domingo, 26 de marzo de 2017

Circulatory System: Body Fluids

In this lesson we are going to analyse the main body fluids, the exchange of fluids that takes place in our body and the conduction system.
Body Fluids
Most of our body is a saline liquid. The main dissolvent is water. Water is our main component due to many reasons: life was originated in water, it is a liquid capable of dissolving many different substances (it is called universal solvent), it allows many different chemical reactions and exchanges and it is a good substance to control abrupt temperature changes, because it warms and cools slowly. 
The amount of water is different in different parts of the body. There are tissues, such as bone or adipose, where the water concentration is very low. Some organs, such as the brain, have high amount of water, even higher than 80% of its weight.  The amount of water is also variable depending on the age: older people usually have lower amount of water. Babies' bodies have a water concentration higher than 75%, whereas old people's bodies have a water concentration lower than 70%.
Losses and additions of water
The human body is not an isolated structure, it is constantly losing water that must be replaced to maintain the hydride balance.
The most relevant ways to lose water are:
  • Exhalation: when our respiratory system releases air, it has a high amount of water vapour
  • Evapotranspiration: water vapour escapes from our body through our skin. It can be divided into two processes:
    • Insensible perspiration: it is the water lost by our skin as water vapour. Our body is 37°C, so some liquid water is transformed into water vapour that escapes from our body through our epidermis tissue. It is nearly constant, because our body temperature is also constant.
    • Sensible perspiration: it mainly comes from our sweat. Sweat is mainly made up of water with mineral salts. It is released to our skin in order to reduce our body temperature; sweat evaporates cooling our skin. This perspiration is very variable, it depends not only on our body temperature (that can rise or drop due to our physical activity), but also on the external temperature. It can variate from less than half a litre to more than ten litres a day.
  • Water in the faeces: it is not a relevant amount of water, lower than half a litre per day. But it can be drastically incremented in some gastric diseases, causing diarrhoea.
  • Water in the urine: the excretory system is the main controller of the homeostasis or, in other words, the amount of water and electrolytes in our body. Kidneys can produce different volume of urine with more or less concentration of substances, depending on the hydric state of the body.
As far as the adding of water is concerned:
  • Drinking: it is the most relevant way to add water. Our brain makes us feel thirsty when it detects water deficit. Voluntary water comsumption is very variable: some people drink less than half a litre of water per day, whereas others drink more than three litres.
  • Water in the food: all the living beings are partially made of water, so when we eat any kind of food, we are also consuming water contained in it. It is variable depending on the kind of food we eat, but it can be higher than one litre per day.
  • Metabolic water: our regular metabolic activity produces water. In the basic respiratory reaction, glucose is burnt and transformed into carbon dioxide and water, releasing energy in the process. It can be higher than half a litre per day.
Body Water distribution
Body water can be divided into two groups, according to its distribution:
  • Intracellular Water: it is in the interior of our cells. It is the most abundant water in our body, around 70% of the total water in our body (or, in other words, 40% of our total weight).
  • Extracellular water: it is in the exterior of our cells. It is around 30% of our total water (or, in other words, 20% of our total wight). It is the place where all the metabolic exchanges between cells or between the organism and the outer media are carried out.
Intracellular water is nearly constant because cells need a precise amount of water to stay alive and small changes in this volume kill them. Each kind of cell has a characteristic volume of inner water.
Extracellular water, however, is more variable. This water can be found in three different spaces:
  • Plasmatic space: it is usually called plasma. Plasma is the liquid part of the blood and it is enclosed into the circulatory system. Its function is transporting nutrients from the digestive and respiratory systems to the cells and tissues and waste products from the cells and tissues to the excretory system. This space, however, does not have direct contact with the cells or the exterior.
  • Interstitial space: it is located between the cells and it is filled with interstitial liquid. It is the liquid that forms the extracellular matrix that separates the cells. It forms the lymph when it enters the lymphatic vessels. It binds with the capillaries and the cell membranes of the cells.
  • Transcellular space: this is the space where different kinds of special liquid can be found. These liquids are built up or confined in several places in order to be eliminated or carry out specific functions. Liquids built up in the gastrointestinal duct or in the urinary system, sweat in the sweat glands, the pleural fluid that surrounds and protect the lungs, the pericardic fluid that surrounds the heart, the cerebrospinal fluid in the central nervous system, the synovial fluid in the synovial joints and the ocular humours are the most typical examples.
Liquid balance and regulation
The water composition is different in these different spaces and its chemical and physical properties must be constant. Inner fluids permanently flow from one space to another, carrying ions and other components dissolved. On the one hand, the osmotic processes play a relevant role in this process, because they promote the movement of water. On the other hand, many substances must be transported from one place to another without forcing water to move with them. The regulation of the osmotic processes is essential: if water floods any organ, tissue or cell it could cause severe damage. When cells accumulate too much, for instance, water they can explode and die.
The extracellular fluid is richer in potassium and chlorine than extracellular fluid. The extracellular fluid, however, is richer in sodium and phosphates. This balance must allow the intracellular fluid to be much richer in proteins and dissolved organic substances without forcing water to move to the interior of the cell due to osmotic processes. 
Water balance must, at the same time, allow the exchange of substances. On the one hand, the liquid in the plasmatic space has an internal pressure, because it is enclosed in a tube (the blood vessels). It is called hydrostatic pressure, and tends to push the liquid to the exterior of the vessels. On the other hand, plasmatic fluid is rich in some special proteins (called oncotic proteins) that cause a osmotic pressure, called oncotic pressure, that tends to pull water from the exterior to the interior of the tubes. As a result, the oncotic pressure, that is opposite to hydrostatic pressure, prevents water from exiting the tubes excesively.
In the arterial part of the capillaries the hydrostatic pressure is stronger than the oncotic pressure. Due to this, the plasma tends to exit the vessel, flooding the interstitial space. In the venous part of the capillaries, however, the hydrostatic pressure is weaker because of the lower amount of plasma (that has moved to the exterior). The oncotic pressure in this part of the capillaries has risen, because there is less water, so the dissolved oncotic proteins, that cannot exit the capillaries, are more concentrated. As a result, in this zone the fluids tend to move from the interstitial space to the interior of the vessels.
Nevertheless, the amount of water that exits the capillaries in the arterial pole is always bigger than the amount of water that gets back the capillaries in the venous pole. Due to this, the plasmatic fluid tends to be built up in the interstitial space. It will be returned to the plasmatic space by the lymphatic system.
Liquid balance in capillaries.
The lymphatic system drains the interstitial space, preventing it from being flood. When this system does not work properly the plasmatic fluid floods the interstitial space causing edema. 
The Blood
General Characteristics
Blood is a fluid made up of a solid and a liquid part. It moves throughout our body enclosed in the circulatory system.
It is the main system to transport substances. It is also important to send messages between different parts of the body. It is essential in the respiratory, nutritive, excretive, defensive and regulatory functions. It is between 6% and 8% of the total weight of the body. It is a viscous liquid with a pH around 7.4.
The blood has two different parts or phases:
  • Liquid part: it is made of a liquid plasma or serum. It is a complex yellow liquid, with many dissolved and suspended components. It is around 55% of the total weight of the blood.
  • Solid part: it is made up of cells also called formed elements. It is around 45% of the total weight of the blood.
Liquid part of the blood: plasma
The most abundant component of this yellow liquid is water, around 91%. The rest of the liquid is made up of different components, many of them solid substances. 7% of the total weight is made of proteins.
The most abundant plasmatic proteins is the albumin. It is responsible for controlling the osmotic blood pressure and transporting some substances, above all steroids.
Another abundant protein is the fibrinogen. It is the precursor of the fibrin, that is responsible for the coagulative process of the blood.
In the plasma there can also be found other dissolved components, such as sugars (above all glucose, with a constant concentration of 100 mg per ml), lipids (there is system to transport lipids called apolipoproteins), nutrients, creatine, bilirubin, vitamins, hormones (a large variety at extremely low concentrations, they can move free or linked to transporters), waste products (such as urea or uric acid), gases (carbon dioxide and oxygen, although this one is mainly transported by erythrocytes) and electrolytes (such as Na+, K+, Ca2+, Mg2+, Cl-, PO43-, HCO3- and SO32-).
Solid part of the blood: formed elements
Blood cells can be divided into three groups: erythrocytes, also called red cells, leucocytes, also called white cells and thrombocytes, also called platelets.
The erythrocytes are, by far, the most abundant cells of the blood: more than 99% of the total blood cells. One cubic millimetre of blood contains around five million erythrocytes.
They are flat and circular, with a shape as a biconcave disc. They don't have nucleus or complex organelles and are just filled with a protein called haemoglobin.
This is a globular protein made of four subunits (two alpha subunits and two beta subunits). Each one has an active centre with a complex organic molecule called heme group, that has iron in its central part (so one haemoglobin molecule has four heme group and each one had one atom of iron). It is responsible for linking oxygen in order to transport it. Summing up, haemoglobin is the protein responsible for transporting oxygen. Ergo erythrocytes are the cells that transport oxygen in the blood. 100 milligrams of blood have between 14 and 20 grams of haemoglobin.
The erythrocytes don't have a nucleus or complex organelles and their metabolic processes are anaerobic (they don't have mitochondrions) to prevent them for consuming the oxygen that are transporting.
They have a complex cytoskeleton that preserve their peculiar cell shape. This shape allows them to move throughout extremely thin blood vessels and capillaries without reducing the blood flow. They can be folded or bent in pronounced curves to move without blocking them.
Due to the lack of organelles erythrocytes can not be repaired, so their life expectancy is very short, around 120 days. Then, they are eliminated by macrophages in the spleen. The heme group must be recycled, the iron is built up forming a molecule called ferritin. The rest of the molecule is transformed into bilirubin, that is released into the faeces by the liver.  
The destroyed erythrocytes must be replaced by new ones to ensure the correct transportation of oxygen. The health disorder caused by low the amount of erythrocytes is called anaemia.
Erythrocyte: shape

Leucocytes are bigger than erythrocytes and have a nucleus and complex organelles (although they don't have haemoglobin). They are responsible for defending the organism against invaders. They can be divided into several groups:
  • Granulocytes: these are leucocytes with lobulated nucleus and grains in the cytoplasm that can be seen using an optic microscope.
    • Neutrophils: they are the most abundant granulocytes. Their function is phagocyting invaders matched by antibodies.
    • Eosinophils: they are not so abundant and their grains are coloured by acid colorants. They phagocyte invaders and are also related to inflammatory processes.
    • Basophils: their grains are coloured by basic colorants. They are related to inflammatory phenomena and they trigger chemical processes that prepare the body to fight against infections when they release the content of their granules. Due to this they are also related to allergies. 
  • Agranulocytes: they don't have cytoplasmic grains visible with the optic microscope. They are two types of agranulocytes.
    • Monocytes: they are the bigger leucocytes, with a bean-shaped nucleus and a special ability to get out of the blood and become macrophages when they reach any connective tissue. Their main function is phagocyting any unknown external agent, such as bacteria or virus, fragmenting it and showing it to the lymphocytes, that are responsible to produce antibodies. According to this, monocytes and macrophages are the first defensive cells that detect invaders.
    • Lymphocytes: they detect invaders that have been phagocyted by monocytes and produce antibodies against these invaders. Antibodies are essential to match the invaders in order to make them easily recognised by other defensive elements, improving the defensive process. There are two types of lymphocytes called T and B. T lymphocytes grow up in the thymus and they produce toxic substances to destroy invaders or even our own cells when they are invaded by virus or have become tumoral. B lymphocytes are responsible for producing antibodies. 
Erythrocyte - Thrombocyte - Leucocyte
These are also known as platelets. They are not real cells, but fragments of cells without nucleus, but rich in grains filled with substances that are responsible for triggering coagulative processes. These cells also have a complex cytoskeleton with contractile proteins in  the cytoplasm. Thanks to these proteins, thrombocytes can group, forming compact groups called thrombi that block extravasations when blood vessels are damaged. 
Blood Cells.
Hematopoiesis is defined as the production of blood cells. It is carried out by the stem cells that are located in the bone marrow of larger bones. The stem cells of the bone marrow differentiate to the different blood cells. There are different cell families that can evolve to form specific blood cells. There are three basic families, one to form erythrocytes, another to form leucocytes and finally another one to form thrombocytes.
It is an extremely controlled process that is activated when the body detects that the amount of some blood cells has decreased. When the body detects, for instance, that the erythrocytes are not able to transport enough oxygen, a hormone called erythropoietin (EPO) is released by the kidneys. As a result, the stem cells of the bone marrow produce erythrocytes.
Haemostasis is defined as the process responsible for preventing the body from haemorrhages. In other words, hemostasis prevents us from losing a large amount of blood due to extravasations related to damage in blood vessels.
The first reaction that occurs when a vessel suffers a severe damage is the contraction of the muscular wall of the vessel. This contraction is called spasm and is triggered by pain receptors in the vessel wall.
The second reaction is the formation of the thrombus made up of thrombocytes. These cells join and release the substances built up in their grains. The substances promote the aggregation of thrombocytes. The contractile proteins of the cells contract, making the aggregation more compact. The group of joined compacted thrombocytes cover the damaged vessel preventing it from the extravasation.
The third reaction is the production of the red thrombus, formed from the solidification of the liquid part of the blood. It is a chain reaction triggered by some substances released by the cell wall of the vessel when they are damaged. The last reaction transforms fibrinogen, a soluble protein in the plasma, into fibrin that is insoluble. These insoluble proteins solidify the plasma.
There are two coagulative pathways. One of them is called the extrinsic pathway, it is the fastest one and takes place after severe damage. It is triggered by proteins released by surrounding tissues after suffering damage. The second one is called the intrinsic pathway. It is slow and complex and it is triggered when the epithelial cells that cover the inner part of the vessels detect damage.

When the damaged blood vessel is repaired, the thrombus and the fibrillar net must be eliminated. This process is carried out by plasmatic enzymes that destroy the fibrin net.

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