Renal System 3 Lecture 25 Flashcards

1
Q

What is the glomerulus?

A

The primary site for filtration. The capillaries here act like a tea strainer: larger components like blood cells and large proteins (e.g., albumin) are retained, while smaller substances such as glucose, sodium, and water pass through. The filtrate that enters the capsular space is plasma-like, minus large proteins and blood cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which force is the main driving force pushing fluid out into the capsular space?

A

The glomerular blood hydrostatic pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

P_GC (Glomerular capillary hydrostatic pressure)

A

The blood pressure within the glomerular capillaries, pushing fluid and solutes out into Bowman’s space. This is the major force driving filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

π_BS (Bowman’s space oncotic pressure)

A

This force is usually negligible in healthy kidneys as large proteins, which would generate oncotic pressure, do not typically enter Bowman’s space.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

P_BS (Bowman’s space hydrostatic pressure)

A

The pressure exerted by the fluid already in Bowman’s space, opposing further filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

π_GC (Glomerular capillary oncotic pressure)

A

The osmotic pressure exerted by proteins remaining in the glomerular capillaries, pulling water back into the capillaries and opposing filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Net Filtration Pressure (NFP) in the glomerulus

A

NFP=GBHP−CHP−BCOP
Where:

GBHP (Glomerular Blood Hydrostatic Pressure): This is the blood pressure within the glomerular capillaries, which pushes fluid out of the capillaries into Bowman’s capsule. This is the driving force for filtration.

CHP (Capsular Hydrostatic Pressure): This is the pressure exerted by the fluid already in Bowman’s space, which resists further filtration.

BCOP (Blood Colloid Osmotic Pressure): This is the osmotic pressure exerted by proteins (mainly albumin) in the blood that pulls water back into the capillaries, opposing filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Components involved in Net Filtration Pressure (NFP) in the kidney and their contributions

A

Net Filtration Pressure (NFP): Determines how much water and small dissolved solutes leave the blood to enter the nephron (~10 mmHg).

Glomerular Blood Hydrostatic Pressure (GBHP): This is the mechanical pressure inside the glomerular capillaries, created by the difference between the afferent and efferent arterioles. It is the driving force for filtration, pushing plasma filtrate from the capillaries into Bowman’s space (~55 mmHg).

Capsular Hydrostatic Pressure (CHP): This pressure opposes filtration by pushing back against the plasma filtrate due to the elastic recoil of the glomerular capsule (~15 mmHg).

Blood Colloid Osmotic Pressure (BCOP): The osmotic pressure exerted by proteins, particularly albumin, remaining in the plasma. These proteins pull water back into the capillaries, opposing filtration (~30 mmHg).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Glomerular blood hydrostatic pressure (GBHP) and how it is regulated by the relative resistance in the afferent and efferent arterioles

A

Afferent and Efferent Arterioles:

The glomerulus is unique in that it has arterioles both before (afferent) and after (efferent) the capillary bed.
This allows for tight regulation of pressure gradients and helps maintain a relatively constant glomerular filtration rate (GFR).
Pressure and Resistance:

Changes in resistance in the afferent or efferent arterioles have little effect on systemic pressure (due to parallel flow), but they can significantly affect glomerular capillary pressure and thus the filtration rate.
Examples of Resistance Changes:

Equal resistance: Both the afferent and efferent arterioles have the same resistance (1.0). The pressure in the glomerular capillaries (P_GC) is 60 mmHg, and the pressure in the peritubular capillaries is 20 mmHg.

Higher afferent resistance: Increasing resistance in the afferent arteriole reduces blood flow into the glomerulus, lowering the glomerular capillary pressure (P_GC) to 40 mmHg and subsequently reducing filtration.

Higher efferent resistance: Increasing resistance in the efferent arteriole creates a “back pressure,” increasing glomerular capillary pressure (P_GC) to 80 mmHg, which increases filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How changes in glomerular blood hydrostatic pressure (P_G) are regulated by adjustments in the resistance of the afferent and efferent arteriole

A

Vasoconstriction of Afferent Arteriole (Top Diagram):
Increased resistance (R_A) in the afferent arteriole reduces renal blood flow into the glomerulus, which lowers both glomerular blood hydrostatic pressure (P_G) and the glomerular filtration rate (GFR).
This mechanism is used to buffer increases in systemic arterial pressure by constricting the afferent arteriole, preventing excessive increases in GFR.

Vasoconstriction of Efferent Arteriole (Bottom Diagram):
Increased resistance (R_E) in the efferent arteriole causes a buildup of pressure within the glomerulus, raising P_G and thus increasing the glomerular filtration rate (GFR).
This mechanism compensates for drops in blood pressure by constricting the efferent arteriole to maintain sufficient glomerular pressure for filtration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Regulation of glomerular filtration

A

Autoregulation:
Myogenic Autoregulation: The smooth muscle in the afferent arteriole responds to changes in blood pressure. If blood pressure increases, the afferent arteriole constricts to maintain a stable glomerular filtration rate (GFR).

Tubuloglomerular Feedback: Involves the macula densa cells detecting changes in sodium chloride levels in the distal tubule. This feedback adjusts the diameter of the afferent arteriole to maintain stable GFR.

Neural Regulation:
Sympathetic Nerve Activity: Increased sympathetic activity causes vasoconstriction, especially of the afferent arteriole, reducing GFR during stress or when blood volume is low (e.g., in dehydration or blood loss).

Hormonal Regulation:
Angiotensin II: Causes vasoconstriction of both afferent and predominantly efferent arterioles. This increases glomerular pressure and thus increases GFR, playing a key role in regulating blood pressure and fluid balance.

Atrial Natriuretic Peptide (ANP): Promotes relaxation of mesangial cells, increasing the surface area available for filtration and thus enhancing GFR.

Factors that regulate glomerular filtration include anything that affects glomerular hydrostatic pressure (such as arteriole resistance) or the surface area available for filtration (regulated by mesangial cell contraction or relaxation).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Autoregulation in the kidney

A

Renal Blood Flow and Glomerular Filtration Rate (Top Graph):

The red line represents the glomerular filtration rate (GFR), and the blue line represents renal blood flow.
Autoregulation ensures that GFR remains relatively constant across a wide range of blood pressures, typically between 80 mmHg and 180 mmHg.
This stability is maintained by mechanisms like myogenic responses and tubuloglomerular feedback, which adjust the resistance in the afferent and efferent arterioles.
Urine Output vs. Mean Arterial Pressure (Bottom Graph):

Unlike GFR, urine output is directly proportional to renal pressure.
As mean arterial pressure (MAP) increases, urine output increases significantly, indicating that autoregulatory mechanisms do not directly control urine output in the same way they control GFR.
Summary:
Blood flow to the kidney is tightly regulated to maintain a stable GFR, preventing fluctuations in filtration even as blood pressure changes.
However, urine output increases proportionally with blood pressure, showing that while filtration is stabilized, the final volume of urine depends more on systemic pressure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Tubuloglomerular feedback mechanism

A

Increased GFR:
An increase in the glomerular filtration rate leads to an increased tubular flow rate, particularly in the ascending limb of the nephron loop (loop of Henle).

Sensing by Macula Densa Cells:
Macula densa cells, located in the distal tubule, detect an increase in sodium (Na⁺), chloride (Cl⁻), and water content in the tubular fluid.
These cells are sensitive to the concentration of these ions, indicating higher filtration and fluid flow through the nephron.

Signal to Juxtaglomerular Apparatus:
The macula densa cells signal the juxtaglomerular apparatus, resulting in a reduction of nitric oxide (NO) release. Nitric oxide is a vasodilator, so reducing its release causes vasoconstriction.

Afferent Arteriole Vasoconstriction:
The signal leads to vasoconstriction of the afferent arteriole, which reduces blood flow into the glomerulus.
This decreases the glomerular blood pressure, which in turn reduces the GFR, bringing it back to a more normal rate.

Summary:
This feedback mechanism is a way for the kidney to regulate its filtration rate based on the composition of the filtrate, preventing excessive filtration and ensuring stable GFR under varying conditions. The macula densa and juxtaglomerular apparatus play key roles in sensing changes in filtrate and adjusting the blood flow accordingly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How many nephrons are there?

A

Two - juxtaglomemedullary and cortical

17
Q

Major Structures of the Nephron

A

Glomerulus:
The glomerulus is a network of capillaries where blood filtration begins. It is enclosed by Bowman’s capsule, which has two layers: the parietal layer and the visceral layer (containing podocytes). The glomerular filtration process occurs here, filtering water, ions, and small solutes into Bowman’s space.

Proximal Convoluted Tubule (PCT):
After filtration, the filtrate enters the proximal convoluted tubule. The PCT cells have microvilli (for increased surface area) and mitochondria (for active transport). The PCT reabsorbs the majority of filtered solutes like glucose, amino acids, sodium, chloride, and water back into the bloodstream.

Loop of Henle:
The loop of Henle consists of descending and ascending limbs, playing a key role in establishing a concentration gradient in the kidney’s medulla.
The thin descending limb is permeable to water but not to solutes.
The thick ascending limb actively transports sodium and chloride out of the filtrate, but it is impermeable to water.

Distal Convoluted Tubule (DCT):
The distal convoluted tubule continues the process of reabsorption and secretion. It fine-tunes the amounts of sodium, potassium, and calcium reabsorbed or excreted into the urine. The cells here are specialized for selective ion transport.

Collecting Duct:
The final part of the nephron, the collecting duct, collects the filtrate from multiple nephrons. The principal cells in the collecting duct regulate water and sodium reabsorption under the influence of hormones like aldosterone and antidiuretic hormone (ADH). This is where the final concentration of urine is determined.

18
Q

What layers are in the glomerular capsule?

A

Parietal and visceral layers

19
Q

What layer is this?

A

Glomerular capsule: visceral layer

20
Q

What layer is this?

A

Glomerular capsule: Parietal layer

21
Q

What cells are these?

A

Proximal convoluted tubule cells

22
Q

What cells are these?

A

Collecting duct cells

23
Q

What cells is this?

A

Loop of Henle

24
Q

What cells is this?

A

Distal convoluted tubule cells

25
Q

Reabsorption in the Proximal Convoluted Tubule

A

60% of the glomerular filtrate:
Approximately 60% of the fluid that is filtered at the glomerulus is reabsorbed in the PCT. This includes essential substances that need to be retained by the body.

60% of NaCl and water:
About 60% of sodium chloride (NaCl) and water is reabsorbed back into the bloodstream at this point. This is crucial for maintaining fluid and electrolyte balance in the body.

100% of glucose:
All filtered glucose is reabsorbed in the PCT under normal conditions, preventing the loss of glucose in the urine. If blood glucose levels are too high (as in diabetes), glucose reabsorption can become saturated, leading to glucose appearing in the urine.

26
Q

Key Features of the PCT

A

Highly Active in Reabsorption:

The PCT is highly active in membrane transport processes, specifically the reabsorption of water, ions, and glucose. This is essential for recovering vital substances from the filtrate.
Brush Border:

The PCT is characterized by a highly developed brush border, as seen in the micrographs. This brush border consists of densely packed microvilli that increase the surface area, allowing for maximum absorption of solutes.
The microvilli are seen in the various magnified images, showing their role in significantly increasing the contact area for reabsorption.

27
Q

Sodium (Na⁺) and glucose reabsorption in the Proximal Convoluted Tubule (PCT) of the nephron

A

Na⁺-K⁺ ATPase Pump:
Sodium is actively pumped out of the proximal convoluted tubule cell into the interstitial space (next to the peritubular capillary) by the Na⁺/K⁺ ATPase pump located on the basal surface of epithelial cells. This process uses ATP (energy) to move sodium against its concentration gradient, establishing a low intracellular Na⁺ concentration.

Sodium Gradient-Driven Symporters and Antiporters:
Symporters: Sodium moves into the PCT cells from the tubular lumen along with glucose via the Na⁺/Glucose symporter. The energy from the Na⁺ gradient drives glucose reabsorption.

Antiporters: Sodium is also reabsorbed in exchange for hydrogen ions (H⁺) via Na⁺/H⁺ antiporters, allowing for the secretion of H⁺ into the tubular fluid, contributing to pH balance.

Glucose Reabsorption:
Glucose is transported into the PCT cells along with Na⁺. Once inside the cell, glucose diffuses down its concentration gradient into the interstitial fluid via facilitated diffusion through a glucose transporter.

Water Reabsorption:
As Na⁺ and glucose are reabsorbed, the movement of these solutes creates an osmotic gradient that drives the reabsorption of water through osmosis, ensuring that water follows the reabsorbed solutes.

Osmolarity:
The osmolarity in the PCT is similar to that of plasma (approximately 290 mOsm/L), indicating that the PCT reabsorbs both solutes and water in a balanced way, maintaining homeostasis in body fluids.

28
Q

Descending Loop of Henle

A

Low Permeability to Ions and Urea:
The descending loop of Henle does not allow significant movement of ions (such as sodium or chloride) or urea. This means that these solutes remain in the tubule and are not reabsorbed in this section.

Highly Permeable to Water:
This segment of the nephron is highly permeable to water. As the filtrate moves down the descending limb, water is drawn out of the tubule into the surrounding interstitial fluid via osmosis.

Concentrated Medulla:
The medullary interstitial fluid is highly concentrated with solutes, creating a strong osmotic gradient that pulls water out of the tubule. This helps concentrate the filtrate as water is reabsorbed into the body.

Increasing Concentration of Filtrate:
By the time the filtrate reaches the bottom of the loop of Henle, it becomes highly concentrated (approximately 1200 mOsm/L), reflecting the high solute concentration in the surrounding interstitial fluid of the kidney’s medulla.

29
Q

Thick Ascending Limb

A

Impermeability to Water:
Unlike the descending limb, the thick ascending limb is impermeable to water. This means that no water is reabsorbed in this section, which helps in creating a dilute filtrate.

Active Reabsorption of Na⁺, K⁺, and Cl⁻:
Sodium (Na⁺), potassium (K⁺), and chloride (Cl⁻) ions are actively reabsorbed from the filtrate into the interstitial fluid. This is facilitated by a Na⁺/K⁺/2Cl⁻ symporter located on the apical membrane of the thick ascending limb cells.
These ions are transported into the interstitial fluid, making the surrounding area more concentrated with ions.

Cation Reabsorption:
Other cations, such as calcium (Ca²⁺) and magnesium (Mg²⁺), also follow the electrochemical gradient and diffuse into the interstitial fluid.

Dilution of Filtrate:
Since the thick ascending limb is impermeable to water but continues to actively reabsorb ions, the filtrate becomes progressively more dilute as it ascends. By the time the filtrate reaches the top of the loop of Henle, it is very dilute with an osmolarity of around 100 mOsm/L.

30
Q

Countercurrent Mechanism

A

Descending Limb:
The descending limb is impermeable to sodium chloride (NaCl) but highly permeable to water.
As filtrate moves down the descending limb, water is reabsorbed into the surrounding interstitial fluid due to the high osmolarity of the medulla (represented by the increasing osmolarity numbers from 300 to 1200 mOsm/L).
This water reabsorption concentrates the filtrate as it moves downward, with the filtrate reaching a concentration of 1200 mOsm/L at the bottom of the loop.

Ascending Limb:
The ascending limb is impermeable to water but actively reabsorbs Na⁺, K⁺, and Cl⁻.
As filtrate ascends, these ions are pumped out into the interstitial fluid, reducing the osmolarity of the filtrate, but since water cannot follow, the filtrate becomes more dilute.
By the time the filtrate reaches the top of the loop of Henle, it is very dilute, typically around 100 mOsm/L.

Concentration Gradient in the Medulla:
The interstitial fluid of the medulla becomes progressively more concentrated as you move deeper into the medulla (down to the tip of the loop). This high concentration of solutes in the medulla is what drives the reabsorption of water in the descending limb and in the collecting duct (under the influence of ADH).
The countercurrent mechanism allows for this concentration gradient to be established and maintained.

31
Q

Key notes on ADH and water movement

A

Absence of ADH: Urine is very dilute, approximately 100 mOsm/L, as a result of getting rid of a large volume of water and retaining ions. In this case, the body eliminates excess water.
Presence of ADH: When dehydrated, the body releases ADH (also called vasopressin), which allows for the production of concentrated urine by promoting water reabsorption in the collecting duct.
Alcohol and ADH: Alcohol inhibits ADH, leading to the production of dilute urine, which can cause dehydration despite fluid intake. This is why drinking water after consuming alcohol can help reduce dehydration.

Water movement:
Freely reabsorbed in the proximal convoluted tubule.
Freely reabsorbed in the descending loop of Henle.
No water reabsorption occurs in the ascending loop of Henle.
Water reabsorption in the collecting duct occurs only in the presence of ADH.
Sodium movement:
Occurs in most parts of the nephron except the descending loop of Henle.
Glucose reabsorption: Occurs entirely in the proximal convoluted tubule.

32
Q
A