Chronic Inflammation and Tuberculosis (TB)

• Lecture is about Chronic Inflammation and Tuberculosis (TB)

Granulomas

• Granulomas can be caused by bacteria, parasites, fungi, or inorganic metals and dust.
• Tuberculosis is a disease that causes granulomas and is caused by the bacteria Mycobacterium Tuberculosis.
• Leprosy is another disease that causes granulomas and is caused by the bacteria Mycobacterium leprae.
• Syphilis is caused by the bacteria Treponema pallidum.
• Cat-scratch disease is caused by Gram-negative bacillus.
• Schistosomiasis is caused by Schistosoma mansoni, S. haematobium, S. japonicum
• Cryptococcosis is caused by Cryptococcus Neoformans
• Coccidiosis is caused by Coccidioides Immitis
• Asbestosis, Silicosis, and Sarcoidosis are caused by inorganic metals and dust, and are immune mediated.

Tissue Reactions in Tuberculosis

• Two types of tissue reactions occur in tuberculosis:
• Proliferative reaction: mainly composed of inflammatory cells.
• Exudative reaction: shows excess inflammatory fluid exudate.

Pathological Features of Proliferative Reaction

• Macroscopic appearance: Microscopic sized tubercles exist, fuse together, and form rounded, grey follicles that are 1-2 mm in diameter with pale yellow caseation.
• Microscopic appearance: the tubercle is a compact collection of epithelioid cells, Langhans' giant cells, and lymphocytes.

Pathological Features of Exudative Reaction

• Occurs when a large number of tubercle bacilli reach lungs, serous membranes and meninges of a sensitized individual, especially those with low body resistance.
• Macroscopic appearance: excessive serous inflammatory fluid exudate appearing clear, yellowish, and containing moderate fibrinogen with frequent caseation.
• Microscopic appearance: fluid exudate with numerous neutrophils and lymphocytes, plus fewer epithelioid and Langhans' giant cells.

Primary Pulmonary Tuberculosis

• The first lung infection with tubercle bacilli and it is called childhood-type as it is frequent in children and is caused by inhalation of the human bacilli.
• The initial lesion occurs in the lung and is called Ghon's focus.
• The Ghon's focus is located at the periphery of the lung underneath the pleura with tubercles showing caseation and is commonly found in the lower portions of the upper lobes, or upper portions of the lower lobes.
• The draining lymphatic vessels show multiple tubercles along their course (tuberculous lymphangitis) and appear beaded then to the draining lymph nodes (tuberculous lymphadenitis).

Primary Pulmonary Complex

• Ghon's focus, tuberculous lymphangitis, and tuberculous lymphadenitis is called the Primary Pulmonary Complex.
• Lesions are usually located in the right lung, under the pleura at the lower part of the upper lobe, and appears as a small area of caseation that heals by fibrosis and calcification.
• Tuberculous lymphangitis: the draining lymph vessels have multiple tubercles and appear beaded.
• Tuberculous lymphadenitis: enlarged hilar lymph nodes are enlarged, matted, fixed, soft, and caseous creating a lesion that is much larger than the Ghon's focus.
• Ghon's focus, tuberculous lymphangitis, and tuberculous lymphadenitis lesions are called primary pulmonary complex.

Fate of Primary Pulmonary TB

• Fate is either healing or encapsulation and reactivation.
• Healing occurs In the majority of cases with mild infection where resistance is good, so the lesion heals.
• Encapsulation and reactivation can occur in the nodal lesion with lowering of body resistance causing lesion reactivation, spreading, and causing any form of TB (SECONDARY PULMONARY TUBERCULOSIS).
• Direct spread of Ghon's focus in the lung tissue results in tuberculous pneumonia, or to the pleura causing tuberculous pleurisy.
• Spread through blood stream, depending on the bacilli amount and patient immunity, may propagate to forming small uniform tuberculous lesion about 1-2 millimeters, miliary tuberculosis, and is rapidly fatal
• Spread through bronchi causes aspiration of the caseous material into the adjacent lung.
• Spreading through bronchi results in aspiration of the caseous material into the adjacent lung tissue causes tuberculous bronchopneumonia.

Fate of Primary Pulmonary Complex

• With high immunity, healing occurs.
• Small lesions lead to fibrosis.
• Large lesions lead to encapsulation and dystrophic calcification; the bacteria may remain alive for many years and become active again when general immunity is lowered (reactivation).
• With low immunity, spread occurs via all method.
• Direct spread to the lung leads to tuberculous pneumonia.
• Direct spread to the pleura leads to tuberculous pleurisy.
• Direct spread to the pericardium leads to tuberculous pericarditis.
• Blood spread effect depends on the number of bacilli:
  • Small numbers are destroyed by RE cells, resulting in no effect.
  • Moderate numbers settle in one organ, resulting in an isolated organ of T.B.
  • Large numbers settle in many organs, resulting in miliary T.B.
• Bronchial spread causes tuberculous bronchopneumonia.

Secondary Pulmonary Tuberculosis

• Adult type of tuberculosis.
• Etiology of infection is either exogenous or endogenous.
  • Exogenous infection involves inhalation of human bacilli.
  • Endogenous infection involves reactivation of a capsulated primary focus.
• It represents the 2nd contact between the lung and tubercle bacilli and may follow inhalation of human-type bacilli or reactivation of an old encapsulated primary focus.
• The infection picture will depend on the dose of bacilli, the state of immunity and the state of hypersensitivity.

Pathogenesis of Tuberculosis

• The lesion usually starts at the apex of the lung (less blood supply and more aeration), commonly the right (right bronchus is more in line with the trachea than the left bronchus) in the form of a small tuberculous focus.
• Course of the disease depends on the dose of infecting bacilli and the state of immunity of the infected person.

Symptoms and Signs of Tuberculosis

• Loss of weight, sweating and night fever due to toxaemia
• Chest pain due to pleurisy and dyspnea due to pleural effusion
• Hemoptysis due to vascular erosion.

Course of the Disease

• Regression can occur in patients with a small number of bacilli and high immunity causing healing by fibrosis and is called Fibrotic Tuberculosis.
• Progression can lead to Chronic Fibro-Caseous Pulmonary Tuberculosis. It occurs with a moderate dose, moderate immunity and moderate hypersensitivity.
• Tuberculous Bronchopneumonia develops with a large dose, low immunity and high hypersensitivity.
• Generalized Miliary Tuberclosis occurs with large dose, low immunity and low hypersensitivity and is a rapidly fatal condition.

Complications of Pulmonary TB

• Hemoptysis
• T.B. tongue ulcer
• Spread to ribs or sternum
• T.B Laryngitis
• Chronic bronchitis
• T.B pericarditis
• Pleura
• Right sided heart failure
• T.B enteritis: due to swallowing of sputum
• Spread
• Amyloidosis of the kidney
• A TB ulcer is characterized by an Undermined edge

Tuberculosis of Bone

• Etiology: infection is usually hematogenous by human or bovine bacilli.
• Direct spread of infection from the joint or soft tissue.
• The vertebrae and ends of long bones are specially affected.
• Infection is hematogenous and commonly affects the lower thoracic and upper lumbar vertebrae called Pott's disease.
• It is always secondary in origin, i.e. the bacilli reach the vertebrae via the blood stream.
• Vertebrae commonly affected are the lumbar (lower), cervical and thoracic.
• The vertebral bodies and intervertebral discs are destroyed.
• Pott's disease is presented by these three features:
  • Deformity, kyphosis (forward curving of vertebral column)
  • Scoliosis (lateral deviation of the vertebral column) rarely occurs.
  • Cold abscess: caseous material collects under the prevertebral fascia anteriorly and spread in various directions according to the site of the lesion.
• Paraplegia: develops in 10% of the cases and results from pressure of inflammatory edema, cold abscess or tuberculous end arteritis of the blood vessels.

Primary Tuberculosis of Intestine

• Caused by swallowing human or bovine tubercle bacilli with dust or infected milk.
• Pathology: the initial lesion usually appears in the terminal ileum with a group of tubercles in the region of the Payer’s patches.
• the covering mucosa may undergo minimal ulceration.
• Tuberculous Lymphangitis occurs.
• Tuberculous Lymphadenitis or tabes mesenterica occurs. The mesenteric lymph nodes are enlarged and show caseating tubercles which may become matted forming a cold abscess.
• The fate of Tuberculosis of the Intestine is one of Localization.
• Spread of Tuberculosis of the Intestine directly and the lymphatic system leads to tuberculous peritonitis and hematogenous spread leads to isolated organ or miliary tuberculosis

Secondary Tuberculosis of Intestine

• Caused by ingestion of infected sputum in patients with chronic fibrocaseous pulmonary tuberculosis.
• The lesions develop mainly in the terminal ileum and adjacent caecum creating Tuberculous ulcers
• The ulcer are Multiple and their edges are ragged and undermined with a yellowish, caseous ulcer floor and are transversely arranged creating girdle ulcers.
• The mesenteric lymph nodes show minimal lesions.
• Complications include intestinal hemorrhage, intestinal fistulae, Perforation of the ulcers leading to septic peritonitis, spread of infection, or fibrosis.

Spread of Infection of Tuberculosis of the Intestine

• Direct and Lymphatic spread causes tuberculous peritonitis.
• Blood spread causes isolated organ or miliary tuberculosis.
• Fibrosis leads to Intestinal obstruction.
• Secondary amyloidosis occurs as a complication.

Primary Tuberculosis of Tonsils

• Caused by swallowing human or bovine tubercle bacilli.
• The initial lesion is a small focus composed of tubercles.
• The covering mucosa of the tonsil may ulcerate.
• Tuberculous lymphangitis occurs.
• Tuberculous lymphadenitis of the cervical lymph nodes become enlarged and show caseating tubercles, matting may occur, a cold abscess may develop, or the overlying skin may develop tuberculous sinuses.
• The fate is 1-Localization. 2-Spread.

Secondary Tuberculosis of Tonsils

• It is usually caused by spread of tubercle bacilli through infected sputum where A tuberculous ulcer with undermined edges develops.

Primary Tuberculosis of Skin Description

• Tubercle bacilli inoculated through a skin abrasion lead to a primary complex, which may localize or spread.

Secondary Tuberculosis of Skin (Lupus Vulgaris)

• The mode of infection is not apparent but is suspected to be due to blood spread.
• The skin of face and neck is the most commonly affected site, showing nodules and ulcers with undermined edges where the lesions are precancerous.

Tuberculous Lymphadenitis

• Tuberculous lymphadenitis occurs as a part of primary complex where The hilar lymph nodes are affected in case of primary pulmonary T.B, the cervical nodes in case of primary T.B of tonsils & the mesenteric nodes in case of primary intestinal T.B.
• The affected nodes are enlarged, first discrete, then may become matted and soft due to marked caseation which leads to a Cold Abscess with Tubercles microscopically.
• Fate & Complications include: Localization.
• Spread:
  • Direct: Cervical lymph nodes cause cervical skin sinus formation, hilar nodes lead tuberculous pericarditis, and mesenteric nodes lead to tuberculous peritonitis.
  • Lymphatic spread to other lymph nodes.
  • Blood spread causing isolated organ or miliary tuberculosis.
  • Bronchial spread due to bronchial erosion from hilar nodes in case of pulmonary tuberculosis.
• Reactivation occurs if immunity is lowered.

Tubercolosis of the Nervous System

• Tuberculoma occurs with a mass of caseation surrounded by gliosis occurring in the brain or spinal cord and may lead to increased intracranial tension and may be clinically and radiologically mistaken for a tumor.
• Tuberculous Meningitis’s Aetiology is Blood-borne infection.
• The pathological Features:
  • Tubercle bacilli are in the pia-arachnoid membranes & within the lining of the ventricles causing tubercles and exudative reaction.
  • Arteries of the subarachnoid space show endarteritis obliterans occurs.
  • The cerebrospinal fluid has Increased tension, Increased protein content, decreased Sugar and chloride contents, and a large number of lymphocytes with Tubercle bacilli that may be detected.
• The Complications include:
  • Spread: via direct leading to tuberculous encephalitis and through blood spread.
  • Fibrosis leading to Hydrocephalus and Cranial nerve paralysis from compression.
  • Infarcts due to endarteritis and thrombosis.

Atypical Mycobacteriosis

• Atypical mycobacteria are a common cause of granulomatous lymphadenitis, particularly in children and may also affect lungs, intestine, skin and other sites.
• They are Microscopically indistinguishable from those of tuberculosis, however associated suppurative changes are common .
• Diagnosis primarily depends on culture characteristics.

Section in large intestine

• Submucosa shows bilharzial reaction formed of deposited living and dead ova
• Submucosa shows multiple bilharzial granuloma formed of Eosinophils, Lymphocytes, and Macrophages

The lesion in lymph node

• Nodal architecture is replaced by multiple granulomas

Describe The Lesion

• Area of central caseation with a surrounding rim of lymphocytes, mononuclear cells, multinucleated giant cells, and fibrosis.

Bilharizasis of urinary bladder

• Hyperplastic transitional epithelium with dipping forms Brunn's nests
• Cystic degeneration of the central cells forms cystitis cystica
• Others are lined by columnar epithelium forming cystitis glandularis