buffers?
- Proteins
- imidazole and alpha- amino groups on proteins that have pKs within the physiologic pH range
- Hb is a major intracellular buffer
- in the physiologic range, deoxyHb is a better buffer than oxyHb
Henderson-Hasselbalch eqn
pH = pK + log [A-]/[HA]

- when [A-] = [HA], the pH equals the pK
where does reabsorption of filtered HCO3- primarily occur?
- in the PT
1. H+ and HCO3- are produced in the PT from CO2 and H2O (H2CO3 is made by intracellular CA, which then dissociates into H+ and HCO3-).
- the H+ is secreted inot the lumen via the Na-H countertransporter
- the HCO3- is reabsorbed
2. in the lumen, the secreted H+ combines with filtered HCO3 -> H2CO3, which dissociates into CO2 and H2O catalyzed by brush boarder CA
- CO2 and H2O diffuse into the cell to start the cycle over again
3. net reabsorption of filtered HCO3-, but NOT net secretion of H+
what regulates the reabsorption of filtered HCO3-?
1. filtered load (increase FL increases HCO3 reabsorption)
2. PCO2 (increase PCO2 increases HCO3 reabsorption)
3. ECF volume (increase volume decreases HCO3 reabsorption)
4. Angiotensin II (stimulates Na-H exchange -> increases HCO3- reabsoption)
how does filtered load affect HCO3- reabsorption?
- increases HCO3- reabsorption.
- if plasma HCO3- is very high however (e.g. metabolic alkalosis), filtered load will exceed reabsorptive capacity, and HCO3- will be excreted in urine)
how may you have high HCO3- plasma levels?
- metabolic alkalosis
how does P_CO2 affect HCO3- reabsorption?
- increases in P_CO2 causes increase HCO3 reabsorption b.c the supply of intracellular H+ for secretion is increased
- this is the basis for renal compensation for respiratory acidosis
how does ECF volume affect HCO3- reabsorption?
- ECF volume expansion results in decreased HCO3- reabsorption
how does angiotensin II affect HCO3- reabsorption?
- stimulates Na-H countertransport exchange and increases HCO3- reabsorption
- contribultes to the contraction alkalosis that occurs secondary to ECF volume contraction
what are the 2 mechanisms of fixed H+ excretion?
1. excretion of H+ as titratable acid (H2PO4-)
2. excretion of H+ as NH4+
how is fixed H+ produced?
- catabolism of protein and phospholipid
excretion of H+ as H2PO4-
(titratable acid)
- amount of H+ excreted depends on the amount of urinary buffer present (HPO4) and the pK of the buffer
1. H+ and HCO3- are made by cell from CO2 and H2O. the H+ is screted into the lumen by H-ATPas, and the HCO3- is reabsorbed. In the urine, the secreted H combines with filtered HPO4-2 to make H2PO4-, which is excreted as a titratable acid
2. results in net secretion of H and net reabsorption of HCO3-
3. b/c of net H+ secretion -> urine pH drops (pH = 4.4)
what increases H-ATPase?
what is the min urinary pH?
excretion of H+ as NH4+
- amoutn of H excreted depends on amount of NH3 syntehsized by renal cells, and urine pH
1. NH3 is produced in renal cells from glutamine. Diffuses down concetration gradient into lumen
2. H+ in lumen (that was secreted via the H-ATPase) combines with NH3 to make NH4+, which is excreted (diffusion trapping)
3. the lower the TF pH, the greater the H+ excretion as NH4+ (at low urine pH, there is more NH4+ relative to NH3)
how is NH3 synthesized?
from glutamine
- made in renal cells
what happens in acidosis (re: NH3)
in acidosis, there is an adaptive increase in NH3 syntehsis -> more excretion of H+
what happens in hyperkalemia (re: NH3)?
- hyperkalemia inhibits NH3 synthesis -> decrease in H+ excretion as NH4 (type 4 renal tubular acidosis)
what is renal tubular acidosis (RTA)?
- kidneys fail to dispose of a normal amount of acid into the urine, which may lead to acidosis.
- due to the renal tubules failing to acidify the urine, rather than acid accumulating in the body due to kidney failure. As such it is a cause of a normal anion gap acidosis.
- In RTA, the renal tubules either fail to appropriately reclaim bicarbonate (in the proximal tubule) or excrete hydrogen ions (in the distal tubule).
Metabolic acidosis
- overproduction or ingestion of fixed acid, or loss of base -> increase in arterial [H+] (acidemia)
- b/c HCO3- is used to buffer extra acid, arterial [HCO3-] decreases <- primary disturbance
what does acidemia cause?
- hyperventilation (Kussmaul breathing), which is the respiratory compensation for metabolic acidosis
Kussmaul breathing
- respiratory compensation for metabolic acidosis
how do you correct metabolic acidosis?
- increased excretion of fixed H+ as a titratable acid (H2PO4) and as NH4
- increase reabsorption of 'new' HCO3- for more buffering capacity
- adaptive increase in NH3 syntehsis in chronic Met acidosis
what adaptive mechanism happens during chronic metabolic acidosis?
adaptive increase in NH3 synthesis
eqn for anion gap
Serum Anion Gap = [Na] - ([Cl] + [HCO3]
- represents unmeasured anions in serum
- normal = 12mEq/L
what are the unmeasured anions in serum?
- phosphate
- citrate
- sulfate
- protein
what happens during metabolic acidosis to serum [HCO3-]?
serum [HCO3-] decreases as it's depleted in buffing fixed acid
- for electroneutrality, the concetration of another anion must be increased ro replace HCO3-
- this anion can be Cl or unmeasured anion
how is the anion gap increased?
- if concentration of unmeasured anion is increased to replace HCO3-
how is the anion gap decreased?
- if concentration of Cl- is increased to replace HCO3- (hyperchloremic metabolic acidosis)
hypercholoremic metabolic acidosis
when Cl- is increased to replace HCO3-
what causes metabolic alkalosis?
1. loss of fixed H+ or
2. gain of base
- produces a decrease in arterial [H+] (alkalemia)
define alkalemia
decrease in arterial [H+]
what happens during metabolic alkalosis?
- increase in arterial [HCO3-] -> this is the primary disturbance
- alkalemia causes hypoventilation (respiratory compensation)
how might you get metabolic alkalosis?
- vomiting (H+ is lost from stomach)
how do you correct metabolic alkalosis?
- increased excretion of HCO3-
- if met alkalosis is accompanied by ECF volume contraction (e.g. vomiting), then the reabsorption of HCO3 increases, worsening the alkalosis (contraction alkalosis)
what causes respiratory acidosis
- decrease in respiratory rate and retention of CO2
- increase in arterial pCO2, which is the primary disturbance, causes and increase in H+ and HCO3- by mass action
describe renal compensation for respiratory acidosis
- increased excretion of H+ as titratable acid and NH4+
- increased reabsorption of new HCO3
- increase PCo2 supplies more H+ to the reanl cells for secretion
renal compensation in acute respriatory acidosis
- renal compensation does not have time to occur
renal compensation in chronic respiratory acidosis
- renal compensation occurs
- increased HCO3 reabsorption -> arterial pH increases towards normal
how does respiratory alkalosis occur?
- increase in respiratory rate and loss of CO2
- decrease in PCO2 is the primary disturbance
- causes a decrease in [H+] and [HCO3] by mass action
- no respiratory compensation
- renal compensation instead
describe renal compensation in respiratory alkalosis
- decreased excretion of H+ as titratable acid and as NH4+
- decreased reabsorption of 'new' HCO3-
- process is aided by decreased pCO2, whcih causes a deficit of H+ in the renal cells for secretion
renal compensation in acute respiratory alkalosis
- not yet occured
renal compensation in chronic respiratory alkalosis
- renal compensation has occured
- decreased HCO3- reabsorption
- arterial pH decreases towards normal (compensation)
what symptom may accompany respiratory alkalosis?
- hypocalcemia
- tingling, numbness, muscle spasm
- occur b/c H+ and Ca2+ compete for bidning sites on plasma proteins
- decrease in [H+] causes increased protein binding of Ca+ and decreased free ionized Ca2+
Metabolic acidosis caused by ketoacidosis
accumulation of b-OH-butyric acid and acetoacetic acid
- increased anion gap
Metabolic acidosis caused by lactic acidosis
- accumulation of lactic acid during hypoxia
- increase in anion gap
Metabolic acidosis caused by Chronic renal failure
- failure to excrete H+ as a titratable acid and NH4+
- increase in anion gap
Metabolic acidosis caused by salicylate intoxication
also causes respiratory alkalosis
- increase in anion gap
Metabolic acidosis caused by methanol/formaldehyde intoxication
- produces formic acid
- increased anion gap
Metabolic acidosis caused by ethylene glycol intoxication
- produces glycolic and oxalic acids
- increase in anion gap
Metabolic acidosis caused by diarrhea
GI loss of HCO3-
- normal anion gap
Metabolic acidosis caused by Type 2 RTA
renal loss of HCO3-
- normal anion gap
Metabolic acidosis caused by Type 1 RTA
- failure to excrete titratable acid and NH4+
- failure to acidify urine
- normal anion gap
Metabolic acidosis caused by Type 4 RTA
- hypoaldosteronism
- failure to excrete NH4+
- hyperkalemia caused by lack of aldosterone inhibits NH3 syntehsis
- normal anion gap
Metabolic acidosis caused by vomiting
- loss of gastric H+
- leaves HCO3- behind in blood
- worsened by volume contraction
- hypokalemia
- may have increased anion gap b/c of production of ketoacids (starvation)
Metabolic acidosis caused by hyperaldosteronism
- increased H+ secretion in DT
- increased new HCO3- reabsorption
Metabolic acidosis caused by loop or thiazide diuretics
- volume contraction alkalosis
Respiratory acidosis caused by opiates, sedatives, or anesthetics
inhibition of medullary respiratory center
Respiratory acidosis caused by Guillain-Barre syndrome, polio, ALS, MS
weakening of respiratory muscles
Respiratory acidosis caused by airway obstruction, adult respiratory distress syndrome (ARDS), COPD
- decrease in CO2 exchange in lungs
Respiratory alkalosis caused by pneumonia, PE
- hypoxemia causes increased ventilation rate
Respiratory alkalosis caused by high altitude
hypoxemia causes increased ventilation rate
Respiratory alkalosis caused by salicylate intoxication
- direct stimulation of the medullary respiratory center
- also causes metabolic acidosis
Diuretic: CA inhibitor
- acts at PT
- inhibits CA
- increase HCO3- excretion
Diuretic: Loop diuretics
- Site of action: TAL
- inhibits Na-K-2Cl cotransport
- increase NaCl excretion
- increase K excretion (increase DT flow rate)
- increase Ca excretion (treats hypercalcemia)
- decreases urine concentrating capacity (decreased corticopapillary gradient)
- decreased ability to dilute urine (inhibiton of diluting segment)
name some loop diuretics
- furosemide
- ethacrynic acid
- bumetanide
Diuretic: Thiazide diuretic
- acts at the early DT (cortical diluting segment)
- inhibits Na-Cl cotransport
- increase NaCl excretion
- increase K excretion (increase DT flow rate)
- decrease Ca excretion (treats hypercalciuria)
- decreased ability to dilute urine (inhibiton of diluting segment)
- no effect on urine concetrating ability
Name some thiazide diuretics
- cholorothiazide
- hydrochlorothiazide
Diuretic: K-sparing diuretic
- acts at the late DT and CD
- inhibits Na reabsorption
- inhibits K secretion
- inhibits H secretion
name some K- sparing diuretics
- spironolactone
- triamterene
- amiloride
why do you get hyperpigmentation with hypoaldosteronism?
- hyperpigmentation is caused by adrenal insufficiency
- decreased cortisol concentrations causes increased ACTH secretion (via neg feedback)
- ACTH has pigmenting effects similar to those of MSH (melanocyte stimulating hormone)