Cell Injury Flashcards
What is the difference between reversible and irreversible cell injury?
in reversible cell injury - cells adapt to changes in environment and the cells return to normal once stimulus is removed
in irreversible cell injury - the effect is permanent and there is cell death as a consequence
What factors affect whether cell injury is reversible or irreversible?
type, duration, severity of injury
the susceptibility/adaptability of the cell: nutritional status, metabolic needs (cardiac vs skeletal muscle).
What can cause cell injury
- hypoxia
- physical agents (radiation – free radicals)
- chemicals/drugs
- infections (bacterial toxins, viruses)
- immunological reactions
- nutritional imbalance
- genetic defects
What can cause hypoxia?
anaemia, respiratory failure
What can happen as a result of hypoxia?
stops oxidation phosphorylation in cell – decreased ATP
cells can still release energy via anaerobic mechanisms
What is ischaemia?
- reduction in blood supply to tissue
- caused by blockage of arterial supply or venous drainage, e.g. atherosclerosis
What is atherosclerosis?
where your arteries become narrowed, making it difficult for blood to flow through them
Why is ischaemia more dangerous than hypoxia?
depletion of not just oxygen but also nutrients, e.g. glucose
more rapid/severe damage than hypoxia- anaerobic energy release will also stop.
What are examples of physical agents that can cause cell injury?
- mechanical trauma – affects structure, cell membranes
- extremes of temperature – affect proteins, chemical reactions
- ionising radiation – DNA damage
- electric shock - burn
What are examples of infectious agents that can cause cell injury?
- bacteria
- viruses
- fungi
- parasites
- protons
What are examples of chemicals/drugs that can cause cell injury?
- simple chemicals (glucose), in excess cause osmotic disturbance
- poisons (cyanide blocks oxidative phosphorylation), environmental (insecticides)
- occupational hazards (asbestos) causes inflammation
- alcohol, smoking and recreational drug
What are immunological reactions that can cause cell injury?
- anaphylaxis (tp 1 hypersensitivity, IgE mediated)
- auto-immune reactions (tp 2, antibodies directed towards host antigens, tp 3 – antigen-antibody complexes)
- damage as a result of inflammation (complement, clotting, neutrophil products, etc)
What are nutritional imbalances that can cause cell injury?
Too little (inadequate intake)
Specific nutrient :scurvy, rickets. Generalized: anorexia
Too much (excessive intake) Specific: hypervitaminosis A/D Generalized :obesity
What are genetic defects that can cause cell injury?
- sickle cell anaemia (haemoglobin chain)
- inborn error of metabolism (lack of enzyme causes build up of enzyme substrate)
- cancer
What does reversible cell injury disturb?
– aerobic respiration/ATP synthesis (mitochondrial damage)
– plasma membrane integrity
– enzyme and structural protein synthesis
– DNA maintenance
Why is there a cloudy swelling of injured cells?
– cells are incapable of maintaining ionic and fluid homeostasis
– failure of energy dependent ion pumps in the cell membrane due to loss of ATP/energy dependent Na pump leading to influx of Na and water (water follows sodium due to osmosis)
– there is also a build up of intracellular metabolites.
Why is there fatty changes in injured cells?
– accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism so that triglycerides cannot be released from the cell, especially in liver.
– macroscopically liver enlarged and pale
What is a common cause of fatty liver?
alcohol consumption, obesity, diabetes
What are the irreversible changes?
membrane rupture - organelles released
breakdown of lysosomes
activation of inflammatory response
If necrosis occurs, what will always be present?
inflammation
What is necrosis?
cell death usually due to pathology after irreversible cell injury (not programmed)
What is the process of necrosis?
- intracellular protein denaturation and lysosomal (from cell) digestion of cell.
- cell membrane is disrupted leading to leakage of cell contents
- inflammatory response in surrounding tissue
- cell remains are removed by phagocytosis
- histopathological changes may take some time to appear.
What are the microscopic changes of necrosis?
pyknosis = nucleus shrinks; darker staining
karyorrhexis = nucleus fragments (K)
karyolysis = the blue staining DNA in nucleus is digested by endonucleases and the blue staining fades away (K)
What enzymes digest DNA?
endonucleases
What are the H&E cytoplasmic changes of necrosis?
appears paler, because swollen
more eosinophilic (pinker) because of denaturation of cytoplasmic structural and enzyme proteins
What are characteristics of coagulative necrosis?
No breakdown of dead cells as enzymes are denatured
Architecture of tissues is preserved for some days
No nucleus; eosinophillic cells.
Firm in texture
Cells digested by lysosomes of leukocytes
What is a localised area of coagulative necrosis called?
infarct
What are characteristics of liquefactive necrosis (colliquative)?
Digestion of dead tissues so tissue in liquid viscous state
Focal bacterial or fungal infections (abscess)
Necrotic material is thick, pale yellow in colour (pus)
What is CNS necrosis as a result of hypoxia often characterised as?
liquefactive necrosis
What are characteristics of caseous necrosis?
Crumbly white appearance (like cheese)
Microscopically; granuloma-fragmented cells and granular debris ( mass apoptosis) surrounded by inflammatory cells
Where is caseous necrosis mostly seen?
tuberculous infection
What are characteristics of fat necrosis?
limited areas of fat destruction.
Fat cells may be liquefied by activated pancreatic enzymes -lipases (acute pancreatitis)
What are characteristics of gangrenous necrosis?
coagulative necrosis with bacterial infection –liquefactive necrosis
What are characteristics of fibrinoid necrosis?
-special type of necrosis seen in immune reactions in blood vessels
-immune (antigen –antibody) complexes are deposited in artery walls together with fibrin that leaks out of the vessels.
- bright pink and amorphous substance in H&E
What are the effects of necrosis?
- release of cell contents activates inflammation
- cell remains are then phagocytosed
- finally the necrotic area is replaced by a scar-i.e. it undergoes organisation or repair
- if remains are not removed then calcium salts may be deposited in necrotic tissue
What is apoptosis and what are the characteristics of it?
Programmed cell death which can be physiological and pathological
Requires energy and does not cause inflammation
Cells shrink not swell
What are pathological triggers for apoptosis?
- hypoxia/ischaemia (protein misfolding)
- viral infection – cytotoxic T-lymphocytes contain enzymes which can induce apoptosis.
- DNA damage- if unrepairable p53 triggers apoptosis
- Caspases are activated enzymes that trigger apoptosis.
- Cell contents are degraded by enzymes activated by the cell.
What are the physiological roles of apoptosis?
- deletion of cells during embryogenesis
- hormone change dependent involution –uterus, breast, ovary
- cell deletion in proliferating cell populations to maintain constant number of cells - epithelium
- deletion of inflammatory cells after an inflammatory response
- deletion of self reactive lymphocytes in the thymus
What does too much apoptosis and too little apoptosis cause?
too much - degenerative disease
too little - cancer
What is the morphology of apoptosis?
- cell shrinkage
- chromatin condensation – packaging up of nucleus
- cell membrane remains intact, with formation of cytoplasmic blebs
- phagocytosed, but no widespread inflammation
What are the types of accumulation that can occur?
excessive normal constituents - glycogen, lipids, water
abnormal endo/exogenous material - carbon, silica, cholesterol
What condition occurs due to high cholesterol accumulation?
atherosclerosis
What is atherosclerosis?
accumulation of cholesterol in macrophages and smooth muscle cells in blood vessel walls
What are foam cells?
lipid ingested macrophages
What is amyloid?
Amyloid is a fibrillar protein that is deposited as a result of pathologic processes
What are the types of amyloid?
AL -(amyloid light chain) derived from light chain antibodies from plasma cells.
AA -(amyloid associated): derived from proteins synthesized in the liver
Aβ -Alzheimer’s disease
What can cause amyloid accumulation?
chronic inflammation, multiple myeloma, ageing, drug abuse
What does amyloid accumulation cause?
The build-up of amyloid proteins (deposits) can make it difficult for the organs and tissues to work properly - organ failure (amyloidosis)
What are examples of endogenous pigmentation accumulation?
Lipofuscin
Melanin
Haemosiderin-localised bruising
Bilirubin
ALL APPEAR BROWN
What are examples of exogenous pathological pigmentation?
Carbon deposition-commonest
Tattoos
Heavy metal salts eg lead
Pigmentation associated with intravascular drug use
Where is carbon deposited?
in macrophages in alveoli of lungs
What is dystrophic pathologic calcification?
-deposits of calcium phosphate in necrotic tissue.
Serum calcium is normal.
Where is dystrophic pathologic calcification seen?
valvular heart disease
What is metastatic pathologic calcification?
deposits of calcium salts in normal, vital tissue
Raised serum calcium levels
Where is metastatic pathologic calcification seen?
connective tissue of blood vessels
nerve fibres
What are causes of hypercalcaemia?
1-increased levels of parathyroid hormone (hyperparathyroidism) parathyroid gland tumour
2-destruction of bone tissue- leukaemia, metastasis to bone, immobilization
3- excess vitamin D
4- renal failure- causes secondary hyperparathyroidism
