blood Flashcards
what is blood
highly dynamic tissue
part of cardiovascular system
homogenous red fluid
describe blood conceptions - way blood was thought of historically (7)
supporter of life - lifeblood - essential
associated with emotions - bad blood
reflective of relationships - blood brothers
ancient chinese medicine - blood flow linked with energy flow/chi/chee
ancient greece - advocated bleeding as treatment for diseases (the humours, get rid of fluids = get rid of disease)
medieval western medicine - blood inhabited by good and evil spirits (leeches to remove bad)
modern days - carrier of diseases
name the 3 main functions of blood
transport
acid-base balance
protection
describe transport (functions of blood)
capillaries transport all throughout body
nutrition
respiratory gasses
excretion of wastes - moving them out
hormone transport - many effects on body function
temperature regulation - core of body is warmer and as blood moves to surface = temp regulation
describe acid-base balance (functions of blood)
normal pH range = 7.30-7.45
must stay in range or affects structure of protein (denaturation)
describe protection (functions of blood)
has rbcs but also wbcs and plasma proteins which fight infection help with clotting and blood loss
describe centrifuged blood
55% plasma
buffy layer - negligible made of wbcs and platelets
45% rbcs
what does blood contain
extracellular fluid - ecf - plasma
intracellular fluid - icf - fluid inside blood cells
how much of body mass does blood account for
~7% of body mass ~ 5L
what is terminology for normal blood volume
normovolemia
what is terminology for lower blood volume
hypovolemia
what is terminology for high blood volume
hypervolemia
what is hematocrit
Ht - useful clinical index
the percentage of blood volume occupied by rbcs
Ht = (height of rbc column/height of whole blood column) x 100
normal ~ 45%
what is volume of blood occupied by rbcs
~2.25 L
what is volume of blood occupied by plasma
~ 2.75L
what is composition of plasma similar to
ISF
describe the components that plasma and isf have in common
> 90% water
ions = Na+, K+, Ca++, Mg++, Cl-. HCO3-, PO4- ~ physiological saline 0.9% NaCl
nutrients, respiratory gasses and wastes = glucose, aas, lipids, oxygen and co2 - transported in small quantities all over body - exchanged a lot
describe what differentiates plasma and isf
proteins - colloids
plasma has large amount ~7%
albumins ~ 60%
globulins ~35%
fibrinogen ~5%
name and briefly describe the ways to separate plasma proteins
differential precipitation by salts like ammonium sulphate
sedimentation in ultracentrifuge - bc have different molecular weights
immunological characteristics - which cell surface proteins are expressed
electrophoretic mobility - electrophoresis
define electrophoresis
fractionation method based on movement of charged particles along a voltage gradient
describe electrophoresis generally
run current through gel/filter paper
proteins at normal pH have excess negative charges
they will go towards anode and migrate towards positive charges
each protein migrates at own characteristic rate
what is rate of migration influenced by in electrophoresis
number and distribution of charges and by molecular weight of each protein
heavier = slower to move
using a stain name the proteins found during electrophoresis
albumin
globulins - alpha 1, alpha 2, beta, gamma
fibrinogen
describe serum electrophoretic pattern
no fibrinogen peak bc using serum and not plasma
it is plasma without clotting factors (easier to work with serum)
describe origins of plasma proteins
albumin, fibrinogen, alpha 1, alpha 2 and beta globulins = from liver
lymphoid tissue (lymphatic) makes gamma globulins (antibodies used to fight infection)
what happens when liver is diseased
liver is diseased plasma protein levels decrease
describe electrophoretic pattern in renal disease
reduced albumin peak
too much permeability at renal tubules and smallest plasma protein (albumin) flows out into urine
describe electrophoretic pattern in bacterial infection
peak in gamma globulin bc fighting infection
describe plasma protein properties (protein - shape - molecular weight - concentration)
albumin - small globular protein - 69kDa (easiest to lose since small) - 4g
globulins - many shapes - 90-800kDa (heterogenous group) - 2.7g
fibrinogen - fibrous and long and thin - 350kDa - 0.3g
describe role of plasma proteins
major role in determining distribution of fluid between plasma and isf compartments by controlling TRANSCAPILLARY DYNAMICS
describe cell membrane
between icf and isf
relatively permeable to ions
describe capillary wall permeability
between isf and plasma
freely permeable to h20 and ions
impermeable to proteins
describe ionic composition of body fluids
ecf can be approximated by 0.9% NaCl solution = 300 mOsm = 6.7 atms ~ 5100 mmHg
pressures important for movement of fluid across capillary wall
describe osmolarity of body fluids
NaCl dissociates into 2 ions
9g/L NaCl –> 9/58.5 (mm) = 0.15 M - 2x molarity so ~0.3 Osm = 300 mOsm
describe common characteristic of isf and plasma - also what is the differentiating component
0.9% NaCl
300 mOsm
op = 6.7 atm = 5100 mmHg
main source of difference = 7g% of proteins in plasma - wont be able to cross capillary wall and this causes imbalance
for a net flow of water between components (over capillary wall) there has to be…
A DIFFERENCE IN OSMOTIC PRESSURE
describe effect of non diffusible solutes
contribute to effective osmotic pressure of a solution
plasma proteins = non diffusible so they can exert osmotic effect
effect = colloidal osmotic (oncotic) pressure of plasma (COP)
describe diffusible solutes and their effect
DO NOT contribute to osmotic effect since they are equally distributed on both sides of membrane
what happens if COP increases
more water will flow into plasma
water wants to go to area with higher solute concentration
what happens if COP decreases
more water will flow into isf
what is the major role of plasma proteins
across capillary wall there is no protein diffusion
proteins make a major contributor to the COP of a solution
name the 2 major forms of fluid transport across capillary wall
flitration and osmotic flow
what determines how much water will flow into or out of capillaries
COP of plasma
define bulk flow
flow of molecules subjected to a pressure difference
ex: turn on water tap
what does magnitude of bulk flow depend on
hydrostatic pressure difference
what is filtration
bulk flow across a porous membrane which acts as sieve withholding some particles
describe filtration across capillary wall - generally
higher pressure and pushes through things that are the right size
hydrostatic pressure contributes
high-low across membrane
describe the 2 Key Mechanisms for Transport Across Capillaries (Transcapillary Dynamics)
1 - filtration = bc fluid in blood vessel is under pressure (heart beats) it tends to push out fluid from inside capillaries into ISF
2 - plasma proteins (restricted to plasma component) tends to pull in or retain fluid inside capillaries
1 & 2 = STARLING FORCES
what is diffusion responsible for
exchange of nutrients, gases and wastes across capillary wall
what do starling forces determine
distribution of ECF volume between plasma and ISF
proper balance of the starling forces determines the distribution of liquid across capillary wall
what is COP due to plasma proteins
25 mmHg of osmotic pressure on plasma side of membrane
describe the simplified circulatory system
heart to artery to arterioles to capillary bed to venules to veins back to heart
describe capillary bed
all exchange happens here - between plasma and ISF
provides oxygen, nutrients and picks up waste
what is a capillary
blood vessel
single layer of endothelial cells
very thin - almost like pores - this is how things diffuse
describe starlings transcapillary dynamics in relation to a capillary
heart = 120/80 (contract/relax) - pressure decreases bc friction along the way - reaches arterial end of capillary bp = 35 mmHg, hydrostatic pressure wants to move fluid out into ISF
at venous end - bp = 15mmHg
cop = 25, so +10 from arteriole end and -10 from venous end - it is the opposing force, wants to pull fluid in
describe filtration and osmotic flow in relation to capillary exchanges
filtration tends to push out fluid from inside capillaries
osmotic flow tends to pull in or retain fluid inside capillaries
where do capillary exchanges takes place
filtration/absorption take place along the whole length of capillary bed and not just at the 2 ends
describe the fluid distributions between the capillaries and lymphatic system
~90% of the fluid filtered out is reabsorbed back into capillaries
10% is drained from tissues by lymphatic vessels
describe the blind ended tubules more in depth
finger like projections
more permeable than capillary wall
picks up any excess fluid and proteins and returns it back to the central circulation
describe lymphatic vessels
a single layer of endothelial cells
highly permeable to all ISF constituents including proteins that leak (picks up and must removes to keep cop in balance)
describe lymphatic vs blood flow volumes
total blood flow = 6000L travel through capillaries
volume flittered into ISF = 20L
volume returned by absorption = 17L
volume returned by lymph drainage = 3L
which proteins contribute the most to COP
osmotic pressure of solution depends on number of osmotically active particles volume
NOT size, configuration or charge
ex: 1kg steel balls vs 1kg feathers (feathers = more osmotic pressure since more particles)
describe the 2 relationships protein fracture exerts on an osmotic pressure
directly related to its concentration in plasma
inversely related to molecular weight of protein
state the COP of the 3 plasma proteins
albumin ~20mmHg
globulins ~5mmHg
fibrinogen ~ <1mmHg
name the 4 factors in transcapillary dynamics
hydrostatic pressure
COP
capillary permeability
lymphatic drainage
what is edema
accumulation of excess fluid in interstitial spaces
decreased venous return
what causes edema (4)
increased hydrostatic pressure
decreased plasma protein (COP)
increased capillary permeability
obstruction of lymphatic drainage
describe increased hydrostatic pressure (causes edema)
high blood pressure
increases blood pressure at arterial end and venous end, causing no net absorption on the venous end, so it cannot pull in fluids
describe decreased COP (causes edema)
ex in liver or renal diseases
causes COP to be equal to pressure on venous end - also causes no net absorption
describe example of edema due to decreased cop
failure to synthesize plasma proteins
eg liver disease
severe protein malnutrition - leads to decreased cop and distended abdomen and fluid leakage
KWASHIORKOR
describe increased capillary permeability (causes edema)
if capillary wall becomes more permeable (in damage/infection)
plasna proteins escape into ISF where they can exert oncotic effect
COP is lowered from 25–>20, so 5 mmHg ISF OP, causing proteins to move in
describe reduced lymphatic drainage (causes edema)
cant bring back that 10% of fluid, so it causes excess fluid in ISF
ex: during breast cancer, can remove some lymphatic tissue and leads to decrease of venous return (edema)
describe example of edema due to obstructed lymphatic drainage
elephantiasis
blockage of lymphatic drainage resulting from parasite infestation
filaria nematode - small worms, adult works block the lymphatic return
name the 3 roles of plasma proteins
determining distribution of fluid
contribute to viscosity of plasma
contribute to buffering power of plasma
describe determining distribution of fluid (roles of plasma proteins)
determines distribution of fluid between plasma and ISF by starling forces controlling transcapillary dynamics
describe contribute to viscosity of plasma (roles of plasma proteins)
how thick/how easily something will move
viscosity contributes to blood pressure
describe contribute to buffering power of plasma (roles of plasma proteins)
buffering pH - having the right amount of ions
normal pH range ~ 7.4
describe fibrinogen and some globulins (specific plasma protein functions)
are essential to clotting
describe gamma globulins (specific plasma protein functions)
aka immunoglobulins
provide specific resistance to infection
describe albumin and some globulins (specific plasma protein functions)
act as carriers for lipids, minerals and hormones
transport nutrients throughout body - move substances without harming the tissues (ex: iron is toxic, but its transported so it wont hurt the body)
name the process that is not subject to transcapillary dynamics
diffusion
what does the buffy layer and red blood cell layer have
different types and functions of blood cells
describe the branches of blood cells
single precursor in bone marrow (blood cells) can produce:
erythrocytes - rbcs
thrombocytes - platelets
leukocytes - wbcs
describe number, diameter and lifespan of rbcs
number = 5x10^6/uL
diameter = 7.2um
lifespan = 120 days
describe number, diameter and lifespan of platelets
number = 250000-400000/uL - lower concentration
diameter = 2-3um
lifespan = 7-8 days
describe number, diameter and lifespan of wbcs
number = 8000-10000/uL - much lower
diameter = 10-18um = large in size, depends on type
lifespan = hours-years, (eg like memory cells, last and protect for a long time )
what is hematopoiesis
all blood cells are derived from a common multipotent (pluripotential) hematopoietic stem cell
one stem cell gives rise to all different blood cell types
name and explain the 3 types of hematopoiesis
erythropoiesis = production of rbcs
thromobopoiesis = production of platelets
leukopoiesis = production of wbcs
what are cytokines
substances (proteins or peptides) that are released by one cell and affect the growth, development and activity of another cell
what are HGFs
Hematopoietic Growth Factors
cytokines that influence the proliferation and differentiate of blood cell precursors
describe hematopoiesis general pattern
starts with pluripotential multipotential stem cell - receives stimulus and is induced - self replication –> 3 types of committed stem cells - other stimulants cause them to develop
leukopoiesis –> leukocytes
thrombopoiesis –> platelets
rrythropoiesis –> erythrocytes
hematopoietic stem cells can either…
divide or differentiate
are the sites of hematopoiesis the same during every life stage
NOOO
depends on the life stage
prenatal and postnatal
describe prenatal hematopoiesis - initial
after fertilization the bloods precursors are going to be formed in the yolk sac (blood islands of the yolk sac of the developing embryo)
describe prenatal hematopoiesis - over course of months
~1month = production of precursors is gonna take over in the liver and spleen - peak at 5 months
halfway - blood production will start at level of bone marrow
describe postnatal hematopoiesis
blood cells are continually produced in the bone marrow
what is bone marrow
spongy tissue inside of bones
describe postnatal hematopoiesis
at beginning of life - lots of production in distal epiphyses of the long bones - so like the top of the femur
at around 20 this declines and it is taken up by the axial skeleton - for the rest of your life
name parts axial skeleton - where hematopoiesis takes place - 7
flat bones of skull
shoulder bones
sternum
vertebrae
ribs
pelvis
proximal epiphyses of long bones
what is main function of rbcs
facilitate transport of respiratory gases
describe rbc characteristics - shape
biconcave disk - thinner in middle than edges (jelly donut/dumbbell shape)
what is rbc shape due to
presence of spectrin = a fibrous protein forming a flexible network linked to cell membranes
what are the advantages of rbc shape - 3
form follows function
maximal surface area and minimal diffusion distance - increases efficiency of oxygen and carbon dioxide diffusion
high degree of flexibility - allows rbcs to squeeze through narrow capillaries
what is cbc
complete blood count
number of rbcs, wbcs, platelets, hematocrit, hemoglobin concentration - can diagnose diseases and stuff
name and describe the 3 cell sizes
normocytic - 7micron size
microcytic - smaller than normal
macrocytic - larger than nornmal
name and describe the 2 cell shapes
sickle cell
shperocyte - loses structure and becomes spherical
what is the amount of rbcs in males and females
males = 5.1-5.5 x 10^6 / uL
female = 4.5 - 4.8 x 10^6 / uL
what is amount of rbcs in blood
~25x10^12 in 5L of blood
huge amount
describe rate of production of rbcs
rate of production = rate of destruction ~ 2x10^6 / sec
describe rbc composition
mostly water
some lipids, proteins and ions
33% hemoglobin
what do rbcs not have
no subcellular organelles
no nucleus or mitochondria
missing from mature rbc
name and describe the 2 important enzyme systems of rbcs
glycolytic enzymes –> generate energy (anaerobically) - since no mitochondria so allows to produce energy
carbonic anhydrase –> CO2 transport
how many O2 molecules can each Hb bind
max of 4O2 molecules
what is Hb called when combined with O2
oxyhemoglobin - HbO2
what is Hb called when O2 is released from it
deoxyhemoglobin - DeoxyHb
describe hemoglobin structure
2 alpha chains, and 2 beta chains
each chain has heme region with iron and heme is where O2 binds
200-300X10^6 molecules / rbc
molecular weight = 64KDa (similar to albumin)
what happens to Hb in lungs
Hb becomes saturated with oxygen - appears bright red
what happens to Hb in tissues
oxygen dissociated from Hb - appears dark red
name the functions of hemoglobin
transport of O2 - reversible binding with Hb
increases O2 solubility in blood (plasma = 0.3mLO2/100mL plasma & blood = 20mLO2/100mL blood)
transport of CO2
acts as buffer
describe transport of CO2
binds to globulin molecules
why have Hb inside rbcs and not dissolved in plasma
has effect on plasma viscosity, COP and on loss via kidney
increases viscosity and COP, easily lost through kidney bc small
describe hemoglobin values in males and females
males = 16g/100mL blood
females = 14g/100mL blood
when Hb is fully saturated with O2 each gram of Hb holds how much O2
1.34 mL O2
O2 carrying capacity of blood is what
20mL O2/100mL blood
(15gx1.34mL = 20)
name the 5 factors that affect the ability of Hb to bind and release O2
temp
ionic composition
pH
pCO2
intracellular enzyme concentration
what is rate of erythropoiesis
2-3 x 10 ^6 per sec
must be balance by rate of destruction
describe pathway of hematopoiesis
under influence of different HGFs
can join lymphoid or myeloid stem cells
becomes committed and differentiates and divides to other cell types
can the injection of bone marrow stem cells do
reconstitute all hematopoietic cell types
repopulates all of them
describe rbc precursor proliferation
differentiates in myeloid pathway
division and differentiation = 3-5 days
then produces rbcs - in first 24 hours of their production they are called reticulocytes (newborns)
after first 24 hours = rbc
erythropoietin stimulates erythropoiesis
describe red cell precursor proliferation steps - 3
1 - decrease in size
2 - loss of nucleus and organelles
3 - accumulation of Hb
stem cell = 18um –> erythrocyte = 7um - shape, size and contents change, loses nucleus and all organelles and accumulates Hb
what is a reticulocyte
newborn blood cell
has not completely gotten ride of subcellular organelles
some ribosomes visible and havent gotten ride of reticulum
what is normal reticulocyte count
<1%
what is reticulocyte index
reflects amount of effective erythropoiesis in bone marrow
medical tests - if its like 5% - raises question of why producing so many rbcs
describe 2 factors determining amount of rbcs
O2 requirements - like training for marathon, increase exercise and production of more rbcs
O2 availability - like at high altitudes, less oxygen availability , higher altitudes = pO2 lower so compensate by producing more O2 bc low availability
what is erythropoietin
EPO
glycoprotein hormone/cytokine produced mainly by kidney
what is stimulus for release of EPO
hypoxia - if body senses hypoxia stimulates more EPO –> more rbcs
what might cause hypoxia - 3 things
decreased rbc count
decreased availability for oxygen to blood
increased tissue demand for O2
describe EPO - genetic manufacturing
EPO has been purified, sequenced, gene has been clone, and has been produced by recombinant DNA technology
uses = stimulate rbcs for sick ppl, or abuse - increase O2 capacity
describe regulation of erythropoiesis (cycle)
kidney = sense hypoxia and increases release of EPO –> increased EPO in plasma –> stimulates RBC production in bone marrow –> increases rbc production (tell by seeing reticulocyte count) –> increased oxygen (carrying capacity) in plasma –> back to kidney (senses increased O2, decreases release of EPO) –> none of other steps happen
describe regulation of erythropoiesis mechanism
negative feedback mechanism - senses high levels and shuts off or senses low levels and turns on
describe regulation of erythropoiesis (statement with words)
EPO released from kidney with hypoxia stimulates bone marrow to produce more rbcs - maintaining homeostasis!
where is EPO synthesized
renal cortex
what does EPO act on
acts on committed rbc precursors
not on pluripotent cells more downstream
most of the processes to maintain homeostasis aree…
NEGATIVE feedback
describe what happens when sever accidental hemorrhage (steps)
severe accidental hemorrhage –> less hb available for oxygen transport –> reduced supply of oxygen to kidneys –> increased production and release of epo –> increased rbc precursor production in bone marrow –> increased discharge of young erythrocytes in blood –> more hb for oxygen transport
describe erythropoietin action
pluripotent stem cell –> committed myeloid stem cell (epo stimulates proliferation - to produce more cells) –> reticulocytes (epo accelerates maturation - helps it move fastser) –> mature rbcs
what is effect of testosterone on epo - 2
increased released of epo
increased sensitivity of RBC to precursors of epo - they will be stimulated at lower concentration than normal - more sensitive to epo
what is effect of estrogen on epo
opposite effects of testosterone = why men have more rbcs than women
what is life span of rbcs
120 days - nothing prolongs rbc lifespan - nothing protecting them so they degenerate over time
during time - each rbc travels equivalent of 300 miles
what happens to old rbcs
recognized as such - old and damaged - and are removed from circulation by highly phagocytic cells known as macrophages
at level of liver and spleen
describe phagocytosis of old rbcs
macrophages eat cells - put out pseudopods - finger like projections and engulf old rbc and uses enzymes to break it down
rbc is digested and contents are released
where do contents of phagocytized rbcs go
they still have valuable materials so constituents are released into cytoplasm to be used
what is function of macrophage
destruction of rbcs and recycling of components
name the 3 main constituents released when rbcs are broken down
globulin
Fe
Hb
describe globulin (constituents released when rbcs are broken down)
break up globulin and free amino acids move into circulation to make new proteins
produces amino acid pool
describe Fe (constituents released when rbcs are broken down)
iron - toxic in blood, 4 molecules of iron/hb
transferrin allows Fe to move through blood safely
ferritin attaches and can be stored in liver, spleen and gut
if body needs iron - then ferritin releases and Fe can be picked up transferrin again and transported to bone marrow for rbc production
describe hb (constituents released when rbcs are broken down)
major component to regulate
hb produces heme - heme is not really used - heme is transformed to bilirubin
bilirubin (1mg/dL) = yellow colour (plasma and urine) most is lost in gut
in liver - converted to biliverdin - to gastrointestinal tract and gives feces colour
what happens if bilirubin concentration is >1mg/dL
jaundice - yellow colouring of skin and eyes
more bilirubin in plasma = everywhere plasma circulated will appear more yellow
what is neonatal jaundice
excess of rbcs and lots of hemolysis after birth - usually subsides/is monitored
phototherapy treatments can be used
name the 3 causes of jaundice
excessive hemolysis
liver damage
bile duct obstruction
describe excessive hemolysis - causes of jaundice
breaking down more blood = more heme to recycle = more bilirubin
describe liver damage - causes of jaundice
liver cannot process bilirubin and moves into intestines for secretion and piles up - leads to jaundice
describe bile duct obstruction - causes of jaundice
blocks bile from entering small intestine and backs up in blood and leads to jaundice
what is a normal dynamic for rbcs
production = destruction
what is polycythemia
production > destruction of rbcs
overproduction
what is anemia
production < destruction
not enough rbcs - cannot pick up enough oxygen
how to know if normal or abnormal dynamics of rbcs - normal, polycythemia or anemia??
use clinical indices = number of rbcs, amount of hb, and hematocrit (easiest)
what can look like polycythemia
dehydration
less than normal body water = less plasma = appears as polycythemia
what can look like anemia
fluid retention
makes plasma compartment more full of water
what are normal hemoglobin levels
16% hb
5-5.5 x 10^6 rbcs/uL
what are polycythemia hemoglobin levels
> 18% hb
6 x 10^6 rbcs/uL
name and describe (gen) the 2 types of polycythemia
relative - due to increased plasma volume - relative to water content
absolute - may be physiological or pathological - related to actual amounts of rbcs
describe physiological polycythemia
secondary effect
occurs due to higher needs for oxygen or lower oxygen availability
describe conditions that would cause physiological polycythemia - 4
something that increases demand for oxygen
at high altitude
increased physical activity
chronic lung disease
heavy smoking (less ability to absorb oxygen in lungs)
describe pathological polycythemia
primary effect that can occur due to tumours of cells producing epo & unregulated production by bone marrow
describe polycythemia vera ex
7-8 x 10^6 rbcs/uL
Ht ~ 70%
due to stem cell dysfunction = unregulated rbc production
why is polycythemia a problem
increases blood viscosity - will be thicker
slow blood flow can lead to blood clots
what is anemia (in words)
decrease in the oxygen carrying capacity of blood
describe the measurements defining anemia
decreased rbc count
- males = <4 x 10^6/uL
- females = <3.2 x 10^6/uL
decreased hb content
- males = <11g%
- females = <9g%
how to classify anemia (morphologic)
by size (volume) and colour
describe sizes (volumes) of morphologic classifications of anemia
microcytic = <80um^3 - small
normocytic = 80-90um^3 - normal
macrocyctic = >94um^3 - too large (cells don’t mature well - part of maturing is shrinking and losing size/contents)
describe colours of morphologic classifications of anemia
hypochromic <33% - less red
normochromic ~33%hb = normal colour, full of
hb
hyperchronic - super packed full and red
name the 3 etiologic classifications of anemia
diminished production
ineffective maturation
increased rbc destruction/reduced rbc survival
what can diminished production (etiological classifications of anemia) be due to - 3
abnormality at site of production (bone marrow)
inadequate stimulus
inadequate raw materials
describe abnormality at site of production (bone marrow) - in diminished production (etiological classification of anemia)
aplastic (hypoplastic) anemia
etiological = unknown, could be exposure to radiation or chemicals or drugs (failure of bone marrow to produce)
classifications = normocytic and normochromic - just not producing enough
describe inadequate stimulus - in diminished production (etiological classification of anemia)
stimulation failure anemia
etiology = renal disease (less epo production)
classification = normocytic and normochromic (normal but not enough)
describe inadequate raw materials - in diminished production (etiological classification of anemia)
iron deficiency anemia (most common)
etiology = increased requirement for Fe or inadequate supply of Fe
classification = microcytic and hypochromic (too small - no iron to make hb, no hb so pale and not filled)
go into more detail about iron deficiency anemia
can happen during period of growth
increased requirement for Fe = during infancy adolescence and pregnancy
inadequate supply of Fe = dietary deficiency, failure to absorb, loss of Fe in hemorrhage (also like ulcers - losing blood to gastrointestinal tract)
what is total amount of iron in body + distributions
4g
65% Hb
30% stored
5% myoglobin
1% enzymes
what is daily intake of iron in diet
~15-20mg per day
describe absorption of iron (numbers/day)
depends on needs of body - usually don’t absorb all iron - just what we need and some stored, don’t want to have too much since it’s toxic
males ~1mgFe/day
females ~2mgFe/day (who menstruate)
why do females who menstruate need more iron than men
menstrual lose ~ 50mL blood per month
1gHb contains 3.5mg Fe, 15gHb/100mL blood = ~ 50mg Fe - so menstruating females lose 25mg iron per month and need 50mg per = ~2mg/day
describe iron use during erythropoiesis and rbc destruction
normal erythropoiesis requires 25 mg per day
normal rbc destruction releases 25mg/day - 1mg is lost and 24 is recycled
describe infective maturation (etiological classifications of anemia)
maturation failure anemia - cells cannot mature fully
etiology = deficiencies of vitamin B12 and folic acid, inadequate supply of iron
classifications = macrocytic normochromic - cell will not mature so they will stay large
what are both vitamin B12 and folic acid required for
DNA synthesis
describe what could cause inadequate supply of iron
dietary deficiencies
failure to absorb
loss of iron in hemorrhage
what is vitamin B12
found only in animal products - usually failure to absorb (sometimes deficiency in vegans)
what is folic acid
found in leafy greens
usually dietary absence/overcooking veggies
describe increased rbc destruction/reduced rbc survival (rbc survival disorders) - (etiological classification of anemia)
hemolytic anemias - may be companied by jaundice
etiological = congenital, acquired (drugs, toxin, antibodies)
name and describe the 3 examples and sub examples of hemolytic anemias
abnormal rbc membrane structure - hereditary spherocytosis - less flexible more fragile, sphere shaped damages membrane and is gotten rid of bc it’s damaged
abnormal enzyme systems - abnormal metabolism
abnormal hb structure - sickle cell, thalassemia (deficient synthesis of globin aa side chains)
what is unique about vitamin B12 absorption
requires intrinsic factor
intrinsic factor binds to vitamin B12 and allows it be carried to ileum (end of small intestine) to be absorbed - vitamin B12 would be destroyed in gastric acid of stomach if it wasn’t bound to intrinsic factor
what would happen if intrinsic factor deficieny
causes pernicious anemia
if don’t have factor (ex could be because part of stomach is removed) or are vitamin B12 deficient = not enough vitamin B13 absorption
what secretes intrinsic factor
released by stomach cells
what type of anemia is pernicious anemia
infective maturation - maturation failure anemia
classification = macrocytic and normochromic
what is hemorrhage
blood loss
what are the types of blood loss
external - blood goes outside the body
internal - into tissues, internal hemorrhage
what is a hematoma
accumulation of blood in tissues
what is hemostasis
arrest of bleeding following vascular injury
what is hemostasis due to
overlapping mechanisms
vascular response
platelet response
clot formation
what is primary hemostasis - def
begins within seconds of injury
lasts only minutes
sometimes enough to stop bleeding - like for small blood loss via capillaries
what mechanisms make up primary hemostasis
vascular response - damaged endothelial cells have their own response
platelet response - critical for stopping blood
what is secondary hemostasis
takes longer
clot formation
name and explain the processes of primary hemostasis
vascular injury - damaged endothelial cells and blood escapes
vasoconstriction - contracting smooth muscle to decrease diameter of vessel - slow blood flow to help
platelet plug formation - aggregate at site of injury and stops bleeding
name and explain the processes of secondary hemostasis
blood clot formation - stop permanently
describe vascular response
vasoconstriction
smooth muscle cells in vessel wall respond to injury by contracting
opposed endothelial cells stick together - they are pushed together
slows blood flow
describe platelet response
forms white thrombus - platelet plug
further blocks release of blood
describe platelet structure
2-4um diameter
no nucleus
~250 000/uL - lot less than rbcs
life span: 7-10 days
not real cells - cell fragments - larger cell pinches off
describe the many granules of platelet structure
factors for vasoconstriction
platelet aggregation / clotting / growth / etc
many filaments
microtubules
mitochondria
SER
where are sites of production of platelets
same as sites of hematopoiesis
describe hematopoiesis - how platelets form
pluripotent hematopoietic stem cell –> myeloid stem cell –> megakaryocyte –> platelets
describe platelet production pathway
pluripotent stem cell –> committed myeloid stem cell (15-20u) –> megakaryocytes (nucleus divides - multilobed) produces granules and cellular organelles (filled with stuff to be released) –> fingerlike projections into blood stream - pinch off and –> platelets
where is thrombopoietin from
mostly from liver
what is the first thing that happens when blood vessel is damaged
expose collagen of endothelial cells and outside vessel
after collagen is exposed what happens
platelets aggregate and stick to collagen - stick part of endothelium allows platelets to adhere
what happens after platelets stick to the exposed collagen
platelets and endothelium cells secrete von willebrand factor
which takes one end of the collagen and sticks it with platelets - fix together
what does adhesion do to platelets
changes their properties
membranes become more sticky and allows them to further aggregate - activation
what do platelets release after adhesion (excluding von willebrand)
ctyokines - thromboxane A2 - consolidation of platelet plug
ADP & serotonin - vasoconstriction
platelet factor 3
what factor does platelet aggregation release
von willebrand - enhances adhesion –> aggregation
what do damaged endothelial cells activate
coagulation pathway
releases thrombin = important for production and formation of clot
what does exposed collagen bind and activate
platelets
what do platelet factors do
released and attract more platelets
what do platelet factors also promote
coagulation scheme
name the 5 functions of platelets
release vasoconstricting agents / cytokines
form platelet plug (white thrombus)
release clotting factors
participate in clot retraction
promote maintenance of endothelial integrity
what is petechia
small red/purple spots caused by bleeding into skin
due to capillaries and platelets not functioning properly
when dont have enough platelets - small bleeding under skin through capillaries cannot be stopped
what does abnormal primary hemostatic response lead to
prolonged bleeding
what could abnormal primary hemostatic response be due to
failure of blood vessel to constrict
platelets deficiencies
name/describe the types of platelet deficiencies
numerical (numbers)- <75000/uL
functional (functions) - congenital or acquired
describe congenital functional platelet deficiencies
cannot produce factors
single factor hereditary deficiencies
describe acquired functional platelet deficiencies
drugs
toxins
antibodies
multifactor deficiencies
targets platelets and makes them stop
what does aspirin do
in small doses
inhibits synthesis and release of thromboxane A2
- helps prevent clotting during heart attack or to prevent heart attacks
what is a blood clot
thrombus
rbcs and wbcs are not required
lots of fibers- causes rbcs to be stuck in it but they do not have any function in a clot
what is clot formation a function of
plasma
no rbcs needed
what is clotting activated by
injury to blood vessel wall
what does clotting result in
sequential activation and interaction of a group of plasma proteins/clotting factors
describe group of plasma proteins/clotting factors that are activated by clotting
act as cofactors or enzymes - activate other factors
in the presence of calcium or some phospholipid agents (for process to take place)
name the 3 stages of clotting
injury to vessel wall
stage 2 happens in cytoplasm - not visible
clot formation - only visible stage
describe step 3 of clotting
fibrinogen (important plasma protein in clotting)
in the presence of thrombin its converted to fibrin = forms mesh that makes blood clot
describe step 2 of clotting
prothrombin activates thrombin
needs calcium
prothrombinase converts prothrombin to thrombin
what is intrinsic pathway
damage leads to exposed collagen
all components are found in plasma
cascade of activation of factors
what is extrinsic pathway
tissue factors (protein and phospholipids) released from damaged cell - outside endothelium activates factors and prothombinase
getting something from inside pathway
which pathway (intrinsic or extrinsic) is longer
Intrinsic = 3-6 mins
Extrinsic = 15-20 seconds
describe feed back of prothombinase
Positive - generally bad since clot would never stop growing
but clot retraction opposes this and stops it
describe the generation of thrombin in extrinsic and intrinsic pathway
small amounts of thrombin generated rapidly in the extrinsic pathway are sufficient to trigger strong positive feedback effects - to generate larger quantities of thrombin in the intrinsic pathway
name the 3 factors in coagulation
calcium
phospholipid
protein plasma factors
what is clotting kept in check by
inhibitors of platelet adhesion
anticoagulants
what is thrombocytopenia
deficiency of platelets in blood
what is PF3
source of phospholipid activity which participates in coagulation
what are anticoagulants
naturally occurring elements that block one or more of the reactions of the coagulation scheme
prostacyclins and NO
give an ex of congenital single factor hereditary deficiency (clotting factor deficiency)
factor VIII
hemophilia - inability to form clots
could also have defects in von willebrand factor
give an ex of acquired multi factor deficiency (clotting factor deficiency)
liver disease - linked to issues with blood clotting
vitamin K deficiency - travels in bile (produced by liver)
what is vitamin K
cofactor in synthesis of prothrombin VII, IX, X
describe clot retraction
clot retraction requires contractile protein - thrombosthenin
released by proteins
only damaged endothelial cells are sticky so its usually very localized
clot retracts from sides
what is clot lysis
fibrinolysis = thrombolysis
describe pathway of clot lysis
intrinsic proactivators or extrinsic proactivators –> plasminogen activator –> converts plasminogen to plasmin –> converts fibrin to fibrin fragments = clot breakdown
describe intrinsic proactivators of clot lysis
factor Xlla
endothelial cell factors
describe extrinsic proactivators of clot lysis
tissue factors
what are other ways to stop formation or get rid of blood clots
inhibitors of platelet adhesion
anticoagulant drugs
thrombolytic drugs
name an inhibitors of platelet adhesion
asprin
what do anticoagulant drugs do
interfere with clot formation
name 2 anticoagulant drugs and describe them
coumarin - blocks synthesis of functional prothrombin, VII, IX, X
heparin - inhibits thrombin activation and action (heparin is also naturally occurring in blood but is also a drug)
what do thrombolytic drugs do
promote clot lysis (helps dissolve clot)
name 2 thrombolytic drugs
tissue plasminogen activator (tPA)
streptokinase
