Anemia

ANEMIA
MR.J.G SAMBAD
MSC.NURSING
IKDRC COLLEGE OF NURSING

BloodBlood
formationformation
SITESSITES
STEPSSTEPS
1-Intrautrine life:1-Intrautrine life:
Blood cells are formed in the liver andBlood cells are formed in the liver and
spleen up to the fifth months.spleen up to the fifth months.
After 5th month : bone marrow share in theAfter 5th month : bone marrow share in the
formation of these cells.formation of these cells.
2-After birth:2-After birth:
Formation of these cells will be restrictedFormation of these cells will be restricted
to the bone morrow.to the bone morrow.

BloodBlood
formationformation
3-Adulthood3-Adulthood
The active bone morrow will be:The active bone morrow will be:
Restricted to axial skeleton : flat bones,Restricted to axial skeleton : flat bones,
vertebrae, ribs, sternum, ilia .vertebrae, ribs, sternum, ilia .
Some extension to the proximal ends ofSome extension to the proximal ends of
long bone mainly femur.long bone mainly femur.
Extramedullary haemopoiesis:Extramedullary haemopoiesis: When demand forWhen demand for
blood formation is increased:blood formation is increased:
The active red BM extends into the shafts ofThe active red BM extends into the shafts of
the long bones.the long bones.
The spleen and liver will regain their abilityThe spleen and liver will regain their ability
to produce blood elements when boneto produce blood elements when bone
morrow is affected by some diseases.morrow is affected by some diseases.
SITESSITES

BloodBlood
formationformation
STEPSSTEPS
Pleuri-potent cellsPleuri-potent cells
ThrambocytopoiesisThrambocytopoiesis
Granulocyto-Granulocyto-
poiesispoiesis
Erthrocyto-Erthrocyto-
poiesispoiesis
CFU-MegaCFU-Mega
MegakaryoblastMegakaryoblast
MegadaryocyteMegadaryocyte
PlateletPlatelet
CFU-MegaCFU-Mega
MegakaryoblastMegakaryoblast
MegadaryocyteMegadaryocyte
PlateletPlatelet
CFU-GCFU-G
MyleloblastMyleloblast
PromyelocytePromyelocyte
MyelocyteMyelocyte
MetamgelocyteMetamgelocyte
JuvenilJuvenil
GranulocyteGranulocyte
(PML)(PML)
CFU-GCFU-G
MyleloblastMyleloblast
PromyelocytePromyelocyte
MyelocyteMyelocyte
MetamgelocyteMetamgelocyte
JuvenilJuvenil
GranulocyteGranulocyte
(PML)(PML)
BFU-EBFU-E
CFU-ECFU-E
ProerythroblastProerythroblast
BasophilicBasophilic
erythroblasterythroblast
PolychromaticPolychromatic
OthrochromaticOthrochromatic
ReticulocytesReticulocytes
BFU-EBFU-E
CFU-ECFU-E
ProerythroblastProerythroblast
BasophilicBasophilic
PolychromaticPolychromatic
OthrochromaticOthrochromatic
ReticulocytesReticulocytes
SITESSITES

BloodBlood
formationformation
STEPSSTEPS

BloodBlood
formationformation
Organelles (formed elements):Organelles (formed elements):
RBCsRBCs
WBCsWBCs
ThrombocytesThrombocytes
Fluid components:Fluid components: plasma in which the aboveplasma in which the above
elements are suspended and containelements are suspended and contain
fibrinogen.fibrinogen.
Blood ConstituentsBlood Constituents

BloodBlood
formationformation
Normal erythrocytopoiesis depends on:Normal erythrocytopoiesis depends on:
Healthy BM:Healthy BM: normal stem cells andnormal stem cells and
architecture.architecture.
Elements essential for erythropoies:Elements essential for erythropoies:
(Maturation factors )(Maturation factors )
Regulatory hormones: GPO, AndrogenRegulatory hormones: GPO, Androgen
thyroxin, cortisol and ACT.thyroxin, cortisol and ACT.
Nutritional elements: Protein (highNutritional elements: Protein (high
biological value),biological value),
Mineral (Iron, cupper, znic, selenium )Mineral (Iron, cupper, znic, selenium )
Vitamins (B, Folic acid, vit c)Vitamins (B, Folic acid, vit c)
ErythrocytopoiesisErythrocytopoiesis

AnemiaAnemia
DefinitionDefinition
TypesTypes
C/PC/P
Anaemia =Anaemia = reduction of Oreduction of O22 carrying capacitycarrying capacity
of the blood with inadequate Oof the blood with inadequate O22 supply tosupply to
tissue .tissue .
Anaemia is diagnosed when there isAnaemia is diagnosed when there is aa
reduction of (RBCs number, or HBLO orreduction of (RBCs number, or HBLO or
PCV) below the reference range for age andPCV) below the reference range for age and
sex of the individual .sex of the individual .
MoreMore accurately is defined asis defined as reduction inreduction in
the red cell massthe red cell mass

AnemiaAnemia
TypesTypes
C/PC/P
A-Dyshaemopoietic anaemia: (Decreased
maturation due to deficiency of maturation
factors essential for erythropoiesis).
Mineral deficiency: iron, zinc, selenium, cupper
Vitamin deficiency: B12, folic acid ; Vit C&
pyridoxine
Hormonal deficiency: anaemia of renal
diseases, pituitary, thyroid or suprarenal
deficiency.
Protein deficiency : high class
AETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.

AnemiaAnemia
TypesTypes
B- Hypoproliferative anaemias (BM failure ):B- Hypoproliferative anaemias (BM failure ):
Aplastic anaemia.Aplastic anaemia.
Myelophthisic anaemia (BM replacementMyelophthisic anaemia (BM replacement
anaemia).anaemia).
Anaemia of chronic diseases.Anaemia of chronic diseases.
AETIOLOGICAL CLASSIFICATIONAETIOLOGICAL CLASSIFICATION
I- Decrease red cell production.I- Decrease red cell production.

AnemiaAnemia
TypesTypes
II- Haemolytic anaemia:II- Haemolytic anaemia:
Short life-span of RBCsShort life-span of RBCs
III- Acute post haemorrhagic anaemia:III- Acute post haemorrhagic anaemia:
Loss of RBCsLoss of RBCs
IV- Mixed anaemia.IV- Mixed anaemia.
eg. Megalobastosis associated with haemolysiseg. Megalobastosis associated with haemolysis
V: Dilutconal anaemia:V: Dilutconal anaemia: (raised plasma volume)(raised plasma volume)
PregnancyPregnancy
Oliguric RFOliguric RF
Volume-overloadVolume-overload
AETIOLOGICAL CLASSIFICATIONAETIOLOGICAL CLASSIFICATION

AnemiaAnemia
TypesTypes
MORPHOLOGICAL CLASSIFICATION
A. Microcytic-hypochromic anaemias:
Thalassaemia.
Iron deficiency anaemia.
Anaemia of chronic disease.
Sideroblastic anaemia:
Hereditary
Chronic lead poisoning.

AnemiaAnemia
TypesTypes
B-Normocytic-normochromic anaemias:
Acute post –haemorrhagic anaemia.
Hemolytic anaemia.
Aplastic anaemia.
Myelophthisic anaemia.
Anaemia of chronic diseases .

AnemiaAnemia
TypesTypes
C- Macrocytic- normochromic anaemias:
Megaloblastic anaemia.
Marked reticulocytosis.
Myelodysplastic syndromes.
Myxoedema.
Acquired sideroblastic anaemia.

AnemiaAnemia
TypesTypes
C/PC/P
1-Tissue Hypoxia
Impaired functions of the tissues, the
degree of impairment depends an the need
of the tissue to O2 so CVS, CNS and
skeletal muscles are much affected.
I- PATHOPHYSIOLOGY
The clinical feature of the anaemia could be
explained by the following factors.

AnemiaAnemia
2- Compensatory mechanisms
Increased COP.
Increased O2 delivery from HB to the tissue.
Increased erythropoietin production with
stimulation of erythropoiesis
Increased plasma volume.
Redistribution of the blood from less to more
vital organs.
I- PATHOPHYSIOLOGYI- PATHOPHYSIOLOGY
C/PC/P

AnemiaAnemia
3-Rate of blood loss:
• The rapid the rate of blood loss, the more the
severe symptoms will occur especially in
elderly. While the slowly falling HB allows for
haemodynamic compensation with less
symptom.
4- Cause:
I- PATHOPHYSIOLOGYI- PATHOPHYSIOLOGY
C/PC/P

AnemiaAnemia
II- GENERAL SYMPTOMS OF ANAEMIA:II- GENERAL SYMPTOMS OF ANAEMIA:
1-Neurological
Dizziness, fainting, lack of concentration
Blurred or diminished vision
Headache, tinnitus
Paraesthesia in the fingers and toes
Insomnia, irritability.
2-CVS:
• Angina, dyspnea, palpitation and intermittent
claudication by exertion
• HF in severe cases or presence of other
organic cardiac disease, it is high COP failure.
3-Musculo skeletal:
Easy fatigability.
Tiredness and lassitude.
C/PC/P

AnemiaAnemia
II- GENERAL SYMPTOMS OF ANAEMIA:II- GENERAL SYMPTOMS OF ANAEMIA:
4-GIT:4-GIT:
Dyspepsia and anorexiaDyspepsia and anorexia
5-Gental5-Gental
Loss of libido & impotenceLoss of libido & impotence
Menstrual abnormalities as amenorrhea.Menstrual abnormalities as amenorrhea.
6-May be polyuria.6-May be polyuria.
C/PC/P

AnemiaAnemia
III- PHYSICAL SIGNS:III- PHYSICAL SIGNS:
Pallor of the skin and mucous membranes
The colour of the skin is unreliable
because it depends upon the degree of
skin pigmentation and the amount of fluid
in the subcutaneous tissues.
Best examined : palmer creases, nail bed,
and mucous membrane .
Peripheral oedema :
Slight oedema of the legs probably due to
increase in the capillary permeability
secondary to hypoxia.
High COP failure.
Fever :
Mild fever may occur in sever anaemia but
other causes should be excluded
C/PC/P

AnemiaAnemia
Fundal changes:Fundal changes:
Retinal hemorrhages of the flame shapeRetinal hemorrhages of the flame shape
type, exudates and rarely papilloedema.type, exudates and rarely papilloedema.
The cardiovascular system:The cardiovascular system:
Increased velocity with decreased viscosityIncreased velocity with decreased viscosity
of the blood in addition to capillaryof the blood in addition to capillary
dilation:dilation:
Pulse; tachycardia, bounding pulsePulse; tachycardia, bounding pulse
Cardiac examination :Cardiac examination :
Loud HSLoud HS
S3 over mitral or tricuspid areaS3 over mitral or tricuspid area
Haemic murmur: ejection systolic,Haemic murmur: ejection systolic,
hearted allover the precordiumhearted allover the precordium
Raised jugular venous pressure.Raised jugular venous pressure.
C/PC/P

AnemiaAnemia
Proteinuria and impairment of theProteinuria and impairment of the
concentrating power of kidneysconcentrating power of kidneys due to anoxiadue to anoxia
of renal tubules.of renal tubules.
IV: SPECIAL MANIFESTATIONS RELATED TO THEIV: SPECIAL MANIFESTATIONS RELATED TO THE
CAUSECAUSEC/PC/P

MicrocyticMicrocytic
AnemiaAnemia
Basic nutritional features and metabolism of ironBasic nutritional features and metabolism of iron
Dietary sources :
Red meat and liver, bread, eggs and green
vegetables, mainly in ferric form,
Daily minimum requirement 10-12mg of which
about 1mg is absorbed.

AnemiaAnemia
In the stomach the iron is released from its
complex form and is reduced to ferrous form
(action of gastrin and Hcl).
Iron absorption takes place in the duodenum
and proximal jejunum.
Factor controlling iron absorption
Iron absorption is under regulatory system
(Apoferritin-Transferrin system ) present in the
intestinal mucosa and regulate absorption of the
iron according to body requirement .
AbsorptionAbsorption

AnemiaAnemia
AbsorptionAbsorption
Factors enhancing iron absorption
Pregnancy
Iron deficiency anaemia
Increased erythropoiesis
Vit. C.
Factors decrease iron absorption :
Excess phosphate, tannates, phytate in diet
Iron overload haemochromatosis
Decreased erythropoies eg a plastic anaemia
Malabsorption syndrome
Decreased HCI atrophic gastritis .

AnemiaAnemia
Transport
There is a diurnal rhythm with higher level in
the morning, iron is transported in the
plasma bound to transferrin.
Utilization : incorporation into Hb, myoglobin
and tissue enzymes.

AnemiaAnemia
Storage :
About two-thirds of the total body iron is in the
circulation as haemoglobin.
Iron is stored in reticulo-endothelial cells,
hepatocytes, spleen, bone marrow and skeletal
muscle about two thirds as ferritin and one-
third as haemosiderin.
Iron loss: (0.5 mg/day). Via
Hair and nail growth
Epithelium of the skin and mucus membrane.
body excreta : stool and urine

AnemiaAnemia
AetiologyAetiology
True deficiency (defective intake) Rare:
 Prolonged starvation and famines.
 Infancy (milk is poor in iron)
Conditioned deficiency (normal demand and
intake but there are defective absorption and
utilization) Not common:
 Ferric form cause.
 Decreased HCL
 Iron binder: phosphate, phytate, tannates
 Malobsorption syndrome.
Relative deficiency : (increased requirement )
common cause.
 Menstruating females.
 Pregnancy, labor.
 Growing children .
 Convalescence from disease.
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DDDD
LabLab
C/PC/P

AnemiaAnemia
AetiologyAetiology
Chronic blood loss : the commonest cause
 Frank blood loss
Menorrhagia
Repeated GI bleeding, haemeptysis,
epistaxis, haematuria
Bleeding tendencies
Repeated blood donation
 Occult blood loss via GIT:
Anckylstoma & schistomiasis
Oozing OV, PU.
Neoplasm.
Inflammatory bowel disease ulcerative
colitis
TB enteritis.

AnemiaAnemia
General manifestations of anaemia
Especial manifestations of iron deficiency
anaemia .
Epithelial changes:
GIT manifestations
Angular stomatitis.
Atrophic glossitis (red, glazed, smooth
tongue).
Atrophy of the gastric mucosa
Small splenomegaly
Dermatological changes
Brittle nails thinning and ridging and loss of
luster.
Koilonychia; spoon-shaped nails in severe
cases:
Brittle hair
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AetiologyAetiology
C/PC/P
LabLab
DDDD

AnemiaAnemia
Features of special types:
1- Plummer-Vinson –syndrome:
 Common in middle aged female
 Postcricoid esophageal web cause
dysphagia
2- Ankylostoma infestation:
 Perverted appetite: (pica) eating mud,
stones and chalk.
 Epigastric pain (DD= D. ulcer ), altering
bowel habits
 Endemic parasites (trapezoid face)
 The symptoms are mild and to variable.
 Investigations:
Stool: Ova.
CBC: eosinphilia.
C/PC/P

AnemiaAnemia
A.A.To diagnose iron deficiency anaemiaTo diagnose iron deficiency anaemia
CBC:
 The red cells are microcytic, (MCV<80f1)
and hypochromic (MCH < 27pg)
anisocytosis and poikilocytosis
(variation in size and shape).
 Eosinophilia is present in cases of
ankylostoma infestation.
Bone Marrow:
 Absent iron store,
 Normoplastic hyperplasia,
 ↓ Hb in maturely erythroblasts.
DDDD
LabLab
C/PC/P
AetiologyAetiology
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AnemiaAnemia
A.A.To diagnose iron deficiency anaemiaTo diagnose iron deficiency anaemia
Serum iron study
 Decreased serum iron (n=70-170 mg%).
 Increased total iron binding capacity
(TIBC).(n=250-450mg%).
 Decreased serum ferritin levels .
Reflect iron stores.
The normal values are 30-300 mg/L in
males and 15-200 mg/L in females and
investigation of gastrointestinal tract
are often required.
Falsely raised value in cases of acute
phase reactant e.g malignancy .
 Decreased transferrin saturation (n=25-
50%)
LabLab

AnemiaAnemia
B-B- Investigation for the causesInvestigation for the causes
Stool analysis:Stool analysis:
 Occult blood , ankylstoma & Bilharizasis .Occult blood , ankylstoma & Bilharizasis .
 GI cause:GI cause:
 Imaging : barium swallow, meal orImaging : barium swallow, meal or
enema.enema.
 Endoscopic studies: upper and lower.Endoscopic studies: upper and lower.
 AchlorhydriaAchlorhydria
Haemostatic profile.Haemostatic profile.
LabLab

AnemiaAnemia
Microcytic anaemiaMicrocytic anaemia
Anaemia of chronic diseaseAnaemia of chronic disease
DDDD
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C/PC/P
LabLab
AetiologyAetiology

AnemiaAnemia
The aim of the treatment is to correct theThe aim of the treatment is to correct the
anaemia and build up iron storesanaemia and build up iron stores
 Correction of underlying cause ifCorrection of underlying cause if
possiblepossible
 Iron replacementIron replacement
Oral iron:Oral iron:
 200 mg anhydrous ferrous sulphate three200 mg anhydrous ferrous sulphate three
times daily.times daily.
 The response is a rise in HbThe response is a rise in Hb
concentration of 1 gm/dl per week,concentration of 1 gm/dl per week,
 Side effects nausea, abdominal pain,Side effects nausea, abdominal pain,
diarrhea or constipation.diarrhea or constipation.
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DDDD
LabLab
C/PC/P
AetiologyAetiology

AnemiaAnemia
Parenteral iron:
Indication :
 General intolerance of oral preparation
even at low dose.
 Severe malabsorption and those who
have gastrointestional diseases.
 Rapid iron loss.
Preparation
Iron sucrose ( ferrosac – venofer)
Good safety and efficacy profile.
Given IV or slowly IV infusion.
Amp: 5ml = 100 mg.
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AnemiaAnemia
Iron dextran (cosmofer - imferon)
 Good efficacy but more side effects.
 Giving IM, or IV infusion.
 Amp 2 ml = 100mg.
 Side effects:
Local pain, staining inflammation,
abscess formation
General: hypersensitivity reaction,
fever, rigor, hypotension
N.B: Test dose is required prior to the use of
iron therapy.
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AnemiaAnemia
Transfusion therapy :
It should be packed RBCs.
Indications:
 Sever (Hb < 7 gm/dl) andsymptomatizing
anemia/dl)
 Complicated anaemia:-HF
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AnemiaAnemia
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LabLab
MechanismMechanism
AetiologyAetiology Type of anaemia may be microcytic
hypochromic or more common normocytic
normochromic .
Endocrinal disorders : hypothyroidism,
hypocorticalisin, hypogonadism in male .
Inflammatory diseases : collagenosis, chron’s
disease.
Chronic infection: as TB, sarcoidosis,
oestomylitis .
Neoplastic diseases .
Malabsorption.
Organ failure, liver and kidney

AnemiaAnemia
Not clear: Seems to be mediated by
inflammatory cytokines IL-1, TNF, and INF.
TTTTTT
LabLab
MechanismMechanism
AetiologyAetiology

AnemiaAnemia
Decreased serum iron and TIBC.
Normal or raised serum ferritin
Normal BM iron.
TTTTTT
LabLab
MechanismMechanism
AetiologyAetiology

AnemiaAnemia
Should be targeting the cause.Should be targeting the cause.
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LabLab
MechanismMechanism
AetiologyAetiology

AnemiaAnemia
AetiologyAetiology
It is a refractory microcytic hypochromic
anaemia (peripheral blood) characterized by
the presence of sidroblasts in the bone
marrow.
Sidroblasts are:
 Erythroblasts inside which iron
accumulate into the mitochondria of
erythroblasts owing to disordered haeme
synthesis .
 A ring of iron granules is formed around
the nucleus.

Microcytic
Anemia
Inherited: X-linked disease transmitted by
females.
Acquired :
 Primary: one of the myelodysplastic
syndromes
 Secondary:
• Other types of myelodysplasia
• Myeloproliferative disorders
• Myeloid leukemia
• Drugs as isoniazid, alcohol, lead
AetiologyAetiology

AnemiaAnemia
Differential diagnosis of Microcytic anaemia:
IronIron
deficiencydeficiency
Anaemia ofAnaemia of
Chronic diseaseChronic disease
ThalassaemThalassaem
iaia
SideroblasticSideroblastic
anaemiaanaemia
MCVMCV ReducedReduced
Low normal orLow normal or
normalnormal
Very lowVery low
Low inLow in
inherited butinherited but
in acquiredin acquired
typetype
Serum ironSerum iron ReducedReduced ReducedReduced NormalNormal RaisedRaised
Serum TIBCSerum TIBC RaisedRaised ReducedReduced NormalNormal NormalNormal
Serum ferritinSerum ferritin ReducedReduced
Normal orNormal or
raisedraised
NormalNormal RaisedRaised
Iron in BMIron in BM AbsentAbsent PresentPresent PresentPresent PresentPresent
Iron inIron in
erythroblastserythroblasts
AbsentAbsent
Absent orAbsent or
reducedreduced
PresentPresent Ring formsRing forms

MacrocyticMacrocytic
AnemiaAnemia
MACROCYTIC ANAEMIAS
This can be divided into:
1-Megaloblastic type.
2-Non megaloblastic types depending on bone
marrow findings.

AnemiaAnemia
MEGALOBLASTIC ANAEMIA
Megaloblastic anaemia
This anaemia in which DNA syntheses is impaired with delayed
nuclear maturation. This will lead to formation of
megaloblast i.e. large cells with large immature nucleic
( cellular gigantism). The cells affected are those rapidly
developing: haematopoietic cells, GI mucosa, and skin.
Megaloblastic changes occur in
1-Vitamin B12 deficiency or abnormal vit. B12 metabolism
2-Folic acid deficiency or abnormal folate metabolism
3-Congenital enzyme deficiencies in DNA synthesis or drugs
interfering with DNA synthesis (hydroxyurea, azathioprine).
4-Myelodysplasia due to dyserythropoiesis.

AnemiaAnemia
Hematological values
1-MCV>96 Fl unless there is a coexisting cause
of microcytosis.
2-The peripheral blood film shows macrocytes
with hypersegmented polymorphs with six or
more lobes in the nucleus. If severe there may
be leucopenia and thrombocytopenia.

AnemiaAnemia
(COBLAMIN)12 VITAMIN B
*Vit B12 is synthesized by certain micro-
organism.
*Sources: meat, fish, eggs, and milk but not
plants
*It is not destroyed by cooking.
*Daily requirement is 1-2 mg / day.
*Storage : the average adult stores 2-3 mg in
the liver, it may take two years or more
before B12 deficiency, develops as the daily
losses are small (1-2mg).

AnemiaAnemia
Absorption: Vit. B12 is liberated in the
stomach, bound by intrinsic factor
(IF) and absorbed through the
terminal ileum, transported by
transcobalamin I and to lesser extend
by transcobalamin II and III.
It is essential for:
1-haematopoiesis
2-GIT mucosa integration
3-Formation of myelin of nervous
system.

AnemiaAnemia
CAUSES OF VIT. B12 DEFICIENCY
I- True deficiency: (Decreased intake)
-Poor socioeconomic status.
-Vegetarians, alcoholic
II-condition deficiency
A-Decreased absorption .
1-Decreased intrinsic factors commonest cause.
*Pernicious anaemia.
*Total or partial gastrectomy
*Atrophic gastritis.
*Gastric cancer.
*Non- Addisonian pernicious anaemia
a- In association with hypogammaglobulinemia,
gastric atrophy, achlorhydria and absent intrinsic
factor but no antibodies
b-In infancy: Selective failure of IF, normal mucosa.
C- Juvenil PA failure of IF secretion with gastric
atrophy rarely with antibodies

AnemiaAnemia
2-Malabsorption syndrome.
3-Ileal diseases:
*Terminal ileum resection
*TB enteritis.
*Chron’s disease.
*Blind loop syndrome with bacterial over-growth.
*Infestation by fish tape worm Diphyllobothrium
latum.

AnemiaAnemia B-Decreased utilization:
*Rare congenital enzyme deficiency.
*Lack of transcoblamin II.
III-Relative deficiency : (increased demand)
*Infancy, pregnancy, lactation
*Haemolylsis and active haematopoiesis
*Malignancy.
*Thyrotoxicosis
IV- Increased loss: Hemodialysis
V- Decrease of stores. Far advanced chronic liver
diseases

AnemiaAnemia
PERNICIOUS ANAEMIA
(ADDISONIAN ANAEMIA)
DEFINITION
Pernicious anaemia (PA) is a condition in which
there is atrophy of the gastric mucosa with
consequent failure of intrinsic factor production and
vitamin B12 malabsorption.

AnemiaAnemia
AETIOLOGY
1-Most probably autoimmune disease with genetic
tendency.
2-There is an association with other autoimmune disease
(Thyroid disease, vitiligo and Addison’s disease).
3-Atrophic gastritis (decrease HCL + IF) associated with
production of parietal cell antibodies
4-Intrinsic factor antibodies which are specific for the
diagnosis and are of two types, blocking antibodies
which inhibit the binding of IF to B12 and precipitating
antibodies which inhibit the binding of B12-IF complex to
its receptor sites in the ileum.
5-It is common in the elderly over 60 years in fair haired
and blue eyed people and in females than males.
6-The relatives may have clinical features of autoimmune
disease

AnemiaAnemia
PATHOPHYSIOLOGY
Both vit Bi2 and folic acid are essential for DNA
synthesis and maturation.
In cases of megaloblastic anaemia there is a
deficient DNA synthesis, so the rate of cell
division of many cells in the body is rate. The
most affected cells are those with rapid rate
of division and growth. i.e. haematoportic
cells (RBC, WBC, platelet ) and, gastric
mucosa + inability to form myelin sheath

AnemiaAnemia RBCs (Megaloblastosis = cellular gigantism)
1-Megaloblasts (cell gigantism ): these are
large cells (megalo) with relatively small
nucleus (blasts). The cytoplasm is markedly
in crease because RNA synthesis is normal
while the nucleus is slowly growing because
deficient DNA synthesis.
2-In BM, the normblast are replaced by these
megaloblasts. Some of these abnormal cells
are destroyed in BM. (intramedullary
haemolysis)

AnemiaAnemia
3-Some of these erythroid megaloblasts lose
their nuclei and joined peripheral blood as
macrocytes, irregular shape with remnant of
the nucleus . these cells are hatched and
destroyed by the spleen. During its
circulation.
4-So anaemia is multifactorial
-Defective erythropoiesis
-Intramedullary haemolysis.
-Destruction by the spleen.
5-Increased Serum bilirubin
-Increased medullary haemolysis.
-Increased splenic destruction of RBCs.

AnemiaAnemia
WBCs: (leucopenia)
Myeloid megaloblasts are present in BM and give
hypersegmented PNL to the peripheral blood.
Leucopenia due to deficient DNA synthesis
ThrombocytopeniaThrombocytopenia
Due to deficient DNA synthesis .Due to deficient DNA synthesis .
NB : Since the three blood elements are effected in
megaloblastic anaemia, it is better to call it
megaloblastic pancytopenia.
GITGIT
Is affected in the same manner, with secondary atrophy
epithelial cells of the tongue, stomach and even
intestine.
Nervous systemNervous system
Only with B12 deficiency., failure of synthesis of myelin
synthesis

AnemiaAnemia CLINICAL FEATURESCLINICAL FEATURES
The onset is insidious.
1- Haemtological manifestations
-General manifestation of anaemia .
-Thrombocytepenia  Bleeding tendencies
-Leucpenia  risk of infection
-Hepatosplenomegaly.
-Colour of the skin is lemon yellow owing to combination
of pallor and jaundice.

AnemiaAnemia 2- GIT manifestations2- GIT manifestations
-Atrophic glossitis, (red – glozed tongue)
-Angular stomatitis .
-Gastric atrophy dyspepsia, anorexia nausea,
vomiting .
-Intestinal atrophy diarrhoea and malabsorption
Cancer stomach on top of atrophic gastritis

AnemiaAnemia
33--Neuropsychatice manifestations (only withNeuropsychatice manifestations (only with
vit B12 deficiencyvit B12 deficiency).).
A-Neurological manifestations (3Ps):
Peripheral neuropathy (LMNL)
Pyramidal tract affection (UMNL) spastic paraplegia.
Posterior column affection  loss of deep sensation and
sensory ataxia.
NB: Combination of the two lessons is called sub acute
combined degeneration of the spinal cord (SCD)
b- Dementia
c- Optic atrophy
d- psychosis rare

AnemiaAnemia
44--Association with other autoimmuneAssociation with other autoimmune
features: (in pernicious anaemiafeatures: (in pernicious anaemia))
11--ThyrotoxcoaisThyrotoxcoais
22--Hashimoto’s diseaseHashimoto’s disease..
33--VitiligoVitiligo
44--Rheumatoid diseaseRheumatoid disease
55--Primary billiard cirrhosisPrimary billiard cirrhosis

AnemiaAnemia
INVESTIGATIONS:INVESTIGATIONS:
I- CBCI- CBC
a- RBCs:
Marocytic normochromic anaemia .
Poikilocytosis and anisocytosis
Howell-Jolly bodies may be present
b-WBCs:
Moderate Leucopenia.
Shift to the right
Giant hyperpigmented neutrophil.
C -Platelets
Moderate thrombocytopenia.
Giant platelets
d-Reticulocyte
are decreased but increased by treatment with vit
B12 or folic acid

AnemiaAnemia II- Bone marrow:
Show megaloblastic erythropoiesis. The most
characteristic is dissociation between nuclear
& cytoplasmic development in erythroblasts
with the nucleus maintaining a primitive
appearance despite maturation and
haemoglobinization of the cytoplasm.
Erythroid hyperplasia, maturation defect in
erythropoiesis, giant metamyelocytes, atypical
megakaryocytes with hypersegmented nuclei.

AnemiaAnemia
III- Estimation of serum B12 level
is low using radioisotope dilution or immunological
assays.
IV. Biochemistry
Serum iron is high, more than 175 mcg/100 ml.
Increased serum indirect bilirubin reflect mild
haemolysis and ineffective erythropoiesis.
Increased serum lactic dehydrogenase (LDH)
reflecting ineffective megaloblastic erythropoiesis.
V. Immunology
Parietal cells antibodies and gastrin receptor
antibodies, present in 70% of patients. (not specific)
Intrinsic factor antibodies type I blocking (more
specific) and type II precipitating antibodies.

AnemiaAnemia
VI- other investigations
***Gastric biopsy: proximal 2/3 of stomach atrophic.
***Augmented histamine test: achlorhydria.
***Schilling test.
*Aim
1-Diagnosis of pernicious anaemia.
2-To detect its cause whether malabsorption or IF
deficiency.
*Methodology
Large dose of unlabelled B12 (1000ug) is given IV to
saturate body sores.
Radiolabelled B12 (lug) is given orally, the amount of
radio labellol B12 on the urine.
Urine of the next 24 hours is measured
Results
If radiolabelled B12 excretion is low there may be
1-Malabsorption
2-Pernicious anaemia.
Repeated the test after giving IF orally if it increase in the
urine, this means that the cause is IF deficiency.

Macrocytic
Anemia
TREATMENT
Treatment of the cause : if possible .
Replacement therapy .
Initial treatment is often as the 1000 mg B12
IM/day for 2 weeks then in a dosage of 1000
mg twice/week till correction of anaemia.
Maintenance therapy 1000 mg IM every 3
months.
Neurological damage can be precipitated by
treating incorrectly with folic acid.
Transfusion therapy by packed RBCs in the flowing
conditions
sever anaemia (Hb < 7 gm/dl )
Heart failure .
Marked symptoms .

AnemiaAnemia
FOLATE DEFICIENCY
Basic nutritional features and metabolism of folate***
Dietary folate source :
***Important sources are liver, kidney and fresh
green vegetables, nuts, yeast, cooking probably
destroys, at least half the folate in food,
***Minimum daily requirements 100-200 ug.
Absorption is chiefly in the jejunum.
Total body store is about 10 mg mainly in the liver
Store is sufficient for 4 months.
Function
It is essential for nucleic acid synthesis maturation. It
is deficiency lead to
Nuclear maturation defect., of blood cells and
megaloblastic erythropoiesis.
GIT: mucosal cells.

AnemiaAnemia
CAUSES OF FOLATE DEFICIENCY:
I- True deficiency (decreased intake)
Poor intake particularly in infancy, old age, poor social
conditions, starvation alcohol excess.
Poor intake due to anorexia as in GIT disease e.g. Partial
gastrectomy, coeliac disease, Crohn’s disease, cancer.

AnemiaAnemia
II- Relative deficiency (increased demand)
Physiological: pregnancy, lactation, prematurity
Pathological:
Haematological disease with excess red cells
production e.g haemolysis.
Malignant disease with increased cell turnover
Inflammatory disease e.g. rheumatoid arthritis,
Crohn’s disease.
Metabolic disease e.g. homocystinuria (rare
congenital defect in the conversion of
homocysteine to cystathion folate).

AnemiaAnemia
III - Conditioned deficiency normal intake and
requirement but their may be :
a) Decreased absorption
* Malabsorption: in small bowel disease.
* Drugs : pill or anticonvulsant.
b) Decreased utilization
* Antifolate drugs. anticonvulsants, methotrexate,
pyrimethamine and trimethoprim
IV- Increased loss
* Haemodialysis or peritoneal dialysis closely bound
to plasma protein, so easily removed.

AnemiaAnemia CLINICAL FEATURES
* May occur at any age, degrees of folate deficiency
are very common and mild deficiency states are
frequently unrecognised.
* The clinical picture is multivarious because of the
variety of possible underlying causes.
* The onset may be insidious or rapid as when
negative folate balance is precipitated by e.g infection
* Anaemia and sometimes slight jaundice.
* Glossitis.
* No defined neurological changes.

AnemiaAnemia INVESTIGATIONS
* Essentially as in vit B12 deficiency .
* Howell Jolly bodies and target cells in the blood
film would suggest splenic atrophy (coeliac disease)
* Bone marrow show megaloblastic changes.
* Reduced folate levels: (N= 2.5-25mg/ml) serum
levels are labile and red cell levels are better
reflection of tissue folate by radioisotope dilution or
immunological methods
N.B Microbiological methods were used in the past
but has the disadvantage that antibiotic therapy
could lead to falsely low results.

AnemiaAnemia
Treatment
1) Folic acid therapy is contraindicated if there is
any suspicion of B12 deficiency (Neurololgical
changes may be precipitated or worsen).
2) Folic acid: 5mg daily is more than adequate.
3) Prophylactic folic acid is also given in chronic
hematological disorders where there is rapid
cell turnover 5mg each week.
4) Prophylactic folic acid (400ug daily) is
recommended in pregnancy.

AnemiaAnemia
MACROCYTOSIS WITHOUT
MEGALOBLASTIC CHANGES
A raised MCV with macrocytosis on the
peripheral blood film can occur with a normablastic
BM. In all these conditions, the level of Vit B12 and
folate are normal.
The exact mechanisms are uncertain, but it
seems there is increased lipid deposition in the red
cell membrane.

AnemiaAnemia
CAUSES
1) Physiological : pregnancy and newborn.
2) Pathological
* Alcohol excess
* Liver disease
* Reticulocytosis
* Hypothyroidism
* Some haematological disorders (e.g aplastic
anaemia, sideroblastic anaemia
* Drugs (e.g cytotoxics as azathioprine)
* Agglutinated red cell measured on red counters.
* Cold agglutinis due to autoagglutination of red cells,
MCV decreases to normal with warming of the
sample to 37OC.
An increased number of reticulocytes lead to a raised
MCV because they are large cells.

AnemiaAnemia
HAEMOLYTIC ANAEMIAS
Definition:
The haemolytic anaemias are a group of diseases
in which red cell life span is shortened.

AnemiaAnemia PATHOPYSIOLOGY:
* Haemolysis of RBC can occur either .
1) Intravascular ie within the circulation .
2) Extra vascular ie : by phagocytes in RES in the
liver, bone, spleen.
* Bone marrow compensatory reactions:
Erythriod hyperplasia in BM, can increase
erythropoiesis several times, so that anaemia
may not develop till RBCs life span is less than
20 days
Reticuylocytosis is hallmark.
Slight macroytosis in the peripheral blood

AnemiaAnemia
Consequences
1) Excess haemolysis increases bilurbin since the liver
can increase its capacity several time, the jaundice is mild
if hot at all.
2) The intravascular librated Hb is bound to &-2 globulin
(haptoglobin) and Hb haptoglobin is rapidly cleared from
the circulation by REs, and plasma level of haptoglobin is
reduced, In cases of excessive IV haemolysis,
haptoglobin is depleted, there is haemoglobinanemia and
haemoglobinuria and dark urine
3) Extramedullary erythropoiesis will cause specific bone
charges .

AnemiaAnemia
CAUSES:
A - CORPUSCULAR CAUSES:
1)Congenital Abnormalities:
Membrane defects:
* Hereditary spherocytosis
* Hereditary elliptocytosis
•Hereditary stomatocytosis
Haemoglobinopathies:
* Sickle cell anaemia
* Thalassaemia
Enzymopathies
1) Abnormal aerobic glycolysis e.g. G6PD deficiency
2) Abnormal anerobic glycolysis e.g pyruvate kinase
deficiency
3) Non glycolytic enzymopathies

HaemolyticHaemolytic
AnemiaAnemia
2) Acquired Abnormalities
1- Paroxysmal nocturnal haemoglobinuria
2- Vitamin E deficiency
B- EXTRACORPUSCULAR CAUSES:
1- Immune mechanisms
a ) Alloimmune antibodies (iso-immune):
* Incompatible blood transfusion
* Haemolytic disease of the newborn
* After allogenic BM or organ transplantation
b) Autoimmune haemolytic anaemias
1-Warm reactive antibodies (react at 37 oC and does not
bring
agglutination type of AB= IgG ).
* Idiopathic
* Secondary to CLL, Lymphoma, SLE and rheumatoid
disease
* Secondary to drugs e.g methyldopa.

AnemiaAnemia
2- Cold reactive antibodies (react at 32oC and
usually agglutinates and haemolyse red cells,
type of AB = IgM).
* Cold haemoagglutinin disease
- Idiopathic
-Secondary (mycopolasma pneunemia infection,
infectious mononucleosis, lymphomas.
* Paroxysmal cold haemoglobinuria
- Idiopathic
-Secondary (some viral infections congenital &
tertiary syphilis).
c) Immunochemical mechanisms: drug
induced haemolytic anaemias

AnemiaAnemia
2- Mechanical injury
* Cardiac haemolytic anaemia (valve prosthesis).
* Microangiopathic haemolytic anaemias.
•March haemoglobinuria.
3- Chemicals and Drugs
* Snake venom
* Lead
* Naphthaline
* Phenacetin
* Sulpha drugs
* Hypophosphataemia

AnemiaAnemia
4- Infections
* Clostridium welchii septicemia (Secondary to
septic abortion)
* Malarial infestation (Black water fever)
5- Metabolic causes
* A betalipoproteinemia : A canthocytosis
* Liver porphyria :
* Spurr cell anaemia
* Zieve’s syndrome
* Wilson disease
* Severe hypophosphataemia
6- Secondary to systemic disease :
* Renal and liver failure
* Burn
7-Hyperslenism

AnemiaAnemia
CLINICAL FEATURES OF HAEMOLYTIC ANAEMIA
General features of anaemia
General features of haemolytic anaemia
1)Haemalytic jaundice .
* Mild degree.
* Skin is lemon yellow
* Sclera tinge of jaundice .
* Dark stool.
* Normal urine which darken on exposure to air
2)Heapatosplenomegaly:
* Common in chronic haemolysis except in cases of
sickle cell anaemia where there self-splenectomy
3) Biliary obstruction and /or gall bladder stones.
* Pigment stones: extra hepatic obstruction .
* Viscid bile: intrahepatic obstruction.
NB. In this situation jaundice becomes, mixed
( haemolytic + obstructive) and abdominal pain my be
present.
4- Leg ulcer:
Chronic leg ulcer surrounded by pigmentation cause
by extra vascular iron deposition . Ulcers develop on the
malleoli

AnemiaAnemia
5-Different types of crisis:
a) Heamolytic crisis
* Fever, rigors: pyrogen release from RBCs .
* Generalized bone pain
* Acute abdominal pain, backache, may be vomiting.
* Aggravation of anaemia (pallor), deepening as jaundice,
and dark colouration of urine
* Investigations:
- Dark urine: haemoglobinuria.
- Increased serum biliurbin
- Reticulocytosis
- BM erythroid hyperplasia.
* Cause may be infection
B- A plastic crisis
* Inability of BM to replaced the destructed RBCs
- Severe anaemia without jaundice.
- Reticulocytopenia .
- BM erythroid hypoplasia.
* Cause: viral infection especially parvovirus B19 and
HBV.

AnemiaAnemia C- Sequestration crisis
Trapping and pooling of RBCs in the spleen (mainly
and liver).
D- Megaloblastic crisis
* Anaemia severe without jaundice .
* Decreased reticulocytic count
* Macrocytic anaemia.
* BM : megabloblastic
Cause: folic acid deficiency.
E- Vaso-occlusive crisis (Thrombotic
phenomenon)
* Painful.
* Only in cases of sickle cell anaemia.

AnemiaAnemia
Features or the cause
e.g thalassaemia, sickle cell anaemia.
COMPLICATIONS
* Haemolytic crisis:.
* A plastic crisis:
* Folate deficiency caused by increased BM requirement
* Gall stones
*In sickle cell anaemia: signs and symptoms of thrombotic
phenomena.

AnemiaAnemia INVESTIGATION FOR CASE OF HAEMOLYTIC
ANAEMIA
1) Diagnosis of Haemolytic anaemia
1- CBC
* Normocytic normochromic anaemia with reticulocytosis
* Microcytic anaemia: thalassaemia, spherocytosis.
* Macrocytic + reticulocytosis: megaloblastic crisis
* Reticytopenia: a plastic crisis .
* Morphological evidence of RBC damage: as red cell
fragment, cell containing malarial parasites.
* Morphology of RBCs: eg spherocytes & sickle cells
* WBCs thrombocytes are normal but may increase due to
bone marrow stimulation.

AnemiaAnemia
2- Short life span of RBCs:
Measured by radioactive corium labeled RBCs
3- Bone marrow
* Hypercellular normabloastic marrow.
* Hypocellular in a plastic crisis.
* Megaloblastic in folate deficiency.
4-Increased serum LDH
5-Incresesd serum biliurbin, fecal
stercobilinogen and urinary urobilinogen.

AnemiaAnemia Tests for detection the site of
haemolysis.
In intravascular haemolysis vs. extravascular the
following parameters are presents.
* Haemoglobin anemia, Haemoglobinuria and
haemosideringuria
* Reduced plasma haptoglobin and haemopexin
* Presence of met haemalbumin in plasma.
Tests for the cause
* RBC morphology.
* Osmotic fragility .
* Hb electrophoeresis.
* Estimation of G6 PD.
* Coomb’s test.

AnemiaAnemia
HEREDITARY SPHEROCYTOSIS
Pathogenesis:
A hereditary autosomal dominant disorder in
which the corpuscular membrane is abnormally less
deformable and more permeable to sodium. This is
due to an abnormality of the protein as pectrin in the
corpuscular membrane which causes water
imbibition and rupture or red blood cells.

AnemiaAnemia
CLINICAL PICTURE:
1) Symptoms usually appear during the first decade of
life, but may be delayed .
2) Common features of haemolytic anaemia .
3) Slight or moderate enlargement of the spleen .
4) Pigment biliary stones in long standing cases .
5) Chronic leg ulcers.

AnemiaAnemia
INVESTIGATIONS:
1- CBC
* Spherocytosis, red cells are spherical instead of being ]
biconcave.
* Reticulocytosis .
* Anaemia of moderate degree.
2- Osmotic fragility
is characteristically increased, haemolysis usually begins
at podium chloride concentration of 0.6 % or even higher
3- Direct coomb’s test is negative, excluding an
autoimmune cause of spherocytosis and haemolysis.

AnemiaAnemia
TREATMENT :
The principal form of treatment is splenectomy
although this should not be performed unless
clinically indicated because of anaemia.
Splenectomy lengthens the life span of redcells,
correct anaemia, prevents haemochromatosis, but
does not affect the character of red cells.

AnemiaAnemia
ELLIPTOCYTOSISELLIPTOCYTOSIS
This has similar clinical and laboratory
features to hereditary spherocytosis except for the
appearance of the blood film, but is usually a
clinically milder. Occasional patients require
splonectomy.

AnemiaAnemia
PAROXYSMAL NOCTARAL HAEMOGLOBINURIAPAROXYSMAL NOCTARAL HAEMOGLOBINURIA
AETIOLOGY
* The only one of corpuscular causes of haemalysis
which is acquired .
* The exact a etiology is unknown.
* It results from increased sensitivity of RBCs
membrane to be damage by the complement system

AnemiaAnemia
CLINICAL FEATURECLINICAL FEATURE
1) Feature of haemolytic anaemia
- Haemolysis occurs mainly after sleep by night
leading haemoglobin anemia and haemoglobinuria.
2) Abnormal platelets  thrombi
3) Abnormal WBCs inspection
4) Abdominal pain due visceral ischemia caused
by
micro thrombi.

AnemiaAnemia
COMPLICATIONSCOMPLICATIONS
1) Thrombosis
2) Plastic anaemia .
3) Acute myeloid leukaemia

AnemiaAnemia
INVESTIGATIONSINVESTIGATIONS
1) General investigation of haemalytic anaemia .
2) Activation of complement to cause haemolysis .
- Ham’s test haemalysis by adding acid to the blood

AnemiaAnemia
TREATMENTTREATMENT ::
1- Symptomatic
2- Prodinisone .
3- BMT .

AnemiaAnemia
HAEMOGLOBINPATHIESHAEMOGLOBINPATHIES
Normally haemoglobin consists of .
* Globin :protein which is formed from 4 polypeptide
chain
* Haem : iron-protoporphyrin complex
Haemoglobinopathies:
These are clinical syndromes resulting from
abnormalities in the structure of globin molecule, with
the production of abnormal haemoglobin.
There are three main categories :There are three main categories :
1 )Structural variant of Hb: e.s HbS.
2) Failure to synthesize Ht: e.g thalassemia.
3)Failure to switch from fetal Hb (HbF) to adult Hb
(HbA) : Heridetary persistence of Fetal Hb
(HPFH).

AnemiaAnemia
Type of Hb Hb Normal % Structure of globin
Normal
A
A2
F
97-98
1-2
1-2
α2 β2 (2 alpha + 2 Beta)
α 2 δ2 (2 alpha+ 2 Deta)
α 2 γ2 ( 2alpha + 2 gamma)
Abnormal
production
H
Barts
-
-
β4 (α-thalassaemia)
γ4(Homozyqous α- thalassaemia)
Abnormal chain
structure
S
C
-
-
α 2 β2 (abnormal β-chain)
α 2 β 2.

AnemiaAnemia SICKLE CELL ANAEMIASICKLE CELL ANAEMIA
Symptoms vary from a mild asymptomatic
disorder to severe haemolytic anaemia and recurrent
severe painful crises.
A herediatary autosomal recessive disorder.
The homozgotic form is due to the presence of the
abnormal haemoglobin, (Hbs), which on exposure to
hypoxia, the deoxygenated Hbs forms in soluble
aggregates that distort the erythrocytes and increase
their rigidity causing sickling deformation and
subsequent fragmentation. In addition, the unyielding
elongate crescentic erythrocytes form aggregates that
block terminal arterioles, capillaries and veins, resulting
in tissue infractions and perivascular oedema in the
involved organs (vascular occlusion)

AnemiaAnemia
CLINICAL FEATURES :
1) The disease is more common among negros.
2) General manifestations of haemolytic anaemia
3) In the older patients, vaso-occlusive problems
occur
owing to sickling in the small vessels of any organ,
typical infarctive sickle crises include

AnemiaAnemia
* Bone pain (most common)
- The hand and foot syndrome due to infarcts of
small bones is quite common in children and may
result in digits of varying lengths.
- Avascular necrosis of the fumoral or humoral
head
* Chest: pleuritic pain, pulmonary infarction
* Cerebral: hemiparesis, fits
* Kideny: papillary necrosis causing hematuria
renal tubular defect resulting in lack of
concentration
of the urine

AnemiaAnemia
* Spleen: painful infarcts, self splenectomy,
fibrosis,
hyposplenism.
* Penis: priapism and impotence.
* Liver: pain with abnormal biochemistry
* Intestine, ischaemia, infarction, abdominal and
fever .
* Ischemic cardiomyopathy
* Eye: retinal detachment and blindness

AnemiaAnemia
4) Attacks of generalized and abdominal pain with low
grade fever last from a few hours to a few days during a
crisis Hb does not fall unless there is one or more of the
following different crisis.:
* Aplasia due to decreased erythropoiesis associated
with viral infections
* Acute sequestration, the liver and spleen become
engorged with sickle cells
* Haemolysis due to drugs, acute infection or
associated (G6PD) deficiency.
5) Increased susceptibility to infection hyposplenisim)
e.g viral, pneumococcal) salmonella.

AnemiaAnemia
COMPLICATIONSCOMPLICATIONS
1) Susceptibility to infections
2) Chronic leg ulcers due to ischemia
3) Gall stones pigment stones from persistant haemolysis
4) A septic necrosis of bone particularly of the femoral
heads
5) Blindness due to retinal detachment and / or
proliferative retinopathy
6) Chronic renal disease.

AnemiaAnemia Investigations:
1) CBC
The level of Hb is in the range 6-8gm/dl with high
reticulocytic count (10-20%).
* Blood films show features of hyposplenism
* Sickling of red cells on a blood film can be induced in
the presence of sodium metabisulphite which cause
hypoxia.
2) Hb electrophoresis:
* There is no Hb A, 80-85% Hb S and 2-20% HbF.
* The parents of the affected child will show features of
sickle cell trait

AnemiaAnemia
TREATMENT :TREATMENT :
a) prophylaxis
* Genetic counseling
* Prenatal diagnosis
* Prevent exposure to hypoxia
* Vaccination
b) Active treatment
1) The “steady state” anaemia requires no treatment
2) Acute attacks require supportive therapy intravenous
fluids, oxygen, antibiotics and adequate analgesia.
3) Folic acid (5mg/day) is given to prevent megalobastosis.

AnemiaAnemia
4) Regular transfusion of packed RBCs are given if there
is severe anaemia or if patients are having frequent
crises in order to suppress the production of HbS
5) Exchange transfusions may be necessary in patient
with severe or recurrent crises
6) Transfusion and splenectomy may be life saving for
young children with splenic sequestration
7) Hydroxyurea increases HbF production by an unknown
mechanism and reduced the frequency of painful crises.

AnemiaAnemia
Sickle cell trait (Heterozygous sickling disorder)
These individuals have no symptoms unless
extreme circumstances cause anoxia such as flying
in non-pressurized aircraft or problems with
anaesthesia.
* Sickle cell trait protects against plasmodium
falciparum malaria.
* 60% Hb A and 40% Hb S
* The blood count and film are normal
* The diagnosis is made by a positive sickle test or
by Hb electrophoresis.

AnemiaAnemia
THE THALASSAEMIASTHE THALASSAEMIAS
The thalassaemia are anaemias originally found
in people living on the shores of the Mediterranean, now
known to affect people throughout the world.
The defective synthesis of globin genes in
thalassaemia leads to imbalanced globin chain
production leading to precipitation of globin chains within
the red cell precursors and resulting in ineffective
erythropoiesis. Precipitation of globin chains in mature
red cell leads to haemolysis.

AnemiaAnemia
TYPES:
Two types named after the chain which is missed.
A- Alpha thalassaemia
Production of alpha chain is decreased. It is replaced by
gamma or beta chain with for motion of Hb Bart (4g) or Hb
H (4b) types.
1- a-Thalassaemia major
- Homozygosis (2abnormal gene)
- Hb Bart & Hb H are 80-90%.
- In compatible with life and results in intrauterine fetal
death from hydrops foetalis
2- a-Thalassaemia minor
- Heterozygous (only one abnormal gene).
- H B Barts & Hb H are 10-20%.
- Presented by mild Microcytic hypochromic anaemia,
jaundice, and splenomegaly
3- a- Thalassaemia silent carrier or trait,
-Asymptomatic

AnemiaAnemia B- Beta- thalassaemias
There is defective production of beta-chain with
excess production of Hb F and Hb A2
Types
1- b-thalassaemia major
-Homozygous (2 abnormal gene)
-Hb F > 80-90%
2- b- thalassaemia minor (trait)
- Heterozygous (only one abnormal gene)
- Both Hb F (10%) and Hb A2 (10%) .
- Presented in adults by mild Microcytic hypothermic
anaemia and splenomegaly.
-Commonly symptomatic and require treatment.
3- b Thalassaemia intermedia
-Mild anaemia
-Rarely requiles treatment.

AnemiaAnemia
b- THALASSEMIA
Thalassemia minor (Trait):
This common carrier state is asymptomatic,
anaemia is mild or absent, the red cells are
hypochromic and microcytic with a low MCV and MCH.
DD: * Iron deficiency anaemia.
* Thalassaemia trait the serum ferritin and the iron
stores are normal,
* Hb electrophoresis usually show a raised Hb A2 and
often a raised HbF.
*Iron should not be given to these patients unless they
develop coincidental iron deficiency.

AnemiaAnemia
Thalassaemia intermedia
* Patients are symptomatic with moderate anaemia and
who do not require transfusions.
* Patients may have splenomegaly and bone
deformities recurrent leg ulcers, gall stones and
infection.

AnemiaAnemia
b- THALASSAEMIA MAJOR (COOLEY’S ANAEMIA
– MEDITERRANEAN ANEAMIA)
CLINICAL PICTURE:
1) The onset is during the first year of life (3-6 mouth )
2) The children fails to grow, (stunted growth)
mongoloid faces, bone deformities .
3) Feature of haemalytic anaemia jaundice and huge
splenomegaly
4) Extramedullary haematopoiesis: that soon cause
hepatosplenomgaly, bone expansion giving rise to
classical thalassaemic facies (mongoloid facies).

AnemiaAnemia
5) Feature of haemochromatosis: liver cirrhosis, bronze
skin, cardiomegaly.
6) The disease is more common among Mediterranians.
7) Positive family history.
8) Usually recurrent bacterial infection.

AnemiaAnemia
INVESTIGATIONS
1) CBC
* Blood film show hypochromic microcytic picture and
target cells.
* The reticulocyte count is raised and nucleated red cells
are present in the peripheral blood.
* The WBC and the number of platelets are normal unless
hypersplenism is present.

AnemiaAnemia
2) Serum iron
decreased serum iron binding capacity and high serum
iron and ferritin levels are caused by multiple blood
transfusion.
3) Hb electrophoresis
shows an increase in HbF, reduced or absent HbA and
Hb A2 is normal or slightly increased.
4) X-ray
* Skull X-ray show the characteristic hair on end
appearance of bony trabeculae as a result of
expansion of bone marrow and thinning of bone
cortex .
* Long bone : thin cortex and wide medulla

AnemiaAnemia TREATMENT
A) Prophylaxis
- genetic counseling
- prenatal diagnosis
B) Active treatment
1. Repeated packed RBCs transfusion to keep Hb > 10-
11gm/dl, Febril transfusion can be prevented by the
use of leucocyte depleted blood.
2. Folic acid supplements are required and regular
transfusions should be given to keep the Hb above 10
gm / dl
3. Splenectomy should be delayed until after the age of 6
years because of the risk of infection, prophylaxis
against infection is required

AnemiaAnemia
4. Iron overload caused by repeated transfusions treated
by iron chelating agent as desferrioxamine, it is given
as
an overnight subcutaneous infusion on 5-7 nights each
week. High doses of desferrioxamin may cause
catarcts, retinal damage and nerve deafness.
5. Ascorbic acid 200 mg daily is given as it increase the
urinary excretion of iron in response to desferroixamine.
6. Bone marrow transplantation has been used in young
patients with HLA-matched siblings
7. Hydroxyurea to increase HbF production

AnemiaAnemia α- THALASSAEMIA
In contrast to β-thalassaemia it is caused by gene
deletions, the gene for α-chains is duplicated on both
chromosomes 16. Deletion of one α chain gene (α+)
or both α chain (αo).
* If all four genes are absent there is no α-chain
synthesis and Hb Barts (γ4) is present. Hb. Barts can
not carry oxygen and is incompatible with life and
infants are either stillborn or die very shortly after
birth. (hydrops fetalis)
* If three genes are deleted there is moderate anaemia
and splenomegaly (Hb H disease). Hb A, Hb Barts and
Hb H (B4) are present, Hb A2 is normal or reduced
* If two genes are deleted (α-thalassaemia trait), there
is microcytosis with or without mild anaemia.

AnemiaAnemia ENZYMOPATHIES
1- GLUCOSE -6- PHOSPHATE DEHYDROGENASE
DEFICIENCY.
Glucose-6- phosphate dehydrogenase (G6 PD)
Functions to reduce nicotinamide adenine dinucleotide
phosphate (NADPH) while oxidizing glucose-6-
phosphate. It is the only source of NADPH in red cells and
as NADPH is needed for the production of reduced
glutathione, a deficiency renders the red cell susceptible
to oxidant stress, and cause oxidation of NADPH which
permits oxidation of protein SH groups I the red cell
membrane and eventually causes irreversible oxidative
denaturation of Hb which becomes attached to red cell
membrane to form Heinz bodies. Red cells containing
such inclusion bodies become destroyed in the lifer and
spleen

AnemiaAnemia
A gents which may cause haemolysis in (g6PD)
deficiency
* Infections and other acute illnesses e.g diabetic
ketoacidosis
* Drugs
1- Sulphonmides e.g co-trimoxazole
2- Ant. Bacterial e.g into furans, chloramphenicol
3- Analgesics e.g aspirin phen a cetin
4- Anti malarial e.g primquine and quinine

AnemiaAnemia
CLINICAL PICTURE
Rapidly developing intravascular haemolysis with
haemoglobinuria precipitated by infecting and other acute
illness, drugs or the ingestion of fava beans.

AnemiaAnemia
DIAGNOSIS:
* Between crises the blood count is normal
* Direct enzyme assay.
* During crisis, the blood film may show contracted
and fragmented cells “bite” cells and blister” cells
which have Red Heinz bodies removed by the
spleen.
* Haemoglobinaemia and haemoglobinuria in
acute stag .

AnemiaAnemia
TREATMENT
-Withdrawal of the drug or toxic substance
-Blood transfusion is life saving in severe
cases.

AnemiaAnemia
2- PYRUVATE KINASE DEFICIENCY.
This is inherited as an autosomal recessive,
the affected patients being homozygous or les
common heterozygous . the red cells become rigid as
result of reduced adenosine triphosphate (ATP)
formation. Direct enzyme asay is needed to make the
diagnosis .

AnemiaAnemia ACQUIRED NON IMMUNE HAEMOLYTIC ANAEMIA
Paroxysmal nocturnal haemoglobinuria (PNH)
This is rare acquired red cell defect in which a
lone of red cells is particularly sensitive to destruction by
activated complement. These cells are continually
haemolysed intravascularly .
The underlying defect is an inability of PNH cells
to make glycosyl-phosphatidylinositol (GPI) which anchors
surface proteins such as delay accelerating factor (DAF)
membrane inhibitor of reactive lysis (MIRL) to cell
membranes. DAF and MIRL and other proteins are
involved in complement degradation and in their absence
the hemolytic action of complement is not regulated.

AnemiaAnemia
CLINICAL PICTURE:-
1) Haemolysis which may be precipitated by infection or
surgery.
2) Urine voided at night and in the morning on waking is
dark in colour, the reason for this phenomenon is not
clear.
3) Venous thrombotic episodes are very common

AnemiaAnemia
INVESTIGATIONS
1) Intra vascular haemolysis
2) Ham’s test. Cells from a patient with PNH lyse
more readily in acidified serum than do normal
cells.

AnemiaAnemia
TREATMENT
1) Blood trans fusion for patients with severe anaemia
2) Long tern anticoagulation may be necessary for
patients with recurrent thrombotic episodes
3) BMT but only in patients under so years with an hla-
identical sibling.

Anemia

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