Download Physiology for Pharmacy Students Tortora 13th Ebaa M Alzayadneh

Physiology for Pharmacy Students
Tortora 13th
Ebaa M Alzayadneh,PhD
Blood
• Liquid connective tissue
• 3 general functions
1. Transportation
– Gases, nutrients, hormones, waste products
2. Regulation
– pH, body temperature, osmotic pressure
3. Protection
– Clotting, white blood cells, proteins
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Components of Blood
– Blood plasma – water liquid extracellular matrix
• 91.5% water, 8.5% solutes (primarily proteins)
• Hepatocytes synthesize most plasma proteins
– Albumins, fibrinogen, antibodies
• Other solutes include electrolytes, nutrients, enzymes,
hormones, gases and waste products
– Formed elements – cells and cell fragments
• Red blood cells (RBCs)
• White blood cells (WBCs)
• Platelets
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Formed Elements of Blood
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Formation of Blood Cells
• Negative feedback systems regulate the total
number of RBCs and platelets in circulation
• Abundance of WBC types based of response
to invading pathogens or foreign antigens
• Hemopoiesis or hemotopoiesis
• Red bone marrow primary site
• Pluripotent stem cells have the ability to
develop into many different types of cells
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Formation of Blood Cells
• Stem cells in bone marrow
– Reproduce themselves
– Proliferate and differentiate
• Cells enter blood stream through sinusoids
• Formed elements do not divide once they
leave red bone marrow
– Exception is lymphocytes
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Formation of Blood Cells
• Pluripotent stem cells produce
– Myeloid stem cells
• Give rise to red blood cells, platelets, monocytes,
neutrophils, eosinophils and basophils
– Lymphoid stem cells give rise to
• Lymphocytes
• Hemopoietic growth factors regulate
differentiation and proliferation
– Erythropoietin – RBCs
– Thrombopoietin – platelets
– Colony-stimulating factors (CSFs) and interleukins –
WBCs
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Red Blood Cells/ Erythrocytes
• Contain oxygen-carrying protein hemoglobin
• Production = destruction with at least 2
million new RBCs per second
• Biconcave disc – increases surface area
• Strong, flexible plasma membrane
• Glycolipids in plasma membrane responsible
for ABO and Rh blood groups
• Lack nucleus and other organelles
– No mitochondria – doesn’t use oxygen
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Hemoglobin
– Globin – 4 polypeptide chains
– Heme in each of 4 chains
– Iron ion can combine reversibly with one oxygen
molecule
– Also transports 23% of total carbon dioxide
• Combines with amino acids of globin
– Nitric oxide (NO) binds to hemoglobin
• Releases NO causing vasodilation to improve blood flow
and oxygen delivery
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Shapes of RBC and Hemoglobin
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Red Blood Cells
• RBC life cycle
– Live only about 120 days
– Cannot synthesize new components – no nucleus
– Ruptured red blood cells removed from circulation
and destroyed by fixed phagocytic macrophages in
spleen and liver
– Breakdown products recycled
• Globin’s amino acids reused
• Iron reused
• Non-iron heme ends as yellow pigment urobilin in urine
or brown pigment stercobilin in feces
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Formation and Destruction of RBC’s
Circulation for about
120 days
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3
Reused for
protein synthesis
Amino
acids
Globin
4
6
5
Fe3+
Fe3+ Transferrin
2 Heme
Fe3+
Ferritin
Transferrin
Bilirubin
9
1 Red blood cell
Biliverdin
Bilirubin
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10
death and
phagocytosis
Small
intestine
Kidney
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Urobilin
Macrophage in
spleen, liver, or
red bone marrow
Bilirubin
Urobilinogen
Stercobilin
Urine
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
8 Erythropoiesis in
red bone marrow
Bacteria
Key:
in blood
Large 14
intestine
in bile
Feces
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Erythropoiesis
– Starts in red bone marrow with
proerythroblast
– Cell near the end of
development ejects nucleus and
becomes a reticulocyte
– Develop into mature RBC within
1-2 days
– Negative feedback balances
production with destruction
– Controlled condition is amount
of oxygen delivery to tissues
– Hypoxia stimulates release of
erythropoietin
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White Blood Cells/ Leukocytes
• Have nuclei
• Do not contain hemoglobin
• Granular or agranular based on staining
highlighting large conspicuous granules
• Granular leukocytes
– Neutrophils, eosinophils, basophils
• Agranular leukocytes
– Lymphocytes and monocytes
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Types of White Blood Cells
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Functions of WBCs
– Usually live a few days
– Except for lymphocytes – live for months or years
– Far less numerous than RBCs
– Leukocytosis is a normal protective response to
invaders, strenuous exercise, anesthesia and
surgery
– Leukopenia is never beneficial
– General function to combat invaders by
phagocytosis or immune responses
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Emigration of WBCs
• Many WBCs leave the
bloodstream
• Emigration (formerly
diapedesis)
• Roll along endothelium
• Stick to and then squeeze
between endothelial cells
• Precise signals vary for
different types of WBCs
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WBCs
• Neutrophils and macrophages are active
phagocytes
– Attracted by chemotaxis
• Neutrophils respond most quickly to tissue
damage by bacteria
– Uses lysozymes, strong oxidants, defensins
• Monocytes take longer to arrive but arrive in
larger numbers and destroy more microbes
– Enlarge and differentiate into macrophages
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WBCs
• Basophils leave capillaries and release
granules containing heparin, histamine and
serotonin, at sites of inflammation
– Intensify inflammatory reaction
– Involved in hypersensitivity reactions (allergies)
• Eosinophils leave capillaries and enter tissue
fluid
– Release histaminase, phagocytize antigenantibody complexes and effective against certain
parasitic worms
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Lymphocytes
• Lymphocytes are the major soldiers of the
immune system
– B cells – destroying bacteria and inactivating their
toxins
– T cells – attack viruses, fungi, transplanted cells,
cancer cells and some bacteria
– Natural Killer (NK) cells – attack a wide variety of
infectious microbes and certain tumor cells
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Platelets/ Thrombocytes
• Myeloid stem cells develop eventually into a
megakaryocyte
• Splinters into 2000-3000 fragments
• Each fragment enclosed in a piece of plasma
membrane
• Disc-shaped with many vesicles but no
nucleus
• Help stop blood loss by forming platelet plug
• Granules contain blood clot promoting
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Stem cell transplants
• Bone marrow transplant
– Recipient's red bone marrow replaced entirely by
healthy, noncancerous cells to establish normal
blood cell counts
– Takes 2-3 weeks to begin producing enough WBCs
to fight off infections
– Graft-versus-host-disease – transplanted red bone
marrow may produce T cells that attack host
tissues
• Cord-blood transplant
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– Stem cells obtained from umbilical cord shortly
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