NEET MDS Lessons
General Pathology
Asthma
Asthma is
(1) An obstructive lung disease characterized by narrowing of the airways.
Inflammation of the airways is a major component of asthma.
(2) Common symptoms are dyspnea, wheezing on expiration, and coughing.
(3) Two types:
(a) Extrinsic (allergic, atopic) asthma
(i) An atopic allergy caused by a type I immediate hypersensitivity immune reaction to an allergen.
(ii) Seen in children, adults.
(b) Intrinsic (nonallergic) asthma
(i) Not caused by an allergic reaction.
(ii) Mostly seen in adults.
The disorder is a chronic inflammatory condition in which the airways develop increased responsiveness to various stimuli, characterized by bronchial hyper-responsiveness, inflammation, increased mucus production, and intermittent airway obstruction.
Signs and symptoms
- The clinical hallmarks of an attack are shortness of breath (dyspnea) and wheezing
- A cough—sometimes producing clear sputum—may also be present
- The onset is often sudden; there is a "sense of constriction" in the chest, breathing becomes difficult, and wheezing occurs
- Signs of an asthmatic episode are wheezing, rapid breathing (tachypnea), prolonged expiration, a rapid heart rate (tachycardia), rhonchous lung sounds (audible through a stethoscope), and over-inflation of the chest.
- During very severe attacks asthma sufferer can turn blue due to lack of oxygen , can experience chest pain or even loss of consciousness, may lead to respiratory arrest and death
Pathophysiology
Bronchoconstriction : asthma is the result of an abnormal immune response in the bronchial airways. The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli, these stimuli include allergens, medications , air pollution, early child hood infection, exercise, emotional stress
Bronchial inflammation asthma resulting from an immune response to inhaled allergens—are the best understood of the causal factors. In both asthmatics and non-asthmatics, inhaled allergens that find their way to the inner airways are ingested by a type of cell known as antigen presenting cells These activate an humoral immune response. The humoral immune system produces antibodies against the inhaled allergen. Later, when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause the airways to constrict and release more mucus, and the cell-mediated arm of the immune system is activated. The inflammatory response is responsible for the clinical manifestations of an asthma attack
Symptomatic Treatment
Episodes of wheeze and shortness of breath generally respond to inhaled bronchodilators which work by relaxing the smooth muscle in the walls of the bronchi., More severe episodes may need short courses of inhaled, oral, or intravenous steroids which suppress inflammation and reduce the swelling of the lining of the airway.
Bronchodilators (usually inhaled)
Short-acting selective beta2-adrenoceptor agonists(salbutamol, terbutaline)
less selective adrenergic agonists, such as inhaled epinephrine and ephedrine tablets
Antimuscarinics
Systemic steroids
Oxygen to alleviate the hypoxia that is the result of extreme asthma attacks.
If chronic acid indigestion ( GERD) is part of the attack, it is necessary to treat it as well or it will restart the inflammatory process
Preventive Treatment
most effective preventive medication are
Inhaled corticosteroids
Long-acting beta2-adrenoceptor agonists
Leukotriene modifiers
Mast cell stabilizers
Methylxanthines (theophylline and aminophylline),
Antihistamines, often used to treat allergic symptoms
Enterococci
Most common are E. fecalis and E. fecium. Cause inflammation at site of colonization.
Serious resistance to antibiotics. E. fecium is now a vancomycin resistant enterococcus (VRE)
Rickets and Osteomalacia
Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion
4. Malabsorption disorders.
Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.
Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.
The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.
The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones
Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.
Microscopic features
• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.
Achrondroplasia
is a major cause of dwarfism. The underlying etiology is a point mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferation, which is associated with suppression of the normal epiphyseal growth plate expansion. Thus, long bone growth is markedly shortened.
The most conspicuous changes include disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic posture.
Microscopically, the cartilage growth plates are disorganized and hypoplastic.
G-6 PD Deficiency
Occurs in Negroes, Mediterranean races, India and far East. It confers a protection Against falciparum malaria.
It is transmitted as X-linked trait of intermediate dominance (variable effect in homozygous females).
Haemolysis may be induced by :
• Primaquin and other anti malarials.
• Other drugs like chloramphenicol , analgesics, antitubercular drugs etc.
• Infections.
• Ingestion of Vicia faba bean (favism).
• Diabetic acidosis
Hematological examination
This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.
Joint pathology
1. Rheumatoid arthritis
a. Cause is autoimmune in nature.
b. More common in women aged 20 to 50.
c. Characterized by inflammation of the synovial membrane. Granulation tissue, known as pannus, will form in the synovium and expand over the articular cartilage. This causes the destruction of the underlying cartilage and results in fibrotic changes and ankylosis.
Scarring, contracture, and deformity of the joints may occur.
d. Clinical symptoms include swollen joints. It can affect any joint in the body.
2. Osteoarthritis
a. Most common arthritis.
b. Cause is unknown.
c. Higher incidence in women, usually after age 50.
d. Characterized by degeneration of the articular cartilage and the formation of osteophytes (bony spurs) at the margins of affected areas.
Clinical signs and symptoms include:
(1) Stiff and painful joints affecting joints in the hand (phalangeal joints) and weight-bearing joints.
(2) Heberden’s nodes—nodules at the distal interphalangeal joint.
(3) Bocard’s nodes—nodules at the proximal interphalangeal joint.