Blood - Summary Human Physiology: From Cells to Systems PDF

Preview

Summary

Chapter 10: Blood
...

Description

Legend: PLT  platelets PL  Plasma HMG  haemoglobin LKC  Leukocytes RBM  red bone marrow; BM  Bone marrow (may be yellow  might have messed up RBM when I meant BM) Introduction o Blood represents 8% of total body weight  avg volume of 5L in women and 5.5L in men o Consists of 3 specialized cell elements: erythrocytes (RBCs), leukocytes (WBCs) and platelets (thrombocytes) suspended in a complex of liquid plasma  All are collectively called blood cells o 99% of the cells in blood are erythrocytes  this means that the hematocrit or packed cell volume represents the % of RBCs in total blood volume. Is between 42-45% (diff btw men and women); rest of the volume is plasma (55% for men, 58% for women) o WBCs and PLT (platelets) are colourless and less dense than RBCs  packed in thin, cream coloured layer, the buffy coat on top of the packed red cell column (hematocrit)  < 1% of total cell volume Plasma o Largest part of blood  being liquid, is 90% water o Serves as a medium for materials that are carried in blood  also important in distributing heat throughout the body; this heat is generated by metabolic activity of tissues o Large number of organic and inorganic substances dissolved in PL  inorganic constituents (NA and CL; less numerous is Ca, K and others) = 1% of PL weight; organic constituents = 6-8% (most of which is protein; other subs include glucose, AAs, lipids, and vitamins), waste products, dissolved gasses and hormones o Plasma proteins  Usually stay in PL and preform many important functions  PL proteins are dispersed as colloid (large, heterogenous solutions). There inability to pass into the ISF through CAP pores means they are able to establish an osmotic gradient between blood and ISF which maintains plasma volume from being loss from CAPs to ISF  PL proteins partially responsible for PLs capacity to buffer changes in pH  Three groups of PL proteins  albumins, globulins and fibrinogen  classified according to physical and chem properties  each has a specific task

1. 2. 3. 4. 5. 



o Albumins: most abundant plasma protein  contributes most extensively to colloid osmotic pressure due to #s also bind to poorly soluble substances to help transfer them in PL o Globulins: consist of 3 subtypes  Alpha globulins and beta globulins: some bind to poorly water soluble substances to aid in transport like albumins, but these are highly specific (ex: thyroid hormone, cholesterol)  Many factors involved in blood clotting process are alpha or beta globulins  Inactivated circulating proteins, which are activated as needed by specific regulatory inputs, belong to the alpha globulin group  activated for certain specific tasks  Gama globulins: are the immunoglobulins (antibodies) which are crucial to the body’s defence mechanism o Fibrinogen: is a key factor in blood clotting Plasma proteins are synthesized in the liver

 o Erythrocytes  5 billion/ml  Structure and function  Suited to carry oxygen and to a lesser extent CO2 and hydrogen ion  Erythrocyte structure o Shaped like a donut, with a flattened center instead of a hole  shape contributes in two ways to function of oxygen transport  Concave shape provides larger SA for diffusion of O2 across the membrane than would a spherical cell  Thinness of cell enables rapid O2 diffusion between exterior and innermost regions of cell o membrane is also very flexible  can squeeze through narrow passages in CAPs o most important feature in oxygen transport is haemoglobin in RBCs  Presence of Haemoglobin o HMG is found only in RBCs; has two parts  Globin portion  protein made up of 4 polypeptide chains  Heme groups: 4 iron containing, non-protein groups bound to polypeptides





Each of the four iron atoms can combine reversibly with one O2 molecule  so one HGM molecule can pick up 4 O2 passengers in lungs  98.5% of O2 carried in blood is bound to HMG o HMG is a pigment  red when with O2 (atrial BL); darker red when lost O2 (venous BL) o HMG can also combine with  CO2  to carry it from tissues back to lungs  Acidic hydrogen ion (H+)  HMG buffers this acid so it minimally affects BL pH  CO  not normally found in BL, but if inhaled binds to O2 sites causing CO poisoning  Nitric oxide (NO)  in lungs, vasodilator NO binds to HMG  Lack of nucleus and organelles o To maximize HMG content, a single RBC is stuffed with 250 HMG molecules  means one RBC can carry 1 billion O2 molecules o RBCs have no nucleus, organelles or ribosomes  make room for more HMG o So, RBCs are basically sacs of HMG  Key erythrocyte enzymes o Glycolytic enzymes: needed for energy generation to fuel active transport mechanism involved in maintaining proper ionic concentrations within the cell  RBCs cant use the O2 they are carrying for energy  lack mitochondria for ATP generation o Carbonic anhydrase: critical for CO2 transport  catalyzes a key reaction that eventually leads to conversion of metabolic CO2 to bicarbonate ion, which is the main form CO2 is transported in the blood (this is a second way in which RBCs contribute to CO2 transport  see above) Bone marrow  Replace short lived RBCs o Erythrocytes short lifespan  Since RBCs have no special cellular machinery for repair, growth and synthesis of imp substances, they have a short lifespan  RBCs survive avg of 120 days (4mos)  As RBCs age, nonrepairable p-membrane becomes fragile and prone to rupture as it squeezes through tight spots  most old RBCs meet final demise in



the spleen, because this organ’s narrow, winding CAP network is a tight fit for fragile RBCs o Erythropoiesis  RBCs must be produced in the erythrocyte factory  the bone marrow which is the soft, highly cellular tissue that fills the internal cavities of bones  Bone marrow usually generates new RBCs by a process known as erythropoiesis at a rate to keep pace with demolition of old cells  In children, most bones filled with red bone marrow capable of RBC production  as person ages, fatty yellow bone marrow (incapable of erythropoiesis) gradually replaces the red bone marrow which remains in few isolated places such as the sternum, ribs and upper ends of the long limb bones  Red bone marrow is also source of leukocytes and PLT  Undifferentiated pluripotent stem cells reside in red marrow  continuously give rise to each type of blood cell o Erythropoietin  Reduction in O2 delivery is the primary stimulus for increased erythrocyte production  However, low O2 levels does not act on red bone marrow directly  reduced O2 to kidneys stimulates them to secrete the hormone erythropoietin (EPO) which then stimulates erythropoiesis by the bone marrow  Stimulates undifferentiated stem cells that are already committed to becoming RBCs  this elevates number of circulating RBCs and thereby restores O2 delivery  More mature cells just need a few days to reach full maturity in response to erythropoietin; less mature cells make take several weeks Blood types  Most common and important blood antigens is the A, B and O antigen system (ABO system), which is associated with the antigens present on the surface of the RBC. A second system of blood typing is the Rh (rhesus) system  ABO blood types





o Surface of RBCs contain inherited antigens that vary depending on blood type o Type A blood  contain A antigens o Type B  contain B antigens o AB  contain both A and B antigens o O  do not have any A or B RBC surface antigens o Antibodies against RBC antigens (A, B or C) begin to appear in human plasma at about 6mos of age  thus type A blood contains anti-B antibodies, type B contains anti-A antibodies o AB blood has no antibodies present o O blood has both anti-A and anti-B antibodies o These antigens and antibodies are able to cause transfusion reactions if they are mixed  this occurs in the PL o The antibodies bind with the RBCs antigens, causing agglutination of the red cells RH blood types o 6 primary antigen groups  D, C, E and d, c, e o A person with C antigen will not have c antigen  same pattern follows for the others o D antigen is frequently found in the population and is the most antigenic  thus most important o The term RH factor (RH+ and RH-) refer to the D antigen o A person either has or does not have RH factor on the surface of their erythrocytes  if they have it they are RH+ and if not RHo RH+ can receive either RH- or RH+ blood; RH- blood should only receive RH- blood o Once someone is typed as A, B, O or AB, they are further classified as + or – depending on RH factor (most people are RH+) Transfusion reaction  see diag pg. 440 (good review) o If someone receives blood from incompatible type, two different antigen-antibody interactions take place  Most serious is the effect the recipients antibodies in the PL on the donors RBCs  may result in agglutination (clumping) or haemolysis (rupture) of the attacked RBCs  Known as transfusion reaction, this can lead to clumps of incoming donor cells plugging up small BVs  also HMG from ruptured RBCs block urine



forming structures in the kidneys leading to kidney failure  Universal blood donors and recipients o Type O has no A or B antigens  so their RBCs will not be attacked by either anti-A or anti-B antibodies  thus it is a universal donor  can be transferred to ppl of any blood type o However, type O can only receive from other type O’s  this is because of their own anti-A and anti-B antibodies which would attack incoming donor RBCs of either A or B types o People of type AB blood are called universal recipients as they lack both anti-A and anti-b antibodies  but they can only donate to other AB people o But RH factor also matters  RH- blood are universal donors, but those with RH+ blood can only donate to other RH+ persons  Reticulocytes o When demand for RBCs is high (ex: during haemorrhage), the bone marrow may release large number of immature erythrocytes, known as reticulocytes into the blood to quickly meet the need o Circulate in blood for about 24 hrs before becoming mature RBCs  Synthetic erythropoietin o This hormone can now be produced in labs o Has led to a reduced need to have blood transfusions Anaemia  Refers to below normal O2 carrying capacity if the blood and is characterized by low haematocrit (% of RBCs in total BL volume)  6 causes o Nutritional anaemia  caused by a dietary deficiency of a factor needed for erythropoiesis  Ex: iron (not produced in body so needed form outside) o Pernicious anaemia: caused by inability to absorb enough vitamin B12 from digestive tract  B12 is essential for normal RBC production and maturation o Aplastic anaemia: caused by failure of bone marrow to produce enough RBCs even though all ingredients necessary for erythropoiesis are available (reduced erythropoietic capability can be caused by destruction of red bone marrow by toxic chemicals, heavy radiation



exposure, invasion of bone marrow by cancer cells, or chemotherapy). Extent on loss depends on location o Renal anaemia: may result from kidney disease  inadequate erythropoietin produced by the damaged kidneys leads to insufficient RBC production o Haemorrhagic anaemia: caused by losing a lot of blood o Haemolytic anaemia: caused by the rupture of too many circulating RBCs  haemolysis is the rupture of RBCs and occurs either because normal cells are induced to rupture by external factors (like a pathogen, ex: malaria) or because the cells are defective (as in sickle cell disease  abnormal RBC shape makes them very fragile and prone to clumping in small BVs leading to pain and tissue dmg; despite elevated erythropoiesis triggered by constant excessive loss of RBCs, production may not be able to keep pace with rate of destruction, resulting in anaemia) Polycythemia  The greater the BLs viscosity, the larger the reduction in BL flow  viscosity is determined by the number of suspended RBCs in the blood  Common method used to measure number of RBCs in blood is haematocrit  if haematocrit is 42%, this means that of that person’s BL volume, 42% is cells (primarily RBCs) and the rest is PL o Normal HCRIT for males is 42%; 38% for females  Polycythemia is a condition associated with increased haematocrit  opposite of anaemia as here we have too many RBCs. There are 2 types depending on cause o Primary polycythemia: caused by a tumor like condition of the bone marrow in which erythropoiesis proceeds at an excessive, uncontrolled rate instead of being subject to the normal erythropoietin regulatory mechanism. This increase in viscosity makes blood move more sluggishly, and may actually reduce O2 delivery  also increases total peripheral resistance which in turn increases BP and the workload on the heart o Secondary polycythemia: in contrast to primary polycythemia, is an appropriate erythropoietin induced adaptive mechanism to improve O2 carrying capacity in response to prolonged reduction in O2 delivery to the tissues  usually occurs in people living at high altitudes where less O2 is available. RBC count is lower than primary polycythemia but still elevated

o Relative polycythemia: caused when the body looses fluids but not RBCs as in dehydration that accompanies heavy sweating, diarrhea, etc. 

Leukocytes o Are WBCs  the mobile units of the body’s immune defence system o Immunity is the ability to eliminate potentially harmful foreign materials or abnormal cells o Leukocytes and their derivatives, along with a variety of PL proteins make up the immune system  internal defence system that recognizes and either destroys or neutralizes materials within the body that are foreign to the normal self o The immune system defends against invading pathogens, identifies and destroys cancer cells that arise in the body, removes worn out cells (such as aged RBCs) and tissue debris o Defence agents  WBCs largely seek out and attack  go to sites of invasion or tissue dmg o 5 types  WBCs lack hemoglobin  thus are colorless  Leukocytes vary in function, structure and number (unlike erythrocytes)  Five types  neutrophils, eosinophils, basophils, monocytes and lymphocytes  These fall into 2 categories depending on appearance of nuclei and presence or absence of granules in their cytoplasm  Polymorphonuclear granulocytes (many shaped nucleus, granulocyte containing cell): neutrophils, eosinophils and basophils  each of these named for dye affinity  eosinophils have affinity for red dye eosin; basophils have affinity for basic blue dye; neutrophils show no dye preference  Mononuclear agranulocytes (single nucleus; no granules): monocytes and lymphocytes (smallest of the leukocytes) o Production  All LKCs originate from the same undifferentiated stem cells in RBM (red bone marrow) that also give rise to RBCs and PLTs  Granulocytes and monocytes are produced only in RBM  then mature versions released into BL  Lymphocytes are originally derived from precursor cells in RBM, but most new ones are produced by lymphocytes already in lymphoid tissues (lymphocyte containing), such as lymph notes and tonsils  Total number of LKC ranges from 5-10 mil cells/ml of BL  avg WBC count  Normally, 2/3rds of circulating LKS are granulocytes, mostly neutrophils; 1/3rd is agranulocytes, mostly lymphocytes  however, total % of each type can vary depending on defence needs (different LKC produced at varying rates)





Chemical messengers arising from invaded or dmg tissue govern production rates of various LKC  specific hormones govern rates of production of various leukocytes  Ex: granulocyte colony-stimulating factor  stimulates increased replication and release of granulocytes, especially neutrophils from RBM Function and lifespans of LKC  Granulocytes  once released into BL from RBM, they stay in transit for less than a day before leaving BVs to enter tissues, where they survive another 3-4 days unless they die sooner in battle. These are derived from Myeloid stem cells o Neutrophils: major function is PGC  can also distribute bacteria catching and killing nets extracellularly.  Are the 1st responders to B infection and are important in inflammatory responses., thus an increase in circulating neutrophils accompany acute B infections  Also act as scavengers to clean up debris o Eosinophils: Major function is PGC of parasites  increase in blood associated with allergic conditions (asthma) and with parasite infestation (ex: worms); attach to worm and secrete subs to kill it o Basophils: Major function is chemotactic factor production  Structurally an functionally similar to mast cells (found in connective tissue)  Both release histamine (allergic reactions) and heparin (removal of fat particles from blood after fatty meal and preventing clotting) substances released on appropriate stimulation  Agranulocytes  derived from lymphoid stem cells o Monocytes: Major function is PGC, antigen presentation, cytokine production and cytotoxicity  Emerge from BM as immature  circulate in BL for only a day or two before settling in tissues  here they mature and greatly enlarge into macrophages (these can live for months to years, unless destroyed sooner while preforming PGC duty as only a limited amt of material can be consumed before it succumbs) o Lymphocytes: major function is lymphocyte activation, cytokine production, antigen recognition, antibody production, memory and cytotoxicity  Two types





B-lymphocytes (B cells): produce antibodies which circulate in BL and are responsible for antibody-mediated or humoral immunity  these bind to specific kinds of foreign matter and mark them for destruction  T Lymphocytes (T cells): do not produce antibodies but instead destroy targets by releasing chemicals that punch holes in the victim cells  a process called cell mediated immunity o Targets include cancer cells and viruses  Live for about 100-300 days during which they continually recycle in lymphocyte tissues, lymph and BL  don’t spend lots of time in BL as a result  Abnormalities in LKC production  Too few or too many LKC can go uncontrolled  BM can slow or stop production when exposed to certain toxins  leads to reduction in immunity  Infectious mononucleosis: increase in LKC in blood and also many LKCs become atypical in structure  Leukaemia: uncontrolled proliferation of WBCs  lead to increased susceptibility to infection (due to immature status of WBCs) and anaemia Platelets and Haemostasis o AKA thrombocytes are a third type of cellular element in blood o 250 million platelets are normally present in each ml of Bl o Are not whole cells but cell fragments shed from outer edges of extraordinarily large bone marrow bound cells known as megakaryocytes  A single one typically produces about 1000 PLTs  PLTs are essentially detached vesicles containing pieces of megakaryocyte cytoplasm wrapped in p-membrane o PLT remain function for 10 days  then removed by tissue macrophages  then PLT is replaced by BM o Hormone thrombopoietin produced in liver increases number of megakaryocytes in BM and stimulates production of more PLT o PLT do not leave BL as WBCs, but about 1/3rd are stored in spleen  can be released via sympathetic splenic contraction into BL when needed (ex: during haemorrhage) o Since PLT are cell fragments, they don’t have nuclei  but they DO have organelles and enzyme systems that generate energy and synthesize secretory products which they store in numerous granules dispersed throughout cytosol

o Also they contain high concentrations of actin and myosin, which enable them to contract  this is important in haemostasis o Haemostasis  Is the stopping of bleeding/haemorrhage from a broken BV through the sealing of any tears  bleeding takes place when pressure inside BV is greater than pressure outside it, forcing blood out through the tear  However, this only works alone in small BVs  larger BV bleeding cannot be stopped by haemostatic mechanisms alone  Involves 3 steps  vascular spasm, platelet plug and blood coagulation (clotting) o Vascular Spasm  a cut or torn BV immediately constricts  this vascular spasm slows blood flow through he defect and thus minimizes...