Metin, Metin, Metin… He is only 13 but he is much more restless and willful than his peers. He tampers with every tool he can find, tries to repair everything and he is usually not successful. After 5 electric shocks in the last 2 months, thank god he lost interest in electricity and sockets.

His new hobby is arts. Well, at least he thinks so. His sharp craft knife that he bought for school is about to cut his deep interest in arts into two within minutes. And his left thumb will also get its share from this sharpness as well as his interest in arts. Finally, Metin will again meet an old friend he calls “Scab” in two weeks.
What is going to happen until this encounter? How will the excellent repair system inside Metin close this wound? How will his lowered defense system protect itself? Let’s have a look inside.
That moment
Let’s rewind a little bit and go back to that unfortunate moment. We see that the sharp end of the craft knife disengages from the cardboard and heads towards its next target, Metin’s unlucky thumb, without slowing down.
First stop Epidermis
In this inevitable encounter, the uppermost layer of Metin’s skin, epidermis, greets the craft knife. The uppermost side of this layer is formed by a layer called Stratum Corneum, made up of dead cells. Right beneath, lie the living cells that have important functions.
A majority of the cells in epidermis are spun with a thin protein network. The main ingredient of this protein network is keratin. Keratin is actually the name for a group of proteins having a fiber structure. Since it lies along the cell in the form of a fiber, it sort of serves as a cellular cement. Keratin provides structural integrity to cells. Indeed, the main reason behind the strength of Metin’s hair and nails is the keratin protein family. Epidermis is 90 % constituted by cells called keratinocytes that are vastly rich in keratin.
As in all the other people, Metin’s epidermis is also continuously in motion. While new cells form under dead skin, old cells are pushed towards the outer surface of the skin in approximately 28 days. While they are being pushed out, they die because they move further from the blood vessels below and they take physical impacts. Finally, dead cells leave the skin. This motion is so effective that Metin loses 30.000-40.000 cells each minute only from his skin.
• Source: Wikimedia
Dead and living cells constituting epidermis are arranged like a puzzle without gaps in between them. In addition, cells are firmly attached to each other by intercellular links called desmosomes. Due to all these properties, Metin’s skin is highly waterproof. This way, excessive water loss from the body is prevented. If this were a 1 mm layer, Metin would lose a significant amount of water and lose his life within a very short time.
Although this firm layer can prevent pathogens and water from entering the body, there is not much it can do against a sharp craft knife coming at full speed. The knife can easily cut through this 1 mm thick outer shield. Indeed, it does. For now, Metin isn’t aware of this accident since the knife didn’t reach free nerve ends right below the epidermis yet. However, he will know soon. So the knife moves on and there is a wide neural network waiting for it right below the epidermis. Somebody will get hurt.
There is no pain, it is in your brain! You bet! 
While the knife moves destroying the tissues and cells on its way, molecules that are normally inside the cell (for example ATP performing cellular energy transfer) start to leak and spread outside the cell. These spreading cellular and molecular corpses are sensed by the free nerve endings in the area and nociceptors understand that there is damage. Similarly, the tension occurring in the cut area start signal transmission in nerve endings. A series of events that will make Metin start crying using his diaphragm to its fullest extent within 1-2 minutes start as of now. Pain signal is started now.
Nerve impulses reach the brain via the spinal cord. Since fast transmission of pain is very important for the brain to take necessary precautions, neurons called A delta neural fiber transmitting the impulse very rapidly are employed on this path. Indeed the neural impulse starting on the finger will be transmitted to Metin’s brain within one tenth of a second.
Although one tenth of a second seems like a short time, it is actually a long time for preventing possible damages. In addition, it will take half a second or one second until the signal reaches brain, reaches related areas, is processed there, becomes meaningful and finally a damage preventing motion is decided. Luckily, Metin’s body can skip all this bureaucracy in the brain and use initiative in such conditions as follows;
Pain signals from the finger (or all other signals) enter the central nervous system through the back door of the spinal cord, the dorsal root. Here, signals split into two; some move towards the brain and others are converted into motion right at that moment on the spinal cord without waiting for the response from the brain. The signal that will make Metin to pull his left hand back goes out from the front door of the spinal cord, the ventral root, and starts travelling to move the muscles in Metin’s left arm. This shortcut, where the bureaucracy in the brain is skipped, is called reflex.
Although spinal cord has already decided to move the left arm back, Metin has to know about this cut. Because, memories and fears that will render him more careful while using the craft knife in his future should be formed.
Signals that will transfer this information to the brain are carried through the spinal cord. The first stop of the pain due to the cut is the thalamus in the brain. This small structure in the size of a half egg in the middle of the brain is the area where all signals from sensory organs (except for smell) are collected before they are distributed. It is sort of a central station.

Sensory signals that come here are directed to the relevant area by thalamus. These areas are various zones that process arriving signals and render them meaningful in the cortex of the brain. For example, data from eyes are sent to the primary visual cortex at the back of the brain and they are rendered meaningful and processed there.

Pain signals from Metin’s left hand, on the other hand, are directed to another area called the primary somatosensory cortex after passing thalamus (somato: body; sensor: sensing element). After somatosensory cortex decodes arriving signals, Metin’s brain is now aware a.) That there is a damage, b.) the damage is on his left thumb, and c.) He shouldn’t do anything (like pulling his hand back). At this point, things get a lot messier. Recent studies show that signals arriving at thalamus are spread to many different cortexes and even to the limbic system, which is responsible for emotions and memories. These studies indicate that these sorts of environmental damages create unforgettable memories and prevent potential accidents.
We spend too much time in the nervous system. While all these are going on in the brain and reflex signals are moving towards Metin’s left arm, our knife also continues its long way. At this point, we leave behind epidermis, which is very poor in terms of blood vessels. Now we see a growing and extending blood vessel network and some other tissues. The craft knife is now in dermis.
While craft knife moves destroying the tissues, we see that fibers too small to be seen with bare eyes touch its sharp end. These fibers are so intense that the speed of the craft knife, which did not drop until now, begins to decrease.

This tissue called dermis lying just beneath epidermis is made up of very strong protein fibers called collagens. It is possible to find collagen in almost every tissue of Metin from his cornea to his tendons. Indeed, collagens constitute 25-30 % of all the proteins in his body. However, although collagens provide physical resistance, they are not very elastic. At this point we see the fibers called elastin that provide elasticity of the skin.


Elastin and Collagen Fibers. Source:
While the speed of the craft knife in decreasing, first encounter with a blood vessel takes place. We are lucky since dermis only contains capillaries. These capillaries both feed the cells in the epidermis above and enable Metin to preserve his body temperature.

The tissue surrounding these capillaries is a layer as thin as just a cell. In other words, it is enough to crush a group of cells to make a hole on the vein’s surface. Being 10 times thinner than a single strand of hair, these veins cannot show much resistance to the knife. While the knife moves on, it wrecks the capillaries in front of it. Since the flow rate is significantly low in the veins, Metin’s blood starts to leak out instead of gushing out. The knife has already destroyed almost 100 capillaries on its way.

At this point, the knife reaches the end of dermis, which is 2 mm thick, and starts moving towards connective tissues located deeper. If Metin’s reflex impulses reach his left arm a bit more later, larger veins below the dermis will also have their share of the knife.

Thank God, the neural impulses sent by the spinal cord reach the muscles in the arm. While his left arm is pulled back, the knife that has already gone 4 mm deep leaves Metin’s skin.

When the knife leaves, Metin has a 1 cm long and 4mm deep wound, destroyed skin tissues, free nerve endings sending signals rapidly and tens of ruined capillaries left. He has nothing to do but cry. However, the things his body is supposed to do are starting just now.

Metin is a willful child, who is only 13 years old. He cut his thumb that he bought because of his interest in arts. This knife cut Metin’s epidermis and dermis; it destroyed many capillaries and tissues on its way. Although bigger damages were avoided thanks to Metin’s reflex, the wound is already there and the work of Metin’s body is starting now.

First order: reestablish balance!
The crisis desk that was formed after Metin’s body was damaged immediately puts a protection-repair plan, made up of many steps, into action. These steps should be realized as soon as possible; because many things need to be accomplished in a very short time…
The first step in repairing damaged tissue starts with reestablishing the balance in the area of crisis. Although Metin doesn’t even know the word “Homeostasis”, his body knows what this term means very well. Homeostasis, in other words the tendency of cells (or a tissue) to protect or reestablish their own order against environmental incidents, is one of the important steps for closing the wound.
However, there is a big obstacle in the way of establishing this balance. Blood leaking out from destroyed blood vessels… Although the leak doesn’t seem to be much, nearly 5 million red blood cells and 10 thousand white blood cells leak out each second. This loss has to be stopped somehow.

Cover the Leaks!
To stop a bleeding in the damaged area, a protein group called Collagens has an important duty. It is possible to find the proteins called collagens in almost every area of Metin’s body. Indeed, the craft knife met collagens while it was cutting through his dermis. These proteins provide structural integrity by functioning as a steel cord in tissues.
Under normal conditions, collagens inside the tissues don’t ever contact the blood circulating through blood vessels until those vessels are torn and the blood starts leaking out, i.e. into the tissues.

Different types of collagen fibers
When the cells called thrombocytes in the blood contact collagen proteins, it means something is wrong. We hear thrombocytes touching collagens say: “Hold on, where did this collagen come from? So, I am not inside a blood vessel anymore. There is a leak. I need to stop it.” These cells hold on tight to the collagen protein they contact. All thrombocytes in the damaged area attach to collagens in similar ways and they form a cluster. However, this cluster is not enough. It has already been 5 minutes since the wound was opened and the leak is still going on. Now we should play better cards to stop this leak: Fibrinogens… Fibrinogens are a big group of proteins that constitute almost 5% of blood plasma. These proteins are normally dissolved in the blood and when they arrive at a damaged area, they are converted to other proteins called fibrins by the aid of environmental stimulations. Fibrin does not dissolve in blood and it covers the damaged area like a net. So that the foundations of the scab, which Metin will try to remove all the time in the coming days, are laid.
Red blood cells held by the fibrin net

It has been 10 minutes since the wound was formed. The leaks are almost stopped. At this point, molecules such as thromboxane and prostaglandin that come out from destroyed cells during wound formation make the blood vessels in that area constrict. Therefore, blood flow in the damaged area is reduced. Blood leaks stop significantly in the 15th minute. And finally so does Metin’s crying…
Scene Investigation
Although constricted blood vessels reduce the bleeding, Metin has a more important problem now: Infection.
The craft knife that Metin accidentally cut his thumb with has fallen on the street, schoolyard and the bathroom several times since it was bought. Now it has many different types of microorganisms and spores on it. Normally, Metin’s skin provides an excellent defense against these microorganisms but the craft knife created a big back door for microbes. Now these microorganisms can pass all defense layers and enter sensitive areas directly. Metin’s body has to do something immediately.
One of the most important members in Metin’s defense system, Neutrophils are about to arrive at the scene. However, flow is very limited since the blood vessels in the area are constricted. Once the leaks are stopped (as of the 20th minute), thrombocytes start to secrete the chemical called Histamine. This molecule dilates the constricted blood vessels. This way, blood flow to the area starts to increase. Reason behind the redness around Metin’s wound is the increased blood flow due to dilated blood vessels.
Metin realizes that the area around his wound is slightly swollen besides the redness. The reason of this swelling is also histamine. That’s because this chemical also increases vein permeability. The increased permeability makes it easier for defense cells to leave circulation and enter damaged tissue. However it also makes some of the water in blood to enter the tissues and the area around the wound becomes slightly swollen.
Defense System is at the Scene!
It has been almost an hour since the wound was formed. Defense cells are starting to take their place in the tissue by the aid of dilated blood vessels. Once the walls of the body (epidermis) have fallen, the most important defense line becomes neutrophils. These cells will have an active role in the damaged area for the next 2 days. They have so much to do. Neutrophils will be working for disintegrating and destroying the dead tissue in the damaged area, eradicating foreign bacteria in the area and removing dead bacteria from the medium for the next two days. When they achieve their mission, they will end their lives by killing themselves. Maybe, Metin will never know the sacrifice of these cells.

Bacteria consumed by neutrophil

It has been 2 days since the wound was formed. Now, neutrophils’ duty is taken over by another cell group called macrophage. These cells coming from the spleen are very insatiate. They consume and digest any kind of foreign tissue no matter dead, alive or bacteria. Macrophages also digest the clot residues around blood vessels and help restore the blood flow in the damaged area. Besides their defense duty, macrophages also secrete growth factors and thus, draw some cells responsible for repair and renewal to the wound area.

Blood Vessels Rising From the Ashes

In the coming days, the deeper and upper parts of the wound will be repaired and closed. However, this process needs a high amount of oxygen, energy and raw materials. A majority of blood vessels, which are the only way to carry these necessary materials, are in a destroyed and cut state. New vascular routes should be established in the damaged area as a first step of the repair.
It has been 3 days since Metin cut his thumb. The leaks were stopped during this process. Possible infections were prevented before they start. Now it is time to do repairs. The repair process starts with fibroblasts arriving at the damaged area. These cells trigger the undamaged blood vessels in the vicinity to form new blood vessels and grow bra nches. Blood vessels in the vicinity form extensions to the areas that need oxygen. In this process, they follow the signals from the scab and damaged tissue. During this process, when blood vessel formation called angiogenesis is increased, Metin’s wound acquires a red-pink color. When oxygen levels in the damaged area reach normal values, blood vessel formation is stopped.

Installation of the Framework
While the blood vessels are forming, active repair process also starts. It has been exactly 1 week since the wound was formed. Now, most of the cells in the damaged area are fibroblasts. These cells are very mobile. They move between two walls of the wound and they form a net of fibrin molecules just like a spider’s web. Although this net helps prevent the weakened damaged area from reopening, it still isn’t enough. There have to be stronger proteins to keep the wound stable: Collagens…
After a while fibroblasts start forming collagen proteins in the damaged area. These proteins will also provide a surface for newly formed cells to adhere while the wound is closing. Repair will be performed on a framework of fibroblast cells inside the wound.
Don’t go near the construction site!
Now, the underside of the scab is completely filled with fiber-like structures and newly formed blood vessels. This scab will fall soon and until then these blood vessels need to be covered with epithelial tissue. During this process, a very familiar group of cells start working… Keratinocytes. They were the first group of epithelial cells that were cut by the knife in the beginning. Now these cells are going back to the area they retreated from. A big keratinocyte migration begins.
The layer rich in terms of fibers and blood vessels in the deeper part of the wound

Keratinocytes migrate from the healthy areas right next to the wound to the area of the cut, right onto the fiber-like structure and under the scab. These cells change shape during migration and become wider and thinner. Their purpose is to cover a larger area with fewer cells. While the wound is closing, another migration wave covers the previous one. Therefore, the wound area is covered layer by layer. As keratinocytes cover the wound, the tissues connecting the scab to the fiber-like structure right below it are separated from each other. These cells also destroy the scab on their way. Metin will soon pull out this scab, which is already moving out of its place.

Until now, the wound is covered only by the migrations from surrounding areas. There is no cell division on the wound. Once the wound is completely healed, this area will experience normal divisions.

Keratinocytes migrating from surrounding areas meet in the center of the wound and that’s when the migration ends. Metin’s wound is finally covered.

A wound is closing!

Craft knife had opened a 5 mm wide wound on Metin’s hand. Although this wound is covered, this kind of width is unacceptable. The wound area should shrink and the cut area should get smaller.

Fibroblasts start working again to bring the two walls of the wound closer. After the wound is closed, these cells turn into another cell like a muscle cell called myofibroblasts. These cells, that can contract and protract like muscle cells and that can also migrate, hold on to the walls facing each other inside the wound or to the fiber-like nets. After they hold on, all myofibroblasts contract and pull two walls of the wound together. In this process, Metin’s wound gets 0.75 mm less wider everyday. When the wound is in normal size, these cells kill themselves and leave the environment.

Maturation Period
It has been 10 days since Metin cut his thumb. The scab fell and his wound is closed. Although Metin doesn’t see it, his body still keeps working inside. Collagen fibers that are rapidly and randomly spread in the wound leave their place to more orderly arranged fibers. Physical resistance of the wound increases as fibers are formed in order. Within 3 months, wound area will reach 50% of the resistance exhibited by other tissues. Within a few years, they will reach 80% of the resistance exhibited by healthy skin.

The End
The 10 day adventure of Metin’s thumb ends here. This repair process explained rather simply took place completely independent from Metin’s awareness. Metin’s body achieved an excellent crisis management on an area of 1 cm, while Metin goes to school, sleeps and watches television. A problem starting with clumsiness was overcome smoothly. Similar repair processes will be repeated hundreds of times, also in Metin’s body and your body. All these are for you to continue your life. Take good care of your body because it takes good care of you.

Wikipedia/Wound Healing:
MedScape/Wound: of Wound Healing:
Tissue Regeneration: