Cell Birth and Death 1 & 2 Flashcards
regeneration, hyperplasia, metaplasia, and dysplasia
- altered proliferative states of cells that are reversible
- proliferation stops when the stimulus that provoked it is removed
neoplasia
- irreversible proliferation
- proliferation continues in the absence of an external stimulus
regeneration
-two examples
- one to one replacement of lost cells by the same cell type
- endothelial cell regeneration following vascular surgery
- liver cell regeneration following partial hepatectomy or live-donor liver transplant (in the donor, not recipient)
hyperplasia
-two examples
increase in the number of cells in a tissue
- hematopoietic cells in the bone marrow following severe blood loss or change in altitude
- thyroid cells in graves disease (hyperthyroidism)
- smooth muscle cells in the arterial wall in athersclerosis follow vascular surgery, termed restenosis (following angioplasty, CABG, arterio-venous shunt)
metaplasia
- adaptive substitution of one cell type for another
- replacement of ciliated collumnar epithelium by stratified squamous epithelium in response to chronic inflammation or other injurious stimuli (smoking)
dysplasia
- activated metabolic pathways for proliferation, loss of orientation in a tissue
- abnormal appearance (pleiotropy disoriented in tissue, huge mitotic rate) of cells
- cervical dysplasia as seen on pap smear in women
- dysplastic moles removed from skin
- often a precursor to cancer, thus the need for careful monitoring or prophylactic surgery when it is detected
Neoplasia
-two flavors
- benign: loos of proliferation control only; fibroids
- malignant: loss of both proliferation control and positional control; metastatic tumors (cancer)
positional control of cell proliferation
-example
- a position of a cell in a tissue can determine its proliferation rate
- in part because information in the extracellular matrix helps regulate cell proliferation
- epithelial cells in the intestinal crypt: slowly dividing stem cells are found at the bottom, rapidly dividing cells are found half way up the vilus and non-dividing, terminally differentiated cells are found at the top
G1
- prepares cells for replicating DNA
- cell is busy doubling its contents in preparation for an eventual cell division
S
DNA replication
G2
prepares cell for segregation/division of cytoplasm
M
chromosome segregation (mitosis) and seperation of daughter cells (cytokinesis)
Regulation of the G1 checkpoint (restriction, or R-point)
- decide whether they have enough nutrients and other factors necessary to sustain them through a round of DNA replication
- if they dont, they will exit the cell cycle and go into G0 (quiescence)
- this works by external signals stimulating synthesis of cycling D and E which partner with CDK4 or CDK6 (D) or cyclin 2 (E)
- these complexes then phosphorylate RB protein, releasing it from its complex with proliferation TF’s and allowing them to bind to DNA
- the TF’s then bind DNA and allow transcription of proteins which push the cell through R and into S phase
- once DNA synthesis is complete, a protease destroys Cyclin D and E, inactivating the complex once again
- this is usually defective in all cancer cells
- 99.9% of cells are in G0
Regulation of M phase
As a result of MPF (cyclin B/CDK1) activation, the following occurs:
- P of lamins, leading to nuclear membrane dissassembly
- P of histones, leading to condensation of chromosomes