Mechanisms of physical damage to cells

Question 1

What are the types of physical damage to cells, tissues and organs?

Answer 1

Mechanical injury due to physical force such as mechanical stress, this obvious manifestation of this is due to traumatic damage
Physical damage may occur via thermal injury such as local heating of tissues and systemic changes in temperature
Physical agents can also cause cell damage by affecting a specific biochemical pathway in the cell or its membrane

Question 2

What can influence mechanical injury to tissues?

Answer 2

This is influenced by the type of force this can be compressive, stretch the tissue, shearing or torsional or a combination of these types
Bending also produces tensile forces
The rate of transfer and surface area of the force are also important influencing the extent and type of damage
Area of the body is significant as there are differences in compressibility of tissue, organs and vessels can also rupture as a result of differences in the compressibility of tissue

Question 3

What are the different types of mechanical injury?

Answer 3

This can be blunt, penetrative and or compressive and includes contusions, abrasians, lacerations and fractures

Question 4

What is an abrasion?

Answer 4

A defect caused by an impact that crushes/scrapes the epithelial surface and leads to disruption of epidermis and dermis. This is a potential point of entry by bacteria, the configuration/impact of the cause is often visible

Question 5

What is a laceration?

Answer 5

A tear in the epidermis, usually due to a greater impact/force than an abrasion it is observed as an irregular split into underlying tissue. Lacerations are deeper than abrasions and more irregular than incised wounds

Question 6

What are contusions?

Answer 6

These are bruises and occur in as a localized area of injury caused by blunt force, compression force distorts and ruptures the small blood vessels in dermis and soft tissue. This damage to capillaries and venulesleading to extravasation of red blood cells. The blood fluid collects under the skin as a hematoma which changes in colour with regards to the age of the contusion

Question 7

How does a hematomas colour show the age of a contusions?

Answer 7

This colour is due to the biochemical breakdown of hemaglobin, a fresh hematoma may be red, this will then turn blue or dark purple within a few hours due to deoxygenated blood, as the reb blood cells are broken down this releases bilirubin and heme causing a yellow or green colour
microscopic evidence of hemosiderin in macrophages

Question 8

What is tensile injury?

Answer 8

Tensile force has different effects in different tissues, some tissues are capable of being stretched or bent however others such as bone are not

Question 9

What is compressive injury?

Answer 9

Compressibility of a tissue is important as some organs can rupture due to the compression of fluid or gas within them, for example abdominal blunt force injury often damages the liver with multiple lacerations

Question 10

What is sheer injury?

Answer 10

Brain injuries can be caused by the rapid deceleration of the moving head on contact with a fixed surface or by acceleration due to a blow. The severe change in de/acceleration produced by the blunt trauma can result in sheering stress within the brain and the interior of the cranium resulting in bruising of the brain and bleeding. This often occurs at the point of impact of the brain against the skull, a countercoup injury can occur directly opposite the site of trauma such as the impact of a head against a windshield in a car accident, at this impact the brain opposite the site of impact accelerates towards the opposite side of the skull and crushes or bounces against the opposite side of the cranium

Question 11

What are terms that describe bleeding in the spaces between the meninges- the fibrous layered coverings of the brain?

Answer 11

Epidural, subdural and subarachnoid haemorrhage accumulation of this fluid can result in an increase in pressure within and compress the brain

Question 12

What is an epidural haemorrhage?

Answer 12

The blood is trapped in a small area and pressure can quickly increase within the epidural surface pushing the clot up against the brain causing coma and significant brain damage. An epidural hematoma may often occur with trauma to the temporal bone located on the side of the head above the ear. This bone is thinner than the other skull bones and the location of the middle meningeal artery that runs just beneath the bone fracture of this bone is associated with tearing of this artery and may lead to an epidural hematoma

Question 13

What is a subarchnoid haemorrhage?

Answer 13

The blood accumulates in the space beneath the inner arachnoid layer of the meninges, this also the space where cerebral spinal fluid flows and affected individuals can develop severe headache, nausea, vomiting and a stiff neck because the blood causes significant irritation to this meningeal layer

Question 14

What is intracerebral haemorrhage?

Answer 14

Where there is bleeding within the brain tissue, there is direct damage to the brain tissue that was injured and edema is the major complication of an intracerebral bleed, treatment of these requires temporary surgical removal of bone to allow the brain to expand

Question 15

How can sheer injury occur to neuronal axons?

Answer 15

The affected individual often appears comatose with no evidence of bleeding within the brain, the mechanism of injury is usually acceleration-deceleration and the nerve endings the connect the brain cells rip apart
Forces produced by violent shaking can result in stretching of axons in cerebral white matter this can shear off axons resulting in the ends retracting into globoid shapes
In adults severe whiplash can involve sever forces that may shake or rotate the brain enough to cause permanent brain damage, concussions may be a potentially milder form of this type of injury

Question 16

What is shaken baby syndrome?

Answer 16

This is when severe shaking stretches and damages neurons, the cerebral lesions that result from blunt trauma in infancy differ to those observed in an adult as the infant skull is thinner, more malleable and has smoother less corrugated inner surface than an adult skull therefore this more typically results in bilateral subdural hematomas. Haemorrhagic retinopathy and also split, lifted or folded retina can also be observed

Question 17

What is cellular wounding?

Answer 17

A physical injury that can occur at the cellular/ sub-cellular for example due to stretch or thermal injury

Question 18

What is stretch injury?

Answer 18

When overextension of cells can result in a stretch injury for example acute lung injury due to hyper ventilation

Question 19

How can neonates show stretch injury?

Answer 19

In neonates the first inflation of the lungs stretches alveolar type 2 cells and via signal transduction activates genes to produce and release surfactant
Pre term babes however do not have a fully mature alveolus as type two pneumocytes are only abundant after this time meaning that the first inhalation cannot activate surfactant production, without surfactant the alveoli collapse at the end of each expiration and this results in neonatal respiratory distress where the lungs are solid, airless and reddish purple with collapsed alveoli and dilated alveolar ducts and respiratory bronchioles. Neonatal respiratory distress requires mechanical ventilation which can also cause further damage through stretch damage which can induce necrosis of immature pulmonary alveolar cells, this triggers an inflammatory response which increases the permeability of the capillaries with the generalized capillary leak so that a protein rich exudate fills the alveoli inhibiting any further development of the alveolus and surfactant production

Question 20

When do alveolar cells undergo elastic deformation?

Answer 20

This occurs at 80% of lung capacity and this can result in capillary basement membrane fracture, while these molecular mechanisms are not well elucidated but this deformation is stimulus for mechanosensing and can activate signalling mechanisms which alter the regulation of gene expression,

Question 21

How do cells respond to mechanical forces including radial stretch and/or shear stress?

Answer 21

Multiple signal transduction cascades which alter gene expression and altered production of proteins, this mechano transduction in the lung involves signalling between type 1 and type 2 alveolar cells, endothelial cells, fibroblasts via physical connections between the extracellular matrix and the cell nucleus such as transmembrane proteins and intracellular scaffolding. The complexity of signal transduction is not well understood and more than 300 genes are affected by stretch in alveolar cells

Question 22

How good is the cell lipid bilayer at resisting stress?

Answer 22

The cell lipid bilayer membrane can withstand 1-3% lateral expansion by unfolding and this can be repaired by lipid trafficking but stretch stress will lead to failure of the membrane and defects in tight junctions between cells and Ca2+ influx into cells

Question 23

What controls the type of damage seen from thermal injury?

Answer 23

The type of damage from thermal injury depends upon whether there is a localized or a general effect, for example frost bite vs hypothermia and burns vs heat stroke

Question 24

What is hypothermia?

Answer 24

When there is a decrease in body temperature below 35 degrees, recovery from this will be possible unless the body temperature falls below 28 degrees. This occurs when heat loss exceeds heat production leading to a fall in body temperature and a decrease in respiratory/heart rate

Question 25

What are the consequences of hypothermia?

Answer 25

One consequence is that the blood viscosity increases and there is an increased risk of cardiac arrhythmia and sudden cardiac arrest
There are no specific morphological changes with hypothermia, however the skin has a red/purple discolouration and the ears and hands are swollen. Pulmonary oedema and haemorrhage and myocytolysis in the heart may also occur

Question 26

What is frostbite?

Answer 26

This is a focal decrease in body temperature that results in local vasoconstriction and freezing of the local tissue water, ice crystals will then form and electrolyte gels are excluded from the cell leading to a drastic change in ionic concentrations within the cell

Question 27

What can occur when thawing a tissue affected by frostbite?

Answer 27

This can cause mechanical damage to membranes with endothelial cells being particularly sensitive to damage affecting small vessel permeability causing extravasation of blood plasma, localized oedema and blisters resulting in vascular occlusion which can lead to gangrene due to ischaemia

Question 28

What are the three types of gangrene?

Answer 28

Dry gangrene where ischaemia leads to tissue necrosis and the tissue becomes mummified, as there is no blood flow there is no phagocytosis, this is a sterile process where the tissue will separate itself from the necrotic area to allow healing of the defect
If this process is not sterile then wet gangrene or gas gangrene will occur.
Wet gangrene is when bacterial infection occurs as a secondary complication and there is putrefaction
Gas gangrene is when ischaemic tissue is infected by an anaerobic bacteria like clostridium perfringens, this bacteria produces a myotoxin which is a phospholipase capable of destroying erythrocyte, muscle and leukocyte membranes resulting in necrotic and liquefied tissue with no neutrophils present, the result of these infections is usually proximal spread and the patient dies of sepsis unless treated

Question 29

What are the effects of hyperthermia?

Answer 29

Increased temperatures result in increased metabolic rate with enzyme systems be disturbed, at high temperatures there is denaturation of proteins and precipitation, for enzymes this denaturation will result in loss of activity.
Lipid bilayers in the membranes to become more fluid and melt

Question 30

What is the only treatment for hyperthermia?

Answer 30

External cooling and electrolyte replacement

Question 31

Is the body more tolerant to low or high temperatures?

Answer 31

The body is more tolerant to low temperatures with Body temperatures of greater than 41 degrees are not compatible with life

Question 32

What are the systemic effects of hyperthermia?

Answer 32

Pyrexia and heatstroke where pyrexia is caused by infections as cytokines released from macrophages act on the hypothalamus to increase heart and respiratory rates with peripheral vasodilation and diaphoresis
Heatstroke typically occurs when there is a very high ambient temperature and conduction and radiation of heat from the skin and sweating is impaired

Question 33

What are burns?

Answer 33

Localized thermal injuries which can occur dueto exposure to fire, hot objects, hot liquids, electricity or radiation
This heating causes damage, 50 degrees celcius can be sustained for 10 minutes without killing cellsbut greater than 70 degrees for several seconds causes cellular necrosis
There is also melting of lipids, denaturation of proteins and the ability of extreme heat o completely carbonize the biological material causing the tissue to appear charred and all cellular structure to be lost

Question 34

What are the three types of burn which can occur to the skin?

Answer 34

These may be superficial, partial or full thickness
Superficial burns involve only the epidermis, are erythematous and painful due to mild endothelial cell injury, vasodilation and slight oedema, there will be congestion and pain but no necrosis as occurs with sunburn
If necrosis occurs this is no longer a superficial burn, if the epidermis and only a portion of the dermis is destroyed then this is a partial thickness burn where blistering is commonly observed with the skin appearing mottled and d causing severe scarring, contraction and the loss of function
If the tissue destruction extends into the entire skin and even the underlying subcutaneous tissue it is a full thickness burn, all skin appendages are burned away with the depth of the injury affecting subsequent healing of the wound, these wounds cannot heal by scarring and require a skin graft

Question 35

What serious systemic complications arise from a denuded skin surface?

Answer 35

There is a loss of body water and if there is also extensive loss of body surface area then the patient will develop shock
There is also acute tubular necrosis due to haemoconcentration and poor vascular perfusion
There is also a risk of lethal infections and sepsis

Question 36

What is inhalation thermal injury?

Answer 36

Acute injury due to inhalation of very high temperature gases can destroy the respiratory tract epithelium, hot and noxious fumes generally cause damage confined to the upper airway, in contrast inhalation of steam can lower airway and alveolar damage
Often the thermal injury produces bruns to the mucosa of the nose, pharynx and larynx
The resulting oedema can cause the tissues of the upper airway to swell and can obstruct the airway particularly via laryngeal spasm with possible suffication