NEET MDS Lessons
General Pathology
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.
Paget Disease (Osteitis Deformans)
This unique bone disease is characterized by repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength. Paget disease usually does not occur until mid-adulthood but becomes progressively more common thereafter. The pathognomonic histologic feature is a mosaic pattern of lamellar bone (likened to a jigsaw puzzle) due to prominent cement lines that haphazardly fuse units of lamellar bone. (Fig. 12-5) The axial skeleton and proximal femur are involved in the majority of cases. In patients with extensive disease, hypervascularity of the marrow spaces can result in high-output congestive heart failure. Cranial nerves impingement also occurs and can lead to head ache and auditory disturbances. Rarely Paget disease is complicated by bone sarcoma (usually osteogenic).
Pheochromocytoma
Pheochromocytomas are neoplasms composed of chromaffin cells, which as their normal counterparts synthesize and release catecholamines.
1. Arise in association with one of several familial syndromes such as MEN syndromes, type 1 neurofibromatosis, von Hippel-Lindau disease, and Sturge-Weber syndrome.
2. Are extra-adrenal, occurring in sites such as the organ of Zuckerkandl and the carotid body, where they are usually called paragangliomas rather than pheochromocytomas.
3. Are bilateral; but in association with familial syndromes, this figure may rise to 50%.
4. Are malignant; frank malignancy, however, is more common in extra-adrenal tumors.
Gross features
- The size of these tumors is quite variable ranging from small to huge masses.
- Sectioning shows yellow-tan, well-defined tumor that compress the adjacent adrenal. Large lesions display areas of hemorrhage, necrosis, and cystic degeneration.
- Incubation of the fresh tissue with potassium dichromate solutions converts the tumor a dark brown color.
Microscopic features
- These tumors are composed of polygonal to spindle-shaped chromaffin cells and their supporting sustentacular cells, arranged in well-defined small nests (Zellballen)," rimmed by a rich vascular network.
- The cytoplasm is often finely granular (catecholamine-containing granules)
- The nuclei are often quite pleomorphic.
- Both capsular and vascular invasion may be encountered in benign lesions, and the presence of mitotic figures per se does not imply malignancy. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone.
The laboratory diagnosis of pheochromocytoma is based on demonstration of increased urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid (VMA)& metanephrines.
Immunoglobulins. (Ig)
These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)
Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).
Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.
Characteristics of Immunoglobulin subclasses
I. Ig G:
(i) Predominant portion (80%) of Ig.
(ii) Molecular weight 150, 000
(iii) Sedimentation coefficient of 7S.
(iv) Crosses placental barrier and to extra cellular fluid.
- (v) Mostly neutralising effect. May be complement fixing.
(vi) Half life of 23 days.
2.IgM :
(i) Pentamer of Ig.
(ii) Molecular weight 900, 000
(iii) 19S.
(iv) More effective complement fixation and cells lysis
(v) Earliest to be produced in infections.
(vi) Does not cross placental barrier.
(vii) Halflife of 5 days.
3. Ig A :
- Secretory antibody. Found in intestinal, respiratory secretions tears, saliva and urine also.
- Secreted usually as a dinner with secretory piece.
- Mol. weight variable (160,000+)
- 7 S to 14 S.
- Half life of 6 days.
4.Ig D :
- Found in traces.
- 7 S.
- Does not cross placenta.
5. Ig E
- Normally not traceable
- 7-8 S (MoL weight 200,000)
- Cytophilic antibody, responsible for some hypersensitivity states,
Acute tubular necrosis
Characterized by impaired kidney functions due to the destruction of the renal tubule epithelium.
Caused by a variety of conditions that lead to ischemia of the renal tubules, usually resulting from renal tubular injury or problems with vascular flow. It can also be induced by ingesting toxins or drug-related toxicity (e.g., gentamicin).
The most common cause of acute renal failure.
Is a reversible condition, although it can be fatal.
SHOCK
Definition. It is a clinical state of acute inadequacy of perfusion to tissues due to fall in effective circulating blood volume.
This inadequacy can be caused by :
- Increased vascular capacity
- Decreased blood volume
- Altered distribution of available blood
- Defective pumping system
Causes:
(1) Hypovolemic
- Massive hamorrhage (external or internal).
- Loss of plasma as in bums.
- Dehydration due to severe vomiting, diarrhea diabetic coma.
- Generalized capillary permeability as in anaphylaxis.
(2) Cardiogenic
- Myocardial infarction.
- Pulmonary embolism.
- Cardiac tamponade
(3) Peripheral pooling:
- Endotoxic shock.
- Disseminated intravascular coagulation (DIC).
(4) Neurogenic:
- Syncope.
- Contributory factor in trauma, bums etc.
Metabolic changes in shock
- Hyperglycaemia due to glycogenolysis.
- Increased blood lactate and pyruvate due to anaerobic glycolysis. This results in metabolic acidosis.
- Protein catabolism and increased blood urea.
- Interference with enzyme systems.
Organs involved in shock
(1) Kidneys:
- Renal tubular necrosis.
- Cortical necrosis.
(2) Lungs:
- Oedema, congestion and haemorrhage.
- Microthrombi.
(3) G.I.T. :
- Mucosal oedema.
- Ulceration and haemorrhage
(4) Degeneration and focal necrosis in:
- Heart.
- Liver.
- Adrenals
(5) Anoxic encephalopathy
VIRAL DISEASES
RABIES (Hydrophobia)
An acute infectious disease of mammals, especially carnivores, characterized by CNS pathology leading to paralysis and death.
Etiology and Epidemiology
Rabies is caused by a neurotropic virus often present in the saliva of rabid animals
Pathology
The virus travels from the site of entry via peripheral nerves to the spinal cord and the brain, where it multiplies; it continues through efferent nerves to the salivary glands and into the saliva.
microscopic examination shows perivascular collections of lymphocytes but little destruction of nerve cells. Intracytoplasmic inclusion bodies (Negri bodies), usually in the cornu Ammonis, are pathognomonic of rabies, but these bodies are not always found.
Sign/Symptoms
In humans, the incubation period varies from 10 days to > 1 yr and averages 30 to 50 days.
Rabies commonly begins with a short period of depression, restlessness, malaise, and fever. Restlessness increases to uncontrollable excitement, with excessive salivation and excruciatingly painful spasms of the laryngeal and pharyngeal muscles. The spasms, which result from reflex irritability of the deglutition and respiration centers, are easily precipitated Hysteria due to fright
Prognosis and Treatment
Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms