Cause and mechanism of injury在线视频

Hello everyone

Today I am going to talk about the causes and mechanisms of injury

So what is injury

When tissues and cells cannot adequately adapt the encountered physiological stress or pathological stimuli

Certain abnormal changes may occur intracellularly and extracellularly as well

These abnormal changes will affect the metabolites chemical ultrastructure and the visible morphology changes both grossly and microscopically

So what kinds of causes may lead to injury

We believe that there are about seven kinds of causes for injury

The first and the most common one is called hypoxia

Hypoxia can be categorized to systemic hypoxia and localized hypoxia

Localized hypoxia is much better understandable which caused by local blood circulation disorders

Local vessel obstruction such as atherosclerosis may result in lack of blood supply to the brain

AS of coronary artery may result in myocardial blood supply deficiency then eventually lead to both cerebral hypoxia and myocardial hypoxia

There are two major categories of systemic hypoxia

One is related to the decreased oxygen carrying capacity of blood as occurs in carbon monoxide poisoning

There are inadequate oxygenation and decreased oxygen carrying ability

The second one is the functional failure of heart and lungs

For example when someone comes to high altitude plateau region

the ability to metabolize oxygen will reduced which belongs to this category

The second category is physical factor

such as extreme high or low temperature

Extreme high temperature can cause burn and sunburn

Whereas extreme cold can lead to frostbite

Mechanical injury such as trauma can cause tissue damage

There are electric shock ionizing radiation as well

There are chemical agents such as stimulation from strong acid and alkali

Yes drugs are also toxic

There are poisonous agents as well

These are chemical factors

Biological factors are also very common causes lead to injury

Varieties of bacteria viruses rickettsia fungi and parasites are all biological factors

Biological factors lead to tissue and cell damage mainly through its production of toxin or metabolites

Another one is closely related to immune response such as allergies reactions glomerulus nephritis or rheumatism

Such patients may have allergic disease which cause injury to their kidney function and myocardial function as well

There are a large class of autoimmune diseases

such as systemic lupus erythematous and rheumatoid arthritis which can damage the body as well

Moreover there is transplant rejection

After organ transplantation patients need to take immunosuppressants

Otherwise the host will damage the donor organ leading to organ necrosis

There is another class of associated with genetic defects

such as alpha-antitrypsin deficiency which may lead to emphysema

Then let's take a look at nutritional disorders

That is called malnutrition which includes both inadequate nutrition and excessive nutrition

Let's take inadequate situation for example

When feeding animals with diet lacking of choline or methionine

liver cirrhosis and fatty liver may occur

Excessive nutrition would be much better understandable

For example it is closely related to high occurrence of obesity and diabetes

Here we introduced reasons of injury

Then how could these cause injury of the organ or tissue

What kind of mechanism lies behind this

Next let's take a look at this together

The mechanism of injury is classified into five categories

The first one and also the most common one is the depletion of ATP or energy

The depletion of energy may affect synthesis and decomposition function of cells

let's take a look at this picture

For example when ischemia occurs the mitochondria becomes starved for oxygen

leads to decreasing oxidative phosphorylation process then results in reduction of ATP

ATP depletion will then affect the function of sodium-potassium-ATP pump on cell membrane

Furthermore glycogen synthesis is also affected

Any kind of biological functions in our body is dependent on oxygen

This is how ATP depletion and hypoxia leads to cell injury

The second mechanisms is the increase of free radicals

So what is free radical

It refers to an atom ion or molecule which contains an unpaired electron in its outer orbital

That means the outermost layer is very unstable

By what means can free radicals be produced

It's generally considered to be associated with the ionized water

or superoxide ions produced in the oxidation-reduction reaction

They have powerful oxidative activity

Because of their very unstable outermost electron orbit

they can damage the cell membrane biomolecular membrane or mitochondria etc

Then let's take a look at this picture

It shows that when free radicals oxygen ions or superoxide ions are generated in the cells

the structure of membrane may be destroyed

Fortunately there is such enzyme called SOD or superoxide dismutase in our body

Those free radicals can be inactivated by SOD

Then cells are able to maintain normal function before they can do any harm

The third mechanism is about the destruction of membrane integrity

Destruction of membrane integrity usually occurs by several means

Such as cell membrane dissolving mediated by complement or by virus directly

Others occur by blocking the ion channels or by the failure of ion pump on the cell membrane

Actually these are all relevant with ATP depletion

At last there is free radical

There are varieties of causes that lead to the destruction of membrane integrity such as oxidation of phospholipid membranes cross-linking of membranous proteins and so on

Here is a picture shows that

the membrane injury may be due to hypoxia induced ATP depletion

Thus certain oxidation process was down-regulated

As we all know that phospholipids play an important role in cell membrane function

So lack of phospholipids may results in membrane damage

We can also see here that there is another reason called an increase of free calcium ions

Therefore the fourth mechanism is the elevation of intracellular free calcium

Under normal circumstances the concentration degree of intracellular free calcium is very low

However under the influence of those injury factors which we have mentioned

there is no way to maintain low calcium concentration by ATP pump and the calcium ions channels

Normally the calcium ions are stored within the mitochondria or endoplasmic reticulum

When injury occurs calcium ions come out to the cytoplasm

This increased the amount of free calcium in the cytoplasm

When this happens a great deal of enzymes may be activated

such as ATPase and phospholipase including proteinase or endonuclease

These may result in reduction of ATP and membrane phospholipids

and the destruction of cytoskeletal proteins as well

In the most severe cases may lead to the damage of chromatin

Eventually cause cell damage through such mechanisms

Then the last mechanism is the irreversible damage to mitochondria

Actually all the injuries mentioned above are due to the change of the mitochondria

Decreased ATP may cause the damage of mitochondria

Increased free radical may also damage the mitochondria

Damage to the mitochondria increase the cell permeability

It may affect the mitochondrial oxidative phosphorylation process

Meantime here shows cytochrome c

Cytochrome c comes from the mitochondria into the cytoplasm due to the leakage

Thus severe damage of tissues or cells even irreversible cell death may occur

Well let's take a look at this picture

There are a lot of organelles inside this normal cell

such as mitochondria and endoplasmic reticulum

When the injury occurs we may find their structural morphological and even functional changes

There are two kinds of changes

One is reversible called reversible injury

There is another category called irreversible injury

Reversible injury is also known as degeneration

Irreversible injury is called necrosis

These are what we are going to learn later

Thank you That's all for today