Test2: Wk6: 3 Tubular Transport of NaCl - Mangiarua Flashcards
Proximal Tubule Na Reabsorption
Na/H Antiport 65%
Thin Descending Limb Na Reabsorption
0%
Thin Ascending Limb Na Reabsorption
0%
Thick Ascending Limb Na Reabsorption
Na-K-2CL multiport, paracellular diffusion
25%
Distal Tubule Na Reabsorption
Na-Cl symport
5%
Collecting Duct Na Reabsorption
Na Channels
5%
Varies depending on Na intake
Na and water freely filtered at the
renal corpuscle
Na in bowmans space is – as plasma
same
Na is reabsorbed along —
the entire nephron
% Na excreted
<1%
Na is — into the interstitium
actively extruded
Na enters — from the tubular lumen
passively
— follow Na
anions
— follows solute
water
water and solutes move by — into —
bulk flow into peritubular capillaries
Na movement across the basolateral membrane is
uphill, by Na-K-ATPase
Na movement across the luminal membrane is
downhill
Major site of salt and water reabsorption
entire proximal tubule
In proximal tubule, Na entry is coupled with — ions using the —
H, NHE3 antiporter
Proximal tubule - Additional Na enters in symport with (3)
with glucose, amino acids, and phosphate.
Proximal tubule - Na is transported to the interstitium mostly via the basolateral — and symport with —
Na,K-ATPase; bicarbonate.
Proximal tubule - Cl that enters in antiport with organic base leaves mostly via — with a substantial amount reabsorbed —
channels; paracellularly
Proximal tubule - Water moves paracellularly and intracellularly via —
aquaporins.
Glomerulotubular balance - changes in GFR is — to filtered load of Na
proportional; always 2/3rds
Glomerulotubular balance - the proximal tubule reabsorbs — of filtered salt and water
constant fraction
Glomerulotubular balance - the amount of filtered salt and water that leaves the proximal tubule — as filtered amount —
increases, increases
the descending loop of Henle does not reabsorb — but does reabsorb —
Na or Cl; water
the ascending loop of Henle reabsorbs — but not —
Na and Cl, water
major transporter in thick ascending limb
NKCC
thick ascending limb contains — in addition to NKCC
ROMK
thick ascending limb - ROMK function
recycle K from the cell interior to the lumen and to the interstitium
thick ascending limb Na can also move — in response to the —
paracellularly; lumen positive potential
thick ascending limb water reabsoprption
not reabsorbed
Bartter’s syndrome
mutations of genes encoding proteins that transport ions
in the thick ascending limb of the nephron, including the Na-K-2Cl cotransporter, the K+
channel, and the Cl- channel.
% Na and %Cl that reach distal tubule
10% and 20%
distal tubule transporter
NCC
Na-Cl symporter
Gitelman’s syndrome
mutations in the gene that codes for the Na-Cl
cotransporter in the distal tubule.
Gitelman’s syndrome characterized by
It is characterized by increased excretion of Na+, Mg2+, Cl-, and K+.
Bartter’s syndrome characterized by
Very large urinary losses of NaCl, hypokalemia. Ca2+ and Mg2+ wasting may also occur
Cortical collecting duct Na reabsoprption
apical Na Channels
apical Na channels controlled by
aldosterone
Cortical collecting duct water reabsorption
aquaporins
aquaporins controlled by
ADH
Liddle’s syndrome
mutations in the gene that codes for the epithelial sodium channel in the principal cells of the collecting duct system inducing excess Na+ reabsorption
Liddle’s syndrome characterized by
early, and severe
hypertension associated with low plasma renin activity, metabolic alkalosis due to
hypokalemia, and hypoaldosteronism.
4 ways reabsorption of Na drives reabsorption of other substances
- create lumen negative transtubular potential difference across the epithelium - diffusion
- Creates transtubular osmolarity difference - osmosis
- reabsorption of many organic nutrients, phosphate, and chloride by
cotransport. - secretion of hydrogen ion (in the proximal tubule) by countertransport - bicarbonate
chloride reabsorption Proximal tubule
Paracellular diffusion in mid-to-late portions; driving force is high luminal chloride
concentration caused by water reabsorption.
chloride reabsorption Thick ascending loop
Secondary active via Na,K,2Cl transporter in luminal membrane.
chloride reabsorption Distal convoluted tubule (2)
(1) Paracellular diffusion; driving force is lumen-negative PD;
(2) Secondary active via Na,Cl cotransporter in luminal membrane.
chloride reabsorption Cortical collecting duct (2)
(1) Paracellular diffusion; driving force is lumen-negative PD;
(2) Secondary active via HCO3-,Cl countertransporter in luminal membrane (sodium
independent) .
9 controllers of Na Reabsorption
- Glomerular tubular balance
- Aldosterone
- PC starling forces hydrostatic pressure
- Renal SNS nerves
- ANGII
- Pressure Natriuresis
- ANP
- ADH
- Dopamine
Glomerular tubular balance
constant proportion of Na reabsorbed
most important controller of Na reabsoption
Aldosterone
Aldosterone is produced
in adrenal cortex
aldosterone stimulates Na reabsorption in
the principal cells of cortical collecting duct
Aldosterone functions to
retain Na
Aldosterone controls % of Na reabsorption
2%
4 Steps of Aldosterone function
- Bind intracellular receptors
- ⬆ mRNA
- ⬆ translation of proteins
- ⬆ expression of luminal Na Channels and basolateral Na-K-ATPase pumps
Aldosterone action on late distal, cortical, and medullary collecting ducts (3)
⬆ Na reabsorption in principal cells
⬆ K secretion in principal cells
⬆ H secretion in intercalated cells
(3) stimulate aldosterone secretion
ANGII
⬆ plasma K conc.
ACTH
(1) inhibits aldosterone secretion
ANP
most important regulator of Aldosterone
ANGII
Plasma ANGII conc. is determined by
plasma Renin conc.
(3) factors that control renin secretion
intrarenal baroreceptors
macula densa
renal SNS nerves
Peritubular capillary starling forces, hydrostatic pressure, and oncotic pressure influence
renal interstitial hydrostatic pressure RIHP
⬆ RIHP ➡ — Na and water
⬇ RIHP ➡ — Na and water
⬆ RIHP ➡ ⬇Na and water
⬇ RIHP ➡ ⬆ Na and water
Renal nerve stimulation stimulates (3)
- renin secretion
- Na reabsorption via direct action on tubular cells
- AA and EA constriction
Renin secretion is activated by — receptors on — cells
Beta1 on granular cells
SNS activates tubular cells on the — tubule
proximal
SNS stimulates AA and EA constriction via — receptor
alpha adrenergic
ANGII — Na reabsorption by — and —
increases, indirect and direct
ANGII indirect effects (2)
⬆ Aldosterone
⬇ RIHP
ANGII direct effects
tubular cells - increases tubular Na reabsoption
Pressure Natriuresis - when renal arterial pressure increases the kidneys show — with little changes in —
rapid increase in Na and water excretion with little changes in GFR
3 possible Pressure Natriuresis intrarenal mechanisms
⬇ renin
⬆ renal paracrine agents that ⬇ Na reabsorption
⬆ RIHP
what causes ANP secretion
increased plasma volume resulting in distension of cardiac atria
ANP Direct effects (2)
- acts directly on inner medullary collecting ducts to ⬇ Na reabsorption
- cGMP inhibition of luminal membrane Na channels
ANP indirect effects (4)
- granular cells ⬇ renin
- adrenal cortex to ⬇ ANG induced aldosterone secretion
- AA and EA constriction
- Dilation of Mesangial cells
dilation of mesangial cells causes
⬆ glomerular Kf ➡ ⬆ GFR ➡ ⬆ Na excretion
what causes ADH release
decreased plasma volume
ADH major function
increase permeability of cortical and medullary collecting ducts to water
ADH also increases
Na reabsorption by cortical collecting ducts
Dopamine inhibits
Na reabsorption
Dopamine is synthesized in
proximal tubule cells from L-DOPA taken up from renal circulation and glomerular filtration
L-DOPA is converted to dopamine where
proximal tubule epithelium
Dopamine is released to act in a — manner
paracrine
2 actions of dopamine
- internalization of NHE antiporters ad Na-K-ATPase pumps to reduce Na reabsoprtion
- reduce expression of all receptors to decrease ability of ANGII to stimulate Na reabsorption
