1. Blood:
    • Plasma and Cellular Elements of Blood
    • Hematopoiesis
    • RBC Physiology
    • Coagulation
  2. 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
  3. 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
  4. Cellular Elements:
    • RBCs (erythrocyes)
    • WBCs (leukocytes)
    • platelets (thrombocytes)
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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)
  13. 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
  14. 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
  15. Instrinsic Pathway:
    collagen exposure; all necessary factos present in blood; slower
  16. Extrinsic Pathway:
    Uses TF released by injured cells and a shortcut
  17. Common Coagulation Pathway:
    Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> clot
  18. 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
  19. Clot Busters:
    • dissolve inappropriate clots
    • enhance fibrinolysis
    • t-PA: tissue plasminogen activator; dissolves clot faster
    • *Vit K necessary for liver to make clotting proteins
  20. 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
  21. Hemophilia:
    • coagulation disorder
    • coagulation cascade lacking or defective
    • Hemophilia A, factor VIII deficiency, most common
    • sex linked, ususally affects only males
  22. Hematocrit:
    • ratio of RBCs to plasma
    • column of packed red cells is measured
    • normal range of hematocrit 40-54% male 37-47% female
  23. 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
  24. 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
  25. On its way to the lungs, air passes through
    the pharynx, the larynx, then the trachea
  26. 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
  27. The ciliated epithelium of the trachea and bronchi helps:
    move mucus to the pharynx
  28. 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
  29. 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
  30. 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
  31. Bends:
    • N2 is important for divers
    • come up too fast N2 bubbles in blood -> Nitrogen Narkosis
  32. Exchange of gases between lung and lung capillaries:
    external respiration!
  33. 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
  34. Spirometry:
    • for pulmonary function tests
    • measures lung volumes during ventilation
  35. Aveolar and Intrapleural Pressures:
    • lungs unable to expand and contract on their own
    • during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated
  36. 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
  37. 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
  38. Airway Resistance:
    • influences work of breathing
    • determinant: airway diameter
    • CO2: bronchodilation
    • parasympathetic neurons: contricts
    • no sympathetic neurons but Beta2 receptors: bronchodilation
    • histamine: contriction
  39. 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
  40. 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)
  41. Gas Exchange and Transport:
    • Dissolve CO2 and 02 for transport
    • Transport 02 - role of hemoglobin
    • Transport CO2
    • Regulate ventilation
  42. 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
  43. Review Dalton's Law:
    Total atmospheric pressure as sea level = 760 mmHg

    • 21% 02 P02= 160 mmHg
    • 78% N2 PN2= 593 mmHg
  44. Gas Exchange in Lungs and Tissues:
    • gases flow from regions of higher partial pressure to regions of lower partial pressure.
    • 02 moves from aveolar (100 mmHg) to capillaries (40 mmHg)
    • P02 is lower in the cells 02 diffuses down its partial pressure gradient from plasma into cells
    • PC02 is higher in tissues than in capillaries
    • PC02 40 mmHg in aveoli 46 mmHg in tissues therefore the gradient causes C02 to diffuse out of the cells into the capillaries
  45. Lower Aveolar P02:
    • Diffusion rate decreases and you don't get enough 02
    • main factor that affects 02 content of air is altitude
    • low aveolar ventillation is know as hypoventillation
    • increased airway resistance
    • decreased lung compliance
    • CNS depression
  46. Pathological Conditions that Reduce Aveolar Ventilation:
    • emphysema: destruction of aveoli = less surface area for gas exchange
    • fibrotic lung disease: thickened aveolar membrane slows gas exchange, loss of lung compliance may decrease aveolar ventilation
    • pulmonary edema: fluid in interstitial space increases diffusion distance
    • asthma: increased airway resistance, decreased aveolar ventilation
  47. Aveolar Membrane Changes:
    • aveolar P02 may be normal but respiratory membrane changes affect gas exchange
    • increased membrane thickness = fibrotic lung disease
    • decreased surface area = emphysema
  48. Oxygen Transport in Blood:
    • 98% carried by Hemoglobin (oxihemoglobin) -> transported inside RBCs
    • rest is dissolved in plasma
    • at the cells where where 02 is used and plasma P02 falls Hb gives up its 02
    • we must have adequate amount of Hb in our blood to survive
  49. 02-Hb Dissociation Curve:
    • 20 mmHg exercising muscle 30%
    • 40 mmHg normal resting cell 75%
    • 100 mmHg normal of aveoli 98%

    • Factors effecting:
    • pH decreases
    • temperature increases (cold = left shift -> gives off less 02 -> stronger affinity to Hb)
    • PC02 increases
    • HbF increases (left shift)
  50. C02 Transport in Blood:
    • 7% directly dissolved in plasma
    • 70% transported as HC0- (bicarbonate) dissolved in plasma; acts as buffer; provides additional means of C02 transport from cells to lungs
    • 23% bound to Hb
    • excess C02 in blood = hypercapnia -> leads to acidosis, CNS depression and coma
  51. Regulation of Ventilation:
    stimuli- emotions and voluntary control -> higher brain centers -> limbic system -> medulla oblongata and pons -> somatic motor neurons for inspriation (effects scalenes, external intercoastals, diaphragm) or expiration (effects internal intercoastals, abdominals)

    stimuli- C02 -> medullary chemoreceptors -> medulla OR carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla

    stimuli- 02 and pH -> carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla oblongata or pons
  52. The Kidneys:
    • regulation of ECF volume and BP
    • regulation of osmolarity
    • maintenance of ion balance
    • homeostatic regulation of pH
    • excretion of wastes
    • production of hormones
  53. Processes of Urinary System:
    • Filtration
    • Reabsorption
    • Secretion
    • Excretion
  54. Filtration:
    • Movement of fluid from blood to lumen nephron
    • composition is like that of plasma - plasma proteins (water and dissolved solutes)
    • once in the lumen, considered outside the body
  55. Renal Corpuscule: Passage across 3 barriers
    • filtration takes place in the Renal Corpuscule
    • 3 barriers:
    • glomular capillary endothelium (fenestrated capillaries= large pores)
    • basement membrane
    • epithelium of bowmans capsule
  56. 3 Types of Pressures Influence Filtration:
    • hydrostatic pressure in capillaries: blood pressure; filtration takes place along nearly the entire length of the glomerular capillaries
    • colloid osmotic pressure: pressure gradient is due to the presence of proteins in the plasma
    • hydrostatic pressure in bowman's capsule: presence of fluid in the capsule creates fluid pressure that opposes fluid movement into the capsule
  57. Glomerular Filtration Rate (GFR):
    • filtration takes place in the glomerulus of a nephron
    • average GFR 180L/day, 60 times per day, 2.5 times per hour
    • amount of fluid filtered into Bowman's capsule per unit of time
    • influenced by: net filtration pressure (determined by renal blood flow and blood pressure) and the filtration coefficient (surface area of glomerular capillaries and permeablity of interface between the capillary and bowman's capsule)
    • surface area of kidneys depends on how many functional nephrons
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