Transcript Blood
Blood
17
Blood is a viscous suspension:
pH 7.35-7.45
Temperature 38C
Volume of blood is about 5L (8% body weight)
A Liquid Tissue
Functions of Blood
Distribution:
Regulation:
O2, nutrients, metabolic products/wastes, hormones, H2O
Temp, pH, fluid volume
Protection:
Fluid/blood loss prevention, prevention of infection
Components of Whole Blood
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes & platelets
(<1% of whole blood)
Formed
elements
1 Withdraw blood &
2 Centrifuge
place in tube
Composition:
Plasma: about 55%
Formed Elements: about 45%
Erythrocytes
(45% of whole blood)
Figure 17.1
Plasma
whole blood
Cells
Plasma
Mostly H2O, straw-colored
> 100 solutes: electrolytes, gases, hormones,
proteins & metabolic products
Predominate protein: Albumin (responsible for
plasma osmotic pressure)
Formed Elements
Erythrocytes (RBCs), leukocytes (WBCs), &
platelets (PLTs)
Only WBCs are complete cells
RBCs have no nuclei or organelles
Platelets are cell fragments
Blood Cell Production
Hematopoiesis
Tissue: Red bone marrow
Flat bones
Epiphysis of femur & humerus
Cell: all blood cells arise from Hematopoietic
Stem Cells (Hemocytoblasts)
Erythrocytes (RBCs)
Biconcave discs, 7.5 microns
Anucleate, essentially no organelles
Filled with hemoglobin (Hb)
Shape is maintained by a protein framework
(spectrin) & other proteins:
Figure 17.3
Gives RBCs their shape & flexibility
RBC function is gas transport/exchange
Erythrocyte Function: Hb
2 a & 2 b chains, each bound to a heme group
Heme:
Fe containing organic ring structure (porphyrin)
Reversibly binds O2 ; each Hb can bind 4 O2
Each RBC has 250 million Hb molecules = 1 billion O2
Hemoglobin
Oxyhemoglobin: Hb bound to O2
Deoxyhemoglobin: Hb after O2 diffuses into tissues
Carbaminohemoglobin: Hb bound to CO2
CO2 is bound to the polypeptide not to the heme group
Carries about 20% of CO2 in the blood
Erythropoiesis (RBC Production):
Hormonal Control
Erythropoietin (EPO) release by the kidneys is triggered by
hypoxia (decreased [O2])
Decreased RBC count
Decreased oxygen availability
Increased tissue demand for oxygen
Effect: EPO causes maturation of precursor cells that are in
a committed RBC line
Erythropoiesis: RBC Line
Effect: EPO causes maturation of precursor cells that are in
a committed RBC line
Erythropoiesis: Iron (Fe)
65% of Fe stored in Hb:
Intracellular Fe stored in protein-Fe complexes (ferritin &
hemosiderin) in liver & spleen
Fe is transported on transferrin (transport protein)
Fe obtained in diet; small daily losses
Other dietary requirements: B12 & folate (needed
for DNA synthesis), other nutrients.
Erythrocyte Disorders
Anemia: blood has abnormally low O2 carrying capacity (A
symptom not a disease itself)
Blood O2 levels cannot support normal metabolism
Signs: fatigue, paleness, shortness of breath, & chills
Anemia
Decreased RBCs
Decreased Hb
Abnormal Hemoglobin
Anemia: Decreased RBCs
Decreased RBCs: increased destruction/loss or decreased
production
Hemorrhagic anemia – blood loss
Hemolytic anemia – RBC destruction (due to abnormal
Hb, infection, trauma etc.)
Aplastic anemia – destruction or inhibition of red bone
marrow (impacts other formed elements)
Anemia: Decreased Hb
Iron-deficiency anemia (small pale RBC): decreased HB
Inadequate Fe intake
Impaired Fe absorption
Secondary to hemorrhagic anemia
Pernicious anemia (large pale RBC):
Deficiency of vitamin B12
Lack of intrinsic factor (required to absorption B12)
Treatment - give B12
Anemia: Abnormal Hemoglobin
Abnormal Hb: due to genetic defect
Thalassemias (Mediterranean ancestry)
Absent or faulty globin chain in Hb:
Fragile RBCs
Thin, delicate, & deficient in Hb
Low RBC count
Anemia: Abnormal Hemoglobin
Sickle-cell anemia: (African ancestry)
Abnormal Hb called HbS
HbS has a single amino acid substitution in the beta chain
Causes RBCs to become sickle-shaped in low O2 situations
RBC debris clog capillaries
Polycythemia
Polycythemia: excess RBCs - increased blood
viscosity/sludging
Three main polycythemias are:
Polycythemia vera
Secondary polycythemia
(may be due to marrow cancer)
(due to erythropoesis)
Blood doping
Fate & Destruction of RBCs
RBCs are anucleate; do not grow, do not make new
protein, do not divide
Old RBCs become rigid & fragile.
The life span of an RBC is 100–120 days
Fate & Destruction of RBCs
Dying RBCs are engulfed by macrophages in the spleen
Heme & globin are separated & the Fe is recycled to ferritin
or hemosiderin
Heme is degraded to bilirubin (yellow)
Bilirubin is secreted by the liver into the intestine as bile
The intestines metabolize it into urobilinogen (green)
then to stercobilin (brown)
Globin portion is metabolized into amino acids & is
released into the circulation
Life Cycle of Red Blood Cells
Figure 17.7
Leukocytes (WBCs): Characteristics
Complete cells: contain nucleus , organelles
Diapedesis: the ability to move out of the bloodstream &
function
Circulatory system used to get WBC to the vicinity
Cellular/chemical signals prompt diapedesis
Amoeboid movement – WBCs travel through tissues to the
target area
Positive chemotaxis: WBCs follow a chemical trail to the target
WBC Function & Classification
Function:
Phagocytosis, antibody production, waste clean-up, act
as chemical “sharpshooters”
Classification:
Based upon appearance after staining
(Wright’s stain)
Granulocytes
Visible granules on staining – lobed nuclei
Neutrophils, eosinophils, & basophils
Granules stain specifically (acidic, basic, or both)
Larger & usually shorter-lived than RBCs
All are phagocytic cells
Figure 17.10a-c
Neutrophils
Multi-lobed nucleus;
neutral staining
Granules take up both
acidic & basic dyes
Contain peroxidases,
hydrolytic enzymes, &
defensins (antibiotic-like
proteins)
Phagocytize bacteria &
some fungi
Eosinophils
Large bilobed nucleus
Red staining (acidophilic)
large, coarse, granules
containing digestive enzymes
Attack parasitic worms by
degranulation
Phagocytize immune
complexes
Basophils
Large, dark (basophilic)
granules containing
histamine
inflammatory chemical;
vasodilator, attracts other
WBCs (antihistamines
counter this effect)
Interact with IgE
antibodies (allergies) to
promote degranulation
Agranulocytes
No visible granules, mononuclear
Monocytes & lymphocytes
Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
Figure 17.10e,d
Monocytes
The largest WBCs
Active phagocytes;
attack viruses
Help activate
lymphocytes (immune
response)
In tissues they
differentiate into
macrophages
Lymphocytes
Most found in lymphoid
tissue (some circulate in the
blood)
Two types of lymphocytes:
T cells – immune system
functions
B cells give rise to plasma
cells, which produce
antibodies
Summary of Formed Elements
Table 17.2
Summary of Formed Elements
Table 17.2
Leukocyte Production
Leukopoiesis - hormonally stimulated by cytokines:
Interleukins
Colony-stimulating factors
Macrophages & T cells are most important sources
of cytokines
Leukocyte (WBC) Formation
All WBCs originate from
hemocytoblasts
Hemocytoblasts
differentiate into
myeloid stem cells &
lymphoid stem cells
Stem cells mature &
differentiate into specific
WBC lines
Figure 17.11
Leukocytes Disorders:
Leukopenia: abnormally low WBC count
some drugs & viruses
Leukocytosis: WBC count greater than 11,000/mm3
Infection and/or stress
Leukemia
Leukemia: cancer involving WBCs
Leukemias are named according to the abnormal WBCs
Myelocytic – involves cells of myeloid lineage
Lymphocytic – involves cells of lymphoid lineage
Leukocyte (WBC) Formation
Figure 17.11
Leukemia (cont)
Acute - involves more primitive cells (blasts) & primarily
affects children
Chronic - more prevalent in older people
Leukemia (cont)
Bone marrow becomes overwhelmed with the clone cell
population.
Cancerous cells crowd out all other cell lines
Anemia
Decrease in all other cell populations
Bleeding problems
The cancerous WBCs are nonfunctional
Death by hemorrhage & overwhelming infections
Treatment - radiation, antileukemic drugs, & bone marrow
transplants
Platelets (PLTs): Characteristics &
Function
Characteristics:
Platelets are not true cells they are fragments of megakaryocytes
Small purple spots on Wright’s stain
Function: granules contain a large number of
chemicals involved in clot formation
Platelet Production: regulated by Thrombopoietin
Platelet Production
Figure 17.12
Hemostasis
A series of reactions designed to stop bleeding
Three phases:
Vascular spasm
Platelet plug formation
Coagulation (blood clotting)
Vascular Spasm
Vascular spasm: vasoconstriction in response to
smooth muscle injury & chemicals from damaged
cells
Platelet Plug Formation
PLT adhesion: PLTs adhere to collagen exposed by
endothelial damage
PLT activation (degranulation): releases chemicals
Serotonin – enhances vasospasm
ADP – attracts more PLTs
Thromboxane A2 – enhances serotonin & ADP release
(positive feedback)
As PLTs aggregate a plug is formed
PGI2 (prostacyclin) a prostaglandin made by endothelium
limits the extent of the plug
Coagulation
Thirteen clotting factors (I – XIII) react to transform blood
from a liquid to a gel
Follow the intrinsic & extrinsic pathways yielding
prothrombin activator
Final Common Pathway: Final three steps of this
series of reactions are:
Prothrombin activator is formed
Prothrombin is converted into thrombin
Thrombin catalyzes the joining of fibrinogen into a fibrin
mesh
Coagulation:
Procoagulants (clotting factors) act as
enzymes that catalyze the conversion of
other factors
Conversion of fibrinogen (a plasma protein)
to fibrin (insoluble protein strands) forms a
net that traps RBCs & PLTs
Coagulation
Figure 17.13
Coagulation:
Final Common Pathway: Final three steps of these reactions;
Prothrombin activator is formed
Prothrombin is converted into thrombin
Thrombin catalyzes the joining of fibrinogen into a fibrin mesh
Clot Retraction & Repair
Clot retraction: PLTs release actin & myosin which contract
& solidify the clot
Repair: Platelet-derived growth factor (PDGF) stimulates
repair of blood vessel wall
Factors Limiting Clot Growth
or Formation
Two homeostatic mechanisms prevent clots from becoming
large
Swift removal of clotting factors
Inhibition of activated clotting factors
Factors Limiting Clot Growth
or Formation
Fibrinolysis: dissolving the clot
Plasminogen is activated by tissue plasminogen
activating factor to form;
Plasmin which digests fibrin
Clot formation must be limited to the area of injury
Dilution: clotting factors must be present in high enough
concentration to interact
Antithrombin III: inactivates thrombin that is not in
association with fibrin
Disorders of Hemostasis :
Thromboembolytic Conditions
Thrombus:
Embolus:
a clot that develops & persists in an unbroken blood vessel
a thrombus broken free & moving in the circulation
Embolism:
an embolus wedged in a vessel
Hemostasis Disorders
Disseminated Intravascular Coagulation (DIC):
runaway coagulation in intact blood vessels
Consumes clotting factors - residual blood cannot clot
Untreated: severe hemorrhage
Hemostasis Disorders:
Bleeding Disorders
Thrombocytopenia: insufficient platelets
Spontaneous bleeding
Petechiae - small bruises
Often due to viral infection
May be due to medication or bone marrow destruction
Liver dysfunction - failure to synthesize procoagulants
May be due to vitamin K deficiency
Hepatitis/cirrhosis
Hemostasis Disorders:
Bleeding Disorders
Hemophilias: hereditary bleeding disorders
Hemophilia A (Classic): factor VIII deficiency
Hemophilia B: factor IX deficiency
Both A & B are sex linked recessive
Hemophilia C: factor XI deficiency, a milder form that can
effect both sexes
Definitions: Blood antigens
Antigen; a substance that is capable of eliciting an immune
response
Antibody; a protein released by the immune system that
binds to a specific antigen
Blood Groups
Humans have >30 varieties of naturally occurring RBC
surface antigens
M, N, Duffy, Kell, & Lewis are mainly used for legalities
Lansteiner (ABO) group:
Corresponding antibodies are naturally present & can
cause vigorous transfusion reactions
Rh Blood Groups
Antibodies to the D (Rh+) antigen are not naturally
present
If an Rh– individual receives Rh+ blood, anti-Rh
antibodies form
A second exposure to Rh+ blood will result in a typical
transfusion reaction
Hemolytic Disease of the
Newborn
First pregnancy: Rh– Mom & Rh+ infant yields no reaction
but, antibodies are formed
Second pregnancy: sensitized Rh– mother with Rh+ infant;
antibodies cross the placenta & attack & destroy the RBCs
the baby
The drug RhoGAM can prevent the Rh– mother from
becoming sensitized
Transfusion
Group/type specific blood (i.e. give A+ patient A+ blood):
cross match
Universal donor (O-)
Neither A nor B nor Rh on cells
Use only packed cells not O- plasma
Autologous transfusion: patient receives their own blood
Transfusion Reaction
Occurs when recipient plasma has antibodies to donor cells
(antigens)
Can involve antigens other than A, B or Rh
Sx (symptoms): fever, chills, hypotension, tachycardia,
nausea/vomiting, etc. Can result in renal failure.