Cell Turnover And Disorders Of Cell Proliferation Amd Differentiation Flashcards
Basic differences in normal and abnormal cell growth and turnover
Normal cell turnover vs
Changes in cell growth (inc and Dec)
Cell death
Abnormalities of cell differentiation
Labile cell types of cell renewal
Steady state renewal
Stable cell type of cell renewal
Conditional cell renewal
Permanent cell type of cell renewal
Non replacing
So no renewal
Normal proliferative capacity of labile cells
High
Do labile cells have the capacity to inc proliferation
Yes
Normal proliferative activity of stable cells
Low
Is there capacity for increased proliferation
Yes
Normal proliferative activity of permanent cells
None
Is there Capacity for increased proliferation in permanent cells
No
Stem cells capacity to divide
Proliferative compartment so can divide and differentiate into different cell types
Transit cells state of cell division
Maturing cells
Limited capacity for division
Mature functional cells state of cell division.
Non dividing
Programmed to die and require replacement
When does the epidermis lose its capacity to divide
3 basic layers, basal, prickle, horny
At the prickle layer they lose their nuclei and capacity to divide
Phases of the cell cycle what they are called and what happens at each
G0 - quiescent phases not dividing can move to dividing G1 with the right signals
G1 - gap1 (pre-synthetic) growth phase
S - synthetic replication DNA
G2 - gap 2 (pre-mitotic) more growth
M - mitotic cell division
At the G1 phase - the cell can become terminally differentiated or go through the cell cycle again
Factors which control cell division
Polypeptide growth factors and cytokines
Cyclins
Inhibitory factors
What do polypeptide growth factors and cytokines do
Act on receptors on the cell surface
Formation of second messenger in cytoplasm
DNA synthesis in the nucleus
What do cyclins do to control the cell cycle
Activate proteins involved in DNA replication and other events on the cell cycle
What are the inhibitor factors which control cell division
Polypeptide growth factors/cytokines
Tumour suppressor genes p53
Cyclin dependent kinase inhibitors p21,27
Patterns of increased growth - normal
Inc number of the cells
Inc the size of the cells
Occurs as a result of increased demand for function
Stimuli may be mechanical, chemical or hormonal
Capacity for cell division governs the pattern of inc growth (and also response to cell loss)
Inc in no of cells is called
What is the stimuli for this
Hyperplasia
Stimulus normal or chemical
Inc in size of cells called and stimulus for this
Hypertrophy
Mechanical stimuli usually
What is the response of labile cells to increased demand for function
Hypertrophy or hyperplasia and the stimulus and response to injury this action causes
Hyperplasia
Chemical or hormonal
Regeneration
What is the response of stable cells to increased demand for function
Hypertrophy or hyperplasia and the stimulus and response to injury this action causes
Hyperplasia
Chemical or hormonal
Regeneration
What is the response of permanent cells to increased demand for function
Hypertrophy or hyperplasia and the stimulus and response to injury this action causes
Hypertrophy
Mechanical
Repair
Types of increased growth
Physiological - changes largely reversible if the stimulus causing them is removed
Pathological - changes less readily reversible
If excessive growth persists may predispose to neoplastic transformation
Examples of normal physiological growth
Pregnancy - uterus - myometrial hypertrophy and hyperplasia due to mechanical factors and oestrogen
Breast - glandular hyperplasia due to oestrogen and progesterone
Skeletal muscle - hypertrophy in athletes
Bone marrow - hyperplasia of erythroid cells in response to blood loss
Example of increased growth - pathological
Left ventricle hypertrophy
Thyroid gland hyperplasia - graves
Cystic hyperplasia of the breast
Pathological left ventricular hypertrophy
Causes -
Systemic hypertension
Aortic value disease (aortic stenosis or incompetence)
Mitral incompetence
Coronary artery atheroma
Consequences
Initially compensates for increased demand
Later leads to cardiac failure (myocardial ischaemia may also occur)
Pathological thyroid hyperplasia - Graves’ disease
Hyperplasia of thyroid gland with increased
production of thyroxine (thyrotoxicosis)
Due to production of thyroid stimulating auto antibodies act on same receptors as TSH
Not susceptible to normal negative feedback mechanism
Pathological cystic hyperplasia of the breast
Proliferation of glandular elements with formation of cysts
Probably due to hormonal factors
- occurs in women between menarche and menopause
- normal variations in breast tissue during the menstrual cycle
What is hypoplasia
Failure of a tissue or organ to reach normal size during development
Causes include: genetic defects, intrauterine infection, toxic insults - limbs in thalidomide effected people
What is atrophy
Decrease in size of tissue or organ at a stage after initial development
Dec cell size or number
Can be physiological - post puberty decline in thymus size
Part of normal ageing process
Causes of pathological atrophy -
Loss of hormonal stimulation e.g. Atrophy of endocrine organs secondary to pituitary disease
Dec workload - disuse atrophy of muscle
Loss of innervation
Factors maintaining normal cell integrity
Cell membrane
ATP generation (mitochondria)
Protein synthesis
Genetic apparatus
Causes of cell injury
Hypoxia
Pro-inflammatory cytokines
Chemical toxins
Bacterial toxins
Early reversible cell injury
Associated with swelling Factors involved - entry of sodium and water into cell (membrane dysfunction) - mitochondrial swelling - dilatation of endoplasmic reticulum morphological terms - hydropic change - vacuoles degeneration - ballooning degeneration
Late irreversible cell injury
Necrosis Nuclear changes -shrinkage (pyknosis) - Fragmentation (karyorrhexis) - disappearance (karyolysis) Cytoplasmic changes - denaturation of proteins -- inc cytoplasmic eosinophilia (coagulation necrosis) - acid liking staining cytoplasm - cell outlines still visible -- occurs in hypoxic/ischaemic injury - enzymatic digestion of the cell -- disappearance of cells (lyric necrosis) -- more common with cytokines mediated injury e.g. Acute viral hepatitis
Morphological features of necrosis - late irreversible cell injury
Time - several hours to develop
Necrosis typically elicits an acute inflammatory reaction around 24 hours after cells death
Apoptosis vs necrosis cellular changes
Apoptosis
Shrinkage
Fragmentation
(Apoptosis bodies)
Necrosis
Swelling
Coagulation or lytic changes
Apoptosis vs necrosis
Pattern of cell involvement
Apoptosis
Single cell
Necrosis
Groups of cells
Apoptosis vs necrosis
Pathogenetic mechanisms
Apoptosis
Energy dependent
Tightly regulated
Necrosis
Energy independent
Loss of cell integrity
Apoptosis vs necrosis
Tissue reaction
Phagocytosis of apoptotic bodies
No inflammation
Necrosis
Inflammation
Apoptosis vs necrosis
Physiological example
Apoptosis yes - normal cell turnover
Necrosis none
Apoptosis vs necrosis
Pathological example
Apoptosis - yes
Necrosis- yes
Types of abnormalities of cell differentiation
Metaplasia
Dysplasia
Define metaplasia
Replacement (potentially reversible) of one differentiated cell type by another differentiated cell type
Usually occurs as response to unfavourable environment for the original cell type
Barrett’s oesophagus
Examples of common metaplasia
Site - bronchus
Original cell type - ciliated columnar (resp epithelium)
Metaplastic cell type - squamous
Cause - cigarette smoking
Site - lower oesophagus (Barrett’s)
Original cell type - squamous
Metaplastic cell type - gastric (columnar lined distal oesophagus)
Cause - acid reflux
Site - stomach
Original cell type - columnar (gastric)
Metaplastic cell type - intestinal
Cause - chronic inflammation- H pylori infection
Consequences - metaplasia
Loss of normal cell function
E.g. Chest infections due to squamous metaplasia in bronchi
Increased risk of malignancy
Definition of dysplasia
Literally ‘disordered development’
Controversial term due to varied usage:
- developmental abnormalities -e.g. Cystic renal dysplasia
- tumour like malformation-e.g. Fibrous dysplasia of bone
- premalignant changes (usually epithelial)
E.g. Epithelial dysplasia in UC
Dysplasia as premalignant condition
Changes resemble those sent in neoplastic cells
Not yet invasive, but potential for progression to invasive carcinoma if untreated
Increasing grades of dysplasia described (mild, moderate, severe)
- potential for reversibility diminishes with progression in grade
- severe dysplasia = carcinoma in situ
Intraepithelial neoplasia now preferred term in many situations
-e.g. Cervical intraepithelial neoplasia or CIN:
CIN grade 1 mild neoplasia, CIN 2 = moderate dysplasia, CIN 3 = severe dysplasia
- basis for screening
