3. Blood Flashcards
functions of blood (3)
- transport
- acid-base balance
- protection
normal pH range of blood
7.35 - 7.45
normovolemia
normal blood volume
hypovolemia
lower blood volume
hypervolemia
higher blood volume
composition of plasma
- water = 90%
- proteins =7%
- ions
- nutrients, respiratory gases, wastes
method to separate plasma proteins
electrophoretic mobility
electrophoresis factors
- number and distribution of charges
- molecular weight of each protein
plasma proteins (3)
- albumin
- fibrinogen
- globulins
plasma proteins (except Y globulin) are synthesised in…
liver
Y globulin is synthesised by…
lymphoid tissue to produce antibodies
plasma protein in highest concentration
albumin: 4%
plasma proteins play a role in…
determining the distribution of fluid between plasma and ISF by controlling transcapillary dynamics
Colloidal Osmotic Pressure (COP)
only non-diffusible solutes contribute to the effective osmotic pressure
COP normal value
25mm Hg
if COP increases…
more water will flow into plasma
if COP decreases…
more water will flow into ISF
bulk flow/filtration
fluid in blood vessel under pressure so tends to push out fluid from capillaries into ISF
osmotic flow/COP
plasma proteins tend to pull in fluid inside capillaries
2 majors forms of fluid transport across capillary wall
- filtration/bulk flow
- COP/osmotic flow
starling forces
maintain the relative distribution of ECF volume between ISF and plasma at a 3:1 ratio through bulk flow and COP
site where exchanges between plasma and ISF take place
capillary bed
blood pressure
hydrostatic pressure = bulk flow
percentage of fluid reabsorbed back into capillaries
90%
where does 10% fluid not reabsorbed into capillaries go?
lymphatic system
each protein exerts an osmotic pressure which is (2):
- directly proportional to its concentration in the plasma
- inversely proportional to the protein’s molecular weight
which plasma protein contributes the most to COP?
Albumin (20mm Hg)
edema (def)
accumulation of excess fluid in interstitial space, leading to swelling
factors leading to edema (4)
- increased hydrostatic pressure: more fluid moving out to ISF
- decreased COP: more fluid moving out to ISF (from liver disease, Kwashiorkor)
- increased capillary permeability: plasma proteins escape into ISF
- reduced lymphatic drainage: less fluid drained from ISF (elephantiasis)
role of plasma proteins (3)
- determining distribution of fluid between plasma and ISF by Starling Forces controlling transcapillary dynamics
- viscosity of plasma –> contributes to blood pressure
- buffering power of plasma: pH = 7.4
plasma proteins essential for clotting
fibrinogen + some globulins
Y globulin function
provide specific resistance to infection by producing immunoglobulins/antibodies
which plasma proteins act as carriers for lipids, minerals, hormones and iron?
albumin + some globulins
RBC lifespan
120 days
Platelet lifespan
7 days
WBC lifespan
Hours - years
RBC aka…
erythrocytes
platelets aka…
thrombocytes
WBC aka…
leukocytes
number of RBCs in blood
5 million / microliter of blood
biggest blood cell
leukocytes
smallest blood cell
platelets
hematopoeisis
all blood cells are dervied from a common multipotent/pluripotent hematopoietic stem cell
processes involved in hematopoiesis (2)
- divison
- differentiation
cytokines
substances released by a cell, affecting growth, development and activity of another cell
Hematopoietic Growth Factors (HGFs)
cytokines that influence the proliferation and differentiation of blood cell precursors
sites of hematopoeisis (prenatal)
- 3-4 weeks: yolk sac
- 4 months: liver and spleen
- bone marrow
sites of hematopoeisis (postnatal)
- bone marrow for entire life
- distal long bones (until 30yo)
RBC function
facilitate transport of respiratory gases
RBC shape and advantages
biconcave disk:
- maximal surface area + minimal diffusion distance for increased diffusion efficiency
- high degree of flexibility to squeeze through narrow capillaries
sickle RBC
too thin, squeezed
spherocyte RBC
too round
normocytic RBC
7 micrometer diameter
microcytic RBC
too small
macrocytic RBC
too big
Complete Blood Count (CBC) includes
- RBC count
- WBC count
- platelet count
- hematocrit
- hemoglobin conc.
RBC count is higher in…
males
RBC rate of production =
RBC rate of destruction
RBC composition
- water
- hemoglobin
- no nucleus
How do RBCs function without a nucleus?
contain enzyme systems:
- generate energy anaerobically
- convert CO2 to bicarbonate to facilitate transport
amount of haemoglobin contained in a RBC (%)
33%
Hemoglobin (Hb) structure
- 4 Heme group attached to 2 alpha and 2 beta chains
- Fe2+ attached to Heme
- Oxygen can attach to Fe2+
how many O2 molecules can 1 Hb carry?
4
HbO2
Hb combined with Oxygen
DeoxyHb
when Oxygen is released from Hb
Hemoglobin functions (3)
- transport O2
- transport CO2
- act as a buffer
O2 carrying capacity of blood
20mol O2 / 100ml blood
Factors affecting ability of Hb to bind/release O2: (5)
- temperature
- ionic composition
- pH
- CO2
- intracellular enzyme concentration
erythropoiesis
production of RBCs
reticulocyte
newly produced RBC, becomes a regular RBC after 24h
normal reticulocyte %:
< 1% of RBCs
RBC precursor proliferation (3)
- decrease in size
- loss of nucleus and organelles
- accumulation of Hb
factors determining number RBCs (2)
- O2 requirements (exercise)
- O2 availability (high altitude)
-> RBC increase in numbers as oxygen decreases
Erythropoietin (EPO)
glycoprotein hormone/cytokine which increases RBC production
Erythropoietin stimulated by…
hypoxia: low oxygen
i.e. decreased RBC count, decreased O2 availability, increased tissue demand for O2
EPO function
- stimulate proliferation
- accelerate maturation
Regulation of erythropoiesis process:
- hypoxia detected in kidney
- kidney releases more EPO
- Increased EPO in plasma stimulates RBC production in bone marrow
- no more hypoxia detected as kidney senses increased O2
- kidney decreases release of EPO: NEGATIVE feedback loop
testosterone effect on EPO
increases EPO release and sensitivity of RBC precursors to EPO
oestrogen effect on EPO
decreases EPO release and sensitivity of RBC precursors to EPO
Destruction of RBCs through phagocytosis
- 120 days max lifespan
- old RBCs recognised and engulfed by macrophage (liver and spleen)
- RBC components digested and recycled
RBC Globin recycling
amino acid pool
(RBC) Iron (Fe) recycling
stored as Transferrin in the liver, spleen and gut
(RBC) Hemoglobin recycling
broken down to Heme and stored as bilirubin in liver to then be excreted
normal bilirubin concentration
1mg/dl
bilirubin > 1mg/dl
jaundice (common in newborns)
causes of non-neonatal jaundice (3)
- excessive hemolysis: too much bilirubin produced
- liver damage: bilirubin can’t move down liver so backed up into blood cells
- bile duct obstruction: bilirubin can’t be excreted so backed up into blood cells
polycythemia
RBC production > destruction
anemia
RBC production < destruction
high hematocrit reasons
- dehydration
- polycythemia
low hematocrit reasons
- fluid retention
- anemia
Hb value in polycythemia
> 18g% Hb
issue with polycythemia
increases blood viscosity which can lead to blood clots
2 types of polycythemia
- physiological
- pathological
physiological polycythemia
normal body response, secondary effect that occurs due to higher O2 needs or lower O2 availability
physiological polycythemia caused by: (4)
- high altitudes
- increased exercise
- heavy smoking
- chronic lung disease
pathological polycythemia
primary effect that occurs due to a problem in the body
pathological polycythemia causes: (2)
- tumors of cells producing EPO
- unregulated RBC production by bone marrow
anemia (def)
decrease in oxygen-carrying capacity of blood
Hb (%) and RBC count in anemia (male)
- < 4 million RBC / microliter blood
- < 11g% Hb
morphological anemia
can be due to reticulocyte production issue during development process
morphological anemia size
- microcytic: smaller
- macrocytic: bigger
morphological anemia colour
hypochromic = more pale, less Hb
etiological anemia causes
- diminished production of RBCs (3)
- ineffective maturation (1)
- increased RBC destruction (1)
types of etiological anemia (5)
- aplastic/hypoplastic anemia
- stimulation failure anemia
- iron deficiency anemia
- maturation failure anemia
- haemolytic anemias: RBC Survival Disorders
aplastic/hypoplastic anemia
- normocytic, normochromic RBCs
- abnormality at bone marrow: diminished production
- etiology: exposure to radiation, drugs
stimulation failure anemia
- normocytic, normochromic RBCs
- etiology: renal disease –> less EPO production = diminished RBC production
iron deficiency anemia
- microcytic, hypochromic RBCs
- etiology: increased requirement for Fe (infancy/adolescence/pregnancy) or inadequate supply of Fe (dietary, failure to absorb)
maturation failure anemia
- macrocytic, normochromic RBCs
- due to ineffective maturation
- etiology: vitamin B12 or folic acid deficiencies, which are required for DNA synthesis
vitamin B12 deficiency cause by
Intrinsic Factor deficiency (required for B12 absorption) –> pernicious anemia
folic acid deficiency caused by
dietary absence (found in leafy greens) or overcooking vegetables
haemolytic anemias: RBC survival disorders
- etiology: congenital or acquired
1. abnormal RBC membrane structure
2. abnormal enzyme systems
3. abnormal Hb structure = Sickle cell anemia
hemostasis
arrest of bleeding following vascular injury
primary hemostasis involves
- vascular response
- platelet response
secondary hemostasis involves
clot formation
hemostasis process (4)
- vascular injury
- vasonstriction: smooth muscles contract to decrease blood loss (vascular response)
- platelet plug formation (platelet response)
- blood clot formation
platelets contain many
granules
platelets have a nucleus. True/False?
False
thrombopoiesis
production of platelets
thrombopoiesis (process)
- thrombopoietin stimulates platelet production
- cell gets larger
- nucleus multiplies, creating megakaryocytic containing granules
- cell fragments filled with granules released into bloodstream
where is thrombopoietin produced
liver
platelet plug formation process
- damaged endothelial cells: collagen exposure
- platelets adhere to collagen which activates and attracts more platelets
- cytokines released
- platelets aggregate, forming platelet plug (=white thrombus)
platelet functions (5)
- release vasoconstriction agents/cytokines
- form platelet plug
- release clotting factor
- participate in clot retraction
- promote maintenance of endothelial integrity
lack of platelet condition
petechia
prolonged bleeding caused by
- failure of blood vessels to constrict
- platelet deficiencies (numerical or functional)
RBC are not necessary for blood clot formation. True/False
True
2 pathways for blood clot formation
- intrinsic
- extrinsic
intrinsic pathway
- slower
- everything needed found inside blood vessels
- damage is to blood vessel
extrinsic pathway
- faster
- requires proteins from outside blood vessels
- damage is to tissue outside blood vessel
- small amount of thrombin rapidly generated sufficient to trigger positive feedback on intrinsic pathway to generate larger thrombin quantities
blood clot formation (process)
- damage to blood vessel (intrinsic) or damage to tissue outside vessel (extrinsic
- interacting plasma factors + Ca2+ + PF3 (intrinsic) or tissue phospholipids (extrinsic) recruit prothrombinase
- prothrombinase converts prothrombin to thrombin with Ca2+ help
- thrombin converts fibrinogen to fibrin
- fibrin cross-linked to factor 8, forming blood clot (=red thrombus)
coagulation factors
- Ca2+
- phospholipids
- protein Plasma Factors (PF)
which coagulation factors can be present in limiting amounts
protein Plasma Factors (PF)
Single factor Hereditary PF deficiencies
haemophilia: factor 8 deficiency
Multi factor PF deficiencies
liver disease or vitamin K deficiency (co-factor)
Clot retraction purpose
consolidate clot making it more stable since smaller size
clot retraction requires…
thrombosthenin, a contractile protein released by platelets
clot lysis: fibrinolysis =
thrombolysis
clot lysis process
- plasminogen activator released by intrinsic and extrinsic proactivators
- plasminogen broken down into plasmin by plasminogen activator
- plasmin breaks fibrin down into fibrin fragments
factors that affect clotting (3)
- inhibitors of platelet adhesion, i.e. aspirin
- anticoagulants
- thrombolytic drugs
anticoagulants (def + examples)
chemicals that block reactions of the coagulation scheme
-> coumarin blocks synthesis of Prothrombin, PF 7, 9 and 10
-> heparin promotes inhibition of thrombin activation and action
thrombolytic drugs (function +examples)
promote clot lysis
-> Tissue Plasminogen Activator (t-PA)
-> Streptokinase
