What are the major causes of disease on a cellular level?
Change in homeostasis caused by;
Retaining more water within the cell- oncosis
Accumulating of fat- steatosis
Autophagy
Atrophy
What is autophagy?
Cells eating itself up
What is atrophy?
Decrease in cell size through autophagy
What are examples of sublethal injury?
Energy failure
Mechanical disruption
Damage to cell membrane caused by free radicals
Blockage of metabolic pathways
Failure of membrane integrity
What are the different types of nature of the injury?
Acute vs chronic
Mild versus severe
Cell type affected
What is necrosis?
The death of tissues following bioenergetic failure and loss of plasma membrane integrity.
What does necrosis induce?
Inflammation and repair.
What can cause necrosis?
Ischaemia, metabolic and trauma.
What are the different categories of necrosis?
Coagulative, colliquative, caseous, gangrene, fibrinoid and fat.
What is coagulative necrosis?
Can happen in most tissues. Appears as a firm pale area.
Where is colliquative necrosis seen?
Seen in the brain.
What is observable in colliquative necrosis?
The dead area is liquified.
Which disease is associated with caseous necrosis?
Tuberculosis
What is observable with caseous necrosis?
There is a pale yellow semi-solid material.
What is putrefaction?
The process of decay or rotting in a body.
Which necrosis involves putrefaction?
Gangrene necrosis.
What does gangrene necrosis follow?
Vascular occlusion or certain infections.
What colour is observable with gangrene necrosis?
Black
What is fibrinoid necrosis?
A microscopic feature in arterioles in malignant hypertension.
What may fat necrosis follow?
Trauma or pancreatitis.
What may be seen with fat necrosis after pancreatitis?
Multiple white spots.
What may be seen with fat necrosis after trauma?
A mass.
Define apoptosis.
The death of cells which occurs as a normal and controlled part of an organism’s development.
What causes reduced apoptosis?
Neoplasia, autoimmune disease and virus infection
What causes increased apoptosis?
Neurodegenerative disorders and HIV infection of T lymphocytes.
What does apoptosis effect?
Single cells
What does necrosis effect?
Cell groups
What are the biochemical events of apoptosis?
Energy-dependent fragmentation of DNA
What are the biochemical events of necrosis?
Abnormal ion homeostasis
Is the cell membrane integrity maintained in apoptosis?
Yes
Is the cell membrane integrity maintained in necrosis?
No
What is the morphology in apoptosis?
Cell shrinkage and fragmentation
What is the morphology in necrosis?
Cell swelling and lysis
What is the fate of dead cells with apoptosis?
Phagocytosed by neighbouring cells
What is the fate of dead cells in necrosis?
Phagocytosed by inflammatory response
What is the commonest type of necrosis?
Coagulative necrosis
What is involved in coagulative necrosis?
Involves coagulation of cellular proteins
What is involved in colliquative necrosis
Liquefaction with formation of cystic spaces
What dominates over coagulation?
Proteolysis
Define proteolysis
The breakdown of proteins or peptides into amino acids by the action of enzymes
What is gas gangrene due to?
C perfringens
What is fibrinoid necrosis most commonly associated with?
Malignant hypertension
What is pyroptosis?
A highly inflammatory form of programmed cell death
When does pyroptosis occur most?
Infection with intracellular pathogens
What stages of response does pyroptosis fall into?
Part of apoptosis but then necrosis
What infection is pyroptosis associated with?
Salmonella infection
Define healing.
Restitution with no, or minimal, residual defect.
What is repair?
Is necessary when there is tissue loss: healing by second intention.
Which tissues can heal?
Blood, skin and gut.
Which tissues can repair?
Liver and kidney.
What is the function of granulation tissue?
Actively contracts to reduce wound size which may result in a stricture later.
What needs to be rapid in order to favour resolution?
Rapid destruction of casual agent and rapid removal of fluid/debris by good local vascular drainage.
Where should injury happen to favour resolution?
In an organ or tissue with regenerative capacity e.g. liver.
What is a factor that favours resolution of an injury?
Minimal cell death and tissue damage.
Define organisation.
Repair of specialised tissue by formation of a scar.
What is formed during organisation?
Granulation tissue.
What is removed during organisation?
Dead tissue by phagocytosis.
What happens to the wound during organisation?
Wound contraction and scarring
What substance favours organisation?
Large amounts of fibrin
What is fibrin?
An insoluble protein formed from fibrinogen during the clotting of blood
What event favours organisation?
Substantial necrosis.
What is granulation tissue formed of?
Loops of capillaries, myofibroblasts, collagen and inflammatory cells.
What organises granulation tissue?
Deposition of collagen and contraction?
What moves towards a clot in healing by first intention?
Neutrophils.
How much cell death is there in healing by first intention?
Limited cell death
What happens to the epidermis in healing by first intention?
It thickens at its cut edges
What do epidermal cells do in healing by first intention?
They migrate along cut margins of dermis.
What do epithelial cells do in healing by first intention?
They fuse in the midline beneath the surface of the scab.
By day 3 what has happened in healing by first intention?
Neutrophils largely replaced by macrophages.
What has happened by day 5 in healing by first intention?
Granulation tissue invades incision space
What happens before the epidermis has recovered normal thickness in healing by first intention?
The collagen fibres bridge the incision.
What is there an accumulation and proliferation of during the second week of healing by first intention?
Accumulation of collagen and proliferation of fibroblasts
What has happened by the end of the 1st month in healing by first intention?
Scar consists of cellular connective tissue. (Tensile strength now increases).
What is healing by first intention?
Wound with opposed edges.
What is healing by second intention?
Wounds with separated intention
Is there extensive cell loss in healing by second intention?
Yes
What is the common denominator in healing by second intention?
A large tissue defect that must be filled
What plays an important role in reducing the size of defect in healing by second intention?
Wound contraction
What is there more of in healing by second intention?
More fibrin and more necrotic tissue
What differentiates between first and secondary healing?
Wound contraction
What has been contraction been ascribed to?
The presence of myofibroblasts.
What are the stages of bone healing?
Repair, remodelling and resolution.
What happens when the liver is damaged?
Necrosis, regeneration, fibrous scarring and architectural disruption.
What are the systemic factors that influence wound healing?
Age, nutrition, metabolic status, circulatory status and hormones.
Why does nutrition affect wound healing?
Affects protein and collagen synthesis
How can hormones affect wound healing?
Glucocorticoids anti-inflammatory but impair collagen synthesis
What local factors may influence wound healing?
Infection, mechanical factors, foreign bodies, size, location and type of wound
What are the two forms of deficient scar formation?
Dehiscence and ulceration
What is a keloid scar?
A tough heaped-up scar that rises above the rest of the skin.
Define oncosis.
Cellular swelling
Define steatosis.
Abnormal condition of fat, any change to pH or other conditions causes a different way of producing fat
What is autophagy?
A process in which lysosomes decompose damaged organelles to reuse their organic monomers.
Define atrophy.
To waste away
What is an acute injury?
An injury with sudden onset and short duration.
What is a chronic injury?
An injury that develops over a long period of time.
What is an hydropic change?
Damage leads to water entering cells to be sequestered into vacuoles.
What defines a mild injury?
Regeneration and no scarring.
What defines a lethal injury?
Irreversible injury that causes cell death
What is a severe injury?
Fibrinous exudate
What is ischaemia?
Lack of blood to a part of the body
What are some examples of apoptosis?
Embryology, lumen of tubes. HIV AIDS-activated T cell death
What cells can be replaced if lost?
Labile and stable
What are the types of permanent tissues?
Neurones and skeletal muscle