FINAL EXAM

• Plasma and Cellular Elements of Blood
• Hematopoiesis
• RBC Physiology
• Coagulation

• 92% water
• 7% proteins
• 1% organic mol (AA, glucose, lipids, N wastes), ions (Na+, K+, Cl-, H+, Ca2+), trace elements, vitamins, O2, and CO2

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

• RBCs (erythrocyes)
• WBCs (leukocytes)
• platelets (thrombocytes)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• 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

• 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

collagen exposure; all necessary factos present in blood; slower

Uses TF released by injured cells and a shortcut

Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> 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

• dissolve inappropriate clots
• enhance fibrinolysis
• t-PA: tissue plasminogen activator; dissolves clot faster
• *Vit K necessary for liver to make clotting proteins

• "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

• coagulation disorder
• coagulation cascade lacking or defective
• Hemophilia A, factor VIII deficiency, most common
• sex linked, ususally affects only males

• ratio of RBCs to plasma
• column of packed red cells is measured
• normal range of hematocrit 40-54% male 37-47% female

• structure and function of respiratory pumps
• gas exchange with blood
• role of surfactant and pressure differences on rate of exchange
• regulation of respiration

• O2 exchange: air -> blood, blood -> cells
• CO2 exchange: cells -> blood, blood -> air
• Regulation of body pH: retaining/ excreting CO2
• Protection of alveoli -> blood
• Vocalization

the pharynx, the larynx, then the trachea

• 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

move mucus to the pharynx

• 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

• 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

• 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

• N2 is important for divers
• come up too fast N2 bubbles in blood -> Nitrogen Narkosis

external respiration!

• 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

• for pulmonary function tests
• measures lung volumes during ventilation

• lungs unable to expand and contract on their own
• during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated

• 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

• 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

• influences work of breathing
• determinant: airway diameter
• CO2: bronchodilation
• parasympathetic neurons: contricts
• no sympathetic neurons but Beta2 receptors: bronchodilation
• histamine: contriction

• 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

• 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)

• Dissolve CO2 and 02 for transport
• Transport 02 - role of hemoglobin
• Transport CO2
• Regulate ventilation

• 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

Total atmospheric pressure as sea level = 760 mmHg

• 21% 02 P02= 160 mmHg
• 78% N2 PN2= 593 mmHg

• 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

• 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

• 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

• aveolar P02 may be normal but respiratory membrane changes affect gas exchange
• increased membrane thickness = fibrotic lung disease
• decreased surface area = emphysema

• 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

• 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)

• 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

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

• regulation of ECF volume and BP
• regulation of osmolarity
• maintenance of ion balance
• homeostatic regulation of Ph
• excretion of wastes
• production of hormones