Cell injury

Cell injury can be caused by many things like: Hypoxia, Ischemia, Chemical agents, Physical agents, Infectious agents, Genetic abnormalities, Lack of substrates. and cells can either adapt to these changes or die.

Variation of injury

Cell injury can be reversible or irreversible depending on severity and duration of injurious insult. This graph sums this idea up nicely. The cell function is lost before you can actually observe signs of injury. Additionally the duration of the injury has a significant effect on the signs of injury.

Stepwise process of injury

A normal cell upon exposure to an stressor or injurious stimulus will either adapt or be injured. If there is a failure to adapt to a stressor injury will result. Injury can be reversible, and the cell will return to normal state after the insult subsides. If it is severe and it doesnt fgo away necrosis and apoptosis will result. (explained later)

Hypoxia in specific

Hypoxia specifically can cause damage because energy obtained from oxidative metabolism needed to maintain the mechanisms of the cell will not be present in high enough concentrations (eg energy for pumps to do their things)

Cell injury signs (morphology)

On microscopy the injured cell can appear swollen and blebbed (with little bits starting to look like its coming away). Accumulations of waste and other substances may also appear in the cytosol.

Cell Adaptations

To an injury a cell can adapt. For example in the harsh conditions of a smokers lung the respiratory epithelia can metaplase into stratifies squamous epithelia. This mean more protection but no mucosal clearance with cilia. This is an example of metaplasia. There are 5? ways adaptions can occur: hyperplasia, hypertrophy, atrophy, metaplasia, dysplasia.

Hyperplasia

In hyperplasia cells multiply to better deal with the stress conditions. We see this in goitre as the cells sense not enough t3 being made and so therefore multiply to make more unfortunatly none will be made as there is usually a lack of iodine

Hypertrophy

This is where the cells enlargen themselves to better deal with stressors eg in high blood pressure an enlargened heart wall is seen as the cardiomyocytes swell in size to be able to pump harder

Atrophy

Atrophy is where a cell decreases in size either as failure to adapt paradoxically or as the current size isnt currently needed

Metaplasia

This occurs in tissues that need to change cell type to survive eg in smokers lung a transition from respiratory epithelia to simple stratified for protection.

Dysplasia

This is where malignancy develops by chance after a metaplasic shift eg rapidly dividing simple stratified epithelia develop into cancer as they are rapidly dividing and accumulate mutations more rapidly, reflecting their high rate of division.

Cell death

Cell death occurs normally or pathologically Normal death is called apoptosis

Many pathways to cause this: dna or protein damage, viral infection, outside influences etc

Occurs after enzyme cascade of  proteolystic caspases which make apoptotic bodies Abnormal, unintended cell death is called necrosis This is where the cell cannot maintain its processes to stay alive, Messy, inflammatory and alarming raising molecules are released There are other mechanisms for cell death eg necroptosis pyroptosis ferroptosis etc) 3 stages of nucleus damage Pyknosis dark pinpoint Karyorrhexis fragmentation Karyolysis nothing

Healing

Healing starts with inflammation

Macrophages play a key role in healing through the removal and cleaning of necrotic tissue and release of TGF-b

Regeneration and scarring - 2 outcomes

Regeneration is possible where there is minimal damage

Scarring is for larger damage

Steps of healing by fibrosis in

  1. Formation of new capillary vessels (angiogenesis)

  2. Budding of new blood vessels from presexisting ones

  3. Driven by Vasculatr endothelial growth factor, fibroblast growth factor, and angiopoetins

  4. Formation of grandulation tissue

  5. Fibroblasts migrate to the site of injurt and proliferate

  6. They make ecm mainly collagen

  7. TGFb id released from macrophages and are the main drivers of this

The mixture of new capillary vessels, fibroblasts, collagen, and remaining inflammatory cells all together make granulation tissue

  1. Maturation and remodeling of the fibrous scar

  2. Granulation tissue matures into a fibrous scar the fibroblasrs and blood vessels decrease and the collagen increases

  3. Excess collagen is degraded by Matrix metalloproteinases

Factors influence the rate of repair

Wound infection

Diabetes

Nutritional status

Poor blood supply

Mechanical factors e.g. Too much movement

Foreign body in wound

Primary intention is easy relatively scar free tissue due to well opposed, close edges

Secondary intention is fat ugly and scarring

Some complications include rupture

Infection

Exuberant granulation tissue

Hypertrophic scar

Keloid

Bone fracture

Haemotoma

Big clot and bleeding

Granulation tissue forms

Soft callus

Bony matrix and some cartilage staryt forming

Hard callus

Ossification forms

Remodeling

Osteo clastic and blastic activity resorbs excess cellus

Complications:

Nonunion

Fibrous union