Glomerular Filtration And It’s Control Flashcards
Main functions of the kidneys
- Filter and excrete - remove metabolic waste products and toxins from blood and excrete into urine.
- Regulate key homeostatic systems - body fluid status, body electrolyte balance and body acid-base balance.
- Produce Hormones - Erythrogenesis, Ca2+ metabolism and regulation of blood pressure and blood flow.
Nephrons
- Functional unit is the nephron, ~1 million nephrons in each human kidney.
- Each nephron is composed of one glomerulus for filtration and one tubule for reabsorption/secretion.
- The kidney cannot regenerate nephrons, they reduce in number with age, but renal function remains until drastic loss.
- Two types - Superficial (Cortical) Nephron (glomerulus is in outer region of cortex, Loop of Henle is short and terminates in outer medulla and efferent arteriole forms only the peritubular capillaries) and Juxtamedullary Nephron (glomerulus is closer to the medulla, Loop of Henle is much longer, extending into inner medulla and efferent arteriole forms peritubular capillaries and vasa recta).
Glomerular Filtration
- 20% circulation delivered to kidneys via renal artery renal blood flow). Renal artery > interlobar artery > arcuate artery > interlobular artery > afferent arteriole.
- Blood is then filtered across the glomerular filter.
- The rest of the blood then exits the glomerular capillaries via the efferent arteriole. Efferent arteriole > peritubular capillaries > interlobular vein.
Renal Blood Supply
Renal Artery > Interlobar Artery > Arcuate Artery > Interlobular Artery > Afferent Arteriole > Glomerulus > Efferent Arteriole > Peritubular Capillaries > Interlobular Vein > Arcuate Vein > Interlobar Vein > Renal Vein
Triple Layer of Glomerulus
- 1 - Endothelial Cells of the Glomerular Capillaries - covered by a glycoalyx with negatively charged molecules. Contain many fenestrations. Pore size ~70nm. Not a barrier to H20 and small solutes (including proteins/large molecules). Mainly limits filtration of cellular elelments e.g. erythrocytes.
- 2 - Basement Membrane of the Capillaries - lies between endothelium and podocytes (modified epithelial cells). Composed of collagen, laminin, and heparin sulphate (contains negatively-charged proteoglycans). Pore size 12-14nm. Restricts intermediate to large sized solutes (molecular weight >1kDa).
- 3 - Foot Processes of the Podocytes - interdigitating processes that cover the basement membrane. These almost “zip” together via slip diaphragms. Contain negatively charged glycoproteins. Pore size 4-10nm.
How does electrical change affect filtration rate?
- Electrical charge affects the filtration rate e.g. dextran.
- For any molecular radius, positively charged molecules are filtered much more readily than negatively charged molecules.
- So large negatively charged proteins e.g. serum albumin are not filtered despite being small enough.
Renal Blood Flow (RBF)
Total volume of blood that traverses the renal artery/vein oer unit time. ~1100ml/min. 20%of total cardiac output.
Renal Plasma Flow (RPF)
Total volume of plasma that traverses the renal artery/vein per unit time. RPF = 55% x 1100 = 600ml/min (if haematocrit is 45%).
Glomerular Filtration Rate (GFR)
Volume of fluid filtered from the glomerular capillaries to the Bowman’s capsule per unit time. ~20% of renal plasma flow, ~120ml/min.
Ultrafiltrate
Filtered fluid entering the Bowman’s capsule. ~180L/day (average GFR/day). Travels along the tubule and will leave via ureter as urine, ~1-1.5L/day.
Generation of Ultrafiltrate
Balance of pressures (Starlings Forces). Two forces supporting ultrafiltration and two forces opposing ultrafiltration.
- Hydrostatic Pressure of Blood (55mmHg - high as afferent arteriole moves into efferent arteriole and not a vein). Supports ultrafiltration - wants things to move out of blood.
- Hydrostatic Pressure of Bowman’s Space (15mmHg). Opposes ultrafiltration - wants things to stay in blood.
- Oncotic Pressure of Blood (30mmHg) - Opposes ultrafiltration.
- Oncotic Pressure of Bowman’s Space (none because proteins don’t cross glomerular filter). Supports ultrafiltration.
Regulation of Glomerular Filtration
-Has 2 major sites of resistance control - afferent arteriole and efferent arteriole. Has 2 capillary beds in series - glomerular capillaries and peritubular capillaries. Consequently significant pressure drops along both arterioles, glomerular capillary pressure is relatively high and peritubular capillary pressure is relatively low.
- If afferent arteriole constricts: hydrostatic pressure of blood in glomerular capillaries decreases, oncotic pressure in blood remains stable, net filtration pressure decreases, so GFR decreases.
- If efferent arteriole constricts: hydrostatic pressure of blood in glomerular capillaries increases, net filtration pressure increases, so GFR increases, BUT THEN oncotic pressure in blood increases so net filtration pressure decreases, and so does GFR.
Autoregulation of Glomerular Filtration Rate and Renal Blood Flow
- Feedback mechanisms intrinsic to the kidneys keep RBF & GFR relatively constant (despite marked changes in arterial blood pressure).
- Autoregulation in the kidneys allows precise control of renal excretion of water and solutes. Prevents large changes in GFR and renal tubules can increase reabsorption (glomerulartubular balance).
- Intrinsic Autoregulation done by myogenic mechanism and/or tubuloglomerular feedback.
- Extrinsic autoregulation done by various hormones, peptides, sympathetic neurotransmitters.
Myogenic Mechanism
Stretch receptors in afferent arteriole respond to changes in arterial blood pressure:
- High arterial BP - detected by stretch receptors in smooth muscle cells, afferent arteriole constricts, hydrostatic pressure in glomerular capillaries decreases, GFR decreases.
- Low arterial BP - detected by stretch receptors in smooth muscle cells. Afferent arteriole dilates. Hydrostatic pressure of glomerular capillaries increases so GFR increases.
Tubuloglomerular Feedback
Concentration of NaCl detected in macula densa cells, GFR can be adjusted.
- Increased GFR/RBF (due to arterial BP incr.) - Filtration fraction increases > more NaCl reaches Macula Densa > more NaCl is reabsorbed by NKCC2 (not enough Na+/K+ ATPases to extrude Na+, cell swells and releases ATP) > ATP converted to adenosine (acts on neighbouring granular cells). - A1 receptors are G-Protein Coupled Receptors, when bound, they increase Ca conc. CAUSES: vasoconstriction of afferent arteriole decreasing GFR & inhibits renin release from granular cells inhibiting activation of RAAS.
- Decreased GFR/RBF - filtration fraction decreases > less Na Cl reaches Macula Densa > less NaCl reabsorbed by NKCC2 into cell > triggers kinase cascades and certain enzymes, PGE2 is released, NO is released > bind/enter neighbouring granular cells > increases cAMP conc. > Vasodilation of afferent arteriole increasing GFR and stimulates renin release, activating RAAS (which increases ECV and BP).
