Glomerular Filtration

Introduction

- The fluid entering the capsular space is known as glomerular filtrate.

- The fraction of blood plasma in the afferent arterioles that becomes glomerular filtrate is termed the filtration fraction, typically ranging from 16-20%.

- Average daily volume of glomerular filtrate: 150 liters in females and 180 liters in males.

- Over 99% of the filtrate returns to the bloodstream via tubular reabsorption; only 1-2 liters are excreted as urine.

Filtration Membrane

- Composed of glomerular capillary endothelial cells and podocytes, forming a leaky barrier.

- Permits filtration of water and small solutes but blocks most plasma proteins, blood cells, and platelets.

- Three filtration barriers: glomerular endothelial cell, basal lamina, and filtration slit formed by a podocyte.

1. Glomerular Endothelial Cells

- Feature large pores (0.07-0.1 µm) that allow solutes in blood plasma to exit but prevent blood cells and platelets.

- Mesangial cells, located among glomerular capillaries, regulate filtration by adjusting surface area.

2. Basal Lamina

- A layer between the endothelium and podocytes, consisting of collagen fibers and proteoglycans.

- Prevents filtration of larger plasma proteins.

3. Podocyte Pedicels

- Thousands of footlike processes (pedicels) form filtration slits.

- Slit membranes permit passage of molecules smaller than 0.006-0.007 µm, including water, glucose, and ions.

- Less than 1% of albumin, due to its size, passes through the slit membrane.

Principle of Filtration

- Utilizes pressure to force fluids and solutes through a membrane, similar to capillaries elsewhere in the body but at a much larger scale in renal corpuscles.

- Three reasons for larger fluid volume filtration:

1. Large Surface Area:

Extensive glomerular capillaries, regulated by mesangial cells.

2. Thin and Porous Membrane:

Despite multiple layers, the filtration membrane is only 0.1 µm thick, making glomerular capillaries highly permeable.

3. High Capillary Blood Pressure:

Due to the smaller diameter of the efferent arteriole compared to the afferent arteriole, resulting in high resistance and pressure.

Net Filtration Pressure (NFP)

- Dependent on three main pressures:

1. Glomerular Blood Hydrostatic Pressure (GBHP):

~55 mmHg, promoting filtration.

2. Capsular Hydrostatic Pressure (CHP):

~15 mmHg, opposing filtration.

3. Blood Colloid Osmotic Pressure (BCOP):

~30 mmHg, also opposing filtration.

- NFP calculation

( NFP = GBHP - (CHP + BCOP) )

- Typical NFP:

( 55 - (15 + 30) = 10 )mmHg, driving filtration.

Glomerular Filtration Rate (GFR)

- The rate of filtrate formation by all renal corpuscles per minute.

- Average GFR: 125 mL/min in males and 105 mL/min in females.

- Essential for homeostasis of body fluids.

- GFR must be maintained within a narrow range to ensure proper reabsorption and excretion of substances.

Regulation of GFR

1. Renal Autoregulation

- Maintains constant renal blood flow and GFR via:

- Myogenic Mechanism: Smooth muscle contraction in afferent arterioles in response to pressure changes.

- Tubuloglomerular Feedback: Macula densa cells regulate GFR based on sodium, chloride, and water levels.

2. Neural Regulation

- Sympathetic ANS fibers release norepinephrine, causing vasoconstriction.

- Moderate stimulation constricts both arterioles equally, slightly reducing GFR.

- Intense stimulation, as in stress, predominantly constricts afferent arterioles, significantly decreasing GFR to conserve blood volume and redirect blood flow.

3. Hormonal Regulation

- Angiotensin II: Reduces GFR by constricting both arterioles, decreasing renal blood flow.

- Atrial Natriuretic Peptide (ANP): Increases GFR by relaxing mesangial cells, expanding the filtration surface area.

These mechanisms collectively ensure the kidneys effectively filter blood while maintaining fluid and electrolyte balance.

Reabsorption Routes and Transport Mechanisms in the Kidneys

Reabsorption Routes

1. Two Routes for Reabsorption:

- Paracellular Reabsorption: Fluid moves between adjacent tubule cells.

- Accounts for up to 50% of ion and water reabsorption via osmosis.

- Transcellular Reabsorption: Fluid moves through individual tubule cells.

- Pathway: Apical membrane → Cytosol → Basolateral membrane → Interstitial fluid.

2. Tight Junctions:

- Surround and join neighboring cells.

- Prevent complete sealing off of interstitial fluid from tubular fluid.

Transport Mechanisms

1. Directional Transport:

- Renal cells transport solutes in one direction only.

- Different transport proteins in apical and basolateral membranes.

2. Sodium Reabsorption:

- Essential due to high passage of Na+ through glomerular filters.

- Sodium-potassium pumps (Na+/K+ ATPases) in basolateral membranes eject Na+ from renal tubule cells.

- Absence of these pumps in apical membrane ensures unidirectional Na+ reabsorption.

3. ATP Consumption:

- Sodium-potassium pumps in renal tubules consume about 6% of the body’s total ATP at rest.

4. Active and Passive Transport:

- Primary Active Transport:

Uses ATP hydrolysis to pump substances across membranes (e.g., sodium-potassium pump).

- Secondary Active Transport:

Uses energy from ion electrochemical gradients to move substances.

- Symporters:

Move substances in the same direction.

- Antiporters:

Move substances in opposite directions.

- Transport maximum (Tm):

Upper limit on the rate of transporter function.

5. Water Reabsorption:

- Driven by solute reabsorption, occurs via osmosis.

- Obligatory Water Reabsorption:

• 90% of water reabsorption with solutes.

• Occurs in proximal convoluted tubule and descending limb of the loop of Henle.

- Facultative Water Reabsorption:

• Final 10%, regulated by antidiuretic hormone.

• Occurs in collecting ducts.

Reabsorption and Secretion in the Proximal Convoluted Tubule (PCT)

Major Reabsorption In The PCT

- Water and Solutes:

Reabsorbs 65% of water, Na⁺, K⁺; 100% of glucose and amino acids; 50% of Cl⁻; 80-90% of HCO₃⁻; 50% of urea; variable amounts of Ca²⁺, Mg²⁺, and HPO₄²⁻.

- Secretion:

Secretes H⁺, NH₄⁺, and urea.

Na⁺ Transport Mechanisms

- Symport and Antiport Mechanisms:

Na⁺ transport involves symporters (e.g., Na⁺-glucose symporter) and antiporters.

- Na⁺-Glucose Symporter:

Transports two Na⁺ and one glucose molecule into PCT cells; glucose exits via facilitated diffusion into peritubular capillaries.

- Other Symporters:

Reclaim HPO₄²⁻, SO₄²⁻, amino acids, and lactic acid.

Na⁺/H⁺ Antiporters

- Secondary Active Transport:

Na⁺ enters PCT cells, H⁺ is secreted into the lumen.

- H⁺ Production:

CO₂ diffuses into cells, reacts with H₂O via carbonic anhydrase to form H₂CO₃, which dissociates into H⁺ and HCO₃⁻.

- HCO₃⁻ Reabsorption:

HCO₃⁻ is reabsorbed into blood, maintaining the body's buffer supply.

Osmosis and Water Reabsorption

- Solute Reabsorption Promotes Osmosis:

Solutes increase osmolarity, drawing water into peritubular capillaries.

- Aquaporin-1:

Integral protein facilitating water movement across cell membranes.

Electrochemical Gradients and Ion Reabsorption

- Electrochemical Gradients:

Promote passive diffusion of Cl⁻, K⁺, Ca²⁺, Mg²⁺, and urea.

- Cl⁻ Concentration:

Highest in the second half of the PCT, promoting reabsorption of cations.

Ammonia and Urea Handling

- Ammonia Production:

Derived from amino acids in the liver, converted to less-toxic urea.

- Excretion:

Urea and ammonia are filtered at the glomerulus and secreted by PCT cells.

- Additional NH₃ Production:

From deamination of glutamine, generating HCO₃⁻ and NH₄⁺, which is secreted into the tubular fluid.

Passive Reabsorption In Second Half Of PCT

Reabsorption Of Glucose

Reabsorption in the Loop of Henle

Overview

- Fluid Entry:

Enters at 40–45 mL/min after 65% water reabsorption in the proximal convoluted tubules.

- Chemical Composition:

Lacks glucose, amino acids, and nutrients; osmolarity close to blood due to balanced water and solute reabsorption.

Reabsorption Rates

- Water:

15% of filtered water.

- Ions:

- Na⁺: 20–30%

- K⁺: 20–30%

- Cl⁻: 35%

- HCO₃⁻: 10–20%

- Variable amounts of Ca²⁺ and Mg²⁺.

Osmosis and Solute Reabsorption

- Water Reabsorption:

Not coupled with solute reabsorption in the loop of Henle.

- Regulation:

Allows independent regulation of fluid volume and osmolarity.

Thick Ascending Limb Mechanism

- Na⁺–K⁺–2Cl⁻ Symporters:

Reclaim one Na⁺, one K⁺, and two Cl⁻ from tubular fluid.

- Na⁺ Transport:

Actively transported into interstitial fluid, diffusing into vasa recta.

- Cl⁻ Transport:

Moves through leakage channels into interstitial fluid and vasa recta.

- K⁺ Transport:

Leaks back into tubular fluid through apical membrane channels, ensuring Na⁺ and Cl⁻ reabsorption.

Electrochemical Gradients

- Cation Reabsorption:

Movement of K⁺ into tubular fluid creates relative negativity in interstitial fluid and blood, promoting Na⁺, K⁺, Ca²⁺, and Mg²⁺ reabsorption via the paracellular route.

Water Reabsorption in Descending and Ascending Limbs

- Descending Limb:

Reabsorbs 15% of filtered water.

- Ascending Limb:

Virtually impermeable to water, leading to decreased osmolarity of tubular fluid as ions are reabsorbed without water.

Thick Ascending Limb Mechanism

- Na⁺–K⁺–2Cl⁻ Symporters

Hormonal Regulation of Tubular Reabsorption and Secretion

Key Hormones and Their Functions

1. Angiotensin II

- Decreases glomerular filtration rate via vasoconstriction.

- Enhances Na⁺, Cl⁻, and water reabsorption in the proximal convoluted tubule.

- Stimulates aldosterone release, increasing Na⁺ and Cl⁻ reabsorption and K⁺ secretion.

2. Aldosterone

- Released by the adrenal cortex.

- Promotes Na⁺ and Cl⁻ reabsorption and K⁺ secretion in collecting ducts.

- Increases blood volume by reducing water excretion.

3. Antidiuretic Hormone (ADH)

- Released by the posterior pituitary.

- Increases water permeability of principal cells in the distal convoluted tubule and collecting duct.

- Promotes water reabsorption, reducing urine volume during dehydration.

- Regulated by plasma osmolarity and blood volume changes.

4. Atrial Natriuretic Peptide (ANP)

- Released in response to increased blood volume.

- Inhibits Na⁺ and water reabsorption in the proximal convoluted tubule and collecting duct.

- Suppresses aldosterone and ADH secretion, increasing urine output and reducing blood volume.

5. Parathyroid Hormone (PTH)

- Released in response to low blood Ca²⁺ levels.

- Stimulates Ca²⁺ reabsorption in the early distal convoluted tubules.

- Inhibits phosphate reabsorption in the proximal convoluted tubules, promoting its excretion.

These hormones play critical roles in maintaining fluid and electrolyte balance by regulating the reabsorption and secretion processes in the renal tubules.

Production of Dilute and Concentrated Urine

Overview

- Fluid Intake Variability: Kidneys regulate body fluid volume by adjusting urine concentration.

- ADH Role: Controls the formation of dilute or concentrated urine.

Formation of Dilute Urine

1. Initial Filtrate:

Glomerular filtrate is isotonic with blood (300 mOsm/liter).

2. Descending Limb of Loop of Henle:

- Water Reabsorption: As fluid descends, water is reabsorbed by osmosis, increasing osmolarity.

3. Thick Ascending Limb:

- Ion Reabsorption: Na⁺, K⁺, and Cl⁻ are reabsorbed.

- Low Water Permeability: Water does not follow solutes, decreasing osmolarity to 150 mOsm/liter.

4. Distal Convoluted Tubule:

- Solute Reabsorption: Further reabsorption of solutes, minimal water reabsorption.

5. Collecting Ducts:

- Low ADH:

Principal cells impermeable to water, further diluting tubular fluid.

- Final Osmolarity:

Urine concentration can be as low as 65–70 mOsm/liter.

Formation of Concentrated Urine

1. ADH Influence:

High ADH levels promote water reabsorption, producing concentrated urine (up to 1200 mOsm/liter).

2. Osmotic Gradient:

Essential for water reabsorption, gradient ranges from 300 mOsm/liter (cortex) to 1200 mOsm/liter (medulla).

3. Solutes Contributing to Gradient:

- Na⁺, Cl⁻, and Urea: Key solutes maintaining high osmolarity in the medulla.

4. Countercurrent Mechanisms:

- Countercurrent Multiplication:

Differences in permeability and reabsorption in loop of Henle and collecting ducts.

- Countercurrent Exchange:

Flow of blood in vasa recta maintains the gradient.

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