Regulation of tissue growth and Principles Flashcards
How is normal tissue architecture maintained?
Maintenance of genomic integrity
When do quantitative changes to cells occur?
- occur during development or in post natal life –
2. be physiological and part of normal processes or a consequence of pathological events
What is atrophy?
an acquired diminution of growth due to a decrease in the size or number of constituent parts (cells) of a tissue
eg decrease in size of ovaries post menopause
What is hypertrophy?
the converse of atrophy - an increase in the size of an organ or tissue due to an increase in the size of individual cells. Hypertrophy is the cellular response to excessive or prolonged demand for increased function. It is seen most dramatically in muscular organs.
eg pregnant uterus- expand to accommodate foetus
What happens when the demand for increased work ceases?
the organ returns to normal size unless there have been irreversible changes in the architecture as a consequence of the prolonged demand
What is hyperplasia?
an increase in the size of an organ due to an increase in the number of the component cells - increased proliferation. eg lactating breast, prostatic enlargement in older men
What are the differences between hyperplasia and neoplasia?
The enhanced proliferation of hyperplasia persists only as long as the “cause” and the architecture of the organ is retained despite the increase in size
Describe the cell cycle
DNA replication or synthesis (S phase) and mitotic cell division (M phase) - the Cell Cycle(G1 = Gap 1; G2 = Gap2; G0 = resting/quiescent phase).
What are the extrinsic factors affecting the cell cycle?
Physical interactions with the environment
Competence factors
Commitment factors
What are physical interactions with the environment?
mammalian cells must adhere to a substratum, such as the extra-cellular matrix or other cells (cell: cell adhesion), before entering the cycle
What are competence factors?
growth factor or ligand for a cell surface receptor to be competent to enter the cycle- the effects of these receptor ligand interactions is to effect transcription of critical genes (enter cycle)
What are commitment factors?
polypeptide growth factors and hormones, which drive expression of genes required for progression through G1
What are the intrinsic factors affecting the cell cycle?
cyclin dependent kinases (cdks) which phosphorylate selected proteins
cyclins so named because their concentrations rise and fall in a regular pattern through the cell cycle
These complexes are regulated by another family of proteins: Cyclin dependent kinase inhibitors (CKIs) effectively the brakes on the cyclin/CDK functions
What are the checkpoints of the cell cycle?
G1/S Checkpoint
G2/M Checkpoint
Spindle assembly checkpoint
Why is the G1 phase crucial?
Period of intense metabolic activity when many cellular components are duplicated
Duration varies in response to external factors such as growth factors and hormones
it contains a critical checkpoint when the cell is committed to replicate its DNA and is no longer influenced by external factors
What are the options for the G1 phase of the cycle to commit to?
- To “recycle” and embark upon another round of DNA replication, chromosome condensation and cell division.
- To “decycle” and enter a resting phase Go, a phase from which the cell can re-enter the cycle if conditions so demand/ quiescence
- To “decycle” permanently and commit itself to functions incompatible with replication – terminal differentiation.
How is G1 progressed to S phase?
Inactive CDK-Cyclin D complex activated by phosphorylation, phosphorylates Rb
Different cyclins and CDKs for different checkpoints
What are the groups cells in animal and cell populations are classified into?
permanent
Conditional renewal populations
Continuously cycling self renewing populations
What are permanent cells?
non-replicating cells such as neurones and striated myocytes which lose the ability to replicate early in post natal life. Fully committed to differentiated function and have a zero or limited proliferative potential, loss of such cells means loss of function
What are conditional renewal populations?
hepatocytes, fibrocytes. Rarely divide and are held in Go. In the face of demand - loss or injury or increased function- the cells enter G1 and cycle until the lost tissue is replaced and then return to Go again.
Differentiation and proliferation not incompatible
What are self renewing populations?
tissues in which there is a functional differentiated fraction with a defined life span. Requirement for the continuous replacement of those cells by self renewal of other cells. Such populations must always consist of 3 compartments
Stem cells- bone marrow, lymphoid tissue
How are tissues organised?
- Stem cell: self renewing & slowly proliferating in niche, stem cell phenotype strictly controlled
- Transit amplifying: commitment to a differentiated lineage & rapid proliferation occur together
- Terminal differentiation: full differentiation (for function), but proliferation is incompatible
Which tissues consists of these populations?
All covering epithelia - skin, gut, urinary, genital etc.
Bone marrow, lymphoid tissues
What is metaplasia?
replacement of one differentiated cell type by another
almost always a response to persistent injury and most commonly involves the replacement of a glandular epithelium by a squamous one
What sites are most commonly affected by metaplasia?
exposure of the bronchial epithelium persistently to tobacco smoke
exposure of the endocervix of the uterus to acid pH, infection, semen leads to squamous metaplasia
What is squamous metaplasia?
Multi layered, stratified, fall off top
New squamous epithelium replaces original glandular epithelium, response to persistent injury, reversible- tissue reverts to normal after injury removed
What is dysplasia?
part of the spectrum of changes of pre-invasive neoplasia, dysplastic changes do not necessarily revert to normal once the injury is removed
What is dysplasia morphologically?
the regular organised appearance of the epithelium is disturbed by:
variations in the shape and size of cells
enlargement of nuclei – increased N:C ratio
pleomorphism – irregularity with variation in nuclear size, shape, chromatin staining,
hyperchromatic (darkly staining) nuclei
increased mitosis
distortion of the proliferating compared to the differentiating compartment
What is a neoplasm?
New growth, irreversible
Is an abnormal mass of tissue
the growth of which exceeds and is uncoordinated with that of the normal tissue
persists in the same excessive manner after the stimulus is removed.
What are the essential features of neoplasia or tumour growth
- composed of living cells
- differ from cells of the normal organ from which the tumour is derived- division/differentiation controls operating in that organ have been deregulated or lost.
- The control of division, differentiation and death may have been lost to the extent that the tumour
(a) loses partially or totally specialised functions (cell appearance changes)
(b) acquires new functions- invasion and metastasis
What is invasion?
the capacity to infiltrate the surrounding tissues and organs
What is metastasis?
The ability to spread to and proliferate in distant parts of the body after tumour cells have been transported by lymph or blood or along body spaces
What is a benign neoplasm?
Those which proliferate and divide but do not invade the surrounding tissues nor metastasize
growth is not life threatening, their clinical course is predictable. They may cause problems due to pressure, obstruction or excessive hormone production.
What is a malignant neoplasm?
Neoplasms which invade and/or metastasize
progressive and unless adequate therapy is available the patient will eventually die as a result of the disease
What are the symptoms of destructive invasive growth?
Blood loss – ulceration and haemorrhage
Pressure and destruction of adjacent tissue
Obstruction or constriction of flow in vital organs
Metabolic effects
general - cachexia
specific – tumour specific products
What are the shapes of neoplasms?
Sessile- sits on top of surface Pedunculated polyp- tag shape Papillary- seaweed like Fungating- growing outward Ulcerated- crater Annular- tubular
What do benign tumours look like?
Intact surface, exophytic growth, homogenous cut surface, circumscribed or encapsulated edge
What do malignant tumours look like?
Heterogenous cut surface due to necrosis, ulcerated surface, endophytic growth, vascular permeation, irregular infiltrated edge
Overview of benign neoplasms
Do not invade or metastasise
Slow growing
Low mitotic rate
Clearly demarcated from surrounding tissue- encapsulated or pseudo capsule
Nuclear morphology often normal
Mitotic figures normal
Clonal chromosome abnormalities- not aneuploid
Overview of malignant neoplasms
Invade and metastasise Not demarcated clearly Surface often ulcerated and necrotic Cut surface heterogenous Often high mitotic rate Rapid growth Nuclei pleomorphic, hyper chromatic Abnormal mitoses Usually aneuploid
