Fluids and Transport 3.

Restriction of fluid losses at injury

sites
Blood
4. Defense against toxins and
What are the components of the
pathogens
cardiovascular system, and their major
functions? 5. Stabilization of body temperature
The Cardiovascular System Whole Blood
 A circulating transport system:  Plasma:
– Is similar to, and exchanges
– a pump (the heart)
fluids with, interstitial fluid
– a conducting system (blood – Is matrix of formed elements
vessels)  Formed elements:
– 3 Types of Formed
– a fluid medium (blood)
Elements:
Functions of the Cardiovascular System: a. Red blood cells
(RBCs) or
 To transport materials to and from erythrocytes
cells: - transport
– oxygen and carbon dioxide oxygen
b. White blood cells
– nutrients (WBCs) or
– hormones leukocytes
- part of the
– immune system components immune
– waste products system
c. Platelets
- cell fragments
What are the important components and involved in
major functions of blood? clotting
 Water
Blood  Dissolved plasma proteins
– Is specialized fluid of connective  Other solutes
tissue Hemopoiesis
– Contains cells suspended in a fluid
matrix – Process of producing formed
elements
5 Functions of Blood: – By myeloid and lymphoid stem cells
1. Transport of dissolved substances Fractionation
2. Regulation of pH and ions – Process of separating whole blood
for clinical analysis:
 – into plasma and formed elements  Globulins (35%)
 Fibrinogen (4%)
3 General Characteristics of Blood
Albumins
 38°C (100.4°F) is normal
temperature Transport substances:
 High viscosity
– fatty acids
 Slightly alkaline pH (7.35–7.45)
– thyroid hormones
Blood Volume
– steroid hormones
 Blood volume (liters) = 7% of body
weight (kilograms): Globulins
– adult male: 5 to 6 liters 1. Antibodies, also called
immunoglobulins
– adult female: 4 to 5 liters
2. Transport globulins (small
molecules):
What is the composition and function of
– hormone-binding proteins
plasma?
– metalloproteins
 Plasma
– Makes up 50–60% of blood – apolipoproteins (lipoproteins)
volume
– steroid-binding proteins
– More than 90% of plasma is
water Fibrinogen
 Extracellular Fluids
– Molecules form clots
– Interstitial fluid (IF) and
– Produce long, insoluble strands of
plasma
fibrin
– Materials plasma and IF
exchange across capillary Serum
walls:
 Liquid part of a blood sample:
 Water
 Ions – in which dissolved fibrinogen
 Small solutes has converted to solid fibrin
Differences between Plasma and IF: Other Plasma Proteins
1. Levels of O2 and CO2  1% of plasma:
2. Dissolved proteins: – changing quantities of
specialized plasma proteins
 plasma proteins do not pass
through capillary walls – enzymes, hormones, and
prohormones
3 Classes of Plasma Proteins:
Origins of Plasma Proteins
 Albumins (60%)
 – 90% made in liver
– Antibodies made by plasma cells
– Peptide hormones made by
endocrine organs
Fun Fact:
 Total blood volume (liters) = 7% of
body weight (kilograms)
 About 1/2 the volume of whole
blood is cells and cell products
 Plasma resembles interstitial fluid,
but contains a unique mixture of
proteins not found in other
extracellular fluids
What are the characteristics
functions of red blood cells?
Red Blood Cells
 Red blood cells (RBCs) make up
99.9% of blood’s formed elements
Measuring RBCs
 Red blood cell count:
– reports the number of RBCs
in 1 microliter whole blood
 Hematocrit (packed cell volume,
PCV):
– percentage of RBCs
centrifuged whole blood
Normal Blood Counts:
 RBC:
 male: 4.5 – 6.3 million
– female: 4.0 – 5.5 million
 Hematocrit:
– male: 4 – 52
– female: 3 – 47
RBC Structure
 Small and highly specialized disc
 Thin in middle and thicker at edge
Importance of RBC Shape and Size
1. High surface-to-volume ratio:
 quickly absorbs and releases
oxygen
2. Discs form stacks:
– smoothes flow through
narrow blood vessels
3. Discs bend and flex entering small
and capillaries:
– 7.8 µm RBC passes through 4
µm capillary
Lifespan of RBCs
 Lack nuclei, mitochondria, and
ribosomes
 Live about 120 days
What is the structure and function of
hemoglobin?
Hemoglobin (Hb)
in  Protein molecule, transports
respiratory gases
 Normal hemoglobin (adult male):
 14 – 18 g/dl whole blood
Hemoglobin Structure
 Complex quaternary structure
 4 globular protein subunits:
 each with 1 molecule of heme
 each heme contains 1 iron ion
  Iron ions easily: Diagnosing Disorders
 associate with oxygen
 Hemoglobinuria:
(oxyhemoglobin)
– hemoglobin breakdown
 dissociate from oxygen
products in urine due to
(deoxyhemoglobin)
excess hemolysis in blood
Fetal Hemoglobin stream
 Hematuria:
 Strong form of hemoglobin found in – whole red blood cells in urine
embryos. due to kidney or tissue
 Takes oxygen from mother’s damage
hemoglobin.
Hemoglobin Recycling
Carbaminohemoglobin
 Phagocytes break hemoglobin into
 With low oxygen (peripheral components:
capillaries):  globular proteins to amino
 hemoglobin releases oxygen acids
 binds carbon dioxide and  heme to biliverdin
carries it to lungs  iron
Anemia Iron Recycling
 Hematocrit or hemoglobin levels are  To transport proteins (transferrin)
below normal
 To storage proteins (feritin and
 Is caused by several conditions hemosiderin)
Breakdown of Biliverdin
How are the components of old or  Biliverdin (green) is converted to
damaged red blood cells recycled?
bilirubin (yellow)
Recycling RBCs  Bilirubin is:
 excreted by liver (bile)
 1% of circulating RBCs wear out per
 jaundice is caused by
day:
bilirubin buildup
 about 3 million RBCs per
 converted by intestinal
second
bacteria to urobilins and
 Macrophages of liver, spleen, and
stercobilins which account
bone marrow: for the yellow brown to
 monitor RBCs brown color of stool.
 engulf RBCs before
membranes rupture
(hemolyze)

What is erythropoiesis? What are the
stages of red blood cell maturation,
and how is red blood cell production
regulated?
Erythropoiesis
 Red blood cell formation
 Occurs only in red bone marrow
(myeloid tissue)
 Stem cells mature to become RBCs
Hemocytoblasts
 Stem cells in bone marrow divide to
produce:
 myeloid stem cells:
 become RBCs, some
WBCs
 lymphoid stem cells:
 become lymphocytes
Stages of RBC Maturation
Myeloid stem cell
Mature RBC
Components
 Building red blood cells requires:
 amino acids
 iron
 vitamins B12, B6, and folic
acid
Pernicious Anemia
 Low RBC production
 Due to unavailability of vitamin B12
(remember the intrinsic factor
produced by the parietal cells in the
gastric glands of the stomach, which
is needed to absorb vitamin B12)
Stimulating Hormones
 Erythropoietin (EPO)
 Also called erythropoiesis-
stimulating hormone:
 secreted when oxygen in
peripheral tissues is low
(hypoxia)
 due to disease or high altitude
Fun Facts:

Proerythroblast  Red blood cells (RBCs) are the most

numerous cells in the body
 RBCs circulate for approximately 4
months before recycling
 Several million are produced each
Erythroblasts second
 Hemoglobin in RBCs transports:
– oxygen from lungs to
peripheral tissues
Reticulocyte – carbon dioxide from tissues
to lungs
What is blood typing, and why is it
important? What is the basis for ABO
and Rh incompatibilities?
Surface Antigens
 Are cell surface proteins that identify
cells to immune system.
 Normal cells are ignored and foreign
cells attacked.
Blood Types
 Are genetically determined
 By presence or absence of RBC
surface antigens A, B, Rh
4 Basic Blood Types:
 A (surface antigen A)
 B (surface antigen B)
 AB (antigens A and B)
 (neither A nor B)
Agglutinogens
 Antigens on surface of RBCs
 Screened by immune system
 Plasma antibodies attack
(agglutinate) foreign antigens
Blood Plasma Antibodies
 Type A:
 type B antibodies
 Type B:
– type A antibodies
 Type AB:
 neither A nor B
 Type O:
– both A and B antibodies
The Rh Factor
– Also called D antigen
– Either Rh positive (Rh+) or Rh
negative (Rh—)
– Only sensitized Rh— blood has anti-
Rh antibodies
Cross-Reaction
– Also called transfusion reaction
– Plasma antibody meets its specific
surface antigen
– Blood will agglutinate and hemolyze
– If donor and recipient blood types
not compatible
Blood Type Test
– Determines blood type and
compatibility
Cross-Match Test
– Performed on donor and recipient
blood for compatibility
– Without cross-match, type O— is
universal donor
Based on structures and functions, what
are the types of white blood cells, and
what factors regulate the production of
each type?
White Blood Cells (WBCs)
– Also called leukocytes
– Do not have hemoglobin
– Have nuclei and other organelles
WBC Functions:
 Defend against pathogens
 Remove toxins and wastes
 Attack abnormal cells
WBC Movement – Pale cytoplasm granules with:
 lysosomal enzymes
– Most WBCs in:
 bactericides (hydrogen
 connective tissue proper peroxide and superoxide)
 lymphatic system organs
Neutrophil Action
– Small numbers in blood:
– Very active, first to attack bacteria
 6000 to 9000 per microliter – Engulf pathogens
– Digest pathogens
Circulating WBCs – Release prostaglandins and
1. Migrate out of bloodstream leukotrienes
2. Have amoeboid movement – Form pus
3. Attracted to chemical stimuli Degranulation
(positive chemotaxis)
4. Some are phagocytic: – Removing granules from cytoplasm
– neutrophils, eosinophils, and – Defensins:
monocytes  peptides from lysosomes
 attack pathogen membranes
Types of WBCs:
Eosinophils
– Also called acidophils
– 2–4% of circulating WBCs
– Attack large parasites
– Excrete toxic compounds:
 nitric oxide
 cytotoxic enzymes
Eosinophil Actions

Types of WBCs: – Are sensitive to allergens

– Control inflammation with enzymes
 Neutrophils that counteract inflammatory effects
 Eosinophils of neutrophils and mast cells
 Basophils
Basophils
 Monocytes
 Lymphocytes – Are less than 1% of circulating
WBCs
– Are small
Neutrophils – Accumulate in damaged tissue
– Also called polymorphonuclear
leukocytes
– 50–70% of circulating WBCs
Basophil Actions  Natural Killer Cells (NK)
 Detect and destroy abnormal
– Release histamine:
tissue cells (cancers)
 dilates blood vessels
– Release heparin: The Differential Count of Circulating
 prevents blood clotting WBCs
Monocytes – Detects changes in WBC populations
– Infections, inflammation, and
– 2–8% of circulating WBCs
allergic reactions
– Are large and spherical
– Enter peripheral tissues and become WBC Disorders
macrophages
 Leukopenia
Macrophage Actions  abnormally low WBC count
– Engulf large particles and pathogens  Leukocytosis
– Secrete substances that attract  abnormally high WBC count
immune system cells and fibroblasts  Leukemia
to injured area  extremely high WBC count

Lymphocytes Fun Fact:

– 20–30% of circulating WBCs  RBCs outnumber WBCs 1000:1

– Are larger than RBCs  WBCs defend against infection,
– Migrate in and out of blood foreign cells, or toxins
– Mostly in connective tissues and  WBCs clean up and repair damaged
lymphatic organs tissues
 The most numerous WBCs:
Lymphocyte Actions
o neutrophils
– Are part of the body’s specific – engulf bacteria
defense system o lymphocytes
3 Classes of Lymphocytes: – are responsible for
specific defenses of
 T cells immune response
 Cell-mediated immunity
WBC Production
 Attack foreign cells directly
 B cells – All blood cells originate from
 Humoral immunity hemocytoblasts:
 Differentiate into plasma  which produce myeloid stem
cells (activated B cells that cells and lymphoid stem cells
secrete antibodies).
 Synthesize antibodies
Myeloid Stem Cells
– Differentiate into progenitor cells:
 which produce all WBCs
except lymphocytes
Lymphocytes
– Are produced by lymphoid stem cells
– Lymphopoiesis:
 the production of
lymphocytes
WBC Development
 WBCs, except monocytes:
– develop fully in bone marrow
 Monocytes:
– develop into macrophages in
peripheral tissues
Other Lymphopoiesis
– Some lymphoid stem cells migrate to
peripheral lymphoid tissues (thymus,
spleen, lymph nodes)
– Also produce lymphocytes
4 Colony-Stimulating Factors (CSFs)
– Hormones that regulate blood cell
populations:
1. M-CSF:
– stimulates monocyte
production
2. G-CSF:
– stimulates granulocyte
production
– neutrophils,
eosinophils, and
basophils
3. GM-CSF:
– stimulates granulocyte
and monocyte
production
4. Multi-CSF:
– accelerates production
of granulocytes,
monocytes, platelets,
and RBCs
What is the structure and function of
platelets, and how are they produced?
Platelets
– Cell fragments involved in human
clotting system
– Nonmammalian vertebrates have
thrombocytes (nucleated cells)
Platelet Circulation
– Circulates for 9–12 days
– Are removed by spleen
– 2/3 are reserved for emergencies
Platelet Counts
– 150,000 to 500,000 per microliter
 Thrombocytopenia:
– abnormally low platelet count
 Thrombocytosis:
– abnormally high platelet
count
Functions of Platelets:
 Release important clotting chemicals
 Temporarily patch damaged vessel
walls
 Actively contract tissue after clot
formation
Platelet Production
– Also called thrombocytopoiesis:
 occurs in bone marrow
Megakaryocytes The Platelet Phase
– Giant cells – Begins within 15 seconds after injury
– Manufacture platelets from
2 Steps of the Platelet Phase
cytoplasm
1. Platelet adhesion (attachment):
Hormonal Controls
– to sticky endothelial surfaces
 Thrombopoietin (TPO) – to basal laminae
 Inteleukin-6 (IL-6) – to exposed collagen fibers
 Multi-CSF 2. Platelet aggregation (stick
together):
– forms platelet plug
What mechanisms control blood loss after – closes small breaks
injury, and what is the reaction sequence Activated Platelets Release Clotting
in blood clotting? Compounds
Hemostasis  Adenosine diphosphate (ADP)
– The cessation of bleeding:  Thromboxane A2 and serotonin
 vascular phase  Clotting factors
 platelet phase  Platelet-derived growth factor
 coagulation phase (PDGF)
 Calcium ions
The Vascular Phase
Platelet Plug: Size Restriction (1 of 2)
– A cut triggers vascular spasm
– 30-minute contraction  Prostacyclin:
– released by endothelial cells
3 Steps of the Vascular Phase – inhibits platelet aggregation
1. Endothelial cells contract:  Inhibitory compounds:
– expose basal lamina to – released by other white blood
bloodstream cells
2. Endothelial cells release:
The Coagulation Phase
– chemical factors:
 ADP, tissue factor, – Begins 30 seconds or more after the
and prostacyclin injury
– local hormones: – Blood clotting (coagulation):
 endothelins  Involves a series of steps
– stimulate smooth muscle  converts circulating
contraction and cell division fibrinogen into insoluble
3. Endothelial cell membranes become fibrin
“sticky”:
– seal off blood flow
Blood Clot The Extrinsic Pathway
– Fibrin network – Damaged cells release tissue factor
– Covers platelet plug (TF)
– Traps blood cells – TF + other compounds = enzyme
– Seals off area complex
– Activates Factor X
Clotting Factors
The Intrinsic Pathway
– Also called procoagulants
– Proteins or ions in plasma – Activation of enzymes by collagen
– Required for normal clotting – Platelets release factors (e.g., PF–3)
– Series of reactions activate Factor X
Plasma Clotting Factors
The Common Pathway
– Enzymes activate Factor X
– Forms enzyme prothrombinase
– Converts prothrombin to thrombin
– Thrombin converts fibrinogen to
fibrin
Functions of Thrombin
– Stimulates formation of tissue factor
Cascade Reactions
 stimulates release of PF-3
– During coagulation phase (platelet factor)
– Chain reactions of enzymes and  forms positive feedback loop
proenzymes (intrinsic and extrinsic):
– Form 3 pathways  accelerates clotting
3 Coagulation Pathways Bleeding Time
 Extrinsic pathway: – Normally, a small puncture wound
– begins in the vessel wall stops bleeding in 1–4 minutes
– outside blood stream
Clotting: Area Restriction
 Intrinsic pathway:
– begins with circulating 1. Anticoagulants (plasma proteins):
proenzymes – antithrombin-III
– within bloodstream – alpha-2-macroglobulin
 Common pathway: 2. Heparin
– where intrinsic and extrinsic 3. Protein C
pathways converge – stimulates plasmin formation
an enzyme that breaks down
fibrin strands (Protein C is
 activated by
thrombomodulin)
4. Prostacyclin also inhibits platelet
aggregation.
Other Factors
– Calcium ions (Ca2+) and vitamin K
are both essential to the clotting
process
Clot Retraction
– After clot has formed:
 Platelets contract and pull
torn area together
– Takes 30–60 minutes
Fibrinolysis
– Slow process of dissolving clot:
 thrombin and tissue
plasminogen activator (t-PA):
 activate plasminogen
– Plasminogen produces plasmin:
 digests fibrin strands
Fun Fact:
 Platelets are involved in coordination
of hemostasis (blood clotting)
 Platelets, activated by abnormal
changes in local environment, release
clotting factors and other chemicals
 Hemostasis is a complex cascade that
builds a fibrous patch that can be
remodeled and removed as the
damaged area is repaired