Glomerular Diseases Overview

Glomerular Diseases

• Glomerular diseases are a group of conditions that damage the glomeruli, the kidney's microscopic filtration units.
• Damage to the glomeruli impairs kidney function, causing issues like proteinuria, hematuria, reduced glomerular filtration rate (GFR), and chronic kidney disease or failure.
• Glomerular diseases can result in significant morbidity and mortality. Complications include hypertension, nephrotic syndrome, and end-stage renal disease, necessitating dialysis or kidney transplantation.
• Early detection and appropriate management are crucial to prevent progression and improve patient outcomes.

Human Kidney Anatomy

• The kidney has an external and internal view. Diagrams of both are shown. Cortical blood vessels, interlobular blood vessels, renal artery, renal vein, ureter, minor calyx, major calyx, medulla, and capsule are depicted.

Renal Anatomy

• The functional unit of the kidney is the nephron; a diagram is provided. Components include the glomerulus, proximal convoluted tubule, distal convoluted tubule, collecting duct. Blood flow is depicted from renal artery to renal vein.

Glomerulus Structure

• Diagrams illustrating the microscopic structure of the glomerulus are present. Components include capillary loops, red blood cells, proximal tubule, urinary space, mesangium, mesangial cells, mesangial matrix, parietal epithelium, endothelium, foot processes, basement membrane and fenestrae in endothelium. All components are labeled directly.

Classification of Glomerular Diseases

• Primary Glomerular Diseases: affect only the kidneys.
  • Minimal change disease (lipoid nephrosis)
  • Acute diffuse proliferative GN (post-streptococcal and non-post-streptococcal)
  • Rapidly progressive GN
  • Membranous GN
  • Membranoproliferative GN
  • Chronic GN
• Secondary Glomerular Diseases: affect other organs and also affect the kidneys.
  • Systemic lupus erythematosus (SLE)
  • Polyarteritis nodosa (PAN)
  • Wegener granulomatosis
  • Diabetes mellitus (diabetic nephropathy)
  • Goodpasture syndrome
  • Amyloidosis

Minimal Change Glomerular Disease

• Etiology & Pathogenesis: Chemical change in glomerular basement membrane causing protein loss.
• Grossly: Mild bilateral kidney enlargement.
• LM (Light Microscope): No abnormalities.
• IF (Immunofluorescence): No immune deposits.
• EM (Electron Microscope): Fusion of foot processes of epithelial cells (podocytes).
• Clinical Picture (CP): Affects children and young adults; causes nephrotic syndrome.
• Fate: Excellent prognosis; most patients respond to corticosteroids with complete resolution of proteinuria.

Post-streptococcal Glomerular Nephritis

• Etiology & Pathogenesis: Immune complex reaction; nephrogenic strains of group A beta hemolytic streptococci + IgG, complex deposited in glomeruli with subsequent complement activation -> acute inflammation.
• Grossly: Mild bilateral kidney enlargement with petechial hemorrhages.
• LM (Light Microscope):
  • Glomeruli: proliferation of endothelial and mesangial cells; glomerular capillaries containing neutrophils; Bowman's space shows neutrophils, RBCs, and some albumin.
  • Tubules: lining cells swollen; lumens show casts (RBC casts, neutrophil casts, and hyaline casts).
  • Interstitium: acute inflammatory reaction.
• IF (Immunofluorescence): Deposition of IgG and C3.
• EM (Electron Microscope): Subepithelial immune complex deposit (humps)
• Clinical Picture (CP): Young child abruptly develops malaise, fever, nausea, oliguria, and hematuria (smoky or cocoa-colored urine) 1-2 weeks after recovery from a sore throat.
• Fate: More than 95% recover with therapy. The rest may develop rapidly progressive glomerulonephritis or chronic glomerulonephritis. In adults, prognosis is bad.

Diagnosis of Glomerular Diseases

• A renal biopsy is taken and examined using three types of microscopes:
  • Light microscope (LM): to examine the structure of glomeruli, tubules, and interstitium.
  • Immunofluorescent microscope (IF): to identify the type of deposited immunoglobulin in the glomeruli.
  • Electron microscope (EM): to determine the site of immune complexes (sub-epithelial, sub-endothelial, mesangial or basement membrane).

Other Glomerular Diseases (Brief Overviews)

• Presents information on both light and electron microscopy views for various aspects of kidney disease. Includes Membranous glomerulopathy, Membranoproliferative GN (Type 1), Diabetic glomerulosclerosis, Amyloidosis, Anti-GBM disease (Goodpasture's syndrome), IgA nephropathy, Henoch-Schönlein Purpura, SLE, Chronic Glomerulonephritis, and other, more general information.

Nephrotic and Nephritic Syndromes

• Nephrotic Syndrome: formed of: proteinuria (>3.5g/24 hrs), hypoproteinemia (<30g/L), edema, and hypercholesterolemia. Minimal change disease in children and membranous nephropathy in adults are common causes. Potential complications = infections, thromboembolism and hyperlipidaemia.
• Nephritic Syndrome: formed of: hematuria, oliguria, periorbital edema, and hypertension. Post-streptococcal GN is a common cause. Electrolyte imbalances and hypertension may be present possibly because of glomerular damage.

Pyelonephritis and Acute Interstitial Nephritis (AIN)

• Pyelonephritis: Inflammation of the tubules, interstitium, and renal pelvis. Two forms:
  • Acute pyelonephritis: Often caused by bacterial infection.
  • Chronic pyelonephritis: More complex, infection plays a role, but reflux and obstruction are also factors. Symptoms of acute pyelonephritis: Fever, chills, tachycardia, tachypnea, flank pain, abdominal pain, nausea, vomiting, dysuria, nocturia, symptoms of recent cystitis or UTI treatment. Predisposing factors = Urinary tract obstruction, Instrumentation, Vesicoureteral reflex, Pregnancy, Preexisting renal lesions, Diabetes mellitus and Immunosuppression, possible complications = Papillary necrosis, Pyonephrosis, and Perinephric abscess.
• Acute Interstitial Nephritis (AIN): Inflammatory condition affecting kidney interstitium (area surrounding renal tubules). Causes = Medications (antibiotics, NSAIDs), Infections, Autoimmune Diseases. Histology = Presence of inflammatory cells (lymphocytes, eosinophils, and sometimes plasma cells) within the interstitium, possible damage to tubules and edema.

Lower Urinary Tract Infections

• Urinary Tract Infections (UTIs): Defined by the presence of microorganisms in bladder urine with or without symptoms or renal disease. Factors normally protecting against UTIs: Washing out bacteria, Low pH, High osmolarity, Tamm-Horsfall protein, Ureterovesical junction valve action.
• Cystitis: Inflammation of bladder; two forms:
  • Bacterial (acute): common, predisposing factors = bladder calculi, urinary obstruction, diabetes mellitus, instrumentation, immune deficiency.
  • Non-bacterial (Interstitial Cystitis): Chronic, non-infectious. Symptoms = Frequency, Urgency, Dysuria, Suprapubic Pain, Cloudy or foul-smelling urine. Etiology includes women, tuberculous cystitis, Candida albicans infections, Schistosomiasis, Chlamydia and Mycoplasma infections.
• Relevant other lower UTI's are also described.

Obstructive Uropathy

• Obstructive uropathy: Functional or anatomic obstruction of urinary tract flow.
  • Causes = Calculus, Chronic infection, Pyogenic granulomatous, Ureter anomalies, Stricture stenosis, Neoplasm, Compression, Trauma.
  • Location
  • Completeness
  • Involvement of one or both upper urinary tracts
  • Duration
  • Cause of any obstruction
  • Physiologic view of urine flow.
  • Pathophysiology (mechanisms) of obstruction related to causes.
• Lower Urinary Tract Obstruction: Urethral stricture, Prostate enlargement, pelvic organ prolapse, Low bladder wall compliance.
  • Neurogenic bladder - Dyssynergia, Detrusor hyperreflexia-overactive, Detrusor areflexia-underactive and Overactive bladder syndrome (OBS) = Frequency, urgency, nocturia.

Urolithiasis (Renal Calculi)

• Definition: Masses of crystals, protein, or other substances forming within and obstructing the urinary tract.
• Types of Renal Stones:
  • Calcium oxalate/phosphate (75%)
  • Struvite (10-15%)
  • Uric acid (6%)
  • Cystine (1-2%)
  • Unknown (?10%)
• Pathogenesis: Variables related to each type of stone.
• Risk Factors: Increased concentration of stone constituents (changes in urinary pH, low pH higher risk), Decrease in urine volume, and urinary tract infection.
• Sites: Unilateral in 80%; common sites = renal calyces, pelvis; stones can be small (2-3 mm), or large (Staghorn).
• Clinical Presentation: Symptoms may occur from obstruction, ulceration, and subsequent bleeding. Smaller stones = pain, hematuria, recurrent UTI. Asymptomatic can occur.
• Laboratory Diagnosis:
  • UEC (Urinalysis shows hematuria, crystals, and pyuria).
  • BUN
  • Other modes of investigation = USS, X-rays, CT scans.
• Prognosis: Generally good; depends on the underlying cause.

Renal Tumors

• Renal Cell Carcinoma: Most common malignant tumor. Epidemiology = Affects adults, 6th/7th decade. Risk factors = smoking, obesity, HTN, exposure to chemicals, estrogen therapy and secondary to dialysis. Clinical presentation = Silent, hematuria, flank pain.

• Renal Oncocytoma: Rare, benign tumor. Epidemiology = More common in men. Clinical presentation = Asymptomatic, flank pain, and hematuria.

• Nephroblastoma (Wilms Tumor): Malignant embryonal tumor occurring in children; common in 3-4 year-old children. Etiology = Genetic alterations. Clinical presentation = Abdominal mass, with sometimes associated pain/hematuria.

  • Associated syndromes = WAGR, Denys-Drash, Beckwith-Wiedemann

This quiz covers essential concepts related to glomerular diseases, including their functions, characteristics, and consequences of damage. Learn about microscopy techniques used in renal biopsies and the clinical presentations associated with various glomerular conditions. Test your knowledge on both primary and secondary glomerular diseases.