Lecture 7.1 - Cellular Adaptations PDF

From unicellular to multicellular: ◦Gametes ◦Zygote ◦Stem cells ◦Cell growth and proliferation ◦Cell division How is cell proliferation controlled?: ◦Largely by chemical signals from the microenvironment which either stimulate or inhibit cell proliferation ◦Wh...

From unicellular to multicellular: ◦Gametes ◦Zygote ◦Stem cells ◦Cell growth and proliferation ◦Cell division How is cell proliferation controlled?: ◦Largely by chemical signals from the microenvironment which either stimulate or inhibit cell proliferation ◦When signalling molecules bind to receptors and result in the modulation of gene expression ◦Receptors usually in cell membrane, but can be in the cytoplasm or nucleus What can chemical signals make the cells do?: ◦Survive -> resist apoptosis ‣ Cells need constant exposure to survival signals (e.g. peptides, hormones) ◦Divide -> enter cell cycle ◦Differentiate -> take on specialised form and function ◦Die -> undergo apoptosis Cell cycle: ◦Mitosis = nuclear division; cytokinesis = cell division How can cell populations increase?: ◦Increased growth occurs by: ‣ Shortening the cell cycle ‣ Conversion of quiescent cells to proliferating cells by making them enter the cell cycle ◦Cells enter the Go phase if they cannot progress or there is a problem in the cycle ‣ Liver cells can re-enter the cycle and continue growing if there is damage ‣ Neurones cannot go back into the cell cycle if damaged has occurred Cell cycle checkpoints:  Restriction (R) point: ◦Most critical checkpoint ◦Majority of cells that pass R point will complete cell cycle - point of no return ◦Most commonly altered checkpoint in cancer cells ◦Checkpoint activation delays cell cycle and triggered DNA repair mechanisms or apoptosis via p53 How is the cell cycle controlled?: ◦Cyclins and cyclin dependent kinases (CDKs) ◦CDKs become active by binding with cyclins Cyclin - cdk activation: Cyclin - cdk interactions: ◦Protein-protein interactions How many times can cells divide?: ◦Leonard Hayflick - Hayflick numbers/limits (1961) ◦Humans = 40-60 divisions  How cells and tissues grow?: ◦Proliferation - increase in numbers ◦Growth - increase in size ◦Differentiation - acquiring a specific morphology and function What determines the size of a cell population: ◦Depends on: ‣ Rate of cell proliferation ‣ Cell differentiation ‣ Cell death by apoptosis ◦Increased numbers are seen with increased proliferation or decreased cell death Cell regeneration: ◦Regeneration - the ability to replace cells or tissues, destroyed by injury or disease (identical functionality) ◦Labile cells - high regenerative ability and turnover (e.g. intestinal epithelium) ◦Stable cells - good regenerative ability and low turnover (e.g. hepatocytes) ◦Permanent cells - no regenerative ability (e.g. neurones) Cellular adaptations: How can cells adapt?: ◦Hyperplasia - cells increase in number above normal ◦Hypertrophy - cells increase in size ◦Atrophy - cells become smaller ◦Metaplasia - cells are replaced by cells of a different type  What is hyperplasia?: ◦Increase in tissue or organ size due to increased cell numbers In which types of tissues does hyperplasia occur?: ◦Labile or stable tissues ◦Caused by increased functional demand or hormonal stimulation ◦Remains under physiological control and is reversible (cf. neoplasia) ◦Can occur secondary to a pathological cause but the proliferation itself is a normal response (cf. neoplasia - the proliferation itself is abnormal) ◦Repeated cell divisions exposes the cell to the risk of mutations and neoplasia -> can lead to cancer Examples of physiological hyperplasia: Examples of pathological hyperplasia: What is hypertrophy?: ◦Increase in tissue or organ size due to increased cell size  In which types of tissue does hypertrophy occur?: ◦Labile, stable and especially permanent tissues ◦Like hyperplasia, caused by increased functional demand or hormonal stimulation ◦Cells contain more structural components - workload is shared by a greater mass of cellular components ◦In labile and stable tissues, hypertrophy usually occurs along with hyperplasia Examples of physiological hypertrophy: Examples of pathological hypertrophy: What is compensatory hypertrophy?: What is atrophy?: ◦Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells What is happening in the cell in atrophy?: ◦Shrinkage in the size of the cell to a size at which survival is still possible ◦Reduced structural components of the cell and cell function  ◦May eventually result in cell death Is tissue atrophy only a result of cell atrophy?: ◦Organ/tissue atrophy typically due to combination of cellular atrophy and apoptosis ◦Is reversible, but only up to a point What happens in tissue atrophy?: Example of physiological atrophy: Examples of pathological atrophy: ◦Reduced functional demand/workload = atrophy of disuse ◦Muscle atrophy after disuse; reversible with activity ◦Loss of innervation = denervation atrophy -> wasted hand muscles after median nerve damage  ◦Inadequate blood supply - thinning of skin on legs with peripheral vascular disease ◦Inadequate nutrition - wasting of muscles with malnutrition ◦Loss of endocrine stimulation - breast, reproductive organs ◦Persistent injury - polymyositis (inflammation of muscle) ◦Ageing = senile atrophy (brain, heart etc) ◦Pressure - tissues around an enlarging benign tumour (probably secondary to ischaemia) What is atrophy of extracellular matrix?: What is metaplasia?: ◦ Reversible change of one differentiated cell type to another ◦May represent adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment ◦Metaplastic cells are fully differentiated and the process is reversible (cf. dysplasia and cancer) ◦Sometimes a prelude to dysplasia and cancer ◦Occurs only in labile or stable cell types ◦Involves expression of a new genetic programme Examples of metaplasia:  Does metaplasia predispose to cancer?: ◦Epithelial metaplasia can be a prelude to dysplasia and cancer ‣ Barrett's epithelium and oesophageal adenocarcinoma ‣ Intestinal metaplasia of the stomach and gastric adenocarcinoma ◦It's not clear why What is aplasia?: ◦Complete failure of a specific tissue or organ to develop ◦An embryonic developmental disorder ◦Examples: ‣ Thymic aplasia - infections and auto-immune problems ‣ Aplasia of a kidney ◦Also used to describe an organ whose cells that ceased to proliferate e.g. aplasia of bone marrow in aplastic anaemia What is hypoplasia?: ◦Underdevelopment or incomplete development of tissue or organ at the embryonic stage, inadequate number of cells ◦In a spectrum with aplasia ◦Not opposite of hyperplasia as it is a congenital condition ◦Examples: ‣ Renal ‣ Breast ‣ Testicular in Klinefelter's syndrome ‣ Chambers of the heart What is involution?: ◦Overlaps with atrophy ◦Normal programmed shrinkage of an organ ◦Uterus after childbirth, thymus in early life, pro and mesonephros What is reconstruction?: ◦Replacement of a lost part of the body ◦Can reconstitution occur in humans? - only in angiogenesis  What is atresia?: ◦No orifice ◦Congenital imperforation of an opening ◦Examples: ‣ Pulmonary valve ‣ Anus (typically in babies) ‣ Vagina ‣ Small bowel What is dysplasia?: ◦Abnormal maturation of cells within a tissue ‣ Normal cell to abnormal cell ◦Potentially reversible ◦Often pre-cancerous condition