1. SOLUTE TRANSPORT MECHANISMS, TUBULAR REABSORPTION AND SECRETION WITH TRANSPORT MAXIMUM SYSTEM
Dr. Shafali Singh

2. OBJECTIVES
• Describe the routes and mechanisms of tubular reabsorption and secretion. • Describe how specific segments of the renal tubule and collecting duct reabsorb water and solutes. • Describe how specific segments of the renal tubule and collecting duct secrete solutes into the urine.

3. Transport Mechanisms
Simple diffusion: net movement represents molecules or ions moving down their electrochemical gradient.
Facilitated diffusion: (facilitated transport) molecule or ion moving across a membrane down its electrochemical gradient attached to a specific membrane bound protein
Active transport: a protein-mediated transport that uses ATP as a source of energy to move a molecule or ion against its electrochemical gradient

4. Characteristics of Different Types of Transport
Electrochemical Gradient
Carrier-Mediated
Metabolic Energy
Na+ Gradient
Simple diffusion
Downhill No
Facilitated diffusion
Yes
Primary active transport
Uphill —
Cotransport
Uphill*
Indirect
Yes, same direction
Countertransport
Yes, opposite direction

5. DYNAMICS OF PROTEIN-MEDIATED TRANSPORT
Uniport: transporter moves a single molecule or ion as in the uptake of glucose into skeletal muscle or adipose tissue. A type of facilitative transport
Symport: (cotransport) a coupled protein transport of 2 or more solutes in the same direction as in Na-glucose, Na-amino acid transporters.
Antiport: (countertransport) a coupled protein transport of 2 or more solutes in the opposite direction

6. Characteristics Common to All Protein-Mediated Transport
Rate of transport
Saturation kinetics: As the concentration of the substance initially increases on one side of the membrane, the transport rate will increase.
Once the transporters become saturated, transport rate is maximal (TM = transport maximum). TM is the transport rate when the carriers are saturated. It is directly proportional to the number of functioning transporters
Rate of transport- substance transported more rapidly than it would be by simple diffusion

8. Q
IF you add additional insulin to the resting muscle cell medium. What happens to the Tmax of glucose?

9. 3.Chemical specificity: To be transported, the substance must have a certain chemical structure. Generally, only the natural isomer will be transported. (e.g, D-glucose but not L-glucose). 4. Competition for carrier: Substances of similar chemical structure may compete for the same transporter. For example, glucose and galactose will generally compete for the same transport protein.

10. Q What’s the likely mechanism of transport ,
if the dynamics of D-glu transport is same as that of L- glucose transport.
If adding galactose to the medium where glucose transport is occuring ,doesn’t change the dynamics of glucose transport.

11. Primary and Secondary Transport

13. Q –What would happen to glucose transport ?
If you increase the Na+ concentration in the tubular lumen?
If you decrease the activity of the Na+ K+ pump?

14. Reabsorption Routes

15. TUBULAR REABSORPTION There are two basic types of active reabsorption based on system dynamics
TM system Gradient–time system.
General characteristics
Carriers appear to be never saturated.(Na carriers)
Carriers have a low affinity for the substrate.
There is high back leak.
General characteristics
Carriers are easily saturated.(limited carrier)
Carriers have a high affinity for the substrate.
There is low back leak.
Summary Statement
The entire filtered load is reabsorbed until the carriers are saturated; then the excess is excreted.
Na active reabsorption in PCT
High back leak means that some of the sodium that is actively reabsorbed back diffuses into the proximal tubule. The proximal tubule has leaky tight junctions to sodium and also to a few other substances, such as potassium, chloride, and water. This means that if GFR and the filtered load of sodium increases, reabsorption in the proximal tubule also increases. This prevents a dramatic increase in the
sodium load delivered distal to the proximal tubule. These segments have a limited capacity to reabsorb sodium. This phenomenon is referred to as glomerular tubular balance

16. Substances Reabsorbed by a TM system.
Almost all natural organic and some inorganic substances that are reabsorbed by the nephron are reabsorbed by a TM system.
These substances include glucose, amino acids, small peptides and proteins, ketone bodies, calcium, and phosphate.
PCT is leaky to Na, k ,Cl

17. An exception with respect to natural organic substances is urea.
Urea is freely filtered and partially reabsorbed, mainly by passive mechanisms.
Urea, as it passes through the nephron, tends to follow the water but not proportionately.
More water is reabsorbed than urea, which creates a net excretion for urea.
Urea excretion is flow dependent

18. Gradient–time Na active reabsorption in PCT

19. Glucose Filtration rate

20. Glucose reabsorption rate
Tmax is a good indicator of number of functioning nephron

23. Dynamics of Glucose Filtration and Reabsorption

24. At low plasma levels, the filtration and reabsorption rates of glucose are equal, thus glucose does not appear in the urine.
l TM is the maximal reabsorption rate of glucose, i.e., the rate when all the carriers are saturated. TM can be used as an index of the number of functioning carriers.
l The rounding of the reabsorption curve into the plateau is called splay. Splay occurs because some nephrons reach TM before others. Thus, TM for the entire kidney is not reached until after the region of splay.
l Plasma (or renal) threshold is the plasma glucose concentration at which glucose first appears in the urine. This occurs at the beginning of splay.

25. The graph below illustrates the relationship between plasma glucose concentration and glucose reabsorption by the kidney. The GFR is 100mL/min. The renal threshold for glucose is
a. 50 mg/dL
b. 100 mg/dL
c. 150 mg/dL
d. 200 mg/dL
e. 500 mg/dL

26. At plasma concentrations of glucose higher than occur at transport maximum (Tm), the
(A) clearance of glucose is zero
(B) excretion rate of glucose equals the filtration rate of glucose
(C) reabsorption rate of glucose equals the filtration rate of glucose
(D) excretion rate of glucose increases with increasing plasma glucose concentrations
(E) renal vein glucose concentration equals the renal artery glucose concentration

27. Q Q. Which point represents greatest filtration rate of glucose?
Q. As you move from D- E; what happens to filtration , reabsorption, excretion
Q. Lowest plasma level of gluc ,where you are reabsorbing at Tm.
Q .Lowest plasma level of gluc ,where glu is appearing in uine

28. Regulation of Tubular Reabsorption

29. Glomerulotubular Balance—The Ability of the Tubules to Increase Reabsorption Rate in Response to Increased Tubular Load.
Peritubular Capillary and Renal Interstitial Fluid Physical Forces

30. Summary of the hydrostatic and colloid osmotic forces that deter-mine fluid reabsorption by the peritubular capillaries. The numeri-cal values shown are estimates of the normal values for humans. The
net reabsorptive pressure is normally about 10 mm Hg, causing fluid
and solutes to be reabsorbed into the peritubular capillaries as they
are transported across the renal tubular cells. ATP, adenosine
triphosphate; Pc, peritubular capillary hydrostatic pressure; P
if, inter-stitial fluid hydrostatic pressure; pc, peritubular capillary colloid
osmotic pressure;pif
, interstitial fluid colloid osmotic pressure.

31. 3. Effect of Arterial Pressure on Urine Output—The Pressure-Natriuresis and Pressure-Diuresis Mechanisms 4. Hormonal Control of Tubular Reabsorption.( A4P) 5. Sympathetic Nervous System Activation Increases Sodium Reabsorption
Activation of the sympathetic nervous system can
decrease sodium and water excretion by constricting
the renal arterioles, thereby reducing GFR. Sympa-thetic activation also increases sodium reabsorption in
the proximal tubule, the thick ascending limb of the
loop of Henle, and perhaps in more distal parts of the
renal tubule. And finally, sympathetic nervous system
stimulation increases renin release and angiotensin II
formation, which adds to the overall effect to increase
tubular reabsorption and decrease renal excretion of
sodium

33. TUBULAR SECRETION p-aminohippuric acid (PAH) secretion
PAH secretion from the peritubular capillaries into the proximal tubule is an example of a transport maximum system

36. At plasma para-aminohippuric acid (PAH) concentrations below the transport maximum (Tm), PAH
(A) reabsorption is not saturated
(B) clearance equals inulin clearance
(C) secretion rate equals PAH excretion rate
(D) concentration in the renal vein is close to zero
(E) concentration in the renal vein equals PAH concentration in the renal artery

37. Substances secreted in the proximal tubule
Penicillin
Furosemide
Acetazolamide
Salicylate

39. NET EFFECTS OF REABSORPTION AND SECRETION

42. Given the following information, calculate the reabsorption rate for glucose.
GFR = 120 mL/min
Plasma glucose = 300 mg/100 mL
Urine flow = 2 mL/min
Urine glucose = 10 mg/mL
mg/min

43. Inulin
Protein
Na, K, urea
PAH
Creatinine
Glucose, bicarbonate