Download Blood Cell Production ~ Hematopoiesis

Dr. Vince Scialli
BSC 1086
BLOOD
Rev. 12-25-06
Blood ~ Fluid component of the cardiovascular system
5 - 8% of total body weight
Male
~
5-6 Liters
~ 1.3 Gallons
Female
~
4-5 Liters
Primary Functions
1.
Distribution ~
oxygen/carbon dioxide
nutrients
metabolic waste
hormones
2.
Regulation ~
body temperature
maintains pH of tissue
fluid volume ~ blood pressure
3.
Protection
~
clotting ~ blood loss
infection ~ WBC’s, antibodies
WHOLE
BLOOD:
Cellular Component
45% (PCV)
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
1
+
Liquid Component
55%
Dr. Vince Scialli
BSC 1086
WHOLE
BLOOD:
Cellular Component
+
Liquid Component
45% (PCV)
55%
Cellular Component ~ “Formed Elements”
1.
Red Blood Cells ~ Erythrocytes ~ RBC’s
MOST abundant cells in blood
2.
3.
White Blood Cells ~ Leukocytes ~ WBC’s
Granulocytes:
Neutrophils
Basophils
Eosinophils
Agranulocytes:
Lymphocytes
Monocytes
Platelets ~ Thrombocytes
Packed Cell Volume ~ 45% of total blood volume
Centrifuged Formed Elements
RBC’s ~ 45%
WBC’s
+
Platelets ~ buffey coat < 1%
Hematocrit ~ packed RBC’s
Male
Female
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
=
=
2
47% + 5%
42% + 5%
Dr. Vince Scialli
BSC 1086
BLOOD:
Cellular Component + Liquid Component
45%
55%
Liquid Component ~ Plasma
Connective tissue MATRIX component
Straw colored ~ thick & sticky
5x more viscous than water
pH 7.4
(Range 7.35 to 7.45)
Temperature ~ 38 oC ~ 100.4 oF
1.
Water ~ 90%
2.
Solutes ~ 10%
Proteins =
80 %
of
Solutes
Albumin ~ 60% ~ carrier proteins
Globulins ~ 35% ~ antibodies
Fibrinogen ~ 4% ~ clotting
Prothrombin ~ clotting
Enzymes ~ metabolism
Hormones ~ several
Cholesterol ~ good & bad
Nitrogen Wastes ~ urea, uric acid, creatinine
Nutrients ~ glucose, CHO, AA, Fats
Electrolytes ~ ions, phosphate, bicarbonate
Blood Gases ~ O2 & CO2
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
FORMED ELEMENTS
Hematopoiesis ~ formed element production
Erythrocytes ~ Red Blood Cells ~ RBC’s
Flat, biconcave disc, flexible shaped ~ 7.5 um
Can “stack” & “flex” ~ get into tiny spaces
NO nuclei or mitochondria ~ NOT a true cell
Come from “hemocytoblasts” in red bone marrow
DO NOT divide ~ replenished in bone marrow
Contain large amounts of HEMOGLOBIN ~ Hb
Each RBC has ~ 280,000,000 hemoglobin molecules
Hemoglobin ~ a “globular” protein ~ 97 % of RBC
Contains HEME ~ a red pigment
O2 binds to iron (Fe) on hemoglobin molecule
RBC Role:
carry O2 ~ to cells . . . carry CO2 ~ to lungs
Life Span ~ 120 days
Old or damaged RBC’s removed from blood by
macrophages of liver and spleen ~ “RBC graveyard”
Hemoglobin & Fe are recycled
Heme degraded to bilirubin ~ bile
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
Normal RBC & Hemoglobin Values
Hematocrit ~ packed RBC’s
“PCV”
Hemoglobin ~ Hb
RBC Count
Male
47% + 5%
Female
42% + 5%
Infant
14-20 gm %
Male
13-18 gm %
Female
12-16 gm %
Male
5.5 million/cu ml
Female
4.7 million/cu ml
Blood Cell Production ~ Hematopoiesis
Body produces 100 billion new RBC’s & WBC’s /day
MOST in red bone marrow ~ myeloid tissue
SOME in lymphoid tissue: lymph nodes, spleen, thymus
Constant BALANCE between production & destruction
LOW RBC’s causes HYPOXIA ~ O2 deprivation to tissue
Anemia ~ blood loss ~ high altitude ~ lung damage
RBC’s produced @ 2.5 million per second
NEED:
Iron (Fe) . . . Amino acids . . . Vitamin B
Hormones ~ erythropoietin & testosterone
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
Erythropoietin ~ EPO
Stimulates RBC production from stem cells
Testosterone ~ stimulates kidneys to produce EPO
RBC Production ~ erythropoiesis
Occurs ONLY in red bone marrow
Hematoblasts ~ stem cells ----> Myeloid Stem Cells
----> Proerythroblast ----> Erythroblast (in marrow)
----> Reticulocyte ~ immature blood cell (in blood)
Represent 1-2% of circulating RBC’s
Indicator of “NEEDED” RBC formation
RBC Production Stimuli
1.
Hemorrhage ~ reduced circulating RBC’s
2.
Anemia reduced RBC production
increased RBC destruction
3.
Reduced O2 availability ~ high altitude
4.
Lung Damage or Disease ~ low O2 exchange
Pneumonia ~ Cancer ~ Emphysema
5.
Increased O2 tissue demands ~ Exercise
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
Diseases & Abnormal RBC Production
Anemia ~ “lack of blood” ~ Lack of O2 carrying capacity
Symptoms: Low blood O2 levels
Fatigue
Shortness of breath
Pale & Chilly
Causes: 1.
Insufficient number of RBC’s
Hemorrhage ~ blood loss
Destruction of RBC’s ~ “Hemolytic”
Bone marrow failure ~ “Aplastic”
2.
Decreased hemoglobin content
Iron deficiency anemia ~ low Fe
Pernicious anemia ~ low B12
3.
Abnormal Hemoglobin
Sickle cell anemia ~ hereditary
4.
Kidney Disease ~ Renal Failure
NO erythropoietin
Polycythemia ~ Excessive RBC’s ~ Hematocrit > 80%
Abnormal viscosity ~ sludge
Polycythemia vera ~ bone marrow cancer
High Altitude
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
FORMED ELEMENTS
Leukocytes – White Blood Cells - WBC’s
True cells ~ Have nuclei & mitochondria
Account for < 1% of total blood volume
Normal Count:
4,000-11,000 WBC’s/ cc
Make up buffey coat ~ centrifuged blood
Body defense against disease
Inflammation & immune function
Migrate into tissue via capillary beds & venules
Gather large numbers at site of tissue damage/infection
Increased production ~ “leukocytosis” > 11000 per cc
Types of White Blood Cells
Granulocytes:
Agranulocytes:
Neutrophils
Basophils
0-1%
Eosinophils
1-4%
Lymphocytes
Monocytes
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
40-70%
8
20-45%
4-8%
Dr. Vince Scialli
BSC 1086
Leukocytes ~ White Blood Cells ~ WBC’s
GRANULOCYTES ~ granules in cytoplasm
Spherical shaped ~ Larger than RBC’s . . . All have nuclei
Shorter lived than RBC’s ~ 12 hrs – to 3 days
Function:
phagocytosis ~ to attack & destroy
“Non-specific” body defenses ~ attack anything
1.
Neutrophils
MOST numerous type ~ up to 70% of WBC’s
Cytoplasm Granules ~ blue & red stain
Polymorphs ~ many shapes ~ 2 to 5 nuclear lobes
Function: Phagocytosis ~ of bacteria & fungi
Neutrophilia ~ INCREASE during infection ~ Pus
2.
Eosinophils
Account for up to 4% of WBC’s
Same size as neutrophils ~ Red stained granules
Function:
attack & destroy parasites ~ worms
Destroy antibody-antigen complex
Allergic response ~ Fire Ant Bites
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
GRANULOCYTES ~ LEUKOCYTES
2.
Basophils
RARE WBC ~ up to 1% of WBC’s
Smaller than neutrophils
Cytoplasm stains blue
Cytoplasm Granules contain HISTAMINE
Histamine ~ inflammatory chemical
Potent vasodilation
Attracts neutrophils to infection site
AGRANULOCYTES
NO GRANULES in cytoplasm
Monocytes & Lymphocytes
Blood life span ~ 100-300 days
Important in immunity ~ antibody formation
1.
Monocytes
Account for up to 8% of WBC’s
Very large ~ LARGEST WBC
Become Macrophages ~ phagocytosis in tissue
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
2.
Lymphocytes
Second most numerous WBC ~ up to 45%
Small Lymphocytes ~ found in blood only
Medium & Large Lymphocytes ~ MOST numerous
Found in lymphatic tissue
Spleen . . . Lymph Nodes . . . Tonsils
T-Lymphocytes ~ T-cells
Immune Response ~ “cell mediated immunity”
Act against virus infected cells
Act against tumor cells
B-Lymphocytes ~ B-cells
Immune Response ~ “humoral immunity”
B-cells become “plasma cells”
Produce antibodies ~ immunoglobulins
NK Cells ~ Natural Killer Cells
Immune Surveillance ~ “on patrol”
Detect & destroy abnormal tissue
Involved in cancer prevention
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
LEUKOCYTE PRODUCTION & LIFE SPAN
Leukopoiesis ~ WBC Leukocyte Production
Stimulated by CYTOKINES
Cytokines produced by:
Macrophages
T-Lymphocytes
Leukocyte Differentiation Pathway
Hemocytoblast
(red bone marrow)
Myeloid Stem Cell
↓
Myeloblast
↓
Monoblast
↓
Promyelocyte
↓
Promonocyte
Lymphoid Stem
↓
Lymphoblast
↓
Prolymphocyte
↓
Band Cells
↓
↓
Monocytes
Lymphocytes
T-Lymphocytes
B-Lymphocytes
↓
↓
(immature)
↓
Eosinophils
Neutrophils
Basophils
Macrophages
(tissues)
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Plasma Cells
(antibodies)
Dr. Vince Scialli
BSC 1086
LEUKOCYTE DISORDERS & ABNORMALATIES
Leukopenia ↓ ↓ ↓
ABNORMAL LOW white cell count < 4000/cc
Cause:
Virus Infection ~ lymphopenia ~ ↓ Lymphocytes
Drugs:
Anti-cancer agents & Glucocorticoids
Leukocytosis ↑ ↑ ↑
Increased WBC count ~ usually neutrophils
Causes: Bacterial Infections ~ moderate increase
Leukemia ~ a specific disease with MANY forms
Over-production of “ABNORMAL” leukocytes
Bone marrow becomes infiltrated with immature &
abnormal WBC’s
Destroys Body defenses & RBC production
Symptoms:
Vary with MANY forms of leukemia
Infectious Mononucleosis ~ a specific disease
Highly contagious viral infection ~ “kissing disease”
Excessive production of monocytes & lymphocytes
Disease runs course in 3-4 weeks
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
FORMED ELEMENTS
Platlets ~ thrombocytes
Fragments of large Megakaryocytes ~ NOT true cells
Megakaryocytes derived from stem Hemocytoblasts
Purple stained cytoplasmic granules
Platelets contain: Ca+, serotonin, enzymes, & ADP
Seratonin causes vascular spasm
Degenerate in ~ 10 days . . . Continuously Produced
Normal Platelet Count ~ 250,000 - 500,000 per cc of blood
Function:
Clotting mechanism
Stick to damaged sites ~ tenaciously adhere to collagen
Form plug to prevent blood loss when blood vessel is
damaged
Response is fast & localized
Hemostasis ~ stop bleeding
Thrombocytosis ~ very HIGH platelet count
Thrombocytopenia ~ very LOW platelet count
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
HEMOSTASIS
Blood Clotting Phases ~ Stop Bleeding in SMALL vessels
VERY RAPID sequence ~ 5 seconds to 30 minutes
Vascular Spasm
Immediate vasoconstriction ~ causes  blood flow
Enhanced by seratonin
Allows time for platelet formation (20-30 minutes)
Platelet Plug Formation ~ Platelet Aggregation
Platelets DO NOT adhere to endothelial lining
Platlet Plug ~ temporarily seals break in vessel wall
Platlets adhere tenaciously to exposed collagen
MORE platelets attracted & stick to area
Coagulation Steps ~ actual blood clotting
Blood transformed from liquid to gel
Prothrombin Activator formed in10-15 sec in Liver
Prothrombin converted to Thrombin ~ enzyme
Thrombin > Fibrinogen in plasma to form a Fibrin
Mesh > Blood Clot
Fibrin mesh traps RBC’s & seals vessel ----> Clot
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
CLOT RETRACTION & REPAIR
Occurs 30 – 60 minutes after clot is stabilized
Platelets induce process
Platelets pull serum from clot ----> compacted clot
Pulls vessel hole or damage together
Vessel wall endothelial cells multiply & restore lining
Fibroblasts form connective tissue patch ----> Scar
Granulation Tissue
FIBRINOLYSIS
Enzyme reactions causing clot to dissolve
Clot digestion follows healing of damaged vessel
Takes several days
Prevents vessels from becoming blocked
Plasmin ----> TPA ----> Plasminogen = Clot Buster
TPA = Tissue Plasminogen Activator
Plasminogen ~ is a clot dissolver
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
OTHER COAGULATION FACTORS . . . REQUIRED
Pro-coagulants ~ “Coagulants” ~ SEVERAL & COMPLEX
Plasma Proteins ~ have direct clotting effects
Prothrombinase ~ Prothrombin ~ Thrombin
Fibrinogen ~ Fibrin
Factors I-XIII ~ several factors involved in clotting
Vitamin K ~ required for factor synthesis
Prostaglandins ~ cause platelet adherence
Aspirin ~ prostaglandin inhibitor ~ anti-coagulant
FACTORS LIMITING CLOT GROWTH ~ Anti-coagulation
PREVENT excessive or unnecessary clot formation
Plasma Anti-coagulants ~ normally circulating
Antithrombin III ~ inhibits Thrombin
Heparin ~ found in basophils & mast cells
Blood Thinner ~ Inhibits Thrombin
Protein C ~ plasma protein inhibits other Pro-coagulants
Breaks down fibrin strands
Tissue Plasminogen Activator ~ Fibrinolysis clot buster
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
HEMOSTASIS DISORDERS
Thrombo-embolytic Conditions
Thrombus ~ NORMAL clot fragments in circulation
Could cause “occlusion” ~ blockage in small vessel
Coronary Thrombosis ~ Heart Attack
Cerebral Thrombosis ~ stroke
Embolism ~ floating clot or air bubble in small vessel
Artherosclerosis ~ rough vessel walls ~ attract platelet
Treatment of Thromboembolic Conditions
Aspirin ~ anti-prostaglandin ~ anti-coagulant
Heparin ~ anti-coagulant ~ blood thinner
Warfarin ~ Coumadin ~ Dicoumarol ~ rat poisons
Vitamin K inhibitor ~ anti-coagulant
Tissue Plasminogen Activator TPA ~ # 1
Plavex ~ prevents platelet adherence to walls
Cardiac Catherization . . . Angioplasty . . . Stent
By-pass surgery as last resort
Cost considerations & vessel condition in options
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
HEMOSTASIS DISORDERS
Bleeding Disorders
Anything that interferes with the clotting mechanism
Thrombocytopenia ~ deficient platelets
Cause: bone marrow suppression
Malignancy
Radiation
Certain drugs
Symptoms ~ spontaneous Petichae Hemorrhage
Impaired Liver Function ~ many conditions
Liver CANNOT produce pro-coagulants
No Prothrombin or Fibrinogen
CANNOT utilize Vitamin K ~ no factor synthesis
Hemophilia
Due to lack of necessary clotting Factors
Sex linked condition ~ X chromosome in males
A ~ Hereditary deficiency ~ Factor VIII – 83%
Von Willebrand Disease
Most common inherited Factor VIII clotting
disorder
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
WHOLE BLOOD TRANSFUSION ~ Blood Replacement
A Normal System minimizes effects of blood loss
Reduced volume of blood in affected vessels - - - ->
Lower Pressure - - - -> vasoconstriction
Increased production of RBC’s occurs immediately
System can be overwhelmed . . . if blood loss to great
“Transfusion” ~ given to replace lost blood
Severe blood loss ~ requires whole blood transfusion
Anemia ~ requires packed red cell replacement
Thrombocytopenia ~ requires platelets only
Transfusion requires knowing specific blood types
HUMAN BLOOD GROUPS ~ Typing or Cross Matching
People have different blood types . . . ABO & Rh
Transfusion of incompatible blood can be fatal
Antigens ~ agglutinogens ~ found on surface of RBC’s
Surface proteins that stimulate antibodies that
attach to RBC ----> agglutination or clumping in
recipient, if the recipient does not have the same
surface antigens on their own RBC’s
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
HUMAN BLOOD GROUPS ~ BLOOD TYPING
Several types of RBC surface antigens can exist
A or B are MOST COMMON & most allergenic antigens
Rh Factor is either present (Rh+) or absent (Rh-)
ABO SYSTEM
A-
=
A surface antigen. No Rh antigen (Rh-)
Will make antibodies against B antigen and Rh+ antigen
A+ =
A surface antigen and Rh antigen ~ Rh+
B-
B surface antigen. No Rh antigen ~ Rh-
=
B+ =
B surface antigen and Rh antigen ~ Rh+
AB- =
A and B surface antigens. No Rh antigen ~ Rh-
AB+ =
A and B surface antigens & Rh antigen ~ Rh+
O-
None of the surface antigens are present ~ Rh-
=
O+ =
Only Rh+ antigen present
If a person receives blood from a type different from their own
(other than type O = no surface A or B antigens), the immune
system will recognize the blood as foreign, and antibodies are
produced. This will cause clumping ~ agglutination
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
ABO BLOOD SYSTEM
Type O = Universal Donor ~ no A or B antigens
Will not be recognized as foreign if injected
into Type A, Type B or Type AB recipients
Types A, B, AB, and O can all receive blood
from Type O
If no A or B antigens, then no antibodies produced
Type O recipient can only receive blood from
Type O donor
Type AB = Universal Recipient ~ both A and B antigens
Type AB recipient will not make antibodies against Type
A or Type B donor blood since both A and B antigens are
already present
Type AB recipient can receive donor blood from Type O
since Type O blood has no surface antigens
Type AB can also receive blood from Type A or Type B
since neither is recognized as foreign
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
ABO BLOOD SYSTEM
Rh Factor
85% of population is Rh+
Problem occurs when Rh- person receives blood from
Rh+ donor
“Sensitizes” Rh- recipient to produce antibodies against
Rh+ blood
First transfusion is not a problem
Causes Hemolysis ~ rupture of RBC’s
Becomes a problem in future transfusions
Must check for “Compatability”
Rh+ fetuses inside Rh- pregnant mothers
Hemolytic Disease of the Newborn ~erythroblastosis
fetailis
Fetus Rh+ blood crosses placenta into Rh- pregnant
mother
Pregnant mother produces antibodies against Rh+
Anti Rh+ Antibodies cross placenta into fetus causing
hemolysis of fetus blood
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
TRANSFUSION REACTIONS
Agglutination & Hemolysis
Donor’s blood is attacked once injected into recipients
blood by recipients antibodies
Reaction Steps:
1.
Agglutination ~ occurs within 1-2 hrs
Clumping of foreign RBC’s due to ABO
Clogging of small vessels
2.
Hemolysis ~ busting of RBC’s due to Rh
Reduces O2 to tissues
RBC’s Destroyed by phagocytosis
Hemoglobin released ~ clogs kidneys
Kidney failure
Symptoms: Fever & Chills
Nausea and Vomiting
Signs of Kidney Failure ~ if severe
Treatment: Reverse Kidney Shutdown
Prevent Renal Damage
Diuretics ~ flush out Hb
Prevent:
Blood Typing ~ Compatability Check
Cross Matching ~ agglutination test
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
PLASMA & BLOOD VOLUME EXPANDERS
Given when replacement fluid volume is necessary
Low Blood Volume ----> circulatory shock
Emergency Situations ~ NO time to type or match
MUST restore adequate circulation fast
No concern for allergic reaction
No RBC’s involved ~ no antigens involved
Synthetic Plasma Expanders
Normal Saline ~ isotonic
Multiple Electrolyte Solution ~ Lactated Ringers ~ iso
Dextran ~ concentrated sugar solutions ~ hypertonic
Plasminate ~ synthetic plasma ~ hypertonic
Serum albumin ~ hypertonic
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
DIAGNOSTIC BLOOD TESTS
Provide information about the blood & body conditions
Evaluates current state of health . . . NOT ABSOLUTE
Types of Tests:
Complete Blood Count ~ CBC
RBC Count
WBC Count ~ with differential
Hemoglobin
Hematocrit ~ PCV
Platelet Count
Differential White Cell Count
Relationship % and absolute numbers of
neutrophils, eosinophils, basophils lymphocytes
and monocytes
Serum Modular Analysis ~ SMA
Serum ~ plasma minus clotting proteins
Blood chemistry profile:
Protein ~ albumin, globulin
Glucose
BUN ~ kidney function
+ many others
Enzymes (many)
Ions ~ Ca+, Na+, K+
Blood Gases
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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Dr. Vince Scialli
BSC 1086
AGE RELATED CHANGES AFFECTING BLOOD
Decreased Hematocrit
Constriction or blockage of peripheral arteries ~ thrombus
Causes Pulmonary Embolism
Pooling of blood in veins of legs ~ varicose veins
Valves not working properly
Blood and Clotting ~ Chapter 19 ~ 4/29/2017
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