HEMA311 Hematology 1 PDF

MIDTERM: RBC STRUCTURE, METABOLISM, DESTRUCTION, FUNCTION BSMLS TERM HEMA311 HEMATOLOGY 1 LECTURE...

MIDTERM: RBC STRUCTURE, METABOLISM, DESTRUCTION, FUNCTION BSMLS TERM HEMA311 HEMATOLOGY 1 LECTURE 3 01 OUTLINE ▪ Kapag ang cell ay nag I increase in size, ‘yung surface area ay nag d-decrease I. RBC Membrane IV. Metabolic Pathways o Acquisition of a biconcave shape Characteristics o Loss of cytoplasmic organelles V. Erythrokinetics o Undergoes active endocytosis and exocytosis II. Structure of RBC which does not occur in mature RBCs Membrane VI. Mechanism of Red Cell Destruction III. Red Cell Membrane Mature Red Blood Cell Membrane Skeleton Constantly changes as it moves through the circulation Soft and pliable ERYTHROCYTES o they are soft and pliable in order for them to pass through capillaries Mature RBCs size 6-8 micron average of 7.5 in diameter o pliable – elastic/flexible; capable sila makapunta o When you cut it cross-sectionally, nagiging sa maliliit na capillaries makapal po siya – 2.5 ‘yung kapal Biconcave shape Has no nucleus nor organelles Consists of a membrane skeleton protein lattice and o Because in the series of maturation of rbc lipid bilayer production mayroong mga stages na stoped na o 40% lipids mostly phospholipids, cholesterol ang mitosis kaya ‘yung mga mature RBC ay o 8% carbohydrate linked to lipid or protein anucleate na. o 52% qlycoproteins Exists in blood circulation for 120 days More than 50 transmembrane proteins have been o In cases of hemolytic anemia, nagkakaroon ng identified and more than half carries blood group antigens premature destruction in which they cannot reach the 120 days. Mas earlier ‘yung destruction ng Deformable and tolerant against mechanical stress and RBC natin. various pH and salt concentrations in vivo and in vitro Limited activity to metabolize fatty acids and amino acids Cell shape changes reversibly Metabolic processes are maintained through different metabolic pathways to produce energy STRUCTURE OF RBC MEMBRANE o Embden-Meyerhof ▪ Source of energy Membrane Lipids ▪ Needed by the RBC for them to have energy Outer layer ▪ produces ATP – responsible for the o Phosphatidyl choline energy of the RBC. o Sphingomyelin o Oxidative or Hexose-Monophosphate shunt Inner layer o Methemoglobin reductase o Phosphatidyl ethanolamine o Leubering-Rapoport o Phosphatidyl serine ▪ These four metabolic pathways will Membrane Proteins help RBC to exist in blood circulation for 120 days Integral Protein RBC MEMBRANE CHARACTERISTICS o Band 3 (anion exchanger protein) o Glycophorin Reticulocyte Membrane o Aquaporin Peripheral protein Young reticulocytes are less stable than those of mature o Spectrin cells o Actin o Immature rbc that can also be seen in peripheral o Protein 4.1 blood circulation o Pallidin (band 4.2) o Ankyrin Possesses a significant amount of tubulin and actin o Adducin o Tubulin – the skeletal system for living cells o Tropomycin o Actin – responsible for contraction and relaxation o Tropomodulin of the membrane ▪ Spectrin, actin, ankyrin – magbibigay ng Transition to mature RBCs has significant changes shape sa ating RBC o Increase in shear resistance o Loss of surface area (SAV) (about 20%) due to loss of membrane lipid BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 1  Aquaporin 1 Selective pores for water transport o Aquaporin is also known as the water transporter Allows RBC to remain in osmotic equilibrium with extracellular fluid o Should always be balanced kasi pag hindi, it will swell at maraming papasok na water and it may burst NOTE: The horizontal interaction will support all the content and structural integrity of the RBC o The horizontal interaction will support lahat ng content, yung band 3, ankyrin, protein 4.2, adducin will support horizontal interaction o Spectrin (alpha and beta), actin, protein 4.1, ankyrin The vertical interaction will stabilize the lipid bilayer membrane and support the internal and external of RBC (band 3, glycophorin) RED CELL MEMBRANE SKELETON Kailangan dikit-dikit sila or may link kasi yan ‘yung nag p Hexagonal lattice with 6 spectrin molecules provide ng stability nila Each linked to multiple Spectrin tetramers Composed of spectrin, actin, protein 4.1 INTEGRAL PROTEIN Ankyrin links the lipid bilayer to membrane via interaction with band 3 Band 3 Spectrin Anion transport o Exchanges bicarbonate for chloride Flexible, rod–like molecule Linkage of lipid bilayer to underlying membrane Responsible for biconcave shape of RBC skeleton o Most abundant peripheral protein o Interaction with ankyrin and protein 4.2, secondarily o Spectrin is the primary cytoskeletal proteins through binding to protein 4.1 o Naka attach siya sa ankyrin Important for prevention of surface loss o Nasa horizontal interaction o Kapag lumalaki ang cell, lumiliit ang surface area Important factor in RBC integrity volume o Because it will bind sa mga peripheral proteins Usually is 80% Pag nag-bind sila it will form the skeletal network of Important binding site of enzyme, cytoplasmic membrane microfilaments o Strengthen the membrane Glycophorin o Control the biconcave shape o Control the deformability of the cell Imparts a negative charge to the cell o Provide stability of RBC o Consist of glycophorin A, B, and C Two sub–units (Alpha and Beta) o Glycophorin is included in vertical interaction o Spectrin is composed of alpha and beta spectrin. Glycophorin A carries MN, Gerbich blood group Beta Spectrin antigens o Attachment for ankyrin neat C terminus (which Glycophorin C, Glycophorin A important for P. binds cytoplasmic tail of band 3) thus attachment falciparum invasion and development in RBC of skeleton to lipid bilayer. At N Terminus Functions o Attachment for 4.1 protein (associated with o Glycophorin is very rich in sialic acid – which will glycophorin C)– second anchor point with lipid need of RBC to become hydrophilic, this will enable membrane them to circulate without adhering to other cells. o Binding sites for actin filaments and protein 4.1– o Principal RBC glycoprotein forming a junctional complex o Accounts for the location of RBC antigens Actin Responsible for contraction and relaxation nung ating membrane Short, uniform filaments Length modulated by tropomyosin/tropomodulin BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 2  o Silang dalawa ang mag c-control sa actin para Cell Shape hindi sila maging long filaments Biconcave disc shape creates advantageous surface area/ Tropomyosin volume relationship. Skeletal RBC protein Facilitates deformation while maintaining constant surface Regulate actin polymerization area. Progressive loss of intracellular and membrane Tropomodulin components results in biconcave shape and improved Control actin filaments deformability. Approximately 6 spectrin ends interface with one actin filament stabilized by protein 4.1 o ‘pag na deformed na ang rbc or nagkaroon na ng shape change, either ang kulang dito ay protein, OTHER PERIPHERAL PROTEIN lipids, or carbohydrates. o Dito nagkakaroon ng spherocytes, acanthocytes, Protein 4.1 eto po ‘yung example ng mga shape na abnormal Stabilizes actin-spectrin interactions SA/V ratio alterations will result in more spherical shape o Nag l-link sa actin and spectrin (spherocytes) with less redundant surface area, and thus less capacity for deformability and diminished survival. Adducin Membrane loss = reduced SA; Increase in cell water content = increased volume Also stabilzes interaction of spectrin with actin o Kapag nagkaroon ng membrane loss, mag r- Influenced by calmodulin (calcium-binding protein) reduce na po ‘yung surface area natin o Therefore, mas increase tayo na magkaroon ng rupture ng RBC natin that will lead to lysis and it Ankyrin will lead to anemia. Dapat yung SAV natin would be okay. Promotes spectrin-actin interactions Interacts with band 3 and spectrin to achieve linkage Membrane deformability/stability between bilayer and skeleton Augmented by protein 4.2 During pressure upon RBC, spectrin molecules undergo o So itong mga ito mga proteins natin would help reversible change in conformation: some uncoiled and each other sila yung magsusuport each other at extended, others compressed and folded. sila yung magiging link para mas maging matibay o Kapag ang RBC ay na exposed na po sa mga at hindi madedeform yung ating Red blood cell stress, possible po na magkaroon ng permanent (RBC) kasi once na nadeformed yung RBC natin deformation or tinatawag na permanent plastic matic na magkakaroon ng problem with the deformation function of the RBC. During extreme or sustained pressure, membrane exhibits permanent "plastic" deformation. RED CELL MECHANICS Deformability can be reduced by increases in associations between skeletal proteins or between skeletal and integral Deformability is an important property of red cell function. (esp band 3) proteins. Influenced by: o Ang plastic deformation ay dyan na magkakaroon o Cell shape (ratio of cell surface area to cell kung may problema na with your carbohydrates, volume) lipids, and proteins. ▪ If the cell is lumalaki in terms of size, o Kapag mayroon ng deformability either dun sa ‘yung SAV or surface area volume is composition ng RBC ang may problema so it’s bumababa or lumiliit between the lipids, carbohydrates and also the o Cytoplasmic viscosity (regulated by MCHC and proteins. thus cell volume) o Pag nagpunta na dun sa shape changes dun na ▪ So kailangan stable yung red blood cell makikita yung mga different types ng shape ng natin kasi pag hindi yan naging stable RBC natin ano mangyayare bakit sila naging Madali po sila madeformed and once na ganun kasi most probably kulang sila ng protein deformed na yung RBC natin yung most probably kulang sila ng lipids kaya function nila ay hindi na magiging okay. nadedeformed ang ating RBC ▪ ‘yung responsible sa pag stable nila are lipids, protein, and carbohydrates. ▪ ‘pag na deform, hindi ma a-achieve Cytoplasmic Characteristics yung biconcave shape at possible ‘di na siya mag f-function. Cytoplasmic contents of RBCs include: potassium ions, o Membrane deformability and stability sodium ions, glucose, intermediate products of glycolysis and enzymes o These are very important for RBC in order for them to survive 120 days BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 3  Embden-Meyerhof pathway (metabolic pathway) utilizes o Kung hindi po ma f-form ang ATP, magkakaroon 90% of rbc total glucose po tayo ng immature cell death or yung Efficient cellular metabolism depends on long-lived destruction ng RBC enzymes o Therefore, kung walang ma p-produce na ATP, o Ang glucose ay dyan nakakasurvive yung RBC hindi ma r-reach yung 120 days kasi natin. magkakaroon na ng premature cell death o Kung long-lived enzymes ito kailangan maganda Maintains pyridine nucleotides in a reduced state to permit din yung Band 3. kasi ang band 3 natin is their function in oxidation-reduction reactions within the important in binding site for the enzymes. cell Deficiencies to production of ATP can be exhibited by: METABOLIC ACTIVITIES o Premature cell death due to inherited defects in glycolysis In order for the RBC to survive kailangan mayroon tayong o Loss of viability during the storage of blood for 4 na pathway na dapat natin malaman ano ba ang mga transfusion purpose nitong pathway natin. ENERGY METABOLISM IN THE ERYTHROCYTE Importance of ATP: ▪ Kapag walang na produce na ATP magkakaroon ng premature cell death, hindi ma r-reach ang 120 days ▪ Nag m-maintain din sila ng shape ng RBC natin and ‘yung deformability ▪ Nagbibigay po ang ATP ng energy ▪ ATP modulates the level of 23DPG o Mayroon po dapat tayo dito maproduce na dalawang ATP o Pag ang ATP ay naging problema natin ang possible ng mangyare kung hindi itong embden- meyerhof pathway ay may problema so hindi tayo magkakaroon ng ATP kung may deficiency tayo in the production of the ATP then therefore Embden-Meyerhof Pathway premature cell death due to inherited defects in glycolysis and loss of viability during the storage of blood for transfusion. o So ano ang ibig sabihin kapag nagkaroon deficiency with your ATP? Ibig lang sabihin na hindi natin mareareach out yung 120 days bakit? Di ba ang ATP natin would be the source also of new energy nung mga RBC. o Major source of the essential cellular energy it’’s because of your production ng ating ATP so dapat tandaan 90% to 95% of the energy that is needed by the RBC ay nanggagaling dito sa embden-meyerhof pathway o Meron pong glycolysis sa ATP and the embden- meyerhof ano po ba ang meron dito? Dapat makapaggenerate sila ng 2 ATP and the embden-meyerhof pathway iaadd up lang natin importante din ito for the shape flexibility bago pa dyan sa power ng RBC for them to survive in 120 Major source of the essential cellular energy days so itong ating embden-meyerhof pathway is o This is the main pathway which is anaerobic po also for the shape flexibility sila. Anaerobic glycolytic pathway o The end product po nito are pyruvate and lactate o Provides majority of energy needed by the RBC o This is the major energy-generating pathway o 90% of glycolysis occurs in this pathway o This pathway converts your glucose into lactic acid then will generate 2 ATP for the energy of RBC Glucose undergoes glycolysis (glucose to lactate) to form ATPs BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 4 Oxidative Pathway or Hexose Monophosphate Shunt sabihin toxic sila sa cell natin kaya dapat mareduce natin yung glutathione para maprevent yung oxidation ng RBC. Tandaan din po dito sa ating hexose monophosphate shunt ito po yung ating 1st diversion pathway. Ngayon kung halimbawa ano kaya yung magiging end product natin dito? End product is glutathione so ang makikita natin na inclusion body would be the presence of Heinz body. So pagnakita na natin yung mga Heinz body na yan ibig pong sabihin ano ba ng Heinz bodies natin? Makakakita ba tayo ng Heinz body dito? YES kasi ang Heinz body ay isa siyang inclusion body/abnormality. Paano mareremove ang Heinz body? Sino ang kukuha sa kanya? It’s your spleen kaya dapat matanggal siya kasi hindi maganda kapag meron tayong Heinz body because Heinz body is abnormal inclusion bodies. So if you have presence of the inclusion bodies dun sa circulation it means that there is what we called oxidized. So ang hexose monophosphate shunt ang end product is glutathione because ang glutathione will prevent yung ating oxidation ng ating RBC. Yung Heinz body po natin o The main enzyme is G6PD – glucose 6 pagmeron tayo nun ibig sabihin meron na pong tinatawag phosphate dehydrogenase (enzyme na involve na denature of hemoglobin kaya abnormality sila. If sa hexose monophosphate shunt) pathway is defective amount of reduce glutathione o Also known as Pentose phosphate pathway becomes insufficient to neutralize oxidant causes o 10% of glycolysis occurs in this pathway and denaturation of globin presence of Heinz body. aerobic po sila Always remember Heinz body are inclusion bodies that are found in RBC which only means that this is an Oxidative catabolism of glucose with reduction of NADP abnormal thing dapat po wala po siyang inclusion bodies (nicotinamide adenine dinucleotide phosphate) to NADPH yung RBC and this can be found using crystal violet (reduced form of NADP) which is required to reduce pwede din yung supravital stains natin glutathione o Convert NADP to NADPH then NADPH will convert po ‘yung glutathione sa reduced Methemoglobin Reductase Pathway Pathway's activity is increased with increased oxidation of glutathione If pathway is defective, amount of reduced glutathione becomes insufficient to neutralize oxidants causes denaturation of globin (Heinz bodies) Mag p-produce po sila ng main enzyme which is G6PD and ang kailangan dito sa oxidative pathway is ‘yung reduce glutathione. o ‘yung reduce glutathione ang pro-protect sa hemoglobin from denaturation or precipitation of free radicals. o Glutathione is an antioxidant so dapat ma reduce siya para ma protektahan niya yung hemoglobin from denaturation or precipitation and para ma prevent ‘yung production ng Heinz bodies which Depends on Embden-Meyerhof pathway for the reduced are inclusion bodies (inclusion bodies po ay mga pyridine nucleotides that keeps hgb in a reduced state abnormal) Prevent the oxidation of heme iron o Hindi po puwede magkaroon ng Heinz bodies sa o Requires the reducing action of NADH and the isang RBC kasi abnormal po ito. Dapat po ang enzyme methemoglobin reductase RBC ay walang inclusion bodies. This pathway is important in maintaining your Ano po kaya ang reason bakit kelangan natin kasi ang end hemoglobin iron in the ferrous state and this will then product ng hexose monophosphate shunt natin would be convert your methemoglobin back to normal the production of glutathione natin bakit natin kelangan hemoglobin using methemoglobin reductase enzyme ireduce? Kelangan natin mareduce glutathione unahin na o This will be corrective mechanism muna natin ano ba yung glutathione natin? Yung o Kailangan laging nasa ferrous state kasi ‘pag glutathione natin will then prevent oxidation ng RBC so nasa ferric wala na silang kakayahan mag bind ang end product ng hexose monophosphate shunt would sa oxygen be magproproduce siya ng glutathione. Ang glutathione natin will prevent oxidation ng RBC kasi itong mga glutathione natin this are free radical ibig BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 5  Laubering-Rapoport Pathway ERYTHROPOIETIN A hormone produced in the kidney in response to tissue hypoxia o Stimulus po natin dito is hypoxia o Hypoxia – decreased oxygen ▪ Mawalan ka lang ng ilang seconds ng oxygen pwede ka na mamatay Specific action of EPO: o EPO will stimulate production of RBC 1. Induces committed progenitor cells in the bone marrow to differentiate and proliferation into pronormoblast 2. Shortens the generation time of pronormoblast Important in the oxygen carrying capacity of 3. Promotes the early release of reticulocytes to the RBCs peripheral blood. This mechanism is low in energy consumption Capable of regulating oxygen transport even with hypoxia and acid-base disorders Permits accumulation of 2,3 DPG Increased in deoxy hemoglobin results to binding of 2,3 DPG which stimulate glycolysis o The Leubering-Rapoport pathway will generate 2,3DPG (2,3 – Diphosphoglycerate) (also called as BPG – Biphosphoglycerate) to regulate the affinity in hemoglobin to oxygen. Stimulus po natin dito is hypoxia then hypoxia will o This pathway will regulate affinity ng hemoglobin natin signal to kidney to release EPO to your oxygen (affinity means binding) o Sa kidney siya nag signal kasi ang EPO o Kapag mababa ang 2,3 DPG therefore, mataas ang naka reside sa peritubular part ng hemoglobin affinity para sa oxygen so shift to the left kidney po tayo. Yellow circle represents the EPO. o Kapag mataas ang 2,3 DPG therefore, bababa ang When the EPO is released it will go to the blood hemoglobin affinity para sa oxygen so shift to the right flow and also in bm po tayo. (these are involve in oxygen dissociation o Hindi lahat ng EPO ay puwede na curve) pumunta sa bm kasi kailangan ng will hemoglobin affinity for oxygen receptor pag pupunta sa bm o Receptor + EPO ang makakapag pass METABOLIC PATHWAYS IN THE ERYTHROCYTE through bm o EPO na may receptor lang ang makakapunta sa bm In bone marrow mag p produce na ng RBC and yung EPO is pabibilisin yung process para magkaroon ng early release of rbc ‘pag napabilis na ng EPO yung process, that’s the time na mag re-release na ng RBC si bm Kapag nag enter na sa blood flow ‘yung RBC hindi na magiging hypoxic ang patient kasi mayroon ng oxygen yung blood flow. Elevated EPO levels are observed in: 1. Erythroid hyperplasia o Lahat po ng nasa series of maturation ay tumataas ERYTHROKINETICS 2. Polycythemia o Increase of RBC Term describing the dynamic of RBC production 3. Hemorrhages (erythropoiesis) and destruction o Tumataas po EPO kasi maraming I c- o There are 2 types of destruction of RBC. We compensate, maraming nawawala RBC kaya have the intravascular and extravascular. kailangan mag produce ng maraming rbc kaya Erythron – name given to the collection of all stages of tataas EPO erythrocytes throughout the body, developing precursor in 4. Inc RBC destruction the bm, and the circulating rbc in peripheral blood. Decrease levels 1. Anemia BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 6  MECHANISM OF RED CELL DESTRUCTION o This occurs when hgb breaks down in the blood and nagkakaroon na po tayo ng free 1. Fragmentation – loss of a portion of the erythrocytes hemoglobin membrane, accompanied by loss of cellular contents o ‘yung free hemoglobin would be release in including hemoglobin plasma o ‘pag sinabing fragmentation – breakdown; small; ▪ Kapag na lyse na yung RBC masisira ng kaunti lalabas na po yung hgb ▪ Kaya ‘pag sa laboratory kailangan 2. Osmotic lysis – passing of water into the red cell as to pa i-stand yung hgb para ma ultimately burst it liberate hgb natin o Mag b-burst ang RBC and ‘pag maraming o Once na release na, pupunta po ito sa affected na RBC it can cause anemia plasma. o ‘yung hemoglobin in plasma will bind to 3. Erythrophagocytosis – ingestion of whole red cells by haptoglobin circulating monocytes or neutrophil or by fixed ▪ Haptoglobin – major free macrophages of the mononuclear phagocyte system hemoglobin transport protein Kasama po dito ‘yung 4. Complement induced cytolysis – complement has the chemotrypsin, yung ability to attach itself to the cells and induce lysis. albumin natin which will be o The mechanism of destruction is through phagocytized by liver antigen-antibody reaction o ‘yung other free hgb ay mapupunta sa: ▪ hemoglobinemia – hemoglobin that 5. Hemoglobin denaturation – when hb is exposed to is present in plasma oxidant stress and the mechanism to protect the cell from ▪ hemoglobinuria – hemoglobin that such damage fails to work, denatured hb precipitates is present in urine forming inclusion bodies known as Heinz bodies. o some of hgb will be taken up by renal tubular o Ito po ay under ng hexose monophosphate shunt cells and they will produce hemosiderin ▪ hemosiderin – is a yellowish-brown 2 TYPES OF DESTRUCTION crystals ‘pag maraming nakitang 1. Intravascular hemolysis hemosiderin sa urine meaning may Lysis of erythrocytes which occurs within the nangyayaring intravascular circulation through the classic pathway hemolysis that can be It is the usual outcome of sensitization of erythrocytes seen in urine 1 week after with complement 10% of aged red cell undergo the destruction 2. Extravascular hemolysis Red blood cells break down in the circulation Free hemoglobin; binds to haptoglobin, oxidized to Lysis of erythrocytes outside the circulation, in the methemoglobin RES of the cell liver, spleen. Heme recovered from haptoglobin, albumin or This is usually happens through phagocytosis hemopexin (formed from methemoglobin) About 90% of aged red cells are destroyed Bilirubin conjugated by hepatocytes, then excreted as urobilinogen and urobilin Involve po dito is more on membrane defects o ‘pag may membrane defects mayroon o Ang involve po dito ay mga enzymes, globin pong kakulangan sa lipids, chains, MAHA, ABO incompatibility carbohydrates, and protein. o G6PD can be present in both intravascular Involve rin po dito ‘yung mga drug induced and extravascular hemolytic anemia and RH incompatibility. Ingestion of red cells by macrophages in the liver, spleen, and bone marrow. Little or no hemoglobin escapes into the circulation Anemia Ito po ‘yung nangyayari sa intravascular hemolysis Decreased haptoglobin Normal plasma hemoglobin BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 7  EXTRAVASCULAR HEMOLYSIS o Bacterial/Viral infections o Drug induced o Autoimmune o Microangiopathic Hemolytic Anemia (MAHA) – malignancy DIC (Disseminated Intravascular Coagulation), TTP (Thrombocytopenic Purpura) , eclampsia o Hemoglobinopathies o Membrane defects – spherocytosis, elliptocytosis (ovalocytes) , acanthocytosis ▪ They are abnormal shape of rbc and ‘pag mayroong ganyan is may problem sa LCP (Lipid, Carbohydrates, Protein) o Metabolic defects – G6PD deficiency / oxidant drugs Extravascular hemolysis occurs when the senescent or old rbc are being phagocytized by macrophage Once na engulf na yung rbc, mag d-divide po ito into three: o Globin ▪ Globin chains are recycled into amino acids for protein synthesis o Iron ▪ Iron will bind to transferrin and this will be transported to bm for new rbc production ▪ Some are stored for future use in the form of ferritin o Protoporphyrin ▪ Protoporphyrin will metabolize to bilirubin and urobilinogen ▪ Once na metabolized na sila, this could be excreted through either feces (stercobilinogen) or through urine (urobilinogen) RES phagocytosis of RBCs RBC membrane is disrupted Lysosomal digestion of hgb Recovered iron transported to bone marrow Protophorphyrin metabolized to bilirubin, conjugated and excreted CAUSES INTRAVASCULAR HEMOLYSIS o ABO mismatched blood transfusion o Cold agglutinin disease (CAD) o Paroxysmal cold hemoglobinuria ▪ Nagkakaroon ng lysis ‘pag malamig ang panahon o Burns ▪ Specially 3rd degree burns o Snake bites o Bacterial – C.perfringens sepsis o Parasitic infection – P.malaria ▪ Lahat ng plasmodium ay puwede po pumasok sa rbc and pag na invade na nila puwede na po ito mag burst and magkaroon ng lysis. o Mechanical heart valvles o Paroxysmal nocturnal hemoglobinuria ▪ Nangyayare ‘yung lysis ‘pag gabi BSMLS | LOBRAMONTE, O.CHUALONG, VILLAMAYOR pg. 8