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Blood

Blood
The only fluid tissue in the human body
Classified as a connective tissue
Components of blood
1) Living cells called ________________
Erythrocytes red blood cells
transports oxygen and carbon dioxide
Leukocytes white blood cells
defend body against pathogens
Platelets cell fragments formed
from megakaryocytes, important in
blood clotting
2) Non-living matrix: plasma is the fluid
and solutes
formed elements

Blood Hematocrit and Beyond


When blood is centrifuged
Erythrocytes sink to the bottom
(45% of blood, a percentage
known as the hematocrit)
Buffy coat contains leukocytes
and platelets (less than 1% of
blood), the buffy coat is a thin,
whitish layer between the
erythrocytes and plasma
__________rises
to the top
Plasma
(55% of blood)
Average blood volume
Women = 5.0 L
Men = 5.5 L

kwashiorkor

280-300 milliosmoles per liter (we will use 300 mOsm/L)

Physical Characteristics of Blood


Blood is used as a vehicle of transport
Color range
Oxygen-rich blood is scarlet red
Oxygen-poor blood is dull red
pH between 7.357.45 (________)
Blood temperature is slightly higher than body temperature at 38
(100.4F), it transfers heat throughout the body

Blood Plasma is ~90% Water


6-8% proteins which: increase osmotic pressure, buffer H+, increase
blood viscosity, provide fuel during starvation
3 Major Classes of Plasma Proteins (synthesized in liver, except some
globulins synthesized by lymphocytes)
Albumins: Major contributor to plasma oncotic osmotic pressure
and act as carriers
Globulins: Carriers, Clotting factors, Precursor proteins
(angiotensinogen), Immunoglobulins
Fibrinogen: Blood Clotting
Nutrients: glucose, amino acids, lipids, vitamins
Wastes: urea, bilirubin, creatinine
Gases (dissolved): oxygen, carbon dioxide
Hormones
Electrolytes (aka _____________)
Relatively high concentrations of Na+ and ClRelatively low concentrations of H+, HCO3-, K+, and Ca2+

Ringers Solution
A solution of distilled water containing electrolytes and compounds
so that the same concentrations as their occurrence in body fluids.
This solution is iso-osmotic to our blood and tissues
Why?
280-300 milliosmoles per liter (we will use __________ mOsm/L)
Blood and tissue osmolarity must be equal to prevent
net movement of fluids

blood

tissue

blood

tissue

Osmosis

Water (solvent) diffuses down its concentration gradient


The Link Between Water and Salt
Solutes in the body include
electrolytes like sodium,
potassium, and calcium ions
More solvent
Changes in electrolyte balance
causes water to move from one
compartment to another which
alters blood volume and blood
pressure and can impair the
activity of cells
Water moves from low [solute] to
high [solute]=high [solvent] to low
[solvent]
Pure water has ______ solute present
Water reabsorption follows solute
reabsorption

Less solvent

Blood Plasma
Acidosis: blood becomes too acidic (less than 7.35)
Alkalosis: blood becomes too basic (greater than 7.45)
In each scenario, the respiratory system and kidneys help
restore blood _________ to normal
Carbon dioxide can dissolve in water (blood plasma) and
form carbonic acid
CO2 + H2O

H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)

Im an acid!

Acid-Base Balance
Normal pH of arterial blood = 7.4
pH < 7.35 = ___________
pH > 7.45 = alkalosis
Most ions originate as by-products
of cellular metabolism
Complications with acid-base
disturbance
Conformation change in protein
structure
Changes in excitability of
neurons
Changes in balance of other ions
Cardiac arrhythmias
Vasodilation/vasoconstriction

Acids and Bases


Acids are proton (H+) donors
Strong acids dissociate completely and liberate all
of their H+ in water
Weak acids, such as carbonic acid, dissociate only
partially
Bases are proton (H+) acceptors
+
Strong bases dissociate easily in water and tie up H
Weak bases, such as bicarbonate ion and ammonia,
are slower to accept H+

Cellular or Formed Elements


Erythrocytes: Red blood cells
(RBCs)
Leukocytes: _________ blood
cells (WBCs)
Platelets (cell fragments)
white

Multipotent stem cell

Developmental Aspects of Blood Cells


Sites of blood cell formation
The fetal liver and spleen are early sites of
blood cell formation
Bone marrow takes over hematopoiesis by
the seventh month
Fetal hemoglobin differs from hemoglobin
produced after birth, fetal hemoglobin has a
gamma subunit in place of the beta subunit and
______________ affinity for oxygen
Physiologic jaundice results when the liver
cannot rid the body of hemoglobin
breakdown products fast enough
HIGHER

Erythrocytes
Erythrocytes (red blood cells or RBCs)
Main function is to carry oxygen
Anatomy of circulating erythrocytes
biconcave disk: large surface area
which favors diffusion
Essentially bags of hemoglobin
Anucleate (no nucleus)
Contain very few organelles
No _________________
mitochondria
Use anaerobic glycolysis
5-6 billion RBCs per ml of blood
Flexible membrane
Also function to maintain osmolarity and
blood/plasma pH

Hemoglobin in RBCs
Hb binds strongly (but reversibly) to oxygen
98.5% oxygen bound to Hb and 1.5% dissolved
in plasma
Each hemoglobin molecule has four oxygen
binding sites
Globin + 4 heme groups = 4 polypeptides and
_______________
= iron-containing group
HEME
Iron-containing protein
Can also bind to CO2 and H+

Formation of Erythrocytes
Mature RBCs are unable to divide, grow, or synthesize proteins
Wear out in 100 to 120 days
When worn out, RBCs are eliminated by phagocytes in the spleen or
liver
Lost cells are replaced by division of hemocytoblasts in the red bone
marrow
__________________ is a component of hemoglobin
Normal hemoglobin content of blood
Men: 13 18 gram /dL
Women: 12 16 gram /dL

Control of Erythrocyte Production


Rate is controlled by a hormone (________________)
Kidneys produce most erythropoietin as a response to reduced
oxygen levels in the blood (sensed by chemoreceptors)
Homeostasis is maintained by negative feedback from blood oxygen
levels

Control of Erythrocyte Production


Normal blood oxygen levels 100 mmHg

Increased
O2- carrying
ability of blood

60 mmHg

Stimulus: Decreased
RBC count, decreased
availability of O2 to
blood, or increased
tissue demands for O2
Reduced O2
levels in blood-sensed
by chemoreceptors

More
RBCs
Enhanced
erythropoiesis
Red bone
marrow

Erythropoietin
stimulates

Kidney releases
erythropoietin

Anemia: Decrease in the oxygen-carrying


capacity of blood
Dietary anemia
Iron: iron-deficiency anemia
Pernicious: lack of Vitamin B12
Hemorrhagic anemia: bleeding
Hemolytic anemia
Malaria or Sickle cell anemia
Aplastic anemia: bone marrow
defect
________ anemia: kidney disease

Anemia

Leukocytes (white blood cells)


Leukocytes (white blood cells or
WBCs)
Crucial in the body s defense
against disease
These are complete cells, with a
nucleus and organelles
Able to move into and out of blood
vessels (diapedesis)
Can move by ____________
amebolic
motion though tissues
Can respond to chemicals released
by damaged tissues (cytokines)
4,000 to 11,000 WBC per cubic
millimeter (microliter) of blood

Types of Leukocytes
Two Major Classes of Leukocytes
Granulocytes
Granules in their cytoplasm can be stained
Possess lobed nuclei
Include 1)neutrophils, 2)eosinophils, and 3)basophils
Agranulocytes
Lack visible cytoplasmic granules
Nuclei are spherical, oval,
or kidney-shaped
Include:
1)lymphocytes
2)_________________

Abundance of Leukocytes
List of the WBCs from most to
least abundant
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils

Easy way to remember


this list
Never
Let
Monkeys
Eat
Bananas

Granulocyte: Neutrophils

Neutrophils are multilobed nucleus with fine granules


40-70% of leukocytes in blood
Phagocytes at active sites of infection
Secretes ____________________
Circulate in blood 7-10 hours
Migrate to tissues for a few days
Increase in number during infections

Granulocyte: Eosinophils

1-4% of leukocytes
Large brick-red cytoplasmic granules
Phagocytes (but ___________ main mechanism of action)
Defend against parasitic invaders (e.g. worms)
Granules contain toxic molecules that attack parasites

Granulocyte: Basophils
<1% of leukocytes
_____________________
May defend against large parasites by releasing toxic substances
Contribute to allergic reactions
Histamine-inflammation
Heparin-anticoagulant

Agranulocytes:
Monocytes become Macrophages
4-8% of leukocytes
__________________
New monocytes circulate in blood for
a few hours then
Migrate to tissues macrophages
Wandering macrophages
Fixed macrophages

Agranulocytes: Lymphocytes

20-45% of WBCs
3 types of Lymphocytes
____ lymphocytes (B cells)
T lymphocytes (T cells)
Null cells (also called
natural killer or NK cells)

Lymphocytes: B Cells
B cells associated with antibodies
2 major classes of B cells:
1)effector B cells become
plasma cells and secrete
antibodies
2) __________________
MEMORY CELLS
B cell contacts antigen then
become a plasma cell
Plasma cell secretes antibodies
(immunoglobulins)
Antibodies mark invaders (called
antigens) for destruction
Anti=antibody and
Gen=generator

Lymphocytes: T Cells
Helper T Cells secrete cytokines that enhance activity of B cells and
other T cells enhances activity of macrophages and NK cells
Cytotoxic T Cells kill virus-infected cells, abnormal cells, and bacteria,
Secretory products form pores in target cell membrane, Kills cells by
lysis
Memory T cells used for ______________________ infection
Suppressor (regulatory) T Cells secrete cytokines that suppress activity
of B cells and other T cells and used to end an immune response

Lymphocytes: Natural Killer Cells


(Null Cells)
Recognize abnormal or infected cells
cause lysis by secreting ____________
Can attack virus-infected cells without
identifying virus
Early defense against viral infections
Cause lysis
Fast acting early immune response

MHC=major histocompatibility complex

(a) Inhibitory NK cell receptors recognize self MHC class I and restrain NK cell
activation.
(b) When unimpeded by the inhibitory receptors, binding of NK cell activation
receptors to their ligands on target cells results in NK cell stimulation.

Leukocyte Issues
Abnormal numbers of leukocytes
Leukocytosis
WBC count above 11,000 leukocytes/mm3
Generally indicates an infection
____________
Abnormally low leukocyte level
Commonly caused by certain drugs such as corticosteroids
and anticancer agents
Leukemia occurs when bone marrow
becomes cancerous, turns out excess
WBC

Platelets
Platelets (a.k.a. thrombocytes)
Derived from ruptured multinucleate cells
( ___________________)
Needed for the clotting process
3
Normal platelet count = 300,000/mm (l)

Characteristics of Formed Elements


of the Blood

Characteristics of Formed Elements


of the Blood

Hematopoiesis
Blood cell formation
Occurs in red bone marrow
All blood cells are derived from
a common stem cell
(hemocytoblast)
Hemocytoblast differentiation
Lymphoid stem (lymphoblast)
cell produces lymphocytes
Myeloid stem (____________)
cell produces all other formed
elements
Erythrocyte synthesis
stimulated by erythropoietin
secreted from kidneys under
conditions of low oxygen levels
in blood flowing to kidneys

monocyte

Formation of White Blood Cells and


Platelets
Controlled by hormones
Colony stimulating factors (CSFs) and _____________
prompt bone marrow to generate leukocytes
Thrombopoietin stimulates production of platelets

Hemostasis
Stoppage of bleeding resulting from a
break in a blood vessel
Hemostasis involves three phases
1) Vascular _________________
SPASMS
Vasoconstriction causes blood vessel to
spasm
Spasms narrow the blood vessel,
decreasing blood loss
2) Platelet plug formation
Collagen fibers are exposed by a break
in a blood vessel a platelets become
sticky and cling to fibers
Anchored platelets release chemicals
to attract more platelets
Platelets pile up to form a platelet plug
3) Coagulation (blood clotting)

Platelet Components

NUCLEUS

Healthy tissue

Platelet Plug needed for


formation of a blood clot
Colorless
Cell fragments
no _______________
has organelles & granules
100,000 500,000 / mL blood

Damaged tissue

Preventing the Spread of Plug


Chemicals that prevent platelet aggregation:
Prostacyclin (PGI2) - produced
in healthy endothelial cells
Nitric oxide released by
healthy endothelial cells
______ is an integral membrane
protein that keeps ADP levels
low
CD39

5 factors that activate a platelet


plug are highlighted

Aspirin
Prevents_____________________activation
PLATELET
Inhibits the activation of thromboxane A2

Hemostasis
Coagulation
Injured tissues release tissue factor (TF)
PF3 (a phospholipid) interacts with TF, blood protein clotting
factors, and calcium ions to trigger a clotting cascade
Prothrombin activator converts prothrombin to thrombin (an
enzyme)
Thrombin joins fibrinogen proteins into hair-like molecules of
insoluble fibrin
Fibrin forms a meshwork
(the basis for a clot)
Blood usually clots within
3 to 6 minutes
The clot remains as
endothelium ____________
REGENERATES
The clot is broken down
after tissue repair

Intrinsic and Extrinsic Coagulation


Pathways
Intrinsic Pathway
trigger = exposed collagen

Extrinsic Pathway
Requires Tissue Factor III

Role of Thrombin in Blood Clotting

Clot Formation
Fibrinogen
Fibrin (mesh)
(Fibrin clot = blood
clot)

Dissolving a Clot
Requires another cascade initiated by exposure of
collagen
Plasminogen
plasminogen activators
Plasmin
Dissolves Clot

Undesirable Clotting
Thrombus
A clot in an unbroken blood vessel
Can be deadly in areas like the
heart or brain
__________________
EMBOLUS
A thrombus that breaks away and
floats freely in the bloodstream
Can later clog vessels in critical
areas such as the brain

Role of Coagulation Factors in Clot


Formation Disorders
Hemophilia: a group of genetic
disorders caused by deficiency of gene
for specific coagulation factors
Von Willebrands disease: reduced
levels of vWf and decreases platelet
plug formation
Vitamin K deficiencies cause decreased
synthesis of clotting factors
_______________________
Platelet deficiency
Even normal movements can cause
bleeding from small blood vessels
that require platelets for clotting
THROMBOCYTOPENIA

Blood Groups and Transfusions


Large __________________
of blood have serious consequences
LOSSES
Loss of 1530% causes weakness
Loss of over 30% causes shock, which can be fatal
Transfusions are the only way to replace blood quickly
Transfused blood must be of the same or compatible blood group(s)

Human Blood Groups


Blood contains genetically
determined proteins
_______________(a
substance the
ANTIGENS
body recognizes as foreign) may be
attacked by the immune system
Antibodies are the recognizers that
attack foreign cells
Blood is typed by using antibodies
that will cause blood with certain
proteins to clump (agglutination)
There are over 30 common red blood
cell antigens
The most vigorous transfusion
reactions are caused by ABO and Rh
blood group antigens

ABO Blood Groups

AB+

O-

ABO Blood Groups


Blood type AB can receive A, B, AB, and O
blood, so AB+ is the universal recipient
Blood type B can receive B
and O blood
Blood type A can receive
A and O blood
Blood type O can receive O blood, so
O- is the universal donor
Blood types: A, B, AB, O
Due to antigens on surface of RBCs
Type ___
A antigens, anti-B antibodies
A
Type B B antigens, anti-A antibodies
Type AB A and B antigens, no A or B
antibodies
Type O no modified antigens, anti-A and
anti B antibodies

Blood Typing
Blood samples are mixed with anti-A
and anti-B serum
______________
or no agglutination
AGGLUTINATION
leads to determining blood type
Typing for ABO and Rh factors is
done in the same manner
Cross matchingtesting for
agglutination of donor RBCs by the
recipient s serum, and vice versa

Rh Blood Groups
Named because of the presence or absence of one of eight
Rh antigens (agglutinogen D) that was originally defined
in Rhesus monkeys
Most Americans are Rh+ (Rh positive)
Problems can occur in mixing Rh+ blood into a body with
Rh (Rh________________) blood
NEGATIVE

Rh Dangers During Pregnancy:


Erythroblastosis fetalis, Rhesus disease
The mismatch of an Rh mother carrying an Rh+ baby can cause
problems for the unborn child
The first pregnancy usually proceeds without problems
The immune system is sensitized after the first pregnancy
In a second pregnancy, the mother s immune system produces
antibodies to attack the Rh+ blood (hemolytic disease of the
newborn)
Danger occurs only when the
mother is Rh and the father
is Rh+, and the child inherits
the Rh+ factor
A R_____________
shot can prevent
hoGAM
formation of anti-Rh+ antibodies
fetal
in mother s blood-it binds to the
rhogam
Rh antigen on 1st baby s fetal blood,
so mom never has an immune response

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