Haemopoiesis lecture 1 Dr. Somaya Taha Saleem - PowerPoint Presentation

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Haemopoiesislecture 1

Dr. Somaya Taha Saleem

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Haemopoiesis

Def: blood cell formation

Formation of red cell : erythropoiesis

Formation of granulocytes and monocytes : myelopoiesis

Formation of platelets : thrompopoiesis

SITE:

Fetus: York sac: first few weeks

Liver and spleen: 6 weeks till 6-7

Bone marrow:5-9 months

Infant: bone marrow(all bones)

Adult: Vertebrae , ribs , sternum ,skull , sacrum , pelvis and proximal ends of femur

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Hematopoiesis

GROWTH FACTORS

ERYTHROPOIESIS

GRANULOPOIESIS

MEGAKARYOPOIESIS

LYMPHOPOIESIS

generation of each specific lineage of mature blood cells is regulated by a specific

set of hematopoietic growth factors.

Examples: IL-1, TNF,GM-CSF, Thrombopoietn , Erythropoietin

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Erythrocytes

Size

Anisocytosis

(an/

iso

/cytosis)

ShapePoikilocytosis (poikilo/cytosis)Fragmented cells

Hemoglobin content of cells and whole bloodHBG and HCTMCH & MCHCMean volume of the RBCs (MCV)

Uniformity (RDW)

Cytoplasmic inclusionsCongenital problemsSickle cell among others

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Anaemia

Definition :

Reduction in the

haemoglobin

concentration in blood below the lower limit of the normal range for the age and sex of the individual.

Normal lower Range:Adult male :13.5 g/dl

Adult female:11.5 g/dlNewborn: 15 g/dlAnemia is usually associated with decreased levels of hemoglobin within each RBCs and/or a decreased packed cell volume (

hematocrit), and/or a decreased RBC count.

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Causes of anemia :

Nutritional deficiencies

External or internal blood loss

Increased destruction of RBCs

Ineffective or decreased production of RBCs

Abnormal hemoglobin synthesis

Bone marrow suppression by toxins, chemicals, or radiationInfectionBone marrow replacement by malignant cells

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Clinical features

: shortness of breath, exercise in tolerance, weakness, palpitation, headache.

Sign

:

Pallor ,tachycardia,

cardiomegally , sign of congestive heart failure,koilonychia (spooning of the nails); in iron def anemiaJaundice in heamolytic and megaloblastic anemia.

Leg ulcers in sickle cell anemiaBone deformity in thalassemiaInvestigation CBC : Hb, MCV , WBC , Platelet, retic countBlood film(CBP)

Bone marrow examinationHb electrophoresis

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Types of anemia

macrocytic

Normochromic

normocytic

Microcytic hypochromic

MCV≥95Megaloblastic anemiaAlcoholLiver diseaseMyelodysplasia

Aplastic anemiaMCV 80-95MCH≥27Many of hemolytic anemiaRenal disease

Acute blood lossBone marrow failure

Anemia of chronic diseaseMCV<80,MCH<27

IDAThalassemiaAnemia of chronic disease

Lead poisioningSideroblastic anemia

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Iron Deficiency Anaemia

Iron is essential for

haemoglobin

synthesis

Daily requirement: 20-50 mg per day

Absorption: duodenum, jejunum.Transport : transferrinStorage :ferritin, haemosidrin

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Iron Deficiency anemia

Causes

1.

Chronic blood loss ,

is the major cause of iron deficiency anemia in adults.Most often causes are menorrhagia

or bleeding gastrointestinal lesions, such as carcinoma of the colon or hookworm disease countries. 2. Dietary deficiency 3. Increased iron requirement may occur during pregnancy;

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Clinical manifestations

Signs and symptoms may include

pallor, fatigue,

or

dyspnea on exertion. glossitis; gastritis; koilonychia (spooning of the nails); or Plummer-Vinson syndrome, (iron deficiency is associated with a partially obstructing upper esophageal web laboratory findings

1. Decreased hemoglobin, hematocrit, and red blood cell count2. Hypochromic microcytic erythrocytes on peripheral smear3. Decreased serum iron and increased total iron-binding capacity (TIBC)

4. Decreased body iron stores, measured by bone marrow examination for stainable hemosiderin or by decreased serum ferritin (serum ferritin is the most sensitive marker for

iron deficiency anemia).

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Megaloblastic Anaemia

Anaemia

due to impaired DNA synthesis

Maturation of the nucleus being delayed relative to that of the cytoplasm.

Characterized by

macrocytosis

.It affects the production red cells, granulocytes and platelets.The most common causes of megaloblastosis

are cobalamin (vitamin B-12) and folate deficiencies.

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Cobalamin (vitamin B-12) deficiency:

causes

Nutritional deficiency rare

Malabsorption

Pernicious anemia: common ,

autoimmune disorder

Gastrectomy.

Severe abnormalities in the terminal ileum due to ileal resection, regional ileitis,tuberculosis or lymphoma.Diphyllobothrium

latum (

ie, fish tapeworm)

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Folate deficiency:

Causes :

Folate

depletion:

Impaired absorption:

Tropical

sprue

, regional enteritis, intestinal lymphoma, surgical intestinal resection, amyloidosis,

Increased turnover or requirements:

pregnancy and lactation. Haemolytic

anaemias

Miscellaneous: hemodialysis ,alcoholism,drugs.

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Clinical findings

- Insidious onset

with extreme reduction of red blood cell count;

-

stomatitis

and glossitis

- subacute combined degeneration of the spinal cord (combined systems disease, posterolateral degeneration Clinical manifestations include ataxic gait, hyperreflexia with extensor plantar reflexes, and impaired position and vibration sensation.

(Neurologic abnormalities are associated with vitamin B12 deficiency, but not with folate deficiency

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laboratory abnormalities

1.

peripheral blood

- pancytopenia

(decreased red cells, white cells, and platelets)

- oval macrocytosis. Mean corpuscular volume (MCV) is often greater than 110 fl(normal about 87 fl).

- Hypersegmented neutrophils (more than five lobes) . Bone marrow: megaloblastic hyperplasia2. levels Vitamin B 12

and folate..

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laboratory findings

pernicious anemia

- anti-intrinsic factor antibodies,

which are rarely found in other conditions;

antiparietal

cell antibodies.- abnormal schilling test, which is characterized by impaired absorption of vitamin B 12 correctable by intrinsic factor1

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Hemolytic anemia INTRODUCTION

The normal life span of RBCs is 120 days in the circulation

;

about 1% of human red blood cells break down each dayThe spleen is the main organ which removes old and damaged RBCs from the circulationHemolytic anemia is defined as those anemias that result from increased rate of RBCs destruction.

The condition is associated with a compensatory bone marrow expansion which leads to marked reticulocytosis.

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Mechanisms of hemolysis

Extravascular

red

cells destruction occurs in reticuloendothelial systemIntravascular

red cells destruction occurs in vascular spaceSigns of hemolytic anemiasSymptoms of anemia – pallor, fatique, rapid pulse

JaundiceSplenomegaly

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Evidence of Hemolysis

investigations

Anemia

(Low Plasma Hb)

Reticulocytosis

Indirect

(Unconjugated) hyperbilirubinemiaIncreased level of

lactate dehydrogenase (LDH) Low RBC survival with chromium tagging study

Hypercelluar BM

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I

n

travascular hemolysis

laboratory

signs

of intravascular hemolysis: -

tests for hemolysis

and aditionally: - hemoglobinemia

- hemoglobinuria - hemosiderynuria

- Absence or reduced haptoglobin

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Complications of increased

,

chronic

hemolysis

Folic acid deficiency Gallstones ThrombosisHemolytic crisis

- rapid destruction of large numbers of red blood cells

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Classification

of

hemolytic

anemias

Hemolytic

anemias are classified into:Hereditary

Intrinsic Membrane defect (spherocytosis, elliptocytosis)Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD)

deficiency,

Pyruvate kinase (PK) deficiency)

Hemoglobinopathies (thalassemias, sickle

cell anemia )AcquiredImmune hemolytic anemias

Nonimmune hemolytic

anemias

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Hereditary membrane defects

Spherocytosis

The most common defect of red cell membrane protein

Inheritance

-

autosomal

dominant

Deficient

of membrane protein

causes change

of shape (round

, no central pallor

)

Clinical features: jaundice, gallstones, splenomegaly, constitutional skeleton changes

.

Laboratory features: anemia, hiperbilirubinemia,

retikulocytosis

,



LDH

-

blood

smear

-

microspherocytes

-

abnormal

osmotic

fragility

test

Treatment

-

splenectomy

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Hereditary metabolic defect

Glucoze-6-Phosphate-Dehydrogenaze (G6PD

)

deficiency

Hemolysis is induce by infections,

ingestion of oxidative foods or drugsHemolysis

is

intravascular

Pyruvate

kinase (PK) deficiency

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Thalassemias

Heritable,

hypochromic

anemias

-varying degrees of severityGenetic defects result in decreased or absent production of globin chain synthesisEither alpha or beta

thalassemia, it is due to reduced amountr of Hb production.

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Hemoglobin Types

Hemoglobin Type

Hgb A1—92%---------

Hgb A2—2.5%--------

Hgb F — <1%---------

Hgb H ------------------Bart’s Hgb--------------Hgb S--------------------Hgb C-------------------

Globin Chainsa2b2a2d2

a2g2b4g4

a2b26 gluval

a2b26 glulys

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Alpha Thalassemias

Result from gene deletions

One deletion—Silent carrier; no clinical significance

Two deletions—

a

Thal trait; mild hypochromic

microcytic anemiaThree deletions—Hgb H; variable severity, but less severe than Beta Thal MajorFour deletions—Bart’s Hgb;

Hydrops Fetalis; In Utero or early neonatal deathUsually no treatment indicated4 deletions incompatible with life3 or fewer deletions have only mild anemia

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Beta Thalassemia Major

Reduced or nonexistent production of

b

-

globin

Increased splenic destruction of dysfunctional RBCsHyperplastic

Bone MarrowIneffective erythropoiesis—RBC precursors destroyedIron overload—increased absorption and transfusionsEndocrine disorders, Cardiomyopathy, Liver failure

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B Thalassaemia

Accoroing

to the level of B-chain, classified into:

Thalassaemia major. Thalassaemia intermedia & Thalassaemia minor.

1- Thalassaemia minor:Usually symptomless, associated with raised Hb A2 levels, which confirms the diagnosis.The importance of diagnosis allows prenatal counselling.

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2 -

Thalassaemia

major:

-Either No chain or small amount of chain are synthesized.

Gamma globulin is produced as a

copensatory mechanism resulting in high Hb F level.Clinical Features:Severe anaemia.Enlarged liver and spleen due to iron overload,

Thalassaemic face and thining of the cortex bossing of the skull with (a hair-end appearance) on X ray

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Complications

: Iron overload results in destruction of many organs…

Skin pigmentation due to

hemosiderin

and melanin.

Infection. -Osteoprosis. Laboratory:-Severe hypochromic microcytic anaemia, High

reticulocytes count, - Hb electrophoresis.

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Sideroblastic

A

Thalassaemia

A of chronic

inflammation

IDA

↓(cong)↓↓/N

↓MCV/MCH

Present

PresentPresent

AbsentBone marrow iron stores

↑N↓↓Serum ironNN

↓↑TIBC

↑NN/↑

↓Serum ferritin

Ring forms

PresentAbsentAbsent

Erythroblast iron

N

HbA2

raised/ HbF

N

N

Hb

electrophoresis

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SICKLE CELL ANEMIA

Definition:

chronic hemolytic anemia characterized by sickle-shaped red cells caused by homozygous inheritance of

Hemoglobin SSickle Cell Disease - Homozygous (SS) - Sickle Cell Trait - Heterozygous (AS)

In homozygotes all HbA is replaced by HbS, whereas in heterozygotes only about half is replaced.

The Sickle b-globin abnormalities is caused by substitution of valine for

glutamic acid at position 6 of the

bchainHbS (a2b26

gluval )is insoluble and forms crystals when exposed to low oxygen tension

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SICKLE CELL ANEMIA-

pathogenesis

- Hemolysis - because sickle RBCs are too fragile to withstand the mechanical trauma of circulation

- Occlusion in microvascular circulation caused by distorted, inflexible RBCs adhering to vascular endothelium

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Clinical features:

IN HOMOZYGOTES

Onset in the first or second year of live

severe chronic hemolytic anemia

Jaundice Period episodes of acute vascular occlussion (painful crisis) Consequences of vaso-occlusion of the microcirculations tissue ischemia and infarction.

Spleen (Children - Splenomegaly) Microvascular Occlusion - Tissue Infarcts and Pain

- Autosplenectomy (Adults) Infections - Salmonella OsteomyelitisAplastic Crisis - Usually Parvovirus

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2.

Acquired

A.

Immune

hemolytic

anemias 1. Autoimmune hemolytic anemia -

caused by warm-reactive antibodies - caused by cold-reactive

antibodies

2. Alloimmune hemolytic anemia (transfusion of

incompatible blood)

B. Nonimmune hemolytic anemias 1. Chemicals 2. Bacterial infections, parasitic

infections (malaria) 3. Hemolysis

due to physical trauma (

e.g. microangiopathic hemolytic anemia)

4. Hypersplenism

5. Paroxysmal nocturnal hemoglobinuria (PNH)

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Aplastic anemia

Aplastic

(

hypoplastic) anaemia is defined as pancytopenia resulting from

aplasia of the bone marrow. It is classified into primary (congenital or acquired) or secondary types.

Primary: Congenital Idiopathic.Secondary: Ionizing radiation Chemicals: benzene, DDT

Pesticides.Drugs.

Viruses: viral hepatitis, EBV

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Clinical features:

Anaemia

.

Infections.

Thrombocytopenia:

haemorrhagic symptoms The lymph nodes, liver and spleen are not enlarged.Laboratory findings:1 -Pancytopenia.

2- The bone marrow shows replacement by fat.

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Thank you