Unit 3 - Pulm Flashcards
Describe the gross anatomy of the lung
- trachea –> bronchus –> bronchiole –> respiratory bronchiole –> alveoli
- 3 lobes in right
- 2 lobes in left
- visceral pleura right on lungs
- parietal pleura on chest cavity (ribs and diaphragm)
- pleural space in between
Define the major phases of lung development including association with approximate weeks of gestation and major structural and biochemical changes (i.e. surfactant secretion) and how this relates to survival of the premature infant
- develop from lung bud of gut tube endoderm –> branches into mesenchyme where pulm circulation forms
1) embryonic phase (26days-6wks):
- endoderm extends into mesenchyme
- 3 rounds of branching to form lung lobes
2) pseudoglandular phase (6-16wks):
- 14 rounds of branching to form terminal bronchioles
3) canalicular phase (16-28wks):
- terminal bronchioles divide into respiratory bronchioles
- start surfactant prod
- premature baby can survive at 26-28wks due to surfactant prod
4) saccular phase (28-36wks):
- respiratory bronchioles branch into terminal sacs
5) alveolar phase (36wks-early childhood):
- alveoli mature
- surfactant prod
- lung growth
Identify the major structural and functional differences between conducting and gas exchanging regions of the lung
Conducting regions
- conduit for gas transfer but do not engage in gas exchange
- 30% of lung
- more cartilage typically in bronchi and trachea
Gas exchanging regions
- engage in gas exchange
- 70% of lung
- loss of cartilage as you go towards alveoli (from bronchi to bronchiole)
What three principal structures make up the airway wall?
1) inner mucosal surface
- epithelial cells
- cilia
- goblet cells
2) smooth muscle layer
3) outer CT layer
What are the two different types of alveolar epithelial cells and what are their functions?
Type I pneumocytes
- squamous lining cells
- 95% of alveolar surface area
- fuse with capillary endothelium for gas exchange facilitation
Type II pneumocytes
- repair or replace damaged Type I pneumocytes
secrete surfactant to dec alveolar surface tension
Describe the basic construction of the lung - lobes, segments, pleura and branching of the conduction and vascular systems, and the relationship of the visceral and parietal pleura to ventilation
- trachea branches into left and right primary bronchi –> secondary/lobar bronchi (3 in right, 2 in left) to each lobe –> segmental bronchi that aerate segments (10 in right, 8 in left)
- each segment has its own air and blood supply as its own subunit
- segmental bronchi –> bronchioles –> terminal cronchioles
- lungs are covered by visceral pleura which has elastic fibrocollagen, smooth muscle, nerves, lymphatics, and blood vessels, covered by mesothelial cells
- parietal pleura is CT that is continuous with periosteum of ribs and intercostal muscles
- pleural space provides pressure differential for breathing
Explain the flow of blood through the lung, both the pulmonary and bronchial systems
- lung receives blood from systemic arteries (bronchial arteries from aorta) and pulmonary arteries (from RV)
- pulm system is low pressure and pulm arteries course along bronchi/conduction system and become capillaries; not part of O2 supply but pick up O2 in alveoli; blood returns to heart through pulm veins which sweep up towards the hilus and via the visceral pleura/intersegmental CT
- bronchial arteries follow bronchi and supply O2 to conduction system; bronchial veins drain CT of hilar region of lungs to azygos vein
Identify a blood vessel (as compared to a bronchus or bronchiole) in the lung
- blood vessels don’t have cartilage or ciliated epithelial cells
Identify the layers of the walls of the conduction system and the functional reasons for their differences, including the trachea, bronchi, bronchioles, and the respiratory bronchioles
Trachea and bronchi:
- trachea has c-shaped cartilage rings and trachealis muscle
- bronchi has segmented cartilagenous plates around entire diameter
- inner pseudostrat epi layer of ciliated, goblet, and basal cells + lamina propria –> mucosa
- submucosa of CT with mucus glands
- cartilage
- adventitia to surrounding tissues
- large bronchi have muscularis smooth muscle between epi and submucosa (but not in trachea or smaller bronchi)
Bronchioles:
- no cartilage or glands
- smooth muscle under lamina propria
- ciliated and goblet cells in epi layer
- as you get more terminal, have more club cells that secrete surfactant
Respiratory bronchioles:
- smooth muscle layer and epi layer of club cells
-
Describe the structure of the alveolar septa, and the functions of their cellular and acellular components
- respiratory bronchioles –> alveolar ducts –> alveolar saccules
- septa are comprised of fibroelastic basal laminae and cells
- capillaries between septa
- type I and II pneumocytes on air facing side
Outline the various defense mechanisms (both in the conduction system and alveoli) that prevent infection
- monocytes/macrophages, neutrophils, and fibroblasts in the loose CT of septa
- ## macrophages phagocytose bacteria and particles and enter mucus and are coughed out or swallowed or can also enter lymphatics and act as antigen presenting cells
Describe the basic process of gas exchange at the blood-air barrier, the important of surfactant, and identify the layers of the blood-air barrier
- capillary endo cells are tightly apposed to basal lamina where type I cells are bound
- passage of gas goes through surfactant, PM of of type I cell, basal lamina, PM of endo cell
- type II cells secrete surfactant (85% phospholipid), which lowers surface tension in alveoli and prevents lung collapse
State the underlying mechanisms for pathologies of the congestive diseases of cystic fibrosis, Kartagener’s syndrome, and the particulate overload diseases such as black lung and silicosis
Cystic fibrosis:
- defective Cl transport in epithelium
- more viscous mucous that is hard to remove
- chronic infections and resp failure
Kartagener’s syndrome:
- genetic defect with chronic resp congestion and infection
- immotile cilia so can’t remove mucus
Excessive smoking/pollution
- loss of ciliated cells
- replaced with squamous cells so chronic cough to clear mucus
Silicosis/black lung
- macrophages engulf particles but can’t digest the material and die in the alveoli
- macrophages digest dead macrophages, but lots of undigestible stuff accumulates
What are the three lines of defense in the lungs?
1) mucus layer of trachea and bronchi
2) nodes of lymphocytes in submucosa of trachea and bronchi that get past mucus and into epi lining
3) alveolar macrophages
What happens in emphysema?
- alpha1 antitrypsin deficiency –> lysis of elastin in alveolar septa –> loss of elasticity so harder to exhale
Describe muscles involved in inspiration and expiration
Inspiration:
- diaphragm contracts during inspiration –> becomes flatter and inc volume
- lower ribs elevate/rotate
- upper ribs draw inwards
- external intercostals pull ribs forward and outward
- SCM and scalenes are used in accessory/increased breathing and elevate rib cage
Expiration:
- usually passive
- abdominal wall muscles push diaphragm upwards to dec volume
- internal intercostals pull ribs inward and downward
Describe how the status of inspiratory muscles during disease can impact breathing
- especially diaphragm
- in chronic obstructive diseases (asthma, bronchitis, emphysema), breather at higher lung volumes –> diaphragm is more contracted and shorter length –> lower tension/pressure generated
Define intrapleural pressure and its role in lung expansion during inspiration
- Pip is intrapleural pressure, which is the pressure outside of the lungs in the intrapleural space
- source is from lung wanting to be smaller and chest wanting to be bigger –> opposing forces result in a negative Pip
- inc vol of chest cavity and pull lungs open
Describe the contribution of elastic recoil pressure to expiration
- lung inherently recoils back to intrinsic equilibrium position –> transient positive Plung –> pushes air out
- problem expiring in emphysema due to loss of this elastic recoil
Describe the importance of lung and chest wall compliance on breathing
- compliance becomes lower as Ptp is greater because the more you inflate, the less you should expand your lungs
- chest wall compliance can have an effect as well: old age = dec chest wall compliance –> dec change in volume during normal breathing –> reduced airflow into lung
Describe airflow during inspiration and expiration
- pressure gradient required between Pmouth and Plung
- inspiration: lung pressure is negative wrt to mouth pressure
- expiration: lung pressure is positive wrt to mouth pressure
- Plung acheives negative values during inspiration due to increase in negativity of Pip due to lung inflation
- Pip inc negativity more quickly than Ptp due to compliance, so Plung is transiently negative during inspiration
- lung elasticity inherently helps in expiration
What is hysteresis?
- compliance is lower during inspiration than during expiration
- need greater change in Ptp to change a given volume during inspiration than expiration
Describe the impact
of surface tension on lung function
- water lines inner surface of alveoli; wants to stay with water and not air, so tension between liquid and air
- 1) prefers smaller alveoli/opposes expansion because fewer H2O molecules at interface when smaller than expanded
- 2) fluid accumulation in alveoli
- 3) collapse of small alveoli; inc pressure in smaller alveoli –> collapse of small alveoli
Describe the physical properties of surfactant and its functions
- surfactant is a mixture of lipids and proteins secreted by type II pneumocytes
- lowers surface tension by intercalating between H2O molecules –> dec attractive forces
- effective at smaller smaller alveoli; dec SA = conc of surfactant inc = dec surface tension
Function:
- inc lung compliance, prevent collapse of small alveoli, prevent accumulation of fluid inside alveoli
Describe the different types of airflow and their relation to airway resistance
- laminar flow: low flow rate; parallel stream lines; flow rate proportional to deltaP; inc radius 2x = inc flow 16x
- turbulent flow: not proportional to deltaP but rather with sqrt of deltaP; less efficient; more likely in large diameter and high flow rates
- lung flow described as transitional flow; turbulence may occur at trachea
- most airway resistance at intermediate/segmental bronchi, not at terminal bronchioles because lots of small bronchioles that dec overall resistance to flow and air turbulence at large airways also no cartilage
Describe factors that can alter airway resistance
1) lung volume:
- airways expand at larger volumes = dec resistance
- inc airway restriction/obstruction –> breathing at higher lung volumes to open airways
2) bronchial smooth muscle tone:
- contraction of smooth muscle –> inc resistance
- smooth muscle innervated by vagus nerve –> (parasymp) stimulation causes bronchoconstriction via ACh but also histamine, TXA2, leukotrienes and low PCO2
- (symp) stimulation by adrenergic receptors and NE/epi –> bronchodilation via B2 receptors
3) dynamic airway collapse
- positive Pip outside of airway –> collapse of airway
Define dynamic airway collapse and its effect on expiration
- positive Pip outside of airway –> collapse of airway
- airways stays open by Pip always being negative –> Ptp is positive (Pairway is greater than Pip)
- Pip can become positive during forced expiration because you have expiratory muscles on top of elastic recoil –> a lot of force on airways to collapse them
- can also happen in cough
- emphysema patients have higher tendency for dynamic airway collapse because loss of elastic recoil means that compression of intrapleural space is more likely –> positive Pip; also loss of supporting CT opening airways
Describe the difference between minute ventilation and alveolar ventilation
- minute ventilation (6L): volume of air flow into or out of lung in one minute
- alveolar ventilation (4.2L): volume of air flow into or out of alveolar space in one minute
- mv > av because mv considers flow through conducting pathways as well
Describe factors that influence lung ventilation, including the role of gravity
1) bronchodilators/constrictors:
- BDs inc alveolar vent
- BCs dec alveolar vent
2) exercise:
- can inc 10x to meet inc CO2 production
3) altitude:
- inc to meet low O2 in the air
4) obstructive/restrictive diseases:
- inc airway resistance or alter lung compliance
- emphysema
5) gravity:
- Pip is greater at apex than at base of lung
- bronchioles and alveoli will have larger volumes higher in lung
- this means they will be less ventilated because they have less compliance at higher volume, so they will undergo a smaller change of volume with each breath –> less ventilation
- bottom of lung almost 2.5x more ventilation than top
Describe the work of breathing and its influence on breathing rate and tidal volume
- ventilation is a flow value but work of breathing is respiration rate and tidal volume which multiply to equal flow
- the work of breathing is done by muscles to a) work against elastic recoil of the lungs and b) work against airway resistance
- small tidal vol and inc freq –> lots of work against resistance because do not inflate lungs to open up airways
- large tidal vol and dec freq –> lots of work against elastic because need to overcome elastic recoil
- minimum work is around 12-15 and 400-500mL
Define anatomical, alveolar, and physiologic dead space
Anatomical deadspace:
- 30% of air inhaled remains in conducting path (70% in alveoli)
- has an effect when we take shallower breaths or snorkeling
Alveolar deadspace:
- well ventilated alveoli but do not participate in gas exchange
- do not eliminate CO2 and do not help bring O2 to the body
- underperfused/lack blood flow/blockage in blood flow
Physiologic deadspace:
- anatomic + alveolar deadspace
Describe different lung volumes and how they are used to diagnose respiratory disorders
Residual volume:
- volume of air remaining after max expiration
Functional residual capacity:
- volume of air in lung at end of normal expiration
Total lung capacity:
- volume in lungs at end of maximal inspiration
Tidal volume:
- difference in lung volume between normal inspiration and normal expiration
Vital capacity:
- volume of air between max expiration and max inspiration
Forced expiratory volume:
- volume exhaled in first second
Forced vital capacity:
- total volume exhaled
- FEV1/FVC = 80%; lower if obstructive
What PFT signs are seen in emphysema?
- it is an obstructive disease so will see:
1) quick inspiration
2) expiration through pursed lips
3) reduced FEV1/FVC
4) inc in FRC
5) unchanged or small inc (but not dec) in vital capacity due to inc compliance
Calculate the partial pressure of oxygen in inspired air PiO2
- O2 is usually 21% of air and you need to take into account water vapor pressure
PiO2 = (PB-47)*.21
PB is 760 at sea level 620 in denver so PiO2 is 150 at sea level and 120 in denver
Define the respiratory exchange ratio and describe why values can vary
- respiratory exchange ratio represents the metabolic activity of the body and basically tells in what ratio CO2 is being produced for the O2 that is being consumed
- if the R is 1, then the amount of O2 that is being consumed is equally replaced by CO2 being produced
Alveolar gas eqn:
PAO2 = PiO2 - PACOS/R
R = CO2 prod/O2 cons and is usually .8
Calculate alveolar PAO2 given known values of PACO2, barometric pressure, and respiratory exchange ratio
PAO2 = (PB-47)*.21-PACO2/R
- basically, R
Describe whether diffusion or ventilation is rate-limiting for CO2 removal
- ventilation is rate-limiting and diffusion is practically instant
- PACO2 = PaCO2
- if ventilation goes down, then PACO2 inc –> PaCO2 inc –> acidosis
Calculate arterial PaCO2 and alveolar PACO2 given known values of alveolar ventilation and CO2 production
PaCO2 = PACO2 = VCO2/VA * k
- VCO2 = CO2 prod
- VA = alveolar ventilation
Define hypoventilation, hyperventilation, and hyperpnia and describe their causes
Hypoventilation:
- alveolar ventilation is abnormally low in relation to CO2 prod/elim
- inc in PACO2
Hyperventilation:
- alveolar ventilation is abnormally high in relation to CO2 prod/elim
- dec in PACO2
- exercise inc VCO2 but also VA so PaCO2 stays the same as at rest so not considered hyperventilation
Hyperpnia:
- increase in ventilation during moderate exercise
How do you estimate alveolar ventilation?
VA = VCO2/PACO2 * k
- VCO2 measured
- PACO2measured from blood PaCO2
What is normal PaCO2 range?
- sea level: 35-45 Torr
- Denver: 30-40 Torr
Define solubility coefficient and describe how they differ for oxygen and CO2
- sol coeff of O2 is a lot smaller than of CO2 (.0013 vs. .03)
- CO2 dissolves more easily than O2
Describe the basic properties of the oxy-hemoglobin dissociation curve (ODC)
- relates O2 say of Hb (SO2) to PO2 in blood
- steeper at lower PO2 and flatter at higher PO2
- allows for dropping off of O2 at O2-def sites and pick up at O2-rich sites
Describe factors that promote rapid oxygen diffusion between alveoli and pulmonary capillaries in a healthy individual and how things can go wrong in disease
- factors that affect diffusion are pressure gradient, area of tissue plane, tissue thickness, and tissue solubility/mol weight of gas
- O2 diffusion is facilitated by:
- -large surface area of alveoli
- -thin membrane width
- -large O2 pressure gradient from low sol of O2 in blood and O2 binding to Hb
- PO2 of blood in pulm arteries is 40 Torr and becomes 100 Torr after 1/3 of the way through lung capillary bed
- PCO2 of blood in pulm arteries goes from 45 Torr to 40 Torr
- O2 diffusion is affected more by disease
Define perfusion and factors that influence it, including the effect of gravity
- perfusion is blood flow through the lung; specifically the blood flow of the pulmonary circulation available for gas exchange and equals cardiac output (~5L/min)
perfusion is influenced by:
- O2 tension: low PAO2 causes hypoxic vasoconstriction –> dec local blood flow
- chemical agents: TXA2 (vasoconstictor) and prostacyclin (vasodilator) which are products of the AA pathway
- capillary recruitment: with an inc in CO, recruit new capillaries and more blood in capillaries
- gravity: BP is higher at base of lung –> more capillaries open and inc blood flow; base is about 6x more flow than apex
Describe the mechanisms by which deadspace, shunts, and V/Q mismatch impact gas exchange
Deadspace:
- unperfused region of lung maybe due to blockage in capillary
- wasted ventilation
Shunts:
- perfusion, but no ventilation
- would inc PCO2 but countered by chemoreceptors that inc ventilation
V/Q mismatch:
- unevenness of V/Q ratios dec arterial oxygenation
Describe how gravity leads to regional variations in ventilation and perfusion in an upright person
- gravity causes inc in ventilation and perfusion in lower parts of lung
- V/Q is higher at apex
- cause 5-10 Torr difference between PaO2 and PAO2
What is CaO2 and its normal value?
- total concentration of O2 in blood
- usually 20.7 mL O2/100mL blood
- most is bound to hemoglobin
- small portion is freely dissolved –> actually reflected in partial pressure value PaO2
What is the difference between perfusion limited and diffusion limited?
- perfusion limited is when there is rapid equilibration of alveolar PO2 and PCO2 with blood PO2 and PCO2 and the only limiting factor is blood flow
- diffusion limited is when there is ineffective equilibration between alveoli and blood
What are two local mechanisms that regulate V/Q mismatch?
1) high V/Q –> PACO2 dec –> inc in local airway resistance –> dec ventilation
2) low V/Q –> PAO2 dec –> hypoxic vasoconstriction –> dec perfusion
Describe the importance of O2 “offloading” from Hb and how it can be affected by various factors
- tissues can only use freely dissolved O2 and fast unbinding from Hb allows O2 to be available to tissues
- CADET shifts ODC to the right (inc in CO2, acid, 2,3DPG, exercise, and temp)
- right shift causes easier offloading of O2 which is beneficial in exercise
Calculate O2 delivery to tissues as a function of CO and arterial O2 content
O2 delivery = CO * arterial O2 content
DO2 = Q*CaO2
CaO2 = (SaO2[Hb]1.39) + (.003*PaO2)
Typical CO = 5000mL/min
Typical CaO2 = 20.7mL/min
DO2 = ~1000mL/min
Calculate O2 consumption from CO and the difference in O2 sat in arterial and venous blood
VO2 = O2 consumtion
VO2 = Q(CaO2-CvO2)
= Q(SaO2-SvO2)[Hb]1.39
Define hypoxia and hypoxemia
- hypoxemia is PaO2
Describe how different causes of hypoxia/hypoxemia can be determined from arterial blood gases
- get A-a gradient?
Describe the ways in which CO2 is carried in blood
1) dissolved CO2: CO2 is more soluble in blood than O2
2) bicarbonate ion (HCO3-): H2O+CO2 H2CO3 H++HCO3-; typical bicarb conc is 24mM; produced from CO2 in RBC to make carbonic acid which dissociates
3) carbamino compounds; CO2 can be bound to proteins; almost all carbamino carriage is by Hb;
What is hypoxemia and what are the main causes?
- hypoxemia is PaO2 dec PAO2 by increasing PACO2
3) diffusion limitations between alveoli and pulmonary capillaries
4) V/Q mismatch
5) shunt
What is the A-a gradient and how does it help in figuring out causes of hypoxemia?
- PO2 difference between alveoli and arteries
- A-a
What is CO’s effect on O2 delivery?
- CO binds to Hb 210x greater affinity than O2
- decreases saturation of Hb with O2 bound to Hb
- CO decreases SaO2 NOT PaO2
- CO shifts ODC curve to left, so O2 cannot leave Hb and diffuse into tissues
- CO can also poison ETC –> anaerobic metabolism
What is hypoxia and what are its causes?
- low O2 at tissue (PO2
What are the effects of low PiO2 (high altitude) on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 dec
- SaO2 dec
- PaCO2 dec (because of hyperventilation)
- A-a gradient normal
- measure PaCO2
What is the relationship between CaO2, SaO2, and PaO2?
- remember that CaO2 is the total concentration of O2, meaning O2 bound to Hb and freely dissolved
- the O2 bound to Hb involves SaO2 and is calculated as SaO2[Hb]1.39
- the freely dissolved O2 is calculated as .003*PaO2
What are the effects of low PAO2 (hypoventilation) on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 dec
- SaO2 dec
- PaCO2 inc
- A-a gradient normal
- measure PaCO2
What are the effects of interstitial disease (dec diffusion) on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 dec
- SaO2 dec
- PaCO2 normal
- A-a gradient inc
- measure CO single breath
What are the effects of V/Q mismatch (COPD) and shunt (pneumonia) on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 dec
- SaO2 dec
- PaCO2 normal
- A-a gradient inc
- differentiate from shunt with 100% O2 (V/Q mismatch improves with 100% O2, shunt doesn’t)
What are the effects of low Hb on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 normal
- SaO2 normal
- PaCO2 normal
- A-a gradient normal
- measure [Hb]
What are the effects of CO poisoning on PaO2, SaO2, PaCO2, A-a gradient? What are special tests to order?
- PaO2 normal
- SaO2 dec
- PaCO2 normal
- A-a gradient normal
- measure [CO-Hb]
Define Henderson-Hasselbach equation for bicarb/CO2
HA A- + H+
K = [H+][A-]/[HA]
[H+] = K[A-]/[HA]
-log[H+] = -log[K] - log([HA]/[A-])
pH = pK + log([A-]/[HA])
bicarb is the conjugate base of carbonic acid
H2CO3 H+ + HCO3-
CO2 is the conjugate acid of bicarb because H2CO3 is converted to CO2
H2O + CO2 H2CO3
pH=pK+log([HCO3-]/[CO2])
[CO2] = .03*PaCO2 pK = 6.1
pH=6.1+log([HCO3-]/(.03PaCO2))
**
List the normal arterial blood gas values for pH, PaCO2, PaO2, and [HCO3-]
normal pH = 7.38-7.48 (7.40+/-.02)
normal PaCO2 = 40 Torr (36+/-2)
normal PaO2 = 70-80 Torr
normal [HCO3-] = 24mM (22+/-2)
Demonstrate how to calculate the anion gap and how it is used clinically
- major cation is Na
- major anions are Cl and bicarb
- other ions that are unmeasured that lead to difference between Na conc and two major anions, called anion gap
AG = Na-(Cl+bicarb)=12+/-2 under normal circumstances
- if large, then additional unmeasured acids in blood –> anion gap metabolic acidosis
- if not elevated, but low pH –> non anion gap metabolic acidosis; probably from GI or renal losses (dec bicarb) or large infusion of saline
What is the normal range of pH in humans (and in Denver)?
- normal 7.38-7.48
- compatible with life 6.8-7.8
- higher in Denver because we hyperventilate due to low PiO2 –> dec PaCO2 –> dec [H+] –> inc pH
Why is bicarb the most important buffer?
1) present in high concentrations (normal 24mM)
2) pK is close to arterial pH
3) conjugate acid CO2 is controlled through ventilation
Why is hemoglobin an important intracellular buffer?
- deoxyHb has a pK of 7.9
- CO2 diffuses into RBCs, converted to HCO3- and protons are buffered by deoxyHb
- venous pH is slightly lower than arterial pH, around 7.37 despite high CO2
What is respiratory acidosis and what are common causes for it and how does the body compensate for it?
- inc in PaCO2 –> inc in [H+] –> dec in pH
- can be caused by hypoventilation
- acute or chronic
- chronic can be from COPD or other diseases (neuromuscular)
- acute can be from drugs that suppress breathing centers in brainstem or muscle fatigue
- compensate by conserving bicarb; mops up extra H+
What is respiratory alkalosis and what are common causes for it and how does the body compensate for it?
- dec in PaCO2 –> dec in [H+] –> inc in pH
- results from excessive ventilation compared to CO2 production; hyperventilation
- acute and chronic
- chronic: from high altitude you hyperventilate due to hypoxia; neurological disorders that dec inhibitory respiratory input; aspirin toxicity
- acute: more common and due to pain/anxiety
- compensate with excretion of bicarb to let H+ inc and dec pH
What is metabolic acidosis and what are common causes for it and how does the body compensate for it?
- addition of acid –> dec in bicarb because being used to mop up H+
- large anion gap but also seen if not a large anion gap and just low pH (usually due to GI/renal loss of bicarb)
- most common causes are MUDPILES (if anion gap)
- Methanols
- Uremia
- Diabetic ketoacidosis (or KA from starving/alcohol)
- Propylene glycol
- Isoniazid
- Lactate
- Ethylene glycol
- Salicylates
- compensate with inc ventilation –> dec PaCO2 –> dec H+ –> inc pH
- calculate expected PCO2 compensation with winter’s formula
expected PCO2 = 1.5*[HCO3-] + 8 +/-2
- if PCO2 is high, then primary metabolic acidosis with respiratory acidosis
What is metabolic alkalosis and what are common causes for it and how does the body compensate for it?
- inc in base such as bicarb or dec in acid –> inc pH
- causes include ingestion of antacids or sodium bicarb; vomiting causes loss of gastric acid; hypovolemia which causes reabsorption of bicarb by kidney –> more bicarb to mop up H+ –> inc pH
- compensation leads to dec in ventilation –> inc PaCO2 –> inc H+ –> dec pH; however respiratory compensation tends to be weak because this reduces alveolar and arterial PO2 –> brain doesn’t let you hypoventilate to hypoxemia
What are the general differences between respiratory and metabolic acid/base disorders?
- if you alter PaCO2, then you get a respiratory disorder
- if you have too much or too little acid, then you have a metabolic disorder
What is the formula for the anion gap?
Na - (Cl+bicarb)
What is winter’s formula and what is it used for?
- measure expected PCO2 compensation in metabolic acidosis
expected PCO2 = 1.5*bicarb + 8 +/- 2
In acute respiratory disturbances, an acute change in PaCO2 of 10 Torr leads to a pH change of how much?
PaC02 10 Torr = -.08 pH
- inc PaCO2 –> dec pH
- acute means not enough time for renal compensation
For chronic respiratory disturbances, a change in PaCO2 of 1 Torr leads to a compensatory change in [bicarb] of how much?
PaCo2 1 Torr = .4meq/L bicarb
- same direction
For metabolic disturbances, a dec/in in [bicarb] of 1meq/L leads to a decrease/inc in PaCO2 of how much?
[bicarb] dec 1 meq/L = PaCO2 dec 1.3 Torr
[bicarb] inc 1 meq/L = PaCO2 inc .7 Torr
Describe the function of the main respiratory center in the brain (medulla)
- medulla generates rhythm spontaneously without input due to rostral ventrolateral medulla (pre-Botzinger complex)
- rhythm drives resp motorneurons and interneurons in spinal cord –> drive resp muscles
- frequency of rhythm can be influenced with inputs to medulla
Describe the locations and functions of peripheral chemoreceptors
Location:
- carotid (small nodules of tissue found bilaterally at bifurcation of common carotid arteries into internal and external carotids) and aortic (around arch of aorta and between arch of aorta and pulm artery)
- stimulated by dec PO2 or inc PCO2
- carotids also stimulated by dec in pH and is dominant
Function:
- sense O2 level
- dec PO2 = inc ventilation
- CO2 changes not as important (only 20% of response), but rapid response to changes in CO2 and pH (important during exercise)
- also important during metabolic acid/base disturbances since sole detectors of arterial pH that can change ventilation
Describe the location and functions of central chemoreceptors and discuss the relative importance of peripheral or central chemoreceptors under different conditions
Location:
- ventral surface of medulla
Function:
- bind to protons in brain but are not sensitive to arterial protons, instead arterial PaCO2 due to BBB
- CO2 crosses BBB into CSF –> combines with H2O –> dissoc into H+ and bicarb –> central chemoreceptors bind H+
- CSF is poorly buffered, so PCO2 changes pH more; central CRs provide a strong response to changes in PCO2, although it takes long
- long term pH recovery due to bicarb takes much longer for CSF
Describe the role of the blood brain barrier in determining the function of central chemoreceptors
- BBB restricts diffusion of ions like H+ between blood and CSF, but allows diffusion of CO2
Describe the integrated response to changes in altitude in terms of the control of respiration
- lower PiO2
- hypoxia stimulates breathing through peripheral chemoreceptors –> leads to dec in PaCO2 and inc in blood/CSF pH which recovers through bicarb (excretion) after a few days
- allows ventilation to inc above initial value and allow blood O2 to rise
- over long time, adapt where inc # of RBCs and inc vascularity of heart and striated muscles –> inc O2 capacity of blood, but also blood viscosity
Describe the integrated response to exercise in terms of the control of respiration
- inc metabolism and demand for O2 delivery and CO2 elimination
- central and peripheral CRs for PCO2 and pH are important
- inc in PaCO2 and dec in pH –> activated CRs –> signals to medulla to inc ventilation –> inc frequency and tidal volume (hyperventilate)
- 10x inc during moderate exercise
Describe other inputs to the respiratory center and their effects
- cortex: voluntary control of breathing; speaking, singing, sniffing, coughing; limbic system/hypothalamus control breathing in emotional stress
- pons: modification of fine control of respiratory rhythm
- pulm stretch receptors: inflation reflex; inhibit inspiration when lungs are inflated
- pulm irritant receptors: reflex of irritants between airway epithelial cells; cause hyperpnea and bronchoconstriction
- juxtapulmonar capillaries: in pulm capillaries; inc pulm interstitial fluid causes reflex apnea, hypotension, and bradycardia
- nose/upper airway receptors:
- other stuff lol
Identify the three major components of routine PFTs and how they are performed/measured
- airflow/spirometry
- lung volumes
- gas exchange
- compliance
- airway responsiveness
- muscle strength
Identify components of and distinguish between volumes and capacities
- volumes are single entities
- capacities are composed of two+ volumes
- e.g. FRC = RV + ERV
Define the determinants of FRC (aka TGV)
FRC = RV + ERV
Identify effort dependent and independent components to pulmonary function testing
Effort dependent:
- inspiratory reserve volume (IRV)
- expiratory reserve volume (ERV)
- residual volume (RV)
- functional residual capacity (FRC)
- inspiratory capacity (IC)
- vital capacity (VC)
- total lung capacity (TLC)
- spirometry
- forced vital capacity (FVC)
- FEV1
Effort independent:
- tidal volume (TV)
Distinguish between obstructive and restrictive patterns on PFTs
- normal FEV1/FVC is .7-.8
- obstructive pattern is .8 or normal but airflows do not diagnose restrictive disease
Identify the 3 major factors contributing to DLCO
1) surface area
2) membrane thickness
3) hemoglobin
Identify major disease processes by PFT patterns integrating airflow, lung volume, and gas exchange measurements
- obstructive: inc lung volumes; dec FEV1/FVC; left shift of flow-volume curve with coving
- restrictive: dec lung volumes; normal/slightly high FEV1/FVC; right shift of flow-volume curve
Describe how pressure-volume curves are performed and assist in the interpretation of abnormal PFTs (specifically in emphysema, asthma, obesity, and fibrotic lung disease); know definitions of compliance and elastance
- measure alveolar pressure in body box
- measure pleural pressure with catheters in pleural spalce or manometer in esophagus
- PV curve plots volume on y axis and Ptp on x-axis so that slope is compliance
- changes in compliance change slope
- some can change PV relationship without changing compliance, so just a shift
Identify how bronchoprovocation testing may be helpful in evaluating suspected asthma including methacholine and exercise testing
- since asthma is intermittent, bronchoprovocation can induce a somewhat asthmatic state to test if asthma really exists
- would see an obstructive pattern that improves with a bronchodilator like a SABA like albuterol (>12% improvement in FEV1 or FVC and >200cc inc in vol of FEV1 or FVC)
- methacholine challenge: patient breathes in gradually greater concentrations of methacholine/histamine which induces bronchoconstriction
- in asthmatic, the concentration required to reduce airflow by 20% is a lot lower that healthy people
What is FRC?
- functional residual capacity
- sum of RV and ERV
- gas in lung at the end of normal exhalation
- point where respiratory system (lung and chest wall) are in equilibrium
What does a significant difference between VC and FVC indicate?
- dynamic airway collapse
What is the difference between intrathoracic and extrathoracic airway resistance?
- intrathoracic: airway is held open during inspiration by negative pleural pressure and closed during expiration
- extrathoracic: trachea is subjected to atmospheric pressure; negative intraluminal pressure during inspiration causes narrowing; airway opens up during expiration
What can inc DLCO?
Inc DLCO:
- polycythemia
- early CHF
- asthma
- alveolar hemorrhage
- things that inc blood in lung
What can dec DLCO?
Dec DLCO:
- emphysema
- pulm vascular disease
- interstitial lung disease
- anemia
What can affect muscle strength and how do you test/measure for it?
1) motorneuron diseases (myasthenia gravis, botulism)
2) diseases of neuronal axon (GBS)
3) diseases of nerve roots in anterior horn of spinal cord (polio, ALS)
- Pimax: inspire forcefully against resistance
- Pemax: expire forcefully against resistance
Define the components of a pulm physical exam
1) inspection
- resp distress
- accessory muscles
- pursed lip
- cyanosis
- body habitus
2) palpation
- areas of tenderness
- tactile fremitus (dec=emphysema, pneumothorax, pleural effusion, atelectasis; inc=consolidation)
- trachea deviation (pushed away from large pleural effusions, large tension pneumothorax; pulled toward volume loss due to scarring, fibrosis, or atelectasis)
3) percussion
- dullness when fluid or solid tissue (pleural effusions, pneumonia, atelectasis)
- resonant when air (pneumothorax, emphysema)
- diaphragmatic excursion
4) auscultation
- normal (vesicular: soft, low pitched, throughout chest, continuous; bronchovesicular: moderate pitch/intensity, over bronchi, gap b/w insp and exp; bronchial: high pitched and over trachea)
- abnormal (crackles/rales: heard during inspiration, alveoli popping open, pulm edema, pneumonia, interstitial lung disease; rhonchi: rumbling, continuous, passage of air through partially obstructed pathway due to mucus; wheeze: continuous high pitched during insp/exp, narrowed airway, diffuse = asthma or bronchiolitis, local = focal obstruction; egophony: E to A over areas of fluid; stridor: upper airway, insp = laryngeal pathology, exp = central airway obstruction within thorax/trachea
Differentiate between deadspace, shunt, and V/Q mismatch
Deadspace:
- ventilated, but no perfusion (emphysema, PAH, thromboembolism)
Shunt:
- perfused, but no ventilation (HF, pneumonia, ARD)
V/Q mismatch:
- airway diseases that affect regional resistance (bronchitis, asthma)
List the major causes of increased deadspace including how different patterns of ventilation can influence the amount of dead space
- deadspace –> wasted ventilation –> dec in PaO2 and CO2 removal
- excess ventilation (inc V)
- hypovolemia, HF, PE (dec Q)
- rapid shallow breathing (gas is staying only in airways)
- acute PE, dec CO, acute pulm HTN (dec Q)
- positive pressure from ventilators (inc V)
- alveolar septal destruction (dec Q)
List the major causes of low V/Q and shunt
- perfusion, but no ventilation (low V/Q)
- caused by atrial/ventricular septal defects, pneumonia
- congenital heart disease, pulm fistula, vascular lung tumor
- acute atelectasis, alveolar fluid, consolidation (pneumonia)
- hypoventilation
Define the five causes of hypoxemia
- low PAO2
1) low PiO2 (altitude)
2) hypoventilation
3) V/Q mismatch (pneumonia, COPD, asthma)
4) shunt
5) diffusion limitations (ARDS)
Why doesn’t a shunt cause a raised PaCO2?
- because even though there is decreased/no ventilation, inc PaCO2 is sensed by central chemoreceptors and increases ventilation
How do you tell the difference between shunt and V/Q mismatch?
- administer 100% O2
- shunt –> does not inc PaO2
- V/Q mismatch –> does inc PaO2 because some ventilation to saturate Hbs