5_HST110 Tubular Transport I and II 2017 Flashcards
What percent of the 180 L/day of filtered blood is excreted in the urine?
<1%
The processes of reabsorption and secretion are mediated by (X) proteins
X = membrane transport
What are 3 mechanisms that solutes can be transported across cell membranes?
Passive transport mechanisms
Active transport mechanisms
Endocytosis
All water movement in the nephron is (X)
X = passive
Diffusion does not require energy (ATP) expenditure, and it can be driven by (X) and (Y)
X = gradients
[chemical (concentration),
electrical (electrical potential difference), and osmotic pressure]
Y = solvent drag
Facilitated diffusion: With coupled transporters, at least one solute is transported against its (X) gradient, driven by the passive downhill movement of one of the other solutes, also called (Y)
X = electrochemical Y = secondary active transport
Active transport usually involves movement of solutes (X) a concentration gradient
X = against
Endocytosis is important for the reabsorption of (X) and macromolecules by the (Y)
X = small proteins Y = proximal tubule
Tight junctions, dividing the apical and basolateral surfaces/memebranes, have some properties of ion channels, which enable select ions to diffuse across the tight junction based on size and charge. This is important in what type of transport?
Transepithelial transport, paracellular transport
What is the transport mechanism of passing from the lumen to the interstitium through cells rather than around them?
Transcellular transport
What are the units of osmolality?
mOsm/kg. Reflects the concentration of substances in a fluid
Osmolality is only effective in driving osmosis when the barrier is (X) permeable to solutes than to water
X = less
Solutes are as permeable as water in the endothelial barrier, so water movement is driven by (X) forces. In the epithelial barrier (tubules), solutes are less permeable than water, so water movement is driven by (Y)
X = Starling Y = osmotic gradients
How many mEq of Na+ and how many L of water a day are reabsorbed by the tubular system?
25000 mEq/day
179 L/day
Proximal vs. Distal: Major function
Proximal: High-capacity reaborption of water and solutes
Distal: “Fine tuning” urine composition and volume
Proximal vs. Distal: Energy requirement for transport
Proximal: Low-energy or passive
Distal: High-energy, active
Proximal vs. Distal: Transport mechanisms
Proximal: Diffusion, facilitated diffusion, coupled transport, solvent drag, active transport
Distal: Active transport
Proximal vs. Distal: Permeability to water
Proximal: Permeable throughout
Distal: Mostly impermeable
Proximal vs. Distal: osmotic gradient
Proximal: Small
Distal: Large
Proximal vs. Distal: Tight junctions
Proximal: Leaky
Distal: Tight
Proximal vs. Distal: Regulation of transport
Proximal: Largely unregulated
Distal: Tightly regulated
What active transporter is critical for the proximal tubule’s ability to reabsorb solutes and water?
Na+-K+-ATPase at the basolateral membrane
3Na+ out, 2K+ in (interior of cell becomes electrically negative with respect to tubular lumen). Na+ drawn into cell from tubular lumen, prompting more ATPase activity to return to normal concentration (low intracellular Na+)
What apical transporters of the 1st half of the PT are important in coupling Na+ reabsorption with H+ export or reabsorption of other organic solutes?
** Important **
Na+-H+ antiporter (NHE3)
Na+ entry coupled with H+ exit into lumen
Responsible for most Na+ reabsorption in PCT
Symporters (coupled transport) Na+-glucose (SGLT2) Na+-amino acid Na+-phosphate Na+-lactate
Glucose and other organic solutes reabsorbed with Na+ leave the cell and enter the blood by (X) mechanisms
(unlike Na+, through its Na+-K+-ATPase). This generates negative transepithelial voltage across PT providing driving force for reabsorption of (Y) in the 2nd half of PCT
X = passive Y = Cl-
What are the transporters for renal handling of glucose? (all filtered is reabsorbed by PT)
Note: Tight junctions have minimal permeability to glucose (no back-leak)
SGLT2 and SGLT1 symporters reabsorb glucose with Na+ from tubular lumen into the cell
GLUT2 uniporter transports
Rate-limiting step of glucose transport is the (X) symporter. Therefore, abnormally high filtered loads of glucose will overwhelm the reabsorptive capacity (plasma glucose above (Y) mg/dL though glucose can be detected in urine when plasma levels exceed 180-200 mg/dL). Spilling of glucose into urine is called (Z)
X = SGLT2 Y = 300 Z = glucosuria
In the 2nd half of PT, Na+ is mainly reabsorbed with (X)
The rise in tubular [(X)] in the first half of the PCT sets up a (X) concentration gradient between tubular lumen and interstitial space. (X) is reabsorbed both in a (Y) and (Z) fashion
X = Cl- Y = transcellular Z = paracellular
In the PT, water diffuses passively from lumen into PT cell via two mechanisms due to transtubular osmotic gradient from solute reabsorption
Aquaporin-1 (AQP1) channels (apical AND basolateral membranes) Paracellular route (with solvent drag)
In the PT, increased water in the interstitial space increases (X) and drives the movement of water and solutes into the peritubular capillaries
X = hydrostatic pressure
In the PT, proteins are reabsorbed via receptor-mediated (X). Endocytosed proteins are (Y) into amino acids inside the proximal tubular cell and recycled to the body
X = endocytosis (megalin/cubulin mediated) Y = enzymatically degraded
Proximal tubular cells can secrete organic anions and cations into the tubular lumen. Many organic anions and cations compete for the same secretory pathways (transporters are (X) and (Y))
X = nonspecific Y = saturable
Hereditary or acquired proximal tubule dysfunction results in impaired ability to reabsorb solutes. Results in inappropriate urinary excretion of glucose, amino acids, phosphate, and/or low molecular weight proteins
Fanconi Syndrome
The (X) of salt and water is characteristic of the LOH
X = separation
What percentage of filtrered NaCl and water is reabsorbed by the LOH?
25% NaCl, 15% water
The thin descending limb of the LOH exhibits no (X) reabsorption and (Y) water reabsorption (AQP1). Thus, tubular [NaCl] (Z)
X = NaCl Y = Passive Z = increases
The thick ascending limb of the LOH exhibits (X) NaCl reabsorption and (Y) water reabsorption. Thus, tubular [NaCl] (Z)
X = Passive Y = no Z = decreases
LOH TAL: Na+ transport steps
1) Na+-K+-ATPase generates electrochemical gradient
2) Na+-K+-2Cl- symporter (NKCC2) reabsorbs Na+ with K+ and 2Cl-
3) K+ channel (ROMK) enables K+ reabsorbed via NKCC2 to recycle back into tubular lumen (“back-leak”)
Required for continued function of NKCC2
4)Na+ leaves cell via Na+-K+-ATPase
“Back-leak” of K+ via ROMK generates a lumen-(X) voltage
X = positive
TAL ROMK lumen positive voltage drives paracellular uptake of various cations, including (X)
X = Na+, K+, Mg2+, and Ca2+
TAL is the main site of (X) reabsorption in the nephron
X = Mg2+
TAL is called the (X) segment of the nephron due to the NaCl reabsorption without water
X = diluting
Set of autosomal recessive inherited diseases characterized by: hypokalemia and metabolic alkalosis
Patients typically also have hypomagnesemia and hypocalcemia
Functionally resembles a patient on loop diuretics
Bartter’s Syndrome
Distal Convoluted Tubule: Na+ reabsorption is mediated by a (X) symporter
Blocked by thiazide diuretics
X = Na+-Cl- (NCC)
DCT is also the major site for regulated reabsorption of (X) (under the control of parathyroid hormone) via apical (X) channels
X = calcium, Ca2+
Autosomal recessive inactivating mutation in Na+-Cl- symporter gene (SLC12A3)
Characterized by metabolic alkalosis, hypokalemia, and hypocalciuria
Patients typically have hypomagnesemia
Functionally resembles a patient on thiazide diuretics
Gitelman’s Syndrome
Steps in CCD Na+ transport
1) Na+-K+-ATPase generates electrochemical gradient
2) Na+ reabsorbed via epithelial Na+ channel (ENaC) at apical membrane (Generates lumen-negative voltage. Blocked by K+ sparing diuretics (e.g. amiloride))
3) Lumen-negative voltage drives secretion of K+ into the lumen via ROMK. Important site of K+ secretion.
4) Na+ leaves cell via Na+-K+-ATPase
CCD Acid-Base Balance
α-intercalated cells: Secrete (X) H+-K+-ATPase H+-ATPase Reabsorb (Y) and (Z)
β-intercalated cells:
Secrete (Y) and reabsorb Cl-
Cl-/HCO3- antiporter (Pendrin)
Reabsorb (X)
X = H+ Y = HCO3- Z = K+
CCD Principal cells Principal cells reabsorb water to a varying degree under the hormonal control of (X). Mediated by aquaporin-2 (AQP2) channels in the (Y) membrane and AQP3 and AQP4 channels in the (Z) membrane
X = antidiuretic hormone (ADH) Y = apical Z = basolateral
Autosomal dominant disorder characterized by early onset:
Hypertension
Hypokalemia
Metabolic alkalosis
Caused by mutations in either the β or γ subunit of ENaC, which increase the number of Na+ channels in the apical cell membrane. Increased Na+ reabsorption leads to increased extracellular volume and hypertension
Liddle Syndrome
Na+ and water reabsorption increase in proportion to the increase in GFR and filtered load of Na+. A constant fraction of filtered Na+ (about 65%) is reabsorbed by the proximal tubule despite changes in GFR. What is this called?
Glomerulotubular Balance. Tubule (not glomerulus) is responding. Intrarenal mechanism, not dependent on external neural or hormonal input
