Chapter 19

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Chapter 19
Blood
Functions of Blood
• Transport of:
– Gases, nutrients, waste products
– Processed molecules
– Regulatory molecules
•
•
•
•
Regulation of pH and osmosis
Maintenance of body temperature
Protection against foreign substances
Clot formation
Blood is circulated by pumping action of the heart, the
valves in blood vessels and the contracting action of calf
muscles.
The total blood volume of an adult female is 4 - 5 L, while
that of an adult male is 5 - 6 L. If a person loses more
than 1/3 of his blood, his life will be in danger.
Blood constitutes about 8% of the total body weight of the
human and the components may be divided with
centrifugation.
Composition of Blood
3.
Blood collection and analysis
Collection of human blood is usually performed from a superficial vein
via a venipuncture or from the fingertip or the sole.
Only when needed an arterial puncture may be performed.
The temperature of blood is about 38˚C and is slightly higher than that
of the body temperature.
Having a large quantity of proteins in plasma (7g/100 ml) and
corpuscles, blood viscosity is more than five times higher than that of
water.
The pH of blood is about 7.4.
a.
Differences between plasma and interstitial fluid
The composition of the plasma and that of interstitial
fluid is about the same, but the former has more
proteins and dissolved gases.
b.
Plasma proteins
7 g/100ml of plasma are plasma proteins.
Albumin: 58% of plasma proteins. Osmotic balance.
Globulin: 38%. Immunoglobulins, lipoproteins and
transport proteins. Antibodies and thyroid-binding
proteins.
Fibrinogen: 4%. Can form large fibrins to form blood
clot.
The 50% of plasma proteins are made in the liver.
Immunoglobulins are produced by plasma cells.
c.
The other substances in plasma
In addition of dissolved proteins, plasma
contains ions, nutrients, waste products, gases
and regulatory substances.
Formed Elements
• Red blood cells (erythrocytes)
• White blood cells (leukocytes)
– Granulocytes
• Neutrophils
• Eosinophils
• Basophils
– Agranulocytes
• Lymphocytes
• Monocytes
• Platelets (thrombocytes)
The hematocrit is about 46% for the males and about 42%
for the females.
Red blood cells - 95% of the formed elements in volume or
4.2 - 6.2 millions/mm3. Erythrocytes are enucleated and
have little organelles
White blood cells (leukocytes) - Have nuclei
Granulocytes are: neutrophils, lymphocytes, monocytes,
eosinophils and basophils
Platelets - Enucleated and have little organelles
Production of Formed Elements
• Hematopoiesis or hemopoiesis: Process of
blood cell production
• Stem cells: All formed elements derived
from single population
– Proerythroblasts: Develop into red blood cells
– Myeloblasts: Develop into basophils,
neutrophils, eosinophils
– Lymphoblasts: Develop into lymphocytes
– Monoblasts: Develop into monocytes
– Megakaryoblasts: Develop into platelets
Hematopoiesis
The major production sites of the formed elements shift:
The first 8 weeks: They start at the embryonic yolk sac and they
begin to settle in the liver, spleen, thymus, and bone marrow. They
become stem cells.
From the 8th week to fifth month: In the liver and spleen are the
primary sites of Hemopoiesis.
After the birth and among children: In most of the red bone marrow.
In the adult: In the red bone marrow of skull, ribs, sternum, vertebrae,
pelvis, proximal femur and proximal humerus.
Observe the hematopoiesis of stem cells in Fig. 19.2.
Stem cells are the origin of all formed elements.
Note the types of blast cells and the final cell types produced.
Erythrocytes
• Structure
– Biconcave, anucleate
• Components
– Hemoglobin
– Lipids, ATP, carbonic
anhydrase
• Function
– Transport oxygen from
lungs to tissues and
carbon dioxide from
tissues to lungs
Red blood cells contain:
Hemoglobin, which binds oxygen at its heme (Oxyhemoglobin) and carbon
dioxide at the N-terminal amino group as (carbaminohemoglobin),
No nucleus or organelles,
Thus, only glycolytic enzymes to form energy by Glycolysis.
Carbonic anhydrase to transport carbon dioxide.
CO2 + H2O ---- H2CO3 == H+ + H2CO3Phospholipids and membrane proteins.
Others: ATP, enzymes, 2,3-diphosphoglycerate
RBC are:
95% in volume of the formed elements.
5.4 million cells/one microliter (mm3) of blood for a man
4.8 for a woman.
260 million RBC/drop of blood
25 trillion RBC in the blood of an adult = 1/3 of all the cells in the
human.
The difference in the hematocrit mention earlier, i.e. 46 to men
and 42 to women, arises from the fact that androgens in men
stimulate erythropoiesis, while estrogens in women are
inhibitory.
The ratio of white cells to red cells is 1 to 1000.
The hematocrit vs. disease: Anemia and polycythemia
The structure of RBC
Uniquely biconcave and flexible RBC (Fig. 19-2), have
excellent exchange of gases between the cells and the
environment. Contrary to a sphere, the RBC has the
maximum surface to volume ratio.
The diameter is 7.5 microns and the thickness varies at
the edge (thick, 1.5 microns) and the center (thinner, 1
micron) making it possible to tumble and bend in tissue
capillaries.
ii.
The primary function of RBC is carried by Hemoglobin
33% of RBC is hemoglobin, Hb, an oxygen and CO2 carrying
protein.
Each Hb consists of two pairs of subunits (alpha and beta) and each
subunit has an oxygen binding heme. (Fig. 19-3)
Since the oxygen binding to heme is reversible, the number of
oxygen bound to heme depends upon the amount of oxygen in the
environment of Hb.
Thus, in the lungs, where oxygen pressure is high, Hb binds oxygen
and carry the gas to the tissues where the oxygen pressure is low.
Binding of CO2 to Hb is not at the heme, but is at the alpha
amino group of the N-terminal ends of four subunits
Binding of CO2 to Hb is not at the heme, but is at
the alpha amino group of the N-terminal ends of
four subunits.
CO2 binding is essentially opposite to that of
oxygen, but again follows the amounts of CO2 in
plasma.
The circulation of CO2 also relies on the
chemically dissolved form of CO2, i.e.,
bicarbonate. This process is facilitated by
carbonic anhydrase.
Thus, carbon dioxide may be transported by: as
carboamino hemoglobin, dissolved bicarbonate
and free carbon dioxide.
iii.
Life span and circulation
Complete circulation of an erythrocyte in a body usually
takes less than a minutes.
During this period, especially while negotiating through
tissue capillaries of less than several microns of diameter,
pulsating motion of blood flow severely stresses the
erythrocytes.
In addition, despite the presence of complex protective
mechanisms, carrying oxygen provide ample
opportunities to cause oxidative damages to the contents
of the cell.
As a consequence, the life span of a red blood cell is
about 120 days.
Since the hematocrit of a normal person is relatively
consistent, the loss of erythrocytes is compensated with
continuous erythropoiesis. (Fig. 19-5,6)
Old erythrocytes are usually phagocytically broken
down in the liver, spleen, bone marrow.
Released Hb, when it is a small quantity, will path
through the kidneys to the urine. If this level goes up,
there will be coloration of the urine - hemoglobinuria.
Erythropoiesis
• Production of red blood cells
– Stem cells
proerythroblasts
early erythroblasts
intermediate
late
reticulocytes
• Erythropoietin: Hormone to stimulate RBC
production
Recycling of RBC/hemoglobin components is as
follows: (Seeley Fig. 19.6)
Macrophage in the spleen, liver and other lymphatic
tissues phagocytically engulf erythrocytes.
Globular proteins are broken down to amino acids for
resumption.
Heme is separated form its iron and becomes biliverdin
(green) then to bilirubin to be absorbed in the livers.
Excrete it in the bile. jaundice.
Iron may be stored with the plasma protein, transferrin
and recycled.
Hemoglobin Breakdown
iv.
Erythropoiesis
When oxygen pressure in blood is lowered, erythropoiesis in
human adults starts in the red marrow of vertebrae, sternum,
ribs, skull, scapulae, pelvis and proximal limb bones. (Fig. 19-5)
Note the sequence of events in Fig. 19-6 and pay attention when
enucleation occurs.
Hemocytoblasts - myeloid stem cells - proerytrhoblast erythroblast stages - reticulocyte - erythrocyte
Erythropoiesis is regulated with erythropoietin from the kidneys,
which appears in the plasma when peripheral tissues are
exposed to low oxygen concentration, hypoxia.
c.
White blood cells - Leukocytes
They are different from RBC because of their nuclei
and lack of hemoglobin.
They are loosely divided into: (Table 19-3/Fig. 19-11)
Granulocytes: neutrophils, eosinophils, basophils
Agranulocytes Monocytes, lymphocytes
As many as 6 - 8,000 leukocytes in 1 microliter of
blood, but most of the leukocytes are found in
peripheral tissues.
ii.
General functions .
General defense: neutrophils, eosinophils,
basophils and monocytes
Specific immunity: Lymphocytes
iii.
Neutrophils:
Polymorphonuclear
Live in the circulation for only 10 - 12 hours, then
move into tissues, where they live up to 1 - 2 days.
Phagocytic and secrete lysozymes to digest
bacteria and others
iv.
Eosinophils
v.
Basophils
Reduce inflammation
Releases histamine, which promotes
inflammation
Releases heparin, which inhibits b
lood clotting.
vi.
Monocytes
Live 2 - 3 days in circulation and to
tissues as macrophages
Phagocytes foreign bodies.
Increased number of monocytes is an indication of
infection.
vii.
Lymphocytes survive years
About the same size as RBC and has a large
nucleus. Most of lymphocytes dwell in the
lymphatic system. There are three types:
1. T cells: Attack foreign bodies
2. B cells: Differentiate into plasma cells,
which secrete antibodies
3. Natural Killer cells (NK cells):
Destroy body’s own abnormal
cells
Thrombocytes
• Cell fragments
pinched off from
megakaryocytes in red
bone marrow
• Important in
preventing blood loss
– Platelet plugs
– Promoting formation
and contraction of clots
c.
Platelets
Megakaryocytes in bone marrow release their fragments into
circulation, which are called platelets.
Platelets have no nuclei.
Participate in blood clotting.
Platelets survive about 10 - 12 days in circulation and are about
150,000 - 300,000 /uL.
Thrombocytopenia is a loss of platelets and is a sign of bleeding
etc.
Thrombocytosis is excess platelets and is a sign of
infection etc.
Hemostasis
• Arrest of bleeding
• Events preventing excessive blood loss
– Vascular spasm: Vasoconstriction of damaged
blood vessels
– Platelet plug formation
– Coagulation or blood clotting
6.
Hemostasis - arrest of bleeding
Prevents loss of blood in three phases:
The vascular phase: Immediate temporary closure of a
blood vessel by contraction of vascular smooth muscles.
The platelet phase: Formation of a platelet plug by platelet
adhesion and aggregation (Fig. 19-13 and 14)
The coagulation phase: For a large blood clot formation by
the network of fibrin from fibrinogen. A large number of steps
involving many factors are required, some of which require
thrombin and Ca++.
Platelet Plug Formation
Coagulation
• Stages
– Activation of
prothrombinase
– Conversion of
prothrombin to
thrombin
– Conversion of
fibrinogen to fibrin
• Pathways
– Extrinsic
– Intrinsic
a.
The clotting process
Clotting is the phenomenon where blood cells are trapped in the
framework of fibers. (Seeley Fig. 19.10, 11)
The clotting process requires calcium and 11 different plasma
proteins, mostly enzymes. The final important step is formation of
fibrin from fibrinogen.
Once the process is triggered by tissue factor of damaged endothelial
cells, by exposing collagen fibers or rough surface, the enzymes are
successively activated to complete the clotting process - a cascade.
The extrinsic pathway is fast, 15 seconds, but the slower intrinsic
pathway add further extensive aggregation.
Thromboplastin formed by either of these pathways triggers the
common pathway that completes the coagulation process by
converting fibrinogen to fibrin.
Clot Formation
b.
Clot retraction and removal
The platelets begin to contract - clot retraction. (Seeley Fig. 19.12)
During repair process of tissue, the clot gradually dissolve fibrinolysis.
The process draws much attention, since dissolving clots in the heart
attack or stroke is clinically important.
To dissolve clot:
Activate plasminogen by tissue plasminogen activator (t-PA). --Plasmin is produced. --- Plasmin digests the fibrin strands to
dissolve the clot.
Fibrinolysis
• Clot dissolved by
activity of plasmin,
an enzyme which
hydrolyzes fibrin
Blood Grouping
• Determined by antigens (agglutinogens) on
surface of RBCs
• Antibodies (agglutinins) can bind to RBC
antigens, resulting in agglutination
(clumping) or hemolysis (rupture) of RBCs
• Groups
– ABO and Rh
7.
Blood types
Genetically determine RBC antigens rest on the surface of
the membrane.
There are at least 50 different kinds of antigens on the
surface of an RBC.
Their antibodies are found in plasma.
One set of important antigens are A and B, though type
A/B antibodies are not found in the blood until about 2
months after birth. (Fig. 19-8) ABO type.
Agglutination Reaction
Blood donor and recipient (Seeley Fig. 19.14)
Type O subject, who has no surface A/B antigen, has
been considered as a universal donor, since the
donated RBC will not be coagulated.
However, the antibodies in the plasma can interact with
the surface antigens of the recipient and may induce
minor reactions. Thus, the word “universal donor” is
misleading.
Rh Blood Group
• First studied in rhesus monkeys
• Types
– Rh positive: Have these antigens present on
surface of RBCs
– Rh negative: Do not have these antigens present
• Hemolytic disease of the newborn (HDN)
– Mother produces anti-Rh antibodies that cross
placenta and cause agglutination and hemolysis
of fetal RBCs
Diagnostic Blood Tests
• Type and crossmatch
• Complete blood count
– Red blood count
– Hemoglobin measurement
– Hematocrit measurement
• White blood count
• Differential white blood
count
• Clotting
Blood Disorders
• Erythrocytosis: RBC
overabundance
• Anemia: Deficiency of
hemoglobin
–
–
–
–
–
Iron-deficiency
Pernicious
Hemorrhagic
Hemolytic
Sickle-cell
•
•
•
•
•
•
Hemophilia
Thrombocytopenia
Leukemia
Septicemia
Malaria
Infectious
mononucleosis
• Hepatitis
8.
Sickle cell anemia (Fig. 19-4)
Genetic disease originated from a point mutation leading
to a replacement of 7th amino acid in the beta chain,
glutamic acid, to valine. Upon removing oxygen, sickle
cell hemoglobin polymerizes to form hard bundles, thus
leading to a deformation of cells. The cells may clog the
blood capillaries to trigger occlusion, thus the onset of
sickle cell episode – a severe pain.
Cells live only 20 -30 days, Hct close to 25%
May be treated with blood transfusion, injection of
hydroxyurea, or bone marrow transplant.
Sickle cell episode is observed only among the
homozygous patients and heterozygous patients show
little sign of the disease.
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