TISSUE RENEWAL, REGENERATION, AND REPAIR Flashcards
Define regeneration and repair, and explain the difference between these two terms.
- Regeneration replaces lost structures. In mammals, this can happen if the cytoskeleton is in tact and stem cells are still present and functional. Common in epithelial tissues of GI tract and skin.
- Repair is the combination of regeneration and fibrosis. Fibrosis (scarring) refers to the deposition of collagen. This is commonly what happens following significant injury.
Based on proliferative activity, list the three types of tissues in the human body.
- Continuously dividing (labile tissues): cells proliferate throughout life, replacing those that are destroyed. In most of these tissues mature cells are derived from adult stem cells(e.g. epithelial tissues).
- Quiescent (stable tissues): cells have a low level of replication, but can undergo rapid division in response to stimuli. (e.g. liver, kidney, pancreas, smooth muscle, fibroblasts, vascular endothelial cells, osteocytes).
- Nondividing (permanent tissues): cells have left the cell cycle (permanently in G0). (e.g. neurons, cardiac muscle and skeletal muscle).
Explain the goal of stem cell therapy.
Repair damaged tissues by either transplanting stem cells into a damaged organ or induce differentiation of endogenous stem cells to replace damaged tissue.
List and describe the two main mechanisms by which cells are stimulated to replicate.
Replication of cells is stimulated by growth factors OR by signaling from extracellular matrix components.
List and describe the three modes of signaling mechanisms in cell growth.
Autocrine, Paracrine & Endocrine
List and describe the four types of receptors involved in signaling induction pathways.
- Receptors with intrinsic tyrosine kinase activity: Binding of the ligand induces dimerization of the receptor, tyrosine phosphorylation, and activation of the receptor tyrosine kinase. The active kinase then phosphorylates (activates) downstream effector molecules, leading to activation of transcription factors.
- Receptors lacking intrinsic tyrosine kinase activity: transmit signals to the nucleus by activating members of the JAK (Janus kinase) family of proteins, resulting in a cascade leading to gene transcription.
- G-protein-coupled receptors: largest family of plasma membrane receptors. ligands examples are chemokines, vasopressin, serotonin, histamine, epinephrine, norepinephrine, calcitonin, glucagon, parathyroid hormone, corticotropin & rhodopsin.
- Steroid hormone receptors: ligands are steroid hormones, thyroid hormone, vitamin D, and retinoids. Involved in a broad range of responses including adipogenesis, inflammation, and atherosclerosis.
State the growth factor most important for fibrosis, and the growth factor most important for angiogenesis.
- Transforming Growth Factor Beta promotes fibrosis.
* Vascular Endothelial Growth Factor (VEGF) promotes angiongenesis.
List and describe the functions of the ECM.
- Mechanical support.
- Control of cell growth.
- Maintenance of cell differentiation.
- Scaffolding for tissue renewal: (regeneration of a tissue will result in restitution of the normal structure only if the ECM is not damaged; disruption of the ECM leads to collagen deposition and scar formation.)
- Establishment of tissue microenvironments (e.g. basement membranes)
- Storage and presentation of regulatory molecules.
What are the two forms of the ECM?
- Interstitial matrix: found in spaces between epithelial, endothelial, smooth muscle cells and in connective tissue; consists mostly of fibrillar and nonfibrillar collagen, elastin, fibronectin, proteoglycans, and hyaluronan.
- Basement membranes: associated with cell surfaces, and consist of nonfibrillar collagen (mostly type IV), laminin, heparin sulfate, and proteoglycans.
List and describe the key steps of repair by tissue collagen deposition.
1) Formation of a BLOOD CLOT: stops bleeding and serves as a scaffolding for migrating cells. Neutrophils arrive w/in 24hrs to start cleaning.
2) Fibroblasts and endothelial cells proliferate in the first 24 to 72 hours to form GRANULATION TISSUE, which is mesenchymal tissue containing proliferating fibroblasts and new small blood vessels (angiogenesis) that are leaky –> localized edema within the extravascular space
3) CELL PROLIF & COLLAGEN DEPOSTION: Neutrophils are largely replaced by macrophages after 48-96 hours. Mac’s are leaders in tissue repair, clearing debris, fibrin, and foreign material, and promoting angiogenesis and ECM deposition.
In 24-48 hours, epithelial cells move from the wound edge, depositing basement membrane material as they move. Collagen fibrils become more abundant, with TGF-Beta serving as the most important fibrogenic agent.
List and describe the key steps of repair by tissue collagen deposition (Ctd.).
4) SCAR FORMATION: By week 2, the leukocyte infiltrate, edema, and increased vascularity largely disappear. By one month, a connective tissue scar is present, devoid of inflammatory infiltrates, and covered by an intact epidermis.
5) WOUND CONTRACTION: mediated by myofibroblasts at the edge of the wound that express smooth muscle alpha-actin and vimentin. Occurs in large wounds. Helps to close the wound.
6) CONNEX TISSUE REMODELING: Replacement of the granulation tissue by fibrous tissue (scar) involves changes in the composition of the ECM. The balance of ECM synthesis and degradation –> remodeling of the connex tissue framework. Some of the growth factors that stimulate synthesis of collagen and ECM tissue molecules also modulate the synthesis and activation of metalloproteinases, enzymes that can degrade these ECM components.
7) RECOVERY OF TENSILE STRENGTH: results from collagen deposition as well as from structural modification of the collagen (cross linking, increased fiber size)…it takes time
Describe the three stages of wound healing.
1) Inflammation - clot formation, chemotaxis
2) Proliferation - Re-epitheliaization, angiogenesis & granulation tissue, provisional matrix
3) Maturation - Collagen matrix, wound contraction
***Callegen deposition increases through the stages.
List the systemic and local factors that influence wound healing.
SYSTEMIC:
*Nutrition: protein deficiency, deficiency in vitamin C impair healing
*Metabolic status (e.g. diabetes associated microangiopathy impairs healing)
*Circulatory status (e.g. impaired blood supply due to arteriosclerosis or venous abnormalities impairs healing)
*Hormones such as glucocorticoids have anti-inflammatory effects that influence the inflammatory response, as well as inhibit collagen synthesis, resulting in impaired healing in acute wounds
LOCAL:
*Infection (most important factor), delays healing b/c leads to inflammatory response; not able to close wound
*Mechanical factors can delay healing
*Foreign bodies can delay healing
*Size, location, and type of wound: wounds in richly vascularized areas heal faster than those in poorly vascularized areas. Small incisional wounds heal faster and with less scar formation than large excisional wounds or wounds caused by blunt trauma.
PATHOLOGY IS DIVIDED INTO TWO DISCIPLINES. Describe them.
ANATOMIC PATHOLOGY includes Surgical pathology, Autopsy pathology and Cytopathology.
*Anatomic Path provides the Pathology Report
CLINICAL PATHOLOGY includes clinical chemistry, hematology, microbiology and blood bank.
*Clin Path provides the Laboratory Test Report
Define accuracy & precision. , prevalence, sensitivity, specificity, and predictive value of both positive and negative tests. Explain the effect of prevalence on the predictive value of a positive test.
Accuracy: ability of the test to actually measure what it claims to measure correctly
Precision: ability of the test to reproduce the same result when repeated.
***Key question for tests ordered for diagnosis or screening: does the test accurately distinguish between patients with the disease in question and those without the disease?
…if a scale is off it is not accurate b/c it’s not measuring your weight. It might be precise, however.
