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
Systemic Candidiasis (Candidosis; Moniliasis)
Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.
Infections due to Candida sp account for about 80% of all major systemic fungal infections.
Symptoms and Signs
Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.
Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.
Pneumoconioses—are environmentally related lung diseases that result from chronic inhalation of various substances.
1. Silicosis (stone mason’s disease)
a. Inhalant: silica dust.
b. Associated with extensive fibrosis of the lungs.
c. Patients have a higher susceptibility to tuberculosis infections.
2. Asbestosis
a. Inhalant: asbestos fibers.
b. Associated with the presence of pleural plaques.
c. Consequences include:
(1) Mesothelioma (malignant mesothelial tumor).
(2) Bronchogenic carcinoma.
3. Anthracosis
a. Inhalant: carbon dust.
b. Usually not as harmful as silicosis or asbestosis.
c. Associated with the presence of macrophages containing carbon.
Graves disease
Graves disease is an organ-specific autoimmune disorder that results in thyrotoxicosis due to overstimulation of the thyroid gland by autoantibodies.
- It is the most common form of thyrotoxicosis, females being affected more than males by 8: 1.
- It is usually associated with a diffuse enlargement of the thyroid.
Pathogenesis
IgG-type immunoglobulins bind to TSH membrane receptors and cause prolonged stimulation of the thyroid, lasting for as long as 12 hours
(cf. 1 hour for TSH). The autoantibody binds at a site different to the hormone-binding locus and is termed the TSH-receptor autoantibody (TRAb); 95% of Graves’ disease patients are positive for TRAbs
Gross features
- The thyroid gland is diffusely and moderately enlarged
- It is usually smooth, soft, and congested
Histologically
- the gland shows diffuse hypertrophy and hyperplasia of acinar epithelium, reduction of stored colloid and local accumulations of lymphocytes with lymphoid follicle formation.
Clinical features
- Exophthalmos (protrusion of the eyeballs in their sockets)—due to the infiltration of orbital tissues by fat, mucopolysaccharides and lymphocytes. May cause compression of the optic nerve, hence blindness. However, only about 5% of Graves’ patients show signs of exophthalmos.
- Thyroid acropachy—enlargement of fingernails.
- Pretibial myxoedema—accumulation of mucoproteins in the deep dermis of the skin.
Treatment is as for thyrotoxicosis.
EXOCRINE PANCREAS
Congenital anomalies
1. Ectopic pancreatic tissue most commonly occurs in the stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. It may be either asymptomatic or cause obstruction, bleeding, intussusception.
2.Annular pancreas is a ring of pancreatic tissue that encircle the duodenum and may cause duodenal obstruction.
Cystic fibrosis
Cystic fibrosis is a systemic disorder of exocrine gland secretion presenting during infancy or childhood.
Incidence is 1:2500 in Caucasians; it is less common in Black and extremely rare in Asians.
Pathogenesis. Cystic fibrosis shows autosomal recessive transmission; heterozygotes are unaffected. It results in a defective chloride channel, which leads to secretion of very thick mucus.
Characteristics
- Tissues other than exocrine glands are normal, and glands are structurally normal until damaged by cystic fibrosis.
- The only characteristic biochemical abnormalities are an elevation of sodium and chloride levels in sweat, and a decrease in water and bicarbonate secretion from pancreatic cells, resulting in a viscous secretion.
Clinical features
- Fifteen percent of cases present with meconium ileus.
- Most cases present during the first year with steatorrhea (with resultant deficiencies of vitamins A, D, E, and K), abdominal distention, and failure to thrive.
Complications are also related to pulmonary infections'and obstructive pulmonary disease as a result of viscous bronchial secretions.
Pathology
- There is mucus plugging of the pancreatic ducts with cystic dilatation, fibrous proliferation, and atrophy. Similar pathology develops in salivary glands.
- Lungs. Mucus impaction leads to bronchiolar dilatation an secondary infection.
- The gastrointestinal tract shows obstruction caused mucus impaction in the intestines with areas of biliary cirrhosis, resulting from intrahepatic bile duct obstruction
Diagnosis depends on demonstrating a "sweat test" abnomality associated with at least one clinical feature In sweat test, high levels of chloride are demonstrated.
Prognosis. Mean survival is age 20; mortality is most often due to pulmonary infections.
Degenerative changes
1. Iron pigmentation (e.g., from hemochromatosis) may be deposited within acinar and islet cells and may cause insulin deficiency.
2. Atrophy
a. Ischemic atrophy is due to atherosclerosis of pancreatic arteries and is usually asymptomatic.
b. Obstruction of pancreatic ducts affects only the exocrine pancreas, which becomes small, fibrous, and nodular.
Acute hemorrhagic pancreatitis
presents as a diffuse necrosis of the pancreas caused by the release of activated pancreatic
enzymes. Associated findings include fat necrosis and hemorrhage into the pancreas.
Incidence. This disorder is most often associated with alcoholism and biliary tract disease.
It affects middle-aged individuals and often occurs after a large meal or excessive alcohol ingestion; approximately 50% of patients have gallstones.
Pathogenesis. There are four theories.
- Obstruction of the pancreatic duct causes an elevated intraductal pressure, which results in leakage of enzymes from small ducts.
- obstruction may be caused by a gallstone at the ampulla of Vater; chronic alcohol ingestion may cause duct obstruction by edema.
- Hypercalcemia may cause activation of trypsinogen; its mechanism is unclear. Pancreatitis occurs in 20% of patients with hyperparathyroidism.
- Direct damage to acinar cells may occur by trauma, ischemia, viruses, and drugs.
- Hyperlipidemia may occur as a result of exogenous estrogen intake and alcohol ingestion.
Clinical features are typically the sudden onset of acute, continuous, and intense abdominal pain, often radiating to the back and accompanied by nausea, vomiting, and fever. This syndrome frequently results in shock.
Laboratory values reveal elevated amylase (lipase elevated after 3-4 days) and leukocytosis. Hypocalcemia is a poor prognostic sign.
Chronic pancreatitis
It refers to remitting and relapsing episodes of mild pancreatitis, causing progressive pancreatic damage.
Incidence is similar to acute pancreatitis. It is also seen in patients with ductal anomalies. Almost half the cases occur without known risk factors.
Pathogenesis is unclear; possibly, there is excess protein secretion by the pancreas, causing ductal obstruction.
Clinical features include flareups precipitated by alcohol and overeating, and drugs. Attacks are characterized by upper abdominal pain, tenderness, fever, and jaundice.
Laboratory values reveal elevated amylase and alkaline phosphatase, X-rays reveal calcifications in the pancreas. Chronic pancreatitis may result in pseudocyst formation, diabetes, and steatorrhea.
Carcinoma of the pancreas
Incidence:
Carcinoma of the pancreas accounts for approximately 5% of all cancer deaths. Increased risk is associated with smoking. high-fat diet, and chemical exposure. There is a higher incidence in the elderly, Blacks, males, and diabetics.
Clinical features
- The disease is usually asymptomatic until late in its course.
- Manifestations include weight loss, abdominal pain frequently radiating to the back, weakness, malaise, anorexia, depression, and ascites.
- There is jaundice in half of the patients who have carcinoma of the head of the pancreas.
- Courvoisier's law holds that painless jaundice with a palpable gallbladder is suggestive of pancreatic cancer.
Pathology
Carcinomas arise in ductal epithelium. Most are adenocarcinomas.
- Carcinoma of the head of the pancreas accounts for 60% of all pancreatic cancers.
- Carcinoma of the body (20%) and tail (5%) produce large indurated masses that spread widely to the liver and lymph nodes.
- In 15% of patients, carcinoma involves the pancreas diffusely.
Complications
include Trousseau's syndrome, a migratory thrombophlebitis that occurs in 10% of patients.
Prognosis is very poor. if resectable, the 5-year survival rate less than 5%. The usual course is rapid decline; on average death occurs 6 months after the onset of symptoms.
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
Congestive heart failure (CHF)
A. Left-sided CHF
1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.
B. Right-sided CHF
1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.