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MEGALOBLASTIC ANEMIA
Macrocyte Megaloblastic Anemia :-
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- Total body Red cell mass
- PCV (Hematocrit)
- Hb Concentration
(Red fluid ? Hemodilution ? Spurious Anemia)
Macrocyte (MCV 100)
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Normal
MCV = 86 ± 10 fL
= 76-96 fL
Megaloblast
Lymphocyte ? Macrocytic RBC ? Anemia
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Megalo blast ? Thrombocytopenia
MSC ? Lencopenia
Pancytopenia
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Erythrogenesis
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Initially cells have more proliferation
As time passes by
Proliferation of cells less.
In Erythropoiesis three things happens
- Size of Cells are Progressively less.
- Nuclear Maturation (Nucleus progressively become condense)
- Cytoplasm Maturation (Heamoglobinisation of Cytoplasm)
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Basophilic ? Eosinophilic (AMD)
For Nuclear Motivation we need a definite No. of cell division & cell division occurs by Mol Replication & for Replication we Need
Vit B12 & Folic acid.
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& Normal Erythropoiesis Occurs
Due to one or of both of Vit B12 & Folic acid deficiency
as cell passes by Nucleus does not Condense.
In absence of Vit B12 & folic acid
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Replication is more severely affected while Transcription is not affected
So Nucleus remains Open
There is Excessive formation of RNA ? Excessive formation of protein (Heamoglobin)
b/c of Excessive Hb Normoblast becomes Over Hb Normoblast with V.V Mature Cytoplasm ? Jurpatre Nucleus
So there is Abnormal Normoblast in Bone Marrow.
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Normal Megaloblast
Normoblast Dysynchronization
Cytoplasm & Nuclear in Maturation
Maturation Maturation of Nucleus & Cytoplasm
Is Synchronized.
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On Normal Cases
Where Nucleus is open Nucleus ? Immature
Cytoplasm is Pink Chromatin Open
is initial sec.
Where Nucleus is Condense Cyto Cytoplasm ? Hb
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Pink ang Normoblast)
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So Mannal No of Megaloblast accumulate in B Marrow Normally they are phagocytose & donot comes into blood.
Due to dep of Vit B12 & Folic acid there is also Maturation problem in Sranulo poises
So we found very large cell in Svanulopart pathway.
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(2-3 times larger than nonmal Myelocyte)
So Such a pt Not Only have Anemia but also have Leukopenia (Neutropenia)
(def B12 & folic acid)
Suchna pt also have ab Mecteration of platelate Co they also has Thrombocytopenia
So the Right Condition is Megaloblastic Pancytopenia
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There B12 & falec aend deficiency also atteds the other rapidly proliferating tissue of body
eg S.I Mucosa
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There are larger cells in G.I.T
eg Cells in Tongues changes
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i'e Upper Surface of Tongue become more Smoothly shiny & glassy (papilla)
Mucosa be come thin
Muscle look through Mucosa liko BEEF.
SOURCES OF VIT B12 & FOLIC ACID
- 2-3 g /all
- Animal product Cobalamine
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Folic acid
- Green leafy vegetable
- Controve fruit (but it is destroyed by Cooking
- (It's dep also Cause Neural tube defects)
- pepsine failure of ant gen
- Nezero pore mancephaly
- Failure of post Nezero pore spina bifid
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Anterior Necropore Closes at day 25th
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Posterior ? Closes at day 27th
Servy day = 50-100gm/day.
R Protein present in plasma 1..e they... ore.
Cobalamine plailure why they are Called Cobalophillic
R binde bind with B12 in stomach
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cafer stomach Enzyme have acted uper Animal protein-
Pepsin act on Animal Protein & release Cobalamine R pr bind with B12 as they reach the duodenum pancacatie
lipase act on R & digest the R So B12 will come out.
No Antrinsic Pactor binds with B12.
In Terminal 900eum Surface receptor will be activated This is Internalized (Endocytosis)
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In these cells 9. factors is digested B12 ic set free.
It is then bind with Trans Co-?
Secrete & into blood. ? B12
Some of it is stored
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will do In-portant functions.
Folic acid in natore is presend in form of poly glutamates.
As there poly glutamates passes through G.I.T
di & Mono folic acid Poly glutamate
glutamate ? duodenum
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THF CH3 ? cell
Folic acid( Poly glutamates Enzyme present in duednum.
di/mono foutamato
? Circulation
THF CAB ? Qilver 2-3m
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Any cell which diurde & Multiply can Express Surface receptor for wit B12 & fave avd.
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Serine Glycine CH?
THE Ethylane THE dinydro Fadle
THE Dinga otorite pedictorse dump TMP
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((B12/CH3 Methyl Cobalamine Thymodate Synthse •Homocysteine
mmm Methyl Transferre Methionine
THE CH3 Bi Metry! (Homocysteine)
through all this procees Polate helps in Maturation of these colls.
If there is folaite deficiency thic process does not Take place
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(Serine prowode 1C atom to THf & THE provide thue to dompdtmp.
In absence of B12 THP will not be demetty late d remains lipind Soluble Comes out of cell ? Intra cellular: Concentration
? Can not be Converted to actiue form.
So all above Systein is disturbed & tore is Megala blastic Anemia.
Deficiency of both B12 & folic and Produce Similar Complications.
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Macrocytic Megaloblastic Anemia with leukepnia / tranbocytopenis & glossitis
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Pt with Bia del & falic acid deficiency both have Same bone M picture & pheripheral blood picture.
Folic acid deficiency donot produce Neurological disorders
Untilo It is produced Periconceptional Br deficiency 20% of people have Neurological Des deficiency.
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Proprionyl CoA Mettmalony! COA
•MCys Methyl Methionine CoA Mutan Bra (adenosy 1) Succinyl CoA
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Methy, malonyl CoA requires adenosyl Cobalamine in absence of Biz Succinylcon doesnot farm.
? Malony L COA1 Proprionyl CoA
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One of most sensitive marker of B12 def is ? Malonyl COA
these Malonyl CoA & Proprionyl CoA acculamulat CNS & PNS.
When these ab FA ace umulates in Myelin Sheath then sheath wild not be stable.
neuron become demyelinated
So Neuron well not conduct more Neuron which ore most mydinated are suffered more
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le AU rapidly conducting neurons are demyelinated becomes dysfunction.
THF BTCNS Homocystein?
B12 def Methionine
we require Methionine for formation of Choline
When Methionineed Choline
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Se Chaline Conta in ing which is requind for Myelination Jed Myelination
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Proprioception:
All Sensation generated fom Locomotor Systems
? Homo Cystein damage the Endothelial cells platclate stock on damage Endothelial Alls Thrombus formation.
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Chronic 1H-Cystein 1 damage of Endo ? Chronic Inflammation ? Atheromou.
Clinical Features
arasthesia (due to de myclimaction of pheripherand Sensory, Hyperasthesia Hypo asthesia
Red Sensation. Jed Censation.
• Demyelination of Dorsal Column medial leminuscus system. So there is loss of Sensation of
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- Position
- Vibration
- Ataxia
• Demyele nation of Cortico Spinal pathway Lower motor neuron released fom Influence of Upper motor neuon
Se CMN Over five So there is Ned Reflexes
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B12 def Can CaurP both UMN LMN lesions.
Rabensaki Sign move upward.
Parastiesie PASE dep Ataxia Spastic parises
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i-e both
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Sensory E Jateral Deminiscos degeneration
Motor degeneration along with Neuropatties...
So most. of pt with B12 def thiere is Macrocytic Megaloblastic anemia + Neurological dis orders
May be pt have Only Macrocytic Megaloblastic Anemin with out Neirological disorders.
( folic acid very attectively absorbed in Jujenum)
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In absence of B12 Level of Malonyl CoA 1es both in Blood S Urine.
• If-Biz is at lower limit of Normal value & we want to see covether it is enough Por Aveh not
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We check Malonyl CoA in blood & Urine it is stilo norma It means this level of Biz is cufficient for such a person s Malonyl CoA does not accumulate.
• If in blood of a pt Only Homocysteine level is high
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•bat is Folic acid deficiency
P Malony! in blood of a pt both COA S Homocysteine Level is wigh Br deficiency.
Br part of Myelin Sheath but false acad does not.
B12 def.
Causes Megaloblastic Anemia (Most Common cause of Mild Magro cytoses rs Alcohal.)
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Macro cytoses With Megaloblast
- Alcohol ?Hypothyrodism
- Ciurhosis
- J. Biz def & fatic acid
- Hemolytic Anemia trexate / distropt. SF-0
- ? Suythropolses (Reticulocytoses) ONA Sym
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Macrocytosis in Cirrohosis ble gr RBC soch a Case Some of becomes the torget cells.
e.g Cirrohosis Normally more tb 46 also present So In the center is at pheripbry Center IS pale
Hemolytic Anemia ? As large No of RBC is destroyed So BM Undergo compensation by the Erythropo isee 480 releasing large No of Reticulocyte into blood
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(Reticulocyte size is greater than Mature RBC)
Pyrimethamme dihydrofolate
Methotrexate dilkyds folate Redutase
(Anhibit DNA Synthesis) THE
Uttan Be & defi Julie Aerd deficiency Vitamines deficiency
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- ? Intake
- ? absorption
- ? Requirment
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Normally we need 2-3 mg 1dl of B12
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9n most of: pt B12 deficiency accors who are Strict vegetariane.
atho Se Biz not commonly occors due to bed Intake
also B12 def is not due to Red demand (blc of B12 stores in body
Most Common deficiency is due to Malabsorption-
Most of patient who have falic acid def is due to bed Intake ted demand.
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lees commonly due to Malabsorption.
In gastrectomy Macrocytic Megaloblastic Anemia Occurs due to def of Intrinsic facter the is is not le nouna.
as Pernicious Anemia.
Pernicious Anemias-
Macrocytic Megaloblastic Anemia due to B12 def wich is due to Intunsic factor deficiency which must be due to Auto Immune dystruction of Sastrich Mucosa.
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anemia is Pernicious Most Common after the age of toyn
Bis def
- strict Vegetarians
- Breast feeding Mother.
- Achyloridia
- Drugs eng Omeprazole (&HCP Secretar
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Auto Immune reaction which OCCURS against Pan etal cells in pernicious Anemia IS 0000 both T Celo mediated Response.
Ab resoponse
Anti parietal Anti Anti
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Ab Intrinsic factor lar Ab Intrinsic F.Ab +Bra
(binds at Bia Binding (binde with Site Complex of IF+B12
So this Complea Can not entors into Alleal Calls.
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Mast Common of these Ab which is dx of pernicious Anemia is "Anti Intrinsic factor antibody"
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? blood is taken from 100 person abave age of 70yrs 10-15%. will have Antipareilal Antibody bat do not have pernicious Anemia So Stell they ?a? enough 1.F to abp Bia.
Pernicious Anemia
? ? Homocysteine ? Melonic Acid
Megaloblast + ?Rag
RBC counte MCU-4 MCH=A MCHC - Norma Anemia
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In pernicious Anemin there is hypercellular B.M In Biz ALU def Erytrard Ned in Size.
Granulo poid 3 Thromolyaid
Megablastic Rin Erythropoitec pattuvay
? Saint cells.
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Circulation Anemia Neutropenia Clouchopenia) (Hypersegmonted Neutrophil lobess) ? Thrombocytopenia
How Anemia OCCUPYS while BM is hyper cellular ble mast of Celos destroyed within B.M whatever celes are produced.
ave Mack cytic & lorge RBC - Undergo hemolysis easily
di Production - RBC J.Surovual RBC
CNS: demyelination of phenipathiral Menue.
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? Sub acute Combined degeneration Demen Va
CIT & Mucosa destruction Infolteration with lymphocyle these Charges con not be reversed by Vit B12 Injection
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ie GIT cells will become megalard & do not absorb well Same charges 5 SIT also Occurs in def of falic anod but Auto Immune reaction does not takes place
So there 10 deficiency of otter vit in body alo b/c of Malabsorption
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1. level of Homocytein Endo damages ? vish of aterial & venoris thrombi
Biz def
- strict Wegetarian
- Pernicious Anemia (Most Common)
- Achlorydia
- fish tapeworm.
- Pancreatic failure.
- Bacterial Overgrowth in GIT
- Gastrectomy
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Malabsorption Synd (Tropical Sprue, attack the villi of Small Intestine) in food &
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Non tropical Sprue (there are Ceilain Substances git develops allergic reaction to that Substance
? chron's disease (autoimmune disease invoke granuloma formation of terminal illeum)
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- G.IT T.B (most common He is Illeum)
- Lymphoma of Illecro.
- (Removal) Ressection of Illeum
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1 NO Intake.
Schilling Testi
Determine the Cauce of deficiency of B12.
Pt-1
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- Give the pt Radio labelled Cobalamine. orally
- B12 IM injection all the binding sites aure loaded.
- of in GIT there is no any abstruction to Bi enters into Circulations As there Jed binding Sites for this Padioactive Biz enter into Kidney Orine.
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When B in Urine It means abs 15 al ng ut the Primary Problem Jed Intake
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Pt-2
Ovally ? Radio labeled B12
(M B12 1 not BI cbest ppears 10 Urine
Now Sive BB + I. factor Now appears in Urine So the problem 1108 Intrinsic factor.
PE-3
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Ovally Ra. Bit
IM B12
Bi does not appear in Urine
Orally Br2 + ? does not appears In Urine Now glue. Anti bacterals
Now appears Urine.
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So the problem is Bac Overgrowith
PE-4
Orally Rad Bi Not appear in Uthe
Rad B +99 + Anti bac
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Problem B2+fontibact Pancreatic Extract B12* appears in Unne
Chronic to Stea torrhea. Pancreatitis Cleads beary, bulky Vav bulky affensive Smelly stool float on pot defticunt to flush dx from Steatorrhea)
pt-5
RodB A not appear in Urinp
Rad B12+ of
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+ Antibac ? Pan. extrate
Problem is any 900eal disease
Folic Acid deficiency
- J. Intake (green leafy vegetable)
- Alkohol (mast Common)
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(Alcohal does not allow Absorption of @lono glutamate)
Contiraceptive pills (does not allow Abp of Momoguita mato)
Alcohol also cause Multi Vitamine def byc Akchal ful foll the need of food So propor food will not be taken
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& Alcohal disrupt the liver function & does not allow the Stores of ferlic and to secrete d.
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? Phenytoin Na block the Enzyme Conjugase
5 1ed de mand
- pregnancy lactation
- Cancer in body growing age
- Hemolytex Anemia ?
- Fron deficiency Anemia St Erythro potste
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Pt with Macrocytic Megaloblastic Anema Danal give folic and alone. blc Hematological recover the B'M abnormalitie but the Neurological disorders blc whatever Small ic also Used in Hematopoitic paltway & thieve ore CNS disturbances.
Test for Falic and def
- Sorum F.A ved
- RBC.P.A ved (more reliables
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blc Serum FA most. rapidly fluctuates Witty food but RBC. P.Acad dop not floc to
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? ? Homocystein (ble In del of folve aced B12 is not Metaylated
So Serine THE E Figto (BA) Monircystein
(TMP) B124 CHa ? Methionine.
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? Homocystem (Homocystein level goes up both in Biz &, falic acid deficiency)
? No alted on Malonyl CoA
? led Urine Figlu in (forminoglutamic acad)
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