Lecture 16: Tubular reabsorption and secretion-Exam 3 Flashcards
Ultrafiltration or bulk flow
Due to hydrostatic and colloid forces
water transported via specific channels: aquaporins
Types of aquaporins
Aquaporin-1: widespread including renal tubules
Aquaporin-2: found in apical membranes of collecting tubules and controlled by ADH
Aquaporin-3: found in basolateral membranes of collecting tubules
Characteristics of ATPases
Establish ionic gradient across nephron cell membranes
Gradient drives reabsorption and/or secretion of solutes
Solutes transported via secondary transport by symporters or antiporters.
Characteristics of channels
ENAC channels: found in apical cell membranes, closed by drug such as amiloride and opened by a number of hormones
CFTR(Cl-) channel and K+ channels: found in apical cell membranes of some segments of nephrons
Uniporters: found in cell membranes and driven by concentration gradientb of substance concerned
Types of transport
facilitated diffusion (glucose transport) occur through channels and uniporters
Active transport directly coupled with energy source
Secondary active transport indirectly coupled with energy source, example like glucose reabsorption y renal tubule
Primary active transporters
Na+K+ ATPase
H+ ATPase
H+K+ATPAse
Calcium ATPase
Sodium glucose transporters
Located on the brush borders of proximal tubule cells
SGLT2 reabsorbs 90% of glucose in early proximal tubule
SGLT1 reabsorbs 10% of glucose i late proximal tubule
Substances that are actively secreted into the renal tubules
Creatinine
Para-Aminohippuric acid
Transport maximum
Limit to the rate at which a solute can be transported
Due to saturation of specific transport system
Threshold for glucose reabsorption
Transport maximum=375 mg/min
Filtered load of glucose=GFR x Plasma glucose=125mg/min
Glucose reabsorption, excretion and transport maximum
Threshold for glucose excretion=200 mg/min even though transport maximum=375 mg/min.
Transport maximum representative of kidney as a whole and each nephron has limit on reabsorption
Reasons for lack of transport maximum
Rate of diffusion determined by electrochemical gradient
Permeability of membrane to the substance
Time that fluid containing substance remains within the tubule
Solvent drag
Movement of solutes(sometimes with existing gradient) due to movement of water by osmosis
Water reabsorption coupled mainly to sodium reabsorption
Coupling reabsorption of water, chloride and urea with sodium reabsorption
Sodium reabsorption–> water reabsorption
Sodium reabsorption–>increase in lumen negative potential
Water reabsorption –> increase chloride ions concentration in lumen and increase urea concentration in lumen
Increase in lumen negative potential and increase concentration of chloride ions—> passive reabsorption of chloride ions
Increase urea concentration in lumen–>passive reabsorption of urea
Characteristics of proximal tubule
Highly metabolic with large numbers of mitochondria
Extensive brush borders on luminal surfaces
Extensive intercellular and basal channels on interstitial surfaces
Processes in proximal tubule
Reabsorb 65% of filtered sodium, potassium, chloride and bicarbonate
Reabsorb all filtered glucose and amino acids
Secrete organic acids, bases and hydrogen ions into tubular lumen
Sodium reabsorption in proximal tubule
In first half ,via cotransport along glucose, AA and other solutes
In second half, mainly with chloride ions
Sodium transport in proximal tubule
Most Na+ entry via antiporter with H+
Na+ pumped out of cell by ATPase pump
Electrical gradient in cytoplasm=-70mV and in lumen=-3 mV
Concentration gradient in cytoplasm=30 mosm and in lumen=140 mosm
Hydrogen and bicarbonate ions in proximal tubule
H+ increases in lumen due t antitransport with Na+
H+ combines with bicarbonate and forms carbonic acid
Carbonic anhydrase splits carbonic acid into CO2 and H20
CO2 and H20 form carbonic acid
Carbonic acid splits into H+ and bicarbonate ions
Bicarbonate ions diffuse into interstitial space
H+ removed from cell via antitransport or H+ATPase
Characteristics of loop of Henle
Thin descending segment highly permeable to water and moderately permeable to most solutes including urea and sodium. It reabsorbs 20% of filtered water
Thick ascending segment impermeable to water and site of action of powerful loop diuretics (Furosemide, ethacrynic acid, bumetanide)
Transport mechanisms in ascending loop of Henle
ATP pump maintains low intracellular sodium concentration and negative electrical potential in the cell (-70 mV) by reabsorption of K+ into cells against concentration gradient
Secondary active transport via cotransporters of 1 sodium, 2 chloride and 1 potassium ions into cells
Slight back leak of potassium ions creates positive charge of + 8mV in lumen which forces cations to diffuse through paracellular pathway
Characteristics of early distal tubule
Forms macula densa
Reabsorbs most ions
Impermeable to water and urea
Possess Na+ Cl- cotransporter inhibited by thiazide diuretics
Characteristics of late distal tubule and collecting duct
Highly convoluted
has characteristics similar to ascending segment
Reabsorbs sodium and water from tubular lumen by principal cells
Secretes K+ into tubular lumen
Primary site of K+ sparing diuretics(Spironolactone, eplerenone, amloride, triameterene)
Intercalated cells reabsorb K+ from tubular lumen and secrete H+ into tubular lumen by H+ATPase
Characteristics of medullary collecting duct
Cuboidal epithelial cells with smooth surface and a few mitochondria
Permeability to water controlled by ADH
Permeable to urea by urea transporter
Capable of secreting H+ against a large concentration gradient
Aldosterone
Produced by adrenal cortex in response to increased extracellular K+ and/or increased level of angiotensin II
Increases sodium reabsorption
Stimulates potassium secretion and Na+K+ pump on basolateral membrane of cortical tubule membrane
Acts on principal cells of cortical collecting ducts
Absence results in marked loss of sodium and accumulation of potassium and causes Addison’s diseases
Hypersecretion leads to Conn’s syndrome
Angiotensin II
Increases sodium and water reabsorption
Returns blood pressure and extracellular volume towards normal
Stimulates aldosterone secretion
Constricts efferent arterioles
ADH (Anti Diuretic Hormone)
Produced by posterior pituitary gland
Increases water reabsorption
Binds to V2 receptors in late distal tubules, collecting tubules and collecting ducts
Increases formation of cAMP by stimulating movement of aquaporin-2 proteins to luminal side of cell membranes (form clusters)
ANP (Atrial Natriuretic Peptide)
Produced by cardiac atrial cells in response to distension
Inhibits reabsorption of sodium and water
Parathyroid hormone
Produced by parathyroid glands
Increases calcium reabsorption
Renal clearance
Volume of plasma that is completely cleared of the substance by the kidney per unit time
Cs x Ps = Us x V
Cs= clearance rate of substance= GFR for substance not reabsorbed r secreted in body
Ps=Plasma concentration of substance
Us= urine concentration of substance
V= Urine flow
Passive routes
For a substance to be reabsorbed it must be transported:
-To the tubular epithelial cells –> renal interstitial fluid
-Through the peritubular capillaries–> renal blood flow
Water is transported from lumen to renal interstitial fluid via transcellular and paracellular routes by osmosis
Plasma flow in the kidney
20% of 625 mL/min=125 mL
