Physiology for MRCEM Primary

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Renal physiology

Tubular transport

[box type=”download”]  Available modes of tubular transport (paracellular and transcellular)  Simple understanding of the difference between primary + secondary active transport  Concept of maximal tubular transport and implications for glucose threshold  Plasma level of glucose above which splay and saturation occur[/box]

In a healthy adult, ∼180 L of filtrate enters the proximal tubules daily.
A significant component must be reabsorbed to prevent the loss of water and solutes.
The net reabsorption or secretion of any substance can be determined from its clearance.

Tubular transport processes

Reabsorption and secretion occur across the tubular epithelium by various means:
–diffusion through tight junctions and lateral intercellular spaces (paracellular pathway).
–driven by concentration, osmotic or electrical gradients.
–or by active transport through the epithelial cells themselves (transcellular pathways).

Active process can occur on either the apical or basolateral cell membrane, with passive diffusion across the opposite membrane driven by the concentration gradient so created.
The movement of solutes between the peritubular space and capillaries is by bulk flow and diffusion;
The movement of water is influenced by Starling’s forces.
Primary active transport uses adenosine triphosphate (ATP) directly, e.g. the Na+–K+ ATPase (Na+ pump).
Secondary active transport uses the concentration gradient(mostly Na+ gradient) created by primary active transport as an energy source.
Symporters (or cotransporters) transport substances in the same direction as (for example) Na+, whereas antiporters transport in the opposite direction.
Diffusion rate is enhanced by ion channels and uniporters (carrying only one substance), which effectively increase membrane permeability to specific substances; this is termed facilitated diffusion, and may be modulated by hormones or drugs.

Tubular transport maximum

For any substance, there is a maximum rate of reabsorption or secretion, – the tubular transport maximum (Tm).
For example, glucose is normally completely reabsorbed in the proximal tubule.
However, when the filtrate glucose concentration rises above the threshold, the transporters saturate, and glucose appears in the urine. Once Tm is reached, excretion increases linearly with filtration.
The threshold concentration is somewhat lower than that required to reach Tm because of the variation in transport maxima between nephrons; this is called splay.
Secretory mechanisms also exhibit Tm. At higher concentrations, PAH secretion becomes saturated, and further excretion is limited to the filtered load.