SICKLE CELL ANEMIA - A Genetic Disorder

1.INTRODUCTION & HISTORY OF SICKLE CELL ANEMIA --- 1. the disease  sickle cell anemia discovered  by William Winter in 1910 . the origine of mutation thot leads to sickle cell gene was initially thought to be in the Arabiciun penisula . 2. PATHAPYSIOLOGY & PATHAPYSIOLOGY OF SICKLE CELL ANEMIA ---  Pathophysiology sickle cell Anemia caused by point mutation in B - globin chain of hoemoglobin . The amino acid  glutamic acid on B - globin chain of hoemoglobin was replaced with hydrophobic amino acid valine of the sixth_position the A - globin gene found on the short arm of chromosome 11 . The association of two mutant B - globin subunites forms haemoglobin s ( Hbs ) under low O2 condition the absence of polar amino acid on sixth position of B - globin chain promotes the non- covalent polymerization of haemoglobin which result into sickle shape of RBCs and decrease their elasticity . The low Oxygen tension result into repeated episodes of sickling damage of cell membrore and decrease in elasticity . Normal cells are quite elastic which allow the cell to deform to pass through capilleries. The sickle cells fails to return to normal shape when normal O2 tension restored. As result cell ( sickle shaped ) pass through the narrow capilleries.There is destruction RBC inside the spleen because the mishapes. The rate of production of RBC inside the bone marrow does not match the rate of destruction inside the spleen. life span of normal RBC 90 - 120 days while the life span of defected sickle RBCs - 10 - 20 days. 3.GENETICS OF SICKLE CELL ANEMIA ---  This genetic disorder caused due to mutation of single nucleotide from- GAG to GIG codon mutation secondary, tertiory and quaternary structure of hoemoglobin. There are two types of sickle cell anemia Heterozygoues and Homozygoes . 4. DISTINGUISHED BETWEEN HETEROZYGOUS & HOMOZYGOUS ---                                  Heterozygos (HbS / H6 ^) 1. The individual having an HIA and one Hbf gene i one sickled cell gene and one nomal such people carrier for disease 2. Normal alleles able to produce over 50t- of Hb (normal) 3. Symptoms if they are deprived of O2 while severally dehydrated.                                             Homozygous (HS / HBS) The individual having both HES alleles gens. in both sickled cell genes. such people are sufferar for disease. 2.due to affected of both alteles does not produce normal hemoglobin. 3. Symptoms due to the presence of long chain polymere of Hbs destort the shape of RBC is sickled shaped.                                                                                                                                             The alleles are responsible for sickle cell anemia is autosomal recessive found on the short arm of chromosome II. The sickle cell anemia inherited from porents to offsprings The some ways are i) four blood type ii) hair color and texture iii) Eye colour traits. The type of heamoglobin making in RBC of person dependent upon which heamoglobin. gene is inherited from his parents conditions are follows 1. If one parent has sickle cell anemia (55) and other carrier (AS) 1) 50% chance to get child having sufferar for disease (ss). 2) 50% chance to get child having carrier for disease (AS) The child having one normal gene HbA and one defective gene Hbf alleles remains healthy but can pass the disease called as cartier. The carriers can produce few sickle shaped RBC only and not causes symptoms hence carrier also get resistance from maleria hence Heterozygoes have higher fitness than homozygoes S called as advantage of heterozygous.                   5. REALATION BETWEEN MALERIA & SICKLE CELL ANEMIA --- The malerial parasite plasmodium have complex life cycle and spend it's part in human erythraydes i.e. RBC ". The sporozoite condition of plasmodium enter the body of individual, If individual (HbA / HbS) carrier for disease, when a plasmodium (sporozoite) enters the blood following events occures in RBCs of individual. (1) When infectious stage of plasmodium i.e. sporozoites enter in RBCs, (f) The defective hemoglobin present in  due to (HBS) alleles (i) when sporozoite rupture RBC_permaturely but defective hoemoglobin in RBC inhabit or unable the plasmodium (sporozoite) asexually reproduction proccess to form merozortes (next stage of plasmodium, (4). ) This result into the non - destruction breakdown of affected (Hb) RBCs hence the formation of haemozoin not takes place result into non occurance of event of High fever and chilling (Hence individual having carrier or sufferer for sickle cell anemia does not cause maleria.                                                          6. CLINICAL SIGN & SYMPTOMS OF SICKLE CELL ANEMIA --- 1. Hemolytic crisis 1) Haemoglobuneria B) Oliguria 2 ii) Urine may be dark in color due to presence of urobilinogen  1) Massive pooling of RBC in visceral organs 2) Splenomegaly, speneoctomy  in hypersensitivity condition.  3. Immuno deficiency i) decrease in the number of antibodies against antigen.  ii) Loss of splenic function the genotype characterized by more rapid haemolysis.  4. Chlornic and hoaemolytic anemia i) Chlornic and haemolytic anemia is a hallmark of sickle cell disease.  vi) deficiency of folic acid and zinc vii) 5. Neurological complications 1. ischaemic attacks 7. Seizures cerebral infraction 8. Vestibular dysfunction 3. Cerebral haemorrhage 9. Sensory hearing loss.  4. unexpected coma 5. CNS infection 6. Spinal coard infraction comprassion .                                                            6. Acute chest syndrome 1. Dyspnea 2. chest pain 3. less commenly abdominal pain 4 fever tachypnea 5. Luecocytosis 6. Pulmonary infilturale 1. Non - cardiogenic pulmonoty edema 8. bone marrow infection 9. dangerous acute chest syndrome i.e. hypoximo + Haepotic Complications 1. Haepatomegaly 2. Transfusional bernosiderosis 3.  8). Renal Complications 1. Mudullary and distal tubular proximal tubular, gtomecular abnormalities 2. Papillary infraction 3. Hematuria 4. Incomplete renal tubular audosis 5. Consumption potassium metabolisoms 9. Cardia complications 1. High cardiac output result into Chlornic chamber enlargement and corrosion 2. Congestive heart feliur  Reduced O2 corrying capacity 4. hypertensions. 20). Life expectancy female - I) 48 years survive ii) male - 42 years survive.         10. Obstetrics and Gynecology problems 1. Dymenothea 2. pelvit infection_, 3. fribrocrystic disease of breast 4. Pregnancy complications i.e placenta blood flow intrauterine growth retardations low birth weight, pre-eclampsia 12. Ocular complications (opthalmological) 1. anterior chamber ischemia 2.ongoid streaks 4. Proliferative ratingpothy 5 Ratinal haemorrhage. Dermatological complications. Bone complications and infections accouure in 5: 6 Anemia.                                                                   7 DIAGNOSIS OF SICKLE CELL ANEMIA ----  Tests for diagnosis in pathology 1. CBC (complete blood count) - hemoglobin amount per 100 ml of blood.  2. Sickle solubility test  3. Electrophoresis 4. High performance required chromatography. 4. Prevention and Management 1. Nutritional management folic acid, iron rich fruits. Zinc rich foods 2. Take 5mg tablet of  folic acid both carrier. and suffering patient from Gov.health.  survice centers 3. The food containing cynate  derivatives ie thiocyanate. (It inhabits the sideling of RBC 4 other treatments also available thats are Intervenous fluid bone marrow transplant, blood transfusion etc.  ---- To fight against disease be educate and educate the people. Thanks!         Copyright ©️ - Gaurav khandare