VIRAL DISEASES

RABIES (Hydrophobia)

An acute infectious disease of mammals, especially carnivores, characterized by CNS pathology leading to paralysis and death.

Etiology and Epidemiology

Rabies is caused by a neurotropic virus often present in the saliva of rabid animals

Pathology

The virus travels from the site of entry via peripheral nerves to the spinal cord and the brain, where it multiplies; it continues through efferent nerves to the salivary glands and into the saliva.

microscopic examination shows perivascular collections of lymphocytes but little destruction of nerve cells. Intracytoplasmic inclusion bodies (Negri bodies), usually in the cornu Ammonis, are pathognomonic of rabies, but these bodies are not always found.

Sign/Symptoms

In humans, the incubation period varies from 10 days to > 1 yr and averages 30 to 50 days.

Rabies commonly begins with a short period of depression, restlessness, malaise, and fever. Restlessness increases to uncontrollable excitement, with excessive salivation and excruciatingly painful spasms of the laryngeal and pharyngeal muscles. The spasms, which result from reflex irritability of the deglutition and respiration centers, are easily precipitated Hysteria due to fright

Prognosis and Treatment

Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms

Bullous and Vesicular Disease
1. There are many diseases characterized by the presence of vesicles and bullae filled  fluid.
2. In pemphigus vulgaris, large, flaccid bullae filled with fluid occur on the skin and within the oral mucosa.
 - immunologic disease with IgG antibodies against the intercellular attachment sites between keratinocytes (type II hypersensitivity).
 - the vesicle in pemphigus vulgaris has a suprabasal location (just above the basal cell layer and resembling "tombstones")
 - scattered keratinocytes in the fluid as a result of acantholysis.
 - Nikolsky's sign is where the epidermis slips when touched with the finger.
 - fatal disease if left untreated (systemic corticosteroids)
3. Bullous pemphigoid is an immunologic vesicular disease whose vesicle are in a subepidermal location.
 - circulating IgG antibody against antigens in the basement membrane (type II hypersensitivity).
4. Dermatitis herpetiformis is an immunologic vesicular lesion characterized by the presence of IgA immune complexes (type III hypersensitivity) at the tips of the dermal papilla at the dermal/epidermal junction producing a subepidermal vesicle filled with neutrophils.
 - strong association with gluten-sensitive enteropathy, or celiac disease. 

Adult Respiratory Distress Syndrome 
A constellation of pathologic and clinical findings initiated by diffuse injury to alveolar capillaries. This syndrome is associated with a multitude of clinical conditions which primarily damage the lung or secondarily as part of a systemic disorder. 

Pathogenesis 
There are many types of injuries which lead to the ultimate, common pathway, i.e., damage to the alveolar capillary unit. The initial injury most frequently affects the endothelium, less frequently the alveolar epithelium. Injury produces increased vascular permeability, edema, fibrin-exudation (hyaline membranes). Leukocytes (primarily neutrophils) plays a key role in endothelial damage. 

Pathology 
Heavy, red lungs showing congestion and edema. The alveoli contain fluid and are lined by hyaline membranes. 

Pathophysiology 
Severe respiratory insufficiency with dyspnea, cyanosis and hypoxemia refractory to oxygen therapy.

Pleural effusion is a medical condition where fluid accumulates in the pleural cavity which surrounds the lungs, making it hard to breathe.

Four main types of fluids can accumulate in the pleural space:

Serous fluid (hydrothorax)

Blood (hemothorax)

Lipid (chylothorax)

Pus (pyothorax or empyema)

Causes:

Pleural effusion can result from reasons such as:

• Cancer, including lung cancer or breast cancer
• Infection such as pneumonia or tuberculosis
• Autoimmune disease such as lupus erythematosus
• Heart failure
• Bleeding, often due to chest trauma (hemothorax)
• Low oncotic pressure of the blood plasma
• lymphatic obstruction
• Accidental infusion of fluids

Congestive heart failure, bacterial pneumonia and lung cancer constitute the vast majority of causes in the developed countries, although tuberculosis is a common cause in the developing world.

Diagnosis:

1. Gram stain and culture - identifies bacterial infections
2. Cell count and differential - differentiates exudative from transudative effusions
3. Cytology - identifies cancer cells, may also identify some infective organisms
4. Chemical composition including protein, lactate dehydrogenase, amylase, pH and glucose - differentiates exudative from transudative effusions
5. Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins

Coccidioidomycosis (Valley Fever; San Joaquin Fever)

A disease caused by the fungus Coccidioides immitis, usually occurring in a primary form as an acute benign asymptomatic or self-limited respiratory infection, occasionally disseminating to cause focal lesions in skin, subcutaneous tissues, lymph nodes, bones, liver, kidneys, meninges, brain, or other tissues.

Primary coccidioidomycosis is usually asymptomatic, but nonspecific respiratory symptoms resembling influenza or acute bronchitis sometimes occur or, less often, acute pneumonia or pleural effusion. Symptoms, in decreasing order of frequency, include fever, cough, chest pain, chills, sputum production, sore throat, and hemoptysis.

Progressive disseminated coccidioidomycosis may develop a few weeks, months, or occasionally years after primary infections,, is more common in men than women and is more likely to occur in association with HIV infection, immunosuppressive therapy

Symptoms often are nonspecific, including low-grade fever, anorexia, weight loss, and weakness. Extensive pulmonary involvement may cause progressive cyanosis, dyspnea, and discharge of mucopurulent or bloody sputum. Extrapulmonary lesions are usually focal, involving one or more tissue sites in bones, joints, skin, subcutaneous tissues, viscera, brain, or meninges. Draining sinus tracts sometimes connect deeper lesions to the skin. Localized extrapulmonary lesions often become chronic and recur frequently, sometimes long after completion of seemingly successful antifungal therapy.

Neuroblastoma and Related Neoplasms
Neuroblastoma is the second most common solid malignancy of childhood after brain tumors, accounting for up to10% of all pediatric neoplasms. They are most common during the first 5 years of life. Neuroblastomas may occur anywhere along the sympathetic nervous system and occasionally within the brain. Most neuroblastomas are sporadic. Spontaneous regression and spontaneous- or therapy-induced maturation are their unique features.  

Gross features
- The adrenal medulla is the commonest site of neuroblastomas. The remainder occur along the sympathetic chain, mostly in the paravertebral region of the abdomen and posterior mediastinum. 
- They range in size from minute nodules to large masses weighing more than 1 kg. 
- Some tumors are delineated by a fibrous pseudo-capsule, but others invade surrounding structures, including the kidneys, renal vein, vena cava, and the aorta. 
- Sectioning shows soft, gray-tan, brain-like tissue. Areas of necrosis, cystic softening, and hemorrhage may be present in large tumors. 

Microscopic features
- Neuroblastomas are composed of small, primitive-appearing neuroblasts with dark nuclei & scant cytoplasm, g rowing in solid sheets.  
- The background consists of light pinkish fibrillary material corresponding to neuritic processes of the primitive cells. 
- Typically, rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with the fibrillary neurites.
- Supporting features include include immunochemical detection of neuron-specific enolase and ultrastructural demonstration of small, membrane-bound, cytoplasmic catecholamine-containing secretory granules.
- Some neoplasms show signs of maturation, either spontaneous or therapy-induced. Larger ganglion-like cells having more abundant cytoplasm with large vesicular nuclei and prominent nucleoli may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma). Further maturation leads to tumors containing many mature ganglion-like cells in the absence of residual neuroblasts (ganglioneuroma). 

Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient. Children below 1 year of age have a much more favorable outlook than do older children at a comparable stage of disease. 

Miscroscopic features are also an independent prognostic factor; evidence of gangliocytic differentiation is indicative of a "favorable" histology. Amplification of the MYCN oncogene in neuroblastomas is a molecular event that has profound impact on prognosis. The greater the number of copies, the worse is the prognosis. MYCN amplification is currently the most important genetic abnormality used in risk stratification of neuroblastic tumors. 

About 90% of neuroblastomas produce catecholamines (as pheochromocytomas), which are an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]).