№ 6. Blood. Blood groups. Blood vessels. Blood circulation.
Blood is a highly specialized circulating tissue consisting of several types of cells suspended in a fluid medium known as plasma. The cellular constituents are: red blood cells, which carry respiratory gases and give it its red color because they contain haemoglobin (an iron-containing protein that binds oxygen in the lungs and transports it to tissues in the body), white blood cells (leukocytes), which fight disease, and platelets, cell fragments which play an important part in the clotting of the blood.
Medical terms related to blood often begin with hemo- or hemato- (BE: haemo- and haemato-) from the Greek word “haima” for “blood.” Anatomically, blood is considered a connective tissue from both its origin in the bones and its function.
Human blood smear: a – erythrocytes; b – neutrophil; c – eosinophil; d – lymphocyte.
Blood is a constantly circulating fluid providing the body with nutrition, oxygen, and waste removal. Blood is mostly liquid, with numerous cells and proteins suspended in it, making blood “thicker” than pure water. The average person has about 5 liters (more than a gallon) of blood.
A liquid called plasma makes up about half of the content of blood. Plasma contains proteins that help blood to clot, transport substances through the blood, and perform other functions. Blood plasma also contains glucose and other dissolved nutrients.
About half of blood volume is composed of blood cells:
• Red blood cells, which carry oxygen to the tissues
• White blood cells, which fight infections
• Platelets, smaller cells that help blood to clot
Blood is conducted through blood vessels (arteries and veins). Blood is prevented from clotting in the blood vessels by their smoothness, and the finely tuned balance of clotting factors.
Blood Conditions
Hemorrhage (bleeding): Blood leaking out of blood vessels may be obvious, as from a wound penetrating the skin. Internal bleeding (such as into the intestines, or after a car accident) may not be immediately apparent.
Hematoma: A collection of blood inside the body tissues. Internal bleeding often causes a hematoma.
Leukemia: A form of blood cancer, in which white blood cells multiply abnormally and circulate through the blood. The excessive large numbers of white cells deposit in the body’s tissues, causing damage.
Multiple myeloma: A form of blood cancer of plasma cells similar to leukemia. Anemia, kidney failure and high blood calcium levels are common in multiple myeloma.
Lymphoma: A form of blood cancer, in which white blood cells multiply abnormally inside lymph nodes and other tissues. The enlarging tissues, and disruption of blood’s functions, can eventually cause organ failure.
Anemia: An abnormally low number of red blood cells in the blood. Fatigue and breathlessness can result, although anemia often causes no noticeable symptoms.
Hemolytic anemia: Anemia caused by rapid bursting of large numbers of red blood cells (hemolysis). An immune system malfunction is one cause.
Hemochromatosis: A disorder causing excessive levels of iron in the blood. The iron deposits in the liver, pancreas and other organs, causing liver problems and diabetes.
Sickle cell disease: A genetic condition in which red blood cells periodically lose their proper shape (appearing like sickles, rather than discs). The deformed blood cells deposit in tissues, causing pain and organ damage.
Bacteremia: Bacterial infection of the blood. Blood infections are serious, and often require hospitalization and continuous antibiotic infusion into the veins.
Malaria: Infection of red blood cells by Plasmodium, a parasite transmitted by mosquitos. Malaria causes episodic fevers, chills, and potentially organ damage.
Thrombocytopenia: Abnormally low numbers of platelets in the blood. Severe thrombocytopenia may lead to bleeding.
Leukopenia: Abnormally low numbers of white blood cells in the blood. Leukopenia can result in difficulty fighting infections.
Disseminated intravascular coagulation (DIC): An uncontrolled process of simultaneous bleeding and clotting in very small blood vessels. DIC usually results from severe infections or cancer.
Hemophilia: An inherited (genetic) deficiency of certain blood clotting proteins. Frequent or uncontrolled bleeding can result from hemophilia.
Hypercoaguable state: Numerous conditions can result in the blood being prone to clotting. A heart attack, stroke, or blood clots in the legs or lungs can result.
Polycythemia: Abnormally high numbers of red blood cells in the blood. Polycythemia can result from low blood oxygen levels, or may occur as a cancer-like condition.
Deep venous thrombosis (DVT): A blood clot in a deep vein, usually in the leg. DVTs are dangerous because they may become dislodged and travel to the lungs, causing a pulmonary embolism (PE).
Myocardial infarction (MI): Commonly called a heart attack, a myocardial infarction occurs when a sudden blood clot develops in one of the coronary arteries, which supply blood to the heart.
Blood Tests
Complete blood count: An analysis of the concentration of red blood cells, white blood cells, and platelets in the blood. Automated cell counters perform this test.
Blood smear: Drops of blood are smeared across a microscope slide, to be examined by an expert in a lab. Leukemia, anemia, malaria, and numerous other blood conditions can be identified with a blood smear.
Blood type: A test for compatibility before receiving a blood transfusion. The major blood types (A, B, AB, and O) are determined by the protein markers (antigens) present on the surface of red blood cells.
Coombs test: A blood test looking for antibodies that could bind to and destroy red blood cells. Pregnant women and people with anemia may undergo Coombs testing.
Blood culture: A blood test looking for infection present in the bloodstream. If bacteria or other organisms are present, they may multiply in the tested blood, allowing their identification.
Mixing study: A blood test to identify the reason for blood being “too thin” (abnormally resistant to clotting). The patient’s blood is mixed in a tube with normal blood, and the mixed blood’s properties may provide a diagnosis.
Bone marrow biopsy: A thick needle is inserted into a large bone (usually in the hip), and bone marrow is drawn out for tests. Bone marrow biopsy can identify blood conditions that simple blood tests cannot.
Blood Treatments
Chemotherapy: Medicines that kill cancer cells. Leukemias and lymphomas are usually treated with chemotherapy.
Blood transfusion: A blood donor’s red blood cells are separated from their plasma and packed into a small bag. Transfusing the concentrated red blood cells into a recipient replaces blood loss.
Platelet transfusion: A blood donor’s platelets are separated from the rest of blood and concentrated into a plastic bag. Platelet transfusion is generally only performed when platelet counts fall to very low levels.
Fresh frozen plasma: A blood donor’s plasma (liquid blood) is separated from the blood cells, and frozen for storage. Plasma transfusion can improve blood clotting and prevent or stop bleeding that’s due to clotting problems.
Cryoprecipitate: Specific proteins are separated from blood and frozen in a small volume of liquid. Cryoprecipitate transfusion can replace specific blood clotting proteins when their levels are low, such as in people with hemophilia.
Anticoagulation: Medicines to “thin” the blood and prevent clotting in people at high risk from blood clots. Heparin, enoxaparin (Lovenox) and warfarin (Coumadin) are the medicines most often used.
Antiplatelet drugs: Aspirin and clopidogrel (Plavix) interfere with platelet function and help prevent blood clots, including those that cause heart attacks and strokes.
Antibiotics: Medicines to kill bacteria and parasites can treat blood infections caused by these organisms.
Erythropoietin: A hormone produced by the kidney that stimulates red blood cell production. A manufactured form of erythropoietin can be given to improve the symptoms of anemia.
Bloodletting: In people with problems caused by too much blood (such as from hemochromatosis or polycythemia), occasional controlled removal of blood may be necessary.
Functions
· Supply of oxygen to tissues (bound to hemoglobin which is carried in red cells)
· Supply of nutrients such as glucose, amino acids and fatty acids (dissolved in the blood or bound to plasma proteins)
· Removal of waste such as carbon dioxide, urea and lactic acid
· Immunological functions, including circulation of white cells, and detection of foreign material by antibodies
· Coagulation, which is one part of the body’s self-repair mechanism
· Messenger functions, including the transport of hormones and the signalling of tissue damage
· Regulation of body pH
· Regulation of core body temperature
· Hydraulic functions, including erection (see also jumping spider)
Problems with blood composition or circulation can lead to downstream tissue dysfunction. The term ischaemia refers to tissue which is inadequately perfused with blood.
The blood is circulated around the lungs and body by the pumping action of the heart. Additional return pressure may be generated by gravity and the actions of skeletal muscles. In mammals, blood is in equilibrium with lymph, which is continuously formed from blood (by capillary ultrafiltration) and returned to the blood (via the thoracic duct). The lymphatic circulation may be thought of as the “second circulation”.
Blood is composed of several kinds of cells (occasionally called corpuscles); these formed elements of the blood constitute about 45% of whole blood by volume, mostly red blood cells. The other 55% is blood plasma, a fluid that is the blood’s liquid medium, appearing yellow in color. The proportion of blood occupied by red blood cells is referred to as the hematocrit.
A scanning electron microscope (SEM) image of normal circulating human blood. One can see red blood cells, several white blood cells including knobby lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.
The normal pH of human arterial blood is approximately 7.40 (normal range is 7.35-7.45), a weak alkaline solution. Blood that has a pH below 7.35 is acidic, while blood pH above 7.45 is alkaline. Blood pH along with arterial carbon dioxide tension (PaCO2) and HCO3 readings are helpful in determining the acid-base balance of the body. The respiratory system and urinary system normally control the acid-base balance of blood as part of homeostasis. Blood is about 7% of the human body weight, so the average adult has a blood volume of about 5 litres, of which 2.7-3 litres is plasma. Human blood density is around 1060 kg/m³. The combined surface area of all the red cells in the human body would be roughly 2,000 times as great as the body’s exterior surface.
The cells are:
Red blood cells or erythrocytes (96%)
In mammals, mature red blood cells lack a nucleus and organelles. They contain the blood’s haemoglobin and distribute oxygen. The red blood cells (together with endothelial vessel cells and some other cells) are also marked by glycoproteins that define the different blood types.
White blood cells or leukocytes (3.0%)
White blood cells are part of the immune system; they destroy infectious agents, pathogens.
Platelets or thrombocytes (1.0%)
Platelets are responsible for blood clotting (coagulation). They change fibrinogen into fibrin. This fibrin creates a mesh onto which red blood cells collect and clot. This clot stops more blood from leaving the body and also helps to prevent bacteria from entering the body.
Blood plasma is essentially an aqueous solution containing 92% water, 8% blood plasma proteins, and trace amounts of other materials. Some components are:
· Blood clotting factors (to facilitate coagulation)
· Immunoglobulins (antibodies)
· Hormones
· Carbon dioxide
· Various other proteins
· Various electrolytes (mainly sodium and chlorine)
Together, plasma and cells form a non-Newtonian fluid whose flow properties are uniquely adapted to the architecture of the blood vessels.
The term serum refers to plasma from which the clotting proteins have been removed. Most of the protein remaining is albumin and immunoglobulins.
Physiology of blood
Production and degradation
Blood cells are produced in the bone marrow, this process is termed hematopoiesis. The proteinaceous component (including clotting proteins) is produced overwhelmingly in the liver, while hormones are produced by the endocrine glands and the watery fraction is regulated by the hypothalamus and maintained by the kidney and indirectly by the gut.
Blood cells are degraded by the spleen and the Kupffer cells in the liver. The liver also clears some proteins, lipids and amino acids. The kidney actively secretes waste products into the urine. Erythrocytes usually live up to 120 days before they are systematically replaced by new erythrocytes created by the process of hematopoiesis.
Transport of oxygen
Blood oxygenation is measured in several ways, but the most important measure is the hemoglobin (Hb) saturation percentage. This is a non-linear (sigmoidal) function of the partial pressure of oxygen. About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at normal pressure is chemically combined with the Hb. Only 1.5% is physically dissolved in the other blood liquids and not connected to Hb. The hemoglobin molecule is the primary transporter of oxygen in mammals and many other species (for exceptions, see below).
With the exception of pulmonary and umbilical arteries and their corresponding veins, arteries carry oxygenated blood away from the heart and deliver it to the body via arterioles and capillaries, where the oxygen is consumed; afterwards, venules and veins carry deoxygenated blood back to the heart.
Differences in infrared absorption between oxygenated and deoxygenated blood form the basis for realtime oxygen saturation measurement in hospitals and ambulances.
Under normal conditions in humans at rest, haemoglobin in blood leaving the lungs is about 98-99% saturated with oxygen. In a healthy adult at rest, deoxygenated blood returning to the lungs is still approximately 75% saturated. Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions. Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia): “As a general rule, any condition which leads to a sustained mixed venous saturation of less than 50% will be poorly tolerated and a mixed venous saturation of less than 30% should be viewed as a medical emergency.”
A fetus, receiving oxygen via the placenta, is exposed to much lower oxygen pressures (about 20% of the level found in an adult’s lungs) and so fetuses produce another form of hemoglobin with a much higher affinity for oxygen (hemoglobin F) in order to extract as much oxygen as possible from this sparse supply.
Substances other than oxygen can bind to the hemoglobin; in some cases this can cause irreversible damage to the body. Carbon monoxide for example is extremely dangerous when absorbed into the blood. When combined with the hemoglobin, it irreversibly makes carboxyhemoglobin which reduces the volume of oxygen that can be carried in the blood. This can very quickly cause suffocation, as oxygen is vital to many organisms (including humans). This damage can occur when smoking a cigarette (or similar item) or in event of a fire. Thus carbon monoxide is considered far more dangerous than the actual fire itself because it reduces the oxygen carrying content of the blood.
Insects
In insects, the blood (more properly called hemolymph) is not involved in the transport of oxygen. (Openings called tracheae allow oxygen from the air to diffuse directly to the tissues). Insect blood moves nutrients to the tissues and removes waste products in an open system.
Small invertebrates
In some small invertebrates like insects, oxygen is simply dissolved in the plasma. Larger animals use respiratory proteins to increase the oxygen carrying capacity. Hemoglobin is the most common respiratory protein found iature. Hemocyanin (blue) contains copper and is found in crustaceans and mollusks. It is thought that tunicates (sea squirts) might use vanabins (proteins containing vanadium) for respiratory pigment (bright green, blue, or orange).
In many invertebrates, these oxygen-carrying proteins are freely soluble in the blood; in vertebrates they are contained in specialized red blood cells, allowing for a higher concentration of respiratory pigments without increasing viscosity or damaging blood filtering organs like the kidneys.
Deep sea invertebrates
Giant tube worms have extraordinary hemoglobins that allow them to live in extraordinary environments. These hemoglobins also carry sulfides normally fatal in other animals.
Transport of carbon dioxide
When systemic arterial blood flows through capillaries, carbon dioxide diffuses from the tissues into the blood. Some carbon dioxide is dissolved in the blood. Some carbon dioxide reacts with hemoglobin and other proteins to form carbamino compounds. The remaining carbon dioxide is converted to bicarbonate and hydrogen ions through the action of RBC carbonic anhydrase. Most carbon dioxide is transported through the blood in the form of bicarbonate ions.
Transport of hydrogen ions
Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin has a much greater affinity for H+ than does oxyhemoglobin so it binds most of the hydrogen ions.
Color
In humans and other hemoglobin-using creatures, oxygenated blood is bright red. This is due to oxygenated iron in the red blood cells. Deoxygenated blood is a darker shade of red, which can be seen during blood donation and when venous blood samples are taken. However, due to an optical effect caused by the way in which light penetrates through the skin, veins typically appear blue in colour. This has led to a common misconception that venous blood is blue before it is exposed to air. Another reason for this misconception is that medical charts always show venous blood as blue in order to distinguish it from arterial blood which is depicted as red on the same chart.
The blood of horseshoe crabs is blue, which is a result of its high content in copper-based hemocyanin instead of the iron-based hemoglobin found, for example, in humans.
Provision of force
In mammals the restriction of blood flow is commonly used as a temporary provision of force, as in an erection.
Blood type (or blood group) is determined, in part, by the ABO blood group antigens present on red blood cells.
A blood type (also called a blood group) is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins or glycolipids, depending on the blood group system, and some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens, that stem from one allele (or very closely linked genes), collectively form a blood group system.
The ABO blood group system and the Rhesus blood group system are more likely to cause harmful immunological reactions than the other blood group systems. In the routine blood transfusion work of a blood bank, the presence or absence of the three most significant blood group antigens, the A antigen, the B antigen and the RhD antigen (also known as the Rhesus factor or Rhesus D antigen), is determined. This gives the ABO blood group and the RhD antigen status, which are reflected in the common terminology A positive, O negative, etc. with the capital letters (A, B or O) referring to the ABO blood group, and positive or negative referring to the presence or absence of the RhD antigen of the Rhesus blood group system. In the routine preparation and selection of donor blood for blood transfusion, it is not necessary to determine the status of any more blood groups (or antigens), because antibody screening and cross-matching prior to transfusion, detects if there are any other blood group incompatibilities between potential donor blood and intended recipients.
If an individual is exposed to a blood group antigen that is not recognised as self, the immune system will produce antibodies that can specifically bind to that particular blood group antigen and an immunological memory against that antigen is formed. The individual will have become sensitized to that blood group antigen. These antibodies can bind to antigens on the surface of transfused red blood cells (or other tissue cells) often leading to destruction of the cells by recruitment of other components of the immune system. It is vital that compatible blood is selected for transfusion and that compatible tissue is selected for organ transplantation. Transfusion reactions involving minor antigens or weak antibodies may lead to minor problems. However, more serious incompatibilities can lead to a more vigorous immune response with massive RBC destruction, low blood pressure, and even death.
Blood types are inherited and represent contributions from both parents. Often, pregnant women carry a fetus with a different blood type from their own, and sometimes the mother forms antibodies against the red blood cells of the fetus, which causes hemolysis of fetal RBCs, and which in turn can lead to low fetal blood counts, a condition known as hemolytic disease of the newborn. Some blood types are associated with inheritance of other diseases; for example, the Kell antigen is associated with McLeod syndrome.[1] Certain blood types may affect susceptibility to infections, an example being the resistance to specific malaria species seen in individuals lacking the Duffy antigen.[2]The Duffy antigen, as a result of natural selection, is more common in ethnic groups from areas with a high incidence of malaria.[3]
The two most significant blood group systems were discovered during early experiments with blood transfusion: the ABO group in 1901[4] and the Rhesus group in 1937.[5] Development of the Coombs test in 1945,[6] the advent of transfusion medicine, and the understanding of hemolytic disease of the newborn led to discovery of more blood groups. Today, a total of 29 human blood group systems are recognized by the International Society of Blood Transfusion (ISBT).[7] A complete blood type would describe a full set of 29 substances on the surface of RBCs, and an individual’s blood type is one of the many possible combinations of blood group antigens. Across the 29 blood groups, over 600 different blood group antigens have been found,[8] but many of these are very rare or are mainly found in certain ethnic groups. Almost always, an individual has the same blood group for life; but very rarely, an individual’s blood type changes through addition or suppression of an antigen in infection, malignancy or autoimmune disease.[9] Blood types have been used in forensic science and in paternity testing, but this use is being replaced by DNA analysis, which provides greater certitude.
BO blood group system – diagram showing the carbohydrate chains which determine the ABO blood group
ABO blood group system
The ABO system is the most important blood group system in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies. ABO IgM antibodies are produced in the first years of life by sensitization to environmental substances such as food, bacteria and viruses. The “O” in ABO is often called “0” (zero/null) in other languages.
Rhesus blood group system
The Rhesus system is the second most significant blood group system in human blood transfusion. The most significant Rhesus antigen is the RhD antigen because it is the most immunogenic of the five main rhesus antigens. It is common for RhD negative individuals not to have any anti-RhD IgG or IgM antibodies, because anti-RhD antibodies are not usually produced by sensitization against environmental substances. However, RhD negative individuals can produce IgG anti-RhD antibodies following a sensitizing event: possibly a fetomaternal transfusion of blood from a fetus in pregnany or occasionally a blood transfusion with RhD positive RBCs.
Table of ABO and Rh distribution by nation
Overall, type O blood is the most common blood type in the world. Type A blood is more prevalent in Central and Eastern Europe countries. Type B blood is most prevalent in Chinese/Asian communities when compared to other races. Type AB blood is easier to find in Japan, China and Pakistan.
The associated anti-A and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses. ABO blood types are also present in some other animals, for example apes such as chimpanzees, bonobos, and gorillas.
History of discoveries
The ABO blood group system is widely credited to have been discovered by the Austrian scientist Karl Landsteiner, who found three different blood types in 1900; he was awarded the Nobel Prize in Physiology or Medicine in 1930 for his work. Due to inadequate communication at the time it was subsequently found that Czech serologist Jan Janský had independently pioneered the classification of human blood into four groups, but Landsteiner’s independent discovery had been accepted by the scientific world while Janský remained in relative obscurity. Janský’s classification is however still used in Russia and states of former USSR (see below). In America, Moss[who?] published his own (very similar) work in 1910.
Landsteiner described A, B, and O; Alfred von Decastello and Adriano Sturli discovered the fourth type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the heritability of ABO blood groups in 1910–11, with Felix Bernstein demonstrating the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Laine’s group (1988) found that the band 3 protein expressed a long polylactosamine chain that contains the major portion of the ABH substances attached. Later, Yamamoto’s group showed the precise glycosyl transferase set that confers the A, B and O epitopes.
ABO antigens
The H antigen is an essential precursor to the ABO blood group antigens. The H locus, which is located on chromosome 19, contains 3 exons that span more than 5 kb of genomic DNA; it encodes a fucosyltransferase that produces the H antigen on RBCs. The H antigen is a carbohydrate sequence with carbohydrates linked mainly to protein (with a minor fraction attached to ceramide moiety). It consists of a chain of β-D-galactose, β-D-N-acetylglucosamine, β-D-galactose, and 2-linked, α-L-fucose, the chain being attached to the protein or ceramide.
The ABO locus, which is located on chromosome 9, contains 7 exons that span more than 18 kb of genomic DNA. Exon 7 is the largest and contains most of the coding sequence. The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to the D-galactose end of the H antigen, producing the A antigen. The B allele encodes a glycosyltransferase that bonds α-D-galactose to the D-galactose end of the H antigen, creating the B antigen.
In the case of the O allele, when compared to the A allele, exon 6 lacks one nucleotide (guanine), which results in a loss of enzymatic activity. This difference, which occurs at position 261, causes a frameshift that results in the premature termination of the translation and, thus, degradation of the mRNA. This results in the H antigen remaining unchanged in case of O groups.
The majority of the ABO antigens are expressed on the ends of long polylactosamine chains attached mainly to band 3 protein, the anion exchange protein of the RBC membrane, and a minority of the epitopes are expressed oeutral glycosphingolipid.
Serology
Anti-A and anti-B antibodies (called isohaemagglutinins), which are not present in the newborn, appear in the first years of life. They are isoantibodies, that is, they are produced by an individual against antigens produced by members of the same species (isoantigens). Anti-A and anti-B antibodies are usually IgM type, which are not able to pass through the placenta to the fetal blood circulation. O-type individuals can produce IgG-type ABO antibodies.
Origin theories
It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have epitopes similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells (RBCs) that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards influenza virus, whose epitopes are similar enough to the α-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria, such as E. coli, cross-reacting with the α-D-galactose on the B glycoprotein.
The “Light in the Dark theory” (DelNagro, 1998) suggests that, when budding viruses acquire host cell membranes from one human patient (in particular, from the lung and mucosal epithelium where they are highly expressed), they also take along ABO blood antigens from those membranes, and may carry them into secondary recipients where these antigens can elicit a host immune response against these non-self foreign blood antigens. These viral-carried human blood antigens may be responsible for priming newborns into producing neutralizing antibodies against foreign blood antigens. Support for this theory has come to light in recent experiments with HIV. HIV can be neutralized in in vitro experiments using antibodies against blood group antigens specifically expressed on the HIV-producing cell lines.
The “Light in the Dark theory” suggests a novel evolutionary hypothesis: there is true communal immunity, which has developed to reduce the inter-transmissibility of viruses within a population. It suggests that individuals in a population supply and make a diversity of unique antigenic moieties so as to keep the population as a whole more resistant to infection. A system set up ideally to work with variable recessive alleles.
However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals.
Nonantigen biology
The carbohydrate molecules on the surfaces of red blood cells have roles in cell membrane integrity, cell adhesion, membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells.
Transfusion reactions
Due to the presence of isoantibodies against non-self blood group antigens, individuals of type A blood group immediately raise anti-B antibodies against B-blood group RBCs if transfused with blood from B group. The anti-B antibodies bind to B antigens on RBCs and cause complement-mediated lysis of the RBCs. The same happens for B and O groups (which raises both anti-A and anti-B antibodies). However, only blood group AB does not have anti-A and anti-B isoantibodies. This is because both A and B-antigens are present on the RBCs and are both self-antigens, hence they can receive blood from all groups and are universal recipients.
As far as transfusion compatibility is concerned, it is not strictly as simple as matching A, B, and O groups. In other words, no individual will ever receive a blood transfusion based on the ABO system alone. The rhesus factor must also be considered. Together, the rhesus factor and ABO grouping are the two most important compatibility factors to consider. An individual may be Rh+ or Rh-. In simpler terms, if an individual is blood type A and positive for the rhesus factor, then he or she is deemed “A+”.
ABO and Rh blood type donation showing matches between donor and recipient types Donors
O+ A+ B+ AB+ O- ** A- B- AB-
Recipients O+ ✔ ✔
A+ ✔ ✔ ✔ ✔
B+ ✔ ✔ ✔ ✔
AB+ * ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
O- ✔
A- ✔ ✔
B- ✔ ✔
AB- ✔ ✔ ✔ ✔
* Type AB+ is the universal recipient: Although those with AB blood type may be referred to as universal recipients, in actuality, type AB+ blood is that of the universal recipient, whereas type AB- is not. This is an important distinction to make.
** Because A-, A+, B-, B+, AB-, AB+, O- and O+ individuals can all receive blood from donors of type O- blood, an individual with type O- blood is deemed a universal donor. In a similar manner, O+ is not the universal donor blood type.
One caveat to this axiom of ‘universal donor’ is that this applies to packed RBCs, and not to whole blood products. Using the first table, type O carries anti-A and anti-B antibodies in the serum. To transfuse a type A, B, or AB recipient with type O whole blood would produce a hemolytic transfusion reaction due to the antibodies found in the serum of whole blood.
No antibodies are formed against the H antigen, except in those individuals with the Bombay phenotype.
In ABH secretors, roughly 80% of the human population, ABH antigens are secreted by most mucus-producing cells of the body interfacing with the environment, including lung, skin, liver, pancreas, stomach, intestines, ovaries, and prostate.
ABO hemolytic disease of the newborn
ABO blood group incompatibilities between the mother and child does not usually cause hemolytic disease of the newborn (HDN) because antibodies to the ABO blood groups are usually of the IgM type, which do not cross the placenta; however, in an O-type mother, IgG ABO antibodies are produced and the baby can develop ABO hemolytic disease of the newborn.
Inheritance
Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene) with three alleles: i, IA, and IB. The gene encodes a glycosyltransferase—that is, an enzyme that modifies the carbohydrate content of the red blood cell antigens. The gene is located on the long arm of the ninth chromosome (9q34).
The IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB are dominant over i, only ii people have type O blood. Individuals with IAIA or IAi have type A blood, and individuals with IBIB or IBi have type B. IAIB people have both phenotypes, because A and B express a special dominance relationship: codominance, which means that type A and B parents can have an AB child. A type A and a type B couple can also have a type O child if they are both heterozygous (IBi,IAi) The cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A1 or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.
Distribution and evolutionary history
The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations.
In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of placenames and to the successive invasions and migrations including Vikings, Danes, Saxons, Celts, and Normans who contributed the morphemes to the placenames and the genes to the population.
Genetics
There are two common O alleles, O01 and O02. These are identical to the group A allele (A01) for the first 261 nucleotides, at which point a guanosine base is deleted, resulting in a frame-shift mutation that produces a premature stop codon and failure to produce a functional A or B transferase. This deletion is found in all populations worldwide and presumably arose before humans migrated out of Africa (50,000 to 100,000 years ago). The second most common allele for group O (termed O02) is considered to be an even more ancient than the O01 allele.
Some evolutionary biologists theorize that the IA allele evolved earliest, followed by O (by the deletion of a single nucleotide, shifting the reading frame) and then IB. This chronology accounts for the percentage of people worldwide with each blood type. It is consistent with the accepted patterns of early population movements and varying prevalent blood types in different parts of the world: for instance, B is very common in populations of Asian descent, but rare in ones of Western European descent. Another theory states that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09, B101, O02 and O01. The continued presence of the O alleles is hypothesized to be the result of balancing selection. Both theories contradict the previously held theory that type O blood evolved earliest.
Other blood group systems
The International Society of Blood Transfusion currently recognizes 29 blood group systems (including the ABO and Rh systems).[7] Thus, in addition to the ABO antigens and Rhesus antigens, many other antigens are expressed on the RBC surface membrane. For example, an individual can be AB RhD positive, and at the same time M and N positive (MNS system), K positive (Kell system
), Lea or Leb negative (Lewis system), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered.
Blood transfusion
Compatibility
Blood products
Red blood cell compatibility
Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene) with three alleles: i, IA, and IB. The gene encodes a glycosyltransferase—that is, an enzyme that modifies the carbohydrate content of the red blood cell antigens. The gene is located on the long arm of the ninth chromosome (9q34).
The IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB are dominant over i, only ii people have type O blood. Individuals with IAIA or IAi have type A blood, and individuals with IBIB or IBi have type B. IAIB people have both phenotypes, because A and B express a special dominance relationship: codominance, which means that type A and B parents can have an AB child. A type A and a type B couple can also have a type O child if they are both heterozygous (IBi,IAi) The cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A1 or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.
Distribution and evolutionary history
The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations.
In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of placenames and to the successive invasions and migrations including Vikings, Danes, Saxons, Celts, and Normans who contributed the morphemes to the placenames and the genes to the population.
Genetics
There are two common O alleles, O01 and O02. These are identical to the group A allele (A01) for the first 261 nucleotides, at which point a guanosine base is deleted, resulting in a frame-shift mutation that produces a premature stop codon and failure to produce a functional A or B transferase. This deletion is found in all populations worldwide and presumably arose before humans migrated out of Africa (50,000 to 100,000 years ago). The second most common allele for group O (termed O02) is considered to be an even more ancient than the O01 allele.
Some evolutionary biologists theorize that the IA allele evolved earliest, followed by O (by the deletion of a single nucleotide, shifting the reading frame) and then IB. This chronology accounts for the percentage of people worldwide with each blood type. It is consistent with the accepted patterns of early population movements and varying prevalent blood types in different parts of the world: for instance, B is very common in populations of Asian descent, but rare in ones of Western European descent. Another theory states that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09, B101, O02 and O01. The continued presence of the O alleles is hypothesized to be the result of balancing selection. Both theories contradict the previously held theory that type O blood evolved earliest.
Other blood group systems
The International Society of Blood Transfusion currently recognizes 29 blood group systems (including the ABO and Rh systems).[7] Thus, in addition to the ABO antigens and Rhesus antigens, many other antigens are expressed on the RBC surface membrane. For example, an individual can be AB RhD positive, and at the same time M and N positive (MNS system), K positive (Kell system
), Lea or Leb negative (Lewis system), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered.
Blood transfusion
Compatibility
Blood products
Red blood cell compatibility
Some Rare Blood Types by Ethnic Group
Native American, Alaskan Native RzRz
Pacific Island, Asian Jk (a-b-)
East European/Russian Jews Dr(a-)
Because the heart is composed primarily of cardiac muscle tissue that continuously contracts and relaxes, it must have a constant supply of oxygen and nutrients. The coronary arteries are the network of blood vessels that carry oxygen- and nutrient-rich blood to the cardiac muscle tissue.
The blood leaving the left ventricle exits through the aorta, the body’s main artery. Two coronary arteries, referred to as the “left” and “right” coronary arteries, emerge from the beginning of the aorta, near the top of the heart.
The initial segment of the left coronary artery is called the left main coronary. This blood vessel is approximately the width of a soda straw and is less than an inch long. It branches into two slightly smaller arteries: the left anterior descending coronary artery and the left circumflex coronary artery. The left anterior descending coronary artery is embedded in the surface of the front side of the heart. The left circumflex coronary artery circles around the left side of the heart and is embedded in the surface of the back of the heart.
Just like branches on a tree, the coronary arteries branch into progressively smaller vessels. The larger vessels travel along the surface of the heart; however, the smaller branches penetrate the heart muscle. The smallest branches, called capillaries, are so narrow that the red blood cells must travel in single file. In the capillaries, the red blood cells provide oxygen and nutrients to the cardiac muscle tissue and bond with carbon dioxide and other metabolic waste products, taking them away from the heart for disposal through the lungs, kidneys and liver.
When cholesterol plaque accumulates to the point of blocking the flow of blood through a coronary artery, the cardiac muscle tissue fed by the coronary artery beyond the point of the blockage is deprived of oxygen and nutrients. This area of cardiac muscle tissue ceases to function properly. The condition when a coronary artery becomes blocked causing damage to the cardiac muscle tissue it serves is called a myocardial infarction or heart attack.
The superior vena cava is one of the two main veins bringing de-oxygenated blood from the body to the heart. Veins from the head and upper body feed into the superior vena cava, which empties into the right atrium of the heart.
The inferior vena cava is one of the two main veins bringing de-oxygenated blood from the body to the heart. Veins from the legs and lower torso feed into the inferior vena cava, which empties into the right atrium of the heart.
The inferior vena cava (or IVC), also known as the posterior vena cava, is the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart.
It is posterior to the abdominal cavity and runs alongside of the vertebral column on its right side (i.e. it is a retroperitoneal structure). It enters the right atrium at the lower right, back side of the heart.
Drainage patterns
The IVC is formed by the joining of the left and right common iliac veins and brings blood into the right atrium of the heart. It also anastomoses with the azygos vein system (which runs on the right side of the vertebral column) and venous plexuses next to the spinal cord.
The caval opening is at T8. The specific levels of the tributaries are as follows:
Vein |
Level |
Hepatic veins |
T8 |
Inferior phrenic vein |
T8 |
Right suprarenal vein |
L1 |
Renal Veins |
L1 |
Right gonadal vein |
L2 |
Lumbar veins |
L1-L5 |
Common iliac veins |
L5 |
Superior vena cava, inferior vena cava, azygos vein and their tributaries.
Because the IVC is not centrally located, there are some asymmetries in drainage patterns. The gonadal veins and suprarenal veins drain into the IVC on the right side, but into the renal vein on the left side, which in turn drains into the IVC. By contrast, all the lumbar veins and hepatic veins usually drain directly into the IVC.
The tributaries of Inferior vena cava can be remembered using the mnemonic, “I Like To Rise So High”, for Illiac vein (common), Lumbar vein, Testicular vein, Renal vein, Suprarenal vein and Hepatic vein.
Note that the vein that carries de-oxygenated blood from the upper half of the body is the superior vena cava.
Pathologies associated with the IVC
Health problems attributed to the IVC are most often associated with it being compressed (ruptures are rare because it has a low intraluminal pressure). Typical sources of external pressure are an enlarged aorta (abdominal aortic aneurysm), the gravid uterus (aortocaval compression syndrome) and abdominal maligancies, such as colorectal cancer, renal cell carcinoma and ovarian cancer. Since the inferior vena cava is primarily a right-sided structure, unconscious pregnant females should be turned on to their left side (the recovery position), to relieve pressure on it and facilitate venous return. In rare cases, straining associated with defecation can lead to restricted blood flow through the IVC and result in syncope (fainting).
Occlusion of the IVC is rare, but considered life-threatening and is an emergency. It is associated with deep vein thrombosis, IVC filters, liver transplantation and instrumentation (e.g. catheter in the femoral vein).
Embryology
In the embryo, the IVC and right atrium are separated by the Eustachian valve, also known in Latin as the valvula venae cavae inferioris (valve of the inferior vena cava). In the adult, this structure typically has totally regressed or remains as a small endocardial fold.
Base and diaphragmatic surface of heart.
The arch of the aorta, and its branches.
The abdominal aorta and its branches.
Inferior vena cava
Inferior vena cava
Inferior vena cava
The aorta is the largest single blood vessel in the body. It is approximately the diameter of your thumb. This vessel carries oxygen-rich blood from the left ventricle to the various parts of the body.
Schematic view of the aorta and a number of its most important branches
The course of the aorta
Course of the aorta in the thorax (anterior view), starting posterior to the main pulmonary artery, but then anterior to the right pulmonary arteries, the trachea and the esophagus, but then turning posteriorly to course dorsally to these structures
The aorta is usually divided into five segments/sections:
1. Ascending aorta—the section between the heart and the arch of aorta
The ascending aorta and arch of aorta with their branches
Components
The aortic root is the portion of the ascending aorta beginning at the aortic annulus and extending to the sinotubular junction. Between each commissure of the aortic valve and opposite the cusps of the aortic valve, three small dilatations called the aortic sinuses.
The sinotubular junction is the point in the ascending aorta where the aortic sinuses end and the aorta becomes a tubular structure.
Relations
At the union of the ascending aorta with the aortic arch the caliber of the vessel is increased, owing to a bulging of its right wall.
This dilatation is termed the bulb of the aorta, and on transverse section presents a somewhat oval figure.
The ascending aorta is contained within the pericardium, and is enclosed in a tube of the serous pericardium, common to it and the pulmonary artery.
The ascending aorta is covered at its commencement by the trunk of the pulmonary artery and the right auricula, and, higher up, is separated from the sternum by the pericardium, the right pleura, the anterior margin of the right lung, some loose areolar tissue, and the remains of the thymus; posteriorly, it rests upon the left atrium and right pulmonary artery.
On the right side, it is in relation with the superior vena cava and right atrium, the former lying partly behind it; on the left side, with the pulmonary artery.
Branches
The only branches of the ascending aorta are the two coronary arteries which supply the heart; they arise near the commencement of the aorta from the aortic sinuses which are opposite the aortic valve.
Thumb Fetal ascending aorta
Ascending aorta
2. Arch of aorta—the peak part that looks somewhat like an inverted “U”. The arch of the aorta or the transverse aortic arch (English pronunciation: /eɪˈɔrtɪk/) is the part of the aorta that begins at the level of the upper border of the second sternocostal articulation of the right side, and runs at first upward, backward, and to the left in front of the trachea; it is then directed backward on the left side of the trachea and finally passes downward on the left side of the body of the fourth thoracic vertebra, at the lower border of which it becomes continuous with the descending aorta.
Related structures
The ligamentum arteriosum connects the commencement of the left pulmonary artery to the aortic arch. The blood bypasses the lungs through the ductus arteriosus during embryonic circulation. This becomes the ligamentum arteriosum postnatal as pulmonary circulation begins.
The aortic knob is the prominent shadow of the aortic arch on a frontal chest radiograph.
Aortopexy is a surgical procedure in which the aortic arch is fixed to the sternum in order to keep the trachea open.
It thus forms two curvatures: one with its convexity upward, the other with its convexity forward and to the left. Its upper border is usually about 2.5 cm. below the superior border to the manubrium sterni. It lies within the mediastinum.
3. Descending aorta—the section from the arch of aorta to the point where it divides into the common iliac arteries. he descending aorta is part of the aorta, the largest artery in the body. The descending aorta is the part of the aorta beginning at the aortic arch that runs down through the chest and abdomen. The descending aorta is divided into two portions, the thoracic and abdominal, in correspondence with the two great cavities of the trunk in which it is situated. Within the abdomen, the descending aorta branches into the two common iliac arteries which serve the pelvis and eventually legs.
4. Thoracic aorta—the half of the descending aorta above the diaphragm. The thoracic aorta is contained in the posterior mediastinal cavity. It begins at the lower border of the fourth thoracic vertebra where it is continuous with the aortic arch, and ends in front of the lower border of the twelfth thoracic vertebra, at the aortic hiatus in the diaphragm where it becomes the abdominal aorta. At its commencement, it is situated on the left of the vertebral column; it approaches the median line as it descends; and, at its termination, lies directly in front of the column. The vessel describes a curve which is concave forward; as the branches given off from it are small, its diminution in size is insignificant. It has a radius of approximately 1.16 cm.
Histopathological image of dissecting aneurysm of thoracic aorta in a patient without evidence of Marfan’s trait. The damaged aorta was surgically removed and replaced by artificial vessel. Victoria blue & HE stain.
It is in relation, anteriorly, from above downward, with the root of the left lung, the pericardium, the esophagus, and the diaphragm; posteriorly, with the vertebral column and the azygos vein; on the right side, with the hemiazygos veins and thoracic duct; on the left side, with the left pleura and lung.
The esophagus, with its accompanying plexus of nerves, lies on the right side of the aorta above; but at the lower part of the thorax it is placed in front of the aorta, and, close to the diaphragm, is situated on its left side.
The initial part of the aorta, the ascending aorta, rises out of the left ventricle, from which it is separated by the aortic valve. The two coronary arteries of the heart arise from the aortic root, just above the cusps of the aortic valve.
The aorta then arches back over the right pulmonary artery. Three vessels come out of the aortic arch, the brachiocephalic artery, the left common carotid artery, and the left subclavian artery. These vessels supply blood to the head, neck, thorax and upper limbs.
Branches of thoracic aorta
The aorta gives off several paired branches as it descends in the thorax. In descending order, these include the
· Bronchial arteries
· Mediastinal arteries
· Esophageal arteries
· Pericardial arteries
· Superior phrenic artery
5. Abdominal aorta—the half of the descending aorta below the diaphragm. The abdominal aorta is the largest artery in the abdominal cavity. As part of the aorta, it is a direct continuation of the descending aorta (of the thorax).
Path
It begins at the level of the diaphragm, crossing it via the aortic hiatus, technically behind the diaphragm, at the vertebral level of T12. It travels down the posterior wall of the abdomen, anterior to the vertebral column. It thus follows the curvature of the lumbar vertebrae, that is, convex anteriorly. The peak of this convexity is at the level of the third lumbar vertebra (L3).
Abdominal aorta
It runs parallel to the inferior vena cava, which is located just to the right of the abdominal aorta, and becomes smaller in diameter as it gives off branches. This is thought to be due to the large size of its principal branches. At the 11th rib, the diameter is 122mm long and 55mm wide and this is because of the constant pressure
Branches
Relations
The abdominal aorta lies slightly to the left of the midline of the body. It is covered, anteriorly, by the lesser omentum and stomach, behind which are the branches of the celiac artery and the celiac plexus; below these, by the lienal vein(splenic artery), the pancreas, the left renal vein, the inferior part of the duodenum, the mesentery, and aortic plexus.
Posteriorly, it is separated from the lumbar vertebrж and intervertebral fibrocartilages by the anterior longitudinal ligament and left lumbar veins.
On the right side it is in relation above with the azygos vein, cisterna chyli, thoracic duct, and the right crus of the diaphragm—the last separating it from the upper part of the inferior vena cava, and from the right celiac ganglion; the inferior vena cava is in contact with the aorta below.
On the left side are the left crus of the diaphragm, the left celiac ganglion, the ascending part of the duodenum, and some coils of the small intestine.
Relationship with inferior vena cava
The abominal aorta’s venous counterpart, the inferior vena cava (IVC), travels parallel to it on its right side.
Above the level of the umbilicus, the aorta is somewhat posterior to the IVC, sending the right renal artery travelling behind it. The IVC likewise sends its opposite side counterpart, the left renal vein, crossing in front of the aorta.
Below the level of the umbilicus, the situation is generally reversed, with the aorta sending its right common iliac artery to cross its opposite side counterpart (the left common iliac vein) anteriorly.
Collateral circulation
The collateral circulation would be carried on by the anastomoses between the internal thoracic artery and the inferior epigastric artery; by the free communication between the superior and inferior mesenterics, if the ligature were placed between these vessels; or by the anastomosis between the inferior mesenteric artery and the internal pudendal artery, when (as is more common) the point of ligature is below the origin of the inferior mesenteric artery; and possibly by the anastomoses of the lumbar arteries with the branches of the internal iliac artery.
The celiac artery and its branches; the stomach has been raised and the peritoneum removed
Transverse section through the middle of the first lumbar vertebra, showing the relations of the pancreas
The pulmonary artery is the vessel transporting de-oxygenated blood from the right ventricle to the lungs. A common misconception is that all arteries carry oxygen-rich blood. It is more appropriate to classify arteries as vessels carrying blood away from the heart.
The pulmonary vein is the vessel transporting oxygen-rich blood from the lungs to the left atrium. A common misconception is that all veins carry de-oxygenated blood. It is more appropriate to classify veins as vessels carrying blood to the heart.
The pulmonary veins are large blood vessels that carry oxygenated blood from the lungs to the left atrium of the heart. In humans there are four pulmonary veins, two from each lung. They carry oxygenated blood, which is unusual since almost all other veins carry deoxygenated blood.
Path
The pulmonary veins carry oxygenated blood from the lungs to the left atrium of the heart. In humans there are normally four pulmonary veins, two from each lung. As part of the pulmonary circulation they carry oxygenated blood back to the heart, as opposed to the veins of the systemic circulation which carry deoxygenated blood.
Occasionally the three veins on the right side remain separate, and not infrequently the two left pulmonary veins end by a common opening into the left atrium. Therefore, the number of pulmonary veins opening into the left atrium can vary between three and five in the healthy population.
The right pulmonary veins (contains deoxygenated blood) pass behind the right atrium and superior vena cava; the left in front of the descending thoracic aorta. At the root of the lung, the superior pulmonary vein lies in front of and a little below the pulmonary artery; the inferior is situated at the lowest part of the hilus of the lung and on a plane posterior to the upper vein. Behind the pulmonary artery is the bronchus. Within the pericardium, their anterior surfaces are invested by the serous layer of this membrane.
The right atrium receives de-oxygenated blood from the body through the superior vena cava (head and upper body) and inferior vena cava (legs and lower torso). The sinoatrial node sends an impulse that causes the cardiac muscle tissue of the atrium to contract in a coordinated, wave-like manner. The tricuspid valve, which separates the right atrium from the right ventricle, opens to allow the de-oxygenated blood collected in the right atrium to flow into the right ventricle.
The right ventricle receives de-oxygenated blood as the right atrium contracts. The pulmonary valve leading into the pulmonary artery is closed, allowing the ventricle to fill with blood. Once the ventricles are full, they contract. As the right ventricle contracts, the tricuspid valve closes and the pulmonary valve opens. The closure of the tricuspid valve prevents blood from backing into the right atrium and the opening of the pulmonary valve allows the blood to flow into the pulmonary artery toward the lungs.
The left atrium receives oxygenated blood from the lungs through the pulmonary vein. As the contraction triggered by the sinoatrial node progresses through the atria, the blood passes through the mitral valve into the left ventricle.
The left ventricle receives oxygenated blood as the left atrium contracts. The blood passes through the mitral valve into the right ventricle. The aortic valve leading into the aorta is closed, allowing the ventricle to fill with blood. Once the ventricles are full, they contract. As the left ventricle contracts, the mitral valve closes and the aortic valve opens. The closure of the mitral valve prevents blood from backing into the left atrium and the opening of the aortic valve allows the blood to flow into the aorta and flow throughout the body.
The papillary muscles attach to the lower portion of the interior wall of the ventricles. They connect to the chordae tendineae, which attach to the tricuspid valve in the right ventricle and the mitral valve in the left ventricle. The contraction of the papillary muscles opens these valves. When the papillary muscles relax, the valves close.
The chordae tendineae are tendons linking the papillary muscles to the tricuspid valve in the right ventricle and the mitral valve in the left ventricle. As the papillary muscles contract and relax, the chordae tendineae transmit the resulting increase and decrease in tension to the respective valves, causing them to open and close. The chordae tendineae are string-like in appearance and are sometimes referred to as “heart strings.”
The chordae tendineae, or heart strings, are cord-like tendons that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart.
Chordae tendineae are approximately 80% collagen, while the remaining 20% is made up of elastin and endothelial cells.
Interior of right side of heart
Mechanism
During atrial systole, blood flows from the atria to ventricles down the pressure gradient. Chordae tendineae are relaxed because the atrioventricular valves are forced open.
When the ventricles of the heart contract in ventricular systole, the increased blood pressures in both chambers push the tricuspid valve and mitral valve to close simultaneously, preventing backflow of blood into the atria. Since the blood pressure in atria is much lower than that in the ventricles, the flaps attempt to evert to the low pressure regions. The chordae tendineae prevent the eversion, prolapse, by becoming tense thus pulling the flaps, holding them in closed position.[1]
Tendon of Todaro
The tendon of Todaro is a continuation of the Eustachian Valve of the Inferior vena cava and the Thebesian valve of the coronary sinus. Along with the opening of the coronary sinus and the septal cusp of the tricuspid valve, it makes up the triangle of Koch. The centre of the triangle of Koch is the location of the atrioventricular node.
The tricuspid valve separates the right atrium from the right ventricle. It opens to allow the de-oxygenated blood collected in the right atrium to flow into the right ventricle. It closes as the right ventricle contracts, preventing blood from returning to the right atrium; thereby, forcing it to exit through the pulmonary valve into the pulmonary artery.
The mitral valve separates the left atrium from the left ventricle. It opens to allow the oxygenated blood collected in the left atrium to flow into the left ventricle. It closes as the left ventricle contracts, preventing blood from returning to the left atrium; thereby, forcing it to exit through the aortic valve into the aorta.
The pulmonary valve separates the right ventricle from the pulmonary artery. As the ventricles contract, it opens to allow the de-oxygenated blood collected in the right ventricle to flow to the lungs. It closes as the ventricles relax, preventing blood from returning to the heart.
The aortic valve separates the left ventricle from the aorta. As the ventricles contract, it opens to allow the oxygenated blood collected in the left ventricle to flow throughout the body. It closes as the ventricles relax, preventing blood from returning to the heart.
Blood vessels
The blood vessels are part of the circulatory system and function to transport blood throughout the body. The most important types, arteries and veins, carry blood away from or towards the heart, respectively.
Anatomy
All blood vessels have the same basic structure. The inner lining is the endothelium and is surrounded by subendthelial connective tissue. Around this there is a layer of vascular smooth muscle, which is highly developed in arteries. Finally, there is a further layer of connective tissue known as the adventitia, which contains nerves that supply the muscular layer, as well as nutrient capillaries in the larger blood vessels.
Capillaries consist of little more than a layer of endothelium and occasional connective tissue.
When blood vessels connect to form a region of diffuse vascular supply it is called an anastamosis (pl. anastomoses). Anastomoses provide critical alternative routes for blood to flow in case of blockages.
Laid end to end, the blood vessels in an average human body will stretch approximately 62,000 miles. 2.5 times around the earth
Types
There are various kinds of blood vessels:
· Arteries
o Aorta (the largest artery, carries blood out of the heart)
o Branches of the aorta, such as the carotid artery, the subclavian artery, the celiac trunk, the mesenteric arteries, the renal artery and the iliac artery.
· Capillaries (the smallest blood vessels)
· Venules
· Veins
o Large collecting vessels, such as the subclavian vein, the jugular vein, the renal vein and the iliac vein.
o Venae cavae (the 2 largest veins, carry blood into the heart)
They are roughly grouped as arterial and venous, determined by whether the blood in it is flowing toward or away from the heart. The term “arterial blood” is nevertheless used to indicate blood high in oxygen, although the pulmonary artery carries “venous blood” and blood flowing in the pulmonary vein is rich in oxygen.
Physiology
Blood vessels do not actively engage in the transport of blood (they have no appreciable peristalsis), but arteries – and veins to a degree – can regulate their inner diameter by contraction of the muscular layer.This changes the blood flow to downstream organs, and is determined by the autonomic nervous system. Vasodilation and vasoconstriction are also used antagonistically as methods of thermoregulation.
Oxygen (bound to hemoglobin in red blood cells) is the most critical nutrient carried by the blood. In all arteries apart from the pulmonary artery, hemoglobin is highly saturated (95-100%) with oxygen. In all veins apart from the pulmonary vein, the hemoglobin is desaturated at about 70%. (The values are reversed in the pulmonary circulation.)
The blood pressure in blood vessels is traditionally expressed in millimetres of mercury (1 mmHg = 133 Pa). In the arterial system, this is usually around 120 mmHg systolic (high pressure wave due to contraction of the heart) and 80 mmHg diastolic (low pressure wave). In contrast, pressures in the venous system are constant and rarely exceed 10 mmHg.
Vasoconstriction is the constriction of blood vessels (narrowing, becoming smaller in cross-sectional area) by contracting the vascular smooth muscle in the vessel walls. It is regulated by vasoconstrictors (agents that cause vasoconstriction). These include paracrine factors (e.g. prostaglandins), a number of hormones (e.g. vasopressin and angiotensin) and neurotransmitters (e.g. epinephrine) from the nervous system.
Vasodilation is a similar process mediated by antagonistically acting mediators. The most prominent vasodilator is nitric oxide (termed endothelium-derived relaxing factor for this reason).
Permeability of the endothelium is pivotal in the release of nutrients to the tissue. It is also increased in inflammation in response to histamine, prostaglandins and interleukins, which leads to most of the symptoms of inflammation (swelling, redness and warmth).
Role in disease
Blood vessels play a role in virtually every medical condition. Cancer, for example, cannot progress unless the tumor causes angiogenesis (formation of new blood vessels) to supply the malignant cells’ metabolic demand. Atherosclerosis, the formation of lipid lumps (atheromas) in the blood vessel wall, is the prime cause of cardiovascular disease, the main cause of death in the Western world.
Blood vessel permeability is increased in inflammation. Damage, due to trauma or spontaneously, may lead to haemorrhage. In contrast, occlusion of the blood vessel (e.g. by a ruptured atherosclerotic plaque, by an embolised blood clot or a foreign body) leads to downstream ischemia (insufficient blood supply) and necrosis (tissue breakdown).
Vasculitis is inflammation of the vessel wall, due to autoimmune disease or infection.
The Heart
The heart is a muscular structure that contracts in a rhythmic pattern to pump blood. Hearts have a variety of forms: chambered hearts in mollusks and vertebrates, tubular hearts of arthropods, and aortic arches of annelids. Accessory hearts are used by insects to boost or supplement the main heart’s actions. Fish, reptiles, and amphibians have lymph hearts that help pump lymph back into veins.
The basic vertebrate heart, such as occurs in fish, has two chambers. An auricle is the chamber of the heart where blood is received from the body. A ventricle pumps the blood it gets through a valve from the auricle out to the gills through an artery.
Amphibians have a three-chambered heart: two atria emptying into a single common ventricle. Some species have a partial separation of the ventricle to reduce the mixing of oxygenated (coming back from the lungs) and deoxygenated blood (coming in from the body). Two sided or two chambered hearts permit pumping at higher pressures and the addition of the pulmonary loop permits blood to go to the lungs at lower pressure yet still go to the systemic loop at higher pressures.
Establishment of the four-chambered heart, along with the pulmonary and systemic circuits, completely separates oxygenated from deoxygenated blood. This allows higher the metabolic rates needed by warm-blooded birds and mammals.
The human heart, as seen in Figure 11, is a two-sided, four-chambered structure with muscular walls. An atrioventricular (AV) valve separates each auricle from ventricle. A semilunar (also known as arterial) valve separates each ventricle from its connecting artery.
The heart beats or contracts approximately 70 times per minute. The human heart will undergo over 3 billion contraction cycles, as shown in Figure 12, during a normal lifetime. The cardiac cycle consists of two parts: systole (contraction of the heart muscle) and diastole (relaxation of the heart muscle). Atria contract while ventricles relax. The pulse is a wave of contraction transmitted along the arteries. Valves in the heart open and close during the cardiac cycle. Heart muscle contraction is due to the presence of nodal tissue in two regions of the heart. The SA node (sinoatrial node) initiates heartbeat. The AV node (atrioventricular node) causes ventricles to contract. The AV node is sometimes called the pacemaker since it keeps heartbeat regular. Heartbeat is also controlled by nerve messages originating from the autonomic nervous system.
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Blood flows through the heart from veins to atria to ventricles out by arteries. Heart valves limit flow to a single direction. One heartbeat, or cardiac cycle, includes atrial contraction and relaxation, ventricular contraction and relaxation, and a short pause. Normal cardiac cycles (at rest) take 0.8 seconds. Blood from the body flows into the vena cava, which empties into the right atrium. At the same time, oxygenated blood from the lungs flows from the pulmonary vein into the left atrium. The muscles of both atria contract, forcing blood downward through each AV valve into each ventricle.
Diastole is the filling of the ventricles with blood. Ventricular systole opens the SL valves, forcing blood out of the ventricles through the pulmonary artery or aorta. The sound of the heart contracting and the valves opening and closing produces a characteristic “lub-dub” sound. Lub is associated with closure of the AV valves, dub is the closing of the SL valves.
Human heartbeats originate from the sinoatrial node (SA node) near the right atrium. Modified muscle cells contract, sending a signal to other muscle cells in the heart to contract. The signal spreads to the atrioventricular node (AV node). Signals carried from the AV node, slightly delayed, through bundle of His fibers and Purkinjie fibers cause the ventricles to contract simultaneously. Figure 13 illustrates several aspects of this.
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Heartbeats are coordinated contractions of heart cardiac cells, shown in an animate GIF image in Figure 14. When two or more of such cells are in proximity to each other their contractions synch up and they beat as one.
Figure 1. Animated GIF image of a single human heart muscle cell beating. |
An electrocardiogram (ECG) measures changes in electrical potential across the heart, and can detect the contraction pulses that pass over the surface of the heart. There are three slow, negative changes, known as P, R, and T as shown in Figure 15 . Positive deflections are the Q and S waves. The P wave represents the contraction impulse of the atria, the T wave the ventricular contraction. ECGs are useful in diagnosing heart abnormalities.
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Diseases of the Heart and Cardiovascular System
Cardiac muscle cells are serviced by a system of coronary arteries. During exercise the flow through these arteries is up to five times normal flow. Blocked flow in coronary arteries can result in death of heart muscle, leading to a heart attack.
Blockage of coronary arteries, shown in Figure 16, is usually the result of gradual buildup of lipids and cholesterol in the inner wall of the coronary artery. Occasional chest pain, angina pectoralis, can result during periods of stress or physical exertion. Angina indicates oxygen demands are greater than capacity to deliver it and that a heart attack may occur in the future. Heart muscle cells that die are not replaced since heart muscle cells do not divide. Heart disease and coronary artery disease are the leading causes of death in the United States.
Hypertension, high blood pressure (the silent killer), occurs when blood pressure is consistently above 140/90. Causes in most cases are unknown, although stress, obesity, high salt intake, and smoking can add to a genetic predisposition. Luckily, when diagnosed, the condition is usually treatable with medicines and diet/exercise.
The Vascular System
Two main routes for circulation are the pulmonary (to and from the lungs) and the systemic (to and from the body). Pulmonary arteries carry blood from the heart to the lungs. In the lungs gas exchange occurs. Pulmonary veins carry blood from lungs to heart. The aorta is the main artery of systemic circuit. The vena cavae are the main veins of the systemic circuit. Coronary arteries deliver oxygenated blood, food, etc. to the heart. Animals often have a portal system, which begins and ends in capillaries, such as between the digestive tract and the liver.
Fish pump blood from the heart to their gills, where gas exchange occurs, and then on to the rest of the body. Mammals pump blood to the lungs for gas exchange, then back to the heart for pumping out to the systemic circulation. Blood flows in only one direction.
Blood
Plasma is the liquid component of the blood. Mammalian blood consists of a liquid (plasma) and a number of cellular and cell fragment components as shown in Figure 21. Plasma is about 60 % of a volume of blood; cells and fragments are 40%. Plasma has 90% water and 10% dissolved materials including proteins, glucose, ions, hormones, and gases. It acts as a buffer, maintaining pH near 7.4. Plasma contains nutrients, wastes, salts, proteins, etc. Proteins in the blood aid in transport of large molecules such as cholesterol.
Red blood cells, also known as erythrocytes, are flattened, doubly concave cells about 7 µm in diameter that carry oxygen associated in the cell’s hemoglobin. Mature erythrocytes lack a nucleus. They are small, 4 to 6 million cells per cubic millimeter of blood, and have 200 million hemoglobin molecules per cell. Humans have a total of 25 trillion red blood cells (about 1/3 of all the cells in the body). Red blood cells are continuously manufactured in red marrow of long bones, ribs, skull, and vertebrae. Life-span of an erythrocyte is only 120 days, after which they are destroyed in liver and spleen. Iron from hemoglobin is recovered and reused by red marrow. The liver degrades the heme units and secretes them as pigment in the bile, responsible for the color of feces. Each second two million red blood cells are produced to replace those thus taken out of circulation.
White blood cells, also known as leukocytes, are larger than erythrocytes, have a nucleus, and lack hemoglobin. They function in the cellular immune response. White blood cells (leukocytes) are less than 1% of the blood’s volume. They are made from stem cells in bone marrow. There are five types of leukocytes, important components of the immune system. Neutrophils enter the tissue fluid by squeezing through capillary walls and phagocytozing foreign substances. Macrophages release white blood cell growth factors, causing a population increase for white blood cells. Lymphocytes fight infection. T-cells attack cells containing viruses. B-cells produce antibodies. Antigen-antibody complexes are phagocytized by a macrophage. White blood cells can squeeze through pores in the capillaries and fight infectious diseases in interstitial areas
Platelets result from cell fragmentation and are involved with clotting, as is shown by Figures 17 and 18. Platelets are cell fragments that bud off megakaryocytes in bone marrow. They carry chemicals essential to blood clotting. Platelets survive for 10 days before being removed by the liver and spleen. There are 150,000 to 300,000 platelets in each milliliter of blood. Platelets stick and adhere to tears in blood vessels; they also release clotting factors. A hemophiliac’s blood cannot clot. Providing correct proteins (clotting factors) has been a common method of treating hemophiliacs. It has also led to HIV transmission due to the use of transfusions and use of contaminated blood products.
Figure 2. Human Red Blood Cells, Platelets and T-lymphocyte (erythocytes = red; platelets = yellow; T-lymphocyte = light green) (SEM x 9,900).
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Figure 3. The formation and actions of blood clots. Images from Purves et al
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Figure 4. Blood Clot Formation
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The Lymphatic System
Water and plasma are forced from the capillaries into intracellular spaces. This interstitial fluid transports materials between cells. Most of this fluid is collected in the capillaries of a secondary circulatory system, the lymphatic system. Fluid in this system is known as lymph.
Lymph flows from small lymph capillaries into lymph vessels that are similar to veins in having valves that prevent backflow. Lymph vessels connect to lymph nodes, lymph organs, or to the cardiovascular system at the thoracic duct and right lymphatic duct.
Lymph nodes are small irregularly shaped masses through which lymph vessels flow. Clusters of nodes occur in the armpits, groin, and neck. Cells of the immune system line channels through the nodes and attack bacteria and viruses traveling in the lymph.
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