Back by popular demand…all two of you…the second chapter of The Clinical Physiology of Acid Base and Electrolyte Disorders.

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Chapter Outline

- Renal Circulation and GFR

    - RBF is 20% of cardiac output

        - In terms of mL per 100 g organ weight it is 4x the liver and exercising muscle and 8x coronary blood flow!

        - After the glomeruli the efferent arteriole have two fates

            - Peritubular capillaries in the cortex

                - Peritubular capillaries are not necessarily associated with their parent glomeruli. Weird.

            - Vasa recta from juxtamedullary glomeruli in the medulla

Joel Says: This seems wrong. Solute balance can be maintained down to a very low GFR. The R^2 here would be very low. Prove me wrong.

    - States that GFR is an important determinant of solute and water excretion.

- Glomerular anatomy and function

    - Structure

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Four editions of the Bud Bible up top and a copy of Bud Light on the bottom.

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        - Glomerulus is a tuft of capillaries

            - Enclosed in a capsule of epithelial cells, called Bowman’s capsule

            - The epithelial cells of Bowman’s capsule are continuous with the epithelial cells of the proximal tubule

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Looking at scanning EMs of the glomerulus is one of life’s simple pleasures—Josh.

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Josh says: Look at the review in Nature Reviews Nephrology from Rachel Lennon’s group

Complexities of the glomerular basement membrane

        - Filtration barrier

            - Epithelial cell (podocyte)

                - Epithelial cells adhere to the basement membrane via foot processes and the foot processes have slit diaphragms 

            - Basement membrane

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New Super-resolution structure of the GBM: https://elifesciences.org/articles/01149 Hi res microscopy is really hi-res. Technique is call ed STORM.

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Melanie talks about conduits through the glomeruli. Here is a cool review:

Why until just now? Undiscovered uniqueness of the human glomerulus! by L. Gabriel Navar, Owen Richfield

Am J Physiol Renal Physiol. 2018 Nov 1; 315(5): F1345–F1346. Published online 2018 Aug 15. doi: 10.1152/ajprenal.00369.2018 PMCID: PMC6293291

                - Produced by both the endothelial cells and podocytes

                - Formed from type IV collagen

                    - Abnormalities of type 4 collagen cause Alport

                        - The gene coding for the alpha 5 chain is the culprit

                        - COL4A5

                    - Abnormal Alpha 3 and 4 chains can also cause hereditary nephritis

                - Has other substances

                    - Laminin

                    - Nidogen

                    - Heparin sulfate proteoglycans

                        - Provides the negative charge

            - Enthothelial cell (fenestrated)

        - Protein excretion

            - Glomerular function: allow filtration of small solutes (Na and urea) while preventing filtration of larger molecules

                - Insulin MW 5,200 is freely filtered (upper range of freely filtered)

                - Preventing loss of protein prevents

                    - Negative nitrogen balance

                    - Development of hypoalbuminemia

                    - Infection from loss of immunoglobulin

                - Size and charge selectivity of the GBM

                    - pores are between cords of type 4 collagen

                    - The epithelial cells and slit diaphragms matter

                        - Macromolecules that pass through GBM can accumulate underneath the epithelial layer

                        - Isolated GBM in invitro studies is much more permeable to than intact glomerulus

                        - There is increased protein filtration in areas where the epithelial cells have detached from the GBM

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