Blood Flashcards
Blood functions
- Transport
- Nutritive
- Respiratory
- Excretory
- Hormone transport
- Temperature regulation - Acid-Base Balance
- normal pH range 7.30-7.45 - Protective
Accounts for what percent of body mass?
Account for 7% of body mass
~5 L
Normovolemia
normal blood volume
Hypovolemia
Lower blood volume
Hypervolemia
Higher blood volume
Total Blood Volume occupied by blood and Plasma
blood ~2.25 L
plasma ~2.75L
Composition of Plasma
- > 90% water
- Na+, K+ , (Ca++, Mg++)
Cl-. HCO3-, (PO4–) - Glucose, amino acids, lipids, O2, CO2
- Proteins (colloids) = 7%g
Albumins
Globulins
Fibrinogen
Separating Plasma Proteins
- Differential Precipitation by Salts
- Sedimentation in Ultracentrifuge
- Electrophoretic Mobility
- Immunological Characteristics
Electrophoresis
- fractionation method based on movement of charged particles along a voltage gradient
- rate of migration is influenced by the number and distribution of charges and by MW of each protein.
Origin of Plasma Proteins
Liver: Albumin, Fibrinogen, alpha1 and 2, Beta globulins
Lymphoid Tissue produces Y globulin
Plasma Proteins Properties
Albumin, 69 MW, 4g% conc.
Globulin, 90-800 MW, 2.7g%
Fibrinogen 350 MW, 0.3g%
Role of Plasma Proteins
- Major role in determining the distribution of fluid between the plasma and the ISF compartments by controlling transcapillary dynamics.
What does Plasma have more of than ISF, in regards to make up?
Plasma and ICF both have somewhat equal conc. of Na, K, Cl, HCO3.
Plasma has more protein than ISF!
Colloidal Osmotic (Oncotic) pressure (C.O.P.) of plasma
Only non-diffusable solutes contribute to the effective Osmotic Pressure of a solution
Diffusible solutes do not contribute
Plasma Proteins are non-diffusible , therefore, they can exert an osmotic effect.
Osmotic flow
tends to “pull in” or retain fluid inside the capillaries.
Starling Forces
- Filtration
2. Osmotic Flow
How much fluid filtered out is reabsorbed directly back into capillaries?
90% reabsorbed
10% is drained by lymphatic vessels
Lymphatic System
-A network of blind-ended terminal Tubules, which coalesce to form larger lymphatic vessels, which converge to form large lymphatic ducts,
which drain into the large veins in the chest
Lymphatic Vessels
- the walls of lymphatic vessels are made up of a single layer of endothelial cells
- they are highly permeable to all ISF constituents, including proteins(which might have leaked out into the ISF from the plasma)
Daily Volume of fluid filtered in ISF by the Capillaries
20L
Daily Total blood flow
6,000 L
Daily Volume of fluid returned to the capillaries by absorption
17 L
Daily volume of fluid returned by lymph drainage into the capillaries
3 L
Each protein fraction exerts an osmotic pressure which is
i. directly related to its conc. in the plasma
ii. inversely related to the molecular Weight of that protein
COP of Plasma Proteins
Albumin ~20 mmHg
Globulins ~5 mmHg
Fibrinogen ~
Factors in Transcapillary Dynamics
- Hydrostatic Pressure
- C.O.P.
- Capillary Permeability
- Lymphatic Drainage
Edema
accumulation of excess fluid in the interstitial spaces.
Under which conditions can edema develop?
- Increased hyrdostatic pressure.
- Decreased C.O.P.
- Increased capillary Permeability
Increased filtration
Decrease in Net absorption
Causes for Decreased C.O.P.
a. Failure to synthesize plasma proteins
b. Severe protein malnutrition
Elephantiasis
blockage of lymphatic drainage resulting from parasite infestation
Role of Plasma Proteins
- Major role in determining the distribution of fluid between the plasma and the ISF compartments by controlling transcapillary dynamics
- Contribute to the viscosity of plasma
(Viscosity is a contributing factor to the maintenance of BP) - Contribute to the buffering power of plasma
-normal pH range ~7.4
Specific Plasma Protein Functions
i. Fibrinogen and some globulins are essential to clotting
ii. Y-globulins (immunoglobulins) provide specific resistance to infection
iii. Albumin and some globulins act as carriers for lipids, minerals, hormones
Blood Cells
- Red Blood Cells - Erythrocytes
- Platelets - thromocytes
- WBC - Leukocytes
Hematopoiesis
- all blood cells are derived from a common multipotential (pluripotential) hematopoietic stem cell
- an inducer will stimulate a Stem cell to progress into a certain type of stem cells
Two phases:
- Division
- Differentiation
Eythropoiesis
production of RBC
Thrombopoiesis
production of platelets
Leukopoiesis
production of WBC
Cytokines
-substances (protein or peptides) which are released by one cell and affect the growth, development, and activity of another cell
Hematopoietic Growth Factors (HGFs)
-cytokines influencing the proliferation and differentiation of blood cell precursors
Sites of Hematopoiesis Prenatal
Yolk Sac, Liver and Spleen
Sites of Hematopoiesis Postnatal
- Distal long bones, Axial Skeleton
- Flat bones of skull, shoulder blades, pelvis, vertebrae, sternum, ribs, proxymal epiphyses of long bones.
Advantage of Shape of RBC (DISK)
- Maximal surface area and minimal diffusion distance for its volume (Increases the efficiency of O2 and CO2 diffusion)
- High degree of flexibility (Allows cells to squeeze through narrow capillaries)
What is there none of in a red blood cells
No subcellular organelles
RBC’s important Enzyme Systems
Glycolytic Enzymes –> Generate Energy
Carbonic Anhydrase –> CO2 Transport
Carrying Capacity of blood
20 ml O2/ 100 mL blood.
Solubility of O2 in plasma is very low: 0.3 mL O2/100 mL plasma
Hb Functions
- Transport of O2
- Transport of CO2
- Acts as a buffer
What are the advantages of having Hb inside the Cell (rather than dissolved in plasma)
i. re Plasma Viscosity
ii. re Plasma C.O.P.
iii. re Loss via kidney
Hemoglobin Values for Males and Females
female - 16g/100 mL blood
male - 14 g/100 mL blood
How much of each gram of Hb holds when it is fully saturated
1.34 mL O2
The O2 carrying capacity of blood
15x1.34 = 20 mL O2/100 mL blood
Factors affecting the ability of Hb to bind and release O2
- Temp
- Ionic Composition
- pH
- pCO2
- Intracellular enzyme conc.
Time period for Division and Differentiation of the RBC
3-5 days,
In circulation 24 hours
Red Cell precursors Proliferation
- Decrease in size
- Lose of nucleus
- Accumulation of Hb
Factors Determining # of RBCs
- O2 requirements
2. O2 availability
How does altitude affect pO2
pO2 decreases with increase of altitude
Erythropoietin
- a glycoprotein hormone/cytokine produced largely by the kidney
- if it has been purified, sequenced, gene has been cloned, and EPO has been produced by recombinant DNA technology.
What is the stimulus for the release of erythropoietin?
Hypoxia: which may result from decreased RBC count, or decreased availability of O2 to blood, or increased tissue demand for O2.
Regulation of Erythropoiesis
Increase in O2 supply –> decreased release of erythropoietin –> erythropoietin in plasma –> bone marrow –> increase in RBCs –> increase in oxygen supply –> back to top
Regulation of Erythropoiesis
Erythropoietin, released from the kidney in presence of hypoxia, stimulates the bone marrow to produce more RBC’s, thereby maintaining homeostasis
Once there is an increase in O2 supply there is a decreased release of erythropoietin
Negative Feedback Loop of Erythropoiesis
Severe accidental hemorrhage –> Less Hb available for O2 transport –> reduced supply of O2 to kidneys –> increased production and release of erythropoietin –> increased production of erythrocyte precursors in bone marrow –> increase discharge of young erythrocytes in blood –> more Hb for O2 transport –> negative feedback to stop production and release of erythropoietin.
Erythropoietin Action
Pluripotent Stem Cell –> Commited Stem Cell (EPO Stimulates Proliferation) –> EPO accelerates Maturation –> Reticulocytes –> Mature RBC
How does testosterone affect erythropoietin
- increase of erythropoietin
- increase in sensitivity of RBC precursors to Erythropoietin
How does estrogen affect erythropoietin
Has opposite effects of testosterone
Life span of RBC’s
120 days
Does anything prolong RBC lifespan
NOTHING!!!!
How are RBC’s removed
Old RBCs are recognized as such and are removed from the circulation by a system of highly phagocytic cells know as macrophages (in liver and spleen)
Jaundice
a medical condition with yellowing of the skin or whites of the eyes, arising from excess of the pigment bilirubin and typically caused by obstruction of the bile duct, by liver disease, or by excessive breakdown of red blood cells.
- excessive hemolysis
- bile duct obstruction causing bilirubin to circulate the body
Hemolysis
the rupture or destruction of red blood cells
Polycythemia
RBC production > destruction
Anemia
RBC production
Normal RBC g%
16 g%
Polycythemia RBC g%
> 18g% Hb
What causes physiological Polycythemia? (secondary of increase in O2 needs or decrease in O2 availability)
- at high altitudes
- increased physical activity
- chronic lung disease
- heavy smoking
- tumors of cells producing erythropoietin
- Unregulated production by bone Marrow
What is the problem in polycythemia?
-Increase in blood viscosity
= sluggish blood flow –> blood clots
Classification of Anemias
Morphologic:
1. Microcytic Normocytic Macrocytic
- Normochromic Hypochromic
Normocytic
Normal RBC, normal size, shape HB, etc. Just abnormal amount in the plasma
Macrocytic
Abnormally large RBC
Microcytic
Abnormally small RBC
Normochromic
form of anemia in which the concentration of hemoglobin in the red blood cells is within the standard range. However, there are insufficient numbers of red blood cells
Hypochromic
red blood cells (erythrocytes) are paler than normal
Total Amount of Iron in Body and proportions in the body
4 g in total 65% Hb 30% stored 5% myoglobin 1% enzyme
Daily intake in Diet of Iron
~15-20 mg
Daily absorption from gut (depending on need by body)
~1 mg Males
~2 mg Females
How much Iron that normal erythropoiesis requires
25 mg Fe/d
Iron in normal RBC destruction
25 mg Fe/d
1mg/d lost, 24 mg/d recycled
What causes Pernicious Anemia?
Intrinsic factor deficiency, which affects Vitamin B12 absorption.
Occurs in the ileum.
Loss of Blood - Hemorrhage
a. External
b. Internal (into tissues)
Hematoma
accumulation of blood in tisses
Hemostasis
the arrest of bleeding following vascular injury
Vascular injury –> Vasoconstriction –> Platelet Plug Formation –> Blood clot formation
Primary Hemostasis
Comprised of:
- Vascular response
- Platelet Response
Begins within seconds of injury, lasts only minutes
Secondary Hemostasis
clot formation
Vascular Response to Injury
- Opposed endothelial cells stick together
- smooth muscle cells in vessel wall respond to injury by contracting
Platelet Response (white thrombus)
platelet plug forms
Platelet Structure
~2-4 um diameter -No nucleus -Many granules: factors for vasoconstriction, platelet aggregation, clotting, growth, etc. many filaments, microtubules, mitochondria, sER. ~ 250,000/uL Life Span: 7-10d
Thrombopoietin
hormone produced by the liver and kidney which regulates the production of platelets.It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets.
Platelet Plug Formation
- Adhesion
- Activation and release of cytokines
- Aggregation
- Consolidation
Platelet Functions
a. Release vasoconstricting agents/ cytokines
b. Form platelet Plug (Red Thrombus)
c. Release clotting factors
d. Participate in Clot retraction
e. Promote maintenance of Endothelial Integrity
Abnormal Primary Hemostatic Response –> Prolonged Bleeding
- Failure of Blood vessel to constrict
- Platelet deficiencies
a. Numerical
b. Functional
How does aspirin affect TXA2
In small doses inhibits synthesis and release
Thrombus
blood clot
Clotting
- initiated by injury to blood vessel wall
- results in sequential activation and interaction of a group of plasma proteins/clotting factors (some acting as enzymes, others as cofactors) in the presence of Ca++ and some phospholipid agents
The effect of small amounts of thrombin?
The small amounts of thrombin generated rapidly by the extrinsic scheme are sufficient to trigger its strongly positive feedback effects on the intrinsic scheme to generate larger quantities of thrombin
Petechaie
a small red or purple spot caused by bleeding into the skin
What keeps clotting in check
Inhibitors of platelet adhesion and anticoagulants (naturally occurring chemicals which block one or more of the reactions of coagulation scheme.
Clotting Factor Deficiencies
Congenital: hereditary deficiencies (usually) of a single factor . e.g. VII (hemophilia)
Acquired: Usually multifactor deficiencies e.g.
i. Liver disease
ii. Vitamin K deficiency
*Vitamin K is a cofactor in synthesis of Prothrombin, VII, IX, X
Thrombosthenin
- contractile protein released by platelets.
- the presence of this determines the retraction of blood.
Clot Lysis (Fibrinolysis)
-break down of clots helped via 1. Inhibitor of Platelet Adhesion(eg. Aspirin) 2. Anticoagulant Drugs (interfere with clot formation) i. Coumarin ii. Heparin 3. Thrombolytic Drugs (promote lysis) i. Tissue Plasminogen Activator (t-PA) ii. Streptokinase
Coumarin
blocks synthesis of functional Prothrombin, VII, IX, X
Heparin
Promotes inhibition of thrombin activation and action
