Pulmonary Edema y What to keep track of for each disease o Airway Resistance o Gas Exchange o Pulmonary Mechanical Function

Pulmonary Edema Definition o The accumulation of Na+ and H20 in the extravascular compartments of the lung.  Pulmonary Interstitium (look for lines in CXR, called Kerley B Lines)  Alveolar (look for fluffy infiltrates). Types of Pulmonary Edema o Permeability  ARDS  Angioedema o Hemodynamic  Heart Failure (a.k.a. cardiogenic)  Kidney Failure  Liver Failure Fluid Movement in the Lung o Plasma Normally leaks from the pulmonary capillaries into the pulmonary interstitium.  Interstitial fluid continuously enters the alveoli. o Alveolar cells keep the alveoli dry.  How? y Type II cells produce surfactant. o Surfactant q the surface tension forces that draw water out of the pulmonary capillaries. y Type I (major player) and II cells transport Na+ and H20 from the alveoli back into the interstitium. o Stimulation of Alveolar Cell (AC) Na+ Transport  2 adrenergic agonists y Up-regulate transcription of ENaCs (apical side) and stimulate Na+-K+ ATPase activity (basilar side).  Glucocorticoids and Aldosterone y Stimulate Na+-K+ ATPase activity.  Growth Factors (EGF and TGF-E) y Stimulate Na+-K+ ATPase activity.

Clinical Application: administration of each of the above agents has mild to moderate effects on the resolving of pulmonary edema, especially 2 agonists. Superoxide (the only thing good about this chemical) y O2- is a byproduct of AC electron transport. y O2-o transcription of ENaCs in the basilar membrane. y O2- production q as PAO2(alveolar oxygen concentration)q. o Decreased O2- may be partly responsible for high-altitude pulmonary edema.

Pulmonary Capillary Hemodynamics o Qf = Kf [(HPc HPis) (OPc OPis)] Q (lymphatic fluid removal)  Kf = Water Permeability  = Barrier to Protein Movement y O = Completely Permeable. o Order of Protein Permeability: HIGHglomerulus (.9), skeletal muscle (.8), pulmonary capillary (.7), hepatic sinusoids (.1) LOW Safety Factors for Prevention of Pulmonary Edema o Sieving Effect  Loss of fluid increases the protein concentration within the capillaries, which will result in a rebound tendency for reabsorption of the lost fluid (occurs b/c proteins cannot pass through the sieve). o Interstitial Space Low Compliance  Small changes in the interstitial volume result in large changes in pressure (hence, the low compliance). This o in hydrostatic pressure will force fluid back into the capillaries. o Lymphatic Flow  Has the capacity to increase 10X before fluid collects in the interstitium.  Problem with heart failure (especially when it progresses to right heart failure) p venous congestion p decreased lymphatic flowp pulmonary edema. Hemodynamic Pulmonary Edema o Initiated by an acuteo in HPc  Interstitial Edema develops when HPc ~ 22 mmHg, Alveolar Edema develops when HPc> 25 mmHg.  Edema develops when HPc< 25 mmHg if plasma albumin concentration is low. y Threshold HPc = 5.7 X Plasma Albumin (g/dL) o The rate of rise in HPc is more important than the absolute magnitude.

Chronic HPc elevation causes pulmonary HTN, which protects the alveoli from edema (thicker surface for diffusion).  Chronic HPc elevation must be > 28 mmHg for hemodynamic edema to occur. o Edema accumulates first in the pulmonary interstitium and then enters the alveoli.  y Pulmonary Mechanics o Static lung compliance q as edema o.  Fluid is difficult to move, which results in a stiff lung. y Patient is going to have to create larger changes in pleural pressure in order to inflate an alveoli to a normal level.  This o the work of breathing. o Lung edema o airway resistance.  Compresses alveolar ducts and respiratory bronchioles.  Stimulates interstitial J receptors that trigger widespread bronchoconstrictionp wheezing. Gas Exchange o Pulmonary blood flow bypasses the fluid-filled alveoli w/o being oxygenated (fluid prevents ventilation).  V/Q = O (a physiologic shunt) pSevere Hypoxemia.  Remember that the capillaries are constricted due to hypoxic vasoconstriction, but b/c V is still zero, the mismatch is O. o PaCO2 varies depending on severity (you would think that it would increase b/c you can t offload CO2 any more than upload O2 in a fluidfilled alveoli)  However, most patients have a q CO2 level. y Applies when edema is confined to the basilar lung segments. o Hypoxemia causes hyperventilation of non-fluid filled apical lung segments, which expels the CO2 that should be building up.  Some patients have an o CO2 level. y Applies when edema is sever and distributed throughout all lung segments. o This matches up with what one would think would happen in you couldn t exchange O2 or CO2. Clinical Manifestations of Hemodynamic Pulmonary Edema y Dyspnea, Orthopnea, and PND y Increased Tactile Fremitus o Water Density is directly proportional to Tactile Fremitus.

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Dullness to Percussion o Solid objects result in a dull (or full) sound Mid-to-Late Inspiratory Crackles o Alveolar are where the bubbles are forming and popping, and are the last place to receive airflow in an inspiration. 3rd Heart Sound at the Cardiac Apex o o or Normal filling of an over-filled heart chamber. PAWP > 22 mmHg (for normal albumin levels) CXR o Cephalization (hypoxic vasoconstriction shunting blood to the apical lung sections). o Bilateral Alveolar Infiltrates (evidence of fluid in the alveoli). o Cardiomegaly (primary cause of hemodynamic pulmonary edema is backflow from a failing heart). o Kerley B line (flat lines that represent fluid in the interstitium).

Permeability Pulmonary Edema(think ARDS) o Qf = Kf [(HPc HPis) (OPc OPis)] Q (lymphatic fluid removal)  Kfo = Water Permeability o  q= Barrier to Protein Movement q(hence the permeability issues) y No sieving effect to protect from edema (need a barrier for the sieving effect)  Should see exudates instead of transudates. o Causes  Infection (H1N1, SARS, severe Sepsis)  Aspiration of Gastric Contents  IV Drug Abuse (heroine)  Multiple Trauma  Inhaled Toxins (Smoke)  Oxygen Toxicity  High-Altitude Sickness o Stages of ARDS  Exudative Phase (from insult to ~ Week) y Acute lung injury causes alveolar macrophages and Type II alveolar cells to release TNF- , IL-1, and IL-8 (begins releasing w/in 30 minutes). o IL-8 attracts circulating neutrophils into alveoli. o Interstitial and alveolar neutrophil accumulation characterizes the exudative (neutrophil-rich fluid) phase of ARDS.

The neutrophils release proteases and O2 free-radicals that destroy surfactant, Type I alveolar cells and capillary endothelial cells (Type II cells are resistant). Proteases and O2 free-radicals also destroy the integrity of the pulmonary capillary. o This o the Kf (filtration coefficient)and q (the osmotic reflection coefficient), which results in the leakage of protein-rich fluid into the alveoli.  Aggregates of protein, surfactant (also protease activity), and alveolar cell debris form hyaline membranes. o Hyaline Membrane + Intra-Alveolar Edema = Severe Hypoxemia.

Proliferative Phase (From day 3 to ~ Week 2) y Cleaning Up the Mess o Type II ACs (which are resistant to neutrophil activity) proliferate and release more cytokines that attract more macrophages. y If the initial acute injury resolves (i.e. if the infection resolves): o The macrophages release proteases that break up the hyaline membranes. o The Type II ACs remove the edema fluid and then differentiate into Type I ACs to restore the normal microanatomy. If the infection persists o Macrophages release more cytokines and growth factors that will stimulate fibroblast proliferation in the alveoli and interstitium (late proliferative phase). o Fibroblast proliferation defines the proliferative phage of the ARDS o Continuing injury causes the fibroblast to secrete collagen into the alveoli and interstitium. o Collagen deposition defines the fibrotic phase of ARDS (3-4 weeks). o Collagen organization leads to interstitial and alveolar fibrosis that decreases compliance and worsens the hypoxemia. o If the injury resolves, there is a gradual but partial resolution of the fibrosis.

Permeability Pulmonary Edema Continued o Two Causes (same dz, but ARDS is a worse version of Acute Lung Injury)  ARDS  Acute Lung Injury Gas Exchange o If PaO2/FiO2 ratio < 200, ARDS exists.  If PaO2 = 50 mmHg and FiO2 = .50, then the PaO2:FiO2 Ratio = 100 and ARDS is present. o If PaO2/FiO2 ratio = 200-300, acute lung injury exists. o Severe hypxemia is cuase by V/Q mismatch, shunt and dead-space ventilation.  Shunt (V/Q = 0) y Fluid-filled Alveoli cannot be ventilated  Dead-Space Ventilation (V/Q = Infinity, Q = 0) y Fibrosis also occurs in the interstitium, where the capillaries are. Fibrosis pq Blood Flow. y Fibrosis obliterates the pulmonary capillaries and prevents blood flow to partially ventilated alveoli. y Since fibrosis is only partly reversible, the greater the dead-space, the higher the mortality (hence, V/Q mismatch o predicts poor prognosis).  PaCO2 is usually low or normal. y Hypoxemia triggers hyperventilation of the nonaffected alveoli (think apical segments), expelling CO2. Lung Mechanics o Fluid-filled lungs are stiff and difficult to inflate (fluid qcompliance).  More work to achieve enough negative intrapleural pressure to inflate the alveoli.  Later On: Fibrotic lungs take more energy to inflate. o o Airway Resistance  Interstitial edema compresses alveolar ducts and respiratory bronchioles ( squeezes them shut )  Interstitial edema also stimulates J receptors which trigger diffuse bronchoconstriction (a vagal reflex) Clinical Manifestations o Symptoms and Signs  Acute onset of severe dyspnea.  Mid-to-late inspiratory crackles.  Normal Heart Exam o CXR  Bilateral alveolar infiltrates.

 Normal heart size. o Hemodynamic Findings  PAWP < 15 mmHg (if its higher than 15 mmHg, suspect contribution from heart failure) o BNP Levels (Brain Natriuretic Peptide)  > 500 = Cardiogenic  < 100 = Non-Cardiogenic