General Path Flashcards
Hyperplasia
- Increase number of cells due to stimulus
- Physiologic hyperplasia
o Breast hyperplasia
o Liver regeneration
o Acute bleeding: EPO - Pathologic hyperplasia
o BPH
o Endometrial
Hypertrophy
- Increase in cell size, no increase in number of cells
- Physiological
o Uterus in pregnancy
o Muscles in bodybuilding - Pathologiical
o Cardiomyopathies
Atrophy
- Reduction in cell size and number due to loss of stimulus, leading to reduced cell size
- Pathologic
o Disuse
o Denervation
o Chronic ischaemia
o Poor nutrition - Physiologic
o Embryonic structures during fetal development
o Uterus after pregnancy
Metaplasia
- Reversible change in which one differentiated cell type is replaced by another type
- Examples
o Smokers – normal ciliated columnar epithelial to stratified squamous
o Barret – squamous to columnar metaplasia
o Connective tissue – myositis ossifcans
Necrosis
6 types:
Necrosis is a pathologic process that is the consequence of severe injury.
- Coagulative: related to ischaemia. Localised area is called infarct.
- Liquefactive: related to infections, brain infarct.
- Gangrenous: similar to coagulative necrosis but in limbs. When superimposed bacterial, wet gangrene
- Caseous: encountered in TB infection. Cheese like. Aggretation of inflmaation in macrophages and T llymphocytes surrounding leading to granumatous
- Fat: fat destruction, as seen in pancreatitis
- Fibrinoiid: vascular damage to blood vessels from immune complex reactions. vasculitis
Necrosis vs apoptosis
Apoptosis
- Controlled cell death. Serves to eliminate unwanted and irreparably damaged cells, with the least possible host reaction
- Physiologic:
The removal of supernumerary cells (in excess of the required number) during development
Involution of hormone-dependent tissues on hormone w drawal, such as endometrial cell breakdown during the menstrual cycle, ovarian follicular atresia in menopause, and regression of the lactating breast after weaning.
Elimination of potentially harmful self-reactive lymphocytes to prevent immune reactions against one’s own tissues - Pathologic
o DNA damage
o Misfolded protein accumulation
Abnormal deposits of materials in cells and tissues are the result of excessive intake or defective transport or catabolism.
- Lipids
o fatty change: excessive intake
o cholesterol deposition: as seen in atherosclerosis - Proteins
o Alpha1 antitrypsin
o Tau proteins - Glycogen
o Diabetes
o Liver, islet cells, renal tubular epithelium
o Glycogen storage disease - Pigments
o Silicosis
o Carbon
o Iron: haemochromatosis
- Dystrophic calcification
o Deposition of calcium at sites of cell injury and necrosis
- Metastatic calcification
o Deposition of calcium in normal tissues, caused by hypercalcemia (usually a consequence of parathyroid hormone excess)
o Hypercalacemia
1o PTH
Hypervitamin D
CRF
Due to cancers such as MM, bone mets, leukaemia
Acute vs chronic inflammation
Acute inflammation steps
(1) Vasodilation: dilation of small vessels leading to an increase in blood flow
(2) Increased permeability of the microvasculature: enabling plasma
(3) Adhesion and emigration of leukocytes through endothelium
(4) Chemotaxis: emigration of leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
- Vasodilation is induced by chemical mediators such as histamine (described later) and is the cause of erythema and increased blood flow.
- Increased vascular permeability is induced by histamine, kinins, and other mediators that produce gaps between endothelial cells and by direct or leukocyte-induced endothelial injury.
- Increased vascular permeability allows plasma proteins and leukocytes, the mediators of host defense, to enter sites of infection or tissue damage. Fluid leak from blood vessels results in edema.
- Lymphatic vessels and lymph nodes are also involved in inflammation and often show redness and swelling.
Chronic inflammation
- response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist in varying combinations.
Chronic inflammation is a prolonged host response to persistent stimuli.
- It is caused by microbes that resist elimination, immune responses against self antigens and environmental antigens, and some toxic substances (e.g., silica), and it underlies many medically important diseases.
- It is characterized by coexisting inflammation, tissue injury, and attempted repair by scarring.
- The cellular infiltrate consists of macrophages, lymphocytes, plasma cells, and other leukocytes.
- It is mediated by cytokines produced by macrophages and lymphocytes (notably T lymphocytes); bidirectional interactions between these cells tend to amplify and prolong the inflammatory reaction.
- Granulomatous inflammation is a pattern of chronic inflammation induced by T-cell and macrophage activation in response to an agent that is resistant to eradication.
REPAIR BY REGENERATION
The ability of tissues to repair themselves is determined, in part, by their intrinsic proliferative capacity and the presence of tissue stem cells. Based on these criteria, the tissues of the body are divided into three groups.
- Labile (continuously dividing) tissues. Cells of these tissues are continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature cells. Labile cells include hematopoietic cells in the bone marrow and the majority of surface epithelia, such as the stratified squamous epithelia of the skin, oral cavity, vagina, and cervix; the cuboidal epithelia of the ducts draining exocrine organs (e.g., salivary glands, pancreas, biliary tract); the columnar epithelium of the gastrointestinal tract, uterus, and fallopian tubes; and the transitional epithelium of the urinary tract. These tissues can readily regenerate after injury as long as the pool of stem cells is preserved.
- Stable tissues. Cells of these tissues are quiescent (in the G 0 stage of the cell cycle) and have only minimal proliferative activity in their normal state. However, these cells are capable of dividing in response to injury or loss of tissue mass. Stable cells constitute the parenchyma of most solid tissues, such as liver, kidney, and pancreas. They also include endothelial cells, fibroblasts, and smooth muscle cells; the proliferation of these cells is particularly important in wound healing. With the exception of liver, stable tissues have a limited capacity to regenerate after injury.
- Permanent tissues. The cells of these tissues are considered to be terminally differentiated and nonproliferative in postnatal life. The majority of neurons and cardiac muscle cells belong to this category. Thus, injury to the brain or heart is irreversible and results in a scar because neurons and cardiac myocytes cannot regenerate. Limited stem cell replication and differentiation occur in some areas of the adult brain, and there is some evidence that heart muscle cells may proliferate after myocardial necrosis. Nevertheless, whatever proliferative capacity may exist in these tissues, it is insufficient to produce tissue regeneration after injury. Skeletal muscle is usually classified as a permanent tissue, but satellite cells attached to the endomysial sheath provide some regenerative capacity for muscle. In permanent tissues, repair is typically dominated by scar formation.
REPAIR BY SCAR FORMATION
If repair cannot be accomplished by regeneration alone, it occurs by replacement of the injured cells with:
Repair of permanent tissue: eg cardiac post heart attack
- Tissues are repaired by replacement with connective tissue and scar formation if the injured tissue is not capable of proliferation or if the structural framework is damaged and cannot support regeneration.
- The main components of connective tissue repair are angiogenesis, migration and proliferation of fibroblasts, collagen synthesis, and connective tissue remodeling.
- Repair by connective tissue starts with the formation of granulation tissue and culminates in the laying down of fibrous tissue.
- Multiple growth factors stimulate the proliferation of the cell types involved in repair.
- TGF-β is a potent fibrogenic agent; ECM deposition depends on the balance between fibrogenic agents, metalloproteinases (MMPs) that digest ECM, and TIMPs.
Healing of Fractures
The reaction to a fracture begins with an organizing hematoma. Within 2 weeks, the two ends of the bone are bridged by a fibrin meshwork in which osteoclasts, osteoblasts, and chondrocytes differentiate from precursors. These cells produce cartilage and bone matrix, which, with adequate immobilization, remodels into normal lamellar bone.
