Transcript Chapter 19 - Martin

Blood
Chapter 19
Functions of blood
• Transportation
–
–
–
–
Oxygen
Carbon dioxide
Nutrients & Hormones
Wastes
• Regulation
– Fluid balance & Thermoregulation
– pH & Electrolytes
• Protection
– Immune System & bodies defenses
– Clotting and wound repair
Physical characteristics of Blood
• Yes, it is thicker than water
• pH between 7.35 (venous) and 7.45 (arterial)
• Volume
– 5 to 6 liters in an average male (1.5 gal or 12 pints)
– 4 to 6 liters in an average female (1.2 gal or 10 pints)
• About 20% of the extracellular fluid
• About 8% of the body mass
Composition of Blood
• Whole blood is divided into plasma and formed
elements
• Plasma:
– 55% of whole blood volume
– 91.5% water
– 7% soluble proteins
• Albumin = 54% (osmotic balance, buffering, transport of
steroid hormones and fatty acids)
• Globulins = 38% (antibodies, etc)
• Fibrinogen = 7% (produced by liver, for clotting)
• 1% other
– Other solutes
• Electrolytes, gases, nutrients, wastes, hormones
Composition
of Blood
Extracellular Fluids
• Interstitial fluid (IF) and plasma
• Materials plasma and IF exchange across
capillary walls:
– water
– ions
– small solutes
Plasma
3 Classes of Plasma Proteins
• Albumins (60%)
• Globulins (35%)
• Fibrinogen (4%)
Origins of Plasma Proteins
• 90% made in liver
• Antibodies made by plasma cells
• Peptide hormones made by endocrine
organs
Formed Elements
• Erythrocytes (a.k.a. red blood cells)
4 to 6 million per mm3 (mL)
About 7 - 8 mm in diameter
Anucleate
Amitotic at maturity
No mitochondria, centrioles, or much else in the way
of cytoplasm. Mostly hemoglobin.
– Live about 90 – 120 days
–
–
–
–
–
• Hematocrit – The total volume of blood occupied
by erythrocytes.
– 38 – 46 % for females, average 42%
– 40 – 54% for males, average 47%
Normal Blood Counts
• RBC:
– male: 4.5–6.3 million
– female: 4.–5.5 million
• Hematocrit:
– male: 4–52
– female: 3–47
Fig.19.02
Formed
elements
An Erythrocyte
Hemopoiesis: formation of blood cells
• Also known as hematopoiesis
• Occurs in the red marrow:
– In adults, mostly in the proximal epiphysis of femur
and bodies of the lumbar vertebrae
– Originally from pluripotent stem cells from
mesenchyme
– In the fetus, hematopoiesis occurs in the liver,
spleen, thymus, lymph nodes and yolk sac
– Red marrow is found in the spaces of spongy bone
• Erythropoietin from the kidneys stimulates
hematopoiesis
Erythrocyte
development
Stages of RBC Maturation
•
•
•
•
•
Myeloid stem cell
Proerythroblast
Erythroblasts
Reticulocyte
Mature RBC
The structure of the hemoglobin
molecule
Hemoglobin (Hb)
• Each RBC contains an average of 250 million
Hb molecules
• Each Hb molecule has 4 oxygen binding sites
• That’s about 1 billion oxygen molecules per
RBC!
• CO (carbon monoxide) has approximately 200
times the affinity for Hb than oxygen and it
fool O2 saturation detectors
Erythrocyte catabolism
• After roughly 120 days red blood cells are worn
out and must be recycled
• This occurs in the spleen and liver
• Iron (Fe+++):
– The Fe+++ is removed from the heme group and
bound to transferrin
– It is stored in the liver, muscle and spleen by
transferring it to ferritin
– It can be transported on demand to the bone marrow
where it can be reincorporated into new Hb
RBC catabolism continued
• The rest of the heme molecule:
– First converted to biliverdin (it is green)
– Then to bilirubin (it is yellow-orange)
– It’s carried in the blood to the liver where it is
secreted into bile
– Bile is stored in the gall bladder (if you have one) and
then into the small intestine
– When it reaches the large intestine it is converted by
bacteria into urobilinogen
– Some is reabsorbed and excreted in the urine (urobilin
or urochrome). The rest is in the feces (stercobilin)
RBC life cycle
Recycling RBCs
• 1% of circulating RBCs wear out per day:
– about 3 million RBCs per second
• Macrophages of liver, spleen, and bone marrow:
– monitor RBCs
– engulf RBCs before membranes rupture
(hemolyze)
Erythrocyte disorders
Anemia & polycythemia
Diagnosing Disorders
• Hemoglobinuria:
– hemoglobin breakdown products in
urine due to excess hemolysis in blood
stream
• Hematuria:
– whole red blood cells in urine due to
kidney or tissue damage
Anemia: Insufficient
Erythrocytes
• Hemorrhagic anemia – result of acute or
chronic loss of blood
• Hemolytic anemia – prematurely ruptured
erythrocytes
• Aplastic anemia – destruction or inhibition
of red bone marrow
Anemia: Decreased Hemoglobin
Content
• Iron-deficiency anemia results from:
– A secondary result of hemorrhagic anemia
– Inadequate intake of iron-containing foods
– Impaired iron absorption
• Pernicious anemia results from:
– Deficiency of vitamin B12
– Lack of intrinsic factor needed for absorption of B12
• Treatment is intramuscular injection of B12
Anemia: Abnormal Hemoglobin
• Thalassemias – absent or faulty globin
chain in hemoglobin
– Erythrocytes are thin, delicate, and deficient in
hemoglobin
• Sickle-cell anemia – results from a
defective gene coding for an abnormal
hemoglobin called hemoglobin S (HbS)
– HbS has a single amino acid substitution in the
beta chain
– This defect causes RBCs to become sickleshaped in low oxygen situations
Polycythemia
• Polycythemia – excess RBCs that increase
blood viscosity
• Three main polycythemias are:
– Polycythemia vera
– Secondary polycythemia
– Blood doping
Sickle
Cell
Disease
RBC
homeostasis
Leukocytes
• White blood cells are important for bodily
defenses and immunity
• 2 General categories:
– Granulocytes
• Neutrophils
• Eosinophils
• Basophils
– Agranulocytes
• Lymphocytes
• Monocytes
Granulocytes
• Granulocytes – neutrophils, eosinophils,
and basophils
– Contain cytoplasmic granules that stain
specifically (acidic, basic, or both) with
Wright’s stain
– Are larger and usually shorter-lived than RBCs
– Have lobed nuclei
– Are all phagocytic cells
Neutrophils
• Neutrophils have two types of granules that:
– Take up both acidic and basic dyes
– Give the cytoplasm a lilac color
– Contain peroxidases, hydrolytic enzymes, and
defensins (antibiotic-like proteins)
• Neutrophils are our body’s bacteria slayers
Eosinophils
• Eosinophils account for 1–4% of WBCs
– Have red-staining, bilobed nuclei connected via
a broad band of nuclear material
– Have red to crimson (acidophilic) large, coarse,
lysosome-like granules
– Lead the body’s counterattack against parasitic
worms
– Lessen the severity of allergies by
phagocytizing immune complexes
Basophils
• Account for 0.5% of WBCs and:
– Have U- or S-shaped nuclei with two or three
conspicuous constrictions
– Are functionally similar to mast cells
– Have large, purplish-black (basophilic)
granules that contain histamine
• Histamine – inflammatory chemical that acts as a
vasodilator and attracts other WBCs (antihistamines
counter this effect)
Agranulocytes
• Agranulocytes – lymphocytes and
monocytes:
– Lack visible cytoplasmic granules
– Are similar structurally, but are functionally
distinct and unrelated cell types
– Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
Lymphocytes
• Account for 25% or more of WBCs and:
– Have large, dark-purple, circular nuclei with a
thin rim of blue cytoplasm
– Are found mostly enmeshed in lymphoid tissue
(some circulate in the blood)
• There are two types of lymphocytes: T cells
and B cells
– T cells function in the immune response
– B cells give rise to plasma cells, which produce
antibodies
Monocytes
• Monocytes account for 4–8% of leukocytes
– They are the largest leukocytes
– They have abundant pale-blue cytoplasms
– They have purple-staining, U- or kidney-shaped
nuclei
– They leave the circulation, enter tissue, and
differentiate into macrophages
Monocytes
• Macrophages:
– Are highly mobile and actively phagocytic
– Activate lymphocytes to mount an immune
response
Leukocytes
WBC
Production
Figure 19–10
4 Colony-Stimulating Factors (CSFs)
• Hormones that regulate blood cell
populations:
1. M-CSF:
• stimulates monocyte production
2. G-CSF:
• stimulates granulocyte production
• neutrophils, eosinophils, and basophils
4 Colony-Stimulating Factors (CSFs)
3. GM-CSF:
• stimulates granulocyte and monocyte
production
4. Multi-CSF:
• accelerates production of
granulocytes, monocytes, platelets,
and RBCs
Chemotaxis of neutrophils
Leukocyte Disorders
• Leukemia
– Acute: uncontrolled production of immature
WBCs.
– Chronic: accumulation of mature WBCs in the
blood
Leukocytes Disorders: Leukemias
• Leukemia refers to cancerous conditions
involving white blood cells
• Leukemias are named according to the
abnormal white blood cells involved
– Myelocytic leukemia – involves myeloblasts
– Lymphocytic leukemia – involves lymphocytes
• Acute leukemia involves blast-type cells
and primarily affects children
• Chronic leukemia is more prevalent in older
people
Leukemia
• Immature white blood cells are found in the
bloodstream in all leukemias
• Bone marrow becomes totally occupied
with cancerous leukocytes
• The white blood cells produced, though
numerous, are not functional
• Death is caused by internal hemorrhage and
overwhelming infections
• Treatments include irradiation, antileukemic
drugs, and bone marrow transplants
Hemostasis & clotting
• Involves:
– platelets (fragments of megakaryocytes)
– Proteins & Fibers (Thrombin & Fibrin)
– Clotting factors
Platelets
• Cell fragments involved in human clotting
system
• Nonmammalian vertebrates have
thrombocytes (nucleated cells)
Platelet Circulation
• Circulates for 9–12 days
• Are removed by spleen
• 2/3 are reserved for emergencies
Platelet Counts
• 150,000 to 500,000 per microliter (mm3)
• Thrombocytopenia:
– abnormally low platelet count
• Thrombocytosis:
– abnormally high platelet count
Hormonal Controls
• Thrombopoietin (TPO)
• Inteleukin-6 (IL-6)
• Multi-CSF
Hemostasis
The Platelet Phase
• Platelet aggregation (stick together):
– forms platelet plug
– closes small breaks
The Platelet Phase
• Platelet adhesion (attachment):
– to sticky endothelial surfaces
– to basal laminae
– to exposed collagen fibers
• Platelet aggregation (stick together):
– forms platelet plug
– closes small breaks
Platelet plug
formation
Plug
formation
Clotting
The Coagulation Phase
Figure 19–12a
Plasma Clotting Factors
Table 19–4
Hemostasis Disorders:
Thromboembolytic Conditions
• Thrombus – a clot that develops and persists
in an unbroken blood vessel
– Thrombi can block circulation, resulting in
tissue death
– Coronary thrombosis – thrombus in blood
vessel of the heart
Hemostasis Disorders:
Thromboembolytic Conditions
• Embolus – a thrombus freely floating in the
blood stream
– Pulmonary emboli can impair the ability of the
body to obtain oxygen
– Cerebral emboli can cause strokes
Prevention of Undesirable Clots
• Substances used to prevent undesirable clots
include:
– Aspirin – an antiprostaglandin that inhibits
thromboxane A2
– Heparin – an anticoagulant used clinically for
pre- and postoperative cardiac care
– Warfarin – used for those prone to atrial
fibrillation
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
Hemostasis Disorders: Bleeding Disorders
• Inability to synthesize procoagulants by the
liver results in severe bleeding disorders
• Causes can range from vitamin K
deficiency to hepatitis and cirrhosis
• Inability to absorb fat can lead to vitamin K
deficiencies as it is a fat-soluble substance
and is absorbed along with fat
• Liver disease can also prevent the liver from
producing bile, which is required for fat and
vitamin K absorption
Hemostasis Disorders: Bleeding
Disorders
• Hemophilias – hereditary bleeding disorders
caused by lack of clotting factors
– Hemophilia A – most common type (83% of all
cases) due to a deficiency of factor VIII
– Hemophilia B – results from a deficiency of
factor IX
– Hemophilia C – mild type, caused by a
deficiency of factor XI
Hemostasis Disorders: Bleeding
Disorders
• Symptoms include prolonged bleeding and
painful and disabled joints
• Treatment is with blood transfusions and the
injection of missing factors
Blood typing – ABO groups
Cross-Reaction
(a.k.a. transfusion reaction)
Figure 19–6b
Blood Type Test
Figure 19–7
ABO groups by frequency in US
population
Rh factor
Blood Transfusions
• Whole blood transfusions are used:
– When blood loss is substantial
– In treating thrombocytopenia
• Packed red cells (cells with plasma
removed) are used to treat anemia