blood physiology part i -cells
TRANSCRIPT
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Composition of Blood
Consists of formed elements (cells)suspended & carried in plasma (fluid
part) Total blood volume is about 5L Plasma is straw-colored liquid consisting
of H 20 & dissolved solutes Includes ions, metabolites, hormones,
antibodies
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Physiology of Blood
-CellsBy
Dr A. K. GuptaMD (Pediatrics)
Ex . J.N. Medical College , A.M.U,AligarhCMO (NFSG) ,Health Dept,GNCT
of Delhi
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Plasma Proteins
Constitute 7-9% of plasma Three types of plasma proteins: albumins,
globulins, & fibrinogen Albumin accounts for 60-80%
Creates colloid osmotic pressure that draws H 20 frominterstitial fluid into capillaries to maintain blood volume &pressure
Globulins carry lipids Gamma globulins are antibodies Fibrinogen serves as clotting factor
Converted to fibrin
Serum is fluid left when blood clots13-8
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Red Blood Cells (Erythrocytes )The major function of red blood cells :
Transport hemoglobin, which carriesoxygen from the lungs to the tissues.
Why Hb Should be inside RBCs :When Hb is free in the plasma, 3 % of Hbwill leak through capillaries into tissue
spaces or glomerular filtrate each time theblood passes through the capillaries.So, Hb must be inside red blood cells toremain in the human blood.
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Red blood cells are responsible formost of the acid-base buffering powerof whole blood? Explain1.RBCs contain carbonic anhydraseenzyme which catalyzes the reversiblereaction between carbon dioxide (CO 2) andwater to form carbonic acid (H 2CO 3). Thisreaction makes it possible for the water of the blood to transport CO 2 in the form of bicarbonate ion (HCO 3 -) from the tissues tothe lungs, where it is reconverted to CO 2 and expelled into the atmosphere as abody waste product.
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Shape and Size of Red Blood Cells. Biconcave discs
Mean diameter -7.8 micrometersThe average volume of the red blood cellis 90 to 95 cubic micrometers.
The shapes of red blood cells canchange as the cells squeeze throughcapillaries . Because the normal RBC has
an excess of cell membrane for thequantity of material inside, deformationwhile passing through smallest cappilariesdoes not affect the membrane,so the RedCells do not rupture passing through
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Concentration of Red Blood Cells inthe Blood. The average number of red blood cells isMen- 5,200,000 (300,000) per cummWomen- 4,700,000 (300,000) per cumm
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Quantity of Haemoglobin inthe Cells & amount of O2carried . MAXIMUM CAPACITY : 34 Gm Hb in100 ml of red cells .Men: Hb: 15 grams per 100 ml of cells;andWomen: Hb: 14 grams per 100 ml.Each gram of pure haemoglobincarries 1.34 ml of oxygen .
Therefore, in man 100 ml of blood can
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HEMOPOIESIS: INTRO Hemo: Referring to blood cells Poiesis: The development or production of The word Hemopoiesis refers to the
production & development of all the bloodcells:
Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis.
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Production of Red Blood Cells Body
Areas of the Body That Produce Red
Blood Cells. In the early weeks of embryonic life - yolk sac. During the middle trimester of
gestation : liver (main), spleen and lymphnodes (additional sites). Then, during the last month of gestationand after birth: exclusively in bone
marrow .- Till 5 yrs age : The bone marrow of essentially all bones 5 20 years age- The marrow of the long
bones, becomes fatty and produces no morered blood cells after about a e 20 ears.
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Genesis of Blood CellsPluripotential Hematopoietic StemCells, Growth Inducers, andDifferentiation Inducers. The blood cells begin their lives in the bonemarrow from pluripotential hematopoieticstem cell (PHSC).There are successive divisions of thepluripotential cells to form the differentcirculating blood cells.The intermediate-stage cells are very muchlike the pluripotential stem cells, but arecommitted to a particular line of cells and
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CLONAL HYPOTHESISPLURIPOTENT STEM CELL
STEM CELL
MULTIPLICATION COMMITTMENT
COMMITTEDSTEM CELL
COMMITTEDSTEM CELL
MULTIPLICATION
PROGENITORCELL
CFU: COLONYFORMING UNIT
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CFUA committed stem cell that produceserythrocytes is called a colony-formingunit-erythrocyte , and the abbreviation CFU-E is used to designate this type of stem cell.Colony-Forming Units which form granulocytesand monocytes have the designation CFU-GM.
Growth Inducers :Growth inducers are proteins that control thegrowth and multiplication of the different stemcells. Eg interleukin-3 , promotes growthand reproduction of all the different types of committed stem cellsDifferentiation InducersDifferentiation inducers are p roteins which
causes differentiation of one type of committed stem cell into a final adult blood
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ERYTHROPOIESIS
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FACTORS REGULATINGFACTORS REGULATINGERYTHROPOIESISERYTHROPOIESIS
SINGLE MOST IMPORTANT REGULATOR: TISSUEOXYGENATION
BURST PROMOTING ACTIVITY ERYTHROPOIETIN IRON
VITAMINS: Vitamin B 12 Folic Acid
MISCELLANEOUS
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ERYTHROPOIETINERYTHROPOIETIN A hormone pro duced by the
Kidne y. A ci rc ul ati ng Gl yc oprote in Now adays availa bl e a s Syn theti c
Epoi eti n BY RE COMBI NANTTECHNOL OGY
Ac ts m ai nly o n CFU E Inc rea se s the number of :
Nucle ate d precur sor s in th e marr ow.
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VITAMINS B 12 : Cyanoc obal amine & F ol ic
Acid: Is also cal led Ex tr insic F actor of
Cast le . Needs the Intr insic Factor from th e
Gastri c j ui ce for ab so rpti on from
Smal l I nt est in e. De ficiency cause s Pernicious (When
IF i s mi ssi ng) or Meg alo blasti cAnemia.
Sti mul ate s Er t hr o oie s is
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IRONIRON Esse nt ia l for the synthes is of
Hemo glo bin . Def ic ie ncy c ause s Mi croc yti c,
Hypo chromi c Ane mi a. The MCV ( ME AN CORP USCUL AR
VOL UME -NORMAL 90) , Co lo rInde x & MCH (MEANCORP USCUL AR HE MOGL OBIN) a relow.
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ERYTHROPOIESIS: SEQUENTIAL CHANGESI II III IVV VIP
RONORM
OBLAST
E
ARLYNB
LAST
I
NTERNB
LAST
L
ATENBL
AST
R
ETICUL
OCYTE
M
ATURER
BC
MITOCHONDRIABASOPHILIAHEMOGLOBIN
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ERYTHROID PROGENITOR CELLS
BF U-E : Bu rst Fo rming Unit Erythroc yte :
Give ri se eac h to th ousan ds ofnuc leate d e ryth roid p re curso r c ell s,in vi tr o .
Undergo some ch an ges to becom e
th e Co lon y F or ming U nit s-Er yth rocyt e ( CFU -E ) Regul ato r: Bur st Pr om ot ing Ac tivi ty
(BPA )
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ERYTHROID PROGENITOR CELLS
CFU- E: C olo ny Formi ng Uni t-Erythroc yte :
We ll d iff eren ti at ed eryt hroi d
proge ni tor cell. Pr ese nt on ly i n th e Re d Bon e
Mar row . Can form up to 64 nuc leate d
eryt hr oid precur sor cell s . Regul ato r: Erythropoietin .
Bo th the se Pro ge nit or c e ll s
cannot be dist ing uis hed ex ce pt
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Normoblastic Precursors
PROE RY THROB LAST(PRONORMOB LAST ) :
Lar ge ce ll : 15 20 Microns indiameter.
Cy to plasm is dee p v iolet- bluestai ning
Has no H emo gl ob in . Lar ge n ucle us 12 Mi crons o ccup ies
3/4 th of th e cel l vol um e. Nucle us has fi ne sti ppled re ticulu m
& man n ucle ol i .
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Normoblastic Precursors
EARLYNORMOBLAST(BASOPHILICERYTHROBLAST):
Smaller in size. Shows active Mitosis. No nucleoli in the nucleus.
Fine chromatin network with fewcondensation nodes found. Hemoglobin begins to form . Cytoplasm still Basophilic.
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Normoblastic Precursors
INTERMEDIATENORMOBLAST(REYTHROBLAST):
Has a diameter of 10 14 Microns. Shows active Mitosis. Increased Hemoglobin content in the
cytoplasm Cytoplasm is Polychromatophilic .
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Normoblastic Precursors
LATE NORMOBLAST : Diameter is 7 10 Microns. Nucleus shrinks with condensed
chromatin. Appears like a Cartwheel Cytoplasm has a Eosinophilic
appearance.
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Normoblastic Precursors RETICULOCYTE:
The penultimate stage cell. Has a fine network of reticulum like
a heavy wreath or as clumps of dots This is the remnant of the basophilic
cytoplasm, comprising RNA. In the Neonates, Count is 2
6/Cu.mm. Falls to
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Normoblastic Precursors
MATURE ERYTHROCYTE: Biconcave disc. No nucleus. About One-third filled with
Hemoglobin.
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Role of the Kidneys in Formation of
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Role of the Kidneys in Formation of Erythropoietin. 1. 90 per cent of all erythropoietin isformed in the kidneys; 10% in theliver.2. in the kidneys the erythropoietin is
formed probably in the renal tubularepithelial cells which secrete theerythropoietin,
3. when BOTH the kidneys aredestroyed by renal disease, theperson invariably becomes very
anemic because erythropoietin formed
Effect of Erythropoietin in
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Effect of Erythropoietin inErythrogenesis. Stimulate the production of Proerythroblasts from hematopoieticstem cells in the bone marrow. Speeds up Erythropoeisis by making
proerythroblasts rapdly pass throughdifferent erythroblastic stages The erythropoietin mechanism forcontrolling red blood cell production isa powerful one . In the absence of erythropoietin , fewred blood cells are formed by the bone
marrow.
Maturation of Red Blood Cells
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Maturation of Red Blood Cells-Requirement for Vitamin B 12 and FolicAcid Vitamin B 12 and folic acid are essential forthe synthesis of DNA as they formthymidine tri-phosphate. Therefore, lack of either of them cause Failure of rapid multiplication of erythroblastic cells. Production of larger than normal red cellscalled macrocytes which are fragile and thus have a short life, one half to one thirdnormal.
Pernicious Anemia.
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In pernicious anemia there is red blood cell maturationfailure due failure to absorb vitamin B 12 from the gastrointestinaltract due to atrophic gastric mucosa .
The parietal cells of the gastric glands secrete a glycoprotein calledintrinsicfactor.
The Intrinsic factor binds tightly with the vitamin B 12 . In this boundstate, the B 12 is protected from digestion by the gastrointestinalsecretions. In the bound state, intrinsic factor binds to specific receptor sites onthe brush border membranes of the mucosal cells in the ileum. Then, vitamin B 12 is transported into the blood during the next fewhours by the process of pinocytosis, carrying intrinsic factor and thevitamin together through the membrane. Lack of intrinsic factor, therefore, causes diminished bsorption of the vitaminB12. Once vitamin B 12 has been absorbed from the gastrointestinal tract,it is first
stored in the liver, then released slowly as needed by thebone marrow.
The minimum amount of vitamin B 12 required each day tomaintain normal red cell maturation
Failure of Maturation Caused by
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Failure of Maturation Caused byDeficiency of Folic Acid(Pteroylglutamic Acid). Folic acid is a normal constituent of greenvegetables, some fruits, and meats(especially liver). It is easily destroyedduring cooking.
In small intestinal disease called sprue,there is highly reduced absorbption of both folic acid and vitamin B 12
Formation of Hemoglobin
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Formation of Hemoglobin Synthesis of hemoglobin begins in theproerythroblasts and continues eveninto the reticulocyte stage of the redblood cells. When reticulocytes leave thebone marrow and pass into the bloodstream, they continue to form minutequantities of hemoglobin for another day orso until they become mature erythrocytes.
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Types of haemoglobins
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Types of haemoglobinsThe different types of chains alphachains, beta chains, gamma chains, anddelta chains form diferent types of haemoglobins:1.HbA: The most common form of hemoglobin in the adult human.It is a combination of two alpha chains and two beta chains.It has a molecular weight of 64,458.A total of four molecules of oxygen (oreight oxygen atoms) that can betrans orted b each hemo lobin
2 The types of hemoglobin chains in
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2. The types of hemoglobin chains inthe hemoglobin molecule determinethe binding affinity of the hemoglobinfor oxygen.For instance, in sickle cell anemia, theamino acid valine is substituted forglutamic acid at one point in each of thetwo beta chains.When this type of hemoglobin is exposed
to low oxygen, it forms elongatedcrystals inside the red blood cellswhich make it almost impossible for
the cells to pass through small
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Iron Metabolism
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Uses of Iron in body:1.For the formation of hemoglobin
2. For formation of other elements like e.g.,myoglobin, cytochromes, cytochrome oxidase,peroxidase, catalase
The total quantity of iron in the body averages4 to 5 grams,1. 65 % in the form of hemoglobin .2. 4 per cent is in the form of myoglobin ,3. 1 per cent is in the form of the variousheme compounds that promote intracellularoxidation,4. 0.1 per cent is combined with the proteintransferrin in the blood plasma,
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Daily Loss of Iron.
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1. Excretion in faeces: 0.6 milligram per day,2. Loss due to bleeding in woman due to menstrual loss :1.3mg/day.
Absorption of Iron from the Intestinal Tract Iron is absorbed from all parts of the small intestine, mostly bythe followingmechanism. The liver secretes moderate amounts of apotransferrin into the bile , which flows through the bile duct into theduodenum. In dudenum the apotransferrin binds with iron andwithhemoglobin and myoglobin from meat. This combination iscalled transferrin.
Transferrin binds with receptors in the membranes of the intestinal epithelial cells . Then, by pinocytosis, the transferrin molecule, carryingits iron store, is absorbed into the epithelial cells andreleased into the blood capillaries beneath these cells in theform of plasma transferrin . Iron absorption from the intestines is very slow , only a
Regulation of Total Body Iron by
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Regulation of Total Body Iron byControlling Rate of Absorption. 2.When the body has become saturatedwith iron so that essentially all apoferritinin the iron storage areas is alreadycombined with iron, the rate of additionaliron absorption from the intestinal tractbecomes greatly decreased.3.On the contrary, when the iron stores
have become depleted, the rate of absorption can increase five times normal.Thus, total body iron is regulated by
altering the rate of absorption.
Life Span and Destruction of Red Blood Cells Body :
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When red blood cells are delivered from the bone marrow intothe circulatory system, they normally circulate an average of 120 days before being destroyed.Even though mature red cells do not have a nucleus,
mitochondria, or endoplasmic reticulum, they do havecytoplasmic enzymes that are capable of metabolizingglucose and forming small amounts of adenosinetriphosphate .
These enzymes also(5)maintain pliability of the cell membrane,(6)maintain membrane transport of ions,(7)keep the iron of the cells' hemoglobin in the ferrous formrather than ferric form, and(8)prevent oxidation of the proteins in the red cells.
Once the red cell membrane becomes fragile many of thered cells self-destruct in the spleen, where they squeezethrough the red pulp of the spleen. There, the spacesbetween the structural trabeculae of the red pulp,through which most of the cells must pass, are only 3
micrometers wide, in comparison with the 8-micrometerdiameter of the red cell.
Destruction of Hemoglobin.
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g When red blood cells burst and release theirhemoglobin, the hemoglobin is phagocytizedalmost immediately by macrophages in manyparts of the body, but mainly Kupffer cells of the liver and macrophages of the spleen andbone marrow. The macrophages release iron from thehemoglobin and pass it back into the blood, tobe carried by transferrin either to the bonemarrow for the production of new red bloodcells or to the liver and other tissues for
storage in the form of ferritin. The porphyrin portion of the hemoglobinmolecule is converted by the macrophages,through a series of stages, into the bile
pigment bilirubin, which is released into theblood and later removed from the bod b
Anemias
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Anemia means deficiency of hemoglobin in theblood, which can be caused by: Blood Loss Anemia. After rapid hemorrhage, the body replaces thefluid portion of the plasma in 1 to 3 days, but thisleaves a low concentration of red blood cells. TheHb returns to normal by 3 to 6 weeks.
In chronic blood loss , a person frequentlycannot absorb enough iron from the intestines toform hemoglobin as rapidly as it is lost. Red cellsare then produced that are much smaller thannormal and have too little hemoglobin inside them,
giving rise to microcytic, hypochromic anemia , which is shown in Figure in next slide.2. Aplastic Anemia. Bone marrow aplasia means lack of functioning bone marrow. For instance, a personexposed to gamma ray radiation from a nuclear
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3. Megaloblastic Anemia.
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. g .Deficiency of Vitamin B 12 , folic acid, andabsence of intrinsic factor from thestomach mucosa lead to slow reproductionof erythroblasts in the bone marrow.As a result, the red cells grow too large,
with odd shapes, and are calledmegaloblasts . Thus, atrophy of the stomach mucosa, as
occurs in pernicious anemia, or loss of the entire stomach after surgical totalgastrectomy can lead to megaloblasticanemia.Also, atients who have intestinal s rue , in
4. Hemolytic Anemia. Due to Breakdownf
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yof RBCs.Inherited defects of Red cell membranemake the cells fragile, so that they ruptureeasily as they go through the capillaries,especially through the spleen.The number of red blood cells formedmay be normal in hemolytic diseases butthe life span of the fragile red cell is soshort that the cells are destroyed fasterthan they can be formed.Ega. hereditary spherocytosis - the red cellsare very small and spherical rather than beingbiconcave discs. These cells cannot withstandcompression forces because they do not have
the normal loose, baglike cell membrane
b. Sickle cell anemia- f
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The RBCs have an abnormal type of hemoglobincalled hemoglobin S, containing faulty beta chains inthe hemoglobin molecule,
When this hemoglobin is exposed to lowconcentrations of oxygen, it precipitates intolong crystals inside the red blood cell.These crystals elongate the cell and give it theappearance of a sickle rather than a biconcave
disc. The precipitated hemoglobin also damages thecell membrane, so that the cells become highlyfragile, leading to serious anemia.Such patients frequently experience a circle of eventscalled a sickle cell disease sicke cell crisis, " in which
low oxygen tension in the tissues causes sickling, whichleads to ruptured red cells, which causes a furtherdecrease in oxygen tension and still more sickling andred cell destruction.c. Erythroblastosis fetalis , Rh-positive red blood cells
in the fetus are attacked by antibodies from an Rh-negative mother. These antibodies make the Rh-
Effects of Anemia on Function of theCi l S
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Circulatory System . The blood viscosity falls. This decreases the resistance to blood flow inthe peripheral blood vessels, so that fargreater than normal quantities of blood flowthrough the tissues and return to the heart,thereby greatly increasing cardiac output. Moreover, hypoxia resulting fromdiminished transport of oxygen by theblood causes the peripheral tissue bloodvessels to dilate, allowing a furtherincrease in the return of blood to theheart and increasing the cardiac outputto a still higher level-sometimes three to fourtimes normal.
Thus, one of the major effects of anemia is
5. When a person with anemia begins to
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p gexercise, the heart is not capable of pumping much greater quantities of bloodthan it is already pumping. Consequently,during exercise, which greatlyincreases tissue demand for oxygen,
extreme tissue hypoxia results, andacute cardiac failure ensues
Polycythemia
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y ySecondary Polycythemia (Production of large number of RBCs) It occurs whenthere is h ypoxia in tissues because of toolittle oxygen in the breathed air, such as athigh altitudes, or because of failure of oxygen
delivery to the tissues, such as in cardiacfailure, so the erythropoeitin stiumuate blood-forming organs to automatically produce largequantities of extra red blood cells.This condition is called secondary polycythemia , and the RBCs count rises to6 - 7 million/mm 3 ie 30 per cent above normal.
Eg physiologic polycythemia , occurs in
Polycythemia Vera (Erythremia). In addition tothose people who have physiologic polycythemia
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those people who have physiologic polycythemia,others have a pathological condition known aspolycythemia vera, in which the red blood cellcount may be 7 to 8 million/mm 3 and thehematocrit may be 60 to 70 per cent instead of thenormal 40 to 45 per cent. Polycythemia vera iscaused by a genetic aberration in thehemocytoblastic cells that produce the blood cells.
The blast cells no longer stop producing red cellswhen too many cells are already present. Thiscauses excess production of red blood cells in thesame manner that a breast tumor causes excessproduction of a specific type of breast cell. It
usually causes excess production of white bloodcells and platelets as well.In polycythemia vera, not only does the hematocritincrease, but the total blood volume also increases,on some occasions to almost twice normal. As aresult, the entire vascular system becomes
Effect of Polycythemia on Function of the
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Circulatory System Because of the greatly increased
viscosity of the blood in polycythemia,blood flow through the peripheral bloodvessels is often very sluggish. The color of the skin depends to a greatextent on the quantity of blood in the skinsubpapillary venous plexus. In polycythemiavera , the quantity of blood in this plexus isgreatly increased. Further, because the bloodpasses slowly through the skin capillariesbefore entering the venous plexus, a largerthan normal quantity of hemoglobin isdeoxygenated. The blue color of all thisdeoxygenated hemoglobin masks the red
Leukocytes (White Blood Cells)
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y ( )The leukocytes, also called white blood cells, They are formed partially in the bonemarrow (granulocytes and monocytes anda few lymphocytes ) andpartially in the lymph tissue( lymphocytes and plasma cells ).After formation, they are transported in theblood to different parts of the body wherethey are needed in areas of seriousinfection and inflammation, thereby
providing a rapid and potent defence
Genesis of leukocytes
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y
Types of White Blood Cells.
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Six types of white blood cells are normallypresent in the blood. They are
1. Polymorphonuclear neutrophils, 2.Polymorphonuclear eosinophils,3. Polymorphonuclear basophils, 4. Monocytes, 5.Lymphocytes, and, 6. occasionally, Plasma cells.
The first three types of cells, thepolymorphonuclear cells, all have a granularappearance, for which reason they arecalled granulocytes, or, in clinical
terminology, "polys," because of themultiple nuclei.The granulocytes and monocytes protectthe body against invading organisms mainly
by ingesting them-that is, by phagocytosis.
Concentrations of the Different White
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Blood Cells in the Blood. Normal WBC count: Total LeukocyteCount (TLC) =7000 per ml of blood (incomparison with 5 million red blood cells).The normal % of the different typescalled Differential Leukocyte Count(DLC) is : Polymorphonuclear neutrophils 62.0%Polymorphonuclear eosinophils 2.3%Polymorphonuclear basophils 0.4%Monocytes 5.3%
L m hoc tes 30.0%
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INTRODUCTION
Leucocytes : Mobile units of thebodys defence mechanism
Formed in the : Bone marrow Lymphoid tissue.
Rapidly deployed through the
blood to areas where: Infection & Inflammation are seen.
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CLASSIFICATION OF LEUCOCYTESLEUCOCYTES
100
GRANULOCYTES AGRANULOCYTES
OSINOPHILS2.3
BASOPHILS0.4
EUTROPHILS
62
MONOCYTES5.3
LYMPHOCYTES
30
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NEUTROPHILS Most numerous Leucocytes ( 50
70%) Are 10 14 Microns in diameter. Have a constantly changing
shape due to amoeboidmovements.
The Nucleus can have 1 7 lobesconnected by a fine strand. The Cytoplasm contains 50 200
fine granules.
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NEUTROPHILIA NEUTROPHILIA: Increased
neutrophil count, can be due to: Release of stored cells from the
bone marrow reserves. Bacterial Infections causing
increased Neutropoiesis.
Exercise can cause release of stored neutrophils.
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Cytoplasmic Granules
Fine, azurophilic (Stain with bothEosin & Methylene blue) innature.
Contain enzymes such as : Cathepsins. Phosphatases.
Nucleases. Granules serve as lysosomes.
NEUTROPHILS & MONOCYTES
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NEUTROPHILS & MONOCYTES:Functions
They seek, attack and destroy invading bacteria, viruses and otherinjurious agents
Neutropils attack and destroybacteria and viruses, even in theblood.
Monocytes are immature until theyenter the tissues. There, they swellup to 80 Microns, develop lysosomes,and become Macrophages, capable of defence.
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Neutrophils & Macrophages
Diapedesis : They squeezethrough the pores of theblood vessels.
Amoeboid movement : Theymove at rates several timestheir own length!
Chemotaxis : Directedmovement cells move towards infected areas.
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EOSINOPHILS 3 8% of the
Leucocytes. Have a typical
Spectacleshaped , bilobednucleus.
Have coarse bright pink staining granules in the cytoplasm.
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8/14/2019 Blood Physiology Part I -Cells
76/119
They are parsiticidal in function. Eosinophilia or increased count
occurs in: P arasitic infestations. Allergic conditions. TPE: Tropical Pulmonary
Eosinophila.
EOSINOPHILS
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77/119
B hil
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78/119
Basophils
Are very few in number: