Blood Flashcards
function of blood
Transport
Temp regulation
pH balance
Protection
Components of blood
Plasma(55%) of total blood volume
Blood Cells (RBCs-erythrocytes and WBCs-leukocytes)
Cell fragments - platelets
Ht
height of RBC column/height of whole blood column times 100 (%)
Plasma composition
- 90% water
- Ions (Na+ and Cl-)
- Nutrients
- O2 and CO2
- Proteins(colloids) = 7g%
- albumins = 60%
- globulins = 35%
- fibrinogen = 5%
Can separate Plasma proteins…
Precipitation by salts
Ultracentrifuge (molecular weight diff)
Electrophoretic mobility
Immunological characteristics
Electrophoresis
Movements of charged particles along a voltage gradient
Order of Migration and Largest area
Albumin, furthest (area is concentration)
Globulins alpha 1,2
Beta migrate
Fibrinogen
Gamma globulin
Serum
Plasma w no fibrinogen
Fibrinogen = clotting
Remove for clearer view
ALBUMIN HAS DARKEST THICKEST BAND
Liver produces
Albumin
Fibirnogen
aplha 1 and 2 and Beta clubilins
Lymphoid tissue produces
Gamma Globulin (antibodies)
Diseased liver…
Plasma proteins decrease
Plasma protein concentrations
4% albumin
2.7 globulins
0.3 fibrinogen
ISF and PLASMA composition have…
Na+ Cl- and HCO3-
Plasma is different how?
7 g% proteins
Plasma proteins….
determine the distribution of fluid between ISF and Plasma compartments
Osmotic Pressure
Pressure required to stop water from diffusing through a membrane by osmosis
Diff in osmotic pressure allows water to move
ONLY non-diffusable solutes contribute to the osmotic pressure of a solution so…
PLASMA PROTEINS EXERT osmotic effect
Colloidal Osmotic Pressure
Osmotic pressure exerted by Plasma proteins
25 mmHg
W/o COP Plasma and ISF rest at
5100 mm Hg
COP increase
More water will move into Plasma
COP decrease
More water will go into ISF
Proteins don’t diffuse through capillary wall, only water can therefore COP
2 forms of fluid transport across capillary wall
COP
BULK FLOW
Bulk Flow
Flow of molecules subjected to a pressure difference
Bulk flow magnitude = hydrostatic pressure diff
Bulk flow acts like a filter/sieve
Favours fluids to move into ISF
Starling Forces
Keep the 3:1 ISF:Plasma ratio 15:5
Starling forces
FILTRATION of bulk flow -> pushes fluid OUT of capilliries (into ISF)
Osmotic flow (COP) -> pulls fluid INTO capillaries (into plasma)
Capillaries
Only place where exchanges b/w plasma and ISF occur
Heart contraction:
120 mm Hg pressure
When blood from ocntraction reaches capillary:
35 mm Hg
Filtration - Arterial end
Fluid exits capillary since capillary hydrostatic pressure is greater then COP
Venous end
Fluid reenters the capillary since hydrostatic pressure is less then blood colloidal osmotic pressure (25 mm Hg)
Hydrostatic pressure
Pressure exerted by fluid in vessel
C
Capillary hydrostatic pressure -> Forces fluid out of capillary
COP -> Forces fluid into capillary
NET filtration: hydrostatic pressure>CC
BP - COP = Net filtration
NET absorbtion: hydrostatic pressure < CC
BP - COP = Blood absorbtion ( negative)
Mid capillary
No movement bc COP = 25 mm Hg (BP)
Filtration
push OUT of capillary -> into ISF, bulk flow
Osmotic flow:
Pull INTO capillary, from ISF, COP
90% of fluid filtered out is absorbed back into the capillary
10% is drained by the lymphatic vessels
Ultimately returned to circulation
Lymphatic vessels
HIGHLY permeable to all ISF components
If 20 L filtered out of capillary into ISF and 17 L brough back then…
3L volume is returned by lymph drainage
Osmotic pressure
NUMBER of osmotically active particles/ unit volume
Osmotic pressure of plasma protein
Directly related to its CONCENTRATION in the plasma
Inversely related to molecular weight (higher molecular weight = lower osmotic pressure)
Albumin = smallest weight
therefore HIGHEST COP
molecular weight: 69
concentration: 4g%
COP: 20 mm Hg
controls fluid shifts across capillary wall
Edema
excess fluid in ISF
- more fluid in ISF, less fluid in plasma
Causes of Edema: Increase in capillary hydrostatic pressure
Normal: 120-35
Edema: 120-55
Therefore 30 mm Hg net filtration out
0 net absorption IN?
Decrease in plasma proteins - decreased COP
Increased capillary permeability
if capillary wall more permeable plasma proteins can escape into ISF
can exert an oncotic (COP) effect
Normal: ISf oncotic pressure = 0
edema: 5 mm Hg
Obstruction of Lymphatic drainage
Inability to reabsorb the 10% of fluid drained out of capillary into ISF
e.g elephantiasis (parasite infection, filaria nermatode)
Hematopoiesis: blood cells
Erythropoiesis: RBCs
Throbopoiesis: Platelets
Leukopoiesis: WBCs
Biggest to smallest Blood cells
WBCS
RBCs
Platelets
Volume of Bloodcells biggest to smallest
RBCs
Platelets
WBCs
Stem cell way
Multipotent hematopoietic stem cells
1) Myeloid (RBC,WBC)
2) Lymphoid
First branching of stem cell gives COMMITTED stem cell, can only do one path (leuhopoiesis, erythropoiesis, thrombopoiesis)
Hematopoiesis general pattern
- Division
- Differentiation
Cytokines
substance released by cell affecting activity of other cell
HGFs
influence proliferation and differentiation of blood cell precursors
Sites of hematopoiesis
Prenatal: yok sac, then liver and spleen
Prenatal at 6 months: bone marrow inside spaces of bone
Children: decrease in production in distal long bones
Adult: Axial Skeleton ( flat bones, pelvis, shoulder blades)
Erythrocyte
Transport gasses b/w lungs and cell
Biconcave disk
Shape is due to SPECTRIN
- fibrous protein forming a flexible network linked to cell membrane
- regulates shape of cell
Biconcave shape advantage
Maximal surace area, minimal volume
Fick’s law: LARGER SURFACE AREA THEREFORE HIGHER DIFFUSION RATE and THINNER = higher diffusion rate
Flexibility (can squeeze through narrow spaces)
Men have more RBC’s then women
Rate of production = rate of destruction
RBC has no subcellular organelles
33% hemolglobin
Water
Lipids, proteins, ions
Important enzyme substance of RBC
Glycolytic enzyme -> energy generator
can break down glucose, RBC has no mitochondria, anaerobic energy generated
Carbonic anhydrase -> CO2 transport
Hemoglobin
Each molecule of Hb can bind a maximum of 4 O2 molecules
O2 = OxyHb
No O2 = deoxyHb
Hemoglobin structure
4 amino acid chains
2 alpha chains, 2 beta
Each chain has pigment mollecule: HEME
HEME has 1 iron associated to it
O2 attaches to the iron
4 hemes = 4 irons = 4O2 can bind
Lungs: Hb becomes saturated with O2 -> appears bright red
Tissues: O2 dissociates from Hb -> appears dark red
Hemoglobin Functions
Transport O2 - solubility of O2 in plasma is v low so need Hb
Thanks to Hb blood can carry 20 mL O2 / 100 mL blood (minimum to be alive)
Why Hb inside cell instead of dissolved in Plasma?
Plasma viscosity ( Hb inside plasma would increase viscosity = thicker)
Would make it harder for blood to be pushed along
Plasma COP -> Hb in plasma would produce v high COP which would pulls all the fluid into capillaries
Loss via kidney - Hb is same size as Albumin, would lose a lot fo Hb along with iron attached
RBC precursors Proliferation
erythropoiesis = production of RBC
Committed stem cell stimulated by cytokine called erythropoietin
- secreted by kidney
division and differentiation from committed stem cell = 3-5 days
Committed stem cell -> reticulocyte
reticulocyte -> RBC takes 24 hours
Changes when reticulocyte becomes RBC
Decrease in size(RBC is smaller)
Loss of nucleus (RBC has no subcellular organelles, Pyknosis -> condensing of nuceli chromatin in nucleus)
Accumulation of Hb
Reticulocytes
Still has some ribosomes - used to recognize as young RBC
After 24 hours loses ribosomal material
Normal reticulyte count < 1 %
- reflects amount of effetive erythropoiesis in bone marrow
- if you lose a lot of blood then reticulocyte rate my go up
2 factors determining num of RBCs
O2 requirements: lots of exercise requires more O2
O2 availability: higher altitudes, need more RBC to carry more O2
Pluripotent hematopoietic stem cell -> myeloid stem cell + influence of HGF (erythropoietin) -> reticulocyte -> erythrocyte
Erythropoitein
cytokine, HGF
glycoprotein hormone
stimulated by Hypoxia (low O2)
may result from less RBCs, less O2 in blood or increased tissue demand for O2
MADE IN KIDNEYS
EPO gene
gene promoting erythropoitein
Regulation of erythropoiesis
O2 supply decreased -> increased release of erythropoietin by kidneys
increased erythropoin in plasma
produces more RBC in bone marrow
increased Hb supply
Testosterone
Stimulates the release of erythropoietin
Accounts for higher heamtocrit in males
Refulation of erythropoiesis: negative feedback loop
More O2 available = less erythropoietin released from kidneys
Hypoxia
Erythropoietin released from kidneys
Stimulates bone marrow to produce more RBC -> maintain homeostasis
Erythropoietin Action
stimulates commited group of RBC to divide and differentiate
Accelerates maturation of reticulocytes
Acts on specifically commintted cells that produce RBC
Does NOT act on pluripotnet stem cell
Function:
1. stimulate division and differentiation of committed group
2. Accelerate maturation of reticulocutes
Testosterone
Increases release of erythropoietin
Increases the sensitivity of RBC precursors to erythropoietin
Estrogen
Decreases the release of erythropoietin
Destruction of RBC
120 days lifespan
ALWAYS 120 days
Nothing prolongs lifespan
Macrophages phagocytose old RBCs in liver and spleen
Some old RBC hemoluze -> break up of RBC - released into blood stream
Phagocytosis of old RBC by macrophage
Macrophage extends pseudopods(extension of cytoplasm) around old RBC, endocytose them
Old RBC is digested by enzymes in macrophage - membrane is digested
Release contents into a macrophage cytoplasm
RBC pathway
erythropoiesis in bone marrow (pluripotent stem cell -> myeloid stem cell + erythropoietin -> reticulocyte -> erythrocyte (RBC)
lasts in blood for 120 days
After 120 days: macrophage phagocytoses old RBC in spleen/liver
Macrophage breaks down RBC: contents released into macrophage cytoplasm can be recycled
Recycling phagocytosed RBC contents
Globulin portion (protein chains) released into amino acid pool
Iron is released from HEME
transferrin takes iron to FERRATIN which stores iron in the liver, spleen, gut bc IRON alone is TOXIC
When needed, transferrin picks up iron from ferratin, delivers it to bone marrow
Heme Oxidized -> biliverdin
released inro circulation and becomes BILIRUBIN -> gives plasma it’s yellow color
picked up by liver and secreted in liver fluid (bile)
Bilirubin is released in the upper portion of small intestine
Eventually released into colon which gives color to feces
Jaundice
Concertation of bilirubin in plasma is higher then normal
Adult: non-harmful, possibly liver disease
Infants: excess of blood cell
-may do sever damage, bilirubin
-can penetrate the brain
Causes of jaundice
Excessive Hemolysis (destruction of RBC) - too much bilirubin released
Hepatic damage (liver damage) - liver doesn’t release bilirubin into small intestine(accumulation of bilirubin)
Bile duct obstruction
- bilirubin released by liver in liver fluid -> bile
carried into the bile ducts
obstructed bile ducts: bile cant flow
Bilirubin accumulates
GALL STONES = may block release of bile
Clinical indices
num of RBCs
Amount of Hb
Hematocrit: % RBC in blood
Hematocrit
Normally 45% - relative to plasma
Anemia
Lower Ht - higher plasma %
Fluid retention
Retain more fluid so plasma volume = Higher -> Ht = lower
Polycethemia
Excess production of RBC
Higher Ht = lower plasma %
Dehydration
Plasma volume is decreased (less fluid) = higher Ht
Polycythemia
Blood cancer in which bone marrow produces excess of RBC
Normal Hb in blood
16% g %
Plycethemia
> 18g%
More RBC means more Hb
Causes:
Relative -> due to decrease in plasma volume
Absolute: Physiological or Pathological
Physiological polycythemia:
Caused by increased O2 needs
Decreased O2 availability
High altitudes -> less O2
increased physical activity
chronic lung disease
less O2 can enter -> hypoxia triggers eythropoietin production = more RBC
heavy smoking -> high CO in blood and lower O2, hypoxia triggers erythopoietin production - more RBCs
Pathological polycemia
tumours of cells producing erythropoietin
unregulated production of RBC by bone marrow
- stem cells in bone marrow go crazy
Decreased Hb content
Males: less than 11%
Females than 9%
NOrmally: males: 16
Females: 11
Anemia
Decrease in the O2 carryinbg capacity of blood
Each Hb can carry 4 O2 NORMALLY
Problem of Polycemia
Increases blood viscosity
Sluggish blood flow
Blood clots
Decreased RBC count
MalesL less then 4*106 RBC
Women: less then 3.2 * 106 RBC
Classification of anemias
Size of RBC -
microcytic
Normocytic
Macrocytic
Hb content in each RBC
Normochromic = regular amount of Hb(33%)
Hypochromic = less then 33%
lighter in colo center = transparent
less Hb means less heme pigment
Causes of anemia
Diminished production
- Stem cells don’t produce enough RBC
Ineffective maturation - reticulocytes dont mature
Increased destruction : more RBC being destroyed then produced
Diminished production of RBC reasons:
Abnormal site of production - problem in bone marrow
APLASTIC(HYPOPLASTIC) ANEMIA - normocytic, normochromic
Abnormal Stimulus -> erythropoietin not doing it’s job
can be caused by renal disease as kidney does not secret erythropoietin
Inadequate raw materials, poor nutrition - cannot produce RBC
- Iron deficiency anemia
need iron for synthesis of Hb
Causes: Failure to absorb, dietatry, more need, loss of iron in hemmorhage, MICROCYTIC (smaller bc less Hb, cant grow to proper size, hypochromic (less Hb))
Iron
Women need more bc they lose blood during periods, 2 mg/day to stay in iron balance
Normally
25 mg iron/ day
RBC destroys 25 mg/iron a day
Maturation Failure Anemia
Reticulocytes dont properpy mature to RBC
Caused by Vitamin B12 deficiency
Folic acid deficiency
Both needed for normal synthesis of DNA
Macrocytic(large bc reticulocytes are big, normochromic)
Folic Acid
Yeast and leafy plants
Deficiency means abnormal erythrocyte precursors -> decreased num of RBC
- overcooking veggies, losing folic acid
Vitamin B12
Required for action of folic acid in DNA synthesis and cell division
Animal products
Deficience -> abonrmal folic acid function -> abnormal erythrocyte precursors -> decreased number of RBC
absorption of B12 needs protein -> intrinsic factor
intrinsic factor deficiency = reduced B12 absorption in ileum of SI
results in pernicous anemia
Intrinsic factor helps the body absorb B12, if B12 not absorbed then folic acid cant be used leading to deficiency
pernicious anemia
Survival disorders -> increased destruction of RBC
Hemolytic Anemias
- maybe jaundice
- bilirubin accumulation
Can be congenital (at birth) or Acquired
Congenital Hemolytic Anemia
Abnormal membrane structure
Hereditary spherocytosis, RBC is a sphere instead of a biconcave disk
Fragile and more likely to be destroyed faster
Abnormal enzyme systems
Abnormal metabolism
More destrution of RBC
Abnormal Hb structure
Hb doesnt function properly
Sickle cell anemia
Thalassemia:
deficient synthesis of globin amino acid chains
Less Hb = hypochromic
More likely to be destroyed
Acquired Hemolytic Anemia
Toxic
Drugs
Antibodies -> against cell membrane component
Hemostasis: arrest of bleeding following vascular injury
Primary Hemostasis: platelet respons +vasuclar response
platelets accumulate at site of imjuryy to form a block
prevent great lose
Vasuclar response: smaller vesciles contrict to decrease blood flow
Secondary hemostasis = clot formation blood coagulates
Homeostasis procedure
Vasoconstriction
Platelet plug formation (temporary)
Blood clot formation (more permanent)
Platelet response (white thrombus)
Temporary response
Limits blood flow temporarily
Forms platelet plug
Platelet
Lives 7 days
smaller then rbc (2-4 micrometers)
No nucleus
Many granules
Mitochondria unlike rbc
Platelet production
Pluripotent stem cell -> myeloid commited stem cell + throbopoietin (LIVER!!!!) -> megakaryocytes in bone marrow -> platelets in blood stream
Platelet plug formation
Adhesion
Activation and release of cytokines
Aggregation
Consolidation
Platelet functions
Release vasoconstricting agents:
Seratonin
Thromboxane A2
Release clotting factors PF3 -> thrombin
For platelet plug
Participate in clot retraction
Consolidated blood clod
PArticipate in secondary hemostasis (blood cloot)
Aspirin
Inhibits synthesis and release of thromoboxane A2
Prevents blood clot formation bc primary hemostasis is inhibited
Abnormal primary hemostatic response
Prolonged bleeding due to blood vessel failure to contrrict which is a genetic abonormality and platelet deficienies thrombocytopenia
Platelet Adhesion inhibitors
Aspirin
Anticoagulant drugs -> interfere with clot formation
cOYMADIN - BLOCKS SYNTHEISS OF PROTHROMBIN , 7, 9 AND 10
Heparin - inhibits thrombin activation + action
Thrombolytic drugs -> promote clot lysis
Tissue plasminogen activator (t-PA) activates plasminogen -> plasmin to digest fibrin
Streptokinase
