HAEMORRHAGIC DISORDERS

Normal homeostasis depends on

 -Capillary integrity and tissue support.

- Platelets; number and function

(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation

(b) Vasoactive substances for vasoconstriction

(c) Platelet factor for coagulation.

(d) clot retraction.

- Fibrinolytic system(mainly Plasmin) : which keeps the coagulation system in check.

Coagulation disorders

These may be factors :

Deficiency .of factors

• Genetic.
• Vitamin K deficiency.
• Liver disease.
• Secondary to disseminated intravascular coagulation.or defibrinatian

Overactive fibrinolytic system.

Inhibitors of  the factors (immune, acquired).

Anticoagulant therapy as in myocardial infarction.

Haemophilia. Genetic disease transmitted as X linked recessive trait. Common in Europe. Defect in fcatorVII   Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).

Features:

• May manifest in infancy or later.
• Severity depends  on degree of deficiency.
• Persistant wound bleeding.
• Easy Bruising with Hematoma formation

Nose bleed , arthrosis, abdominal pain with fever and leukocytosis

Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.

Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally

Vitamin K  Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.

Deficiency maybe due to:

Obstructive jaundice.

Steatorrhoea.

Gut sterilisation by antibiotics.

Liver disease results in :

Deficient synthesis of factor I II, V, Vll, IX and X  Incseased fibrinolysis (as liver is the site of detoxification of activators ).

Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.

Causes

Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .

Hypersensitivity reactions.

Disseminated malignancy.

Snake bite.

Vascular defects : (Non thrombocytopenic purpura).

Acquired :

Simple purpura a seen in women. It is probably endocrinal

Senile parpura in old people due to reduced tissue support to vessels

Allergic or toxic damage to endothelium due to  Infections like Typhoid Septicemia

Col!agen diseases.

Scurvy

Uraemia damage to  endothelium (platelet defects).

Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.

Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff

It manifests as :

Pulrpurric rashes.

Arthralgia.

Abdominal pain.

Nephritis and haematuria.

Hereditary :

(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.

(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease

.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.

Platelet defects

These may be :

(I) Qualitative thromboasthenia and thrombocytopathy.

(2) Thrombocytopenia :Reduction in number.

(a) Primary or idiopathic thrombocytopenic purpura.

(b) Secondary to :

(i) Drugs especially sedormid

(ii) Leukaemias

(iii) Aplastic-anaemia.

Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.

Manifests as :

Acute self limiting type.

Chronic recurring type.

Features:

(i) Spontaneous bleeding and easy bruisability

(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.

Thrombocytopenia with abnormal forms of platelets.

Marrow shows increased megakaryocytes with immature forms, vacuolation, and lack of platelet budding.

Pathogenesis:

hypersensitivity to infective agent in acute type.

Plasma thrombocytopenic factor ( Antibody in nature) in chronic type

Emphysema

Emphysema is a chronic lung disease. It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke.

Signs and symptoms

loss of elasticity of the lung tissue

destruction of structures supporting the alveoli

destruction of capillaries feeding the alveoli

The result is that the small airways collapse during expiration, leading to an obstructive form of lung disease

Features are: shortness of breath on exertion

 hyperventilation and an expanded chest.

As emphysema progresses, clubbing of the fingers may be observed, a feature of longstanding hypoxia.

Emphysema patients are sometimes referred to as "pink puffers". This is because emphysema sufferers may hyperventilate to maintain adequate blood oxygen levels. Hyperventilation explains why emphysema patients do not appear cyanotic as chronic bronchitis (another COPD disorder) sufferers often do; hence they are "pink" puffers (adequate oxygen levels in the blood) and not "blue" bloaters (cyanosis; inadequate oxygen in the blood).

Diagnosis

spirometry (lung function testing), including diffusion testing

X-rays,  high resolution spiral chest CT-scan,

Bronchoscopy, blood tests, pulse oximetry and arterial blood gas sampling.

Pathophysiology :

Permanent destructive enlargement of the airspaces distal to the terminal bronchioles without obvious fibrosis

Oxygen is inhaled in normal breathing

When toxins such as smoke are breathed into the lungs, the particles are trapped by the hairs and cannot be exhaled, leading to a localised inflammatory response. Chemicals released during the inflammatory response (trypsin, elastase, etc.) are released and begin breaking down the walls of alveoli. This leads to fewer but larger alveoli, with a decreased surface area and a decreased ability to take up oxygen and loose carbon dioxide. The activity of another molecule called alpha 1-antitrypsin normally neutralizes the destructive action of one of these damaging molecules.

After a prolonged period, hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood, and the body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension. This leads to enlargement and increased strain on the right side of the heart, which in turn leads to peripheral edema (swelling of the peripherals) as blood gets backed up in the systemic circulation, causing fluid to leave the circulatory system and accumulate in the tissues.

Emphysema occurs in a higher proportion in patient with decreased alpha 1-antitrypsin (A1AT) levels

Prognosis and treatment

Emphysema is an irreversible degenerative condition

Supportive  treatmentis by supporting the breathing with anticholinergics, bronchodilators and (inhaled or oral) steroid medication, and supplemental oxygen as required

Lung volume reduction surgery (LVRS) can improve the quality of life for only  selected patients.

ADRENOCORTICAL TUMORS

Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features. 

Patholgical features
Adrenocortical adenomas

- They are generally small, 1 to 2 cm in diameter. 
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells 
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content. 

Adrenocortical carcinomas 

These are rare and may occur at any age, including in childhood.  
- Carcinomas are generally large, invasive lesions. 
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.  

Herpes zoster, or shingles
 - represents reactivation of a latent varicella-zoster infection.
 - virus lies dormant in sensory dorsal root ganglia and when activated involves the distribution (dermatome) of the sensory nerve with a painful vesicular eruption.
 - trigeminal verve distribution → Ramsay Hunt syndrome
 - may indicate the presence of advanced neoplastic disease or be a complication of chemotherapy.

PARASITIC DISEASES

AMEBIASIS (Entamebiasis)

Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.

Etiology and Pathogenesis 

Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.

Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.

Symptoms and Signs 

Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.

Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.

Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.

Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common
 

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).