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
Glycogen storage diseases (glycogenoses)
1. Genetic transmission: autosomal recessive.
2. This group of diseases is characterized by a deficiency of a particular enzyme involved in either glycogen production or degradative pathways.
Diseases include:
on Gierke disease (type I)
(a) Deficient enzyme: glucose-6-phosphatase.
(b) Major organ affected by the buildup of glycogen: liver.
Pompe disease (type II)
(1) Deficient enzyme: α-glucosidase(acid maltase).
(2) Major organ affected by the buildup of glycogen: heart.
Cori disease (type III)
(1) Deficient enzyme: debranching enzyme (amylo-1,6-glucosidase).
(2) Organs affected by the buildup of glycogen: varies between the heart, liver, or skeletal muscle.
Brancher glycogenosis (type IV)
(1) Deficient enzyme: branching enzyme.
(2) Organs affected by the buildup of glycogen: liver, heart, skeletal muscle, and brain.
McArdle syndrome (type V)
(1) Deficient enzyme: muscle phosphorylase.
(2) Major organ affected by the buildup of glycogen: skeletal muscle.
Cushing’s syndrome
The symptoms and signs of Cushing’s syndrome are associated with prolonged inappropriate elevation of free corticosteroid levels.
Clinical features
- Central obesity and moon face.
- Plethora and acne.
- Menstrual irregularity.
- Hirsutism and hair thinning.
- Hypertension.
- Diabetes.
- Osteoporosis—may cause collapse of vertebrae, rib fractures.
- Muscle wasting and weakness.
- Atrophy of skin and dermis—paper thin skin with bruising tendency, purple striae.
Aetiopathogenesis — patients with Cushing’s syndrome can be classified into two groups on the basis of whether the aetiology of the condition is ACTH dependent or independent.
Classification of Cushing's syndrome
ACTH dependent- Iatrogenic (ACTH therapy) Pituitary hypersecretion of ACTH Ectopic ACTH syndrome (benign or malignant non-endocrine tumour)
Non-ACTH dependent - Iatrogenic, e.g. prednisolone Adrenal cortical adenoma , Adrenal cortical carcinoma
ACTH-dependent aetiology:
- Pituitary hypersecretion of ACTH (Cushing’s disease)—bilateral adrenal hyperplasia secondary to excessive secretion of ACTH by a corticotroph adenoma of the pituitary gland.
- Production of ectopic ACTH or corticotrophin- releasing hormone (CRH) by non-endocrine neoplasm, e.g. small cell lung cancer and some carcinoid tumours. In cases of malignant bronchial tumour, the patient rarely survives long enough to develop any physical features of Cushing’s syndrome.
Non-ACTH-dependent aetiology
Iatrogenic steroid therapy—most common cause of Cushing’s syndrome.
Adrenal cortical adenoma—well-circumscribed yellow tumour usually 2–5 cm in diameter.
Extremely common as an incidental finding in up to 30% of all post-mortem examinations. The yellow colour is due to stored lipid (mainly cholesterol) from which the hormones are synthesised. The vast majority have no clinical effects (i.e. they are non-functioning adenomas), with only a small percentage producing Cushing’s syndrome.
Adrenal cortical carcinoma—rare and almost always associated with the overproduction of hormones, usually glucocorticoids and sex steroids.
Cushing’s syndrome mixed with androgenic effects which are particularly noticeable in women. Tumours are usually large and yellowish white in colour. Local invasion and metastatic spread are common.
Irrespective of the aetiology, the diagnosis is based on clinical features and the demonstration of a raised plasma cortisol level.
The aetiology of the disorder is elucidated through:
- Raised urinary cortisol in the first instance, but further testing is required.
- Low-dose dexamethasone suppression test (suppression of cortisol levels in Cushing’s disease due to suppression of pituitary ACTH secretion, but a lack of suppression suggests ACTH-independent Cushing’s syndrome).
- MRI and CT scan visualisation of pituitary and adrenal glands.
- Analysis of blood ACTH (high = pituitary adenoma or ectopic ACTH source; low = primary adrenal tumour due to feedback suppression).
- Treatment of the underlying cause is essential as untreated Cushing’s syndrome has a 50% 5-year mortality rate.
The therapeutic administration of glucocorticosteroids (e.g. prednisolone) is a common cause of the features of Cushing’s syndrome.
Primary vs. secondary disorders - Most nutritional disorders in developed countries are not due to simple dietary deficiencies but are rather a secondary manifestation of an underlying primary condition or disorder.
• Chronic alcoholism
• Pregnancy and lactation
• Renal dialysis
• Eating disorders
• Prolonged use of diuretics
• Malabsorption syndromes
• Neoplasms
• Food fads
• Vegans
• AIDS
Paroxysmal nocturnal haemoglobinuria (PNH).
Feature:
- Acquired RBC rnembrane defect rendering it susceptible to complement lysis.
- Features of intravascular haemolysis.
- Blood picture of haemolysis anemais with pancytopenia.
- Ham’s acid serum test (lysis at 37COin acid pH) + ve
Ichthyosis vulgaris is a genetic disease characterized by increased cohesiveness of the cells in the stratum corneum, resulting up in a piling up stratum corneum (scales like a fish).
PERTUSSIS (Whooping Cough)
An acute, highly communicable bacterial disease caused by Bordetella pertussis and characterized by a paroxysmal or spasmodic cough that usually ends in a prolonged, high-pitched, crowing inspiration (the whoop).
Transmission is by aspiration of B. pertussis
Symptoms and Signs
The incubation period averages 7 to 14 days (maximum, 3 wk). B. pertussis invades the mucosa of the nasopharynx, trachea, bronchi, and bronchioles, increasing the secretion of mucus, which is initially thin and later viscid and tenacious. The uncomplicated disease lasts about 6 to 10 wk and consists of three stages: catarrhal, paroxysmal, and convalescent.