Test2: Wk7: 4 Bridge to pharmacology - renal transport mechanism - Puri Flashcards
Na transport along the nephron: thin loops only use — transport
passive
Na transport along the nephron: PCT 3 transporters
NHE
SGLT2
Na-AA-Cotransporter
66%
Na transport along the nephron TAL 2 transporters
NKCC2
ROMK
25%
Na transport along the nephron DCT 2 transporters
Na-Cl cotransport
Epi Ca Channels
5%
Na transport along the nephron CT 3 transporters
Epi Na Channels
ROMK
H-ATPase/ K-H exchanger
3%`
Na transport along the nephron: — can absorb 100% of Na
TAL
Na transport along the nephron: — is the only site of active reabsorptions of Ca
DCT
% Na filtered appears in urine
~1%
Cortical Collecting Tubule: Na+ resorption by
ENaC
Cortical Collecting Tubule: Na+ resorption creates
luminal negativity
luminal negativity leads to
K+ secretion
H+ secretion
3.Antidiuretic hormone (ADH) inserts — channels in the luminal membrane
H2O
— sensitive to amiloride
ENaC
𝜶-intercalated cells in the Cortical Collecting Tubule/Duct Primary Transporter
H-ATPase
𝜶-intercalated cells in the Cortical Collecting Tubule/Duct Secondary Transporter
HK- antiport
Aldosterone has three effects
Directly stimulate H-ATPase
- ↑Na-K-ATPase, which ↑Na gradient to enter the cell
- ↑ENaC activity and number—↑Luminal negativity—More H+ can be secreted
Na+ resorption in CT is key to — and —
excretion → activated by —
Na+ resorption in CT is key to K+ and H+
excretion → activated by aldosterone
Aldosterone — Na+ and K+ channel activity and
the activity of the Na/K-ATPase
Aldosterone ↑ Na+ and K+ channel activity and
the activity of the Na/K-ATPase
Na+ resorption creates luminal
negativity
3.Luminal negativity “draws” out
K
aldosterone “exchanges” — for —-
in the lumen of the distal nephron
Na for K
Luminal negativity also facilities H+ secretion
by
H-ATPase
when is aldosterone activated
when circulating blood volume is decreased
increased luminal flow increases K secretion resulting in
increased urine flow and increased K excretion
Hypokalemia promotes —- exchange in
the distal nephron
Hypokalemia promotes H/K exchange in
the distal nephron
Potassium-Sparing Diuretics prevent
hypokalemic alkalosis
DCT Transport water
impermeable to water, does not respond to ADH
DCT Transport Na and Cl cross by —
cotransport
DCT Transport Reabsorbs about % of filtered NaCl
5%
DCT Transport Thiazide diuretics bind to the
Cl- site on NaCl cotransporter
Thiazide Diuretics pH
alkalosis
Thiazide Diuretics K
hypokalemia
Thiazide Diuretics Na
hyponatremia
Thiazide Diuretics Ca
potential hypercalcemia
Thiazide Diuretics Mg
potential decrease with prolonged use
Thiazide Diuretics major use
Diuretic especially for hypertension
Thiazide Diuretics cause — loss leading to
Na loss leading to water loss
Potassium-Sparing Diuretics pH
acidosis
Potassium-Sparing Diuretics Na
decrease reabsorption
Potassium-Sparing Diuretics H
increase excretion
Potassium-Sparing Diuretics K
hyperkalemia
Thiazides Toxicities and Interactions: -Na+ and volume depletion activates — and can cause —-
RAAS; dehydration
Thiazides Toxicities and Interactions: Metabolic — and —
Metabolic alkalosis and hypokalemia
Thiazides Toxicities and Interactions Hypo
HYPO—kalemia, natremia, magnesemia
Thiazides Toxicities and Interactions Hyper
uricemia, glycemia, calcemia
Thiazides Toxicities and Interactions can cause — by causing hypokalemia
digoxin toxicity
K competes with — for binding to Na/K-ATPase
K competes with
digoxin for binding to Na/K-ATPase
TAL Transport % Na reabsorbed
25%
TAL Transport NaCl reabsorption occurs by
NKCC2
Thick ascending limb water permeability
not permeable
Thick ascending limb Lumen is positively charged making it a key site for
key site for
Ca++ and Mg++ resorption
luminal membrane is hyperpolarized
K+ leaving
basal membrane is depolarized
Cl- leaving
luminal membrane is depolarized
Na+ entering
basal membrane is hyperpolarized
K+ leaving
If the luminal membrane is hyperpolarized (K+ leaving) and/or the basal membrane is depolarized (Cl- leaving) the potential difference between the lumen and the interstitium is lumen
positive
If the luminal membrane is depolarized (Na+ entering)
and/or the basal membrane is hyperpolarized (K+
leaving) the potential difference between the lumen
and the interstitium is lumen
negative
Loop Diuretics urine effects
increase in Na+, K+, Mg2+, Ca2+, and urine flow rate
Loop Diuretics ph
alkalosis
Loop Diuretics K
hypokalemia
Loop Diuretics Mg
Hypomagnesemia
Loop Diuretics Ca
hypocalcemia - rare
Loop Diuretics bock — increasing renal blood flow
Flow sensing mechanism TGF
most effective Diuretic
Loop Diuretic
Loop Diuretic inhibit — which abolishes —
NKCC2; luminal positivity
Bartters Syndrome: Defective — or —
NKCC2 or ROMK -
hypoklaemia, metabolic alkalosis and hyperaldosteronism
Loop Diuretics Toxicities and Interactions hypo
HYPO—kalemia, magnesemia
Loop Diuretics Toxicities and Interactions hyper
HYPER—uricemia
Loop Diuretics can cause — and —
Metabolic alkalosis and dehydration
Loop Diuretics can cause — toxicity
digoxin
Loop Diuretics can cause — which is reversibly
ototoxicity
PCT Transport
NHE3
NHE3 is stimulated by
SNS and angiotensin II
Proximal Tubule water
freely permeable
Hyperglycemia causes
osmotic diuresis
Glucose
holds water in urine
Carbonic Anhydrase Inhibitors Major Use
Limited usefulness as diuretic
Treatment of glaucoma—topical dorzolamide
Carbonic Anhydrase Inhibitors pH
decrease bicarb leading to acidosis
Carbonic Anhydrase Inhibitors Cl
hyperchloremia
Carbonic Anhydrase Inhibitors K
hypokalemia
