Blood Week 6 Dr. Walid Daoud, A. Professor. Blood ____________________________ Blood...

BloodBlood

Week 6Week 6

Dr. Walid Daoud,Dr. Walid Daoud,

A. ProfessorA. Professor

BloodBlood________________________________________________________

Blood is a part of extracellular fluid and Blood is a part of extracellular fluid and composed of 2 partscomposed of 2 parts::

11 - -Fluid part or Plasma (55%)Fluid part or Plasma (55%)..

22 - -Cellular part (45%)Cellular part (45%)::

. .Red blood corpuscles (erythrocytes)Red blood corpuscles (erythrocytes)..

. . White blood cells (leukocytes)White blood cells (leukocytes)..

. . Platelets (thrombocytes)Platelets (thrombocytes)..

PlasmaPlasma________________________________________________________A yellow clear fluid, 3.5 L, clots on standingA yellow clear fluid, 3.5 L, clots on standing..

CompositionComposition::

11--Water (90%)Water (90%)..

22--Organic substances (9.1%)Organic substances (9.1%)::

Plasma proteins, lipids, glucose, amino acids, Plasma proteins, lipids, glucose, amino acids, vitamins, enzymes & waste products vitamins, enzymes & waste products..

33--Inorganic constituents (0.9%)Inorganic constituents (0.9%)::

NaNa++, Cl, Cl--, HCO, HCO33--, phosphates and sulphates, phosphates and sulphates . .

44--Blood gases:Blood gases: O O22, CO, CO22 and N and N22 . .

Plasma ProteinsPlasma Proteins________________________________________________________Types: Conc. (g/dl) Mol. WeightTypes: Conc. (g/dl) Mol. Weight

11 - -Albumin:Albumin: 3.5-5 69,000 3.5-5 69,00022 - -Globulins:Globulins: 2.5 90,000-156,000 2.5 90,000-156,000

33 - -Fibrinogen:Fibrinogen: 0.4 340,000 0.4 340,00044 - -Prothrombin:Prothrombin: 0.01 68,700 0.01 68,700

Sites of FormationSites of Formation::11 - -Albumin, Fibrinogen, Prothrombin in liverAlbumin, Fibrinogen, Prothrombin in liver..

22 - -Globulins: 50% in liver, 50% in plasma cellsGlobulins: 50% in liver, 50% in plasma cellsAlbumin/Globulin (A/G) ratio: 1.2-1.6Albumin/Globulin (A/G) ratio: 1.2-1.6

It decreases in liver and kidney diseasesIt decreases in liver and kidney diseases . .

Functions of Plasma ProteinsFunctions of Plasma Proteins____________________________________________________

11 - -Osmotic functionOsmotic function..22 - -Transport functionTransport function..

33 - -Defensive function (immunoglobulins)Defensive function (immunoglobulins)..44 - -Blood clotting functionBlood clotting function..

55 - -ViscosityViscosity..66 - -Capillary functionCapillary function..

77 - -Buffer functionBuffer function..88 - -Function as a source of tissue proteinsFunction as a source of tissue proteins..

Red Blood CorpusclesRed Blood Corpuscles________________________________________________________

- -Non-nucleated biconcave discsNon-nucleated biconcave discs.. - -Adult male: 5.4 million / mmAdult male: 5.4 million / mm33

- -Adult female: 4.8 million / mmAdult female: 4.8 million / mm33

Structure of RBCStructure of RBC:: - -Has a plastic membrane (easily molded)Has a plastic membrane (easily molded)..

- -Contains hemoglobin (Hb)Contains hemoglobin (Hb)..

- -Contains carbonic anhydrase for COContains carbonic anhydrase for CO22 transport transport..

- -KK++ is the main intracellular cation is the main intracellular cation.. - -No mitochondria & derives energy from anaerobic No mitochondria & derives energy from anaerobic

metabolism of glucose (glycolysis) metabolism of glucose (glycolysis)..

Hemoglobin (Hb)Hemoglobin (Hb)________________________________________________________

- -Oxygen-carrying red pigment of RBCsOxygen-carrying red pigment of RBCs..

- -Adult male: 15-16 g / dlAdult male: 15-16 g / dl..

- -Adult female: 13-14 g / dlAdult female: 13-14 g / dl

- -Newborn: 19 g / dlNewborn: 19 g / dl

Structure of Hb:Structure of Hb: 4 subunits 4 subunits::

- -Each subunit = polypeptide chain + hemeEach subunit = polypeptide chain + heme

- -The 4 plypeptide chains are called globinThe 4 plypeptide chains are called globin..

- -Heme is iron protoporphyrin (ferrous iron)Heme is iron protoporphyrin (ferrous iron)..

Chemical Reactions of HbChemical Reactions of Hb________________________________________________________

11 - -With OxygenWith Oxygen::

Hb + OHb + O2 → 2 → Oxyhemoglobin ( HbOOxyhemoglobin ( HbO2 2 ))

- -Each OEach O22 molecule attaches to ferrous molecule attaches to ferrous iron in heme iron in heme..

- - Each Hb molecule can combine with 4 OEach Hb molecule can combine with 4 O22 molecules molecules . .

- - Each gram of Hb can combine with 1.33 mlEach gram of Hb can combine with 1.33 ml of oxygen to be fully saturatedof oxygen to be fully saturated..

- - OO22 capacity of 100 ml blood = 16 x 1.33capacity of 100 ml blood = 16 x 1.33

= =2121 ml Oml O22

Chemical Reactions of HbChemical Reactions of Hb______________________________________________________

Affinity of hemoglobin to oxygenAffinity of hemoglobin to oxygen

Causes of increased affinityCauses of increased affinity::

↓ - ↓ -HH+ + (alkalis), ↓ temperature, ↓ 2,3-DPG(alkalis), ↓ temperature, ↓ 2,3-DPG..

Causes of decreased affinityCauses of decreased affinity::

↑ - ↑ -HH+ + (acids), ↑ temperature, ↑ 2,3-DPG.(acids), ↑ temperature, ↑ 2,3-DPG. Hydrogen ions and 2,3-DPG compete Hydrogen ions and 2,3-DPG compete with with OO2 2 to combine with iron of heme part to combine with iron of heme part

of Hb, so affinity of Hb for O of Hb, so affinity of Hb for O2 2 decreasesdecreases . .


22 - -With Carbon Dioxide (COWith Carbon Dioxide (CO22))::

Hb + COHb + CO2 → 2 → Carbamino compoundsCarbamino compounds

COCO2 2 attaches to protein part of Hbattaches to protein part of Hb..


33 - -With carbon monoxide (CO)With carbon monoxide (CO)::

Hb + COHb + CO → → CarboxyhemoglobinCarboxyhemoglobin

- -CO combines with iron and displaces OCO combines with iron and displaces O2 2

from Hbfrom Hb..

- - The affinity of Hb for CO is 210 times The affinity of Hb for CO is 210 times that for O that for O22, so CO prevents binding of , so CO prevents binding of

OO22 to Hb and to Hb and ↓ ↓ OO2 2 binding capacity of Hbbinding capacity of Hb . .


44 - -With strong oxidizing agentsWith strong oxidizing agents::

Met-hemoglobinMet-hemoglobin

Ferrous iron (FeFerrous iron (Fe2+2+) in Hb becomes oxidized ) in Hb becomes oxidized in presence of strong oxidizing agents to in presence of strong oxidizing agents to ferric iron (Fe ferric iron (Fe3+3+), forming met-hemoglobin, ), forming met-hemoglobin,

which can not combine with oxygen which can not combine with oxygen..

Types of HemoglobinTypes of Hemoglobin________________________________________________________

11--Adult hemoglobin (HbA)Adult hemoglobin (HbA)::

It contains 2 It contains 2 αα and 2 and 2 ββ polypeptide chains polypeptide chains

and called and called αα22 ββ2 2 HbHb..

22--Fetal hemoglobin (HbF)Fetal hemoglobin (HbF)::

It contains 2 It contains 2 αα and 2 and 2 γγ chains ( chains (αα22 γγ22Hb)Hb)

HbF has higher affinity to oxygen than HbA HbF has higher affinity to oxygen than HbA which facilitates movement of oxygen from which facilitates movement of oxygen from

maternal to fetal blood maternal to fetal blood . .

Functions of RBCsFunctions of RBCs________________________________________________________A- Functions of HbA- Functions of Hb::

11--Transport of OTransport of O22 from lung to tissues and from lung to tissues and CO CO22 from tissues to lung by carbonic from tissues to lung by carbonic

anhydrase in RBCs anhydrase in RBCs..

COCO22 + H + H22O O → → HH22COCO3 → 3 → HH++ + HCO+ HCO--

33

22--Buffer HBuffer H++ inside RBCs and can carry COinside RBCs and can carry CO2 2

with minimal change in pH. DeoxyHb is a with minimal change in pH. DeoxyHb is a stronger buffer than oxyHb as it forms stronger buffer than oxyHb as it forms weaker acidsweaker acids..

Functions of RBCsFunctions of RBCsB-Functions of MembraneB-Functions of Membrane::

11--Plastic membrane allows changes in Plastic membrane allows changes in volume of RBCs with minimal change volume of RBCs with minimal change in tension on the membrane in tension on the membrane..

22--Biconcave shape is suitable for diffusion Biconcave shape is suitable for diffusion of gases as it gives maximal surface area of gases as it gives maximal surface area

33--Membrane keeps Hb inside RBCsMembrane keeps Hb inside RBCs . . If HB passes to plasmaIf HB passes to plasma : :

--It blocks renal capillaries: renal failure. It blocks renal capillaries: renal failure. -Increases blood viscosity & blood pressure-Increases blood viscosity & blood pressure . .

--Increases colloidal osmotic pressure of Increases colloidal osmotic pressure of plasma proteins: increases heart workplasma proteins: increases heart work..

Life Span and Fate of RBCsLife Span and Fate of RBCs________________________________________________________

Life span:Life span: 120 days 120 days..

Fate:Fate: old RBCs have fragile walls and rupture old RBCs have fragile walls and rupture easily when pass through narrow blood easily when pass through narrow blood vessels especially in the spleenvessels especially in the spleen..

Hb is rapidly captured by cells of RES and Hb is rapidly captured by cells of RES and broken into heme and globinbroken into heme and globin..

Heme gives iron and protoporphyrin (bilirubin)Heme gives iron and protoporphyrin (bilirubin)

ErythropoiesisErythropoiesis________________________________________________________

It is the process of formation of RBCsIt is the process of formation of RBCs..

SitesSites::

--In fetus: In fetus: liver (mainly) and spleenliver (mainly) and spleen..

--After birth: After birth: bone marrow of long bonesbone marrow of long bones..

--By age of 20: By age of 20: Bone marrow of long bones Bone marrow of long bones can not produce RBCs can not produce RBCs..

--After age of 20: After age of 20: Bone marrow of flat bonesBone marrow of flat bones..

Stages of differentiation of RBCsStages of differentiation of RBCs________________________________________________________Pluripotential stem cells in bone marrow can Pluripotential stem cells in bone marrow can develop in any type of blood celldevelop in any type of blood cell::

Pluripotential stem cellsPluripotential stem cells

↓↓

Colony-forming unit-erythrocyte (CFU-E)Colony-forming unit-erythrocyte (CFU-E)

↓ ↓ ErythropoietinErythropoietin

ErythroblastsErythroblasts↓↓

ErythrocytesErythrocytes

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________

I -OI -O2 2 supply to tissues-role of erythropoietinsupply to tissues-role of erythropoietin::

Tissue hypoxia stimulates production of Tissue hypoxia stimulates production of erythropoietin hormone from kidney & liver erythropoietin hormone from kidney & liver which stimulates production of RBCs. e.g which stimulates production of RBCs. e.g,,

11 - -HemorrhageHemorrhage..

22 - -High altitudeHigh altitude..

33 - -AthletesAthletes..

44 - -Heart failureHeart failure..

55 - -Lung diseasesLung diseases..


A- ProteinsA- Proteins::

Proteins containing essential amino acids Proteins containing essential amino acids are needed for formation of globin part are needed for formation of globin part of Hemoglobin (Hb) of Hemoglobin (Hb)..

Decrease dietary protiens leads to failure Decrease dietary protiens leads to failure of Hb formation of Hb formation..

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________B- VitaminsB- Vitamins::

11 - -Vitamin BVitamin B12 (Cyanocobalamine or Extrinsic or Maturation Factor):

Function: Essential for transformation of mRNA into

DNA and nuclear maturation in RBCs. Absorption:

Vitamin BVitamin B12 combines with intrinsic factor in the stomach and absorbed from terminal ileum then passes to blood.


Causes of Vitamin BCauses of Vitamin B12 12 deficiencydeficiency : :

11 - -Absence of intrinsic factor due to atrophy Absence of intrinsic factor due to atrophy of gastric mucosa (pernicious anemia) of gastric mucosa (pernicious anemia)..

22 - -Liver diseasesLiver diseases..

33 - -Vitamin BVitamin B1212 deficiency in diet (rare)deficiency in diet (rare)..

Effects of Vitamin BEffects of Vitamin B12 12 deficiencydeficiency::

11 - -Megaloblastic or macrocytic anemiaMegaloblastic or macrocytic anemia.. 22 - -Decreased number of RBCs in bloodDecreased number of RBCs in blood..

33 - -Neurological symptomsNeurological symptoms..


22--Folic Acid (one of B complex vitamins)Folic Acid (one of B complex vitamins):: FunctionsFunctions::

Needed for DNA synthsesis maturation of Needed for DNA synthsesis maturation of RBCs RBCs..

Causes of Folic Acid deficiencyCauses of Folic Acid deficiency:: --Dietary deficiencyDietary deficiency..

--GIT diseases interfering with its absorptionGIT diseases interfering with its absorption.. Effects of Folic Acid deficiencyEffects of Folic Acid deficiency::

Macrocytic anemiaMacrocytic anemia..


II- DietII- Diet::

A. ProteinsA. Proteins::..

B. VitaminsB. Vitamins::

C- IronC- Iron..

D- Trace elementsD- Trace elements..

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________C-Iron:C-Iron: Functions:Functions: -- Formation of hemoglobin in RBCs and Formation of hemoglobin in RBCs and

myoglobin in muscles.myoglobin in muscles. - As co-factor for oxidation enzymes e.g., - As co-factor for oxidation enzymes e.g.,

catalase, peroxidase, cytochrome oxidase.catalase, peroxidase, cytochrome oxidase. Total body iron: Total body iron: 4 g.4 g. 70% in Hb, 3% in myoglobin, 1% in 70% in Hb, 3% in myoglobin, 1% in oxidative enzymes, 26% in liver & spleen.oxidative enzymes, 26% in liver & spleen.

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________Iron absorption, transport and storageIron absorption, transport and storage::

--Dietary iron (ferric FeDietary iron (ferric Fe3+3+) changes to absorbable ) changes to absorbable (ferrous Fe (ferrous Fe2+2+) by gastric HCl and vitamin C) by gastric HCl and vitamin C..

--Phytic acid, oxalates, phosphates prevent iron Phytic acid, oxalates, phosphates prevent iron absorption by forming insoluble saltsabsorption by forming insoluble salts..

--Iron is absorbed in upper part of small intestine Iron is absorbed in upper part of small intestine by active process. In blood iron is carried by by active process. In blood iron is carried by plasma protein (transferrin), then iron is plasma protein (transferrin), then iron is transported to bone marrow to form Hb and transported to bone marrow to form Hb and to muscles to form myoglobin. Excess iron is to muscles to form myoglobin. Excess iron is stored in liver & spleen as ferritinstored in liver & spleen as ferritin..

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________Causes of iron deficiency anemiaCauses of iron deficiency anemia::

- -Decreased iron intake in dietDecreased iron intake in diet..

- -Failure of iron absorptionFailure of iron absorption..

- -Chronic blood lossChronic blood loss..

D- Trace elementsD- Trace elements::

- -Cupper: Cupper: co-factor for synthesis of Hb but co-factor for synthesis of Hb but does not enter in its formation does not enter in its formation..

- -Cobalt: Cobalt: stimulates erythropoiesis and stimulates erythropoiesis and enters in vitamin B enters in vitamin B12 12 formationformation . .

Factors Affecting ErythropoiesisFactors Affecting Erythropoiesis________________________________________________________III- HormonesIII- Hormones::

11--thyroxinethyroxine regulates metabolism regulates metabolism..

22--AndrogensAndrogens stimulates erythropoietin stimulates erythropoietin..

33--GlucocorticoidsGlucocorticoids increase formation of RBCs increase formation of RBCs

IV-Healthy bone marrowIV-Healthy bone marrow::

Bone marrow destruction leads to decrease Bone marrow destruction leads to decrease in all types of blood cells in all types of blood cells..

V- Healthy liverV- Healthy liver::

Liver diseases are associated with anemiaLiver diseases are associated with anemia..

Blood Week 6 Dr. Walid Daoud, A. Professor. Blood ____________________________ Blood...

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