Pathology - Exogenous injury

Exogenous agents are, Hypoxia, Physical, thermal, Microbial and radiation. 

Acute and transient injurious stimuli results in acute but reversible damage

 Chronic, progressive and severe injurious stimuli results in an irreversible injury and leads to cell death

Hypoxia means insufficient supply of oxygen to the cells and tissues. The shortage in oxygen supply leads to reduced aerobic oxidative phosphorylation. Its the most common cause of cell injury. Hypoxia can also be the consequence of other exogenous agents. Cells may be able to either adapt, go through injury or can die depending on the severity of Hypoxia. In severe cases necrosis and cell death is the end result.

Major causes of hypoxia

Ischaemia means reduced arterial blood flow to the tissues. it can lead to hypoxia. One example of Ischaemia is atherosclerosis. The build up of lipids (dead white blood cell remnants) in the walls of the artery which leads to reduced blood flow to the tissues leading to hypoxia.

Hypoxaemia is the decrease in oxygen levels of plasma due to cardiorespiratory failure. Hypoxaemia is seen in conditions like atelectasis. Atelectasis is the partial collapse or incomplete inflation of the lungs.

Anaemia is reduced levels of haemoglobin. It can lead to hypoxia due to reduced oxygen-carrying capacity of the blood (due to low haemoglobin levels). It can be the cause of severe blood loss or carbon monoxide poisoning.

Histoxia (histotoxic hypoxia) - Tissues unable to use available oxygen

Physical agents can be such as trauma. Trauma is the most common physical agent that causes cell injury due to the increased incidences of road traffic accidents and physical violence. The physical agents also include thermal injury, electrical injury and radiation.

Mechanical trauma leads to the separation and damage to cells. Mechanical trauma can lead to contusion (bruising). This normally happens when an object that is not sharp causes damage to the subsurface tissue and blood vessels but does not cause harm to the skin. (internal bleeding). Blood vessel ruptures and that leads to leakage of the blood to the surrounding connective tissues. This triggers the immune system and the released blood cells that disturb the surrounding tissues are phagocytosed by macrophages.The colours of a bruise are caused by the phagocytosis and breakdown of haemoglobin in the red blood cells.The phagocytic cells  The contents of haemoglobin are released and the iron from haemoglobin is stored as haemosiderin. The browning of the phagocytic cells is caused by the high levels of haemosiderin in the phagocytes.

Mechanical trauma is not always harmless e.g Brain haemorrhage. A mechanical trauma to the head leads to the rupture of the blood vessel and the blood is released into a small cramped up space(cranium). As there is limited space for swelling in the cranium, the pressure rises. The rise in pressure leads to closure of the capillaries. This can lead to hypoxia. It can also lead to nerve compression as the nerve is pressed/squashed in between the surrounding tissues due to the high pressure. The ending result is coma.

Exposure to excessive heat or excessive cold can lead to cell injury. The severity of the injury depends upon the temperature and the length of the exposure.Burns are the most common cause of thermal injury (exposure to excessive heat). The clinical seriousness of a burn depends on the deepness of the burn, the area of the involved surface, if there are any internal injuries due to the presence of the toxic fumes like CO and the quality of the treatment given.

How the burns are classified  :

1. The superficial epidermal burns affect solely the epidermal layer of the skin. There is no presence of blisters or broken skin and the area is slightly swollen and painful. It heals pretty well.
2. Superficlal dermal burns/superficial partial thickness (second degree) injure the epidermal and the upper part of the dermal layer. There is formation of small blisters and the skin tends to be pink and pale. Deep dermal burns/deep partial thickness involve injury to epidermis and dermis. The damage is deeper into the dermal layer. There is presense of blisters and the skin can be dry or moist.
3. Full thickness burns (third degree) - The burn is deeper and extends to subcutaneous tissue affecting all the 3 layers of the skin; epidermis ---> Dermis ----> subcutaneous. The skin is deeply burnt and the tissue underneath looks pale or blackened. There is no presense of blisters and there is no pain as the damage is so extensive that the nerves are damaged. The healing is very poor. The full thickness burns also involve fourth degree burns where the injury not only involves 3rd degree burns, but also the fascia, muscle and bones are affected. Very poor healiing.

What occurs after burn injuries?

Blister formation is the separation of the epidermis from the underlying dermis. The blister can be filled with serum, plasma, blood or pus(infected).

Hypovolaemic shock is the consequence of burn injuries. In very severe burns, the cells goes through dehydration and alot of fluid and ions are lost due to the burns leading to hypovolemic shock. There is an immediate release of body fluid out of the cells into the interstitial tissue at the site of injury.This can also happen systematically leading to hyopvolemic shock. Interstitial tissue is the connective and supporting tissue within and surrounding the major functional elements of an organ.

Oedema - The burn injuries can also lead to oedema due to the release of proteins from the blood into the interstitial tissues decreasing the colloid pressure. The osmotic gradient reduces because of lower levels of proteins at the arterial end in the capillary so the fluid moving into the capillary at the venous end decreases and there is an imbalance of fluidity leading to oedema.

What occurs after burn injuries?

Blister formation is the separation of the epidermis from the underlying dermis. The blister can be filled with serum, plasma, blood or pus(infected).

Hypovolaemic shock is the consequence of burn injuries. In very severe burns, the cells goes through dehydration and alot of fluid and ions are lost due to the burns leading to hypovolemic shock. There is an immediate release of body fluid out of the cells into the interstitial tissue at the site of injury.This can also happen systematically leading to hyopvolemic shock. Interstitial tissue is the connective and supporting tissue within and surrounding the major functional elements of an organ.

Oedema - The burn injuries can also lead to oedema due to the release of proteins from the blood into the interstitial tissues decreasing the colloid pressure. The osmotic gradient reduces because of lower levels of proteins at the arterial end in the capillary so the fluid moving into the capillary at the venous end decreases and there is a build up of fluid into the tissues leading to oedema.

Electrolyte imbalance

There are two types of electrolyte imbalance which can occur following burn injuries

• Hyponatremia where the sodium ions are lost following loss of water
• Hyperkalemia - Potassium ions from the damaged cells and tissues are released into the blood stream hence the levels of potassium ions in the blood stream increase (potassium needed in muscle cells for muscle contraction)

Causes damage in two ways

Direct way is the immediate freezing of water which leads to the physical distruptions of organelles within cells. The tissues are frozen. The crystallisation of intercellular and extracellular water leads to high salt concentration in the cytosol which leads to osmosis, swelling and burst. Severe damage can lead to formation of a blood clot (thrombosis) in blood vessels. the tissue appears to be blackened due to erythrocyte leakage and destruction.

Indirect way is due to changes in blood flow via ischaemia.The sudden drop in temperature induces vasoconstriction and and makes the blood thicker (viscous). This leads to reduced blood flow to the tissues (ischaemia) leading to hypoxia (insufficient oxygen). The prepheral sympathetic noradrenergic nerves enhance the vasoconstriction of vessels.This leads to reduced blood supply and reduction of blood supply leads to the reduced supply of oxygen and nutrients to the affected tissues. 

Injury to the endothelial lining of the capillaries leads to the increased permeability of the capillaries. This leads to localised oedema and blisters.

Hypothermia leads to increased diuresis (urine production). The loss of fluid leads to increased blood viscosity. That leads to reduction of the blood volume leading to ischaemia. The decreased  blood flow reduces the oxygen reaching to the tissues. (hypoxia). This leads to denaturation of macromolecules. If the tissue temperature stays reduced for long, it can lead to endothelial cell damage resulting in the formation of a thrombus or vascular occlusion ( blockage of vessels). This can result in dead tissue (necrosis and gangrene) causing trench foot.

Toxicology (Science of poisons) studies the distribution, effects and mechanism of action of toxic agents.

Exposure to chemical agents can be due to :

Environmental chemicals - Xenobiotics are exogenous chemicals in the environment in the air, water, food and soil that may be absorbed into the body through inhalation, ingestion or skin contact. Xenobiotics may act at the site of injury or they can be spread around the body through blood and can act at different sites of the body. They can enter the cells in different organs and can change the structure of the macromolecules inside the cells eg. DNA. Some exogenous agents in the body are metabolised to form inactive water-soluble products which are then eliminated from the body (detoxification). In contrast, some agents are metabolised to form reactive metabolites which can be toxic to the cell's components.

Air pollutants

• CO, NO2, SO2
• Acid aerosols - Acidic liquid or solid particles small enough to become airborne particles. They can irritate the lungs and are associated with alot of respiratory diseases like asthma.

Heavy metals as environmental pollutants : Lead, Mercury, Arsenic, Cadmium