Cellular Adaptations PDF

Cellular adaptations Session two MOD module. Prof. Dr. Hadeel Karbal. Objectives: Describe cell signaling pathways Introduce the cell cycle Focus on adaptive responses in cell growth & differentiation Control of cell growth Cells in a multicellular organism communicate...

Cellular adaptations Session two MOD module. Prof. Dr. Hadeel Karbal. Objectives: Describe cell signaling pathways Introduce the cell cycle Focus on adaptive responses in cell growth & differentiation Control of cell growth Cells in a multicellular organism communicate through chemical signals Hormones act over a long range Local mediators are secreted into the local environment (paracrine / autocrine) Some cells communicate through direct cell-cell contact  Cells are stimulated when extracellular signaling molecules bind to a receptor Each receptor recognizes a specific protein (ligand) Receptors act as transducers that convert the signal from one physical form to another. Signaling molecules Hormones – Insulin, – Cortisol Local mediators – Epidermal Growth Factor (EGF), – Platelet Derived Growth Factor (PDGF) – Fibroblast Growth Factor (FGF) – TGFβ – Cytokines, e.g. Interferons, Tumour necrosis factor(TNF). Receptors There are 2 main types of receptors that are important in cell growth.... G-protein-linked receptors Enzyme-linked receptors G-protein-linked receptors G-protein-linked receptors activate GTP- binding proteins (G-proteins) G proteins are molecular switches They are turned on for brief periods while bound to GTP They switch themselves off by hydrolysing GTP to GDP Enzyme-linked receptors Have intracellular domains with enzyme function Most are receptor tyrosine-kinases These receptors are activated by growth factors, thus being important in cell proliferation Some activate a small GTP-binding protein, Ras (important in cancer) The cell cycle The eukaryotic cell cycle consists of distinct phases The most dramatic events are nuclear division (mitosis) and cytoplasmic division (cytokinesis) This is the M phase The rest of the cell cycle is called interphase which appears, deceptively, uneventful During interphase the cell replicates its DNA, transcribes genes, synthesizes proteins and grows in mass Describe the different phases of the cell cycle and their control The restriction (R) point, towards the end of G1, is the most critical checkpoint. Passage beyond the R point is governed by the phosphorylation of the Retinoblastoma Protein (pRb) Describe Labile, stable and permanent cells Labile Cell populations Stem cells divide persistently to replenish losses. E.g. Epithelial or haematopoietic cells Normal state is active cell division: G1 – M - G1 Usually rapid proliferation Stable Cell populations E.g. Hepatocytes, osteoblasts, fibroblasts Resting state: G0 Stem cells normally quiescent or proliferate very slowly Proliferate persistently when required Permanent Cell Populations E.g. Neurones, cardiac myocytes Stem cells present, but cannot mount an effective proliferative response to significant cell loss  Growth and differentiation responses Hyperplasia – increase in cell number in a tissue or organ above normal Hypertrophy – acquired Increase in size of a cell (tissue or organ) Atrophy – acquired decrease in size of a cell (tissue or organ) Metaplasia – change of one differentiated cell type to another Hyperplasia Increase in the number of cells in an organ or tissue above normal, which may then have an increased size Hyperplasia: causes Hyperplasia can only occur in tissues containing labile or stable cells Hyperplasia may occur under pathological or physiological conditions Physiological Hyperplasia 1) hormonal hyperplasia , proliferation of the glandular epithelium of the female breast at puberty and during pregnancy 2) compensatory hyperplasia, in which residual tissue grows after removal or loss of part of an organ. e. g. when part of a liver is resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight. Pathological hyperplasia Occurs in several situations : Excessive hormone/growth factor stimulation Associated with increased risk for cancer e.g. Prostate, endometrium. An important point is that in all of these situations, the hyperplastic process remains controlled; if the signals that initiate it abate, the hyperplasia disappears. Hypertrophy Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ hypertrophy occurs when cells have a limited capacity to divide. In practice, an increase in functional cell mass is often a combination of hyperplasia and hypertrophy Hypertrophy: causes Occurs in permanent cells Due to synthesis of more cellular structural components Physiological or pathological causes Physiological hypertrophy Hormonal effect: The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen- stimulated smooth muscle hypertrophy and smooth muscle hyperplasia increased demand the striated muscle cells in both the skeletal muscle t can undergo only hyper- trophy because adult muscle cells have a limited capacity to divide. Pathological hypertrophy Increased functional demand e.g. cardiac muscle – Hypertension – valvular heart disease  Atrophy Shrinkage in the size of the cell by the loss of cell substance When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, becoming atrophic Atrophy: causes Reduced workload e. g. immobilization of a limb to permit healing of a fracture. Loss of innervation Reduced blood supply Inadequate nutrition Loss of endocrine stimulation Ageing Metaplasia Metaplasia is a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. Metaplasia is thought to arise by reprogramming of stem cells to differentiate along a new pathway Metaplasia: causes An adaptive response to various stimuli New cell type is better adapted to exposure to the stimulus The stimulus that induced metaplasia may, later, induce cancer, e.g. squamous cell carcinoma of the bronchus Metaplasia in mesenchymal tissues is often less clearly adaptive E. g. squamous change that occurs in the respiratory epithelium of habitual cigarette smokers Example of metaplasia E. g. squamous change that occurs in the respiratory epithelium of habitual cigarette smokers. Although the metaplastic squamous epithelium has survival advantages, important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter. Epithelial metaplasia is therefore a double-edged sword. Moreover, the influences that induce metaplastic change, if persistent, may predispose to malignant transformation of the epithelium.  Aplasia – Complete failure of a specific tissue or organ to develop Hypoplasia – Incomplete development of a tissue or organ Dysplasia – Abnormal maturation of cells within a tissue