Overview
This lecture covers the core mechanisms of glomerular filtration, determinants of the glomerular filtration rate (GFR), structural properties of the filtration membrane, and regulation of renal blood flow.
Glomerular Filtration: Introduction
- Glomerular filtration is the first step in urine formation, filtering plasma components (not proteins/cells) from blood into Bowman’s capsule.
- Human kidneys filter about 180 liters of fluid per day, excreting only about 1 liter as urine.
- High filtration rates depend on both high kidney blood flow and unique properties of glomerular capillaries.
Glomerular Filtration Barrier & Filterability
- The filtration barrier has three layers: endothelium (with fenestrations), basement membrane, and podocytes (with slit pores).
- Barrier is highly permeable to water, small ions (e.g. sodium), and glucose, but not to proteins or blood cells.
- Negative charges on the basement membrane and podocytes repel negatively charged proteins, preventing their filtration.
- Filterability of substances is inversely related to size; larger molecules filter less.
- Positively charged molecules filter more easily than negatively charged ones of the same size.
Determinants of Glomerular Filtration Rate (GFR)
- GFR = Filtration coefficient (Kf) × Net filtration pressure (NFP).
- NFP = (Glomerular hydrostatic pressure) – (Bowman’s capsule hydrostatic pressure + Glomerular oncotic pressure).
- Typical values: Glomerular hydrostatic pressure = 60 mmHg, Bowman’s capsule pressure = 18 mmHg, glomerular oncotic pressure = 32 mmHg; thus NFP ≈ 10 mmHg.
- Filtration coefficient (Kf) depends on permeability and surface area of glomerular capillaries.
Regulation of GFR & Renal Blood Flow
- Major factors affecting GFR: hydrostatic and oncotic pressures, arteriolar resistances, Kf.
- Constriction of afferent arteriole ↓ GFR; constriction of efferent arteriole can ↑ or ↓ GFR based on severity.
- High renal blood flow (≈1100 mL/min) permits high GFR and is much greater than the metabolic needs of the kidney.
Physiological & Hormonal Control
- Sympathetic stimulation, norepinephrine, epinephrine, and endothelin cause vasoconstriction, reducing renal blood flow and GFR.
- Angiotensin II preferentially constricts efferent arteriole, maintaining GFR during low blood pressure but reducing renal blood flow.
- Prostaglandins, bradykinin, and nitric oxide dilate renal vessels and increase GFR.
- Kidneys autoregulate GFR and blood flow across a wide range of blood pressures, mainly via tubuloglomerular feedback and myogenic response.
Tubuloglomerular Feedback & Autoregulation
- Macula densa cells sense NaCl in distal tubule; low NaCl triggers afferent arteriole dilation and renin release (activating angiotensin II).
- This feedback maintains relatively constant GFR despite changes in systemic blood pressure.
- Myogenic mechanism: increased arterial pressure causes arteriole constriction, protecting glomeruli.
Effects of Diet & Disease
- High protein or glucose intake increases GFR and renal blood flow.
- Minimal change nephropathy increases glomerular permeability to proteins, causing proteinuria.
Key Terms & Definitions
- GFR (Glomerular Filtration Rate) — Volume of fluid filtered from glomerular capillaries into Bowman’s capsule per minute.
- Filtration Coefficient (Kf) — Product of capillary permeability and surface area.
- Net Filtration Pressure (NFP) — Difference in pressures driving and opposing filtration.
- Podocytes — Specialized epithelial cells forming filtration slits in glomerulus.
- Macula Densa — Distal tubule cells sensing sodium and regulating GFR.
- Proteinuria — Presence of excess protein in urine.
Action Items / Next Steps
- Review diagrams of the nephron structure and pressure gradients.
- Learn and memorize the GFR equation and factors affecting it.
- Read related textbook sections on glomerular filtration and autoregulation mechanisms.