Glomerular Filtration Rate (GFR) and Forces😊, JG Apparatus

Normal Glomerulus Histology:

• Outer membrane: Bowman's capsule.

• Contains: Capillary loops.

• Between capillary loops:
• Mesangial cells (bluish nuclei)
• Macrophages of the kidney
• Site of amyloid deposition.
• M for Mesangium, M for Macrophages, M for Middle

Glomerular Filtration Barrier (GFB):

• Location: Filtration membrane

• Components (Trilaminar):

Layer	Component	ㅤ
Outside	Epithelium	Visceral Bowman's capsule/ Foot processes of Podocytes
In between	GBM	Type IV collagen
Inside	Endothelium	Capillary endothelium

• All layers: Negatively charged
• Repels negatively charged molecules.

Structure	Surface Coating	Gap size
Endothelium	Glycocalyx (glycosaminoglycan) ↳ glycoCalyx (Capillaries)	Fenestrated capillaries (gap: 70 nm).
Basement membrane	Heparan sulfate	Gap: 10 nm.
Podocyte foot processes	Glycoprotein ↳ glycoProtein (Podocytes)	Slit pore gap: 25 nm.
Slit diaphragm	Covered Slit pore	4 to 14 nm.
Minimum gap in GFB	ㅤ	4 nm

Filterability of Substances

• Depends on:
• Molecular radius
• Charge

Charge	Effect
Positively charged (cationic)	Filtered more
Neutral	Intermediate filtration
Negatively charged (anionic)	Filtered less / not at all

• Curve A (highest filterability) → Cationic.

• Curve B (intermediate) → Neutral.

• Curve C (lowest) → Anionic.

Why Hemoglobin Cannot Pass Through Glomerulus

• Reason: Hb is a large molecule

GFR Equation and Filtration Coefficient (KF)

KF depends on:

• Surface area of glomerular capillaries

• Capillary permeability

• ↓ Surface area / permeability
• E.g., fibrosis
• ↓↓ KF → ↓↓ GFR

Effects of Arteriolar Resistance on RPF and GFR

• Mnemonic:
• ACE → Angiotensin constrict efferent
• PDA → Prostaglandin dilates afferent

Note

• Efferent arteriolar constriction → ↑ πc in peritubular capillaries.
• [πc = Oncotic pressure in peritubular capillaries]
• Explanation:
• Efferent constriction → ↑↑ filtration fraction →
• ↑↑ protein concentration in peritubular capillaries → ↑ πc

• ACE inhibitors are contraindicated in B/L renal artery stenosis.
• This is because efferent axis is responsible for maintaining blood flow

• Effect of NSAIDs on PGE2
• PGE2 is produced by Renal medullary interstitial cells (RMIC)
• NSAIDs → ⛔ COX enzymes → ↓↓ PGE2
• ↓↓ vasodilation of afferent arteriole → Vasoconstriction → ↓ GFR

Graphical Summary:

• Afferent arteriolar resistance ↑ → RPF ↓, GFR ↓

• Efferent arteriolar resistance ↑ → RPF ↓, GFR initially ↑ then ↓

Regulation of GFR

1. Autoregulation

2. Constriction of efferent and afferent arteriole

3. Mesangial cell contraction § relaxation

Renal Autoregulation:

• During BP changes between 80-180 mmHg.
• Maintains constant
• Renal Plasma Flow (RPF)
• GFR

• Vital organs: Kidney, brain, heart.

• Works in denervated kidney (no neural influence).

Mechanisms involved:

JG Apparatus [3 Cell Types]

JG Cells (Juxtaglomerular / Granular Cells):

• Location: Modified smooth muscle cells of afferent arteriole.

• Function: 
• Intrarenal baroreceptors
• Release renin
• RAAS → Angiotensin II mediated vasoconstriction

• Conditions that ↑↑ renin release:
• Hypotension in afferent arteriole
• Low sodium
• Sympathetic stimulation
• Diuretics
• Hemorrhage

• Conditions that ↓↓ renin release:
• ↑↑ pressure in afferent arteriole.
• Angiotensin II 
• ADH 

Macula Densa Cells:

• Location: 
• Uppermost portion of Thick Ascending Limb
• Junction TAL & DCT

• Function: 
• Acts as a GFR/NaCl sensor (Chemoreceptors).

• Sense: 
• Chloride > sodium for stimulation in TAL lumen

• Tubuloglomerular feedback
• ↑ GFR
• → ↑ NaCl filtration (in distal tubule)
• → Sensed by macula densa
• → Releases adenosine
• → Constriction of afferent arteriole
• → ↓ GFR

Water Clearance

• Positive free-water clearance
• Excess water excreted
• Dilute urine

• Negative free-water clearance
• Excess solutes excreted
• Water conserved
• Concentrated urine