Sickle Cell Anemia

Causes:

Sickle-cell anaemia is an autosomal recessive genetic disorder caused by a mutation on the HBB gene located on the short of arm of chromosome eleven.  This gene is responsible for hemoglobin production.  There are actually several possible mutations of this gene that can cause sickle-cell

anaemia, however the most common mutation is the Hb S analog.  In a normal, healthy human being, the DNA sequence of the HBB gene would be as follows: CTG-ACT-CCT-GAG-GAG-AAG-TCT.  However, a person with the Hb s mutation possessing the following variation on the HBB gene: CTG-ACT-CCT-GTG-GAG-AAG-TCT.  Here, in place of the usual GAG, a patient with sickle-cell anaemia possessing the tri-nucleotide sequence GTG.  Those familiar with the central dogma of biology will recognize that because every three DNA bases translate to an mRNA codon that subsequently codes with a complimentary amino acid, this substitution of GAG for GTG alters the protein structure of hemoglobin.  More specifically, the Hb S mutation replaces the hydrophilic glutamic acid with the hydrophobic amino acid, valine.  While this mutation only swaps out one amino acid in the entire protein, the fact that valine is hydrophobic means that the mutation has very heavy implications.  A normal red blood cell consists of to alpha chains as well as two beta chains.  However, the mutation creates a hydrophobic region on the outside of the protein.  This hydrophobic component then fastens to another hydrophobic region of the adjacent beta molecular chain.  This structural alternation is known as polymerization.  It is this variation of the shape of the hemoglobin molecules causes red

blood cells to sickle.  Additionally, the polymerization of the hemoglobin protein does not occur until red blood cells release oxygen molecules.  When a red blood cell with the Hb S mutation is carrying oxygen, it reverts back to the typical red blood cell shape and depolymerizes.  The protein therefore constantly switches between polymerization and depolymerization, which causes the membranes of red blood cells to become rigid.  The abnormal shape of the red blood cells as well as the membranes' rigidity causes an obstruction in smaller sized blood vessels, damaging organs.




Implications:

Because of the red blood cell's abnormal shape during sickle-cell anaemia, each red blood cell dies after ten to twenty days after its genesis.  In contrast, a normal red blood cell can survive in the body for approximately 120 days.  As a result of the blood cell's extremely short life span, the bone marrow

(responsible for red blood cell production) cannot replace the dead blood cells fast enough.  In addition, the blood cell's abnormal shape and rigidity prevents proper blood flow through capillaries, facilitating poor oxidation of organs and tissue.  This, coupled with the gradual organ damage that sickle-cell anaemia causes makes for a very bleak prognosis for sickle-cell anaemia patients.

Most of sickle-cell anaemia's implications are non-lethal.  In fact, the most well-known implication is referred to as the sickle cell crisis.  This event is characterized by a long-lasting incidence of pain.  The event most often occurs in regions of the body where accumulations of sickle-cells exist, specifically the lungs, bone, brain, liver, eyes, spleen, penis, and kidneys.  A person experiencing a sickle cell crisis will feel extreme, localized pain in one of these regions for anywhere between 3-14 days.

There are also several other non-lethal implications associated with sickle-cell anaemia, including acute chest syndrome.  Here, a patient will experience acute chest pain associated with coughing up blood. Impairment of the central nervous system and eye function are some other significant implications of sickle-cell anaemia.

A very thorough list of symptoms associated with sickle-cell anaemia can be found here: http://www.mayoclinic.com/health/sickle-cell-anemia/DS00324/DSECTION=symptoms

Treatment:

In almost every case, sickle-cell anaemia has no cure.  However, on a very rare occasion blood and marrow stem cell transplants can act as a cure for the disease.  The primary objective while treating a patient with sickle cell anaemia is to alleviate as much pain as possible during the patient's life.  Treatments also often try to prevent some of the complications associated with the disease as well as prevent organ damage.  Usual treatments to address crises and acute pain attacks caused by sickle-cell anaemia oxygen therapy as well as the use of powerful pain medications called opioids.

Particularly severe cases of sickle-cell anaemia are sometimes treated with a substance called hydroxyurea.  This medication induced your body into created fetal hemoglobin, which can sometimes prevent red blood cells from sickling.  However, this drug reduces the quantity of white blood cells found in the body and can therefore make patients with sickle-cell anaemia more vulnerable to infection.

Additionally, there are various treatments that aim to address the complications of sickle-cell anaemia.  These will be addressed below in the complications section.

Complications:

The primary complications associated with sickle-cell anaemia include stroke, pulmonary hypertension, organ damage, blindness, skin ulcers, and gallstones.  Patients with sickle-cell anaemia are more susceptible to strokes due to the sickle-shaped red blood cells blocking blood flow to the brain.  Additionally, these cardiovascular blockages can also cause high blood pressure in the lungs, defined as pulmonary hypertension.  This complication can potentially be fatal.  Similar to the causes of other complications, a lack of oxygen-rich blood flow to the body's organs can damage tissues, organs, and nerves throughout the body, as well as damage to the retina of the eye, causing blindness.  Lastly, the decomposition of red blood cells in the body releases bilirubin, which in high quantities can cause gallstones.

Works Cited:

"What Is Sickle Cell Anemia? - NHLBI, NIH." NIH Heart, Lung and Blood Institute. N.p., n.d. Web. 28 Mar. 2013. <http://www.nhlbi.nih.gov/health/health-topics/topics/sca/>.

"Sickle cell anemia - MayoClinic.com."Mayo Clinic. N.p., n.d. Web. 28 Mar. 2013. <http://www.mayoclinic.com/health/sickle-cell-anemia/DS00324>

"Sickle Cell Anemia Gene." Oak Ridge National Laboratory. N.p., n.d. Web. 28 Mar. 2013. <http://www.ornl.gov/sci/techresources>

"HBB - hemoglobin, beta - Genetics Home Reference." Genetics Home Reference - Your guide to understanding genetic conditions. N.p., n.d. Web. 28 Mar. 2013. <http://ghr.nlm.nih.gov/gene/HBB>