HematologyHematology

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Immune MechanismsImmune Mechanisms

Tutor: Prof Mohan DikshitTutor: Prof Mohan Dikshit

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Objectives: Composition of blood & RBCObjectives: Composition of blood & RBC

Describe the cellular and non-cellular components of Describe the cellular and non-cellular components of blood blood

Enumerate functions of the non-cellular part. Enumerate functions of the non-cellular part. Describe the physical characteristics of the RBCDescribe the physical characteristics of the RBC Describe functions of RBC.Describe functions of RBC. Describe the life cycle of RBCsDescribe the life cycle of RBCs Describe the process of erythropoiesisDescribe the process of erythropoiesis List the factors that affect erythropoiesis List the factors that affect erythropoiesis

State the normal values for Hemoglobin percentage State the normal values for Hemoglobin percentage and RBC count in males and females and RBC count in males and females

Define anemia, and recognize different types of Define anemia, and recognize different types of anemia, and that iron deficiency anemia is the anemia, and that iron deficiency anemia is the commonest variety world wide commonest variety world wide

List the common symptoms of anemiaList the common symptoms of anemia Define Polycythemia and give an exampleDefine Polycythemia and give an example

Recommended reading: Tortora & Derrickson . Principles of Recommended reading: Tortora & Derrickson . Principles of

Anatomy and Physiology.12th edn. 2009. Volume 2Anatomy and Physiology.12th edn. 2009. Volume 2 2

Physical characteristics of Physical characteristics of bloodblood

Thicker than water with a Specific gravity Thicker than water with a Specific gravity around 1.58around 1.58

pH 7.35-7.45pH 7.35-7.45 Colour: bright red when oxygenatedColour: bright red when oxygenated dark red when de-oxygenateddark red when de-oxygenated 8% body weight8% body weight 20% of ECF20% of ECF Volume about 5 l (70 ml/Kg body wt.)Volume about 5 l (70 ml/Kg body wt.) Sampling by venipuncture; finger Sampling by venipuncture; finger

pick/heel prickpick/heel prick arterial puncturearterial puncture

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Plasma 55%Formed elements 45%Formed elements 45%

Constituents of bloodConstituents of blood

91.5% water91.5% water

7% gm% proteins7% gm% proteins3.8gm % albumin (54%)3.8gm % albumin (54%)2.7gm% globulin (38%)2.7gm% globulin (38%)0.5gm % fibrinogen (7%)0.5gm % fibrinogen (7%)

1.5% 1.5% ElectrolytesElectrolytesNutrientsNutrientsGasesGasesRegulatory substancesRegulatory substancesWaste productsWaste products

RBCs 5 million/cumm (µl)RBCs 5 million/cumm (µl)

WBCs 10,000/cumm (µl)WBCs 10,000/cumm (µl) NeutrophilsNeutrophilsEosinophilsEosinophilsBasophilsBasophilsMonocytesMonocytesLymphocytes neutrophils 60-70% Lymphocytes neutrophils 60-70% lymphocytesd 25-30% lymphocytesd 25-30% monocytes 3-8% monocytes 3-8%

basophils 1%basophils 1%Platelets 140-400000/µlPlatelets 140-400000/µl

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Constituents of blood

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Functions of bloodFunctions of blood

1. Transportation of1. Transportation of respiratory gases; nutrients ; respiratory gases; nutrients ;

hormones; hormones;

waste productswaste products

2. Regulatory: body temperature; pH 2. Regulatory: body temperature; pH

3. Protection 3. Protection against disease (immune functions); against disease (immune functions); against blood loss (coagulation) against blood loss (coagulation)

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Origin: STEM CELLS (stem cell pool) in the bone Origin: STEM CELLS (stem cell pool) in the bone marrowmarrow

Stem cells may beStem cells may be

i. Pluripotent (multipotential), i. Pluripotent (multipotential), ii. Committed (unipotential) COLONY forming ii. Committed (unipotential) COLONY forming

Units (CFUs).Units (CFUs). Hematopoesis : process of forming blood cellsHematopoesis : process of forming blood cells

continues life longcontinues life long, , is modulated by requirements of the body. is modulated by requirements of the body. - - It increases in anemia, blood loss, infection by:It increases in anemia, blood loss, infection by: i. reconversion of old yellow bone marrow into red i. reconversion of old yellow bone marrow into red

marrow; marrow; ii. daughter cells differentiate faster; iii. faster ii. daughter cells differentiate faster; iii. faster

proliferation of stem cellsproliferation of stem cells

Some times even in adults Some times even in adults EXTRA MEDULLARYEXTRA MEDULLARY hematopoesis occurs in hematopoesis occurs in liver, spleenliver, spleen

In blood cancer, hematopoesis becomes abnormal In blood cancer, hematopoesis becomes abnormal 8

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Red Blood Cells Red Blood Cells (eryrthrocytes)(eryrthrocytes)

No. 4-5 million/cumm (No. 4-5 million/cumm (μμL)L)

Size 7Size 7μμ, bi-concave discs, bi-concave discs

No nucleus: No nucleus: can not reproduce = can not reproduce = More surface area & center becomes More surface area & center becomes thinner (biconcave):thinner (biconcave):- More O- More O22 can be carried can be carried- Squeeze into narrow capillaries- Squeeze into narrow capillaries- Allow O- Allow O22 & CO & CO22 Diffusion Diffusion

NO mitochondria: ATP by anaerobic NO mitochondria: ATP by anaerobic means (advantage: do not use up Omeans (advantage: do not use up O22 they carry)they carry)

Life span 120 days Life span 120 days

Destroyed in the body by RE cells: by Destroyed in the body by RE cells: by products are recycled (mostly at products are recycled (mostly at Spleen)Spleen)

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Live only 120 days, Why?While Moving in and out of capillaries the RBC are torn and damaged, and due to the absence of Nucleus, healing doesn’t occur.

Thus each Hb molecule carries 4 OThus each Hb molecule carries 4 O22 molecules molecules- Iron is what attaches Oxygen- Iron is what attaches Oxygen

Hb and OHb and O2 2 binding is a loose chemical one: easily binding is a loose chemical one: easily released by Hbreleased by Hb

Globin 4 Heme molsEach having Iron mol

Hemoglobin

Physiology of RBCs1. Main function: transport of OXYGEN bound to

2 alpha chains

2 beta chains

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Hb : also carries Hb : also carries COCO2 2 but only about 15%but only about 15%

Nitric Oxide (NO) – allows blood to go through narrow Nitric Oxide (NO) – allows blood to go through narrow capillariescapillaries

RBCs carry blood group antigens (A,B, O) on their cell membranesRBCs carry blood group antigens (A,B, O) on their cell membranes

RBC Life cycle: 120 days

Macrophages in spleen liver, marrow break up RBCs

heme globin

Ironbiliverdin

Bilirubin in liverexcreted

increase leads to jaundice

recycled

Amino Acids recycled

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Erythropoeisis: formation of RBCErythropoeisis: formation of RBC

Before birthBefore birth in in yolk sacyolk sac liver and spleenliver and spleen

After birthAfter birth

In bone marrowIn bone marrow long bones up to about 20 yrlong bones up to about 20 yr flat bones later in lifeflat bones later in life

About 2.5 million RBC are formed/secAbout 2.5 million RBC are formed/sec

Extra medullary erythropeisisExtra medullary erythropeisis Under severe stress of anemia in post natal lifeUnder severe stress of anemia in post natal life Liver and spleenLiver and spleen

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ProerythroblastProerythroblast

Basophil erythroblastBasophil erythroblast ( Hb just introduced); B( Hb just introduced); B99 B B1212

Orthochromatic erythroOrthochromatic erythro

PolychromatophilPolychromatophilerythroblasterythroblast

ReticulocyteReticulocyteIn circulation for 1-2 daysIn circulation for 1-2 days

ERYTHROCYTERYTHROCYTEE

Normal erythropoiesisNormal erythropoiesisProgenitor cell in bone Progenitor cell in bone marrowmarrow: : Pluripotent hemopoeitic Pluripotent hemopoeitic stem cellstem cellColony forming unit Colony forming unit ErythrocyteErythrocyte (Stimulated by (Stimulated by erythropoeitin)erythropoeitin)

Process takes about 1 week

15Large no of Reticulocytes means that the bone marrow is working

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Factors affecting erythropoeisis:Factors affecting erythropoeisis:

ErythropoeitinErythropoeitin from the kidneys is most importantfrom the kidneys is most important Erythropoietin increases inErythropoietin increases in hypoxia, chronic lung disease, anemia, low blood hypoxia, chronic lung disease, anemia, low blood

volumevolumethat’s why people living in high mountains have larger that’s why people living in high mountains have larger numbers of RBC = HYPOXIAnumbers of RBC = HYPOXIA

(other sources of Erythropoietin: liver)(other sources of Erythropoietin: liver)

-- TestosteroneTestosterone Vit BVit B1212, Folic acid (B, Folic acid (B99), ), IronIron Thyroid hormone Thyroid hormone

Normal Reticulocyte count about 1% of RBCNormal Reticulocyte count about 1% of RBC

If bone marrow is hypoactiveIf bone marrow is hypoactive reticulocyte count will go downreticulocyte count will go down

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Normal HB levelNormal HB level Male: about 13-15 gm%Male: about 13-15 gm% Female about 12-14 gm%Female about 12-14 gm%

Clinical implicationsClinical implications

Anemia means a deficiency of Hb which Anemia means a deficiency of Hb which can be caused by either too few RBCs or can be caused by either too few RBCs or too little Hb in the cells. too little Hb in the cells.

For diagnosis of anemia:For diagnosis of anemia: HemoglobinHemoglobin <<13.0 g/dl for males13.0 g/dl for males << 12.0 g/dl. for females 12.0 g/dl. for females

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Causes of anemiaCauses of anemia

i.i. reduced/defective RBC reduced/defective RBC formationformation

ii. blood lossii. blood loss iii. excessive destruction (iii. excessive destruction (ريبَخ� �َخريبَت ::(( َت iv. combination of all the aboveiv. combination of all the above

The commonest cause of anaemia The commonest cause of anaemia world wide is IRON deficiency : world wide is IRON deficiency : IDAIDA

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Common symptoms of anemiaCommon symptoms of anemia weaknessweakness lethargylethargy lack of concentrationlack of concentration breathlessness – to begin with on breathlessness – to begin with on

exerciseexercise heart failure in severe anemiaheart failure in severe anemia

Investigations:Investigations:

Hb/RBC countHb/RBC count

TreatmentTreatment: iron; diet; remove obvious : iron; diet; remove obvious cause cause

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Polycythemia:Polycythemia: Excess formation of RBC (> 6-7 million/µl)Excess formation of RBC (> 6-7 million/µl)

i. Classically : high altitude exposurei. Classically : high altitude exposure

ii. Polycythemia Rubraii. Polycythemia Rubra

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RECAPRECAP

Blood constituents Blood constituents

Functions of the non-cellular part. Functions of the non-cellular part. RBC: characretristics, functions & and RBC: characretristics, functions & and

formationformation Life cycle of RBCsLife cycle of RBCs

Normal values for Hemoglobin percentage Normal values for Hemoglobin percentage and RBC count in males and females and RBC count in males and females

Anemia, and recognize different symptoms Anemia, and recognize different symptoms of anemiaof anemia

Iron deficiency anemia is the commonest Iron deficiency anemia is the commonest variety world wide variety world wide

Define Polycythemia and give an exampleDefine Polycythemia and give an example

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