HEMOGLOBINOPATHIES prt.1

Question 1

Chromosome 16

Answer 1

→ Alpha and Zeta Globin genes
→ Referred as: Alpha-like genes

Question 2

Chromosome 11

Answer 2

→ Beta, gamma, delta and epsilon globin genes
→ Referred as: Beta-like genes

Question 3

is a tetramer of four globin chains with a heme attached to each globin chain.

Answer 3

Hemoglobin

Question 4

Heme biosynthesis starts with

Answer 4

Glucine
Succinyl CoA

Question 5

What converts protoporphyrinogen IX to protoporphyrin IX

Answer 5

Protoporphyrinogen oxidase

Question 6

Protoporphyrin IX to HEME

Answer 6

Ferrochelatase

Question 7

Coproporphyrin III to Protoporphyrin IX

Answer 7

Coproporphyrinogen oxidase

Question 8

symptoms of the disease have been traced in one Ghanaian family

Answer 8

1670

Question 9

Sickle cell anemia was 1st reported by a Chicago cardiologist, Herrick, in a West Indiana Student with severe anemia

Answer 9

1910

Question 10

Emmel recorded that sickling occurred in non-anemic patients and in patients who were severely anemic.

Answer 10

1917

Question 11

_________described the pathologic basis of the disorder and its relationship to the hemoglobin molecule.
• Sickling occurred deficient in oxygen and the shape of the RBCs was reversible when oxygenated again.

Answer 11

1927
Hahn and Gillespie

Question 12

_____reported that malarial parasites were present less often in blood films from patients with SCD that in individuals without SCD

Answer 12

1946
Beet

Question 13

_______showed that when Hb S is subjected to electrophoresis, it migrates differently than does Hb A

Answer 13

1949
Pauling

Question 14

More severe disease

Answer 14

Homozygotes (Hb SS)

Question 15

Less severe disease

Answer 15

Heterozygotes Hb S (Hb SC
or Hb S-B-thal)

Question 16

May dovelop when subjected to
extreme exertion
Asymptomatic but may have mild symptoms
Military boot camp and High level athlectics

Answer 16

Heteroyzgotes (Hb AS)

Question 17

On the Beta chain at_____
_____ is replaced by____

Mutation occurs in______
____ replaces ______, resulting in A change in codon____ and the substitution of GTG for GAG

Answer 17

Position 6

Glutamic acid (GAG) is replaced
by Valine(GTG)

nucleotide 17

Thymine replaces adenine

6

Question 18

Amino acid substitution produces a change in charge of (____) - affects electrophoretic mobility

• Also affects the way how molecules interact with one another within the erythrocyte cytosol

Answer 18

+1

Question 19

Quaternary structure of the molecule does not produce a hydrophobic pocket for valine
• Remain soluble like Hb A and with normal RBC shape

Answer 19

(HbS)- fully oxygenated

Question 20

Creates a hydrophobic pocket Phe 85 & Leu 88

Allows the valines from adjacent Hb
S molecules to BIND

Answer 20

Hb S - deoxygenated

Question 21

Creates a hydrophobic pocket Phe 85 & Leu 88

Allows the valines from adjacent Hb
S molecules to BIND

Answer 21

Hb S - deoxygenated

Question 22

Homozygotes
Sickling begins - oxygen saturation decreases to______

Heterozygotes
Sickling begins - Oxygen saturation is reduced to______

Answer 22

less than 85%

less than 40%

Question 23

Hb S-containing RBCs that change shape in response to oxygen tension
-Circulate as normal biconcave discs when fully oxygenated, but undergo hemoglobin polymerization, show increased viscosity, and change shape on deoxygenation

Answer 23

Reversible sickle cell

Question 24

DO NOT CHANGE their shape REGARDLESS OF CHANGE in oxygen tension or degree of hemoglobin polymerization.

Seen on peripheral blood film as elongated sickle cells with a point on each end

-RECOGNIZED ABNORMAL by the spleen and REMOVED FROM CIRCULATION, preventing them to enter the microcirculation and causing vasoocclusion

Answer 24

IRREVERSIBLE SICKLE-CELL

Question 25

Other Reasons Affecting Sickling Process

Answer 25

Cellular dust

Question 26

More than____ hemoglobin variants are known;

Answer 26

1200

Question 27

8 genotypes cause SEVERE DISEASES

Answer 27

1. Hb SS, 2. Hb S-BO-thal, 3. severe Hb S-B1-thal, 4. Hb SD-Punjab, 5. Hb SO-Arab, 6. Hb SC-Harlem, 7. Hb CS-Antilles, and 8. Hb S-Quebec-CHORI.

Question 28

3 genotypes cause MODERATE DISEASES:

Answer 28

1. Hb SC 2. moderate Hb S-B1-thal, and 3. Hb AS-Oman.

Question 29

3 genotypes cause mild disease

Answer 29

1. Mild Hb S-bsilent-thal 2. Hb SE 3. Hb SA -Jamaica plain

Question 30

2 produce very mild disease:

Answer 30

1. Hb S-HPFH 2. Hb S with a variety of mild variants

Question 31

Clinical Features of Sickle Cell Disease

Answer 31

Vasocclusion Bacterial infections Hematologic defects Cardiac defects Others Stunted growth High-risk pregnancy

Question 32

• Hallmark of SCD : Accounts for most hospital and emergency department visits

Answer 32

Vasoocclusive Crisis

Question 33

Frequency of painful episodes varies from none to six per year Average: episodes persists for 4-5 days or may last for weeks

Answer 33

Vasoocclusive Crisis

Question 34

Characterized by a sudden trapping of blood in the spleen Leads to rapid decline in hemoglobin(<6 g/dL) • Occurs most often in infants young children whose spleens are chronically enlarged.

Answer 34

SPLENIC SEQUESTRATION AND INFARCTS

Question 35

Autosplenectomy Gradual loss of splenic function PBS- Evidence of______ and_____ in RBCs Increases risk of bacterial infection

Answer 35

SPLENIC SEQUESTRATION AND INFARCTS Howell-Jolly and Pappenheimer Bodies

Question 36

Acute illness with fever and/or other symptoms that displays pulmonary infiltrates on chest radiograph. • 2nd most common cause of hospitalization • 3rd most common cause of death among adults with SCD

Answer 36

Acute Chest Syndrome (ACS)

Question 37

• Resulting in a decreased alveolar oxygen tension that induces Hb S polymerization and Sickle cell formation. • Treatment and continuous monitoring must be promptly initiated to reduce morbidity and mortality. • Oxygen is administered to maintain saturation at greater than or equal to 95% and intravenous fluids to prevent dehydration

Answer 37

Acute Chest Syndrome (ACS)

Question 38

is a rare but often fatal sequalae of SCD • It occurs more often in often in Hb SC (43%) and at similar frequency in Hb S-b1-thal (17%) and Hb SS (19%).

Answer 38

Fat Embolism Syndrome (FES) and Bone Marrow Necrosis (BMN)

Question 39

Is a serious and potentially fatal sequelae of SCD • nserious ton ote then ata sequed between the development of PHT and the nitrous oxide (NO) pathway, • Patients with SCD have decrease in NO, and leads to vasoconstriction and hypertension.

Answer 39

Pulmonary Hypertension (PHT)

Question 40

: Preased supeeptibity to lie threatening infecions from Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. • Common cause of death, especially in the first 3 years of life Septicemia are exacerbated by the autosplenectomy effect

Answer 40

Bacterial Infections

Question 41

Shortened RBC survival (between 16-20 days) Continuous screening and removal of sickle cells by the spleen perpetuate the chronic hemolytic anemia and autosplenectomy effect

Answer 41

Chronic Hemolysis

Question 42

• Result from the sudden arrest of erythropoiesis caused by ***folate depletion*** • Folic acid deficiency as a cause of exaggerated anemia in SCD Prescribe prophylactic folic acid for patients with SCD

Answer 42

Megaloblastic Episodes

Question 43

• Most common life-threatening hematologic complications and usually associated with infection • Are short lived, Require no therapy • Sickle cell patients usually can compensate for the decrease in RBC survival by increasing bone marrow output.

Answer 43

Aplastic Episode (Bone Marrow Failure)

Question 44

In patients with severe anemia, cardiomegaly can develop as the heart works harder to maintain adequate blood flow and tissue oxygenation.

Answer 44

Cardiac Abnormalities

Question 45

• Impaired blood supply to the head of the femur and humerus results in a condition called______ • 50% of patients with SCD developed AVN by age 35 years

Answer 45

Bone and skin abnormalities avascular necrosis (AVN)

Question 46

Hemorrhagic or ischemic stroke occurs in approximately 11% of children with SCD before age 20 years.

Answer 46

Stroke

Question 47

occurs at a rate of 45% in patients with Hb SC, 11% with Hb SS, and 17% with Hb S-B-thal by early adulthood.

Answer 47

Retinopathy

Question 48

occurs at a rate of 45% in patients with Hb SC, 11% with Hb SS, and 17% with Hb S-B-thal by early adulthood.

Answer 48

Retinopathy