Lecture Notes: Nephrotic Syndrome

Introduction

• Topic: Nephrotic Syndrome (a type of glomerulonephritis)
• Aim: Simplify understanding and reduce anxiety for students.
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Glomerular Filtration Barrier (GFB)

• Components of GFB
  • Fenestrated Capillaries:
    • Red capillaries that are porous and allow selective substances to filter through.
  • Glomerular Basement Membrane:
    • Negatively charged membrane that repels large proteins due to like-charge repulsion.
  • Podocytes:
    • Cells with foot processes creating filtration slits.

Importance of GFB

• Regulates substances entering Bowman’s space:
  • Allows sodium, water, electrolytes, and nutrients.
  • Blocks red blood cells, white blood cells, and proteins.

Pathophysiology of Nephrotic Syndrome

• Podocyte Injury:
  • Damage to podocytes leads to loss of protein regulation.
  • Result: Heavy proteinuria (protein loss in urine).
• Key Features of Nephrotic Syndrome:
  • Heavy proteinuria: >3.5 grams per day.
  • Hypoalbuminemia: Low albumin in blood due to loss.
  • Edema: Fluid retention in tissues due to low oncotic pressure.
  • Hyperlipidemia: Increased lipids due to compensatory mechanisms in response to low albumin.

Clinical Manifestations

• Edema:
  • Peripheral edema, pulmonary edema, ascites, periorbital edema.
• Hyperlipidemia:
  • Increased triglycerides and cholesterol in blood, leading to further complications (e.g., xanthomas, atherosclerosis).
• Increased Risk of Clots:
  • Loss of antithrombin III leading to venous clots (e.g., DVT, PE).
• Increased Infection Risk:
  • Loss of immunoglobulins; high susceptibility to infections, particularly Streptococcus pneumoniae.

Types of Nephrotic Syndrome

1. Minimal Change Disease

• Demographics: Common in children.
• Primary Cause: Idiopathic.
• Secondary Causes:
  • Infections, Hodgkin's lymphoma, NSAID use.
• Mechanism: T-cell mediated cytokine release damages podocytes leading to effacement.

2. Membranous Nephropathy

• Demographics: Adults, often Caucasians.
• Primary Cause: Anti-PLA2 receptor antibody.
• Secondary Causes: Hepatitis B, C, syphilis, gold, penicillamine.
• Mechanism: Immune complex deposition in subepithelial space activates complement, causing inflammation and podocyte damage.

3. Focal Segmental Glomerulosclerosis (FSGS)

• Demographics: More common in African-American and Hispanic adults.
• Primary Cause: Idiopathic.
• Secondary Causes: HIV, heroin use, obesity, sickle cell disease.
• Mechanism: Hyalinosis and sclerosis lead to podocyte effacement.

4. Diabetic Nephropathy

• Demographics: Patients with diabetes.
• Mechanism: Non-enzymatic glycation causes arteriole sclerosis leading to increased intraglomerular pressure and podocyte damage.

5. Amyloidosis

• Mechanism: Abnormal protein deposition due to chronic inflammation or multiple myeloma.

Diagnosis

• Urinalysis:
  • Nephrotic Syndrome: Heavy proteinuria, lipiduria, fat oval bodies.
  • Nephritic Syndrome: Hematuria, pyuria, less protein loss.
• Quantitative Tests:
  • 24-hour urine protein or urine albumin-creatinine ratio to differentiate nephrotic (>3.5g) vs. nephritic (<3.5g).

Treatment

General Treatment Strategies

• Complications:
  • Proteinuria: ACE inhibitors/ARBs to reduce protein loss and hypertension.
  • Hyperlipidemia: Dietary changes, statins.
  • Edema: Fluid/sodium restriction, diuretics.
  • Hypercoagulability: Anticoagulation therapy.
  • Vaccination against pneumococcus to reduce infection risk.

Specific Treatments

• Primary Nephrotic Syndromes:
  • Minimal Change Disease: Steroids as first-line treatment; good response indicates minimal change.
  • Membranous Nephropathy & FSGS: Long-term immunosuppressants if steroids aren’t effective; risk of chronic kidney disease.

Secondary Causes

• Must treat the underlying cause (e.g. infections, diabetes management, etc.).

Conclusion

• Understanding nephrotic syndrome involves recognizing its presentation, differentiating types, and addressing both complications and underlying causes.