The Blood
The Blood
Definition
Blood is a connective tissue, not a body fluid, made of fluid (plasma)
and cellular elements (RBC, WBC, and platelets)
Its volume is 5-6 L in males and 4-5 L in females
It is slightly alkaline, with a pH of ~ 7.4
Its color varies from bright to dark red
It has a salty metallic taste
The Blood
Functions
The blood is vehicular organ that reaches all the other tissues
Transports oxygen and nutrients
Removes CO2 and other by-products of cell activity
Pivotal in maintaining homeostasis, growth and tissue repair
Participates in the defense against infection
Participates in hemostasis
Participates in body heat distribution and regulation
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
The Blood
Plasma
Straw colored fluid made of water (~90%), other contents include:
Proteins make the bulk of the solutes:
Albumens (60%), manufactured in the liver are the most abundant
Globulins (36%) are immune bodies
Fibrinogen (4%) for blood clotting
Nutrients: glucose, amino acids, lipids, cholesterol
Electrolytes: Na+, K+, Ca++, Mg++, H+, Cl-, HCO3-, PO4--, SO4-Waste: urea, creatinine, uric acid, bilirubin
Gases: O2 , CO2 , N2
Protein bound hormones
Plasma without clotting factors is called “serum”
Peripheral blood smear
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
Electron micrograph of blood smear
Pathophysiology McCance & Huether fifth edition Elsevier Mosby
The Blood
RBC
An RBC is a 7.5 micron disc shaped body with a central depression
The cell is without a nucleus or mitochondria
AN RBC contains hemoglobin and filamentous proteins attached to the
cell wall to impart flexibility on it
Antigens are embedded in the cell membrane, they decide the blood group
The RBC cytoplasm provides energy to maintain intracellular homostasis
This energy is generated mostly through anaerobic glycolysis
RBCs function is gas exchange: O2 to the tissues and CO2 to the lungs
The Blood
RBC
Structure of Hemoglobin
Each hemoglobin molecule is made up of four globin chains and four
heme molecules
Heme molecule is a porphyrin type pigment with a ferrous ion (Fe++)
Globin is a 287 amino acid protein made of two α, and two non α chains
Adult hemoglobin A is (αα/ββ), fetal hemoglobin F is ( αα/γγ)
An enzyme, 2,3 diphosphoglycerate (2,3 DPG) binds to hemoglobin
molecule, it lowers its affinity to O2
Binding of O2 to heme breaks some of the globin bonds exposing more
heme molecules to bind with O2
Structure of hemoglobin
Each heme molecule combines with one oxygen atom
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
Structure of hemoglobin and the oxygen dissociation curve
Davidson’s Principles and Practice of Medicine eighth edition, Churchill Livingstone
The Blood
RBC
Development of RBCs
Hypoxia → erythropoietin (kidney)→ red marrow of long bones→
erythroid stem cell→ erythroblasts cell division→ smaller cells loosing nucleus
and gaining hemoglobin → reticulocyte→ mature RBC
Reticulocytes contain remnants of cell organelles
Their presence in excess in the peripheral blood (>2%) indicates
excessive RBC destruction
The normal number of RBCs is 4.3-5 million/mm3 in the female and
5.1-5.8 million/mm3 in the male
The normal values for Hgb are 13-15 gm/dl for females and
14-16 gm/dl in males
Amino acids, lipids, carbohdrates, iron, vitamin B12 and folic acid are essntial
for hemoglobin synthesis
The Blood
RBC
Hemoglobin has a remarkable ability to bind with oxygen
forming oxyhemoglobin
It can also release the oxygen to the tissues becoming
deoxyhemoglobin
Hemoglobin combines with CO2 forming carbaminohemoglobin
The Blood
RBC
Destruction
Life span ~ 120 days
RBCs are phagocytosed by the reticulo-endothlial cells of the spleen
Globulin is hydrolyzed to amino acids that are recycled
Iron is removed from heme and reused to synthesize Hgb
Heme remnant converted to bilirubin
Bilirubin is conjugated with glucoronic acid, and secreted in bile
In the intestine most is converted to stercobilin and excreted
A small amount of stercobilin is absorbed by the kidney and
secreted as urobilinogen
The Blood
RBC
Disorders of RBCs
Anemia is reduced RBC count
Anemias can be caused by
RBC loss or reduced production
Hemorrhage, hemolysis, depressed bone marrow
Reduced hemoglobin content of RBCs
Iron, intrinsic factor, folic acid, or B12 deficiency
Congenital hemoglobin defects
Thalassemia, sickle cell anemia, spherocytosis
The Blood
RBC
Disorders of RBCs
Plolycythemia
Bone marrow disorder causing an increased number of
circulating RBCs and increased blood viscosity
Aplastic anemia
Results from bone marrow suppression or destruction (radiation,
drugs, chemicals)
All the blood elements are deficient
Normal and sickle cell RBC
In sickle cell disease hemoglobin S replaces the β chain
In thalassemias, the α or β chains can be absent or defective
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
The Blood
White Blood Cells (WBC)
Function
Lymphocytes are the effectors of the immune function
WBCs main function is to fight bacterial infections
WBCs are the only nucleated blood formed elements
They exercise their functions in the tissues not the blood stream
Selectines induce the WBC to adhere to capillary endothelium
WBC migrate to the tissue spaces by diapeditic movement between
endothelial cell, diapedesis is initiated by chemical attraction to
the infection site initiated by damaged cells “chemotaxis”
WBC destroy the bacterial cell wall by oxidation and digestion by
proteins “defensisns”
The Blood
White Blood Cells (WBC)
Types
The total number of WBCs is 4000 to 10,000/mm3
There two main types of WBCs: granulucytes and agranulocytes
Granulocytes, are of three types
Neutrophils (polymorphs) 50-70%, oxidize bacteria
Eosinophils, 2-4% bilobed nuclei, attack parasites
Basophils, 1% in peripheral blood, reside in the tissues,
contain histamine, involved in hypersensitivity reaction
The Blood
White Blood Cells (WBC)
Types
Agranulocytes are of two types
Lymphocytes, the smallest and second most abundant
T cells (80%) mediate cellular immunity, express CD1,2,3,4,5,7 & 8
B cells mediate humoral immunity, express immunoglobulin light
chains on the surface
Monocytes, the largest, migrate to the tissues and become
macrophages involved in cellular immunity, secrete IL1 , TNF, and
CSF
White blood cells, the granulcytes
Davidson’s The Priciples and Practice of Medicine, eigthteenth edition Churchill Livingstone
Monocytes and lymphocytes
Davidson’s The Priciples and Practice of Medicine, eighteenth edition Churchill Livingstone
The Blood
WBC
Development
WBC production is Stimulated by two types of messengers
Inerleukins: IL-3 stimulates basophils (also RBCs and platelets)
IL-5 stimulates eosinophils
IL-3, IL-4 and IL-7 stimulate B lymphocytes
IL-2, IL-4 and IL-7 stimulate T lymphocytes
Colony stimulating factors (CSF)
G-CSF stimulate neutrophils (granulocytes)
GM-CSF stimulate eosinophils and monocytes
WBC life span is 1 to 9 days
Development of blood cells
Vander’s Physiology eighth edition, Mc Graw Hill
The Blood
WBC
Leukemias
A single unspecialised WBC precursor cell “clones” itself uncontrollably
The resulting “leukemia” is therefore “monclonal”
The more undifferentiated cells produce acute (blastic) leukemias
The more differentiated (cytic) cells produce chronic types
A leukemia is called according to the producing cell
Leukemias impair the bone marrow, and other blood cells functions
Death is inevitable unless treated, it results from bleeding or sepsis
The Blood
Blood Coagulation
Coagulation is a natural mechanism that acts to diminish blood loss
from hemorrhage
Coagulation (thrombosis) especially in the microcirculation is also a
manifestation of inflammation and sepsis
Coagulation occurs in three Stages
Platelet plug
The cascade leading to fibrin (clot) formation
Clot retraction and repair (PDGF)
The Blood
Blood Coagulation
The Platelets
Structure and Function
Platelets are discoid shaped bodies of 2-4 μm
Derived from megacaryocytes arising from lineage committed stem cells
They are fragments of cells, they have no nuclei
They contain three types of granules in the cytoplasm
Alpha granules contain fibrinogen and von Willebrand factor (vWF)
Delta (dense) granules store adenosine diphosphate and serotonin
Lysosomes, contain acid hydrolases
The Blood
Blood Coagulation
The Platelets
Platelets are activated by thrombin, collagen, or ADP, they discharge
their content which leads to the formation of thrombaxane A2
Platelets adhere to exposed collagen in the presence of
von Willebrand factor (vWF)
Their life span is 8-14 days, they are destroyed in the cells of the RE
system
The structure of a platelet
Davidson’s The Priciples and Practice of Medicine, eighteenth edition Churchill Livingstone
Initial vasoconstriction and platelet plug
Vander’s
Physiology eighth edition Mc Graw Hill
v
Intrinsic and extrinsic coagulation pathways
Calcium ions are essential for the coagulation cascade
Vander’s Physiology eighth edition Mc Graw Hill
The role of the liver in blood coagulation
Vander’s Physiology eighth edition Mc graw Hill
EM of a blood clot: RBC’s and fibrin
NIBSC?Science Photo Libraray – Taken from Vander Physiology eighth edition Mc Graw Hill
Prostacyclin (PGI2 ) and nitric oxide inhibit platelet aggregation
Vander’s Physiology eighth edition Mc graw Hill
The Blood
Anticoagulation
Natural Anticoagulants
Tissue factor pathway inhibitor (TFPI)
Plasminogen - plasmin
Heparin
Antithrombin III
Protein C
Protein S
Vitamin E quinone
Natural anticoagulants also have anti inflammatory activity
The Blood
Anticoagulation
Massive blood flow
The (Intact) Endothelium
Prevents platelet contact with collagen
Displays heparin on its surface
Secretes prostacyclin (PGAI2) and nitric oxide
Activates protein C via attached thrombomodulin-thrombin complex
Secretes tissue plasminogen activator
The Blood
Anticoagulation
Heparin
Is a natural anticoagulant found in the body
Can be given by IV or subcutaneous routes for anticoagulation
Can be easily neutralized (its action reversed) by protamine
It has an antithrombin effect
Inhibits platelet functions
Its effect is measured by estimating the partial prothrombin time (PTT)
The Blood
Antigoagulation
Aspirin (ASA)
Inhibits cyclooygenase (COX) that catalyzes the formation of thrombaxane
Mature platelets can not make new thrombaxane because their COX is
blocked
Endothelial cells can synthesize new COX, therefore they are not affected
by ASA
Thrombaxane is important for platelet aggregation
Platelet function is assessed by the bleeding time
New drugs that interfere with fibrinogen/platelet binding are now
available
The Blood
Anticoagulation
Vitamin K antagonists
Warfarin, also known as coumadin
Interfere with the liver synthesis of coagulation factors
Effect measure by checking the protime (PT) now reported as
international normalized ratio (INR)
Vitamin E quinone is a potent anticoagulant
Inactivation of Factors VIII & V by thrombin activated protein C
Vander’s Physiology eighth edition Mc Graw Hill
Fibrinolysis, a mechanism for clot resorption
Vander’s Physiology eighth edition Mc Graw Hill
The Blood
Thrombolytics
Plasminogen activates plasmin, a natural fibrinolytic agent
Tissue Plasminogen Activator (t-PTA) activates plasminogen
Plasmin dissolves an already formed clot (thrombolytic therapy)
Streptokinase and Urokinase
Thrombolytic action
Streptokinase has side effects but less costly
Urokinase has less side effects but more expensive
New drugs that interfere with fibrinogen/platelet binding are now available
The Blood
Transfusion
The following blood elements can be transfused to cover a deficiency
in quantity or quality of one or more of the blood components
Whole blood does not allow time for checking for the presence of
infectious agents
Packed RBC’c for low Hb
Platelets for thrompcytopenia and bleeding
Plasma (fresh frozen) to replace deficient intrinsic factors
Cryoprecipitate for hemophilia
The Blood
Transfusion
Stored blood is acidified with citrates to prevent coagulation
It looses its platelets
Has more potassium, and accumulates ammonia
More hemolysed RBC as the storage is prolonged
Hemoglobin tends to hold more to O2 because of the reduction in
2,3 diphophoglyceric acid (2.3 DPG)
The life span of RBCs stored at 4o C is about 28 days
The Blood
Blood Types
RBC’s have surface antigens
RBC’s can be grouped according to the presence or absence of certain
antigens
There are many RBC antigens but only a A, B, AB and the Rh are of
clinical significance
Each one of the four types can be Rh positive or negative
Donor blood is mixed with recipient serum to decide compatibility,
donor cell clumping indicate incompatibility
Major blood groups
A certain group posseses its antigen on the RBC surface and antibodies against the others
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
The Blood
Transfusion
Transfusion of incompatible RBCs results in their hemolysis in the donor
This leads to blockage of the renal tubules, hypotension, fever, back pain,
and may prove fatal
This is treated by stopping the transfusion, hydration, and alkalinization of
the urine
Not every reaction to transfusion is due to infused RBC hemolysis,
other less severe reactions can occur
Identification of the RBC group
Marieb and Hoehn Human Anatomy & Physiology seventh edition Pearson Benjamin Cummings
The Blood
Rh Factor
There are no preformed Rh antibodies in Rh- individuals
They develop after exposure to Rh+ factors (antigens)
This explains the fact that an Rh+ fetus of an Rh- mother
does not usually suffer
But the Rh- mother can be sensitized to the Rh+ antigens during the
first pregnancy, especially during delivery
Subsequent fetuses can suffer from the mother’s Rh antibodies passed
to it and its blood hemolyzes
This can be prevented by giving the mother serum that blocks the Rh+
factors antigenicity
The Blood
Rh Factor
Eighty five percent of the population have Rh antigens (Rh+)
There are several Rh groups (factors, antigens)
Three groups: Rh, C, D, and E, are of clinical importance
An Rh- mother may develop antibodies against her Rh+ fetus
The Rh- mother antibodies can pass to the Rh+ fetus resulting in
hemolysis of its RBCs, a condition know as erythroblastosis fetalis
This sequence usually occurs after the first pregnancy