SOLUTE TRANSPORT MECHANISMS, TUBULAR REABSORPTION AND SECRETION

WITH TRANSPORT MAXIMUM SYSTEM

Dr. Shafali Singh

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.

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

Characteristics of Different Types of Transport

TypeElectrochemic

al GradientCarrier-

MediatedMetabolic

EnergyNa+

Gradient

Simple diffusion Downhill No No NoFacilitated diffusion Downhill Yes No No

Primary active transport Uphill Yes Yes —

Cotransport Uphill* Yes IndirectYes, same direction

Countertransport Uphill* Yes IndirectYes, opposite direction

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

Characteristics Common to All Protein-Mediated Transport

1. Rate of transport2. 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

Q

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

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.

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.

Primary and Secondary Transport

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?

Reabsorption Routes

TUBULAR REABSORPTION There are two basic types of active reabsorption based on system dynamics

TM system Gradient–time system. General characteristics

•Carriers are easily saturated.(limited carrier)•Carriers have a high affinity for the substrate.•There is low back leak.

Summary StatementThe entire filtered load is reabsorbed until the carriers are saturated; then the excess is excreted.

General characteristics

•Carriers appear to be never saturated.(Na carriers)•Carriers have a low affinity for the substrate.•There is high back leak.

Na active reabsorption in PCT

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.

• 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.

Gradient–time Na active reabsorption in PCT

Glucose Filtration rate

Glucose reabsorption rate

Dynamics of Glucose Filtration and Reabsorption

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.

• 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

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

Q

Regulation of TubularReabsorption

1. Glomerulotubular Balance—The Ability of the Tubules to Increase Reabsorption Rate in Response to Increased Tubular Load.

2. Peritubular Capillary and Renal Interstitial Fluid Physical Forces

3. Effect of Arterial Pressure on Urine Output—The Pressure-Natriuresis and Pressure-Diuresis Mechanisms4. Hormonal Control of Tubular Reabsorption.( A4P)5. Sympathetic Nervous System Activation Increases Sodium Reabsorption

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

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

Substances secreted in the proximal tubule

• Penicillin• Furosemide• Acetazolamide• Salicylate

NET EFFECTS OF REABSORPTION AND SECRETION

• 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

InulinProteinNa, K, ureaPAHCreatinineGlucose, bicarbonate