Cell injury, adaption and cell death

what is cellular stress

A state of imbalance where cells experience damage or dysfunction due to the challenging environment or physiological conditions

What are the possible cellular responses to stress?

Adapation

reversible injury

irreversible injury, leading to cell death

Name the main types of cellular adaptation

Atrophy, hypertrophy, hyperplasia, metaplasia.

Define hypertrophy

When cell size increases, leading to an increase in organ/tissue size

Can be physiologic or pathalogic: Caused by increased demand or growth factor/hormone stimulation

stages if cellular response to stress

normal cells under stress—→cell injury which try to adjust to new circumstances—→if there is too much stress the cell cannot adapt—→ there is cell injury leading to cell death—→ however the damaged cells can be reversed but if the stress is lethal then the process become irreversible

Define hyperplasia

Increase of the number of cells in an organ due to increased proliferation

Can be physiologic or pathalogic: stimulated by hormones/growth factors

Give two examples of hyperplasia.

Hormonal hyperplasia (e.g., breast epithelium at puberty/pregnancy)

compensatory hyperplasia (e.g., liver regrowth after resection).

Define hypoxia vs ischemia.

hypoxia is oxygen deficiency

ischemia is a lack of blood supply and nutrients

what is Atrophy

reduction size and number of cells leading to the reduction size of an organ or tissue due to ageing, denervation, malnutrition, diminished endocrine stimulation and disuse.

What is the most common cause of hypoxia?

Ischemia due to an artery blockage

metaplasia

change in which one adult cell type is replaced by another adult cell type

What are free radicals (ROS/RNS) and why are they harmful?

Free radicals are highly reactive molecules with unpaired electrons

they can damage lpis, proteins and DNA leading to cell injury and cell death

List key sources of free radicals.

Normal mitochondrial metabolism, inflammation (neutrophils/macrophages), radiation, pollutants/cigarette smoke, heavy metals (iron/copper), drugs/toxins (e.g., acetaminophen overdose), reperfusion injury, aging/disease.

What are the two main types of cell death?

Apoptosis and necrosis

Which type of cell death is always pathological?

Necrosis (typically after severe injury; membrane breakdown; inflammation).

What determines whether cell injury is reversible or irreversible?

• Nature and duration of injury

• Type of cell

• Regenerative capacity of tissue

What are free radicals

Highly reactive molecules with unpaired electrons

Why are free radicals harmful

They damage lipids, proteins and DNA which lead to cell injury/cell death

Main sources of free radicals?

• Mitochondria (normal metabolism)

• Inflammation (neutrophils/macrophages)

• Radiation

• Drugs & toxins

• Reperfusion injury

• Ageing

Define necrosis.

Pathological cell death with membrane breakdown and inflammation.

Pathological cell death with membrane breakdown and inflammation.

Nuclear changes in necrosis (order).

Coagulative necrosis – where & why?

• Due to ischemia

• Common in solid organs (heart, kidney)

• Tissue architecture preserved initially

Liquefactive necrosis – where?

• Brain infarcts

• Bacterial/fungal infections

• Produces pus → abscess

Caseous necrosis – classic association?

Caseous necrosis – classic association?

Gangrenous necrosis – what is it?

Gangrenous necrosis – what is it?

• Dry gangrene: coagulative

• Wet gangrene: liquefactive + infection

Fat necrosis – cause and feature?

Fibrinoid necrosis – where seen?

• Immune-mediated vasculitis

• Severe hypertension

• Transplant rejection

What is metastatic calcification?

Calcium deposition in normal tissues due to hypercalcemia.