Abnormal Growth Flashcards
(106 cards)
1
Q
What are adaptations?
A
Cellular changes in response to changes in environment or demand (size, number, phenotype, metabolic activity, function).
REVERSIBLE
2
Q
What is homeostasis?
A
Homeostasis is the ability to maintain a relatively stable internal state that persists despite changes in the world outside.
3
Q
Are adaptations reversible?
A
Often reversible (compared with cell injury and neoplasia)
4
Q
What can trigger an adaptation?
A
Reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli.
5
Q
What is the result of an adaptation?
A
New but altered steady states are achieved, allowing the cell to survive and continue to function
6
Q
What is hypertrophy?
A
Increase in SIZE of cells and eventually size of organ
7
Q
What is hyperplasia?
A
Increase in NUMBER of cells caused by cell division
8
Q
What causes hypertrophy?
A
Increased synthesis of structural components (proteins) caused by increase in functional demand (or hormones)
9
Q
Where is hypertrophy particularly seen?
A
In permanent cell populations (very limited capacity for division) especially cardiac and skeletal muscle
10
Q
What does hypertrophy lead to?
A
Increase in functional capacity and increased metabolism
11
Q
What is the most common stimulant of hypertrophy for muscles?
A
Increased workload
12
Q
Ability to adapt varies in different cell types. Why do fibroblasts not need to adapt?
A
Survive severe metabolic stress without harm. e.g absence of oxygen
13
Q
Why can epithelial cells adapt easily?
A
- Labile cell population
- Active stem cell compartment
- Highly adaptive in number and function
14
Q
Why can cerebral neurons not adapt?
A
- Terminally differentiated and permanent cell population
- Highly specialised function and easily damaged
15
Q
Why is physiological adaptation?
A
Responding to normal changes in physiology or demand
16
Q
What is pathological adaptation?
A
Responding to disease related changes
17
Q
What are the 3 types of adaptive responses?
A
- Increased cellular activity (Increased size or number of cells)
- Decreased cellular activity (Decreased size or number of cells)
- Change of cell function and/or morphology
18
Q
What is a good example of a hormone-induced increase in the size of an organ that results mainly from hypertrophy of muscle fibres?
A
The massive physiologic growth of the uterus during pregnancy
19
Q
What stimulates cellular enlargement of the uterus?
A
Oestrogenic hormones acting on smooth muscle oestrogen receptors, eventually resulting in increased synthesis of smooth muscle proteins and an increase in cell size.
20
Q
What causes the prostate to enlarge?
A
Ageing process –> by adenomyomatous hyperplasia
Detrusor muscle has to work harder during micturition and undergoes hypertrophy (trabeculated appearance)
21
Q
How can the enlargement of the prostate affect the bladder?
A
Can lead to bladder outlet obstruction
Herniation of mucosa between the hyperplastic muscle trabeculae leading to the formation of a bladder diverticulum (prominent opening)
22
Q
What are permanent cells?
A
Permanent cells are cells that are incapable of regeneration. These cells are considered to be terminally differentiated and non-proliferative in postnatal life.
23
Q
What are examples of permanent cells?
A
Neurons, heart cells, skeletal muscle cells and red blood cells
24
Q
How can hypertension lead to hypertrophy
A
Hypertension leads to increased peripheral resistance –> increases work required by left ventricle –> hypertrophy
The hypertrophy will compensate for some time, but if the hypertension is untreated the compensation may eventually fail.
25
Subcellular organelle may also undergo selective hypertrophy. What is an example of a drug that can stimulate this?
Barbiturates
26
What is the adaptive response of barbiturates?
Individuals treated with drugs such as barbiturates
| show hypertrophy of the smooth endoplasmic reticulum (ER) in hepatocytes
27
What is the purpose of this adaptive response after treatment with barbiturates?
Increases the amount of enzymes (cytochrome P-450 mixed function oxidases)
available to detoxify the drugs.
N.B. after a while the patient will not respond as well to these drugs due to increased metabolism
28
What is non-dividing cell increased tissue mass due to?
Hypertrophy
29
What are the 2 types of hyperplasia?
1. Physiological
| 2. Pathological
30
What can physiological hyperplasia be divided into?
Hormonal and compensatory
31
What is hormonal hyperplasia? What is an example?
Increases the functional capacity of a tissue when needed.
E.g. the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy) of the glandular epithelial cells
32
What is compensatory hyperplasia? What is an example?
Increases tissue mass after damage or partial resection.
E.g. capacity of the liver to regenerate
33
Where is hyperplasia possible?
In labile and stable cell populations
34
Can hyperplasia and hypertrophy occur together?
Hyperplasia and hypertrophy are distinct processes but frequently occur together.
Both can triggered by the same external stimulus.
35
What are most forms of pathological hyperplasia caused by?
Excesses of hormones or growth factors acting on target cells
36
What causes benign prostatic hyperplasia?
A common example of pathologic hyperplasia induced by responses to hormones, in this case, androgens
37
Where is hyperplasia seen in Grave's disease?
An autoantibody binds to and switches on the TSH receptor in the thyroid, leading to prolonged, uncontrolled hyperplasia of the thyroid and hyperthyroidism (thyrotoxicosis).
38
What is atrophy?
Reduction in size of organ or tissue by decrease in cell size and number.
It can be physiological or pathological.
39
What can cause pathological atrophy?
- Decrease workload (disuse atrophy)
- Loss of innervation (denervation atrophy)
- Diminished blood supply
- Inadequate nutrition (e.g. cachexia)
- Loss of endocrine stimulation
- Pressure
40
What is an example of disuse atrophy?
When a fractured bone is immobilised in a plaster cast
41
What can cause denervation atrophy?
Damage to nerves
42
What type of atrophy can slowly developing arterial occlusive disease cause?
Diminished blood supply
43
What is an example of atrophy caused by loss of endocrine stimulation?
The loss of oestrogen stimulation after menopause results in physiologic atrophy of the endometrium, vaginal epithelium, and breast.
44
How can pressure cause atrophy?
Tissue compression for any length of time can cause atrophy. An enlarging benign tumour can cause atrophy in the surrounding uninvolved tissues.
Atrophy in this setting is probably the result of ischaemic changes caused by compromise of the blood supply by the pressure exerted by the expanding mass.
45
What is an example of physiological atrophy?
Physiologic atrophy is common during normal
development.
- Some embryonic structures, such as the notochord
and thyroglossal duct, undergo atrophy during fetal
development.
- The uterus decreases in size shortly after
parturition.
46
What are the mechanisms of atrophy?
- Reduction in volume of individual cells
| - Death of individual cells
47
What does atrophy result from?
Decreased protein synthesis and increased protein degradation
48
What causes decreased protein synthesis?
Reduced metabolic activity
49
In many situations, atrophy is also accompanied by increased autophagy. What is autophagy?
The process in which the starved cell eats its own components in an attempt to find nutrients and survive
50
What is senile atrophy?
The brain may undergo progressive atrophy, mainly because of reduced blood supply as a result of atherosclerosis.
This is called senile atrophy; it also affects the heart.
51
What is metaplasia?
Transformation of one differentiated cell type into another (reversible)
52
What is the purpose of metaplasia?
It may represent an adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment
53
What metaplasia occurs in the oesohagus in response to gastric reflux?
Glandular, or Barrett’s, metaplasia of the normal oesophageal squamous mucosa --> into gastric type columnar mucosa
54
What is the transformation zone?
Columnar cells are constantly changing into squamous cells in an area of the cervix called the transformation (transitional) zone.
55
Where is the most common place on the cervix for abnormal cells to develop?
The transformation zone - these can be detected on a smear test
56
What stimulus can cause pseudostratified ciliated bronchial epithelium to change to squamous epithelium?
Cigarette smoke (this is a protective response)
57
What is the result of pseudostratified ciliated bronchial epithelium changing to squamous epithelium?
You lose some of your natural protection against infection as normal bronchial epithelium secrete mucus and have cilia
More prone to infection and malignant transformation due to constant metaplasia (squamous cell carcinoma)
58
What stimulus can cause transitional epithelium of the bladder to change to squamous epithelium?
Bladder calculus, schistomosiasis, longstanding catheter
59
What stimulus can cause fibrocollagenous tissue to change to bone?
Chronic trauma
60
What stimulus can cause oesophageal squamous epithelium to change to columnar (glandular) epithelium?
Acid reflux
Predisposes cancer formation
61
What is neoplasia?
the uncontrolled, abnormal growth of cells or tissues in the body
62
What neoplasia can glandular metaplasia in the oesophagus lead to?
Adenocarcinoma
63
What neoplasia can squamous metaplasia in the cervix lead to?
CIN and squamous cell carcinoma
64
What neoplasia can endometrial hyperplasia due to increased oestrogens lead to?
Adenocarcinoma
65
What neoplasia can squamous metaplasia in the bronchus lead to?
Dysplasia and squamous cell carcinoma
66
What neoplasia can squamous metaplasia in the bladder lead to?
Squamous cell carcinoma
67
What neoplasia can parathyroid hyperplasia due to chronic renal failure lead to?
Adenoma
68
What is dysplasia?
Earliest morphological manifestation of multistage process of neoplasia
69
Is dysplasia reversible?
No
70
Is dysplasia invasive?
No - In-situ disease that shows cytological features of malignancy, but no invasion
71
What does the recognition of dysplasia allow?
Gives us a chance to treat a potentially fatal tumour before it arises
The abnormal cells have not yet acquired the capacity for invasion so they cannot spread.
72
What forms the basis of the cervical screening process?
The recognition of dysplasia
73
What does 'carcinoma in situ' mean?
Just another term for severe dysplasia
74
Term for:
An increase in the size of cells that results in an increase in the size of the affected organ.
Hypertrophy
75
Term for:
An increase in the number of cells in an organ or tissue in response to a stimulus.
Hyperplasia
76
Term for:
A reduction in the size of an organ or tissue due to a decrease in cell size and number.
Atrophy
77
Term for:
A reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.
Metaplasia
78
Examples of physiological stimuli adaptation:
- Pregnancy
- Bodybuilders
- Liver
- Hormonal
Uterus hypertrophy during pregnancy.
Muscle bulk gain in bodybuilders due to individual muscle fibres hypertrophy.
Hormonal hyperplasia: breast glandular epithelium proliferation and epithelial hypertrophy during pregnancy. Endometrial proliferation
Liver regeneration
79
What pathological stimuli adaptation would be caused by LHF due to the increased pressure overload?
Hypertrophy of myocardiocytes
80
What pathological stimuli adaptation would be caused by increased androgens?
Prostate hyperplasia
81
What pathological stimuli adaptation would be caused by insufficient nutrition?
Denervation athrophy
82
What drives hyperplasia?
Growth factor–driven proliferation of mature cells and, in some cases, by increased output of new cells from tissue stem cells.
83
What does atrophy result from?
Atrophy results from decreased protein synthesis and increased protein degradation in cells.
Protein synthesis decreases because of reduced trophic signals (e.g., those produced by growth receptors), which enhance uptake of nutrients and increase mRNA translation.
84
How does cigarette smoking cause metaplasia?
Cigarette smoking caused columnar to squamous epithelium metaplasia in trachea and bronchi.
85
How do gallstones cause metaplasia?
Cause metaplasia of secretory columnar epithelium to squamous
86
How does Barrett's oesophagus cause metaplasia?
Gastric reflux caused oesophageal squamous epithelium change to intestinal columnar
87
What does metaplasia result from?
Metaplasia does not result from a change in the phenotype of an already differentiated cell type; rather, it results from either reprogramming of local tissue stem cells or, alternatively, colonisation by differentiated cell populations from adjacent sites.
88
8 hallmarks of cancer?
1. Sustaining proliferative signalling
2. Evading growth suppressors
3. Avoiding immune destruction
4. Enabling replicative immortality
5. Activating invasion and metastasis
6. Inducing angiogenesis
7. Resisting cell death
8. Deregulating cellular energetics
89
How do cancer cells resist cell death?
Produce anti-apoptotic proteins
90
How do cancer cells induce angiogenesis?
VEGF and bFGF expressed
| By cancer cells
91
What is VEGF?
Vascular endothelial growth factor (VEGF) is a signalling protein that promotes the growth of new blood vessels.
92
How do cancer cells deregulate cellular energetics?
Undergo aerobic glycolysis
Glucose --> lactate
This process increases glucose expression, allowing more glucose uptake
93
Define anaplasia
Anaplasia is a term used to describe cells that have lost the unique characteristics that define them as a certain tissue type
94
Describe difference between benign and malignant:
a) invasion
b) metastasis
c) rate of growth
d) differentiation
e) fatal
Benign:
a) neoplasm does NOT invade surrounding tissue
b) do not metastasise
c) slow rate of growth
d) usually well differentiated
e) rarely fatal (unless CNS)
Malignant:
a) neoplasm DOES invade surrounding tissues
b) may metastasise
c) fast rate of growth (division exceeds cell death)
d) well --> moderate --> poorly differentiated --> anaplastic
e) often fatal
95
What is pleomorphism?
Irregularities in both nuclear shape and size
96
Is pleomorphism a hallmark of cancer?
Why?
Cellular and nuclear pleomorphism is one of the earliest hallmarks of cancer progression and a feature characteristic of malignant neoplasms and dysplasia.
Several key determinants of cell and nuclear size, like ploidy and the regulation of cellular metabolism, are commonly disrupted in tumours
97
What is atypia?
Atypia means abnormal cell type from normal which can be cancerous, or due to inflammation, infection and irritation.
98
What is a liposarcoma?
Malignant neoplasia of adipose tissue
99
What is a paraneoplastic syndrome?
Signs and symptoms that are NOT related to local effects of the primary or metastatic tumours.
100
What do paraneoplastic syndromes develop as a result of?
Proteins/ hormones secreted by tumour cells
OR
Immune cross reactivity between tumour cells and normal tissues
101
Why do 1/3 of people with cancer develop hypercalcaemia?
1. PTHrP secretion by the tumour
| 2. Local osteolytic hypercalcaemia
102
What is PTHrP? What cancers is it secreted in?
Parathyroid hormone-related protein occasionally secreted by cancer cells:
- Squamous cell carcinomas
- Renal cancer
- Bladder cancer
- Breast cancer
- Ovarian cancer
103
How does PTHrP induce hypercalcaemia?
PTHrP leads to hypercalcemia by stimulating calcium resorption from bone and reabsorption in the kidneys.
104
What does local osteolytic hypercalcaemia refer to?
What cancers is it seen in?
The local destruction of bone by tumour with calcium release --> osteolytic activity at sites of skeletal metastases
- Multiple myeloma
- Breast cancer
105
What 4 cancers have the highest incidence in the UK?
Bowel, Lung, Breast and Prostate are the cancers with the highest incidence in the UK (excluding SCC and BCC of the skin)
106
Location of compensatory vs hormonal hyperplasia?
Compensatory hyperplasia occurs in organs that regenerate, like the skin, lining of the intestines, the liver, and bone marrow.
Hormonal hyperplasia occurs in organs that are regulated by hormones like organs in the endocrine and reproductive system.
