3. Fluids of the Body
• Cells of the body are serviced by 2 fluids
– blood
• composed of plasma and a variety of cells
• transports nutrients and wastes
– interstitial fluid
• bathes the cells of the body
• Nutrients and oxygen diffuse from the
blood into the interstitial fluid & then into
the cells
• Wastes move in the reverse direction
• Hematology is study of blood and blood
disorders
4. Physical Characteristics of
Blood
• Thicker (more viscous) than water and flows more
slowly than water
• Temperature of 100.4 degrees F
• pH 7.4 (7.35-7.45)
• 8 % of total body weight
• Blood volume
– 5 to 6 liters in average male
– 4 to 5 liters in average female
– hormonal negative feedback systems maintain constant
blood volume and osmotic pressure
5. Functions of Blood
• Transportation
– O2, CO2, metabolic wastes, nutrients, heat &
hormones
• Regulation
– helps regulate pH through buffers
– helps regulate body temperature
• coolant properties of water
• vasodilatation of surface vessels dump heat
– helps regulate water content of cells by
interactions with dissolved ions and proteins
• Protection from disease & loss of blood
6. Blood components
• 55% plasma: 7 to 8% dissolved substances
(sugars, amino acids, lipids & vitamins), ions,
dissolved gases, hormones
– most of the proteins are plasma proteins: provide a
role in balancing osmotic pressure and water flow
between the blood and extracellular fluid/tissues
– loss of plasma proteins from blood – decreases
osmotic pressure in blood and results in water flow
out of blood into tissues – swelling
– most common plasma proteins: albumin, globulins,
clotting proteins (fibrin)
7.
8. Blood: Cellular elements
• 45% of blood is the cellular elements or formed
elements
• 99% of this (44.55% of total blood) is erythrocytes or
RBCs
– formed by differentiation of hematopoietic stem cells (HSCs) in
the red bone marrow of long bones and pelvis – makes about 2
million per second!
– most numerous cell type in the body – 4 to 6 million per ul blood
– as they mature in the marrow they lose most organelles and its
nucleus
– lack mitochondria and cannot use the oxygen they transport for
ATP synthesis
– lives only about 120 days – destroyed by the liver and spleen
– liver degrades the hemoglobin to its globin component and the
heme is degraded to a pigment called bilirubin - bile
– Iron(Fe+3)
• transported in blood attached to transferrin protein
• stored in liver, muscle or spleen
• attached to ferritin or hemosiderin protein
• in bone marrow being used for hemoglobin synthesis
9. • 1% found in the Buffy coat :
– -leukocytes (WBCs) and platelets (thromobocytes)
– -neutrophils: phagocytic properties
– -release lysozymes which destroy/digest bacteria
– -release defensin proteins that act like antibiotics & poke holes in bacterial cell walls
destroying them
– -release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria
– - releases cytokines that attract other neutrophils
– -eosinophils: parasitic defense cells
– -also involved in the allergic response
– -release histaminase
– slows down inflammation caused by
– basophils
– -basophils: heparin, histamine & serotonin
– -heighten the inflammatory response and account for hypersensitivity (allergic)
reaction
– -monocytes: enter various tissues and
– differentiate into phagocytic macrophages
– -lymphocytes: T and B cells
10. Blood Plasma
Composed of approximately 90 percent
water
Includes many dissolved substances
Nutrients, Salts (metal ions)
Respiratory gases
Hormones
Proteins, Waste products
11. FORMED ELEMENTS OF
BLOOD
• Red blood cells ( erythrocytes )
• White blood cells ( leukocytes )
– granular leukocytes
• neutrophils
• eosinophils
• basophils
– agranular leukocytes
• lymphocytes = T cells, B cells, and natural
killer cells
• monocytes
• Platelets (special cell fragments)
12. Erythrocytes (Red Blood Cells)
The main function is to carry oxygen
Anatomy of circulating erythrocytes
Biconcave disks
Essentially bags of hemoglobin
Anucleate (no nucleus)
Contain very few organelles
Outnumber white blood cells 1000:1
13. • Contain oxygen-carrying protein
hemoglobin that gives blood its red color
– 1/3 of cell’s weight is hemoglobin
• Biconcave disk 8 microns in diameter
– increased surface area/volume ratio
– flexible shape for narrow passages
– no nucleus or other organelles
• no cell division or mitochondrial ATP
formation
• Normal RBC count
– male 5.4 million/drop ---- female 4.8 million/drop
– new RBCs enter circulation at 2 million/second
15. Iron-containing protein
Binds strongly, but reversibly, to oxygen
Each hemoglobin molecule has four oxygen binding sites
Each erythrocyte has 250 million hemoglobin molecules
• Globin protein consisting of 4 polypeptide chains
• One heme pigment attached to each polypeptide
chain
– each heme contains an iron ion (Fe+2) that can combine
reversibly with one oxygen molecule
16. • Each hemoglobin molecule can carry 4 oxygen
molecules from lungs to tissue cells
• Hemoglobin transports 23% of total CO2 waste from
tissue cells to lungs for release
– combines with amino acids in globin portion of Hb
• Hemoglobin transports nitric oxide & super nitric
oxide helping to regulate BP
– iron ions pick up nitric oxide (NO) & super nitric
oxide (SNO)& transport it to & from the lungs
– NO causing vasoconstriction is released in the
lungs
– SNO causing vasodilation is picked up in the
lungs
17. • Production of abnormal hemoglobin can
result in serious blood disorders such as
thalassemia and sickle cell anemia.
• The blood test, hemoglobin A1c, can be
used to monitor blood glucose levels in
diabetics
18. Hematocrit
• Percentage of blood occupied by cells
– female normal range
• 38 - 46% (average of 42%)
– male normal range
• 40 - 54% (average of 46%)
• testosterone
• Anemia
– not enough RBCs or not enough hemoglobin
• Polycythemia
– too many RBCs (over 65%)
– dehydration, tissue hypoxia, blood doping in athletes
19. Erythropoiesis: Production of
RBCs
• Erythrocyte formation, called erythropoiesis, occurs in
adult red bone marrow of certain bones.
• The main stimulus for erythropoiesis is hypoxia.
• Proerythroblast starts to produce hemoglobin
• Many steps later, nucleus is ejected & a reticulocyte is
formed
– orange in color with traces of visible rough ER
• Reticulocytes escape from bone marrow into the blood
• In 1-2 days, they eject the remaining organelles to
become a mature RBC
20. ANEMIA
• Symptoms
– oxygen-carrying capacity of blood is reduced
– fatigue, cold intolerance & paleness
• lack of O2 for ATP & heat production
• Types of anemia
– iron-deficiency = lack of absorption or loss of iron
• type of nutritional anemia
• failure to take in essential raw ingredients not made by the body
– pernicious = lack of intrinsic factor for vitamin B12 absorption from
the digestive tract
• B12 is essential for normal RBC formation and maturation
• binding of B12 to intrinsic factor allows its absorption
• intrinsic factor – synthesized by the small intestine
21. – hemorrhagic = loss of RBCs due to bleeding (ulcer)
– hemolytic = defects in cell membranes cause rupture
• rupture of too many RBCs by external factors such as malaria
(normal RBCs) or genetic disorders like sickle cell anemia
(defective RBCs)
– thalassemia = hereditary deficiency of hemoglobin
– aplastic = destruction of bone marrow (radiation/toxins)
• failure of the bone marrow to produce enough RBCs
• may selectively destroy the ability to produce RBCs only
• but may also destroy the myeloid stem cells – affect WBCs
and platelets
22. WHITE BLOOD CELLS
• Leukocytes (white blood cells or WBCs) are nucleated cells and do not
contain hemoglobin. Two principal types are granular (neutrophils,
eosinophils, basophils) and agranular (lymphocytes and monocytes).
– Granular leukocytes include eosinophils, basophils, and neutrophils
based on the straining of the granules.
– Agranular leukocytes do not have cytoplasmic granules and include
the lymphocytes and monocytes, which differentiate into
macrophages (fixed and wandering).
• Leukocytes have surface proteins, as do erythrocytes. They are called
major histocompatibility antigens (MHC), are unique for each person
(except for identical siblings), and can be used to identify a tissue.
23. • Less numerous than RBCs
– 5000 to 10,000 cells per drop of blood
– 1 WBC for every 700 RBC
• Leukocytosis is a high white blood cell count
– microbes, strenuous exercise, anesthesia or surgery
• Leukopenia is low white blood cell count
– radiation, shock or chemotherapy
• Only 2% of total WBC population is in circulating blood
at any given time
– rest is in lymphatic fluid, skin, lungs, lymph nodes &
spleen
24. • WBCs leave the blood stream by
emigration.
• Some WBCs, particularly neutrophils and
macrophages, are active in phagocytosis.
• The chemical attraction of WBCs to a
disease or injury site is termed
chemotaxis.
25. • WBCs roll along endothelium, stick to it &
squeeze between cells.
– adhesion molecules (selectins) help WBCs stick
to endothelium
• displayed near site of injury
– molecules (integrins) found on neutrophils
assist in movement through wall
• Neutrophils & macrophages phagocytize
bacteria & debris
– chemotaxis of both
• kinins from injury site & toxins
26. Types of Leukocytes
Granulocytes
Granules in their cytoplasm can be stained
Include neutrophils, eosinophils, and basophils
Agranulocytes
Lack visible cytoplasmic granules
Include lymphocytes and monocytes
27. Granulocytes
Neutrophils
Multilobed nucleus with fine granules
Act as phagocytes at active sites of infection
• Fastest response of all WBC to bacteria
• Direct actions against bacteria
– release lysozymes which destroy/digest bacteria
– release defensin proteins that act like antibiotics &
poke holes in bacterial cell walls destroying them
– release strong oxidants (bleach-like, strong
chemicals ) that destroy bacteria
28. Eosinophils
Large brick-red cytoplasmic granules
Found in repsonse to allergies and parasitic
worms
• Leave capillaries to enter tissue fluid
• Release histaminase
– slows down inflammation caused by basophils
• Attack parasitic worms
• Phagocytize antibody-antigen complexes
29. Basophils
Have histamine-containing granules
Initiate inflammation
• Involved in inflammatory and allergy reactions
• Leave capillaries & enter connective tissue as mast
cells
• Release heparin, histamine & serotonin
– heighten the inflammatory response and account for
hypersensitivity (allergic) reaction
30. Agranulocytes
Monocytes
Largest of the white blood cells
Function as macrophages
Important in fighting chronic infection
• Take longer to get to site of infection, but arrive in larger numbers
• Become wandering macrophages, once they leave the capillaries
• Destroy microbes and clean up dead tissue following an infection
31. Lymphocytes
Nucleus fills most of the cell
Play an important role in the immune response
• B cells
– destroy bacteria and their toxins
– turn into plasma cells that produces antibodies
• T cells
– attack viruses, fungi, transplanted organs, cancer cells
& some bacteria
• Natural killer cells
– attack many different microbes & some tumor cells
– destroy foreign invaders by direct attack
32. Platelets
Derived from ruptured multinucleate cells (megakaryocytes)
Needed for the clotting process
Normal platelet count = 300,000/mm3
33. • Thrombopoietin stimulates myeloid stem cells to produce
platelets.
• Myeloid stem cells develop into megakaryocyte-colony-
forming cells that develop into megakaryoblasts.
• Megakaryoblasts transform into megakaryocytes which
fragment.
• Each fragment, enclosed by a piece of cell membrane, is a
platelet (thrombocyte).
• Normal blood contains 250,000 to 400,000 platelets/mm3.
Platelets have a life span of only 5 to 9 days; aged and
dead platelets are removed by fixed macrophages in the
spleen and liver.
34. • Disc-shaped, 2 - 4 micron cell
fragment with no nucleus
• Normal platelet count is 150,000-
400,000/drop of blood
• Other blood cell counts
– 5 million red & 5-10,000 white blood
cells
35. HEMOSTASIS
• A clot is a gel consisting of a network of insoluble protein
fibers (fibrin) in which formed elements of blood are trapped.
• The chemicals involved in clotting are known as coagulation
(clotting) factors; most are in blood plasma, some are
released by platelets, and one is released from damaged
tissue cells.
• Blood clotting involves a cascade of reactions that may be
divided into three stages: formation of prothrombinase
(prothrombin activator), conversion of prothrombin into
thrombin, and conversion of soluble fibrinogen into insoluble
fibrin.
36. • Stoppage of bleeding in a quick &
localized fashion when blood vessels are
damaged
• Prevents hemorrhage (loss of a large
amount of blood)
• Methods utilized
– vascular spasm
– platelet plug formation
– blood clotting (coagulation = formation of fibrin
threads)
37. Platelet Plug Formation
• Platelets store a lot of chemicals in granules needed for platelet plug
formation
– alpha granules
• clotting factors
• platelet-derived growth factor
– cause proliferation of vascular endothelial cells, smooth
muscle & fibroblasts to repair damaged vessels
– dense granules
• ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, &
enzymes that produce thromboxane A2
• Steps in the process
– (1) platelet adhesion (2) platelet release reaction (3) platelet
aggregation
38. Blood Clotting
• Blood drawn from the body thickens into a gel
– gel separates into liquid (serum) and a clot of insoluble
fibers (fibrin) in which the cells are trapped
• If clotting occurs in an unbroken vessel is called a
thrombosis
• Substances required for clotting are Ca+2, enzymes
synthesized by liver cells and substances released by
platelets or damaged tissues
• Clotting is a cascade of reactions in which each clotting
factor activates the next in a fixed sequence resulting in the
formation of fibrin threads
– prothrombinase & Ca+2 convert prothrombin into
thrombin
– thrombin converts fibrinogen into fibrin threads
39. • Prothrombinase is formed by either
the intrinsic or extrinsic pathway
• Final common pathway produces
fibrin threads
40. Extrinsic Pathway
• Damaged tissues leak tissue factor
(thromboplastin) into bloodstream
• Prothrombinase forms in seconds
• In the presence of Ca+2, clotting factor X
combines with V to form prothrombinase
41. Intrinsic Pathway
• Activation occurs
– endothelium is damaged &
platelets come in contact with
collagen of blood vessel wall
– platelets damaged & release
phospholipids
• Requires several minutes for reaction
to occur
• Substances involved: Ca+2 and
clotting factors XII, X and V
42. Final Common Pathway
• Prothrombinase and Ca+2
– catalyze the conversion of prothrombin to
thrombin
• Thrombin
– in the presence of Ca+2 converts soluble
fibrinogen to insoluble fibrin threads
– activates fibrin stabilizing factor XIII
– positive feedback effects of thrombin
• accelerates formation of prothrombinase
• activates platelets to release phospholipids
43. Anticoagulants and Thrombolytic
Agents
• Anticoagulants suppress or prevent blood clotting
– heparin
• administered during hemodialysis and surgery
– warfarin (Coumadin)
• antagonist to vitamin K so blocks synthesis of clotting
factors
• slower than heparin
– stored blood in blood banks treated with citrate phosphate
dextrose (CPD) that removes Ca+2
• Thrombolytic agents are injected to dissolve clots
– directly or indirectly activate plasminogen
– streptokinase or tissue plasminogen activator (t-PA)
