A presentation made about Sickle cell disease by Yara Mostafa, Yasser Osama, Yaser Mostafa ,Ain shams university, Medicine faculty, first year students.
This a series of notes on hematology useful for undergraduate and postgraduate medical and paramedical students. Notes are prepared from standard texts and are easy to reproduce in exams.
A presentation made about Sickle cell disease by Yara Mostafa, Yasser Osama, Yaser Mostafa ,Ain shams university, Medicine faculty, first year students.
This a series of notes on hematology useful for undergraduate and postgraduate medical and paramedical students. Notes are prepared from standard texts and are easy to reproduce in exams.
Sickle Cell disease: is a genetic disorder that affects erythrocytes (RBC) causing them
to become sickle or crescent shaped.
The effects of this condition due to an abnormality of the hemoglobin molecules found
in erythrocytes.
Sickle cell anemia is a serious disease in which the body makes sickle-shaped red blood
cells. “Sickle-shaped” means that the red blood cells are shaped like a "C."
Normal red blood cells are disc-shaped and look like doughnuts without holes in the
center. They move easily through your blood vessels. Red blood cells contain the
protein hemoglobin. This iron-rich protein gives blood its red color and carries oxygen
from the lungs to the rest of the body.
Sickle cell Anemia is known as being a fatal hereditary form of anemia, it is recognized
by its abnormal red blood cells having a crescent shape due to the effect of hemoglobin
S found in the cells.
Aplastic anemia is one of the stem cell disorder which leads to pancytopenia in the peripheral blood and decrease production of all cell line in bone marrow. it require bone marrow transplantation to cure the patient.
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
Sickle Cell disease: is a genetic disorder that affects erythrocytes (RBC) causing them
to become sickle or crescent shaped.
The effects of this condition due to an abnormality of the hemoglobin molecules found
in erythrocytes.
Sickle cell anemia is a serious disease in which the body makes sickle-shaped red blood
cells. “Sickle-shaped” means that the red blood cells are shaped like a "C."
Normal red blood cells are disc-shaped and look like doughnuts without holes in the
center. They move easily through your blood vessels. Red blood cells contain the
protein hemoglobin. This iron-rich protein gives blood its red color and carries oxygen
from the lungs to the rest of the body.
Sickle cell Anemia is known as being a fatal hereditary form of anemia, it is recognized
by its abnormal red blood cells having a crescent shape due to the effect of hemoglobin
S found in the cells.
Aplastic anemia is one of the stem cell disorder which leads to pancytopenia in the peripheral blood and decrease production of all cell line in bone marrow. it require bone marrow transplantation to cure the patient.
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
Glucose tolerance test- Indications, contraindications, preparation of a patient, precautions, types of GTT, normal curve, diabetic curve, renal glycosuria, lag curve, Criteria for diagnosis of DM
RNA- A polymer of ribonucleotides, is a single stranded structure. There are three major types of RNA- m RNA,t RNA and r RNA. Besides that there are small nuclear,micro RNAs, small interfering and heterogeneous RNAs. Each of them has a specific structure and performs a specific function.
Alcohol induced metabolic alterations - A Case based discussionNamrata Chhabra
I shall proceed through a case based discussion and highlight a few of the metabolic alterations that have been found in the patient under study and of course these are the commonest metabolic alterations that change the whole scenario.
The objective of my discussion is to provide you with a solid foundation of alcohol induced metabolic alterations. The knowledge thus acquired will help you to make spontaneous diagnosis and plan the relevant treatment in the clinical settings.
The case details are with you. There are 3 questions related to the problems the patient is having in this case, and there are 4 options for each of the questions. Using your prior knowledge, try to select the most appropriate answer, you have only one minute to solve the answer.
Copper- sources, daily requirement, absorption, transportation, storage, excretion, role in enzymatic action, role in iron metabolism, role in elastin maturation, role in bone formation, copper deficiency, copper toxicity, Wilson disease, Menkes disease.
Folic acid- Chemistry, One carbon metabolism and megaloblastic anemiaNamrata Chhabra
Folic acid- Structure, forms, absorption, transportation, storage, excretion, role in one-carbon metabolism, role in methionine synthesis, role in nucleotide biosynthesis, folate trap, folate antagonists, megaloblastic anemia
Sugar derivatives and reactions of monosaccharidesNamrata Chhabra
Reactions of monosaccharides, osazone formation, reduction, oxidation, reaction with acids and alkalies, ester formation and formation of amino sugars, amino sugar acids and deoxy sugars.
Definition of ELISA, Immunochemical principle of ELISA, Direct, Indirect, Sandwich and Competitive ELISA, applications of ELISA in the diagnostic field, and benefits/drawbacks of ELISA.
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...Namrata Chhabra
Regulation of gene expression in prokaryotes and eukaryotes, Recombinant DNA technology, Southern hybridization, Northern Hybridization, Western hybridization, cloning, PCR, Applications of RDT, Animal cloning, Multiple choice questions
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
For more information, visit-www.vavaclasses.com
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
2. Normal Structure of hemoglobin
Normal hemoglobin has four subunits called
globins.
Adult hemoglobin has two α (α 1and α 2) and two
β (β 1 and β 2) globin chains.
Each globin chain has an associated heme prosthetic
group, which is the site of oxygen binding and release.
The quaternary structure of HbA can be described
as a dimer of α 1 β 1 and α 2 β 2 dimers.
The αβ dimers move relative to one another during
the binding and release of oxygen.
2/17/2013 Biochemistry For Medics 2
3. Structure of Hemoglobin
All globin chains have similar
primary sequences.
The secondary structure of
globin chains consists of
approximately 75 percent α-
helix.
The similar primary sequence
promotes a similar tertiary
structure in all globins that is
called the globin fold, which is
compact and globular in overall
conformation.
2/17/2013 Biochemistry For Medics 3
4. Normal Structure of hemoglobin
Hemoglobin must remain soluble at high
concentrations within the red blood cell to support
normal oxygen binding and release properties.
This is made possible by a distribution of amino acid
side chains in which hydrophobic residues are
sequestered in the interior core of the folded globin
subunits, while hydrophilic residues dominate the
water-exposed surface of the globin fold.
The disk-shaped heme prosthetic group is inserted
into a hydrophobic pocket formed by the globin.
2/17/2013 Biochemistry For Medics 4
5. Sickle cell disease- Biochemical
Defect
In Sickle cell disease, also called as sickle cell anemia, a
single nucleotide alteration (point mutation) in the β globin
gene of hemoglobin causes a change of thymine for adenine
(GAG to GTG.), at the sixth codon of the ß gene.
This change encodes Valine instead of Glutamic acid in the
sixth position on the ß-globin molecule.
The charge at this site is altered and allows for
polymerization of hemoglobin under conditions of hypoxia.
These properties are responsible for the profound clinical
expressions of the sickling syndromes.
The mutant β globin chain is designated as βs , and the
resulting hemoglobin is referred as HbS.
2/17/2013 Biochemistry For Medics 5
7. Sickle cell disease- Biochemical Defect
The continuous formation and destruction of sickled cells contributes
to severe hemolytic anemia. These rigid cells may initiate small vessel
occlusions.
2/17/2013 Biochemistry For Medics 7
8. Sickle cell disease- Inheritance
It is a homozygous recessive
disorder.
It occurs in individuals who have
inherited two abnormal genes (one
from each parent) that code for the
synthesis of β chain of the Hb
molecule.
Heterozygotes have on normal and
one sickle cell gene.
The blood cells of these individuals
contain both HbS and HbA.
These individuals have sickle cell
trait and they usually do not show
the clinical symptoms and Biochemistry For Medics
2/17/2013
can have a 8
normal life span.
9. Sickle cell disease-Frequency
Sickle cell disease has been recognized
in the malarial areas of the world.
In malarial areas there is a selective
advantage to the heterozygote (Hb AS),
Individuals with sickle cell trait have
lower levels of Plasmodium falciparum
parasitemia, higher hemoglobin
counts, and less severe reinfections than
individuals with homozygous Hb A.
2/17/2013 Biochemistry For Medics 9
10. Protection against Malaria ?
Sickling might protect a person from malaria
by either of the following:
Making it more difficult for the parasite to
metabolize or to enter the sickled cell
By accelerating Sickling parasitized cells are
quickly removed
While children with sickle cell trait Hb SA
seem to have a milder form of falciparum
malaria, those with homozygous Hb S have a
severe form that is associated with very high
mortality rate.
2/17/2013 Biochemistry For Medics 10
12. Sickle cell disease-Frequency
Sickle cell disease is
most common in
individuals of African
descent but is seen in
Hispanics, Arabians, Indian
s, and whites.
In the United States the
incidence is 1 in 625 live
births to African-
Americans.
2/17/2013 Biochemistry For Medics 12
13. Biochemical Basis for Sickling
The substitution of the nonpolar Valine for a
charged glutamate forms a protrusion on the β
–globin that fits in to a complementary site on
the α –chain of another hemoglobin molecule
in the cell.
At low oxygen tension, HbS polymerizes
inside the red blood cells, first forming a gel,
then subsequently assembling in to a net work
of fibrous polymers that stiffen and distort the
cell, producing rigid misshapen erythrocytes-
sickle shaped erythrocytes.
2/17/2013 Biochemistry For Medics 13
15. Biochemical Basis for Sickling
After recurrent episodes of sickling, membrane
damage occurs and the cells are no longer capable of
resuming the biconcave shape upon reoxygenation.
Thus, they become irreversibly sickled cells (ISCs).
From 5-50% of RBCs permanently remain in the
sickled shape.
The life span of an erythrocyte homozygous for HbS
is approximately 20 days compared to 120 days for a
normal RBC.
2/17/2013 Biochemistry For Medics 15
16. Factors affecting Sickling of Red
blood cells
The extent of Sickling depends on the
factors that increase the proportion of HbS
in the deoxy state. These factors include –
Decreased oxygen tension as a result of
high altitude or flying in nonpressurized
plane,
Increased pCO2
Decreased pH and
Increased concentration of 2, 3
bisphosphoglycerate.
2/17/2013 Biochemistry For Medics 16
17. Consequences Of Sickling
Reduced life span of red blood cells
Sickled cells frequently block the flow of blood in
the narrow capillaries.
The interruption in the supply of oxygen leads to
tissue anoxia, causing pain and eventually death of
cells (infarction) in the vicinity of blockage.
Because of the disruption of the red cell
membrane, the increased adhesiveness of sickle
reticulocyte, and the increased leukocyte count
there is a thrombotic coagulopathy associated
with sickle cell anemia that contributes to the
severity of the disease.
2/17/2013 Biochemistry For Medics 17
18. Sickle cell disease(SCD)- Clinical
Manifestations
The presenting symptoms of SCD involve pain and
anemia.
SCD usually manifests early in childhood. For the
first 6 months of life, infants are protected largely by
elevated levels of Hb F
The disease is associated with growth retardation,
delayed sexual maturation, and being underweight
Anemia is universally present. It is chronic and
hemolytic in nature and usually very well tolerated.
Anemia may be complicated with Megaloblastic
changes secondary to folate
2/17/2013 Biochemistry For Medics 18
19. Sickle cell disease(SCD)- Clinical
Manifestations- Cont.
The spleen enlarges in the latter part of the first
year of life.
Pneumococcal infections are common in childhood.
The most common clinical picture during adult life is
vasoocclusive crisis.
Many individuals with Hb S disease experience
chronic low-level pain, mainly in bones and joints.
The acute chest syndrome consisting of chest
pain, fever, tachypnea, leukocytosis, and pulmonary
infiltrates may be there
Central nervous system involvement is one of the
most devastating aspects of SCD.Medics
2/17/2013 Biochemistry For 19
20. Sickle cell disease(SCD)- Clinical
Manifestations- Cont.
The heart is involved due to chronic anemia and micro
infarcts.
Chronic hemolysis with hyperbilirubinemia is
associated with the formation of bile stones.
Cholelithiasis may be asymptomatic or result in acute
cholecystitis, requiring surgical intervention Repeated
infarction of joints, bones, and growth plates leads to
aseptic necrosis
Blood in the pulmonary circulation is deoxygenated,
resulting in a high degree of polymer formation.
Pulmonary hypertension may develop
The kidneys lose concentrating capacity
Leg ulcers are a chronic painful problem
Chronic organ damage- Most common are lungs,
kidneys, liver, skeleton and skin.
2/17/2013 Biochemistry For Medics 20
21. Laboratory Findings
1) A complete blood cell count usually
reveals an increased reticulocytes count (5–
15%),
2) Total Leukocyte count (12,000–
20,000/mm3), upper limit of normal or
greater.
3) Differential Leukocyte count- normal (or
predominance of neutrophils
4) Mean corpuscular volume (MCV) normal
(unless thalassemic hemoglobin is present),
5) Hb- mild to moderate anemia (5–9g/dL),
6) Platelet count- normal to increased,
2/17/2013 Biochemistry For Medics 21
22. Laboratory Findings-Contd.
7) Blood smear- A diagnosis of sickle cell disease can
be suspected by examination of the peripheral blood
film and that shows the presence of target
cells, poikilocytes, hypochromasia, sickle red
cells, nucleated RBCs, and Howell-Jolly bodies
2/17/2013 Biochemistry For Medics 22
23. Laboratory Findings-Contd.
8) Sickle solubility test-A mixture of hemoglobin S
(Hb S) in a reducing solution (such as sodium
dithionite) gives a turbid appearance, whereas
normal Hb gives a clear solution.
9)Hemoglobin electrophoresis-The substitution
of the nonpolar Valine for the charged Glutamic
acid results in decreased mobility of the HbS in
the electric field as compared to HbA. This altered
mobility is due to the presence of less negative
charge on the two β –globin chains
10) HPLC-The diagnosis is confirmed by high-
pressure liquid chromatography (HPLC).
2/17/2013 Biochemistry For Medics 23
24. Laboratory Findings-Contd.
10) Bone marrow is markedly hyper plastic with
erythroid predominance.
11) Radiological studies may reveal characteristic
bony findings of sickle cell disease in the
vertebral bodies, mild expansion of the marrow
cavities, osteoporosis, and possibly sclerosis of
the long bones and femoral heads.
12) Liver function tests, as well as
BUN, creatinine, and serum electrolytes are also
required to be performed.
2/17/2013 Biochemistry For Medics 24
25. Treatment
Treatment strategies include the following 7 goals:
(1) management of vasoocclusive crisis,
(2) management of chronic pain syndromes,
(3) management of the chronic hemolytic anemia,
(4) prevention and treatment of infections,
(5) management of the complications and the
various organ damage syndromes associated with
the disease,
(6) prevention of stroke, and
(7) detection and treatment of pulmonary
hypertension.
2/17/2013 Biochemistry For Medics 25
26. Treatment (Contd.)
Vasoocclusive crisis is treated with vigorous hydration
and analgesics.
Pain control is best achieved by the administration of
opioids.
Prevention of infection improves chances of survival in
SCD.
Allogeneic bone marrow transplantation (BMT) can cure
the disease, but it is difficult to decide which patients
should be offered BMT.
Therapy with hydroxyurea- Hydroxyurea increases the
production of Hb F, which retards gelation and sickling.
Blood transfusion is indicated only in specific situations
Surgical care is limitedBiochemistry For Medics
2/17/2013
to treating disease complications. 26
27. Prevention of sickle cell disease
Screen for Hb S at birth. This method of
case finding allows institution of early
treatment and control.
Prenatal diagnosis is also available. The
laboratory procedures employed in
prenatal testing are sensitive and rapid.
Prenatal testing must be accompanied
with genetic and psychological counseling.
2/17/2013 Biochemistry For Medics 27
28. Prognosis
Because this is a lifelong disease,
prognosis is guarded.
The goal is to achieve a normal life span
with minimal morbidity.
As therapy improves, the prognosis also
improves
2/17/2013 Biochemistry For Medics 28
29. Sickle cell trait
About 8% of African Americans and about 30% of
Nigerians are heterozygous for sickle cell trait.
HbS heterozygotes have minimal clinical
problems
Overall life expectancy is similar to normal
individuals
Individuals with sickle cell trait may develop
sickle cell crisis if they become severely hypoxic
May have recurrent episodes of painless
hematuria due to impaired ability to form
concentrated urine.
These individuals are not placed at high risk.
2/17/2013 Biochemistry For Medics 29
30. Sickle beta Thalassemia
Commonly encountered from Mediterranean
countries as well as from central Africa
Patients have congenital hemolytic anemia of
varying severity, accompanied by splenomegaly in
70 % of cases.
Sickle β0 Thalassemia have vaso- occlusive
manifestations comparable to homozygous SS
disease.
Sickle β+ Thalassemia have less severe
anemia, fewer pain crisis and less organ damage
2/17/2013 Biochemistry For Medics 30
31. Sickle C disease
Hb electrophoresis reveals 50% HbS and 50%
Hb C
One of the beta chain gene is defective for
Hb S and the other is defective for Hb C( The 6th
position in beta chain is replaced by Lysine in
place of Glutamic acid
There is increased tendency for SC cells to
sickle cell as compared to sickle cell trait
Occasional painful crisis or organ infarcts
High rate of complications during pregnancy
2/17/2013 Biochemistry For Medics 31