sickle cell anemia

Question 1

what is sickle cell anemia caused by?

Answer 1

change in one nucleotide in the gene for the beta chain component of hemoglobin. The presence of this allele in a person’s DNA alters one of the codons in mRNA. This means that a different tRNA enters the ribosome and a different amino acid is added to the growing polypeptide chain. In this case, valine is added to the polypeptide instead of glutamic acid

Question 2

significance of valine

Answer 2

the side chain of valine consists solely of carbons and hydrogens, making valine a non-polar amino acid. That means it is hydrophobic and so will do everything it can to avoid the aqueous environment of the cytosol

Question 3

glutamic acid

Answer 3

side chain includes a carboxyl (COOH) group that can give up its hydrogen atom to become negatively charged. As a result, glutamic acid is hydrophilic, plus it can bind to positively charged amino acids - valine can’t do this.

Question 4

what happens when valine is replaced by glutamic acid?

Answer 4

alters shape of protein

Question 5

where are erythrocytes produced?

Answer 5

from stem cells that reside in the marrow of the large bones in the body.

Question 6

how long rbcs develop and release back into blood stream

Answer 6

development takes about 7 days, after which they are released into the bloodstream where they live for about 120 days

Question 7

define hematocrit

Answer 7

percent of the blood made up of red blood cells

Question 8

hematocrit ranges

Answer 8

40% to 50% in men and 35 to 45% in women.

Question 9

define anemia

Answer 9

condition in which the number of circulating red blood cells, and thus the hematocrit, is below this normal range.

Question 10

primary function of rbcs

Answer 10

take up oxygen as they pass through the lungs and release it in the tissues.

Question 11

how many hemoglobin molecules does each rbc contain? and how many globin proteins in each?

Answer 11

250 million, 4 globin proteins

Question 12

globin proteins

Answer 12

Two of the globin proteins are called alpha chains and two are called beta chains. Each chain is bound to a pigment known as heme, hence the name hemoglobin

Question 13

how can each rbc transport about a billion molecules of oxygen?

Answer 13

Because each heme group contains an atom of iron that can carry one molecule of oxygen, each hemoglobin molecule can bind and release up to four molecules of oxygen

Question 14

why is the color of blood red?

Answer 14

due to the interactions between the heme molecules with oxygen.

Question 15

what gives rbc a biconcave disc shape?

Answer 15

their plasma membranes are comprised of proteins and lipids

Question 16

what is the significance of the biconcave disc shape?

Answer 16

gives them the stability they need to withstand the forces exerted by the heart, the ability to deform so they can squeeze through tiny capillaries, and the large surface area needed to facilitate the diffusion of oxygen into and out of these cells.

Question 17

blood flow through the heart

Answer 17

Blood returning from most of the body enters the right atrium and then flows into the right ventricle. The red blood cells entering the right side of the heart are deoxygenated, as their hemoglobin molecules had previously released some of the bound oxygen molecules as they passed through the tissues.

Question 18

oxygenated blood

Answer 18

The right ventricle pumps these cells through the pulmonary circulation, and eventually through the capillaries that surround the alveoli, small sacs in the lungs. This is where the hemoglobin molecules bind oxygen molecules, rendering them oxygenated. This newly oxygenated blood returning from the lungs enters the left atrium and flows into the left ventricle. The left ventricle pumps the oxygenated blood out through the aorta and its tributaries to provide oxygen molecules to the rest of the body.

Question 19

deoxygenated blood

Answer 19

As the deoxygenated red blood cells make their way through the capillaries surrounding the alveoli, oxygen in the air within the alveoli is at a higher partial pressure than it is in the blood. Consequently, oxygen molecules diffuse from the alveoli into the blood and into the red blood cells where they bind to hemoglobin. About 98% of the oxygen carried in blood is bound to hemoglobin.

Question 20

deoxygenated to oxygenated

Answer 20

Although each iron moiety in the four heme components of hemoglobin can bind an oxygen molecule, the average hemoglobin in the blood entering the pulmonary capillaries contains 3 oxygen molecules. At this point, the blood is considered ‘deoxygenated’ or ‘venous’ and is maroon in color. When the iron molecule in the remaining heme component binds the fourth oxygen molecule. As a result, the hemoglobin molecule undergoes a slight change in shape, known as a ‘conformational change’. In doing so, the hemoglobin molecules and the red blood cells themselves change from the maroon color that typifies venous blood to the scarlet red color of arterial blood. At this point, the hemoglobin molecules are 100% saturated with oxygen.

Question 21

oxygenated to deoxygenated

Answer 21

when the red blood cells traverse the capillary beds in the tissues where the partial pressure of oxygen is lower relative to its partial pressure in the blood. No doubt you’ll recall from courses you’ve taken 1) the air we breathe is a mixture of gases including oxygen, 2) each of these gases exerts a pressure called its partial pressure, 3) diffusion of a gas across cell membranes occurs if there’s a difference in the partial pressure of that gas across the membrane, and 4) the gas diffuses from where its partial pressure is higher to where it is lower.
Depending on the partial pressure of oxygen in the tissue, the heme components of hemoglobin will release one or more of the four oxygen molecules to the nearby cells. The conformational changes in the hemoglobin molecules associated with ‘off-loading’ of the oxygen molecules causes the red blood cells to return to the maroon color. The fact that some of the arterial blood pumped by the heart bypasses some tissue beds accounts for the finding that hemoglobin in the venous blood returning to the heart typically is 75% saturated (i.e., on average, oxygen molecules are bound to 3 of the 4 heme moieties).

Question 22

sickle cell gene inheritance

Answer 22

autosomal recessive manner, meaning that the gene causing the condition is not on a sex (X or Y) chromosome. Also, the gene responsible for the disease must be inherited from both parents for their child to have the disease. Children that inherit a single mutant gene are referred to as having the sickle cell trait, otherwise known as the ‘carrier’ state. If two people having the trait mate, there is a 25% chance that their offspring will inherit both mutant genes and develop sickle cell anemia. Based on epidemiologic data, as many as 300 million people in Africa, the Middle East, the Indian subcontinent and the Caribbean islands have the sickle cell trait. While the condition often is assumed to affect only African Americans in the United States, this is not the case. Based on a recent study, the sickle cell trait was detected in 73 of 1000 newborn African Americans, 7 of 1000 Hispanics, and 3 of 1000 Caucasians

Question 23

for children with two sickle cell genes, when does anemia and symptoms occur?

Answer 23

~4 months of age

Question 24

why is there a delay on the onset of anemia and symptoms with children with two sickle cell genes?

Answer 24

1) fetal hemoglobin molecules, commonly called hemoglobin F, fail to form the fibers that give red blood cells the sickle shape, 2) their bone marrow doesn’t start producing the adult form of hemoglobin until they are about this age, and 3) around this time, the rate at which the affected red blood cells are removed from circulation starts to exceed the rate at which the bone marrow can produce new cells; this results in anemia. In the United States and many developed countries, all newborn children are screened for potential hemoglobin abnormalities including those for sickle cell disease. However, this does not always occur in some countries. Consequently, children immigrating from places where sickle cell disease is highly prevalent may not have been tested.

Question 25

clinical signs associated with sickle cell anemia

Answer 25

dehydration and acidosis: the fluid lost in sweat and the cellular switch from aerobic to anaerobic metabolic pathways could account for the dehydration and acidosis that exacerbate the disease in young children

extreme fatigue and periodic episodes of pain: In contrast to normal red blood cells that have a lifespan of about 120 days, sickle cells typically last 10 to 20 days. The feeling of being fatigued is because far fewer red blood cells are available to deliver oxygen to the tissues where ATP can be generated. The painful episodes occur when the sickled cells aggregate in small blood vessels, preventing perfusion of the tissues. This often occurs in the chest, abdomen and joints, and can result in ulcers and joint damage. Consequently, some patients refer to the disease as “Sick as hell anemia

Question 26

sickle cell disease and sickle cell trait manifest quite differently.

Answer 26

Because less than half of the hemoglobin molecules in the red blood cells of a person with sickle cell trait carry the mutant gene, they do not sickle when they release oxygen in the tissues. As a result, people with sickle cell trait typically are not ill under normal circumstances. In fact, the majority of the 3 million Americans with the sickle cell trait will never have any medical consequences.

People with sickle cell trait can develop clinical problems when they are in extremely harsh environments, such as at high altitudes where the partial pressure of oxygen in the air is low or after extreme exertion. In those circumstances, their red blood cells can deoxygenate sufficiently to change shape. Consequently, the NCAA recommends that student athletes with sickle cell trait proactively set their own pace, recover fully between episodes of high intensity activity, stay well hydrated, and seek medical attention if clinical symptoms, such as muscle or abdominal pain, occur. They also recommend that athletes with sickle cell trait be excused from contests requiring extreme exertion for longer than 2-3 minutes.

Question 27

the prevalence of the sickle cell trait in different parts of the world has changed over time due to forced human migration from the slave trade as well as the effects of colonialism

Answer 27

the improved prognosis for people with sickle cell anemia can result in an increase in the number of patients who can pass the sickle cell genes to their offspring.

Question 28

sickle cell trait resistance to malaria

Answer 28

As human populations increased and people began living closer together, this facilitated the transmission the organism causing malaria, namely Plasmodium vivax. As a result, malaria became more prevalent and remains one of the most common causes of morbidity and mortality in tropical and subtropical climates. This parasite invades and multiplies in red blood cells where the parasites consume more than 80% of the hemoglobin molecules. They do this because they are unable to generate amino acids on their own, and so break down the hemoglobin molecules to gain access to those amino acids. Eventually, the red blood cells lyse, releasing factors that result in the symptoms of the disease including chills, high fever, nausea, vomiting, and anemia.

Although the malaria parasite can infect the red blood cells of people with the sickle cell trait, the parasite has trouble engulfing their hemoglobin molecules, because some of those molecules polymerize. As a result, the parasite fails to multiply, causing people with sickle cell trait to be resistant to the most severe forms of malaria with more than 90% of them surviving. This protection appears to be partially responsible for the higher prevalence of sickle cell trait in those areas of the world where malaria is endemic. Think of it this way - having a single mutant gene (i.e., sickle cell trait) helps protect against malaria, while having two mutant genes is harmful as it results in sickle cell disease.