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blood
is the only Fluid tissue -Continuously regenerated connective tissue - made up of formed elements and plasma
formed elements
Cells are living blood cells are suspended in plasma
Plasma
Matrix is nonliving fluid
Erythrocytes
(red blood cells) transport respiratory gases in theblood
Leukocytes
(white blood cells) defend against pathogens
Platelets
help form clots to preventblood loss
blood transport
• Delivering O2 and nutrients to body cells
• Transporting metabolic waste
• Transporting hormones
blood regulation
• Maintaining body temperature
• Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions
• Maintaining adequate fluid volume
blood protection
• Preventing blood loss - Plasma proteins and platelets in blood initiate clot formation
• Preventing infection - Agents of immunity are carried in blood.
volume of blood
Adults have approximately 5 L of blood. Approximately 8% of our total body weight.
Viscosity of blood
blood is 4-5 times thicker than water. Depends on amount of dissolved and suspended substances relative to amount of fluid
blood ph
is slightly alkaline - pH 7.35-7.45
blood color
Color varies with oxygen content
High levels - bright red, Low levels - dark red
Plasma Concentration
of solutes (for example, proteins, ions)
Determines the direction of osmosis across capillary walls
centrifuged blood
Whole blood (plasma and formed elements) separated into parts by centrifuge
Erythrocytes in centrifuge
Bottom, red layer
About 44% of sample
buffy coat in centrifuge
Very thin (1%) middle layer with gray-white color Composed of leukocytes and platelets
plasma in centrifuge
Straw-colored liquid at top of tube
About 55% of sample
Hematocrit
- Percentage of volume of all formed elements
- Clinical definition: percentage of only erythrocytes
- Adult males: 42 to 56%; females 38 to 46%
Blood smear
- Thin layer of blood placed on microscope slide and stained
- Formed elements differ in appearance
- Erythrocytes are most numerous - pink, anucleate, biconcave discs
- Leukocytes - larger than erythrocytes, varied in form, noticeable nucleus
- Platelets - small fragments of cells
Blood Plasma
is straw-colored sticky extracellular fluid
- Similar in composition to interstitial fluid
- About 90-92% water, but plasma has a high protein composition
Over 100 dissolved solutes
nutrients, gases, hormones, wastes, proteins, inorganic ions
- Plasma proteins are most abundant solutes (7%)
- Remain in blood; not taken up by cells
- Proteins produced mostly by liver
blood is a Colloid
Plasma contains dispersed proteins
variety of plasma proteins
Albumin, globulins, fibrinogen and other clotting proteins, enzymes, and some hormones
Albumin
makes up 60% of plasma proteins
- Functions as carrier of other molecules, as blood buffer, and contributes to plasma osmotic pressure
plasma proteins exert colloid osmotic pressure
•Prevents loss of fluid from blood as it moves through capillaries
•Helps maintain blood volume and blood pressure
•Can be decreased with diseases, resulting in fluid loss from blood and tissue swelling
•E.g., liver diseases that decrease production of plasma proteins
•E.g., kidney diseases that increase elimination of plasma proteins
Albumins 2
Smallest and most abundant group of plasma proteins(58%)
- Exert greatest colloid osmotic pressure; transport proteins for some lipids, hormones, and ions
Globulins
Second largest group of plasma proteins (37%)
- Smaller alpha-globulins and larger beta-globulins
- Transport some water-insoluble molecules, hormones, metals, ions
Gamma globulins
(immunoglobulins or antibodies) - Part of body's defenses
Fibrinogens
Makes up only 4% of plasma proteins
- Contributes to blood clot formation
regulatory proteins
(Includes enzymes and hormones)
- less than 1% of total proteins
Hematopoiesis
production of formed elements
- Occurs in red bone marrow of certain bones
Hemocytoblast
Hematopoietic stem cells gives rise to all formed elements
- Pluripotent: can differentiate into many types of cells
- Produce two different lines: myeloid line and lymphoid line
Myeloid line
forms erythrocytes, all leukocytes except lymphocytes, and megakaryocytes (cells that produce platelets
lymphoid line
forms only lymphocytes
Colony-stimulating factors (CSFs)
stimulate hematopoiesis
- Hormones and growth factors push cell toward specific pathway of blood cell development
Erythropoiesis
red blood cell production - takes about 15 days
Erythropoiesis requires
iron, B vitamins like B12, folic acid, amino acids
myeloid stem cells
responds to multi-CSF- Forms progenitor cell
Proerythroblast
a large nucleated cell
erythroblast
smaller, produces hemoglobin
Normoblast
still smaller, more hemoglobin, anucleate
Reticulocyte
lacks organelles except ribosomes that make hemoglobin
- Reticulocyte count indicates rate of RBC formation
Erythrocyte
ribosomes have degenerated
Leukopoiesis
production of leukocytes (granulocytes, agranulocytes)
Granulocytes
are neutrophils, basophils, and eosinophils
- Multi-CSF and GM-CSF cause myeloid stem cell to form progenitor cell
-Progenitor cell becomes myeloblast that becomes a granulocyte
Monocyte
(agranulocyte) also derived from myeloid stem cells
- Stem cell differentiates into progenitor cell
- M-CSF prompts progenitor cell to become a monoblast
- Monoblast becomes a promonocyte, which matures into a monocyte
Lymphocytes
(agranulocyte) are derived from lymphoid stem cells
- Stem cells differentiate into B-lymphoblasts and T-lymphoblasts
- Lymphoblasts mature into B-lymphocytes and T-lymphocytes
Thrombopoiesis
platelet production
Megakaryoblast
produced from myeloid stem cell
- Forms megakaryocyte under influence of thrombopoietin
- Large size and multilobed nucleus
megakaryocyte
produces thousands of platelets
- Large cell produces proplatelets—long extensions
- These extend through blood vessel wall into bloodstream
- Blood flow "slices" off fragments which are platelets
Formed elements are
RBCs, WBCs, and platelets
Only WBCs are
complete cells
-RBCs have no nuclei or other organelles
-Platelets are cell fragments
Most formed elements survive
in bloodstream only few days
- WBCs and platelets - a few days
- RBCs survive for 120 days
Most blood cells originate in bone marrow and do not divide
RBC Erythrocytes
contribute to gastransport
RBC cell
has biconcave disc shape, is anucleate, and essentially has no organelles
RBC filled with
hemoglobin (Hb) for gas transport (>250 million Hb molecules)
RBC diameters
are larger than some capillaries, but flexibility to change shape
RBC Biconcave shape offers
huge surface area relative to volume for gas exchange
Hemoglobin makes up
97% of cell volume (not counting water)
RBCs have no
mitochondria
• ATP production is anaerobic, so they do not consume O2 they transport
RBCs are dedicated to
respiratory gas transport
Hemoglobin binds
reversibly with oxygen
Normal values of hemoglobin
Males: 13-18 g/100ml; Females: 12-16 g/100ml.
Hemoglobin consists of
red heme pigment bound to the protein globin
Globin is
composed of four polypeptide chains
- Two alpha and two beta chains = 4 O2 carried maximum
- A heme pigment is bonded to each globin chain
- Gives blood red color
Oxyhemoglobin
Each Hb molecule can transport four O2 (loads in lung)
Each RBC contains
250 million Hb molecules
Deoxyhemoglobin
if unloading O2 tissues
Carbaminohemoglobin
CO2 loading in tissues, 20% of CO2 in blood binds to Hb, producing
oxygen binds to
iron weakly
Rapid attachment in lungs and rapid detachment in body tissues
carbon dioxide binds to
globin protein (not iron) weakly
Attachment in body tissue and detachment in lungs
regulation and requirements of erythropoiesis
* Too few RBCs lead to tissue hypoxia
* Too many RBCs increase blood viscosity
* > 2 million RBCs are made per second
*Balance between RBC production and destruction depends on
- Hormonal controls
- Dietary requirements
Hormonal Control (Erythropoietin, EPO)
controls erythropoiesis
Hormone produced primarily in the kidneys (a little in liver)
Secretion is stimulated by a decrease in blood oxygen
Red marrow myeloid cells respond to EPO - make more RBC's
The erythrocytes increase blood's oxygen carrying capacity
The increase in blood oxygen inhibits EPO release
Testosterone stimulates EPO production in kidney
Therefore, males have higher erythrocyte count, higher hematocrit
Environmental factors such as altitude influence EPO levels
low oxygen levels at high altitude stimulate EPO
some athletes abuse artificial epo
Use of EPO increases hematocrit, which allows athlete to increase stamina and performance
Dangerous consequences of artificial EPO
EPO can increase hematocrit from45% up to even 65%, with dehydration concentrating blood even more
Blood becomes like sludge and can cause clotting, stroke, or heart failure
date and destruction of erythrocytes
Life span: 100-120 days
RBCs are anucleate, so cannot synthesize new proteins, or grow or divide
Old RBCs become fragile, and Hb begins to degenerate
Globins and membrane proteins are broken into amino acids
Used by body for protein synthesis
Iron from hemoglobin transported by transferrin protein to liver
Bound to storage proteins: ferritin, hemosiderin
Most is bound to ferritin and stored in liver and spleen
Transported to red bone marrow as needed for erythrocyte production
Heme group (without Fe2+ )
Converted within macrophages into green pigment, biliverdin
Eventually converted into yellowish pigment, bilirubin
Transported by albumin to liver
Becomes part of bile (used in digestive system)
Bilirubin converted to urobilinogen in small intestine
May continue thorough intestine, be converted by bacteria to stercobilin, and be expelled from body as brown pigment in feces
May be absorbed back into blood, converted to urobilin, and be excreted from kidneys as yellow
anemia
ow number of RBCs or low hemoglobin
• Abnormally low O2-carrying capacity too low to support normal metabolism
hemorrhagic anemia
• Rapid blood loss (example: severe wound)
• Treated by blood replacement
chronic hemorrhagic anemia
• Slight but persistent blood loss
• Example: hemorrhoids, bleeding ulcer
• Primary problem must be treated to stop blood loss
iron deficiency anemia
• Can be caused by hemorrhagic anemia, but also by low iron intake or impaired absorption
• RBCs produced = pale microcytes
• Cannot synthesize hemoglobin because there is a lack of iron• Treatment: iron supplements
pernicious anemia
• Autoimmune disease that destroys stomach mucosa that produces intrinsic factor (needed to absorb B12)
• B12 = helps RBCs divide
• Without B12 RBCs enlarge but cannot divide, resulting in macrocytes/megaloblasts
• Treatment: B12 injections, sublingual, or nasal gel
• Can also be caused by low dietary intake of B12
• Can be a problem for vegetarians
renal anemia
• Kidneys cannot produce enough EPO
• Often accompanies renal disease
• Treatment: synthetic EPO
aplastic anemia
• Destruction or inhibition of red bone marrow
• Can be caused by drugs, chemicals, radiation, or viruses - 50% of cases have unknown cause
• All formed element cell lines are affected
• Results in anemia as well as clotting and immunity defects
• Treatment: short-term with transfusions, long-term with transplanted stem cells
Anemia due to Excessive RBC Destruction
• Premature lysis of RBCs = hemolytic anemias
• Can be caused by:
• Incompatible transfusions or infections
• Hemoglobin abnormalities: usually genetic disorder resulting in abnormal globin
• Thalassemias
• Sickle-cell anemia
Thalassemias
• Typically found in people of Mediterranean ancestry
• One globin chain is absent or faulty
• RBCs are thin, delicate, and deficient in hemoglobin
• Many subtypes that range in severity from mild to extremely severe
• Very severe cases may require monthly blood transfusions
sickle cell anemia
• Hemoglobin S: mutated hemoglobin - only 1 amino acid wrong
• RBCs become crescent shaped when O2 levels are low(exercise)
• Misshaped RBCs rupture easily and block small vessels leads to organ failure
• Results in poor O2 delivery and pain
• Prevalent in people of the African malarial belt and their descendants - possible benefit: people with sickle cell do not contract malaria
Polycythemia
• Abnormal excess of RBCs; increases blood viscosity, causing sluggish blood flow
• Polycythemia vera: Bone marrow cancer leading to excess RBCs
• Hematocrit may go as high as 80%• Treatment: therapeutic phlebotomy
• Secondary polycythemia: caused by low O2 levels (example: high altitude) or increased EPO production
• Blood doping: athletes remove, store, and reinfuse RBCs before an event to increase O2 levels for stamina
Dietary requirements for erythropoiesis
Amino acids, lipids, and carbohydrates
Iron: available from diet
65% of iron is found in hemoglobin, with the rest in liver, spleen, and bone marrow
Free iron ions are toxic so iron is bound with proteins
Stored in cells as ferritin and hemosiderin Transported in blood bound to protein transferrin