Test 2 (Tubular Transport: Basic Principles, Organic Solute Transport) Flashcards
(33 cards)
“Logic” of Renal Handling of Substances
- Bulk filtration of all small molecules into Bowman’s Capsule
- Selective retention of useful materials by Tubular Reabsorption
- Unwanted material pass into urine
- Some transport processes are Physiologically regulated to CONTROL AMOUNTS of SUBSTANCES in Body Fluids
Renal Handling of Water, Sodium, Glucose, and Urea
1) Water:
a) Amount filtered per day:
- 180 g
b) Amount Excreted:
- 1.8 g
c) Percent Reabsorbed:
- 99%
2) Sodium:
a) Amount filtered per day:
- 630 g
b) Amount Excreted:
- 3.2 g
c) Percent Reabsorbed:
- 99.5%
3) Glucose:
a) Amount filtered per day:
- 180 g
b) Amount Excreted:
- 0 g
c) Percent Reabsorbed:
- 100%
4) Urea:
a) Amount filtered per day:
- 56 g
b) Amount Excreted:
- 28 g
c) Percent Reabsorbed:
- 50%
Structure of Tubular Epithelium
- Basement Membrane
- Basolateral Membrane
- Interstitial Fluid
- Tight Junction
- Luminal Membrane
Transcellular vs Paracellular Movement
Transcellular:
- Movement of Solute and Water THROUGH the CELL
Paracellular:
- Movement of Solute and Water THROUGH the TIGHT JUNCTION
Basic Mechanisms for Transcellular Solute Movement
PASSIVE (“Downhill”) TRANSPORT
PASSIVE (“Downhill”) TRANSPORT:
1) Simple Diffusion:
- “Down” electrochemical gradient via LIPID BILAYER or Aqueous Channels
2) Facilitated Diffusion:
- “Down” electrochemical gradient; SPECIFIC CARRIERS REQUIRED
Basic Mechanisms for Transcellular Solute Movement
ENERGY–DEPENDENT (“Uphill”) PROCESSES
ENERGY–DEPENDENT (“Uphill”) PROCESSES:
1) Primary Active Transport:
- AGAINST Electrochemical Gradient; ATP HYDROLYSIS provides Energy
2) Secondary Active Transport:
- “Downhill” movement of one substance provides ENERGY for “Uphill” movement of another substance
- Cotransport, Countertransport
3) Pinocytosis:
- Protein Reabsorption
Proximal Tubular Transport
- Proximal Tubule Reabsorbs most of FILTERED Water, Na+, K+, Cl-, Bicarbonate, Ca2+, Phosphate
- Normally, reabsorbs ALL the FILTERED Glucose, Amino Acids
- Several Organic Anions and Cations (Including Drugs, Dug Metabolites, Creatinine, Urate) are secreted in PROXIMAL TUBULE
TF/ Plasma Concentration Ratios Provide information on Tubular Handling of Substances
- What fraction of filtered water is reabsorbed in Proximal Tubule?
(HINT: Look at INULIN Concentration Ratio)
- Na+ Concentration DOESNT CHANGE- does this mean Na+ isn’t Reabsorbed???
- Concentration fo Urea and Cl- INCREASE Somewhat, are these compounds secreted by Proximal Tubule? What about PAH?
TF/ P Ration in Proximal Tubular Lumen: INULIN
TF/ P = 3!!!!!
TF/ P Ration in Proximal Tubular Lumen: GLUCOSE
TF/ P = 0!!!!!
TF/ P Ration in Proximal Tubular Lumen: PAH
TF/ P = 10!!!!
Proximal Tubular Na+ Reabsorption
- Provides driving force for Reabsorption of Water, other solutes
- Polarity of Epithelial Cell membranes facilitates net UNIDIRECTIONAL TRANSPORT
- Ultimately powers by Na+, K+, ATPase in Basolateral membrane
- Na+ Reabsorption usually coupled to Transport of/ Exchange for another solute
Sodium Reabsorption is linked to Transcellular Transport of other substances
LUMEN:
1) Na+ and Glucose (Same direction)
2) Na+ and H+ (Opposite)
3) Na+, K+, Cl- (Same Direction but move 2 Cl-)
INTERSTITIUM:
1) Na+ and K+ (Opposite)
- Na+, K+, ATPase
Water Reabsorption follows Na+ Reabsorption
- In Proximal Convoluted Tubule, BULK FLOW!!!!
Paracellular Reabsorption of Cl- and Urea in Early PCT
- Not ACTIVE process, but ultimately DEPENDENT on Na+ and Water Reabsorption
- As Na+ and Water are Reabsorbed, Cl- and Urea become more concentrated in Luminal Fluid
- Modest concentration Gradient between Lumen and Peritubular Interstitial provides driving force for PARACELLULAR REABSORPTION
TF/P Concentration Ratios
- Note modest INCREASE in UREA and CL- Concentrations in Tubular Lumen
Factors Promoting Fluid Movement into Peritubular Capillaries
1) HIGH PLASMA COLLOID OSMOTIC PRESSURE in the Peritubular Capillary Blood (Due to Filtration of Fluid in Glomerulus)
2) LOW HYDROSTATIC PRESSURE in these Capillaries
3) CONSEQUENCE: Almost as much Fluid is Reabsorbed as was initially Filtered into Bowman’s Capsule
Impact of Organic Nutrient Handling
- Large amount of Nutrients (Glucose, Amino Acids) filtered each day; must be RETAINED
a) Small molecules: free filtered
b) Completely reabsorbed by Proxima Tubule
c) Mo reabsorption in more Distal Segments
- Kidneys DONT regulate PLASMA CONCENTRATION of Glucose and Amino acids, Liver and Endocrine systems do!!!
Basic Mechanism of Tubular Reabsorption of Glucose and Amino Acids
- Secondary ACTIVE TRANSPORT; Transcellular only
- Uptake accrois Luminal Membrane:
a) Against Concentration Gradient
b) Coupled to Na+ entry down its Electrochemical Gradient
c) Ultimately dependent on Na+, K+, ATPase
- Exits Cells through BASOLATERAL MEMBRANE by FACILITATED DIFFUSION
Mechanisms of Glucose Reabsorption
Luminal Membrane:
1) Na-Glucose COTRANSPORT
Basolateral Membrane:
1) Facilitated Diffusion
Glucose reabsorption is Saturable
- Limited number of Na+, Glucose Cotransproters in Luminal Membrane
- If filtered amount (load) of Glucose (=GFR x Pglucose) EXCEEDS a CERTAIN RATE:
a) Capacity of Nephrons to Reabsorb all the Filtered Glucose is exceeded
b) Glucose appears in the Urine (GLUCOSURIA)
- Identify a disease in which saturation occurs
- Same principles apply to Amino Acid Transport
Glucose Reabsorption is Saturable
- TmG= Tubular Glucose Maximum
Ex: Maximum rate of Glucose Reabsorption by all the Nephrons COMBINED
Questions for Discussion
- Would the Filtered Load of Glucose change if GFR INCREASED by Plasma Glucose Concentration remained Constant? How would this affect the Threshold Value?
- Would an inhibitor of the Renal Tubular Na+, K+ ATPase affect Reabsorption of Glucose? Why?
- Urine Output increases in Diabetes. Why?
- Why would a Diabetic patient by thirsty?
Consequences of Osmotic Diuretics
- INCREASED Water Excretion
- INCREASED Sodium Excretion (Why?)
