Flashcards in Lecture 17: Tubular Reabsorption And Secretion Deck (28)
Describe the passive transport route
* For a substance to be reabsorbed, it must first be transported:
- Across the tubular epithelial membranes into the renal interstitial fluid.
- Through the peritubular capillary membrane back into the blood.
* Water is transported from the lumen through the tubular cells into the interstitium via both transcellular and paracellular routes by osmosis.
- See Slide 5
Describe ultrafiltration and bulk flow
* Water is transported by way of specific water channels:
- Aquaporins (AQP):
-- Aquaporin-1 is widespread, incl. renal tubules.
-- Aquaporin-2: Present in apical membranes of collecting tubule cells and Controlled by ADH
--Aquaporin-3: Present in basolateral membranes of collecting tubule cells.
* ATPases establish ionic gradients across nephron cell membranes:
- Gradients drive reabsorption or secretion of many other solutes.
- These are then transported by way of “secondary” active transport.
-- Solute moves with Na+ gradient
- Antiport (countertransport)
-- Solute moves opposite to Na+ gradient
Describe ATPases and their association with channel movement
* ENaC channel
- Found in apical membrane of nephron cells
- Closed by drug amiloride
- Opened by a number of hormones
* CFTR (chloride) channels and K+ channels also found in apical membranes of some segments of nephron.
* Uniporters are also found in cell membranes:
- Driven by concentration gradient of substance concerned
* Transport occurring through channels or uniporters
- Facilitated transport
- i.e.: glucose transport
* Transport directly coupled to an energy source
- = active transport
* Transport that is coupled indirectly to an energy source (i.e., ion gradient)
- = secondary active transport
What enzymes are primary active transporters?
* Calcium ATPase
- Study Fig. 28-2
- See Slide 12
Describe secondary active transport
* Reabsorption of glucose or amino acids by renal tubule are examples of secondary active transport:
- Sodium-glucose co-transporters on brush border of proximal tubule cells:
-- SGLT2: Reabsorbs 90% of glucose in early proximal tubule
-- SGLT1: Reabsorbs 10% of glucose in late proximal tubule
- See Slide 14
List substances that are actively secreted into the renal tubules.
* Para-aminohippuric acid
Describe the transport maximum
* Limit to the rate at which the solute can be transported:
* Due to saturation of a specific transport system
* Threshold for glucose reabsorption:
- Transport max. for glucose = 375 mg/min
- Filtered load for glucose = 125 mg/min
- GFR x plasma glucose = 125 ml/min x 1 mg/ml
- See Slide 18
What are some reasons that some passively reabsorbed substances do not have a transport maximum
* Rate of diffusion is determined by electrochemical gradient of the substance
* Permeability of the membrane for the substance
* Time that the fluid containing the substance remains within the tubule
What is the Gradient-Time Transport
* Rate of transport depends on:
- The electrochemical gradient
- Time the substance is in the tubule:
-- Depends on tubular flow rate
* Characteristic of some passively reabsorbed substances
* Includes some other substances that are actively transported
What is solvent drag
* Passive water reabsorption by osmosis is coupled mainly to sodium reabsorption.
* Osmotic movement of water can also carry some solutes =
- Solvent drag
- See slide 22
Describe the proximal tubule
* Highly metabolic w/large numbers of mitochondria
* Extensive brush borders on luminal surfaces
* Extensive intercellular and basal channels on interstitial surfaces
- 65% of filtered sodium, chloride, bicarbonate and potassium
- Reabsorb all filtered glucose and amino acids
- See Slides 26-29
- Organic acids, bases and hydrogen ions into tubular lumen
* Sodium reabsorption:
- In first half of proximal tubule:
-- Reabsorption is via co-transport along with glucose, amino acids, and other solutes.
- In second half of proximal tubule:
-- Reabsorption is mainly with chloride ions
Describe sodium transport in the proximal tubule
* Most Na+entry is via antiport with H+
* Na+ is pumped out of cell via Na+K+ATPase pump
- 3Na+: 2K+
- K+ can easily diffuse back out of cell.
* Electrical gradient:
- Cytoplasm = -70 mV
- Tubular lumen = -3 mV
* Concentration gradient:
- Luminal Na+ concentration = 140 mOsm
- Cytoplasmic Na+ concentration = 30 mOsm
Describe Hydrogen and bicarbonate ions in the proximal tubule
* [H+] increases in lumen due to antiport transport with Na+
* H+combines with luminal bicarbonate
* Forms carbonic acid
* Carbonic anhydrase in lumen splits carbonic acid into carbon dioxide and water.
Describe what occurs when carbon dioxide and water enter cell in the proximal tubule
* Carbon dioxide and water combine to form carbonic acid.
* Carbonic acid dissociates to form bicarbonate ion and H+
* Bicarbonate ion diffuses out of cell into interstitial space.
* H+removed from cell via:
- Antiport with Na+
Describe the Thin Descending Segment of the Loop Of Henle
* Highly permeable to water and moderately permeable to most solutes, including urea and sodium
* Reabsorbs about 20% of filtered water
* Impermeable to water
Describe the thick ascending segment of the Loop Of Henle
* Na+K+ATPase pump in basolateral membranes:
- Drives reabsorption of K+ into cell against concentration gradient.
* Sodium, Potassium, Chloride co-transporter:
- Moves 1-sodium, 2-chloride, 1 potassium into cell.
* Slight back leak of K+ into lumen:
- Creates positive charge of +8 mv.
- Forces Mg++ and Ca++ to diffuse through tubular lumen through paracellular space into interstitial fluid.
* Impermeable to water
* Site of action of powerful “loop” diuretics:
- Ethacrynic acid
- See Slide 34-35
Describe the distal tubule
* First portion forms macula densa.
* Next part is highly convoluted and has characteristics similar to thick ascending segment of loop of Henle.
* Reabsorbs most of the ions but is impermeable to water and urea:
- Therefore, referred to as diluting segment.
- Na+-Cl─ co-transporter (luminal membrane)
- Na+K+ATPase pump (basolateral membrane)
- See Slide 39-40
Describe the principle cells of the Late Distal Tubule/Cortical Collecting Tubule
* Reabsorb Na+ and water from tubular lumen.
* Secrete K+ into tubular lumen.
* Uses Na+K+ATPase pump.
* Primary site of K+sparing diuretics:
- Spironolactone, eplerenone, amiloride, triameterene
- See Slide 42-43
Describe the intercalated cells of the Late Distal Tubule/Cortical Collecting Tubule
* Reabsorb K+ from tubular lumen.
* Secrete H+ into tubular lumen:
- Mediated by a H+ATPase transporter.
- H+is generated through the action of carbonic anhydrase.
- For each H+ secreted, a bicarbonate ion is reabsorbed across the basolateral membrane.
See Slide 45
Describe the Medullary Collecting Duct
* Epithelial cells are cuboidal:
- Smooth surfaces
- Few mitochondria
* Permeability to water controlled by ADH.
* Permeable to urea:
- Urea transporters
* Capable of secreting H+ against a large concentration gradient.
See Slides 47-52
For aldosterone, describe the source, function, site of actin, and stimulus for secretion
- Adrenal cortex
- Increases sodium reabsorption and stimulates potassium secretion.
-- Stimulates Na+K+ATPase pump on basolateral side of cortical collecting tubule membrane.
* Site of action:
- Major site of action is on the principal cells of cortical collecting ducts.
* Stimulus for secretion:
- Increased extracellular potassium
- Increased levels of angiotensin II
* Absence of:
- Addison’s disease
- Results in marked loss of sodium and accumulation of potassium
- Conn’s syndrome
Describe the function and effects of angiotensin II
- Increased sodium and water reabsorption
- Returns blood pressure and extracellular volume toward normal
- Stimulates aldosterone secretion
- Constricts efferent arterioles
- Directly stimulates sodium reabsorption in proximal tubules, loops of Henle, distal tubules, and collecting tubules
- See Slide 57
Describe the source, function, and effects of ADH
- Posterior pituitary
- Increases water reabsorption
- Binds to V2receptors in late distal tubules, collecting tubules, and collecting ducts
- Increases formation of cAMP
-- Stimulates movement of aquaporin-2 proteins to luminal side of cell membranes (form clusters)
Describe the source and function on ANP
- Cardiac atrial cells in response to distension
- Inhibits reabsorption of sodium and water
Describe the source and function of parathyroid hormone
- Parathyroid glands
- Increases calcium reabsorption
Define and give the equation for renal clearance
* Renal clearance of a substance:
- = volume of plasma that is completely cleared of the substance by the kidneys per unit time.
- Example: If 1 ml of plasma contains 1 mg of a substance, and if 1 mg of this substance is excreted in the urine per minute:
-- Then 1 ml/min of the plasma is cleared of the substance.
* Cs x Ps = Us x V
- Cs = clearance rate of substance s
- Ps = plasma concentration of substance s
- Us = urine concentration of substance s
- V = urine flow 63
* Cs = (Us x V)Ps