Cell injury/death Flashcards
how can cell injury be visualised?
gross appearance
microscopic features
ultrastructural features
intercellular Ca2+ levels ….. during cell injury. Why?
Increase
b/c of low ATP levels, low Ca pump activity, and plasma membrane damage
How does cellular pH change during cell injury?
pH decreases
due to failure of aerobic glycolysis, ditch to anaerobic glycolysis and build up of lactic acid.
how does fat necrosis occur?
adipocytes destroyed due to trauma or release of lipases from damaged pancreatic tissues
intracellular Na+ ….. during cell injury. Why?
increase
b/c low ATP disrupts na/K pump, water build up in cell
How is apoptosis regulated?
Genes
inhibitors - growth factors, sex steroids, ECM
inducers - viruses, loss of matrix attachment
what condition would you see Mallory hyaline?
Alchohol lover diesease
in apoptosis cell size is ……..
reduced
in apoptosis plasma membrane is ………
intact
in necrosis cell size is ……….
enlarged
in necrosis plasma membrane is ……….
disrupted
necrosis is a …….. cause of cell death
pathological
what 2 mechanisms can lead to cell death?
necrosis
apoptosis
what are capsizes?
family of protease enzymes
essential role in programmed cell death
examples of physiological apoptosis
embryogenesis/fetal development
death of cells that have served purpose
hormone dependent involution - shedding of lining during menstruation
what are heat shock proteins?
family of chaperone proteins
induced during environmental, physical or chemical stress
limit damage and facilitate cellular recovery
example of heat shock protein?
ubiquitin
examples of apoptosis inducers?
growth factor withdrawal
glucocorticoids
free radicals
examples of apoptosis inhibitors
growth factors
sex steroids
viral proteins
examples of chemical agents and drugs that can cause cellular injury
Cyanide
alcohol or therapeutic drugs
O2 in high concentrations
examples of dietary imbalance that could cause cellular injury
insufficiency - anorexia, malnourished
excess - obesity or diabetes
What are some examples of enzymes that Ca2+ activates in irreversible injury?
Proteases
phospholipases
endonucleases
ATPases
What are some examples of immunological reactions that can cause cellular injury?
self antigen reaction
hypersensivity reactions
examples of infections that can cause cell injury
Worms
viruses
examples of pathological apoptosis
Neoplasia
Autoimmune
AIDS
examples of physical agents that can cause cell injury
direct trauma
extremes of temperature
radiation
electric shock
What are the 2 pathways for apoptosis?
Extrinsic - external death receptors activated by ligand
Intrinsic - withdrawal of growth factors/hormones, molecules released form mitochondria
What are the 2 types of calcification?
Dystrophic
Metastatic
What are the 3 main effects at a cellular level of reduced ATP?
Reduced activity of Na+ pumps
Increased anaerobic glycolysis
detachment of ribosomes
What are the 3 phases of apoptosis?
initiation
execution
degradation/phagocytosis
What are the 3 stages of nuclear change in irreversible injury?
Pyknosis - nuclei condensed and dense
karyorrhexis- nuclei break into fragments
karyolysis - nuclei dissolved
What are the external receptors in extrinisic apoptosis?
Fas Receptor
TNF receptor
What are the type of necrosis?
Coagulative - protein denaturation
Liquefactive - degradation of tissue by enzymes
Caseous necrosis - chess like
Fat necrosis
Fibrinoid necrosis
What are the types of gangrene
wet gangrene - bacteria
Dry gangrene - air
Gas gangrene - gas forming bacteria
What are white deposits made of in fat necrosis
Fatty acids and calcium
What are white infarcts
Arterial insufficiency due to robust stromal support preventing haemorrahage entering necrotic area
what can cause a Hypoxaemic hypoxia
low arterial O2 content
high altitude
cardiorespiratory failure
What can cause an infarction
Thrombosis
Embolism
External compression of vessel
what can cause anaemic hypoxia
low O2 carrying capacity
anaemia
CO poisoning
causes of cell injury (7)
Hypoxia
chemical agents and drugs
Infections
immunological reactions
dietary imbalance
genetics
physical agents
what can cause histiocytic hypoxia
disabled oxidative phosphorylation
cyanide
paracetamol poisoning
what can cause hypoxia(4)
Hypoxaemic hypoxia
anaemic hypoxia
ischaemic hypoxia
histiocytic hypoxia
What can cause ischaemic hypoxia
interruption to blood supply
blocked vessel
heart failure
What can cause metastatic calcification
Parathyroid overactivity
Vitamin D overdose
Maligant tumour (PTHrp)
Prolonged immobilisation
What can occur to a cell that cannot adapt to a stress
Cell injury occurs
What can occur to a cell that cannot adapt to a stress
Cell injury occurs
What caspase do both extrinsic and intrinsic pathway for apoptosis activate
Caspase 3
What colour urine seen in myoglobinuria
Brown
breakdown of muscle cause damage to kidneys
What do the consequences of infarct depend on
if tissue has alternative blood supply
How quickly ischaemia occured
How vulnerable tissue is to hypoxia
Oxygen content of blood
What factors released from mitochondria in intrinsic apoptosis
Bcl2
Bax
p53
What is apoptosis
Energy dependant programmed cell death
What is calcification
Abnormal deposition of calcium salts in tissues
What is gangrene
clinical term to describe visible necrosis
What is haemosiderin
iron storage complex
iron released from heme stored as haemosiderin
What is infarction
obstruction of blood vessel to organ or region of tissue
What is ischaemia-Reperfusion injury
Return of blood to ischemic tissue results in production of O2 -derived free radicals, which further damage tissue.
What is mallory’s hyaline
Damaged protein seen in hepatocytes
what is oncosis
Cell death with swelling which eventually leads to necrosis
What is Steatosis
abnormal retention of fat (lipids) within a cell or organ
What is the appearance in fibrinoid necrosis
Bright pink and amorphous appearance
What is the apperance of caseous necrosis
Cheese like appearance
What is the effect of detachment of ribosomes in cell injury
Decreased protein synthesis
lipid deposition
What is the function of caspase 3
Cleave proteins leading to chromatin condensation
nuclear fragmentation and blebbing occurs
What is the gross apperance in coagulative necrosis
Firm
Pale wedge of tissue
What is the morphological hallmark of cell death?
Loss of the nucleus
What is the morphological hallmark of irreversible cellular injury?
Membrane damage
What is the morphological hallmark of reversible cell injury?
Cellular swelling
most dangerous/reactive free radical?
Hydroxyl
What is the only organ that does not yield coagulative necrosis following an ischaemic infarct?
Brain
What is the role of Bcl2?
Prevent cytochrome C release from mitochondria hence inhibits apoptosis
What molecules are released by cells due to cell injury and death
Potassium
Enzymes
myoglobin
What molecules can accumulate intracellularly(5)
Water
lipids
proteins
carbohydrates
pigments
What occurs if cell injury is severe and progressive
Irreversible injury occurs
What occurs to a cell when the stress applied is mild
Injury can be reversible and homeostasis can be returned
What pattern of necrosis is characteristic of pancreatitis-mediated damage of peripancreatic fat?
Fat necrosis
What pattern of necrosis is characteristically seen in Tuberculosis?
Caseous necrosis; with granulomas
What physiological process does hypoxia affect
Oxidative phosphorylation
What structural changes occur in irreversible cell injury
membrane blebbing
lysosomes rupture
swelling of ER and loss of ribosomes
swollen mitochondria
nuclear condensation
myelin figures appear
What structural changes occur in reversible cell injury
clumping of chromatin
swelling of ER and mitochondria
What two main processes are seen in necrosis
Denaturation of intracellular proteins
Enzymatic digestion by lysosomes
What type of free radical is made through inflammation?
Superoxide Ions via NADPH Oxidase action
Made during oxygen-dependent killing by neutrophils.
What type of free radicals are formed via ionising radiation?
Hydroxyl (OH) free radicals
via hydrolysis of water
What type of free radicals are made via the Fenton Reaction?
Hydroxyl radicals
via Fe2+
What type of tissue calcification is associated with normal serum Ca?
Dystrophic calcification
Metastatic calcification occurs in normal tissue.
Dystrophic calcification occurs in necrotic tissue.
What ultrastructural components of the cell are involved in morphological changes in cell injury?
Cell membranes
nucleus
proteins
mitochondria
Where are lipofuscin granules usually seen
liver and heart
Where can free radicals be produced from(5)
Chemical and radiation injury
ischaemia-reperfusion
Cellular ageing
high O2 concentration
Phagocytosis
Where do red infarcts occur
Organs with dual blood supply
Organs with loose stromal support
Where do red infarcts occur
Organs with dual blood supply
Organs with loose stromal support
Where is caseous necrosis seen in
Granulomatous
inflammation
Where is dystrophic calcification seen
necrotic tissue
Where is fat necrosis seen
Breast tissue where it can mimic a breast tumour
Pancreas in pancreatitis where lipase released from pancreas
Where is fibrinoid necrosis usually seen
immune reactions with blood vessels
Where is liquefactive necrosis usually seen
Brain and abscess formation
Which enzyme functions to eliminate H2O2?
catalase
Which enzyme functions to eliminate Superoxide Radicals?
superoxide dismutase
Which enzyme functions to primarily eliminate Hydroxyl radicals (OH)?
Glutathione peroxidase
Which enzyme secreted by CD8+ T cells functions to create pores in the membrane of target cells
perforin
Which enzyme secreted by CD8+ T cells functions to enter the pores made by Perforin and activate Caspases?
granzyme
Which mechanism of cell death is always followed by acute inflammation?
necrosis
Which mechanism of cell death is associated with shrunken cells with more eosinophilic cytoplasm?
apoptosis
Which mechanism of cell death is not followed by acute inflammation?
apoptosis
Which metabolic process is the source of physiological generation of free radicals?
oxidative phosphorylation
Which organs are white infarcts commonly seen
heart
Spleen
kidney
Why does a cell swell in reversible injury
Reduced activity of Na pump
Na accumulates in cell
H2O follows Na
H2O retained by cell
Why is necrotic material in liquefactive necrosis creamy yellow
Presence of dead leukocytes and is called pus
Why is rhabdomyolysis serious
Myoglobin produced as a breakdown product of muscle and causes damage to kidneys and eventually renal failure
…….. is a protein that leaks out of the inner mitochondrial matrix when Bcl2 is inactivated.
cytochrome c
then activates capsize and starts apoptosis
……..is a cause of decreased O2 carrying capacity that classically presents with cyanosis and chocolate-coloured blood.
Methaemoglobinaemia
involves oxidation of haem Fe2+ to Fe3+, which cannot bind to O2.
……..is a phenomenon seen in fat necrosis that involves the release of fatty acids via trauma or pancreatic lipase and subsequent joining of Ca with those fatty acids.
Saponification
