CARDIOVASCULAR SYSTEM: Blood: Chapter 19
Cardiovascular System Consists of:
1. a pump
2. a transport system
3. a fluid medium
Components of Blood: specialized fluid of connective tissue
Plasma
Formed Elements
Erythrocytes, leukocytes, platelets
buffy coat
Functions of Blood
1. Delivery of
from the lungs &
from the digestive tract to
2. Transport of wastes (CO2 & metabolic wastes) to
3. Transport of
.
from the endocrine organs to their target organs.
4. Maintenance of body temperature
5. Maintenance of normal pH in body tissues
6. Maintenance of blood volume
7. Prevention of blood loss
8. Prevention of infection
Characteristics of Blood:
1. color:
2. pH
3. temperature
4. volume: normovolemic (7% of body weight)
hypovolemic:
Hypervolemic
How does blood volume effect blood pressure (BP)?
PLASMA: makes up 50-60% of blood volume
•clear, pale yellow
•90% water
↑ water = ↑ plasma volume (clinically plasma volume expanders)
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•also contains:
a. proteins (plasma proteins): synthesized in
-albumin: carrier protein, buffer, maintains osmotic pressure
-globulins
immunoglobulins: IgG, IgA, IgM
transport globulins
hormone binding proteins: TBG
metalloproteins: transferrin
apolipoproteins - (lipoprotein)
-fibrinogen
-other plasma proteins: hormones, enzymes
b. other: dissolved gasses, nutrients
•serum: plasma without clotting proteins
Key Differences between Plasma and IF
1.) Levels of O2 and CO2
2.) Concentrations & types of dissolved proteins
Plasma contains more protein
Plasma proteins do not pass through capillary walls
FORMED ELEMENTS: (p. 658 table 19-3)
Formation of Formed Elements
•hemopoiesis (hematopoiesis)
hemocytoblast:
3 Types of Formed Elements:
1.) RBC or Erythrocytes
2.) WBC or Leukocytes
3.) Platelets
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1. Erythrocytes:
•anucleate – can’t undergo mitosis – continuously formed in bone marrow
live for aprx. 3-4 months
• also lack mitochondria – rely on anaerobic metabolism
packets of hemoglobin (Hb)
• disc shaped, flexible
Importance of RBC Shape and Size
 High surface-to-volume ratio
▪ Quickly absorbs and releases oxygen
▪
 Discs form stacks called rouleaux
▪ Smooth the flow through narrow blood vessels
▪
 Discs bend and flex entering small capillaries:
▪ 7.8 µm RBC passes through 4 µm capillary
• most numerous of the formed elements: 1 mm3 (µl) contains aprx. 5 million RBCs
• hematocrit (VPRC or PCV):
Normally - females 36-42%, males 44-50%
Hct increases during dehydration
Hct decreases if internal bleeding or RBC formation problems
Viscosity:
• each RBC contains hemoglobin:
Globin
Heme pigment
Fe
-expressed as grams/100 ml of whole blood, normal 12 - 18g/dl
-oxyhemoglobin (HbO2)
-reduced or deoxyhemoglobin (HHb)
- carbaminohemoglobin (HbCO2)
- release nitric oxide to dilate blood vessels
Fetal Hemoglobin:
Storage form of Hb found in embryos
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Formation of Erythrocytes:
erythropoiesis:
3 million/second
As cells differentiate, accumulate hemoglobin then lose organelles and nucleus
Reticulocyte released from bone marrow, matures into erythrocyte in blood
Reticulocyte count shows
erythropoietin (EPO) – from kidneys
released during hypoxia- stimulates hemopoiesis
renal failure reduces EPO production
(note testosterone also increases EPO production)
Blood Doping: artificially boosting Hct to increase O2 delivery to cells & aerobic performance
Dietary requirements:
Carbohydrates /Fat intake
Folic Acid: necessary for protein synthesis
B12 & intrinsic factor –
Destruction of Erythrocytes
RBC phagocytized (hemolysis) by macrophages
in the liver, spleen and bone marrow
(some RBC hemolyze in the bloodstream
& Hb excreted by kidneys in urine, if
excessive= hemoglobinuria)
RBC - Hb split off and broken down into heme
and globin
globin portion:
iron: stored or transported via transferrin
heme portion → Fe stripped and remainder is
biliverdin → bilirubin →bloodstream to liver for
excretion in bile→ large intestine
jaundice: bilirubin diffuses into skin/sclera
urobilin — yellow
stercobilin: brown
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Transfusion and Blood Replacement
Blood Groups or Types are genetically determined
ABO Blood Groups
Antigen (termed agglutinogens): antigen A or B
cell membrane surface proteins – cellular “ID” cards
Antibody (agglutinins): found in plasma, Anti-A or Anti-B
Identify and attack foreign antigens: form antigen-antibody complex (agglutination) or clumping &
hemolyze
Called a cross (transfusion) reaction:
ABO Blood Typing: Named for presence/absence of RBC antigen
Blood Group
RBC antigens
Plasma
antibodies
Blood that can be
received
A
B
AB
O
AB is universal recipient:
O is universal donor:
Rh (D) Blood Groups: Rh antigen either (+) or (-)
Rh + is dominant: R
RR or Rr are:
rr is:
Normally Rh- does not have Rh antibodies
Only forms them if sensitized (exposed): concern if Rh- mother (Rh+ father) has Rh+ fetus
Hemolytic Disease of the Newborn
Mom type O blood & baby A or B
Mom’s anti-A and Anti-B antibodies can cross placenta
Mom Rh- & baby Rh+
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2. Leukocytes: aprx. 5000 – 10000 per mm3
• circulate for short periods
• have nuclei
• Functions:
1.) defend against pathogens\
2.) remove toxins and wastes
3.) attack
• capable of amoeboid movement and can migrate from the blood vessel and travel to the injury site
diapedesis (emigration):
• find infections/damaged tissues via positive chemotaxis
• neutrophils, eosinophils and monocytes capable of phagocytosis
Granulocytes and Agranulocytes: under control of colony-stimulating factors & cytokines
Granulocytes: (derived from myeloblast)
stimulated by G-CSF & GM-CSF
1. Neutrophil (polymorphonuclear leukocytes PMNs):
1st on site
Pale cytoplasm with granules
attack bacteria marked by antibodies or complement
engulf bacteria/pathogens - metabolism increases (respiratory burst) results in H2O2 and superoxide
anions which kill bacteria
secrete defensins to kill pathogen (bacteria, fungi, viruses)
release prostaglandins and leukotrienes
2. Eosinophils:
attack anything coated with antibodies
use phagocytosis and exocytosis (nitric oxide & cytotoxic enzymes)
sensitive to allergens
also moderate inflammation from mast cells & neutrophils
3. Basophils: rarest of the leukocytes
important for triggering the inflammatory response
release histamine and heparin
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Agranulocytes:
1. Lymphocytes (derived from lymphoblast)
Second most numerous
some circulate/migrate
mostly found in
Part of the body’s specific defense system
Three Classes of Lymphocytes:
1.) T Cells: cell-mediated immunity
2.) B Cells: humoral immunity
3.) NK (natural killer) cells: immune surveillance
Destroy and kill abnormal cells
2. Monocytes (derived from monoblast)
stimulated by M-CSF and GM-CSF
tissue macrophages
Differential Count: detects changes in WBC populations
Leucopenia (leukopenia):
Leukocytosis
Leukemia
Regulation of WBC Production
Colony-stimulating factors = CSFs :
Hormones that regulate blood cell populations:
1. M-CSF stimulates monocyte production
2. G-CSF stimulates granulocyte (neutrophils, eosinophils, and basophils) production
3. GM-CSF stimulates granulocyte and monocyte production
4. Multi-CSF accelerates production of granulocytes, monocytes, platelets, and RBCs
3. Platelets (megakaryocytes) or thrombocytes (derived from progenitor cells)
• 150,000 – 400,000 per mm3 of blood
• not typical cell – more like cell fragment with chemicals
• megakaryocyte can form aprx. 4000 platelets
• only live for
• stored in
• functions: release chemicals for clotting, form platelet plug, clot retraction
thrombocytopoiesis: in bone marrow
TPO (thrombopoietin), IL-6 stimulate platelet formation
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thrombocytopenia:
thrombocytosis
HEMOSTASIS
1. Vascular phase
2. Platelet phase
3. Coagulation phase
Step 1: Vascular Phase: immediate response
• Vascular Spasm• Endothelial cells release chemicals & hormones (ADP, prostacyclin, endothelians)
• Endothelial cell membranes become sticky
Step 2: Platelet Phase: begins within 15 seconds
• Platelets become sticky - platelet adhesion & aggregation forms platelet plug
Platelets stick to
•Normally platelets don't cling to each other or the smooth lining of blood vessels.
injury causes platelets to become activated: release chemicals
1.) ADP (adenosine diphosphate) –
2.) thromboxane A2 –
3.) serotonin –
4.) platelet-derived growth factor (PDGF) –
5.) calcium ions –
6.) prostacyclin –
7.) protein C or S
• positive feedback of activation & attraction of platelets to the area.
Step 3: Coagulation Phase (Blood Clotting): begins 30 seconds or more after the injury
• Requires clotting factors (procoagulants): proteins or ions in plasma
• Extrinsic pathway begins in vessel wall (outside of bloodstream) – TF (Factor III)
“short-cut” to final steps • Intrinsic pathway– begins in bloodstream – PF-3
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• Common pathway – begins when enzymes from either activate Factor X forming
prothrombinase
1.) Prothrombinase is formed
2.) Converts proenzyme prothrombin into enzyme thrombin
3.) Finally thrombin catalyzes the joining of the protein fibrinogen molecules present in the plasma into
a fibrin mesh
Procoagulants: enhance clot formation
Anticoagulants: inhibit clot formation
heparin, prostacyclin, protein C,
antithrombin-III, aspirin
Normally anticoagulants dominate & clotting is
prevented, but when a vessel is ruptured
procoagulant activity increases
Clot formation normally complete w/i 3-6 min.
Clotting process needs Ca++ and vitamin K
After clot is formed, clot retraction occurs.
ruptured vessel edges are drawn together –
easier for repair by fibroblasts, smooth muscle cells, endothelial cells
When healing is complete, clot digestion (fibrinolysis) occurs.
t-PA activates plasminogen into plasmin
"Clinically Speaking" (see applications manual)
1. Anemia: decreased ability to carry/deliver oxygen
A. Insufficient numbers of RBC:
-hemorrhagic anemia: due to internal or external bleeding
-hemolytic anemia: RBC are prematurely lysed
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-aplastic anemia- caused by destruction of the bone marrow
Can be hereditary or caused by drugs
-pernicious anemia: lack of vitamin B12
B. Decreased ability of Hb to carry O2:
-iron deficiency anemia: more common in women
C. Abnormal Hb
-sickle cell anemia: hypoxia caused hemoglobin to change shape which changes shape of RBC
2. Polycythemia:
-blood doping
3. Leukemias:
Bone marrow cancer that results in large numbers of abnormal WBCs
These cells “crowds out” the RBC and platelets
Abnormal WBCs can migrate
4. Infectious Mononucleosis:
Caused by Epstein-Barr virus
Flu-like symptoms
5. Thromboembolytic conditions:
thrombus: abnormal stationary blood clot
caused by: genetics, lack of anti-coagulants
embolism: travelling blood clot
dangerous if becomes stuck in smaller blood vessel
Tx: heparin, coumadin (warfarin), dicumarol, TPA, streptokinase, aspirin
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6. Hemophilias:
x-linked genetic disorder
problems with clotting
7. Impaired liver function: liver unable to synthesize procoagulants
Liver also needs vitamin K to make clotting factors
Common hematology diagnostics: see pages 123-126 in Applications Manual
Other:
Synthetic Blood
Genetically engineered
Platelet Rich Plasma Therapy
Speeds recovery from damaged ligaments & tendons (may regenerate fibers)
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