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.

Microbiological examination

 This is a method by which body fluids, excised tissue, etc. are examined by microscopical, cultural and serological techniques to identify micro-organisms Microbiological examination responsible for many diseases.

ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

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 .

AMYLOIDOSIS

Definition. Extra cellular  deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical  states.

Staining reactions

Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive  (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.

Amyloid is called typical if it given the above staining  reactions Other wise it is termed atypical or para-amyloid.

Classification 

1.    Systemic  amyloidosis associated with underlying disease (secondary),

(A) Chronic infections like 

- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.

(B) Chronic inflammations of varied etiology:

- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.

(C) Neoplastic proliferations:

- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.

II Systemic primary amyloidosis  with no underlying cause.

III Heredofamilial types.

- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy

IV. Localised amyloidosis:

- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.

Deposition sites
In relation to reticulin  and collagen fibres and to basement, membranes especially
subendothelial. 

Organs involved commonly are : 

Secondary amyloidosis

- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.

Primary amyloidosis

- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.

Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns

- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)

- In addition to these, extracts of crude amyloid contain  mucopolysacharides complement and gamma globulins.

- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response

The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.

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