Acid base, nephrotic and nephritic syndrome , casts in urine, acute kidney injury, acute cystitis.
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I now have comprehensive content from authoritative textbooks. Let me compile the full structured response.Here is a comprehensive, exam-ready breakdown of all five topics, drawn from Brenner & Rector's The Kidney, Goldman-Cecil Medicine, Comprehensive Clinical Nephrology, Ganong's Review, Robbins Pathology, Frameworks for Internal Medicine, and Tintinalli's Emergency Medicine.
1. ACID-BASE DISORDERS
Core Concepts
The body maintains blood pH between 7.35-7.45. The Henderson-Hasselbalch relationship governs this:
pH = 6.1 + log([HCO₃⁻] / 0.03 × PaCO₂)
- Acidosis: pH < 7.35
- Alkalosis: pH > 7.45
- Respiratory component: PaCO₂ (normal = 35-45 mmHg)
- Metabolic component: HCO₃⁻ (normal = 22-26 mEq/L)
The Four Primary Disorders
| Disorder | pH | Primary Change | Compensation |
|---|---|---|---|
| Metabolic Acidosis | ↓ | ↓ HCO₃⁻ | ↓ PaCO₂ (hyperventilation) |
| Metabolic Alkalosis | ↑ | ↑ HCO₃⁻ | ↑ PaCO₂ (hypoventilation) |
| Respiratory Acidosis | ↓ | ↑ PaCO₂ | ↑ HCO₃⁻ (renal) |
| Respiratory Alkalosis | ↑ | ↓ PaCO₂ | ↓ HCO₃⁻ (renal) |
Compensation is never complete (except respiratory alkalosis, which can normalize pH). Respiratory compensation is fast (minutes); renal compensation is slow (days).
Compensation Formulas
| Disorder | Expected Compensation |
|---|---|
| Metabolic Acidosis | PaCO₂ = (1.5 × HCO₃⁻) + 8 ± 2 (Winter's formula) |
| Metabolic Alkalosis | PaCO₂ increases 0.7 mmHg per 1 mEq/L ↑ HCO₃⁻ |
| Acute Resp. Acidosis | HCO₃⁻ rises 1 mEq/L per 10 mmHg ↑ PaCO₂ |
| Chronic Resp. Acidosis | HCO₃⁻ rises 3.5 mEq/L per 10 mmHg ↑ PaCO₂ |
| Acute Resp. Alkalosis | HCO₃⁻ falls 2 mEq/L per 10 mmHg ↓ PaCO₂ |
| Chronic Resp. Alkalosis | HCO₃⁻ falls 5 mEq/L per 10 mmHg ↓ PaCO₂ |
If measured PaCO₂ is higher than Winter's formula predicts in metabolic acidosis → concomitant respiratory acidosis. If lower → concomitant respiratory alkalosis.
Anion Gap
AG = Na⁺ - (Cl⁻ + HCO₃⁻) | Normal = ~12 mEq/L (or ~8-10 if albumin-corrected)
Corrected AG = measured AG + 2.5 × (4 - albumin g/dL)
High Anion Gap Metabolic Acidosis (MUDPILES)
| Mnemonic | Cause |
|---|---|
| M | Methanol |
| U | Uremia |
| D | DKA / alcoholic KA |
| P | Propylene glycol / Paracetamol |
| I | Isoniazid / Inborn errors |
| L | Lactic acidosis |
| E | Ethylene glycol |
| S | Salicylates |
Normal Anion Gap Metabolic Acidosis (HARD-UP or DURHAM)
Causes: GI HCO₃⁻ loss (diarrhea), Renal tubular acidosis (RTA), dilutional, carbonic anhydrase inhibitors, ureteral diversion, early CKD.
Metabolic Alkalosis - Causes
- Saline-responsive (urine Cl⁻ < 20 mEq/L): vomiting, NG suction, diuretics (after stopped), post-hypercapnia
- Saline-resistant (urine Cl⁻ > 20 mEq/L): hyperaldosteronism, Cushing's, Bartter syndrome, Gitelman syndrome
Respiratory Acidosis - Causes
Hypoventilation: COPD, sedatives/opioids, neuromuscular disease, obesity hypoventilation, severe pneumonia
Respiratory Alkalosis - Causes
Hyperventilation: anxiety, pain, fever, early salicylate toxicity, hepatic failure, pregnancy (normal), hypoxia (altitude, PE)
2. NEPHROTIC SYNDROME
Definition
Proteinuria > 3.5 g/day (or > 40 mg/m²/hr in children), accompanied by:
- Hypoalbuminemia (< 3 g/dL)
- Edema (periorbital, peripheral, ascites)
- Hyperlipidemia (LDL, cholesterol - reactive hepatic synthesis)
- Lipiduria (fatty casts, oval fat bodies, Maltese crosses under polarized light)
- Hypercoagulability (loss of antithrombin III, protein C, S → renal vein thrombosis risk)
Causes
Primary (Idiopathic)
| Disease | Age/Feature | Pathology |
|---|---|---|
| Minimal Change Disease (MCD) | Children (most common in kids), responds to steroids | LM: normal; EM: effacement of podocyte foot processes |
| Focal Segmental Glomerulosclerosis (FSGS) | Adults, African Americans, HIV, heroin | LM: focal, segmental scarring; IF: IgM, C3 nonspecific |
| Membranous Nephropathy | Adults, most common nephrotic in adults | LM: thickened GBM, "spike and dome"; IF: granular IgG, C3 along GBM |
| Membranoproliferative GN (MPGN) | Young adults, low C3 | LM: double contour/tram-track GBM; IF: C3, IgG |
Secondary Causes
- Diabetes mellitus: Kimmelstiel-Wilson nodules
- SLE: lupus nephritis class V (membranous)
- Amyloidosis: Congo red staining, apple-green birefringence
- Medications: NSAIDs, gold, penicillamine, heroin, captopril, interferon-α, lithium
- Infections: HIV, HBV, HCV, malaria, syphilis
- Malignancy: Hodgkin's (MCD), solid tumors (membranous)
Complications
- Thromboembolism (renal vein thrombosis - especially membranous)
- Infections (loss of IgG, opsonins → encapsulated organisms)
- Atherosclerosis (hyperlipidemia)
- AKI (hypovolemia, thrombosis)
3. NEPHRITIC SYNDROME
Definition
Classic triad:
- Hematuria - dysmorphic RBCs and/or RBC casts
- Hypertension
- Oliguria with azotemia (reduced GFR, elevated creatinine)
- Mild to moderate proteinuria (non-nephrotic range, usually < 3.5 g/day)
- Edema (from Na/water retention)
"Nephritic syndrome is defined as glomerular hematuria in the form of dysmorphic red blood cells or RBC casts, in combination with hypertension, edema, reduced GFR, and non-nephrotic-range proteinuria." - National Kidney Foundation Primer
Causes
| Cause | Key Features |
|---|---|
| Post-streptococcal GN (PSGN) | 1-3 wks after pharyngitis, 3-6 wks after skin infection; low C3; lumpy-bumpy IgG on IF; subepithelial "humps" on EM |
| IgA Nephropathy (Berger's) | Most common GN worldwide; synpharyngitic hematuria (concurrent with URTI); mesangial IgA on IF |
| Lupus nephritis | Class III/IV; "wire loop" lesions; low C3, C4, ANA, anti-dsDNA |
| ANCA-associated GN | Pauci-immune (no immune deposits); MPO-ANCA (MPA) or PR3-ANCA (GPA); often crescentic |
| Anti-GBM disease (Goodpasture's) | Linear IgG on IF; pulmonary-renal syndrome |
| MPGN | Double contour GBM; persistent hypocomplementemia |
Rapidly Progressive GN (RPGN)
RPGN = rapid loss of renal function over days-weeks in setting of nephritic syndrome. Defined histologically by > 50% crescents on biopsy (crescent = parietal epithelial cell + monocyte proliferation in Bowman's space). Three types:
- Type 1: Anti-GBM (Goodpasture)
- Type 2: Immune complex (SLE, PSGN, IgAN)
- Type 3: Pauci-immune / ANCA
Nephrotic vs. Nephritic - Key Comparison
| Feature | Nephrotic | Nephritic |
|---|---|---|
| Proteinuria | > 3.5 g/day | < 3.5 g/day (non-nephrotic) |
| Hematuria | Absent/minimal | Prominent, dysmorphic RBCs |
| RBC casts | Absent | Present |
| Hypertension | Variable | Common |
| Edema | Massive (anasarca) | Mild-moderate |
| BP | Often normal | Elevated |
| Complement | Variable | Low in many (PSGN, SLE, MPGN) |
4. CASTS IN URINE
Casts form in the distal nephron/collecting duct. They take on the cylindrical shape of the tubule and are composed of a Tamm-Horsfall protein (uromodulin) matrix.
Types and Clinical Significance
| Cast Type | Composition | Clinical Meaning |
|---|---|---|
| Hyaline | Tamm-Horsfall protein alone | Normal (increases with exercise, dehydration, fever, diuretics) - non-specific |
| Granular ("muddy brown") | Degenerated tubular cell debris | ATN (acute tubular necrosis) - hallmark |
| RBC casts | Red blood cells embedded in matrix | Glomerulonephritis (hallmark) - indicates glomerular bleeding |
| WBC casts | White blood cells in matrix | Pyelonephritis (most common); also AIN, lupus nephritis, ANCA GN |
| Tubular epithelial cell casts | Shed tubular epithelial cells | ATN, nephrotoxic injury (aminoglycosides, contrast) |
| Waxy/broad casts | Highly degenerated, wide | Advanced CKD / oliguria - "renal failure casts"; dilated tubules |
| Fatty casts / oval fat bodies | Lipid droplets; Maltese cross polarized light | Nephrotic syndrome |
| Pigmented granular | Myoglobin/hemoglobin-tinged granular | Rhabdomyolysis (myoglobinuria) |
| Eosinophil casts | Eosinophils | Allergic interstitial nephritis (AIN) |
Key rule: RBC casts = glomerulonephritis until proven otherwise. WBC casts = infection/inflammation of renal parenchyma.
5. ACUTE KIDNEY INJURY (AKI)
Definition (KDIGO 2012)
Any of the following within 48 hours:
- Serum creatinine rise ≥ 0.3 mg/dL
- Serum creatinine rise ≥ 1.5× baseline within 7 days
- Urine output < 0.5 mL/kg/hr for ≥ 6 hours
KDIGO Staging
| Stage | Serum Creatinine | Urine Output |
|---|---|---|
| 1 | 1.5-1.9× baseline or ≥ 0.3 mg/dL rise | < 0.5 mL/kg/hr for 6-12h |
| 2 | 2.0-2.9× baseline | < 0.5 mL/kg/hr for ≥ 12h |
| 3 | ≥ 3× baseline or ≥ 4.0 mg/dL or RRT initiated | < 0.3 mL/kg/hr for ≥ 24h or anuria ≥ 12h |
Classification
Pre-renal AKI
Cause: Reduced renal perfusion (hypovolemia, heart failure, liver failure, sepsis, NSAID/ACEi)
- Urine Na < 20 mEq/L
- FENa < 1% (FeNa = [UNa × PCr] / [PNa × UCr] × 100)
- Urine osmolality > 500 mOsm/kg
- BUN:Cr ratio > 20:1
- Urinalysis: normal or hyaline casts only
Intrinsic (Renal) AKI
| Category | Cause | Urinalysis Findings |
|---|---|---|
| ATN (most common) | Ischemia (shock, post-prerenal), nephrotoxins (contrast, aminoglycosides, myoglobin) | Muddy brown granular casts, tubular epithelial cells; FENa > 2% |
| AIN (Acute Interstitial Nephritis) | Drugs (NSAIDs, PCN, PPIs), infections, autoimmune | WBC casts, eosinophiluria, mild proteinuria, hematuria |
| Glomerulonephritis | As above (nephritic) | RBC casts, dysmorphic RBCs, proteinuria |
| Vascular | Renal artery thrombosis, TMA (HUS/TTP), cholesterol emboli | Variable; eosinophilia in atheroemboli |
Post-renal AKI
Cause: Obstruction (BPH, stones, bladder cancer, retroperitoneal fibrosis, bilateral ureteral obstruction)
- Urine Na variable; BUN:Cr ratio may be elevated early
- Ultrasound shows hydronephrosis
- Relief of obstruction = post-obstructive diuresis
Useful Diagnostic Indices
| Index | Pre-renal | ATN |
|---|---|---|
| FENa | < 1% | > 2% |
| Urine Na | < 20 mEq/L | > 40 mEq/L |
| Urine Osmolality | > 500 | < 350 |
| BUN:Cr | > 20:1 | ~10-15:1 |
| Urinalysis | Normal/hyaline casts | Granular/tubular casts |
Note: FENa is unreliable in contrast nephropathy, myoglobinuria, early obstruction, and on diuretics. Use FEUrea (< 35% = pre-renal) when on diuretics.
Complications of AKI
- Acidosis (metabolic)
- Electrolytes (hyperkalemia - most dangerous acutely; hyponatremia, hyperphosphatemia)
- Infections
- Overload (fluid)
- Uremia (pericarditis, encephalopathy, bleeding)
Indications for Emergent Dialysis (AEIOU)
Acidosis (pH < 7.1, refractory), Electrolytes (refractory hyperkalemia), Intoxication (dialyzable toxins), Overload (refractory pulmonary edema), Uremia (symptomatic)
Long-term Consequences
AKI significantly increases the risk of CKD and ESKD. Among patients requiring dialysis for AKI, incidence of chronic dialysis is 2.63/100 person-years vs. 0.91 in controls (HR 3.23). Those without prior CKD have a 15.5-fold increased risk of developing chronic dialysis.
(Brenner & Rector's The Kidney)
6. ACUTE CYSTITIS
Definition
Bacterial infection of the bladder (lower urinary tract), most often uncomplicated in young healthy women.
Etiology
- E. coli (80-85% of uncomplicated cases)
- Staphylococcus saprophyticus (young sexually active women)
- Klebsiella, Proteus, Enterococcus (less common)
Clinical Features
- Dysuria, frequency, urgency
- Suprapubic pain/discomfort
- No fever, no flank pain (distinguishes from pyelonephritis)
- Urine: pyuria (WBCs), bacteriuria, hematuria possible
Diagnosis
- Urinalysis: + leukocyte esterase, + nitrites (gram-negative organisms)
- Microscopy: >10 WBC/hpf (pyuria)
- Urine culture: >10³-10⁵ CFU/mL (threshold varies by population)
- Culture not required for uncomplicated cystitis in young women
Treatment (Uncomplicated, Adult Female)
(Tintinalli's Emergency Medicine / IDSA 2010 guidelines)
| Drug | Dose | Duration |
|---|---|---|
| Nitrofurantoin (macrocrystals) | 100 mg BID | 5 days |
| TMP-SMX DS | 160/800 mg BID | 3 days (avoid if local resistance > 20%) |
| Fosfomycin | 3 g single dose | 1 day |
| Pivmecillinam | 400 mg BID | 5 days (where available) |
- Fluoroquinolones: effective but reserved as second-line due to resistance and side effects
- Amoxicillin-clavulanate and aminopenicillins: not first-line (lower efficacy, selects resistant organisms)
- Third-generation cephalosporins: effective alternative when ESBL suspected
Complicated vs. Uncomplicated
| Feature | Uncomplicated | Complicated |
|---|---|---|
| Patient | Young, healthy, non-pregnant woman | Male, pregnant, catheterized, immunocompromised, structural abnormality, DM |
| Duration of treatment | 3-5 days | 7-14 days |
| Need for culture | No | Yes |
Quick Reference Summary Table
| Condition | Key Finding | Pathognomonic Feature |
|---|---|---|
| Nephrotic | Proteinuria > 3.5 g/day, hypoalbuminemia | Fatty casts / Maltese cross |
| Nephritic | Hematuria + HTN + oliguria | RBC casts |
| ATN | Muddy brown granular casts | FENa > 2% |
| AIN | WBC casts + eosinophiluria | Drug history |
| PSGN | Low C3, 2-3 wks post-strep | Subepithelial "humps" on EM |
| Cystitis | Dysuria, frequency, pyuria | No fever/flank pain |
| Metabolic Acidosis | Low pH, low HCO₃⁻ | Winter's formula for PaCO₂ |
*Sources: Brenner & Rector's The Kidney (2-Volume Set); Comprehensive Clinical Nephrology 7th Ed.; National Kidney Foundation Primer on Kidney Diseases 8th Ed.; Goldman-Cecil Medicine; Robbins & Cotran Pathologic Basis of Disease; Ganong's Review of Medical Physiology 26th Ed.; Frameworks for Internal Medicine; Tintinalli's Emergency Medicine.*All five topics have been covered in depth. Here's a summary of what was included:
What's Covered
1. Acid-Base Disorders
- The 4 primary disorders with pH, primary change, and compensation
- Compensation formulas including Winter's formula for metabolic acidosis
- Anion gap calculation and MUDPILES mnemonic for high-AG metabolic acidosis
- Normal-AG causes (diarrhea, RTA, dilution)
- Causes of metabolic alkalosis (saline-responsive vs. resistant) and respiratory disorders
2. Nephrotic Syndrome
- Definition (proteinuria > 3.5 g/day + the classic tetrad)
- Primary causes: MCD, FSGS, Membranous, MPGN - with histology highlights
- Secondary causes (DM, SLE, amyloidosis, drugs, infections, malignancy)
- Complications (thromboembolism, infections, AV disease)
3. Nephritic Syndrome
- Classic triad + definition of RPGN
- Causes: PSGN, IgA nephropathy, lupus nephritis, ANCA GN, anti-GBM
- RPGN types 1/2/3 with crescents on biopsy
- Nephrotic vs. Nephritic comparison table
4. Urine Casts
- Full table: Hyaline, Granular (muddy brown), RBC, WBC, tubular epithelial, waxy/broad, fatty, pigmented, eosinophil - each with composition and clinical meaning
5. Acute Kidney Injury
- KDIGO definition and staging (stages 1-3)
- Pre-renal, intrinsic (ATN, AIN, GN, vascular), post-renal - with urine indices
- Diagnostic indices table (FENa, urine Na, osmolality, BUN:Cr)
- AEIOU indications for emergency dialysis
- Long-term CKD/ESKD risk after AKI
6. Acute Cystitis
- Etiology (E. coli most common), clinical features
- Diagnosis (UA, culture thresholds)
- First-line antibiotics with doses and durations (IDSA guidelines)
- Complicated vs. uncomplicated distinction
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