CLASE TEÓRICA 8 - ENFERMEDADES GRANULOMATOSAS PARTE 1

Granulomatous Diseases Overview

Introduction to Granulomatous Diseases

• The session is led by Dr. Burgos, focusing on practical work number 8 regarding granulomatous diseases, which are characterized by the formation of granulomas.

• Key diseases discussed include tuberculosis, syphilis, leprosy, certain deep mycoses, and sarcoidosis.

Understanding Granulomas

• A granuloma is defined as a small inflammatory nodule typical of specific chronic inflammation. It represents a type of hypersensitivity reaction (Type 4 or cell-mediated).

• Tuberculoid granulomas have a distinct pattern associated with tuberculosis; they consist mainly of modified macrophages known as epithelioid cells.

Composition and Formation of Granulomas

• Granulomas contain macrophages (epithelioid cells), a collar of mononuclear leukocytes, multinucleated giant cells, peripheral fibrosis, and may exhibit central caseous necrosis.

• The formation process begins when harmful agents (bacteria or substances) that are difficult to degrade trigger an inflammatory response leading to granuloma development.

Immune Response Mechanism

• Upon entry into alveolar macrophages via aerosol droplets from infected individuals, the bacillus replicates within the macrophage without being destroyed initially. This phase can involve active circulation in the bloodstream before immune activation occurs.

• Macrophages present antigens to CD4 positive T-cells using interleukins and other substances; this activates T-cells which proliferate and recruit more monocytes from the blood for further differentiation into epithelioid cells.

Characteristics of Tuberculosis Granulomas

• The structure includes a core made up primarily of epithelioid cells surrounded by lymphocytes and fibroblasts; giant cells may also be present due to fusion processes among monocytes. These giant cells often display nuclei arranged in a horseshoe shape (Langhans giant cells).

Microscopic Examination of Granulomas

Microscopy Insights

• Two microscopic images illustrate tuberculous granulomas: one shows central caseous necrosis with surrounding epithelioid cells and lymphocytes interspersed with fibroblasts; another provides greater detail on multinucleated giant cell structures amidst these components.

Epidemiology and Impact of Tuberculosis

Societal Context

Understanding the Complex of Ghon in Tuberculosis

Formation and Drainage of Ghon Complex

• The organism enters through aerosol droplets from saliva, localizing in the lungs where it forms a nodule known as the Ghon nodule. This nodule is located subpleurally, just beneath the pleura.

• The Ghon nodule naturally drains into regional lymph nodes, specifically the hilar lymph nodes, via lymphatic ducts. This creates what is referred to as the "Ghon complex," consisting of the Ghon nodule, hilar lymph node, and involved lymphatics.

Evolution of Ghon Complex

• Typically, the Ghon complex evolves towards calcification and fibrosis; however, in severe cases, it may lead to miliary dissemination or affect other organs. Most commonly, it remains latent for extended periods after fibrosing or calcifying.

• A special staining technique called Syd Nielsen is used to identify this acid-fast bacillus in tissue samples since it cannot be recognized otherwise. The pink images observed correspond to this bacillus under microscopy.

Secondary Tuberculosis: Reactivation and Presentation

Mechanisms of Secondary Tuberculosis

• Secondary tuberculosis can arise from reactivation of previously latent bacilli or new exposure to the bacteria during periods of decreased immunity. It primarily affects individuals with weakened immune systems.

• Lesions typically present in the apex of the lung due to higher oxygen concentration favorable for bacilli growth; these nodules are deeper than primary ones (1-2 cm below pleura). They may fibrose but often grow larger over time.

Clinical Manifestations

• Characteristic lesions include granulomas with caseous necrosis that erode tissues such as bronchi and blood vessels, leading to hemoptysis (coughing up blood) during active infection phases when patients are contagious.

• Tuberculosis can manifest as larger nodular forms or resemble pneumonia; complications may involve pleuritis with pleural effusion or endobronchial involvement affecting trachea and larynx. Severe cases can lead to miliary tuberculosis characterized by small seed-like lesions throughout affected organs via hematogenous spread.

Atypical Presentations and Complications of Tuberculosis

Isolated Tuberculosis Manifestations

• Isolated manifestations occur when bacilli remain dormant in various organs post-blood dissemination; they reactivate during immunocompromised states causing significant lesions across different body parts including meningitis tuberculosa at brain base—a severe complication associated with tuberculosis infection.

Organ-Specific Involvement

Tuberculosis: Pathology and Epidemiology

Overview of Tuberculosis Manifestations

• The presence of multiple small, uniform nodules on the lung surface is indicative of miliary tuberculosis, resembling small seeds.

• A macroscopic cut of the spleen shows similar small nodules, confirming the diagnosis of miliary tuberculosis in this organ as well.

• In kidney pathology, a large amorphous white mass indicates gas necrosis due to tuberculosis; additional images show typical miliary nodules on the kidney surface.

• An intravenous pyelogram reveals significant dilation and distortion in the renal collecting system caused by renal tuberculosis.

Meningitis and Central Nervous System Involvement

• The brain exhibits signs of tuberculous meningitis with a delicate, congested appearance; central areas show amorphous white substance indicating severe infection.

• A tuberculoma is identified as a tumor-like nodule in the brain associated with meningitis; it represents an inflammatory response rather than malignancy.

• Spinal involvement shows compression and destruction of vertebrae due to osteomyelitis from tuberculosis, referred to as "mal de Pot."

Epidemiological Insights

• Tuberculosis is closely linked to poverty, overcrowding, and poor living conditions; its prevalence highlights significant public health concerns in affected populations.

• Vaccination against tuberculosis is crucial in high-prevalence areas; it activates immune responses without causing disease but prepares individuals for potential exposure.

Immune Response and Diagnostic Techniques

• The vaccination induces hypersensitivity rather than immunity; it primes the immune system for future encounters with Mycobacterium tuberculosis.

• The Mantoux test assesses hypersensitivity to tuberculin; positive results indicate prior exposure or vaccination rather than active disease in vaccinated populations.

Differential Diagnosis Considerations