Blood
• Blood accounts for approximately 8% of
body weight
• The pH of blood is 7.35–7.45
• Temperature is 38C, slightly higher than
“normal” body temperature
• Average volume of blood is 5–6 L for
males, and 4–5 L for females
• RBC circulate for approximately 4 months.
Functions of Circulatory System
• Transport
– O2, CO2, nutrients, wastes, hormones, and heat
• Protection
– WBCs, antibodies, and platelets
• Regulation fluid volume in the circulatory system
• When the blood has a high osmolarity water will leave the
tissues and go into blood.
– This is why excessive consumption of certain
electrolytes raises BP
– low osmolarity
• When blood has a low osmolarity excessive fluid follows
an osmotic gradient into the tissues which may result in
edema
Erythrocytes (RBCs)
• Biconcave discs, anucleate,
essentially no organelles
• Filled with hemoglobin (Hb)
– a protein that functions in gas
transport
• Contain the plasma
membrane protein spectrin
and other proteins that:
– Give erythrocytes their
flexibility
– Allow them to change shape
as necessary
Production of Erythrocytes
• Hematopoiesis – blood cell formation
• Hematopoiesis occurs in the red bone
marrow of the:
– Axial skeleton and girdles
– Epiphyses of the humerus and femur
• Hemocytoblasts give rise to all formed
elements
Bone Marrow in an Adult
Hemopoiesis
Hormonal Control of Erythropoiesis
• Chemoreceptors in the kidneys detect a
decrease in P02
– They respond by secreting the hormone
Erythropoietin. (EPO)
• (EPO) is triggered by:
– Hypoxia( low oxygen levels) due to decreased RBCs
• anemia
– Decreased oxygen availability
• High altitude, pulmonary infections
– Increased tissue demand for oxygen
• exercise
• Erythropoesis increases the:
– RBC count in circulating blood
– Oxygen carrying ability of the blood
Erythropoietin Mechanism
Start
Normal blood oxygen levels
Increases
O2-carrying
ability of blood
Stimulus: Hypoxia due to
decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2
Reduces O2
levels in blood
Enhanced
erythropoiesis
increases RBC
count
Erythropoietin
stimulates red
bone marrow
Kidney (and liver to a
smaller extent) releases
erythropoietin
Erythrocyte Disorders
• Polycythemia - an excess of RBCs
– primary polycythemia (Polycythemia Vera )
• cancers of erythropoietic cell line in red bone marrow
– secondary polycythemia (ENVIORMENTAL)
• from dehydration, emphysema, high altitude, or physical
conditioning and blood doping
• Dangers of polycythemia
– increased RBC’s will result in increases in:
• blood volume (water following their osmotic gradient)
• Viscosity (stickiness ,thicker) heart works harder greater
resistance
• Blood pressure (Both increases in vessel resistance and volume
will increase the pressure in the vessel.
– can lead to embolism, stroke or heart failure
Diagnostic Value In Examining
RBCs
• Diabetes: Chronically elevated BGLs will increase glycosylated
hemoglobin ( A1c).
– This reflects average BGL over the several months.
• Essential fatty acid composition: Looks at composition of fatty
acids that make up cell membranes.
– Low omega 3 and high omega 6 and saturated fatty acids predispose
you to inflammation and disease.
• Magnesium levels: measures mag levels inside the RBCs
opposed to just looking at serum levels.
– Signs and symptoms of magnesium deficiency include fatigue,
weakness, heart disturbances, mental confusion, muscle cramps, loss of
appetite, and insomnia.
Leukocytes (WBCs)
• Leukocytes, the only blood cells that are
considered complete cells:
– Are less numerous than RBCs and only make
up 1% of the total blood volume
• 1/750 ratio to RBC
• ( Buffy white coat)
– Can leave capillaries via diapedesis and
move through tissue spaces in response to
bacterial or viral invasion
Leukopoiesis
Fig. 18.18
Platelets
• Small fragments of megakaryocyte
cytoplasm
– Normal Count - 130,000 to 400,000 platelets/L
• Functions
– secrete clotting factors and growth factors for
vessel repair
– initiate formation of clot-dissolving enzyme
– phagocytize bacteria
– chemically attract neutrophils and monocytes to
sites of inflammation
Genesis of Platelets
• The stem cell for platelets is the hemocytoblast
• The sequential developmental pathway from
hemocytoblast to megakaryocytes.
• These cells produce platelets by
– Pieces of cytoplasm splits off (cell fragments) that enter
bloodstream as platelets (live for 10 days)
– some stored in spleen
Hemostasis
• Normally blood will flow smoothly though an intact artery. If there is a
disruption in the endothelium; hemorrhaging may result. The artery will
protect itself through a process called hemostasis.
– It involves 3 major phases
Hemostasis - Vascular Spasm
• The initial response of
the damaged blood
vessel is to constrict
preventing additional
blood lose.
• This is accomplished
through activation of:
•
pain receptors : directly
innervate constrictors.
•
•
smooth muscle injury
results in reflexive spasm
platelets release serotonin
(vasoconstrictor)
Hemostasis -Platelet Plug Formation
• Platelet plug formation:
•
broken vessel exposes
collagen which attracts
platelets
• Platelets form pseudopods
enabling them stick to
damaged vessel. Platelets
produce releasing a variety
of substances
•
serotonin is a
vasoconstrictor
• ADP attracts more
platelets (positive
feedback)
Hemostasis - Coagulation
• Clotting - most effective defense against bleeding
– Procoagulants (clotting factors) are present in plasma
undergo series of biochemical reactions.
– activate one factor and it will activate the next to form a
reaction cascade.
• Extrinsic pathway : initiated by damaged tissues
• Intrinsic pathway: platelet plug produces clotting
factors.
• Both pathways lead to the production of factor X
– The final result is conversion of fibrinogen into fibrin
Coagulation Pathways
• Extrinsic pathway
– initiated by tissue
thromboplastin
• Intrinsic pathway
– initiated by factor
XII
– Both produce factor
X which leads to:
• Prothrombin
activator: converts
of fibrinogen to
Fibrin
• Clotting requires
many steps to
ensure clots don’t
happen without
cause.
Hemostasis Disorders: Bleeding
Disorders
• Thrombocytopenia – condition where the number of
circulating platelets is deficient.
– Patients show petechiae (small purple blotches on the
skin) due to spontaneous, widespread hemorrhage.
– Caused by suppression or destruction of bone
marrow (e.g., malignancy, radiation)
– Platelet counts less than 50,000/mm3 is diagnostic for
this condition.
– Treated with whole blood transfusions.
• Hemophilia
– Genetic lack of any clotting factor affects coagulation
Coagulation Disorders
• What effect does stress have on platelet aggregation?
– Epinephrine increases likely of forming clots by making the platelets
more sticky.
• Thrombosis - abnormal clotting in unbroken vessel which will narrow
the lumen for blood to flow .
– most likely to occur in leg veins of inactive people because
stagnant blood tends to form clots.
– The formation of a dangerous thrombi can block circulation
resulting in tissue death
– Coronary thrombosis – thrombus in blood vessel of the heart
• Embolism – The thrombus over time can break of and travel throughout
the in a vessel until it gets stuck.
– Infarction may occur if clot blocks blood supply to an organ (MI or
stroke)
– pulmonary embolism - clot may break free, travel from veins to
lungs
– Cerebral emboli results in CVA (cerebral vascular accidents)
stroke.
Lymphatic System
• Immunity
– fluids from all capillary beds are
filtered
– immune cells stand ready to
respond to foreign cells or
chemicals encountered
• Lipid absorption
– Lacteals in small intestine
absorb dietary lipids
• Fluid recovery
– absorbs plasma proteins and
fluid (2 to 4 L/day) from tissues
and returns it to the
bloodstream
• interference with lymphatic
drainage leads to severe
edema
Lymphatic System
Immunity: Two Intrinsic Defense Systems
•
•
•
The function of the immune system is to protect the body from
pathogens.
It is composed of 2 major divisions
Innate (nonspecific)
1.
•
The body’s first line of defense system consists of:
• intact skin and mucosa
2. The inflammation process
3. Macrophages such as monocytes which phagocytose
foreign invaders.
4. NK cells. The bodies nonspecific assassins
Acquired (specific) system
– Following ingestion of a pathogen by a macrophage
lymphocytes become sensitive to that specific pathogens
•
•
–
–
B-lymphocytes function in the body fluid such as blood
T lymphocytes work in infected cells.
takes longer to react than the innate system
this system has memory
Mechanism of Phagocytosis
Innate Immunity
Inflammation: Tissue Response
to Injury
• The inflammatory response is triggered
whenever body tissues are injured
– Prevents the spread of damaging agents to
nearby tissues
– Disposes of cell debris and pathogens
– Sets the stage for repair processes
• The four cardinal signs of acute
inflammation are redness, heat, swelling,
and pain
Inflammatory Response: Phagocytic
Mobilization
4 Positive
chemotaxis
1 Neutrophils
enter blood
from bone
marrow
Capillary wall
Inflammatory
chemicals
diffusing from
the inflamed
site act as
chemotactic
agents
3 Diapedesis
2 Margination
Endothelium
Basal lamina
Natural Killer (NK) Cells
• They are considered part of the non specific immune
system
• Natural killer cells:
– Are a small, distinct group of large granular lymphocytes
– React nonspecifically and eliminate cancerous and virus-infected
cells
– Kill their target cells by releasing perforins and other cytolytic
(cell- lysing) chemicals
– Secrete potent chemicals that enhance the inflammatory
response
Adaptive Immune Defenses
• The adaptive immune system is antigen-specific, systemic and has
memory. The adaptive (specific) immune system:
– Recognizes specific foreign substances (Antigens) :
• Substances that can mobilize the immune system and provoke an
immune response
– This the body sees as foreign (bad)
– Acts to immobilize, neutralize, or destroy these antigens
– Amplifies inflammatory response and activates complement
• It has two separate but overlapping arms of defense.
– Humoral, or antibody-mediated immunity
• B lymphocytes – oversee humoral immunity
• Extracellular (antigens)pathogens bacteria
– Cellular, or cell-mediated immunity
• T lymphocytes – non-antibody-producing cells that constitute the
cell-mediated arm of immunity
• intracellular antigens such viruses and cancer
Lymphocytes
• Immature lymphocytes released from bone
marrow are essentially identical
• Whether a lymphocyte matures into a B
cell or a T cell depends on where in the
body it becomes Immunocompetent
(Functional)
– B cells mature in the bone marrow
• Humoral division
– T cells mature in the thymus
• Cellular division
Major Types of T Cells
Cell-Mediated Immune Response
• Since antibodies are useless against
intracellular antigens, cell-mediated immunity is
needed
• Two major populations of T cells mediate
cellular immunity
– CD4 cells (T4 cells) are primarily helper T cells (TH)
– CD8 cells (T8 cells) are cytotoxic T cells (TC) that
destroy cells harboring foreign antigens
• Other types of T cells are:
– Suppressor T cells (TS) Turn down immune response
once threat is over.
– Memory T cells : reduce response time of future
attacks.
Antigen Presenting Cell
• Once a macrophage
has eaten an antigen
it becomes an
Antigen-presenting
cells (APCs):
– Do not respond to
specific antigens
– They present antigen
to TH-cell which alerts
both B and T cells of
the specific antigen.
Helper T Cells (TH)
• Regulatory cells that play a central role in
the immune response
• Once primed by APC presentation of
antigen, they:
– Chemically or directly stimulate proliferation of
other T cells
– Stimulate B cells that have already become
bound to antigen
• Without TH, there is no immune response
– AIDS cripples the immune system by effecting
the # of TH cells.
Role of Helper T Cells
• Secretes interleukins
(chemical messages between
cells to mobilize the response!)
– attract neutrophils, NK
cells, macrophages
• stimulate phagocytosis
– stimulate T and B cell
mitosis and maturation
• Coordinate humoral
and cellular immunity
Cytotoxic T Cell (Tc)
• TC cells, or killer T cells, are the only T cells that
can directly attack and kill other cells
• They circulate throughout the body in search of
body cells that display the antigen to which they
have been sensitized
• Their targets include:
–
–
–
–
Virus-infected cells
Cells with intracellular bacteria or parasites
Cancer cells
Foreign cells from blood transfusions or transplants
Mechanisms of Tc Action
• TC cells:
– Bind to the target cell
and release perforins
into its membrane
• perforin causes cell
lysis
Humoral Response
• The B-cells produce soluble antibodies that
interact in extracellular environments such as:
–
–
–
–
body secretions
tissue fluid
blood
lymph
• Antibodies surround and incapacitate the
antigens by
– Preventing viruses from entering the cell
– Neutralize release of endotoxins from bacteria
– Surrounds antigens allowing phagocyte time to engulf
them.
Clonal Selection
Humoral Immunity
• B-cells are presented with an antigen directly or by Thelper cell
• This activated clone B-cells with a specific antigen
receptor to identify the specific antigen
• The clones produce plasma cells which will produce the
antibodies specific for that antigen.
• Antigen will become surrounded by antibodies disabling
it allowing for a phagocyte to come and finish it off.
• Some B-Cells will become memory B-Cells which
circulate until the next time the body is presented with
that antigen.
– This is why the body responds faster the next time you are
exposed
Summary of the Primary Immune Response
Blood And Immunity Screen
•
•
•
•
•
•
•
•
•
•
•
•
Skin color changes
Shortness of breath
Blood pressure changes
Dizziness
Body weight changes
Easy bruising, bleeding
Sensory changes in hands and feet
Swollen lymph nodes
Fever
Changes in heart rate
Autonomic dysfunction
Anemia (sickle cell )
• Leukemia hx of blood transfusions.