L4 Glomerular Filtration Flashcards
What determines selectively of the filtration barrier in Bowman’s Capsule?
Molecular size of intravascular components
Electrical charge of filtration barrier components (all three negatively charged)
Layers of the Glomerular Filtration Barrier?
Capillary Endothelium (fenestrae 70-100nm)
Basement Membrane: NON-Cellular mesh like negatively charged barrier
Filtration slits between adjacent podocytes (secondary processes), of 25-65nm, are the key selectively barrier in filtration
What determines the composition of the plasma ultrafiltrate?
Glomerular Filtration Barrier
Most ions and low molecular weight components (<7kDa) are freely filtered
Near total exclusion of larger plasma proteins such as albumin (~66kDa) and of substances bound to large plasma proteins (i.e. 40% of Ca2+is not filtered as bound to large plasma proteins)
Range of FIltration by glomerular Filtration Barrier?
Amount filtered between 7 –66kDa becomes progressively smaller as the molecules become larger
Role of Charge on Glomerular Filtration?
Negatively charged macromolecules are filtered to a lesser extent, and positively charged macromolecules to a greater extent, than neutral molecules
Urinary Excretion = __________ + __________ – __________
Urinary Excretion = Filtration + Secretion – Reabsorption
Typical renal blood flow (RBF)?
605mL/min
Kidneys Receive 20% (1.1L/min) of the total cardiac output (~55% of blood volume is plasma)
Typical glomerular filtration rate (GFR)?
125mL/min (180L/day)
How many times a dail is the entire palsma volume of blood filtered?
With a plasma volume ~3L, entire plasma volume is filtered by the kidneys 60 times daily
___________ = Filtration coefficient (Kf) x ___________________
What influences Kf?
GFR = Filtration coefficient (Kf) x Net filtration pressure (NFP)
- Kf is influenced by:
- Glomerular capillary permeability (Lp)
- Total glomerular capillary surface area (S)
The total amount of any substance freely filtered (not hindered by Glomerular Filtration Barrier) from renal glomerular capillaries into Bowman’s space?
How is this calculated?
Filtered Load
Filtered load of substance X = GFR x [X] in the plasma
Rise in blood pressure causes an increased excretion of salt and water?
Pressure Natriuresis
The kidney has control mechanisms in place that keep RBF (and therefore the GFR) relatively constant as arterial blood pressure increases between ______ and ________. This process is known as __________________
The kidney has control mechanisms in place that keep RBF (and therefore the GFR) relatively constant as arterial blood pressure increases between 90 and 180mmHg. This process is known as Autoregulation
Mechanisms Responsible for Autoregulation of RBF and GFR?
Myogenic mechanism
- Vascular smooth muscle tends to contract when stretched
- Very fast acting; protects from short-term fluctuations in blood pressure
Tubuloglomerular Feedback
- Macula densa cells act as salt sensors detecting [NaCl] in tubular fluid (filtrate)
- High levels of Na+ flowing past the macula densa cells => decrease in GFR (by afferent arteriole constriction)
On which arteriole do both autoregulatory control mechanisms of RBF and GFR act?
Both factors regulate the tone of the Afferent Arteriole
- When blood pressure increases across the afferent arteriole, the smooth muscle cell (SMC) membrane is stretched _______ opening stretch activated _________ channels.
- _______enters the SMC => depolarizes the cells
- Depolarization of cells opens _____________ on the ________________
- ________ binding ___________causes myofilaments to contract, opposing stretch of cell membrane caused by elevated BP and thus maintain a steady RBF and GFR.
- When blood pressure increases across the afferent arteriole, the smooth muscle cell (SMC) membrane is stretched inward opening stretch activated Ca2+(and Na+) channels.
- Ca2+ (and Na+) enters the SMC => depolarizes the cells
- Depolarization of cells opens voltage-gated Ca2+ channels (on sarcoplasmic reticulum)
- Ca2+ binding Actin causes myofilaments to contract, opposing stretch of cell membrane caused by elevated BP and thus maintain a steady RBF and GFR.
Tubuloglomerular feedback on Autoregulation of GFR and RBF:
- Increase in GFR elevates [NaCl] in tubular fluid at the _______________
- Enhanced uptake of NaCl by ________ via ________ channel leads to increased [______] and [__________]
- ATP binds ______ receptors and ADO binds ________ receptors on smooth muscle cells (SMCs) of afferen arteriole
- Receptor binding results in an increase in ________ in SMCs inducing __________ of afferent arteriole leading to a ___________ of GFR
- Increase in GFR elevates [NaCl] in tubule fluid_at the macula densa (MD)
- Enhanced uptake of NaCl across MD cells via NKCC2 channel leads to increased [ATP] and [adenosine] (ADO)
- ATP binds P2X receptors and ADO binds Adenosine A1 receptors on smooth muscle cells (SMCs) of afferent arteriole
- Receptor binding results in an increase in [Ca2+] in SMCs inducing vasoconstriction of afferent arteriole leading to a decrease in GFR
MOA of Sympathetic Nerves on GFR?
Norepinephrine and epinephrine cause vasoconstriction by binding a1- adrenoceptors (located mainly on AA) => Decreased GFR
Vasoactive Factors Leading to Vasoconstriction of Renal Arterioles?
Angiotensin 2: Produced systemically and locally => vasoconstriction of AA and EA (EA more sensitive to ANG2)
Endothelin: Vasoconstrictor produced by Endothelial Cells, mesangial cells and Distal Convoluting cells => vasoconstriction of AA and EA
Vasoactive Factors Leading to Vasodilation of Renal Arterioles?
Nitric Oxide: Vasodilator produced by ECs, macula densa and SMCs. Counteracts vasoconstriction of ANG2 and sympathetic input
Prostaglandins: Vasodilator produced locally in the kidney by ANG2 stimulation. Counteracts vasoconstriction of ANG2 and sympathetic input
What determines renal Net Filtration Pressure (NFP)
Net filtration pressure is determined by renal artery pressures, resistance in the afferent and efferent arterioles, and plasma oncotic pressures
____________ of any substance is the volume of plasma from which that substance is completely removed by the kidneys per unit time
Equation?
Renal clearance of any substance is the volume of plasma from which that substance is completely removed (“cleared”) by the kidneys per unit time
Clearance of a substance that is freely filtered, not reabsorbed, and fully secreted?
Example?
Clearance of PAH equals renal plasma flow via the renal artery i.e. ~605ml/min
Para Aminohippurate (PAH) behaves in this manner
Clearance of a substance that is freely filtered, not reabsorbed, not secreted?
Example?
The filtered load is equal to the mass of inulin excreted. : Clearance of substance neither reabsorbed nor secreted, just filtered, equals GFR ~125ml/min
Inulin behaves in this manner
Clearance of a substance that is freely filtered, fully reabsorbed, not secreted?
Example?
Renal clearance = 0ml/min
Glucose and Amino Acids behave in this manner
Although ____________ is a valuable clinical measure of GFR, it is far more common to measure ___________ and use this as an indicator of GFR
Although creatinine clearance is a valuable clinical measure of GFR, it is far more common to measure plasma creatinine and use this as an indicator of GFR.
Rising plasma creatine = indicator of kidney failure
