NEET MDS Lessons
General Pathology
ESOPHAGUS Pathology
Congenital malformations
1. A tracheoesophageal fistula (the most prevalent esophageal anomaly) occurs most commonly as an upper esophageal blind pouch with a fistula between the lower segment of the esophagus and the trachea. It is associated with hydramnios, congenital heart disease, and other gastrointestinal malformation.
2. Esophageal atresia is associated with VATER syndrome (vertebra1 defects, anal atresia, tracheoesophageal fistula, and renal dysplasia)
3. Stenosis refers to a narrowed esophagus with a small lumen. lt may be congenital or acquired, e.g., through trauma or inflammation.
Inflammatory disorders
Esophagitis
most often involves the lower half of the esophagus. Caused by the reflux of gastric contents (juices) into the lower esophagus. One of the most common GI disorders.
Clinical features.
Patients experience substernal burning associated with regurgitation, mild anemia, dysphagia, hematemesis, and melena. Esophagitis may predispose to esophageal cancer.
Etiology
- Reflux esophagitis is due to an incompetent lower esophageal sphincter that permits reflux of gastric juice into the lower esophagus.
- Irritants such as citric acid, hot liquids, alcohol, smoking, corrosive chemicals, and certain drugs, such as tetracycline, may provoke inflammation.
- Infectious etiologies include herpes, CMV, and C. albicans. The immunocompromised host is particularly susceptible to infectious esophagitis.
Although chronic or severe reflux disease is uncommon, consequences of these conditions can lead to Barrett’s esophagus, development of a stricture, or hemorrhage.
Pathology
-Grossly, there is hyperemia, edema, inflammation, and superficial necrosis.
Complications include ulceration, bleeding, stenosis, and squamous carcinoma.
Treatment: diet control, antacids, and medications that decrease the production of gastric acid (e.g., H blockers).
Barrett's esophagus,
gastric or intestinal columnar epithelium replaces normal squamous epithelium in response to chronic reflux.- A complication of chronic gastroesophageal reflux disease.
- Histologic findings include the replacement of squamous epithelium with metaplastic columnar epithelium.
- Complications include increased incidence of esophageal adenocarcinoma, stricture formation, or hemorrhage (ulceration).
Motor disorders.
Normal motor function requires effective peristalsis and relaxation of the lower esophageal sphincter.
Achalasia is a lack of relaxation of the lower esophageal sphincter (LES), which may be associated with aperistalsis of the esophagus and increased basal tone of the LES.
Clinical features. Achalasia occurs most commonly between the ages of 30 and 50. Typical symptoms are dysphagia, regurgitation, aspiration, and chest pain. The lack of motility promotes stagnation and predisposes to carcinoma.
Hiatal hernia is the herniation of the abdominal esophagus, the stomach, or both, through the esophageal hiatus in the diaphragm.
Scleroderma is a collagen vascular disease, seen primarily in women, that causes subcutaneous fibrosis and widespread degenerative changes. (A mild variant is known as CREST syndrome which stands for calcinosis. raynaud's phenomenon , esophageal dysfunction, sclerodactyly and telengectseia. esophagus is the most frequently involved region of the gastrointestinal tract.
Clinical features are mainly dysphagia and heartburn due to reflux oesophagitis caused by aperlistalsis and incompetent LES.
Rings and webs
1. Webs are mucosal folds in the upper esophagus above the aortic arch.
2. Schatzki rings are mucosal rings at the squamocolumnarjunction below the aortic arch.
3. Plummer Vinson Syndrome consist of triad of dysphagia, atrophic glossitis, and anemia. Webs are found in the upper esophagus. The syndrome is associated specifically with iron deficiency anemia and sometimes hypochlorhydria. Patients are at increased risk for carcinoma of the pharynx or esophagus.
Mallory-Weiss syndrome
Mallory-Weiss tears refers to small mucosal tears at the gastroesophageal junction secondary to recurrent forceful vomiting. The tears occur along the long axis an result in hematemesis (sometimes massive).
- Characterized by lacerations (tears) in the esophagus.
- Most commonly occurs from vomiting (alcoholics).
- A related condition, known as Boerhaave syndrome, occurs when the esophagus ruptures, causing massive upper GI hemorrhage.
Esophageal varices
- The formation of varices (collateral channels) occurs from portal hypertension.
Causes of portal hypertension include blockage of the portal vein or liver disease (cirrhosis).
- Rupture of esophageal varices results in massive hemorrhage into the esophagus and hematemesis.
- Common in patients with liver cirrhosis.
Diverticula
are sac-like protrusions of one or more layers of pharyngeal or esophageal wall.
Tumors
- Benign tumors are rare.
- Carcinoma of the esophagus most commonly occurs after 50 and has a male:female ratio of 4.1.
Etiology: alcohal ingestion, smoking, nitrosamines in food, achalasia , web ring, Barrettes esophagus, and deficiencies of vitamins A and C , riboflavin, and some trace minerals
Clinical features include dysphagia (first to solids), retrosternal pain, anorexia, weight loss, melena, and symptoms secondary to metastases.
Pathology
- 50% occur in the middle third of the esophagus, 30% in the lower third, and 20% in the upper third. Most esophageal cancers are squamous cell carcinomas.
Adenocarcinomas arise mostly out of Barrett's esophagus.
Prognosis
is poor. Fewer than 10% of patients survive 5 years, usually because diagnosis is made at a late stage. The most common sites of metastasis are the liver and lung. The combination of cigarette smoking and alcohol is particularly causative for esophageal cancer (over l00% risk compared to nondrinkers/nonsmokers).
Biochemical examination
This is a method by which the metabolic disturbances of disease are investigated by assay of various normal and abnormal compounds in the blood, urine, etc.
Pheochromocytoma
Pheochromocytomas are neoplasms composed of chromaffin cells, which as their normal counterparts synthesize and release catecholamines.
1. Arise in association with one of several familial syndromes such as MEN syndromes, type 1 neurofibromatosis, von Hippel-Lindau disease, and Sturge-Weber syndrome.
2. Are extra-adrenal, occurring in sites such as the organ of Zuckerkandl and the carotid body, where they are usually called paragangliomas rather than pheochromocytomas.
3. Are bilateral; but in association with familial syndromes, this figure may rise to 50%.
4. Are malignant; frank malignancy, however, is more common in extra-adrenal tumors.
Gross features
- The size of these tumors is quite variable ranging from small to huge masses.
- Sectioning shows yellow-tan, well-defined tumor that compress the adjacent adrenal. Large lesions display areas of hemorrhage, necrosis, and cystic degeneration.
- Incubation of the fresh tissue with potassium dichromate solutions converts the tumor a dark brown color.
Microscopic features
- These tumors are composed of polygonal to spindle-shaped chromaffin cells and their supporting sustentacular cells, arranged in well-defined small nests (Zellballen)," rimmed by a rich vascular network.
- The cytoplasm is often finely granular (catecholamine-containing granules)
- The nuclei are often quite pleomorphic.
- Both capsular and vascular invasion may be encountered in benign lesions, and the presence of mitotic figures per se does not imply malignancy. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone.
The laboratory diagnosis of pheochromocytoma is based on demonstration of increased urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid (VMA)& metanephrines.
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.
Bacterial endocarditis
Endocarditis is an infection of the endocardium of the heart, most often affecting the heart valves.
A. Acute endocarditis
1. Most commonly caused by Staphylococcus aureus.
2. It occurs most frequently in intravenous drug users, where it usually affects the tricuspid valve.
B. Subacute endocarditis
1. Most commonly caused by less virulent organisms, such as intraoral Streptococcus viridans that can be introduced systemically via dental procedures.
2. Pathogenesis: occurs when a thrombus or vegetation forms on a previously damaged or congenitally abnormal valve. These vegetations contain bacteria and inflammatory cells. Complications can arise if the thrombus embolizes, causing septic infarcts.
Other complications include valvular dysfunction or abscess formation.
3. Symptoms can remain hidden for months.
4. Valves affected (listed most to least common):
a. Mitral valve (most frequent).
b. Aortic valve.
c. Tricuspid (except in IV drug users, where the tricuspid valve is most often affected).
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