Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 15 Sickle Cell Anemia Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Sickle Cel Anemia
Case
? A 15-year-old African-American female presents to the emergency
room with complaints of bilateral thigh and hip pain. The pain has
been present for 1 day and is steadily increasing in severity.
Acetaminophen and ibuprofen have not relieved her symptoms. She
denies any recent trauma or excessive exercise.
? She does report feeling fatigued and has been having burning with
urination along with urinating frequently. She reports having similar
pain episodes in the past, sometimes requiring hospitalization.
? On examination, she is afebrile (without fever) and in no acute
distress. No one in her family has similar episodes.
? Her conjunctiva and mucosal membranes are slightly pale in
coloration.
? She has nonspecific bilateral anterior thigh pain with no abnormalities
appreciated. The remainder of her examination is completely normal.
? Her white blood cell count is elevated at 17,000/mm3, and her
hemoglobin (Hb) level is decreased at 7.1 g/dL. The urinalysis
demonstrated an abnormal number of numerous bacteria.
Learning objectives
? What is the most likely diagnosis?
? What is the molecular genetics behind this disorder?
? What is the pathophysiologic mechanism of her symptoms?
Hemoglobinopathies
1. Group of genetic disorders caused by production of a structural y
abnormal hemoglobin molecule(Qualitative);
2. Synthesis of insufficient quantities of normal
haemoglobin(Quantitative);
? or, rarely, both.
Diagnosis of Case: Sickle cel Anemia
Molecular Mechanism
? Autosomal Recessive
? GTG GAG at 6th position of globin chain.
? The replacement of the charged glutamate with the nonpolar valine
on surface of globin chain
? The intrinsic oxygen binding properties of HbA and HbS are the same,
however, the solubility of deoxy HbS is reduced because of exposure
of Val-6 at the surface of the -chain.
? Since hemoglobin is present at very high concentrations in the red
blood cell, deoxy HbS wil precipitate inside the cell.
? The precipitate takes the form of elongated fibers because of the
association of complementary hydrophobic surfaces on the - chains
of deoxy HbS.
? At oxygen saturations found in arterial blood, the oxy HbS
predominates and HbS does not precipitate because Val-6 of the -
chain is not exposed to the surface
Hydrophobic Sticky Patch of deoxy HbS
? At low oxygen tension, deoxyhemoglobin S polymerizes inside the
RBC, forming a network of insoluble fibrous polymers that stiffen and
distort the cell, producing rigid, misshapen RBC. Such sickled cells
frequently block the flow of blood in the narrow capillaries
Pathophysiologic Mechanism of Symptoms
? This interruption in the supply of oxygen leads to localized anoxia
(oxygen deprivation) in the tissue, causing pain and eventually death
(infarction) of cells in the vicinity of the blockage.
? Sickle cell crisis
Pathophysiology of Sickle cel Crisis
Symptoms of SCD
? Vaso-occlusive events result in tissue ischemia leading to acute and
chronic pain as well as organ damage that can affect any organ
system, including the bones, spleen, liver, brain, lungs, kidneys, and
joints.
? Dactylitis (pain and/or swelling of the hands or feet) is often the
earliest manifestation of SCD.
? In children, the spleen can become engorged with blood cells in a
"Splenic sequestration.".
Symptoms of SCD
? The spleen is particularly vulnerable to infarction and the majority of
individuals with SCD who are not on hydroxyurea or transfusion
therapy become functionally asplenic in early childhood, increasing
their risk for certain types of bacterial infections.
? Acute chest syndrome is a major cause of mortality in SCD.
? Chronic hemolysis can result in varying degrees of anemia, jaundice,
cholelithiasis, and delayed growth and sexual maturation.
Bender MA1. Sickle Cel Disease. GeneReviews? [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2003 Sep 15 [updated 2017 Aug 17].
Possible selective advantage of the
heterozygous state
? high frequency of the bS mutation among black Africans
Diagnosis
? Hemoglobin Electrophoresis
? Ful blood count
? Peripheral blood smear.
http://www.hematology.org/Fel ows/Case-Studies/725.aspx
Hb Electrophoresis
Treatment
? Management of pain episodes includes hydration, anti-inflammatory
agents, and pain medication
? Fever and suspected infection is treated with appropriate antibiotics
? Life-threatening or severe complications (e.g., severe acute chest
syndrome, aplastic crisis, and stroke) are often treated with red
blood cell transfusion
? Splenectomy may be necessary for splenic sequestration
? Hydroxyurea can decrease the frequency and severity of vaso-
occlusive processes, reduce transfusion needs, and increase life span.
Sickle Cell Disease.
Bender MA.
GeneReviews?[Internet]. updated 2017
Treatment
? Hydroxyurea(FDA Approved):
By inhibiting the enzyme ribonucleotide reductase, hydroxyurea has
been shown to increase the levels of fetal Hb (HbF, 22) by
mechanisms not fully understood.
Increase in HbF concentrations has the effect of decreasing HbS levels
and its polymerisation in the red blood cell.
? Glutamine has received FDA approval for the prevention of acute
complications in individuals with SCD age five years and
older(antioxidant).
? Stem cell transplantation may be an option in selected individuals
Summary and Discussion of the Case
? This 15-year-old female's description of her pain is typical of a sickle
cell pain crisis.
? Many times, infection is a trigger, most commonly pneumonia or a
urinary tract infection. This case is consistent with a urinary tract
infection, indicated by her symptoms of urinary frequency, and
burning with urination (dysuria). Her white blood cell count is
elevated in response to the infection.
? The low hemoglobin level is consistent with sickle cell anemia
Summary
? Since she is homozygous (both genes coding for sickle hemoglobin),
both her parents have sickle cell trait (heterozygous) and thus do not
have symptoms.
? The diagnosis can be established with hemoglobin electrophoresis.
? The tendency for deoxy HbS to precipitate is why clinical
manifestations of sickle cell anemia are brought on by exertion and
why treatment includes administration of oxygen.
Thank You!
This post was last modified on 05 April 2022