Flashcards in MOD 4 Deck (82)
Is the growth of cells and tissues to replace lost structures.
Another term for regeneration, therefore it is the growth of cells and tissues to replace lost structures.
What is a labile tissue? Give some examples:
Continuously dividing tissues - proliferate throughout life continuously replacing cells that are lost through stem cells. E.g. surface epithelia, lining mucosa of secretory ducts of the glands of the body, columnar epithelia of GI tract and uterus, transitional epithelium of urinary tract, cells of bone marrow and haematopoietic tissues.
What is a stable (quiescent) tissue? Give some examples:
Tissues that normally have a low level of replication but cells in these tissues can undergo rapid division in response to stimuli and can reconstruct the tissue of origin. E.g. parenchymal cells of the liver, kidneys and pancreas, mesenchymal cells such as fibroblasts and smooth muscle cells, vascular endothelial cells, resting lymphocytes and other white blood cells.
What is a permanent tissue? Give some examples:
These are non-dividing tissues, containing cells that have left the cell cycle and can't undergo mitotic division in postnatal life e.g. neurones, skeletal and cardiac muscle cells. They have no or only a few stem cells (that can't mount an effective proliferative response to significant cell loss) to replace cells.
What are the roles of stem cells?
Stem cells can replace terminally differentiated cells that are lost - in tissues where regeneration is possible.
Define unipotent stem cells
Stem cells that can only give rise to one type of adult cell - lineage specific.
Define multipotent stem cells
Stem cells that can produce several types of differentiated cell e.g. haematopoietic cells.
Define totipotent stem cells
Stem cells that can give rise to any tissue in the body.
What is fibrous repair?
Replacement of tissue with fibrovascular connective tissues.
How does fibrous repair differ from regeneration/resolution?
Regeneration restores a tissue back to its full functionality and normal appearance.
List the steps involved in fibrous repair:
1. Phagocytosis of necrotic tissue debris
3. Formation of granulation tissue - proliferation of fibroblasts and myofibroblasts
4. Granulation tissue becomes less vascular -> fibrous scar
5. Scar matures and shrinks due to contraction of fibrils of myofibroblasts
What cells are involved in fibrous repair?
What is angiogenesis?
The physiological process through which new blood vessels form from pre-existing vessels.
What are the components of granulation tissue?
1. Cellular components: fibroblast, myofibroblasts, endothelial cells
2. Non-cellular components: collagen (intially type 3 then replaced by stronger type 1), fibrin and plasma fluid.
What types of collagen are their?
27 different types. Type I (fibrillar) is the most common type in the body.
How is fibrillar collagen synthesised?
It is synthesised by fibroblasts and myofibroblasts:
1. Preprocollagen synthesised into ER
2. Modified to procollagen which takes on a triple helix form and is secreted from the cell
3. Procollagen cleaved to produce fibrillar collagen
4. Cross-linking between fibrils to give tensile strength
List some diseases caused by defects in collagen synthesis:
What is the mechanism behind the disease scurvy?
Scurvy is caused by a deficiency of vitamin C. This is a cofactor for the enzymes prolyl hydroxylase and lysyl hydroxylase which hydroxylate proline and lysine residues on procollagen, enabling it to hydrogen bond into its triple helix form. Without as many hydrogen bonds, these triple helices are weak and therefore the collagen is weak. People with scurvy therefore are unable to heal wounds adequately and have a tendency to bleed.
What is the mechanism behind the disease Ehlers-danlos syndrome?
It is a heterogenous group of 6 inherited disorders where the collagen fibres lack adequate tensile strength. Skin is hyperextensible, fragile and susceptible to injury and joints are hypermobile. Wound healing is poor and patients have a predisposition to joint dislocation. Because the collagen in internal organs is also affected patients can suffer form rupture of the colon and , in some forms, large arteries. Corneal rupture and retinal detachment can also be seen.
What is the mechanism behind the disease osteogenesis imperfecta (brittle bones disease) ?
People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen. Patients have too little bone tissue and hence extreme skeletal fragility. They also have blue sclera as there is too little collagen in the sclerae making them translucent. They also can have hearing impairment and dental abnormalities.
What is the mechanism behind the disease Alport syndrome?
Usually an X-linked disease. Type 4 collagen is abnormal and this results in dysfunction of the glomerular basement membrane, the cochlear of the ear and the lens of the eye. Patients, usually male, present with haematuria as children or adolescents. This progresses to chronic renal failure. They also have neural deafness and eye disorders.
How is cell reparation and growth controlled?
The control mechanisms are poorly understood, but cells communicate with each other to produce a fibropoliferative response. This communication can be via local mediators (such as growth factors), hormone or by direct cell-cell stroma contact.
What are the different modes of action of growth factors
autocrine, paracrine, endocrine signalling
What is autocrine signalling?
Cells respond to signalling molecules that they themselves produce.
What is paracrine signalling?
Cells produce the signalling molecule, this acts on adjacent cells. The responding cells are close to the signalling cells and are often of a different type.
What is endocrine signalling?
Hormones are synthesised by cells in an endocrine organ, they are conveyed in the blood stream to target cells to effect physiological activity.
What is the importance of adhesion molecules?
These proteins allows cells to adhere to each other (called cadherins) and the extracellular matrix (integrins). They are important in contact inhibition and wound healing.
Explain the concept of contact inhibition:
Normally cells that have become isolated from surrounding cells will replicate until they have cells touching them and then stop. In this way they form monolayer sheets of cells with no overlap. This is altered in malignant cells.