CIRCULATORY SYSTEM

CIRCULATORY SYSTEM

The circulatory system is an organ system that passes nutrients , gases, hormones,blood cells, etc. to and from cells in the body to help fight diseases, stabilize body temperature and pH, and to mainta in homeostasis.

This system may be seen strictly as a blood distribution network, but some consider the circulatory system as composed of the cardiovascular system, which distributes blood, and the lymphatic system, which returns excess filtered blood plasma from the interstitial fluid (between cells) as lymph. While humans, as well as other vertebrates, have a closed cardiovascular system (meaning that the blood never leaves the network of arteries, veins and capillaries), some invertebrate groups have an open cardiovascular system. The most primitive animal phyla lack circulatory systems. The lymphatic system, on the other hand, is an open system providing an accessory route for excess interstitial fluid to get returned to the blood.

Two types of fluids move through the circulatory system: blood and lymph. Lymph is essentially recycled blood plasma after it has been filtered from the blood cells and returned to the lymphatic system. The blood, heart, and blood vessels form the cardiovascular (from Latin words meaning 'heart'-'vessel') system. The lymph, lymph nodes, and lymph vessels form the lymphatic system. The cardiovascular system and the lymphatic system collectively make up the circulatory system.

Coagulation 

Coagulation is the process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel. Disorders of coagulation can lead to an increased risk of bleeding (hemorrhage) or obstructive clotting (thrombosis).

Coagulation is highly conserved throughout biology; in all mammals, coagulation involves both a cellular (platelet) and a protein (coagulation factor) component. The system in humans has been the most extensively researched and is therefore the best understood.

Coagulation begins almost instantly after an injury to the blood vessel has damaged the endothelium lining the vessel. Exposure of the blood to proteins such as tissue factor initiates changes to blood platelets and the plasma protein fibrinogen, a clotting factor. Platelets immediately form a plug at the site of injury; this is called primary hemostasis. Secondary hemostasis occurs simultaneously: Proteins in the blood plasma, called coagulation factors or clotting factors, respond in a complex cascade to form fibrin strands, which strengthen the platelet plug.

Blood Test

A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via finger prick. Blood tests are used to determine physiological and biochemical states, such as disease, mineral content, drug effectiveness, and organ function. They are also used in drug tests.

Biochemical analysis

A basic metabolic panel measures sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), magnesium, creatinine,glucose, and sometimes includes calcium. Blood tests focusing on cholesterol levels can determine LDL and HDL cholesterol levels, as well as triglyceride levels.

Some blood tests, such as those that measure glucose, cholesterol, or for determining the existence or lack of STD, require fasting (or no food consumption) eight to twelve hours prior to the drawing of the blood sample.

For the majority of blood tests, blood is usually obtained from the patient's vein. However, other specialized blood tests, such as the arterial blood gas, require blood extracted from an artery. Blood gas analysis of arterial blood is primarily used to monitor carbon dioxide and oxygen levels related to pulmonary function, but it is also used to measure blood pH and bicarbonate levels for certain metabolic conditions.

While the regular glucose test is taken at a certain point in time, the glucose tolerance test involves repeated testing to determine the rate at which glucose is processed by the body.

Physical Properties of Blood and Plasma

• The Average adult has a blood volume of approximately 5 liters, which composes about 8% of the body's weight.
• Osmolality of blood is 275-295 milliosmoles per kg.
• Plasma constitutes approximately 55% of blood's volume.
• Plasma Composition:
• 90% Water
• 8% Protein
• 0.9% Inorganic Salts
• Sodium 135-146 mM
• Potassium 3.5-5.2 mM
• Calcium 2.1-2.7 mM
• Carbonate 23-31 mM
• Phosphate 0.7-1.4 mM
• 1.1% organic substances
• It is estimated that plasma may contain as many as 40,000 different proteins from about 500 gene products. Approximately 1,000 proteins have been detected.
• Plasma contains 50-70 mg of protein per ml.
• Approx. 70% Albumin (35-50 mg/ml)
• Approx. 10% IgG (5-7 mg/ml)

Blood Composition on the Cellular Level

For every 600 red blood cells, there are approximately 40 platelets and one white cell.

Red Blood Cells (Erythrocytes)

• Typically 4-8 x 10⁶ cells per µl
• Composed approx 90% hemoglobin
• RBCs have a life-span of approx. 120 days before they are removed by the spleen

Platelets (Thrombocytes)

• Typically 150,000-350,000 per µl
• Produced by megakaryocytes stimulated by thrombopoietin.
• Platelets circulate for an average of 9-10 days before removal by the spleen.
• Participate in hemostasis/coagulation

White Blood Cells (Leukocytes)

• Granulocytes
      Neutrophils
      Eosinophils
      Basophils
• Lymphocytes
• Monocytes

– Neutrophils (polymorphonuclear leucocytes)

• Phagocytic
• Compose approximately 56% of the white blood count
• Chemotactic-directed phagocytic action in response to interleukin-1 from macrophages, histamine from basophils, mast cells and platelets and complement proteins C3a and C5a in the plasma.

– Eosinophils

• Phagocytic & Cytotoxic
• Compose approximately 4% of the white blood count.
• Bind via C3b receptors resulting from parasitic alternative pathway complement activation.
• Granules release proteins cytoxic to parasites: MBP, peroxidase, arylsulphatase B, phospholipase D and histaminase.

– Basophils

• Smallest granulocytes
• Non-Phogocytic
• Compose approximately 3% of the white blood count.
• Involved in Type I hypersensitivity
• Binding of IgE to the Fc receptors on basophils stimulate release of histamine and heparin
• Upon stimulation, basophils release TNF- and IL-4, that modulate endothelial adhesion molecules.
• Basophils express integrins as receptors to the endothelial membrane proteins ICAM-1,ELAM-1and VCAM-1

– Lymphocytes

• Compose approximately 25% of the white blood count
• Produced by bone marrow.
• Termed B cells when they achieve immune-competence within marrow
• Termed T cells when they achieve immune-competence within thymus
• B Cells respond to antigens by the production of antibodies, B and T cells produce lymphokines that control immune response

– Monocytes

• Within approximately one day from being produced in the marrow, monocytes are transported to various organs where they become tissue macrophages via the influence of cytokines.
• kidney - mesangial cells
• bone - osteoclasts
• liver - Kupfer cells
• brain - microglia

·         Tests of the Coagulation Cascade

·         These in vitro tests—the activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT)—measure the time elapsed from activation of the coagulation cascade  at different points to the generation of fibrin.

·          

·         The coagulation cascade. Bold type indicates the starting point of the coagulation test noted.

·         Activated Partial Thromboplastin Time

·         Definition

·         The aPTT measures the time necessary to generate fibrin from initiation of the intrinsic pathway Activation of factor XII is accomplished with an external agent (e.g., kaolin) capable of activating factor XII without activating factor VII. Since platelet factors are necessary for the cascade to function normally, the test is performed in the presence of a phospholipid emulsion that takes the place of these factors. The classic partial thromboplastin time depends on contact with a glass tube for activation. Since this is considered a difficult variable to control, the "activated" test uses an external source of activation.

·         Technique

·         Citrated plasma, an activating agent, and phospholipid are added together and incubated at 37°C. Calcium is added, and the time necessary for the clumping of kaolin is measured. The normal time is usually reported as less than 30 to 35 seconds depending on the technique used. In fact, there is a normal range of about 10 seconds (e.g., 25 to 35), and decreased values ("short") may also be abnormal.

·         Basic Science

·         This test is abnormal in the presence of reduced quantities of factors XII, IX, XI, VIII, X, V, prothrombin, and fibrinogen (all integral parts of the "intrinsic" and "common" pathway. It is usually prolonged if a patient has less than approximately 30% normal activity. It can also be abnormal in the presence of a circulating inhibitor to any of the intrinsic pathway factors. The differentiation of inhibitors from factor depletion is important and can best be accomplished by a mixing study in which patient and normal plasma are combined in a 1:1 ratio and the test is repeated on the mixed sample. If the abnormal value is corrected completely, the problem is factor deficiency. If the result does not change or the abnormality is corrected only partially, an inhibitor is present. This difference stems from the above mentioned fact that the aPTT will be normal in the presence of 50% normal activity.

·         Clinical Significance

·         The aPTT is a good screening test for inherited or acquired factor deficiencies. Inherited disorders including classic hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency, or Christmas disease) are well-known diseases in which the aPTT is prolonged. Other intrinsic and common pathway factors may also be congenitally absent. These conditions are rare but have been described for all factors. A number of kindreds with abnormalities of factor XII activation have been described. They are usually associated with a prolonged aPTT without clinical signs of bleeding. Acquired factor deficiency is common. Vitamin K deficiency, liver dysfunction, and iatrogenic anticoagulation with warfarin are most common. Factor depletion may also occur in the setting of disseminated intravascular coagulation (DIC), prolonged bleeding, and massive transfusion.

·         A prolonged aPTT that cannot be completely normalized with the addition of normal plasma can be explained only by the presence of a circulating inhibitor of coagulation. The presence of these inhibitors is almost always acquired, and their exact nature is not always apparent. From a clinical point of view, the most common inhibitors should be considered antithrombins. These compounds inhibit the activity of thrombin on the conversion of fibrinogen to fibrin. The two most common inhibitors are heparin, which acts through the naturally occurring protein antithrombin III (AT III), and fibrin degradation products (FDP), formed by the action of plasmin on the fibrin clot and usually present in elevated concentrations in DIC and primary fibrinolysis.

·         Other inhibitors appear to be antibodies. The easiest to understand is the antibody against factor VIII in patients with hemophilia A treated with factor VIII concentrate. Inhibitors against other factors have been described with a variety of diseases that follow a variable course. When characterized, they have been immunoglobulins.

·         A particular problem may be seen in patients suffering from systemic lupus erythematosus. These patients may present with a prolonged aPTT without evidence of bleeding. Some present with thrombosis. The abnormality cannot be corrected with normal plasma and has been referred to as the "lupus anticoagulant." This phenomenon does not represent an in vivo problem with the coagulation cascade. Rather, it is a laboratory abnormality caused by the presence of a serum constituent that interferes with the in vitro partial thromboplastin test.

·         Occasionally the reported value of the aPTT will be lower than normal. This "shortened" time may reflect the presence of increased levels of activated factors in context of a "hypercoagulable state." It is seen in some patients in the early stages of DIC but should not be considered diagnostic for that entity.

·         Prothrombin Time

·         Definition

·         The PT measures the time necessary to generate fibrin after activation of factor VII. It measures the integrity of the "extrinsic" and "common" pathways (factors VII, V, X, prothrombin, and fibrinogen).

·         Technique

·         Citrated plasma and an activating agent (usually thromboplastin extracted from animal brain) are incubated at 37°C. The plasma is recalcified and the time is measured until fibrin filaments are observed. Each laboratory has its own normal value, usually between 12 and 15 seconds.

·         Basic Science

·         As with the interpretation of a prolonged aPTT, a prolonged PT may reflect either factor deficiency or a circulating inhibitor of coagulation. The distinction is made by repeating the test after a 1:1 mix with normal plasma.

·         The test is more sensitive than the aPTT for deficient levels of factors, and a relatively small drop in factor VII levels may prolong the PT.

·         Clinical Significance

·         Inherited deficiency of factor VII is a rare bleeding disorder characterized by a prolonged PT and a normal aPTT. The PT completely corrects when mixed with normal plasma. Acquired deficiencies are usually related to liver disease, warfarin therapy, or depletion secondary to consumptive coagulopathy, severe bleeding, or massive transfusion.

·         Circulating inhibitors are most often directed at factor X or thrombin. Most common are heparin or products of fibrinolysis. In their presence the prolonged PT cannot be completely corrected to normal in a 1:1 mixing study.

·         Thrombin Time

           Definition

·         This test measures the time necessary to drive the reaction of fibrinogen to fibrin in the presence of thrombin. It measures the integrity of this reaction and isolates an abnormality to either a decrease in normal fibrinogen or an inhibitor to its activation.

·         Technique

·         Citrated plasma is incubated at 37°C and thrombin is added to the solution. Time is measured from the addition of thrombin to the generation of fibrin filaments. Calcium is unnecessary.

·         Basic Science

·         Abnormalities can be explained in one of three ways: deficient fibrinogen (< 100 mg/dl), abnormal fibrinogen, or an inhibitor to the reaction. As with other tests of the coagulation cascade, if a 1:1 mixing study normalizes the prolonged time, one is dealing with factor deficiency. As it pertains to fibrinogen, however, one must distinguish a decrease in normal fibrinogen from the production of an abnormal fibrinogen (dysfibrinogenemia).

·         Clinical Significance

·         Acquired deficiency of fibrinogen is usually due to a consumptive coagulopathy or, less often, severe liver disease. Hereditary deficiencies exist, but with variable clinical presentations. Afibrinogenemia is an often fatal childhood condition.

·         Abnormal fibrinogen (dysfibrinogenemia) can be acquired or inherited. The acquired form is usually found in association with severe liver disease, but has been reported in other diseases. The congenital form is rare, usually autosomal dominant. A discordance between immunologic and physiologic measurements of fibrinogen is the key to diagnosis.

·         The most common acquired inhibitors of this reaction are heparin and fibrin degradation products (FDP). The effect of heparin can be eliminated by catalyzing the reaction with reptilase, which, unlike thrombin, is insensitive to heparin. FDP are commonly seen in consumptive coagulopathies and primary fibrinolytic states.

Analysis of bone marrow

 A bone marrow biopsy removes a small amount of bone and a small amount of fluid and cells from inside the bone (bone marrow). A bone marrow aspiration removes only the marrow. These tests are often done to find the reason for many blood disorders and may be used to find out if cancer or infection has spread to the bone marrow.

• Bone marrow aspiration removes a small amount of bone marrow fluid and cells through a needle put into a bone. The bone marrow fluid and cells are checked for problems with any of the blood cells made in the bone marrow. Cells can be checked for chromosome problems. Cultures can also be done to look for infection.
• A bone marrow biopsy removes bone with the marrow inside to look at under a microscope. The aspiration (taking fluid) is usually done first, and then the biopsy.

A bone marrow aspiration can also be done to collect bone marrow for medical procedures, such as stem cell transplant or chromosomal analysis. For a stem cell transplant, bone marrow aspiration will be done at several places on the body (generally from the back of the pelvic bone) to remove enough bone marrow cells for the transplant to work.

 Blood Transfusion

A blood transfusion is a safe, common procedure in which you receive blood through an intravenous (IV) line inserted into one of your blood vessels.

Blood transfusions are used to replace blood lost during surgery or a serious injury. A transfusion also might be done if your body can't make blood properly because of an illness.

During a blood transfusion, a small needle is used to insert an IV line into one of your blood vessels. Through this line, you receive healthy blood. The procedure usually takes 1 to 4 hours, depending on how much blood you need.

Blood transfusions are very common. Each year, almost 5 million Americans need a blood transfusion. Most blood transfusions go well. Mild complications can occur. Very rarely, serious problems develop.

Leukemia

The term leukemia refers to cancers of the white blood cells (also called leukocytes or WBCs). When a child has leukemia, large numbers of abnormal white blood cells are produced in the bone marrow. These abnormal white cells crowd the bone marrow and flood the bloodstream, but they cannot perform their proper role of protecting the body against disease because they are defective.

As leukemia progresses, the cancer interferes with the body's production of other types of blood cells, including red blood cells and platelets. This results in anemia (low numbers of red cells) and bleeding problems, in addition to the increased risk of infection caused by white cell abnormalities.

As a group, leukemias account for about 25% of all childhood cancers and affect about 2,200 American young people each year. Luckily, the chances for a cure are very good with leukemia. With treatment, most children with leukemia will be free of the disease without it coming back.

Types of Leukemia

In general, leukemias are classified into acute (rapidly developing) and chronic (slowly developing) forms. In children, about 98% of leukemias are acute.

Acute childhood leukemias are also divided into acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), depending on whether specific white blood cells called lymphyocytes (or myelocytes), which are linked to immune defenses, are involved.

Approximately 60% of children with leukemia have ALL, and about 38% have AML. Although slow-growing chronic myelogenous leukemia (CML) may also be seen in children, it is very rare, accounting for fewer than 50 cases of childhood leukemia each year in the United States.

Thrombocytopenia

Thrombocytopenia is any disorder in which there is an abnormally low amount of platelets. Platelets are parts of the blood that help blood to clot. This condition is sometimes associated with abnormal bleeding.

Causes

Thrombocytopenia is often divided into three major causes of low platelets:

1. Not enough platelets are made in the bone marrow
2. Increased breakdown of platelets in the bloodstream
3. Increased breakdown of platelets in the spleen or liver

Your bone marrow may not make enough platelets if you have:

• Aplastic anemia
• Cancer in the bone marrow such as leukemia
• Cirrhosis (liver scarring)
• Folate deficiency
• Infections in the bone marrow (very rare)
• Myelodysplasia
• Vitamin B12 deficiency

Use of certain drugs may also lead to a low production of platelets in the bone marrow. The most common example is chemotherapy treatment.

The following health conditions cause increased breakdown of platelets:

• Disseminated intravascular coagulation (DIC)
• Drug-induced nonimmune thrombocytopenia
• Drug-induced immune thrombocytopenia
• Hypersplenism (swollen spleen)
• Immune thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura

Symptoms

You may not have any symptoms. General symptoms include:

• Bleeding in the mouth and gums
• Bruising
• Nosebleeds
• Rash (pinpoint red spots called petechia)

Other symptoms depend on the cause.

Treatment

Treatment depends on the cause of the condition. In some cases, a transfusion of platelets may be required to stop or prevent bleeding.

The outcome depends on the disorder causing the low platelet counts.

Iron in the blood 

 High iron in the blood is most commonly caused by hemochromatosis, a common genetic disorder. Symptoms of high iron in the blood include fatigue, weakness and pain in the abdomen near the liver. This condition is manageable through prescribed treatments and drugs, but these can cause severe damage to the internal organs if not managed properly. If you have high iron levels, avoid alcohol, shellfish and nutritional supplements containing iron.

Facts

Increased iron levels can be a symptom of a wide variety of problems, including genetic disorders such as hereditary hemochromatosis, hemolytic anemia, multiple blood transfusions, a high dietary intake of iron and even alcoholism. According to the Centers for Disease Control (CDC), high iron in the blood is usually caused by a genetic disorder where a person inherits a defective gene from both parents. The Mayo Clinic adds that middle-aged men of northern European descent are the most likely group to present symptoms of inherited disease causing high iron in the blood.

Symptoms

Fatigue is the complaint that brings most people who have high iron in the blood to the doctor. A person experiencing iron overload feels extremely tired all the time, has muscle weakness, may experience unhealthy weight loss, and will experience pain in the abdomen near the liver and in the joints. Since the symptoms for both high and low iron in the blood are similar, your doctor must perform laboratory tests to determine which extreme is causing your complaints.

Solutions

High iron in the blood can be treated to make you more comfortable, but hemochromatosis is typically genetic in origin--so the disease will not go away. The CDC states that patients are often treated by removing blood from the body periodically to induce mild anemia. Some chelation therapies have been used with success, as well as eliminating iron supplements and reducing the patient's intake of iron-rich foods.