11 red blood cell disorders

8/11/2019 11 Red Blood Cell Disorders

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11 Red Blood Cell Disorders

Erythropoiesis

Erythropoiesis is the production of RBCs in the bone marrow and is dependent on the

release of erythropoietin from the kidneys.

Erythropoiesis

Erythropoiesis is the production of RBCs in the bone marrow and is dependent on the

release of erythropoietin from the kidneys.

Erythropoiesis and erythropoietin (EPO)EPO increases the O2carryin! capacity of blood by stimulatin! erythroid stemcells to di"ide. Epoetin alfa# a form of EPO produced by recombinant $%&

technolo!y# is fre'uently abused by athletes to increase their ener!y le"el. talso is used in the treatment of anemia associated with renal failure# chronicdisease# and chemotherapy.

. *timuli for EPO releaseo +ypo,emia# se"ere anemia# leftshifted O2bindin! cur"e (OBC)# hi!h altitude

2. ncreased O2content suppresses EPO release (e.!.# polycythemia "era).-. Other sources of EPO

o Ectopic production by renal cell carcinoma and hepatocellular carcinoma

. Peripheral blood markers of erythropoiesis

a. Reticulocytes are newly released RBCs from the bone marrow.b. /hey are identified with supra"ital stains.

$etect threadlike R%& filaments in the cytoplasm

c. n 2 hours# they become mature RBCs.

Reticulocyte count

. 0arker of effecti"e erythropoiesis (bone marrow response to anemia)2. Reported as a percenta!e (normal# 1-)-. Percenta!e count is falsely increased in anemia.

a. nitial percenta!e must be corrected for the de!ree of anemia.b. Corrected reticulocyte count 3 (actual +ct45) 6 reticulocyte count# where 5

represents the normal hematocrit (+ct)c. E,ample

i. +ct 5# reticulocyte count 7ii. Corrected reticulocyte count is 8 (545 6 7 3 8)

. Corrected reticulocyte count at or abo"e -a. 9ood bone marrow response to anemia (i.e.# effecti"e erythropoiesis)b. E,ampleshemolytic anemia: after treatment of iron deficiency with iron

5. Corrected reticulocyte count below -


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a. Poor bone marrow response to anemia (i.e.# ineffecti"e erythropoiesis)

b. E,amplesuntreated iron deficiency: aplastic anemia

E,tramedullary hematopoiesis (E0+)

RBC# white blood cell (;BC)# and platelet production that occurs outside the bone

marrow

. Common sites of E0+ are the li"er and spleen.2. Patho!enesis

a. ntrinsic bone marrow disease (e.!.# myelofibrosis)b. &ccelerated erythropoiesis (e.!.# se"ere hemolysis in sickle cell disease)

i. E,pands the bone marrow ca"ityii. Radio!raph of the skull shows a


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newborn# which occurs - days from birth.

. ?actors affectin! the normal ran!e (reference inter"al)a. %ewborns

i. %ewborns ha"e hi!her normal ran!es than do infants and children.ii. +b? (2A42 !lobin chains) shifts the OBC to the left causin! the release

of EPO. EPO causes an increase in +b# +ct# and RBC count.

iii. &fter birth# the +b drops from 7.5!4d to !4d (physiolo!ic anemia).i". +b?containin! cells are replaced by RBCs containin! +b& (D=>)# +b&2

(12.5)# and +b? (1).b. *e, of the patient

0en ha"e hi!her normal ran!es due to increased testosterone(stimulates erythropoiesis) and lack of cyclic bleedin!.

b. Pre!nancy

i. Pre!nant women ha"e lower normal ran!es than nonpre!nant women.

ii. /here is an increase in plasma "olume and RBC mass (i.e.# more RBCsare produced). Plasma "olume is twice !reater than RBC mass causin! a sli!ht

decrease in +b (dilutional effect).

2. Chan!es in thalassemia (i.e.# a !enetic !lobin chain disorder)

b. +b and +ct are decreased.c. RBC count is increased (unknown mechanism).

-. &nemia

d. $ecrease in +b# +ct# or RBC concentration

e. *i!n of an underlyin! disease rather than of a specific dia!nosisf. Clinical findin!s

?ati!ue# dyspnea with e,ertion# inability to concentrate# diiness

RBC indices

. 0ean corpuscular "olume (0CF)a. &"era!e "olume of RBCsb. Gsed to classify anemia

0icrocytic (17H Im-

)# normocytic (7HHH Im-

)# macrocytic (DHH Im-

)2. 0ean corpuscular hemo!lobin concentration (0C+C)

a. &"era!e +b concentration in RBCsb. $ecreased 0C+C

ii Correlates with decreased synthesis of +b (e.!.# microcytic anemias)

iii Central area of pallor is !reater than normal (called hypochromasia).

b. ncreased 0C+C


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ii Correlates with the presence of spherical RBCs (e.!.# hereditary

spherocytosis)iii /here is no central area of pallor.

R$;

. Reflects "ariation in sie of RBCs in the peripheral blood (anisocytosis)2. ncreased if RBCs are notuniformally the same sie

o E,amplemi,ture of microcytic and normocytic cells

-. ron deficiency

o Only microcytic anemia with an increased R$; due to a mi,ture of normocytic

and microcytic RBCs

Characteristics of mature RBCspa!e =7

pa!e ==

. &naerobic !lycolysisa. 0ain source of adenosine triphosphate (&/P)b. actic acid is the end product of RBC metabolism.

2. Pentose phosphate pathwaya. *ynthesies !lutathione (9*+)# an antio,idant that neutralies hydro!en pero,ideb. +ydro!en pero,ide is a product of o,idati"e metabolism.

-. 0ethemo!lobin reductase pathwaya. 0ethemo!lobin (met+b) refers to heme iron that is o,idied (?e-J).

0et+b cannotbind O2.

b. Reductase system con"erts iron to ferrous (?e2J) so that the RBCs can bind O2.. ueberin!Rapaport pathway

a. *ynthesies 2#-bisphospho!lycerate (BP9)

b. Re'uired to ri!htshift the OBC (i.e.# release O2to tissue)5. 0ature RBCs lack mitochondria.8. *enescent RBCs

a. Remo"ed by splenic macropha!es

b. End product of heme de!radation in macropha!es is uncon@u!ated bilirubin.

;BC count and differential

. HHcell differential count subdi"ides leukocytes by percenta!e.

2. ?urther classifies neutrophils as se!mented or band neutrophils

Platelet count

Platelets are anucleate cells deri"ed from cytoplasmic buddin! of me!akaryocytes.


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ron studiespa!e 2HH

pa!e 2H

. *erum ferritina. ?erritin is the primary soluble iron stora!e protein.

i. Primary stora!e site is in the bone marrow macropha!es. *ee shaded area in the small bo, in

ii. *erum le"els correlate with ferritin stores in the macropha!es.iii. *ynthesis of ferritin in macropha!es increases in inflammation.

$ue to release of interleukin and tumor necrosis factorA

b. $ecreased serum ferritin

$ia!nostic of iron deficiencyb. ncreased serum ferritin

i. &nemia of chronic disease (&C$)ii. ron o"erload disease

b. +emosiderini. nsoluble de!radation product of ferritinii. $ecreased and increased le"els correlate with chan!es in ferritin stores

2. *erum iron

c. Represents iron bound to transferrin# the bindin! protein of ironi. /ransferrin is synthesied in the li"er.ii. *erum iron is the shaded area of the column in

%ote that the normal serum iron is HH I!4d.

d. $ecreased serum ironi. ron deficiencyii. &C$

e. ncreased serum iron

ron o"erload diseasesii *erum total iron bindin! capacity (/BC)

a. *erum /BC correlates with the concentration of transferrin.

i. +ei!ht of the column in correlates with serum transferrin and /BCii. %ote that the normal /BC is -HH I!4d.

f. Relationship of transferrin synthesis with ferritin stores in macropha!esi. $ecreased ferritin stores cause increased synthesis of transferrin

ncrease in transferrin and /BC is present in iron deficiency.

ii. ncreased ferritin stores causes decreased synthesis of transferrin $ecrease in transferrin and /BC occurs in &C$ and iron

o"erload disease

-. ron saturation ()

!. Represents the percenta!e of bindin! sites on transferrin occupied by ironi. ron saturation () 3 serum iron4/BC 6 HHii. n the normal saturation is HH4-HH 6 HH or --.

h. $ecreased percenta!e of iron saturation


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i. ron deficiencyii. &C$

i. ncreased percenta!e of iron saturation

ron o"erload disease

+b electrophoresis

a. Primary use is to detect hemo!lobinopathies.i. &bnormality in !lobin chain structure (e.!.# sickle cell disease)ii. &bnormality in !lobin chain synthesis (e.!.# thalassemia)

b. /ypes of normal +b detectedi. +b& has 2A42K !lobin chains (=> in adults).ii. +b&2has 2A42L !lobin chains (2 in adults).

iii. +b? has 2A42 !lobin chains ( in adults).

Microcytic Anemias

/ypes of microcytic anemias

. ron deficiency (most common)2. &nemia of chronic disease (&C$)-. /halassemia (A and K)

4. *ideroblastic anemias (least common)

/ypes of microcytic anemias

. ron deficiency (most common)2. &nemia of chronic disease (&C$)-. /halassemia (A and K)

. *ideroblastic anemias (least common)

Patho!enesis

. $efects in the synthesis of +bo +b 3 heme J !lobin chains

2. $efects in the synthesis of heme (i.e.# iron J protoporphyrin)o ron deficiency# &C$# sideroblastic anemias

-. $efects in the synthesis of !lobin chains (i.e.# A or K)o A/halassemia and Kthalassemia (thal)


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ron deficiency anemia

Table 111! Causes o" #ron De"iciency Anemia

Classi"ication Causes Discussion

Blood loss 9astrointestinal loss 0eckel di"erticulum (in older children)PG$ (most common cause in men 1 5H years old)9astritis (e.!.# %*&$)+ookworm infestationPolyps4colorectal cancer (most common cause in adults D5H years old)

0enorrha!ia 0ost common cause in women 1 5H years old

ncreased utiliation Pre!nancy4lactationnfants4children

$aily iron re'uirement is -.m! durin! pre!nancy and2.5-.Hm! durin! lactationron re'uired for tissue !rowth and e,pansion of blood"olume

$ecreased intake nfants4children

Elderly

0ost common cause of iron deficiency in youn! children

Restricted diets with little meat (lack of heme iron)$ecreasedabsorption

Celiac sprue &bsence of "illous surface in the duodenum

ntra"ascularhemolysis

0icroan!iopathic hemolyticanemiaP%+

Chronic loss of +b in urine leads to iron deficiency

+b# hemo!lobin: %*&$# nonsteroidal antiinflammatory dru!: P%+# paro,ysmal nocturnal hemo!lobinuria: PG$# peptic ulcerdisease.

pa!e 2H2

pa!e 2H-

/he sta!es of iron deficiency in se'uence are as followsM absent iron stores:decreased serum ferritin: decreased serum iron# increased /BC# decreasediron saturation (): normocytic normochromic anemia: microcytichypochromic anemia.

. Epidemiolo!ya. t is the most common anemia.b. Causes of iron deficiency

2. Patho!enesis

o $ecreased synthesis of heme2. Clinical and laboratory findin!s

a. PlummerFinson syndromei. Caused by chronic iron deficiencyii. Esopha!eal web (dyspha!ia for solids but notli'uids)iii. &chlorhydria (absent acid in the stomach)i". 9lossitis (inflammation of the ton!ue)# spoon nails (koilonychia)

b. aboratory findin!si. $ecreased 0CF# serum iron# iron saturation ()# ferritin (1-Hn!4m)ii. ncreased /BC# R$;iii. 0icrocytic and normocytic cells with decreased central area of pallori". /hrombocytosis is a common findin! in chronic iron deficiency.


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". eukocyte count is usually normal. Eosinophilia occurs in hookworm infestations.

&nemia of chronic disease (&C$) pa!e 2H-

pa!e 2H

. Epidemiolo!ya. 0ost common anemia in hospitalied patientsb. Common causes

i. Chronic inflammation (e.!.# rheumatoid arthritis# tuberculosis)ii. &lcoholism (most common anemia)iii. 0ali!nancy (most common anemia)

2. Patho!enesisa. $ecreased synthesis of hemeb. n some cases# there is a decrease renal production of EPO.c. i"er synthesis and release of hepcidin

i. &ntimicrobial peptideii. &cute phase reactant released by the li"er in response to inflammationiii. Enters macropha!es and pre"ents the release of iron to transferrini". ?erritin synthesis and iron stores increase in bone marrow macropha!es

-. aboratory findin!sa. $ecreased 0CF# serum iron# /BC# and iron saturation ()

b. ncreased serum ferritin (DHHn!4m)

/halassemia (thal: A and K)pa!e 2H

pa!e 2H5

+b electrophoresis is normal# because all +b types re'uire A!lobin chains./he +b concentration is decreased: howe"er# the relati"e proportions of thenormal +bs remains the same.

%ormal K!lobin chain synthesis is desi!nated K: some K!lobin chainsynthesis is desi!nated KJ: and# no K!lobin chain synthesis is desi!nated KH.

pa!e 2H5

pa!e 2H8

. Epidemiolo!y

a. &utosomal recessi"e disordersb. A/hal is common in *outheast &sia and in black &mericans.c. K/hal is common in black &mericans# 9reeks# and talians.

2. Patho!enesis of Athala. $ecrease in A!lobin chain synthesis due to !ene deletions

?our !enes control A!lobin chain synthesis.

b. One !ene deletion produces a silent carrier. Notassociated with anemia


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c. /he combination of two !ene deletions is called Athal trait.

ii 0ild anemia with an increased RBC count

iii Black &merican type

&ssociated with a loss of one !ene on eachchromosome (A4 A4)

iiii &sian type

&ssociated with a loss of both !enes on the samechromosome

(4 A4A) ncreased risk for de"elopin! more se"ere types of Athal

ivi $ecreased 0CF# +b# and +ct

vi ncreased RBC count

vii %ormal R$;# serum ferritin# and +b electrophoresis

viii /here is no treatment.

b. /he combinations of three !ene deletions is called +b+ (four Kchains) disease.ii *e"ere hemolytic anemia

E,cess Kchain inclusions cause macropha!e destruction of the

RBCs.iii +b electrophoresis detects +b+.

c. /he combination of four !ene deletions is called +b Bart (four chains) disease.ii ncompatible with life

iii +b electrophoresis shows an increase in +b Bart.

2. Patho!enesis of Kthala. $ecrease in K!lobin chain synthesis

ii 0ild anemia is most often due to $%& splicin! defects.

iii *e"ere anemia is due to a nonsense mutation with formation of a stop

codon. Premature termination of K!lobin chain synthesis or absent K

!lobin chain synthesis.b. %ormal synthesis of A# L# !lobin chains.c. K/hal minor (K4KJ)

ii 0ild microcytic anemia

iii 0ild protecti"e effect a!ainst falciparum malaria RBC life span is shorter than normal.

iiii $ecreased 0CF# +b# and +ct

ivi ncreased RBC count

vi %ormal R$; and serum ferritin

vii +b electrophoresis

$ecreased +b& (2A42K)

ncreased +b&2(2A42L) and +b? (2A42)

viii /here is no treatment.

d. K/hal ma@or (CooleyNs anemia: KH4KH)ii *e"ere hemolytic anemia

RBCs with Achain inclusions are remo"ed by macropha!es in

the spleen. Causes an increase in uncon@u!ated bilirubin

RBCs with Achain inclusions under!o apoptosis in the bone

marrow (ineffecti"e erythropoiesis).iii E,tramedullary hematopoiesis

iiii ncreased R$; and reticulocytes

ivi +b electrophoresis

Nosynthesis of +b&

ncrease in +b&2and +b?


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vi on!term transfusion re'uirement

$an!er of iron o"erload (called hemosiderosis)

*ideroblastic anemia

pa!e 2H7

/ubular dama!e by lead produces ?anconiNs syndrome. /he syndromeincludes pro,imal renal tubular acidosis (loss of bicarbonate in urine)#aminoaciduria# phosphaturia# and !lucosuria.

. Epidemiolo!ya. Chronic alcoholism (most common cause)b. Pyrido,ine ("itamin B8) deficiency

c. ead (Pb) poisonin!2. Patho!enesis

a. $efect in heme synthesis within the mitochondriab. ron accumulates in the mitochondria formin! rin!ed sideroblastsc. rono"erload type of anemia

ncrease in iron stores in the bone marrow macropha!es

-. Chronic alcoholisma. &lcohol is a mitochondrial to,in.

$ama!es heme biosynthetic pathways in the mitochondria

b. *ideroblastic anemia occurs in-H of hospitalied chronic alcoholics.. Pyrido,ine deficiency

a. Fitamin B8is a cofactor for Laminole"ulinic acid synthase. Ratelimitin! reaction of heme synthesis

b. 0ost common cause of deficiency is isoniaid (%+) therapy. %+ is used in the treatment of tuberculosis.

5. ead (Pb) poisonin!a. Epidemiolo!y

ii Pica (abnormal cra"in!) for eatin! leadbased paint

Common cause of childhood lead poisonin! in inner cities

iii Pottery painter

Pbbased paints are commonly used for decoration.

iiii ;orkin! in a battery or ammunition factory

b. Pb denatures enymesMii ?errochelatase (heme synthase)

ron cannot bind with protoporphyrin to form heme.

ncrease in protoporphyrin# which is pro,imal to the enyme block

iii &minole"ulinic acid (&&) dehydrase

Causes an increase in L& which is pro,imal to the enyme

blockiiii Ribonuclease

Ribosomes cannot be de!raded and persist in the RBC.

Produces coarse basophilic stipplin!

c. Clinical and laboratory findin!s


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ii &bdominal colic with diarrhea

Pb is "isible in the !astrointestinal tract on plain abdominal

radio!raphs.iii Encephalopathy in children

L&& dama!es neurons# increases "essel permeability (cerebral

edema)# and causes demyelination.

iiii 9rowth retardation in children Pb deposits in the epiphysis of !rowin! bone.

Radio!raphs show increased density in the epiphyses.

ivi Peripheral neuropathy in adults

E,amplefootdrop (peroneal ner"e palsy)

vi %ephroto,ic dama!e to pro,imal renal tubules

vii ncreased whole blood and urine Pb le"els

Best screen and confirmatory test for Pb poisonin!

2. aboratory findin!s in sideroblastic anemiasa. ncreased serum iron# iron saturation ()# and ferritinb. $ecreased 0CF and /BCc. Rin!ed sideroblasts are present in a bone marrow aspirate.

3. *ummary table of microcytic anemias

Table 11$! %aboratory &indin's in Microcytic Anemias

Test#ronDe"iciency

Anemia o" ChronicDisease

Thal*ThalMinor

%ead+oisonin'

0CF

*erum iron %ormal

/BC %ormal

Percent saturation %ormal

*erum ferritin %ormal R$; %ormal %ormal %ormal

RBC count

+b electrophoresis %ormal %ormal A/halassemiaMnormalK/halM +b +b&2#+b?

Rin!ed sideroblasts %one %one %one Present

Coarse basophilicstipplin!

%one %one %one Present

+b# hemo!lobin: 0CF# mean corpuscular "olume: R$;# red blood cell distribution width: /BC# total ironbindin! capacity.

Macrocytic Anemias

0acrocytic anemias are most often caused by folate or "itamin B2deficiency.

Fitamin B2metabolismpa!e 2H7

pa!e 2H=


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. Present in meat# e!!s# and dairy products2. Parietal cells synthesie intrinsic factor (?) and hydrochloric acid.-. 9astric acid con"erts pepsino!en to pepsin.

o Pepsin frees "itamin B2from in!ested proteins.

. ?ree "itamin B2is bound to Rbinders synthesied in the sali"ary !lands.5. Pancreatic enymes in the duodenum clea"e off the Rbinders.

o Fitamin B2binds to ? to form a comple,.8. Fitamin B2? comple, is reabsorbed in the terminal ileum.>. Fitamin B2binds to transcobalamin and is secreted into plasma.

o $eli"ered to metabolically acti"e cells or stored in the li"er (8= year supply).

Causes of "itamin B2deficiency

Table 11,! Causes o" -itamin B1$De"iciency

Classi"ication Causes Associated &actors

$ecreased intake Pure "e!an diet0alnutrition

Breastfed infants of pure "e!ans may de"elop deficiency0ay occur in elderly patients

0alabsorption ntrinsic factor9astric acidntestinalreabsorption

&utoimmune destruction of parietal cells (i.e.# pernicious anemia)Cannot acti"ate pepsino!en to release "itamin B2CrohnNs disease or celiac disease in"ol"in! terminal ileum(destruction of absorpti"e cells)Bacterial o"er!rowth (bacterial utiliation of a"ailable "itamin B2)?ish tapewormChronic pancreatitis (cannot clea"e off Rbinder)

ncreasedutiliation

Pre!nancy4lactation $eficiency is more likely in a pure "e!an

?olate metabolism

. Present in !reen "e!etables and animal proteinso n the form of poly!lutamates

2. Con"erted to mono!lutamates by intestinal con@u!aseo ntestinal con@u!ase is inhibited by phenytoin.

-. 0ono!lutamates are reabsorbed in the @e@unum.

a. Con"erted to methyltetrahydrofolate# the circulatin! form of folate

b. Reabsorption is blocked by alcohol and oral contracepti"es.

2. /here is only a - to month supply of folate in the li"er.

Causes of folate deficiency

Table 11.! Causes o" &olate De"iciency

Classi"ication Causes Comment and Associated &actors


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$ecreased intake 0alnutritionnfants4elderlyChronic alcoholics9oatNs milk

$ecreased intake most common cause of folate deficiency

0alabsorption Celiac diseaseBacterial o"er!rowth

$eficiency usually occurs in association with other "itamindeficiencies (fat and water soluble)

$ru! inhibition 5?luorouracil

0ethotre,ate#trimethoprimsulfaPhenytoinOral contracepti"es#alcohol

nhibits thymidylate synthase

nhibit dihydrofolate reductasenhibits intestinal con@u!asenhibit uptake of mono!lutamate in @e@unum

&lcohol also inhibits the release of folate from the li"er.

ncreasedutiliation

Pre!nancy4lactation$isseminated mali!nancy*e"ere hemolytic anemia

ncreased utiliation of folate in $%& synthesis

Patho!enesis of macrocytic anemia in folate and "itamin B2deficiencypa!e 2H=

pa!e 2H

. mpaired $%& synthesisa. $elayed nuclear maturation

i. Causes a block in cell di"ision leadin! to lar!e# nucleated hematopoieticcells

ii. Enlar!ed cells are called me!aloblasts.b. &ffects all rapidly di"idin! cells

E,amplesRBCs# leukocytes# platelets# intestinal epitheliumb. Cellular R%& and protein synthesis continue unabated.

Cytoplasmic "olume continues to e,pand.ii neffecti"e erythropoiesis

a. 0e!aloblastic precursors outside the bone marrow sinusoids are pha!ocytosed

by macropha!es.b. 0e!aloblastic precursors under!o apoptosis causin! pancytopenia.

&nemia# neutropenia# and thrombocytopenia

Fitamin B2and folate in $%& synthesis

?olate deficiency is the most common cause of increased serum

homocysteine le"els in the Gnited *tates. +omocysteine dama!es endothelialcells leadin! to "essel thrombosis.

. Fitamin B2remo"es the methyl !roup from methyltetrahydrofolate (%5methyl?+).

a. Produces tetrahydrofolate (?+)b. 0ethylB2transfers the methyl !roup to homocysteine to produce methionine.c. $eficiency of folate or "itamin B2increases plasma homocysteine.

2. /hymidylate synthase con"erts deo,yuridine monophosphate (dG0P) to deo,ythymidine


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monophosphate (d/0P).

o /hymidylate synthase is inhibited by 5fluorouracil.2. $ihydrofolate reductase con"erts dihydrofolate (?+2) to ?+.

o $ihydrofolate reductase is inhibited by methotre,ate and trimethoprimsulfametho,aole.

Fitamin B2in oddchain fatty acid metabolismpa!e 2H

pa!e 2

. Propionyl Co& is con"erted to methylmalonyl Co&.2. 0ethylmalonyl Co& is con"erted to succinyl Co&.

o Fitamin B2is a cofactor for methylmalonyl Co& mutase.

-. Fitamin B2deficiency causes an increase in propionyl and methylmalonyl Co& and theircorrespondin! acids.

o Propionyl Co& replaces acetyl Co& in neuronal membranes resultin! in

demyelination.

Clinical findin!s in "itamin B2deficiency

. ?indin!s in pernicious anemiaa. &chlorhydria (lack of !astric acid) due to destruction of parietal cells

i. 0aldi!estion of foodii. +yper!astrinemia due to loss of acid inhibition of !astrin

b. &ntibodies associated with pernicious anemiai. &ntibodies directed a!ainst the proton pump in parietal cellsii. &ntibodies that block bindin! of "itamin B2to ?

0ost specific test for pernicious anemia

iii. &ntibodies that pre"ent bindin! of "itamin B2? comple,es to ilealreceptors

c. &ntibody destruction of parietal cells causes chronic atrophic !astritis of the bodyand fundus.

ncreased incidence of !astric adenocarcinomaii *mooth# sore ton!ue with atrophy of papillae

ii %eurolo!ic disease

a. Peripheral neuropathy with sensorimotor dysfunctionb. Posterior column dysfunction

$ecrease in "ibratory sensation and proprioception (@oint sense)c. ateral corticospinal tract dysfunction with spasticity

d. $ementia


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aboratory findin!s in "itamin B2deficiency

. $ecreased serum "itamin B22. ncreased serum homocysteine and methylmalonic acid (=5 of cases)-. Peripheral blood findin!s

a. Pancytopeniab. O"al macrocytesc. +yperse!mented neutrophils

0ore than fi"e nuclear lobes

. Bone marrow findin!s

o 0e!aloblastic nucleated cells with primiti"e open (lacy) chromatin pattern2. *chillin! test localies some of the causes of "itamin B2deficiency

i. Gtilies oral administration of radioacti"e "itamin B2ii. Reabsorption of radioacti"e "itamin B2

ndicates dietary deficiency of "itamin B2(e.!.# pure "e!an)

iii. Reabsorption of radioacti"e "itamin B2after administration of ? ndicates pernicious anemia# where there is a lack of ?

i". Reabsorption of radioacti"e "itamin B2after administration of antibiotics ndicates bacterial o"er!rowth with destruction of "itamin B2? comple,

". Reabsorption of radioacti"e B2after administration of pancreatic e,tract ndicates chronic pancreatitis with lack of enymes to clea"e off Rbinder

Clinical findin!s in folate deficiency

. *imilar to "itamin B2deficiency with the exceptionof neurolo!ic disease.2. ncreased risk for open neural tube defects in the fetus

o $ue to decreased maternal intake of folatepriorto conception

aboratory findin!s in folate deficiencypa!e 22

pa!e 2-

. Peripheral blood and bone marrow findin!s are similar to "itamin B2deficiency.

2. $ecreased serum folate and RBC folate (best screenin! test)

t is important to distin!uish folate from "itamin B2deficiency. Pharmacolo!icdoses of folate can correct the hematolo!ic findin!s in both folate and "itaminB2deficiency: howe"er# neurolo!ic disease is notcorrected.

Comparison table of "itamin B2and folate deficiency


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Table 11/! Clinical and %aboratory &indin's in -itamin B1$and &olateDe"iciencies

%aboratoryClinical

&indin'

+ernicious

Anemia

Other -itamin B1$

De"iciencies

&olate

De"iciency&chlorhydria Present &bsent &bsent

&utoantibodies Present &bsent &bsent

Chronic atrophic !astritis Present &bsent &bsent

9astric carcinoma risk %one %one

+yperse!mented neutrophils Present Present Present

0ean corpuscular "olume

%eurolo!ic disease Present Present %one

Pancytopenia Present Present Present

Plasma homocysteine

*erum !astrin le"el %ormal %ormal

Grine methylmalonic acid %ormal

0ormocytic Anemias Corrected Reticulocyte Count or #nde2 Belo3 ,4

&nemias under this classification include acute blood loss# early iron deficiency or anemia

of chronic disease (&C$)# aplastic anemia# and chronic renal failure.

&cute blood loss

. Epidemiolo!ya. E,ternal blood loss (e.!.# peptic ulcer)

0ay result in iron deficiencyb. nternal blood loss (e.!.# ruptured abdominal aortic aneurysm)

2. Clinical and laboratory findin!s

-. Re'uires 5 to > days before a reticulocyte response is obser"ed

Early iron deficiency or &C$

. &nemia is normocytic beforeit becomes microcytic.o &C$ is microcytic in only H to -H of cases.

2. *erum ferritin is most useful in distin!uishin! the two anemias.

&plastic anemia

Table 115! Causes o" Aplastic Anemia


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Classi"icationE2amples and Discussion

diopathic &ppro,imately 5H>H of cases are idiopathic

$ru!s 0ost common known cause of aplastic anemia$oserelated causes are usually re"ersible (e.!.# alkylatin! a!ents)diosyncratic reactions are fre'uently irre"ersible (e.!.# chloramphenicol)

Chemical a!ents /o,ic chemicals in industry and a!riculture (e.!.# benene# insecticides$$/# parathion)

nfection 0ay in"ol"e all hematopoietic cell lines (pancytopenia) or erythroid cell line alone (pureRBC aplasia)E,amplesEBF: C0F: par"o"irus: non nonB hepatitis (most common)

Physical a!ents ;holebody ioniin! radiation (therapeutic or nuclear accident)

0iscellaneous /hymoma (may be associated with pure RBC aplasia)Paro,ysmal nocturnal hemo!lobinuria

C0F# cytome!alo"irus: EBF# EpsteinBarr "irus: RBC# red blood cell.pa!e 2-

pa!e 2

. Causes2. Patho!enesis

a. &nti!enic alteration of multipotent myeloid stem cells

Causes /cell acti"ation and release of cytokines that suppress stemcells

b. $efecti"e or deficient stem cells (ac'uired or hereditary)-. Clinical findin!s

a. ?e"er due to infection associated with neutropeniab. Bleedin! due to thrombocytopeniac. ?ati!ue due to anemia

. aboratory findin!sa. Pancytopeniab. Reticulocytopeniac. +ypocellular bone marrow

5. Complete reco"ery occurs in less than H of cases.

Chronic renal failure (CR?)

. Patho!enesiso $ecreased synthesis of EPO (most common cause)

2. aboratory findin!s

a. %ormocytic anemia

b. Presence of burr cells (i.e.# RBCs with an undulatin! membrane)

c. Platelet dysfunction

i. /hrombocytopeniaii. $efect in platelet a!!re!ation that is re"ersible with dialysis

Prolon!ed bleedin! time


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0ormocytic Anemias Corrected Reticulocyte Count at or Abo6e ,4

&nemias include the hemolytic anemias due to defects within the RBC (intrinsic) or

factors outside the RBC (e,trinsic).

Patho!enesis of hemolytic anemiaspa!e 2

pa!e 25

+apto!lobin is an acute phase reactant that combines with +b to form acomple, that is pha!ocytosed and de!raded by macropha!es causin! adecrease in serum hapto!lobin. /he amount of +b in the comple,es is sosmall that uncon@u!ated bilirubin is notsi!nificantly increased.

. ntrinsic or e,trinsic hemolytic anemiasa. ntrinsic refers to a defect in the RBC causin! the anemia.

E,amplesmembrane defects# abnormal +b# enyme deficiency

b. E,trinsic refers to factors outside the RBC causin! hemolysis. E,amplesstenotic aortic "al"e# immune destruction

2. 0echanisms of hemolysisa. E,tra"ascular hemolysis

ii RBC pha!ocytosis by macropha!es in the spleen (most common site)

and li"eriii Reasons for pha!ocytosis

RBCs coated by !9 with or without C-b

&bnormally shaped RBCs (e.!.# spherocytes# sickle cells)

iiii ncrease in serum uncon@u!ated bilirubin

End product of macropha!e de!radation of +b

ivincreased serum lactate dehydro!enase ($+) from hemolyed RBCs.

b. ntra"ascular hemolysisii +emolysis occurs within blood "essels.

iii Causes of hemolysis

Enyme deficiency (e.!.# deficiency of !lucose8phosphate

dehydro!enase) Complement destruction (e.!.# !0mediated hemolysis)

0echanical dama!e (e.!.# calcific aortic "al"e stenosis)

iiii ncreased plasma and urine +b

ivi +emosiderinuria

Renal tubules con"ert iron in +b into hemosiderin.

vi $ecreased serum hapto!lobin

vii ncreased serum $+ from hemolyed RBCs.

+ereditary spherocytosis

. Patho!enesisa. &utosomal dominant disorder


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b. ntrinsic defect with e,tra"ascular hemolysisc. 0embrane protein defect results in the loss of RBC membrane and spherocyte

formation.i. 0utation in ankyrin is the most common defect.ii. 0utation in band 2# spectrin (A and K)# or band - account for other

defects.d. ncreased permeability of spherocytes to sodium

$ue to membrane defect and dysfunctional %aJ4J&/Pase pumpii Clinical findin!s

a. aundice due to increased uncon@u!ated bilirubinb. ncreased incidence of calcium bilirubinate !allstones

$ue to increased concentration of con@u!ated bilirubin in bilec. *plenome!alyd. &plastic crisis

0ay occur in children especially after a "iral infection (e.!.# par"o"irus)ii aboratory findin!s

a. %ormocytic anemia with spherocytosisb. ncreased 0C+C

c. ncreased RBC osmotic fra!ility

i. ncreased permeability of spherocytes to sodium and waterii. *pherocytes rupture in mildly hypotonic salt solutions.

2. /reatment is splenectomy

o *pherocytes remain in the peripheral blood.

+ereditary elliptocytosis

. Patho!enesisa. &utosomal dominant disorderb. $efecti"e spectrin and band .

2. Clinical findin!sa. 0a@ority ha"e no anemia or a mild hemolytic anemiab. *plenome!aly

-. aboratory findin!sa. Elliptocytes !reater than 25 of RBCs in peripheral bloodb. ncreased osmotic fra!ility

. /reatment is splenectomy in symptomatic patients

Paro,ysmal nocturnal hemo!lobinuria (P%+)pa!e 28

pa!e 2>

. Patho!enesisa. &c'uired membrane defect in multipotent myeloid stem cells

i. 0utation causes loss of the anchor for decay acceleratin! factor ($&?).ii. %ormally $&? neutralies complement attached to RBCs# neutrophils#


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and platelets.b. ntra"ascular complementmediated lysis of RBCs# neutrophils# and platelets

Occurs at ni!ht# because respiratory acidosis enhances complementattachment to these cells

ii Clinical findin!s

a. Episodic hemo!lobinuria 0ay cause iron deficiency

b. ncreased incidence of "essel thrombosis (e.!.# hepatic "ein) $ue to the release of a!!re!atin! a!ents from destroyed platelets

c. ncreased risk for de"elopin! acute myelo!enous leukemiaii aboratory findin!s

a. *creenin! test is the sucrose hemolysis test (su!ar water test). *ucrose enhances complement destruction of RBCs.

b. Confirmatory test is the acidified serum test (+am test). &cidified serum acti"ates the alternati"e pathway causin! hemolysis.

c. Peripheral blood findin!s

i. %ormocytic anemia with pancytopenia

0icrocytic if iron deficiency de"elops from hemo!lobinuriaii. $ecreased leukocyte alkaline phosphatase

b. $ecreased serum hapto!lobin

c. ncreased serum4urine +b

*ickle cell anemia

pa!e 27

pa!e 2=pa!e 2=

pa!e 22H

. Epidemiolo!ya. &utosomal recessi"e disorderb. 0ost common hemo!lobinopathy in black &mericansc. +eteroy!ote condition (sickle cell trait# +b&*) has no anemia.

Present in 7 to H of black &mericans

d. +omoy!ous condition (+b**) produces anemia.e. Protecti"e a!ainst Plasmodium falciparummalaria

2. Patho!enesisa. Predominantly e,tra"ascular hemolysis of sickle cellsb. 0issense point mutation

*ubstitution of "aline for !lutamic acid at si,th position of K!lobin chain

c. Causes of sicklin!

ii +b* molecules a!!re!ate and polymerie into lon! needlelike fibers

RBCs assume a sickle or boatlike shape

iii *ickle +b (+b*) concentration !reater than 8H is the most important

factor for sicklin!. +b* concentration is too low in +b&* to produce sicklin! in the

peripheral blood.


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iiii ncrease in deo,yhemo!lobin increases the risk for sicklin!.

&cidosis (causes O2release from RBCs)

Folume depletion (intracellular dehydration causes an increase in

concentration of deo,yhemo!lobin) +ypo,emia (decrease in arterial PO2decreases O2saturation of

+b)

b. Re"ersible and irre"ersible sicklin!ii nitial sicklin! is re"ersible with administration of o,y!en.

iii Recurrent sicklin! causes irre"ersible sicklin! due to membrane dama!e.

iiii rre"ersibly sickled cells ha"e increased adherence to endothelial cells in

the microcirculation. 0icro"ascular occlusions ("asoocclusi"e crises) produce

ischemic dama!e.c. +b? pre"ents sicklin!.

ii ncreased +b? at birth pre"ents sicklin! in +b** for 5 to 8 months.

iii +ydro,yurea increases the synthesis of +b?.

d. ey patholo!ic processes in +b**ii *e"ere hemolytic anemia

iiiFasoocclusi"e crises2. Clinical findin!s in +b**

a. $actylitis

Painful swellin! of hands and feet in infants (usually 8= months old) is

due to bone infarcts.b. &cute chest syndrome

ii Fasoocclusion of pulmonary capillaries

iii Chest pain# lun! infiltrates# hypo,emia

iiii 0ost common cause of death in adults

b. &septic necrosis of the femoral headc. &utosplenectomy

ii *pleen is enlar!ed but dysfunctional by 2 years of a!e. %uclear remnants (+owellolly bodies) appear in RBCs

indicatin! loss of macropha!e functioniii *pleen is fibrosed and diminished in sie in youn! adults.

d. ncreased susceptibility to infectionsii $ue to dysfunctional spleen and impaired opsoniation of encapsulated

bacteriaiii Children are at risk for Streptococcus pneumoniaesepsis.

0ost common cause of death in children

iiii ncreased incidence of osteomyelitis due to Salmonella paratyphi

e. &plastic crisisii Reticulocytopenia

iii &ssociation with par"o"irus

f. *e'uestration crisisii Rapid splenic enlar!ement with entrapment of RBCs causin!

hypo"olemiaiii Reticulocytosis

!. ncreased risk for calcium bilirubinate !allstones

$ue to increased con@u!ated bilirubin in bile from chronic hemolysis

ii Renal findin!s in +b&* (also in +b**)


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a. *icklin! may occur in peritubular capillaries in the medulla. $ue to the low O2tension in the medulla

b. Presents with microhematuria due to infarctionsc. Renal papillary necrosis may occur.

oss of concentration and dilution

ii aboratory findin!s

a. *ickle cell screen *odium metabisulfite reduces O2tension# which induces sicklin!

b. +b electrophoresis

ii +b&* profile+b& 55 to 8H# +b* H to 5

iii +b** profile+b* =H to =5# +b? 5 to H# no +b&

h. Peripheral blood findin!sii %ormal peripheral blood in +b&*

iii n +b**# there are sickle cells and tar!et cells.

i. Prenatal screenin!

&nalysis of fetal $%& to detect the point mutation

9lucose8phosphate dehydro!enase (98P$) deficiency$ecrease in %&$P+ impairs neutrophils and monocyte killin! of bacteria bythe O2dependent myelopero,idase system which re'uires %&$P+ as acofactor for %&$P+ o,idase.

pa!e 22H

pa!e 22

. Epidemiolo!ya. Qlinked recessi"e disorderb. *ubtypes of 98P$ deficiency

i. 0editerranean "ariant in 9reeks and taliansii. Black &merican "ariant

c. Protecti"e a!ainst Plasmodium falciparummalaria2. Patho!enesis

a. ntrinsic defect with predominantly intra"ascular hemolysis

0ild component of e,tra"ascular hemolysis

b. $ecreased synthesis of %&$P+ and !lutathione (9*+) in the pentose phosphatepathway

i. 9*+ normally neutralies hydro!en pero,ide# an o,idant product in RBCmetabolism.

ii. n 98P$ deficiency# pero,ide o,idies +b# which precipitates in the formof +ein bodies.

+ein bodies dama!e the RBC membranes causin!

intra"ascular hemolysis.


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+ein bodies remo"ed from RBC membranes by splenic

macropha!es produce bite cells.b. +alflife of 98P$ in the 0editerranean "ariant is markedly reduced.

Produces a se"ere# chronic hemolytic anemiab. +alflife of 98P$ in the black &merican "ariant is moderately reduced.

Episodic type of hemolytic anemia after e,posure to o,idant stresses.c. O,idant stresses inducin! hemolysis

i. nfection (most common)ii. $ru!s

E,amplesprima'uine# chloro'uine# dapsone# sulfonamides

iii. ?a"a beans (mainly in 0editerranean "ariant)

-. Clinical findin!s

o *udden onset of back pain with hemo!lobinuria 2 to - days after an o,idantstress

2.aboratory findin!s

a. %ormocytic anemiab. +ein bodies

i. dentified with a supra"ital stainii. Best screen durin! acti"e hemolysis

c. RBC enyme analysisi. Confirmatory test afterhemolysis has subsided

d. Peripheral blood findin!s

i. Bite cells (macropha!e remo"al of membrane)

Pyru"ate kinase (P) deficiency

. Epidemiolo!ya. &utosomal recessi"e diseaseb. 0ost common enyme deficiency in the Embden0eyerhof pathway

P normally con"erts phosphoenolpyru"ate to pyru"ate leadin! to a net

!ain of 2 &/P.2. Patho!enesis

a. ntrinsic defect with e,tra"ascular hemolysisb. Chronic lack of &/P causes membrane dama!e.

Results in dehydration of the RBC (echinocytes)-. Clinical findin!s

a. +emolytic anemia with @aundice be!innin! at birthb. ncrease in 2#-BP9 synthesis pro,imal to enyme block

Ri!ht shift of OBC causes increased release of O2# which offsets the

clinical effects of the anemia.. aboratory findin!s

a. %ormocytic anemia


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b. RBCs with thorny pro@ections (echinocytes)

c. RBC enyme assay is the confirmatory test.

mmune hemolytic anemias

Table 117! Classi"ication o" #mmune 8emolytic Anemias

Type o" #mmune8emolytic Anemia E2amples

Autoimmune

;arm antibodies (!9) Primary or idiopathic (no underlyin! cause)*econdary (e.!.# *E)

Cold antibodies (!0) Primary or idiopathic*econdary

Mycoplasma pneumoniae(anti antibodies)

nfectious mononucleosis (antii antibodies)

Dru'induced $ru! adsorption (e.!.# penicillin)M !9 antibody directed a!ainst the dru!attached to the RBC membranemmunocomple, (e.!.# 'uinidine)M dru!!0 immunocomple, deposits on theRBC causin! intra"ascular hemolysis

&utoantibody induction (e.!.# Amethyldopa)M dru! alters Rh anti!ens on RBCscausin! synthesis of autoantibodies a!ainst Rh anti!ens

Alloimmune +emolytic transfusion reaction&BO hemolytic disease of newbornRh hemolytic disease of newborn

RBC# red blood cell: *E# systemic lupus erythematosus.pa!e 22

pa!e 222

9roup of e,trinsic hemolytic anemias with e,tra"ascular or intra"ascular hemolysis.

. Classificationa. &utoimmune

i. 0ost common type of immune hemolytic anemiaii. 0ore common in women than men

*E is the most common cause of autoimmune hemolytic

anemia (&+&).iii. >H are warm type (!9 antibodies) of &+&i". -H are cold type (!0 antibodies) of &+&

b. $ru!induced

c. &lloimmune2. Patho!enesis

a. !9mediated hemolysisi. RBCs coated by !9 are pha!ocytosed by splenic macropha!es

(e,tra"ascular hemolysis).ii. *pherocytes are produced if a small portion of the membrane is

remo"ed.b. Complementmediated hemolysis

i. RBCs coated by C-b alone are pha!ocytosed by li"er macropha!es


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(e,tra"ascular hemolysis).ii. RBCs coated by C5C= under!o intra"ascular hemolysis.iii. RBCs coated by !9 and C-b are pha!ocytosed by li"er and splenic

macropha!es (e.!.# *E).c. !0mediated hemolysis

0ay be e,tra"ascular or intra"ascular dependin! on the de!ree ofcomplement acti"ation

ii Clinical findin!s

a. aundice due to uncon@u!ated hyperbilirubinemia Occurs in e,tra"ascular types of hemolysis

b. +epatosplenome!aly $ue to work hyperplasia of splenic and li"er macropha!es

c. RaynaudNs phenomenon 0ay occur in cold types of &+&

ii aboratory findin!s

a. Positi"e direct antihuman !lobulin test ($&/: CoombsN test) $&/ detects RBCs sensitied with !9 and4or C-b.

b. Positi"e indirect antihuman !lobulin test (indirect CoombsN test) $etects antibodies in the serum (e.!.# anti$ antibodies)

c. Gncon@u!ated hyperbilirubinemia in e,tra"ascular hemolysis is present.d. +emo!lobinuria# decreased serum hapto!lobin in intra"ascular hemolysise. Peripheral blood findin!s

i. %ormocytic anemia

ii. *pherocytosis due to macropha!e remo"al of RBC membrane

0icro and macroan!iopathic hemolytic anemias (0+&)

Table 119! Causes o" Micro and Macroan'iopathic 8emolytic Anemia

Types E2amples

Microan'iopathic

Platelet thrombi +emolytic uremic syndrome/hrombotic thrombocytopenic purpura

?ibrin thrombi $isseminated intra"ascular coa!ulation+EP syndromeM +# hemolytic anemia: E# ele"ated transaminases: P# low platelets:associated with preeclampsia

Macroan'iopathic&ortic stenosis (most common cause)Prosthetic heart "al"es

. Causes2. Patho!enesis

a. E,trinsic defect with intra"ascular hemolysisb. 0icroan!iopathic

0icrocirculatory lesions cause RBC fra!mentation (schistocytes

c. 0acroan!iopathic


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+emolytic process caused by "al"ular defects (e.!.# aortic stenosis)

-. aboratory findin!sa. %ormocytic anemia

on!standin! hemo!lobinuria causes iron deficiency anemia.

b. $ecreased serum hapto!lobin# hemo!lobinuriac. *chistocytes in the peripheral blood

0alaria

. Epidemiolo!yo ?emaleAnophelesmos'uito transmits Plasmodiato humans.

2. Patho!enesis

a. ntraerythrocytic parasite causes intra"ascular hemolysis.

Correlates with fe"er spikes

b. E,trinsic defect with predominantly intra"ascular hemolysis

0inor component of e,tra"ascular hemolysis

2. Clinical findin!sa. ?e"er and splenome!aly

b. Plasmodium vivax

ii 0ost common type

iii /ertian fe"er pattern (e"ery 7 hours)

b. Plasmodium falciparum

ii 0ost lethal type

iii uotidian fe"er pattern (daily spikes with no pattern)

c. Plasmodium malariae

ii &ssociation with nephrotic syndrome

iii uartan fe"er pattern (e"ery >2 hours)

2. aboratory findin!s

o /hin and thick smears identify or!anisms in RBCs

*ummary table of normocytic anemias

Table 11:! Summary o" 0ormocytic Anemias

Anemia +atho'enesis Discussion

Reticulocytosis ; ,4 &cute blood loss oss of whole blood nitial +b and +ct normal

*i!ns of "olume depletion

Early iron deficiency $ecreased iron stores %ormocytic beforemicrocyticron studies abnormal

Early &C$ ron trapped in macropha!es byhepcidin

%ormocytic beforemicrocyticron studies abnormal

&plastic anemia *uppression or deficiency ofmultipotent myeloid stem cells

Pancytopenia+ypocellular marrow

Chronic renal failure $eficiency of EPO Presence of burr cells


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Reticulocytosis ,4

+ereditary spherocytosis &$ disorder$efect in ankyrinE,tra"ascular hemolysis

ncreased osmotic fra!ilityR, with splenectomy

+ereditary elliptocytosis &$ disorder$efect in spectrin and band .E,tra"ascular hemolysis

Elliptocytes D 25

Paro,ysmal nocturnalhemo!lobinuria

oss of anchor for $&? in myeloidstem cellComplement destruction ofhematopoietic cellsntra"ascular hemolysis

PancytopeniaPositi"e su!ar water test (screen) andacidified serum test (confirmatory test)

*ickle cell anemia &R disorder Faline substitution for !lutamic acid K!lobin chainE,tra"ascular hemolysis

+b&*M +b& 558H: +b* H5+b**M +b* =H=5: +b? 5H: no+b&

98P$ deficiency QR disorder $eficiency 9*+ causes o,idantdama!e to +b and RBC membranentra"ascular hemolysis

+ein body preparationM screen durin!acti"e hemolysisEnyme assayM confirmatory test whenhemolysis subsides

Pyru"ate kinase deficiency &R disease&/P synthesisE,tra"ascular hemolysis

2#-BP9 ri!ht shifts OBC$ehydrated RBCs with thornypro@ections (echinocytes)

&cute blood loss oss of whole bloodReticulocytosis 5> days

+b# +ct# RBC count

;arm &+& !9 with or without C-bE,tra"ascular hemolysis

Positi"e direct CoombsN test*E most common cause

Cold &+& !0 with C-bE,tra"ascular or intra"ascularhemolysis

&ssociation with Mycoplasmapneumoniae: EBF

$ru!induced immunehemolytic anemia

$ru! haptenM penicillin E,tra"ascularhemolysismmunocomple,M 'uinidinentra"ascular hemolysis

&utoantibodyM methyldopaE,tra"ascular hemolysis

Positi"e direct CoombsN test

&lloimmune hemolyticanemia

&ntibodies a!ainst forei!n RBCanti!ens

E,tra"ascular hemolysis

+emolytic transfusion reaction&BO and Rh +$%

Positi"e direct CoombsN test

0icro and macroan!iopathichemolytic anemia

0echanical destruction of RBCs withformation of schistocytesntra"ascular hemolysis

Calcific aortic stenosis most commoncauseChronic hemo!lobinuria causes irondeficiency

0alaria /ransmitted by femaleAnophelesmos'uitontra"ascular hemolysis

Rupture of RBCs corresponds with fe"er

&$# autosomal dominant: &R# autosomal recessi"e: BP9# bisphospho!lycerate: $&?# decay acceleratin! factor: EBF# EpsteinBarr "irus: EPO# erythropoietin: 98P$# !lucose8phasphate dehydro!enase: 9*+# !lutathione: +b# hema!labin: +b&*#sickle cell trait: +b**# +ct# hematocrit: sickle cell disease: OBC# o,y!en bindin! cur"e: RBC# red blood cell: R,# treatment:*E# systemic lupus erythematosus: QR# Qlinked recessi"e.


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11 red blood cell disorders

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