Part A

BASED ON DR. DILIP MMS LECTURES

Haema
tology
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 Basics of Haematology
BONE
ummm
MARROW
www.pi l
Red Bone Marrow Yellow Bone Marrow
Haematopoietic Non haematopoielic fatty
site Flat Bones skull site Diaphysis1shaftof
Pelvis1sternum1Ribs bones
long
vertebrae
EpilMetaphysicsoflong
bones

Otherfeatures
of a Bone Marrow
Cellularity too Age
14
Newborn 100
child I 10yrs 290
Adult 30 70
I
30 toy
d d
Hypocellular Hypercellular

Lineages Lymphoid to 25 even in P D

p
T CellLas B cell 35 1 Tall Ball
in Plasma O y 3.9
Myeloid 60 75
a Neutrophils 50 654
 b Eosinophils I5 5
c Basophils 6 Mastcells so aye

Erythroid 20 404
Megakanyocytes O5 a
of nucleatedcells
of BM
stromalcells Not haematopoietic
Adventitia reticularcells form as fatty tissue
Mesenchymal Stem cells Multipotent Adipocytes
Macrophages
Macrophages aroundsinusoids
Fibroblasts
Osteoblasts clasts
Chondrocytes
Myocytes
Endothelial Cells

Supportive Growthfactors
support
a
b
encept Epo cenythropoietin
kidney
b TPO Thrombigpoietin
Chinen
BM
mm
EXAMINATIONS
mmmm

Indications
Diagnostic UnexplainedAnemia
Unenplained cytopenia
Aplastic Anemia
 Pancytopenia PyreniaofUnknownorigin
Poo
MDS MultipleMyeloma Ee
Leukemia Plasma cell dyscrasia
MP D Storagedisorders
Granulomatousdis leg Gaucher'sdis
istsite to be Amyloidosis Go AD
leg TB
infected in lung is ALI NHL
Alveolarmacrophages marrow infiltration

REMI After chemotherapy

Px
ofisolated cytopenia
BM transplantation followup
contra indications No absolute CII

SITES
mum
OF BM BIOPSY
mm
e

Posterior Iliac Crests

mk Ee most
preferred site
Anterior Iliac crest
d Lateral
Paone
position decubitus
2.5 5cm posterior to ASIS
preferredonly in last whole
Posterior Iliac Chests are not
foundcold landmarks are not
palpableas in obese
sternum
Manubrium sterni landlord Ics
done in 12 in 12 bones are soft
yrsage group ages yrs
Ee have risk
of perforation
Otherssites8 Tibia Antero Medial Position in 12 13months
Vertebral body agegroup

NEEDLES 8
Aspiration needle Bx needle
particles
Bonespicules Body petard
thinishmt weeklong
Procedure

Needles
for Aspiration 8 Needles
for Biopsy E
Salah's needle Jamshid needle
Kilmer needle Osgood needle
Islam needle Islam needle
Procedure
of Bx Trephine Biopsy
Jamshidneedle same needle used
for both aspiration
G Biopsy
Islam needle used bothaspiration a Biopsy but different
forneedles
types of are used

Retroperitoneal Haematoma After the procedure if Pt complains

of severebackpain Ee
Hb drop
BP d
Alt d
CTscan largebloodcollectionin
eutropenitonealregion
Complications Bleeding lmk
rare
Injury to nearby structures
Infections
All sites can be chosen for both Aspiration Ee B
But sternum only for Aspination

HAEMO POIES IS
mmmm
c AGE
Yolk sac till 3rdweek 16thday
Liven Spleen a 7 months
Bone marrow
starts from 5 months
from 7 months only BM
Overlap blue Liver SpleenEe
BM from 5 7months
Birth only BMbones
call
age9 flat
as bones take
over haemopoiesis
 Basics of RBC - Introduction
STEM CELLS
mmmm 4 GROWTH
mm
FACTORS
mmmm
e

PlainepotentHaematopoietic
Stem cell 8
Characteristics

non connected 1no lineage

specific markers
stem cell Markers
y
most a CD34 helpsattachment
of
imp stemcells Bonestromal
cells
to
b CD117CC Kit SCF
CMsurvivalEeproliferation
c CD133 maintains numb
protrusions
d CD 110 TPor E MPL
promotes stem cell growth

HSC Homecoming cells in BM Ee preventing

attachingthe stem
them from leaning out
a CXcry forstemcells
b SDF I for stroma
stem cell Harvesting's in PeripheralBlood
tethods
directly collect from BM
from culture
from Peripheralblood
Plauen cry 0 DetachesstemcellsfromBone
afire
G CSF f Stromalcells
1
stem cellscomeintoPB Epenipheral
Bloody
1
stemcells collected
d
Harvested Eemultiplied

CommonMyeloid Progenitor
alsoknown as CFU GEMM
Multi1Oligopotent
Marker CD11C

Erythroidseries
a BFU E c Erythroblast
series
forums Erythroid d Reticulocyte
needs Erythropoietin EPO
e RBC
b CFU E
needs EPO
Epo is mostimportantfor
CEU E It can'tsurvive
withoutEPO

aM CSF
forms weanulocytes Ee
Monocytes
It is overlapping
But is alsoimportant
for otherlineages also
 ERYTHROID
mmmm
SERIES
run
ee

CFU GEMM
b
BFU E
Nuclearl
f
cytoplasm
p Proerythroblast Pronormoblast

Ety Normoblast
6
Intermediate Normoblast
i
hate Normoblast
6
Reticulocyte
b
Mature RBC
size
Cellsize Progressively I CEncept granulocyteseries
I
Myeloblast small
I
PromyelocyteChange
Nucleus a
sized
b becomes compact chromatin becomescondenses

c Nucleolidisappear dark Blue

Cytoplasm size9 less Basophilic

I MatureRBC More cytoplasm cytoplasm 9 but no nucleus

NIC I ratio
 Leis basophilic salmon Pink in colour
II Proengthnoblast cytoplasm bis
Hbstarts here
chromatin open

II Early NormOblast Basophilic

HI Intermediate Noumoblast Polychromatophilic Noumoblast
Hb is first detected here
stains
by normal
HI hate Normoblast OrthochromaticNoumoblast
Pyknotic nucleus fragmented a destroyed
from here nucleus entruded
So Reticulocyte Ee MatureRBC have nonucleus
G they also don't undergomitosis
I erythroblastgives rise to 16RBC
most mitotic cell in erythroidseries Proenythrobhast

Reticulocyte no nucleus
MatureRBC no mitosis
no EPO receptors
no response to EPO

Nucleated RBC Non nucleated RBC

ProerythroblastsI Reticulocyte 1matureRBC
Noumoblasts
Not seen in peripheral Seen in Peripheral Blood
Blood
HaveEPO r Don't have EPO r
Both nucleated Ee non nucleated RBC can be seen in BM
Nucleated RBC can be seen in Peripheral Bloodwhen there is
Accelerated erythropoiesis

u
Reticulocyte Mature RBC
Large small
Basophilic salmonfpink
I NO RNA
special stains suprauitalstains
needed
for staining Reticulocytes
Is
They are New Methylene Blue
Brilliant beesyl Blue
I
They stain only truecells
Reliculocytes are basophilic dlt
RNAfragments

Timetaken a mature RBC to be formed

for
Pronounoblast 5 7days
from a
Time taken to form a matureRBC from a neticulocytt 1.5 2days

man effectofEPOis

ego
Feticulocyte
d
Epo X Mature Reticulocyte

huge
EE
so spanof RBC is not
affected by EPOdeficiency
ERYTHROPOIETIN
mmmm
It is a hormone

synthesised from kidney 901 Peuttubular

dealer 10 Interstitial
Fibroblast likecells
EPO deficient in CKDIAOCKD Ee man deficient in Chronic Interstitial
Kidney Disease
most Emp determinant
of secretion Oalension

pay Hypoxia
Hydnonylast Epoto EpoA
HDD
JAP HE
UHL binds to OH
groups
breaks HIF14
ppg ixTHE
yd EPO Ip bonds toEPO

HIF T ttt
dedi PEPO CHIE HyponiaInducible
Oa 121Ip Factor
b yPHD
A NHL
man Epor
on CFU E
man effect Epo
of
no EPor ReticulocytestMatureRBC

EPO receptorsee n RI k lnon ReceptorTyrosine Kinase

I
TAK
d
STAT 7 Cellular
effects I
GATA 11FDGI
veryimportantfor
erythroidlineage
PERIPHERAL
mmmm
SMEAR
mmmm

RBC morphology NO Biconcave

O
Spherocyte
O
RBC Lifespan 90 120days
RBC size compared to nucleus of a small lymphocyte

Different Psg
DacrocytesteaudnopRBc
seen in Entramedullary Hematopoiesis
O Thalassemia
Myelofiberosis
splenomegaly

DrepanocyteslsickleRBCs Macroovalocytelmegalocyte
loss
ofcentralpallor
macrocylosis
Megaloblastic DNA
O maturation impairment
0 dHBizatolatedef
O Non megaloblastic
ditchronicalcholism

FragmentedRBGCSchistocytes
causes MAHA leg HUS TTPIDIC
O CdltRBC parsingthroughmicrovasculatured
MacroangiegpathylegeeLVADIDialysis
Prostheticvalue
IdltrBCparsingthrough
0 O O mech structureresultingin sheaustreld
 Spherocytes
A pautofthememb.isremoved dsurfaceAnd
loss centralPallor VolumeEe MCU
of
ego Hereditary spherocytosis
Otherhemolytic intravascular AHA
Gentravasculae ABO incompatibility

Elliptocytosis Codocytesltargetcells Bulliseye

eeg Hereditary centralhyperchromic

elliptocytosis area c a clearhalo
Thalassemia 0 around it
0
IDA Ong Hemoglobinopathy
Thalassemia
Myeloffbrosis O Liverdisease
Post splenectomy
Spiculated RBCs
LEATdeficiency
1 I
Acanthocytes Echinocytes
Stomatocyte
irregular
cytoplasmicprojections
Bmws Hepaticdis
Hemolyticanime
qg regular
y6 cytoplasmic
I
projections
Hereditary
stomatocytosis
MDS Lievesyndrome
Postsplenectomy tiemolylidanemia BitelBlustercells
Neurodegenerative GBarraud
disorders all are
transient chronic 0 Bite
cell
alcoholism
Hereditary
Abetalipoprotenemia Blister
cholestage HYfEmhHa
CBassenlkornyweig
syndrome
jaundice
cello
Uremia
cause a6PDdeficiency
pyeuwatekenasedef cdenaeweedH.is
getdeposited on
thememb gisengulfed
Artefacts bymacrophages
 e
INCLUSIONS
mmmm

a Basophilic Stippling Pappenheimerbodies

Types composed
ofFe
coarse headpoisoning sideroblastic
sideroblastican anemia
diff Fine Thalassemia
Hemolytican
Hemoglobin
Megaloblastic pathies rare

Pappenheimerbodies
Ringed sideroblast
only RBcinclusion
PearlsPrussian notfoundinps
Bluestain butfoundinBM
equivalent to
Papenheimerbodies
Fe accumulation
around nucleus
Caboteeing HavelJolley Bodies
Remnant
ofmitotic composed of
spindle DNAllittle
insidelhememb
figureof8 appearance o
condition causing Posteplenectomy
any 0 Asplenia
ineffectiveerythropoiesis
Megalobahastic
GeorollMDSIMegalo
blasticanemia Hemolylican

Heingbodiest Golf Ball cells

denaturedHb HbHC3agenedel
attachedtothememb O Thalassemia
66PDdef pal.pro ed
UnstableHb debt tppy
Hbk
Vy iscalled HbBarts
 Heme Synthesis & Porphyrias
RBC
mm
METABOLISM
mmmm

RBC features no organelles

no nucleus so can'treplicate loan't multiplicate
no mitochondria no TCA cycle Clersenergy
complete energy isfrom EMP
lot Calycolysispathway

NADPH protectsRBC
901
tomonidative free
radicaldestruction
ie onidatinestres
d
2,3BPG binds
to deonyHb f Ozreleasepromoted

ODCshifts right
HMP
G6p Pageboy NADPH G S S Gr Hao x2 HeinyBodies
x A
Ch6PDdef NADP onidanttt denaturedlmbl
asH
reduced
I leg Ha0F 0210th RBCmemb
stores H
Intravascular
BBC
mm
MEMBRANE
mm
hemolysis

PeripheralproteinsECHorigontalInteraction
a Ankyrin e Actin
b aspectuin f 4.2 allidin Proteus

g ftp.eomfsin put protein

itoniointedra
 Globin Synthesis & ODC

GLOBIN
ummm
SYNTHESIS
my
Home

Adult Hbk HBA 98 994

I
Tetramer
Kapa
Typesof Hebe
Chromosome 16

L X f
n

p Lalpp HBA GGlpp Portlandia

98991 AdultHb EmbryonicHb
8 22 88 HbAa
E3 t AdultHD
r
xalrrutbfeelrreelmbfoma.edu'd
E HEE Camera GHEE Chowerl
EmbryonicHb EmbryonicHb

Thalassemia minor
ft HbAa 3.5 p
Hbf moreaffinity to02 shiftofODC toleft
till 5 7months of fetalage 7100 Hbf
5 7 monthsfetalage
p chainsynthesisstarts
Birth 85 Hbf
15 HBA
HBA Transition from Hbf to HBAtakes placearound
3 6months Postnatal
of age
chmqgqthbacmmten
ge.IS
6weeks Yolksac Embryonic Hb
6 30weeks Hbf Calm
30wks Hbf HBA 95 51
Birth Hbf HBA 80 85 15 201
3OwksPostnatal Hbf HbA a 98 l Gransition from v top
ie Hbf to HBA complete

Ch16 Chu

sites
of
Hematopoiesis

x
Hbf X µbFC80 HBA 98994
Abed

X
HBA 20D
HBAT
X Hbf Ll 2

Gwks
O
O
6wks regression ofembryonicAbee start ofHbf
Variants
of Hb
Hbs
dlt point mutations eye Hbs sickleHb
Hbc
infoglobin chain Cpglobinchain 6thposition
Hbo Calutaminreplaced
ABE
by
valine
VARIANTS
mm
OF Hb
Variants
l p
p
Based on affinity UnstableHb

99affinity a COHb Hb Koln lmk unstable Hb

CarbonyHb
ODCshifts
CCOhas256timesmore HbZurich
to left affinity toHbthanOz Hb Tacoma
b MetHb Hb biloba
1 I
c Hb Chesapeake Hs
UnstableHb can
form Heinzbodies
It affinity a HbKansas Bilecells Blistercells
DcshiftstoRt

aide EEENSIERE
Oatransport 98 Hb02 measured
by spOa dS.aOz
b arterial sat
Pulseonimetry saturation
byABGanalysis
2
by Pao arterial
DeusduedOa measured

CO2transport 75 HCG Buffer

20 Hb GarbarinoHb
5 Dissolved CO2 Paco amt
of CO2dissolved
in blood
BOHR
mm
HALDANE
mmm
EFFECT
mm

Bohr effect occurs in periphery

Haldaneeffect occurs in lung
 Bohr Effect HaldaneEffect
1,02affinity x didCO2affinity a
µp fzpp
Occurs Occurs in alveoli lung
Periphery

favours 02delivery chlorideshift HC05either

when te concentration P
moves out Bohr'seffect1moves
02affinity ofHbdi EeOz in Haldaneeffect in enchange
released from Hb to co referred to aschloride
shift
DoubleBohr Effect8
Occursduring Pregnancy fetal circuit
Placental
CQ GOzvaries in both placental fetalcirculation doublesided
variation so that CO2 movesfrom fetal to maternal blood 602
moves from maternal to fetal blood

e DISTRIBUTION CIRIE
Saturation so
Sao a flat

sofsat
tmfoop
ativity
I
i g
PO Pa02
P50
 addition one molecule ofOz to Hb 9 affinity to further
Cooperatively of
02 molecules

Hb is in tenseform CdeonyHb Addition 1st Q istough

Initially of
Cso curve is a 9 Ee wine rises smooth
flatinitially slowly affinity
Paso Partial premiere ofOz which Hbis 50 saturated
26 27mmHg Aug 267mmHg
Pso 26.7mmHg ODC shifts to Right Ozrelease
Pso 267 mmHg ODC shifts to Left Ozbinds toHb

Rightshift causes Gavours Ozreleased

APC02 Others howaffinityHb HbKansas
9 Ht t.PH Acidosis Enemies
t 2,3 DPA ColeonyHb High Altitude
A Temperature

Left Shift Causes CteRelease Ctaffinity forOz

d PCO PaffinityHb Hbf
I Cut MPH Alkalosis Myoglobin
to2,3 DPG COHb
deTemp HbBarts crytetramers
MetHb
Hypophosphatania
Chesapeake
Aasediscursion An ICU patient 1doing well ppaaqq.ly

But Sao z d
H
D Acidosis CODC
shift to Rt
same PO Sao would be led
for
critical Paa
Pack L 60mmHg because less thanthis the values lies in the
sao steep part of the curve
11
En there will be a bigchange in Sa02 even E a
little change in Pack Pao 60mmHg

x X XX
Paoz
amiamr.im.maim
so in case Px of Pli in critical care Respifailure
of
Goat ee Pack 60mmHg
 Pulse Oximetry & Dyshaemoglobins
 Basics of Anemia
Anemia I no
ofcirculating RBCs But this doesn't happenalways
CRITERIA
nvm

Acc to WHO Hb Hct SevereAnemia

ChildCamo 5yrs Hg't 2334 s7g
Child 5 Hyrs Lil 5g 234 28gal
Child 1a Byrd slagel 2361 7g
33
Pregnant Lug't style
Non Pregnant f 2kg4 36 8g
Males 8 Cl3g 239
8g
DIAGNOSTICS
mummmm

Hb
Haematocrit Hct cellular component of Blood RBC contribute
to a 99
changes in Hot directly affectRBC
depends on a no
of RBC
b size the RBC
But of
Thalessemia Minor Tno of RBC weenpectHetton But Heth
because RBcherearemierocytic 2
Megaloblasticanemia Pseege
ofRBC weenpectHettor But Hett
because no OfRBC 2
Normal values 4 36 40
45
Aug
8 41 ggy
RBC indices
Microcylic
a Mcv NO 80 100 fl
Normagene too Macrocytic
baize
Aug of a single rage
28 Hypochromia
b MCH a8 gu
pg
Normachrome 34 Hyperchromic

avg Hb conc of a singleRBC

c Mcmc
Hbconc is less in Blood compared to RBC because bloodis
diluted by RBC
Csuprauital stains are used
30 50gIdl

Reticulocytecount
measure of Erythropoietic activity BM
of
O5 I 5
Relic count is measured by comparing to surrounding RBC
mature RBC 6 in number Reticcount may appearto A falsely
If
correctedReticCount ReticulocyleInder RI
Reliccount x
AdjuataHI y 51 45,1 a 08

Goodresponse 3
Poor response a

Reticulocyti ProductionInden RI
Goodresponse 3 Retic MaturationTime

Poorresponse a
 ReedCell Distribution Width ee

tells about Anisopoikilocytosis

13 15
1
I I

Iron DefAnemia Anemia chronicDisease

of
Anemia Thalersemia Minor
Megaloblastic
Haemolytic anemia
Thalassemiamajor

CLASSIFICATION
rumrunner OF ANEMIA
mum

MICROCYTIC NORMOCYTIC MACROCYTIC

MCV 280 80 100 3100
Etiology HABE HemolyticCRI at Megaloblastic
Fe Protopophyrin a Hemoglobinemia ImpairedDNA
Ttb b Enzymedef synthesis maturation
themed Globin e Membranedefects Hyperpigmented
Hbd d AlHA PMN t
e MAHA MCV 120ft
H
Microcytosis f Macroangiopathy
Non megaloblastic
a Iron DefAnemia 8 Infections RICHE
AOCD DNAsynthesis
Non Hemolytic maturation NO
bsideroblasticAnemia a Aplasticanemia
NoHyperpigmented
c Thalassemia b IDAIAOCD PMN
Early
Cudeficiency Recent bloodlog MCV 100 110ft
copperdeficiency CRI 2
 Causes
of MacrocyticApemiak
i l
Megalobbastic Non Megaloblastic

Bulfolatedef Alcohol Mk
MDS Liverdisease
Onolicaciduria
Sweeny Cuitodef
Fanconi
Hypothyroidism
ThiamineResponsiveMegaloblastic
Anemia IRMA E Multiple Myeloma
SLC19A'smutation Post Bariatric
thiaminetransportertrend
Down's syndrome
HI AnemialDM SMHL
Diamond blackfanndynd
Re highdoseThiamine Post Splenectomy
Druggie
Induce Interferest SpuriousReticulocytosis
Megaloblastosis Balfolate de
asagathiopaine
wnqsedaaugebn.MYmew.fm
asptenyeoin
b 5 FolloMP b Metformin
c clavibine
c Octueotide
d Hydnonyurea mum
e Wrye d Cholestyramine
AplasticAnemia
Lidovudinel e Antibiotics MDSIMPD

p i.fm ngmwnin
rici
a MethotrexateIMyco chloramphenicol
geEg
phenolateMofetil w
Nituofurantoin
il Pentostatin Ampicillin
g Allopurinol
 Basics of Iron Metabolism
TOTAL BODY IRON
mm mm

TBI
I 1
Functional Felsoy storage Fe 20.1
Hb 65 701 Ferritin Principle forms
Hemosidemen
Myoglobin 3.5 4 3 ofstorage
0.5 11
Linen
Hemeenzymes

AverageValues Females
13g
Males 6g

BEA of_EREN
Absorbed
RDA
longlday
c o Inglday

Only'fthereis u
no additional to compensatefollowwhichis inglday
loss He
waysoffelors Bloodloss usually does
not happen
Urinelfaeceslsweatlfined
Additional Feisneededfor leers
µ
Pregnant 27mgId 0.5 inglday
Menstruating f 18mglol Mentraction

y µ agouqmntftf.us
8 Hmgld
Homeostasis RDA absoubtion loss
Equivalent notequal

SOURCES
mmmm

Animalsources Meat Hemetype 9bawo.mjfny.gs Betterabsorption

Plant sources
a Fruits
pelteme
Nonty Affaffetion Poorabsorption
be Vanquishes

Factors
affectingabsorption of Fe in Plant qources
Aabsorption toabsorption
Ferrous Feta Fet3 most non HemeIron
Acids Fe13 speed Alkali APIs HablockersArtaud
Ascorbicacid
Eg Hell

Solubilising agents Precipitating agents Phytates

sugars Aa famatestPhosphates Tealca't
Ineffective erythropoiesis Reduced erythropoiesis
limproper RBCformed

I Sr Hepuedin T Sr Hepcidin fine AcutePhase

reactant
Pregnancy chronic inflammation
Hemochromatosis
Hereditary
 IRON
mm
METABOLISM
mm

Non Herne Fe Herne Fe Direct Fe

t n de
Fet Feta Enters the cell E ferricinonenters
the help ACP 1
entersintothecell
of
CHbcarriaeProteinD
directly through

with the help DMT I Integuinp 3

of
Divalent MetallicTransporter 1 Hemonygenase
u
in enchange for Itt to 4 Intracellular
Biliuerdin Fe transport by
CMT I carries Fe146 4 CO
Mobilferrin
nt4Mn 4Co 4Cdt4Pb Biliuerdin
reductase
V
e'in the cellis carried Biliuvedin

by Mobilferrin intracellular
transporter hiver

t 12
Fe
 Fett Inside the cell
1 I 1
Fate1 Fated
I Hepcidin
4
Intracellularstorage carriedoutsidethe
in the formof TsrFe Isr Fe
cell throughFoveopoulin I d
ftp.ofeevutineefovutin THepcidin titepaedin
ti te
Fetz spet3
Shld Haphaestin
tfumopontin TFerroport
activity activity
f Apotnansferrin t d
Transferrin
TTIntracellular Present
intothe
Apotransferrentfets storage blood
Transferrin
Apotransferrin Holotransferrin
Y fet3 i'CDifernic I
A transferrin TTransport
Hi
Transport
RECYCLING
mm
OF IRON
mm

senescent
RBCs
Senescent RBCsE
senescent RBCsenterthe
Undergoes Enythrophagocytosis
Erythrophagosome
Hi
Hemet Globin
1
carriedoutside Reduced to
theerythrophagosome Aminoacids
c thehelp HRG1
of
HernePugulatorycompound
Gene 1
to
Iron pool Fe t Bthuendin CO
I Biliuendin reductase
Billuendin

from Transferrin
pet3 fromTransferrin Tfp 1 endosome centersinto
transferrin
Receptor 1
x cenits
3 reduced 12
pet Fe Outside
STEAP3 ppg
Endosome
Cnnto t b reductase
ly
From Haptoglobin Hb Complen Iron Pool
Free Hbcauses Kidney injury
more Oa affinity more 0a delivery
I
so mostly Hb is in boundforms Tissuedamage
Haptoglobin Haemoglobin complex
Hb from this complex enters the cell through CD163Ee contributes
to Heme in the endosome
 From Hemopenin e
Hemopenin is a transport Hemel Enters the cell
form of free
through CD91 Ee contributes to heme in endosome
Fate of Hemein Endosome
Heme leaves the endosome through HRh I actedupon
bythe
Hemonygenase Bilineudin is formed

Fate of Iron in Iron Pool

Fate1 stored fee leavesthrough Ferropoutin outside thecell
Hepcidin 0 Ferropoutin
He
9 Hepcidin I ferroportin Pstored Fe
t Hepetdin r Feuropoutin deFe

After leaving thecell Fet is converted to Fe13 E

2 Colello
pet plasmin Ee13
l
p p
Transported Recygled
to Targetorgans
I RES
byTransferrin
HEPClmm
DIN ee
It is a hormone iron regulatinghormone
sizeee 25 Aa
Bactericidal
HAMP Chee19
gene
the AcutePhaseReactant
 Function Fennipoutincintheliuen
dimenisation Hengunenflin
mouBponhgenica BMp gI THEY YTTRI Hepatocyte
protein 4
1 e
Tfr binding to HFE can
txt SMAPIJ
I only activate HFECnotttrD
N
HAMI Hepadin

Matuiptased
Fu 0
Is.Featransferrintepiferrictransferrin

I t
cleavesHJUG 9
BMP6
freeTfr
g Ufthoffated
f
thisbinds cancompete
0 to HFE Ttratobined
to HFE
0 thffe condition IS.ee condition
04 A 0
Fpninum Fpnin RES Factors regulating Hepcidine
aletbsXorption Fberelefase
Activate Inhibit
d Feabsorption sffrager IL 6ItueAPR PEPO
Gr Ferritin gaitepcidinated trenylhoopoies

Epode Utyponia
AFpeabs.pe ynllidldpntfrytes
Matriptased
i Hepcidin
d
p d
Ellythne
L
HAMP
RBkRetic
fenone
Appliedaspectsof Hepeidin
AOCD linflammation a egoe AdultonsetPCKD
I
6 EPO
6
TIL 6 ftp.udine dEeeytnofeweone
Hue APR
felt D Functional
absorption
Fe release Fe def

ltueAPRFTpstr.Femitin Paradonically
Inflammation still can'tutilise Fe
itself can cause
p Sr Reuniting
HHC HFEgenemutation C2824 Hb3D
14
function

v µ
HPUmutation BMPG
HTT
HAE
CJuvenileHomo 6 Fe sensing is
chromatosis SMAD tasty
HAMP HepciXdin b u
unregulated Fe
FeOverloads absorption from an

Mutation HIV Juvenile Hemochromatosis

of
Matriptased def Iron Refractory IDA
0 HJVPP P BMP6 ASMAD
to
 6
041T Peaks ftp.cidins AHAMP
Id
Severe IDA
beefuactorytomalfe
14
Re IV Fe
IDA ee Isr Fe
t CFenopoeetin
bHepaedin Fpn active are absorbing potential
for Fe is 99
6
Aabsorption to 20 30
12 3times 9
Intracellular
IRB GIRE
y Full IRB binolto
MINAS 791 IRES inlowIeeon
mRNAs
to
state
Iron O_0 d
High Iron state
ResponseElements BTginning IRPs are alreadybond
mRNA
tope sotheydon't
p bind to IRE
P O
Ending
 IRON
mum
INDICES
mmmm
8

Characteristic 9 I
Sneek 8 55 160µgIdl fluctuating Fe overload Iron deficiency
Anemia
Of 40 150mgtell feintake AND
50 150 recent
Aug
Ferreting 8 12300nglmllstparametentode Fe overload IDA earliest
Sideroblasticparameter to
to 150mgIme Eesinglebestpara anemia
meteufouDin beAlchanged
Aug 20 too Iron Deficiency Megaloblasticcentuemely
Anemia anemia
specific
canalsobetinlditnomatura
e tionano Nephroticsynd
inflammation utilisation
unaybedlthers
of ferritin
Positive APR AND

TSATE 8 do 50 Seriffed too Feouveload IDA

sideroblastic Nephroticsynd
transferrin 0 15 504
anemia
Saturation Ao
Avg 25 451 Megaloblastic
anemia
Transferrin 170 370mgldl TBC 1.389X T AOCD
Transferrin pueegdftoc.rs Fe overload
progesterone Nephroticsynd
 Characteristic 9 I
TIBCE 250 450mgtell TlBC 78 same as for
1.389
Gffmansffnff
TBC UIBC is.pe Transferring

Stereo 8 a 2single cleaned Tfr Inondef AND

Golubletran ta from Menlo Feoverload
gerrinReceptor
f y.ymgle
Hu
Hemolysis
d
ESA Nephroticsydal
Erythropoiesis
ErythroidSti Alransferrinemia
pe iilymutatingagents notuansferrin
receptor at all
STER ee Fedef 22 IDA AND
logferritin AND I coexist
may
ratio StFRP
Feely
blogferritin
AOCD STERN
Hogfevitin

IDA Sr ferritin de
AOCD Sr ferritin 19
Alert
equivalentto
TBC
Remaining SrIron cremainingtransferrin

equivalent
to Srtransferrin
 Microcytic Anemia - 1

MICROCYTIC
mmmm
ANEMIA
mm

Enamples Iron Deficiency AnemiaCIDA

Thalassemia Early IDAG
AOCD are
sideroblastic Anemia
Normocytic
Anemiaof chronic Disease CAOCD

Etiology CIRIDA rare cause

Chronic bleeding IFesupply A Demand
61 90 bleeding Malnutrition Children
malignancy a coeliacdisease Adolescents
Menstruallosses
b Crohn'sdis Pregnancy
Parasites hookworm c TaastricPH
Epo stimulating
NSAIDsCPepticulwe AtrophicGastritis
Agents CESAR
Disease d Gastrectomy
e Baniatricsx
Malabsorption

Clf GeneralSymptomsEesignsof Anemia

lethargyIfatiguelpallon
tachycardia'lpedaloedemalBasaloupitations suggest
cardiacfailure
Brittlenailslkoilonychialhaiutors
I
Beadtest sabeadwhenkeptonthenail retention
of the bead suggests Koilonychia
piuacpacophage.at Dyyphagia

Angulancheilitis
Atrophic glossitis smooth bald tongue
Plummer Vinson syndrome UpperEsophagealWebs
I
Postalicoid Premalignant Secof
responds top
dysplasia upper esophagus
BuelUnotelegelers thewebs
EstepPPhmageae IDA I Endoscopy
webs Bariumswallow
B Fe supply Balloon
dilatation
Investigations
RBCindices Hbd d no of circulating
Hette RBC
dcytosolic red formation of Reticulocytes
Hb
medp 3
Mmg
yf
meth
f2fx
YIgpmouttmomi.EE
yici.RDWT
Anemia
IReticulocyle
CAnisopoikilocytiosis Hypoproliferative d
is anemia dRBC
veryhigh
Ps Microcytic Hypochromia RBC
SizeofRBC nucleus
Microcytic of lymphocyte
Hypochromic centralPallor 13
Fe Indices
a Sr Fe
b Sr Ferritin
c t Transferrinsaturation
d PTransferrin Receptor Ster STER
e Total Iron Binding capacity P loglfovietin
 n PIS Tfrp
Transferrin
Transferrin

ABC I puitin srfemitinfitf.ae

Sr Fe
Bloodstones
SrFew
f s
Nostores list tochange
TSAI IDA
BATH 16TSAI Sr Fett
MBC pp
Other Investigations
BM Fe stains Absent Nonstaining
fvohdstd.TL
pearlsPeuusianBlueStain
But notusednow
It Hepcidin Isr Fe dHepcidin
FreeErythrocyte Protophyuin FEMA
Evaluation cause PeiotoporpMhyrint
H
of
L lsideroblast
a Upper GI symptoms OGIendoscopydone Heme Globin anemia
b Lower GI symptoms eg Diarrhoea X
d
Riskfactor
for
Malignancy
Hb
family Houdoncancer
Elderlylarge 50
A
colonoscopy done
c Asymptomatic Inolocalising symptoms
d Premenopausal Reproductive f Trial of Oral Fe
Postmenopausal
tf God Endoscopy WAI endoscopy
coeliacdis Anti7Th
it10 IgA
stooloccultblood Colonoscopy
ImmuneResistantIDA stoolroutinelovalupts NO
CIRIDA
Angularcheilitis web Koilonychia BeadTest

0 09Hb
o

0 ONHb RBC
gypochromic

HypochromiaRBC BoneMarrow CNO Fe in BM DimorphicRBC

CresponsetoFed
you start R Ee there is response
Once
Relic Countstarts increasing

Stages of IDA
LatentFeedef Classic IDA
I
Iron def I anemia Inon def anemia
BM stores Fe 0 clinically labaltered
of
Sr Ferritin

FORMS
mum
OF IRON
mum
Px

Oneal Fe 6 wks to correct anemia

6months to replete stones
toruiactest to test for occultblood in stool Oneal Fe
based on retention Heme in stools will not
of giveTue
SIE MK GI symptoms1intolerance d doses of Fe
metallictaste change to a tablet I 6
Fe content
 Fe Oxidising agent releases free radicals into GIT

Formulations
of Fe
FoveousGluconate Ferrous Sulphate FerrousFumarate
ElementalFe 712 1204 33

peogfg
37mg
eleFe soong citing soongaiotmg

Dose variable Itab TDS Italo BD

Response clinical Lab findings CHemat
subjective Symptoms ist BM erythroid hyperplasia Edd
improve first
1st picatmproues pretic Hb 3 4days
Kia 24hrs3 G 1week
Reticulocytosis
fatiguelimitability
duh prBccountIPHb
1S
Epithelialsigns RDW correction last
Ctawks
CAngulancheilitist
Replenishment
ofBM FeStokes Gmo
alorsitis
Target Hb Rateofrise agldl
Koilonychiacomonths enemy weeks
3
if this is not happening Poounesponse
Reasons Poor Responseee
for
Non compliance
Hemorrhage continuousbleeding
wrong Accouldbe othercauses
Mined
def
Others MalignancyIAOCD
Malabsorption
Slow Release Preparations
 i v Iron
Indications Intolerance to Oneal Fe
CKD on Hemodialysis 1 CHF cancer

CPHepcidin 0 Fe absorption from all

Before ESA Px
Emersive persistent GI losses
Pt prefers quick Px
In Pregnancy Near term IDA
Cole 20wks Hb 7 9glee
Preparations
Concentration TestDose Dosage

ferricGluconate 125mgIml X 125 1875mg X multiple

Iron sucrose 20mgIme x doo 300mg x multiple
Fenumonytal 30mgIml X 510mg 51Omg
lHighestMolecularwtf
LAW Dentuan 50mgIml 100mg multiple11000mg x
Civ I i m single
FerricCartoonyMaltose 50mgIml X 750mg tapdatt 750mg

FerricIsomaltosidase 100mgIml X 500mg x 3 doseslower7days

9 20mg1kg singledose

Preservative used in Ferric Gluconate Benzyl Alcohol

Bright signals on MRI can be seen c Ferrumonytalupto
3 months
SIEee Early Flushing 1Metallic
hate Myalgia I Arthralgia Lymphadenopathy

calculation
of Dose
Crangonimethod outdated 4 x 15 Hb x Bodywt t Feneeded
forstores
I500 1000mg
Newermethod Ed145 x Iu Itb Body wt
Fe needed stores
for
yya x desiredHb ActualHb X LeanBody Wtf
t 026 XLeanBody htt
v
Ca CH Hb x BW t Ee forstores
In caseof ongoing bloodloss Emt ofbloodlostCml x HCI

BloodTransfusion
Indications Hb C 8 cardiovasculardisease egfailure
Hb s 8 Acute Blood loss
All stable pts t Hb C 7
Symptomatic pts t Hb 7 9 l
g
Pregnancy Hbc 5g regardless ofGestationalAge
Hb 5 7 t near term or labour
U
Fe Infusions are given when Hb ft 9 nearteam

Other
mm Microcytic
mm
Anemias
mm

ImmuneResistant IDA Ri i v Fe
EMatriptase a deficiency
Atransferrinemia CAR Microcyticitypochromic Anemia
DMTI def anemia Sr Fed
CSCLIIAD EAR NBC de
d S TFR 0
Micuocytictypochromic s Ferritint
Anemia f EPP
MCVI
8 Fet
S Ferritint
TSATT J
STER T
S transparent
f EPP
 Microcytic Anemia - 2

ANEMIA
mum
OF CHRONIC
mm
DISEASE mm

and mk cause Anemia in the world Clstmk IDA

of
dit chronic inflammation
pathophysiology
T cytokines CAcutt PhaseReactants
M 61 TNFX
d
THepcidin E oferroportin
L d
Feabsorption t.fenekasl y.grferritin It
AIT RES
i cstores It
I
Isr Fee ferritin tueAPR
TSATI MUFFLEY Tmmanfpfffriffpy
SHRI a
GHB ferritin
logNON
IRBCcount Hereticcount Stblettrd
MicrocyticitypochromicAnemia Sr Transferrin6
He
NBCte
r r

seek Ferritin
Sa If
s snorts
s.e
ran a TSAFI
 CancerPresenting like IDA coloncarcinoma

Etiology ChronicInflammation Autoimmune

Malignancies Breastthing1lymphoma
chronicInfectionGB HID

Investigations
RBCindices Hbd Mcvdi Earlyphase MCU NO

dRBCcount CdReliccount AOCD I feed

Fe indices ITSAT14STFr I I s Tr Hypoproliferative

47413C I theticulocytes
IN Sr Ferritin
SHR I specific
logFerritin
A fEP non specific canbe in Thalassemia
PI Microcytic
Hypochromia
ICarly stage NormoyleNormochromig

RIE Treat the underlying cause AOCD IDA Sr ferritin

Iron euplacement Ciii cwmmODDoestnoteeuleoul

Inidication sr.ferritin Goo coenisting IDA

Coe
7SAT 20 Avoid PRBCtransfusions
ESA Ind ee EPO s 500
Malignancy Croat cancercure but forPalliative
Re ESA can beused
Anemiacausing Heartfailure ESA can't beused 1becausethere
is notime to wait forResponse
SIDEROBLASTICANEMIAE
murmur mum

theme syntheses tee Protopophyuinsd

Httpoor mmmm
Jitemed
utilisation Globin
of
intracellularFe 16
I Microcytic
CAND Poor utilisation
entracellulate fed
of
Intracellularfe
In mitochondria 1
aroundthenucleus BM erythroidprecursors
ofRBC r Ridgedsideroblasts
a
PearlsPrussian See seen'm BM not Rs
a
Bluestaining PappenheimerBodies
Tonic
He
might be seen if RBC
d Erythroiddevelopment mature
lemonaccumulates in
the RBC
Etiology SuccinylCoA Glycine
e Home
Vit.BG ALA Synthase y
t Mitochondria Panotoporphyrin
8 ALA l
L l
l
l s
l
l
l
l l
I i
k i
f ALA
ALAdehydratase
PBG t
l l
l
t
 Thalassemia - 1
 Thalassemia - 2
B THALASSEMIA
mmmm

x Thalassemia is mainly dit genedeletions

p Thalassemia dit pointmutations frameshift mutations

Pathogenesis

fstop
penalanemia
ummm I 1
1
de
enons
Introns p p
Inoglobinchain somepglobinchain
µ de de
mRNA mmmm

Introns Enonmutation Intronesplicing

removed mutation
mm
ienons usually produce
coding splicing
stopcodong promotermutation
H d
Bchain I pt
B
GENETICS
mm
Homogenous Heterogenous
Bo popolnopglobin po1p
Ghatmajor Cooley'san Thalminorltraittenaeintermedia
ispossiblebut
B ftp.tcuaeuable pt1p rare
That.int majoD Thalminoeltrait

compoundHeterogenous 8 poet That majorlintermedia

Major Intermedia Minor

88 Boot pop
popt Btp Btp
ftp.t Bp
B rare
 Sickle Cell Anaemia
Thalersemia Quantitativedecline
of f globin syntheses
SCA Qualitative problem
of f globin synthesis
Gmail Papua of_SEA
AutosomalRecursive
common in Africa a African Americans Caribeans

Evolutionary relationship c Malaria sickle cell Trait peu se gives

protectionagainst Malariafalciparum
sicklecellDisease Homogenous mutation both chainsaffected
p HbSST
sicklecell Trait Heterogenousmutation Onepchainaffected HbAD
d
Malaria falciparum believed tobe an evolutionarymeasure
protective
for
forprotectionagainstfalciparum
GENETICS
mmmm

pointmutation
Hb Hbs
Hydrophobic
Bchain 6thposition Glutamate valine
6
DNA Gene Cr
CAA CTG
Feo
philic chain haschanged hydrophobicfromhydrophild
p
PATHOPHYSIOLOGY
muumuu

All1Mostof the problemsof SickleCellAnemia arisedueto Deony stateof t

Hb Deony state Hb's insoluble
censeform I
Polymenise
O A
1 sickie
ChangeRBCshapeto
crystals bis deformable
 sickledRBC can'tpassthrough micro circulation a getstuck
Other RBCattackto d Ee
mummmmm
P Selectin in Endothelium's present form RBCaggregnates
in Weibel PalladeBodies CatovWF I
etsIPmImiuouaswegeoawsion
i E.IT Endothelial activation 1 Platelets activation
P selectin P selectin

6
RBC aggregation PMN adhesioncarouing
local hyponia infarctionetc canalsooccur
c
Formation
mum
of sticky Ends
Hb
valid a
valine
Op sickleHbhasValine
0 cytosolicend Replacement
by whichishydrophobic
cytosolic
Hao CHOI valineinpchain
08 9 eemovesaway from

stickyends acceptorsite
prf
sticky
ends
cytosolicCHO side

I Filament made
of 2 strandsof pglobin
I chains

made Centralcore 2 filaments

Polymer of 4Strands
b Outersheath 75filamen
Polymer
IFqqeaµ IOstrands
Epchainsareinside mmmm
paved Acceplorsile P85Phenylalanine sickleshaped RBCIs
Tite B Leucine called'Dnepenocyte'in
Alanine P
These polymers form'sicklerpoir YYms
 Introduction to Hemolytic Anemia

HEMOLYTIC
mmmm
ANEMIA
mm

Normocytic Anemia
RI Peripheral bloodreticulocysis occurs
a
certain PNH variants RILL
P LDH
Enamples of Normocytic Anemia
Hemolytic Anemia
Aplastic Anemia Pancytopenia NormocyticlNormochromic Anemia

EarlyIDAIAOCD REID
Acute BloodhorsCRI 2 LDH

Uarsimkeathmofltemm.name
I Based on location
of Hemolysis
Location Mechanism Etiology Inherited
Intrinsic Enzymedef a6PD Pyruvate kinase
corpuscular Phosphofeuectokinasedef
Memb.ab HSI µmfm Liverdisease
Hemoglobinopathy sickle cellDislthalousemia
V
Acquired
Intrinsic Immunemediated AlHAIDruginduced
Centracorpuscular Traumatic MAHAL Microangiopathy
Adare acquired DirectInfections MalarialBabes.la Venoms
Tonins Nilsondis Hypotonicinfusions
Entrapment Hypensplenism
Hereditary Membrane defects causing hemolysis
HEREDITARY
mm
SPHEROCYTES
mm

2 mile mutation
O Ankyrin
Mutations Ankyrin Band3
protein x spectrin Palladio
04 4.2protein
t O
03

Inheritance8
AD 75 common in
AR 254 North Europe

History Family Ho Jaundice Splenectomy

ccholelilhias.es

Ho Cholelithiasis lies childhood

CIF presentation Anemia Jaundice Neonatal 1Splenomegaly
1 I
Age Variable dlt Entravasculate spleen chiefsite
hemolysis
I ofEVhemolysis
9 Bilirubin
Gtallstones
Bilirubin Pigmentstones
Chronic Anemia
legulcers
Types
ee Mild HS Cao't Asymptomatic
Moderate HS175D Infancy1 childhood
severe AS 15 Newborns Deathin utero
 removed
DE
volume Mcu
Spherocytes
0 O SA d
Membrane Spherocyte Townie
formssurfaceArea HSA y
Now the contents
posmolicfragility have to be packedin
a sphere
RBC Indicesee MCV I
lots
MCHC TP G 36 of Pallor

III This P Eee

V u
Both are possible Cruleout AIHA
Reticulocytes have TMCD

Confirmations HemolyticAnemia

Eosin 5 MaleimidelEMA GoldStd

de
Band3 Rh proteins Reticulocytes

binding to EMA'd
8M O Basophilic
Poor binding CPolychromato

I philic
its confirmed
ensitivity 93 1Specificity 99 I EMAbinding

preferred test because its

results comefaster knees Gsmall
ant blood needed
of
Flowcytometry
 Enzyme Deficiencies Causing Haemolysis
GGPD
mm
DEFICIENCY
mm
ANEMIA
mlc enzymedeficiency causing hemolysis1 hemolyticanemia
mlc enzyme deficiency in the world

Conidised
t

Fatima.is E.a agE

G S Hye HAUPT
Reduced
µ
Proteins pronidative
denatureollonidised damage
CO Oti
legee Hb denatured
He
settle in RBCmembidteingBodies

Intravascular Entravascular
Bitecells Blistercells O.O
Bitten
by
hemolysis macrophage

Typeslvaniations
I Cly very severe
chronicINon spherocyticHemolysis
Mk cloy severe Acutel Intermittent Hemolysis
CMediterraneans trequentlattstrusttriggers
Blacks 10 601 Moderate Occasional hemolysis

so
F 60 150 NO Asymptomatic
called
I yigoy Asymptomatic
acepDinhibitors's'abPD blacks
Triggers Infection

Drugs Sulfonamides Infections I NADPH Prespiratory

Burst
Dapsone Ptotedantstras
Nitrofurantoin
Primaquine Diabetic ketoacidosisCDKA
Donorubicin Food Fava beans previously
Rasbunicase called as Flawesm
Dabrofenib
Methylblue
4ft Asymptomatic Mk
Symptomatic iv hemolysis Acutilchronic
1 Ps PeripheralSmears
a Heinzbodies
b Bitecells1Bbislercells
Fluorescent spot Csemiquantitative not performed
Quantitative GoPD levels in Acutestages

Acute Hemolysis Reticulocytes Fresh Falsely GGPDlevels

Old Hemolysis Reticulocytes Dead
BE Avoidtriggers

PYRUVATE
mmmm
KINASE
mm
DEFICIENCY
mm

Pyruvate kinase66 ATP I Membgraneintegrity

Entravascular Hemolysis
curable
 Immune Haemolytic Anemia
 Macrocytic Anemia
 Marrow Failure Syndromes
 WBC Basics
 Disorders of Neutrophils
Flow cytometry of CGD
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