A&P Ch 14 The Blood

Coagulation

Blood coagulation is a chemical cascade of reactions that ends in a final clot. It involves 13 factors that help the reactions to proceed. If a person is missing just one of these factors, they won't be able to form clots in response to injury. An example of this would be a hemophiliac. Most hemophiliacs are missing factor VIII so the cascade stops before the final clot is made. They are given synthetic factor VIII in order to compensate for this.

The main function of erythrocytes (red blood cells) is to pick up oxygen from the lungs and release it into the tissues of the body. In order to do this they contain a protein called hemoglobin.

Hemoglobin is made up of protein (the globin part), and a red pigment molecule containing iron (the heme part). There are 4 globin molecules in one hemoglobin, 2 alpha and 2 beta. Each of these globin chains contains a heme molecule.

The factors involved in blood clotting are proteins produced in the liver.

If you follow through the clotting cascade above you will notice that they are not in order from I - XII. This is because they were named in order of discovery, not in order of use.

If a mother is Rh negative and dad is Rh positive, mom can carry an Rh positive baby. When this baby is born, there is a feto maternal bleed that allows the mother's and baby's blood to make contact. When this happens, the mother has now been exposed to the Rh antigen. Mom will start making Rh antibodies but this won't affect the first baby as it has already been born. If mom gets pregnant again with an Rh positive child, her Rh antibodies now can now destroy fetal red blood cells and could be fatal to the fetus. The condition is called hemolytic disease of the newborn or erythroblastosis fetalis. Any subsequent pregnancy with an Rh positive child would react the same way.

In order to prevent this from happening, there was an antibody developed called RhoGAM that prevents the mom from developing Rh antibodies in the first place. So if a pregnant woman is Rh negative, she is typically given a RhoGAM shot at seven months gestation and then again within 72 hours after the birth of the baby. This is done with every pregnancy in order to prevent the mother from ever producing Rh antibodies.

Embolism

this is a trapped embolus. It may become trapped in the heart and cause a heart attack, or the brain and cause a stroke, or even in the lungs causing a pulmonary embolus. All of these are life threatening.

Thrombus

this is an aggregation of platelets, red blood cells and even sometimes white blood cells within the fibrin strands. These adhere to the vessel wall and either slow down the flow of blood or may block it completely.

As you learned last quarter, blood is a fluid connective tissue. It contains erythrocytes (red blood cells), leukocytes (white blood cells) and platelets.

Remember, these are made in the red bone marrow that you find in cancellous (spongy) bone. The blood vessels run throughout the body delivering nutrients and picking up wastes via the blood.

Leukocytes cannot squeeze through the capillaries to enter brain tissue

TRUE

Vascular Spasm

The blood vessel walls are composed of smooth muscle. The smooth muscle contracts dramatically near the site of injury so that blood flow to the area will decrease. It is currently believed that there are chemicals released from the endothelium that triggers this vascular spasm.

Usually when someone has their blood typed they will also receive their Rh result which is either positive or negative. 85% of Caucasians have the Rh antigen on their erythrocytes so they are Rh positive.

The reason it is called Rh is because Rhesus monkeys were initially used in the research to make antiserums.

'Leuko' means white so they are also known as white blood cells. The function of leukocytes is to help fight off infections and act as the clean up crew of the body by removing debris, toxins and infectious agents.

While erythrocytes do not leave the bloodstream unless there is a tear in a blood vessel wall, leukocytes can move out of the bloodstream into the surrounding tissue through a process called emigration. The cell wall of capillaries is made up of simple squamous epithelium. As such, there are areas between the squamous cells where the leukocytes can squeeze through into the tissues.

The cardiovascular system consists of

the heart, the blood and all the blood vessels.

The functions of blood can be classified into three main areas: Distribution, Regulation and Protection.

1.Distribution 1.Transports oxygen from the lungs to body cells 2.Transports nutrients from the digestive tract to the body 3.Moves metabolic wastes such as CO2 from the cells to the lungs for removal. 4.Transfers hormones in the endocrine system to target organs 2.Regulation (Homeostasis) 1.Maintains blood volume 2.Maintains normal blood pH 3.Regulates body temperature 3.Protection 1.Prevents infection by transporting immune elements 2.Prevents blood loss by transporting clotting factors

There are two main categories of leukocytes based on whether granules can be seen in their cytoplasm when using a light microscope and a stain:

1.Granulocytes - when viewed under a microscope, granules are seen in the cytoplasm. The granulocytes all end in 'phil' and are the neutrophils, eosinophils and the basophils. So if you remember, 'Phil' has freckles you'll remember which ones are granulocytes. 2.Agranulocytes - these are leukocytes without granules in their cytoplasm. They are the lymphocytes and monocytes. Each of these cells have functions that involve immunity, phagocytosis (eating of cells or other debris) or secretion (which is the release of chemicals.

Each of the formed elements looks different from the other types; to understand these differences the anatomy of each will be briefly described.

Also, each formed element type has a different function from the other types. This makes sense because why would you need many different cells to carry out one function?

Leukemia is due to an overproduction of a certain type of white blood cell. Knowing the pathway for hematopoiesis, why would leukemia reduce the number of erythrocytes and platelets?

It would because the 'partially committed precursor cell' would be receiving signals to keep producing that type of white blood cell thus decreasing the signals that trigger red blood cell and platelet production

The ABO blood group are the most important and most widely known blood types. These were discovered by a scientist, Karl Landsteiner, who also received the Nobel prize for his work.

There are 4 types: A, B, O and AB. An antigen (a surface protein) on the erythrocyte gives the name to each blood type. For example, if a person has an A antigen on their red blood cells then they are Type A. There are only 2 types of antigens, A and B. If the red blood cells lack these two antigens then it is referred to as Type O as they have zero of the A or B antigens on their erythrocytes.

The body can undergo physiological stress from many things even something as simple as taking an anatomy and physiology course! In the realm of erythrocytes however, the body can undergo physiological stress due to decreased levels of oxygen. Decreased levels of oxygen can be caused by things such as:

•Decreased oxygen in the atmosphere - this would occur at a higher altitude. •Inadequate hemoglobin - such as occurs in anemia •Low erythrocyte count - this could also occur in anemia

four steps to blood clotting:

1. Injury, 2. Vascular Spasm, 3. Platelet Plug Formation and 4. Coagulation

There are a lot of steps involved in hematopoiesis. The 'precursor cells' can become one of two types of cells which then determines which branch of blood cells they are going to become. The stages are:

1.Myeloid stem cell - The myeloid stem cell is the precursor to all the blood cells with the exception of the lymphocytes. So platelets, erythrocytes, and four of the leukocytes come from this branch. So the myeloid stem cell is still only 'partially committed' as it can become any of those types of blood cells. 2.Lymphoid stem cell- The lymphocyte, one of the five types of leukocytes, develops from the lymphoid stem cell. The lymphoid stem cell is 'committed' as it will only become a lymphocyte.

When this occurs, the body responds by eliciting a negative feedback response. It does this in the following way:

1.Reduced oxygen in blood 2.Triggers the kidneys to release erythropoietin 3.Erythropoietin travels through the bloodstream to the red bone marrow 4.Stimulates an increase in red blood cell production 5.Homeostasis is returned

The coagulation cascade is a very lengthy process that I don't want you to memorize so I'm not giving the whole cascade except the parts I do want you to know. From the diagram above on the clotting cascade, refer to the common pathway.

1.The cascade leads to the activation of prothrombin. Prothrombin is a plasma protein made by the liver and would normally be moving through the bloodstream. When it is activated at the site of injury, it then becomes an enzyme called thrombin. This is one of the few enzymes we will come across in anatomy and physiology that does not end in -ase. The conversion of prothrombin to thrombin requires an enzyme that is released by the platelets called thrombinase. Does this enzyme name seem like it should come from platelets? Why or why not? 2.Thrombin is then used to convert fibrinogen (another plasma protein made by the liver) to the final fibrin clot. Fibrin is a threadlike protein that forms a mesh which is quite strong and prevents anything from going through the damaged vessel. We could also expect fibrinogen to move normally through the bloodstream, but would we expect fibrin to? Why or why not?

Plasma is about 92% water. There are many substances that are dissolved in the plasma with many of them being proteins but most of them are in very low quantity.

7% of the plasma are plasma proteins. These are the albumins, globulins and fibrinogen.

Injury

A break in a blood vessel may occur from a paper cut or when cutting up fruit. When this tear occurs, blood begins to flow out which includes erythrocytes and leukocytes. This exposes certain substances that are not normally released that allow the platelets to begin sticking.

Platelets flow freely through the bloodstream and cannot adhere to a blood vessel unless there is a tear or damage to that blood vessel.

An injury to a blood vessel initiates the process of hemostasis. Blood clotting involves three steps. First, vascular spasm constricts the flow of blood. Next, a platelet plug forms to temporarily seal small openings in the vessel. Coagulation then enables the repair of the vessel wall once the leakage of blood has stopped.

Formed elements are the living blood cells. That is, the erythrocytes, leukocytes, and platelets. The platelets are a bit different from the other two as they are literally cell fragments that have broken off from a larger cell in the red bone marrow.

As fragments you wouldn't expect them to do very much but they play a significant role in blood clotting.

The pluripotent stem cells found in the red bone marrow are called hemocytoblasts. This is to separate it from other stem cells in our body. Anytime there is a suffix of 'blast', it means it is an immature cell.

As you already know, 'cyto' stands for cell, and the prefix 'hemo' comes from the Greek root "haima" which means blood. If you combine these, you have 'blood cell immature'.

The hemocytoblast undergoes mitosis in the red bone marrow to form two types of cells. One is a new stem cell so that the supply of stem cells remains steady. The other cell is a precursor cell that is now partially committed to becoming one of the types of blood cells. By partially committed, I mean that this cell still needs a chemical such as a hormone ( I thought we were done with those...aagghhh) to signal its production. Examples are:

Erythropoietin - This is a hormone produced in the kidneys that stimulates the hemocytoblasts to divide ultimately into erythroblasts. These will continue to divide until they are erythrocytes. Then the erythrocytes are released into the blood stream.This process will be discussed in more detail in erythropoiesis. Thrombopoietin - This is a hormone produced by the liver and kidneys that stimulates the hemocytoblasts to develop into megakaryocytes. These megakaryocytes break off pieces into the bloodstream which are the actual platelets.

Blood is red in color and the color comes from the millions of erythrocytes that are moving in the bloodstream. Blood consists of two parts: the formed elements (leukocytes, erythrocytes and platelets) and the plasma which is actually a yellowish liquid. You may see the words plasma and serum sometimes used interchangeably but there is a distinct difference between these two. Plasma is the liquid portion of our blood when it has not coagulated. In our body, blood flows along in a non-coagulated liquid state, so this portion is called plasma.

In the medical lab, when a tube of blood that contains no additives is spun down, the formed elements are clotted in the bottom of the tube and the liquid portion is now called serum. This serum portion is used to measure chemicals in the blood such as glucose, liver enzymes and cholesterol. However if a tube of blood contains an additive such as EDTA, which is an anticoagulant, and is spun down, the liquid portion is now called the plasma. This uncoagulated blood is used to measure things such as erythrocytes and hemoglobin.

hormone called erythropoietin, that is made by the kidneys, which triggers the production of erythrocytes.

It's bad enough that this hormone is difficult to pronounce but the production of red blood cells is called erythropoiesis. So sorry but that's the way it is.

Because the erythrocytes lack a nucleus in the bloodstream, they are not really functional cells. In reality, they are temporary hemoglobin-filled containers that transport oxygen and also carbon dioxide in the blood stream.

One interesting thing to note is that the erythrocyte does not use the oxygen it carries. The red blood lacks mitochondria and also ribosomes. Also, without a nucleus,. the erythrocytes cannot survive very long. The maximum amount of time they survive in the bloodstream is 120 days.

Platelets are quite a bit different than leukocytes or erythrocytes. One thing is that they aren't really cells, instead they are fragments of a much larger cell called a megakaryocyte. In the bone marrow, platelets are derived from the myeloid branch of the stem cell which goes through stages into the megakaryocyte.

Pieces break off of the megakaryocyte into the bloodstream and these are the platelets. Similar to the red blood cell they do not contain a nucleus in the bloodstream. In contrast to erythrocytes, platelets generally only live for 10 days. The function of platelets is to aid in blood clotting.

Platelets, also called thrombocytes, are essential for blood clotting. The cessation of bleeding is called hemostasis. This process of forming a blood clot (coagulation) is needed in order to prevent continued blood loss from damaged blood vessels or tissues.

Platelets start the process by forming a platelet plug at the area of damage and then there are a number of clotting factors that are initiated to participate in a coagulation cascade to form a final fibrin clot.

In order of prevalence in the bloodstream, you can remember the mnemonic 'Never Let Monkeys Eat Bananas'.

So, neutrophils are in greatest number in the blood, encompassing around 60%, lymphocytes at around 20%, monocytes about 8% with eosinophils about 5% of the leukocytes, and basophils are pretty scarce as they are only about 1% of the leukocyte population. These numbers are only estimates but you should know the relative order of population.

1.Albumins - most of the plasma proteins are albumins. These are made in the liver and help to maintain the blood's osmotic pressure which is the water balance. Albumins will pull water from the extracellular fluid to keep this balance intact. 2.Globulins - there are three types of globulins: alpha, beta and gamma. The alpha and beta are responsible for transporting lipids through the bloodstream. The gamma globulins are involved in immunity and are best known as antibodies. 3.Fibrinogen - this is produced by the liver and, like the platelets, plays a role in blood clotting.

The other 1% of plasma is composed of substances like electrolytes, gases such as oxygen, vitamins and wastes.

Platelet Plug Formation

The platelets start to adhere to the collagen fibers and endothelial lining of the ruptured vessel. As they collect, they clump together becoming very sticky with spiky extensions radiating out from the platelets. As the platelets are stuck together, they form what is called the platelet plug. They release certain chemicals that will contribute to hemostasis but the plug itself just buys some time until the vessel can be repaired.

Each of the blood cells and platelets develop from an immature precursor cell located in the bone marrow. This process is called hematopiesis and it is currently believed that all blood cells are made from a single type of cell which gives rise to all the mature blood cells in the body.

The precursor cell is called a stem cell and is referred to as 'pluripotent' since it has the capability to become any of the many types of blood cells.

Blood type is 100% genetic and also codes for a particular antibody to be made according to that blood type. An antibody is a protein in the plasma that is usually made in response to a foreign antigen. However, these antibodies for blood type are already pre-formed prior to birth. For instance, if a person's blood type is A, they already have pre-formed antibodies to B.

These antibodies to B would travel through their plasma and not cause a problem since there is not B antigen on the erythrocytes, only A antigen. However, if the person with blood type A was injected with blood type B there would be a reaction causing agglutination of the red blood cells which occurs from antibody B binding to antigen B.

A big difference between Rh and the ABO blood type is that antibodies for Rh are not pre-formed. So a person with Rh negative blood does not have Rh antibodies in their bloodstream.

They will only form Rh antibodies if they are exposed to Rh positive blood. This might happen in a transfusion or, more commonly, in childbirth.

Fibrin forms an interwoven network that keeps the vessel plugged. Factor XIII, sews up the clot further stabilizing it.

This clot must eventually be removed and that process is called fibrinolysis. 'Lysis' means the breakdown of. The action of fibrinolysis is another complicated pathway which is beyond the scope of this course.

Each iron in the heme molecule can bind to 1 oxygen molecule; therefore one hemoglobin molecule can transport up to 4 oxygen molecules. Think about this for a minute and make sure you can visualize it.

This may not seem like much but each erythrocyte contains upwards of 300 million hemoglobin molecules. So how many oxygen molecules could a red blood cell carry? The actual pickup and transfer of oxygen will be discussed in more detail in the respiratory system.

The production of erythrocytes begins in the red bone marrow and starts from a myeloid stem cell. This stem cell goes through mitotic division until it reaches a cell called an erythroblast. This erythroblast contains a nucleus but when it is released into the bloodstream the nucleus is ejected for disposal and the erythrocyte is now ready to carry oxygen.

Without this nucleus, the red blood cell looks like a biconcave disc which gives the erythrocyte an increase in surface area. This is important as it allows more gas exchange to occur. The erythrocytes are also extremely small; so small that a drop of blood contains a million red blood cells and just thousands of white blood cells.

Remember some of the functions of blood as you read about the functions of each of the types of formed elements.

You will see many of these functions are carried out by the different cells. Note that any of the functions that are not handled by the formed elements are probably carried out by the plasma.

Embolus

blood clot (thrombus) that is freely moving in the bloodstream. These can be extremely large if the thrombus has been attached to the vessel long enough to grow to a large size. If it is quite large, it can block blood flow to an organ.