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).

Pathology

The branch of medicine dealing with the essential nature of disease, especially changes in body tissues aorgans that cause or are caused by disease. Pathology is the structural and functional manifestations of disease.

Anatomic pathology  the anatomical study of changes in the function, structure, or appearance of organs or tissues,including postmortem examinations and the study of biopsy specimens.

Cellular pathology  - Cytopathology is a diagnostic technique that examines cells from various body sites to determine the cause or the nature of disease.

Clinical pathology  pathology applied to the solution of clinical problems, especially the use of laboratory 

methods inclinical diagnosis.

Comparative pathology  that which considers human disease processes in comparison with those of other 

animals.

Oral pathology  that treating of conditions causing or resulting from morbid anatomic or functional changes in thestructures of the mouth.

Surgical pathology  the pathology of disease processes that are surgically accessible for diagnosis or treatment.

Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a phenotypic marker for an insulin-receptor abnormality as well as a marker for adenocarcinoma, most commonly of gastric origin.

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. 

Osteoporosis
 
is characterized by increased porosity of the skeleton resulting from reduced bone mass. The disorder may be localized to a certain bone (s), as in disuse osteoporosis of a limb, or generalized involving the entire skeleton. Generalized osteoporosis may be primary, or secondary

Primary generalized osteoporosis
• Postmenopausal
• Senile
Secondary generalized osteoporosis

A. Endocrine disorders
• Hyperparathyroidism
• Hypo or hyperthyroidism
• Others

B. Neoplasia
• Multiple myeloma
• Carcinomatosis 

C. Gastrointestinal disorders
• Malnutrition & malabsorption
• Vit D & C deficiency
• Hepatic insufficiency 

D. Drugs
• Corticosteroids
• Anticoagulants
• Chemotherapy
• Alcohol 

E. Miscellaneous
• osteogenesis imperfecta
• immobilization
• pulmonary disease 

Senile and postmenopausal osteoporosis are the most common forms. In the fourth decade in both sexes, bone resorption begins to overrun bone deposition. Such losses generally occur in areas containing abundant cancelloues bone such as the vertebrae & femoral neck. The postmenopausal state accelerates the rate of loss; that is why females are more susceptible to osteoporosis and its complications. 

Gross features
• Because of bone loss, the bony trabeculae are thinner and more widely separated than usual. This leads to obvious porosity of otherwise spongy cancellous bones

Microscopic features
• There is thinning of the trabeculae and widening of Haversian canals.
• The mineral content of the thinned bone is normal, and thus there is no alteration in the ratio of minerals to protein matrix

Etiology & Pathogenesis

• Osteoporosis involves an imbalance of bone formation, bone resorption, & regulation of osteoclast activation. It occurs when the balance tilts in favor of resorption.
• Osteoclasts (as macrophages) bear receptors (called RANK receptors) that when stimulated activate the nuclear factor (NFκB) transcriptional pathway. RANK ligand synthesized by bone stromal cells and osteoblasts activates RANK. RANK activation converts macrophages into bone-crunching osteoclasts and is therefore a major stimulus for bone resorption.
• Osteoprotegerin (OPG) is a receptor secreted by osteoblasts and stromal cells, which can bind RANK ligand and by doing so makes the ligand unavailable to activate RANK, thus limiting osteoclast bone-resorbing activity.
• Dysregulation of RANK, RANK ligand, and OPG interactions seems to be a major contributor in the pathogenesis of osteoporosis. Such dysregulation can occur for a variety of reasons, including aging and estrogen deficiency.
• Influence of age: with increasing age, osteoblasts synthetic activity of bone matrix progressively diminished in the face of fully active osteoclasts.
• The hypoestrogenic effects: the decline in estrogen levels associated with menopause correlates with an annual decline of as much as 2% of cortical bone and 9% of cancellous bone. The hypoestrogenic effects are attributable in part to augmented cytokine production (especially interleukin-1 and TNF). These translate into increased RANK-RANK ligand activity and diminished OPG.
• Physical activity: reduced physical activity increases bone loss. This effect is obvious in an immobilized limb, but also occurs diffusely with decreased physical activity in older individuals.
• Genetic factors: these influence vitamin D receptors efficiency, calcium uptake, or PTH synthesis and responses.
• Calcium nutritional insufficiency: the majority of adolescent girls (but not boys) have insufficient dietary intake of calcium. As a result, they do not achieve the maximal peak bone mass, and are therefore likely to develop clinically significant osteoporosis at an earlier age.
• Secondary causes of osteoporosis: these include prolonged glucocorticoid therapy (increases bone resorption and reduce bone synthesis.)
The clinical outcome of osteoporosis depends on which bones are involved. Thoracic and lumbar vertebral fractures are extremely common, and produce loss of height and various deformities, including kyphoscoliosis that can compromise respiratory function. Pulmonary embolism and pneumonia are common complications of fractures of the femoral neck, pelvis, or spine. 

Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
 - genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
 - the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
 - the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
 - the characteristic histologic features of psoriasis include:
 - hyperkeratosis
 - absence of the granulosa cells (present in lichen planus).
 - parakeratosis
 - regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
 - characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
 - 7% develop HLA B27 positive psoriatic arthritis