BSCI202 Exam #1

functions of blood

distribution (gases, hormones, nutrients), waste elimination, regulation (pH, temperature, electrolytes), immune protection

composition of blood

plasma (non-living fluid matrix), formed elements (living blood cells - erythrocytes, leukocytes, platelets)

formed elements are derived from

hematopoietic stem cells (HSC) and formed in the red bone marrow

hematopoietic stem cells mature into

myeloid stem cells and lymphoid stem cells

myeloid stem cells mature into

megakaryocytes, erythrocytes, myeloblasts

megakaryocytes fragment into

thrombocytes (platelets)

myeloblasts mature into

basophils, neutrophils, eosinophils, monocytes

granular vs agranular leukocytes

-granular (neutrophils, eosinophils, basophils): membrane-bound granules filled with chemicals released to destroy pathogens/signal other immune cells
-agranular (lymphocytes, monocytes): targeted immune response/becoming macrophages

monocytes mature into

macrophages

lymphoid stem cells mature into

lymphocytes

distribution in volume of blood

plasma 55%, buffy coat 1%, erythrocytes 45%

abundance ranking of components of blood

erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils

plasma cellular characteristics

>90% water, >100 dissolved solutes (plasma proteins are the most abundant)

serum

plasma without clotting factors

erythrocyte: function, shape of cell, granules, cell contents

-gas (O2 and CO2) transport
-biconcave disc shape provides high surface-area-to-volume ratio that increases gas exchange efficiency
-the spectrin (protein) network allows them to flexibly squeeze through capillaries
-filled with hemoglobin (protein that binds reversibly to oxygen)
-doesn’t have organelles so that they don’t consume the O2 they transport - instead do anaerobic fermentation

erythropoietin (EPO) regulates

erythropoiesis (production of red blood cells)

mechanism for gas transport (erythryoctes)

The iron, which “grabs” the O2 reversibly, is located at the very center of a heme group to keep it stable. There are four heme groups per hemoglobin (one bound to each of the four globin polypeptide chains), 4 O2 molecules attach to each hemoglobin complex.

when/where O2 loading and unloading happens

-O2 loading: in lungs when concentration is high to produce oxyhemoglobin (ruby red)
-O2 unloading: in tissues to produce deoxyhemoglobin (dark red)

leukocytes: function, shape of cell, granules, cell contents

-immune defense
-performs diapedesis
-divided into granulocytes and agranulocytes
-complete cells

diapedesis

slips out of blood vessels and enters tissues to reach the site of an infection

platelets: function, shape of cell, granules, cell contents

-function: hemostasis (stopping blood loss by clotting)
-shape of cell: when inactive, circulate freely. when activated by damaged vessel swell and form “spikes” that help them stick to each other and the vessel wall through the von Willebrand factor
-granules that contain the chemicals needed for repair but there is NO nucleus
-are fragments of megakaryocytes

hemopoiesis (aka hematopoiesis)

the broad umbrella term for production of all formed elements in the blood - occurs in red bone marrow originated from HSC

leukopoiesis

process of producing white blood cells (leukocytes)

erythropoiesis

the process of producing erythrocytes

thrombopoiesis

the process of producing thrombocytes (platelets) by fragmenting megakaryocytes

hemostasis

blood clotting

hemolysis

the rupture/destruction of red blood cells

whole blood vs plasma vs serum

-whole blood contains plasma and formed elements - used to measure parameters like hematocrit
-plasma is the non-living fluid matrix containing the plasma proteins and clotting factors
-serum is plasma without the clotting factors (fibrinogen)

the three main phases of hemostasis

1) vasoconstriction by vascular spasm: constriction of vessels by contracting surrounding smooth muscle
2) platelet plug formation: activated platelets act as temporary plugs that stick to collagen fibers, swell/become spiked and sticky, and release chemical messengers
3) coagulation - contact activation (intrinsic) pathway and tissue factor (extrinsic) pathway

difference between intrinsic and extrinsic coagulation pathway

-intrinsic (contact activation): caused by internal trauma and triggered by negatively charged surfaces (aka contact with collagen and activated platelets)
-extrinsic (tissue factor): clotting factors activated by tissue factor from damaged neighboring tissue, faster

common pathway in hemostasis

-activated by intrinsic and extrinsic pathways once prothrombin activator is formed: where they converge
-reinforces platelet plug with fibrin meshwork
-blood transformed from liquid to gel
-mechanism: prothrombinase (formed from intrinsic and extrinsic pathways) activates prothrombin and converts it enzyme thrombin. Thrombin converts the soluble fibrinogen in the plasma to insoluble fibrin, which means it begins to precipitate out as solid, thread-like strands that then cross-links to form a fibrin mesh that traps RBCs and platelets flowing by.

negative feedback loops in hemostasis: fibrinolysis

fibrinolysis: the final “brake” that removes unneeded clots after healing

mechanism: activators that are released by health endothelial cells surrounding the clot once the vessel begins to heal converts the inactive plasminogen in the fibrin mesh into active enzyme plasmin. Plasmin breaks down the fibrin mesh and inactivates clotting factors to prevent new clotting; this returns the blood vessel to its original, unobstructed state.

positive feedback loops in hemostasis

during platelet plug formation, activated platelets further activate platelets until the platelet plug is complete

the steps of the hormonal regulation involved in the maintenance of blood functions through erythropoietin (6)

1) stimulus: hypoxia (inadequate O2 delivery)
2) kidney (and liver a bit) releases erythropoietin
3) erythropoietin stimulates red bone marrow
4) enhanced erythropoiesis increases RBC count
5) O2-carrying ability of blood rises
6) kidneys detect the correction and inhibit further EPO release

the hormone erythropoietin is released when .. in order to …

the kidneys sense low O2 in renal tissue in order to increase circulating reticulocyte (premature RBC that finishes maturation in the blood)

testosterone affects erythropoietin production by

enhancing it - higher RBC counts in males

hypoxia can be caused by (3)

1) reduced numbers of RBCs
2) reduced availability of oxygen
3) increased tissue demands for oxygen

relationship between hematocrit and viscosity in blood

as hematocrit (% of RBCs) increases, viscosity increases because the cells bump into each other more frequently and creates more resistance to flow

consequences of high viscosity (polycythemia)

Thick blood flows more slowly, heart has to contract with much more force to push the blood through the circuit, and more likely to have spontaneous clotting

consequences of low viscosity (anemia)

blood becomes thinner and flows more easily, carried much less oxygen so there can be tissue hypoxia, fatigue, and shortness of breath

anemia: description and broad causes

blood has abnormally low O2-carrying capacity because of blood loss, low RBC production, high RBC destruction, or hemoglobin abnormalities

low-RBC production anemias

-iron-deficiency anemia (iron is limiting factor)
-renal anemia (lack of EPO production)
-pernicious anemia (no intrinsic factor so RBCs grow but cannot divide)
-aplastic anemia (destruction/inhibition of red bone marrow)

high-RBC destruction anemias

-sickle-call anemia: hemoglobin becomes spiky and RBCs become crescent-shaped so can block small blood vessels/rupture
-thalassemias: genetic disorder where one of the globin chains is faulty so RBCs are thin/delicate so lyse more easily
-hemolytic anemias: premature RBC lysis

leukocyte disorders

-leukemia: group of cancers involving overproduction of abnormal, non-functional WBCs

polycythemia vera vs secondary polycythemia

Polycythemia vera is permanent due to bone marrow cancer and leads to severely increased blood viscosity. Secondary polycythemia is temporary because of less O2/increased EPO production and is blood doping.

thrombus vs embolus

-thrombus: blood clot
-embolus: unattached mass that travels in the bloodstream

retrograde vs anterograde thromboembolism

thromboembolism: a blood clot that has broken free and is now traveling through bloodstream as embolus
-retrograde: embolus moving against natural flow
-anterograde: embolus moving with the natural flow

thrombocytopenia

deficient number of circulating platelets

bleeding disorders

inability to synthesize procoagulants due to impaired liver function
-hemophilia

disseminated intravascular coagulation (DIC)

widespread clotting in intact vessels and severe bleeding because of reduced availability of clotting factors/platelets

hemoglobin bound to CO2

carbaminohemoglobin - formed in tissues during CO2 loading where CO2 levels are high - binds to the amino acids of the globin

production of RBC: name, site, vitamins needed, hormonal control

name: erythropoiesis
site: red bone marrow
vitamins needed: vitamin B12 and folic acid, iron, amino acids
hormonal control: triggered by EPO from the kidneys

as RBCs age…

they lose their flexibility and become trapped in tiny circulatory channels of the spleen

organs of destruction for RBCs

spleen, liver, bone marrow

what happens to the components of the RBC once destroyed

-globin: broken down into amino acids and released back into the blood
-iron: salvaged for reuse in liver and spleen
-heme: degraded to yellow pigment (bilirubin) and picked up by liver, then secreted into the intestines as part of bile

relationship of RBCs to bile, feces, and urine

-bile: heme is degraded into yellow pigment bilirubin, which is secreted by the liver and serves in bile production
-feces/urine: bilirubin is degraded into pigment, which leaves the body by giving feces/urine its colors

when checking for blood transfusion compatibility, look at

Donor's Antigens and the Recipient's Antibodies

what determines blood group

the type of antigen on the surface of RBC

blood type A: antigen on RBC, antibody in plasma, can receive from…

antigen A, anti-B (IgM), can receive from A/O

blood type B: antigen on RBC, antibody in plasma, can receive from…

antigen B, anti-A, can receive from B/O

blood type AB: antigen on RBC, antibody in plasma, can receive from…

antigens A and B, no antibodies, A/B/AB/O (universal recipient)

blood type O: antigen on RBC, antibody in plasma, can receive from…

no antigens, anti-A & anti-B antibodies, can receive from O

describe the Rh blood group

based on the D antigen and are not born with these antibodies

-Rh positive: have the D antigen, will never make anti-D
-Rh negative: lack the D antigen, will only make Anti-D (IgG) if exposed to Rh+ blood via transfusion or pregnancy

why do incompatibilities between blood types occur?

a recipient’s antibodies (the “soldiers”) find their matching antigen “tag” on a donor’s blood cells and immediately recognize them as foreign invaders. Because antibodies have multiple binding sites, they grab several red blood cells at once and aggregate them into clumps that plug up small blood vessels. The immune system activates “complement” proteins (MAC - membrane attack complex) that punch holes in the donor’s RBC membranes and causes them to lyse and release so much hemoglobin into the bloodstream

results of incompatible transfusion reactions

-diminished oxygen-carrying capacity: the foreign RBCs are being hemolyzed so the total # of functional RBC in circulation drops sharply
-diminished blood flow beyond blocked vessels: tissues “downstream” from blockage are cut off from blood flow
-hemoglobin in kidney tubules (renal injury): the hemoglobin from the burst RBCs are dumped into the plasma; the kidneys are designed to filter waste from the plasma but the hemoglobin precipitates inside the renal tubules and plugs the kidneys

difference in antibody type between ABO and Rh systems

-ABO: IgM antibody: large pentamer that can’t pass through placenta that is naturally occurring
-Rh: IgG antibody: small monomer that can pass through placenta that requires exposure

difference in impact on pregnancy ABO vs Rh

-ABO: matters less because mother’s anti-A and anti-B antibodies are IgM so can’t pass through placental barrier and baby remains safe
-Rh: the baby is fine for the first pregnancy of Rh- mother carrying Rh+ fetus, but the blood mixes during birth and so the mother creates anti-D IgG antibodies. if the same mother carries another Rh+ fetus, her immune system is actively producing anti-D IgG, which crosses the placenta and enters the fetal bloodstream and marks the baby’s RBCs for destruction

functions of the lymphatic system

-drains excess interstitial fluid to return to blood (maintains circulating blood volume)
-transports dietary lipids
-carries out immune responses (contains most lymphocytes)

how is lymph formed

lymph = fluid in vessels

1) 20 liters of plasma “leaks” out in spaces between cells daily - ISF. 17 liters are sucked back into the veins but the remaining 3 cannot be.
2) Hydrostatic pressure pushes the fluid in the tissues into the empty lymph capillary and oncotic pressure pulls the fluid into the lymph capillary.

how is lymph returned to the bloodstream

After ISF enters the lymphatic capillaries, it “becomes” lymph that travels through the lymphatic vessels, which converge into larger lymphatic trunks that then empty into two main ducts (right and thoracic). Both ducts join the systemic blood circulation.

purpose of lymph nodes

cleanse lymph because of the connective tissue mesh (reticular fibers) that acts as a spider web to catch foreign materials - macrophages engulf these.

what circumstances can increase the volume of lymph

when there is an increase in ISF left behind in the tissues (increased capillary hydrostatic pressure that increases the “pushing” pressure inside the blood capillaries and forces out more fluid into the tissue OR decreased plasma oncotic pressure that decreases blood’s “pulling power”)

characteristics of lymphatic capillaries

-blind-ended: closed at one end like a pocket
-endothelial flaps (minivalves) that prevent backflow: high ISF pressure pushes these flaps inward like a swinging door so that everything can rush into the capillary, but once the pressure inside the capillary increases the flap is pushed outward to “seal” the door

characteristics of lymphatic vessels

-unidirectional valves: “flap-like” structures located at frequent intervals along the vessel that ensure the lymph only flows in one direction by snapping shut once the lymph is pushed forward
-smooth muscle cells: perform rhythmic contractions to help push lymph along the vessel

exudation

the rush of self and foreign material into lymphatic vessels

name the two primary lymphatic organs and describe their major roles

-red bone marrow: where all lymphocytes are initially produced and B lymphocytes mature
-thymus: where T lymphocytes mature

name the three secondary lymphatic organs and describe their major roles

-spleen: filters blood and contains lymphoid tissue that monitors blood for pathogens
-tonsils: first line of immune defense and “immune memory”
-lymph nodes and vessels: cleanse lymph, house lymphocytes, and provide site for dendritic cells to present antigens

innate vs adaptive immune system

-innate (nonspecific): fast, just attacks
-adaptive (acquired, specific): requires “priming” period, “third line of defense”

neutrophils: major role, characteristics, adaptive/innate, granulocyte/agranulocyte

-highly phagocytic “first responders” that die in process of fighting infection
-innate
-granulocyte

eosinophil: major role, characteristics, adaptive/innate, granulocyte/agranulocyte

-counterattack against parasitic worms, allergies, asthma
-innate
-granulocyte

basophil: major role, characteristics, adaptive/innate, granulocyte/agranulocyte

-alarm system by promoting inflammation
-granules contain histamine (vasodilator that increases blood flow and attracts other white blood cells to inflamed sites)
-innate
-granulocyte

lymphocyte: major role, characteristics, adaptive/innate, granulocyte/agranulocyte

-cornerstone of the adaptive immune system
-types: T lymphocytes & B lymphocytes
-adaptive but natural killer cells are a type of large granular lymphocyte that belongs to the innate system and attack cells lacking MHC receptors
-agranulocyte

monocytes: major role, characteristics, adaptive/innate, granulocyte/agranulocyte

-part of the innate system
-differentiates into macrophages
-robust, long-lived phagocytic cells that also act as antigen-presenting cells to activate the adaptive immune system
-agranulocyte

define antigen vs. antibody

-antigen: “ID tag/target”: any substance that can mobilize the adaptive defenses and provoke an immune response

-antibody: “missile”: protein secreted by plasmocytes that circulate in the blood/lymph and bind to antigens to tag them for destruction by macrophages

antibody specificity

an antibody is specific to only one type of antigen
-there is cross-reactivity, which is when two different antigens happen to have very similar shapes so one antibody could bind to two different things

positive selection in B and T lymphocytes

the step during lymphocyte maturation when only lymphocytes that bind to (recognize) the self MHC tag (aka HLA tag) are selected

negative selection in B and T lymphocytes

the step during lymphocyte maturation when lymphocytes that are responsive to “self” antigens are deleted because they would cause your body to attack itself

lymphocyte maturation area for B vs T cells

-B cells - red bone marrow
-T cells - thymus

role and goal of antigen-presenting cells

-to bridge the gap between innate and adaptive immunity by engulfing a foreign pathogen, breaking it into tiny fragments (antigens), and then migrating to a lymph node
-to find a T cell that has a receptor matching that specific antigens

major types of antigen-presenting cells

dendritic cells, macrophages, B cells

class I MHC proteins: location, role, message

-all nucleated body cells (so not red blood cells)
-display fragments of proteins found inside the cell (“self-antigens” if cell is healthy, “alien” antigens if infected)
-”i’m infected! kill me!”

class II MHC proteins: location, role, message

-only on APCs (dendritic cells, macrophages, B cells)
-display fragments of pathogens that the APC has eaten from the outside in order to activate helper T cells
-”i found this invader! let’s start a war!”

how does the major histocompatibility complex (MHC) activate the immune response

two “handshakes”
1) T cell receptor binds to the MHC-antigen complex on the APC (CD4+ T cells to MHCII and CD8+ to MHCI) to recognize the presenting cell as a “self” cell
2) APC and T cell exchange chemical signals (cytokines) to confirm the threat is real

CD4 vs CD8 naive T cells

-CD4+ cells: “managers”: restricted to binding with MHCII on APCs: release cytokines that tell B cells to start mass-producing antibodies, macrophages to become “hungry”, and CD8+ cells that it’s time to start killing
-CD8+ cells: “assassins”: restricted to binding with MHCI: the only T cells that can directly kill other human cells by punching holes in target cell’s membrane (through perforins) and triggering apoptosis

B cells mature into ___ to stimulate the ___ response

plasmocytes to stimulate the humoral response

humoral immunity

antibody-mediated with extracellular targets, mostly B cells

-targets pathogens that are “out in the open” (in blood, lymph, ISF) by producing plasmocytes that pump out thousands of antibodies
-these bind temporarily to target cells’ antigen to temporarily inactivate the target cell (neutralization, agglutination)
-the target cells are marked for destruction (opsonization)

cellular immunity

cell-mediated that targets pathogens that have entered your body’s own cells, mostly T cells

-direct attack: cytotoxic T cells physically bind to the infected cell and blow it up
-indirect: helper T cells release chemicals that manage the overall immune response

cells involved in innate vs adaptive immunity

-innate: phagocytes (neutrophils and macrophages), natural killer cells, granulocytes
-adaptive: B lymphocytes, T lymphocytes, antigen-presenting cells

complement system

cascading groups of proteins that form membrane attack complexes

first line of defense for innate immune system

prevents entry: skin, mucous membranes, tears, saliva