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General Pathology

Urticaria (hives) refers to the presence of edema within the dermis and itchy elevations of the skin which may relate to either a Type I (MC) or Type III hypersensitivity reaction.

Type III hypersensitivity reaction.

 - exaggerated venular permeability MC related to IgE mediated disease and release of histamine from mast cells.

Cells Of  The Exudate

Granulocytes (Neutrophils, eosinophils, and basophils)

Monocytes (and tissue macrophages)

Lymphocytes

Neutrophils (polymorphs).

Characteristics

(1) Cell of acute inflammation.

(2) Actively motile.

(3) Phagocytic.

(4) Respond to chemotactic agents like.

Complement products.

Bacterial products.

Tissue breakdown

Lysosomal enzymes of other polymorphs

Functions

(1) Phagocytosis and intracellular digestion of bacteria.

(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.

Eosinophils

Characteristics

(I) Cell of allergjc and immunologic inflammation.

(2) Motile and phagocytic but less so than a neutrophil.

(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.

(4) Steroids cause depletion of eosinophils.

Functions

(1) Contain most of the lysosomal enzymes that polymorphs have

(2) control of Histamine release and degradation in inflammation

Basophils (and mast cells)

Characteristics

(1) Contain coarse metachromatic granules.

(2) Contain, histamine and proteolytic enzymes

Functions

Histamine: release which causes some of the changes of inflammation and allergic

reactions. .

Monocytes .

Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :

(a) Fixed phagocytic. cells:

  • Kuffer cell of liver.
  • Sinusoidal lining cells of spleen and lymph nodes.
  • Pleural and peritoneal macrophages
  • Alveolar macrophages.
  • Microglial cells.

(b) Wandering macrophages or tissue histiocytes.

The tissue histiocytes are derived from blood monocytes.

Characteristics

.(1)Seen in inflammation of some duration, as they -outlive polymorphs.

(2) Actively phagocytic and motile.

(3) Fuse readily to from giant cells in certain situations.

Function

(1) Phagocytosis.

(2) Lysosomal enzyme secretion.

(3) Site of synthesis of some components of complement.

(4) Antigen handling and processing before presenting it to the Immune  competent cell.

(5) Secretion of lysosyme and interferon.

Giant cells can be

(A) Physiological

Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.

(B) Pathological:

Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.

Langhan's type: a variant of foreign body giant cell seen in tuberculosis.

Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.

(iv) Aschoff cell in rheumatic carditis.

(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.

Lymphocytes and Plasma cells

These are the small mononuclear cell comprising the immune system

They are less motile than_macrophages and  neutrophils and are seen in chronic inflammation and immune based diseases.

Histopathological techniques

Histopathological examination studies tissues under the microscope. During this study, the pathologist looks for abnormal structures in the tissue. Tissues for histopathological examination are obtained by biopsy. Biopsy is a tissue sample from a living person to identify the disease. Biopsy can be either incisional or excisional.

Once the tissue is removed from the patient, it has to be immediately fixed by putting it into adequate amount of 10% Formaldehyde (10% formalin) before sending it to the pathologist.

The purpose of fixation is:

1. to prevent autolysis and bacterial decomposition and putrefaction

2. to coagulate the tissue to prevent loss of easily diffusible substances

3. to fortify the tissue against the deleterious effects of the various stages in the preparation of sections and tissue processing.

 4. to leave the tissues in a condition which facilitates differential staining with dyes and other reagents.

Metastatic Tumors 

These are the most common malignant tumor of bone. Certain tumors exhibit a distinct skeletal prediliction. In adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. In children, neuroblastoma, Wilms' tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the common sources of bony metastases. Most metastases involve the axial skeleton (vertebral column, pelvis, ribs, skull, sternum), proximal femur, and humerus. The radiologic appearance of metastases can be purely osteolytic, purely osteoblastic, or mixed osteolytic-osteoblastic (majority of cases). In lytic lesions (e.g., kidney& lung), the metastatic cells secrete substances such as prostaglandins, interleukins, etc. that stimulate osteoclastic bone resorption; the tumor cells themselves do not directly resorb bone. Similarly, metastases that elicit a blastic response (e.g., prostate adenocarcinoma) do so by stimulating osteoblastic bone formation.

Erythema nodosum is the MCC of inflammation of subcutaneous fat (panniculitis).
 - it may be associated with tuberculosis, leprosy, certain drugs (sulfonamides), and is commonly a harbinger of coccidioidomycosis and sarcoidosis.
 - commonly presents on the lower extremities with exquisitely tender, raised erythematous plaques and nodules.
 - self-limited disease.

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.

Achrondroplasia 
is a major cause of dwarfism. The underlying etiology is a point mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferation, which is associated with suppression of the normal epiphyseal growth plate expansion. Thus, long bone growth is markedly shortened.
The most conspicuous changes include disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic posture. 

Microscopically, the cartilage growth plates are disorganized and hypoplastic. 

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