Week 3 - Blood Flashcards
Blood Function
transport of O2 + CO2
protection - restricts fluid loss from damaged BV (platelets + clotting proteins)
regulation - of pH, electrolyte composition (interstitial fluid), body temp
-provides mechanism for rapid transport (nutrients, waste products, respiratory gases)
Blood is powered by…
the pumping action of the heart
Hemoglobin
oxygen carrying protein found in RBCs
-approx 280 million hemoglobin molecules in blood
-pigment containing iron (changes color based on oxygenation)
-globulin portion: transports CO2, carbonic anyhrase, nitric oxide
-heme groups (4): transport O2 (iron requred for O2 transport); each bound to a polypeptide; 4 binding sites for O2
within RBCs
COPD in Relation to Hemoglobin
hypoxemia stimulates erythropoeitin
-hemoglobin will appear both blue and red
Hemoglobin + O2
hemoglobin + O2 = weak bond
Hemoglobin + CO
hemoglobin + CO = strong bond
-binds 200x more avidly than O2
knocks O2 off of hemoglobin
Nitric Oxide
inactivated by Hemoglobin
Circulatory System
composed of cardiovascular system + lymphatic system
Cardiovascular System
Characteristics + Function
BV, heart + blood
function : transport nutrients, gases, hormones to cells and pick up wastes for transport for excretion
Lymphatic System
Characteristics + Function
network of vessels that return fluid escaped from blood vessels to bloodstream
-lymphocytes + lymphoid tissue
-fight against infections and provide immunity to disease
-detrimental -> metastases of cancer easily circulate
Blood Cells
Blood Composition
formed cells (34-54%)
-platelets/WBCs (“buffy coat”) = 0.1%
-RBCs = 99.9%
Plasma
Blood Composition
fluid portion and fibrinogen (46-63%)
pH of Blood
7.35-7.45
Blood Volume
Male v. Female
female: 4-5 L
male: 5-6 L
CBC
(“spun down”)
-plasma: 55% of whole blood
-“buffy coat” : <1% (platelets + WBCs)
-RBCs = 45%
Packed Cell Volume
RBC count / approximation of hematocrit %
Hematocrit
approximation of RBCs
-normal = 45%
Why are there less RBCs in females than males?
menstruation
Albumin
(Plasma Protein)
plasma proteins contributing to osmotic pressure of plasma
-transports lipids and steroid hormones
-aids w/ electrical components, pumps, and pressure gradients to keep everything in the body moving
most abundant
Plasma
-regulates body temp
-contains electrolytes
-transports blood cells, digestion and hormones
(90% water, nonliving part of blood)
RBC Function
-transport O2 from lungs to tissues
-transport CO2 from tissues to lungs
Components of RBCs
hemoglobin, lipids, ATP, carbonic anhydrase
Erythrocytes
transport O2 from lungs to tissues and CO2 from tissues to lungs
-production of HCO3 due to RBC carbonic anyhydrase
-made in red bone marrow (long bones, cranial bones, ribs, sternum and vertebrae)
-biconcave shape to squeeze through small spaces (30% more surface area for diffusion of O2 across membrane)
-lifespan = 100-120 days
-no organelles, ribosomes or nuclei
components: Hemoglobin, lipids, ATP, carbonic anhydrase
Leukocytes
WBCs for immune system defense
Platelets
(Function)
stops bleeding from damaged vessel (hemostasis)
-vascular spasm
-formation of platelet plug
-blood coagulation
Platelets
(Characteristics)
cell fragments necessary for hemostasis (clotting) shed from megakaryocytes
-remain functional for 10 days (removed by macrophages)
-do not leave blood (1/3 stored in spleen + released due to splenic contraction)
thrombocytes
Components of Plasma
90% H2O, 6-8% plasma proteins, 1% electrolytes (Na+/Cl-)
-nutrients (ex. glucose and amino acids)
-hormones (ex. cortisol and thyroxine)
-wastes (ex. urea)
-blood gases (ex. CO2 and O2)
Plasma Proteins
most produced in the liver (6-8% the plasma’s weight)
-albumins
-globulins (alpha, beta, gamma)
-fibrinogen
-functions: buffer pH, maintain osmotic pressure, antibodies, clotting factors
H2O
Plasma
90%; transport medium carrying heat
Electrolytes
Plasma
-membrane excitability
-osmotic distribution of fluid between ECF + ICF
-buffer pH changes
Nutrients, wastes, gases, hormones
Plasma
transported within the blood
blood gas CO2 plays role in acid-base balance
Plasma Proteins
Plasma
-exert osmotic effect (albumins) important in distribution of ECF between vascular and interstitial compartments
-buffer pH changes
-transport of hormones
-antibodies (gamma/immunoglobulins)
-clotting factors (fibrinogen)
albumins, globulins, fibrinogen
Albumins
Plasma Proteins
transport many substances, contribute most to colloid pressure
most abundant plasma protein
Alpha and Beta Globulins
Plasma Proteins
transport may water insoluble substances; clotting factors are alpha and beta; inactive precursor molecules (ex. angiotensin)
Alpha Globulins
Plasma Proteins
carries thyroid hormones
ex. angiotensin
Beta Globulins
Plasma Proteins
lipoprotein carrying Cholesterol + iron (Fe)
Gamma Globulins
Plasma Proteins
antibodies
Fibrinogen
Plasma Proteins
inactive precursor for fibrin meshwork of a clot
produced in liver
Hematopoiesis
(aka Hemopoiesis)
process of blood cell production
Stem Cell
cell in which all formed elements (other cells) are derived from
ability to develop into many different cell types
Reticulocyte
reticulocyte -> erythrocyte
-remain reticulocyte for 1-2 days in circulation
-make up 1-2% of erythrocytes
immature RBCs
Reticulocytes in Sickle Cell Patients
immature RBCs kicked out prematurely to keep up with production of RBCs
Lymphoblast
develops into lymphocytes
Proerythroblast
proerthyroblast -> early erythroblast -> late erythroblast -> normoblast -> reticulocyte -> erythrocyte
-committed cells (progenitor cells)
-activated by erythropoietin
-eject nucleus to turn into reticulocyte
in red marrow; develops into RBC
Myeloblast
myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band cell -> [baso/neutro/eosino-phil]
develops into basophils, neutrophils, and eosinophils
eventually form leukocytes
Monoblast
monoblast -> promonocyte -> monocyte
develops into monocytes
enlarge and form macrophages
Megakaryoblast
megakaryoblast -> promegakaryocyte -> megakaryocyte -> platelets
-develops into platelets
(clotting)
Genesis of Erythrocytes
proerthyroblast -> early erythroblast -> late erythroblast -> normoblast -> reticulocyte -> erythrocyte
Genesis of Leukocytes
myeloblast -> promyelocyte -> myelocyte -> metamyelocyte -> band cell -> [baso/neutro/eosino-phil]
Regulation of total number of RBCs + platelets in circulation by…
negative feedback system
-increase WBC types based on response to pathogen
Besides the heart, the majority of blood goes…
to the brain, liver and kidneys
Kidney Function in Blood
stimulates marrow to increase RBC production if blood / O2 flow is low
-hypoxia in kidneys stimulates release of erythropoietin
-get 20% of blood volume w/ every heart beat
-production stops once kidney has received full 20% (negative feedback loop)
Control of Erythropoiesis by Kidneys: Process
- Kidneys detect reduced O2 carrying capacity of blood
- Less O2 delivered to kidneys -> secretion of hormone erythropoietin into the blood
- Erythropoietin stimulates erythropoiesis by bone marrow
- Additional circulating erythrocytes increase O2 carrying capacity
- Increased O2 carrying capacity relieves initial stimulus that triggered erythropoietin secretion
- Production of erythropoietin stops once kidney has received their 20% of oxygenated blood supply
Erythropoietin
hormone stimulating RBC production
Anemia
refers to below normal O2 carrying capacity of blood
(about 30% hematocrit)
characterized by low hematocrit/low Hb
Microcytic Anemia
(Nutritional Anemia)
iron deficiency
Macrocytic Anemia
(Nutritional Anemia)
low B12 or folate
Megaloblastic Anemia
(Nutritional Anemia)
B9 (folic acid) deficiency
impaired DNA/RNA synthesis -> cells grow without dividing
Pernicious Anemia
lack of intrinsic factor
-genetic
-atrophic gastritis, loss of parietal cells, gastric bypass, gastrectomy
Aplastic Anemia
chemotherapy agents, radiation, etc.
-bone marrow shuts off
Renal Anemia
renal (kidney) failure
-lack of erythropoietin
Hemorrhagic Anemia
-GI: bleeding, ulcer, GERD
-menstruation
-bleeding disorders
Hemolytic Anemia
ex. sickle cell
Polycythemia
characterized by too many circulating RBCs and elevated hematocrit
-two types: primary & secondary
about 70% hematocrit
Primary Polycythemia
(Polycythemia Vera)
caused by tumor like condition of bone marrow
-erythropoiesis proceeds at uncontrolled rate
Secondary Polycythemia
erythropoietin induced adaptive mechanism to improve blood’s oxygen carrying capacity in response to prolonged oxygen delivery to tissues
-occurs normally in people living at high altitudes + COPD
Myeloid Stem Cells form:
-RBCs
-platelets
-monocytes
-neutrophils (bacterial infection)
-eosinophils (allergic reaction)
-basophils
Lymphoid Stem Cells form:
lymphocytes
Leukocytes
WBCs for immune defense
-function outside of bloodstream in loose connective tissue
-have a nucleus
-larger than RBCs
-produced in bone marrow
-lifespan: 12 hour-several years
-two types: granulocytes + agranulocytes
Granulocytes
Leukocytes
-Neutrophils (40-70%)
-Eosinophils (1-4%)
-Basophils (0-1%)
Agranulocytes
Leukocytes
-Lymphocytes (20-45%)
-Monocytes (4-8%)
Leukocyte Function
- defend against invading pathogens
- identify and destroy cancer cells
- removes worn out cells and tissue debris
Differential WBC Count
-contains formed elements (platelets, leukocytes, erythrocytes)
-Granulocytes (neutrophils, eosinophils, basophils)
-Agranulocytes (lymphocytes + monocytes)
Neutrophils
(polymorphonuclear granulocyte)
Leukocytes
-function: phagocytic cells destroy bacteria
-60-70% volume
-blue granules/nucleus w/ interconnected lobes
-most numerous + important WBC
-1st wave of cells in inflammation
Eosinophils
(polymorphonuclear granulocyte)
Leukocytes
-function: role in allergic reactions, detoxify chemicals, reduce inflammation, attack parasitic worms
-2-4%
-bilobed nuclei; pink or yellow granules containing digestive enzymes
Eosinophilia
increase in circulating eosinophils due to:
-allergic rxns
-asthma
-hay fever
-parasitic worm infection
Basophils
(polymorphonuclear granulocyte)
Leukocytes
-function: inflammation
-<1%
-release heparin (clears fat from blood) + histamine to increase inflammatory response
-bilobed nuceli w/ large purple granules full of chemical mediators for inflammation
least numerous
Heparin
(Basophils)
Leukocytes
-blood thinner
-clears fat from the blood
-activates anti-thrombin 3
-prevent clotting of blood samples
-used as anticoagulant drug
Histamine
(Basophils)
Leukocytes
increases capillary permeability
-released due to allergic rxn
Lymphocytes (B + T)
(mononuclear agranulocyte)
Leukocytes
-function: effective in fighting serious infections; act against specific molecule (antigen)
-20-25%
-dense purple staining round nucleus with little cytoplasm
main fucntional cells of adaptive immune system
B Lymphocytes
Leukocytes
plasma cells -> antibodies
-antibody mediate (humoral) immunity
T Lymphocytes
Leukocytes
directly destroy virus invaded cells and cancer cells
-do not produce antibodies
-punch holes in victim cell
-cell mediated immunity
Monocytes
(mononuclear agranulocyte)
Leukocytes
-function: transform into macrophages; phagocytic cells
-4-8%
-largest leukocyte; kidney shaped nucleus
-emerge from bone marrow while immature
-circulate for 1-2 days
-mature/enlarge in resident tissues to become macrophages (65% in liver)
-lifespan = several months. -years
What cell type would increase with a bacterial infection?
neutrophils
What cell type would increase with a viral infection?
lymphocytes
What cell type would increase with a parasitic infection?
eosinophils
Thrombocytes
(Platelets)
cell fragments pinched off from megakaryocytes in red bone marrow
-important in preventing blood loss (platelet plugs, promotion of clots)
-lack nuclei
-organelles w/ enzymes for generating energy
-high conc. of actin and myosin
-lifespan = 10 days
-do not leave blood (1/3 stored in spleen; released upon splenic contraction)
Thrombopoietin
hormone produced by liver increases number of megakaryocytes
-increase platelet production
Growth Factors
needed to regulate differentiation and proliferation of different stem cells
-erythropoietin (RBCs)
-thrombopoietin (platelets)
-colony stimulating factors/CSFs + interleukins (WBCs)
Heme
prosthetic group (Fe2+)
-acts as cofactor delivering O2 to tissues
-reversibly binds
-coenzyme = attached temporarily
-prosthetic group = attached permanently
Carbon Monoxide (CO) + Hemoglobin
pushes O2 off hemoglobin
-brain is deprived of O2
-no O2 circulating
Sulf-Hb
Abnormal Hemoglobin
forms due to increased sulfur in blood (irreversible reaction)
Carboxy-Hb
Abnormal Hemoglobin
CO2 replaces O2 and binds 220x tighter than O2
ex. smokers -> acidic state
Met-Hb
Abnormal Hemoglobin
contains oxidized Fe3+ that cannot carry O2
Fetal Hemoglobin (HbF)
higher affinity for O2 than HbA (adult)
-maternal Hb (HbA) delivers HbF across placenta (fetal circulation)
Erythropoiesis
production of RBCs; occurs in red bone marrow
-controlled by CNS neurotransmitters (found in hypothalamus)
stimulated by kidneys
Erythropoiesis: Process
- starts in red bone marrow with proerythroblast
- cells near the end of development eject nucleus -> reticulocyte
- develop into mature RBC in 1-2 days
- negative feedback balances production with destruction
- controlled condition is amount of oxygen delivery to tissues
- hypoxia stimulates release of erythropoietin
Spleen Function in Blood
removes old erythrocytes from circulation
Negative Feedback System in Blood
(Kidneys)
stops the secretion of erythropoietin once O2 delivery to kidneys returns to normal (20%)
Hemostasis
platelets role in stopping bleeding
-damaged BV sends signals for platelets -> vasoconstrict -> platelet plug -> clot reinforces plug
-3 steps:
1. vascular spasm
2. formation of plateelt plus
3. blood coagulation (clotting)
Step 1:
Damage to BV -> Vascular Spasm
Hemostasis
immediate constriction of BV to minimize blood loss
-vessel walls press together (sticky/adherent)
Step 2:
Platelet Plug Formation
Hemostasis
platelets attach to exposed collagen
-aggregation of platelets causes release of chemical mediators (ADP and Thromboxane A2)
-ADP = attracts more platelets
-Thromboxane A2 = powerful vasoconstrictor promoting aggregation and increased ADP
positive feedback loop
Thromboxane A2
(Platelet Plug)
Hemostasis
powerful vasoconstrictor promoting aggregation and increasing ADP
ADP
(Platelet Plug)
Hemostasis
attracts more platelets
Prostacyclin
(Platelet Plug)
Hemostasis
inhibits platelet aggregation on normal, undamaged endothelium
Step 3:
Blood Coagulation
(clot formation/cascade)
transformation of liquid blood to solid -> clot reinforces the plug (ex. scab)
1. activation of prothrombinase
2. conversion of prothrombin -> thrombin
3. conversion of fibrinogen -> fibrin (instrinsic clotting path)
extrinsic and intrinsic pathways
Fibrin
meshwork of the clot
-contraction of platelets pulls damaged vessel close together
forms from fibrinogen by intrinsic clotting pathway
Clotting Factors
always present in blood plasma (inactive form)
Clotting Cascade
12 clotting factors leading to final conversion of fibrinogen -> stabilized fibrin mesh
-induced by vessel damage that exposes collagen
-converts fibrinogen to fibrin by instrinsic clotting pathway
Intrinsic Pathway
(Clotting Casacde)
activated by contact w/ exposed collagen/stops internal bleeding
-7 steps
-sets off with Factor 12 (Hageman factor)
Extrinsic Pathway
(Clotting Casacde)
-requires contact w/ tissue factors external to blood
-4 steps
-full break in the vessel (more dangerous/important)
-tissue thromboplastin released from traumatized tissue activates Factor X
Intrinsic Pathway: Steps
(Clotting Cascade)
- Inactive factor 12 activated by damaged vessel -> Active Factor 12 (Hageman Factor)
- Inactive Factor 11 is activated by Factor 12 -> Active Factor 11
- Ca2+ (Factor 4) activates Factor 9
- Ca2+, Factor 8 & PF3 activate Factor 10
- Ca2+, Factor 5 & PF3 activate prothrombin (Factor 2) to Thrombin
- Fibrinogen (factor 1) activated by Thrombin -> Fibrin (loose mesh)
- Thrombin activates Factor 13 -> Fibrin (stabilized mesh)
- Entrapment of blood cells -> clot
Extrinsic Pathway: Steps
(Clotting Cascade)
- Tissue damage -> tissue Thromboplastin (Factor 3)
- Ca2+ & Factor 7 activate Factor 10
- Ca2+, Factor 5 & PF3 activate prothrombin (Factor 2) to Thrombin
- Fibrinogen (factor 1) activated by Thrombin -> Fibrin (loose mesh)
- Thrombin activates Factor 13 -> Fibrin (stabilized mesh)
- Entrapment of blood cells -> clot
Thrombus
abnormal intravascular clot attached to vessel wall
Plasmin
Clot Dissolution
“fibrin splitting” enzyme that dissolves clot
breaks down Fibrin meshwork
Plasminogen
Clot DIssolution
inactive pre-cursor activated by Factor 12 (Hageman Factor)
Fibrinolysis
clot dissolved by activity of plasmin
Emboli
freely floating clots
Factors Causing Thromboembolism
(3)
- roughened vessel surface w/ atherosclerosis (build up on inside = not smooth, causes embolism -> turbulent blood flow knocks off plaque/plugs something -> triggers clotting path)
- stagnant blood forms clot; slow moving blood (broken leg -> DVT)
- occassionally triggered by release of tissue thromboplastin into blood from large amounts of traumatized tissue
- imbalances in clotting-anti-clotting system
Hemophilia
excessive bleeding caused by deficiency of clotting factor
-cannot form clotting pathway -> bleed non-stop, not clot forms
commonly Factor 8 deficiency
Thrombocyte Deficiency
low platelets
-can also lead to diffused hemorrhages
Von Wildebrand’s Disease
condition causing extended or excessive bleeding
-often genetic (inherited)
-deficiency or impairment of Von Wildebrand Factor (vWF)
-vWF = allows platelets to stick to collagen (bridge for glycoprotein and collagen)
-cannot complete cascade = bleed
vWF
(von Wildebrand Factor)
allows platelets to stick to collagen (bridge for glycoprotein and collagen)
Blood Grouping
determined by antigens (agglutinogens) on RBC surface
Agglutination
(clumping)
antibodies (agglutinins) bind to RBC antigens
can also lead to hemolysis (rupture) of RBCs
Type A Blood
A antigens, anti-B antibodies
Type B Blood
B antigens, anti-A antibodies
Type AB Blood
A + B antigens, no antibodies
Type O Blood
no antigens, anti-A + anti-B antibodies
Rh +
have Rh factor
-most of population
Rh -
do not have Rh factor
Hemolytic Disease of Newborn (HDN)
mother produces anti-Rh antibodies (during first childbirth) that cross placenta (during second childbirth) and cause agglutination and hemolysis of RBCs
