haemoglobin metabolism and.its clinical applications pptx
TRANSCRIPT
![Page 1: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/1.jpg)
Hemoglobinmetabolismanditsclinicalapplications
Dr.Rohini CSane
![Page 2: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/2.jpg)
![Page 3: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/3.jpg)
![Page 4: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/4.jpg)
![Page 5: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/5.jpg)
![Page 6: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/6.jpg)
FunctionsofHemoglobinmoleculeinoxygentransport
![Page 7: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/7.jpg)
FunctionsofHemoglobinmoleculeincarbondioxidetransport
![Page 8: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/8.jpg)
![Page 9: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/9.jpg)
DegradationofHemetobilepigments
Macrophagesofreticuloendothelial (RE)inspleen/liver/bonemarrow-Hb
RBCà 12Odays
Nonprotein‘Heme’Globin
6gm /dayheme brokendown/resynthesisà Bilirubin(300mg/day)=250mg/dayHb+50mg/daymyoglobin
![Page 10: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/10.jpg)
![Page 11: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/11.jpg)
![Page 12: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/12.jpg)
![Page 13: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/13.jpg)
Fateglobin(reutilization)
• FormationofHb(resynthesis)• Degradedtoaminoacids–metabolismincludingformationofHb
![Page 14: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/14.jpg)
![Page 15: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/15.jpg)
![Page 16: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/16.jpg)
![Page 17: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/17.jpg)
SourcesofHeme
Heme
20%immatureRBC/Myoglobin/globin/cytochrome/peroxidase/catalaseTrppyrrolase80%RBCHb
![Page 18: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/18.jpg)
(GREEN–excretedbybirds&hibians)→
Transferrin
←αGlobinchains
←βGlobinchains
RBC(Agederythrocytes)withHbphagocytosisbymacrophages→
specificityforα methylenebridge←
Presenceinmammals←
Yellowwith36H←
→Bilirubin- AlbumincomplexinBlood
+
![Page 19: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/19.jpg)
Hemeoxygenase
1. Microsomalenzymes2. NADPH,O₂,Methylenebridgesbetweentwopyrroleringsà
biliverdin3. Fe²⁺à Fe³⁺
Heme oxygenaseHemeBiliverdin+Fe³⁺+CO• Biliverdinà excretedbybirds,amphibians&mammals
![Page 20: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/20.jpg)
DegradationofHemetobilepigments
BiliverdinreductaseBiliverdin(green) Bilirubin(nonfunctionalthereforeexcreted)1gmhemoglobin*à 35mgBilirubinBiliverdin+ Bilirubinà Hemederivatives• (*sources- 80%RBC+10%ineffectiveerythropoiesis+10%Myoglobin)• 6gm /dayheme brokendown/resynthesisà Bilirubin(300mg/day)=250mg/dayHb+50mg/daymyoglobin
![Page 21: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/21.jpg)
TransportofBilirubintoLiver
• Bilirubin- (lipophilic–insolubleinwater)• Bilirubin+Albuminà Transportedinplasma• Per100mlplasmaà 25mgBilirubinboundtighttoAlbumin• BilirubinhaslowaffinityforAlbuminà easilydetached&entertissue
![Page 22: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/22.jpg)
![Page 23: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/23.jpg)
Drugs :sulphonomides /salicylates/PenicillindisplaceBilirubinfromAlbuminbindingsites
BilirubinentersCNS
Damagetoneuronsà Kernicterus
DegradationofHemetobilepigments
![Page 24: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/24.jpg)
![Page 25: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/25.jpg)
![Page 26: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/26.jpg)
Conjugation0fBilirubinLiverAlbumin–Bilirubincomplex
IUptake carriermediatedactivetransportSinusoidalsurfaceofhepatocytes
Bilirubin+protein(Ligandin )2UDPGlucoronate
IIConjugation UDPEndoplasmic-reticulum(hepaticmicroosomes ) BilirubinGlucuronyl transferase(chromosome2)
Bilirubin+2moleculesofGlucuronate80%BilirubinDiglucuronide+20%Bilirubinmonoglucuronide
(MOAT–multiplespecificorganiciontransport)-presentincanalculi
IIIsecretionBilirubinOligonucleotide
Bilesalts
FateofBilirubininhumanbody
![Page 27: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/27.jpg)
![Page 28: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/28.jpg)
![Page 29: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/29.jpg)
FactorsaffectingconjugationofBilirubininliver
1. DrugslikePrimaquine/Novobiocin/Chloramphenicol,/Androgen/Pregnanediolinterferewithconjugationprocessmaycausejaundice.
2. DecreaseconcentrationofUDP-Glucuronyl Transferase3. PhenobarbitalinducesUDP-Glucuronyl Transferase
![Page 30: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/30.jpg)
Production&excretionofBilirubinRetiiculoendothelialsystem(RES)
Hb↓
Biliverdin(38H)↓
Bilirubin(36H)
LiverBilirubin
Diglucuronide
BilirubinDiglucuronide↓DeconjugationFreeBilirubin(36H)
↓reductionUrobilinogen (44H)byEcoli
(colorless)
Reductionofvinylgroupofstercobilinogen (48H)
↓stercoblin(46H)
DARKBROWN /200MG/DAY
BLOODUROBILINOGEN
KIDNEYUROBILINOGEN
UROBILLINOGEN(44H)↓
UROBILININURINE(42H)(<4GM/DAY)
BILEDUCT→←PORTALCIRCULATION
EHC↓
←SMALLPORTION
EHC–Entero hepaticcirculation
![Page 31: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/31.jpg)
![Page 32: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/32.jpg)
![Page 33: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/33.jpg)
![Page 34: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/34.jpg)
ExcretionofBilirubinintobile
ConjugatedBilirubinActivetransport*(againstconcentrationgradient)Ratelimitingstep
Bile>98%Bilirubinentersbileinconjugatedform
*InducedbyPhenobarbitone
![Page 35: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/35.jpg)
![Page 36: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/36.jpg)
Production&excretionofBilirubin
• ExcretionofBiliverdinà greencolorstool(children&prolongedantibioticstherapy)• Blackcolorstoolduringconstipation• Schlesingertest:Stercobilin (SB)&Urobilin (UB)+Zn²⁺à greenfluroscent
![Page 37: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/37.jpg)
Fouchet’s DiagnostictestforBilirubininurine
![Page 38: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/38.jpg)
![Page 39: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/39.jpg)
Bilirubin–yellow,Biliverdin–green ,Bilinofuschin –Red, Bilicyanin-violet
![Page 40: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/40.jpg)
←URINE→
Gmelin’s Test
←CONCHNO₃→
Bilirubin–yellow,Biliverdin–green ,Bilifuschin–Red, Bilicyanin-violet
![Page 41: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/41.jpg)
![Page 42: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/42.jpg)
![Page 43: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/43.jpg)
![Page 44: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/44.jpg)
FateofBilirubinBilirubinGlucuronides
Hydrolysis↓bacterialenzyme(β Glucuronidase )Bilirubin↓smallportionreabsorbed
Urobilinogen (colorless)à SBG(Erhlich +ve )↙↘
Stercobilin Urobilin(excretedinstool-)(excretedinurinebykidney)↓↓BrowncolorofstoolpaleyellowcolorofurineSerumBilirubinà VanDerBergTest,UrineBilirubinà Fouchet’s Test,Gmelin Test
![Page 45: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/45.jpg)
![Page 46: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/46.jpg)
![Page 47: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/47.jpg)
![Page 48: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/48.jpg)
![Page 49: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/49.jpg)
Conjugatedandunconjugatedbilirubin(Directandindirectbilirubin)
![Page 50: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/50.jpg)
Stercobilin andUrobilin
![Page 51: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/51.jpg)
FormationofconjugatedbilirubininHepatocytes
![Page 52: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/52.jpg)
TypesofBilirubinFreebilirubin Conjugatedbilirubin
1 InH₂O insoluble soluble2 Inalcohol soluble soluble3 Normalplasmalevels 0.2mg/dl 0.2-0.8mg/dl4 Inbile Absent present5 Inurine Alwaysabsent Normallyabsent(presentin
hemolytic&Obstructivejaundice)6 AbsorptionfromGIT Absorbed NotAbsorbed7 Diffusionintissue Diffusestocauseyellow Dosenotdiffuse
8 VanderBerghTest Indirectpositive directpositive
![Page 53: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/53.jpg)
Bilirubin&itsreductionproductsnumberofHatoms color
Bilirubin(BR) 36 RedyellowMeso bilirubin(MB) 40 yellowUrobillinogen (UBG) 44 colorlessStercobilinogen (SBG) 48 colorlessUrobilin (UB) 42 OrangebrownStercobillin (SB) 46 Darkbrown
![Page 54: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/54.jpg)
Jaundice- HyperbilirubinemiaPhysiological– TotalBilirubinconcentrationinserum=(0.2- 0.8mg/dl)
0.2-0.6mg/dl(unconjugated)0- 0.2mg/dl(conjugated)Yellowcolorsclera&skin(depositionofbilirubin)-conc ofserumbilirubin>2mg/dl
q ConjugatedHyperbilirubinemiaq UnconjugatedHyperbilirubinemiavSymptoms1. Nausea2. Vomiting3. AppetiteØ LatentJaundice(1-2mg/dl)
![Page 55: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/55.jpg)
*Diagnosticlaboratorytosetupownqualitycontrolsforreferenceranges
![Page 56: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/56.jpg)
Prehepatic,Hepaticandposthepaticjaundice– aclassificationbasedonsite(causeofofHyperbilirubinemia)
![Page 57: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/57.jpg)
ClassificationofJaundicebasedontypeofBilirubin
![Page 58: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/58.jpg)
Intrahepaticjaundice(Genetic/inheritedcauses)
![Page 59: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/59.jpg)
Cause• HemolyticJaundice
• Causes– HemolysisMalariabloodtransfusionsicklecellanemia
• LiverfailstoconjugateexcessofBilirubin
• Therefore↑unconjugatedbilirubin↑Urobilinogen↑stercobilinogen(browncolorstool)
• SGPT/ALP-Normal
• HepaticJaundice• Causes–dysfunctionofLiverHepatitisalinfectionpoisons/toxinscirrhosis/CCF
• ↑unconjugatedbilirubin↑conjugatedbilirubin↑Urobilinogen↑stercobilinogen(browncolorstool)↑SGPT/ALP
• ObstructiveJaundice• Gallstonestoolcontainsfatunavailabilityofbilesalts
• ↑conjugatedbilirubin↑Urobilinogen↓ stercobilinogen (palecolorstool)↑SGPT/ALP
ComparisonofHemolytic/hepaticandobstructiveJaundice
![Page 60: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/60.jpg)
DifferentialdiagnosisJaundice/Icterus
![Page 61: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/61.jpg)
HemolyticDiseaseofAdultsà unconjugatedHyperbilirubinemia
1. increaseinunconjugatedbilirubininblood2. Absenceofbilirubininurine3. Excretionofurobilinogenà (EhrlichTestpositive)4. Excretionofstercobilinogen infaecesvDiseasesassociatedwitha) congenitalspherocytosisb) G6PDdeficiencyc) Autoimmunehemolyticanemiad) Toxincarbontetrachloride
![Page 62: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/62.jpg)
HemolyticDiseaseofAdultsà unconjugatedHyperbilirubinemiaIncompatibilitybetweenmaternal&fetalbloodgroupsAntiantibodiesABOIgM typecannotbetransferredtoplacentavRh incompatibilityFetusmotherRh(+ve )Rh(-ve )RBCRBC elicitimmuneresponseAnti-D(IgG)
Destruction Anti-D (IgG )
Of RBC←Placenta
Secondpregnancy(beforebirth–destructionofRBC)à CHILDbornwithseverehemolyticdiseaseàErythroblastosis fetalis
![Page 63: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/63.jpg)
Erythroblastosis Fetalis• SerumBilirubinà >20mg/dlà nomoreboundtoAlbumin
• BilirubinBrain(Kernicterus-depositionofbilirubininbrain)• Basalgangliaàmentalretardation• ↓ATPasemitochondriaà fits,spasticity,toxicencephalitis• Treatment:(1)phototherapybeforeage<1yearà
isomerizationZZà ZE(2)Bloodtransfusion
![Page 64: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/64.jpg)
![Page 65: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/65.jpg)
![Page 66: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/66.jpg)
![Page 67: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/67.jpg)
![Page 68: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/68.jpg)
![Page 69: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/69.jpg)
![Page 70: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/70.jpg)
![Page 71: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/71.jpg)
![Page 72: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/72.jpg)
HepatocellularJaundice
1. ViralHepatitis(virusesA,B,C,DorG)à purehepatocellulardiseases
2. ↓conjugatedbilirubintherefore↑freeBilirubin3. Inflammatoryodemaofcellsà intracellularcanalculicompressed
à obstruction(atsiteofbileformation)4. Increaseobstructionà↑obstructionà↑conjugatedBilirubin
thereforeBiphasic5. Bilirubinuria6. UrobilinogenàNORMAL ordecreasedinhepatocellularJaundice
![Page 73: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/73.jpg)
ObstructiveJaundiceà conjugatedHyperbilirubinemia1. ↑conjugatedbilirubin2. Bilirubininurine3. ↓urobilinogen (nilifobstructiveiscomplete)4. Faeces claycolor(↓stercobilinogen )5. Absenceofbilesaltsà Stetorrhoeamayresult6. CausesIIntrahepaticCholestasisa) Activehepatitisb) Biliarycirrhosisc) Lymphomasd) Hepatomae) Viralhepatitis
![Page 74: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/74.jpg)
ObstructiveJaundiceà conjugatedHyperbilirubinemia
• CausesIIExtrahepaticCholestasis1. Stonesinbiliarytract2. Stonesingallbladder3. Biliaryatresia4. Carcinomaheadofpancreasà lymphglandsenlarged5. Porta hepatitis
![Page 75: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/75.jpg)
Acquiredhyperbilinogen(unconjugatedhyperbilinogen)
vPhysiologicalJaundiceofnewborn(neonates)1. Afterseconddayoflife,transienthyperbilinogen –Jaundice2. ↑rateofdestructionofRBC(transient)3. à immaturehepaticsystemofconjugation4. à Bilirubindonot exceed5mg/dl5. à 2weeksphototherapy+barbitonetoinduceconjugation(ZZ
bilirubinà ZE+EEà excretedwithoutconjugationinurine)6. Undueprolongationà crenism7. Breastmilkjaundice(estrogenà↓enzymeGlucuronyl transferase)
![Page 76: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/76.jpg)
![Page 77: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/77.jpg)
Bilepigment DiagnosticTestBilirubin VanDerBergh(serum),Fouchet’s Test&Gmelin ‘stest
inUrineUrobilinogen (UBG) Ehrlich’sTestUrobilin Schlesinger’stest
![Page 78: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/78.jpg)
DIRECTBILIRUBIIN- Azo pigment(pH5)àPURPLECOLOR-↓
INDIRECTREACTION–FREEBILIRUBIN(H2Oinsoluble,alcoholsoluble)
![Page 79: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/79.jpg)
![Page 80: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/80.jpg)
*Diagnosticlaboratorytosetupownqualitycontrolsforreferenceranges
EnzymeestimationshelpindifferentialdiagnosisofJaundice
![Page 81: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/81.jpg)
EnzymeestimationshelpindifferentialdiagnosisofJaundice
*Diagnosticlaboratorytosetupownqualitycontrolsforreferenceranges
![Page 82: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/82.jpg)
EnzymesindicatingHepatocellulardamage
v↑ALT↑ASTViralHepatitis
v↑IHDHepatocellularnecrosis
v ALT/ALT>1AlcoholliverdiseaseObstructiveliverdisease:cholestasis/hepaticcarcinoma/parenchymalcell
damage
![Page 83: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/83.jpg)
Parameter HemolyticJaundice HepaticJaundice
ObstructiveJaundice
1 Bloodfreebilirubin ↑ ↑ normal2 Conjugatedbilirubin normal ↑ ↑
3 ALP normal ↑ ↑↑
4 Bilesalts Nil Nil PRESENT5 UrineBilirubin Nil Nil PRESENT6 Urineurobilinogen ↑ Nil Nil7 Stool Darkbrown Claycolor
DifferentialDiagnosisofJaundice
![Page 84: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/84.jpg)
![Page 85: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/85.jpg)
![Page 86: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/86.jpg)
![Page 87: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/87.jpg)
FateofBilirubin
![Page 88: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/88.jpg)
![Page 89: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/89.jpg)
![Page 90: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/90.jpg)
CongenitalHyperbilirubinemiavAbnormaluptake,conjugationorexcretionofbilirubinduetoinheriteddefects• 1.GilbertDisease–defectinuptake• 2.CriglerNajjar syndrome–defectinconjugation
![Page 91: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/91.jpg)
CongenitalHyperbilirubinemiav(1) Gilbert’sDiseasea) Autosomaldominanttraitb) DefectuptakeofBilirubinc) Asymptomaticd) Presenceofjaundice(Bilirubinà 3mg/dl)
![Page 92: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/92.jpg)
CongenitalHyperbilirubinemia(2)CriglerNajjar syndrome:DefectinconjugationTypeIa) CongenitalnonhemolyticJaundiceb) DeficiencyofUDP–Glucuronyl transferasec) Fatal(deathbeforetwoyearsofage)d) Jaundiceappearswithin24hrsoflifee) Unconjugatedbilirubin(>20mg/dl)f) Kernicterusg) Barbituratesnoeffect(enzymenodefect)
![Page 93: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/93.jpg)
CongenitalHyperbilirubinemia(2)CriglerNajjar syndrome:DefectinconjugationTypeIIa) CongenitalnonhemolyticJaundiceb) DeficiencyofUDP–Glucuronyl transferasec) Diseaserunsmorebenigncoursed) Bilirubin–mononucleotidepresente) Totalbilirubinseldome rises:Unconjugatedbilirubin(>15mg/dl)f) NoKernicterusg) Barbituratesuseintreatmentà Jaundiceimproves
![Page 94: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/94.jpg)
ManagementofCrigler Najjar Syndrome
![Page 95: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/95.jpg)
CongenitalHyperbilirubinemiavDubin Johnson’ssyndromea) Autosomalrecessivetraitb) ↑conjugatedbilirubininbloodc) DefectinexcretionofconjugatedBilirubin(ATPase dependent
organicanionTransporterprotein-MOATmutationd) DefectATPdependentorganicaniontransportinbilecanalculie) BilirubingetsdepositedinliverthereforeBilirubingetsdepositedin
liver(BlackLiverJaundice)f) DiagnosticTest:BromosulphthaleinTest
![Page 96: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/96.jpg)
CongenitalHyperbilirubinemiavDubin Johnson’ssyndromeDiagnosticTest:BromosulphthaleinTest250mgBromosulphthalein(intravenous)
Normal(dyeremainingplasma) Dubin Johnson’ssyndrome(dyeremainingplasma)
45min <5% >2hrslevels(<2%)2hrs <2% <45minlevels(>5%)
(2hrlevelmorethan45min)
At45minBSPtakenupbyhepatocytes/thereforedecreaseinblood levels
EXCRETORYDEFECT:BSPregurgates inblood
![Page 97: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/97.jpg)
CongenitalHyperbilirubinemiavRotorsyndromea) Causenotknown(autosomalrecessive)b) Bilirubinexcretiondefectivec) Nodepositionofpigmentinliver
?
![Page 98: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/98.jpg)
ComparisonofDubin Johnson’sandRotor‘ssyndrome
![Page 99: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/99.jpg)
ComparisonofGilbert‘sandCrigler- Najjar syndrome
![Page 100: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/100.jpg)
![Page 101: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/101.jpg)
![Page 102: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/102.jpg)
BiosynthesisofHeme(Porphyrinring)• Siteà Liver/RBCproducingcellsofbonemarrow(erythroid cells)/othertissue• ExcretiontoruleàmatureRBClackingmitochondria• IFormationofδ aminoLevulinate (mitochondria)Glycine+succinylCoA
* Pyridoxalphosphatedependentδ aminoLevulinate synthtase
δ aminoLevulinate (ALA)*ratecontrollingstep
![Page 103: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/103.jpg)
BiosynthesisofHeme(Porphyrinring)IISynthesisofPorphobilinogen2. δ aminoLevulinate (ALA)
ALADehydratase *
Porphobilinogen(PBG)• ActivitydecreasesbyPb /Hg&Zinccontainingenzyme
![Page 104: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/104.jpg)
BiosynthesisofHeme(Porphyrinring)1. SuccinylCoA+Glycine→ALA2. ALA+ALAà Porphobilinogen(PBG)+2H₂O3. 4X(PBG)4. Uroporbilinogen III(UBG)5. Coporphyrinogen III(CPGIII)+CO₂6. Protoporphyrinogen III(PPGIII)7. HEME
![Page 105: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/105.jpg)
BiosynthesisofHeme(Porphyrinring)
SuccinylCoA+Glycine→ALA
ALA+ALAà Porphobilinogen(PBG)+2H₂O4
4X(PBG)Uroporphyrinogen
Coporphyrinogen III(CPGIII))
Protoporphyrinogen III(PPGIII)
HEME
HEMGLOBIN1. ALA SYNTHTASE 2.ALA DEHYDRATASE 3.PBG DEAMINASE&UPGIIICOSYNTHTASE 4.UROPORPHYRIN
DECARBOXYLASE 5COPORPHYRINOGENOXIDASE 6.Hemesynthtase
→4CO₂
NADP+O₂→ →NADPH+H+2CO₂
ACETYLàMETHYL
PROPINYLàVINYL
![Page 106: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/106.jpg)
ACETYLàMETHYL,4CO₂
PROPINYLà VINYL+2CO₂
BiosynthesisofHeme
![Page 107: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/107.jpg)
![Page 108: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/108.jpg)
![Page 109: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/109.jpg)
![Page 110: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/110.jpg)
Metallo- porphyrin
1. UroporphyrinI&III2. Coporphyrin I&III3. PROTOPORPHYRINIX&HEMEvHemecontainingproteins- hemoglobin,cytochromes,catalase,tryptophanpyrrolase
![Page 111: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/111.jpg)
Hemesynthesis
• Site :mitochondriaofallmammalian tissueexceptRBCpredominantlyinLiver&bonemarrow
vStepI :*ALAsynthasePLP CO₂CoASH
SuccinylCoA+Glycineδ ALA• δ ALA:DeltaaminoLevullinic acid• *Regulatoryenzyme=ratelimitingstepqINHtreatmentà PLP↓à ALASYNTHESIS↓
![Page 112: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/112.jpg)
Hemesynthesis
vStepII :Site–MITOCHONDRIA
*ALADEHYDRATASEPLP 2H₂O2MoleculesofALAPorphobilinogen(PBG )*activitydecreasedbyheavymetals
![Page 113: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/113.jpg)
Hemesynthesis
vStepIII : Site–MITOCHONDRIA
*PBGDEAMINASE4NH₃4MoleculesofPBGUroporphyrinogen(UBG )
• *UroporphyrinogenIsynthtase&UroporphyrinogenIIIsynthtase• *deficiencyofUroporphyrinogenIIIsynthtaseleadstoformationofTypeIUBGà Porphyria
![Page 114: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/114.jpg)
Hemesynthesis
vStepIV :Site–MITOCHONDRIA
*Uroporphyrinogendecarboxylase4CO₂• Uroporphyrinogen(UBG )Type III CoproporphyrinogenIII
• *AcetylàMethyl• *deficiencyofà Porphyria
![Page 115: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/115.jpg)
Hemesynthesis
vStepV : Site-CYTOSOLIC
*Coproporphyrinogenoxidase2CO₂Coproporphyrinogen IIIProtoporphyrinogenIII
O₂• *Methylà Vinyl• *deficiencyofCoproporphyrinogenoxidaseà Porphyria
![Page 116: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/116.jpg)
Hemesynthesis
vStepVI :Site-CYTOSOLIC
*Protoporphyrinogenoxidase4HProtoporphyrinogenIIIProtoporphyrin III (IX)
Methylene(CH2)àMethenyl (CH- )• *deficiencyofProtoporphyrinogen oxidaseà Porphyria
![Page 117: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/117.jpg)
Hemesynthesis
vStepVII :Site-CYTOSOLIC
*HemesynthtaseProtoporphyrinIII (IX)Heme
Fe²⁺• Ferrochelatase• Heme+ Protein= HEMOGLOBIN
![Page 118: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/118.jpg)
![Page 119: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/119.jpg)
![Page 120: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/120.jpg)
![Page 121: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/121.jpg)
![Page 122: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/122.jpg)
![Page 123: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/123.jpg)
![Page 124: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/124.jpg)
1.SuccinylCoA+Glycineà
ALA
ALA
2.ALAà PBG
3.PBGà UBGIII 4.UBGà CPGIII
CPGIII
CPGIII
5.CPGIIIàPPGIII 6.PPGà PP 7.PPà HEME
CYTOSOLIC-2,3,4
MITOCHONDRIAL
HEMESYNTHESIS
![Page 125: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/125.jpg)
RegulationofHemesynthesis1.↑Glucoseà↑catabolismofCRP(repressorprotein)à decreaseALA(inductionprevented,Glucoseadministeredfortreatmentofporphyria
2.↓ALAsynthasebyHematin,ExcessoffreeHeme(Fe²⁺à Fe³⁺)
3.Compartmentizationofenzymesà easierforregulation,ratelimitingstepsinmitochondria
4. Hemesynthesiscontrolledbya)globinsynthesisb)Druglikebarbiturates(requirecytochrome450)
5.lead/Mercury↓ALASynthase↓Ferrochelatase
![Page 126: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/126.jpg)
![Page 127: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/127.jpg)
RegulationofHemesynthesis
ThreemechanismscontrollingactivityofALAsynthasebyHeme/HematinFe³⁺
a.Feedbackinhibition(Heme/HematinFe³⁺)
b.RepressionofALAsynthase
C.InhibitionofALAsynthasetransportfromcytosoltomitochondria(thesiteofaction)
Hemesynthesissite:liver(ALAsynthaseà regulatoryenzyme)
![Page 128: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/128.jpg)
![Page 129: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/129.jpg)
EffectofdrugsonALAsynthaseactivity1. *Phenobarbital2. *Insecticides ↑activityofALAsynthase3. *Carcinogen* MetabolizedbyHEMEcontainingproteincytochrome450
↓IncreasedincorporationofHemeincytochrome450
↓↓cellularlevelofHeme
↓↑ALAsynthase(derepression)tomeetcellulardemands
![Page 130: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/130.jpg)
RegulationintheErythroidcells
vALAsynthasedosenotregulateHemesynthesisinErythroidcellsvUroporphyrinogensynthase&Ferrochelatase regulateHemesynthesis
vCellularuptakeofironregulateHemesynthesisvHemestimulateglobinsynthesis
![Page 131: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/131.jpg)
RegulationofHemesynthesis
![Page 132: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/132.jpg)
Porphyrin&BilirubinMetabolism
• Porphyrin :Groupofcompoundsof4substitutedpyrroleringslinkedbyMethanebridges•à formationofcomplexeswithmetalionsboundtoN₂atomofpyrrolering
IRON
Heme
Hb
MAGNASIUM
Chlorophyll
Photosynthetic pigment
![Page 133: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/133.jpg)
Porphyrin&BilirubinMetabolism
vIronPorphyrins :1. Hemoglobin2. Myooglobin3. Cytochrome4. Catalase&peroxidase5. Tryptophanpyrrolase
![Page 134: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/134.jpg)
![Page 135: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/135.jpg)
PorphyrinMetabolism• Porphyria's:GroupofinbornerrorsofmetabolismassociatedwiththebiosynthesisofHeme• Characteristics of Porphyrias :increaseinproduction&excretionofporphyrin&theirporphyrinprecursorsALA&PBG• AutosomaldominantorAutosomalrecessive• Diagnosis ofPorphyria's:• 1.urine(exoposure toUVà red fluorescence )• 2.urine+CHCl₃à extraction• Aqueouslayer(PBG)+Ehrlichreagentà pink color
![Page 136: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/136.jpg)
![Page 137: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/137.jpg)
![Page 138: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/138.jpg)
Porphyria's:
• TypesPorphyria's:1.inheriteda) Erythropoietin :enzymesdeficiencyoccursinerythrocytesb) Hepatic : enzymesdeficiencyliesintheliver2.Acquired💟
![Page 139: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/139.jpg)
![Page 140: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/140.jpg)
![Page 141: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/141.jpg)
![Page 142: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/142.jpg)
![Page 143: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/143.jpg)
![Page 144: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/144.jpg)
![Page 145: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/145.jpg)
Autosomalrecessive
Autosomaldominant
Erythrodontia
RBC-FLUORESCENCE
Liver,skinfluorescence
![Page 146: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/146.jpg)
AcuteintermittentPorphyrias• DeficiencyofenzymesUroporphyrinogensynthaseI
SuccinylCoA+Glycine
δ aminolevilinate(ALA)↑
Porphobilinogen ↑
UroporphyrinogenIII
δ aminolevilinatesynthase
ALADehydratase
Uroporphyrinogen synthase
Uroporphyrinogen I
↑ALA↑PORPHYRINOGEN
![Page 147: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/147.jpg)
![Page 148: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/148.jpg)
![Page 149: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/149.jpg)
1.AcuteintermittentPorphyria• Age :afterpuberty(Artist–Vincet ,KingGeorgeIII–MAD)• Deficient enzyme :UroporphyrinogensynthaseI(↑ALA–nofeedbackmechanism)• Noporphyria,nophotosensitivity• Excretion inurine:δ aminolevilinate(ALA)&porphobilinogen (PBG)• Exposureofporphobilinogen (PBG)toairdarkens(formationofPorphobilin )• Diagnosis:urinaryconc ofPBG(darkenson exposuretoair)• Symptoms:Abdominalpain,Vomiting,cardiovascularabnormalities,neuropsychiatricdisturbances(therefore↓Trppyrrolase ,↑Trp,5ʹOHTyramine• Treatment:Hematinà↓ALA, ↓PBG• Adverse effects :Barbiturate(ppt ofattack)à↑ALAsynthase(ascytochrome450)àPBG↑,increasewithcarbohydratediet&menopause
![Page 150: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/150.jpg)
![Page 151: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/151.jpg)
2.Congenital erythropoietin PorphyriavCongenitalvDeficient enzyme :↓UroporphyrinogencosynthtaseIII• Excretioninurine:UroporphyrinogenI&Coporphyrinogen Ià
↓oxidation↓UroporphyrinI&Coporphyrin I
Symptoms :1.↑Hemolysis2.Erythrodontia(teeth),portwinecolorurine3.ExposureOFSKINà UVsensitizationofporphyrinà absorbed&emitredfluorescentlight4.Dermatitis,scarringburning&itchingofskin- ear&nose(Leprosylike),(asROS↑à accumulationofPorphyrin)5.portwinecolorurine(UroporphyrinI&Coporphyrin I)
![Page 152: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/152.jpg)
Congenital erythropoietin Porphyria
PhotosensitivityErythrodontia (teeth )
![Page 153: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/153.jpg)
Congenital erythropoietin Porphyria
Dermatitis,scarringburning&itchingofskin- ear&nose(Leprosylike,(asROS↑à accumulationofPorphyrins )
![Page 154: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/154.jpg)
Dermatitis,scarringburning&itchingofskin- ear&nose(Leprosylike)(asROS↑à accumulationofPorphyrins
Congenital erythropoietin Porphyria
![Page 155: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/155.jpg)
![Page 156: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/156.jpg)
3.Porphyria Cutanea Tarda• Cutaneoushepaticporphyria• Deficient enzyme :↓Uroporphyrinogendecarboxylase• Excretioninurine:Porphobilinogen&Uroporphyrin(I&III)rarely• Symptoms :1. Cutaneous2. Photosensitivity3. LiverexhibitsfluorescenceTreatment :Hematin(↓ALAsynthase,↓accumulationvariousintermediate)
![Page 157: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/157.jpg)
4.Hereditary Coporphyria• Deficient enzyme :↓Coporphyrinogenoxidase• Excretioninurine:UroporphyrinogenI&Coporphyrinogen Ià
↓oxidation↓UroporphyrinI&Coporphyrin I
• Urinedarkcolor:presenceof UroporphyrinI ,Coporphyrin I,ALA,PBG• Treatment :Hematin(↓ALAsynthase,↓accumulationvariousintermediate)•
![Page 158: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/158.jpg)
![Page 159: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/159.jpg)
5.Variegate porphyria• Deficient enzyme :Protoporphyrinogen oxidase• Accumulationinplasma&excretioninurineof:PorphobilinogenUroporphyrinogen,Uroporphyrin,Coproporphyrinogen,Coproporphyrin,Protoporphyrin(↓Hemesynthesis)• Photosensitivity exhibited• Plasmaexhibitsredfluorescence(duepresenceofCoproporphyrinogen• Neuropsychiatric manifestation
![Page 160: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/160.jpg)
![Page 161: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/161.jpg)
6.Herediatory Protophyria (Erythropoietic protoporphyria )
• Deficient enzyme:Ferrochelatase• Accumulationinplasma(increaseinconcentration) ,excretioninurine (increaseinconcentration)& faeces (increaseinconcentration)of:PROTOPORPHYRINIX• RBC,skinexhibitredfluorescence•
![Page 162: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/162.jpg)
7.Acquired (toxic )Porphyrias• Exposureofbodytotoxiccompounds(toys/Xeroxink)Examples:Heavymetals(Lead)↓ALADehydratase
Hexchlorobenzene ↓UroporphyrinsynthaseIDrugs(Griseoflavin )↓Ferrochelatase
Therefore↓Heme↑ALAsynthaseAquried porphyrias associatedwithanamia
![Page 163: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/163.jpg)
![Page 164: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/164.jpg)
![Page 165: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/165.jpg)
ReactionsofHeme synthesis
![Page 166: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/166.jpg)
PrenataldiagnosisofPorphyriasEnzymeestimations/PCR
![Page 167: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/167.jpg)
Anemia• 75%Indianpopulationsufferfromanemia• Hbconcentrationdecreasesinanemia<10gm%(normalconcentrationofbloodHb– 14-16mg%-male,13-15mg%-female)vIIronDeficiencyanemia–mostcommona) Nutritionalb) LackofabsorptionofIron(Gastrectomy&Achlorhydria )c) Hookworminfection(0.3ml/day/hookworm)d) Repeatedpregnancy(↓hemoglobin-1gmperdelivery)e) Nephrosisà Glomerularfiltration→proteinuriaf) LossofHaptoglobin/Hemopexin /Transferring) Heavymetalpoisoningh) Lossofblood(menustrual cycle,piles,pepticulcers,Uterinehemorrhages)
![Page 168: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/168.jpg)
AnemiaII-ImpairedproductionofRBC
DefectinHemesynthesis
• Nutritional• Deficiencyofiron,Copper,VitaminB12,VitaminC
• Leadpoisoning
DeficiencyofERYTHROPOITIN
• Physiological–kidneycellssynthesizeERYTHROPOIETIN
↓• ↑RBCsynthesis• Chronicrenalfailureàno ERYTHROPOIETIN
Decreaseinstemcells
• APLASTICANEMIA
• MALIGNANTINFITRATION
• INFLECTION
![Page 169: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/169.jpg)
![Page 170: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/170.jpg)
Hemin crystals
• Fe²⁺↔Fe³⁺à Fe³⁺+Cl⁻à HematinchlorideorHEMINvMedicallegalcases• Blood+Bloodstains+Nippe ’sfluid(1%KCL+KBr +KI+Glacialaceticacidà darkbrownRHOMBICcrystalàmicroscopicinspectionHemepartofBloodà Testpositive
![Page 171: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/171.jpg)
Hemin crystals
![Page 172: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/172.jpg)
HemoglobinestimationvDrabkin’s TestforHemoglobinestimation:Cyanmeth HemoglobinMethod• Blood(Hb)+Drabkin’s reagentàCyanmeth Hemoglobin(Absorbance-540nm)à colorimetricestimation• Hb+potassiumferricyanideàMeth- Hb
![Page 173: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/173.jpg)
![Page 174: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/174.jpg)
Sulph Hemoglobinemia• Oxy–Hb+H₂Sà Sulph –Hb(absorptionpeakat620nm)
vFormationofSulph –Hbbysulphonamide ,Phenacetin ,Dapsone ,AcetonevBasophilicstripingofRBC
←Irreversible
![Page 175: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/175.jpg)
![Page 176: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/176.jpg)
AbnormalHborHbvariants1.Sicklesyndromea) 1. sicklecelltrait(AS)b) 2.sicklecelldiseasewithSS,SC,SD,SO,Sβ Thalassemia2.UnstableHaemoglobinsCongenitalHeinzbodyanemia–Hb Zurich3.HbwithabnormaloxygenaffinityA.Highaffinityà Polycythemia(familial)à HbChesapeake,OlympiaB.Low affinityà Cyanosis(familial)à HbM,Hb–Kansas,Hb- Hoppe4. StructuralvariationleadingtoThalassemia'sphenotypeA. AlphaThalassemiaà HbConstantspring,DeltabetaThalassemia,Hb–
LeporeB. BetaThalassemia:HbQuongC. 5.Hemoglobinthatdonot produceanyclinicalsymptoms:HbP HbQ ,HbJ
![Page 177: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/177.jpg)
![Page 178: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/178.jpg)
SICKLE CELL DISEASEvCharacteristics of Sickle cell disease a) Glutamicacidà Valine (6th positiononbetachain)b) Hydrophilicà Hydrophobic(stickinessonsurfaceofmolecule)c) PolymerizationofHb inRBCàdistortionofRBCintosickleshapedd) DeoxyHbS hasprotrusionononeside&cavityonothersideà
manymoleculesadheretogether
![Page 179: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/179.jpg)
![Page 180: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/180.jpg)
![Page 181: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/181.jpg)
![Page 182: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/182.jpg)
![Page 183: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/183.jpg)
![Page 184: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/184.jpg)
![Page 185: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/185.jpg)
![Page 186: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/186.jpg)
![Page 187: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/187.jpg)
![Page 188: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/188.jpg)
SICKLE CELL DISEASE
![Page 189: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/189.jpg)
![Page 190: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/190.jpg)
![Page 191: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/191.jpg)
![Page 192: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/192.jpg)
![Page 193: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/193.jpg)
![Page 194: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/194.jpg)
![Page 195: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/195.jpg)
![Page 196: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/196.jpg)
SignsandsymptomsofThalassemiamajor
![Page 197: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/197.jpg)
![Page 198: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/198.jpg)
![Page 199: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/199.jpg)
![Page 200: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/200.jpg)
InheritanceofThalassemia
![Page 201: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/201.jpg)
![Page 202: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/202.jpg)
![Page 203: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/203.jpg)
AbnormalHborHbvariantsIIIHemolyticanaemias duetointra-corpusculardefecta) Hemoglobinopathies :HbS ,Hbc ,HbMb) Thalessemias :major&minorc) Abnormalshapespherocytosis&elliptocytosisd) Enzymedeficiencyà Glucose6PhosphodehydrogenaseIVHemolyticanemiadueextracorpuscularcause/defectsa) Infection–malarialparasites,streptococcusb) AutoimmuneHemolysis–RBCmembranecomponent,Syphilis,
Lympholenticular neoplasiac) Isoimmune hemolysisà RhincompatibilityinNewbornd) Hemolysisduetodrugsensitization–Dopa quinone (fixedonRBC)à
Abnormalantibodies againstalteredmembrane
![Page 204: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/204.jpg)
AbnormalHborHbvariantsVhemorrhages
a) Hematuriab) Hematomesisc) Hemoptysisd) Pepticulcerse) Hemorrhoidesf) Thrombocytopeniag) Menorrhagiah) Bleedingtendencies
![Page 205: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/205.jpg)
![Page 206: Haemoglobin metabolism and.its clinical applications pptx](https://reader033.vdocument.in/reader033/viewer/2022042511/58eef7701a28ab635e8b45a9/html5/thumbnails/206.jpg)