Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

Cartilage-Forming Tumors

1. Osteochondroma (Exostosis) is a relatively common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood (male-to-female ratio of 3:1); multiple osteochondromas become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder. Inactivation of both copies of the EXT gene (a tumor suppressor gne) in chondrocytes is implicated in both sporadic and hereditary osteochondromas. Osteochondromas develop only in bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones, especially about the knee. They tend to stop growing once the normal growth of the skeleton is completed. Occasionally they develop from flat bones (pelvis, scapula, and ribs). Rarely, exostoses involve the short tubular bones of hands and feet.

Pathological features

• Osteochondromas vary from 1-20cm in size.
• The cap is benign hyaline cartilage. 
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with cortex of the host bone.
Osteochondromas are slow-growing masses that may be painful. Osteochondromas rarely progress to chondrosarcoma or other sarcoma, although patients with the multiple hereditary exostoses are at increased risk of malignant transformation. 

2. Chondroma 

It is a benign tumor of hyaline cartilage. When it arises within the medullary cavity, it is termed enchondroma; when on the bone surface it is called juxtacortical chondroma. Enchondromas are usually diagnosed in persons between ages 20 and 50 years; they are typically solitary and located in the metaphyseal region of tubular bones, the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas preferentially involving one side of the body. Chondromas probably develop from slowly proliferating rests of growth plate cartilage.

Pathological features 

• Enchondromas are gray-blue, translucent nodules usually smaller than 3 cm.
• Microscopically, there is well-circumscribed hyaline matrix and cytologically benign chondrocytes.
Most enchondromas are detected as incidental findings; occasionally they are painful or cause pathologic fractures. Solitary chondromas rarely undergo malignant transformation, but those associated with enchondromatosis are at increased risk. 

3. Chondrosarcomas are malignant tumors of cartilage forming tissues. They are divided into conventional chondrosarcomas and chondrosarcoma variants. Each of these categories comprises several distinct types, some defined on microscopic grounds & others on the basis of location within the affected bone, for e.g. they are divided into central (medullary), peripheral (cortical), and juxtacortical (periosteal). The common denominator of chondrosarcoma is the production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells (cf osteosarcoma). Chondrosarcomas occur roughly half as frequently as osteosarcomas; most patients age 40 years or more, with men affected twice as frequently as women 

Pathological features 
Conventional chondrosarcomas arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex. They exhibit malignant hyaline or myxoid stroma. Spotty calcifications are typically present. The tumor grows with broad pushing fronts into marrow spaces and the surrounding soft tissue. Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity. Low-grade tumors resemble normal cartilage. Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes. Dedifferentiated chondrosarcomas refers to the presence of a poorly differentiated sarcomatous component at the periphery of an otherwise typical low-grade chondrosarcoma. Other histologic variants include myxoid, clear-cell and mesenchymal chondrosarcomas. Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs. A slowly growing lowgrade tumor causes reactive thickening of the cortex, whereas a more aggressive high-grade neoplasm destroys the cortex and forms a soft tissue mass. There is also a direct correlation between grade and biologic behavior. 
Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors. High-grade Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.

Thalassaemia. Genetic based defect in synthesis of one of the normal chains.

Beta thalassaemia --->  reduced Hb A and increased HbF (α2, Y2) HBA2(α2)

Alpha thalassaemia  --->   reduced  Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.

Features:
•    Microcytic hypochromic RBC is in iron deficjency.
•    Marked anisopoikilocytsis  with prominent target cells.
•    Reticulocytosis and nucleated RBC seen.
•    Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
•    Decreased osmotic. fragility.
•    Increased marrow iron (important difference from iron deficiency anaemia).
•    Haemosiderosis, especially with repeated transfusions.

Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).

PNEUMONIAS  

Pneumonia is defined as acute inflammation of the lung parenchyma distal to the terminal bronchioles which consist of the respiratory bronchiole, alveolar ducts, alveolar sacs and alveoli. The terms 'pneumonia' and 'pneumonitis' are often used synonymously for inflammation of the lungs, while 'consolidation' (meaning solidification) is the term used for macroscopic and radiologic appearance of the lungs in pneumonia.

 PATHOGENESIS. 
 The microorganisms gain entry into the lungs by one of the following four routes: 
 1. Inhalation of the microbes. 
 2. Aspiration of organisms. 
 3. Haematogenous spread from a distant focus. 
 4.  Direct spread from an adjoining site of infection.

Failure of defense mechanisms and presence of certain predisposing factors result in pneumonias. 
 
 These conditions are as under: 
 1. Altered consciousness. 
 2. Depressed cough and glottic reflexes. 
 3. Impaired mucociliary transport. 
 4. Impaired alveolar macrophage function. 
 5. Endobronchial obstruction. 
 6. Leucocyte dysfunctions. 
 
 
 CLASSIFICATION. On the basis of the anatomic part of the lung parenchyma involved, pneumonias are traditionally classified into 3 main types: 
 
 1. Lobar pneumonia. 
 2. Bronchopneumonia (or Lobular pneumonia). 
 3. Interstitial pneumonia. 
 
BACTERIAL PNEUMONIA  

Bacterial infection of the lung parenchyma is the most common cause of pneumonia or consolidation of one or both the lungs. Two types of acute bacterial pneumonias are distinguished—lobar pneumonia and broncho-lobular pneumonia, each with distinct etiologic agent and morphologic changes. 
 
  1.    Lobar Pneumonia  
 Lobar pneumonia is an acute bacterial infection of a part of a lobe, the entire lobe, or even two lobes of one or both the lungs. 
 
 ETIOLOGY. 
 Following types are described: 
 1.  Pneumococcal pneumonia. More than 90% of all lobar pneumonias are caused by Streptococcus pneumoniae, a lancet-shaped diplococcus. Out of various types, type 3-S. pneumoniae causes particularly virulent form of lobar pneumonia. 
 
 2. Staphylococcal pneumonia. Staphylococcus aureus causes pneumonia by haematogenous spread of infection. 
 
 3.  Streptococcal pneumonia, β-haemolytic streptococci may rarely cause pneumonia such as in children after measles or influenza. 
 
 4.  Pneumonia by gram-negative aerobic bacteria. Less common causes of lobar pneumonia are gram-negative bacteria like Haemophilus influenzae, Klebsiella pneumoniae (Friedlander's bacillus), Pseudomonas, Proteus and Escherichia coli. 
 
 MORPHOLOGY. Laennec's original description divides lobar pneumonia into 4 sequential pathologic phases: 
 
 1.   STAGE OF CONGESTION: INITIAL PHASE 
 The initial phase represents the early acute inflammatory response to bacterial infection and lasts for 1 to 2 days. 
 
The affected lobe is enlarged, heavy, dark red and congested. Cut surface exudes blood-stained frothy fluid. 
 
Microscopic Examination 
 i) Dilatation and congestion of the capillaries in the alveolar walls. 
 ii)   Pale eosinophilic oedema fluid in the air spaces.
 iii)  A few red cells and neutrophils in the intra-alveolar fluid. 
 iv) Numerous bacteria demonstrated in the alveolar fluid by Gram's staining. 
 
  2.   RED HEPATISATION: EARLY CONSOLIDATION  
 This phase lasts for2 to 4 days. The term hepatisation in pneumonia refers to liver-like consistency of the affected lobe on cut section. 
 
 The affected lobe is red, firm and consolidated. The cut surface of the involved lobe is airless, red-pink, dry, granular and has liver-like consistency. 
 
Microscopic Examination   
 i) The oedema fluid of the preceding stage is replaced by strands of fibrin. 
 ii)   There is marked cellular exudate of neutrophils and extravasation of red cells. 
 iii)  Many neutrophils show ingested bacteria. 
 iv) The alveolar septa are less prominent than in the first stage due to cellular exudation. 
 
 3.   GREY HEPATISATION: LATE CONSOLIDATION This phase lasts for4 to 8 days. 
The affected lobe Is firm and heavy. The cut surface is dry, granular and grey in appearance with liver-like consistency. The change in colour from red to grey begins at the hilum and spreads towards the periphery. Fibrinous pleurisy is prominent. 
 
Microscopic Examination   
 i) The fibrin strands are dense and more numerous. 
 ii)   The cellular exudate of neutrophils is reduced due to disintegration of many inflammatory cells. The red cells are also fewer. The macrophages begin to appear in the exudate. 
 iii) The cellular exudate is often separated from the septal walls by a thin clear space. 
 iv) The organisms are less numerous and appear as degenerated forms. 
 
  COMPLICATIONS. Since the advent of antibiotics, serious complications of lobar pneumonia are uncommon. However, they may develop in neglected cases and in patients with impaired immunologic defenses.

 These are as under: 
 1.  Organisation. In about 3% of cases, resolution of the exudate does not occur but instead it is organised. There is ingrowth of fibroblasts from the alveolar septa resulting in fibrosed, tough, airless leathery lung tissue. 
 2.  Pleural effusion. About 5% of treated cases of lobar pneumonia develop inflammation of the pleura with effusion. 
 3.   Empyema. Less than 1% of treated cases of lobar pneumonia develop encysted pus in the pleural cavity termed empyema. 
 4.   Lung abscess. A rare complication of lobar pneumonia is formation of lung abscess. 
 5.   Metastatic infection. Occasionally, infection in the lungs and pleural cavity in lobar pneumonia may extend into the pericardium and the heart causing purulent pericarditis, bacterial endocarditis and myocarditis. 
 
 
 CLINICAL FEATURES. The major symptoms are: shaking chills, fever, malaise with pleuritic chest pain, dyspnoea and cough with expectoration which may be mucoid, purulent or even bloody. The common physical findings are fever, tachycardia, and tachypnoea, and sometimes cyanosis if the patient is severely hypoxaemic. There is generally a marked neutrophilic leucocytosis. Blood cultures are positive in about 30% of cases. Chest radiograph may reveal consolidation. 
 
 II.   Bronchopneumonia (Lobular Pneumonia)  
  Bronchopneumonia or lobular pneumonia is infection of the terminal bronchioles that extends into the surrounding alveoli resulting in patchy consolidation of the lung. The condition is particularly frequent at extremes of life (i.e. in infancy and old age), as a terminal event in chronic debilitating diseases and as a secondary infection following viral respiratory infections such as influenza, measles etc, 
 
  ETIOLOGY.

The common organisms responsible for bronchopneumonia are staphylococci, streptococci, pneumococci, Klebsiella pneumoniae, Haemophilus influenzae, and gram-negative bacilli like Pseudomonas and coliform bacteria. 
 
 Bronchopneumonia is identified by patchy areas of red or grey consolidation affecting one or more lobes, frequently found bilaterally and more often involving the lower zones of the lungs due to gravitation of the secretions. On cut surface, these patchy consolidated lesions are dry, granular, firm, red or grey in colour, 3 to 4 cm in diameter, slightly elevated over the surface and are often centred around a bronchiole. These patchy areas are best picked up by passing the fingertips on the cut surface. 
 
Microscopic Examination 

i) Acute bronchiolitis, ii) Suppurative exudate, consisting chiefly of neutrophils, in the peribronchiolar alveoli, iii) Thickening of the alveolar septa by congested capillaries and leucocytic infiltration, iv) Less involved alveoli contain oedema fluid. 
 
 COMPLICATIONS. 
 
 The complications of lobar pneumonia may occur in bronchopneumonia as well. However, complete resolution of bronchopneumonia is uncommon. There is generally some degree of destruction of the bronchioles resulting in foci of bronchiolar fibrosis that may eventually cause bronchiectasis.
 
 CLINICAL FEATURES. The patients of bronchopneumonia are generally infants or elderly individuals. There may be history of preceding bed-ridden illness, chronic debility, aspiration of gastric contents or upper respiratory infection. 
 
  VIRAL AND MYCOPLASMAL PNEUMONIA (PRIMARY ATYPICAL PNEUMONIA)  
 
 Viral and mycoplasmal pneumonia is characterised by patchy inflammatory changes, largely confined to interstitial tissue of the lungs, without any alveolar exudate. Other terms used for these respiratory tract infections are interstitial pneumonitis, reflecting the interstitial location of the inflammation, andprimary atypical pneumonia, atypicality being the absence of alveolar exudate commonly present in other pneumonias. Interstitial pneumonitis may occur in all ages. 
 
ETIOLOGY. Interstitial pneumonitis is caused by a wide variety of agents, the most common being respiratory syncytial virus (RSV). Others are Mycoplasma pneumoniae and  many viruses such as influenza and parainfluenza viruses, adenoviruses, rhinoviruses, coxsackieviruses and cytomegaloviruses (CMV). 
 
 Depending upon the severity of infection, the involvement may be patchy to massive and widespread consolidation of one or both the lungs. The lungs are heavy, congested and subcrepitant. Sectioned surface of the lung exudes small amount of frothy or bloody fluid. 
  
Microscopic Examination 

 I) Interstitial Inflammation: There is thickening of alveolar walls due to congestion, oedema and mononuclear inflammatory infiltrate comprised by lymphocytes, macrophages and some plasma cells. illness, chronic debility, aspiration of gastric contents or upper respiratory infection.
 ii)  Necrotising bronchiolitis: This is characterised by foci of necrosis of the bronchiolar epithelium, inspissated secretions in the lumina and mononuclear infiltrate in the walls and lumina. 
 
 iii) Reactive changes: The lining epithelial cells of the bronchioles and alveoli proliferate in the presence of virus and may form multinucleate giant cells and syncytia in the bronchiolar and alveolar walls. 
 
 iv) Alveolar changes: In severe cases, the alveolar lumina may contain oedema fluid, fibrin, scanty inflammatory exudate and coating of alveolar walls by pink, hyaline membrane similar to the one seen in respiratory distress syndrome. 
 
 COMPLICATIONS. 
 
 The major complication of interstitial pneumonitis is superimposed bacterial infection and its complications. Most cases of interstitial pneumonitis recover completely.
 
 CLINICAL FEATURES. 
 
 Majority of cases of interstitial pneumonitis initially have upper respiratory symptoms with fever, headache and muscle-aches. A few days later appears dry, hacking, non-productive cough with retrosternal burning due to tracheitis and bronchitis. Chest radiograph may show patchy or diffuse consolidation.  
 
  C. OTHERTYPES OF PNEUMONIAS  
 
 I.     Pneumocystis carinii Pneumonia  
 
 Pneumocystis carinii, a protozoon widespread in the environment, causes pneumonia by inhalation of the organisms as an opportunistic infection in neonates and immunosuppressed people. Almost 100% cases of AIDS develop opportunistic infection, most commonly Pneumocystis carinii pneumonia. 
 
 II.     Legionella Pneumonia 

 Legionella pneumonia or legionnaire's disease is an epidemic illness caused by gramnegative bacilli, Legionella pneumophila that thrives in aquatic environment. It was first recognised following investigation into high mortality among those attending American Legion Convention in Philadelphia in July 1976. The epidemic occurs in summer months by spread of organisms through contaminated drinking water or in air-conditioning cooling towers. Impaired host defenses in the form of immunodeficiency, corticosteroid therapy, old age and cigarette smoking play important roles. 
 
 III. Aspiration (Inhalation) Pneumonia  
 
 Aspiration or inhalation pneumonia results from inhaling different agents into the lungs. These substances include food, gastric contents, foreign body and infected material from oral cavity. A number of factors predispose to inhalation pneumonia which include: unconsciousness, drunkenness, neurological disorders affecting swallowing, drowning, necrotic oropharyngeal tumours, in premature infants and congenital tracheo-oesophageal fistula. 
 
 1.   Aspiration of small amount of sterile foreign matter such as acidic gastric contents produce chemical pneumonitis. It is characterised by haemorrhagic pulmonary oedema with presence of particles in the bronchioles. 
 
 2.    Non-sterile aspirate causes widespread bronchopneumonia with multiple areas of necrosis and suppuration. 
 
IV. Hypostatic Pneumonia 

 Hypostatic pneumonia is the term used for collection of oedema fluid and secretions in the dependent parts of the lungs in severely debilitated, bedridden patients. The accumulated fluid in the basal zone and posterior part of lungs gets infected by bacteria from the upper respiratory tract and sets in bacterial pneumonia.

 V. Lipid Pneumonia  Another variety of noninfective pneumonia is lipid pneumonia. It is of 2 types: 
 
 1.   Exogenous lipid pneumonia. This is caused by aspiration of a variety of oily materials. These are: inhalation of oily nasal drops, regurgitation of oily medicines from stomach (e.g. liquid paraffin), administration of oily vitamin preparation to reluctant children or to debilitated old patients. 
 
 2.   Endogenous lipid pneumonia. Endogenous origin of lipids causing pneumonic consolidation is more common. The sources of origin are tissue breakdown following obstruction to airways e.g. obstruction by bronchogenic cancer, tuberculosis and bronchiectasis. 

Osteogenesis Imperfecta (OI) (Brittle bone diseases) 

It is a group of hereditary disorders caused by gene mutations that eventuate in defective synthesis of and thus premature degradation of type I collagen. The fundamental abnormality in all forms of OI is too little bone, resulting in extreme susceptibility to fractures. The bones show marked cortical thinning and attenuation of trabeculae. 

Extraskeletal manifestations also occur because type I collagen is a major component of extracellular matrix in other parts of the body. The classic finding of blue sclerae  is attributable to decreased scleral collagen content; this causes a relative transparency that allows the underlying choroid to be seen. Hearing loss can be related to conduction defects in the middle and inner ear bones, and small misshapen teeth are a result of dentin deficiency 

Hepatitis

Hepatitis viruses—this group of viruses causes hepatitis, a disease affecting the liver.
1. General characteristics of hepatitis.
a. The general presentation of hepatitis is the same regardless of the infecting virus; however, the time and severity of symptoms may differ.
b. Symptoms of hepatitis include fever, anorexia, malaise, nausea, jaundice, and brown-colored urine.
c. Complications of a hepatitis infection include cirrhosis, liver failure, and hepatorenal failure.