Basic Principles Of Pathobiology Flashcards
What are the 4 basic cellular functions that molecular adaptations may affect?
1) . Synthesis
2) . Secretion
3) . Enzyme function
4) . Activation of proteins
What are 5 basic cellular changes that may occur in response to disease?
1) . Changes in proliferation
2) . Changes in size
3) . Changes in apoptosis
4) . Changes in differentiation
5) . Changes in migration
What are the main organ changes that may occur in response to disease?
Hypertrophy or atrophy, Hyperplasia or involution, Metaplasia, Fibrosis, Neoplasia.
What kinds of environmental changes may a cell be exposed to?
Environmental stimuli may be physiological or pathological.
Changes that may be physiological or pathological include nutritional changes, immune changes, endocrine changes and physical agents.
Pathological changes include those caused by chemical agents, infections, anoxia and genetic factors.
If environmental stimuli are causing an increase in functional demand what might the cellular response be?
If the environmental stimuli is causing an increase in functional demand this can be met by two main responses, hypertrophy and hyperplasia. These may occur independently or together. This will be reflected by the increase in size/weight of an organ.
Give an example of an environmental stimuli that can lead to increased functional demand.
One example of a stimuli that can lead to an increased functional demand is increased growth factors (e.g. due to a tumour producing growth factors). Growth factors and their receptors control cell growth. In disease cellular adaptations are controlled by the actions of growth factors linking to nuclear transcription factors via a secondary messenger system.
Give an example of physiological hypertrophy.
Skeletal muscle hypertrophy in response to exercise.
Give an example of pathological hypertrophy.
Pathological hypertrophy of the myocardium in hypertensive heart disease.
Give an example of physiological hyperplasia.
Physiological hyperplasia of the endometrium in the menstrual cycle (driven by oestrogen).
Give an example of pathological hyperplasia.
Pathological hyperplasia occurs in skin after trauma (e.g. calluses).
What kind of hyperplasia may be seen in the breast and prostate?
Nodular hyperplasia. It may occur in a non-uniform pattern.
Nodular hyperplasia in prostate can cause obstruction.
If there is a decrease in functional demand the cell stress response may be initiated. What is the cell stress response?
The cell stress response allows cells to survive pathological stimuli. Housekeeping genes are switched off and cell stress genes are switched on.
Cell stress proteins are cryoprotective proteins expressed in the cells.
One example of cell stress proteins are the cell stress proteins that act as molecular chaperones and prevent misfolding of proteins.
Describe the cell stress responses to damaging stimuli including the ubiquitin system and autophagy.
The ubiquitin system. Ubiquitin tagging usually deals with damaged and misfolded proteins and results in them being escorted to the proteosome.
When you get damaging stimuli resulting in reduction of cellular demand you may get cellular atrophy. Cell components are removed by degradative systems such as cytosolic proteolysis via the ubiquitin system.
You may also get autophagy of organelles whereby elements are enwrapped by internal membrane system and fused with the lysosomal system for degradation.
One of the manifestations of autophagy is the production of vacuoles containing lipid material. This is seen as a brown material termed lipofuscin and is caused by indigestible bodies.
What is one of the manifestations of autophagy that can be seen microscopically?
One of the manifestations of autophagy is the production of vacuoles containing lipid material. This is seen as a brown material termed lipofuscin and is caused by indigestible bodies.
Decreased functional demand due to environmental stimuli can lead to apoptosis. Describe the basic process of apoptosis.
Certain tropic signals can lead to cells death via apoptosis. This is brought about by a precise cellular system.
1) . Cells round lose contact, round up and nuclear condensation takes place.
2) . Apoptotic cells undergoes fragmentation to form apoptotic bodies.
3) . Apoptotic fragments are recognised by adjacent cells and internalised and degraded,
Apoptosis is programmed, organised destruction without the release of cellular content into the environment.
Cell death pathway exists in the cell metabolism controlled by the action of protease enzymes termed caspases. DNA is cleaved into fragments in between nucleosomes by endonucleases. Protein in cells is cross linked by transglutaminases.
How can apoptosis pathways be triggered?
1) . Surface receptor activation
2) . Surface membrane damage
3) . DNA damage - p53 is activating by DNA damage and then either activates DNA repair or apoptosis depending on the level of damage.
Whether a cell lives or dies depends on the balance between _________ and ________ signals.
Whether a cell lives or dies depends on the balance between pro apoptotic and anti apoptotic signals.
Reduced demand for cell activity can lead to atrophy. What is atrophy?
Atrophy is the reduction in cell volume and reduction in cell number.
Cell loss is commonly replaced by either adipose or fibrous tissue.
Atrophy is reflected in a reduced size and mass of organ.
What are some common causes of atrophy?
Denervation, Immobilisation, Reduced endocrine stimulation, Ischaemia, Ageing
Give an example of pathological atrophy.
Atrophy in denervated skeletal muscle due to reduction in trophic factors that nerves give to muscles. Loss of growth factors leads to a decrease in muscle mass.
Disuse of muscles can also lead to atrophy.
What are some causes of small organs other than atrophy?
Hypoplasia - incomplete organ growth.
Agenesis - complete failure of organ to develop during embryogenesis.
What is physiological atrophy termed?
Involution.
Give some examples of involution.
Most instances of involution are the result of withdrawal of an endocrine stimulus.
E.g. Breast involution after cessation of lactation.
Uterus after parturition.
Thymus involution post puberty.
Give some examples of where metaplasia occurs.
Bladder stones can cause increased pressure on bladder walls and cause transitional epithelium to change to squamous epithelium.
Oesophageal squamous epithelium changes to columnar epithelium in response to acid reflux in a process called Barrett’s metaplasia. This is associated with an increased risk of oesophageal adenocarcinoma.
Columnar epithelia can change to squamous epithelia in the lungs due to smoking.
Trauma may result in collagenous tissue converting to osseous tissue.
In the uterine cervix during growth columnar epithelia converts to squamous epithelia.
What is the basic flow of events in cellular adaptations to disease?
Pathological stimuli / environmental stimuli / pathological stimuli»_space;> molecular changes»_space;> cellular changes»_space;> organ changes.
Cell changes can only go in a limited number of directions.
What will dictate the cellular response to injury?
Nature of stimulus,
Magnitude of stimulus,
Nature of the cell (robust or vulnerable)
List some of the possible causes of cell damage.
Hypoxia, Toxins, Metabolic causes, Infections, Ischaemia, Physical agents.
What is ischaemia?
Ischaemia is the failure of blood supply to a tissue or organ. May be caused by vessel blockage or severely reduced blood pressure. Cells exposed to ischaemia develop abnormalities in multiple cell systems such as mitochondria (can lead to depletion of ATP, membrane ion pumps, protein synthesis and fall in pH).
How might a cell respond to sub-lethal damage?
Cells exposed to deleterious changes in their environment may start to fail. Cell failure can manifest in structural changes. These changes are called cellular degenerations and are potentially recoverable.
One of the manifestations of injury is vacuolation. In a damaged cell the mechanisms which maintain ion pups may fail. This can result in water being retained by the cell. The membrane systems become dilated with fluid and the cells become vacuolated and pale-stained.
What is a vacuole? What do physiological vacuoles contain? What do pathological vacuoles usually contain?
A vacuole is a large space within a cell filled with a substance. A cell is said to show vacuolation when it has developed vacuoles. Examples of normal vacuolation include mucin and glycogen vacuolation. Pathological vacuoles often contain water.
What is hydropic vacuolation?
A cell which is severely vacuolated as a result of pathological fluid accumulation is said to have undergone hydropic degeneration.
I which tissues might hydropic degeneration be seen?
Hydropic degeneration is not seen in all tissues but is seen in the liver and renal tubules.
In addition to hydropic vacuolation, sub-lethal damage in some cell types can cause fatty change. What is fatty change?
Another manifestation of pathological vacuolation is fatty change. Sub lethal damage in some cell types may alter the metabolism of the cell. The cell then accumulates triglycerides. The accumulated fat distends the cytoplasm of the cell. The accumulated fat forms vacuoles in a process termed fatty change,
What is the commonest example of fatty change?
The commonest example of fatty change is seen on the liver in response to ethanol.
What are some causes of fatty change?
Ethanol in the liver.
Hypoxia, diabetes, toxins, malnutrition.
Where might fatty change be seen other than in the liver?
Fatty change is also seen on some conditions in renal tubual epithelial cells and some cardiac muscle cells.
What does fatty change look like under the microscope?
It looks similar to hydropic change because neither water or fat stain.
What happens in sub lethal cellular injury when the pathological stimulus is removed?
With sub lethal injury when the stimulus is removed the various damaged cellular components can undergo autophagy, proteolysis, re synthesis and the cell can recover. Residual materials may remain as inclusion bodies (stigmata of damage). For example lipofuscin bodies.
What might happen to the cell if the cellular damage is severe or maintained?
If cellular damage is severe or maintained it may lead to cell death.
Cell death may occur in the form of tissue necrosis which is typically uncontrolled.
Macroscopically different types of necrosis can be seen depending aetiology.
Cell death may also occur as apoptosis.
What type of cell death can massive instant damage lead to? What type of stimulus can cause this type of cell damage?
Massive damage can lead to instant cell death which can result in coagulated necrosis where the proteins all become coagulated.
Some stimuli such as extreme heat, extreme pH change can cause proteins to instantly coagulate. It is a relatively uncommon clinical situation.
What happens if cell damage is above a level from which it is capable of recovery (but not massive instant damage)?
Liquefactive necrosis takes place. Cell death is followed by a series of structural changes called necrosis.
Liquefactive necrosis is the most common form of necrosis.
What happens in liquefaction necrosis? What brings about the changes that occur in necrosis?
In liquefactive necrosis cell death is accompanied by spillage of cellular components into the environment. These components can affect adjacent cells.
As part of necrosis you get pyknosis where the nucleus shrinks and begins to break up. Eventually the nucleus will break up via karyorrhexis. This happens rapidly in an uncontrollable manner. Unlike the controlled condensation of apoptosis. Cell then essentially becomes a liquified mess.
Most of the changes in necrosis are brought about by disruption of internal membrane systems. Release of lysosomal hydrolase brings about cell structural changes. Membrane loss allows proteins to leak from the cells into the tissue fluids, eventually being detected on blood. Blood tests can be a measure of tissue damage.
Look at the schematic of necrosis.
What are the consequences of necrosis?
Necrosis stimulates a tissue response to injury,
Necrosis stimulates cell proteins into tissue fluids,
The tissue response to injury recruits neutrophils and other cells in a process called inflammation (have local and long range neutrophil recruitment effects). Inflammation aims to limit the amount of damage caused by prolonged stimulus.
What processes may initiate apoptosis?
Surface receptor activation,
Surface membrane damage,
Mitochondrial membrane damage,
DNA damage.
Does apoptosis result in the spillage of cellular contents into the environment?
No. Apoptosis is programmed cell death. It is more ordered and there is no spillage of content into the environment.
Cells are broken up into small fragments which are then internalised and processed by adjacent cells.
What are the benefits of apoptosis over necrosis?
Damaged cells are removed cleanly,
Does not stimulate a tissue response to injury.
How can patterns of necrosis be used to indicate the cause of a disease process?
Tissue patterns of necrosis can be seen at a macroscopic and histological level. These different patterns of necrosis are associated with different causes.
Identification of a specific pattern of necrosis in a tissue biopsy may indicate the cause of the disease process.
What does coagulative necrosis look like histologically?
Coagulative necrosis shows cell and tissue outlines preserved but complete loss of cellular features.
What is the most common cause of coagulative necrosis?
Sudden rapid ischaemia.
What does liquefactive necrosis look like histologically?
No normal tissue remains in liquefactive necrosis, just sheets of macrophages.
Tissue architecture is effaced rapidly leaving liquid material and macrophages. Due to release of hydrolytic enzymes. Frequently occurs in the brain, you get an inflammation response and neutrophils recruited which then undergo necrosis.
What does caseous necrosis look like under histological examination?
Caseous necrosis macroscopically looks like cheese.
Sheets of homogenous unstructured, proteinase material.
Frequently seen in TB and other mycobacterial infections.
How does gummatous necrosis appear on histological examination?
Rubbery, firm texture,
Densely packed proteinaceous material,
May be caused by Treponema Pallidum (Syphilis),
Rare in UK.
What can cause gummatous necrosis?
Treponema Pallidum (syphylis)
What can cause caseous necrosis?
Tuberculosis.
