Chronic myelocytic leukaemia
Commoner in adults (except the Juvenile type)

Features:

- Anaemia.
- Massive splenomegaly
- Bleeding tendencies.
- Sternal tenderness.
- Gout and skin manifestations

Blood picture:

- Marked leucocytosis of 50,-1000,000 cu.mm, often more
- Immature cells of the series with 20-50 % myelocytes
- Blasts form upto 5-10% of cells
- Basophils may be increased
- Leuocyte alkaline phosphate is reduced
- Anaemia with reticutosis and nucleated RBC
- Platelets initially high levels may fall later if patient goes into blast crisis.

Bone marrow:
- Hyper cellular marrow.
- Myeloid hyperplasia with more of immature forms, persominatly myelocytes.

Chromosomal finding. Philadelphia (Phi) chromosome is positive adult cases .It is a short chromosome due to deletion  of long arm of chromosome 22 (translocated to no.9),

Juvenile type :- This is Ph1 negative  has more nodal enlargement and has a worse prognosis, with a greater proneness to infections and haemorrhage
 

Multiple myeloma.

Blood picture:

- Marked rouleaux formation.
- Normpcytic normochromic anaemia.
- There may be leucopenia or leucoery!hrohlastic reaction.
- Atypical plasma cells may be seen in some patients
- Raised ESR
- Monoclonal hypergammaglobulinaemia 
- If light chains are produced in excess, they are excreted in urine as bence jones protein

Bone marrow

- Hyper cellular
- Plasma cells from at least 15 – 30% atypical forms and myeloma cells are seen.
 

Hyperparathyroidism 

Abnormally high levels of parathyroid hormone (PTH) cause hypercalcemia. This can result from either primary or secondary causes. Primary hyperparathyroidism is caused usually by a parathyroid adenoma, which is associated with autonomous PTH secretion. Secondary  hyperparathyroidism, on the other hand, can occur in the setting of chronic renal failure. In either situation, the presence of excessive amounts of this hormone leads to significant skeletal changes related to a persistently exuberant osteoclast activity that is associated with increased bone resorption and calcium mobilization. The entire skeleton is affected. PTH is directly responsible for the bone changes seen in primary hyperparathyroidism, but in secondary hyperparathyroidism additional influences also contribute. In chronic renal failure there is inadequate 1,25- (OH)2-D synthesis that ultimately affects gastrointestinal calcium absorption. The hyperphosphatemia of renal
failure also suppresses renal α1-hydroxylase, which further impair vitamin D synthesis; all these eventuate in hypocalcemia, which stimulates excessive secretion of PTH by the parathyroid glands, & hence elevation in PTH serum levels. 

Gross features
• There is increased osteoclastic activity, with bone resorption. Cortical and trabecular bone are lost and replaced by loose connective tissue. 
• Bone resorption is especially pronounced in the subperiosteal regions and produces characteristic radiographic changes, best seen along the radial aspect of the middle phalanges of the second and third fingers.

Microscopical features

• There is increased numbers of osteoclasts and accompanying erosion of bone surfaces.
• The marrow space contains increased amounts of loose fibrovascular tissue.
• Hemosiderin deposits are present, reflecting episodes of hemorrhage resulting from microfractures of the weakened bone.
• In some instances, collections of osteoclasts, reactive giant cells, and hemorrhagic debris form a distinct mass, termed "brown tumor of hyperparathyroidism". Cystic change is common in such lesions (hence the name osteitis fibrosa cystica). Patients with hyperparathyroidism have reduced bone mass, and hence are increasingly susceptible to fractures and bone deformities.

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. 

Haemolysis due to drugs and chemicals

This can be caused by :

1. Direct toxic action.
    -> Naphthalene.
    -> Nitrobenzene.
    -> Phenacetin.
    -> Lead.

Heinz bodies are seen in abundance.

2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be : 
    -> Drug induced  autoantibody haemolysis, Antibodies are directed against RBC.
    -> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.
 

Pathology gives explanations of a disease by studying the following four aspects of the disease.

1. Etiology,

2. Pathogenesis,

3. Morphologic changes and

4. Functional derangements and clinical significance.

1. Etiology Etiology of a disease means the cause of the disease. If the cause of a disease is known it is called primary etiology. If the cause of the disease is unknown it is called idiopathic. Knowledge or discovery of the primary cause remains the backbone on which a diagnosis can be made, a disease understood, & a treatment developed. There are two major classes of etiologic factors: genetic and acquired (infectious, nutritional, chemical, physical, etc).

2. Pathogenesis Pathogenesis means the mechanism through which the cause operates to produce the pathological and clinical manifestations. The pathogenetic mechanisms could take place in the latent or incubation period. Pathogenesis leads to morphologic changes.

3. Morphologic changes The morphologic changes refer to the structural alterations in cells or tissues that occur following the pathogenetic mechanisms. The structural changes in the organ can be seen with the naked eye or they may only be seen under the microscope. Those changes that can be seen with the naked eye are called gross morphologic changes & those that are seen under the microscope are called microscopic changes. the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease.

4. Functional derangements and clinical significance The morphologic changes in the organ influence the normal function of the organ. By doing so, they determine the clinical features (symptoms and signs), course, and prognosis of the disease.