Cellular Injury and Death 2 PATHO

What can cell injury be?

Sublethal or lethal

Why can cell injury be sublethal?

It has the possibility to be reversed if it's corrected in time (if not it can be lethal)

Is cell injury a death sentence?

No

What is anoxia?

A condition when there is a complete lack of oxygen in the body

Which cells are more vulnerable to lack of oxygen?

Brain cells, they can only survive 3 to 6 minutes without oxygen

What does etiology lead to?

Etiology or cause is what leads to the results or pathogenic processes that lead to the signs and symptoms of

What can lead to hypoxia injury?

If it involves blood flow and circulation (infarct/ischemia), the pulmonary system and any problems with erythrocytes

When does cellular injury occur?

When any factor disrupts cell structure or function, putting the cell's ability to maintain homeostasis in jeopardy

When does cellular death occur?

When there is an overwhelming insult to the cell and it is no longer able to survive

Cell injury can be caused by

Many factors in the internal and external environment

When is cellular injury reversible?

If the cell adapts or the stressor is removed, which is why cellular adaptation is so important to the cell's survival

What are consequences of cellular injury?

Sodium potassium pump dysfunction

Loss of plasma membrane integrity

Intracellular accumulation

Protein synthesis defects

DNA damage

What does the sodium potassium pump do?

Expels 3 sodium out of the cell in exchange for 2 potassium moving in

What does the sodium postassium pump require?

Energy and oxygen

What must the cell maintain for optimum cell functioning?

A higher concentration of potassium inside the cell and a higher concentration of sodium outside of the cell

How many sodium for how many potassium?

3 sodium out of the cell for 2 potassium inside the cell

What is the sodium potassium pump responsible for maintaining?

The action potential in muscle and nerve cells and the fluid balance inside and outside the cell

What does the sodium potassium pump require energy in the form of?

In the form of ATP produced by mitochondria and the mitochondria require oxygen to produce 34 ATP

Why does hypoxia injury begin when oxygen delivery is disrupted?

Mitochondria require oxygen so when there is no oxygen the cell switches to glycolysis to produce 2 ATP but cells cannot maintain this for very long bc it is not enough energy plus lactic acid byproduct, so the pump shuts down which causes sodium to stay inside the cell and water to follow so the cell swells)

What is hypoxia?

Oxygen deprivation

What is the most common cause of cell injury?

Oxygen deprivation (hypoxia)

What can hypoxic injury occur from?

Impaired blood flow or anemia, or also when oxygen availability is low or gas exchange is impaired by lung disease

Regardless of the cause, hypoxia causes a

Power failure in the cell

What happens when hypoxia happens to the cell?

Cellular swelling/lysis (sodium potassium pump)

Lactic acid accumulation

Damaged plasma membrane/organelles

Impaired protein synthesis

Cellular power failure is decreased production of

ATP

What happens with cellular power failure?

Cellular swelling/lysis

Lactic acid accumulation

Damaged plasma membrane/organelles

Impaired protein synthesis

How does cellular swelling/lysis relate to the sodium potassium pump?

Without oxygen to produce energy, the pump fails so sodium stays inside the cell and attracts water. As water accumulates in the cell it swells and lysis becomes a risk

What is lactic acid accumulation or how does it happen?

When cells switch to anaerobic metabolism to keep functioning, lactic acid accumulates which is toxic to cells

Why is there impaired protein synthesis?

A lack of ATP interrupts protein synthesis so cellular processes begin to fail

What is the most common accumulation injury?

Water

What cells tolerate lactic acid accumulation the most?

Muscle cells, but pain is an indicator that injury is occurring (like when you are sore)

Skin that gets wrinkly from being in the water is called what?

Macerated skin and it is very prone to additional injury (like how you can easily peel it off)

What is an example of exogenous water accumulation?

Macerated skin

Water follows sodium but does sodium follow water?

No

Many cells can recover from swelling, but which can't?

Brain cells because of the skull, there is no room to swell and this causes increased intracranial pressure)

Once brain cells are lost what happens

They can't regenerate

What other exchange other than the sodium potassium pump happens across the plasma membrane?

Sodium calcium exchange

Cell injury can lead to calcium

Accumulation or calcification injury

Where does calcification most commonly occur?

With cardiac valves, when they get injured they start to accumulate calcium inside those cells

What is a very common cause for heart failure?

Calcification because cardiac valves get very stiff when they have cardiac deposits

What are hepatocytes particularly vulnerable to?

Lipid accumulation

What is "fatty liver"?

When lipids accumulate in hepatocytes and can lead to cirrhosis (liver failure)

What is Tay-Sachs disease?

A genetic disorder that causes lipid accumulation in the CNS due to the patients missing an enzyme that degrades lipids, so the lipids start to accumulate in the CNS

What is ALD?

A genetic disorder that causes the accumulation of bad lipids and the deterioration of good lipids because of a missing enzyme (dietary solution to help)

What can protein accumulation do?

There are several central nervous system disorders that involve an accumulation of abnormal proteins in the brain that slowly impair neurological function

Alzheimer's leads to an accumulation of

Amyloid beta and tau protein which leads to progressive neurodegeneration and dementia

Huntington's is a

Genetic disorder that leads to the accumulation of Huntington's protein in the basal ganglia and is passed on from generation to generation (leads to cognitive decline and motor deficits)

What is hemosiderin?

A yellow brown pigment berated as hemoglobin is broken down by macrophages

What does hemosiderin accumulation cause?

Discolored lower extremities, veins in the leg are overfilled with blood so the red blood cells get squeezed out of the veins and the macrophages can't clean up fast enough so the iron component gets into the subcutaneous tissue and stains it

What is it that we see when we have a bruise but the WBCs clean it up?

Hemosiderin

What is bilirubin?

Another pigment that accumulates in the b,old when red blood cell recycling is impaired

Where does bilirubin deposit and what does it do?

Deposits in the skin and sclera and causes jaundice

What can bilirubin accumulation be from?

Liver failure bc the liver isn't processing the hemoglobin or from immature liver in premies

Where is the first place you would see jaundice?

Slcera

What do both bilirubin and hemosiderin have to do with?

Iron component in the blood

What is urate?

Or uric acid, the end product of purine metabolism

What happens with urate accumulation?

Excess amounts can crystallize and deposit in joints causing inflammation known as gout

What happens with the accumulation of environmental substances?

Causes injury with the lungs and skin being particularly susceptible to harm

What is an example of how the lungs can be affected by environment?

Black lung

What is an example of the skin being affected by the environment?

Excessive external moisture makes the skin vulnerable (macerated skin) which is why it is important to keep the patient's skin dry

Physical injury may be what?

Intentional or accidental

What do all physical injury involve?

An external mechanical force such as trauma or surgery

How is the extent of an injury determined by?

The number of cells that are irreversibly damaged or potentially injured with that insult

What are the mechanical forces?

Crush injury and GSW

Blunt/sharp force injuries

Laceration/incision

Stab/puncture

Contusion/hematoma

Abrasion

Avulsion

Friction/shearing

What is a laceration?

A cut or tear in the skin commonly considered to be accidental (non intentional)

What is an incision?

A cut longer than it is deep and most commonly thought of as intentional such as a surgical incision

What is a stab wound?

Deeper than it is wide

If there is a stab wound what should you do?

Leave the object in there

What is a puncture wound?

Comes from a pointed object or bite

What is an example of a puncture wound?

Fish hook or bite

What is a contusion?

Bruising injury with intact skin

What is a hematoma?

Injury involving significant blood vessel injury

How are contusions and hematomas different?

Contusion is a bruise and doesn't have as much blood vessel damage. A hematoma needs to be marked to make sure it doesn't keep growing because it can keep bleeding inside

What is an abrasion?

A scarred area of skin

What is an example of an abrasion?

A rug burn or road rash

What is an avulsion?

A term reserved for injury involving a large detachment of tissue

Why shouldn't you wear earrings in clinical?

So you don't have an avulsed earlobe from someone tearing your earring

What is a friction/shearing injury

Occurs when tissue layers slide in opposing directions, skin tear

What is the reason we use a draw sheet?

So we don't get a friction/shearing injury on the back

Who are susceptible to friction/shearing injuries?

The elderly because their skin is so frail

What are the types of thermal injuries?

Temperature extremes, radiation and electrical

What are temperature extreme injuries?

Heat stroke all the way to frostbite

How can temperature extreme injuries lead to hypoxia injury?

Cold initiates vasoconstriction so it reduces blood flow and this causes an increase risk of hypoxia injury which can even lead to frostbite

What do radiation injuries include?

Both ultraviolet and ionizing

What do both types of radiation cause?

DNA damage and this is why sun or radiation exposure is often a precursor to cancer

Why do we use radiation to treat cancer?

We can point the beams right at a tumor and it destroys those cells

What are electrical injuries?

Extensive tissue damage at the entry and the exit, but along the route you can also get extensive internal injuries and many patients that are electrocuted and survive have permanent cardiac arrhythmias because the heart is linked to electrical activity

Where do chemical injuries come from?

Outside exposure

What are other things that can cause chemical injury?

Imbalances of exogenous things like electrolytes

Exogenous chemicals can injure cells with examples being

Lead

Arsenic

Carbon monoxide

Mercury

Alcohol

Drugs

Is lead toxicity potentially lethal?

Yes

What does lead toxicity do?

The body can't remove lead and it affects the shape and function of oxygen carrying red blood cells (so it would affect hypoxia)

What does lead toxicity uniquely do?

Causes a blue line along the gums

What negatively affects RBCs

Lead toxicity

What test can they perform if they suspect lead toxicity?

A specific stain of RBCs and it will show blue dots on the inside of the erythrocyte if there is toxicity (linked to hypoxia injury bc it involves erythrocytes)

What is arsenic?

Naturally occurring substance as rock is broken down but we have additional amounts being introduced into our water supply due to industrial agricultural ways

What does arsenic cause?

GI issues but uniquely causes hyperpigmentation of the hands and the soles of the feet

What will carbon monoxide ultimately lead to?

Hypoxic injury because the carbon monoxide is occupying the RBC instead of the oxygen

Where is the carbon monoxide risk greatest?

Poorly ventilated garages or homes

What is the unique post mortem feature of carbon monoxide poisoning?

Cherry blossom pink skin from head to toe