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Blood:
- Plasma and Cellular Elements of Blood
- Hematopoiesis
- RBC Physiology
- Coagulation
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Plasma:
- 92% water
- 7% proteins
- 1% organic mol (AA, glucose, lipids, N wastes), ions (Na+, K+, Cl-, H+, Ca2+), trace elements, vitamins, O2, and CO2
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Plasma Proteins:
albumins *60% (prescence of proteins makes osmotic pressure higher; carriers)
- globulins (clotting, enzymes, antibodies, carriers)
- fibrinogen (essential to clotting) *30%
- transferrin (transports iron)
immunoglobulins (antibodies; secreted by specialized blood cells rather than by liver)
- Functions:
- clotting
- defense against foreign invaders
- carriers for steroid hormones, cholesterol, drugs, and iron
- act as hormones or enzymes
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Cellular Elements:
- RBCs (erythrocyes)
- WBCs (leukocytes)
- platelets (thrombocytes)
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RBCs:
- have lost their nucleus by the time they enter the blood stream
- play key role in transporting O2 from lungs -> tissues
- CO2 from tissues -> lungs
shape creates greater surface area for fast diffusion
25% of blood cells being produced by marrow, have a longer life span
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WBCs:
- only fully functional cells in circulation
- play key role in body's immune response
- defend against foregin invaders
- work is usually carried out in tissues rather than in circulatory system
- Five types of WBCs:
- lymphocytes *immunocytes
monocytes (in tissues: macrophages) *phagocytes
- neutrophils
- eosinophils *granulocytes
- basophils (mast cells)
Diapedesis: WBC leaves
Are replaced more frequently because they have a shorter life span, 75% of blood cells being produced by marrow
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Platelets:
- lack a nucelus
- split off parent cell, megakaryocyte
- short lived, 10 days
- many nuclei
- contain granules filled with clotting proteins and cytokines
- activated when blood vessel wall damaged
- play a role in coagulation
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Hematopoiesis:
- the synthesis of blood cells
- embryo forms clusters -> blood cells -> liver, spleen, and bone marrow produce -> liver and spleen dont produce after birth -> production continues in the marrow until age 5 -> continues to decrease as we age
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Cytokines:
- control hematopoiesis
- peptide proteins released from one cell that affect the growth or activity of another cell
- erythropoietin - controls RBC synthesis, hormone; but made on demand rather than stored in vesicles; produced in kidney cells
- CSF - made by endothelial and WBCs
- IL -vreleased by one WBC to act on another, role in immune system; mobilizes hematopoietic stem cells
- thrombopoietin - produced by liver, influences growth of megakaryocytes
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Erythropoiesis:
- RBC production controlled by erythropoietin (EPO) and several cytokine
- hypoxia: low O2 levels in the tissues (HIF-1) stimulates EPO synthesis and release
- put more hemoglobin into circulation to carry O2
- EPO gene cloned in 1985 -> now available
- used in therapy, abuse in sport
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Hemoglobin:
- 4 subunits
- HbA- Adult
- HbF - Fetal; increased affinity to O2; pulls O2 from HbA (mother)
- Requires iron Fe from diet -> absorbed to small intestine by active transport -> transported in blood by transferrin -> RBC use Fe to make heme group of hemoglobin -> excess iron stored (liver) as ferritin -> bone marrow uses to make Hb -> liver metabolizes biliruben; execretes in bile -> metabolites execreted in urine or feces
- Vit B12; intrinsic factor to absorb
- HbS - sickle cell
- elevated biliruben levels in blood = jaundice, causes skin and white of the eyes to take on a yellow cast. normally occurs in newborns whos fetal Hb is being broken down and replaced with adult Hb; also liver disease causes jaundice, liver is unable to process or excrete biliruben
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RBC Disorders:
- Polycythemia vera- people in high altitudes, too many RBC, viscocity makes heart work harder, may be due to BM cancers
- Anemias-
- hemorrhagic: Fe deficiency; common in women
- hemolytic: due to genetic diseases or infections, autoimmune or drug induced, malaria
- pernicious: B12 deficiency or instrinsic factor lacking (stomach)
- renal: kidneys dont produce (EPO)
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Sickle Cell Anemia:
- abnormal hemoglobin
- crystallizes when it gives up its oxygen
- sickle cells become tangled with other sickle cells causing cells to jam and block blood flow in tissues
- creates tissue damage and pain from hypoxia
- NO being tested as treatment
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Hemostasis:
- stopage of bleeding
- too little: hemophiliac -> bleed too much
- too much: thrombus/ emboli -> blood clots
- Three major steps -
- vasconstriction - vessels constrict; paracrines released by endothelium -> decreases blood flow and pressure in vessel
- platelet plug - temporary blockage of hole; platelets stick to exposed collagen -> releases cytokines -> released more platelets that stick to each other
- coagulation - clot formation seals hole until tissue is repaired; series of enzymatic reactions end in formation of fibrin protein fiber mesh that stabalize platelet plug
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Instrinsic Pathway:
collagen exposure; all necessary factos present in blood; slower
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Extrinsic Pathway:
Uses TF released by injured cells and a shortcut
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Common Coagulation Pathway:
Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> clot
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Structure of Blood Clot:
- as it forms it incorporates plasmin, the seeds of its own destruction
- Plasmin: enzyme from plasminogen, activated by thrombin, breaks down fibrin polymers into fibrin fragments (fibrinolysis) -> removes clot
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Clot Busters:
- dissolve inappropriate clots
- enhance fibrinolysis
- t-PA: tissue plasminogen activator; dissolves clot faster
- *Vit K necessary for liver to make clotting proteins
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Anticoagulants:
- "blood thinner" prevent blood from clotting
- by blocking one or more steps in fibrin forming cascade
- ihhibit platelet adhesion -> plug prevention
- Ex. asprin -> inhibits plug, heparin -> inhibits thrombin, Protein C -> inhibits clotting factors V and VIII
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Hemophilia:
- coagulation disorder
- coagulation cascade lacking or defective
- Hemophilia A, factor VIII deficiency, most common
- sex linked, ususally affects only males
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Hematocrit:
- ratio of RBCs to plasma
- column of packed red cells is measured
- normal range of hematocrit 40-54% male 37-47% female
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Mechanics of Breathing:
- structure and function of respiratory pumps
- gas exchange with blood
- role of surfactant and pressure differences on rate of exchange
- regulation of respiration
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Functions of Respiratory System:
- O2 exchange: air -> blood, blood -> cells
- CO2 exchange: cells -> blood, blood -> air
- Regulation of body pH: retaining/ excreting CO2
- Protection of alveoli -> blood
- Vocalization
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On its way to the lungs, air passes through
the pharynx, the larynx, then the trachea
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External Respiration:
- the exchange of air between the atomosphere and the lungs
- the exchange of O2 and CO2 between the lungs and blood
- the transport of O2 and CO2 by the blood
- the exchange of gases between blood and the cells
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The ciliated epithelium of the trachea and bronchi helps:
move mucus to the pharynx
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The Airways:
- 3 upper airway functions -
- warming, humidifying, and filtering
- mucocilary escalator depends on secretion of watery saline - cystic fibrosis
- mucus
- H2O
- pseudostratified columnar epithelium
- goblet cells: secrete mucus
- alveoli: function is the exchange of gases between themselves and blood type II secrete surfactant: chemical mixes with thin fluid lining the alveoli to aid lungs as they expand during breathing
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Pulmonary Circulation:
- pulmonary trunk; receives low-02 blood from R. ventricle -> divides into 2 pulmonary arteries -> 02 blood returns to L atrium via pulmonary veins
- high flow rate, but pulmonary BP is low
- distance shorter, resistance is low; R. ventricle doesnt have to pump as forcefully
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Gas Laws:
- Dalton's: total P exerted by a misture of gases is the sum of P exerted by individual gases
- air we breath: N2 78%, 02 21%, H20/ vapors
- P @ sea level: 760 mmHg
- Boyle's: P1V1=P2V2
- gases move down pressure gradients
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Bends:
- N2 is important for divers
- come up too fast N2 bubbles in blood -> Nitrogen Narkosis
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Exchange of gases between lung and lung capillaries:
external respiration!
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Ventillation:
- air flows due to pressure gradients
- inspiration: contraction of diaphragm 60-75% volume change
- 25-40% due to external intercoastals and scalene muscles
- expiration: relaxation of inspiratory muscles
- elastic recoil of pleura and lung tissue reinforce muscle recoil
- passive unless forced -> internal intercoastals and abdominal muscles
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Spirometry:
- for pulmonary function tests
- measures lung volumes during ventilation
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Aveolar and Intrapleural Pressures:
- lungs unable to expand and contract on their own
- during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated
- pneumothorax: air in the pleural cavity
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Surfactant:
- from aveolar type II cells
- detergent like complex of proteins and PL; disrupts cohesive forces between water molecules -> decreased surface tension -> decreased work of breathing
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Lung Compliance and Elastance:
- compliance: ability of lungs to stretch
- low compliance in fibrotic lungs (and other lung diseases) and when not enough surfactant
- elasticity: ability to return to original shape
- low elasticity in case of emphysema due to destruction of elastic fibers
- normal lung is both compliant and elastic
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Airway Resistance:
- influences work of breathing
- determinant: airway diameter
- CO2: bronchodilation
- parasympathetic neurons: contricts
- no sympathetic neurons but Beta2 receptors: bronchodilation
- histamine: contriction
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Efficiency of Breathing: Rate and Depth:
- heart efficiency? CO= HR x SV
- pulmonary ventilation: PV= RR x LV (tidal volume) 12x 500
- 150 ml anatomic dead space
- alveolar ventilation: RR x 350
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Matching Ventilation with Aveolar Blood Flow:
- lung has collapsible capillaries -> reduced blood flow at rest in lung apex
- increased CO2 in exhaled air -> bronchodilation
- decreased 02 in ECF around pulmonary arterioles -> vasoconstriction of arteriole (blood diverted)
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Gas Exchange and Transport:
- Dissolve CO2 and 02 for transport
- Transport 02 - role of hemoglobin
- Transport CO2
- Regulate ventilation
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Diffusion and Solubility of Gases:
- Ficks: diffusion rate surface rate x conc. gradient x mem. permeability\ membrane thickness
- diffusion is most rapid over short distances
- solubility of a gas depends on solubility of mol. in particular liquid and on pressure gradient and temperature
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