Renal Blood Flow and Glomerular Filtration Rate Flashcards
Filtration
- blood to lumen
- Formation of a cell- and mostly protein-free plasma filtrate in the glomerulus. Filtration of the blood by the glomerulus forms the ultrafiltrate. At this point the ultrafiltrate has the same composition as blood, except for protein and blood cell components of blood. The ultrafiltrate enters the Bowman’s capsule and flows through the lumen of the renal tubule. As it flows through the lumen its composition and volume are altered by tubular activity, i.e. by reabsorption and secretion.
Rebasorption
- lumen to blood
- Movement (transport) of a substance out of the tubular lumen. Most substances eg salt and water, cross the epithelial layer of the tubule (ie enter via the apical membrane, and cross the basolateral membrane, or via paracellular pathways). These substances then enter the renal interstitium and are returned back to the bloodstream via uptake into nearby capillaries. However, reabsorption can also involve the uptake of a substance from the tubular lumen into tubular epithelial cells, where it is degraded or metabolized
Secretion
- blood to lumen
- Movement (transport) a substance into the tubular lumen. This involves transport of a substance from peritubular capillary blood, across the epithelial layer of the tubule (ie across the basolateral membrane and then the apical membrane, into the tubular lumen. However, some substances are added to the tubular lumen after synthesis by the epithelial cells (Note: glomerular filtration is NOT a form of secretion)
Excretion
- lumen to external environment
- Elimination of a substance from the body in the final urine. The net effects of filtration, reabsorption and secretion determine the rate at which a substance is excreted.
Quantitative Relationship between Filtration, Reabsorption, Secretion & Excretion
Excreted/min= Filtered/min – Reabsorbed/min + Secreted/min
Basic Physiological Functions of the KIdney
- Eliminate METABOLIC WASTE PRODUCTS
- Eliminate FOREIGN COMPOUNDS
- Regulate BODY FLUID OSMOLALITY
- Regulate plasma IONIC COMPOSITION
- Regulate EXTRACELLULAR FLUID VOLUME
- Help regulate ARTERIAL PRESSURE
- Help maintain ACID-BASE BALANCE
- Metabolize POLYPEPTIDE HORMONES
- Act as an ENDOCRINE organ:
»Erythropoietin
» 1,25-(OH)2vitamin D3
»Renin
Two Types of Postglomerular Capillaries
- pertitubular capillaris in the cortex
- vasa recta in the medulla (only 10% of renal blood flow)
Ultrafiltration
- The formation of a virtually protein-free filtrate of plasma as blood passes through the glomerular capillaries
- The glomerular ultrafiltrate has a composition identical to plasma except for the almost complete absence of protein.
‘• The ultrafiltrate is formed as fluid passes through the walls of the glomerular capillaries and into Bowman’s space (from whence it can enter the proximal convoluted tubule)
Inulin
•filtered and secreted
Sodium
•filtered and partially reabsorbed and excreted
Glucose
•filtered and completely rebasorbed
PAH
•filtered and secreted and excreted
Important Characteristics of Renal Blood Flow
- Essentially all blood flows through glomeruli.
- Blood traverses sequentially through the following structures: Aorta, renal artery (and large branches), interlobar artery, arcuate artery, interlobular artery, afferent arteriole, glomerular capillaries, efferent arteriole, postglomerular capillaries (peritubular capillaries in cortex; vasa recta in medulla), venules, interlobular vein, arcuate vein, interlobar vein, renal vein (see video on hold in library)
- Unusual aspects of this vascular anatomy:
- The inflow and outflow vessels of the glomerular capillaries are both arterioles (high resistance).
- There are 2 capillary beds (glomerular and postglomerular) arranged in sequence. These capillary beds are specialized for either filtration (glomerular capillaries) or absorption (postglomerular capillaries).
The ease with which a solute can pass across the filtration barrier is determined by:
- Molecular Size
- Electrical Charge
- Molecular Shape
Molecular Size
•Freely filtered: substances with low molecular weight (<5500 Da) and small effective molecular radius (<2 nm). These substances are present in Bowman’s space at the same concentration as in plasma.
-Examples: urea, glucose, inulin.
• Solute passage is increasingly restricted as molecular weights exceed 14 kDa and effective molecular radii exceed 2 nm.
-Albumin has a molecular weight of 69 kDa and a 3.6 nm molecular radius — characteristics that limit its passage across the filtration barrier.
Electrical Charge
- Macromolecular substances with a negative charge pass less readily than neutral substances. This phenomenon is termed electrostatic restriction. In turn, positively charged macromolecules pass more readily than neutral substances.
- Albumin (the primary plasma protein) has a valence of –18 at pH 7.4. Thus, in addition to the molecular size of albumin, its passage across the filtration barrier is also impeded by its polyanionic nature.
Molecular Shape
•Loosely coiled, elongated molecules without tertiary structure (which are relatively deformable) can cross the filtration barrier more readily than globular proteins of equivalent molecular weights and hydrodynamic radii. This phenomenon is termed steric hindrance.
What characteristics of the ultrafiltration barrier give it the ability to restrict solute passage on the basis of size, charge and shape?
Ultrafiltrate is formed as components of plasma in the capillary lumen pass through
- endothelial fenestrations
- the basal lamina (basement membrane)
- filtration slits (the space between pedicels) into Bowman’s space
Size Barrier
No discrete structure of the capillary wall has an obvious dimensional configuration that might provide the size barrier.
- Endothelial fenestrations (70 nm diameter) and filtration slits (25-60 nm diameter) are far too large!
- Traditionally, the size barrier function has been ascribed to the basement membrane (300-350 nm thick), which consists of a highly cross-linked type IV collagen framework containing sialoglycoprotein and sulfated glycoprotein fibers in a hydrated gel. Steric hindrance is thought to occur as globular macromolecules interact with this meshwork.
- The slit diaphragm (which spans the filtration slits) is emerging as an important size barrier limiting filtration of plasma protein. Its structure is assembled in a highly organized, almost zipper-like fashion. Novel proteins (nephrin, podocin, etc) represent integral components of this structure. Deletions or mutations of the genes encoding any one of these proteins results in a nephrotic syndrome (the term applied to array of diseases that result in the excretion of massive amounts of protein in the urine). As slit diaphragm structure and function are becoming better understood, the glomerular basement membrane is beginning to be viewed as a “prefilter,” with the slit diaphragm viewed as the final critical size barrier
Components of the Slit Diaphragm and their Relationship to Foot Processes
Forces Involved in Glomerular Filtration
Kf
Kf × Net Filtration Pressure = Fluid Movement
- Kf is filtration coefficient and is determined by surface area and hydraulic conductivity
- Kf is much greater in the glomerular capillaries
- Surface area and hydraulic conductivityboth higher and contribute to the high Kf in glomeruli
GFR in Glomerulus
Net Filtration Pressure (10 mmHg) is similar in glomerular and non-renal capillaries.
- However, Glomerular Filtration Rate (GFR) is about 125 ml/min (normal range = 80−140 ml/min). This is ≈60 times greater than the rate of filtration by all of the non-renal capillaries in the entire body (≈2 ml/min)!
- If Fluid Movement = Kf × Net Filtration Pressure, and if Net Filtration Pressures are similar in renal and non-renal capillary beds, then the glomerular filtration coefficient (Kf) must be very high.
-Indeed, both surface area and hydraulic conductivity are greater in glomerular capillaries than in non-renal capillary beds.
Constriction of Afferent Arterioles
Constriction of the afferent arteriole increases resistance and decreases RBF, PGC and GFR.
Constriction of Efferent Arterioles
Constriction of the efferent arteriole increases resistance and decreases RBF, but increases PGC and GFR.
TubuloGlomerular Feedback
- Tubuloglomerular feedback provides a mechanism by which changes in GFR can be detected and rapidly corrected for, on a minute-to-minute basis, as well as over sustained periods
- Regulation of GFR requires a detector for inappropriate GFR and an effector to correct GFR
- The macula densa = detector, glomerulus = effector
- The macula densa uses the composition of the tubular fluid as an indicator of GFR
- High NaCl concentration in tubule indicative of elevated GFR Na-K-2Cl cotransporter (NKCC2, apical membrane)
- in presence of higher Na in tubule increases activity (sensed by macula densa) detection of elevated NaCl uptake triggers the release of signaling molecules from the macula densa Result: Glomerulus reduces GFR. Mediated largely by constriction of the afferent arteriole (ATP, adenosine, Ca+, one of the proposed mechanisms, following change in membrane potential due to increase activity of NKCC2)
Autoregulation of GFR and RBF Limits
Lower than 80 mm Hg
Higher than 160 mm Hg
Cannot maintain GFR/autoregulation
Plasma Flow Dependence of GFR
• Changes in plasma flow influence the rate at which πGC increases along the length of the capillary.
- Increased plasma flow more rapidly provides “fresh” plasma for ultrafiltration, effectively slowing the buildup of proteins in the capillary that results from removal of the protein-free ultrafiltrate.
- Slowing the rise in πGC shifts the point of filtration equilibrium toward the efferent arteriolar end of the capillaries (and may prevent filtration equilibrium). This also increases the area designated PUF – thus increasing GFR.
