RBCs Flashcards
(43 cards)
1
Q
RBC Path-Terms
A
- 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%
2
Q
RBC Morphology
A
- 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
3
Q
RBC Morphology (2)
A
- 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
4
Q
Hemolytic Anemia Outline
A
- “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 & 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
5
Q
Hemolytic Anemia (Intrinsic)
A
- 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
6
Q
Hemolytic anemia (Extrinsic)
A
- Exaggeration of normal mech of removing aged RBCs
- RBCs recognized as abnormal by Recticulo-endothelial system <u><strong>(LYMPH & 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
7
Q
Haptoglobin (RBC breakdown)
A
-
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
8
Q
Hemopexin (RBC breakdown)
A
- 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
9
Q
RBC breakdown
A
- Iron released from Heme & combines with transferritin 1/3 saturated (iron-binding protein)
- 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
10
Q
Hereditary Spherocytosis (HS)
A
- 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
11
Q
HS lab investigations
A
- 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
12
Q
HS Clinical Features
A
- 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 & herpes virus)</u>
- Treatment: Splenectomy <u><strong>(done after 7 yrs immune system established)</strong></u>
13
Q
G6PD def properties
A
- 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)
14
Q
G6PD def Pathogenesis
A
- 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
15
Q
G6PD def Lab diagnosis
A
- 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 & can last 7 days)</strong></u>
- Associated stressors: Anti-malarial, infection, fava bean
16
Q
HbS-Extravascular Hemolysis
A
- 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)
17
Q
HbS Lab investigations
A
- 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
18
Q
HbS Clinical Features
A
- 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
19
Q
HbS Sequestration crises
A
- 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>
20
Q
Beta Thalassemias properties
A
- Beta = Def synthesis (B+) or TOTAL ABSENCE (B0) -Chromosome 11
- genetic point mutation
- Lack of adequate HbA (a2b2)=<u><strong>Microcytic&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
21
Q
Beta Thalassemia Major Lab/Features
A
- 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)
22
Q
Beta Thalessemia Minor
A
- 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
23
Q
Alpha Thalassemia
A
- 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
24
Q
Hydrops fetalis & Alpha Thalassemia
A
- 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
25
Paroxysmal nocturnal hemoglobinuria
* Rare & chronic (STEM CELL DISORDER AFFECTS ALL CELL LINES)
* ***Intravascular hemolysis-***Intermittent hemoglobinuria (@ night resp acidosis=Comp activation)
* Defect in Red cell membrane (DAF)
* **_Pathogenesis:_**
* Mutation in ***phophatidylinositol glycan-A*** gene X-linked (PIGA)
* **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
26
PNH Features
* ***Aquired later in life***
* Low lvls of MAC inhibitor **CD-59**
* Low lvls of ***C8 (comp system)***
* Passage of ***red/brown urine in morning*** (night resp acidosis-comp activation=LOW PH)
* Chronic hemolysis-**Hemosideriuria** (Excess binding of Hapto-Hb is excreted)
* 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 (increased erythropoesis)
* **Screening test =** Sucrose hemolysis (LOW-IONIC SOL observe for LYSIS)
27
Immunohemolytic Anemias **_(warm-IgG)_**
* **_IgG auto-immune_** (assoc w/SLE & CLC)
* ***Extravascular hemolysis*** by splenic macrophages-\>Eat away membrane=**_Spherocytes_**
* **_Primary_** (idiopathic-Spontaneous)
* _**Secondary:** _
* B-cell lymphoid neoplasms (CHRONIC LYMPOCYTIC LEUKEMIA)
* Autoimmune (SLE)
* ***Drugs*** (a-methyldopa, penicillin, quinidine)
* **_Clinical presentations-_**
* Severe anemia
* Increased MCV (MORE RETICULOCYTES)
* Hyperbilirubemia (extavascular hemolysis) Conjugated or unconj
* Diagnose w/**Direct coomb's test**
* **_B-cell neo:_** ***bone marrow (IgG)***
28
Immunohemolytic Anemias **_(cold-IgM)_**
* **IgM Ab** in Cold can **coagulate** = Reynaud's syndrome (WHITE & PAINFUL)
* ***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)**
29
Hemolytic Anemia-mech trauma
* **_Microangiopathic hemolytic anemia_**
* **Cardiac valvle prostesis**
* Narrowing or partial obstruction of vasculture
* Blood smear shows fragmented RBCS (Schistocytes)
* **_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**
30
Malarial Parasites (intravascular w/SOME extravascular)
* Transmitted from salvia (SPOROZONITES) of infected female
* Infects live liver parenchymal remain dormant (hypozonites)
* Parenchymal cells rupture ***w/meronts*** released into blood (INFECT RBCs)
* **_P. Falciparum =_** MOST COMMON & deadly
* RBCs burst everyday aquire ***CHARGED ***proteins (PECAM-CD31 & ICAM-1)
* RBCs aggregrate/lyse-**_in postcap venules_** (MICROTRHOMBI->COMA->CONVULSION & DEATH)
* **_Plasmodium vivax & ovale:_** **burst loose** **_every other day_**
* Symptoms = Fever/chills, drenching sweats (TERTIAN MALARIA)
* **_Plasmodium malariae: Burst @ 72 hours_**
* Symptoms = Fever/chills (Quartan malaria)
31
Iron Absorption
* 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*** (sequesters Iron so bacteria cannot use it to divide)
* Also put into storage form **_Ferritin_**
* **_Hemosidrin:_** degraded/aggregated**_ _**of ferritin ID by Prussian blue
* Small scattered blue granules in cytoplasm of macrophages (ALSO GOLDEN-BROWN)
* 40% of normoblasts small blue granules=Sideroblasts OR if nucleus expelled Siderocytes
32
Transferrin & Ferritin
* Transferrin-Has 2 binding sites for ferric iron (Fe+2) BUT common only 1/3 binding sites occupied
* Unbound Iron is ***TOXIC*** (catalyst of free radical formation)
* Normal conc is 60-150 = (LARGE PORTIN is BOUND IRON-Transferrin)
* **TIBC=unbound transferrin + bound transferrin **= MAX cap from iron binding (300-360)
* ***% of transferrin saturated w/Ferric*** is best indicator of stored iron
* **_Transferrin transports iron to:_**
* Hemoglobin/Erythropoeisis
* Ferritin (storage form of Fe+3 in liver/Heart)
* Other proceses (5-15%)
* **_Exceptions of Ferritin increase:_**
* ***chronic inflammation***
* In heptocellular disease
* in neoplasias (abnormal cell growth)
33
Iron Def. anemia general
* **_4 reasons:_**
* Diet LACK
* Impaired absorption
* Increased requirements (menstruation/Pregers)
* **_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***
34
Iron def anemia Lab findings
* Microcytic & hypochromic (central pallor)
* ***Ansiocytosis*** (RBCs various sizes)
* ***Poikilocytosis*** (RBCs variation in shape)
* Increase in platelet count-Thrombocytosis 3x increase from normal 150-350 (unknown)
* **_Bone marrow:_**
* Hyperplastic
* Microctic maturation
* LOSS of stainable iron in macrophage (prussian blue)
* **_Biochem tests:_**
* ***FEP increased*** (free protoporphirin-no iron to bind)
* Iron & ferritin DECREASED
* TIBC (total iron binding capacity)-measure of amount of transferritin in blood=INCREASED
35
Iron def anemia-Clinical features
* ***Early stage = Normocytic anemia***
* Fatigue & Tachycardia
* PICA
* ***Pallor & glossitis*** (smooth red tongue)
* Angular chlilitis (inflammtion on side mouth)
* ***Kolionychia*** _(spoon shaped concavity of nails)_
* **_Plummer-Vinson Syndrome_** (Triad findings):
* ***Microcytic hypochromic anemia***
* Atrophic glossitis
* esophageal webbing (Protruding part of esophagus membrane)-***Dysphsia problems w/shallowing ***
36
Anemia of Chronic Disease
* 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
37
Sideroblastic Anemia
* **_Defect in protoporphyrin production_**
* Genetic defect ***rate limiting step ALAS***
* All have ***abnormal erythropoesis*** in ***bone marrow*** (mitochondria)
* ***Abnormal intramitochondrial accumulation of iron*** (pre-cursor RBCs)
* **_Sideroblast_** = Erythroblasts ***w/Iron granules in their cytoplasm*** (ring)
* Defect in _heme synthesis w/in mitochondria_
* **_Lab:_** RBCs are dimorphic (micro & macro), sideroblats, siderocytes (non-heme iron)
* **_Bone marrow:_** Hyperplasic (ring sideroblasts w/Prussian blue)
* **_Secondary:_** seen in ***pyridoxine antagonists used in Tb*** (isoniazid)-**Vit B6 def-**needed in ALAS
* ***Lead*** (denature ALAD/Ferrochelatalase)
38
Megaloblastic Anemia
* **_2 causes:_**
* Folate def
* B12 def (pernicious anemia)
* **Intrisic factor def in stomach**
* Absorbed in terminal Illeum
* Both are co-enzymes required in synthesis of Thymidine (DNA)
* **_Def =_** defective nuclear muturation (DELAY/BLOCK in CELL DIVISION)
* ***Increase in homocysteine*** _(CH3-transfer)_
* Cytoplasmic maturation unaffected (Nuclear/Cytoplasmic asynchrony seen)
* ***Cellular RNA & protein synthesis OK***
* Granulocytic precursors LARGE & abnormally **immature chromatin**
* ***Multiloped Neutrophils***
39
Folate Def
* Increased requirements (pregers)
* **_Decreased intake:_**
* Fruits & Vegetables
* Alcoholism
* Phenytoin (anticonvulsant)
* Oral contraceptives (interfere w/absorption)
* **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***
40
Pernecious Anemia
* Auto-immune destruction of ***Parietal cells***
* Older age group-50 to 80
* Common cause ***Vit B12 def.***
* **Hypersegmented Neutrophils** seen in EARLY STAGE before anemia
* **_Pathogenesis:_**
* **Chronic atrophic gastritis** (autoimmune of parietal cells)-_atrophy of fundic glands_
* **Achlorhydria** **(reduced gastric acid-related with intrisic factor def)**
* **MCV =** 110 fL (normal 82-92)
* Large platelets (pancytopenia=Issues with cell lineage)
* **_Bone marrow =_** Nuclear features, **lace-like chromatin**, Large nuclei
* **_Urine =_** increased Methylmalonic acid
41
Pernicious Anemia (Types)
* **_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 (Burning pain on swallowing)
* Sysmetric numbness
* Tingling
* Loss of gait & position
* Demyla of Post/Lat columns(spastic ataxia)
* Supplemeting B12-***FAILS*** to resolve Neuro
* **Schilling test =** Radioactive B12 ingested
* **Histamine test =** stim parietal cells
42
Aplastic anemia
* **_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*** (HYPOCELLULAR)
* **NO splenomegaly**
* ***Reticulocytosis ABSENT***
* Bone Marrow transplantation effective
43
Aplastic like symptoms
* **_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
