RBCs

Question 1

RBC Path-Terms

Answer 1

• MCV (mean cell volume): Average volume of RBC expressed in fentoliters (um3)
• NORM value = 80-96 fL
• MCH (mean cell hemoglobin): Average content mass of Hb per RBC (Picograms)-^{<u><strong>Should be about the SAME SIZE as Macrophage</strong></u>}
• NORM 27-31 picograms/cell
• MCHC (Mean cell Hb content)=Average conc of Hb in given volume of packed RBCs-Hgb/Hct
• NORM 32 to 36 grams/deciliter
• RBC distrubution width (RDW): Coefficient of variation of RBC vol
• NORM 11.5-14.5%

Question 2

RBC Morphology

Answer 2

• Normal RBC = same size as macrophage w/small hole in middle
• Howell-Jolly Body = RBC w/nuclear material present ^{<u><strong>ALWAYS a SIGN OF SPLENIC DYSFUNCTION</strong></u>}
• Microcytic/Hypochromic = anemia with a LOW MCH
• Target Cell = Seen in hemoglobin C (crystal) or Beta & Alpha thalassemia ^{<u><strong>(Target appearance due to Bleb in center)</strong></u>}
• Spherocyte: Loss of bi-concave appearance found in hereditary spherocytosis & autoimmune hemolytic anemia

Question 3

RBC Morphology (2)

Answer 3

• Schistocytes=fragmented RBC “helmet appearance found in Micoangiopathic hemolytic anemia ^{<u><strong>(MAHA)</strong></u>}
• Nucleated RBC=Found in fetus/New born beyond that shows disorder w/blood producing mech
• Reticulocyte=Stain blue and show mesh like network of RNA ^{<u><strong>(immature RBCs)</strong></u>}
  
  • Polychromatopheila ^{<u><strong>(LARGE # of immature RBCs seen)</strong></u>}
  • Supravital stain ^{<u><strong>(Blue staining of RNA ribosome)</strong></u>}
• Basophilic stippling=Tiny blue dots found around RBC associated w/Lead poisoning

Question 4

Hemolytic Anemia Outline

Answer 4

• “Normocytic”
• Results from INCREASE in rate of RBC destruction
• Premature destruction of RBCs dut to:
• Intrisic ^{<u><strong>(Heptaglobin increased to save Iron)</strong></u>}
• Extrinsic ^{<u><strong>(Jaundice &amp; Splenomegaly)</strong></u>}
• Hemolytic anemias are classfied based on intrisic or extrinsic causes
• Site of destruction: Based on presence or absence of FREE Hb & Hb products
• Shortened RBC life span = bone marrow hyperplasia
• “Compensated hemolytic disorders” = Anemia is absent BUT reticulocytosis & erythroid hyperplasia of marrow SEEN

Question 5

Hemolytic Anemia (Intrinsic)

Answer 5

• Normocytic
• Acute process
• Destruction of RBCs w/in circulation W/release of Free Hb ^{<u><strong>(incomp blood transfusion)</strong></u>}
• **Haptoglobin decrease **^{<strong>(binds to Hb)</strong>}
• Membrane defects:
• Hereditary spherocytosis ^{<strong>(Cytoskeleton membrane tethering-Spectin, ankryin, Band 3.1)</strong>}
• Hb Defects:
• Sickle cell disease
• Thalassemias
• Enzyme defects:
• G6PD def
• Acquired:
• Paroxysmal nocturnal hemoglob

Question 6

Hemolytic anemia (Extrinsic)

Answer 6

• Exaggeration of normal mech of removing aged RBCs
• RBCs recognized as abnormal by Recticulo-endothelial system ^{<u><strong>(LYMPH &amp; SPLEEN)</strong></u>}= Phagocytosed prematurely ^{<u><strong>(Hereditary Spherocytosis)</strong></u>}
• Acquired-
• Immune mech:
• Hemolytic disease of newborn
• Incomp blood transfusion
• Drug induces
• Non-immune:
• Mechanical-Mico angiopathic hemolytic anemia (MAHA)
• Cardiac prosthetic valve
• Misc:Due to infections, burns, lead poisoning

Question 7

Haptoglobin (RBC breakdown)

Answer 7

• Increased Hb breakdown intravas & extravas:
  Haptoglobin made in liver & binds to free Hb (Fe+3)
• Hb small enough to pass thru the normal glomerulus (Iron wasted)
• HB + haptoglobin large and cannot be excreted
• Following release of Hb into circulation-Plasma Haptoglobin lvls fall & return to normal after 3-6 days
• Presistant hemoysis = LOW haptoglobin lvls
• Haptoglobin (Hb only) reduced in BOTH types Intrinsic & extrinsic

Question 8

Hemopexin (RBC breakdown)

Answer 8

• Plasma Hemopexin:
• Binds to FREE HEME in 1:1 ratio
• NO bind to Hb
• If Hb from hemoysis exceeds haptoglobin lvls-Hb turned into Metheglobin
• Methemoglobin turns into ferriheme & globin
• Ferriheme BINDS to hemopexin-LOST through glomerular filtration
• Associated w/Intravascular hemolysis=LOW hemopexin lvls

Question 9

RBC breakdown

Answer 9

1. Iron released from Heme & combines with transferritin 1/3 saturated (iron-binding protein)
2. Carried to bone marrow or body iron stores (Ferritin/Hemosiderin-Storage form)

• Increased Extravascular (reticulo):
• Jaundice due to Hyperbilirubinemia
• Bilirubin is unconj & does not appear in urine
• Increased Intravascular = Low hemopexin lvls
• Reticulocytes: (Normal 0.2 to 2%)
• Bone marrow hyperplasia ^{<u><strong>(erythroid)</strong></u>}
• Extra medullary hematopoiesis ^{<u><strong>(liver, spleen)</strong></u>}
• Cholelithiasis^{<u><strong> (pigment gall stones)</strong></u>}
• Skeletal abnormalites

Question 10

Hereditary Spherocytosis (HS)

Answer 10

• Inherited disorder due to intrisic defects in RBC membrane
• Vulnerable to splenic sequestration & distortion = ^{<u><strong>Phagocytosed by macrophages</strong></u>}
• Mutation of ankyrin & Spectrin:
• Increaed permeability to Na+=countered by active transport out of Na+
• Result is increase in glycolytic rate = DEPLETES ATP
• PH falls = Inhibiting glycoloysis membrane LOSS
• Increase in MCHC

Question 11

HS lab investigations

Answer 11

• Hb: Decreased
• Histo:
• Spherocytes
• absence of central pallor
• anisocytosis - RBCs are of un = size
• Howell-Jolly Bodies = Small dark nuclear remnants - Asplenic pts
• Osmotic fragility test:
• Normal RBCs able to increase in size w/increasing hypotonic conc of saline sol.
• BUT spherocytes RUPTURE
• Reticulocytes increased
• Extravascular hemolysis = Increased serum bilirubin - Unconj-Gallstones

Question 12

HS Clinical Features

Answer 12

• Anemia
• Splenomegaly
• Jaundice
• Gall Stones ^{<strong>(increase unconj bilirubin)</strong>}
• Aplastic crisis=^{Associated w/<strong>Parvovirus 19:</strong>}
• Virus kills RBCs progenitors
• Worsens already anemic pts
• Further REDUCED reticulocytes
• Hemolytic crisis:
• Increased splenic destruction of spherocytes
• Darkening of unrine
• Can be assoc w/infectious mononucleosis ^{<u>(Epstein-barr &amp; herpes virus)</u>}
• Treatment: Splenectomy ^{<u><strong>(done after 7 yrs immune system established)</strong></u>}

Question 13

G6PD def properties

Answer 13

• X-linked Recessive
• Glucose-6 phosphate dehydrogenase reduces NADP to NADPH
• NADPH helps in the conversion of ^{<u><strong>OXIDIZED</strong></u>} glutathione to ^{<u><strong>REDUCED</strong></u>} glutathione
• This reduction helps w/Oxidant injury ^{<u><strong>(FREE RADICALS H2O2 build up in Def.)</strong></u>}
• Def-Leads to reduced levels of G6PD:
• Neutrophils & macrophages poor bactericidal properties
• Back pain assoc hemogloburia hours after oxidative stress ^{(anti-malarials, Fava beans)}

Question 14

G6PD def Pathogenesis

Answer 14

• Hemolysis occurs due to oxidative stress from:
• Drugs - anti malarials (Primaquine, Chloroquine, sulfonamides)
• Infections - Viral hep, pneumonia, typhoid fever
• Fava bean (mediterrian G6PD) - Favism in children or immunocomprimised people
• G6PD def RBCs:
• Exposed to oxidants = Oxidation of reactive sulfhydryl group on Hb Chain
• Chain is denatured = membrane bound inclusion^{<u><strong> (HEINZ BODY)</strong></u>}
• Heinz body damages cell membrane=^{<u><strong>INTRAVASCULAR HEMOLYSIS</strong></u>}
• Spleen macrophages eat heinz = Bite cells

Question 15

G6PD def Lab diagnosis

Answer 15

• Hb: Decreased can be mild or severe
• Histo: Heinz bodies & Bite cells
• Low G6PD lvls:
• plasma Hb = increased ^{<u><strong>(hemoglobinemia)</strong></u>}
• Haptogloben = reduced
• Hemoglobinuria
• Clinical features:
• Acute hemolysis^{<u><strong> (2 to 3 days following oxidant stress &amp; can last 7 days)</strong></u>}
• Associated stressors: Anti-malarial, infection, fava bean

Question 16

HbS-Extravascular Hemolysis

Answer 16

• Sickle Cell anemia (HbS)
• Point mutation @ 6th pos of Beta globin chain = Sub of Valine for Glutamic acid
• Homozygous state almost ALL Hb in RBCs are HbS (90-95%)
• Heterozygous (carrier)-undergo sickling ONLY under severe hypoxic states
• Pathogenesis:
• Distorted/rigid RBCs block small BVs = Ischemia
• Repeated sickle-unsickle cycles results in ^{<u><strong>RBCs MORE FRAGILE</strong></u>} - Then REMOVED by splenic macrophage
• Sickling REDUCES flow rate & RBCs begin to adhere ^(STAGNATE)=Further reduces O2 tension MORE sickling
• FInal result = Ischemia ^{(painful crisis)}

Question 17

HbS Lab investigations

Answer 17

• Hb = Decreased
• RBC measurement = Increased MCHC ^{<u><strong>(mean corp hemoglobin conc)</strong></u>}
• HIsto:
• Micocytic & Hypochromic
• 10-15% are sickled RBCs
• Sickling test-
• observering for RBC sickling when treated w/2% Na+ Metabisulfite (Hetero & Homo)
• Hb electrophoresis:Sep based on charge
• Chorionic Villi biopsy-Fetal DNA analysis in 1st trimester

Question 18

HbS Clinical Features

Answer 18

• Severe anemia
• Vaso-oculsive complications:
• Hypoxic injury & infarction
• Severe pain
• “Hand-Foot” syndrome = Dactylitis ^{<u><strong>(redness/swelling in palms and soles)</strong></u>}
• Micro-infarction of carpal & tarsal bones
• Acute-chest syndrome-Fever, dry cough, chest pain & pulmonary infiltrates ^{<u><strong>(due to SLUGGISH pulmonary blood flow)</strong></u>}
• Due pneumonia infection
• CNS=seizures/strokes hypoxia
• Aplastic crises-Transient bone marrow failure of erythropoiesis
• Infection by parvovirus B19=Worsening anemia & reduced reticulocytes
• Chronic hyperbilirubinemia (extavascular hemolysis) = Gallstones

Question 19

HbS Sequestration crises

Answer 19

• Sequestration Crises:
• Massive sequestration of sickled cells in spleen
• Rapid splenic enlargement, hypovolemia, ^{<u><strong>POSSIBLE SHOCK-</strong></u>}Seen in children
• Susceptibility to early infections due to:
• Congestion & poor blood flow in spleen ^{<u><strong>(Immune center)</strong></u>} in children
• Infarction & autosplenectomy ^{<u><strong>(shrunken)</strong></u>} in adults
• Infections:
• Pneumococci ^{<u><strong>(sepsis)</strong></u>} & hemophilus influenzae
• Osteomyelitis by salmonella parathyphi
• Loss of renal function ^{<u><strong>(vasocculsive)</strong></u>}

Question 20

Beta Thalassemias properties

Answer 20

• Beta = Def synthesis (B+) or TOTAL ABSENCE (B0) -Chromosome 11
• genetic point mutation
• Lack of adequate HbA (a2b2)=^{<u><strong>Microcytic&amp;hypochromic</strong></u>}
• Excess free Alpha chains in comparison to reduced Beta chains
• Insol. precipitated aggregates in RBCs=destroyed & ineffective erythropoiesis
• INCREASED absorption of Iron
• Secondary hemochromatosis
• Inclusions of alpha chains damages cell membrane = vulnerable to phagocytosis ^{<strong>(extra-vascular hemolysis)</strong>}
• Beta Carriers are protected from plasmodium malaria

Question 21

Beta Thalassemia Major Lab/Features

Answer 21

• Hb: Severe anemia
• _HIsto: _
• Anisopoikilocytosis (RBCs vary in size)
• Target cells-Fargmented RBCs, reticulocytosis, nucleated RBCs
• Biochem studies:
• Bilirubin & Iron
• Clinical features:
• Pallor & Jaundice
• Bone marrow transfusion ^{<u><strong>Lead to secondary hemochromatosis</strong></u>}(excess iron)
• Bronze Diabetes - Overload of iron due to melanin to unexposed skin-_^{<strong>Use penacillamine to get rid of iron</strong>}_
• Growth retardation
• Skeletal system abnormalites ^{<u><strong>(Crewcut skull)</strong></u>}
• Gall stones
• Infections-Parovirus B19 (aplastic)

Question 22

Beta Thalessemia Minor

Answer 22

• Diff from Iron def anemia
• Iron def anemia improved w/Iron therapy
• B-thalassemia trait (minor) worse with Iron therapy
• Important for Lab:
• Serum Iron
• Ferritin
• Transferrin
• Total iron binding capacity (TIBC):
• Increased in Iron Def
• NORMAL in B-thalassemia minor
• Serum iron & ferritin:
• Decreased in iron def
• Normal or slightly increased in thalassemia minor

Question 23

Alpha Thalassemia

Answer 23

• Due to deletion of alpha synthesis
• Affects: Hb-A, Hb-A2 & Hb-F
• Severity depends on # of Alpha chains missing
• 4 alleles on Chormosome 16
• Silent carrier = Deletion of single alpha chain
• Alpha trait = deletion of 2 alpha chains
• HbH = Deletions of 3 alpha chains (B4)
• Barts = 4 gamma chains-VERY HIGH Affinity for O2=NO O2 delivered to periphery
• Clinical picture similar to SEVERE Rh-Incompatibility

Question 24

Hydrops fetalis & Alpha Thalassemia

Answer 24

• Hydrops fetalis: deletion of all 4 alpha chains ^{<u><strong>(Barts)</strong></u>}
• Fetal distress occurs @ 3rd trimester = Intrauterine DEATH
• CIS deletion spontaneous abortion Asians
• Fetus characteristics:
• Pallor
• Generlized edema
• MASSIVE hepatosplenomegaly
• Mother has frequent toxemia (TOXINS in blood) of pregers

Question 25

Paroxysmal nocturnal hemoglobinuria

Answer 25

• Rare & chronic ^{<u><strong>(STEM CELL DISORDER AFFECTS ALL CELL LINES)</strong></u>}
• Intravascular hemolysis-Intermittent hemoglobinuria ^{<u><strong>(@ night resp acidosis=Comp activation)</strong></u>}
• Defect in Red cell membrane (DAF)
• Pathogenesis:
• Mutation in phophatidylinositol glycan-A gene X-linked ^{<u><strong>(PIGA)</strong></u>}
• PIGA-enzyme important for production of cell surface proteins
• Ex. Decay accelerating factor-CD55/DAF deficient due to gene mutation
• This deficiency=abnormal sensitivity of erythrocytes to complement mediated hemolysis ^{(Includes neutrophils&Platelets)}
• Comp activation = Fall in PH, infections, Surgery, Strenuous exercise

Question 26

PNH Features

Answer 26

• Aquired later in life
• Low lvls of MAC inhibitor CD-59
• Low lvls of C8 (comp system)
• Passage of red/brown urine in morning ^{<u><strong>(night resp acidosis-comp activation=LOW PH)</strong></u>}
• Chronic hemolysis-Hemosideriuria ^{<u><strong>(Excess binding of Hapto-Hb is excreted)</strong></u>}
• Affects platelets-Thrombosis (liver, dermal cerebral) main cause of DEATH
• Lab findings:
• Hb = low @ time of diagnosis
• Reticulocyte = Increase
• WBC = Reduced
• Platelets = Reduced
• Bone marrow = hyperplastic ^{<u><strong>(increased erythropoesis)</strong></u>}
• Screening test = Sucrose hemolysis ^{<u><strong>(LOW-IONIC SOL observe for LYSIS)</strong></u>}

Question 27

Immunohemolytic Anemias (warm-IgG)

Answer 27

• IgG auto-immune ^{<strong>(assoc w/SLE & CLC)</strong>}
• Extravascular hemolysis by splenic macrophages->Eat away membrane=Spherocytes
• Primary (idiopathic-Spontaneous)
• _Secondary: _
• B-cell lymphoid neoplasms ^{<strong>(CHRONIC LYMPOCYTIC LEUKEMIA)</strong>}
• Autoimmune ^{<strong>(SLE)</strong>}
• Drugs ^{<strong>(a-methyldopa, penicillin, quinidine)</strong>}
• Clinical presentations-
• Severe anemia
• Increased MCV^{<u><strong> (MORE RETICULOCYTES)</strong></u>}
• Hyperbilirubemia ^{<u><strong>(extavascular hemolysis) </strong></u>}Conjugated or unconj
• Diagnose w/Direct coomb’s test
• B-cell neo: bone marrow (IgG)

Question 28

Immunohemolytic Anemias (cold-IgM)

Answer 28

• IgM Ab in Cold can coagulate = Reynaud’s syndrome ^{<strong>(WHITE & PAINFUL)</strong>}
• Intravascular Fixes comp
• Associated w/extremeties
• Acute Causes:
• Mycoplasma infection (WALKING PNEUMONIA=Productive cough)
• Infectious mononucleosis (EpsteinBarr & 1 type of herpes Virus)
• Histo: Shows Clumping-AutoAb against erythrocyte membrane
• Chronic:
• Idiopathic
• B-cell lymphoid neoplasms:
• Lymph (IgM)

Question 29

Hemolytic Anemia-mech trauma

Answer 29

• Microangiopathic hemolytic anemia
• Cardiac valvle prostesis
• Narrowing or partial obstruction of vasculture
• Blood smear shows fragmented RBCS ^{<strong>(Schistocytes)</strong>}
• TTP & HUS present similar BUT:
• TTP-Defect in Adams 13 (stabilizes w/VwF&FACTOR 8)
• Purpura
• Mental confusion
• **_HUS-_Caused by 0157:H7 E.coli **
• Acute kidney failure
• Affects children
• DIC also shows similar symptoms BUT BT, PT, PTT are INCREASED

Question 30

Malarial Parasites (intravascular w/SOME extravascular)

Answer 30

• Transmitted from salvia ^{<u><strong>(SPOROZONITES) </strong></u>}of infected female
• Infects live liver parenchymal remain dormant ^{<strong>(hypozonites)</strong>}
• Parenchymal cells rupture w/meronts released into blood ^{<strong>(INFECT RBCs)</strong>}
• P. Falciparum = MOST COMMON & deadly
• RBCs burst everyday aquire **CHARGED **proteins ^{<strong>(PECAM-CD31 & ICAM-1)</strong>}
• RBCs aggregrate/lyse-in postcap venules ^{<strong>(MICROTRHOMBI->COMA->CONVULSION & DEATH)</strong>}
• Plasmodium vivax & ovale: burst loose every other day
• Symptoms = Fever/chills, drenching sweats ^{<em><strong>(TERTIAN MALARIA)</strong></em>}
• Plasmodium malariae: Burst @ 72 hours
• Symptoms = Fever/chills ^{<em><strong>(Quartan malaria)</strong></em>}

Question 31

Iron Absorption

Answer 31

• Daily diet (10-20Mg) & absorb 1-2 mg/Lose 1-2 mg from desqua of GI epithelia
• Absorbed by Duodenum in Ferric form (Fe+2) converted by Dcytb enzyme
• DMT1 tansports ferric iron in
• Ferroportion transport iron out
• Once in circulation Hepcidin (^{<strong>sequesters Iron so bacteria cannot use it to divide)</strong>}
• Also put into storage form Ferritin
• Hemosidrin: degraded/aggregated_ _of ferritin ID by Prussian blue
• Small scattered blue granules in cytoplasm of macrophages ^{<strong>(ALSO GOLDEN-BROWN)</strong>}
• 40% of normoblasts small blue granules=^{<strong><u>Sideroblasts</u> OR if nucleus expelled <u>Siderocytes</u></strong>}

Question 32

Transferrin & Ferritin

Answer 32

• Transferrin-Has 2 binding sites for ferric iron (Fe+2) BUT common only 1/3 binding sites occupied
• Unbound Iron is TOXIC ^{<strong>(catalyst of free radical formation)</strong>}
• Normal conc is 60-150 = ^{<strong>(LARGE PORTIN is BOUND IRON-Transferrin)</strong>}
• TIBC=_{unbound transferrin + bound transferrin} = _{<strong>MAX cap</strong>} from iron binding ^{<strong>(300-360)</strong>}
• % of transferrin saturated w/Ferric is best indicator of stored iron
• Transferrin transports iron to:
• Hemoglobin/Erythropoeisis
• Ferritin ^{<strong>(storage form of Fe+3 in liver/Heart)</strong>}
• Other proceses (5-15%)
• Exceptions of Ferritin increase:
• chronic inflammation
• In heptocellular disease
• in neoplasias (abnormal cell growth)

Question 33

Iron Def. anemia general

Answer 33

• 4 reasons:
• Diet LACK
• Impaired absorption
• Increased requirements ^{<strong>(menstruation/Pregers)</strong>}
• Chronic Blood loss:
• Peptic ulcer
• Hemorrhoids
• carcinoma stomach/colon (60 yr male)
• Menorragha (50 yr female)
• Aspirin
• HOOK worm
• Esophageal varices
• Lab Diagnosis:
• Hb - reduced
• Hematocrit - reduced
• RBCs - MCV, MCH, MCHC all Decreased
• Ferritin - Down and TIBC - Up

Question 34

Iron def anemia Lab findings

Answer 34

• Microcytic & hypochromic ^{<strong>(central pallor)</strong>}
• Ansiocytosis ^{<strong>(RBCs various sizes)</strong>}
• Poikilocytosis (^{<strong>RBCs variation in shape)</strong>}
• Increase in platelet count-Thrombocytosis 3x increase from normal 150-350 ^{<strong>(unknown)</strong>}
• Bone marrow:
• Hyperplastic
• Microctic maturation
• LOSS of stainable iron in macrophage ^{<strong>(prussian blue)</strong>}
• Biochem tests:
• FEP increased (free protoporphirin-no iron to bind)
• Iron & ferritin ^{<strong>DECREASED</strong>}
• TIBC ^{<strong>(total iron binding capacity)</strong>}-measure of amount of transferritin in blood=^{<strong>INCREASED</strong>}

Question 35

Iron def anemia-Clinical features

Answer 35

• Early stage = Normocytic anemia
• Fatigue & Tachycardia
• PICA
• Pallor & glossitis ^{<strong>(smooth red tongue)</strong>}
• Angular chlilitis ^{<strong>(inflammtion on side mouth)</strong>}
• Kolionychia ^{(spoon shaped concavity of nails)}
• Plummer-Vinson Syndrome ^{<strong>(Triad findings)</strong>}:
• Microcytic hypochromic anemia
• Atrophic glossitis
• esophageal webbing (Protruding part of esophagus membrane)-**Dysphsia problems w/shallowing **

Question 36

Anemia of Chronic Disease

Answer 36

• Liver will secrete Hepcidin (sequesters Iron) - due to chronic infections (IL-6)
• Examples:
• Chronic microbal infections (Osteomyelitis, Bacterial endocarditis, Lung Abscess)
• Chronic immune disorders (Rheumatoid arthritis)
• Neoplasms (Hodgkin Lymphoma)
• Lab Findings:
• Normocytic-Normochromic
• circulating Iron reduced
• Ferritin is INCREASED ^{(Bronze Diabetes)}
• TIBC REDUCED
• Bone marrow = Iron increased

Question 37

Sideroblastic Anemia

Answer 37

• Defect in protoporphyrin production
• Genetic defect rate limiting step ALAS
• All have abnormal erythropoesis in bone marrow ^{<strong>(mitochondria)</strong>}
• Abnormal intramitochondrial accumulation of iron ^{<strong>(pre-cursor RBCs)</strong>}
• Sideroblast = Erythroblasts w/Iron granules in their cytoplasm ^{<strong>(ring)</strong>}
• Defect in heme synthesis w/in mitochondria
• Lab: RBCs are dimorphic ^{<strong>(micro & macro)</strong>}, sideroblats, siderocytes ^{<strong>(non-heme iron)</strong>}
• Bone marrow: Hyperplasic ^{<strong>(ring sideroblasts w/Prussian blue)</strong>}
• Secondary: seen in pyridoxine antagonists used in Tb (isoniazid)-Vit B6 def-needed in ALAS
• Lead ^{(denature ALAD/Ferrochelatalase)}

Question 38

Megaloblastic Anemia

Answer 38

• 2 causes:
• Folate def
• B12 def ^{<strong>(pernicious anemia)</strong>}
  
  • ^{Intrisic factor def in stomach}
  • ^{<strong>Absorbed in terminal Illeum</strong>}
• Both are co-enzymes required in synthesis of Thymidine ^{<strong>(DNA)</strong>}
• Def = defective nuclear muturation ^{<strong>(DELAY/BLOCK in CELL DIVISION)</strong>}
• Increase in homocysteine ^{(CH3-transfer)}
• Cytoplasmic maturation unaffected ^{<strong>(Nuclear/Cytoplasmic asynchrony seen)</strong>}
• Cellular RNA & protein synthesis OK
• Granulocytic precursors LARGE & abnormally immature chromatin
• Multiloped Neutrophils

Question 39

Folate Def

Answer 39

• Increased requirements ^{<strong>(pregers)</strong>}
• Decreased intake:
• Fruits & Vegetables
• Alcoholism
• Phenytoin ^{<strong>(anticonvulsant)</strong>}
• Oral contraceptives ^{<strong>(interfere w/absorption)</strong>}
• Imparied utilization-Folic acid antagonists (Methothrexate-Anti-cancer)
• Clinical features are similar to Vit B12 except No neuro
• Body stores are minimal
• Lab values:
• increased Homocysteine
• Normal methyl malenoic
• Absorbed in Jejunum

Question 40

Pernecious Anemia

Answer 40

• Auto-immune destruction of Parietal cells
• Older age group-50 to 80
• Common cause Vit B12 def.
• Hypersegmented Neutrophils seen in ^{<strong>EARLY STAGE</strong>} before anemia
• Pathogenesis:
• Chronic atrophic gastritis ^{<strong>(autoimmune of parietal cells)-</strong>}atrophy of fundic glands
• Achlorhydria ^{(reduced gastric acid-related with intrisic factor def)}
• MCV = 110 fL^{<strong> (normal 82-92)</strong>}
• Large platelets ^{<strong>(pancytopenia=Issues with cell lineage)</strong>}
• Bone marrow = Nuclear features, lace-like chromatin, Large nuclei
• Urine = increased Methylmalonic acid

Question 41

Pernicious Anemia (Types)

Answer 41

• Type 1 Ab - Blocks binding of VitB12 to IF
• Type 2 Ab - Blocks binding of VitB12-IF complex to ileal receptors
• Type 3 Ab - Produced against alpha & beta subunits of gastric proton pump
• Clinical (Anemia + Neuro)-
• ^{Syphilus presents same neuro symptoms}
• Lemon tint (skin)- anemia
• Glazed & beefy red tongue-Atrophy of papillae^{<strong> (Burning pain on swallowing)</strong>}
• Sysmetric numbness
• Tingling
• Loss of gait & position
• Demyla of Post/Lat columns^{<strong>(spastic ataxia)</strong>}
• Supplemeting B12-FAILS to resolve Neuro
• Schilling test = Radioactive B12 ingested
• Histamine test = stim parietal cells

Question 42

Aplastic anemia

Answer 42

• _Pancytopenia: _genetically altered stem cells due to drug exposure/infection
• Activates TH1 T-cell = ^{IL-1, TNF, IFN-G}=Kill hemapoietic progenitors
• Anemia, leukopenia, thrombocytopenia
• Results from aplasia of BM=Reduction of hemopoietic tissue & Increase in fatty marrow
• BM test=Fat & glycogen ^{<strong>(HYPOCELLULAR)</strong>}
• NO splenomegaly
• Reticulocytosis ABSENT
• Bone Marrow transplantation effective

Question 43

Aplastic like symptoms

Answer 43

• Myelodysplasia= fibrosis & malignant caused by Radiation or household chems
• • Leukemia & Hairy cell*
• Tear drop RBCs due to no where in marrow to mature - leukoerythroblastosis
• Marrow myelofibrosis - Bone marrow issue=Tear drop RBCs
• Clinical features-
• Pallor
• Weakness
• Easy bruising
• Infections