Glomerular structure and function

Glomerular structure and function

Glomerular structure and function

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Glomerular Filtration Barrier - The Kidney's Sieve

Glomerular structure and filtration barrier

The filtration barrier is selectively permeable, determined by size and charge.

  • Three Layers:

    • Fenestrated capillary endothelium: Blocks cells (RBCs, platelets). First size barrier.
    • Glomerular basement membrane (GBM): Fused basal laminae with Type IV collagen and heparan sulfate (negative charge). Main charge barrier.
    • Podocyte foot processes (visceral layer): Slit diaphragms between pedicels. Final size barrier.
  • Selectivity:

    • Size Barrier: Restricts molecules > 70 kDa (e.g., albumin).
    • Charge Barrier: Repels anionic molecules (e.g., albumin) due to negative charges in the GBM.

⭐ In Alport syndrome, a mutation in Type IV collagen disrupts the GBM, leading to hematuria and progressive renal failure. 📌 Mnemonic: "Can't see, can't pee, can't hear a bee."

Starling Forces - Pressure Cooker Physics

Glomerular Filtration and Starling Forces

Net filtration pressure (NFP) dictates glomerular filtration, governed by opposing hydrostatic and oncotic pressures.

  • Outward Force (Favors Filtration)
    • Glomerular Hydrostatic Pressure (PGC): Blood pressure in glomerular capillaries. The primary driver of filtration. (≈ 55 mmHg)
  • Inward Forces (Oppose Filtration)
    • Bowman's Capsule Hydrostatic Pressure (PBC): Fluid pressure in Bowman's space. (≈ 15 mmHg)
    • Glomerular Oncotic Pressure (πGC): Osmotic pull from proteins in capillary blood. (≈ 30 mmHg)

Filtration occurs because PGC > (PBC + πGC).

Net Filtration Pressure (NFP) is calculated as: $NFP = P_{GC} - (P_{BC} + oldsymbol{\pi}_{GC})$

⭐ GFR is directly proportional to the Net Filtration Pressure. Any factor that alters Starling forces (e.g., ↓ RBF, ureteric obstruction) will directly impact GFR.

GFR & Clearance - Bean Counter's Math

Clearance of glucose, inulin, and PAH relative to GFR

  • Glomerular Filtration Rate (GFR): Volume of plasma filtered per unit time.

    • Normal GFR ≈ 100-125 mL/min.
    • Gold standard for measurement is Inulin clearance because it is freely filtered and is not reabsorbed or secreted.
  • Renal Clearance ($C_x$): Volume of plasma completely cleared of a substance (X) per unit time.

    • Formula: $C_x = (U_x \times V) / P_x$
    • $U_x$ = urine concentration, $V$ = urine flow rate, $P_x$ = plasma concentration.
  • Interpreting Clearance:

    • $C_x < GFR$ → Net tubular reabsorption.
    • $C_x > GFR$ → Net tubular secretion.
    • $C_x = GFR$ → No net reabsorption or secretion (Inulin).

⭐ A doubling of serum creatinine (e.g., from 1 to 2 mg/dL) suggests an approximate 50% reduction in GFR.

  • 📌 Creatinine is Casually Secreted, so its Clearance slightly overestimates GFR.

GFR Regulation - Tapping the Brakes

  • Myogenic Mechanism: Intrinsic reflex of the afferent arteriole to changes in blood pressure.
    • ↑ Stretch from high BP → arteriolar vasoconstriction → ↓ RBF & GFR.
    • ↓ Stretch from low BP → arteriolar vasodilation → ↑ RBF & GFR.
  • Tubuloglomerular Feedback (TGF): Macula densa cells in the JGA sense distal tubular flow.
    • ↑ GFR → ↑ NaCl delivery to macula densa → release of adenosine → afferent arteriole vasoconstriction → ↓ GFR.

Renal Corpuscle and Juxtaglomerular Apparatus

⭐ NSAIDs inhibit prostaglandins, which normally dilate the afferent arteriole. This causes unopposed constriction, leading to a ↓ GFR, especially in CKD or heart failure patients.

High‑Yield Points - ⚡ Biggest Takeaways

  • The glomerular filtration barrier has three layers: fenestrated endothelium, the glomerular basement membrane (GBM), and podocyte foot processes.
  • A negative charge barrier, from heparan sulfate in the GBM, is crucial for repelling proteins like albumin.
  • The barrier is also size-selective, restricting molecules larger than ~70 kDa.
  • Podocyte effacement (flattening) is a key pathologic finding in nephrotic syndrome.
  • Mesangial cells provide structural support, control filtration area, and perform phagocytosis.

Practice Questions: Glomerular structure and function

Test your understanding with these related questions

A 55-year-old woman presents to a physician’s clinic for a diabetes follow-up. She recently lost weight and believes the diabetes is ‘winding down’ because the urinary frequency has slowed down compared to when her diabetes was "at its worst". She had been poorly compliant with medications, but she is now asking if she can decrease her medications as she feels like her diabetes is improving. Due to the decrease in urinary frequency, the physician is interested in interrogating her renal function. Which substance can be used to most accurately assess the glomerular filtration rate (GFR) in this patient?

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Flashcards: Glomerular structure and function

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NSAIDs cause vasoconstriction of the _____ arteriole of the kidney, which decreases GFR

TAP TO REVEAL ANSWER

NSAIDs cause vasoconstriction of the _____ arteriole of the kidney, which decreases GFR

afferent

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