Sickle Cell

Sickle cell is a term used to describe any condition that involves inherited sickle-cell-shaped hemoglobin of the blood.

There are many different causes of human disease: malnutrition, infection, radiation, physical injury, and mistakes in body chemistry. Sickle cell disease is the result of the last one. It cannot be outgrown, and those who are not born with it cannot contract it. It is not contagious and not caused by anything with which a person might come in contact.

Painful episodes are characteristic. Other problems also include the vulnerability to infection, anemia, organ damage, and a tendency to form gallstones. Understandably, emotional problems can be expected to follow the physical ones.

Normal hemoglobin, called hemoglobin A or hemoglobin C, is characterized by rounded red blood cells which flow easily through the body’s vessels.

Sickle-cell hemoglobin, called hemoglobin S (HbS) is contained in sickle-shaped, elongated cells that resist flow and cause obstructions in circulation (microinfarctions), a lack of oxygen to the tissues (hypoxia), and the proliferation of additional sickle cells.

Sickle cells also have a shorter than average lifetime – 20 days as opposed to 120 of normal red blood cells. Sickle-cell disease occurs when hemoglobin A is changed to hemoglobin S by a genetic substitution of one amino acid in the hemoglobin chain.

When sickle cell hemoglobin cannot reach other parts of the body, a series of problems develop, often referred to as a ‘crisis’. Hemoglobin travels inside a red blood cell which must squeeze through tiny blood vessels, as well as the larger ones. Normally, squeezing through tiny capillaries poses no problem because the disc-shaped cell is always soft and flexible. However, inside a sickled red blood cell, crystals form that twist the cell out of shape, causing it to lose softness and flexibility, which damages the cell membrane itself.

This type of damage has the following effects. Since the red blood cells cannot squeeze through small blood vessels, the vessels become clogged and blood flow backs up so that oxygen cannot be delivered to organs and tissues. When an organ has its oxygen supply cut off, damage begins, causing pain and other problems.

The damage can be serious and the pain excruciating. When red blood cells are damaged, the body destroys them, but so many are damaged and destroyed in sickle cell crisis that the patient suffers from chronic anemia. Therefore, such people are more susceptible to infections and are frequently incapacitated.

Sickle cell disease is most common among those of African descent and those with ancestors from Puerto Rico, Cuba, Haiti, Jamaica, Italy, Sicily, Greece, Cyprus, Turkey, Syria, and South India. It affects about one in 375 Americans of African descent, and the trait is present in one out of every ten. Some of these individuals know they carry the gene. Others do not.

However, many people do not realize that whites can also carry the sickle cell gene. A blonde-haired, blue-eyed person can have sickle cell disease, which occurs mainly among whites from the Middle East, India, and the Mediterranean. It is also common among Israeli Arabs, Saudis, and Turks. The case that led to the important discovery by Dr. William Castle in 1938 that sickling slows down the blood flow, involved a white woman from Cleveland, Ohio, whose family was Italian.

Various forms of sickle cell are often used interchangeable, but the correct terms are as follows:

Sickle cell anemia: This is the homozygous form. (Homozygous refers to two genes at the same loci on different chromosomes relating to the same characteristic. The two genes in this case are identical – both are either recessive or dominant). Sickle cell anemia is actually a group of diseases collectively termed hemoglobinopathies in which normal adult hemoglobin (HbA) is partly or completely replaced by abnormal sickle hemoglobin (HbS). Other correct terms are SS and homozygous sickle cell disease.

Sickle cell trait: This is the heterozygous form (HbA and HbS or HbAS). (Heterozygous refers to the presence of two genes at the same loci on different chromosomes that relate to the same characteristic. The two genes in this case are different – one is recessive, the other dominant). Sickle cell trait never progresses to sickle cell disease. Those with sickle cell trait are carriers, and 20% to 40% of their total hemoglobin is HbS while the rest is normal HbA. Although each parent makes an equal contribution to a child’s heredity, not all genes have an equal effect. Some are dominant and mask the presence of recessive genes. For such traits as A and B blood types, each parental gene is equally influential or codominant. Sometimes traits are formed through a mutation, or altered gene. Many such formations are harmless, but more than 2,000 diseases, including sickle cell disease, are known to be caused by mutations of a single gene; and another 2,000, at least, are suspected to be.

Sickle cell disease (SCD):This includes all those hereditary disorders, plus the clinical, hematologic, and pathologic features which are related to the presence of HbS. For this reason, this category will also include sickle cell anemia and sickle cell trait. Sickle cell disease occurs when both copies of a single hemoglobin gene are altered. Since sickle cells have a shorter life span than normal cells, their rapid breakdown rate results in a lowered hemoglobin level, or anemia. Thus, sickle-cell disease is often referred to as sickle-cell anemia; but this is technically incorrect. The most common forms of SCD are:

• Sickle cell-C disease (sickle cell-hemoglobin C disease) is a heterozygous variant of SCD, including both HbS and HbC found primarily among people from West Africa.
• Sickle cell-hemoglobin E disease is a variant of SCD in which glutamic acid has been substituted for lysine in the number 26 position of the beta chain.
• Sickle thalassemia disease (hemoglobin S-beta-thalassemia) is a combination of sickle cell trait and beta-thalassemia trait. In beta thalassemia, the amount, rather than the kind, of hemoglobin is abnormal. It is found primarily among people from areas around the Mediterranean Sea – which is how the disease obtained its name as thalassa is the Greek word for “sea”.

Acquiring sickle cell
The following six scenarios will show the probability of acquiring the sickle cell gene.

• Both parents have sickle cell disease. Since sickle cell disease is recessive, both parents must have two copies of the HbS gene or they would not have the disease. Therefore, no matter which gametes combine to form a child, the results will be the same; and every child of this union will receive one HbS gene from its mother and one from its father. All children born to this couple will have sickle cell disease.
• One parent has sickle cell disease and the other has the sickle cell trait. The parent with the disease has only the HbS genes. Therefore, all of his/her gametes will have HbS genes. The other parent has one HbS gene and one HbA gene. Therefore, the odds of that parent transmitting either gene are 50/50. For this couple, two types of conception are equally possible – one between two gametes carrying HbS genes, and one between a gamete carrying an HbS gene and a gamete carrying an HbA gene. All children born to this couple will display either sickle cell disease or sickle cell trait. The odds are 50/50 for each.
• One parent has sickle cell disease and the other parent is normal. In this case, “normal” means that both of the hemoglobin genes are HbA. All gametes of the sickle cell parent will carry the HbS gene and all the gametes of the normal parent will carry the HbA gene. Therefore, all their children will inherit one normal and one sickle cell gene and all the children will have the sickle cell trait.
• Both parents have the sickle cell trait. Both parents have an equal chance of transmitting either gene. Half of the time, one parent will transmit the HbS gene which will have an equal chance of combining with another HbS gene or with an HbA gene from the other parent. The other half of the time, the first parent will transmit an HbA gene which will also have an equal chance of combining with an HbS gene or an HbA gene from the other parent. This all means that there is a 25% chance that there will be a union of an HbS gene with another HbS gene, a 50% chance that there will be a union of an HbS gene with an HbA gene, and a 25% chance of a union between an HbA gene and another HbA gene. Therefore, children born to this couple will have a 25% chance of contracting sickle cell disease, a 50% chance of carrying sickle cell trait, and a 25% chance of being normal.
• One parent has sickle cell trait and the other is normal. Half of the gametes of the parent with the sickle cell trait will carry the HbS gene and half will carry the HbA gene. Since all the gametes of the other normal parent will carry an HbA gene, half of the conceptions will result in a union of an HbS gene with an HbA gene and half will result in a union of two HbA genes. All the children of this couple will either display sickle cell trait or be normal – the chances are 50/50 for each.
• Both parents are normal. Neither parent has a sickle cell gene to transmit. All children born to this couple will be normal. This will be the case even if the preceding generation (the parents) carried sickle cell genes.

Lifetime outline
The following is an outline of a lifetime and what can be expected by a sickle cell patient. However, not all are alike and will not display every complication of the disease. In addition, some complications are common while others are rare, occurring only in acute episodes.

Infancy: Prior to birth, both normal and sickle cell fetuses make HbF (fetal hemoglobin) blood. After birth, HbF production is replaced by HbA in healthy babies and by HbS gene in sickle cell babies. Although HbA is generally referred to as “adult” hemoglobin, it would be more accurate to refer to it as “after birth” hemoglobin. During early infancy, depending on how long it takes for HbS to become the dominant form, the baby with sickle cell disease is usually without symptoms. Early symptoms may include listlessness; aches in the arms, legs, stomach, and back; poor appetite; and pallor. Infections usually start after two or three months, but many children remain symptom-free for a year or more. In the absence of prophylactic antibiotics, children die of infections between the ages of one and three years. As screening of newborns becomes more prevalent, such early deaths will decrease.

Early childhood: Hand-foot syndrome is often the first problem to present itself. This syndrome is characterized by swelling and pain in the joints of the hands and feet. Infections, especially those of the lungs and kidneys, begin to occur at the same time, although their incidence can be reduced through the use of prophylactic antibiotics (the choice can be either pharmaceutical drugs or plant-based remedies). Pneumococcal septicemia is one of the more common problems. Infections are often associated with painful episodes which can produce organ damage. By the age of two, the child usually has an enlarged spleen and there is a danger of splenic sequestration. Other problems common to early childhood include anemia and gallstones. Occasionally, young boys can suffer episodes of priapism (painful, abnormal, and persistent erection).

In splenic sequestration, the enlarged spleen traps a large portion of the body’s red blood cells so that inadequate numbers circulate. In acute cases of splenic sequestration, the entrapment of a major portion of the body’s red blood cells causes an acute, life-threatening anemia that must be treated by transfusion. Even more red blood cells are destroyed by the enlarged spleen, and the life of the already shortened lifespan of the blood cell becomes even less. This takes a heavy toll on the body, which is already struggling to provide energy and nutrients to meet the demands of the perpetual blood cell production. Hence, children with hypersplenism are usually smaller for their age than even other sickle cell children who are smaller than normal themselves. Their enlarged abdomens usually reflect the size of their enlarged organs.

Mid to late childhood: Splenic sequestration and hand-foot syndrome usually are not problems for children after the age of five, and infections become less frequent by age ten. However, strokes, which were not very common in the very first years of life, increase in frequency. Strokes can affect intellectual ability, eyesight, speech, as well as the ability to move or to sense the environment and can bring death. Priapism also increases in frequency in later childhood. Painful episodes and their accompanying organ damage increase. Physical growth is retarded and malnourishment is common. Since the nutritional demands of massive red blood cell production and constant tissue repair may not be met by most diets and the slower growth rates could be due to this undernourishment.

Adolescence: On entering adolescence, sickle cell children find themselves smaller, lighter, and less sexually developed than their peers. The bodily hair patterns that signal maturity are late in coming for both sexes, and boys may have smaller testicles than their healthier peers and correspondingly lower levels of the testosterone hormone. Girls may lag a year or more behind their peers in the onset of menstruation and breast development. Menstruation is likely to be painful and less regular. Nevertheless, pregnancy can still be achieved. A manifestation of sickle cell disease that becomes frequent in adolescence, especially boys, is leg ulcerations. In addition to being painful and a potential source of infection, these open sores often interfere with social activities and employment opportunities. Painful episodes become more frequent and a hip-joint injury may become extensive enough to curtail ordinary activities, necessitating surgery or the use of crutches. Bed-wetting is common, and a painful priapism (n erect penis or clitoris which does not return to normal) disrupts sleep.

Adulthood: Painful episodes and leg ulcerations become less frequent for the adult. However, strokes, which were common in early childhood, re-emerge as a threat during the third decade of life. In the kidney, repeated injuries and scarring accumulate, which lessen the organ’s ability to function. Chronic kidney failure, which increases with age, causes illness and death. Heart failure may also strike sooner.

Pregnancy: Pregnancy used to present a major risk to women with sickle cell disease, but maternal mortality rates have steadily declined over the years with today’s rates being very low. Prenatal care from the very beginning is strongly recommended since the woman with sickle cell disease is not starting out in top notch condition and she may not thrive with the added physical demands of a pregnancy. Toxemia, thrombophlebitis, kidney disease, heart failure, and spontaneous abortions occur with greater frequency in a sickle cell woman who is pregnant than in those who do not carry the disease. In addition, anemia, bone pain, and chest pain become more common during pregnancy. Additional folic acid and iron supplements will be prescribed to reduce the likelihood of anemia. The placenta, with its numerous tiny blood vessels and sinusoids and its high oxygen needs, is particularly vulnerable to blood flow blockage. In the late stages of pregnancy, other organs commonly undergo blood vessel blockage, including the lungs, kidneys, and the brain. Even in the face of such problems, sickle cell mothers can have successful pregnancies.

Sickle Cell Trait: Those with sickle cell trait are very much like those with two HbA genes. Sickle cell traits run in the same families as the disease, but those with the traits do not have the disease. They can, however, pass these traits on to their children who could have the disease. Those with the sickle cell trait live as long and are not hospitalized any more often than those with normal hemoglobin. They do not have episodes of sickle cell disease unless they are subject to extreme oxygen deprivation. However, people with sickle cell trait do occasionally display symptoms. Some cannot produce concentrated urine and, as a result, need to urinate more frequently. Some may find blood in their urine occasionally caused by sickling in the kidneys, but this is not associated with painful episodes. Sometimes, sickling occurs in the spleen and, very rarely, in other organs. All in all, people with sickle cell trait tend to lead relatively normal lives, and the only thing to worry about is family planning.

Crisis
Sickle cell disease is painful. Not always, and not necessarily often, but painful episodes are characteristic of the disease and are often referred to as “crisis” periods. These may last a few days or sometimes for weeks and are often preceded by an infection, cold, or sore throat. Crisis may recur several times a year with the patient remaining quite healthy between occurrences. Crisis periods may range in intensity from annoying to excruciating.

Most of the painful episodes occur when abnormal blood cells block small blood vessels. When these vessels are blocked, blood cannot flow through them and deliver oxygen to the parts of the body supplied by these vessels. When the body parts are deprived of oxygen, they release chemicals that cause pain; and, if the blood flow is not restored, tissue damage follows. Where tissue is damaged, the area becomes inflamed; and this, too, becomes a source of pain. Fever often accompanies painful episodes.

There are several types of sickle cell crisis which can occur, including vaso-occlusives (VOCs), acute splenic squestration, aplastic, hyperhemolytic, stroke, chest syndrome, and infection.

These crises may occur individually or with one or more of the other crisis.

• Vaso-occlusive crises (VOCs) are the most common, non-life-threatening crises. They are the result of sickled cells obstructing the blood vessels, causing occlusion, ischemia, and potentially necrosis. VOCs can result in a variety of skeletal problems and one of the more frequent is “hand-foot syndrome”.
• Megaloblastic anemia is attributed to an excessive nutritional need for folic acid and/or vitamin B12 during periods of pronounced erythropoiesis. Therefore, it is possible that such a deficiency can precede aplastic or hypoplastic crises.
• Hyperhemolytic crisis occurs when there is an accelerated rate of RBC destruction characterized by anemia, jaundice, and reticulocytosis. This complication frequently suggests such other coexisting conditions as viral illness, transfusion reactions to alloantibodies, or glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is also common in black persons.

It is difficult to predict what will trigger a painful episode, but some indications point to infections, too little fluid intake, cold weather, excessive physical stress, and emotional pain. The parts of the body in which painful episodes are most common are the bones, chest, and abdomen.

Bones: Like other living tissues, bones need a constant supply of blood, but sometimes this circulation faces obstacles. Although the average lifespan of a normal red blood cell is 120 days, the average for a sickled blood cell is only 20 days. This means that the red cell production must proceed at an accelerated rate to replace all those that are being destroyed, and the bone marrow may not be able to keep up with demand. Among the materials needed for red blood cell production is a vitamin called folic acid, or folacin. Since red blood cells are in full-time production in sickle cell disease, large amounts of this vitamin are used and, therefore, required.

Blood must travel through many tiny openings called sinusoids, which are the sponge-like areas of the bone. In sickle cell disease, the inflexible and sickled blood cells often become trapped in the sinusoids. This blocks circulation and causes bone and joint pain which generally lasts several days. In the very young, blocked blood flow in the bones of the hands and feet causes local swelling accompanied by pain and fever. This is called hand-foot syndrome and is often the first symptom of the disease a child may display. Its appearance is often the ugly message to parents that their child has sickle cell disease. Hand-foot syndrome usually lasts about a week, with or without medical treatment, and it can recur.

The location of the bone pain generally changes as people grow. Older children often suffer episodes of pain in the bones of their arms and legs, which may be accompanied by swelling and fever. The hip and shoulder joints are common sites of pain in the adolescent and the adult. The hip joint, which bears much of weight in daily routine, can suffer serious damage if not cared for by resting during these episodes. Although back pain is also common, facial bone pain is not.

Chest: The lungs are where the red blood cells obtain the oxygen they need to deliver to every cell in the body and where they get rid of the carbon dioxide waste. Oxygen enters the lungs through chest expansion as fresh air is inhaled. In sickle cell disease individuals, the chest is often narrower and the heart larger than normal. Both these conditions leave less room for the lungs to expand and, therefore, less oxygen is inhaled.

In addition, the volume of blood that passes through the lungs of the sickle cell patient is larger than that of healthy individuals, so more work is required by the lungs. Therefore, when the lungs of a sickle cell person undergoes blood vessel blockage or become infected, the situation is especially dangerous. Patients may be stricken with severe chest pain, fever, coughing, and difficulty breathing. This is known as acute chest syndrome.

There can also be accompanying bone pain. Since lung involvement can spread and even be fatal if appropriate treatment is not given, hospitalization is required. Repeated episodes of acute chest syndrome can lead to chronic lung disease.

Abdomen: Blockage of blood vessels serving the abdominal region gives rise to abdominal pain that generally persists for four or five days. Two vulnerable organs are the liver and spleen.

The liver plays a significant role in digestion, excretion of waste material, energy metabolism, the removal of toxic products from the blood, and blood cell and nutrient storage. Blood cells often become trapped in the liver of sickle cell disease patients. The organ then builds up pigment, deposits, injuries, and scarring. When the liver becomes infected in such a manner, patients feel pain in the upper right side of the abdomen. They will likely develop a yellowing of the skin and the whites of the eyes (sclera), a condition known as jaundice. Fever can also accompany the condition.

The source of the yellowing is the pigment called bilirubin, a hemoglobin waste product that is supposed to be removed from the blood plasma by the liver; but, if the liver is not able to function properly, there will be too much bilirubin to process. Continued buildup of wastes in the liver will eventually damage the organ. Another way the liver can be damaged is not from the disease, but from the treatment. Blood transfusions are a frequent therapy for certain sickle cell disease symptoms. This type of treatment occasionally introduces such viruses as hepatitis.

The spleen is an important antibody-producing organ of the immune system and combats infections in at least two different ways – by engulfing bacteria and by producing chemicals that attack foreign material. People with damaged spleens are more prone to infections, especially when they are young. The spleen is located in the upper left side of the abdomen and serves as a blood reservoir. It stores blood when circulation is decreased as when the body is at rest, and releases blood when circulation increases as during exercise or bleeding episodes.

Normally, blood undergoes cleaning as it travels through the spleen. This is where old, damaged, and abnormal blood cells are destroyed. In a healthy individual, every few minutes, about 200 million old blood cells are destroyed and an equal number of new ones are made. The hemoglobin from the destroyed cells is converted to bilirubin in the spleen and excreted by the liver. The leftover cellular material is taken up by phagocytes in the spleen. These phagocytes also remove bacteria and other foreign material.

Blood traveling through the spleen must work its way through an intricate network of finely branched vessels and squeeze through numerous tiny sinusoids. Since the red blood cells in sickle cell disease are not very flexible, they often become stuck in the spleen, causing the organ to become swollen and decrease in function. This commonly begins in very early childhood and progressively loses its ability to function. Over the years, with repeated damage and scarring, it gradually becomes smaller and smaller; but, sometimes, it can become chronically enlarged.

A splenectomy, or surgical removal of the spleen, is sometimes performed to prevent recurrence of the episode, but the decision to perform a splenectomy is a difficult one to make since its removal will greatly hinder the immune system, causing the patient to become even more susceptible to infection.

Any and all organs can be damaged by sickle cell disease and most of it is caused by blocked blood vessels, a characteristic of sickle cell disease. The following areas are examples of such damage that can occur:

Eyes:They can be damaged and vision affected to various degrees. The vision is affected when blood vessels become blocked in the conjunctiva, choroid, or retina. In turn, this may cause anterior segment ischemia, pupil irregularity, iris atrophy, retinal degeneration, and loss of visual field.A serious condition called sickle-cell retinopathy is a common result of sickle-cell disease. As vessels within the peripheral sections of retina become blocked, the retina becomes starved for oxygen. It develops new vessels that tend to be weak and hemorrhage. The neovascularization may cause leakage into the vitreous or retinal detachment and a loss of vision results. Once neovascularization has begun, photocoagulation therapy (laser treatments) is performed. This may stop the hemorrhaging, but can cause such complications as vitreal neovascularization. Cryotherapy (freezing treatments) may be performed on the smaller areas of neovascularization.

A procedure called ‘sclera buckling’ may be used to reduce the traction that causes retinal detachment. This normally simple procedure is difficult in cases of sickle-cell disease because there may be overlying bleeding that interferes with localization of the hemorrhage source, and the procedure may trigger necrosis (localized tissue death), in anterior areas.

Hearing: Some hearing loss is also not unusual, likely because of an inadequate blood flow to the inner ear.

Ulcerations: Skin lesions can occur either spontaneously or in response to an injury. These chronic sores on the lower legs are usually located near the ankle and can be as wide as seven inches. Ulcerations are more common in adult men and may take months or years to heal, if they ever do. This is an area of concern as it is an ever-present source of potential infection. Even after healing, the scar tissue may break down and ulceration may occur again.

Kidneys: They are a common site of blood vessel blockage in sickle cell disease, causing them to become increasingly damaged with age. Chronic kidney disease is another route to other forms of anemia perhaps, as a result of the accumulation of marrow-depressing toxins in the blood normally removed by the kidneys. Another reason may be because of a reduction in the amount of erythropoietin produced. Erythropoietin is a hormone made in the kidneys that tells the bone marrow to make new red blood cells. If this organ is damaged, less erythropoietin is made, causing a smaller number of red blood cells. The kidneys are essential to life: responsible for filtering out metabolic wastes from the blood, forming urine, and retaining the proper sodium balance in the body. Damaged kidneys cannot concentrate urine normally, which leads to frequent urination in adults and bed-wetting in children.

Enlarged organs: They are common in sickle cell disease, and the heart is no exception. As the heart enlarges because of the added workload, it does not respond effectively to activity. Nevertheless, this organ seems relatively resistant to sickle cell disease damage, and patients do not demonstrate the symptoms of cardiovascular disease prevalent in the general American population. In later life, however, congestive heart failure commonly develops.

Penis: Like the spleen, the penis has a complex network of blood vessels that is particularly vulnerable to blockage in sickle cell disease. Blockage of the outflow vessels can cause priapism which may be accompanied by swelling and added pain during urination. Priapism can occur in young boys, as well as older males, and may be associated with sexual activity, with or without a partner. In some cases, erection lasts for a few hours at most and may not be particularly painful, but it often recurs. In other cases, priapism may persist for days or even weeks, leading to impotence.

Brain: The brain is the center of perception, learning, memory, and behavior. It is the central nervous system’s command and control center. Different regions of the brain are the headquarters for different functions. Consequently, when there is any failure of oxygen delivery to the brain, the resulting effects will be determined where the failure occurs and how extensive it is.

The brain accounts for about 20% of the body’s oxygen consumption, and its need for a constant supply is absolute. The red blood cells of the sickle cell patient carry less oxygen than do normal red blood cells. To compensate, larger volumes of blood is delivered to the brain. In some people, the pressure this elevated volume produces appears to be the cause of severe headaches.

Strokes may occur as the brain cells do not receive adequate amounts of oxygen. When young children suffer strokes, they are usually caused by the blockage of some of the brain’s blood vessels. In older children and adults, strokes usually originate from the bleeding of blood vessels within the brain. Strokes can result in paralysis of various parts of the body, other major disabilities, or death. Sometimes patients undergo convulsions and slip into a coma after a stroke. Strokes tend to recur often in the sickle cell disease patient but when chronic blood transfusions are given every month or so, the likelihood of re-occurrence is greatly reduced.

Gallbladder: The gallbladder is another area of concern. A by-product of red cell destruction is bilirubin, a pigment excreted by the liver into the bile. Because so many red blood cells are destroyed in sickle cell disease, bilirubin is produced in very high amounts and the excess increases the likelihood of gallstone formation. Not only do these stones contain bilirubin, but calcium, phosphates, cholesterol, and bile salts as well. Stones can form in the gallbladder or in the bile passages.

With sickle cell disease, gallstones form even in very young children with the likelihood of their production increasing with age. When gallstones are accompanied by symptoms, surgical removal of the gallbladder is the standard recommended treatment; and most people do very well without the organ.

Gallstones may produce no symptoms or they may cause such chronic problems as a bloating discomfort after eating, nausea, vomiting, and abdominal pain. Acute problems can result in fever, chills, and severe pain. Symptoms are the result of inflammation or to an obstruction of the bile ducts; and their severity depends on the size and number of the stones, where they have lodged, and the damage they have caused in the process. Problems intensify if infection sets in.

Infection: This is a chronic worry to the sickle cell patient. Many of the sickle-cell crisis symptoms are caused by lack of oxygen, but some could also be from infections. Microorganisms are everywhere just waiting for an opportune moment to begin to multiply. The spleen is a major barrier to these infections.

Since the spleen is damaged and sometimes destroyed or surgically removed in sickle cell patients, these individuals become particularly vulnerable to infection. The younger the patient is when spleen damage begins, the more dangerous the situation becomes as he/she grows older. Other immune system components in the sickle cell patient also become abnormal in their function. Therefore, once infected, the sickle cell patient becomes harder to treat. Thus, an aggressive program at the onset is considered essential.

Certain microorganisms seem to ravage the sickle cell patient more than others. Among these are Streptococcus pneumoniae, which is especially dangerous to very young children; but such cases are rare as the patient becomes older. In the absence of antibiotics, this organism can multiply profusely in the blood stream, causing septicemia (blood poisoning) or in the spinal fluid (meningitis). Entry into the bloodstream can be through inhalation or into the spinal fluid via an ear infection.

Other microorganisms of concern to the sickle cell patient are Hemophilus influenzae, Salmonella, and Escherichia coli. H. influenzae is the cause of nose, throat, and ear infections, pneumonia, and meningitis. Streptococcus pneumonia and Haemophilus influenzae type b are the major causes of death in children under the age of five with sickle cell disease. Salmonella is the frequent cause of osteomyelitis (bone inflammation) in young sickle cell patients. E. coli is the most common microorganism found in human and animal feces.

Psychological Damage
Another aspect of sickle cell disease that few address involves the psychological effects. Any chronic disease will have an emotional impact both on the individual and the family. Since the disease begins from birth, it is the children who suffer the most. By the time adulthood is reached, compensatory techniques have usually been adopted.

During hospital stays, sickle cell children must be separated from their families, causing some to fear abandonment. Severe pain, isolation, and disability take their toll on them and their families. Anxiety is common and for some, the fear of death. Sickle cell children are often smaller and thinner than their healthy peers. They look different and may find themselves less intellectually competent since many lose time from school as a result of crisis episodes. Low self esteem is common in children and adolescents, who may become socially withdrawn. Some suffer from depression, which seems to be associated with episodes of pain. Consequently, they become dependent on, and sometimes addicted to, drugs.

All sickle cell patients, regardless of age, need sound emotional support.