L4 Glomerular Filtration

Question 1

What determines selectively of the filtration barrier in Bowman’s Capsule?

Answer 1

Molecular size of intravascular components

Electrical charge of filtration barrier components (all three negatively charged)

Question 2

Layers of the Glomerular Filtration Barrier?

Answer 2

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

Question 3

What determines the composition of the plasma ultrafiltrate?

Answer 3

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)

Question 4

Range of FIltration by glomerular Filtration Barrier?

Answer 4

Amount filtered between 7 –66kDa becomes progressively smaller as the molecules become larger

Question 5

Role of Charge on Glomerular Filtration?

Answer 5

Negatively charged macromolecules are filtered to a lesser extent, and positively charged macromolecules to a greater extent, than neutral molecules

Question 6

Urinary Excretion = __________ + __________ – __________

Answer 6

Urinary Excretion = Filtration + Secretion – Reabsorption

Question 7

Typical renal blood flow (RBF)?

Answer 7

605mL/min

Kidneys Receive 20% (1.1L/min) of the total cardiac output (~55% of blood volume is plasma)

Question 8

Typical glomerular filtration rate (GFR)?

Answer 8

125mL/min (180L/day)

Question 9

How many times a dail is the entire palsma volume of blood filtered?

Answer 9

With a plasma volume ~3L, entire plasma volume is filtered by the kidneys 60 times daily

Question 10

___________ = Filtration coefficient (Kf) x ___________________

What influences Kf?

Answer 10

GFR = Filtration coefficient (Kf) x Net filtration pressure (NFP)

• Kf is influenced by:
• Glomerular capillary permeability (Lp)
• Total glomerular capillary surface area (S)

Question 11

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?

Answer 11

Filtered Load

Filtered load of substance X = GFR x [X] in the plasma

Question 12

Rise in blood pressure causes an increased excretion of salt and water?

Answer 12

Pressure Natriuresis

Question 13

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 __________________

Answer 13

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

Question 14

Mechanisms Responsible for Autoregulation of RBF and GFR?

Answer 14

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)

Question 15

On which arteriole do both autoregulatory control mechanisms of RBF and GFR act?

Answer 15

Both factors regulate the tone of the Afferent Arteriole

Question 16

1. When blood pressure increases across the afferent arteriole, the smooth muscle cell (SMC) membrane is stretched _______ opening stretch activated _________ channels.
2. _______enters the SMC => depolarizes the cells
3. Depolarization of cells opens _____________ on the ________________
4. ________ binding ___________causes myofilaments to contract, opposing stretch of cell membrane caused by elevated BP and thus maintain a steady RBF and GFR.

Answer 16

1. When blood pressure increases across the afferent arteriole, the smooth muscle cell (SMC) membrane is stretched inward opening stretch activated Ca2+(and Na+) channels.
2. Ca2+ (and Na+) enters the SMC => depolarizes the cells
3. Depolarization of cells opens voltage-gated Ca2+ channels (on sarcoplasmic reticulum)
4. Ca2+ binding Actin causes myofilaments to contract, opposing stretch of cell membrane caused by elevated BP and thus maintain a steady RBF and GFR.

Question 17

Tubuloglomerular feedback on Autoregulation of GFR and RBF:

1. Increase in GFR elevates [NaCl] in tubular fluid at the _______________
2. Enhanced uptake of NaCl by ________ via ________ channel leads to increased [______] and [__________]
3. ATP binds ______ receptors and ADO binds ________ receptors on smooth muscle cells (SMCs) of afferen arteriole
4. Receptor binding results in an increase in ________ in SMCs inducing __________ of afferent arteriole leading to a ___________ of GFR

Answer 17

1. Increase in GFR elevates [NaCl] in tubule fluid_at the macula densa (MD)
2. Enhanced uptake of NaCl across MD cells via NKCC2 channel leads to increased [ATP] and [adenosine] (ADO)
3. ATP binds P2X receptors and ADO binds Adenosine A1 receptors on smooth muscle cells (SMCs) of afferent arteriole
4. Receptor binding results in an increase in [Ca2+] in SMCs inducing vasoconstriction of afferent arteriole leading to a decrease in GFR

Question 18

MOA of Sympathetic Nerves on GFR?

Answer 18

Norepinephrine and epinephrine cause vasoconstriction by binding a1- adrenoceptors (located mainly on AA) => Decreased GFR

Question 19

Vasoactive Factors Leading to Vasoconstriction of Renal Arterioles?

Answer 19

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

Question 20

Vasoactive Factors Leading to Vasodilation of Renal Arterioles?

Answer 20

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

Question 21

What determines renal Net Filtration Pressure (NFP)

Answer 21

Net filtration pressure is determined by renal artery pressures, resistance in the afferent and efferent arterioles, and plasma oncotic pressures

Question 22

____________ of any substance is the volume of plasma from which that substance is completely removed by the kidneys per unit time

Equation?

Answer 22

Renal clearance of any substance is the volume of plasma from which that substance is completely removed (“cleared”) by the kidneys per unit time

Question 23

Clearance of a substance that is freely filtered, not reabsorbed, and fully secreted?

Example?

Answer 23

Clearance of PAH equals renal plasma flow via the renal artery i.e. ~605ml/min

Para Aminohippurate (PAH) behaves in this manner

Question 24

Clearance of a substance that is freely filtered, not reabsorbed, not secreted?

Example?

Answer 24

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

Question 25

Clearance of a substance that is freely filtered, fully reabsorbed, not secreted?

Example?

Answer 25

Renal clearance = 0ml/min

Glucose and Amino Acids behave in this manner

Question 26

Although ____________ is a valuable clinical measure of GFR, it is far more common to measure ___________ and use this as an indicator of GFR

Answer 26

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