1. Adaptation

2. Injury

3. Cell Death

4. Aging

5. Neoplasia

1. Disuse- atrophy due to a decreased workload "use it or lose it" economy of biology. An example of this is an atrophied skeletal muscle of a broken arm that has been in a cast for awhile.

2. Blood Supply Decrease- atrophy due to no longer getting adequate blood supply to the area, causing your cells to adapt. An example is the thinning of skin and loss of hair growth in the foot resulting from poor blood circulation consequent of chronic heart failure.

3. Inadequate Nutrition- atrophy due to not having the essential nutrients to create proteins and fule the body and cells. An example of this would be the atrophy of the kidneys due to atherosclerosis.

4. Change in Hormonal Stimulation- atrophy due to some sort of change in hormones. This occurs through a negative feedback loop and an example of this is pregnancy and the use of anabolic steriods.

5. Loss of Innervation- atrophy due to the loss of innervation, which subsequently leads to the muscle cells going away with the nerve cells. An example of this would be atrophy of the muscle cells in a denervated leg muscle after a spinal cord injury

These cells would have an increased presence and size of lysosomes (autophagic vacules filled with lytic enzymes that break up molecules and connect with macrophages to get rid of garbage in the cells). These cells would also have shrunken functional components, and there would also be accumulations of unremovable byproducts (products that cannot be broken down by macrophages) such as:

• Lipofuscin, an oily remnant of fat breakdown that is pinkishy/yellow and found in some cells that are post-mitotic (why a 100 year old heart may look yellow)
• Myelin Figures- organelle membranes that resemble an onion and are partially digested proteins that just can't be broken down further
• Hemosiderin- observabe on the gross examination and the byproduct of etrythocyte turnover that results in a reddish-brown stain on the skin.

Intracellular accumulations are the response to atrophy that results in the production and accumulation of unremovable byproducts of the cell. These unremovable byproducts cannot be broken down by macrophages. Four different types of accumulations are:

1. Lipofuscin

2. Myelin Figures

3. Hemosiderin 

Hypertrophy is the increase in the functional components of the cell, but is not cellular swelling. The most common example of this is in skeletal muscles where, when lifting weights, your muscles begin to make more functional components causing your muscles to get larger. Hypertrophy is the increase in the size of the tissues or organs due to an enlargment of individual cells. Hypertrophy is also rarely pathologic, and actually thought to be a trait of normal physiology.

Hyperplasia, on the otherhand, is the increased size of tissues and organs caused by an increase in the number of cells (NOT AN INCREASE IN THEIR SIZE, LIKE HYPERTROPHY). Hyperplasia essentially means that cells are dividing faster than they are dying, leading to increased size of the organ or thickening of the tissue.

The four different types of hyperplasia are:

1. Compensatory Hyperplasia- hyperplasia in response to some sort of stimulation that causes the cell to divide. There are two types of compensatory hyperplasia- regenerative, which is the adaptive mechanism to a stimulus (think of alcoholics enlarged livers caused by the increased need for the liver to take care of the ETOH) and mechanical,  which is hyperplasia caused by continual mechanical stimulation resulting in the proliferation of cells (callous').

2. Hormonal-caused Hyperplasia- An increase in the number of cells caused by a hormone. An example of this is the hyperplasia of breast tissue and uterine tissue due to the hormones released by the pituitary.

3. Pathologic Hyperplasia- The abnormal proliferation (hyperplasia) of normal cells. This hyperlasia is different from a tumor because it involves normal cells. An example of this is a hemangioma, or the proliferation of capillaries near the skin surface resulting in a large red colored spot on the skin.

4. Atypical Hyperplasia- also known as dysplasia, the proliferation of abnormal cells, size, shape, organization of mature cells. Not quite an adaptive change, but not cancer either. An example of this would be found during a Pap smear or cervical scrap (dx with atypical dysplasia).

The three mechanisms through which infectious agents cause cell injury are:

1. Direct Destruction- The infectious agent directly destroys the cell/parts of the cell. An example of this is with a strept infection, which invades the epithelium of the pharynx, turning it to mush.

2. Release of Toxins- The infectious agent causes toxins to be released when they are in the right conditions. An example of this would be clostridium tetani, which releases a neurotoxin when in the right concentration of oxygen, and stimulates the neurotransmitter- ACH- to be released resulting in uncontrolled muscle contractions

3. Hypersensitivity to Invader- cellular injury occurs when the infectious agent causes the immune system to go into overdrive trying to protect the body, which in turn damages the cells. An example of this is tuberculosis, which the bacterium isn't so bad, but the hypersensitivity of your body to it causes a reaction which damages the cells. 

1. Hypoxia

2. Chemicals/Toxins

3. Infectious Agents

4. Immune Response

5. Nutritional Imbalances

6. Physical Agents

You have an overwhelming dose

The virus is particularly virulent

You have decreased defenses

1. Temperature Extremes

2. Pressure changes

3. Ionizing Radiation

4. Mechanical Factors

When explosions occur, we are introduced to a wave of high pressure followed by a wave of low pressure. This rapid compression to expansion causes tissue tearing. Since we're mostly liquid, we don't worry too much since the water acts as a cushion. However, one area that we worry about are the lungs and external tissue such as the ear drum. The effects on the lungs can lead to a massive pulmonary bleed due to alveolar destruction. 

In the case of scuba diving, we can compress gasses, but not liquid. As you dive, the gasses get squeezed into your blood, which is why you have to come up very slowly. If you go up too fast, the bubbles effervese and the gasses shoot right out. These bubbles don't squish through the capillaries and actually act to block them... leading to major tissue anoxia. 

Caisson disease

1. Starvation- when you're body needs energy, it breaks down fat first. However since you're malnourished, your body doesn't have the enzymes to break down fats. So, these fats begin to accumulate, leading to enlargement of whatever tissue it is. One that we specifically talked about was the enlargment of the liver, which is where you break down fat.

2. Genetic Disease- there are a variety of genetic diseases that can lead to an abnormal storage of lipids.

3. Toxins- ethyl alcohol...

1. Dystrophic calcification- the calcium of dead or dying cells is released and allowed to accumulate.  (atherosclerosis?) This types of calcification is patchy and diffuse.

2. Medistatic Calcificaiton- this is the calcification that takes place everywhere, or widespread calcification. This means there is greater than the therapeutic level of calcium in the blood, most of the time due to a hormonal irregularity/imbalance. 

Besides the tissue changes (autolysis and immune response, there are three different nuclear changes that can take place. (Immune responses occur when the body can't recognize the tissue due to the cell death that's occurred. The body tries to respond by trying to remove the dead cells). 

1. Presence of pyknotic nuclei- the cell begins to appear dense due to nuclear clumping. With the increased dumping, there is increased acid... a process called "Pyknosis". 

2. Nuclear Membrane falls apart- karolysis, the nuclear membrane begins to dissolve because of the increased acid created during pyknosis.

3. The organelles disappear and begin to dissolve- this may happen because of pyknosis and karyolysis. The cell begins to look more like a prokaryote and is uniformly granular inside is a process called karyorrhexis. 

1. Coagulative Necrosis- the proteins are denatured, but maintain the structure/architecture of that organ. So, even though the proteins shrivel, we can still tell what the tissue is. An example of this is in the necrosis that follows a myocardial infarction. 

2. Liquifactive Necrosis- this type of necrosis happens where there are areas with a lot of hydrolytic enzymes... which are released during the cell death and cause the lead to a rapid dissolution/liquifaction. A capsule forms around this area of injury, causing it to become encapsulated. An example of this is with glial scars in the brain or sebaceous cysts which can result from a bacterial invasion

3. Caseous Necrosis- this type of necrosis deals with the "chunking" and liquifaction. The chunks are a mixture of necrotic material. An example of this is what's found in the lungs with a tuberculosis infection

4. Fat Necrosis- necrosis that is represented by white granular stuff (soap) in the abdominal cavity. An example of this is with pancreatic cancer, which secretes the digestive enzyme, lipase. In the presense of the base, NaHCO3, the lipases cleave off and form sodium salts in the process of saponification

1. Algor Mortis- (algor=cold) is the decrease in body temperatures that occur after death. In the standard sense, it's how long it takes your body to come down to ambient (room) temperature. This usually takes 24 hours (depends case to case). It is usually tested with a meat thermometer to the liver.

2. Livor Mortis- (black and blue spots) is bruising, but not in the typical sense. It's the settling of blood into the dependent (areas of highest gravity) areas... so it all depends on the position. This occurs because the usually elastic arteries begin to relax after somatic death and the blood begins to settle in the veins. This can occur within an hour.

3. Rigor Mortis- (stiffness of death) has to do with muscle contraction due to the neuron causing depolarization across the muscle, effecting the permeability of the sarcoplasmic reticulum and stimulating the release of calcium without the release of  ATP (which is not produced in death).  the membranes disintigrate, which is why the sarcoplasmic reticulum are so permeable, and also causes them to leak calcium. Because of this, the myosin cross bridges attach with the actin and there is a change in the configuration, caused by the pull on the actin. However, because ATP is not produced, the actin will never be released and the muscles will never relax. It takes rigot mortis about 12 hours to complete and occurs in the smallest muscles first. 

4. Postmortem Autolysis- dissolution of the cells caused by lysosomal enzymes, which digest the cells. The return of the body to faccidity, usually about 24 hours (after rigor mortis)

Intracellular fluid contributes to about 40% of a persons body weight and is only the fluid found within the cell. 

Extracellular fluid takes up two different compartments, the interstitial fluid (ISF), which is fluid around tissues and surrrounds our cells, contributing to about 15% of our body weight) The second compartment of ECF is the intravascular fluid (IVF), which is fluid inside the vessels and makes up about 5% of our body weight (plasma fluid..pure water, but not the other parts).

Intracellular Fluid- 40% body weight

Extracellular- 20% total- 15% in interstitial fluids, 5% in intravascular fluids.

That means that about 60% of our body weight is water. We do store other water in lymph, cerebrospinal fluid, synovial, ocular, and bile compartments.