Environmental Toxicology Diary

We are going to move to a bit complexed subject. We have learned toxicology and epidemiology study, the characteristics and the comparison between them. Now it is time to discuss about the inside process of how toxic chemicals enter the body. When the toxic chemicals enter the body via absorption, the process of distribution, metabolism and elimination begin. So the entry of the substances into the cells inside our body is the main point here, and the absorption plays a very crucial element.

Substances may enter body via inhalation, ingestion and dermal (skin) contact. There is an addition which is injection, but this is common only in a laboratory. At this time, I will not discuss the routes of exposure instead the process how substances can enter our body. It is always a good point to learn the basic properties and functions of our body. When substances try to penetrate our protector which is skin, it involves a variety filters before it get succeed to enter our inside cells.

Cell Structure

Our cells are mainly composed of phospholipids (around 75%), proteins (20%) and carbohydrates (5%). Phospholipids comprise of two parallel layers, these layers are main gates of our body and chemicals or substances are transported through these layers depend on their lipid solubility which will be describe below. Let us not forget proteins. Proteins appear “float” on the phospholipid layers either single or pairly. Proteins may form a “protein channel” (carrier molecules) composed of two sided proteins attached at both sides of phospholipid layers. This channel can also act as a path for substances to enter our body and released at inside cell membranes. Depends on the water solubility of the substances, some substances may be transported readily through this channel. These components form our cell membrane and act as a guard of our body because it has a selective permeability for substances that try to go inside our cells.

Cell Membrane Permeability

Not all substances can be absorbed readily by our cells. At least they must pass 4 filters before they successfully pass through the layers.

First, the molecule size of substances. Large molecules may difficult to sneak in between phospholipid layers of the cell membranes.

Second, the molecular charge. Of course if the molecule’s charge is negative and the cell’s charge is also negative, the cells will repel this substances, vice versa.

Third, remember that 75% of cell membranes are composed of phospholipid layers, so lipid soluble chemicals such as ethanol is absorbed readily by cells lining the stomach and the intestine. The same way of Xylene, readily absorbed by skin because it is lipid solubility chemicals.

Fourth, the carrier molecules. Special molecules can attract and transport a substance accross the cell membrane regardless of lipid solubility, electrical charge or molecular size.

Fifth, the arrangement of the cells in the tissue. The cells lining on the lungs, digestive tract, blood vessels, exterior surface of organs as well as cells compose the outer layer of cells are called epithelial cells. There is a composition when only a single layer epithelial cells lining on the organs such as lungs and a portion of digestive tract, and there is also two layer of epithelial cells are formed especially in skin and another part of digestive part. Absorption will of course become easier for absorption with only a single epithelial cells is present. The intercellular space between cells also affect the rate of absorption. Little of no intercellular space will decrease or inhibit the absorption process.

Endoplasmic Reticulum

Endoplasmic reticulum is a membranous system within the cells for intracellular transportation, storage and secretion of molecules. Regarding of secretion of molecules I have not found the details about what is secreted by the molecules. Endoplasmic reticulum is associated with other system ribosomes that has function to synthesize enzyme.

Mitochondria

Another important system is mitochondria. You most probably already know that there are two shape of mitochondria, spherical shape and rod-shape.

Spherical shape:

Rod-shape:

As you can see there are two layers of membranes, but the inner one is the most important membrane. Why? it is because the all chemical reactions are actually taken place on inner membranes. It is a place to produce energy as a form of Adenosine Triphosphate (ATP). The energy is important to maintain the function of other systems for molecules transportation and protein synthesis by ribosomes.

Transport Mechanisms

So we know why our cell structure is selective permeable. There are four factors affecting substances to be transported accross the cells, they are molecule size, electrical charge, lipid solubility and the last carrier molecule. Substances that are going to be carried in to our cells are delivered by two major mechanisms, active and passive transport. Since the cell cannot distinguish which substance is bad and which one is good boy, so all substances work these two ways, either by active or passive transport. I am going to explain passive transport first as this is major mechanism used on the transportation of a substance.

Passive Transport

Passive transport does not require the expenditure of energy. This mechanism relies on equilibrium process, in this case concentration gradiet. Passive transport is divided into three method: diffusion, osmosis and facilitated diffusion.

Diffusion is the transportation of molecules from higher concentration fraction to lower concentration part inside the cell without the need to spend energy. The principle is simple, the molecule will move from more molecule (higher concentration) to the area having less molecule (lower concentration). The movement is random and constant until the molecule is balance when the net movement of molecule is zero. The net movement here is the resultant of the movement of molecule up and down, means the number of molecules move to a certain area is equal with molecules move to the opposite direction. In this case, the the equilibrium is reached and no diffusion is occured. Simple example is our respiratory system. When we breathe, we inhale oxygen, passing lungs and when oxygen in the bloodstream is less than in the lungs, then oxygen will be absorbed. On the opposite, when the carbon dioxide in the bloodstrem is more than in the lungs, then carbon dioxide will be transported to the lungs for exhaling. Carbon monoxide and diethyl eter are absorbed into our bloodstream as a result of diffusion.

Osmosis is similar with diffusion. The only different, the movement is conducted by water (solvent) with the present of selectively membrane permeable. As you can see in below picture, let us assume the molecule is sugar. We see that in the left part there are fewer sugar molecules than right side. This means less water molecule in the right side. Because of this, water will move to the right side accross the selective membrane permeable to balance the molecule of water with the molecule of sugar. The selective membrane permeable blocks the sugar.

Facilitated diffusion is undergone with the help of the presence of protein carrier molecules. As I have explained above, the carrier molecules are embedded on the phospholipid layer as displayed in the picture below.

Some people say the exact mechanism is still uncertain, however it is believed that this protein is attached in the phospholipid bilayer and attract the substance, and it changes the shape of the protein carrier molecule to build sort of “channel” thus allows substances to be transported to the other side of the cell. Glucose works with this mechanism. To better understand the process, take a look at the picture below.

Active Transport

Active transport consists of several steps with the help of protein carrier molecule attached on the cell membrane. The carrier molecule attaches to a substance outside the cell which then will be transported across the cell membrane inside. Inside, the carrier attaches to another molecules and releases them outside. This activity requires enery in term of ATP which during the transportation is converted into ADP (Adenosine Diphosphate). The mechanism works against concentration gradient. Heavy metals are thought to use this mechanism during the absorption inside our body.

There are two kinds of active transports mechanisms I think we are already familiar with. They are phagocytosis and pynocitosis. Phagocytosis is a process simply transporting a molecule outside the cell into inside the cell with expenditure of energy. The particle or molecule is surrounded by an extension cell called pseudopodia. Pseudopodia will then fuse and form a membranous sac (vesicle) that will transport molecule or particle inside the cell. Phagocytosis is used by white blood in lungs (respiratory system) to destroy a harmful toxic such as silica or asbestos. Pinocytosis has same principle with phagocytosis. The only different pinocytosis tranports liquid. Pseudopodia does not form, but vesicle is formed that will release the liquid inside the cell. This mechanism is common method in the small intestine, metals such as lead or cadmium may be absorbed by this mechanism.

phagocytosis:

pinocytosis: