Respiratory Function lessons 5-8
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Pulmonary arterial pressure is low or high? Why?
Low b/c resistances to blood flow in pulmonary arterioles is about 10x less than in systemic vascular bed. (Ohm's Law)
How are pulmonary pressures measured (units)?
in cm H2O rather than mmHg
1mm Hg = 1.33 cm H2O
What attributes to low resistance in pulmonary vessels?
- 1. total length of pulmonary circuit < systemic circuit
- 2. large # of pulmonary capillaries in parallel
- 3. Highly compliant pulmonary vessels are easily distended by blood thus reducing resistance to flow
- 4. absence of precapillary sphincters in pulmonary arterioles (are normally dilated)
- Poiseuille's law: R = 8ln / pie r4low R to flow in pulmonary circuit allows right ventricle to maintain CO2 w/o expenditure of large amount of metabolic energy
What are other characteristics of pulmonary vascular?
- 1. pulmonary arteries carry deoxygenated blood and pulmonary veins carry oxygenated blood
- 2. no active sympathetic (neurogenic) control of pulmonary vascular R
- 3. volume of blood in pulmonary capillaries is about = to normal resting stroke volume
What part of the lung is blood flow the greatest?
base (bottom) of lung (with respect to gravity) and decreases proportionally to top of lung
What happens to pulmonary driving pressure as you travel from base to top of lung?
due to low pulmonary driving pressure and effect of gravity on hydrostatic pressure of blood, driving pressure for flow progressively decreases
What is zone 1 of the lung?
region of lung where pulmonary flow is 0 b/c pulmonary arterial pressure is < alveolar pressure. pressure in alveoli presses againist pulmonary capillaries in alveolar wall causing them to collapse
What are causes of zone 1 in the lung?
- 1.alveolar pressure slightly below and above atmospheric during inspiration and expiration respectively. thus pulmonary arterial pressure would have to be 0 in this region to produce zone 1
- 2.during + pressure mechanical ventilation, alveolar pressure can be very high so assisted ventilation will always produce region of zone 1
- 3. always occurs at top of lungs 1st
- 4. b/c alveoli in this region are ventilated but not perfused, alveolar volume of zone I would contribute to alveolar dead space and wasted ventilation
What is zone II in the lungs?
region of long b/t zones I and III
What is zone III in the lungs?
region of lung in which flow is determined by difference b/t arterial and venous pressure as in systemic vessels
What causes zone III in lungs?
- 1. occupies the dependent (below heart) portion of lung
- 2. majority of pulmonary blood flow occurs in this region
- 3. flow increases from top to bottom of this region b/c gravity acts to pull blood toward lower part of lung, causing lower pulmonary vessels to distend. distension of lower pulmonary capillaries increases thier radius, increasing BF through them
What is zone IV in the lungs?
region of lung below zone III with impeded flow of blood due to edema
What causes zone IV in lungs?
- 1. present only when an abnormally high pulmonary venous pressure (L heart failure). Occurs at base of lung and reduces BF
- 2. results from edema around blood vessels, vascular cuffing- causes pulmonary vessels to collapse (tamponade). Results: increased R to BF causing flow to decrease
What are factors that affect zones of the lung?
- 1. Posture: vertical distance b/t top and bottom of lung is decreased in supine position. Thus > proportion of lung is occupied by zone III in this position
- 2. Decreasing pulmonary arterial pressure (hemorrhage or shock) increases zone I
- 3. + pressure ventilation: increases alveolar pressure and increases region of zone I
What is significance of lungs in supine position?
heart is b/t lungs and decreases pressure to profuse top of lung. Most of lungs in zone III
What is passive regulation?
increasing pulmonary arterial pressure causes vascular R to decrease b/c of recruitment and distension
What is recruitment?
increasing pulmonary arterial pressure initiates flow through previously unperfused pulmonary capillaries in upper parts of lung
What is distension?
increasing blood volume in pulmonary arteries distends pulmonary capillaries thus increasing flow (mainly zone III). inflation of lung during inspiration pulls blood into the chest and distends the pulmonary capillaries. Thus pulmonary flow is facilitated during inspiration.
Do you use all capillaries in lungs @ rest?
What happens to capillaries during recruitment?
more capillaries are used and are in parallel so decreases R, increases BF, vessels are more complient and also increases r, this also decreases R
What do capillaries do during distention?
r is increased so R is decreased
What is active regulation?
- 1. no neurogenic regulation of pulmonary vascular R
- 2. Pulmonary arterioles respond to several metabolic factors
What happens during hypoxic pulmonary vasoconstriction?
- 1. decreased PO2 in alveoli constricts Pulmonary arterioles locally
- 2. increased PO2 in alveoli dilates Pulmonary arterioles locally
- 3. functional advantage: diverts blood away from poorly ventilated areas of lung by locally increases vascular R
- 4. PO2 in venous blood does not affect response
- 5. primary mechanism for local control of BF w/in lungs
What are vascular endothelial factors?
- 1. endothelin 1 (ET-1): potent pulmonary vasoconstricor
- 2. Prostacyclin (PGI2) and NO: potent pulmonary vasodilators
What are Starling forces for fluid movement across pulmonary capillaries?
- normally pulmonary interstitial space is dry b/c capillary oncotic forces are slightly > capillary hydrostatic forces in upper lung, thus little fluid enters spaces from pulmonary capillaries. Fluid that does enter interstitial spaces in lower regions of lung are rapidly removed by pulmonary lymphatic system
- 2. lower parts of lung exhibit > amount of fluid entering interstitial space due to higher hydrostatic pressures
- 3. Fluid exchange across pulmonary capillaries obeys Starling's law. A blance b/t hydrostatic and oncotic forces
For Starling Forces: outward force is + or -?
+. If + fluid will tend to leave capillary
For Starling Forces: inward force is + or -?
-. negative fluid will enter capillaries
What forces favor fluid movement out of capillaries?
- 1. PHcap = pulmonary capillary hydrostatic pressure (> @ bottom)
- 2. PHis = pulmonary interstitial hydrostatic pressure (hydrostatic pressure in interstitium is slightly -, favors flid movement out of capillary)
- 3. P(pie)is = interstitial oncotic pressure
What are forces favoring fluid movement into the capillary?
P(pie)cap = pulmonary capillary oncotic pressure
What are factors that promote pulmonary edema (Interstitial pulmonary edema)?
- 1. increased pulmonary capillary hydrostatic pressure (L heart failure and pulmonary hypertension)
- 2. Lymphatic obstruction-->due to obstruction/inflammation due to lymphatic ducts
- 3. Increased permeability of capillary membrane due to release of infammatory mediators (pneumonia)
- 4. Decrease plasma oncotic pressure due to depletion of plasma proteins (liver or renal disease)
- ***promotes formation of zone IV in lungs
What is another factor of pulmonary edema?
alveolar edema: more sever stage of pulmonary edema where interstitial fluid accumulates to extent that overcomes stabilizing force of surfactant and fills alveoli
What is a shunt?
BF that bypasses either pulmonary or systemic circuit
What is right to left shunt?
causes deoxygentated (systemic venous) blood to mix with oxygentated blood. Causes PO2 in arterial blood to decresae (hypoxemia) and results in cyanosis and inadequate O2 delivery to tissue
What happens in right to left shunt?
- 1. BF bypasses pulmonary circuit
- 2. Systemic flow > pulmonary flow
- 3. Eisenmenger's Syndrome: combo of ventricular septal defect with pulmonary hypertenstion
- 4. Natural shunts: bronchial circulation, thebesian veins empty into pulmonary veins and contributes to right to left shunt
What is a pulmonary shunt?
ventilation to an alveolus receiving BF falls to 0. where deoxygentated blood passes into systemic circulation
When does pulmonary shunt happen?
- 1. airway obstruction: bronchospasm, asthma, bronchitis, mucus plug: cystic fibrosis or foreign object
- 2. suppressed ventilation (respiratory arrest)
- 3. Alveolar edema or fibrosis (decrease diffusion capcity)
- 4. Atelectasis (alveolar collapse)
What are compensatory responses to limit pulmonary shunts?
- 1. increase minute ventilation
- 2. local pulmonary capillaries vasoconstrict in response to low PAO2 (hypoxic pulmonary vasoconstriction) to limit profusion
When does left to right shunt occur?
- 1. Ventricular septal defects, patent ductus
- 2. BF bypasses systemic circuit
- 3. pulmonary flow > systemic flow
- 4. cause systemic hypotension due to low systemic BF and engorgement of pulmonary circulation with blood to cause pulomonary edema
What are 2 disorders of pulmonary circulation?
- 1. Pulmonary hypertenstion
- 2. Pulmonary embolism
What happens in pulmonary embolism?
- 1. obstruction of part of Pulmonary circulation due to clot or air bubble
- 2. V/Q mismatch (increased dead space)
- 3. accompanied by rapid onset of breathlessness in pt w/ unexplained hyperventilation
What happens in Pulmonary hypertension?
- 1. Vasoconstriction (acidemia pH = 7.2)
- 2. Obstruction: Pulmonary embolism or tumor
amount of gas transferred is propotional to area, a diffusion constant, and the difference in partial pressure, and is inversely proportional to thickness
How is diffusion capacity used to measure diffusion impairments?
determine rate of uptake of gas w/ high diffusion constant
What are conditions that decrease diffusion capacity (increaese distance O2 needs to diffuse to get into blood stream)?
- 1. Thickening of respiratory membrane: alveolar edema or Pulmonary fibrosis
- 2. decreased surface area of respiratory membrane: emphysema, alveolar dead space, tumors
- 3. Vent./perfusion mismatch which causes right to left shunts
- 4.Right to left shunts: intracardiac shunts, intrapulmonic shunts (atelectasis)
What is Dalton's Law?
total pressure exerted by a gas mixture (air) = to sum of parital pressures of each constituent gas
What is partial pressure?
pressure exerted by any one of gas constitutes = fraction of gas in mixture
partial pressure of O2 in alveoli
partial pressure of O2 in arterial blood
Normal values for partial pressures of gasis in air, alveoli, and blood are at what level?
Which substance is easier to diffuse? O2 or CO2?
CO2- less force is needed to move
What is CO2 in arterial blood dependent upon?
rate of alveolar ventilation and metabolic rate
Under normal conditions PaCO2 and PACO2 are maintained constant by what?
chemoreceptor reflex influence central respiratory centers to adjust VT and breathing frequency
When PaCO2 is above normal levels (>40mmHg) what happens?
- 1. hypercapnia- retain CO2
- 2. alveolar vent. is too low for level of metabolic activity present
- 3. hypoventilation
When PaCO2 is below normal levels (<40mmHg) what happens?
- 1. hypocapnia (gets rid of too much CO2)
- 2. alveolar vent. is too high for level of metabolic activity present
- 3. hyperventilation
CO2 adds H+ to extracellular fluid b/c of what?
enzyme carbonic anhydrase (found in reanl cells and RBCs)
PaCO2 is major determinate of what?
pH of blood- Henderson- Hasselbach
Kidneys help to maintian what?
normal blood pH by regulating plasma (HCO3-)
Ventilation helps maintain what?
normal blood pH by regulating plasma (CO2)
What are some acid/base disorders due to inappropriate ventialtion?
1. Hypoventilation (PaCO2 to rise) = acidosis and hyperventilation (PaCO2 to fall) = alkalosis
Respiratory acidosis is caused by what factors?
- 1. suppression of central nervous respiratory centers by trauma, drugs, anestetics
- 2. disease of respiratory muscles
- 3.compensatory resonse to metabolic a
Causes of respiratory alkalosis are what?
- 1. stress, pain, fever
- 2. high altitiude
- 3. progesterone
- 4. compensatory response to metabolic acidosis
What 2 ways is O2 carride in blood?
- 1. Dissoved in plasma
- 2. Bound to hemoglobin in RBCs
What is O2-hemoglobin dissociation curve?
one molecule of Hb can bind 4 molecules of O2. The "driving" pressure for loading O2 onto Hb is arterial O2 gas pressure (PaO2), which is exerted by the amount of O2 physically dissolved in solution. Hb is 90% saturated with O2 even when arterial falls to 60 mmHg. This is b/c Hb affinity for O2 dramatically increases as 2 or more O2 molecules bind onto Hb.
What is O2 partial pressure?
partial pressure of O2 in blood is proportional to amount of O2 dissolved in blood (amount as free gas). O2 bound to Hb no longer acts as a gas to exert a pressure.
T/F: although lying in recumbent position helps to minimize zone I and alveola dead space, it aggravates zone 4 and pulmonary edema
T: in recumbent position, a larger area of lung is exposed to higher hydrostatic pressures and more susceptible to edema formations. Pt's with pulmonary edema sleep better in sitting position: minimize amount of lung exposed to edema formation.
T/F: high attitude promotes pulmonary edema in some individuals b/c of hypoxic pulmonary vasoconstriction?
T: amount of O2 in air decreases with altitude ascends. When PO2 drops sufficiently, whole pulmonary capillary network constricts, elevating pulmonary hydrostatic pressure and causing edema. Susceptible individual who stay @ altitude can develop pulmonary hypertension and cor pulmonale
T/F: when person increases alveolar vent. for exercise, they hyperventilate.
F: when person increases vent. for exercsie, normally don't hypervent. b/c PaCO2 is maintained @ normal level when increased in vent. is more accurately called hyperpnea
T/F: A patient who is hypoventilating can be assumed to have problem with control of ventilation?
F: While hypovent. often results of impaired control of breathing, could be normal compensatory response (resp. acidosis) to metabolic alkalosis
What is dissolved O2?
amount of O2 dissolved in plasma, as a gas is very small.
What is P50?
O2 tenstion requried to saturate 50% of Hb
What is O2 content (CaO2)?
total amount of O2 in a deciliter of blood and includes both dissolved and hemoglobin-bound O2, but dissolved O2 is normally negligible.
What is O2 capacity of blood?
max content of O2 that can be carried by a given amount of Hb in blood. 100% saturated.
What is O2 saturation?
fraction or % of all hemoglobin binding sites that are currently occupied by O2
What is significance of sigmoid curve?
normally Hb gives up about 25% of its bound O2 w/ passage through systemic capillaries. There is reserve in system. If system capillary falls further (in exercise) there is plenty of additional O2 available for Hb.
What are changes in Hb affinity for O2 resulting in a change in P50?
- 1. Increased Hb affinity for O2: O2 dissociation curve shifts to left and P50 is reduced
- 2. Decreased Hb affinity for O2: O2 dissociation curve shifts to right and P50 is increased
a shift in oxyhemoglobin dissociation curve has a minimal effect on what?
minimal effects on O2 loading in lung b/c O2 dissociation curve is failry flat at a PO2
What does a shift in oxyhemoglobin dissociation curve has a maximal effect on what?
on oxygen unloading at the tissues b/c curve is steep at venous PO2
Increase in Hydrogen Ion shifts the oxyhemoglobin dissociation curve which way?
decreases pH and increases P50 (decreases O2 affinity) and shifts the curve to the R.
Decrease in Hydrogen Ion shifts the oxyhemoglobin dissociation curve which way?
To the left. Decreasing H+, increases pH, decreases P50 (increases O2 affinity)
Acidosis promotes oxygen loading or unloading?
Alkalosis promotes oxygen loading or unloading?
Carbon dioxide (Bohr Effect) does what?
- 1. Major portion of Bohr effect is due to fact that increasing PCO2 causes decrease RBC pH (acidosis)
- 2. Secondary part of Bohr effect is due to fact that CO2 reacts covalently w/ Hb to form carbamino Hb, which reduces O2 affinity
- 3. Plays significant role in O2 unloading under normal, physiological conditions.
Increase in temperature does what to P50?
Decrease in temperature does what to P50?
What does exercise do to P50?
increase temperature, increases PCO2 and decreases pH all promote oxygen unloading at the tissues by increasing P50 (decreasing affinity)
2,3-DPG does what to P50?
is a glycolytic intermediate, which accumulates to uniquely high levels in RBCs. Increased levels increases P50; decreased levels decrease P50.
Increased levels of 2,3-DPG occur in association with hypoxia. When is this seen?
- 1. acclimatization to high altitudes
- 2. Chronic lung disease; emphysema
- 3. anemia
- 4. hyperthyroidism
- 5. R to L cardiac shunt
- 6. congential heart disease
- 7. pulmonary vascualr disease
What can happen during blood bank storage?
blood storage in citrate-phosphate-dextrose solution for as short as 1 wk can lead to significant 2,3-DPG depletion and left shifted O2 dissociation curves
Changes in O2 carrying capacity of Hb happens when?
- 1. Hb concentration: will change from normal value as hematorcrit changes
- 2. Carbon Monoxide: binds to Hb at O2 binding sites to form carboxyhemoglobin and has 210x affinity of oxygen
- 3. Methemoglobin: heme groups of hemoglobin normally contains ferrous iron whether bound to O2 or not
What is anemia?
decrease O2 carrying capacity of blood w/o independently altering the P50 of blood
what is polycythemia
increases the O2 carrying capacity of blood w/o independently altering the P50 of blood
What are oxidizing Agents?
certain drugs and chemicals can oxidize heme Fe++ to Fe+++. causes methemoglobin and does not bind to O2. Total O2 carrying capacity is reduced by amount of hemoglobin that is methemoglobin
In what 2 forms is CO2 carried in plasma?
- 1. Dissolved CO2
- 2. Carbamino compounds: CO2 binds the amine groups of plasma proteins to form carbamino compounds. Plasma proteins buffer the H+ ions formed
How is CO2 carried by RBCs (3 forms)?
- 1. Dissolved CO2
- 2. Carbamino compounds
- 3. Bicarbonate: carbonic anhydrase is present in RBCs and catalzye the formation of carbonic acid, which dissociated to hydrogen ion and bicarbonate. H+ is buffered by Hb
What is chloride shift?
as HCO3- is formed it diffuses out of RBCs. Cl- diffuses into RBC to maintain electroneutrality. (Hamburger Shift).
What happens in CO2 dissociation curve?
total CO2 content of blood can be plotted as a function of PCO2. Relationship is nearly linear for total CO2.
What are all the ways CO2 is transported?
- 1. 90% of arterial CO2 stores are carried as HCO3-, 5% of stores as carbamino compounds, and 5% of stores carried as dissolved CO2
- 2. Only 10% of CO2 in alveolar capillary blood enters into alveoli for expiration. Remaining 90% remains in blood (mainly in form of HCO3-) for acid base regulation
What is haldane effect?
Increasing O2 tension decreases affinity of hemoglobin for CO2. As result CO2 "dissociation curve" shifts to R. High PO2 promotes CO2 unloading in lungs. Low PO2 promotes CO2 loading in periphery
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