11 - Cellular Adaptations Flashcards
What genes regulate normal cell proliferation?
Protooncogenes
How can you increase growth of a tissue?
- Shorten cell cycle
- Convert quiescent cells to proliferating cells
What are the three checkpoints in the cell cycle?
- Restriction point at end of G1 (most critical and those that pass will go through full cycle but if activated p53 comes into play)
- G1/S transition: DNA damage before replication
- G2/M transition: DNA damage after replication
What is the relevance of the restriction checkpoint?
- Cells that pass this point normally complete the full cell cycle
- If checkpoint activation here p53 protein stops cell cycle and triggers DNA repair mechanisms or apoptosis if irreparable damage
What does the p53 protein do?
Tumour supression gene, regulates cell cycle
What is the likely outcome of faulty cell cycle checkpoints?
Cancer
How is the cell cycle controlled?
- Proteins called cyclins work with enzymes CDKs
- CDK activated by binding and complexing with cyclins
- Activated CDKs phosphorylate proteins e.g RB protein, that are needed for progression of the cell cycle
- Activated CDK complexes regulated by CDK inhibitors and growth factors stimulate production of cyclins and shut off CDK inhibitors
What is a retinoblastoma susceptibility (RB) protein?
- Tumour suppressor gene that is often defective in cancer, causing retinoblastoma
- Inactivated by phosphorylation by CDK4
What is a cell adaptation and what are the different adaptations?
State between an unstressed cell and an overstressed injured cell, usually reversible
- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia
What is hyperplasia and where does it occur?
- Increase in tissue size due to increased cell numbers
- Occurs in labile or stable cell populations and is reversible
- Hormonal or compensatory
- Controlled and reversible but repeated division exposes cell to risk of mutations and neoplasia
What is the difference between hormonal and compensatory hyperplasia?
Physiological hyperplasia
- Hormonal: increase in functional capacity
- Compensatory: increase in tissue mass e.g after injury
Why does pathological hyperplasia usually occur?
- Secondary to excessive hormonal stimulation or growth factor production
- Normal response to abnormal condition
What are some examples of physiological and pathological hyperplasia?
- Physiological: Proliferative endothelium and increased bone marrow production of RBC at altitude
- Pathological: goitre in iodine deficiency, epidermal thickening in chronic eczema and psoriasis
What is hypertrophy and where does it occur?
- Mainly in permanent tissues as they have little replicatitive ability
- Response to increase in functional demand and/or hormone stimulation
- Cells synthesise more cytoplasm and may also undergo hyperplasia in response to endocrine stimulation
What are some examples of physiological and pathological hypertropy?
Physiological: skeletal muscle of bodybuilder, pregnant uterus under influence of oestrogen with hypertrophy and hyperplasia
Pathological: cardiac muscle hypertrophy due to valve disease/hypertension, smoot muscle hypertrophy of SI due to intestinal stenosis, bladder muscle hypertropy due to enlarged prostate
What happens when the stimulus for hypertrophy and hyperplasia is removed?
Cells and organs become normal size again
What is compensatory hypertrophy?
When looking at pair of organs, if one is removed the other enlarges, often by hyperplasia and hypertrophy
What is atrophy and how does it occur?
- Reduced supply of growth factors and/or nutrients in disease
- Cell shrinks to size at which survival is still possible by reducing components of cell
- Cell apoptosis also occurs and mainly parenchymal cells killed before stromal so atrophic organs have a lot of connective tissue
- Reversible up to a point
What are examples of physiological atrophy?
- Ovarian atropy in post-menopausal women
- Decrease in size of uterus after pregnancy
What is the best way to treat atrophy?
Remove the cause
What are some examples of pathological atrophy?
- Reduced functional demand/disuse e.g cast
- Loss of innervation
- Inadequate blood supply e.g thinning of skin on legs due to peripheral vascular disease
- Inadequate nutrition
- Loss of endocrine stimuli e.g wasting of adrenal with loss of ACTH
- Persistent injury e.g polymyositis
- Senile Aging e.g in permanent tissues like brain
- Pressure e.g ischemia from a tumour
- Occlusion of secretory duct e.g parenchymal cells undergo apoptosis
- Toxic agents and drugs
- X-rays
- Immunological mechanisms e.g in pernicious anaemia where antibodies against parenchymal gastric cells
What is atrophy of extracellular bone matrix callled?
Osteoporosis
What is metaplasia and why does it occur?
- Genetic reprogramming of stem cells so stressed cells replaced by different type
- Still reversible but a prelude to dysplasia and cancer
- No metaplasia over germ layers
- Only in labile and stable cell types
- Allows cells to be more suited to the environment
Where is metaplasia most commnly found and what is the issue with it?
- Epithelium of columnar to squamous
- On surface linings as exposed to insult
- Epithelium may lose function e.g mucus secretion los
What is the difference between metaplasia and dysplasia?
Dysplasia is disorganis abnormal differention whereas metaplastic is fully differentiated
When can metaplasia be useful?
- Bone marrow disease: destroys marrow so splenic tissue differentiates to bone marrow, myeloid metaplasia
- Columnar epithelium lining ducts can undergo metaplasia to squamous when there is chronic irritation by stones as squamous more resistant to abrasion
What types of epithelial metaplasia can predispose to malignant epithelial cancer?
- Barret’s epithelium: oesophageal adenocarcinoma
- Intestinal metaplasia of the stomach: by chronic infection with Helicobacter pylori causing gastric adenocarcinoma
What is Barrett’s oesophagus?
- Persistent acid reflux can cause stratified squamous epithelium in lower oesophagus to convert to glandular epithelium to produce mucins against acid
What are some examples of metaplasia with no function or causing detrimental effects?
- Barrett’s oesophagus
- Bronchial pseudostratified ciliate epithelium to stratified squamous from smoke and this cannot produce mucus or move mucus as no cilia
- Traumatic myositis ossificans where bone develops in skeletal muscle following trauma so fibroblasts turn to osteoblasts. Young people when return to activity too soon before healing
What is aplasia?
- Complete failure of specific tissue or organ to develop, embryonic development issue
e.g thymic aplasia which leads to autoimmune and infection issues, kidney aplasia
- Also when cells of organ cease to proliferate
e.g aplastic anaemia
What is hypoplasia?
- Underdevelopment or incomplete development of a tissue or organ, inadequate number of cells in tissue
- Spectrum with aplasia
e. g renal, breast, testicles in Klinefelters, chambers of heart
What is atresia?
Congenital imperforation of an opening
e.g vagina, anus, valve, small bowel
What is reconstitution?
Replacement of lost body part not small group of cells, not really possible in humans, we cannot even reconstitute hair follicles as we have hairless scars
What is dysplasia?
Abnormal maturation of cells in a tissue, maybe reversible, but often pre cancerous condition
How often do stem cells divide?
Not very often, they divide to form short lived progenitor cells which then divide to prevent mutations surviving through generations
Would a cancer want more or less retinoblastoma protein?
- Less, it is a tumour supressor gene as it holds onto molecules that are needed to enter the cell cycle
- They are stimulated to release these by CDK’s
A patient is taking tamoxifen as she had breast cancer in the past, she has some vaginal bleeding so has a biopsy of her uterus. What is the diagnosis and why is it important to note she is obese? (one on left is normal)
- Endometrial hyperplasia
- She has more adipose so more oestrogen produced and therefore more growth as it is a GF
- Tamoxifen is a partial agonist and can lead to uterine cancer
What are some causes of cardiac hypertrophy and why can it cause someone to suddenly collapse and die?
- Systemic hypertension, aortic coarctation, valve stenosis
- Can cause the heart to go into arrythmia as there is interstitial fibrosis
- Also, lack of oxygen and blood supply due to the larger diffusion distance
What is the naming system of a metaplasia and what are the long term complications of squamous metaplasia in the bronchioles from smoking?
- Named by what cell it turns into
- Can lead to squamous cell carcinoma and squamous cells in bronchioles exposed to carcinogens from smoking
What is Barett’s oesophagus and what tumour can this predispose the bronchioles to?
- When someone has chronic acid reflux the distal oesophagus undergoes metaplasia from squamous epithelium to glandular columnar epithelium to secrete mucus to protect against acid
- Adenocarcinoma
Which part of the prostate is benign prostatic hyperplasia affecting and what effects can it have?
- Periurethral part
- Bladder distension and retention
- Doesn’t predispose to prostraic carcinoma
