Manuscripts of Chapter-3 Blood

8/8/2019 Manuscripts of Chapter-3 Blood

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Chapter 3 blood preface1. purpose and reqirement(1) the components of blood(2) properties of blood cells

(3) blood types and blood transfusion

2. introductionBlood is composed of formed elements suspended in liquid called plasma;

Formed elements: cells and cells fragments suspended in blood, includingerythrocytes (Red blood cells), leukocyte (white blood cells), platelets.

PPT-4\PPT-5: this figure show us that the blood occupies 8% weight of whole body, the others like other fluids and tissues are 92%; the whole blood composes of blood plasma, which is approximately 55% of whole blood volume; formed elementsincluding RBC, WBC and platelets are 45%; plasma is liquid, which composed of

proteins (7%) and water(91.5%); there are mainly three kinds of protein in plasma,Albumins(54% of whole proteins of plasma),Globulins (38%) and Fibrinogen (7%)and the others(1%). There are also other solutes in the plasma, which are 1.5% totally,including electrolytes, nutrients, gases, vitamins and waste products, and so on.Formed elements are compounded by RBC, WBC and Platelets. The volume of RBC(Erythrocytes), are about 45% of blood volume, which called Hematocrit (Definition:the percentage of blood volume occupied by erythrocytes. 40%-50% for man; 37%-48% for woman); and the numbers of RBC are approximately 4.5-5.5 million per l;the numbers of WBC(Leukocytes) are 5,000-10,000 per l , and Platelets are150,000-400,000 per l; the WBC are divided into five types of cells, which are

Neutrophils (60-70% of WBC), Lymphocytes(20-25%), Monocytes(3-8%),Eosinophils(2-4%), Basophils(0.5-1.0%).

ppt-6: withdraw the blood from the vessel of elbow usually, which was added withanti-clotting reagent such as heparin or sodium citrate , and put the mixture into atube. Spinning at high speed which up to about 3,000-4,000rpm. The blood will bedivided to three layers. On the top, 55% of blood volume is plasma, which color isstraw color; the middle layer is composed of leukocytes and platelets; on the bottomof the tube, Erythrocytes are occupied about 45% of blood volume.Ppt-7: if the volume of blood in an average-size person is approximately 5.5L, so hiserythrocyte volume= 5.5L45%=2.5LSince the volume of leukocytes and platelets is very small so that normally negligible,

the plasma volume equals the difference between blood volume and erythrocytevolume, plasma volume=5.5L-2.5L=3.0L.Ppt-8: the plasma, straw-colored(A pale yellow color like that of straw ) liquidconsisting of water and dissolved solutes; among the solutes, sodium ion is the major solute in terms of its concentration; plasma also contains many other salts and ions,such as metabolites, hormones, enzymes, antibodies and other proteins.

Ppt-9: plasma proteins: in total about 7% of blood weight. Albumins : (4.2g/100ml),Globulins : (2.8g/100ml) ,

both albumins and globulins are produced by liver; they provide nonpenetrating

solutes of plasma, they produce osmotic pressure which can keep the balance of water between blood and interstitial fluid; act as buffers; bind and transport other plasma


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constituents (liquid, hormones, vitamins, metals, etc.); clotting factors; enzymes,enzyme precursors; antibodies (immune globulins); hormones.

Fibrinogen : (0.3g/100ml), involves in clotting, we will talk about in detail in the latter part of this chapter

Ppt-10 plasma pHThe plasma pH is maintained in a very narrow range ( 7.35-7.45) through numerousmechanisms. There are many buffering systems such as bicarbonate which can buffer the acids in the blood. Except for the buffering substances in blood, the lungs andkidneys also involve in maintaining the blood pH.Ppt-11 Serum, what is it? And what are differences between plasma and serum?Serum is plasma from which fibrinogen and other proteins involved in clotting have

been removed as a result of clotting. The color of Serum is same as that of plasma,fade yellow color just like straw.

Except for plasma proteins, and organic solutes, including nutrients, metabolic waste products, and hormones, plasma contains a variety of mineral electrolytes. For example, sodium, potassium, calcium, magnesium, hydrogen, chloride, bicarbonate,

phosphate, sulfates. These ions are smaller, lighter than plasma proteins, but thenumbers of those are much more than those of proteins. Therefore, ions numbersinvolve in keeping balance of water between intracellular and extracellular fluid

because of their no freely penetrating (spreading deeply or widely) in or out of cells.

Ppt-12: Then, we have learned about the components of blood, next, we will studythe properties of blood cells. Here, we will just learn three types of blood cells, RBC,WBC and platelets.

Ppt-13: we can see three kinds of blood cells in this electro microscope photograph of blood cells. Erythrocytes, platelets, leukocytes.

Ppt-14,15: Erythrocytes, their shape are unique which just like a flat biconcave(concave on both sides, thicker at the edges than in the middle) discs which are about7m in diameter and 2.2 m in thick . Special shape will provide an increased surfacearea, which relates to the transportation of oxygen and carbon dioxide. For transporting oxygen, the numbers of RBC are very large, for about 4.5-5.5 million inmale and 3.8-4.6 million in female per micro liter blood. The numbers of RBC arevery different in different ageing stage, there are more numbers in newborn babies,

and get decreasing less and less during childhood. But at the end of adolescence, thenumbers increase up to those in adults.

Ppt-16: Hemoglobin is a protein which is a mainly type of protein composed of erythrocytes. Its function is carry gases, oxygen and carbon dioxide. Theconcentrations of Hemoglobin are 16g/100l in male, and 14g/100ml in female.

Ppt-17: now, we will talk about the functions of RBC. The most important functionof RBC is transport oxygen and carbon dioxide. RBCs transport the oxygen from thelungs to the tissue, which based on hemoglobin; RBCs also transport carbon dioxide,which is produced during metabolism of tissues, to lungs. When carrying oxygen,

RBC appears fresh red color; when carrying carbon dioxide, RBC looks darkness redcolor. Fresh red color, rich in oxygen of blood is called arterial blood which usually


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flows inside the artery. Darkness red color, poor oxygen and rich in carbon dioxide of blood are called venous blood which usually flows inside vein.

Ppt-18: RBCs have a short life span only about 120d, because of their lack of nucleusand organelles. Therefore, they can neither reproduce themselves nor maintain their

normal structure for very long. Almost 1% of the bodys RBCs are replaced everyday. They are produced by red bone marrow, and destroyed in the liver, spleen.

bilirubin (An orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile(A bitter greenish-brown alkaline fluid that aidsdigestion and is secreted by the liver and stored in the gallbladder))

Ppt-19: RBCs are destroyed in liver and spleen. The components of RBCs including proteins and iron are usually used for new hemoglobin synthesis. Both vitamin B12and folic acid are necessary co-factors. They improve DNA synthesis, which isessential for maturation of RBCs.

Ppt-20: we will talk about the Hemoglobin formation materials in details.Protein: enough intake from food;Iron: 3-4g/person totally, mainly in Hb(70%). Iron for formation of Hb mostly comefrom reusing (from degrading Hb, about95%), and the others come from food (about5%, 1mg/d intake). If lack of iron, there will appear microcytic hypochromicanemia( ). See the photograph of bone marrow in themicroscope. The anemia appears small, little and red-fade color RBCs, and abnormalshape of RBCs.

Ppt-21: microcytic hypochromic anemia is caused by lack of iron, so we can intakethe iron from food such as meat, liver, shellfish, egg yolk, beans, nuts, and cereals.Losing iron is probably from urine, feces, sweat, and cells sloughed from the skin.Women lose an additional amount via menstrual blood (connected with the time whena woman menstruates each month).Store: mainly in the liver, bound up in a protein called ferritin (A protein produced inmammalian metabolism that serves to store iron in the tissues). Ferritin serves as a

buffer against iron deficiency. About 50% of the total body iron is in hemoglobin,25% is in liver ferritin. A significant iron balance is destroyed, leading to irondeficiency (for example, microcytic hypochromic anemia), or hemochromatosis(pathology in which iron accumulates in the tissues; characterized by bronzed skinand enlarged liver and diabetes mellitus and abnormalities of the pancreas and the

joints, )

Ppt-22: the maturation of RBCs is affected greatly by a persons nutritional status.Especially important for final maturation of the RBCs are two vitamins, vitamin B12and folic acid. Both of these are essential for the synthesis of DNA. Therefore, lack of either vitamin B12 or folic acid causes abnormal and diminished DNA andconsequently, failure of nuclear maturation and cell division. Furthermore, theerythroblastic cells of the bone marrow, in addition to failing to proliferate rapidly,

produce mainly larger than normal red cells called macrocytes, the cell has a flimsymembrane and is often irregular, large, and oval instead of the usual biconcave disc.These poorly formed cells can also carry oxygen normally, but they have a short life.

Vitamin B12 is absorbed from gastrointestinal tract, mainly in terminal ileum. The parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor. The


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intrinsic factor protects Vitamin B12 from digestion by the gastrointestinal secretions.Then, vitamin B12 is transported into blood. Defective B12 absorption usually causesmaturation failure anemia when absent of intrinsic factor secreted by gastric diseases.

Ppt-23: folic acid is a normal constituent of green vegetables, some fruits, and meats

(especially liver). It is easily destroyed during cooking. People with gastrointestinalabsorption abnormalities often have serious difficulty absorbing both folic acid andVitamin B12.

Ppt 24: lack of folic acid and Vitamin B12 induced DNA of RBCs failure to mature,causing megaloblastic anemia. The RBCs are abnormal, large, irregular, oval shape.

Ppt-25, 26: Erythropoiesis: the production of new RBCs.(1) Areas of the body that produce RBCs:

Prenatal: in the early weeks of embryonic life (first month): primitive, nucleatedred blood cells are produced in the yolk sac

(2) Third month(during the middle trimester of gestation), liver is the main organ for production of RBCs, but numbers are also produced in spleen and lymph nodes

(3) Fourth month(during the last mont or so of gestation and after birth,): bonemarrow , according to researches, before 5 years old, the bone marrow of essentialall bones produces RBCs; after about 20 years old, marrow of the long bones,except for the proximal portions of the humeri( )and tibiae( ), becomes quitefatty and produces no more RBCs. Beyond this age, most RBCs continues to be

produced in the marrow of the membranous bones, such as the vertebrae ,sternum( ), ribs, and ilia( ischium pubis pelvis) .

Ppt-27: there exits a balance between production and destruction of RBCs. If thenumbers of RBCs decrease, anemia occurs.

Ppt-28: how does bone marrow produce RBCs? Then next we will talk about genesisof blood cells. All the cells of the circulating blood are derived from a single type of cell called the pluripotential hematopoietic stem cell (HSCs) in bone marrow. HSCsare multipotent stem cells that give rise to all the blood cell types including myeloid(monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes,megakaryocytes/platelets, dendritic cells ) and lymphoid lineages (T-cells, B-cells, NK-cells)From the figure, it shows the successive divisions of the pluripotential cells to formthe different circulating blood cells.

Ppt-29,30: regulation of erythropoiesis(1) the role of erythropoietin: the erythropoietin(EPO) can stimulate RBCs

production, and its formation increase in response to hypoxia. In the absence of erythropoietin, hypoxia has little or no effect in stimulating RBCs production. Inthe normal person, about 90% of all EPO is formed in the kidneys; the others areformed mainly in the liver. It is not know exactly where in the kidneys theerythropoietin is formed. It likely possibility is that the renal tubular epithelialcells secrete the EPO. Then, the kidneys are removed or destroyed by the renaldisease, the person becomes very anemic because 10% of the normal EPOformed in other tissues (mainly in liver) cause only one third to one half the

RBCs formation needed by the body. EPO can also stimulate the proliferationand differentiation of the committed red cell precursor. Secondly, it can


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accelerate synthesis of hemoglobin; last, it can shorten the period of reddevelopment in the bone marrow.

(2) Other hormones: androgen (A male sex hormone, such as testosterone, that is produced in the testes and responsible for typical male sexual characteristics). Itmay be a reason that numbers of RBCs in male are more than those in female.

Thyroid hormone (The thyroid hormones, thyroxine (T4) and triiodothyronine(T3), are tyrosine-based hormones produced by the thyroid gland primarilyresponsible for regulation of metabolism. An important component in thesynthesis of thyroid hormones is iodine).

Ppt-31: Leucocytes(leukocytes) , white blood cells(WBCs). Leukocytes are themobile units of the bodys protective system, partially in the bone marrow and in thelymph tissue. After formation, they go to different parts of the body where they areneeded. They provide a rapid and potent defense against infection and inflammationinduced by infections agents

Ppt-32, 33, 34, 35: Characteristics of leukocytes: about five types of WBCs arenormally in the blood. They are classified according to their structure and affinity for various dyes. Polymorphonuclear granulocytes (have multilobed nuclei and abundantmembrane-surrounded granules), refers to the three classes: eosinophils (can take upthe red dye eosin), basophil (have an affinity for a blue dye termed basic dye),neutrophils (little affinity for either dye); monocytes (larger the granulocyte , singleoval or horseshoe-shaped mucleus and relatively few cytoplasmic granules.),lymphocytes(little cytoplasm a single relatively large nucleus).

Ppt-36,37 platelets: colorless cell fragments contain numerous granules and aremuch smaller than erythrocytes. They are budded off from the cytoplasm of themegakarycytos (large bone narrow cells). A EM picture of platelet.

Ppt-38: functions of plateletsA, play a key role in hemostasis;B, repair the minor breaks, maintains the integrity of vascular endothelium

The regulation of blood cell production:Bone marrow produces blood cells. All blood cells are descended from a single

population of bone marrow cells called pluripotent hematopoietic stemm cells(HSCs).

They differentiate into two types of pluripotent stem cells: lymphoid stem cells andmyeloid stem cells.(we can see that in the figure 3-6 page 71) . the lymphoid stemcells proliferate and differentiate into lymphocyte cells; myeloid stem cells intoerythrocytes, neutrophil, monocyte, eosinophil, basophil, and megakarocyte(platelets).

Ppt-39 Section 2 Hemostasis, blood coagulation and Fibrnolysis.

Ppt-40 hemostasis: what is the hemostasis? (dont confuse this word withhomeostasis: the balance of environment inside body), Before answer this question, I

just want to ask you anther question, what do think about bleeding and stopping

bleeding?


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Definition: a series of events involves in stopping the bleeding automatically within afew minutes when a small blood vessel is severed or ruptured, this process to arrestthe bleeding is called hemostasis . Sometimes, if the blood accumulates in the tissuesas a result of bleeding from any vessel, that is termed hematoma.

Ppt-41: mechanisms of hemostasis includes three steps:1) vascular constriction2) formation of a platelet plug;3) formation of a blood clot as a result of blood coagulation;(what are the mechanisms of hemostasis?)

Ppt-42 Step-1 of hemostasis is vascular constriction. It is nervous reflex; localmyogen spasm; and involvement of chemical factors (from wounded tissue and blood

platelets): 5-HT, endothelia and thromboxane A2.

Ppt-43 show the vascular constriction;

Ppt-44 ,45 formation of the platelet plug:

We can see this step of hemostasis in the figure 3-7 in p73. when vessel is damaged,the exposed collagen under the vessel endothelial surface causes platelets activatedand aggregated. The platelets adhere to the exposed collagen and release a variety of chemical agents (ADP, thromboxaneA2).Ppt-46 the released agents (ADP and thromboxane A2) can cause activation andaggregation of platelets by multiple changing in shape, metabolism, even somesurface proteins. Platelet activation and aggregation rapidly creates a platelet pluginside the vessel.Ppt-47 the picture shows us the step 2 of hemostasis: processing of platelet plugformation.The third step, fibrinogen, a plasma protein, plays very crucial role in the plateletaggregation.According to factors above, the platelet plug formats and completely seal small breaksin blood vessel walls. Other factors such as PGI2 (prostaglandin I2) and NO (nitricoxide) inhibit platelet aggregation and prevent the spread of platelet aggregation for adamaged site.Ppt-48 blood coagulation: or clotting, Blood coagulation just is the formation of

blood clot. What is clotting? It is the transformation of blood into a solid gel termed a

clot or thrombus and consisting mainly of a protein polymer known as fibrin.

Ppt-49: in this process of blood from liquid to colloid, a serious of enzymes involves.Coagulation factors: involved in the blood coagulation;

There are twelve clotting factors which were founded up to now.Only FIII comes from tissue and others come from plasma;FIV is Ca2+ , a nonorganic ion, others are proteins;FII, VII, IX, XII exist as proenzymes. Proenzyme is inactiveenzyme (show the proenzyme is activated ).

Ppt-51show us all clotting factors in the blood.


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Ppt-52,53: in general, clotting includes three steps: formation of prothrombinactivator; second, prothrombin is activated to thrombin; the third, fibrinogenmonomer is formed by fibrinogen in the activation of thrombin.

Ppt-54 from this figure (see figure3-11 in p76), two clotting pathway called intrinsic

and extrinsic involve in the generation of thrombin. Intrinsic clotting pathway means,all factors involve in clotting come from plasma; extrinsic clotting pathway means,factors engaged in clotting come from tissue and plasma.

From the figure, we can conclude some differences between two clotting pathway. What are differences between intrinsic and extrinsic clotting pathway?

Ppt-55 intrinsic pathway: begins from factor XII; the steps of the intrinsic clottingcascade are much more so that is very slowly; factors involving in clotting all exit invessels;

Extrinsic pathway: started from factor FIII (tissue factor); the steps of intrinsicclotting cascade are less so that is very fast; factor III is a clotting factor exiting intissue, outside of vessels;

Except for factors above, calcium is other important element involving inclotting. If calcium is deleted, the clotting would not continue. Then, in somesituations, we can block the clotting for keeping blood in liquid with sodium citrate.Sodium citrate combines calcium in blood to be a complex, so that the blood is notclotting.

Finally, it should be noted that the liver plays several important indirect rolesin clotting, and liver disease often causes serious bleeding problems. First, liver is thesite of production for many of the plasma clotting factors. Second, the liver plays acrucial role in normal intestinal absorption of the vitamin K. Vitamin K involves inclotting

.Ppt-56 this photo show us the clot, composed of a meshwork of fibrin fibers,entrapping many blood cells, platelets and plasma. From this photo, we can see thatthe clot must be very tight, hard, and large enough to block injury of the vessels ,staunching of bleeding.

Ppt-57: within a few minutes after a clot is formed, it begins to contract andcompresses the fluid inside clot within 20-60 minutes. The fluid is called serum, inwhich all fibrinogen and most of clotting factors have been removed. This is crucialdifferent between serum and plasma.

Ppt-58: the role of platelets in Hemostasis, we have talked a little bit about this before.When the vessels are wounded, platelets are triggered to adhere, aggregate, secrete,contract, finally formation of platelet plug. Platelets participate in the bloodcoagulation directly and indirectly. As above, the formation of platelet plug is thesecond step of blood coagulation (the first is constriction of wounded vessels). But the

platelet plug is very loose and small not enough to block some serious injury vessels,then the clotting is needed.Platelet also maintains the integrity and reparation of the vascular endothelium. If

platelet has some problems, the wall of vessels would be easier to wounded and the bleeding would not be easier to block.


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such as Heparin, Streptokinase, and sodium citrate, and so on. Heparin and sodiumcitrate are usually used to prevent clotting for storing of blood in vitro. Streptokinase ,an enzyme produced by some strains of streptococcus (one kind of bacteria) that canliquefy blood clots by converting plasminogen to plasmin; used medicinally in somecases of myocardial infarction (destruction of heart tissue resulting from obstruction

of the blood supply to the heart muscle) and pulmonary embolism(blockage of the pulmonary artery by foreign matter or by a blood clot).

Ppt-69,70,71,72 blood types: we will talk about blood grouping and blood transfusion.

What do you know about blood groups?The story of discovery of blood groups: before the First World War, there are many

people to die from wounded. Among them, most of people died from bleeding notfrom serious wounded. So some doctors tried to block the bleeding and give bloodsupplying. But poor acknowledgements of blood still caused many wounded patientsto die. The situation was not improved until the discovery of blood groups byAustrian Karl Landsteiner, in 1901. Karl found that there exited four types of blood inhuman. Blood transfusion must be according to patients blood group. That meansthat the antigens present on erythrocytes of donors will be not response to antibodiesin serum of recipients. So O group blood is called universal donors because he or shehas no antigens present on erythrocytes, and AB is called universal recipient becausehe or she has no antibodies in serum. Karl Landsteiner saved much more lives basingon his theory of blood groups and awarded the Nobel Prize in physiology or medicinein 1930. except for ABO blood groups, there are at least more than 30 different bloodgroups. Among these blood groups, Rh blood groups are anther important bloodgroup. This blood type was also found by Landstainer in 1940. when he did someexperiments on Rhesus Monkey, he found the new blood type except ABO. Morethan 80% of Caucasians are Rh positive, about 15% of them are Rh negative. But inChinese, less than 1% of Han are negative, most of them are positive. So we call thiskind of blood type (such as Rh and others) panda blood.

How to distinguish the blood group?There are two different antigens that present on the erythrocytes, A and B antigens(any substance (as a toxin or enzyme) that stimulates an immune response in the body (especiallythe production of antibodies)) . Persons with type A blood have A antigens; those withtype B, B antigens; those with type AB, both A and B antigens; and with type O,neither A and B antigens. In addition, there are also two different antibodies to A, Bantigens in serum. Persons dont have antibody which in response to themselvesantigens in their serum. (any of a large variety of proteins normally present in the body or

produced in response to an antigen which it neutralizes, thus producing an immune response) ; Itmeans group A serum has no antibodies to A antigens, but has antibodies to Bantigens; group B serum has no antibodies to B antigens, but has antibodies to Aantigens; group AB serum has no antibodies to both A and B; group O serum hasantibodies to both A and B.Yes, as we know, our blood types includes four groups, A, B, AB, and O; in Chinese,some research showed that the distribution of ABO blood group are A=31.3%,B=28%, O= 30.9%, AB=9.8%; in middle region of Europe, A is more than 40%,B=10%, O=40%, AB=6%

Ppt-74 : blood transfusion :


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Manuscripts of Chapter-3 Blood