Renal Physiology: Guyton Chapter 26 - 27

Question 1

[16-minute video]: Guyton and Hall Medical Physiology (Chapter 26) - The Urinary System

Answer 1

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Question 2

[19-minute video]: Guyton and Hall Medical Physiology (Chapter 27) - Glomerular Filtration, Renal Blood Flow and Their Control

Answer 2

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Question 3

Briefly discuss the composition of glomerular filtrate.

Answer 3

💧 protein-free and devoid of cellular components
💧 The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma.

Question 4

What are the exceptions to the generalization that the glomerular filtrate has similar concentrations of constituents as plasma?

Answer 4

Exceptions include low-molecular-weight substances like calcium and fatty acids that are partially bound to plasma proteins. Almost half of the plasma calcium and most of the plasma fatty acids are bound to proteins and are not filtered through the glomerular capillaries.

Question 5

What determines the rate of fluid filtration in glomerular capillaries?

Answer 5

The rate of fluid filtration in glomerular capillaries is determined by:
(1) the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane, and
(2) the capillary filtration coefficient (Kf), which is the product of the permeability and filtering surface area of the capillaries.

Question 6

Why do glomerular capillaries have a higher rate of filtration compared to most other capillaries?

Answer 6

Glomerular capillaries have a higher rate of filtration due to high glomerular hydrostatic pressure and a large capillary filtration coefficient (Kf).

Question 7

What are the three major layers of the glomerular capillary membrane?

Answer 7

The three major layers are:
(1) the endothelium of the capillary,
(2) a basement membrane,
(3) a layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane.

Question 8

What are fenestrae in the context of the glomerular capillary membrane?

Answer 8

Fenestrae are thousands of small holes in the capillary endothelium, similar to those found in the liver, but smaller. They are richly endowed with fixed negative charges that hinder the passage of plasma proteins.

[Diagram] [Image 1] [Image 2]

Question 9

What is the role of the basement membrane in the glomerular capillary membrane?

Answer 9

The basement membrane consists of a meshwork of collagen and proteoglycan fibrillae with large spaces for filtering water and small solutes. It hinders the filtration of plasma proteins due to strong negative electrical charges associated with the proteoglycans.

Question 10

How do podocytes contribute to the filtration process in the glomerular capillary membrane?

Answer 10

Podocytes line the outer surface of the glomerulus with long footlike processes (pedicels) that encircle the capillaries. The foot processes are separated by slit pores through which the glomerular filtrate moves, providing additional restriction to the filtration of plasma proteins.

Podocyte gallery: [Image 1] [Image 2] [Diagram 1] [Diagram 2] [Diagram 3]

Question 11

Why are negatively charged large molecules filtered less easily than positively charged molecules of equal size in the glomerulus?

Answer 11

Negatively charged large molecules are filtered less easily due to electrostatic repulsion from the negative charges of the glomerular capillary wall proteoglycans. For example, albumin, with a molecular diameter of about 6 nanometers, is restricted from filtration despite the glomerular membrane pores being about 8 nanometers. [Diagram]

Question 12

How does electrical charge affect the filtration of different molecular weight dextrans by the glomerulus?

Answer 12

Positively charged molecules are filtered more readily than negatively charged molecules of the same molecular radius. Neutral dextrans are also filtered more easily than negatively charged dextrans. The negative charges of the basement membrane and podocytes restrict large negatively charged molecules, including plasma proteins.

Question 13

What is minimal-change nephropathy and how does it affect glomerular permeability?

Answer 13

In minimal-change nephropathy, the glomeruli become more permeable to plasma proteins, even though they may look normal under a standard light microscope. Under an electron microscope, the glomeruli usually display flattened podocytes with foot processes that may be detached from the glomerular basement membrane (podocyte effacement).

This increased permeability permits the proteins to be filtered by the glomerular capillaries and excreted in the urine, a condition known as proteinuria or albuminuria.

[Diagram 1] [Diagram 2] [Diagram 3] [Diagram 4] [Image 1]

Question 14

What are the causes and common occurrences of minimal-change nephropathy?

Answer 14

The causes of minimal-change nephropathy are unclear but may be related to an immunological response and abnormal T-cell secretion of cytokines that injure the podocytes. This condition is most common in young children but can also occur in adults, especially those with autoimmune disorders.

Question 15

What determines the Glomerular Filtration Rate (GFR) and how is it expressed mathematically?

Answer 15

The GFR is determined by:
(1) the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure; and
(2) the glomerular Kf.

Expressed mathematically, the GFR equals the product of Kf and the net filtration pressure: GFR = Kf × Net filtration pressure.

Question 16

What forces contribute to the net filtration pressure across the glomerular capillaries?

Answer 16

The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that favor or oppose filtration across the glomerular capillaries. These forces include:
(a) Hydrostatic pressure inside the glomerular capillaries (PG), which promotes filtration.
(b) Hydrostatic pressure in Bowman’s capsule (PB) outside the capillaries, which opposes filtration.
(c) Colloid osmotic pressure of the glomerular capillary plasma proteins (πG), which opposes filtration.
(d) Colloid osmotic pressure of the proteins in Bowman’s capsule (πB), which promotes filtration. Under normal conditions, the colloid osmotic pressure of the Bowman’s capsule fluid is considered to be zero.
[Diagram 1] [Diagram 2]

Question 17

Write an expression for GFR using PG, PB, πG and πB.

Answer 17

GFR = Kf × (PG – PB – πG + πB )

Question 18

What is the standard working value for GFR in a healthy human adult?

Answer 18

125 ml/min (180 L/day)
[both kidneys combined]

Question 19

What are three factors that control the glomerular hydrostatic pressure?

Answer 19

(1) arterial pressure
(2) afferent arteriolar resistance
(3) efferent arteriolar resistance

Question 20

State three hormones that constrict afferent and efferent arterioles in the kidney. Also state where they are produced.

Answer 20

norepinephrine [adrenal medulla], epinephrine [adrenal medulla], endothelin [released by damaged vascular endothelial cells of the kidneys and other tissues], angiotensin II

Question 21

How are afferent arterioles protected from angiotensin II-mediated constriction?

Answer 21

Afferent arterioles are protected from angiotensin II-mediated constriction by the release of vasodilators, especially nitric oxide and prostaglandins, which counteract the vasoconstrictor effects.

Question 22

What are two factors that influence the glomerular capillary colloid osmotic pressure?

Answer 22

(1) the arterial plasma colloid osmotic pressure; and
(2) the fraction of plasma filtered by the glomerular capillaries (filtration fraction)
[Diagram]

Question 23

What circumstances lead to increased angiotensin II formation?

Answer 23

Increased angiotensin II formation usually occurs in circumstances associated with decreased arterial pressure or volume depletion, such as a low-sodium diet or reduced renal perfusion pressure due to renal artery stenosis.

Question 24

How does angiotensin II help maintain GFR and blood pressure during volume depletion?

Answer 24

Angiotensin II constricts efferent arterioles, helping to maintain glomerular hydrostatic pressure and GFR. It also increases tubular reabsorption of sodium and water, which helps restore blood volume and blood pressure.

Question 25

How does hydrostatic pressure in Bowman’s capsule affect GFR and what are the implications of increased pressure?

Answer 25

[Direct measurements suggest Bowman’s capsule pressure in humans is about 18 mm Hg under normal conditions.]

Increasing Bowman’s capsule pressure reduces GFR, while decreasing it raises GFR. Changes in Bowman’s capsule pressure are not a primary means for regulating GFR. However, in pathological states like urinary tract obstruction, increased pressure can significantly reduce GFR, potentially causing hydronephrosis and kidney damage if not relieved.

Question 26

What is the role of endothelial-derived nitric oxide in renal function?

Answer 26

Endothelial-derived nitric oxide decreases renal vascular resistance and increases glomerular filtration rate (GFR). It is important for maintaining vasodilation of the kidneys and normal excretion of sodium and water.

Question 27

What is the primary effect of angiotensin II on renal arterioles?

Answer 27

Angiotensin II preferentially constricts efferent arterioles, increasing glomerular hydrostatic pressure while reducing renal blood flow.

Question 28

What are the effects of inhibiting nitric oxide formation on renal function?

Answer 28

Inhibiting nitric oxide formation increases renal vascular resistance, decreases GFR and urinary sodium excretion, and can eventually cause high blood pressure. In patients with atherosclerosis or hypertension, impaired nitric oxide production may contribute to increased renal vasoconstriction and elevated blood pressure.

Question 29

What is renal autoregulation?

Answer 29

This refers to the kidney’s ability to maintain relatively constant GFR and renal blood flow.

Question 30

What is the juxtaglomerular apparatus/complex and what are its components?

Answer 30

This is a specialized structure in the kidneys that plays a crucial role in regulating blood pressure and GFR. It comprises two main components:
(1) Juxtaglomerular cells: specialized cells located in the walls of the afferent arteriole. They produce and secrete renin, an enzyme that helps regulate blood pressure.
(2) Macula densa: this is a group of specialized epithelial cells in the distal convoluted tubule that are in close contact with the juxtaglomerular cells.

[Diagram 1] [Diagram 2]

[5-minute video]: Juxtaglomerular Apparatus

Question 31

What do macula densa cells sense?

Answer 31

Macula densa cells sense changes in sodium chloride delivery to the distal tubule.

Question 32

Tubuloglomerular mechanism of autoregulation

What happens when there is a decrease in sodium chloride concentration at the macula densa cells?

Answer 32

(1) A decrease in sodium chloride concentration at the macula densa cells initiates a signal that decreases resistance to blood flow in the afferent arterioles, raising glomerular hydrostatic pressure and helping return GFR toward normal.

(2) It also increases renin release from the juxtaglomerular cells. Renin released from these cells then functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II. Finally, angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and helping return GFR toward normal.

Question 33

What is the myogenic mechanism and how does it contribute to renal blood flow and GFR maintenance?

Answer 33

The myogenic mechanism is the ability of individual blood vessels to resist stretching during increased arterial pressure. It involves the contraction of vascular smooth muscle in response to increased wall tension, which prevents excessive vessel stretch and raises vascular resistance. This helps maintain a relatively constant renal blood flow and GFR, and protects the kidney from hypertension-induced injury by attenuating the transmission of increased arterial pressure to the glomerular capillaries.

Question 34

Which of the following is filtered most readily by the glomerular capillaries?
(a) Red blood cells
(b) Polycationic dextran with a molecular weight of 25,000
(c) Neutral dextran with a molecular weight of 25,000
(d) Polyanionic dextran with a molecular weight of 25,000
(e) Albumin in plasma

Answer 34

(b) Polycationic dextran with a molecular weight of 25,000

Question 35

The main barrier precluding the free passage of albumin across the glomerular capillary walls is formed by:
(a) anionic proteoglycan clusters within the glomerular basement membrane
(b) the filtration slits in between visceral epithelial cells (podocytes)
(c) the fenestrated glomerular endothelium
(d) all are correct
(e) none are correct

Answer 35

(a) anionic proteoglycan clusters within the glomerular basement membrane

Question 36

The glomerular filtration barrier is composed of all the following except ____________.
(a) macula densa
(b) podocytes
(c) basement membrane
(d) fenestrated capillary endothelium
(e) mesangial cells

Answer 36

(a) macula densa

Further notes:
Mesangial cells provide structural support but are not part of the filtration barrier itself.