blood

• blood is transport vehicle of the cardiovascular system
• blood functions include transport, regulation, and protection
• transportation functions

  -delivers O2 and nutrients to body cells

  -transporting metabolic wastes to lungs and kidneys for elimination

  -transporting hormones from endocrine organs to target organs
• regulation functions of blood:

  -maintaining body temperature by absorbing and distributing heat

  -maintaining normal pH using buffers; alkaline reserve of bicarbonate ions

  -maintains adequate fluid volume in circulatory system
• protection functions of blood

  -preventing blood loss (plasma proteins and platelets in blood initiate clot formation)

  -prevents infections (agents of immunity are carried in blood; antibodies, complement proteins, white blood cells)
• blood is the only fluid tissue, it is also a type of connective tissue
• blood matrix is a nonliving fluid aka plasma
• cells in blood are living and are called formed elements

  • cells are suspended in plasma
  • formed elements:
  • erythrocytes (red blood cells or RBC)
  • leukocytes (white blood cells or WBC)
  • platelets
• a spun tube of blood has three layers:

  -erythrocytes on the bottom (~45% of whole blood)

  • hematocrit: percent of blood that is RBC (normal values in females is 42% ± 5%, in males it is 47% ± 5%_

  -WBCs and platelets in Buffy coat (<1%)

  • thin, whitish layer between RBCs and plasma layers

  -Plasma on top (~55%)
• -blood is sticky, opaque fluid with metallic taste

  -color varies with O2 content (high O2 level is a scarlet red and a low O2 level is a dark red)

  -pH 7.35-7.45

  -makes up ~8% of body weight

  -average volume in a female is 4-5L and in a male 5-6L
• blood plasma is straw-colored sticky fluid that is about 90% water

  -over 100 dissolved solutes

  • nutrients, gases, hormones, wastes, proteins, inorganic ions
  • plasma proteins are most abundant solutes (remain in blood, are not taken up by cells 😟; proteins produced mostly by liver; albumin males up 60% of plasma proteins and functions as carrier of other molecules, as blood buffer, and contributes to plasma osmotic pressure)
• formed elements in blood are RBCs, WBCs, and platelets

  -only WBCs are complete cells, RBCs have no nuclei or other organelles, and platelets are cell fragments

  -most formed elements survive in bloodstream only few days

  -most blood cells originate in bone marrow and don't divide 🙅‍♀️
• structural characteristics of erythrocytes

  -are small-diameter (7.5μm) cells that contribute to gas transport

  -cell has biconcave disc shape, is anucleate, and essentially has no organelles

  -filled with hemoglobin (Hb) for gas transport

  -RBC diameters are larger than some capillaries

  -contain plasma membrane protein spectrin and other proteins, spectrin provides flexibility to change
• structural characteristics of erythrocytes cont.:

  -superb💅 example of complementarity of structure and function

  -three features make for efficient gas transport:

  • bioconcave shape offers huge surface area relative to volume for gas exchange
  • hemoglobin makes up 97% of cell volume (not counting water)
  • RBCs have no mitochondria; ATP production is anaerobic so they don't consume O2 they transport
• functions of eythrocytes

  -RBCs are dedicated to respiratory gas transport

  -Hemoglobin binds reversibly with oxygen

  -normal values in females is 12-16 g/100ml and in males 13-18g/100ml

  -hemoglobin consists of red heme pigment bound to the protein globin

  • globin is composed of four polypeptide chains: two alpha and two beta chains
  • Aheme pigment is bonded to each globin chain; it gives blood its red color and each heme's central iron atom binds to one O2
• functions of erythrocytes cont

  -each Hb molecule can transport four O2

  -each RBC contains 250 million Hb molecules

  -O2 loading in lungs produces oxyhemoglobin (ruby red)

  -O2 unloading in tissues produces deoxyhemoglobin or reduced hemoglobin (dark red)

  -CO2 loading in tissues 20% of CO2 in blood binds to Hb, producing carbaminohemoglobin
• hematopoiesis: formation of all blood cells. occurs in red bone marrow; composed of reticular connective tissue and blood sinusoids. (in adult, found in axial skeleton, girdles, and proximal epiphyses of humerus and femur)
• hematopoietic stem cells (hemocytoblasts):

  -stem cells that gives rise to all formed elements

  -hormones and growth factors push cell toward specific pathway of blood cell development

  -committed cells cannot change

  -new blood cells enter blood sinusoids
• stages of erythropoiesis

  -erythropoiesis: process of formation of RBCs that takes about 15 days

  -stages of transformations

  1. hematopoietic stem cell: transforms into myeloid stem cell
  2. myeloid stem cell: transforms into proerythroblast
  3. proerythroblast: divides many times, transforming into basophilic erythoblasts
  4. basophilic erythroblasts: synthesize many ribosomes which stain blue
  5. polychromatic erythroblasts: synthesize large amounts of red-hued hemoglobin; cell now shows both pink and blue areas
• stages of erythropoiesis cont.

  (6)orthochromatic erythroblasts: contain mostly hemoglobin, (appear pink); eject most organelles; nucleus degrades, causing concave shape

  (7)reticulocytes: still contain small amount of ribosomes

  (8)mature erythocyte: in 2 days, ribosomes degrade, transforming into mature RBC

  -reticulocyte count indicates rate of RBC formation
• -too few RBCs lead to tissue hypoxia

  -too many RBCs increase blood viscosity

  ->2 million RBCs are made per second

  -balance between RBC production and destruction depends on hormonal controls and dietary requirements
• hormonal control:

  -erythropoietion (EPO): hormone that stimulates formation of RBCs

  • always small amount of EPO in blood to maintain basal rate
  • released by kidneys (some from liver) in response to hypoxia
  • at low O2 levels, oxygen-sensitive enzymes in kidney cells cannot degrade hypoxia-inducible factor (HIF), HIF can accumulate which triggers synthesis of EPO
• causes of hypoxia:

  -decreased RBC numbers due to hemorrhage or increased destruction

  -insufficient hemoglobin per RBC (ex: iron deficiency)

  -reduced availability of O2 (ex: high altitudes or lung problems such as pneumonia)

  -too many erythrocytes or high oxygen levels in blood inhibit EPO production

  -EPO causes erythrocytes to mature faster

  • testosterone enhances EPO production, resulting in higher RBC counts in males
• use of EPO increases hematocrit, which allows athletes to increase stamina and performance, which leads to them abusing artificial EPO. this is dangerous because is can increase hematocrit from 45% up to 65%, with dehydration concentrating blood even more. blood becomes like sludge and can cause clotting, stroke, or heart failure
• dietary requirements for erythropoiesis:

  -amino acids. lipids, and carbohydrates

  -iron available from diet 65% of iron is found in hemoglobin with the rest in liver, spleen, and bone marrow. free iron are toxic so iron is bound with proteins (stored in cells as ferritin and hemosiderin, transported in blood bound to protein transferrin)

  -vitamin B12 and folic acid are necessary for DNA synthesis for rapidly dividing cells such as developing RBCS
• fate and destruction of erythrocytes

  -life span: 100-120 days

  -RBCs are anucleate, so cannot synthesize new proteins, or grow or divide

  -old RBCs become fragile, and Hb begins to degenerate

  -can get trapped in smaller circulatory channels, especially in the spleen

  -macrophages in spleen engulf and breakdown dying RBCs
• fate and destruction of erythrocytes (cont.)

  -RBC breakdown: heme, iron, and globin are separated

  -iron binds to ferridin or hemosiderin and is stored for reuse

  -heme is degraded to yellow pigment bilirubin

  -liver secretes bilirubin (in bile) into intestines, where it is degraded to pigment urobilinogen (is transformed into brown pigment stercobilin that leaves body in feces)

  -globin is metabolized into amino acids, released into circulation
• most erythrocyte disorders are classified as either anemia or polycythemia
• anemia:

  -blood has abnormally low O2 carrying capacity that is too low to support normal metabolism

  -sign of problem rather than disease itself

  -symptoms: fatigue, pallor, dyspnea, and chills

  -three groups based on cause: blood loss, not enough RBCs being produced, and too many RBCs being destroyed
• anemia blood loss:

  -hemorrhagic anemia: rapid blood loss (ex. severe wound), treated by blood replacement

  -chronic hemorrhagic anemia: slight but persistent blood loss (ex. hemorrhoids, bleeding ulcer), primary problem must be treated to stop blood loss
• anemia-> not enough RBCs being produced:

  -iron deficiency anemia: can be caused by hemorrhagic anemia, but also by low iron intake or impaired absorption. RBCs produced are called microcytes (small, pale in color; cannot synthesize hemoglobin b/c lack of iron) treatment is iron supplements

  -pernicious anemia: autoimmune disease that destroys stomach mucosa that produces intrinsic factor, which is needed to absorb B12. B12 is needed to help RBCs divide, without it they will enlarge but not divide, resulting in large macrocytes. treatment: B12 injections or nasal gel. no B12 intake can cause it
• anemia not enough RBCs being produced:

  -renal anemia: caused by lack of EPO, often accompanies renal disease (kidneys cannot produce enough EPO), treatment: synthetic EPO

  -aplastic anemia: destruction or inhibition of red bone marrow; can be caused by drugs, chemicals, radiation, or viruses (usually cause is unknown); all formed element cell lines are affected (results on anemia as well as clotting and immunity defects; treatment: short-term with transfusions, long-term with transplanted stem cells
• anemia too many RBCs destroyed disorders:

  -premature lysis of RBCs, referred to as hemolytic anemias. Can be caused by incompatible transfusions or infections, hemoglobin abnormalities usually genetic disorder resulting in abnormal globin (thalassemias and sickle-cell anemia)
• anemia too many RBCs destroyed disorders:

  -thalassemias: typically found in people of Mediterranean ancestry; one globin chain is absent or faulty; RBCs are thin, delicate, and deficient in hemoglobin; many subtypes that range in severity from mild to extremely severe (very severe cases may require monthly blood transfusions)
• anemia too many RBCs destroyed disorders:

  -sickle-cell anemia: hemoglobin S (mutated hemoglobin) only 1 amino acid s wrong in globin beta chain of 146 amino acids.

  -RBCs become crescent shaped when O2 levels are low (ex. during exercise)

  -misshaped RBCs rupture easily and block small vessels which results in poor O2 delivery and pain

  -prevalent in black people of African malarial belt and descendants

  -possible benefit: people with sickle cell do not contract malaria

  -malaria kills 1 M a year, individuals w/ only one copt have milder disease and better chance of surviving malaria
• anemia too many RBCs destroyed disorders:

  -sickle cell anemia cont.

  • treatment: acute crisis treated with transfusions; inhaled nitric oxide
  • prevention of sickling: hydroxyurea induces formation of fetal hemoglobin (doesn't sickle); stem cell transplants; gene therapy; and nitric oxide for vasodilation
• polycythemia (erythrocyte disorder):

  -abnormal excess of RBCs; increases bloos viscosity, causing sluggish blood flow

  -polycythemia vera: bone marrow cancer leading to excess RBCs; hematocrit may go as high as 80%, treatment is therapeutic phlebotomy

  -secondary polycythemia: caused by low O2 levels (ex. high altitude) or increased EPO production

  -blood doping: athletes remove, store, and reinfuse RBCs before an event to increase O2 levels for stamina
• leukocytes or WBCs are the only formed element that is complete cell with nuclei and organelles

  -make up <1% of total blood volume (4800 to 10800 WBCs per μl blood)

  -function in defense against disease; can leave capillaries via diapedesis, move through tissue spaces by amoeboid motion and positive chemotaxis
• -leukocytosis: WBC count over 11,000 per μl; increase is a normal response to infection

  -leukocytes grouped into two major categories:

  • granulocytes: contain visible cytoplasmic granules
  • agranulocytes: do not contain visible cytoplasmic granules; two types

  -mnemonic to remember decreasing abundance in blood:

  Never Let Monkeys Eat Bananas
• -granulocytes: three types neutrophils, eosinophils, basophils

  -larger and shorter-lived than RBCs

  -contain lobed, rather than circular, nuclei

  -cytoplasmic granules stain specifically with Wright's stain

  -all are phagocytic to some degree