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This interactive tutorial focuses on how the transport of solutes occurs in the proximal tubule of the kidney and how these systems are regulated by hormones and nerves. The tutorial complements lectures and practical classes for medical, health sciences, physiology and physiotherapy students. It aims to improve understanding of:
- functional and structural relations between parts of the nephron
- filtrate composition and solute movements across the proximal tubule epithelium
- cellular mechanisms at work in a proximal tubule epithelial cell
- how transport of solutes may be limited
- how hormones can regulate solute transport.
The tutorial begins with the anatomy of the kidney and nephron. You can explore photographs and diagrams of the kidney and nephron and view enhanced electronmicrographs of the proximal tubule.
Analysis of proximal tubule transport is introduced with explanations of the use of inulin and creatinine as markers for water reabsorption and how their clearance can be used to estimate glomerular filtration rate (GFR). You take samples to determine concentrations in tubular fluid and compare TF/P ratios along the proximal tubule of sodium, potassium, chloride, bicarbonate, glucose, amino acids, inulin, and osmotic concentration to decide whether each is reabsorbed or secreted or not reabsorbed or secreted.
You are then asked to construct a functioning proximal tubule epithelial cell capable of reabsorbing sodium, chloride, bicarbonate, glucose, amino acids and water by placing membrane transporters and channels on a cell template. Click "start cell" at any stage to begin the animation and see the ions and solutes move according to your design. Context-sensitive hints and feedback guide you toward the correct positioning of the Na+K+ATPase, Na+H+ exchanger, K+ channel, Na+HCO3- cotransporter, solute (X) transporter and Na+X cotransporter. Putting transporters in incorrect positions and watching the animated outcome is quite entertaining, and setting up an unworkable arrangement and watching it unfold to its logical conclusion helps to build stronger understanding and problem-solving skills.
You investigate the saturation of transporters in the proximal tubule through an interactive animation of the renal threshold for glucose. Various rates of glucose filtration are applied to illustrate the concept of maximum transport. The tasks include questions on diabetes.
To view an example of a control mechanism for sodium reabsorption, you apply angiotensin II to your model of a proximal tubule cell with an AT1 receptor in place. You investigate the effect of applying an AT1 blocker.
Part A of the tutorial ends with a look at the relation between filtration and reabsorption in a superficial proximal tubule.
In Part B, you investigate the control by various hormones and neurotransmitters of reabsorption of water and solutes in the proximal tubule using the cell model you constructed. The model now has basolateral receptors for ANF (atrial natriuretic factor), endothelin, insulin, angiotension II and noradrenaline. You can apply these hormones, and also AT1 antagonist (AT1-receptor blocker) and amiloride, to the cell to investigate the effects on sodium reabsorption, specifically its suppression.
Authors: Debbi Weaver, Robert Kemm, Lea Delbridge, Tom Petrovic, Peter Harris
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