ICL 1.5: Renal Physiology III Flashcards
how much of your body is made of water? how is it divided into the different parts of the body?
~ 60% of the body weight is made up of water
the collective volume of all the cells in the body →intracellular fluid(ICF)
ICF contains roughly 2/3 of the body osmotic content and therefore 2/3 of the water
extracellular fluid(ECF), is mostly interstitial fluid and blood plasma, and contains the remaining 1/3
what is the osmotic equilibrium relationship of the ECF and iCF?
ECF and ICF are in osmotic equilibrium
the total of the 2 volumes varies with gain and loss of H2O
the relative proportion in each compartment is influenced by gain and loss of Na+
additions or losses of Na+ from the body are mostly to or from the ECF
this is because the actions of cellular Na-K-ATPases prevent major changes in intracellular Na+ concentration
if the addition or loss of fluid is isotonic Na+, then only the volume of the ECF is affected
administration of normal saline:
A. increases osmolarity of ECF
B. decreases osmolarity of ECF
C. increases osmolarity of ICF
D. decreases osmolarity of ECF
E. none of the above
E. none of the above
normal saline is isotonic with the ECF so none of the solution will go into the ICF and it will just increase the volume of the ECF! it doesn’t change the osmolarity of any part of the body
loss of water by diarrhea:
A. decreases ECF volume
B. decreases ICF
C. decreases ICF and ECF
A. decreases ECF volume
water lost through diarrhea is isotonic so it’s just the loss of isotonic solution which decreases the volume of the ECF without changing osmolarity of any compartment
ICF doesn’t move to ECF because there’s no change in somalrity!
if you take a salt tablet:
A. move water from ICF to ECF
B. moves water from ECF to ICF
C. no water movement
A. move water from ICF to ECF
salt remains in ECF because that’s the compartment where your blood is! so the ECF osmolarity has increased and to neutralize this, the water in the ICF shifts to the ECF and the cells shrink
how does the kidney conserve water?
be excreting concentrated urine!
the ability of the kidney to form urine more concentrated than plasma is essential for our survival
when there is awaterdeficit in the body, the kidneys form concentrated urine by continuing to excrete solutes while increasingwaterreabsorption and decreasing the volume of urine formed
maximal urine concentration of human kidney is 1200 mOsm/L → 4-5 times plasma osmolarity
a normal 70-kg human must excrete ~ 600 milliosmoles of solute/day of toxic products
what is the obligatory urine volume?
the minimal volume of urine that must be excreted
600 milliosmoles/day/1200 most/L = 0.5 L/day
this is why we can’t last long without water because we have to excrete at least this much urine to remove toxic products
what is urine specific gravity?
provides a rapid estimate of urine solute concentration (often used in clinical settings)
more concentrated the urine, higher its specific gravity.
a measure of the weight of solutes in a given volume of urine
it’s determined by the number AND size of the solute molecules (osmolarity is determined only by the number)
how is water and NaCl transported in the body?
H20 and NaCl are all freely filterable at the renal corpuscle
but then > 99% undergo tubular reabsorption with no tubular secretion!!
Na+ reabsorption is possible because of the Na/K ATPases; reabsorption of Cl- (and other anions) is facilitated by the electrochemical gradient since the lumen is slightly negative
movement of Na+ and anions creates an osmotic gradient that favors the parallel movement of water since the cells have increased solute concentration since all of these ions are moving into the cells from the lumen
the PCT epithelium is very permeable to H20 so it can move trans or paracelluarlly (aquaporins are everywhere in the nephron except the DCT and ascending limb of Henle’s loop)
solutes and H20 move from interstitium into peritubular capillaries (systemic circulation)
where is sodium reabsorbed in the nephron?
in ALL nephron segments, the transcellular Na+ reabsorption is through the Na-K-ATPase pumps in the basolateral membrane, which maintains a low intracellular [Na+]
the resulting electronegativity drives Na+ ions to enter from the lumen to the cell passively either via channels or in symport or antiport with other substances
most of the Na+ reabsorption is in the PCT (67%) but there’s NO Na+ reabsorption in the descending thin limb of the Henle’s loop
how is water reabsorbed in the nephron in hydrated vs. dehydrated states?
with ingestion of a large H2O load, there is a large volume of very dilute urine so urine osmolality < blood plasma
during a state of dehydration, the urine volume is low and very concentrated so urine osmolality > blood plasma
water reabsorption parallels salt reabsorption in the proximal tubule (about 65% of both) but differs in the loop of Henle and beyond
where is water reabsorbed in the nephron?
65% is in the PCT via aquaporins and tight junctions
it’s also absorbed in the descending thin limb of Henle’s loop and collecting ducts –> collecting duct permeability is intrinsically low
there is NO water reabsorption in the ascending limb of Henle’s loop or the DCT; they are impermeable to H2O
basolateral membranes of ALL renal cells are permeable to H2O via aquaporins
how is chloride reabsorbed?
Cl- reabsorption similar to Na+ so > 60% of Cl- reabsorbed in PCT
in active transcellular Cl- reabsorption the critical step is transport from lumen to cell due to the negative membrane potential in the lumen (due to Na/K ATPase)
luminal membrane Cl- transporters use energy to move Cl- against its electrochemical gradient –> it follows Na+ across the cell membrane via the Na+/2Cl-/K+ pump from the lumen into the cell in the TAL
then the high intracellular [Cl- ] drives it across the basolateral membrane
serum [Na+] is way higher than K+ because most of the K+ is in the intracellular compartments so when you get a blood sample, [K+] is way lower
also Na+ is neutralized by Cl- and HCO3- so there isn’t a Cl- for every Na+ so that’s why by the time you get to the thick ascending loop of Henle there’s still Na+ that can be reabsorbed but not necessarily a corresponding Cl- to be reabsorbed
how are NaCl and water reabsorbed in the PCT?
- Na+ entry is coupled to the secretion/uptake of variety of substances
NHE-3 antiporter: Na+ goes into the peritubular capillaries and H+ secreted into the lumen but there’s a recycling mechanism to make sure you aren’t losing too much H+ –> there’s another antiporter that brings Cl- into the cell and an organic base leaves into the lumen in exchange
so then you have a H+ and an organic base in the lumen which combine to form a weak acid that goes back into the cell and dissociates so that they’re recycled and you have H+ and base to run the Na+/H+ and Cl-/base antiporters on the apical surface
- Na+ is transported to the interstitium via the basolateral Na-K-ATPase (predominantly) or in symport with HCO3- which creates a concentration gradient for Na+ to enter from the lumen into the peritubular capillaries
- most Cl- reabsorbed paracellularly but any Cl- that enters the cell in antiport with organic base leaves via channels
- water moves paracellularly or transcellularly (via aquaporins)
tight junctions are permeable to H2O
what is the osmolarity of the distal nephron relative to the plasma?
the fluid delivered to the distal nephron is hypoosmotic relative to the plasma
water and Na+ are lost in the same proportion in the PCT but then during the loop of Henle more Na+ than H2O is lost so the fluid that gets to the distal nephron is hypoosmotic relative to the plasma so it’s very diluted!!
how is water reabsorbed in the loop of Henle?
the thin descending limb reabsorbs H2O but NOT NaCl because the descending limbs have luminal aquaporins and 20% of H2O is reabsorbed in Henle’s loop (in the descending limb)
however, there are no luminal aquaporins and very low water permeability in remaining portions of Henle’s loop
the majority of nephrons extend only to the border between the outer and inner medulla and so majority of the H2O reabsorption is in the outer medulla near the cortex
how is NaCl reabsorbed in the loop of Henle?
theascendinglimbs (thin and thick) are referred to as the “diluting segment” because they reabsorb NaCl but very little H2O
H2O reabsorption in descending limb favors passive reabsorption of NaCl in the thin ascending limb
the Cl- channels on both the luminal and basolateral membranes favor passive Cl- reabsorption –> the tight junctions allow paracellular Na+ transport and this happens because there’s a basolateral Cl- transporter pumping Cl- into the interstitum
the key Na+ transporter is the luminal Na-K-2Cl symporter (NKCC) and then there’s K+ channels that recycle K+ from the cell back into the lumen (ROMK) and to the interstitium (for the Na/K ATPase pump)
considerable Na+ movement happens paracellularly because K+ is being pumped out via ROMK channels into the lumen and this causes an excess negative charge
the Na/K/2Cl- transporter in the ascending limb is the target of which drug?
loop diuretics
what is Bartter’s syndrome?
Na/K/2Cl is the target for inhibition by loop diuretics like furosemide and bumetanide
defects in NKCC lead to type 1 Bartter’s syndrome (Type 1)
defects in the recycling potassium channel (ROMK) lead to types 2
defects in the basolateral chloride channel (ClC-Kb) leads to type 3 Bartter’s syndrome
which hormones effect the DCT?
water is regulated here!! it’s regulated via ADH!! this is the ADH sensitive region of the nephron
distal convoluted tubule, connecting tubule, and cortical collecting duct (exist only in the cortex) and outer and inner medullary collecting ducts - “distal nephron”
cells of the late distal tubule and beyond regulated in part by the hormone aldosterone, are called the “aldosterone-sensitive distal nephron”
aldosterone
A. increases K+ secretion
B. increases Na+ reabsorption
C. increases K+ reabsorption
D. A and B
E. B and C
D. A and B
so it increases K+ secretion and Na+ reabsorption
it increases K+ secretion via the principal cells by recruiting ROMK channels on the luminal membrane (reabsorbption of K+ is through alpha-intercalated cells)
