Pathology 2

• Tissue proliferative capacity is the ability of tissues or cells to continuously divide and proliferate throughout life, replacing those destroyed.
• Labile tissues or cells proliferate throughout life replacing those destroyed, including surface epithelia, lining mucosa of all excretory ducts of glands, columnar epithelium of GIT and uterus, transitional epithelim of urinary tract, cells of bone marrow & haematopoietic tissues.
• Stable tissues or cells have a low level of replication but can undergo rapid division in response to stimuli, enabling them to reconstitute tissue of origin.
• Parenchymal cells of liver, kidneys, pancreas; mesenchymal cells such as fibroblasts, smooth muscle cells, vascular endothelial cells and lymphocytes and leukocytes are examples of stable tissues or cells.
• Regardless of site, an inflammatory reaction elicited by the injury contains the damage, removes injured tissue, promotes deposition of ECM components at the area of the injury, and stimulates angiogenesis.
• Liver are quiescent cells and it takes several hours for them to enter the cell cycle.
• Regeneration of hepatocytes is triggered by combined actions of cytokines and polypeptide growth factors.
• If tissue injury is severe or chronic, and results in damage of both parenchymal cells & stroma, then healing cannot be accomplished by regeneration alone.
• The liver has a remarkable capacity to regenerate as demonstrated by its growth after partial hepatectomy, which is a procedure used in cases of liver tumour or living-donor hepatic transplantation.
• Resection of 60% of liver in living donors results in doubling of the liver remnant in about 1 month, in which the remnant liver rapidly expands and reaches the mass of original liver, without regrowth of resected lobes, a process known as compensatory growth or hyperplasia.
• The main healing process in such conditions is repair by deposition of collagen & other ECM components, causing the formation of scar.
• Injury to a tissue that has limited regenerative capacity first induces inflammation, which clears dead cells and microbes, forms a vascularised granulation tissue, and deposition of ECM, leading to scar formation.
• Growth factors and cytokines such as HGF and IL-6 are produced by hepatic non-parenchymal cells, which make the quiescent hepatocytes competent to enter the cell cycle.
• Persistence of injury leads to chronic inflammation → fibrosis/ fibrotic disorders.
• A skin ulcer with a large gap between the edges of the lesion.
• Complications of wound healing include deficient scar formation, excessive formation of the repair component, and formation of contractures.
• Fibrotic disorders include liver cirrhosis, systemic sclerosis, and fibrosing diseases of lung.
• A thin layer of epidermal re-epithelialization and extensive granulation tissue formation in the dermis.
• The continuing re-epithelialization of the epidermis and wound contraction.
• Local & systemic factors that influence wound healing include nutrition, metabolic status, circulatory status, hormones, age, smoking, alcohol, infection, mechanical factors, foreign bodies, size, location & type of wound, moisture, ionizing radiation, and low oxygen tension.
• If damage persists, inflammation becomes chronic → excessive deposition of connective tissue known as fibrosis (excessive deposition of collagen).
• The histologic slides show B.
• Pressure ulcer of the skin, commonly found in diabetic patients.
• Fibrous structural proteins in the ECM provide tensile strength & recoil, while adhesive glycoproteins connect matrix elements to one another & to cells.
• Non dividing tissues/cells (Permanent) cannot undergo mitosis in postnatal life and include neurons, skeletal muscle and cardiac muscle cells.
• The extracellular matrix (ECM) plays a crucial role in tissue repair and regeneration as it regulates growth, proliferation, movement & differentiation of cells living within it.
• The ECM sequesters water for turgor of soft tissue, and sequesters mineral for rigidity to bone.
• Growth factors may have restricted or multiple cell targets, also promote cell survival, locomotion, contractility, differentiation & angiogenesis.
• ECM components are essential for healing as they provide a framework for cell migration, scaffolding of tissue renewal, maintain correct cell polarity for the reassembly of multilayer structures, participate in the formation of new blood vessels, and cells in the ECM (fibroblasts, macrophages) produce regulatory molecules such as growth factors, cytokines and chemokines which are critical for regeneration & repair.
• Each cell cycle is dependent on the proper activation and completion of the previous one.
• The cell cycle is a tightly regulated process that is stimulated by growth factors or by signaling from the extracellular matrix (ECM) through integrins.
• The ECM undergoes remodeling and regeneration, wound healing, chronic fibrotic processes, tumour invasion & metastasis.
• The cell cycle plays a central role in maintaining tissue homeostasis and regulating physiologic growth process such as regeneration and repair.
• The regulation of cell cycle replication is driven by polypeptides known as growth factors (GF).
• Stem cells need to be maintained during the life of the organism to give rise to these lineages.
• Stem cells are at the forefront of modern-day biomedical investigations and are characterized by their self-renewal properties and capacity to generate differentiated cell lineages.
• All growth factors function as ligands and bind to specific receptors to deliver signals to target cells, including genes that control cell cycle entry and progression.
• Collagen is the most common protein and provides the extracellular framework.
• Elastin, fibrilin and elastic fibres are proteins that provide tissues such as blood vessels, skin, uterus and lungs with elasticity for their function.
• Cell adhesion molecules (CAMs) can bind to similar or different molecules in other cells, providing interaction between same cells or different cells.