4 Cellular Adaptation & Inflammation

• Adaptations are are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
• Physiologic adaptations represents responses of cells to normal stimulation by hormones or endogenous chemical mediators, or to the demands of mechanical stress
• Pathologic adaptations responses to stress that allow cells to modulate their structure and function and thus escape injury, but at the expense of normal function
• 4 Forms of adaptation (HHAM):

  • Hypertrophy
  • Hyperplasia
  • Atrophy
  • Metaplasia
• An adaptation to stress such as hypertrophy can progress to functionally significant cell injury if the stress is not relieved
• Hyperplasia is an increase in number of cells in an organ that stems from increased proliferation, either of differentiated cells or, in some instances, less differentiated progenitor cells; it is due to proliferative actions of growth factor, and/or stem cells.
• Physiologic hypertrophy:

  • bulging muscles of bodybuilders
  • estrogen-induced enlargement of uterus during pregnancy

  Pathologic:

  • cardiac enlargement that occurs with hypertension or aortic valve disease
• Physiologic hyperplasia:

  • Hormonal → proliferation of the glandular epithelium of the female breast at puberty and during pregnancy
  • Compensatory → residual tissue grows after removal or loss of part of an organ

  Pathologic:

  • Excess Hormonal Stimulation → Increased Estrogen ► Endometrial hyperplasia = abnormal menstrual bleeding.
  • Excess Growth Hormone Stimulation → Papillomavirus mucosal lesions
• The hyperplastic process remains controlled if the signals that initiate it abate, the hyperplasia disappears.
• Atrophy is a shrinkage in the size of cells by the loss of cell substance; causes the cells to have diminished functions, but is not dead.
• Cellular atrophy results from a combination of decreased protein synthesis and increased protein degradation.
• Physiologic atrophy:

  • in puberty when the thymus and the lymphoid organs decrease in size.
• Pathologic atrophy types:

  • Atrophy of disuse → decreased workload, diminished function of organ
  • Vascular → diminished blood supply
  • Starvation → inadequate nutrition of cell
  • Loss of endocrine stimulation → decrease of regulating hormones
  • Pressure → as in growth of tumors
  • Exhaustion → increase in metabolism resulting to increase of metabolites and loss of the actual cell space
• Metaplasia is a change in which one adult cell type epithelial or mesenchymal is replaced by another adult cell type; it is due to reprogramming of existing stem cells in normal tissue, or of undifferentiated mesenchymal cells in order to withstand adverse environment.
• Examples of metaplasia:

  • Barrett esophagus → where a squamous cells of esophagus are replaced by intestinal-like columnar cells in response to refluxed acid.
  • Habitual cigarette smokers → where ciliated columnar cells of trachea and bronchi are replaced by stratified squamous cells.
• The influences that induce metaplastic change in an epithelium, if persistent, may predispose to malignant transformation
• Abnormal deposits of materials in cells and tissues are the result of excessive intake or defective transport or catabolism.
• Fatty change or steatosis is an accumulation of free triglycerides in cells, resulting from excessive intake or defective transport; manifestation of reversible cell injury.
• Cholesterol deposition is a result of defective catabolism and excessive intake; seen in macrophages and smooth muscle cells of vessel walls in atherosclerosis.
• Deposition of Glycogen happens in macrophages of patients with defects in lysosomal enzymes that break down glycogen
• Lipofuscin or the “wear-and-tear pigment”; insoluble brownish-yellow granular intracellular material that accumulates in a variety of tissues (particularly the heart, liver, and brain) with aging or atrophy.
• Melanin is an endogenous, brown-black pigment that is synthesized by melanocytes located in the epidermis and acts as a screen against harmful 8V radiation; adjacent basal keratinocytes in the skin can accumulate the pigment
• Hemosiderin is a hemoglobin-derived granular pigment that is golden yellow to brown and accumulates in tissues when there is a local or systemic excess of iron.
• Dystrophic calcification is a deposition of calcium at sites of cell injury and necrosis.
• Metastatic calcification is a deposition of calcium in normal tissues, caused by hypercalcemia
• Inflammation is a response of vascularized tissues to infections and tissue damage that brings cells and molecules of host defense from circulation to the sites where they are needed, to eliminate the offending agents.
• Mediators of defense in inflammation includes (PAC):

  • Phagocytic leukocytes
  • Antibodies
  • Complement proteins
• 5 cardinal signs of inflammation:

  • Rubor – redness; caused by hyperemia.
  • Calor – heat; also caused by hyperemia.
  • Tumor – swelling; caused by fluid exudation and hyperemia.
  • Dolor – pain; resulting from release of bradykinin and PGE2.
  • Functio laesa – loss of function; caused by the combined effects of the first 4 cardinal signs
• Hyperemia is a condition where blood vessels are filled with more blood than usual, making the affected area red and warm.
• Bradykinin is among the major pain mediators during inflammation; causes pain by directly stimulating primary sensory neurons.
• The 5 R's in the steps of inflammation in general:

  • Recognize
  • Recruit
  • Remove
  • Regulate
  • Repair
• Vascular dilatation is the relaxation of vascular smooth muscle leads to engorgement of tissue with blood = leads to ↑ blood flow.
• Endothelial activation is the increased endothelial permeability allows plasma proteins to pass into tissues
• Neutrophil activation & migration is the expression of adhesion molecules causes neutrophils to adhere to endothelium; increased capacity for bacterial killing
• The vascular reactions of acute inflammation consist of changes in the flow of blood and the permeability of vessels, both designed to maximize the movement of plasma proteins and leukocytes out of the circulation and into the site of infection or injury
• Infections such as bacterial, viral, fungal, parasitic and microbial toxins are among the most common and medically important causes of inflammation
• Different infectious pathogens elicit distinct inflammatory responses, from mild acute inflammation that causes little or no lasting damage and successfully eradicates the infection, to severe systemic reactions that can be fatal, to prolonged chronic reactions that cause extensive tissue injury.
• Tissue necrosis elicits inflammation regardless of the cause of cell death.
• Foreign bodies may elicit inflammation by themselves or because they cause traumatic tissue injury or carry microbes
• Immune reactions aka Hypersensitivity, are reactions in which the normally protective immune system damages the individual’s own tissues.