Cell Turnover and Disorders of Cell Proliferation and Differentiation Flashcards
Labile cells
- Describe them in a few words
- What is their normal level of proliferative activity?
- Do they have capacity for increased proliferation?
- Give examples
- steady state renewal
- high
- yes
- surface epithelia e.g. skin, gut, haemopoietic cells
Stable cells
- Describe them in a few words
- What is their normal level of proliferative activity?
- Do they have capacity for increased proliferation?
- Give examples
- conditional renewal
- low
- yes
- parenchymal cells of glandular organs e.g. liver, kidney, thyroid
Permanent cells
- Describe them in a few words
- What is their normal level of proliferative activity?
- Do they have capacity for increased proliferation?
- Give examples
- non-replacing
- none
- no
- neurones, cardiac muscle, skeletal muscle
Describe the states of cell division of
- stem cells
- transit cells
- mature functional cells
Stem cells = proliferative compartment
Transit cells = maturing cells, limited capacity for division
Mature functional cells = non dividing, programmed to die and require replacement
- Increased growth can be due to an increase in ……….. or ……… of cells
- Usually occurs as a result of ……. ……. ….. …….
- Stimuli may be ………….. , ………….. or ………..
- Capacity for cell division governs the patter of increased growth (and response to cell loss)
- Increased growth can be due to an increase in NUMBER or SIZE of cells
- Usually occurs as a result of INCREASED DEMAND FOR GROWTH
- Stimuli may be CHEMICAL, MECHANICAL or HORMONAL
- Capacity for cell division governs the patter of increased growth (and response to cell loss)
What are the two main patterns of increased growth>
hyperplasia and hypertrophy
What is the difference between hypertrophy and hyperplasia?
How are their stimuli different?
Hyperplasia - increase in number of cells - stimulus is usually hormonal or chemical Hypertrophy - increase in size of cells - stimulus is usually mechanical
Do the following cells respond with hyperplasia or hypertrophy?
- labile
- stable
- permanent
Labile - hyperplasia Stable - hyperplasia Permeneant - hypertrophy
How are pathological and physiological increased growth different?
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
Give 3 examples of physiological increased growth
- Pregnancy
- uterus - myocetrial hypertrophy and hyperplasia due to mechanical factors and oestrogen
- breast - glandular hyperplasia due to oestrogen and progesterone - Skeletal muscle
- hypertrophy ocurrido in athletes - Bone marrow
- hyperplasia of erythroid cells in response to blood loss
Give 3 examples of pathological increased growth
- left ventricular hypertrophy
- thyroid gland hyperplasia (Graves disease)
- cystic hyperplasia of the breast
What are the causes of left ventricular hypertrophy?
- systemic hypertension
- aortic valve disease (aortic stenosis or incompetence)
- mitral incompetence
- coronary artery atheroma (loss of some fibres so other fibres enlarge)
What are the consequences of left ventricular hypertrophy?
- initially compensates for increased demand
- later leads to cardiac failure (myocardial ischaemia may also occur)
What is graves disease and what is the cause?
- hyperplasia of the thyroid gland with increased prodcitin of thyroxine (thyrotoxicosis)
- due to production of thyroid stimulating autoantibodies (Ig’s) which act on same receptors as thyroid stimulating hormone
- not susceptible to normal negative feedback mechanism
What is 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 variation in breast tissue during menstrual cycle
What is hypoplasia?
What are the causes?
NOT the opposite of hyperplasia
- failure of a tissue or organ to reach normal size during development
- causes include genetic defects, intrauterine infection, toxic insults e.g. hypo plastic limbs related to thalidomide
What is atrophy>
- decrease in size of tissue or organ at a stage after initial development
- may be due to decrease in cell size or number
- can be physiological e.g. thymic atrophy
- part of ‘normal’ ageing process
What are the pathological causes of atrophy?
- loss of hormonal stimulation e.g. atrophy of endocrine organs secondary to pituitary disease
- reduction in blood supply
- decreased workload e.g. disuse atrophy of muscle
- loss of innervation
What 4 factors maintain normal cell integrity?
- cell membrane
- ATP generation
- protein synthesis
- genetic apparatus
What are the 4 causes of cell injury?
- hypoxia
- pro-inflammatory cytokines
- chemical toxins
- bacterial toxins
What factors are involved in early (reversible) cell injury?
Give some morphological terms
Typically associated with cell swelling Factors involved - entry of Na+ and water into cell (membrane dysfunction) - mitochondrial swelling - dilation of endoplasmic reticulum Morphological terms - hydropic change - vacuolar degeneration - ballooning degeneration
What is the word for late (irreversible) cell injury?
Describe the nuclear changes in later (irreversible) cell injury.
NECROSIS Nuclear changes - shrinkage (pynknosis) - fragmentation (karyorrhexis) - disappearance (karyolysis)
Describe the cytoplasmic changes seen in necrosis
Denaturation of proteins
- increased cytoplasmic eosinophilia (coagulative necrosis)
- typically occurs in hypoxic/ischaemic injury e.g. MI
Enzymatic digestion of cell
- disappearance of cells (lytic necrosis)
- more common with cytokine-mediated injury e.g. acute viral hepatitis
APOPTOSIS
- describe the cellular changes
- pattern of cell involvement
- pathogenetic mechanisms
- tissue reaction
- physiological examples
- pathological examples
APOPTOSIS
- describe the cellular changes
- shrinkage, fragmentation (apoptotic bodies) - pattern of cell involvement
- single cells - pathogenetic mechanisms
- energy dependent, tightly regulated - tissue reaction
- phagocytosis of apoptotic bodies, no inflammation - physiological examples
- UES, normal cell turnover, organ development - pathological examples
- Yes, including same factors as those cause necrosis
NECROSIS
- describe the cellular changes
- pattern of cell involvement
- pathogenetic mechanisms
- tissue reaction
- physiological examples
- pathological examples
NECROSIS
- describe the cellular changes
- swelling, coagulative or lytic damage - pattern of cell involvement
- groups of cells - pathogenetic mechanisms
- energy-independent
- loss of cell integrity - tissue reaction
- inflammation - physiological examples
- No - pathological examples
- Yes
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
For the following sites give the original cell type, the metaplastic cell type and the cause:
- Bronchus
- Lower oesophagus
- Stomach
- Bronchus
- ciliated columnar
- squamous
- cigarette smoking - Lower oesophagus
- squamous
- gastric
- acid reflux - Stomach
- columnar
- intestinal
- chronic inflammation e.g. H.pylori infection
What are the consequences of metaplasia?
- loss of normal function e.g. chest infections due to squamous metaplasia in bronchi
- increased risk of malignancy
Describe the varied usage of the term dysplasia
- literally means disordered development
Developmental abnormalities
e.g. cystic renal dysplasia
Tumour like malformations - fibbers dysplasia of bone
Premalignant changes (usually epithelial)
e.g. epithelial dysplasia in UC
Describe how dysplasia is a premalignant condition
- changes resemble those seen in neoplastic cells
- not yet invasive, but potential for precession to invasive carcinoma if untreated
- increasing grads of dysplasia described (mild, moderate, severe)
- potential for reversibility dimness with progression in grade
- severe dysplasia = carcinoma in situ
- intraepithelial neoplasia now preferred term in many situations e.g. cervical intraepithelial neoplasm or CIN
- basis for screening
