TUBERCULOSIS

A chronic, recurrent infection, most commonly in the lungs

Etiology, Epidemiology, and Incidence

TB refers only to disease caused by Mycobacterium tuberculosis, M. bovis, or M. africanum. Other mycobacteria cause diseases similar to TB

Pathogenesis

The stages of TB are primary or initial infection, latent or dormant infection, and recrudescent or adult-type TB.

Primary TB may become active at any age, producing clinical TB in any organ, most often the apical area of the lung but also the kidney, long bones, vertebrae, lymph nodes, and other sites. Often, activation occurs within 1 to 2 yr of initial infection, but may be delayed years or decades and activate after onset of diabetes mellitus, during periods of stress, after treatment with corticosteroids or other immunosuppressants, in adolescence, or in later life (> 70 yr of age), but especially after HIV infection. The initial infection leaves nodular scars in the apices of one or both lungs, called Simon foci, which are the most common seeds for later active TB. The frequency of activation seems unaffected by calcified scars of primary infection (Ghon foci) or by residual calcified hilar lymph nodes. Subtotal gastrectomy and silicosis also predispose to development of active TB.

Pulmonary Tuberculosis

recrudescent disease occurs in nodular scars in the apex of one or both lungs (Simon foci) and may spread through the bronchi to other portions

Recrudescence may occur while a primary focus of TB is still healing but is more often delayed until some other disease facilitates reactivation of the infection.

In an immunocompetent person whose tuberculin test is positive (>= 10 mm), exposure to TB rarely results in a new infection, because T-lymphocyte immunity controls small, exogenous inocula promptly and completely.

Symptoms and Signs:

Cough is the most common symptom,

At first, it is minimally productive of yellow or green mucus, usually on rising in the morning, but becomes more productive as the disease progresses

Dyspnea may result from rupture of the lung or from a pleural effusion caused by a vigorous inflammatory reaction

Hilar lymphadenopathy is the most common finding in children. due to lymphatic drainage from a small lesion, usually located in the best ventilated portions of the lung (lower and middle lobes), where most of the inhaled organisms are carried.

swelling of the nodes is common

Untreated infection may progress to miliary TB or tuberculous meningitis and, if long neglected, rarely may lead to pulmonary cavitation.

TB in the elderly presents special problems. Long-dormant infection may reactivate, most commonly in the lung but sometimes in the brain or a kidney, long bone, vertebra, lymph node, or anywhere that bacilli were seeded during the primary infection earlier in life

TB may develop when infection in an old calcific lymph node reactivates and leaks caseous material into a lobar or segmental bronchus, causing a pneumonia that persists despite broad-spectrum antibiotic therapy.

With HIV infection, progression to clinical TB is much more common and rapid.

HIV also reduces both inflammatory reaction and cavitation of pulmonary lesions. As a result, a patient's chest x-ray may be normal, even though AFB are present in sufficient numbers to show on a sputum smear. Recrudescent TB is almost always indicated when such an infection develops while the CD4⁺ T-lymphocyte count is >= 200/µL. By contrast, the diagnosis is usually infection by M. avium-intracellulare if the CD4+ count is < 50. The latter is noninfectious for others.

Pleural TB develops when a small subpleural pulmonary lesion ruptures, extruding caseous material into the pleural space. The most common type, serous exudate, results from rupture of a pimple-sized lesion of primary TB and contains very few organisms.

Tuberculous empyema with or without bronchopleural fistula is caused by a more massive contamination of the pleural space resulting from rupture of a large tuberculous lesion. Such a rupture allows air to escape and collapse the lung. Either type requires prompt drainage of pus and initiation of multiple drug therapy

Extrapulmonary Tuberculosis

Remote tuberculous lesions can be considered as metastases from the primary site in the lung, comparable to metastases from a primary neoplasm. TB of the tonsils, lymph nodes, abdominal organs, bones, and joints were once commonly caused by ingestion of milk infected with M. bovis.

GENITOURINARY TUBERCULOSIS

The kidney is one of the most common sites for extrapulmonary (metastatic) TB. Often after decades of dormancy, a small cortical focus may enlarge and destroy a large part of the renal parenchyma.

Salpingo-oophoritis can be a complication of primary TB after onset of menarche, when the fallopian tubes become vascular.

TUBERCULOUS MENINGITIS

Spread of TB to the subarachnoid space may occur as part of generalized dissemination through the bloodstream or from a superficial tubercle in the brain

Symptoms are fever (temperature rising to 38.3° C [101° F]), unremitting headache, nausea, and drowsiness, which may progress to stupor and coma. Stiff neck (Brudzinski's sign) and straight leg raising are inconstant but are helpful signs, if present. Stages of tuberculous meningitis are (1) clear sensorium with abnormal CSF, (2) drowsiness or stupor with focal neurologic signs, and (3) coma. Likelihood that CNS defects will become permanent increases with the stage. Symptoms may progress suddenly if the lesion causes thrombosis of a major cerebral vessel.

Diagnosis is made by examining CSF. The most helpful CSF findings include a glucose level < 1/2 that in the serum and an elevated protein level along with a pleocytosis, largely of lymphocytes. Examination of CSF by PCR is most helpful, rapid, and highly specific.

MILIARY TUBERCULOSIS

When a tuberculous lesion leaks into a blood vessel, massive dissemination of organisms may occur, causing millions of 1- to 3-mm metastatic lesions. Such spread, named miliary because the lesions resemble millet seeds, is most common in children < 4 yr and in the elderly.

TUBERCULOUS LYMPHADENITIS

In primary infection with M. tuberculosis, the infection spreads from the infected site in the lung to the hilar nodes. If the inoculum is not too large, other nodes generally are not involved. However, if the infection is not controlled, other nodes in the superior mediastinum may become involved. If organisms reach the thoracic duct, general dissemination may occur. From the supraclavicular area, nodes in the anterior cervical chain may be inoculated, thus sowing the seeds for tuberculous lymphadenitis at a later time. Most infected nodes heal, but the organisms may lie dormant and viable for years or decades and can again multiply and produce active disease.

Smallpox (variola)
 - vesicles are well synchronized (same stage of development) and cover the skin and mucous membranes.
 - vesicles rupture and leave pock marks with permanent scarring.

Clinical & biologic death

Clinical death

Clinical death is the reversible transmission between life and biologic death. Clinical death is defined as the period of respiratory, circulatory and brain arrest during which initiation of resuscitation can lead to recovery.

Signs indicating clinical death are

• The patient is without pulse or blood pressure and is completely unresponsive to the most painful stimulus.

• The pupils are widely dilated

• Some reflex reactions to external stimulation are preserved. For example, during intubations, respiration may be restored in response to stimulation of the receptors of the superior laryngeal nerve, the nucleus of which is located in the medulla oblongata near the respiratory center.

• Recovery can occur with resuscitation. 

Biological Death

Biological death (sure sign of death), which sets in after clinical death, is an irreversible state

of cellular destruction. It manifests with irreversible cessation of circulatory and respiratory

functions, or irreversible cessation of all functions of the entire brain, including brain stem.

EMBOLISM

Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.

Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour

Thromboembolism 
This is the commonest type of embolus and may be formed of the primary thrombus  or more often of propagated clot region which is loosely attached.

Emboli from venous thrombi can result In impaction in the pulmonary  arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.

Gaseous
This occurs when gas is introduced into the circulation:
•    Accidental opening of large veins during surgery.
•    Mismanaged transfusion. .
As air is  readily absorbed into blood only  sudden introduction or large quantities of air produces effects
Caisson’s Disease  bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.

Fat Embolism
Causes
•    Fractures especially of long bones and multiple
•    Crush injuries.

Sites of impaction:

o    Lungs.
o    Systemic: causing -
    →    petechial skin haemorrhages.
    →    Embolism to brain leading to coma and death.
    →     Conjunctival and retinal haemorrhages
    
Tumor Embolism.

Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
•    Metastatic deposits,
•    DlC
 

Urinary tract infection
Most often caused by gram-negative, rod-shaped bacteria that are normal residents of the enteric tract, especially Escherichia coli.

Clinical manifestations: 

frequent urination, dysuria, pyuria (increased PMNs), hematuria, and bacteriuria.

May lead to infection of the urinary bladder (cystitis) or kidney (pyelonephritis).

INFARCTION

Definition : a localized area of ischaemic necrosis in an organ infarcts may be:
Pale :as in
    →    Arterial obstruction.
    →    solid organs.
Red as in
    →    Venous occlusion
    →    Loose tissue.

Morphology
Gross: infarcts are usually wedge shaped the apex towards the occluded vessel They are
separated from the surrounding tissue by an hyperemic inflammatory zone

Microscopic:
- An area of coagulative necrosis with a rim of congested vessels and acute inflammatory infiltration of the tissue .
- The polymorphs ale later replaced by mononuclear cells and granulation tissue.
- With time, scar tissue replaces necrosed tissue.