Responses to Cell and Tissue Injury Flashcards
What are possible causes to sub-lethal injury ?
Hydropic change
Fatty change/steatosis
What happens if sub-lethal injury occurs over a long period of time ?
Autophagy (cell shrinks in size because cell delivers cytoplasmic constituents to lysosomes) or Atrophy (wasting away because of degeneration of cells)
What are possible reasons for hydropic change or fatty change to occur ?
Failure of membrane functional integrity, blockage of metabolic pathways, interruption of protein synthesis.
In microscopy in liver cells, how does hydropic change look ?
Cells bigger and no longer pink since proteins (which may it pink) now diluted
In microscopy in liver cells, how does hydropic change look ?
Nucleus is no longer visible since fatty pushes nucleus to the side.
Which of lethal or sublethal injury is reversible ?
Sublethal injury
What is necrosis ? What are possible causes for it ? What is the consequence of it ?
Uncontrolled death of tissue following bioenergetic failure and loss of plasma membrane integrity
- May be caused by ischaemia, metabolic or trauma
- Results in inflammation since contents of the cell leaks (hence scarring and possible loss of function) and repair
What are the different kinds of necrosis ?
Coagulative necrosis - seen in most tissues. Involves coagulation of cellular proteins. Initially firm but later soft. Firm pale areas with ghost outlines in microscopy
Colliquative necrosis- seen in the brain. Dead area liquified (proteolysis dominates over coagulation) with formation of cystic spaces. Not much inflammation because cells are dead.
Caseous necrosis- seen in tuberculosis. Pale yellow semi-solid material.
Gangrenous necrosis- necrosis with putrefaction following vascular occlusions or certain infections. Black. May be wet or dry.
Fibrinoid necrosis- seen as a microscopic feature in arterioles in malignant hypertension.
Fat necrosis- May follow trauma and cause a mass, or follow pancreatitis and cause multiple white spots.
What are the main features of apoptosis ? What are the steps of it ?
Removal of cells discreetly without inflammatory response.
Takes out individual cells rather than groups of them
Requires energy
-Cell condenses, shrinks, loses water and breaks up. Fragments are still membrane bound until phagocytosed (e.g. by macrophage), so no inflammation.
What is the difference between Programmed Cell Death and Apoptosis ? Give examples of PCD.
PCD is about intent, Apoptosis is a morphological process. PCD usually through apoptosis but not always..
-lumen of tubes, menstrual cycle, death of neutrophils, T and killer cell responses, self destruction in autoimmune diseases, HIV and activated R cell death, prevention of mutations to prevent tumors
What are other types of PCD ?
- Ferroptosis
- Necroptosis
- Pryoptosis (part apoptosis but then necrosis, associated with salmonelle infection)
In microscopy, how can you recognize a cell undergoing apoptosis ?
It is shrinking and its nucleus also shrinking.
Can apoptosis go wrong ? In which specific conditions?
1) Reduced apoptosis in: neoplasia, autoimmune disease, viral infection or cancer.
2) Increased apoptosis in: neurodegenerative disorders and HIV infection of T lymphocytes
What are the main differences between necrosis and apoptosis in terms of: Induction Extent Biochem events Cell membrane integrity Morphology Inflammatory response Fate of dead cells
Apoptosis :
- Pathological or physiological
- Single cells
- Energy dependant fragmentation of DNA
- Maintained
- Cell shrinkage and fragmentation
- None
- Phagocytosed by neighbouring cells
Necrosis: Always pathological Groups of cells Abnormal ion homeostasis Lost Cell swelling and lysis Usual Phagocytosed by inflammatory cells
What occurs after injury ?
Either death, healing, or repair
What are the categories of cells used to describe their ability to be be replaced when lost ?
Labile and stable may be replaced
Permanent may not
What is healing ? Give examples.
Restitution with no or minimal residual defect. Abrasion to skin healing by first intention
What is repair ? Give examples.
When there is tissue lost, healing by second intention. Heart or lung damage result in a fibrous scar.
Why can labile populations be replaced ? Give examples of labile populations.
Because constant proliferation and turnover.
Skin, blood, gut.
Why can stable populations be replaced ? Give examples of stable populations.
Because although might have long time for turnover, able to regenerate if need be.
Liver, kidney.
Why can’t permanent populations be replaced ? Give examples of permanent populations.
Because their ability to proliferate is close to 0.
Neurones, skeletal muscle.
What is granulation tissue?
A tissue produced as part of a repair phenomenon.
Made of loops of new capillaries, proliferating myofibroblasts, possible inflammatory cells and collagen.
This tissue contacts to reduce wound size, which may result in stricture.
If a scar forms then it’s repair but not healing
Which factors favour resolution ?
Minimal cell death and tissue damage
Occurrence in organ/tissue with regenerative capacity
Rapid destruction of causal agent
Rapid removal of fluid and debris by good local vascular drainage
What is organisation ?
Repair of specialised tissued by formation of scar.
What are the steps to organisation ?
1) Formation of granulation tissue, new blood vessels and macrophage conducting fibroblasts
2) Removal of dead cells by phagocyotsis
3) Wound contraction and scarring (may limit movement in joint)
Which factors favour organisation ?
Maximal cell death and tissue damage
Exudate and debris cannot be removed or discharged
Large amounts of fibrin
Which kind of post-injury does acute lobar pneumonia result in? Is there any exception to that?
Complete healing.
If S. Aureus infection then toxins cause necrosis of epithelial cells and enzymes of those dead cells may destroy collagen of alveolar cells.
What is the diagnostic feature of healing by primary intention ?
Edges come together (opposite edges).
What are the initial state of an injury healing by primary intention ?
Limited cell death but BM disrupted
What is the diagnostic feature of healing by secondary intention ?
Wounds with separate edges (means we cannot minimise inflammation)
What are the initial state of an injury healing by secondary intention ?
Extensive cell lost
What are the major differences of healing by secondary intention compared to healing by primary intention ?
- More haemorrhage
- More necrotic tissue
- More fibrin
- Inflammation reaction more intense (so more macrophages, fibroblasts, new blood vessels, more collagen = BIG SCAR)
- Much larger amount of granulation tissue
- Contraction occurs to reduce size of the defect thanks to myofibroblasts (does not occur in healing by primary intention)
- Skin regenerates from sides across granulation tissue rather than bottom up.
What are the similarities between healing by primary and secondary intention ?
Large tissue defect which must be filled.
When would healing by secondary intention be chosen over healing by primary intention ?
If there is a risk of foreign body or infective agent being left in the incisional space promoting inflammation and formation of an abscess.
Which kind of tissue is bone (labile, stable or permanent ?)
Stable, able to proliferate if necessary
What are the steps involved in bone healing ?
Fracture —> haemorrhage/necrosis/inflammation —> granulation tissue produced = new vessels + myofibroblasts + oedema + collagen (if acute inflammation lasts enough to turn into chronic inflammation) —> Osteoid also produced so this specialised granulation tissue morphs into bone matrix —> matrix becomes calcified —-> Remodelling of scar —> HEALING AND RESOLUTION (through repair + remodelling)
What is the name given to the specialised granulation tissue in bone healing ?
Callus
What are the steps to liver repair ?
Necrosis —> Regeneration —> Fibrous scarring —> Architectural disruption
How does cirrhosis occur ?
Repeated damage (Scar tissue + regeneration) over time —> chronic inflammation —-> activated fibroblasts new vessel formation granulation tissue = Scar formation (fibrosis)
How does wound strength alter over time ?
Suture removed at end of week 1- 10% initial strength (weak collagen)
Strength rapidly increase over following 4 weeks then rate of increase slows
3rd month- 70-80% (stronger collagen)
Full strength may never be recovered
What are factors affecting wound healing ?
Systemic factors which include-
- Age
- Nutrition (affects protein and collagen synthesis)
- Metabolic status (healing delayed in diabetics)
- Circulatory status (adequate blood supply essential)
- Hormones (glucocorticoids are anti-inflammatory but impair collagen synthesis)
- Genetics
Local factors which include)
- Infection
- Foreign bodies (e.g sutures or glass)
- Mechanical factors (early movement of wounds delays healing)
- Size, location and type of wound (heals better in richly vascularised areas)
What are examples of abnormal wound ?
-Deficient scar formation
Dehiscence (collagen not strong enough)
Ulceration
-Excess formation of repair components
Keloid scar (excessive fibroblast proliferation and collagen production resulting in huge scars)
-Formation of contractures (=”abnormal shortening of muscle tissue, rendering the muscle highly resistant to stretching”)
Exaggerated contraction
Deformity of the wound and surrounding tissues
What are the pros of scars ?
- Provides permanent patch
- Allows surrounding tissue to continue to function
What are the cons of scars ?
-Cosmetic problems
-Functional problems
Site- E.g. Stricture (“abnormal narrowing of a body passage”)
Size- E.g. Healed myocardial infarct
