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
What is needed in a complete assessment of arterial oxygenation status?
1) PaO2
2) SaO2
3) A-a gradient
4) CaO2
Identify the major types of lung diseases manifest by airflow obstruction and their anatomic correlation (bronchus vs. bronchioles)
- asthma, bronchiectasis, bronchitis, bronchiolitis, COPD, cystic fibrosis, upper airway obstruction
- emphysema: alveolar septa degradation
- bronchitis: inflammation of airways/bronchi
- asthma: inc in smooth muscle tone and airway inflammation
Describe the major clinical, physiologic, and pathologic components of obstructive diseases
- common symptoms: cough, wheeze, breathlessness
Describe how the function of the diaphragm is impaired in obstructive lung diseases and how this further contributes to decreased airflow
- hyperinflation in obstructive airway diseases to dec resistance/open airways
- this flattens the diaphragm and makes its length shorter
- muscles work less optimally at shorter lengths
Identify how bronchoprovocation testing may be helpful in evaluating suspected asthma (including methacholine and exercise testing)
- asthma is recurrent so we induce airway obstruction with methacholine or histamine
- the conc required to lower airflow by 20% is a lot lower for asthmatics than healthy people
Describe the major components of asthma and corresponding treatments
- primary an inflammatory disorder
- chronic inflam –> wheezing, SOB, chest tightness, coughing that is recurrent
- type 1 asthma: hypersensitivity due to outside agent (extrinsic)
- type 2 asthma: non-immune; viral infection, cold, irritation, stress, exercise (intrinsic)
- persistent airway inflammation of medium sized bronchi mainly
- mast cells release histamine, LTs, and PGs –> bronchoconst
- eosinophils release epithelial damaging protein
- T cells, dendritic cells, macrophages, and neutrophils
- inc in airway smooth muscle tone –> airway narrowing
- airway narrowing –> air trapping, inc FRC, and hyperinflation –> inc in work of breathing on diaphragm
What are treatments for asthma?
Reduce airway inflammation:
- inhaled corticosteroids
- mast cell stabilizer
- LT inhibitor
- anti IgE therapy
Reduce bronchoconstriction
- short acting beta agonists (albuterol)
- anticholinergic
- LT inhibitor
What are the categories of severity for asthma?
- intermittent: symptoms 2x/week, 2wake/month
- moderate persistent: daily symptoms, >1 wake/week
- severe persistent: continual symptoms, nightly wake up
What is chronic bronchitis?
- productive cough present for three months/year over a two year period without another medical cause
- pursed lips, tripodding
- hypertrophied submucosal glands
- inc goblet cell
- squamous metaplasia
- smooth muscle inc
- narrow lumen –> dec airflow
- disease of the airways
- NOT really reversible
- see normal DLCO
What is emphysema?
- characterized by abnormal, permanent enlargement of air spaces distal to terminal bronchioles
- destruction of alveolar septal walls without fibrosis
- NOT reversible and NOT disease of airway
- obstruction due to airway collapse during expiration
- centriacinar emphysema: starts in resp bronchiole; scarring –> enlarged air spaces
- panacinar emphysema: alpha1 antitypsin deficiency; involves entire respiratory bronchiole to the alveoli
- dec breath sounds, hyper-resonant
- see dec DLCO
How is the severity of COPD categorized?
GOLD classification:
- GOLD I: mild COPD; FEV1/FVC80%
- GOLD II: moderate COPD; FEV1/FVC
How do you treat COPD?
- relieve symptoms and dec severity/freq of exacerbations
- anticholinergics, beta agonists to dec smooth muscle tone
- corticosteroids to dec inflammation
- these don’t help in pure emphysema but there is usually an overlap with bronchitis
What is bronchiectasis?
- abnormal dilation of proximal medium-sized bronchi due to destruction of muscular and elastic components of their walls
- bacterial infection leading to inflam and sputum production leading to airflow obstruction
- impaired tracheobronchial clearance
- caused by pulm infection damaging airway epithelium; bronchial obstruction; lack of mucociliary clearance; immunodeficiencies
- treat with treatment of underlying condition; prevent exacerbations; chest physical therapy
What is cystic fibrosis?
- mutation leading to dysfunctional CL transport across epithelial surfaces affecting lung and pancreas
- recurrent infections
- recruit neutrophils into lung –> widespread inflammation and destruction of airway
- airflow obstruction with hyperinflation
- treat with CFTR modulators; ABx for infections; bronchodilators; nebulized hypertonic saline for hydration
What is bronchiolitis?
- inflammation of bronchiole membrane
- begins as viral and then fever, cough, dyspnea in children
- in adults, usually not infectious
- inspiratory squeak
What happens in vocal cord dysfuntcion/upper airway obstruction?
- inappropriate vocal cord motion
- mimics asthma
- inspiratory stridor
- flattened inspiration
- fiberoptic laryngoscopy
- anxiolytics for acute
- speech therapy for chronic
Discuss the role of the available medications used to either relieve (quick-relief agents) or prevent (long-term control meds) symptoms of obstructive lung disease
- reduce freq and intensity of asthma symptoms: dec cough, chest tightness, dyspnea
- prevent exacerbations
- SABA –> low does ICS –> low dose ICS + LABA –> medium dose ICS + LABA –> high dose ICS + LABA –> high dose ICS + LABA + oral corticosteroid
Identify the management principles for chronic obstructive pulmonary disease
- reduce smooth muscle tone w/ beta adrenergic agonists or anticholinergic
- dec airway inflammation with corticosteroids
- stop smoking; O2; rehab
Describe the major functions of the pulmonary circulation
- deliver blood under low pressure to microcirculation of lung for CO2 and O2 exchange
- low resistance high volume vascular bed for gas exchange
- two major functions: 1) gas exchange and 2) water/solute balance in lung
Describe the major determinants of blood flow distribution in the lung
- inc CO = dec resistance by 1) high distensibility of perfused vessels and 2) recruiting previously underperfused vessels
Define the three physiologic zones of the lung
West zones:
1) PA>Pa>Pv: alveolar pressure is greater than arterial pressure, so blood flow is dec; usually in apex of lung
2) Pa>PA>Pv: arterial is greater than alveolar; flow greater than zone 1
3) Pa>Pv>PA: arterial and vein are greater than alveoli; greatest blood flow
Explain determinants of water and solute balance in the lung and types of pulmonary edema
- pulm edema is accumulation of excess water in interstitial space and alveoli
- balance between hydrostatic and oncotic pressures
Define pulm HTN and its causes
- PH is characterized by an inc in pulm arterial pressure due to inc resistance to blood flow through lungs
- normal PA pressuers is 25/10; mean 15
- mean PA pressure >25 is PH
- PA pressure can be elevated by inc in CO, PVR, Pleftatrium
Recognize the Dana-Point classification of pulm HTN
1) PAH:
- idiopathic
- heritable
- drugs/toxins
- CT disease
- portal HTN
2) PH due to left heart disease
- LV dysfunction
- congenital heart disease
3) PH due to lung disease/hypoxia
- COPD
- interstitial lung disease
4) chronic thromboembolic PH
5) miscellaneous
- hemolytic anemia
- sarcoidosis
- pulm histiocytosis
- systemic disorders
- metabolic disorders
Describe the clinical presentation, diagnostic evaluation and treatment of acute PE
- risk factors: DVTs due to stasis, endo damage, hypercoaguability
- diagnose with duplex ultrasound
- dec compressibility
- PE occurs –> inc in pulm vascular resistance –> acute hypoxemia or RV failure
- chest xrays are usually normal but may see atelectasis or pleural effusion or wedge shaped infarct (hamptons hump)
- EKG shows S1Q3T3
- inc A-a gradient
- inc D dimer
- gold standard is pulm angiography, but use CT scans more or VQ imaging
Describe the therapeutic treatment options for PAH
- PA vasodilators
targets are:
1) endothelin pathway:
- potent vasoconstrictor
- endothelin receptor antagonists –> vasodilation
2) NO pathway:
- potent vasodilator
- stimulate pathway
- phosphodiesterase inhibitors so cGMP last longer and more vasodilation
3) prostacyclin pathway:
- potent vasodilators
4) Ca channel blockers:
- block Ca channels in arterial beds –> vasorelaxation
How does the lung act against pulmonary edema?
- dec in interstitial oncotic pressure: fluid left during hydrostatic pressure decreases interstitial oncotic pressure, so more fluid leaks back out
- inc interstirial hydrostatic pressure: more fluid outside vessel resists fluid flow out of vessel
- inc in plasma oncotic pressure: extreme; albumin conc increased
- lymphatics:
Primary vascular disorders (WHO Group 1)
- pre-capillary PH
- purely a blood vessel issue
- no pulm edema or parenchymal lung disease
- low DLCO with normal PFTs
PH associated with lung diseases/hypoxia (WHO Group 3)
- parenchymal/pleural disease leading to PH
- emphysema (chronic hypoxia and obliteration of capillaries)
- interstitial lung disease (IPF, sarcoidosis, asbestos)
- impaired ventilation –> resultant hypoxemia –> hypoxic vasoconstriction
- DLCO dec proportionately with FEV1 and FVC
- alveolar hypoventilation caused by neuromuscular disease, obesity, etc. –> low PO2 –> vasoconstriction
How do you distinguish between pre and post capillary PH?
- pre capillary will NOT result in edema because before capillaries
- post capillary WILL result in edema because downstream from capillaries
Define the primary physiologic abnormalities in restrictive lung disease
- compliance of lung is dec; airway resistance is dec
- rest disease inc elastic work to distend lung
Describe the general mechanism that leads to restrictive physiology (i.e. disease and/or processes)
1) inc thickness of lung interstitium
- chronic interstitial lung disease
- injury –> fibroblast production of collagen and elastin
2) inc lung water
- CHF –> pulm edema
3) inc alveolar surface tension
- collapse of alveoli; harder to inflate –> dec compliance
- pulm edema can inc ST
- ARDS: causes dysfunctional surfactant due to injury to type 2 pneumocytes
Determine how PFTs can distinguish between inc lung elastic recoil vs. inc chest wall resistance (i.e. differentiate between restrictive physiology and restrictive lung disease)
- TLC, FRC, RV all dec in rest lung disease
- PV curve shifts right/down; lower slope if compliance dec
- airflows normal/higher than expected
- dec DLCO if interstitial effects from dec lung vol and dec alveolar surface area and dec diffusion due to inc thickness; if really a diffusion problem then doesn’t correct with DLCO/VA
- chest wall resistance does not change compliance, so PV curve doesn’t change slope; also see a corrected DLCO/VA
Determine how PFTs are interpreted in patients with mixed obstructive/restrictive lung disease
- e.g. obese patient with asthma; pulm fibrosis and emphysema
- dec in TLC or FRC (restrictive) with a dec FEV1/FRC (obstructive) and also markedly dec DLCO
Describe the diagnostic approach to interstitial lung diseases and review basic differences between different forms of ILD
Etiology:
- idiopathic
- autoimmune
- exposure to inorganic dusts (asbestos, silica)
- exposure to organic molecules (hypersensitivity pneumonitis)
- drug effect
Presentation:
- insidious onset of dyspnea on exertion
- nonproductive cough
- restrictive PFTs; dec DLCO
Treatment:
- immunosuppression
- remove inciting drugs/exposures
What happens in sarcoidosis?
- presents before 40yo
- systemic granulomatous disease
- noncaseating granulomas
- african american 3x more likely
- granulomas are macrophages combining to form multinucleated giant cells that are surrounded by lymphocytes
- pulm findings: bilateral hilar lymphadenopathy; interstitial infiltrates/nodules; pulm fibrosis
- lungs, eyes, skin affected
What happens in idiopathic pulm fibrosis?
- scarring lung disease with usual interstitial pneumonia
- older patients
- tobacco use
- cough, DOE, fatigue
- crackles in base of lungs
imaging:
- peripheral/basial reticulation
- traction bronchiectasis
- honeycombing
- *paucity of ground glass
pathology:
- heterogeneous fibrosis
What happens in nonspecific interstitial pneumonia?
- collagen vascular disease related sometimes (RA, sjogrens, scleroderma)
- younger, female
- responds to anti-inflammatory treatment
- better prognosis than UIP/IPF
- DOE, cough, crackles
imaging:
- base reticulation; volume loss; *ground glass opacity
pathology:
- homogeneous fibrosis; varying degrees of inflam and fibrosis
What happens in smoking related ILD?
- respiratory bronchiolitis (airway thickening; dusty brown macrophages)
- desquamative interstitial pneumonia (more severe but on spectrum of RB; ground glass, basilar; dusty brown macrophages)
- pulm langerhans cell histiocytosis (young smokers, spontaneous pneumothorax; cysts/nodules, upper lobes)
What happens in organizing pneumonia?
- subacute to chronic
- noninfectious pneumonia
- bilateral peripheral alveolar opacities (fuzzy nodules)
- ground glass and consolidation on imaging
- intraluminal granulation tissue and fibrosis distal to bronchioles
- responds to steroids
What happens in eosinophilic pneumonia?
acute:
- mimics ARDS
- results in acute resp failure
- diffuse bilateral alveolar infiltrates
- septal eosinophilic infiltrates
- steroids
chronic:
- subacute onset
- nonsmokers and women
- assoc with asthma
- steroids
- peripheral eosinophilia, fibrosis, macrophages
What happens in lymphangioleiomyomatosis (LAM)?
- cystic lung disease
- young women
- peribronchovascular proliferation of smooth muscle cells
- lymphatic occlusion
- obstructive pattern
- pleural effusion and spontaneous pneumothorax
Identify the pulmonary manifestations associated with various systemic diseases
anatomic differential:
- airways
- alveoli
- interstitium
- vascular
- pleura
- chest wall
- extrathoracic
ALS:
- muscle weakness –> dysphagia, aspiraton, inadequation ventilation/hypoventilation, weak cough
- CXR inflitrates
- restr PFTs
- dec FEV1, FVC, TLC
- normal FRC, FEV1/FVC
- dec MIP, MEP
- hypecarbia
- treat with CPAP
RA:
- pleural disease, pneumothorax, pneumonia, ILD, nodules, PAH, vasculitis
- restr PFTs
- dec DLCO
Goodpasture’s:
- antibody to BM in lungs
- hemoptysis
- dec urinary urgency
- test for antibody in blood
- acute renal failure
- patchy alv infiltrates
- restr PFTs
- inc DLCO (inc blood in alveoli)
- treat with IS
IBD:
- obst: tracheobronchitis, subglottic stenosis, bronchiectasis, bronchiolitis
- restr: pleural effusion, ILD, PE, drugs, infections
- productive cough w/ sputum = bronchiectasis
- dilation of bronchi
- treat with steroids
Sickle cell:
- PE from BM infarct, fat emboli, infarct from in-situ thrombosis, hypoventilation, pulm edema, PH
- fever, cough, tachypnea, chest pain, SOB
- bilateral diffuse alveolar infiltrates
- treat with antibiotics, O2, transfusion, support
HIV:
- infection (pneumonia due to bacteria, fungus, virus; TB; parasite)
- non-infection (Kaposi’s, NHL, lung cancer, emphysema, ILD)
- CD4 count is predictive
- treat underlying cause and manage HIV
Describe the approach to formulating a DDx and clinical decision making
VINDICATE:
- Vascular
- Inflammatory
- Neoplasm
- Degenerative/deficiency
- Idiopathic/intoxication
- Congenital
- Autoimmune/allergic
- Traumatic
- Endocrine
VITAMINC
- Vascular
- Infection/inflammatory
- Trauma
- Autoimmune
- Metabolic
- Idiopathic/iatrogenic
- Neoplastic
- Congenital
Recognize the components of the airways and the types of bronchitis and bronchiolitis
- bronchi have cartilage, smooth muscle, and mucus glands
- bronchi epithelium have ciliated columnar cells and goblet cells
- bronchioles do not have cartilage
Bronchitis:
- acute: neutrophils in airway lumen and infiltrate wall; infectious
- chronic: lymphocytes; squamous metaplasia; mucus gland hypertrophy
Bronchiolitis:
- chronic: inflammation in walls that don’t have cartilage; lymphocytes predominate from infection or AI disease
- follicular bronchiolitis: lymphoid aggregates with germinal centers
- constrictive/obliterative bronchiolitis: fibrosis/inflam between mucosa and smooth muscle squeezes airway shut; mosaic airtrapping
- granulomatous bronchiolitis: granulomas composed of histiocytes and multinucleated giant cells; necrotizing (infection) or not (infection, sarcoid, beryllium)
Identify the main histologic changes that are associated with asthma
- thickened subbasal lamina (pink band under epithelium)
- eosinophilic inflammation (under subbasal lamina)
- mucus hypersecretion
- smooth muscle hyperplasia
Contrast and compare between acute, aspiration, eosinophilic, and organizing pneumonia
Acute pneumonia:
- neutrophils, macrophages, fibrin in airspaces
- infectious
Aspiration pneumonia:
- artifact on histology
- foreign material in multinuc giant cell
Eosinophilic pneumonia:
- eosinophils, macrophages, fibrin in airspaces
Organizing pneumonia:
- loose myxoid fibroblastic tissue plugs airways
- patchy and densely consolidated areas
- intermixed pink fibrin
Identify the main forms of smoking related lung disease
Respiratory bronchiolitis:
- brown pigmented macrophages in airspaces near bronchioles; block airways
Desquamative Interstitial Pneumonia:
- pigmented macrophages in all airspaces (similar to RB but everywhere; on a spectrum)
Differentiate emphysema related to smoking from emphysema secondary to alpha1 antitrypsin deficiency
general:
- enlarged airspaces
- broken septa with knobby ends
- smoking related emphysema is worse in upper lobes and around bronchioles/airways (centrilobular emphysema); “smoke rises”
- alpha1 antitrypsin def related emphysema is worse in lower lobes and NOT worse around airways but equally bad everywhere
Recognize the main histologic features of acute lung injury/diffuse alveolar damage
DAD:
- hyaline membranes (fibrin ribbons in airspaces lining septa)
- alveolar septa expanded by inflammation and fibroblastic tissue
- histology corresponds to ARDS
Identify the most common patterns of interstitial lung disease: UIP, NSIP, HP
UIP:
- patchy, heterogeneous fibrosis of septa
- fibroblastic foci (compact fibroblasts and myxoid stroma bulging into airspaces); OP in airspace, but for UIP in interstitium
- honeycombing cystic change (lung remodeling with mucus filled cysts; worse in lower lobes)
NSIP:
- uniform homogeneous inflammation, fibrosis, or both
- few fibroblastic foci
- little honeycombing
HP:
- airway centered chronic inflammation (lymphocytes and histiocytes)
- nonnecrotizing granulomas w/ multinuc giant cells
- focal organizing pneumonia
- variable fibrosis
- response to foreign antigens (bird, mold, hot tub bacteria, etc.)
Recognize the histologic features seen in patients with pulm HTN and thromboembolic disease
Thromboembolic disease:
- organizing fibrin clots in pulm arteries
- may form in situ or embolise
- talc embolism: polarized crystals around vessels; maybe multinuc giant cells; IV drug use
Pulm HTN:
- muscular hypertrophy of pulm arteries
- muscularization of arterioles
- plexiform lesions (endo and SM cells with slits)
Identify the main types of benign nodular processes in the lung: granulomas and pulmonary Langerhan’s cell histiocytosis
Pulm Langerhan’s Cell Histiocytosis/Eosinophilic granuloma:
- langerhan’s histiocytes
- variable inflammation including eosinophils
- fibrotic; stellate scar around airway
- smoking related
Recognize the appearance of neoplastic tumors in the lung and discuss how they are different from inflammatory nodules
Carcinoid:
- nests of neuroendocrine cells with powdery salt and pepper chromatin
Small cell carcinoma:
- small, blue, easily-crushed cells with little cytoplasm
- stains positive for neuroendocrine markers
- high mitotic rate and lots of necrosis
Squamous cell carcinoma:
- large cells with dark nuclei and lots of cytoplasm
- keratinizing and keratin pearls
Adenocarcinoma:
- cells with large nuclei
- glandlike structures
Large cell carcinoma:
- large, bizarre shaped, malignant cells that lack typical features of other cancers
Differentiate between acute and chronic bronchitis
Bronchitis:
- acute: neutrophils in airway lumen and infiltrate wall; infectious
- chronic: lymphocytes; squamous metaplasia; mucus gland hypertrophy
What is seen in bronchiectasis?
- often the consequence of chronic infections
- airway is dilated a lot compared to artery
Differentiate between the different types of bronchiolitis
Bronchiolitis:
- chronic: inflammation in walls that don’t have cartilage; lymphocytes predominate from infection or AI disease
- follicular bronchiolitis: lymphoid aggregates with germinal centers
- constrictive/obliterative bronchiolitis: fibrosis/inflam between mucosa and smooth muscle squeezes airway shut; mosaic airtrapping
- granulomatous bronchiolitis: granulomas composed of histiocytes and multinucleated giant cells; necrotizing (infection) or not (infection, sarcoid, beryllium)
What are the histologic features of diffuse alveolar hemorrhage?
- blood and iron containing macrophages in airspaces
- alveolar septa thickened by inflammation and fibroblasts
- assoc with neutrophils attacking capillaries
What are the histiologic features of pulmonary alveolar proteinosis?
- airspaces filled by pink fluid and macrophages; fluid tends to crack
What are the histiologic findings in vasculitis?
- inflammation in vessel wall
- alveolar hemorrhage
- AI or infection
What are the histiologic findings in sarcoid/chronic beryllium disease?
- nonnecrotizing granulomas
- concentric collagen deposition
- lymphatic distribution (near vessels, airways, pleura)
Identify the anatomic relationships of the CV, resp, endocrine, and GI systems within the mediastinum and the compartments of the mediastinum
Anterior
- thymus gland
- aortic root/great vessels
- substernal thyroid and parathyroid tissue
- lymphatic vessels and nodes
- inferior trachea and esophagus
Middle
- pericardial sac
- heart
- innominate veins and SVC
- hila
- lymph nodes
- phrenic, upper vagus, and recurrent laryngeal nerves
Posterior
- esophagus
- descending aorta
- azygos, hemiazygos veins
- thoracic duct
- lymph nodes
- lower vagus nerve
- sympathetic chains
Define the major symptoms and clinical syndromes associated with mediastinal diseases and how they relate to the mediastinal compartment
symptoms assoc w/ obstruction of contiguous organs
- dysphagia, hoarseness
- UE swelling
- cough, stridor, hemoptysis, SOB
B symptoms
- fevers
- weight loss
- night sweats
List the types of masses found in the mediastinum including frequency and clinical evaluation of these masses
asymptomatic or symptomatic
- local symptoms: compression of adjacent structures
- systemic symptoms: fever, anorexia, weight loss, endocrine, AI
benign or malignant
- 80% of asymptomatic masses are benign
- 50% of symptomatic masses are malignant
List the diagnostic procedures used to evaluate abnormalities of the pleural space
DDx by location
DDx by age:
- adults: 65% anterior
- children 65% posterior
Identify the difference between transudative and exudative pleural effusions
- transudative: alteration in hydrostatic forces; CHF, cirrhosis
- exudative: alterations in permeability of pleura and protein concentration changes; viral, bacterial infection; neoplasm; PE; GI
- dyspnea, chest pain, cough
- dec breath sounds, dull percussion, dec fremitus
- Light’s criteria:
- LDHpl/LDHser transudate
- LDHpl/LDHser >0.6 AND protpl/protser >0.5 –> exudate
List the types of tumors found in the pleural space
- lung, breast, lymphoma, GI, GU
What masses are found in the anterior mediastinal compartment?
4 Terrible Ts
- thymic neoplasm
- teratoma (germ cell tumor)
- (terrible) lymphoma (H, NH)
- thyroid neoplasm
- mesenchymal neoplasm
- diaphragmatic hernia
- primary carcinoma
What masses are found in the middle mediastinal compartment?
- LAD (reactive and granulomatous inflam)
- lymphoma
- cysts
- metastasis
- lymphoma
- pericardial cyst
- vascular enlargements
- diaphragmatic hernia
What masses are found in the posterior mediastinal compartment?
- neurogenic tumors (peripheral nerve, sympathetic ganglia, paragang tissue)
- meningocele
- esophageal lesions (carcinoma, diverticuli)
- diaphragmatic hernia
What happens in tension pneumothorax?
- intrapleural pressure > atmospheric pressure throughout expiration and often during inspiration
- *air in pleural space under a lot of pressure (ventilator, lung puncture during IJ cath placement)
- dec venous resturn and dec CO
- tachycardia, hypotension, cyanosis, resp distress
- treat with angiocath in 2nd intercostal space; place chest tube
What happens in superior vena cava syndrome?
- malignant obstruction of SVC
- dilated veins in neck and head
- edema of face
- headache, vision changes
- treat with steroids and standard oncology care
What lab findings are used for mediastinal diseases?
- Labs: beta HCG, alpha-fetoprotein (neoplasm)
- Imaging: CXR, CT, MRI, US
- Tissue: needle aspiration
- Surgical biopsy: mediastinoscopy
What happens in pneumothorax?
- air in pleural space
- spontaneous
- traumatic
- chest pain and dyspnea
- hyper resonance, dec breath sounds, dec fremitus
- chest xray/CT confirm
- treat with supplemental O2, simple aspiration, tube thoracostomy
Outline how to counsel patients on the health benefits of quitting and initiate effective treatment interventions to aid patients in smoking cessation efforts
Ask - identify all tobacco users at every visit
Advise - strongly advise all patients to quit; clear strong and personalized advice;
Assess - how willing is a patient to quit and how dependent are they on tobacco now? do they want to quit?
Assist - counseling and pharmacotherapy
Arrange - follow up and prevent relapse
What are pharmacotherapy options for smoking cessation?
- nicotine replacement
- bupropion (dec reuptake of dopamine –> dec cravings)
- varenicline (partial agonist at nicotine receptor)
- cytisine
Tobacco statistics
- 500k die each year from tobacco related causes in US
- 6million in world
- high relation with mental illness
- affects those with least info and least access to cessation
- 40million smokers in US
Define and discuss the features of pneumonia
- infection of lung parenchyma (alveoli) and accumulation of abnormal alveolar filling with fluid of lung tissue (bacterial, fungal, viral) –> purulence that fills alveoli
- CAP: infection acquired outside of hospitals
- HCAP: recently been hospitalized w/in 90 days; nursing home; chemotherapy; wound care w/in 30 days
- HAP: pneumonia that occurs 48hrs or more after hospital admission that was not present at time of admission
- VAP: occurs 48hr or more after endotracheal intubation
Describe the pathogenesis of pneumonia
- *inhalation of infectious particles (CAP: legionella, m. tuberculosis)
- aspiration of oropharyngeal or gastric contents
- hematogenous spread
- infection from adjacent or contiguous structures
- direct inoculation
- reactivation (TB)
- occurs when immune system is compromised
Discuss pneumonia classifications or types
- CAP: infection acquired outside of hospitals; 14days before
- HCAP: recently been hospitalized w/in 90 days; nursing home; chemotherapy; wound care w/in 30 days
- HAP: pneumonia that occurs 48hrs or more after hospital admission that was not present at time of admission
- VAP: occurs 48hr or more after endotracheal intubation
Discuss a differential diagnosis of pneumonia
- Age: elderly more common
- Presentation: acute, subacute, chronic
- Personal factors: smoking, alcohol/drug, HIV, occupational history, allergies
- Underlying CV/pulm disease
- clinical signs include fever, chills, pleuritic chest pain, dyspnea, productive cough; sometimes N/V/D, mental status changes
- on exam: febrile, tachypnic, tachycardic; crackles, rhonchi; egophony and dullness to percussion if consolidation
- gold standard is CXR with appropriate clinical and microbiological features; findings include lobar consolidation, interstitial infiltrates, cavitation
- DDx: organizing pneumonia, bronchiectasis, bronchopulm sequestration, bronchocentric granulomatosis, alveolar hemorrhage* (renal involvement, hemoptysis, AI), eosinophilic lung disease* (really sick, give steroids), hypersensitivity pneumonitis, ARDS
Identify the main organisms associated with pneumonia types
- typical: s pneumoniae, h influenzae, s aureus, group A streptococci, etc.
- atypical: legionella, m pneumoniae, c pneumoniae, c psittaci
- cannot differentiate on xray; need culture or PCR
- CAP: s. pneumoniae*, h influenzae, s. aureus, GAS, anaerobes, aerobic gram negative, legionella, m pneumoniae, c pneumoniae
- HAP/VAP/HCAP: multidrug resistant pathogens (SPACE): serratia, pseudomonas, acinetobacter, citrobacter, enterobacter, e coli*; gram positive MRSA
Discuss the basics of pneumonia treatment
- once diagnosed, decided whether to admit or not
- focus antibiotic therapy after getting sputum sample but start with broad ABx
- most cases are fine with 7 days of antibiotics
- may need longer treatment for legionella, s aureua, pseudomonas due to tissue necrosis
- CAP: macrolide or doxycycline, resp fluoroquinolone, beta lactam+macrolide
- HAP/VAP/HCAP: antipseudomonal (cephalosporin, carbapenam+fluoroquinolone)
Influenza
- outbreaks
- headache, myalgia, weakness, URT/LRT involvement, N/V/D, runny nose, sore throat, fever, lethargy, cough,
- IFN A virus undergoes changes in antigenic characteristic of envelope glycoproteins
- transmission requires close contact
- diagnose with PCR from URT with nasal swab
- treat with neurominidase inhibitors (oseltamivir, zanamivir)
- complications include primary influenza pneumonia, secondary bacterial pneumonia, myositis/rhabdomyolysis, CNS and heart affected
Describe the pathophysiology of upper airway collapse
- high upper airway recruitment threshold; inc duration of obstructive events
- high loop gain; greater sensitivity to CO2 and O2 –> hyperventilation –> hypocapnia –> dec upper airway muscle tone
- low arousal threshold: frequent arousals –> hyperventilation –> hypocapnia –> dec upper airway muscle tone
Discuss the spectrum, epidemiology, and complications of sleep disordered breathing
- snoring
- upper airway resistance syndrome
- sleep apnea syndrome (85% obstructive)
- cheyne stokes respiration (greater hypercapneic respiratory drive –> overshooting PaCO2 below apneic threshold; greater sensitivity to CO2 results in hyperventilation; arousals occur at peak of ventilation)
Discuss the clinical features and diagnostic approach to obstructive sleep apnea syndrome
- high risk: obese, CHF, atrial fibrillation, diabetes
- PMH: chronic rhinitis, acromegaly, neuromuscular disorder
- FH: first degree relative with OSA
- SH: smoking, alcohol
- meds: sedatives, opioids
- symptoms: daytime sleepiness, snoring, gasping at night, nonrefreshing sleep, *attention deficit and hyperactivity in children
- sleep study/polysomnography
Describe the therapeutic approach to obstructive sleep apnea syndrome
- avoid sedatives, stop smoking
- reduce weight
- treat hypothyroidism if there
- CPAP
- tracheostomy for severe life-threatening OSA
- maxillomandibular adavancement
- uvulopalatopharyngoplasty
- tonsillectomy/adenoidectomy (effective in children with OSA)
Describe the epidemiology of lung cancer in the US, including risk factors for disease development
- ~90% of all lung cancer caused by tobacco
- 1 in 14 US will develop lung cancer
- 1 in 9 are smokers
- after 15yrs of cessation, CHD risk is similar to those who never smoked, but lung cancer risk never returns to normal
- obstructive disease/chronic bronchitis –> 4-5x more likely for lung cancer
List the characteristics of solitary pulmonary nodules and the goals of evaluation
- lesion 3 called a mass)
- round or oval and smooth
- surrounded by aerated lung
- no satellite lesions
- no atelectasis, pneumonitis, or adenopathy
- goals are to expedite resection of curable cancer; minimize resection of benign nodules
guidelines:
- look at all previous CXRs
- if stable for >2yrs, benign, then no evaluation need
- all resections include a lymph node dissection
Describe how to stage a subject with lung cancer and which broad treatment categories are applied to the various stages
Tumor size:
- T1a: tumor atelectasis
- T2b: 5-7cm
- T3: >7cm
- T4: more invasive
Lymph nodes:
- N0: no regional node metastases
- N1: metastases in ipsilateral hilar node
- N2: metastases in mediastinal lymphnodes
- N3: metastases to contraleteral hilar nodes
Metastases:
- M1a: primary tumor with nodules in lung
- M1b: distance metastases
Describe common genetic alterations in non small cell lung cancer and how these form the basis of targeted therapy
- mutations in epidermal growth factor (ERB1 or EGFR) in 50-80% of NSCLC; exons 19-21
- drugs designed: erlotinib, gefitinib, cetuiximab, afatinib
- mutation in ERGB2 Her2/neu; 10% of NSCLC; trastuzumab
- vEGF overexpressed; bevacizumab
- Ras mutations
Discuss the concepts of early detection, screening, and chemoprevention as they apply to lung cancer
- goals are to diagnose at early stage and dec mortality through CXR, sputum cytology, *spiral CT, and bronchosopy
- NNS to find 1 lung cancer = 320
- NNS to prevent one death = 219
- screening should be stopped when they have not smoked for 15yrs or develop a health problem the dec life expectancy
- chemoprevention: reverse, suppress, prevent carcinogenesis iwht drugs, but no clearcut ones for lung cancer right now
- Stage 1: smoking cessation
- Stage 2: identify highest risk groups
- Stage 3: presence of premalignant lesions with alterations
General info: Lung cancer
- highest death rate from cancer
- 90% of cases due to smoking (but only 10% of smoker develop cancer)
- symptoms: cough, anorexia, weakness, weight loss; paraneoplastic syndrome, especially small cell
- imaging: find a solitary pumonary nodule; chest film; tissue study; cytology; mediastinoscopy; metabolic tests
- treat by resection (except for small cell); radiation therapy
Squamous cell (NSCLC)
- 25-40% of cases
- strongly linked to smoking
- squamous metaplasia of major branches of bronchial tree (proximal)
- cytology: bright orange irregular cells
- histology: irregular nests and keratin pearls
- gross: ulcerated, mucosal roughening, erythema, white invasive tumor tissue around anthocotic lymph node
- ## surgical resection (+chemo)
Adenocarcinoma (NSCLC)
- 25-40% of cases
- most common type in women and nonsmokers
- peripheral; arise from scars; form glandlike structures
- surgical resection (+chemo)
Large cell (NSCLC)
- 10-15% of cases
- undifferntiated; high grade cancer; anaplastic appearing
- surgical resection (+chemo)
Small cell (oat cell)
- 20-25% of cases
- strongly linked to smoking
- aggressive and widely metastatic; bad prognosis
- no differentiaton
- cells are small and dark with little cytoplasm
- stain + for neuroendocrine markers (NCAM and TTF1 stains)
- treat with chemo only
Screening for lung cancer
- sputum cytology not predictive
- CXR dec fatality, not mortality
- CT better than CXR at dec mortality (NNT = 320)
- lead time bias
- chemoprevention showed no benefit or inc risk
Staging
T = primary tumor size (T0-T4) N = lymph nodes affected (N0-N3) M = metastases (M0-M1b)
Describe the major anatomical and functional relationships of the upper airway
- sinuses, oral cavity, lungs
- 5 layers covering vocal folds: epithelium (ciliated cells move mucus from trachea to postglottis), superficial lamina propria, intermediate lamina propria, deep lamina propria, vocalis muscle
- trachea, bronchi, lungs, thorax
- abdomen supports mechanism and expiratory force
- diaphragm aids in inspiratory force
- infrahyoid and suprahyoid muscles
- thyroid, cricoid, arytenoid cartilages
- vagus nerve, superior laryngeal nerve, recurrent laryngeal nerve (all intrinsic muscle but CT)
Define how the complex of symptoms called hoarseness is characterized and evaluated
- abnormal voice changes, breathy, raspy, strained, weak
- **viral laryngitis - acute
- *reflux - chronic
- vocal abuse, allergies, cough, nodules
- see a doctor if hoarse for >2-3wks or if associate with pain, hemoptysis, dysphagia, lump in neck
Causes of stridor
- inspiratory: supraglottic, extrathoracic
- expiratory: tracheal, large bronchi intrathoracic
- biphasic: laryngeal, immediate subglottis
Voice abnormalities
- hoarseness: abnormal voice changes, breathy, raspy, strained, weak
- dysphonia: change in voice quality
- dysarthria: defect in articulation
- stridor: indicates obstruction
- stertor: snoring sound
- wheezing
Describe vocal nodules, vocal fold cysts, and vocal fold polyps
Vocal nodules:
- symmetric development of calluses from overuse
- voice therapy treatment
Vocal fold cysts:
- trauma, previous injury
- treat with voice therapy, surgery
Vocal fold polyps:
- trauma, predisposition
- hemorrhagic vs. fibrotic
- treat with surgery or self-resolve
Describe granulomas, Reinke’s edema, and vocal fold hemorrhage
Granulomas:
- reflex, vocal abuse
- treat underlying etiology
- surgery/botox
Reinke’s edema:
- smoker
- edema, erythema
- correct cause, surgery
Vocal fold hemorrhage
- trauma
- strict voice test
Describe vocal fold tear, sulcuses/webs, and presbyphonia and vocal fold bowing
Vocal fold tear:
- hemorrhage/trauma or intubation
- strict voice test
Sulcuses/webs
- grooves/fusion of vocal folds
- asymptomatic maybe
- possible surgery
- congenital/traumatic
Presbyphonia/vocal fold bowing:
- degrading of vocal fold with age
- superior laryngeal nerve paralysis
- inc vocal fold bulk with therapy surgery,
Describe laryngeal trauma, immobile vocal fold, and laryngopharyngeal reflux
Laryngeal trauma:
- skeleton injuries, arytenoid dislocations
- quick diagnosis is important
Immobile vocal fold:
- occurs with dislocation, RA, polychondritis
- CT scan of skull base; laryngeal EMG
- Laryngopharyngeal reflux:
- escape of acids from stomach into esophagus through sphincter
- hoarseness, cough, tracheal stenosis; bad breath, bitter taste in morning, horaseness in morning or after meals; +/- heartburn
Describe precancerous/cancerous lesions, papillomas, and leukoplasia
(Pre)cancerous lesions
- smokers/drinkers
- stage and type important
- chemoreadiation; larynectomy
Papillomas:
- adult vs juvenile onset
- viral, lifelong disease
- can become cancer
Leukoplasia
- keratotic white plaques on vocal cords
Describe the function and physiological mechanisms of cough
- clears pathogens, particulates, foreign bodies from airways and larynx/pharynx
- vagus nerve has rapidly adapting receptors, slow adapting stretch receptors, and C-fibers that are sensitive to mech stimuli (bronchial obstruction and lung inflation) and noxious chemical stimuli
- 1) inspiratory phase: inhale then glottis closes
- 2) compressive phase: thoracic and ab muscle contract against fixed diaphragm (like valsalva) and inc intrathoracic pressure
- 3) expiratory phase: glottis opens and air is epelled
- 4) relaxation phase: chest wall and ab muscles relax
- impaired cough caused by anesthesia, sedation, intoxication, neuromuscual diseases
Classify cough according to its duration (acute, subacute, chronic)
Acute cough:
- 8wks duration
Identify the most common causes of acute and chronic cough in adults
acute:
- life-threatening or not? (pneumonia, COPD/asthma exacerbation, PE, HF)
- non -life threatening:
- -URT infection/common cold; virus induced post nasal drainage irritates larynx
- -LRT infection/acute bronchitis; usually viral
- -asthma or COPD exacerbation
- -environmental exposures to allergens and irritants
chronic:
- immunocompetent adult with normal CXR –> UACS, asthma, GERD, NAEB
Discuss the role of ABx in the treatment of acute cough
- usually not viral so avoid ABx usage if URT infection; occasionally LRT infection is bacterial
Identify the symptoms, signs, and empiric treatment for the 4 most common causes of chronic cough in adults (UACS, asthma, GERD, NAEB)
UACS
- postnasal drip syndrome
- stimulation of upper airway cough recetors by seretions from nose/paranasal sinuses
- tickle in throat; hoarseness; nasal congestion
- cobblestone appearance of oropharyngeal mucosa, mucus in nasal passage
- treat with 1st gen antihistamine for >2wks
Asthma:
- chronic inflammatory airway disorder
- stimulate cough receptors by inflammatory mediators, mucus, bronchoconstriction
- symptoms are intermittent wheezing, dyspnea, cough
- signs are bilateral expiratory wheezing, but intermittent
- diagnose with PFT and >12%/200ml inc in FEV1 after albuterol or methacholine test
- treat with bronchodilatory and inhaled corticosteroid for >8wks
GERD:
- backflow of stomach contents into esophagus
- irritate URT/LRT or esophageal bronchial cough reflex
- symptoms are cough, w/(o) phlegm; heartburn; hoarseness
- diagnose with 24hr esophageal pH monitoring
- treat with proton pump inhibitor for >2mos and diet /lifestyle changes
NAEB:
- nonasthmatic eosinophilic bronchitis
- eosinophilic airway inflammation; like asthma but no variable airflow limitation or airway hyperresponsiveness
- occupational/environmental exposures
- stimulate lower airway cough receptors by inflam mediators
- symptoms are cough without wheezing/dyspnea
- wheezing on chest exam
- diagnose with normal PFTs and normal methacholine challenge but sputum shows >3% eosinophils
- treat with inhaled corticosteroids for >4wks
Neuropathic cough:
- changes in temp, deep breath, laughing, etc. triggers cough
- repeated throat clearing, chest tightness, hoarseness
- hypersensitivty caused by denervation of upper airways
- usually suspected if other diagnoss are excluded
Recognize important differences between chronic cough in children and adults
- most common cause of cough in children is acute URT infection from a virus that usually resolves in 1-3wks
What is the algorithm for diagnosing acute cough?
- get history, exam, etc.
- lifethreatening or non lifethreatening?
- if LT –> pneumonia, COPD/asthma exacerbation, PE, HF, etc.
if nonLT –> URTI/LRTI; asthma/bronchiectasis/UACS/COPD; environmental
What is the algorithm for diagnosing subacute cough?
- if not post infection then same as chronic cough
- if post infection, then pneumonia or pertussis or bronchitis or exacerbation of preexisting condition (UACS/asthma/GERD/NAEB)
What is the algorithm for diagnosing chronic cough?
- smoking/ACEI –> stop
- look at UACS, asthma, NAEB, GERD
List the major classes or generations of antihistamine (H1 antagonists) and describe their primary pharmacological actions, as well as the advantages and disadvantages of each
- H1 receptor blockade (reversible/competitive)
- 1st gen block at H1 but also at non-H1 receptors
- muscarinic receptor blockade
- sedation from 1st gen crossing BBB
- 2nd gen more H1 selective (less muscarinic block) and less BBB crossing, so less sedation
- 1st gen blocks M and H1 in brain –> dec motion sickness, but 2nd gen doesn’t
- 1st gen blocks peripheral muscarinic receptors –> block secretion (dry mouth), but not 2nd gen
- block Na channel –> local anesthetic
- block alpha 1 receptor –> vasodilation?
- orally administered; quick effect (w/in hrs)
- metabolized by liver
- 2nd gen have longer duration
- basically:
1st gen: - crosses BBB –> dec motion sickness, insomnia; causes sedation
- blocks H1 receptor –> dec congestion/rhinorrhea
- blocks peripheral muscarinic receptor –> dec secretion
- block alpha1 receptor –> vasodilation?
- block Na channel –> local anesthetic
- hepatic elimination; shorter duration than 2nd gen
- blocks VSSC in afferent and efferent for cough center –> dec cough
- dec insomnia by crossing BBB
- side effects: sedation, dry mouth, postural hypotension
2nd gen:
- H1 selective
- less muscarinic blocking due to less BBB crossing –> dec sedation
- longer duration with renal elimination
Describe mechanism/site of action, pharmacokinetic factors, major clinical uses, most common and most sever side effects, significant contraindications for diphenhydramine/meclizine
Mechanism:
- 1st gen antihistamine
- H1 receptor antagonist
- muscarinic, Na channel, and alpha 1 receptor blocker
Pharmacokinetic factors:
Major clinical uses:
- allergic rhinitis
- anaphylactic reaction (also epi)
- motion sickness
- insomnia
- cough suppression
- sedation
Most common/sever side effects:
- sedation
- dry mouth, blurred vision (muscarinic)
- dec in pain and cough (afferents to cough center)
- alpha 1 block –> orthostatic hypotension
Significant contraindications:
- chronic use may dec effect
Describe mechanism/site of action, pharmacokinetic factors, major clinical uses, most common and most sever side effects, significant contraindications for loratadine
Mechanism:
- 2nd gen antihistamine
- little CNS penetration
- selective for H1 receptor blocking (nothing else really)
Pharmacokinetic factors:
Major clinical uses:
- allergic rhinitis
Most common/sever side effects:
- mild sedation
Significant contraindications:
- chronic use may dec effect
Describe the mechanism, relative efficacy, route of administration, side effects, ad/disad of decongestants
Mechanism:
- activate alpha1 receptors of vascular smooth muscle –> vasoconstriction of nasal blood vessels that are dilated by histamine/inflammation
- phenylephrine acts directly on alpha1 receptor; shorter duration (4hrs) (topical); oral version has hard to predict blood levels
- oxymetazoline/xylometazoline are longer acting (topical)
- pseudoephedrine inc NE; most effective (oral)
Relative efficacy:
Route of administration:
- topical or oral
Side effects:
- rebound congestion due to ischemia/local irritation with topical decongenstants
- oral affects other vascular beds –> headaches, dizziness, nausea
Adv/disadv:
Describe the mechanism, relative efficacy, route of administration, side effects, ad/disad of pseudoephedrine/ phenylephrine
Mechanism:
- stimulate alpha1 receptors –> vasoconstriction
Relative efficacy:
Route of administration:
- pseudoephedrine oral; phenylephrine oral or topical
- oral is longer acting
Side effects:
- rebound congestion with topical use
- headache, nausea, etc with oral use
Adv/disadv:
- use in allergic rhinitis or cold (viral rhinitis)
Describe the mechanism, relative efficacy, route of administration, side effects, ad/disad of antitussive agents
Mechanism:
- agonists for mu opioid receptors –> dec cough
- 1st gen antihistamines are less effective
Relative efficacy:
- for acute cough due to common cold: 1st gen antihistamine+decongestant; aleve for inflammation
- for cough due to UACS (postnasal drip): 1st gen antihistamine+decongestant
Route of administration:
- oral
- most common is dextromethorphan
Side effects:
- codeine, hydrocodone, dextromethorphan can cause nausea, drowsiness, constipation, allergic rxns
- diphenhydramine has sedation and antimuscarinic side effects
- benzonatate is a tetracaine congener (local anesthetic to numb throat)
Adv/disadv:
Describe the mechanism, relative efficacy, route of administration, side effects, ad/disad of expectorants
Mechanism:
- stimulate resp tract secretions –> dec viscosity –> inc mucociliary mechanism for removal
Relative efficacy:
- drinking more, using mist or steam probably as effective
Side effects:
- GI upset
Adv/disadv:
- guaifenesin is generally safe
Describe the mechanism, relative efficacy, route of administration, side effects, ad/disad of mucolytics
Mechanism:
- split disulfide linkage between mucoproteins –> dec viscosity of mucus
Relative efficacy:
Route of administration:
- inhaled
Side effects:
- major concern with COPD is irritation to cause bronchospasm (should give with bronchodilator)
- N/V, stomatitis, rhinorrhea
Adv/disadv:
- n-acetyl cystein
Drug targets for bronchial smooth muscle changes
- muscarinic receptors –> bronchoconstriction
- leukotriene rs –> bronchoconstriction
- histamine H1 rs –> bronchoconstriction
- beta2 adrenergic receptors –> bronchodilation
Drug targets for secretion changes
- muscarinic receptors –> inc secretion
Drug targets for blood vessel changes
- alpha1 adrenergic receptors –> vasoconstriction
- muscarinic receptors –> vasodilation
- histamine H1 receptors –> vasodilation
- bradykinin receptors –> vasodilation
Drug targets for cough changes
- mu opioid receptors –> suppress cough reflex
Drug targets for sensory pain afferents
- bradykinin receptors –> inc pain
- histamine H1 receptors –> inc pain
Distinguish how the lung discriminates between harmful and harmless materials
- lots of mechanisms to survey and respond to inhaled particles
- smaller particles deposit in lower airways and removed by mucociliary escalator
- presence of PAMPs
- recognition by dendritic cells
- if no PAMPs, then recognized by dendritic cells –> go to lymph nodes to promote tolerance –> SIRPa inhibits NFxB response
- if PAMPs, then activate innate immunity –> inflam mediatory production –> neutrophils –> dendritic cells to lymph nodes for T cell proliferation –> macrophages initiate inflammation –> activates NFxB
Describe the generation of an adaptive immune response in the lung
- activated by exposure of dendritic cells to PAMPs and antigens
- B and T cells
- immune memory makes stronger secondary immune response
Describe the defense mechanisms of the lung
- clearance of particles from epithelial surface
- cellular host responses
- configuration of nasopharynx and serial branching of airways allows for particles deposition proximal to more vulnerable alveolar structures
- mucociliary clearance and cough
- macrophages/immune alveolar clearance
Identify individuals who should be targeted for tuberculin skin testing to diagnose latent tuberculosis infection
- immunosuppressed patients
- HIV
- recent close contact with active TB
- organ transplant
- anti TNFa therapy
- immigrants
- homeless
- predisposing medical conditions (diabetes, dialysis, etc.)
- *HIV positive
- *immigrants
Identify the optimal pharmacologic regiment for treatment of latent tuberculosis infection
- 9 months isoniazid OR rifampin daily 4 months OR isoniazid + rifampin daily 3 months
- 3mo had better results, but were under observed therapy because important to adhere to schedule
Describe the chronology of TB pathogenesis
- MTB ingested by macrophages
- usually killed through apoptosis, but if through necrotic death, then MTB survives and gets spread by being consumed by more macrophages
- creates an early primary tubercle with macrophages trying to consume MTB
- T cells begin to activate macrophages or kill them to prevent spread of MTB
- form granulomas and contain infection
- solid caseous center and sort of a stalemate
- when immunosuppressed, lose integrity of granuloma –> liquefaction of caseous center –> cavity formation –> rupture and spreads to other parts of lung
What are positive PPD test indications?
- > 5mm induration in IS patients or recent close contact to active TB
- > 10mm induration for immigrants, other high risk groups
- > 15mm everyone else
- false positive though in patients who received vaccine or if infected with environmental mycobateria
- false negatives if T cell depleted due to IS
What are alternatives to TSTs?
- quantiferon and T SPOT TB detect in IFNgamma
- adv: only one visit, quantifying IFNgamma is more objective
- sensitivity for LTBI is good or better than TST
- specificity for LTBI is better than TST
- disadv are high rate of baseline false positive and false conversions and cross react with nonTB mycobacterium
Define the types and pathophysiology of respiratory failure
hypoxemic RF
- RF due to dec oxygenation
- caused by impaired O2 transport across alveolar/capillary barrier (left HF w/ pulm edema, pneumonia, hemorrhage, ARDS)
- treat with ventilation
hypercapneic RF
- inadequate ventilation/dec CO2 removal
- caused by anything that impairs ventilation (obst/restr lung disease)
- can’t/won’t breathe
Identify ONLY FOUR mechanical ventilatory parameters and describe how one can use these to manage the majority of intubated and ventilated patients
1) FIO2 - fraction of inspired O2 between 21%-100%
2) PEEP - positive end expiratory pressure
3) respiratory rate
4) tidal volume
- 3 and 4 are determinants of ventilation
- 1 and 2 are determinants of oxygenation
Discuss the basic definition of pathogenesis of ARDS and the conditions that predispose to its development
1) diffuse bilateral radiographic infiltrates
2) PaO2:FiO2 ratio
Describe the management strategies that improve survival in ARDS
- *ventilation with low tidal volumes (28day survival advantage if ventilated with 6 cc/kg vs 12 cc/kg)
- prone positioning in severe disease dec 28day mortality by >50%
Important compensation rules for acute and chronic respiratory acidosis
acute resp acidosis
- 1 mEq/L [HCO3-] = 10mmHg PaCO2
- deltapH = .008*(40-PaCO2)
- (35-PaCO2) in denver
chronic respiratory acidosis
- 4 mEq/L [HCO3-] = 10mmHg PaCO2
- deltapH = .003*(40-PaCO2)
- (35-PaCO2) in denver
Define the major determinants of site and severity of lung disease
1) dose = duration x concentration
2) solubility (water soluble = upper airway; less water soluble = distal airway)
3) particle size (>10microns filtered in upper airway;
Identify the clinical tools/questions used in evaluation of occupational lung disease
- focus on occupational history
- where do you work?
- what job titles have you had?
- what were your specific job duties?
- look at specific exposures
- description of workplace
- use of protection
- similar symptoms in co workers
Define the two major categories of occupational/environmental lung diseases
airways disease:
- immunologic/occupational asthma
- irritant asthma (reactive airway distress syndrom RADS)
- emphysema/COPD (coal mine dust)
- bronchiolitis (obliterative/constrictive)
interstitial disease:
- 3 major types of pneumoconioses (dust based lung disease that causes scarring and inflammation)
1) asbestos related
2) silicosis
3) coal workers (black lung)
4) chronic beryllium disease
5) hypersensitivity pneumonitis
Define the four types of airways diseases and state examples of each
- obstructive pattern; dec DLCO
- immunologic/occupational asthma (asthma with latency due to isocyanates)
- irritant asthma (reactive airway distress syndrom RADS) (strong acids and bases; NO LATENCY)
- emphysema/COPD (coal mine dust/silica)
- bronchiolitis (obliterative/constrictive) (flavoring chemicals diacetyl, oxides of nitrogen, deployment particulate matter)
Define the five types of interstitial lung diseases and state examples of each
- inflammation and fibrosis of interstitium
- restrictive pattern, dec DLCO
1) asbestos related (non malignant –> pleural thickening/plaques; malignant –> lung cancer and mesothelioma)
2) silicosis (fibrotic lung disease and scarring; long latency 10-30yrs)
3) coal workers (black lung; cough, SOB)
4) chronic beryllium disease (granulomatous; similar to sarcoidosis; immune response to beryllium)
5) hypersensitivity pneumonitis (immune response to animal proteins; T cell med immune response; flu like illness)
Determine the inspired PO2 (PiO2) at various barometric pressures and use this to understand the limitations of human exploration at high altitude
- FiO2 stays at .21 but PiO2 changes with barometric pressure
Describe the ventilatory and cardiac adaptations to high altitude
- inc cardiac outpuf with inc in HR; vasodilation (–> dec afterload and inc SV); acute and returns to normal in days
- inc ventilation; hypoxia sensed by carotid bodies –> hyperventilation lasting for weeks and is most useful short term adaptive response
- chronic adaptive response includes inc [Hb] and red blood cell mass
What is acute mountain sickness and its prevention and treatment
Acute Mountain Sickness:
- most common; mildest
- headache, nausea, malaise, insomnia, anorexia
- caused by inc in brain volume due to hypoxia/cerebral edema or inc blood flow
- cerebral edema due to in gene expression of hypoxia induced proteins that inc capillary permeability
- usually resolve w/o treatment, but analgesic for headache
- if symptomatic, then dexamethasone (corticosteroid that blocks vessel permeability) OR acetazolamide (diuretic that dec bicarc and causes resp alkalosis and inc ventilation); can start before
What happens when diving really deep?
- 1 atm for every 10meters
- have in airway pressure to prevent being crushed, but this means inc density of gas due to compression –> inc resistive work of breathing
- if you have COPD or asthma, this can be problematic
- inc venous return
- abdominal compression upwards to dec lung volume
Name several diseases which increase the risk of exposure to extreme environments (i.e. those with gas exchange, cardiac, or airflow limitations)
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High altitude pulm edema and its prevention and treatment
HAPE
- life threatening
- symptoms are cough w/ pink sputum, SOB, fatigue
- signs are hypoxia, lung rales, infiltrates on CXR
- some have AMS
- noncardiogenic because wedge pressure is normal
- see pulm HTN due to hypoxia
- can lead to plasma/blood leakage into alveoli
- treat with descent to lower altitude; vasodilators to dec pulm HTN (nifedipine)
- prevent using vasodilators
Chronic mountain sickness and its prevention and treatment
CMS:
- infants have lower birth weights and higher mortality at elevation
- higher rates of pre-eclampsia
- *polycythemia and pulm HTN
High altitude cerebral edema and its prevention and treatment
HACE:
- most extreme form of AMS
- med emergency
- symptoms similar to AMS (headache, nausea, etc.) but can get worse to ataxia, confusion, coma
- treat with descent, O2, and IV dexamethasone
Describe the major clinical syndromes associated with diving with either breathholding or compressed gas breathing
Pulmonary barotrauma
- pressure difference b/w trachea and pleura inc so that gas is pushed into interstitium (from alveoli) and moves to mediastinum causing a pneumomediastinum or a pneumothorax.
- air embolism can also occur
- asthma inc risk
The bends:
- as inc pressure, partial pressure of nitrogen inc in blood and in tissues
- decompression sickness occurs with too rapid of an ascent
- supersaturated tissue form bubbles as pressure dec
- symptoms are confusion, MSK pain, dyspnea, stroke, coma, seizures, death
- recompress with hyperbaric chamber and gradual ascent
Nitrogen narcosis:
- breathing compressed air –> bizarre behavior and euphoria due to narcotic effect of nitrogen
Shallow water blackout:
- hyperventilate before holding breath
- PaCO2 is trigger for dyspnea (more than hypoxema) so dec in PaO2 after hyperventilating causes unconsciousness before dyspnea
Discuss the differences between adult and pediatric pulmonary physiology
1) infants’ larynx and trachea are smaller than adults’
2) narrowest part of pediatric airway is just below vocal cords at level of cricoid cartilage (in adults it is the vocal cords)
3) given small diameter of airway in kids, radius dec results in a much larger inc in resistance
Laryngomalacia
- benign congenital; underdeveloped cartilage support of supraglottic structures
- most common cause of persisten stridor
- stridor in supine position; URTI
- diagnose with laryngoscopy
- resolves on its own but surgery if severe
Croup
- acute inflam of larynx; laryngotracheobronchitis
- most common cause is virus especially parainfluenza
- barking cough and stridor
- fever is absent or low
- diagnose with neck radiographs showing subglottic narrow
- usually self resolve
- if stridor at rest, then nebulized epinephrine and glucocorticoids
Epiglottitis
- medical emergency
- h. influenzae b
- inflammation/edema –> upper airway obstruction
- sudden high fever; dysphagia; drooling
- sniffing dog position
- visualize airway
- immediately intubate for 1-2days
- IV antibiotics for 2-3days
Bacterial tracheitis
- life threatening form of laryngotracheobronchitis
- s. aureus
- inflam edema, purulent secretions, after viral croup
- resembles viral croup but then high fever, toxicity, and sever airway obstructuon
- high incidence of sudden resp arrest/progressive resp failure
- bronchoscopy shows normal epiglottis and purulent tracheal secretions
- intubate; debridement of tracheal secretions; IV antibiotics
Pediatric bronchiolitis
- most common serious lung disease in kids
- RSV is most common cause (respiratory syncytial virus)
- 1-2 days of fever, rhinorrhea, cough, wheezing, tachypnea, resp distress
- can turn into asthma
- URTI, tachypnea, hypoxemia
- CXR shows hyperinflation, inc interstitial markings
- prevent with monoclonal antibody (palivizumab) in infants with high risk
Pediatric asthma
- most common chronic lung disease
- recurrent cough, wheeze, SOB, chest tightness with specific triggers
- rule out other causes
- SABA for acute; ICS +/- LABA for chronic
Pediatric viral or bacterial pneumonia
- LRTI –> usually viral but can be bacterial
- fever, tachypnea, cough
- crackles, dec breath sounds
- no ABx if viral
- if bacterial, ampicliin or amoxicillin depending on age
Bronchopulmonary dysplasia
- signficant sequelae of acute resp distress in NICU
- 30% of infants w/ birth weight
Cystic fibrosis
- AR inheritance
- mutation in Cl transport
- thick mucus that can’t be cleared because of cilia damage
- productive cough, recurrent pneumonias, bronchiectasis
- pancreatic insufficiency
- diagnose with sweat Cl test and genetic testing
- chest therapy, inhaled mucolytics, ABx, bronchodilators
