Category: H

The heart is a muscular organ in both humans and other animals, which pumps blood through the blood vessels of the circulatory system. Blood provides the body with oxygen and nutrients, and also assists in the removal of metabolic wastes. The heart is located in the middle compartment of the mediastinum in the chest.

In humans, other mammals and birds the heart is divided into four chambers: upper left and right atria; and lower left and right ventricles. Commonly the right atrium and ventricle are referred together as the right heart and their left counterparts as the left heart. Fish in contrast have two chambers, an atrium and a ventricle, while reptiles have three chambers. In a healthy heart blood flows one way through the heart due to heart valves, which prevent backflow. The heart is enclosed in a protective sac, the pericardium, which also contains a small amount of fluid. The wall of the heart is made up of three layers: epicardium; myocardium; and endocardium.

The heart pumps blood through both circulatory systems. Blood low in oxygen from the systemic circulation enters the right atrium from the superior and inferior vena cavae and passes to the right ventricle. From here it is pumped into thepulmonary circulation, through the lungs where it receives oxygen and gives off carbon dioxide. Oxygenated blood then returns to the left atrium, passes through the left ventricle and is pumped out through the aorta to the systemic circulation−where the oxygen is used and metabolized to carbon dioxide. In addition the blood carries nutrients from the liver and gastrointestinal tract to various organs of the body, while transporting waste to the liver and kidneys. Normally with each heartbeat, the right ventricle pumps the same amount of blood into the lungs as the left ventricle pumps out into the body. Veins transport blood to the heart, while arteries transport blood away from the heart. Veins normally have lower pressures than arteries. The heart contracts at a rate of around 72 beats per minute, at rest. Exercise temporarily increases this rate, but lowers resting heart rate in the long term, and is good for heart health.

Cardiovascular diseases (CVD) were the most common cause of death globally in 2008. CVD accounted for 30% of death cases during this year alone. Of these deaths more than three quarters were due to coronary artery disease and stroke. Risk factors include: smoking, being overweight, not enough exercise, high cholesterol, high blood pressure, and poorly controlled diabetes among others. Diagnosis of CVD is often done by listening to the heart-sounds with astethoscope, ECG or by ultrasound. Diseases of the heart are primarily treated by cardiologists, although many specialties of medicine may be involved.

The hematocrit (Ht or HCT, British English spelling haematocrit), also known as packed cell volume (PCV) orerythrocyte volume fraction (EVF), is the volume percentage (%) of red blood cells in blood. It is normally 45% for men and 40% for women. It is considered an integral part of a person’s complete blood count results, along with hemoglobinconcentration, white blood cell count, and platelet count. Because the purpose of red blood cells is to transfer oxygen from the lungs to body tissues, a blood sample’s hematocrit—the red blood cell volume percentage—can become a point of reference of its capability of delivering oxygen. Additionally, the measure of a subject’s blood sample’s hematocrit levels may expose possible diseases in the subject. Anemia refers to an abnormally low hematocrit, as opposed topolycythemia, which refers to an abnormally high hematocrit. For a condition such as anemia that goes unnoticed, one way it can be diagnosed is by measuring the hematocrit levels in the blood. Both are potentially life-threatening disorders.

Hematology, also spelled haematology (from the Greek αἷμα, haima “blood” and -λoγία), is the branch of medicine concerned with the study, diagnosis, treatment, and prevention of diseases related to the blood. Hematology includes the study of etiology. It involves treating diseases that affect the production of blood and its components, such as blood cells, hemoglobin, blood proteins, and the mechanism of coagulation. The laboratory work that goes into the study of blood is frequently performed by a medical technologist. Hematologists also conduct studies in oncology—the medical treatment of cancer.

Physicians specialized in hematology are known as hematologists or haematologists. Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewing blood films and bone marrow slides under the microscope, interpreting various hematological test results and blood clotting test results. In some institutions, hematologists also manage the hematology laboratory. Physicians who work in hematology laboratories, and most commonly manage them, are pathologists specialized in the diagnosis of hematological diseases, referred to as hematopathologists or haematopathologists. Hematologists and hematopathologists generally work in conjunction to formulate a diagnosis and deliver the most appropriate therapy if needed. Hematology is a distinct subspecialty of internal medicine, separate from but overlapping with the subspecialty of medical oncology. Hematologists may specialize further or have special interests, for example, in:

• treating bleeding disorders such as hemophilia and idiopathic thrombocytopenic purpura
• treating hematological malignacies such as lymphoma and leukemia
• treating hemoglobinopathies
• in the science of blood transfusion and the work of a blood bank
• in bone marrow and stem cell transplantation

Hemoglobin (also spelled haemoglobin and abbreviated Hb or Hgb), is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates (with the exception of the fish family Channichthyidae) as well as the tissues of some invertebrates. Hemoglobin in the blood carries oxygen from the respiratory organs (lungs or gills) to the rest of the body (i.e. the tissues). There it releases the oxygen to permitaerobic respiration to provide energy to power the functions of the organism in the process called metabolism.

In mammals, the protein makes up about 96% of the red blood cells’ dry content (by weight), and around 35% of the total content (including water). Hemoglobin has an oxygen-binding capacity of 1.34 mL O2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. The mammalian hemoglobin molecule can bind (carry) up to four oxygen molecules.

Hemoglobin is involved in the transport of other gases: It carries some of the body’s respiratory carbon dioxide (about 10% of the total) as carbaminohemoglobin, in which CO2 is bound to the globin protein. The molecule also carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen.

Hemoglobin is also found outside red blood cells and their progenitor lines. Other cells that contain hemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, and mesangial cells in the kidney. In these tissues, hemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism.

Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. In these organisms, hemoglobins may carry oxygen, or they may act to transport and regulate other things such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghemoglobin, is used to scavenge oxygen away from anaerobic systems, such as the nitrogen-fixing nodules of leguminous plants, before the oxygen can poison the system.

Haemophilia (also spelled hemophilia in North America) is a group of hereditary genetic disorders that impair the body’s ability to control blood clotting, which is used to stop bleeding when a blood vessel is broken.

Haemophilia A (clotting factor VIII deficiency) is the most common form of the disorder, present in about 1 in 5,000–10,000 male births.

Haemophilia B (factor IX deficiency) occurs in around 1 in about 20,000–34,000 male births.

Like most recessive sex-linked, X chromosome disorders, haemophilia is more likely to occur in males than females. This is because females have two X chromosomes while males have only one, so the defective gene is guaranteed to manifest in any male who carries it. Because females have two X chromosomes and haemophilia is rare, the chance of a female having two defective copies of the gene is very remote, so females are almost exclusively asymptomatic carriersof the disorder. Female carriers can inherit the defective gene from either their mother or father, or it may be a new mutation. Although it is not impossible for a female to have haemophilia, it is unusual: a female with haemophilia A or B would have to be the daughter of both a male haemophiliac and a female carrier, while the non-sex-linked haemophilia C due to coagulant factor XI deficiency, which can affect either sex, is more common in Jews of Ashkenazi (east European) descent but rare in other population groups.

Haemophilia patients have lower clotting factor level of blood plasma or impaired activity of the coagulation factors needed for a normal clotting process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent fibrin formation, which is necessary to maintain the blood clot. A haemophiliac does not bleed more intensely than a person without it, but can bleed for a much longer time. In severe haemophiliacs even a minor injury can result in blood loss lasting days or weeks, or even never healing completely. In areas such as the brain or inside joints, this can be fatal or permanently debilitating.

Hemophilia A (also known as haemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. About 70% of the time it is inherited as an X-linked recessive trait, but around 30% of cases arise from spontaneous mutations.

Hemophilia A is inherited as an X-linked recessive trait, and thus occurs in males and in homozygous females. However, mild hemophilia A (and B) is known to occur in heterozygous females due to X-inactivation, so it is recommended that levels of factor VIII and IX be measured in all known or potential carriers prior to surgery and in the event of clinically significant bleeding.

5-10% of patients with hemophilia A are affected because they make a dysfunctional version of the factor VIII protein (qualitative deficiency), while the remainder are affected because they produced factor VIII in insufficient amounts (quantitative deficiency). Of those who have severe deficiency (defined as <1% activity of factor VIII), 45-50% have the same mutation, an inversion within the factor VIII gene that results in total elimination of protein production. However, since both forms of hemophilia can be caused by a variety of different mutations, initial diagnosis and classification is done by measurement of protein activity rather than by genetic tests, though genetic tests are recommended for testing of family members once a known case of hemophilia B is identified.

Haemophilia B (or hemophilia B) is a blood clotting disorder caused by a mutation of the factor IX gene, leading to a deficiency of factor IX. It is the second-most common form of hemophilia, rarer than hemophilia A. It is sometimes called Christmas disease, named after Stephen Christmas, the first patient described with this disease. In addition, the first report of its identification was published in the Christmas edition of the British Medical Journal.

The factor IX gene is located on the X chromosome (Xq27.1-q27.2). It is an X-linked recessive trait, which explains why, as in hemophilia A, usually only males are affected. One in 20,000–30,000 males are affected.

Hemostasis or haemostasis is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves blood changing from a liquid to a gel. Intact blood vessels are central to moderating blood’s tendency to clot. The endothelial cells of intact vessels prevent blood clotting with a heparin-like molecule andthrombomodulin and prevent platelet aggregation with nitric oxide and prostacyclin. When endothelial injury occurs, the endothelial cells stop secretion of coagulation and aggregation inhibitors and instead secrete von Willebrand factor which initiate the maintenance of hemostasis after injury. Hemostasis has three major steps: 1) vasoconstriction, 2) temporary blockage of a break by a platelet plug, and 3) blood coagulation, or formation of a fibrin clot. These processes seal the hole until tissues are repaired.

PROCESS

Hemostasis occurs when blood is present outside of the body or blood vessels. It is the instinctive response for the body to stop bleeding and loss of blood. During hemostasis three steps occur in a rapid sequence. Vascular spasm is the first response as the blood vessels constrict to allow less blood to be lost. In the second step, platelet plug formation, platelets stick together to form a temporary seal to cover the break in the vessel wall. The third and last step is called coagulation or blood clotting. Coagulation reinforces the platelet plug with fibrin threads that act as a “molecular glue”. Platelets are a large factor in the hemostatic process. They allow for the creation of the “platelet plug” that forms almost directly after a blood vessel has been ruptured. Within seconds of a blood vessel’s epithelial wall being disrupted platelets begin to adhere to the sub-endotheliumsurface. It takes approximately sixty seconds until the first fibrin strands begin to intersperse among the wound. After several minutes the platelet plug is completely formed by fibrin. Hemostasis is maintained in the body via three mechanisms:

1. Vascular spasm – Damaged blood vessels constrict. Vascular spasm is the blood vessels’ first response to injury. The damaged vessels will constrict (vasoconstrict) which reduces the amount of blood flow through the area and limits the amount of blood loss. This response is triggered by factors such as a direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, and reflexes initiated by local pain receptors. The spasm response becomes more effective as the amount of damage is increased. Vascular spasm is much more effective in smaller blood vessels.

2. Platelet plug formation – Platelets adhere to damaged endothelium to form platelet plug (primary hemostasis) and then degranulate. This process is regulated through thromboregulation. Platelets play one of the biggest factors in the hemostatic process. Being the second step in the sequence they stick together (aggregation) to form a plug that temporarily seals the break in the vessel wall. As platelets adhere to the collagen fibers of a wound they become spiked and much stickier. They then release chemical messengers such as adenosine diphosphate (ADP), serotonin and thromboxane A2. These chemicals are released to cause more platelets to stick to the area and release their contents and enhance vascular spasms. As more chemicals are released more platelets stick and release their chemicals; creating a platelet plug and continuing the process in a positive feedback loop. Platelets alone are responsible for stopping the bleeding of unnoticed wear and tear of our skin on a daily basis.

The second stage of hemostasis involves platelets that move throughout the blood. When the platelets find an exposed area or an injury, they begin to form what is called a platelet plug. The platelet plug formation is activated by a glycoprotein called the Von Willebrand factor (vWF), which are found in the body’s blood plasma. When the platelets in the blood are activated, they then become very sticky so allowing them to stick to other platelets and adhere to the injured area.

There are a dozen proteins that travel along the blood plasma in an inactive state and are known as clotting factors. Once the platelet plug has been formed by the platelets, the clotting factors begin creating the Blood Clot. When this occurs the clotting factors begin to form a collagen fiber called fibrin. Fibrin mesh is then produced all around the platelet plug, which helps hold the fibrin in place. Once this begins, red and white blood cells become caught up in the fibrin mesh which causes the clot to become even stronger.

3. Blood coagulation – Clots form upon the conversion of fibrinogen to fibrin, and its addition to the platelet plug (secondary hemostasis). Coagulation: The third and final step in this rapid response reinforces the platelet plug. Coagulation or blood clotting uses fibrin threads that act as a glue for the sticky platelets. As the fibrin mesh begins to form the blood is also transformed from a liquid to a gel like substance through involvement of clotting factors and pro-coagulants. The coagulation process is useful in closing up and maintaining the platelet plug on larger wounds. The release of Prothrombin also plays an essential part in the coagulation process because it allows for the formation of a thrombus, or clot, to form. This final step forces blood cells and platelets to stay trapped in the wounded area. Though this is often a good step for wound healing, it has the ability to cause severe health problems if the thrombus becomes detached from the vessel wall and travels through the circulatory system; If it reaches the brain, heart or lungs it could lead to stroke, heart attack, or pulmonary embolism respectively. However, without this process the healing of a wound would not be possible.

DISORDERS

The body’s hemostasis system requires careful regulation in order to work properly. If the blood does not clot sufficiently, it may be due to bleeding disorders such ashemophilia; this requires careful investigation. Over-active clotting can also cause problems; thrombosis, where blood clots form abnormally, can potentially causeembolisms, where blood clots break off and subsequently become lodged in a vein or artery.

Hemostasis disorders can develop for many different reasons. They may be congenital, due to a deficiency or defect in an individual’s platelets or clotting factors. A number of disorders can be acquired as well.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB (Granzyme B), and tumor metastasis. HS has been shown to serve as cellular receptor for a number of viruses including the respiratory syncytial virus.

Heparin, also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and renal dialysis machines.

Although it is used principally in medicine for anticoagulation, its true physiological role in the body remains unclear, because blood anticoagulation is achieved mostly by heparan sulfate proteoglycans derived from endothelial cells. Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials. In addition, it is observed across a number of widely different species, including some invertebrates that do not have a similar blood coagulation system.

It is on the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.

Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate (“minor antithrombin”).

The product encoded by this gene is a serine proteinase inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. The gene contains five exons and four introns. This protein shares homology with antithrombin III and other members of the alpha 1-antitrypsin superfamily. Mutations in this gene are associated with heparin cofactor II deficiency. Heparin Cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state.

Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis, the abnormal formation of blood clots inside a blood vessel, and when thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood tests.

The treatment of HIT requires both protection from thrombosis and choice of an agent that will not reduce the platelet count further. Several agents exist for this purpose, mainly lepirudin and argatroban. While heparin was discovered in the 1930s, HIT was not reported until the 1960s and 1970s.

Hereditary angioedema (types I, II and III) (also known as “HAE”) is a rare, autosomal dominantly inherited blood disorder that causes episodic attacks of swelling that may affect the face, extremities, genitals, gastrointestinal tract and upper airways. Swellings of the intestinal mucosa may lead to vomiting and painful, colic-like intestinal spasms that may mimic intestinal obstruction. Airway edema may be life-threatening. Episodes may be triggered by trauma, surgery, dental work, menstruation, some medications, viral illness and stress; however, this is not always readily determined. This disorder affects approximately one in 10,000–50,000 people.

HAE type I primarily caused because of abnormally low concentration some complex blood proteins (C1 esterase inhibitors), also called complements. These help to control various body functions such as the flow of body fluids in and out of cells. It is responsible for approximately 80-85% of this disorder.

HAE type II is a more infrequent form of this disorder. It occurs due to the fabrication of atypical complement proteins and accounts for about 15-20% of this disorder . Type III is not common and was documented recently. This type mainly afflicts females and it is influenced by contact with estrogens and also by hormone replacement therapy (e.g. oral contraceptives and pregnancy) and this is not connected with the deficiency of C1-INH.

HAE type III is not necessarily caused by C1-INH deficiency; it is credited to a rise in the action of the enzyme kininogenase’s and this then leads to rise in the levels of bradykinin. Some patients who have the type III HAE will have an alteration in the F12 gene and this produces a protein which participates in the clotting of blood . Some patients with type III HAE have a mutation in the F12 gene which produces a protein involved in blood clotting.

The underlying cause of HAE is attributed to autosomal dominant inheritance of mutations in the C1 inhibitor (C1-INH gene or SERPING1 gene), which is mapped to chromosome 11 (11q12-q13.1).To date there are over 300 known genetic mutations that result in a deficiency of functional C1 Inhibitor. 2-4 The majority of HAE patients have a family history; however, 25% are the result of new mutations. The low level of C1 inhibitor in the plasma leads to increased activation of pathways that release bradykinin, the chemical responsible for the angioedema due to increased vascular permeability, and the pain seen in individuals with HAE.

High molecular weight kininogen (HMWK or HK) is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the Kallikrein-kinin system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation.

Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin.

A key event in the final stages of blood coagulation is the conversion of fibrinogen into fibrin by the serine protease enzyme thrombin. Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor), in the final states of coagulation. Fibrin is then cross linked by factor XIII (Fibrin Stabilizing Factor) to form a blood clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin. Similar to antithrombin III, the anticoagulatant activity of hirudin is based on its ability to inhibit the procoagulant activity of thrombin.

Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin, hirudin binds to and inhibits only the activity of thrombin, with a specific activity on fibrinogen. Therefore, hirudin prevents or dissolves the formation of clots and thrombi (i.e., it has a thrombolytic activity), and has therapeutic value in blood coagulation disorders, in the treatment of skin hematomas and of superficial varicose veins, either as an injectable or a topical application cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum proteins, and can also act on complexed thrombin.

It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein using recombinant biotechnology has been developed. This has led to the development and marketing of a number of hirudin-based anticoagulant pharmaceutical products. Several other direct thrombin inhibitors are derived chemically from hirudin.

The fibrinolysis system is responsible for removing blood clots. Hyperfibrinolysis describes a situation with markedly enhanced fibrinolytic activity, resulting in increased, sometimes catastrophic bleeding. Hyperfibrinolysis can be caused by acquired or congenital reasons. Among the congenital conditions for hyperfibrinolysis, deficiency of alpha-2-antiplasmin (alpha-2-plasmin inhibitor) or plasminogen activator inhibitor type 1 (PAI-1) are very rare. The affected individuals show ahemophilia-like bleeding phenotype. Acquired hyperfibrinolysis is found in liver disease, in patients with severe trauma, during major surgical procedures, and other conditions. A special situation with temporarily enhanced fibrinolysis is thrombolytic therapy with drugs which activate plasminogen, e.g. for use in acute ischemicevents or in patients with stroke. In patients with severe trauma, hyperfibrinolysis is associated with poor outcome.

Bleeding is caused by the generation of fibrinogen degradation products which interfere with regular fibrin polymerization and inhibit platelet aggregation. Moreover, plasmin which is formed in excess in hyperfibrinolysis can proteolytically activate or inactivate many plasmatic or cellular proteins involved in hemostasis. Especially the degradation of fibrinogen, an essential protein for platelet aggregation and clot stability, may be a major cause for clinical bleeding.