BIO 313 exam 1

functions of blood

• transport: o2/co2, hemoglobin, metabolic waste, hormones

• protection: restrict fluid loss (clotting), defense against disease

• regulation: pH and ion composition, stabilizing body temperature

components of blood

• matrix- plasma (55%)

• formed elements (45%): RBC, WBC, platelets

plasma

MOSTLY WATER

• concentration similar to ISF (K+ inside, Na+ coutside)

• plasma proteins: albumin (most abundant) major contributer to osmotic pressure

• globulins: transport ions, hormones, lipids, immune function

• fibrinogen: essential for clotting

• regulatory proteins: enzymes, proenzymes, hormones

• clotting factor (other solutes): electrolytes, organic nutrients, organic wastes

structure of RBC

erythrocytes

most abundant formed element

contain hemoglobin

measured in hematocrit (% of RBC in whole blood)

• biconcave disc

  • large surface area to volume

  • forms stacks for easy movement

  • flexibility

• no nucleus, no mito, no DNA

• 120 day lifespan

RBC

• hemoglobin is over 95% of intracellular protein in RBC

• hemoglobin combines with and transports o2 or co2

• relaxed form favors o2 binding, which makes it taut, the taut shape favors co2 binding

→ blood can transport o2 without hemoglobin but it’s 3mL versus 200mL

erythropoiesis (RBC formation)

• red bone marrow

1. hematopoietic stem cells (hemocytoblasts)

2. myeliod cells (also produce lymphoid cells)

3. phase 1:ribosome synthesis

4. phase 2: hemoglobin accumulation

5. phase 3: ejection of nucleus (becomes reticulocyte)

-17 days

regulation of erythropoiesis

1. hypoxia (low o2 or inadequate delivery)

• low o2 availability

• low rbc count

• low amt of hemoglobin

2. kidnet produces EPO (erythropoietin)- helps make rbc

3. red marrow stimulation in bone for rbc production

4. increased rbc count from erythropoiesis: amino acids, iron, b12, folic acid

5. restored o2 carrying in blood

RBC degredation

in liver and spleen, monitored by macrophages and uses hemolysis to break

• chains broken down and heme released

• heme degraded to biliruben

• iron escorted by transferrin to bone marrow

artificial EPO

blood doping

• increase rate of production of rbc without reduced o2 delivery

• EPO increases hematocrit to increase stamina and performance

• dangers: can increase hematocrit from 45-65%, and mixed with dehydration is very high blood conc

• blood is thick and can clot, stroke, heart failure

• reinfusion of packed cell volumes can have same consequences

anemia

• iron is hard to replace

• o2 capacity is too low to support metabolism or high/moderate activity

• storage and recycling of iron are highly developed because dietary iron can be a limiting factor of RBC formation

• causes: blood loss (hemorrhage), not enough rbc produced, too many rbc destroyed (sickle cell anemia)

if there’s an increase in bilirubin in the liver that usually means rbc breakdown which is bad

disorders of RBC numbers

normal levels: male-42-52%, females 37-47

anema- low hematocrit

polycynthemia- high hematocrit

dehydration- high hematocrit, low plasma

types of anemia

1. nutritional anemia- Fe, B vitamins, folic acid, dietary deficiency

2. pernicious anemia- “intrinsic factor“ not produced by stomach, B12 not absorbed

3. renal anemia- insufficient amounts of EPO from kidneys

4. aplastic anemia-hematopoietic stem cell failure, often bc of destruction by toxic chemicals, radiation, or cancer

5. hemorrhagic anemia- acute or chronic

6. hemolytic anemia-rupture of excessive rbs’s, multiple causes

7. sickle cell anemia-mutation in hb molecule

sickle cell anemia

• high frequency found in tropical africa, most common in places with malaria

• point mutation in hemoglobin that leads to malformed rbc

• genetic disorder

• changes shape of rbc that can clog vessels, interfere with o2 delivery, cause pain

platelet formation

thrombopoiesis using thrombopoietin hormone from kidney/liver

• stem cell that devleops into megakaryocye, ends break off and become platelets

hemostasis

• prevent the loss of blood

• supplies framework for tissue repair

• 3 phases: vascular, platelet, coagulation

• platelets do not stick in undamaged tissue

3 phases of hemostasis

1. vascular spasm: smooth muscle contracts, causing vasoconstriction to decrease initial blood loss

• release hormones and factors to stimulate contraction/cell division

• endothelial cells become sticky
  2. platelet plug formation (platelet phase): attachment of platelets to sticky endothelium, platelet aggregation, platelet plug formed using positive feedback

• attachment of platelets: collagen exposed, bridge between collagen and platelets, activated platelets release ADP, thromoxane A2, seratonin, PDGF, calcium
  3. coagulation phase: goal is convert fibrinogen to fibrin using intrinsic and extrinsic pathwyas, involves Ca2+ and 11 different proteins produced in liver, one activated the next causing cascade

coagulation phase

phase 1: two pathways to prothrombin activator, intrinsic and extrinsic pathways

• intrinsic is damage inside the BV

• extrinsic is damage outside the BV

Clotting factors- proteins produced by liver, Vitamin K, Ca2+: When activated become the enzyme for the next step

Factor 7 from extrinsic goes to intrinsic to help activate IX and surface aggregated platelets

phase 2: common pathway to thrombin

• need calcium, vitamin K, V(5)

• factor X aids in formation of Prothrombinase, requires Ca2+ and PF3

• prothrombinase is an enzyme, converts prothrombin into thrombin

phase 3: common pathway to fibrin mesh

• thrombin converts fibrogen into fibrin to create cross linked fiber mesh

POSITIVE FEEDBACK

→ thrombin accelerates production of prothrombinase which converts more prothrombin to thrombin

clot retraction

• pulls the torn edges together

• reduction of size of damaged area

fibrinolysis

• clot dissolves using enzyme plasmin

• -removes unneeded clots after healing
  -kallikrein (enzyme) -> makes plasminogen activator which converts plasminogen -> plasmin and then plasmin digests fibrin

relative proportions of leukocyes in blood

Neutrophil (45-70%)

Lymphocytes (25-45%)

Monocytes (3-8%)

Eosinophils (2-4%)

Basophils(0-1%)

neutrophils

• phagocytic

• kills microbes through respiratory bursts

  • cell synthesizes potent oxidizing substances (bleach or hydrogen peroxide)

• defensin granules merge with phagosome

  • form spears that pierce holes in membrane of ingested microbe

eosinophils

• red stained granules containing digestive enzymes

• release enzymes on large parasitic worms, digesting their surface and killing them

• play a role in allergies and asthma, and as immune response modulators

basophils

• large granules containing histamine (allergic responses)

• secrete histamine and heparin

  • histamine: inflammatory chemical acting as vasodilator and attracts WBC to inflamed sites

  • heparin: anticoagulant, doesn’t allow thrombin to function leading to no fibrin, no clotting

• functionally similar to mast cells

lymphocytes

• mostly found in lymphoid tissue (lymph nodes, spleen) but a few circulate in blood

• crucial for immunity

• type types T and B cells

  • T cells: act against virus infected cells and tumor cells

  • B cells: give rise to plasma cells producing antibodies

monocytes

• leave circulation, enter tissues, and differentiate into macrophages (phagocytosis)

• actively phagocytic cells, crucial against viruses, intracellular bacterial parasites, and chronic infections

• activate lymphocytes to mount an immune response

leukopoiesis: WBC production

stimulated by two chemical messengers: interleukins and colony stimulating factors (CSF)

• EPOs or CSFs can be used to increase production rates of RBC/WBC in patients with cancer or depressed immune systems(aids)

granulocyte production

form neutrophils, basophils, eosinophils

1. myeloblasts: arise from myeloid stem cells

2. promyelocytes: accumulate lysosomes

3. myelocytes: accumulate granules

4. band cells: nuclei form curved arc

5. mature granulocyte: nuclei become segmented before being released into blood

lymphocyte production

form lymphocytes and monocytes

1. T lymphocyte precursors give rise to immature T lymphocytes that mature in thymus

2. B lymphocyte precursors give rise to immature B lymphocytes that mature with bone marrow

3. lymphocytes live from a few hours to decades

leukocyte disorders

overproduction of normal WBC: leukemias

• myeloid versus lymphatic

• acute versus chronic

• infectious mononucleosis

abnormally low WBC count: leukopenia

• can be drug induced, particularly by anticancer drugs or glucocorticoids

• poisoning by lead, arsenic, mercury

antigens

complex molecules on surface of cell membrane that activate an immune response

• genetically unique to individuals

• used to distinguish self from foreign matter

• foreign antigens generate an immune response

agglutinogens: antigens on surface of the RBC that are basis for blood typins, promote agglutination (clumping)

complete:

• immunogenicity: evokes a lymphocyte response

• reactivity: ability to react with cells and antibodies

incomplete:

• not immunogenic unless with body protein

• allergens

blood typing

type A: A antigen, Anti B antibodies (can receive A, O blood)

type B: B antigen, anti A antibodies (can receive B, O blood)

type AB: A and B antigens, no antibodies (can receive AB, A, B, O)

type O: no antigens, anti A and B antibodies (can receive O)

• type O is universal donor

• type AB is universal recipient

Rh blood groups

• 52 names Rh agglutinogens=Rh factors

• can be Rh+ or Rh-

• antibodies do not form spontaneously, only if exposed (transfusion or pregnancy)

• treatment with RhoGAM, serum containing anti Rh antibodies, prevents immune response of mother by agglutinating the Rh factor

if mother Rh- and baby Rh+, mother with make antibody in response to Rh+ antigen, if she has another pregnancy those antigens will pass to the baby and destroy RBC which causes hemolytic disease

innate immune response

-innate = everyone is born with it
-1st line: surface barriers (to external environment)
-skin and mucous membranes
-2nd line: internal defenses
-phagocytes
-natural killer cells
-inflammation
-antimicrobial proteins
-fever

first line of defense

skin:

• physical barrier

• keratin resists bacterial enzymes/infections

• secretions of PH, chemicals, lysozymes, antibodies

mucosae

• lines body cavities: epithelial tissue

• secretes hcl in stomach

• saliva and lacrimal fluid secrete lysozymes

• mucus traps bacteria

if it cant get in it cant cause disease, if it gets stuck or destroyed it cant cause disease

second line of defense

1. phagocytosis (neutrophils (microphage), monocytes(macrophage), eosinophils (microphage))

free macrophage search out invaders, fixed stay in organs

• phagocytosis uses endocytosis to make capsule with pathogens to release enzymes to destroy them and then uses exocytosis

2. natural killer cells
-virally infected, cancerous, bacterial

-non specific killing, not specific to an antigen
-induce apoptosis in target cells through poking holes, and secrete chemicals to induce inflammation
3. inflammation
-WBCs recruited and come to scene to help
-4 signs: heat, red, swelling, pain

slows spread of pathogens, mobilizes defenses, stage for repair
4. antimicrobial proteins
-interferons: go to nearby cells to promote antiviral protein production
-producing signals that affects neighbor "cell to cell", calling in other cells to tell them to destroy cell
-complement proteins: found normally circulating in plasma and can be activated when needed; forms a (MAC- membrane attack complex) in target cell causing lysis
5. fever
-immune response to combat something
-elevated set point
-pyrogens (released by leukocytes) are sensed by hypothalamus, cause elevated body temp, when infection ends defervescence returns body temp to normal

inflammation

• heat, redness, pain, swelling

injury

• release of histamine: increases vessel permeability, fluid and clotting factors leave bloodstream (swelling)

• accelerated blood flow: redness, elevates tissue temp (phagocytic activity and denaturing of proteins)

• increased pressure and temp causes pain

• activation of neutrophils

adaptive immunity

• response directed against specific antigen

• global response to pathogen

• remembers antigens it has come in contact with

has humoral (antibody mediated) immunity and cell mediated immunity

Cellular immunity (adaptive)

-T cells
-mature in thymus
-must develop immunocompetence and self-tolerance (should recognize self MHC, should not recognize self antigen)
-three types:
1. killer (cytotoxic): destroy virus infected cells, foreign cells from transfusions/implants
2. helper: boosts immune response by activating killer T cells and stimulating antibody production (B cells making plasma)
3. regulatory: maintain tolerance to self antigens; prevent autoimmune disease
-memory T cells: remembers antigen so that it can respond quickly to same antigen in future encounters

Humoral immunity (adaptive)

-B cells, indirect method of defense, mature in bone marrow
-market for destruction
-effector B cells are plasma cells that produce antibodies

• recognition is the first encounter, naive b cells are circulating. activation of b cells are when antigen binds to receptor and waits for signal from helper t cells to trigger clonal selection

• colonal selection b cell grows and divides, makes clones of the same antigen receptor, some go to memory some go to plasma

• plasma cells make antibodies
  -memory B cells: primed to respond to same antigen
  -mature in the bone marrow
  -must develop immunocompetence and self-tolerance

primary and secondary immune responses

primary: first exposure, lag of 3-6 days where it grows and divides for cloning

secondary: memory b cells encounter antigen, fast response of a few hours because body knows it

4 stages of humoral immunity

active(antigens):

• naturally acquired: infection contact with pathogen (cold/flu)

• artificially acquired: vaccine or pathogens

passive(antibodies):

• naturally acquired: antibodies passed from mother to fetus or in breastmilk

• artificially acquired: injection of antibodies (plasma infusion)

antigens in defense

-substances that can mobilize adaptive defenses; the "targets" of responses
-foreign antigens are NOT normally present in the body; so immune system considers them "nonself" (intruders)
-cells are identified as "self" via unique MHC proteins which hold either a "self antigen" or a foreign antigen

cardiovascular system

• heart, blood vessels, and blood

• lymphatic system parallels venous system

• rapidly transports substances over long distances between tissues and organs

why do large multicellular organisms need capillaries

• small multicellular organisms diffuse oxygen easily between cells and environment

• large multicellular organisms would have too slow of diffusion, they need delivery of oxygen and nutrients within a few cell diameters of all cells in the body

  • use capillaries

blood flow

arteries carry oxygenated blood away from the heart, veins carry deoxygenated blood to the heart

• doesn’t necessarily mean veins are lower in oxygen than arteries, it just shows direction

capillaries are where veins and arteries connect, capillary beds are where gas and nutrient exchange happen

arrangement

• right ventricular output is lungs (pulmonary circulation)

• left ventricular output is all organs for systemic and cardiac circulation (has more pressure/muscle than right)

• uses parallel vasculature to transport blood so all of body can be recieving blood quickly at the same time

coronary circulation

blood supply to the heart for function

• arteries deliver blood when the heart is relaxed

• venous circulation empties into right atrium

homeostatic imbalance (decrease blood supply to heart):

• angina pectoris short (fleeting) deficiency in blood supply to heart

• myocardial infarction- heart attack where myocardial cells die

heart coverings

pericardium

• serous membrane with 2 layers

• visceral pericardium: epicardium on organ

• parietal pericardium: fibrous and serous covering chamber, it attaches to vessels and diaphragm but not the heart itself so that it can pump

pericardial fluid

pericardial sac:

• fibrous pericardium

• stabilizes the heart/ keeps it in place

• pericardial cavity is filled with pericardial fluid, if it is too filled the heart cant pump correctly= cardiac tamponade

• outer fibrous covering (fibrous pericardium), secretory lining (serous pericardium)

layers of the heart

epicardium: visceral pericardium

myocardium: heart muscle, connective tissue network

endocardium: endothelium

external heart

atria: receive and discharge

• receiving chambers, auricles, superior/inferior vena cava, pulmonary veins, coronary sinus

ventricles: sending out

• discharging chambers, pulmonary trunk, aorta, coronary arteries

pathway of blood

in superior/inferior vena cava, right atrium, right AV valve, right ventricle, pulmonary semiulunar valve, pulmonary trunk, pulmonary arteries (out), pulmonary veins (in), left atrium, left AV valve, left ventricle, aortic semilunar valve, aorta, brachiocephalic trunk/common carotid artery/subclavian artery

heart valves

-ensure one way blood flow to prevent backflow

-made of fibrous flaps

-AV valves: attach to papillary muscle by chorda tendinea, preventing prolapse of valve or backflow of blood during contraction

-semilunar valves

function of AV valves

pressure in atria:

-blood returning fills atria, pressure forces AV valves open, as ventricles fill AV valves hang limp, atria contracts forcing additional blood into ventricles

pressure in ventricle:

-ventricles contract forcing blood against AV valve cusps, AV valves close, papillary muscles contract and chorda tendinea tighten preventing eversion of flaps

chorda tendinea prevent the eversion of AV valves and backflow of blood during ventricular contraction

function of semilunar valves

-ventricles contract and interventricular pressure rises, blood pushed against semilunar valves forcing them open

-ventricles relax and interventricular pressure falls, blood flows back from arteries filling the cusps of semilunar valves forcing them to close

incompetent valves

• valve defects

• heart murmurs (systolic versus diastolic): valves fail to fully open or close

• stenosis/insufficiency: stenosis fails to fully open, insufficiency fails to fully close

• patent ductus arteriosus: temporary blood vessel between aorta and pulmonary artery fails to close after birth, allows o2 blood to mix with deo2 blood in pulmonary artery

cardiac muscle fibers

atrial and ventricular muscle

• contractive, striated (short, 1 to 2 nuclei per cell), typical myofibrils, intercalated discs, functional syncytium (contract in uniform) atrial and ventricle (push blood out of atrium/ventricles)

excitatory/conductive muscles

• non contractive initiates contractive actions

intercalated discs

interdigitating folds: interlock adjacent cells

mechanical junctions: spot welds, hold adjacent cells together during contraction, desmosomes holding together myocytes

electrical (gap) junctions: allows ion flow between adjacent cells, they connect myocytes

T tubules and SR

• many mitochondria

• SR not as extensive as skeletal muscle, still stores releases and reuptake Ca+

• transsverse tubules: larger in diameter than skeletal muscle, larger volume of ISF, allow ca+ to leak into membrane

cross bridge cycling

1. ca+ binds to troponin, tropomyosin uncovers the binding sites

2. myosin cross bridge attaches to actin myofilament,

3. power/working stroke: ADP and Pi released, myosin head pivots and bends pulling actin filament towards M line

4. new ATP attaches to myosin head, cross bridge detaches

5. ATP is split into ADP and Pi, recocking myosin head

roles of Ca in regulating crossbridge in cardiac muscle

• low calcium=relaxed muscle, cross bridge cannot bind to actin

• calcium is the switch that turns on crossbridge

• high calcium=activated muscle, cross bridge can attach and generate force

differences in cardiac muscle contraction to skeletal muscle

• pacemaker cells

• heart contracts as a unit: gap junctions

• Ca2+ from ECF triggers release of more Ca2+ from SR vs only SR in sk.m.

• no tetanus/summation

• aerobic respiration only

action potential skeletal muscle

1. signals arriving at axon hillock until threshold reached, Na+ slowly coming in

2. depolarization: Na+ gated channels fully open, K+ open very slow, pos feedback

3. action potential reached: polarity is reversed, Na+channels close, K+ channels open

4. repolarization: K+ channels fully open, K+ efflux

5. hyperpolarization: K+ channels stay open too long, overshoots threshold, Na/K pump balances it

action potential cardiac muscle

1. depolarization: fast, voltage gated Na+ channels open

2. prolonged depolarization: open slow voltage gated Ca channels (in), K+ channels are closed

3. repolarization: K+ gated channels fully open, K+ out/efflux. both Ca and Na channels closed

prolonged depolarization- we don’t want summation or fatigue, heart needs to keep pumping, and needs to relax to fill with blood