T5: Abnormal Growth and Differentiation Flashcards
What is adaptation?
Adaptations are cellular changes in response to changes in environment or demand.
A normal cell is confined to a narrow range of function and structure by differentiation, specialisation, metabolic ability, substrate for neighbouring cells etc. It maintains homeostasis despite this.
Adaptations are generally reversible and response to more severe changes. When the stress is eliminated it should be able to recover back to its originate state without having acquired any damage.
How do cells vary in ability to adapt?
Some do not need to adapt such as fibroblasts which can survive severe metabolic stress without harm e.g. absence of oxygen.
Some adapt easily such as epithelial cells. These have a labile cell population with an active stem cell compartment. They are highly adaptive in number and function.
Some cannot adapt such as cerebral neurons. They have terminally differentiated and permanent cell population. They have a highly specialised function and are easily damaged.
What are types of adaptive responses?
Types of adaptive response
• Increased cellular activity usually leads to a increased in size or number of cells
• Decreased cellular activity These usually lead to a decrease of size or number of cell
• Change of cell function and/or morphology
Define hypertrophy.
Hypertrophy - increase in the size of the cell and eventually the size of the organ. There is no new cell. This is due to the synthesis of structural components and increased metabolism. Particularly seen in permanent cell populations especially cardiac and skeletal muscle as they have a limited capacity for division. Caused by an increased functional demand or by stimulation by hormones and growth factors.
Give examples of physiological hypertophy.
The most common stimulus for hypertrophy in muscle is increased work load. In the heart is usually chronic overload e.g. HTN or faulty valves.
Another example includes the uterus during pregnancy due to oestrogenic influence.
The prostate due to age undergoes hyperplasia and gets bigger and more nodular. Due to its position around the prosthetic urethra this can lead to obstruction. The destructor muscle that needs to push urine out of the bladder must work harder and so undergoes hypertrophy.
Give examples of pathological hypertrophy.
Calcific aortic stenosis - The heart has to work harder against the valvular obstruction increasing demand leading to hypertrophy. The aortic valve is nodular and calcified, it also only has 2 cusps instead of 3. Congenital bicuspid valves are more likely to be calcified.
Another cause is they due to HTN, increasing the work load to the left ventricle. Over time and untreated the compensation can final leading to LV failure.
Give an example of subcellular hypertrophy and hyperplasia.
Sometime a subcellular component can undergo hypertrophy such as a subcellular organelle. For example in treatment of drugs such as barbiturate they show hypertrophy of smooth ER in hepatocytes. This increases the number of enzymes for detoxification. There is increased P450 mixed function oxidase. Over time they respond less to the drug because of the adaption and so may need more overtime. This also may change the way the liver metabolises other drugs. E.g. alcohol also causes hypertrophy of smooth ER and so you may need to reduce levels of barbiturates being at taken at the same time.
Define hyperplasia.
The increase in the number of cell caused by cell division.
Give examples of physiological hyperplasia.
Can be either physiological which can be hormonal when needed or compensatory after damage or partial resection e.g. after liver resection.
A compensatory mechanism due to congenital hypoplasia of one kidney leads to hyperplasia of the other kidney. The bigger kidney is able to make up the function.
Give examples of pathological hyperplasia.
An example of this is endometrial hyperplasia - abnormal hormone induce hyperplasia. After a period normally there is a rapid burst of proliferative activity in the epithelium that is stimulated by hormones. This is brought to a halt in the increase level of progesterone. In some instances the balance between oestrogen and progesterone is disturbed and so this can lead to increased oestrogen leading to a prolonged stimulation of the epithelium. This can lead to a cause of prolonged menstrual bleeding. Causes include diabetes, polycystic ovarian syndrome, obesity etc. These all cause increase in hormone, then prolonged proliferation and increased output.
Another example includes gynecomastia. This is enlargements of the male breasts due to hyperplasia of the glandular and stromal tissue in the breasts. This can be physiological at puberty or pathological related to drugs (recreation or medical), or cirrhosis of the liver where the abnormalities in the processing of the liver and so excess stimulation of male tissue.
In graves’ disease an autoantibody is formed which switches on TSH in the thyroid leading to prolonged uncontrolled stimulation of the thyroid leading to hyperplasia and therefore thyrotoxicosis.
In a cirrhotic liver the abnormal healing regenerative process leads to the formation of hyperplastic nodules. This is pathological. It can also be physiological in individuals how donate a lobe of the liver, the remining part grows back. It is the same response in the liver but because of different stimuli.
Define atrophy.
Atrophy This is a reduction in the size of an organ or tissue in cell size or number. This can be physiological or pathological.
Give examples of causes of pathological atrophy.
Pathological atrophy can have many causes, it can be localised or generalised. Examples include:
- Decreased workload - Disuse atrophy (e.g. broken bone muscle atrophies) - Loss of innervation (denervation atrophy) - Diminished blood supply 'Inadequate nutrition (e.g. cachexia) - Loss of endocrine stimulation after menopause leads to atrophy of the breasts, endometrium and vaginal epithelium - Pressure - tumours can cause atrophy in the surrounding tissue, there is most likely ischaemic consequence also
Give an example of physiological atrophy.
Physiological atrophy is common in development some structures such as the notochord undergo atrophy. It can be physiological after pregnancy or menopause of the uterus.
Another examples is when a large proportion of the thymus has been replaced by fat in ages. Also atrophy due to a loss of endocrine therapy. B is someone who has been on long term steroid therapy. If you stop the steroid however the patient will be in trouble. You therefore must ween them of gradually.
Define agenesis.
Agenesis - failure to develop
Define aplasia.
Aplasia - failure to retain size or function but there is a bit of tissue recognisable
