NEET MDS Lessons
General Pathology
The Specific Immune Response
Definition
The immune response comprises all the phenomenon resulting from specific interaction of cells of the immune-system with antigen. As a consequence of this interaction cells appear that mediate cellular immune response as well cells that synthesis and secrete immunoglobulins
Hence the immune response has 2 components.
1. Cell mediated immunity (CMI).
2:. Humoral immunity (antibodies)
(I) Macrophages. Constituent of the M. P. S. These engulf the antigenic material.
(i) Most of the engulfed antigen is destroyed to' prevent a high dose paralysis of the Immune competent cells.
(ii) Some of it persists in the macrophage, retaining immunogenecity for continued stimulus to the immune system.
(iii)The antigenic information is passed on to effectors cells. There are two proposed mechanisms for this:
(a) As messenger RNA with code for the specific antibody.
(b) As antigen-RNA complexes.
(2) Lymphocytes. There are 2 main classes recognized by surface characteristics.
(A) T-Lymyhocytes (thymus dependant) :- These are responsible for cellular immunity . On exposure to antigen
- They transform to immunoblasts which divide to form the effectors cells.
- They secrete lymphokines These are
- Monocyte migration inhibition factor
- Macrophage activation factor
- Chemotactic factor
- Mitogenic factor
- Transfer factor
- Lymphotoxin which kills target cell
- Interferon.
- Inflammatory factor which increases permeability. .
- Some remain as 1onglived memory cell for a quicker recognition on re-exposure
- They also modify immune response by other lymphocytes in the form of “T – helper cells “ and “T-suppressor” cells
- They are responsible for graft rejection
(B) B-Lymphocytes (Bursa dependent). In birds the Bursa of Fabricious controls
these cells. In man, its role is taken up by," gut associated lymphoid tissue)
(i) They are responsible for antibody synthesis. On stimulation they undergo blastic transformation and then differentiation to plasma cells, the site of immunoglobulin synthesis.
(ii) They also form memory cells. But these are probably short lived.
(C) In addition to T & B lymphocytes, there are some lymphocytes without the surface markers of either of them. These are 'null' cells-the-natural Killer (N,K.) cells and cells responsible for antibody dependent cellular-cytotoxicity.
(3) Plasma cells. These are the effectors cells of humoral immunity. They produce the immunoglobins, which are the effector molecules.
Cholecystitis
It is inflammation of the gall bladder. It may be acute or chronic.
In 80-90% of cases, it is associated with gall stones (Calcular cholecystis).
Causes and pathogenesis:-
Obstruction of cystic or common bile duct- By stones, strictures, pressure from the outside, tumors etc.
Obstruction , chemical irritation of the gall bladder, Secondary bacterial infection, stone formation, trauma to the wall of gall
bladder
Secondary bacterial infection
Usually by intestinal commensals E.coli, streptococcus fecalis. They reach the gall bladder by lymphatics.
S.typhi reaches the gall bladder after systemic infection
Acute cholecystitis
Gall bladder is enlarged edematous and fiery red in color.
- Wall is edematous, hyperemic, may show abscesses or gangrenous dark brown or green or black foci which may perforate.
Serous covering show fibrinosuppurative inflammation and exudation. Mucosa is edematous, hyperemic and ulcerated.
- If associated with stones, obstruction results in accumulation of pus leading to Empyaema of the gall bladder.
Fate:- Healing by fibrosis and adhesions.
Complications:-
- Pericholecystic abscess.
- Rupture leading to acute peritonitis.
- Ascending suppurative cholangitis and liver abscess
Chronic cholecystitis
May follow Acute cholecystitis or starts chronic. Gall stones are usually present.
Pathology
1. If associated with obstruction: Gall bladder is dilated. Wall may be thickened or thinned out. Contents may be clear, turbid or purulent.
2. If not associated with obstruction: - Gall bladder is contracted, wall is markedly thickened.
3. Serosa is smooth with fibrous adhesions. Draining lymph nodes are enlarged.
4. Wall is thickened, opaque and gray-white with red tinge.
5. Mucosa is gray- red with ulcerations and pouches.
6. Stones are usually present
Rheumatic fever
Before antibiotic therapy, this was the most common cause of valvular disease.
1. Usually preceded by a group A streptococci respiratory infection; for example, strep throat.
2. All three layers of the heart may be affected. The pathologic findings include Aschoff bodies, which are areas of focal necrosis surrounded by a dense inflammatory infiltration.
3. Most commonly affects the mitral valve, resulting in mitral valve stenosis, regurgitation, or both.
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.
Cardiac arrhythmia
Cardiac arrhythmia is a group of conditions in which muscle contraction of the heart is irregular for any reason.
Tachycardia :A rhythm of the heart at a rate of more than 100 beats/minute , palpitation present
Causes : stress, caffeine, alcohol, hyperthyroidism or drugs
Bradycardia : slow rhythm of the heart at a rate less than 60 beats/min
Atrial Arrhythmias
- Atrial fibrillation
Atrial Dysrhythmias
- Premature atrial contraction
- Atrial flutter
- Supraventricular tachycardia
- Sick sinus syndrome
Ventricular Arrhythmias
- Ventricular fibrillation
Ventricular Dysrhythmias
- Premature ventricular contraction
- Pulseless electrical activity
- Ventricular tachycardia
- Asystole
Heart Blocks
- First degree heart block
- Second degree heart block
o Type 1 Second degree heart block a.k.a. Mobitz I or Wenckebach
o Type 2 Second degree heart block a.k.a. Mobitz II
- Third degree heart block a.k.a. complete heart block
Atrial fibrillation
Atrial fibrillation is a cardiac arrhythmia (an abnormality of heart rate or rhythm) originating in the atria.
AF is the most common cardiac arrhythmia
Signs and symptoms
Rapid and irregular heart rates
palpitations, exercise intolerance, and occasionally produce angina and congestive symptoms of shortness of breath or edema
Paroxysmal atrial fibrillation is the episodic occurence of the arrhythmia Episodes may occur with sleep or with exercise
Diagnosis:
Electrocardiogram
- absence of P waves
- unorganized electrical activity in their place
- irregularity of R-R interval due to irregular conduction of impulses to the ventricles
Causes:
- Arterial hypertension
- Mitral valve disease (e.g. due to rheumatic heart disease or mitral valve prolapse)
- Heart surgery
- Coronary heart disease
- Excessive alcohol consumption ("binge drinking" or "holiday heart")
- Hyperthyroidism
- Hyperstimulation of the vagus nerve, usually by having large meals
Treatment
Rate control by
Beta blockers (e.g. metoprolol)
Digoxin
Calcium channel blockers (e.g. verapamil)
Rhythm control
Electrical cardioverion by application of a DC electrical shock
Chemical cardioversion is performed with drugs eg amiodarone
Radiofrequency ablation : uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue It is used in recurrent AF
In confirmed AF, anticoagulant treatment is a crucial way to prevent stroke
Atrial flutter
Atrial flutter is a regular, rhythmic tachycardia originating in the atria. The rate in the atria is over 220 beats/minute, and typically about 300 beats/minute
he morphology on the surface EKG is typically a sawtooth pattern.
The ventricles do not beat as fast as the atria in atrial flutter
Supraventricular tachycardia
apid rhythm of the heart in which the origin of the electrical signal is either the atria or the AV node
it is important to determine whether a wide-complex tachycardia is an SVT or a ventricular tachycardia, since they are treated differently
Sick sinus syndrome : a group of abnormal heartbeats (arrhythmias) presumably caused by a malfunction of the sinus node, the heart's "natural" pacemaker.
Ventricular fibrillation
is a cardiac condition which consists of a lack of coordination of the contraction of the muscle tissue of the large chambers of the heart. The ventricular muscle twitches randomly, rather than contracting in unison, and so the ventricles fail to pump blood into the arteries and into systemic circulation.
Ventricular fibrillation is a medical emergency: if the arrhythmia continues for more than a few seconds, blood circulation will cease, as evidenced by lack of pulse, blood pressure and respiration, and death will occur. Ventricular fibrillation is a cause of cardiac arrest and sudden cardiac death
Lysosomal (lipid) storage diseases
- Genetic transmission: autosomal recessive.
- This group of diseases is characterized by a deficiency of a particular lysosomal enzyme. This results in an accumulation of the metabolite, which would have otherwise been degraded by the presence of normal levels of this specific enzyme.
Diseases include:
Gaucher’s disease
(1) Deficient enzyme: glucocerebrosidase.
(2) Metabolite that accumulates: glucocerebroside.
(3) Important cells affected: macrophages.
Tay-Sachs disease
(1) Deficient enzyme: hexosaminidase A.
(2) Metabolite that accumulates: GM2 ganglioside.
(3) Important cells affected: neurons.
(4) Symptoms include motor and mental deterioration, blindness, and dementia.
(5) Common in the Ashkenazi Jews.
Niemann-Pick disease
(1) Deficient enzyme: sphingomyelinase.
(2) Metabolite that accumulates: sphingomyelin.
(3) Important cells affected: neurons.
Pulmonary Hypertension
Sustained elevation of mean pulmonary arterial pressure.
Pathogenesis
Elevated pressure, through endothelial cell dysfunction, produces structural changes in the pulmonary vasculature. These changes ultimately decrease pulmonary blood flow and stress the heart to the point of failure. Based on etiology, pulmonary hypertension is divided into two categories.
Primary (idiopathic): The cause is unknown.
Secondary: The hypertension is secondary to a variety of conditions which increase pulmonary blood flow or increase resistance to blood flow. Example: Interstitial fibrosis.
Pathology
The changes involve large and small pulmonary blood vessels and range from mild to severe. The major changes include atherosclerosis, striking medial hypertrophy and intimal fibrosis of small arteries and arterioles, and plexogenic arteriopathy. Refer to Figure 15-7 in your textbook.
Pathophysiology
Dyspnea and fatigue eventually give way to irreversible respiratory insufficiency, cyanosis and cor pulmonale.