Chapter 2 High return facts
1 Cellular and tissue growth is a normal component of normal physiology. Complex intra- and intercellular signalling mechanisms control the rate and extent of growth. Many disease processes are characterized by alterations in the rate and control of cellular and tissue turnover. Defects in these normal control mechanisms may lead to disease states such as neoplasia.
2 There are several ways in which the constituents of the body can alter in size in association with a normal physiological mechanism or as part of a disease process. Cells and tissues may increase in size via hyperplasia or hypertrophy, while a decrease in size occurs via atrophy. Metaplasia is the process whereby differentiated (i.e. mature) cells change from one type to another. Cells die in two major mechanisms: apoptosis and necrosis.
3 Inflammation is a major component of the response to cellular and tissue injury. It is characterized by increased blood flow (redness and warmth: rubor and calor), swelling (tumor) and pain (dolor) within the affected area, as well as systemic effects including malaise and pyrexia.
4 Acute inflammation occurs during the early phase of a reaction to cellular/tissue damage. It is characterized histologically by the presence of acute inflammatory cells (neutrophils) within the affected tissue. Acute inflammation may resolve if the underlying stimulus is removed, or it may progress to chronic inflammation.
5 Acute inflammation occurs through the release of inflammatory mediators from damaged tissues and other cells. This leads to a combination of increased vascular permeability and chemotaxis: attraction of inflammatory cells to the area secondary to the release of chemicals from the site of inflammation.
6 Chronic inflammation may occur de novo or develop as a sequel to acute inflammation, especially if the source of cellular/tissue damage persists. It is characterized histologically by the presence of chronic inflammatory cells: lymphocytes, plasma cells and macrophages. Granulomatous inflammation is a special form of chronic inflammation characterized histologically by the presence of granulomas: localized collections of macrophages. Multinucleate giant cells may also be present. Causes of granulomatous inflammation include tuberculosis, fungal infections, tissue reactions to foreign material and specific diseases such as sarcoidosis and Crohn’s disease.
7 The resolution of inflammation is associated with organization of the inflammatory reaction: granulation tissue formation and myofibroblast proliferation. This is followed by a variable degree of collagen deposition (fibrous scarring). Collagen deposition is generally more pronounced if the inflammatory process has been prolonged.
8 A range of chemicals that are released from damaged tissues and inflammatory cells orchestrates the inflammatory process (e.g. histamine, prostaglandins, leukotrienes). Protein cascades originating within the plasma are also important in regulating the response to tissue injury (e.g. coagulation, fibrinolytic, complement and kinin cascades).
9 Cells and tissues may be damaged by a range of insults; these may be physical (trauma and extremes of heat), chemical (e.g. acid), neoplastic (e.g. cancers infiltrating adjacent tissue), infective (e.g. bacterial pneumonia), immune (e.g. autoimmune diseases such as rheumatoid arthritis) or iatrogenic (e.g. drugs causing gastric ulceration).
10 There are two major mechanisms by which cells can die. Apoptosis (programmed cell death) is an energy-requiring process leading to death of individual cells, which does not incite an inflammatory reaction. Apoptosis may be physiological or pathological in nature. Necrosis does not require energy, usually affects groups of cells and typically incites an inflammatory reaction—usually acute in nature.
11 Various degenerative processes can occur within cells and tissues as a result of disease states. For example, calcification may occur if the serum calcium concentration is chronically elevated (‘metastatic’ calcification) or within an abnormal tissue (e.g. a tumour or focus of chronic inflammation; ‘dystrophic’ calcification). Amyloid is an insoluble protein with a β-pleated sheet structure that is deposited either locally or in a widespread manner in various chronic disease states such as chronic inflammatory conditions (e.g. tuberculosis) or low-grade neoplasms of B-lymphocyte lineage (e.g. lymphoplasmacytic lymphoma). Other forms of degenerative change include glycogen accumulation, hyaline change and myxomatous change.
12 Haemosiderin is an iron-containing pigment that may be deposited in tissues following red cell destruction and haemoglobin breakdown (e.g. after a haemorrhage) or within organs such as the liver in genetic haemochromatosis. Lipofuscin is a wear-and-tear pigment that is deposited in organs such as the heart and liver. Melanin is produced by melanocytes in the skin and is commonly found in tumours showing melanocytic differentiation (e.g. malignant melanoma). Bilirubin is a bile pigment that accumulates in jaundice, either in conjugated or unconjugated form.
13 Shock is a clinical condition characterized by a fast pulse rate (usually > 100 beats/min) and a low blood pressure (systolic blood pressure usually < 100 mmHg). Common types of shock are hypovolaemic (low blood volume, e.g. in haemorrhage), cardiogenic (heart pump failure, e.g. in myocardial infarction) and septic (severe infection). Less common types are anaphylactic (type I hypersensitivity reaction, e.g. peanut allergy) and neurogenic (loss of sympathetic vasomotor tone, e.g. in a spinal cord injury).
14 Tissue injury is usually followed by haemostasis, an inflammatory response and tissue restructuring, with a variable degree of scarring. Factors impairing healing include old age, poor nutritional state, excessive tissue damage, poor apposition of the wound edges (or bony fragments after a fracture), the presence of foreign material, poor blood supply and infection.
15 Vasculitis is inflammation of blood vessel walls. It most commonly occurs as part of an autoimmune disease. Blood vessel wall inflammation may lead to leakage of blood from the vessel or to lumenal thrombosis and, therefore, to tissue ischaemia.
16 The body possesses many mechanisms that aim to protect against potentially injurious agents. These mechanisms may be behavioural, anatomical or immunological in nature.
17 Complex systems exist to protect the body from microorganisms. Some of these systems are innate and have a broad-based action while others are acquired and act more specifically. The functions of the immune system are carried out by immunoreactive cells circulating within the blood and present within tissues, as well as by circulating antibodies.
18 Autoimmune diseases occur when the immune system attacks ‘self’ cells and tissues; this is referred to as a breakdown of ‘immune tolerance’. This leads to inflammation and tissue damage, which may be highly localized (e.g. type 1 diabetes mellitus) or generalized (e.g. systemic lupus erythematosus) in nature.
19 Defects may occur within the immune system. These may be congenital (e.g. severe combined immunodeficiency) or acquired (e.g. reaction to chemotherapy, infection with the human immunodeficiency virus (HIV)) in nature. Such defects may affect a specific component of the immune system or have more widespread effects within several components. Defects usually lead to increased susceptibility to a range of infections.
20 Neoplasia means ‘new growth’ and indicates the presence of cells or tissues showing evidence of abnormally controlled or disordered growth. Neoplasms comprise cells that show differentiation along one or more pathways of development. Benign neoplasms expand locally but do not invade adjacent tissues or spread to distant sites, while the latter two features are characteristics of malignant neoplasms (‘cancers’).
21 Genetic and environmental factors influence the development of neoplasia. Most germline (i.e. inherited and present in all cells) genetic influences on neoplasm development are polygenic in nature, while a minority of neoplasms occur in association with a clearly defined inherited defect in a single gene. Neoplasms vary in their relative incidence between populations and different geographical areas, as a result of differences in gene pools and environmental contributors to disease development.
22 Neoplasm development is characterized by the accumulation of genetic defects within the neoplastic cells. In some neoplasms, this sequence is well characterized, while in others specific genetic mutations are found sufficiently commonly that their detection may be used to confirm the diagnosis of tissue type or to help to determine the likely biological behaviour of the neoplasm (i.e. how aggressively the neoplasm is likely to grow).
23 Benign tumours may compress adjacent tissue but do not invade it. Malignant tumours grow locally, infiltrate adjacent tissue and metastasize via lymphatic channels and blood vessels to distant sites.
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