Lecture 8

Question 1

mutations of globin genes

Answer 1

most common single gene hereditary disease in humans

Question 2

sickle-cell disease

Answer 2

a single altered amino acid in beta globin, gene on chromosome 11

Question 3

elongated RBC’s

Answer 3

block capillaires and rupture, causing inflammation and considerable pain

Question 4

most common clinical manifestation of SCD

Answer 4

vaso-occlusive crisis, when the microcirculation is obstructed by sickled RBC’s, causing ischemic injury to the organ supplied and resultant pain

Question 5

oral clinical manifestation of SCD

Answer 5

caries, periodontal disease, oral surgical procedures have the highest probability of causing an oral infection. the enamel is hard but thin and deficient in amount, caused by defective enamel matrix formation

Question 6

molecular cause for SCD

Answer 6

substitution of a valine residue for a glutamate residue at position 6 in the beta chain (single gene on chromosome 11)

Question 7

molecular cause for mild SCD

Answer 7

substitution of lysine for the glutamate residue at position 6 (hemoglobin C disease). milder anemia

Question 8

high isoelectric point in SCD

Answer 8

SCD tend to have more positive/less negative charge because of the substitution of a valine residue for glutamate residue

Question 9

thalassemias

Answer 9

caused by an imbalanced production of hemoglobin chains that interferes with formation of a soluble cooperative tetramer
- loss of alpha or beta chains

Question 10

clinical manifestations for thalassemia

Answer 10

anemia from low levels of functional hemoglobin, faster turnover of RBCs, decreased production of red blood cells, enlarged spleen, bone deformities due to overexpansion of the ineffective marrow

Question 11

alpha globin hemoglobinopathies

Answer 11

symptomatic in utero and after birth

Question 12

beta globin hemoglobinopathies

Answer 12

tend to be asymptomatic until 3-9 months of age, when HbA has largely replaced HbF

Question 13

treatment of alpha/beta thalassemia

Answer 13

regular blood transfusion combined with iron chelation, folate supplementation, and the judicious use of splenectomy, gene therapy

Question 14

dental implications of thalassemias

Answer 14

• bony changes, called cooley facies, caused by ineffective erythropoiesis
• the development of bone-expanding erythroid masses
• occlusal abnormalities and bimaxillary protrusions are frequent in patients with beta thalassemia major
• facial and dental abnormalities include marked opened bite, poor spacing
• the skeletal changes result in upper lip retraction giving the child a “chipmunk facies”

Question 15

heinz bodies

Answer 15

inclusions within red blood cells composed of denatured hemoglobin, found in sickle cell disease, thalassemias, and other hemoglobinopathies
- clinically detectable by staining with dyes such as methylene blue
- not enough beta or alpha globin causes precipitation of hemoglobin

Question 16

alpha thalassemia

Answer 16

• alpha chain of Hb not produced in sufficient quantity
• consequently Hb tetramers form that only contain the beta chain
• binds oxygen with high affinity and no cooperativity, beta 4 will release some oxygen but not as efficiently
• also results from abnormally long alpha globin molecules due to mutation of the normal stop codon UAA

Question 17

beta thalassemia

Answer 17

• worse than alpha, beta chain of hemoglobin is not produced in sufficient quantity, causing hemoglobin tetramers of alpha hemoglobin (alpha 4) lacking oxygen cooperativity that tend to be insoluble and precipitate quickly

Question 18

beta thalassemia major

Answer 18

both beta globin genes are affected, excess alpha chains damage red blood cell precursors and red cells leading to profound anemia (precipitates in bone marrow)
- expansion of the ineffective marrow, severe effects on development, bone formation and growth

Question 19

beta thalassemia minor

Answer 19

caused by a mutation in only one of the two beta globin genes, may be symptomless or not

Question 20

carbon monoxide poisoning

Answer 20

CO has higher affinity for Hb than oxygen, CO can replace oxygen and diminish O2 delivery
- higher affinity, favors oxygen loading, oxygen does not get delivered to tissues

Question 21

methemoglobinemia

Answer 21

oxidation of heme ferrous to ferric; bluish-brown muddy color resembling cyanosis, does not bind oxygen
- stabilizes R conformation: remaining non-oxidized ferrous binding sites of the tetramer; little oxygen delivery
- toxins that oxidize heme iron, notably nitrate and nitrate-containing compounds, including drugs commonly used in cardiology and anesthesiology such as prilocaine and benzocaine

Question 22

product recall- orajel

Answer 22

over-the-counter teething products for infants containing the pain reliever benzocaine following accumulating evidence regarding benzocaine’s association with methemoglobinemia

Question 23

sulfhemoglobinemia

Answer 23

a greenish derivative of hemoglobin which cannot be converted back to normal hemoglobin, usually drug induced (sulfa drugs)

Question 24

pulse oximeters

Answer 24

measure heart rate and % hemoglobin oxygenation
- light goes through tissues of the finger, absorbance on the adjacent sensor is measured