WHEN CELLS WORK MORE

Cells can function through two different ways: 

• PERTROPHY: the functionality of a tissue or organ may increase because individual cells increase in volume but do not increase in number
• HYPERPLASIA: the function of a tissue or organ may increase because cells increase in number

What types of cells can become hypertrophic in our bodies? 

All types of cells since, hypertrophy, is a condition that does not assume the maintenance in differentiated cells of the ability to proliferate. This adaptation does not imply that cells are still capable of proliferating once they have reached the full degree of differentiation. 

Instead, only cells that, even when differentiated, retain the ability to proliferate (labile cells and stable cells) can become hyperplastic.

In this regard there is a classification made by dr. Bizzozzero who subdivided the cells into: 

• labile
• stable
• perennial

We talked about hypertrophy and hyperplasia as responses to an increased functional demand, it goes without saying that, depending on the type of cell, there are situations in which a stimulus can induce both hypertrophy and hyperplasia. 

HYPERTHROPHY 

In hypertrophy the cells increase their functionality by increasing in volume and there is no production of new cells. We speak of "true" hypertrophy only when the increase in cell volume and, consequently, of the tissue and organ, increases because the living matter increases. So a cell is hypertrophic because the volume has increased but as a result of functioning organic matter (such as cellular organelles). We do not speak of hypertrophy if the volume of a cell increases due to the increase of substances other than living matter. With regard to a tissue or organ, one does not speak of hypertrophy if it has a greater volume because it has become infilled with blood. It is not even called hypertrophy if the cells are filled with a material that does not increase the functionality of the cell itself. 

Glycogenosis is a pathology caused by an accumulation of glycogen in the cell for a variety of reasons, this accumulation does not increase the functionality, on the contrary, it tends to decrease it. 

So hypertrophy means an increase in volume due to an increase in living matter, that is an increase in the functional components of the cell. 

What happens to cells that become hypertrophic?

They increase the production of proteins that are specific to how they function. For example, striated muscle cells that become hypertrophic will increase their production of actin and myosin, which are histotype-specific proteins. 

What is the mechanism that leads to increased production of these specific proteins?

It increases gene expression by increasing transcription factors or it can be achieved by increasing the translation efficiency of the corresponding mRNA. 

Thus in hypertrophy the cells prioritize the production of proteins that serve the specific response and, at the same time, degrade the proteins that do not contribute to the necessary response because through these they regain the amino acids that they will use for the synthesis of the specific proteins needed to activate the response. 

These are the changes that occur in all cell types that become hypertrophic. 

There are also changes that contribute to hypertrophy but they are either cell-specific or tissue-specific. In general some tissues may respond to increased functional demand by decreasing what is death by apoptosis. In one very specific tissue, namely skeletal muscle, hypertrophy also causes recruitment of satellite cells (i.e., new cells).

PHYSIOLOGICAL HYPERTROPHY

An increased functional demand on a cell can be achieved through increased stimulation. The stimulation can be hormonal and in this case the organs involved are: 

• Uterus, Mammary Gland and Thyroid, during pregnancy
• Sexual organs during puberty
• Endometrium during the early stages of the menstrual cycle to create the optimal condition for an eventual implantation of a fertilized egg.

A condition of physiological hypertrophy can be brought on by stimulation that can increase the workload: 

• Striated and cardiac muscle tissue in athletes

PATHOLOGICAL HYPERTROPHY

The causes are the same as those of physiological hypertrophy but the context in which they take place changes. 

Pathological hypertrophy: increased hormonal stimulation

• Onset of Goiter: is an enlargement of the thyroid due to hypertrophy and hyperplasia on the basis of a pathological stimulus. Why iodine deficiency can cause pathological hypertrophy at the level of the thyroid?  From a metabolic point of view thyroid hormones contain iodine (or 3 or 4 atoms), under physiological conditions, when the amount of iodine intake is normal, the thyroid synthesizes thyroid hormones, pours them into the circulation (through which they go to stimulate the target districts) and these also exert a negative feedback control on the synthesis of TSH. So if thyroid hormones are in your bloodstream, the amount of TSH produced will be decreased. If the correct amount of iodine is not taken, thyroid cells will not release T3 and T4 into the circulation and therefore, in addition to the lack of biological effect of these hormones, the control on TSH production will be lacking: TSH production will increase and will stimulate thyrocytes that will become hypertrophic (as a result of increased hormonal stimulation) but it will be a pathological hypertrophy because the amount of TSH produced is abnormal. 
• Neoplasm (tumor) that produces a certain hormone: there are tumors defined as hormone-secreting, i.e. their cells secrete hormones. If the number of tumor cells increases then the production of hormones produced by them will also increase and these will lead to pathological hypertrophy in the target cells.
• Anabolic substances: (substances that should not be used in the gym.) The final effect will be the same as physiological hypertrophy from workload: there will be a muscular hypertrophy, only that if you lift 50 kilos at a time will be physiological and in the case of the assumption of anabolic substances the muscles will have a pathological hypertrophy.

Pathological hypertrophy: an increased workload:

• Left ventricle in hypertensive subjects: because when we talk about hypertension z we refer to an increase in blood pressure due to an increase in peripheral resistances. Peripheral resistance refers to an increase in the obstruction to blood flow in peripheral vessels. In a hypertensive subject and at the level of peripheral vessels there is an obstacle to blood flow and this condition means that the heart must work harder (increases the workload) and the potion that is most affected by having to carry this load is the left ventricle. In this case there is a pathological hypertrophy limited to a portion of the heart. 
• Heart valve defects: may affect only one portion of the heart. In a heart valve that is not functioning properly and is an obstacle to the passage of blood, the entire upstream portion of the heart muscle will become hypertrophied because it must work harder to overcome this obstacle.
• Big beer drinkers: there is a situation in which the whole heart becomes hypertrophic. This pathological situation is caused by an increase in blood volume and therefore concerns the volemia (the total blood content in the living organism.): having a greater volume of blood to move will become hypertrophic both the portion that must push the whole circulatory tree and the portion that receives a greater volume. Why does beer increase blood volume and not water? When we talk about "big beer drinkers" we mean individuals who drink 4/5 L of beer a day and water is not addictive unlike beer. Why is beer addictive and not super alcohols? Because no one will ever be able to drink such high quantities of super alcohols because other mechanisms will come into operation to block the excessive intake.
• Prolonged intake of drugs: all exogenous substances are metabolized at the hepatic level where there is the metabolism processing system is called DRAG metabolising system and is located at the level of REL, and exogenous substances are metabolized at the level of cytochromeB-450 in the smooth endoplasmic reticulum of hepatocytes. If I take drugs (e.g., barbiturates) for a prolonged period, they will stimulate the production of REL in order to be metabolized. Then the prolonged intake of drugs transformed at the level of REL determines pathological hypertrophy of hepatocytes that increase in volume because REL increases. A similar discourse occurs as a result of the assumption of other drugs: hypoepidemic drugs (decrease the levels of cholesterol and triglycerides in the blood). Until recently, drugs were used as hypoepidemic drugs that, in addition to their function in the blood, stimulated the production and activity of peroxisomes in hepatocytes. In the peroxisomes the beta-oxidation of fatty acids takes place. So if you take for a prolonged time these drugs (hypoepidemic or barbiturate) hepatocytes become hypertrophic because they increase peroxisomes or REL.
• Organ/tissue hypertrophy following partial or total resection. If you undergo, from a surgical point of view, the exportation of a section of the liver, you will have to replace functionally the hepatocytes that have been lost through the remaining ones that will become hypertrophic. Same goes for the kidney in the case of renal agenesis: with only one kidney you survive because the cells of the present kidney become hypertrophic, so they increase in volume to function more.

Hepatocytes are almost the only example of a stable cell: if differentiated, they do not proliferate. The percentage of proliferating hepatocytes in a normal adult liver is as low as 1%. But, in the event of hepatocyte loss, stable hepatocytes can reenter the cycle to replace the lost ones.

PHYSIOLOGICAL HYPERPLASIA

Physiologic hyperplasia: increased hormonal stimulation

• Uterus, Mammary Gland and Thyroid are stimulated more, on a hormonal basis, during pregnancy. They can become hypertrophic and even hyperplastic because they are made up of cells capable of proliferating 
• the same goes for the Endometrium during the first phases of the menstrual cycle: it becomes both hypertrophic and hyperplastic

Physiological hyperplasia: an increase in workload

• In a prolonged stay at high altitude the partial pressure of oxygen would be reduced and, therefore, in order to be able to have the necessary amount of oxygen, the number of red blood cells will have to be increased. To do this, the bone marrow will have to become hyperplastic. It also becomes hyperplastic when it must produce more erythrocytes because there has been either a hemorrhage or a phenomenon of hemolysis (loss of erythrocytes). The difference between "hemorrhage" and "hemolysis" is that the former is a loss of blood while the latter is a process of elimination of red blood cells. There are also hemolytic anemias in which I have an increase in what is the normal hemocateresis of erythrocytes and, therefore, this induces bone marrow hyperplasia.
• Epidermis during the healing process: if there has been an event of an injurious type / a wound the epidermis becomes hyperplastic because it must go to replace the elements that have been lost. 
• Lymphocytes during the immune response
• Granulocytes (especially neutrophils) during the inflammatory process

Physiological hyperplasia has the purpose of replacing lost cells (compensatory hyperplasia): 

• in the case of a partial removal of an organ, for example of a part of the liver or kidney. Or if a part of these have undergone cellular damage, the surviving cells can become hyperplastic because they are hepatocytes, i.e., stable cells and the kidney cells are also able to proliferate.

PATHOLOGICAL HYPERPLASIA

Increased abnormal hormonal stimulation: 

• the Endometrium: during the first phase of the menstrual cycle this becomes both hypertrophic and hyperplastic but, in the event that the nidation of the fertilized embryo does not occur, it will undergo remodeling. This physiological process, during the second phase of the menstrual cycle, is due to a change in the estrogen-progesterone ratio: this ratio decreases and the endometrium is remodeled. If, however, this ratio continues to be high, what was an induction of physiological hyperplasia shifts towards a situation of pathological hyperplasia and then there will be an inappropriate increase in the volume of the endometrium that will lead to a pathology: Adenomatous hyperplasia of the endometrium 
• at the level of the PROSTATE in adult men: Prostatic hyperplasia.

Persistent mechanical stress: 

• Example: "Where, when writing , does a thickening of the skin occur at the level of the finger where the pen rests?" Usually on the index, middle, or hand where the barbells are held. These conditions are pathological hyperplasias and have their cause in persistent abnormal mechanical stress. So Bunions and Durons are manifestations of pathological hyperplasia.