Blood and its components

BLOOD ANATOMY
BY DR. SUMAIYA TAREEN

BLOOD AND ITS COMPONENTS

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

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

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

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)

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

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

Blood Plasma
Composed of approximately 90 percent water
Includes many dissolved substances
Nutrients, Salts (metal ions)
Respiratory gases
Hormones
Proteins, Waste products

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)

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

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

HAEMOGLOBIN

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

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

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

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

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

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

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

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 majorhistocompatibility antigens (MHC), are unique for each person (except for identical siblings), and can be used to identify a tissue.

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

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.

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

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

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

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

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

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

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

Platelets
Derived from ruptured multinucleate cells (megakaryocytes)
Needed for the clotting process
Normal platelet count = 300,000/mm3

Thrombopoietin stimulates myeloid stem cells to produce platelets.
Myeloid stem cells develop into megakaryocyte-colony-forming cells that develop into megakaryoblasts.
Megakaryoblasts transform into megakaryocyteswhich 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.

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

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.

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)

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

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

Prothrombinase is formed by either the intrinsic or extrinsic pathway
Final common pathway produces fibrin threads

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

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

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

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)

Blood and its components

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Blood and its components Presentation Transcript