Glomerular Filtration and Rate of Renal Blood Flow (Physiology)

𖹭 A clump of capillaries and Bowman’s capsule: The renal corpuscle consists of these components.

𖹭 To coat the outer surface of the capillaries (podocytes): The epithelium of Bowman’s capsule is invaginated to cover the capillaries.

𖹭 Afferent arteriole: Supplies blood to the glomerulus.

𖹭 Efferent arteriole: Carries blood away from the glomerulus.

𖹭 The space where the filtrate collects: It is the area between the visceral and parietal layers of Bowman’s capsule.

𖹭 It is a passive ultrafiltrate of plasma: Plasma proteins are filtered out, resulting in glomerular fluid.

𖹭 Concentration in glomerular fluid = concentration in plasma: Small solutes pass through the filtration barrier.

𖹭 Concentration in glomerular fluid = almost zero: Plasma proteins are largely excluded from the filtrate.

𖹭 Proteinuria is a sign of renal/urinary tract disease: Presence of protein in urine indicates a potential problem with kidney function.

𖹭 A net pressure drop across the glomerular membrane: This pressure differential facilitates the filtration of plasma into the glomerular fluid.

𖹭 An imbalance of Starling forces: This imbalance is crucial for the filtration process.

𖹭 Around 50 mmHg: This pressure pushes fluid out of the capillaries.

𖹭 25 mmHg: This pressure opposes filtration by drawing fluid back into the capillaries.

𖹭 10 mmHg: This pressure also opposes filtration by pushing fluid back into the capillaries.

𖹭 Capillary blood pressure (50 mmHg) pushes fluid out, while plasma colloid osmotic pressure (25 mmHg) and Bowman’s space pressure (10 mmHg) oppose this, leading to a net filtration pressure.

𖹭 The glomerular membrane consists of:

-Podocyte foot processes (pedicels)

-Basal lamina (lamina rara, lamina densa, lamina rara)

-Fenestrated endothelium of the capillary

𖹭 Podocytes form the epithelial layer of Bowman’s capsule and create filtration slits with their foot processes.

𖹭 Gaps between the foot processes of podocytes that allow for filtration of small molecules.

The basal lamina includes:

Lamina rara

Lamina densa

Lamina rara (repeated)

𖹭 Fenestrated endothelium, which contains pores to facilitate filtration.

𖹭 Central spine with lateral rungs: Subdivides the filtration slit into smaller pores.

𖹭 Pores: Approximately 4 nm wide.

𖹭 Made of proteins nephrin & podocin.

𖹭 4 nm: These small pores allow for the passage of molecules such as albumin.

𖹭 Nephrin & podocin: Deficiency of these proteins can lead to nephrotic syndrome.

𖹭 An albumin molecule is approximately 4 nm across, which is similar in size to the pores in filtration slits.

𖹭 Nephrotic syndrome: A disorder characterized by proteinuria, hypoalbuminemia, and edema.

𖹭 The fenestrated endothelium of the glomerular capillary: It allows the passage of molecules based on their size.

𖹭 Each molecule has a radius of 11 nm.

𖹭 Ferritin freely permeates through the fenestral apertures of the endothelium.

𖹭 The fenestral apertures in the endothelium, which act as pores for molecular passage.

𖹭 Epithelial cells or podocytes: Their foot processes create filtration slits through which molecules pass.

𖹭 Myeloperoxidase penetrates through the basal lamina but accumulates at the filtration slits.

𖹭 Myeloperoxidase is approximately the same size as albumin molecules.

𖹭 None of the myeloperoxidase penetrates into the urinary space; it accumulates at the filtration slits.

𖹭 Myeloperoxidase accumulates specifically at the filtration slits, without penetrating into the urinary space.

𖹭 It suggests that myeloperoxidase is held up at the filtration slits, indicating a selective barrier to its passage.

𖹭 Low glomerular blood pressure may lead to decreased glomerular filtration rate (GFR) and reduced urine formation.

𖹭 High glomerular blood pressure can cause damage to the glomerular capillaries and lead to increased glomerular filtration rate (GFR), potentially causing kidney damage over time.

𖹭 Pressure within the glomerular capillaries is regulated through autoregulation mechanisms within the kidney and extrinsic mechanisms involving the peripheral nervous system (PNS).

𖹭 Autoregulation mechanisms include the Bayliss myogenic response and tubuloglomerular feedback, both of which operate within the kidney.

𖹭 The Bayliss myogenic response is a mechanism within the kidney that helps to regulate glomerular blood pressure by adjusting the diameter of the afferent arteriole in response to changes in blood pressure.

𖹭 Tubuloglomerular feedback is a mechanism that involves communication between the macula densa cells of the distal tubule and the afferent arteriole to regulate glomerular blood pressure based on changes in tubular fluid composition.

𖹭 The Bayliss myogenic response is a mechanism that regulates renal blood flow in response to changes in perfusion pressure.

𖹭 When there is an increase in perfusion pressure, there is an immediate increase in the radius of the afferent arteriole, leading to a brief increase in blood flow. However, this stretch of the smooth muscle in the arteriole triggers its contraction, reducing its diameter and increasing resistance, which returns blood flow to the control value within about 30 seconds.

𖹭 The equation is F = ∆P / R, where F represents blood flow, ∆P represents the change in pressure, and R represents resistance.

𖹭 During the Bayliss myogenic response, the afferent arteriole initially dilates in response to increased perfusion pressure, leading to increased blood flow. However, this dilation triggers smooth muscle contraction in the arteriole, reducing its diameter and increasing resistance, which restores blood flow to its control value.

𖹭 The players are the macula densa and juxtaglomerular (JG) cells.

𖹭 The macula densa consists of specialized epithelial cells located in the distal convoluted tubule near the glomerulus.

𖹭 JG cells are modified smooth muscle cells found in the walls of the afferent arteriole proximal to the glomerulus.

𖹭 JG cells store inactive pro-renin and play a key role in regulating renal blood flow and glomerular filtration rate.

𖹭 Macula densa cells detect increased flow mechanically via cell surface cilia and chemically via increased sodium chloride concentration ([NaCl]).

𖹭 The mechanisms include mechanical detection via cell surface cilia and chemical detection via elevated sodium chloride concentration ([NaCl]).

𖹭 Macula densa cells release ATP, which triggers the contraction of the afferent arteriole.

𖹭 Change in flow and sodium chloride concentration ([NaCl]) in the distal convoluted tubule (DCT) are sensed by the macula densa, which induces the release of paracrine vasoactive agents, leading to changes in the diameter and resistance of the afferent arterioles. This ultimately restores RBF and GFR.

𖹭 Renal sympathetic nerves, which release noradrenaline and induce vasoconstriction, can reduce GFR by re-setting autoregulation to a lower level.

𖹭 This occurs in conditions such as standing upright (orthostasis), heavy exercise, and haemorrhage or other forms of clinical shock.

𖹭In shock, these sympathetic actions are further aided by circulating vasoconstrictor hormones such as adrenaline, angiotensin, and vasopressin, all aimed at conserving body fluid volume during physical stress.

𖹭 The two major clinical disorders of the GFR are:

Increased permeability of glomeruli to plasma proteins:

Condition: Nephrotic syndrome (e.g., filtration slit disordered by nephrin deficiency)

Symptoms:

Proteinuria (excess protein in the urine)

Hypoproteinaemia (low levels of protein in the blood)

Oedema (swelling due to fluid retention)

Decreased GFR:

Condition: Chronic glomerulonephritis leading to nonfunctioning glomeruli

Criteria: When GFR is less than 30 ml/min, this condition is termed chronic renal failure.

Treatment: Respond well to steroids