Blood Flashcards
What are the main blood functions?
- Transport:
- Nutritive
- Respiratory
- Excretory
- Hormone
Temperature regulation - Acid-Base balance:
- Normal pH range - Protective:
- some blood cells and some proteins
What is the composition of blood (%)?
55% Plasma (liquid part)
45% Erythrocytes/RBC
Buffer layer (WBC and platelets)
*Plasma counts ECF (plasma) and ICF (inside blood cells)
around 7% of body mass
What are the terms for:
Normal blood volume
Lower blood volume
Higher blood volume
Normal = Normovolemia
Lower = Hypovolemia
Higher = Hypervolemia
What is the Hematocrit?
Clinical index
Percentage of blood volume occupied by RBC
Measured with column –>
height of RBC/hiegh of whole *100%
Normal Ht = 45%
Voir p.12 for example
What is the global composition of plasma?
What is the main difference between composition of Plasma and ISF
- more than 90% = water
- ions
- Nutrients (Glucose, amino acids, lipids) wastes (urea, lactic acid, etc.)
- Resp. Gases: O2, CO2 (in small concentration because rapid exchanges with other parts of the body)
- proteins (colloid) = 7g%
- Albumins 60%
- Globulins 35%
- Fibrinogen 5%
*Main difference = presence of protein in plasma
What are the different ways to separate Plasma proteins?
- Differential Precipitation by Salts
- Sedimentation in Ultracentrifuge
- Electrophoretic Mobility (most clinically used)
- Immunological Characteristics
How does electrophoresis work?
1 of the ways to separate plasma proteins
Fractionation method based on mvt of charged particles along voltage gradient (migrate from anod- to catod+)
Rate of migration influenced by number and distribution of charges + by MW of each protein
Make stains –> area under peak in scan = concentration in blood
When concentration changes –> disease
Voir p.17-18
Where do the plasma proteins come from?
Liver:
Albumin, Fibrinogen, Globulins (a1, a2, b)
Lymphoid Tissue:
y Globulins (bc they are antibodies)
*When liver diseased –> plasma protein level decrease
What is the shape, the MW range, the concentration and COP of the different plasma proteins?
Albumin:
small oval, 69Kd, 4g%, 20 mm Hg
Globulins:
heterogenous, 90-800Kd, 2.7g%, 5 mm Hg
Fibrogen:
long fiber(oval), 350Kd, 0.3g%, < 1mm Hg
*total of 7g% (= 7g/dl = 70g/L?)
*total odf 25 mm Hg
What in the role of plasma proteins?
Determine distribution of fluid between plasma and ISF compartment by controlling transcapillaries dynamics
(ISF doesn’t have proteins)
What is the difference between the cell membrane and the cappillary walls?
Cell membrane = impermeable to ions
Capillary walls =
freely permeable to H2O and ions
What is the approximated concentration of ions in ECF?
0.9g% solution of NaCl = 300 Osm (6.7 atm or 5100 mm Hg)
*ECF = ISF + Plasma
*Ions = diffusible
How is osmolarity calculated?
1 M of solution = 1mol/L = x g/L –> Molarity
concentration in g/L / 1M =
Osmolarity = when dissolved (ions separated)
if seperated into 3 ions, Osm = 3xMolarity
*Practice calculating
What is required to have a net flow of water between compartments?
Has to be a difference in osmotic pressure (between both sides of capillary walls)
*Only Non-diffusible solutes contribute to the effective o.p. (can’t go through the capillary wall bc else, become =lly distributed)
Plasma proteins = non-diffusible proteins (only in plasma)
What is the main difference between ISF and Plasma?
How does the net flow change?
The presence of plasma protein –> non-diffusible
They then create osmotic effect –> Colloid Osmotic/Oncotic Pressure (C.O.P.) of Plasma = 25 mm Hg
If COP changes, net flow changes:
If COP ↑, water flow into Plasma (to ↓ concentration)
If COP ↓, water flow into ISF (to ↑ plasma concentration that just ↓)
Which are the 2 major forms of fluid tranport across the capillary wall?
- The COP fo plasma determines amount water move into/out of capillaries
- Bulk Flow: flow of molecules subjected to pressure difference
magnitude of Bulk Flow directly proportional to hydrostatic pressure difference
Filtration across porous membrane (like sieve)
What are the 2 important transport mechanism across capillaries?
How are these forces refered to?
STARLING FORCES
1. Filtration:
push out fluid from inside capillaries
- Osmotic Flow: (due tu plasma prots)
pull in/retain fluid inside capillaries
What is th capillary bed?
site where exchanges take place between plasma and ISF
Filtration in 1st half and absorption in 2nd half
How do nutrients, wastes, O2 and CO2 move in and out of the capillaries?
by simple diffusion
What do starling forces determine?
How much is filtered out and reabsorbed directly?
Distribution of EFC volume between Plasma and ISF
90% bc 10% is drained by lymphatic vessels
How are the wall of lymphatic vessels?
Single layer of endothelial cells
Highly permeable to all ISF constituents (including proteins which may have leaked out of plasma)
What is considered part of the lymphatic system?
Lymph nodes
Thymus
Spleen
Bone marrow
Converges and drained into larg veins in the chest
What impacts the colloid osmotic pressure?
The NUMBER of osmotically active molecules/unit volume (not size or charge)
Each protein fraction = osmotic pressure:
Directly related to concentration in plasma
Inversly related to molecular weight
Which are the factors that influence the trasncapillaries dynamics?
- Hydrostatic pressure
- C.O.P
- Capillary permeability (some may become more permeable and allow some proteins to go in ISF)
- Lymphatic drainage
What is EDEMA?
What are the conditions leading to it?
accumulation of excess fluid in interstitial space
- ↑ Hydrostatic pressure
- ↓ Plasma proteins (COP)
- ↑Capillary permeability
- X obstruction of lymphatic drainage
What can cause a decreased COP?
Voir slides 63-65 pour autres choses
- Failure to synthesis plasma proteins (ex: liver disease)
- Sever malnutrition (no amino acids)
1st to 2nd baby syndrom –> Kwashiorkor
What is the role of plasma proteins?
- Major role in determining the distribution of fluid between the plasma and ISF by controlling transcapillaries dynamics
- Contribute to viscosity of plasma (maintenance of blood pressure)
- Contribute to buffering power of plasma (normal pH range aroung 7.4)
What is the function of:
fibrinogen and some globulins?
y-globulins (immunoglobulins)?
Albumins and some globulins?
fibrinogen and some globulins:
clotting
y-globulins (immunoglobulins): specific resistance to infection
Albumins and some globulins:
carriers for lipids, minerals, hormones
What is the word that refers to the production of blood cell?
to the production of RBC?
to the production of platelets?
to the production of WBC?
all blood cells: Hematopoiesis
RBC: Erythropoiesis
platelets: Thrombopoiesis
WBC: Leukopoiesis
What is the process of Hematopoiesis?
Which are the sites of Hematopoiesis?
pluripotent hematopoietic stem cell are differentiated into Lymphoid stem cells or Myeloid stem cells under influence of HGFs
Myeloid then in redifferentiated into erythrocytes and many other Leukocytes
- Pluripotential Stem Cell do self-replication (inducer) –> division
- They are diferentiated by stimulant? into committed Stem Cells (Leukocytes, Platelets/Thrombocytes and Erythrocytes)
Yolk sac (1 month and 9 months) and Liver and Spleen (3-7 months) for prenatal
Postnatal –> Bone marrow (axial skeleton)
What are Cytokines?
What is the specific/important one in our blood?
Proteins or peptides which are released by one cell and affect the growth, development and activity of another cell
Hematopoietic Growth Factors (HGFs) influence proliferation and differentiation of blood cell precursors
What is the fonction of Erythrocytes?
Facilitate transport of respiratory gases between lungs and cells
What shape do Erythrocytes have and what the characterstics of it?
How many are there in the body?
Biconcave disk
Shape due to presence of spectrin (fibrous protein)
Adantages of that shape:
1. Maximal surface area and minimal diffusion distance for volume –> more efficient O2 and CO2 diffusion
- High flexibility (squeeze through narrow capillaries)
Male –> 5.1-5.5x 10^6 / microL
Female –> 4.5-4.8 x 10^6/ microL
*Rate of production = rate of destruction = environ 2 x 10^6/sec
*In RBC no ribosome nor nucleus, just solutes dissolved in water (33% Hb)
What 2 enzyme systems do RBC have?
Glycolytic enzymes –> generate Energy
Carbonic Anhydrase –> CO2 transport
How does Hb (hemoglobin) interact with O2?
*Voir p.86-87 schema
Each molecule of Hb can bind with max 4 O2 molecules
When combined with O2 = OXYHb
When released from Hb = DeoxyHb
(needs feritin to bind??)
What are Hb functions?
- Transport O2
- Transport CO2
- Act as a buffer
Where is hemoglobin in the blood? What are the advantages of that?
Inside the cell (RBC) instead of dissolved in plasma
Advantages:
1. reduce? Plasma viscosity
2. re Plasma COP
3. re Loss via Kidney
- Solubility of O2 in plasma = very low: 0.3 mL O2/100mL plasma
but in blood, bc Hb carrying capacity = 20mL O2/ 100mL blood
Which are the factors affectiong the ability of Hb to bind and release O2?
- Temperature
- Ionic Composition
- pH
- pCO2
- Intracellular enzyme concentration
How does the RBC change to be differentiated from Stem cell (18μm) to Erythrocyte (7μm)?
- Decease in size
- Loss of nucleus
- Accumulation of Hb
What are reticulocytes?
Reticulocytes = immature RBC
Reticulocyte count reflects the amount of effective erythropoiesis in bone marrow
Normal count < 1%
What factors determine the # of RBC?
- O2 requirements
- O2 availability
What happens when we go up in altitude?
pO2 (mm Hg) decreases –> less availability
RBC increase –> be able to carry more
What is Erythropoietin?
How is its production regulated?
A glycoprotein hormone/cytokine produced largely by the kidney
Hypoxia (not enough O2) stimulates its release –> may come from ↓ # RBC, ↓ availability of O2, ↑ tissue demand for O2
*Erythrpoiesis regulated by release of not of Erythropoietin in kidney depending on its O2 supply –> goes in plasma to bone marrow where RBC produced
–> maintain of HOMEOSTASIS
What happens in case of severe accidental hemorrhage?
- ↓ Hb available for O2 transport
- ↓ supply of O2 to kidneys
- ↑ production and release of erythropoietin
- ↑ produciton of erythrocyte precursors in bone marrow
- ↑ discharge of young erythrocytes in blood
- ↑ More Hb for O2 transport
On which cell does erythropoietin act?
EPO stimulates proliferation of Committed stem cells (already committed to becoming RBC), does not act of pluripotent stem cells
Accelerated maturation from committed stem cells ot reticulocytes (not from reticulocytes to mature RBC)
What effects do hormones have on erythropoietin?
testosterone ↑ release of EPO
testosterons ↑ sensitivity of RBC precursors to EPO
Estrogen ha opposite effects
*This is why men have more RBC than women
What is the lifespan of RBC?
How are they disposed of?
120 days (nothing prolonges it!!)
Old RBC are recognized and removed by phagocytosis by macrophages in the spleen (some in the liver)
Some also hemolyze in the blood stream
When phagocytosed, old RBC are digested (cell membrane) by enzymes in cytoplasme of macrophage and contente released in its cytoplasme
What happens when the content of RBC is released after it has been phagocytosed by a macrophage?
Voir p.119
Hb is divide back into heme and globin
Globin –> amino acid pool (reutilized for protein synthesis)
Heme –> oxydized into another pigment Biliverdin (green) –> Bilirubin (yellow) –> into liver which converts it into bile (with other things) –> intestianl tract (color fecal matter)
Iron picked up by Transferrin (albumin) bc toxic and reused as non-toxic way –> if no immediate need, stored in Liver, Spleen, Gut
What quantity of bilirubin must be present in plasma?
What effect does a high quantity will have? How does it happen?
1mg/dL in plasma –> gives the yellow cooler
If concentration is to high –> jaundice (Icterus)
Causes:
1. Because excessive Hemolysis
2. Hepatic Damage (liver damage)
3. Bile duct obstruction (carries bile from Liver to intestinal tract)
Neonatal jaundice –> excess of blood cells –> to much bilirubin –> can penetrate into brain if not treated
What are the clinical indices for RBC?
- # of RBC
- Amount of Hb
- Hematocrit
Does a low of high hematocrit always mean there is anemia or polycythemia?
No, because plasma fluctuates with the amount of water in the body
High hematocrit = polycemia OR dehydratation
Low hematocrit = Anemia OR fluid retention
What is polycythemia?
what are the 2 types?
WHat is the problem with polycythemia?
When the hematocrit is to high
> 18g% Hb or > 6x10^6 RBC/µL
Normal = 16g% or %-5.5x10^6 RBC/µL
Relative –> due to ↓ plasma volume
Absolute :
1. Physiological
2. Pathological
Problem: ↑ blood vicosity –> sluggish blood flow –> blood clots
What can cause physiological (absolute) polycythemia ?
*Too high hematocrit
secondary to ↑ O2 needs, ↓O2 availability
- high altitude
- ↑ physical activity
- chronic lung disease (ex: emphysema)
- heavy smoking (high CO in blood)
What can cause pathological (absolute) polycythemia ?
*Too high hematocrit
- Tumors of cells producing Erythropoietin
- Unregulated Production by Bone Marrow
Polycythemia vera - 7-8x10^6 RBC/uL or Ht 70%
What is anemia ?
↓ in the oxygen-carrying capacity of blood
1. RBC count ↓ (< 4x10^6/uL for male, < 3.2x10^6/uL for female)
2. Hb content ↓ (<11g% for male, < 9g% for female)
What are the different types/classifications of anemia?
Morphologic:
- Microcytic (<80 u cube) –> smaller
- Normcytic (80-94)
- Macrocytic (> 94) –> larger
- Normochromic (33%) –> darker bc 1/3 volume is Hb
- Hypochromic (< 33%) –> less Hb
What are the Etiologic Classes of Anemia?
- Diminished Production
- Ineffective Maturation
- Increased Destruction
What are the 3 types of diminished production (Etiologic Classification of Anemia)?
3 causes:
1. Abnormal site:
Aplastic (hypoplastic) Anemia
Problem with functionning of stem cells in bone marrow
Etiology(causes): unknown, exposure to radiation, chemicals or drugs
Classification: Normocytic, Normochromic
- Abnormal stimulus:
Stimulation failure
Etiology: renal disease
Classification: Normocytic, Normochromic - Inadequate raw materials:
Iron deficiency Anemia (most common)
Etiology: - ↑ (infant, ado, pregnancy bc muscle growth for example)
- Inadequate supplies du to : loss Fe in hemorrhage, Dietary deficiency, failure to absorb Fe
Classification: Microcytic, Hypochromic
What is the distribution of iron in our body?
And our daily intake?
Total amount = 4g
65% Hb, 30% stored, 5% myoglobin, 1% enzymes
Daily intake in diet : about 15-20 mg
Daily absorption from gut: 1mg for male , 2mg for females
How much iron is requiered for normal erythropoiesis?
And released in normal RBC destruction?
erythropoiesis requires 25 mg/day
normal RBC destruction releases 25 mg/day :
1mg lost, 24 mg recycled
so 1mg/d (for male) and 2mg fo female is requiered to be absorbed by the guts
What are the proportion of iron (Fe) in the blood?
What portion of Fe is lost in blood?
1g Hb contains 3.5 mg Fe
and 15g Hb/100mL blood so 50mg Fe/100mL of blood
Menstrual loss = 50 mL blood/month = 25mg Fe
So lose 25mg Fe/month in period + 28mg Fe/months (bc 1mg/day in RBC destruction) = aroung 50 mg/months so 2mg/day for female
What is the etiology and classification of Anemia caused by Ineffective Maturation?
(maturation failure anemia)
Etiology :
deficiency in vitamine B12 (usually absorption failure) and Folic Acid (usually dietary absence) (both required for synthesis of DNA)
Classification:
Macrocytic, Normochromic
Voirp.145 for vitamine B12 absorption in IF-B12 complex (intrinsic factor has to be secreted)
What is anemia caused by survival disorders (Failure to survive)?
Etiology (cause):
Congenital:
- Abnormal membrane structure of RBC (less flexible, more fragile, will breakup in narrow capillaries, sphere shape instead of dumb-bell)
- Abnormal Enzyme systems
- Abnormal Hb structure (ex: Thalassemia - deficiency synthesis of globin amino acids)
Acquiered:
- Toxins
- Drugs
- Antibodies
What are the 3 general causes of anemia?
- Failure to produce
- Failure to mature
- Failure to survive
What word describes and accumulation of blood in tissues?
What word discribes the arrest of bleeding?
What mechanisms are included in the primary and secondary responses of this phenom?
accumulation of blood in tissues = Hematoma
arrest of bleeding = Hemostasis
Pimary Hemostasis = Vascular response + platelet reponse
Secondary Hemostasis = clot formation
What are the 4 steps of hemostasis?
- Vascular injury
- Vasoconstriction
- Platelet Plug Formation
- Blood Clot Formation (remains until healing has occured)
What happens in the Vasoconstriction phase of hemostasis?
- nervous reflex
Opposed endothelial cells stick together - myogenic response
smooth muscle cells in vessel wall respond to injury by contracting - Chemical vasoconstrictors
What happens in the Vasoconstriction phase of hemostasis?
platelets (white thrombus) form plug to block the blood from flowing out of the constricted vessel
- Adhesion
von Willebrand Factor provoke adhesion and activation - Activaiton and release of cytokines
- Aggregation
Collagen will bind and activate platelets
Platelets factors are released and attract more platelets - Consolidation
When platelet clot formed, consolidate by releasing Thromboxane A2, membrane of platelets also releases ADP and serotonin (vasoconstrictors) and von Willebrand Factor releases PF3 (phospholipids)
revoir p.160
What is the platelet’s structure?
Who are they produced?
2-4um diameter
No nucleus
Many granules –> factors for vasoconstriction, platelet aggregation, clotting, growth, etc.
Many filaments, mitochondria, microtubule, etc.
Life span: 7-10 days
250 000/uL
Pluripotential stem cells –> Committed stem cells (15-20um) (Trombopoietin mostly from liver) –> nucleus divide but doesn’t separate (megakaryocytes, 60-80um) in Bone Marrow –> little fragments with cell membrane and granules break off and go into blood stream
What are platelets functions?
- Release vasoconstrictors
- Form Platelets plug
- Release Clotting factors
- Participate in clot retraction
- Promote Maintenance of Endothelial Integrity
What is Petechiae?
breakup of capillaries under skin = small red/purple spots
What can cause an abnormal primary hemostatic response (prolonged bleeding)
- Failure of blood vessels to constrict
- Platelets deficiencies
- Numerical < 75, 000/uL
- functional (congenital, acquired)
*acquiered: Aspirin (in small doses) inhibits synthesis and release of TXA2
