Session 7 Flashcards
What genes code for growth factors?
Proto oncogenes
How does increased growth of a tissue occur?
By shortening the cell cycle or by conversion of quiescent cells to proliferating cell by making them enter the cell cycle.
What are the main cell cycle checkpoints that sense damaged DNA?
Restriction point (main) towards the end of G1. If this checkpoint is activated the p53 protein suspends the cell cycle and triggers DNA repair or apoptosis if repair is not possible.
G1/S transition checks for DNA damage before replication
S/G2 transition checks for DNA damage after replication
What molecules regulate progression through the cell cycle?
Proteins called Cyclins and enzymes called cyclin dependent kinases (CDKs). Activated CDKs drive the cell cycle by phosphorylating critical proteins for the progression of the cell cycle (eg pRb). The activity of cyclin-CDK complexes is regulated by CDK inhibitors.
Growth factors can either increase Cyclins or decrease CDK inhibitors.
What is cell adaptation and what are the different types?
The state between a normal unstressed cell and an over stressed injured cell. It is usually reversible.
The main types are regeneration, hyperplasia, hypertrophy, atrophy and Metaplasia.
What is regeneration and when is it possible?
The replacement of cell losses by identical cells to maintain the size of the tissue/organ. It can be a normal process (e.g. Replacement of rbcs) or can occur after injury if there is limited tissue damage.
Regeneration is not possible if the harmful agent persists, if there is extensive damage or in permanent tissues and results in a scar.
What is hyperplasia?
An increase in tissue/organ size due in increased cell numbers. It is a response to an increased functional demand and/or external stimulation. It only occurs in labile/stable cell populations.
What is the difference between hyperplasia and neoplasia?
Hyperplasia is under physiological control and is reversible.
Neoplasia is not under physiological control and is irreversible.
Neoplasia is a risk in hyperplastic tissue as the repeated cell divisions expose the cell to risk of mutations.
When does pathological and physiological hyperplasia occur?
Physiological - either hormonal to increase functional capacity or compensatory when there is an increase in tissue mass after damage.
Pathological - usually occurs secondary to excessive hormonal stimulation or growth factor production.
Give examples of pathological and physiological hyperplasia
Pathological - epidermal thickening from eczema/psoriasis. Goitre of thyroid.
Physiological - increased bone marrow production of erythrocytes in response to low O2. Proliferation of the endometrium due to oestrogen.
What is hypertrophy and where is it seen?
An increase in tissue/organ in size due to an increase in cell size. Cells contain more structural components and are bigger. It is a response to increased functional demand and/or hormonal stimulation.
Especially seen in permanent cell tissues but can also occur alongside hyperplasia in cells where division is possible.
Give examples of physiological and pathological hypertrophy
Physiological - skeletal and cardiac muscle in athletes and smooth muscle of uterus (alongside hyperplasia)
Pathological - ventricular cardiac muscle (in systemic hypertension or valvular disease), smooth muscle above an intestinal stenosis and in bladder smooth muscle with bladder obstruction due to enlarged prostate gland.
What is the difference between physiological cardiac hypertrophy in athletes and pathological hypertrophy in patients with hypertension or valvular heart disease.
The heart has time to recover between strains. There is relative anoxia in pathological hypertrophy because the number of capillaries does not increase significantly to satisfy the increased muscle mass. Cell damage occurs and fibrosis is seen, decreasing the effectiveness of the muscle.
What is atrophy?
The shrinkage of a tissue or organ due to a decrease in the number (apoptosis) and/or size (cellular atrophy) of cells.
Why do atrophic organs contain a high proportion of connective tissue?
Organs undergoing atrophy do cell deletion lose parenchymal cells before stroll cells
What are examples of physiological atrophy?
Ovarian atrophy in post menopausal women
Decrease in the size of the uterus after childbirth
What are examples of pathological atrophy?
Atrophy of disuse
Denervation atrophy - e.g. Thenar wasting after median nerve damage
Inadequate blood supply - e.g. Thinning of legs in peripheral vascular disease
Inadequate nutrition
Loss of endocrine stimulation - e.g. Wasting of adrenal gland with no ACTH
Persistent injury
Aging (senile atrophy- heart and brain)
Immunological mechanisms
Pressure -e.g. Tissues around a benign tumour
What is Metaplasia and how does it occur?
The reversible replacement of one differentiated cell type to another more suited to an altered environment.
The stem cells are reprogrammed (varied gene expression) to produce a different type of cell. Cells of one phenotype are removed and replaced by cells of a different phenotype.
Where does Metaplasia occur?
Only occurs within varieties of connective tissue or epithelia. Does not occur across germ layers.
Give examples of when Metaplasia can be useful.
Myeloid Metaplasia - if bone marrow is destroyed the spleen can undergo Metaplasia to bone marrow
Columnar epithelium lining ducts can change to stratified squamous epithelia secondary to chronic irritation by stones - more resilient.
Give examples of when Metaplasia can be detrimental
Bronchial pseudostratified -> stratified epithelium in response to cigarette smoke. No cleansing mucus is produced and there is no cilia to move it along.
Barrett’s oesophagus - stratified squamous -> gastric type epithelium in response to continues acid reflux. Predisposes to cancer.
Traumatic myositis ossificans - Metaplastic none develops in skeletal muscle following trauma. Fibroblasts change to osteoblasts.
Intestinal Metaplasia of the stomach by Helicobacter pylori predisposes to dysplasia and cancer.
What is aplasia?
The complete failure of an organ/tissue to develop (embryonic disorder).
What is hypoplasia?
The congenital underdevelopment or incomplete development of a tissue/organ. It is in a spectrum with aplasia.
What is involution?
The normal programmed shrinkage of an organ. Overlaps with atrophy. E.g. Thymus in early life.
