4. Cell injury, cell death & how the body responds

What damages a cell

Hypoxia/ischaemia

physical agents

chemical agents + drugs

infections

Immune system

Generic abnormalities

Nutritional imbalances

What’s hypoxia & why’s it suck.

Less circulating oxygen. Waste can be removed.

no oxygen = less oxidative phosphorylation in the mitochondria. so no ATP.

What’s ischaemia

hypoxia due to reduced blood flow. no way to take waste out

What’s anaemia

having less blood cells

how can the immune system be detrimental. and what’s the name of this

they can attack their own cells (Autoimmune disease)

What two things can cell injuries be

reversible or irreversible

3 outcomes of irreversible cell injuries

Necrosis

Apoptosis

Necroptosis + pyroptosis

What’s necrosis

accidental/unregulated cell death

what can it be caused by

ischaemia, toxins, infections, trauma

is necrosis pathological or physiological

pathological. always.

what happens during necrosis

• enzymes break down the cell membrane

• cell contents leak out

what happens in mitochondria specifically

• influx of calcium opens the mitochondrial membrane pores

• this depletes ATP

• The Ca also activates enzymes that kill the membrane, proteins and DNA

what do free radicals do here

• attack and modify adjacent molecules of DNA and proteins

• these could convert the DNA & molecules into free radicals too

causes of free radicals

radiation, toxins, ischaemia, reperfusion, inflammation, chemicals/drugs

what stops free radicals and how

antioxidants, which block or inactivate them

examples of antioxidants

Vitamin A, C, E, glutathione

Types of necrosis

Coagulative

Liquefactive

Gangrenous

Caseous

Fat

Fibrinoid

What’s Coagulative necrosis caused by

Ischaemia or arterial infection

CN in the kidney?

a renal infract forms, which is an area of ischemia caused by CN of the kidney

This is caused by thromboembolism (thrombus breaks off and travels through blood vessels… and getting stuck)

Where is liquefactive necrosis seen in

ischemic strokes- ischemia to the brain

what happens in liquifactive necrosis (and ischemic strokes specifically)

• dead brain cells are digested, tissue turning into liquid

• a cerebral artery is blocked cuz of thromboembolism, damaging enzymes

What’s gangarenous necrosis

a combination of coagulative and liquefactive

Where is gangrenous necrosis seen in

Gangrne

what happens in gangrene

patient has peripheral vascular disease, linked w diabetes

the diabetes causes damage in small vessels. smaller vessels = not enough getting to the tissue. so tissue breaks down into disgusting shi

What does caseous necrosis form

a cheesy material

when does caseous necrosis happen

in tuberculosis

What happens in fat necrosis

pancreatic enzymes are released, causing necrosis around fat tissue

What’s fibrinoid necrosis

inflammation of blood vessels

why does fibrinoid necrosis happen

deposition of immune complexes in the cell wall

What’s apoptosis

Highly regulated/programmed cell death

what’s apoptosis caused by

protein of DNA damage, loss of hormone stimulation or membrane receptor activation

do we know it’s happening? why

no, cuz there’s no loss of membrane integrity (cuz it’s an energy dependant process, keeping membrane to the last second) & no inflammatory reaction

How does apoptosis happen

the cell shrinks, so everything’s more compact

nucleus fragments

small apoptotic bodies form on the membrane

Is apoptosis physiological or pathological

both :)

how can it be physiological (10. lock in)

• reaction to hormone withdrawl

• elimination of inflammatory cells

• radiation

• hypoxia

• cytotoxic drugs

• DNA damage

• protein misfolding

• Viral infection

• organ rejection

• duct obstruction

two pathological ways of apoptosis

Intrinsic (mitochondrial) and extrinsic (death receptor initiated)

how’s intrinsic happen

triggered by cell injury, DNA damage or decreased hormonal stimulation

activates enzymes called caspase 9, which break down cell proteins

how’s extrinsic happen

triggered by a FAS ligand binding to an FAS death receptor (CD95) on the target cell.

this activates caspases 8 & 10

How are apoptoic cells removed

the cells secrete soluble factors that recruit macrophafes

the cells get coated w Thrombospondin, attracting macrophages that gobble it up

how long does the removal process take

minutes :3

What’s necroptosis

smth w features of necrosis and apoptosis

What’s necroptosis engaged by

initiated by engagement of TNF receptors via kinase activation

where does necroptosis happen

fatty liver disease

what’s pyroptosis

cell death w a fever

what happens in pyroptosis

inflammasome (danger-sensing protein complex) is activated, causing caspase activation

What are three ways of adaptation

hypertrophy

hyperplasia

metaplasia

atrophy

What’s hypertrophy

Increase of the size of cells, which increases organ size

what’s hypertrophy due to

increased workload

when is hypertrophy physiological

uterus during pregnancy

when is hypertrophy pathological

heart muscles during hypertension or valvular heart disease- bigger to help the heart pump

what cells is hypertrophy seen in

cells that don’t divide (e.g. muscles)

what’s hyperplasia

increased no. cells in an organ/tissue in response to a stimulus (like a hormone or growth factor)

What type of cells does hyperplasia happen in

cells that divide

where is hyperplasia physiological

increasing function of an organ

when’s hyperplasia pathological

excessive/inappropriate actions of hormones or growth factors on target cells, dividing mature cells or making more stem cells specialise.

how does hyperplasia stop

if the stimulus is removed

endometrial hyperplasia? and what’s it before

causes abnormal bleeding due to prolonged stimulation of the endometrium by oestrogen… and is a frequent precursor to endometrial cardinoma.

What’s metaplasia

reversible change when 1 differentiated cell type is replaced by another cell type (specifically changing stem cells)

why’s metaplasia happen

cuz 1 cell type’s better to respond to a changed environment

problem w metaplasia

if stimulus persists, dysplasia can happen, forming an invasive carcinoma

Body site

stimulus

native cell

metaplastic cell

metaplasia

tumour risk

for respiratory tract

Respiratory tract

cigarette smoke

columnar cell

squamous cell

squamous metaplasia

squamous cell carcinoma

Body site

stimulus

native cell

metaplastic cell

metaplasia

tumour risk

for lower oesophagus

lower oesophagus

acid reflux from stomach

squamous cell

goblet cell

intestinal metaplasia

adenocarcinoma

can dysplasia be stopped at all

early ones, yh, if the stimulus is removed

What’s Atrophy

reduction in the size of an organ or tissue due to a decrease in cell size, organelle size & number of cells

atrophy: physiological or pathological

both

e.g. of physiological atrophy

alzheimer’s causing autophagy of the brain cuz blood supply decreases, making the brain smaller

e.g.s of pathological atrophy

disuse atrophy

denervation atrophy

diminished blood supply

inadequate nutrition

loss of endocrine stimulation

what’s disuse atrophy

someone being in bed for too long

what’s denervation atrophy

damage to nerves that supply a muscle. causing muscles to yh

what’s inadequate nutrution’s problem

causes the body to use skeletal muscle as a source of nutrition, causing muscle wasting.

what 2 things are activated

Protostomes, which aids atrophy

And autophagy