Cell Injury & Fate Flashcards
What results in cell injury and death (overview) ?
The injurious stimulus to the normal cell such as decreasesin O2 or poison. Or the inability to adapt bc of stress etc. (heart can’t pump hard enough…)
What is lethal vs sublethal cell injury?
Lethal = cell death sublethal = produces injury that doesn't amount in cell death but it may progress to it or maybe reversible
What is an example of muscle cell injury?
ischaemia - death would be infarction
What is the acronym for cell injury causes?
A PIG COIN
What does A stand for in the acronym for cell injury?
Aging
What does PIG stand for in the acronym for cell injury?
Physical agents - trauma or radiation
Infectious Agents - virus, bacteria, multicellular parasites
Genetic defects - sickle cell..
What does COIN stand for in the cell injury in the acronym for cell injury?
Chemical agents - weed killer, drugs
Oxygen deprivation
Immunological deprivation - direct cell injury and those that can be triggered by infectious agents
Nutritional imbalance- too much or too little. - increase mass, diabetes … or not enough nutrients or proteins
What is a myocardial infarction caused by?
oxygen deprivation - cell death due to ischaemia
What does the cellular response to injurious stimuli depend on?
- Type of injury
- Duration - e.g. in MI you be able to lyse clot
- Severity
What do the consequences of an injurious stimulus depend on?
- Type of Cell - some cells are more resilient to injury e.g. bone, cartilage = low metabolic requirements and so can go on long w out o2 before cell death whereas brain = opposite
- Cell status - proliferating cells may be more subject to injury e.g. by cancer-causing injury
Which intracellular systems are particularly vulnerable to cell injury?
- Cell membrane integrity
- ATP generation
- Protein synthesis
- Genetic apparatus integrity
Why can multiple secondary effects rapidly occur?
the structural and biochemical components of a cell are high integrated… e.g. loss of ATP… cant maintain membrane etc
What are ways of adapting to cell injury?
Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia
What is atrophy?
Shrinkage of size of cell/organ
- by loss of cell substance.
e.g. neuralatrophy in dementia - gyri = thinner, sulci = thicker (gaps)
or muscle atrophy - whole muscle will get smaller
What is hypertrophy?
increase in size of cells
consequently an increase in size of organ
can be physiological ( process in normal healthy people, or pathological (part of a disease)
tends to increase mass
What is hypertrophy caused by?
increased functional demand or specific hormone stimulation
Example of physiological hypertrophy?
uterus in pregnancy (increases size)
Example of pathological hypertrophy that can also be physiological
larger myocyte - normal for athletes but can be in response to hypertension or valve abnormality (patho)
What is Hyperplasia?
Increase in number of cells in an organ - mitosis
can be pathological or physiological
leads to an increase in hormone size
Types of physiological hyperplasia?
hormonal or compensatory
Types of pathological hyperplasia?
excessive hormonal or GH stimulation
Example of physiological hyperplasia?
proliferative endometrium : 1st phase of menstrual cycle- oestrogen drivers proliferation of endometrial layer
Example of pathological hyperplasia?
Carcinoma - cancer
What is metaplasia?
REVERSIBLE change in which 1 adult cell type is replaced by another
can be physiological or pathological
an example of physiological metaplasia
cervix expands:
during pregnancy outside cervix columnar epithelial changes to squamous to change in pH of vagina -> inside cervix changes back to columnar
bone can also form within muscle??
What happens in Barretts?
Acid refulx leads to metaplasia in the oesophageal cells - squamous change to columnar (matching those of stomach )
Why does metaplasia occur in oesophageal cells?
to protect from stomach acid and is reversible early on
What happens if metaplasia in oesophageal cells is not treated appropriately?
if no antacids or proton pump inhibitors (PPIs) given it can lead to dysplasia and cancer. can also lose weight to treat
What is dysplasia?
These are precancerous cells that show genetic and cytological features of malignancy but aren’t invading underlying tissue.
essentially have all the features e.g. big nuclei, increased mitosis but are constrained
What ratio can increase during dysplasia?
nuclear: cytoplasmic
What are some light microscope changes associated w reversible injury
fatty change
cellular swelling
degenerative changes (ie associated with cell and tissue damage)
e.g. acoholic fatty changes - hepatocytes have increased fat due to increased alcohol
Ballooning degradation - cytoskeleton damage of hepatocyte & so proteins accumulate and cause cell to swell
What is necrosis?
Confluent cell death associated with inflammation
(light microscopic changes associated with irreversible injury)
- infiltration of neutrophils
What are the 4 types of necrosis?
Coagulative
Liquefactive
Caseous
Fat
What happens in coagulative necrosis?
the structure becomes fixed e.g. albumin shape doesn’t change, just solidifies (egg white)
What is an example of coagulative necrosis?
Myocardial Infarct:
What happens in liquefactive necrosis?
in the brain: tissue becomes liquefied - bc brain doesn’t have a lot of connective tissue to keep it in place (cerebral infarct)
What is caseous necrosis?
cheesy, oozy and structureless cells
Examples of where caseous necrosis can occur?
Lung - pulmonary TB
Kidney
What is fat necrosis?
pancreatic digestive enzymes* become activated in the pancreas rather than in the duodenum and so start to digest tissue around it.
*lipases, proteases, elastases
can cause ACUTE PANCREATITIS
What is caused by abnormal lipase release?
necrosis: liquify fat , cells can look blue bc of calcium deposition:
lipases split trigly into gly and fatty acids. the fatty acids bind to calcium in all fluid compartments and then precipitate out.
What is apoptosis?
Programmed cell death
not associated with inflammation (unlike necrosis)
can be physiological (unlike necrosis)
active energy dependant process (unlike necrosis)
apoptosis vs necrosis
necrosis = inflamm, apop = NOT
apop can be physiological, necrosis cannot
apop is energy dependant, necrosis is not.
necrosis forms blebs then enzymatic digestion occurs and cellular content leaks after cell membrane loses its integrity internally and externally. - inflammation response to dead tissue may damage healthy around it :(
apoptosis forms bleb but everything remains intact - fragmented nucleus and then those fragments are phagocytosed (Neat and clean)
What are the causes of apoptosis?
- embryogenesis - finger gaps, intestine hole…
- Deletion of auto-reactive T cells in thymus (to prevent autoimmune diseases)
- Hormone dependant physiological involution (after hyperplasia in menstrual cycle - hormonl support is withdrawn)
- Cell deletion in proliferating populations
- A variety of mild injurious stimuli that cause irreparable DNA damage hat, in turn, triggers cell suicide pathways
pathway of determining apoptosis
healthy cell with genetic errors due to injury:
if errors cannot be fixed and additional injury occurs, then apoptosis will occur
What is necroptosis?
Programmed cell death associated with inflammation
many causes e.g. viral infection * refer to all diagrams
