NEET MDS Lessons
General Pathology
Emphysema
Emphysema is a chronic lung disease. It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke.
Signs and symptoms
loss of elasticity of the lung tissue
destruction of structures supporting the alveoli
destruction of capillaries feeding the alveoli
The result is that the small airways collapse during expiration, leading to an obstructive form of lung disease
Features are: shortness of breath on exertion
hyperventilation and an expanded chest.
As emphysema progresses, clubbing of the fingers may be observed, a feature of longstanding hypoxia.
Emphysema patients are sometimes referred to as "pink puffers". This is because emphysema sufferers may hyperventilate to maintain adequate blood oxygen levels. Hyperventilation explains why emphysema patients do not appear cyanotic as chronic bronchitis (another COPD disorder) sufferers often do; hence they are "pink" puffers (adequate oxygen levels in the blood) and not "blue" bloaters (cyanosis; inadequate oxygen in the blood).
Diagnosis
spirometry (lung function testing), including diffusion testing
X-rays, high resolution spiral chest CT-scan,
Bronchoscopy, blood tests, pulse oximetry and arterial blood gas sampling.
Pathophysiology :
Permanent destructive enlargement of the airspaces distal to the terminal bronchioles without obvious fibrosis
Oxygen is inhaled in normal breathing
When toxins such as smoke are breathed into the lungs, the particles are trapped by the hairs and cannot be exhaled, leading to a localised inflammatory response. Chemicals released during the inflammatory response (trypsin, elastase, etc.) are released and begin breaking down the walls of alveoli. This leads to fewer but larger alveoli, with a decreased surface area and a decreased ability to take up oxygen and loose carbon dioxide. The activity of another molecule called alpha 1-antitrypsin normally neutralizes the destructive action of one of these damaging molecules.
After a prolonged period, hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood, and the body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension. This leads to enlargement and increased strain on the right side of the heart, which in turn leads to peripheral edema (swelling of the peripherals) as blood gets backed up in the systemic circulation, causing fluid to leave the circulatory system and accumulate in the tissues.
Emphysema occurs in a higher proportion in patient with decreased alpha 1-antitrypsin (A1AT) levels
Prognosis and treatment
Emphysema is an irreversible degenerative condition
Supportive treatmentis by supporting the breathing with anticholinergics, bronchodilators and (inhaled or oral) steroid medication, and supplemental oxygen as required
Lung volume reduction surgery (LVRS) can improve the quality of life for only selected patients.
Tuberculosis
Causative organism
-Mycobacterium tuberculosis
-Strict aerobe
-Pathogenic strains
-hominis, bovis, avium, murine& cold blooded vertebrate strain
Koch’s bacillus
-small slender, rod like bacillus, 4umnon-motile, aerobic -high lipid content
-divides every 16 to 20 hours, an extremely slow rate
-stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolicacid content of its cell wall
-can withstand weak disinfectant and survive in a dry state for weeks.
Demonstrated by
-ZiehlNeelsenstaining
-Fluorescent dye method
-Culture in LJ media
-Guinea pig inoculation
Modes of transmission
Inhalation , Ingestion, Inoculation , Transplacental
Route Spread
Local , Lymphatic , Haematogenous , By natural passages,
Pathogenesis
- Anti‐mycobacterial CMI, confers resistance to bacteria → dev. of HS to tubercular Ag
- Bacilli enters macrophages
- Replicates in phagosomeby blocking fusion of phagosome& lysosome, continues for 3 weeks →bacteremiabut asymptomatic
- After 3 wks, T helper response is mounted by IL‐12 produced by macrophages
- T cells produce IFN, activates macrophages → bactericidal activity, structural changes
- Macrophages secrete TNF→ macrophage recruitment, granuloma& necrosis
Fate of granuloma
- Caseousmaterial undergo liquefaction---cold abscess
- Bones, joints, lymph nodes & epididymis---sinuses are formed & sinus tract lined by tuberculousgranulation tissue
- Dystrophic calcification
Types of TB
1. Primary Pulmonary TB
2. secondary TB (miliary, fibrocaseous, cavitary)
3. Extra-pulmonary TB (bone, joints, renal, adrenal, skin… )
Primary TB
Infection in an individual who has not been previously infected or immunised
Primary complex
Sites
-lungs, hilarlymph nodes
-tonsils, cervical lymph nodes
-small intestine, mesenteric lymph nodes
Primary TB
In the lung, Ghon’scomplex has 3 components:
1. Pulmonary component -Inhalation of airborne droplet ~ 3 microns.
-Bacilli locate in the subpleuralmid zone of lung
-Brief acute inflammation –neutrophils.
-5-6 days-invoke granulomaformation.
-2 to 8 weeks –healing –single round ;1-1.5 cm-Ghon focus.
2. Lymphatic vessel component
3. Lymph node component
Fate of primary tuberculosis
- Lesions heal by fibrosis, may undergo calcification, ossification
-a few viable bacilli may remain in these areas
-bacteria goes into a dormant state, as long as the person's immune system remains active
- Progressive primary tuberculosis: primary focus continues to grow & caseousmaterial disseminated to other parts of lung
- Primary miliarytuberculosis: bacilli may enter circulation through erosion of blood vessel
- Progressive secondary tuberculosis: healed lesions are reactivated, in children & in lower resistance
Secondary tuberculosis
-Post-primary/ reinfection/ chronic TB
-Occurs in immunized individuals.
-Infection acquired from
-endogenous source/ reactivation
-exogenous source/ reinfection
Reactivation
-when immune system is depressed
-Common in low prevalence areas.
-Occurs in 10-15% of patients
-Slowly progressive (several months)
Re-infection
-when large innoculum of bacteria occurs
-In areas with increased personal contact
Secondary TB
-Sites-Lungs 1-2 cm apical consolidation with caseation
-Other sites -tonsils, pharynx, larynx, small intestine & skin
Fate of secondary tuberculosis
•Heal with fibrous scarring & calcification
•Progressive secondary pulmonary tuberculosis:
-fibrocaseoustuberculosis
-tuberculouscaseouspneumonia
-miliarytuberculosis
Complications:
a) aneurysm of arteries–hemoptysis
b) bronchopleuralfistula
c) tuberculousempyema
MiliaryTB
• Millet like, yellowish, firm areas without caseation
• Extensive spread through lympho-hematogenousroute
• Low immunity
• Pulmonary involvement via pulmonary artery
• Systemic through pulmonary vein:
-LN: scrofula, most common
-kidney, spleen, adrenal, brain, bone marrow
Signs and Symptoms of Active TB
• Pulmonary-cough, hemoptysis, dyspnea
• Systemic:
• fever
• night sweats
• loss of appetite
• weight loss
• chest pain,fatigue
•If symptoms persist for at least 2 weeks, evaluate for possible TB infection
Diagnosis
•Sputum-Ziehl Neelsen stain –10,000 bacilli, 60% sensitivity
-release of acid-fast bacilli from cavities intermittent.
-3 negative smears : low infectivity
•Culture most sensitive and specific test.
-Conventional Lowenstein Jensen media-10 wks.
-Liquid culture: 2 weeks
•Automated techniques within days
should only be performed by experienced laboratories (10 bacilli)
•PPD for clinical activity / exposure sometime in life
•X-ray chest
•FNAC
PPD Tuberculin Testing
- Read after 72 hours.
- Indurationsize -5-10 mm
- Does not d/s b/w active and latent infection
- False +: atypical mycobacterium
- False -: malnutrition, HD, viral, overwhelming infection, immunosuppression
- BCG gives + result.
Tuberculosis Atypical mycobacteria
- Photochromogens---M.kansasii
- Scotochromogens---M.scrofulaceum
- Non-chromogens---M.avium-intracellulare
- Rapid growers---M.fortuitum, M.chelonei
5 patterns of disease
- Pulmonary—M.kansasii, M.avium-intracellulare
- Lymphadenitis----M.avium-intracellulare, M.scrofulaceum
- Ulcerated skin lesions----M.ulcerans, M.marinum
- Abscess----M.fortuitum, M.chelonei
- Bacteraemias----M.avium-intracellulare as in AIDS
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.
Cor pulmonale
a failure of the right side of the heart. It is caused by prolonged high blood pressure in the right ventricle of the heart, which in turn is most often caused by pulmonary hypertension - prolonged high blood pressure in the arteries or veins of the lungs. People with heart disease, or lung diseases such as cystic fibrosis, are at greater risk.
Pathophysiology
There are several mechanisms leading to pulmonary hypertension and cor pulmonale:
Pulmonary vasoconstriction
Anatomic changes in vascularisation
Increased blood viscosity
Primary pulmonary hypertension
Causes
Acute:
• Massive pulmonary embolization
• Exacerbation of chronic cor pulmonale
Chronic:
• COPD
• Loss of lung tissue following trauma or surgery
Adrenocortical Hyperfunction (Hyperadrenalism)
Hypercortisolism (Cushing Syndrome) is caused by any condition that produces an elevation in glucocorticoid levels. The causes of this syndrome are
A. Exogenous through administration of exogenous glucocorticoids; the most common causeB. Endogenous
1. Hypothalamic-pituitary diseases causing hypersecretion of ACTH (Cushing disease)
2. Adrenocortical hyperplasia or neoplasia
3. Ectopic ACTH secretion by nonendocrine neoplasms (paraneoplastic)
Pathological features
- The main lesions of Cushing syndrome are found in the pituitary and adrenal glands.
- The most common change in the pituitary, results from high levels of endogenous or exogenous glucocorticoids, is termed Crooke hyaline change. In this condition, the normal granular, basophilic cytoplasm of the ACTH-producing cells in the anterior pituitary is replaced by homogeneous, lightly basophilic material. This is due to accumulation of intermediate keratin filaments in the cytoplasm.
- There is one of four changes in the adrenal glands, which depends on the cause.
1. Cortical atrophy
2. Diffuse hyperplasia
3. Nodular hyperplasia
4. Adenoma, rarely a carcinoma
1. In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in bilateral cortical atrophy, due to a lack of stimulation of the cortex by ACTH. In cases of endogenous hypercortisolism, in contrast, the adrenals either are hyperplastic or contain a cortical neoplasm.
2. In Diffuse hyperplasia the adrenal cortex is diffusely thickened and yellow, as a result of an increase in the size and number of lipid-rich cells in the zonae fasciculata and reticularis.
3. Nodular hyperplasia, which takes the form of bilateral, up to 2.0-cm, yellow nodules scattered throughout the cortex.
4. Primary adrenocortical neoplasms causing Cushing syndrome may be benign or malignant. The adrenocortical adenomas are yellow tumors surrounded by capsules, and most weigh < 30 gm .
Avitaminoses - Vitamin deficiencies are more commonly secondary disorders associated with malabsorption conditions and chronic alcoholism.
A. Vitamin A - (retinoids, fat soluble compounds derived from ß-carotene) The best-known effect of deficiency is an inability to see in weak light (night blindness due to decreased rhodopsin).
-> The pathology is also characterized by skin lesions (rash on the extremities with punctate erythematous lesions). In malnourished children, vitamin A supplements reduce the incidence of infections such as measles, even in children without signs of preexisting deficiency.
B. Vitamin D - (1, 25 OH2 D3) Deficiency produces osteomalacia (called rickets in children). Many of the effects of osteomalacia overlap with the more common osteoporosis, but the two disordersare significantly different.
-> The specific alteration in osteomalacia and rickets is a failure of mineralization of the osteoid matrix resulting in decreased appositional bone growth.
C. Vitamin E - Very rare. Occurs as a secondary disorder in conditions associated with fat maladsorption such as cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction).
-> Vitamin E deficiency causes a neurological disorder characterized by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage.
D. Vitamin K - (phylloquinone) Present in most leafy plants and also synthesized by intestinal bacteria. Vitamin K is required for the production of specific clotting factors and a deficiency is characterized by impaired coagulation (elevated clotting times). Although this can occur in newborns that are given breast milk low in vitamin K, the deficiency is almost always secondarily associated with the use of certain anti-coagulants or disorders such as obstructive jaundice, celiac, or pancreatic disease.
E. Thiamine - (B1) The deficiency is known as beriberi. Thiamine deficiency is characterized by a peripheral neuropathy that affects sensation particularly in the legs (associated with demyelination of peripheral nerves), in more severe cases Korsakoff syndrome (neuropathy characterized by impaired ocular motility, ataxia, and mental confusion) and cardiomyopathy can occur.
F. Nicotinamide (niacin) - The deficiency is known as pellagra. Primary deficiencies are associated with diets that consist primarily of a single low quality protein source (i.e. corn). It results most commonly as a complication of alcoholism.
-> The pathology is characterized by hyperkeratosis and vesiculation of skin, atrophy of the tongue epithelium, and a neuropathy that can affect cortex and peripheral neurons.
- Initial symptoms include a smooth, red tongue, a sore mouth, and ulceration of the inside of the cheeks.
- The skin on the neck, chest, and back of the hands may become brown and scaly.
- Often there is nausea, vomiting, and diarrhea. There may also be insomnia, depression, confusion, and rapid changes of mood. Long-standing pellagra can result in dementia and death.
G. Vitamin B12 - (cobalamin) Because cobalamin is synthesized by intestinal bacteria and is widely available in many foods, deficiencies are almost always secondary disorders associated with gastric atrophy (and decreased uptake via intrinsic factor), microbial proliferation (AIDS), long-term antacids, chronic alcoholism, idiopathic (age-related).
In addition to anemia, the primary clinical symptoms include a sensory neuropathy (polyneuropathy), sclerosis of the spinal cord and atrophy of some mucous tissues.
H. Vitamin C - (ascorbic acid) The classic deficiency is known as scurvy. The essential pathology involves an inability to produce mature collagen and hence affects connective tissue.
This is characterized by an inability to synthesize osteoid and dentin (and results in decreased wound healing) and a loss of integrity of blood vessel walls.
Oral lesions are only a feature of the advanced form of the disease; early signs include fatigue, dermatitis, and purpura. There can be abnormalities in the growing bones of infants.
I. Vitamin B6 - (Pyridoxine) A deficiency can lead to peripheral neuropathy, most commonly associated with multivitamin B deficiencies in malnutrition and alcoholism.
V. Major Minerals - Sodium, potassium, chlorine, and magnesium are required for life but dietary deficiencies do not develop.
A. Iodine - Essential for the synthesis of thyroid hormones, and severe iodine deficiency is associated with hypothyroidism. The compensatory activity of the thyroid gland causes a characteristic enlargement called goiter.
B. Calcium - Required for bone mineralization, the RDA for adults is 800 mg/day. Clinical trials have shown that 1000-2000 mg/day can delay the bone loss observed in the elderly and decrease the risk of osteoporosis. See also section IV B.
VI. Trace Elements - At least 10 elements (examples: Co, Mn, Si) are required in minute amounts for normal development and metabolism.
A. Zinc - A deficiency can result from inadequate amounts given during total parenteral nutrition or as a secondary effect of acrodermatitis enteropathica (autosomal recessive trait characterized by alopecia, dermatitis, and diarrhea - the disease responds to administration of zinc).
B. Copper - Deficiencies are rare and primarily associated with malabsorption syndromes and total parenteral nutrition. Copper is required for normal hematopoiesis and bone growth. A deficiency resembles iron deficiency anemia and osteoporosis.
C. Fluoride - Levels in drinking water greater than 1 ppm cause mottling of teeth and in areas with chronic naturally induced fluorosis there is abnormal calcification of ligaments and tendons.
Lymphocytosis:
Causes
-Infections in children and the neutropenic infections in adults.
-Lymphocytic leukaemia.
-Infectious mononucleosis.
-Toxdplasmosis.
-Myast'henia gravis.