Nephrotic vs nephritic syndrome from harrison book in notes concise form
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Nephrotic vs. Nephritic Syndrome
From Harrison's Principles of Internal Medicine, 22nd Ed. (2025)
QUICK COMPARISON TABLE
| Feature | Nephrotic | Nephritic |
|---|---|---|
| Defining lesion | Loss of glomerular charge/size barrier → protein leak | Glomerular inflammation → hematuria + reduced GFR |
| Proteinuria | >3.5 g/day (heavy) | Mild-moderate (<3.5 g/day usually) |
| Hematuria | Minimal | Prominent (dysmorphic RBCs, RBC casts) |
| BP | May be normal or elevated | Hypertension (common, prominent) |
| Edema | Severe, generalized (periorbital, scrotal, facial) | Mild-moderate |
| GFR/Oliguria | Usually preserved early | Reduced GFR; oliguria/anuria common |
| Urine sediment | "Bland" - fatty casts, oval fat bodies, Maltese crosses | "Active" - RBC casts, pyuria, dysmorphic RBCs |
| Serum albumin | Low (<3.5 g/dL) | Usually normal |
| Lipids | High LDL, low HDL, lipiduria | Usually normal |
| Complement | Normal (most causes) | Often low C3 (immune complex diseases) |
NEPHRITIC SYNDROME
Definition
Inflammation of the kidney (glomerulonephritis). Presents with:
- Hematuria (macro or micro; cola/tea-colored urine = hematin from RBCs in acid urine)
- Pyuria + RBC casts on urinalysis (most important finding)
- Hypertension + volume expansion (edema, orthopnea)
- Oliguria / anuria - reduced urine Na, concentrated urine
- Mild-moderate proteinuria
- Dysmorphic RBCs (misshapen as they cross the glomerular barrier)
Mechanism
Inflammatory damage to glomeruli → fall in GFR → salt and water retention → edema + hypertension. Can be acute, subacute, or chronic.
Key Subtypes (Harrison's)
1. Acute Nephritic (Poststreptococcal GN) - prototype
- Children 2-14 years (developing); elderly in developed countries
- 1-3 weeks after pharyngitis, 2-6 weeks after skin infection
- Nephritogenic antigens: SPEB (cysteine proteinase) + NAPlr
- Biopsy: hypercellularity (mesangial + endothelial), PMN infiltrates, subepithelial "humps" (IgG, IgM, C3)
- Labs: depressed CH50 + low C3 (normal C4) in 90% in first week; streptozyme positive 80-95%
- 5% children / 20% adults may have nephrotic-range proteinuria
- Treatment: supportive (antihypertensives, diuretics, dialysis if needed) + antibiotics for active strep
2. RPGN (Rapidly Progressive GN)
- Three types by ANCA/anti-GBM/immune complex status
- Pauci-immune (ANCA+), anti-GBM (Goodpasture's), immune complex (low C3)
3. Hereditary Nephritis - Alport Syndrome
- COL4A5 mutation → type IV collagen defect in GBM
- X-linked; males most severe (renal failure middle age)
- Features: microscopic hematuria + sensorineural deafness + ocular deformities
Complement Pattern in Nephritic Diseases
- Low C3, normal C4 - poststrep GN, MPGN type II (C3 nephropathy), endocarditis
- Low C3 + low C4 - lupus nephritis, cryoglobulinemia, MPGN type I
- Normal complement - IgA nephropathy, anti-GBM, ANCA vasculitis
NEPHROTIC SYNDROME
Definition (Harrison's triad)
- Proteinuria >3.5 g/day
- Hypoalbuminemia <3.5 g/dL
- Edema
Plus associated features: hypercholesterolemia (high LDL, low HDL), lipiduria, hypercoagulable state
Clinical Features
- Edema: generalized - periorbital/facial/eyelid swelling (contrast with heart failure where orthopnea dominates); scrotal/penile edema; skin may "weep" large bullae; hoarseness from vocal cord edema
- Urine: foamy urine; fatty casts, oval fat bodies, Maltese crosses under polarized light
- Occasionally nephrotic-range proteinuria WITHOUT edema (e.g., HIV-associated nephropathy / HIVAN in African Americans)
Pathophysiology of Complications
| Complication | Mechanism |
|---|---|
| Edema | Hypoalbuminemia → reduced oncotic pressure → fluid shift; + salt/water retention |
| Hyperlipidemia | Liver upregulates lipoprotein synthesis to compensate lost oncotic pressure |
| Hypercoagulability | Loss of antithrombin III, protein C, S; renal vein thrombosis risk |
| Infections | Loss of immunoglobulins, complement; susceptibility to encapsulated bacteria |
| Thyroid/drug binding | Loss of thyroid-binding globulin → altered TFT results |
Management Principles (Harrison's)
- Hypercholesterolemia: statins (increased cardiovascular risk)
- Edema: diuretics (avoid intravascular volume depletion)
- Hypercoagulability: anticoagulation if thrombosis
- Proteinuria/progression: ACE inhibitors / ARBs + SGLT2 inhibitors (newer - Harrison's 22e explicitly mentions SGLT2i to lower urinary protein and preserve kidney function)
Primary Causes by Frequency
| Cause | Key Points |
|---|---|
| Minimal Change Disease (MCD) | 70-90% in children; 10-15% in adults; "nil lesion" on light microscopy; EM: foot process effacement; responds to steroids; T-cell dysfunction (IL-13, IL-4); also anti-nephrin antibodies |
| FSGS | Most common nephrotic syndrome in adults; APOL1 mutations (African ancestry); secondary FSGS from reduced nephron mass |
| Membranous Nephropathy | Adults; anti-PLA2R antibodies (primary); secondary to HBV, SLE, malignancy |
| MPGN | Can overlap with nephritic features (mixed picture) |
| Diabetic Nephropathy | Microalbuminuria (30-300 mg/day) → overt proteinuria; coincident retinopathy |
KEY DISTINCTIONS TO REMEMBER
| Urine Finding | Syndrome |
|---|---|
| RBC casts | Nephritic (pathognomonic of GN) |
| Fatty casts / oval fat bodies / Maltese crosses | Nephrotic |
| Dysmorphic RBCs | Nephritic |
| Heavy protein, bland sediment | Nephrotic |
- Subnephrotic proteinuria (<3.5 g/day) = focal disease (<50% glomeruli)
- Nephrotic-range proteinuria = diffuse disease (most glomeruli involved)
- MPGN is the exception - can present with overlapping nephrotic + nephritic features
- Dipstick only detects acidic proteins (albumin) - misses kappa/lambda light chains (myeloma) - need urine protein immunoelectrophoresis
- Higher 24-hour urine protein → faster GFR decline
Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025) - Chapters 319 and 320
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