Amyloidosis - Robbins & Cotran Pathologic Basis of Disease

IMAGE 1 - Mechanism of Amyloid Deposition (Fig. 6.44 / Robbins & Cotran)

Exam point: All amyloid proteins converge on the same final common pathway - misfolded protein → β-pleated fibril → extracellular deposition.

IMAGE 2 - Pathogenesis of Amyloidosis (Fig. 6.45 / Robbins & Cotran)

Exam point (INICET favourite): AA amyloidosis is the type associated with chronic inflammatory diseases (rheumatoid arthritis, tuberculosis, Crohn disease). The precursor protein is SAA (Serum Amyloid A), synthesized in the liver.

IMAGE 3 - Amyloid Structure (Fig. 5.35 / Robbins Basic Pathology)

Panel A - Amyloid fibril schematic:

Panel B - Apple-green birefringence under polarized light:

Top INICET exam point: Congo red stain → pink/red under ordinary light; apple-green birefringence under polarized light - this is diagnostic. The birefringence is due to the cross β-pleated sheet configuration of amyloid fibrils.

IMAGE 4 - Histology: Congo Red Stain + Renal Amyloidosis (Fig. 6.46 / Robbins & Cotran; also Fig. 5.37 / Robbins Basic Pathology)

Exam points from this image:

• Kidney is the most common and most serious organ involved in systemic amyloidosis
• Amyloid begins in the mesangium and along the glomerular basement membrane
• Leads to nephrotic syndrome → renal failure → most common cause of death in amyloidosis
• In liver: amyloid first appears in the space of Disse (between hepatocytes and sinusoids)

Classification Table (Table 6.17 / Robbins & Cotran)

Key INICET Exam Points - Amyloidosis

Biofilm on a Catheter

What is a Biofilm?

Scanning Electron Microscopy - S. epidermidis Biofilm on Catheter

How a Catheter Biofilm Forms - Step by Step

Why Biofilms are Clinically Dangerous

• Antibiotic resistance: The EPS matrix acts as a physical barrier that prevents antibiotics from penetrating and reaching bacteria. Organisms in biofilms can be 100-1000x more resistant to antibiotics than free-floating (planktonic) bacteria.
• Immune evasion: Protected from neutrophils, complement, and host immune defenses.
• Slow growth: Bacteria in biofilms often grow slowly, making antibiotics (which target active metabolism) even less effective.
• Persistent seeding: Biofilm acts as a chronic reservoir - bacteria shed from the biofilm cause repeated episodes of bacteremia or UTI.
• Device-associated infection: Removal of the contaminated device is often the only sure way to eliminate infection.

Organisms Commonly Forming Catheter Biofilms

Types of Catheter Biofilm Infection

• Bacteria enter at the urethral orifice or drainage bag, biofilm ascends the catheter
• Bacteriuria rate: 3-7% per day with indwelling urinary catheter
• Initially single organism; becomes polymicrobial in chronic catheters
• Proteus mirabilis causes crystalline biofilm → can obstruct the catheter

• Biofilm forms on inner lumen of central venous catheters (CVCs)
• Common in ICU patients - a major cause of nosocomial sepsis

• Biofilm forms on tunneled HD catheters; thrombus inside catheter acts as a nidus for biofilm
• Management: antibiotic lock therapy ± catheter exchange over guidewire

Key Clinical Points

• "Low-grade fever" in a patient with an indwelling device = think biofilm infection until proven otherwise
• Diagnosis: blood cultures (for CLABSI) or urine culture (for CAUTI)
• Treatment: systemic antibiotics + device removal/exchange - antibiotics alone rarely cure biofilm infections
• Antibiotic lock therapy (instilling high-concentration antibiotic directly into catheter lumen) is used for catheter salvage in CLABSI
• Prevention: antimicrobial-coated catheters, minimizing catheter dwell time, aseptic technique