Cell and tissue growth disorders and dysplasia Flashcards
What are the cellular responses to stress and noxious stimuli?
- Cellular adaptation
- Subcellular adaptation
- Cell injury
- Cell death
What is hyperplasia?
- Increase in cell number (increase in organ or tissue size)
- Occurs if mitotic division is possible - otherwise hypertrophy
When does physiological hyperlasia occur?
- Normal hyperplasia - increased functional capacity of the tissue when needed, eg breast hyperplasia at puberty or pregnancy
- Compensatory hyperplasia - increased tissue mass after damage or partial resection eg unilateral nephrectomy
When does pathological hyperplasia occur?
- Hormonal stimulation eg endometrial and prostatic hyperplasia, adrenal cortical hyperplasia in Cushings due to ACTh secreting pituitary adenoma
- Autoimmune phenomenon - Graves
- Wound healing
- Viral wart
Why would we get thyroid hyperplasia?
- A lack of secreting tissue (cretinism)
- Lack of substrate (iodine deficiency)
- Lack of enzymes in pathway
- All cause hyperplasia via normal feedback mechanisms - Need TH for bone growth
What causes graves?
- TSH autoantibodies
- Causes thyrotoxicosis
What is hypertrophy?
- Increased synthesis of structural components, increased cell size (eg myocardial fibres, skeletal muscle fibres)
When does physiological hypertrophy occur?
- Increased functional demand eg muscle hypertrophy after regular exercise
- Hormonal stimulation eg myometrial hypertrophy in pregnancy
When does pathological hypertrophy occur?
- Increased load placed on organ or tissue eg left ventricular hypertrophy in hypertension or in rheumatic aortic valve
- BPH
What are 5 symptoms of BPH?
- obstruction of the outflow tract
- urinary retention
- failure to empty the bladder fully leading to nocturia
- poor flow
- interference with the sphincter
- difficulty starting and stopping micturition, terminal dribbling
- recurrent UTI
What is atrophy?
- Reduction in cellular component, decrease in size and number of cells, decreased organ size
When does physiological atrophy occur?
- embryological structures undergo atrophy during foetal develop eg thyroglossal duct
- Thymic atrophy at puberty
- Uterus after parturition
When does pathological atrophy occur?
- Decreased workload
- Loss of innervation or blood supply
- Compression (lose blood supply)
- Inadequate nutrition
- loss of endocrine stimulation
- Aging
What is metaplasia?
- Adaptive substitution of cells by cell types better able to withstand the adverse environment
- Reversible replacement of one mature tissue type by another
What are some common examples of metaplasia?
- Squamous metaplasia
- Intestinal metaplasia
- Connective tissue metaplasia
Where does squamous metaplasia occur?
Columnar to squamous epithelium (squamous metaplasia)
- respiratory tract due to chronic irritation (bronchus of smokers)
- Stones in excretory ducts eg salivary gland, pancreas, bile ducts
- Endocervix as it everts at puberty
Where does intestinal metaplasia occur?
Squamous to columnar
- Barrett’s oesophagus - regular reflux of gastric acid into the oesophagus
- H.pylori infected stomach
Where does connective tissue metaplasia occur?
- Myositis ossificans - bone formation in muscle due to injury
What is agenesis?
- Complete absence of an organ and its primordium
What is aplasia?
- Absence of an organ, but due to incorrect development of primordium
What is atresia?
- Absence of opening, usually of a hollow organ eg intestine
What is hypoplasia?
- Incomplete development of an organ with decreased number of cells
What is dysplasia?
- Abnormal organisation of cells
What is heterotopia?
- Well developed tissue but at the wrong site
- eg gastric or pancreatic heterotopia within a Meckel’s diverticulum
What is hamartoma?
- Mass of disorganised but mature tissue appropriate to a site
- eg bronchial hamartoma is composed of islands of cartilage and respiratory epithelium embedded in smooth muscle and fibrous tissue
What is anaplasia?
Lack of differentiation - “hallmark of malignancy”
What are some characteristic cytological features of dysplastic and malignant cells?
- Nuclear pleomorphism = variation in shape and size
- Nuclear hyperchromatism = variation in darkness of nuclear staining (reflects amount of chromatin)
- Increased nuclear:cytoplasmic ration (1:1 or 1:2 rather than normal 1:4)
- Increased mitoses visible = often remain in mitotic phase for longer than normal
- Atypical mitoses = often have unequal split of chromatin results in aneuploidy
When is dysplasia most likely to cause cancer?
- Different levels of dysplasia can occur
- mild-moderate-high grade
- When it is the full thickness of the tissue = carcinoma in situ
- It becomes invasive and very likely to be metastatic when the tumour cells get beyond the basement membrane
- Dysplasia isnt necessarily going to progress to cancer, mild/moderate changes may be reversible
Give 4 examples of sites that are very likely to become malignant from dysplasia?
- Dysplasia of squamous mucosa in bronchus of smokers
- Dysplasia of squamous epithelium of cervical transformation zone in patients with HPV
- Dysplasia of Barrett’s epithelium in GORD patients
- Dysplasia of intestinal epitheium in H.pylori gastritis
What can increase the likelihood of developing a cancer?
- genetic disposition - inherited cancer syndromes (germline mutations) can increase risk of developing a malignancy eg retinoblastoma
- Non-hereditary predisposition = environment, behaviour, clinical conditions etc
Premalignant vs predisposing conditions
- Predisposing (infection of cervix with HPV 16/18, or H pylori gastritis) - give an increase in risk of development
- Premalignant - (non-neoplastic disorders with well-defined association with malignancy; high grade dysplasia and ulcerative colitis) - if you have these, you will definitely get cancer
What are some characteristics of neoplasms?
- Autonomous growth, not sensitive to feedback mechanisms
- DNA mutation in a cell (usually several mutations) confers a survival advantage
- DNA mutations are often caused by carcinogens but may arise spontaneously
- Monoclonal tumour cell population due to derivation from single cell - mutations in daughter cell may give different characteristics, known as tumour heterogeneity
What are stem cells?
- enable tissues to renew themselves, they proliferate and differentiate into mature tissue types
- Stem cells have cytoprotective mechanisms which prevent harm from drugs
- Not all are locally derived
What are cancer stem cells?
- Mutated versions of normal stem cells
- Less than 4% of tumour cells can form independently viable clones in culture, the rest die
- these immortalised cells are thought to drive tumour growth
Why will a mutation cause uncontrolled growth?
- process may be unregulated by the checkpoints
- Mutation may affect daughter cells or stem cells, which may continue to drive growth instead of ceasing cell division after differentiation
