MOD 7 Flashcards
What is autocrine signalling?
Cells responding to signals that they themselves produce.
What is intracrine signalling?
A type of autocrine signalling where a cell synthesises a factor which has an effect by binding to intracellular receptors within that cell, the factor is therefore not secreted by the cell.
What is paracrine signalling?
A cell produces the signalling molecule, this acts on adjacent cells. The responding cells are close to the secreting cell and are often of a different type.
What is endocrine signalling?
Hormones are synthesised by cells in an endocrine organs, they are then conveyed in the blood stream to target cells to effect physiological activity.
What are growth factors?
Are a type of local mediator that are particularly important for cell proliferation. They are polypeptides that act on specific cell surface receptors. They can be considered as ‘local hormones’ as they only act over short distances or even on the secreting cell itself. They are coded for by proto-oncogenes.
Name the different phases of the cell cycle?
- G1 - gap 1 phase
- S - synthesis phase
- G2 - gap 2 phase
- M - mitotic phase
(5. G0 - resting phase)
The phases between the M-phase are collectively called interphase.
What are the checkpoints of the cell cycle?
- Restriction (R) point towards the end of G1 = most critical (the majority of cells that pass this point will complete the full cell cycle)
- G1/S transition (checks for DNA damage before replication)
- G2/M (checks for DNA damage after replication)
What are the role of cyclins in the cell cycle?
They tightly regulate the cell cycle by binding to and complexing with cyclin-dependent kinases (CDKs).
What are the role of CDKs in the cell cycle?
Cyclin-bound (activated ) CDKs drive the cell cycle by phosphorylating proteins, e.g. RB protein, which are critical for progression of the cycle to the next stage.
What is the role of the RB protein in the cell cycle?
It inhibits the cell cycle until it is phosphorylated by CDKs -> its deactivation.
What are labile tissues?
Tissues which can proliferate even though they consist of mature differentiated cells. This is because the cells in this tissue are short-lived and are continually being replaced by cells derived from stem cells.
Give examples of labile tissues:
- EPITHELIUM e.g. epidermis or bowel epithelium (replaced by stem cells situated in basal layer of epidermis and epithelial crypts in the bowel)
- BONE MARROW - stem cells continuously divide to replenish loss.
What are permanent tissues?
Tissues where cells have terminally differentiated (left the cell cycle and cannot replicate). In these tissues although stem cells can be present, they cannot mount an effective proliferative response to significant cell loss.
Give examples of permanent tissues:
- Cardiac muscle
- Skeletal muscle
- Neural tissue
What are stable tissues?
Are intermediate between labile and permanent tissues. In these tissues the mature cells as well as stem cells are involved in proliferation. These mature cells are usually non-replicating but can be induced to enter the cell cycle and replicate if necessary (e.g. they are in G0 but can enter G1). This requires activation of a number of genes (proto-oncogenes, genes for ribosome synthesis and protein translation). Stem cells are present in these tissues and are normally quiescent or proliferate very slowly but can proliferate perisistently when required.
Give examples of stable tissues:
- Liver hepatocytes
- Kidney cells
- Fibroblasts
- Smooth muscle cells
- Vascular endothelial cells
- Osteoclasts
What are stem cells?
They are present in many adult tissues. They are cells with prolonged proliferative activity which show assymetric replication.
Define regeneration:
A type of cell adaptation in which cells multiplies to replace losses with identical cells in order to maintain the size of a tissue or organ.
Which tissues can undergo regeneration and which cannot?
- Liver - after partial hepatectomy
- Epidermis - following a skin burn
- Bone marrow - replaced lost RBCs and WBCs
- After injury - if harmful agent removed and there is limited tissue damage
Define hyperplasia:
An increase in tissue or organ size due to increased cell numbers. It is a response to a functional demand and/or external stimulation. It is under physiological control and is reversible (cf to neoplasia). It is biologically similar to regeneration but causes an increase in the size of tissue or organ.
Which tissues can undergo hyperplasia?
It can only occur in labile or stable cell populations.
When does physiological hyperplasia occur? Give an example of physiological hyperplasia:
Either hormonal (-> increased functional capacity) or compensatory (increase in tissue mass after tissue damage), e.g:
- Increased bone marrow production production of RBCs in response to low oxygen
- Proliferation of endometrium under the influence of oestrogen.
When does pathological hyperplasia occur? Give an example of pathological hyperplasia:
This usually occurs secondary to excessive hormonal stimulation or growth factor production e.g. epidermal thickening in chronic eczema or psoriasis and enlargement of the thyroid gland in response to iodine deficiency.
Define hypertrophy:
An increase in tissue or organ size due to an increase in cell size without an increase in cell numbers. Cells become bigger, not due to swelling, but because they contain more structural components. It is a response to increased functional demand and/or hormonal stimulation. Due to the increased structural components the cellular workload is shared by a greater mass of cellular components.
Which tissues can undergo hypertrophy?
It can occur in many tissues but is seen especially in permanent cell populations as these cell populations have little of no replicative potential and so any increase in organ size must occur via hypertrophy. In cells where division is still possible, hypertrophy may still occur but often alongside hyperplasia.
Give an example of physiological hypertrophy:
- Skeletal muscle hypertrophy in a body-builder
- SMC hypertrophy in pregnant uterus (hyperplasia also occurs) - increases 70 fold during pregnancy!
- Cardiac heart muscle in athletes (this is not pathological like the hypertrophy seen in systemic hypertension because the heart has time to recover after exercise).
Give an example of pathological hypertrophy:
- Ventricular cardiac muscle hypertrophy in response to systemic hypertension of valvular disease
- SMC hypertrophy above an intestinal stenosis due to extra work-load pushing intenstinal contents through the narrowing.
- SMC hypertrophy with bladder obstruction e.g. caused by prostate enlargement.
What is compensatory hyperplasia?
An increase in size of an organ or part of an organ or tissue, when called upon to do additional work or perform the work of destroyed tissue or of a paired organ (e.g. removal of one kidney).
Define atrophy:
The shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells. Cellular atrophy is a decrease in size, whereas organ/tissue atrophy is typically due to a combination of cellular atrophy and apoptosis and occurs when many cells in the tissue undergo atrophy and apoptosis. Whether atrophy occurs by cell deletion or cell shrinkage depends on the tissue involved.
Give an example of physiological atrophy:
- Ovarian atrophy in post-menopausal women
2. Decrease in size of uterus after partuition
Give an example of pathological atrophy:
- Reduced functional demand/workload (atrophy of disuse) e.g. muscle atrophy after disuse due to immobilisation in a cast
- Loss of innervation (denervation atrophy) e.g. wasted striated thenar muscles after median nerve damage.
- Inadequate blood supply e.g. thinning of skin on legs with peripheral vascular disease.
Define metaplasia:
The reversible replacement of one adult DIFFERENTIATED cell type by another of a different cell type. Cells of one type are eliminated and replaced by cells of a different phenotype. The stem cells within the tissue are reprogrammed and switch to producing a different type of progeny.
Why does metaplasia occur?
It occurs secondary to signals from molecules such as cytokines and growth factors. It is often induced by stimuli that cause cell proliferation e.g. chemical or mechanical irritant (cigarette smoke). These result in expression of a new genetic programme (different activation of genes) which results in cells assuming a different structure and different function.
Give some examples of useful metaplasia:
- Columnar epithelium (fragile) lining ducts can change to squamous epithelium (more resilient), secondary to chronic irritation by stones.
- If bone marrow is destoyed by disease splenic tissue undergoes metaplasia to bone marrow (myeloid metaplasia).
Define aplasia:
The complete failure of a specific tissue or organ to develop. It is an embryological developmental disorder e.g. aplasia of a kidney. Aplasia is also used to describe an organ whose cells have ceased to proliferate e.g. aplasia of bone marrow in aplastic anaemia.
Define involution:
This term overlaps with atrophy. It is the normal programmed shrinkage of an organ e.g. uterus after childbirth, thymus in early life, temporary foetal organs such as the pro- and mesonephros.
Define hypoplasia:
Congenital underdevelopment or incomplete development of a tissue or organ = an inadequate number of cells within the tissue which is present. It is an embryological disorder which is on a spectrum with aplasia. It is not the opposite of hyperplasia as it is a congenital condition.
Define atresia:
‘no orifice’ - the congenital imperforation of an opening, e.g. atresia of the anus or vagina.
Define dysplasia:
Abnormal maturation of cells within a tissue. It is potentially reversible but is often a pre-cancerous condition.
What factors determine the size of a cell population? When does a cell population increase?
- Rate of cell proliferation
- Rate of cell differentiation
- Rate of apoptosis
Therefore increased numbers are seen when there is either increased proliferation or decreased cell death.
What are the role of proto-oncogenes?
They regulate normal cell proliferation.
