Pulmonary Physiology PDF

**Pulmonary Physiology** A. **Pulmonary Volumes** a. **Tidal Volume (TV) -** Volume of air inhaled and exhaled with each normal breath. Equal to about 500 mL. i. **[Minute TV]** -- volume of air inhaled and exhaled during 1 minute. Calculated by multiplying the...

**Pulmonary Physiology** A. **Pulmonary Volumes** a. **Tidal Volume (TV) -** Volume of air inhaled and exhaled with each normal breath. Equal to about 500 mL. i. **[Minute TV]** -- volume of air inhaled and exhaled during 1 minute. Calculated by multiplying the TV by the respiratory rate. Equal to 8L ii. **[Alveolar volume]** -- TV minus the dead space volume. Equal to about 350 mL (500-150 dead space) iii. **[Average minute alveolar volume]** is about 5600 mL (500-150 dead space x 16 breaths per minute) b. **Inspiratory Reserve Volume (IRV) --** extra volume of air that can be inhaled beyond the normal tidal volume. Equal to about 3000 mL. iv. Measure of effectiveness of **pulmonary compliance and inspiratory muscle strength.** v. A decrease in IRV is associated with disorders that reduce lung compliance, weaken inspiratory muscle, or both. 1. Restrictive disorders and end-stage COPD may have reduced IRV c. **Expiratory Reserve Volume (ERV) --** volume of air that can be forcefully exhaled after a normal tidal inhalation. Equal to 1100 mL. vi. Indicator of **airway patency and expiratory muscle strength** vii. **Increased ERV is** an indication of improved respiratory muscle strength viii. **Decreased ERV is** associated with weaker musculature, airway obstruction, and restrictive disorders d. **Residual Volume (RV) --** volume of air still remaining in the lungs after the most forceful exhalation. Equal to 1200 mL. ix. Indicator of **airway patency and effectiveness of elastic recoil** x. Increased RV occurs with aging effectiveness of ventilation is reduced e. **Forced Expiratory Flow (FEF) or Peak Expiratory Flow (PEF/PEFR) --** flow rate/speed of air being exhaled during the middle portion of a forced expiration xi. Indicator of **airway patency** xii. Usually the only PFT is clinical setting. Reductions greater than 25% of a person's PEFR is an early indicator of obstructive disorders. f. **Forced Expiratory Volume 1 (FEV1) --** maximum amount of air that a person can forcefully expel during the first second of exhalation after a maximal inhalation. Normal is 80% of an individual's normal average. xiii. Most sensitive clinical and rapid test for the need for intervention r/t to airway obstruction, especially acute asthma g. **Diffusing capacity of lung carbon monoxide (DLCO) --** how well gas moves from the alveoli into the erythrocytes in pulmonary circulation. xiv. Helpful in determining alveolar dysfunction **--** test is near normal in people with asthma or bronchitis and is greatly reduced in the presence of emphysema, pneumonia, and pulmonary edema B. **Pulmonary Capacities** h. **Inspiratory Capacity (IC)** -- composed of the tidal volume and inspiratory reserve volume. Equal to 3500 mL. xv. Maximum amount of air that can be inspired xvi. Reduction=restrictive, especially fibrosing disorders i. **Functional residual capacity (FRC) --** composed of the expiratory reserve volume and the residual volume. Equal to 2300 mL. xvii. Amount of air remaining in the lungs at the end of normal tidal respiration xviii. Increased in obstructive disorders (can't get it all out). j. **Vital capacity (VC) --** composed of inspiratory reserve volume + tidal volume + expiratory reserve volume. Equal to 4600 mL. xix. Maximum amount of air that can be expelled from the lungs after filling the lungs to the maximum extent k. **Total lung capacity (TLC) --** composed of tidal volume, inspiratory reserve volume, expiratory reserve volume, and the residual volume. Equal to 6L. xx. Maximum volume that the lung can hold with the greatest inspiratory effort xxi. Reduced in restrictive disorders xxii. Increased in severe long standing COPD l. **Forced Vital Capacity (FVC) --** maximum amount of air that can be exhaled as quickly as possible after maximal inhalation. xxiii. Indicates respiratory muscle strength and ventilatory reserve xxiv. Average VC for men = 4800 mL, Average VC for women = 3500 mL xxv. Reduced in both obstructive and restrictive disease C. **Pulmonary Functions** m. Regulation of oxygenation and gas exchange n. Protection (macrophages, surfactant) o. Maintenance of cardiac output and blood pressure p. Immunity q. Fluid, electrolyte, and acid-base balance D. **Processes Involved with Pulmonary Function** r. **Ventilation** -- movement of atmospheric air into and out from lungs for gas exchange s. **Perfusion** -- circulation of blood through tissues and organs for gas exchange t. **Diffusion for gas exchange** -- movement of O2 and CO2 molecules across permeable membranes from an area of higher partial pressures to areas of lower partial pressures E. Pulmonary Anatomy u. Easier for things to be aspirated into right bronchus because it is shorter and more vertical v. Most respiratory function in right because it is larger; left lung is smaller due to heart leaning left. w. By adulthood, 500 million alveoli; alveoli amount depends on how active they are -- alveoli development stops at older adolescence x. Goblet cells produce mucus y. Cilia beat towards throat z. **Dead Spaces** xxvi. Anatomic dead space: anatomic areas (beyond the larynx -- conducting airways) where normal structures are too thick for gas diffusion. Average=150 mL xxvii. Physiologic dead space (includes anatomic dead space -- do not add): all areas (beyond the larynx) in which gas diffusion does not occur 2. Includes normal anatomic structures and areas of pathology (pulmonary embolism) xxviii. In health, physiologic and anatomic dead spaces are equal. F. **Airway Pressure and Flow** a. Resistance is the reciprocal of flow (anything resistant to flow, slows flow) b. Factors that affect airway resistance include: airway length (increased length, increased resistance), airway radius (decreased radius, slows flow), and flow rate. xxix. Trachea and bronchi have least impedance to flow c. **Boyle's Law** xxx. Mass and temperature are constant -- pressure is increased or decreased -- volume of gas will vary inversely with the pressure xxxi. **Inhalation: atmospheric air\>intrathoracic pressure (air will go from area of low pressurehigh pressure).** xxxii. **Exhalation: intrathoracic pressure\> atmospheric pressure** G. **Perfusion: Pulmonary Circulation** d. Two separate systems, one smaller to oxygenate pulmonary structures and one larger to provide gas exchange for systemic circulation e. 9% of total blood volume f. Low pressure, high flow system g. Small increases in pulmonary capillary pressure can result in transudation and edema h. Serves as reservoir with great compliance i. Pulmonary artery (away from heart, towards lungs) j. Pulmonary veins (away from lungs, toward heart) H. **Ventilation and Perfusion** k. Gas exchange depends on both ventilation and perfusion l. Ratio unequal in different areas of the normal lungs (position and gravity, blood vessel distribution, and unequal alveolar filling) m. **When ventilation is 0, there is no ventilation** xxxiii. Alveolar pressure=capillary gas pressure (no exchange) n. **When perfusion is 0, Va/Q=infinity** xxxiv. No perfusion and alveolar gas pressure = those of atmospheric air o. **High V/Q = \>ventilation than blood flow (pulmonary embolism, wasting ventilation)** p. **Low V/Q = \> blood flow than ventilation (wasting blood flow -- pulmonary edema, pneumonia, asthma)** I. **Diffusion and Gas Exchange** q. **Rate of gaseous diffusion depends on:** xxxv. Pressure gradient xxxvi. Amount of diffusible surface area xxxvii. Degree of gas solubility xxxviii. Thickness of the diffusing membrane r. Higher altitudes pressure changes (Ex: In Denver, atmospheric pressure is 655 mmHg -- harder to inhale) s. CO2 has a high solubility and diffusiblity coefficient xxxix. Crosses easier into alveoli vs O2 into capillary will see hypoxia before hypercarbia xl. Hypercarbia is a sign that disease has been going on for awhile J. **Surfactant and Surface Tension** t. Family of lipoproteins secreted by type II pneumocytes, starting late in fetal life u. Reduce surface tension by preventing the formation of an air-water interface with a very high surface tension v. Surfactant is between water molecules to keep them separate so alveoli won't collapse -- decreased surface tension, especially in smaller alveoli w. Smaller alveoli are inherently unstable -- greater tendency to collapse (Surface tension is inversely proportional to the radius of the alveoli) x. Surfactant increases the compliance of each alveolus so less work or effort is needed to expand the entire lung and reduces the risk of pulmonary edema by preventing transudation y. **Law of LaPlace** K. **Compliance** -- how much lung can expand z. Expandability/distensibility of lungs and thorax a. Volume increases in the lungs for each unit increase in intra-alveolar pressure b. How much volume increases depends on the compliance of chest wall and alveoli c. When alveolar pressure increases by 0.7 mmHg (0.95 cm H2O), lung volume expands by 130 mL d. Compliance = change in volume/change in pressure L. **Elastance** -- ability of lungs to go back to normal shape after expansion e. Interaction between the recoil of the lung (alveoli) and the recoil of the chest f. Resistance and elastance are the reciprocal of compliance g. Tendency of the lung and chest wall to spring back to their original shape after expansion M. **Gaseous Transport** h. **Hemoglobin is an allosteric molecule meaning the process by which oxygen binding to one subunit of hemoglobin affects the binding of oxygen to other subunits. The binding of oxygen to one subunit causes conformational changes that are relayed to other subunits, increasing their affinity for oxygen.** i. j. **Haldane Effect** -- increased O2 binding to Hgb, decreased Hgb affinity for CO2 (facilitates CO2 release from lungs) k. **Bohr Effect** -- decreased pH = increased CO2, decreased Hgb affinity for O2 (facilities O2 to be released into tissues) l. **Carbon Dioxide Transport** xli. **CO2 is always transported more easily and in greater quantities in the blood than is O2** xlii. **Mostly as bicarbonate (70%), in combination with plasma proteins (23%)** m. **Carbon Monoxide Transport** xliii. CO binds competitively at the same site on Hgb where O2 binds xliv. CO binds 200x more tightly than O2; Hgb will selectively bind with CO over O2 xlv. Patient will not be cyanotic with CO poisoning N. **Autonomic Regulation of Ventilation (occurs in brainstem)** n. **Dorsal Respiratory Group (DRG)** xlvi. Responsible for basic rhythms of ventilation xlvii. Contains both inspiratory and expiratory areas in separate but interconnected oscillatory circuits that are mutually inhibitory to prevent simultaneous inspiration and expiration xlviii. Primarily inspiratory, does not vary in rhythm, only in pattern o. **Ventral Respiratory Group (VRG)** xlix. Only acting during overdrive to augment both inspiratory and expiration l. Activates abdominal muscles for more effective expiation during heavy exercise li. VRG is not needed during quiet ventilation p. **Inspiratory "Ramp"** -- progressive excitation in inspiratory neurons, increasing firing rate and numbers firing. The purpose of the ramp is to allow smooth, progressive filling of the lungs instead of "gasps" q. **Central Chemoreceptor Regulation (responsive to increased CO2 and H+)** r. **Peripheral Chemoreceptors (more responsive to decreased O2/hypoxia)** lii. Located in highly metabolic/active tissues such as aortic arch and carotid sinus **Obstructive Pulmonary Problems** A. **General Pathology** a. Pathology reduces airway lumen resulting from an increase in resistance to air flow at any level of the bronchia tree b. Anatomic airway narrowing, deceased elastic recoil c. Chronic airflow limitation B. **PFT Abnormalities w/ Disease** d. **Restrictive Disease** - Decreased VC, FEV1, PERF, FRC, RV, and TLV - Normal FEV1/FVC e. **Severe Obstructive Disease** - Decreased VC, FEV1, FEV1/FVC, PERF - Increased FRC, RV, TLC C. **Emphysema - trouble getting air out** f. **Patho** - Permanent enlargement of acini and destruction of alveolar walls without fibrosis - Enzymatic degradation of elastin in alveoli and airways 1. Alveoli lose elasticity and recoil 2. Small airways collapse or narrow 3. Alveoli become large and flabby -- air becomes trapped in the lungs 4. Alveolar destruction 5. Air-filled spaces (bullae) - Decreased area for functional gas exchange -- retaining CO2 - Primary pathological changes -- loss of lung elasticity and lung hyperinflation - Collapse/narrowing of smaller bronchioles g. **S/S** - Increased WOB - Dyspnea and increased RR - Hyperinflated lung flattens diaphragm -- additional muscles (accessory muscles) in the neck, chest wall, abdomen needed to inhale/exhale - Air hunger sensation due to increased effort which increases the need for O2 and metabolic nutrients - Inhalation begins before exhalation is completed, resulting in dyspnea with an uncoordinated breathing pattern D. **Bronchitis/Bronchiolitis -- trouble getting air in** h. **Patho** - Inflammation of the bronchi and bronchioles from continuous exposure to infectious or noninfectious irritants, especially tobacco smoke and vaping chemicals - Irritants cause an inflammatory response, vasodilation, congestion, mucosal edema, and bronchospasm - Affects airways rather than alveoli - Chronic inflammation results in mucous gland hypertrophy and hyperplasia, which produces large amount of thick mucus - Bronchial walls thicken and impair airflow -- small airways affected before large airways - PaO2 decreases and PaCO2 increases respiratory acidosis E. **COPD** i. **Risk factors** - Deficiency of alpha 1 antitrypsin (AAT) 6. Mutated gene -- cannot get rid of proteases, which will destroy elastin in lungs - Cigarette smoking - Chronic exposure to inhalation irritants - Air pollution - Vaping j. Complications - Hypoxemia and acidosis - Respiratory infections - Cardiac failure (Cor pulmonae) - Cardiac dysrhythmias - Activity limitations - Premature death k. S/s General: - Thin, decreased muscle mass (except lung muscles) - Slow moving, slightly stooped "tripod position" - Reduced hunger, nutritional deficits - **Fatigue (short on O2, fatigue will be a huge symptom)** l. **S/s Respiratory:** - Rapid, shallow respirations - Use of accessory muscles - Abnormal breathing patterns - Decreased excursion, decreased fremitus, hyperresonant - Crackles - Dyspnea - Barrel chest (increased anterior-posterior ratio) - Non-cyanotic "pink puffer" -- emphysema dominates with CO2 retention - Cyanotic, blue tinged, dusky appearance (chronic bronchitis dominates, "Blue bloater" - Excessive sputum - Clubbing of the fingers - Decreased capillary refill - **[Acute respiratory acidosis]** 1. Decreased pH -- 7.25 2. Normal-ish HCO3 -- 22 mEq/L 3. Increased PCO2 -- 70 mmHg 4. Decreased PO2 -- 55 mmHg m. **Compensation for Respiratory Acidosis** - Process in which the body uses its three regulatory mechanisms to correct for changes in the pH of body fluids - If a lung problem causes retention of CO2, the healthy kidney compensates by increasing the amount of bicarbonate that is produced and retained 7. The kidney is the best at getting rid of H+ 8. **Renal compensation/Increased Bicarb = longer or chronic problem** - **Partial Compensation** 9. Decreased pH -- 7.26 10. Increased HCO3 \-- 30 mEq/L 11. Increased PCO2 -- 80 mmHg 12. Decreased PO2 -- 65 mmHg - **Full compensation (complete)** 13. Decreased pH **-- 7.33** 14. Increased HCO3 -- 38 mEq/L 15. Increased PCO2 -- 85 mmHg 16. Decreased PO2 -- 68 mmHg F. **Asthma** n. **Pathology** - Condition of **intermittent, reversible** airflow limitation from narrowed airways - Constriction of bronchiolar smooth muscle (allergen, irritants) 17. Exercise 18. Upper respiratory infections 19. Genetic factors - Edema of luminal mucosa inflammation (obstructed lumen), eosinophilia (75% of asthmatics release IL-5), reactive mast cells, neutrophilia 20. Specific allergens include: cold, dry air; fine airborne particle microorganisms, air pollution, chemical fumes, GERD, aspirin - Increased pulmonary secretions - Bronchoconstriction alone triggers receptors in airway mucosa, activating a protective response of reducing airway diameter to limit exposure to the trigger - **[Inflammatory response ]** 21. **Early --** acute bronchoconstriction on trigger exposure caused by mucosal responses of inflammation a. Begins within 30 mins with release of inflammatory mediators causing increased capillary permeability, edema, increased mucous, bronchoconstriction, and airway narrowing b. Can resolve in 1-3 hours 22. **Late** c. Usually 4-8 hours after early response d. Increased airway hyperresponsiveness e. Latent release of initial mediators and increased synthesis of more mediators, especially from eosinophils which induce tissue damage f. Crystals and debris from cells further obstruct the airway, injure cilia, hypertrophy of goblet cells g. Over time, airways remodel and fibrose 23. Presence of chronic inflammation leads to damage and hyperplasia of bronchial cells and of smooth muscle 24. With frequent attacks, exposure even to reduced levels of triggering agent/event stimulate attacks 25. Severe chronic asthma can result in such bronchial tissue damage that cor pulmonale results o. **S/s** (may not have symptoms between attacks) - Chest tightness - Shortness of breath - Audible wheeze (1^st^ on exhalation) - Cough (often nonproductive early) - Increased RR - Use of accessory muscles - Difficulty talking - Activity intolerance - Sleep interruption with cough/wheeze - Barrel chest (late with severe disease) - Hypoxia -- decreased pulse ox, cyanosis, tachycardia, altered LOC - Labs: acute respiratory acidosis, elevated eosinophils, elevated IgE levels, sputum may have Curschman spiral and/or Charcot-Leyden crystals (fragmentation of eosinophils) G. **Obstructive Sleep Apnea (OSA)** p. **Pathology** - Disordered breathing pattern during sleep with intermittent cessation of ventilation - Not associated with disruption of CNS or brainstem stimulation for ventilation - **Purely mechanical problem** and very under diagnosed -- bidirectional disorders q. **Risk factors** - Obesity - Male - Large uvula - Enlarged tonsils/adenoids - Short neck - Oropharyngeal edema - Smoking/vaping - Oral cavity/pharyngeal malformations - Increasing age - Diabetes, HTN, allergies, other obstructive disorders, stroke r. **Diagnostic Criteria** - Apnea only during sleep, each episode lasts at least 10 seconds, pattern repeats a minimum of 5x each hour - Hypopnea and relaxation of oral and neck muscles displaces tongue, soft palate, and uvula - Snoring precedes complete airway obstruction - Ventilation and gas exchange are inhibited, O2 falls, CO2 rises, stimulating central receptors - Increased effort wakens person **Pulmonary Problems: Infectious Disorders -** lungs are very susceptible to infection due to anatomic location to outside world A. **Acute Epiglottitis** a. **Pathophysiology** - Inflammation of epiglottis (may also include supraglottic structures) -- edema and swelling - Most common causes are viral (RSV) and bacterial (Strep) infection - Also caused by thermal, smoke inhalation, chemical injuries, traumatic intubation - Life-threatening with airway obstruction 1. Nonverbal children and adults are most at risk for death because you cannot tell change in voice quality 2. Non- ambulatory children and adults are also at more risk for death - Most common in younger children 3. Children under 12 months are most at risk for death b. **S/s:** - Fever (more with bacterial) - Sore throat (bacterial and viral) - Change in voice quality, muffled - Difficulty breathing, stridor - Difficulty swallowing, drooling - Worse lying down/leaning backward - Rapid onset in children (hours) - Slower onset in adults (days) c. **Diagnosis and Management** - Diagnosis by symptoms, not direct throat examination - Management -- secure airway (may need emergency trach) and reduce swelling B. **Pneumonia** d. **Pathophysiology** - An inflammatory process resulting in edema of lung tissue with movement of fluid into alveoli, interstitial spaces, and bronchioles causing hypoxemia - Pathogens successfully penetrate the airway mucus and multiply in the alveolar spaces - Organisms multiply, fluid and exudates form -- WBCs migrate into alveoli and thicken the alveolar wall - RBCs and fibrin move into the alveoli (red hepatization phase) - Fluid fills alveoli, protecting the organisms from phagocytosis and helping to move the organisms to other alveoli - If the invading organism obtain access to the bloodstream, septicemia results - If the infection extends into the pleural cavity, an abscess or empyema results (must drain this, tx not effective with abx) - The fibrin and edema stiffen the lungs, decreasing lung compliance and vital capacity - Atelectasis occurs (no gas exchange) - Some venous blood is not oxygenated, causing hypoxemia (increased shunting) -- thickened areas cannot participate in gas exchange 4. One area becomes hypoxic due to pneumonia -- blood can be shunted to areas of lung w/ better ventilation - Most common bacteria for pneumonia is Strep - **Community Acquired** (no association with healthcare) 5. Older adult 6. No hx of pneumococcal vaccination 7. No hx of recent flu shot 8. Chronic disease of any kind 9. Recent exposure to respiratory infections 10. Hx of alcohol and/or tobacco use 11. Aspiration - **Hospital Acquired** 12. Older adult 13. Chronic lung disease 14. Gram negative organism in upper ruct 15. Altered LOC (more at risk of aspiration) 16. Aspiration 17. Respiratory/NG tubes (microorganisms vegetate) 18. Poor nutritional status 19. Immunocompromised status 20. Meds that increase gastric pH or delay emptying (GLP-1 agonist) 21. Mechanical ventilation e. **S/s** - Fever, headache, chills, myalgia -- bacterial - Cough (not in older adults) - Tachypnea, tachycardia, dyspnea - Decreased oxygen saturation (hypoxic and hypoxemic) - Sputum production -- older adults may not cough which can lead to increased consolidation - Use of accessory muscles - Crackles, wheezing - Pleuritic pain/discomfort - Dehydration, hypotension (lose body fluid in exhaled air) - Confusion (1^st^ sign in older adults, later in younger adults) - Increased fremitus (sound waves travel better through denser tissue) - Decreased resonance (fewer air filled spaces, alveolar wall is thickened) - E-A egophony (will hear "A" when you tell patient to say "E") C. **ALI/ARDS (ALI ARDS if untreated)** f. **Pathophysiology** - Interconnected disorders occurring in response to sudden onset pulmonary assaults from internal or external sources - Represents serious lung inflammation continuum - ALI can occur w/o ARDS; ARDS generally follows ALI -- both occur r/t other pathologic events - Most common cause -- general sepsis 22. **ALI** -- acute inflammation with injury in association with any event disrupting integrity of endothelial/epithelial barrier at alveolocapillary membranes; 40% of ALI progresses to ARDS 23. **ARDS** -- respiratory insufficiency from severe injury and inflammation with progressive hypoxemia refractory to high concentration O2 therapy g. **ALI** - **Direct causes** 24. Chest trauma/pulmonary contusions 25. Inhale toxic gases/fumes 26. Aspiration 27. Near-drowning 28. Fat embolism syndrome 29. Bacterial/viral pneumonia (including COVID) 30. Drug/chemical exposures (dipyriduum, opioid overdose) 31. Oxygen toxicity 32. High altitude (rapid ascent) - **Indirect causes** 33. Sepsis with SIRS 34. MODS 35. DIC 36. Massive transfusion (TRALI) 37. Pancreatitis (enzymes can get into lungs) 38. Any wide-spread inflammation h. **ARDS** - Almost always follows ALI - By time manifestations present (sudden dyspnea), patho process is well underway - Innate immune responses (neutrophils and macrophages) -- secretion of proinflammatory cytokines in alveoli, intersitium, vasculature -- cytokine storm (IL-1, IL-6, IL-8, IL-10). TNFa -- causes most damage, prolonged inflammation - Areas of involvement are discontinuous - Increased release of proteases and lytic enzymes from inflammatory cells, liquefaction necrosis of type I and II pneumocytes - Decreased presence of surfactants -- lack of type II pneumocytes, which makes ARDS so deadly - Increased production and release of PDFG and FGFB -- lead to unregulated growth of fibroblasts - Damage occurs to both epithelial and endothelial cells (more scarring and fibrosis, which decreases compliance) - **S/s:** 39. Formation of hyaline membranes (forms barrier to gas exchange, alveolar deposits of protein substances from blood vessels and cellular debris) 40. Denudement of basement membranes (lose inducing factors to grow more type I pneumocytes) 41. Fibrosis of alveolar walls 42. Loss of alveolar volume 43. Reduced total lung volume 44. Atelectasis 45. Pneumonia - **Phases** - **Acute Exudative Phase** - Usually 1-3 days after a cause - Neutrophilia and inflammatory cell migration in response to chemotaxins from injured cells and macrophages - Extends disruption of alveolocapillary membranes (discontinuously)---occurs in patches - Cell sloughing and proteins from hyaline membranes that "stiffen" lungs and reduce compliance - Cytokine storm, liquefaction necrosis - Dyspnea with chest tightness/stiffness - Tachypnea and Tachycardia - Hypoxemia from pulmonary shunting - X-ray, bilateral infiltrates (patchy) -- whited out/ground glass appearance - **Fibroproliferative phase (inflammatory phase)** - Usually lasts 7-10 days - Increased work of breathing - Dyspnea - Tachycardia and tachypnea - Refractory hypoxemia - Respiratory acidosis, hypercarbia - Increased infiltrates - Pulmonary hypertension -- indictors of RHF - Pulmonary fibrosis - May progress or halt at this point - **Fibrotic Phase** - Profound respiratory distress - Significant remodeling of pulmonary architecture - Critically refractory hypoxemia - Cyanosis - Mental status change - Infiltrates coalesce into "white out" - Frank right sided heart failure - Presence of dense fibrotic tissue - Continued hypercarbia and acidosis - Death - **Resolution** - If it occurs, begins within 14-21 days - Active inflammation and fibrosis halts - Macrophages stimulate debris clean up and removal - Protein-containing fluid shifts into systemic circulation (stops transudation) - Depends on intact BM, alveolar regeneration, number of type II cells that still work - Remodeling of ECM with reduction of cartilage - Restoration of alveolocapillary barrier -- depends on residual and permanent impairment of ventilation and gas exchange D. **Bronchiectasis (always secondary to another pulmonary infection)** i. **Pathophysiology** - Inflammatory destruction of smooth muscle and elastic tissues in lower airways secondary to severe or recurrent and persistent pulmonary infections that lead to permanent bronchi and bronchiolar dilation - Mucoid, purulent excretions present and often organism-filled, resistant to therapy - Persists beyond causative infections and becomes gas exchange problem - Fusion of bronchial tissue together -- anyone over 70 may have some degree of bronchiectasis j. **Predisposing Conditions** - Congenital or acquired ciliary disorders (rare) - Severe, overwhelming pulmonary infection - Conditions that increase risk for aspiration of GI secretion (GERD) - Immune disorders (both immunity reduction and autoimmune disorders (RA) - Internal and external bronchial obstruction organism filled, resistant to therapy - Persists beyond causative infections and becomes major gas exchange problem k. **S/s:** - Chronic airway obstruction (esp smaller) - Reduced gas exchange - Chronic inflammation leading to necrosis, fibrosis, obliteration of some airways and alveoli - Abscess formation - Empyema (area in b/w lung and chest wall) - Reseeding with organisms - Systemic infection and sepsis E. **TB** l. **Risk Factors** - Living with person who has active, untreated TB - HIV - Living in crowded conditions - Older homeless individuals - Abuse of alcohol or injection drugs - Disadvantaged social group - Foreign immigrants from TB highly burdened areas - Health care providers m. Pathophysiology - When inhaled, bacilli reach alveolar macrophages and begin to multiply - Starts local exudative response with non-specific pneumonitis (primary response) that may allow immunity to halt spread and progression, entering a "dormant' but living state of non-infectious "latent" TB - With immunosuppression, primary response progresses to active TB, either immediately or later in life n. **Latent TB** - PPD remains positive and non-infectious - Asymptomatic decades for decades if not immunocompromised - Confined and held in check, but can progress to fulminant TB with immunosuppression - 80-90% never progresses to active TB o. **Progressive (Secondary) TB** - Develops at any time with reduced immunity - Living TB escape macrophage control and proliferate 46. Enters circulation and lymph, infect other organs (fallopian tubes -- infertility) 47. Miliary TB -- TB that has spread to other organs - Liquefication necrosis consumes lung tissue, cavitation p. **Fulminant Active TB S/s:** - Progressive fatigue, lethargy - Nausea, anorexia, weight loss - Irregular menses - **Low grade fever** - **Night sweats** - Cough with mucoid, mucopurulent or bloody sputum - Chest tightness - Dull, aching chest pain constantly - Hypoxemia and fatigue - Death by hemorrhage-vessel erosion **Complex Pulmonary Problems** A. **Pulmonary Arterial Hypertension (Pulmonary Hypertension)** a. **Pathophysiology** - Sustained mean pulmonary artery pressure \>20 mmHg, which is chronic, progressive and lethal - **[WHO Categories:]** - PAH is predominant feature, but also veno-occlusive disease, pulmonary cap hemangiomas - PH secondary to left heart disease - PH secondary to lung disease/hypoxemia - Chronic thromboembolic PH - PH of miscellaneous/uncertain cause a. Associated with connective tissue disease (systemic sclerosis, SLE), congenital heart disease, liver disease with portan HTN, HIV - Main pathology is proliferative vasculopathy and remodeling of distal arterial bed - Increased and disorganized endothelial growth - Increased in vascular smooth muscle growth - Lumen of arteries/arterioles gets smaller more pressure required to get blood through b. **Hereditary PAH** - Mutations in one of several interrelated genes - BMPR2 -- primary mutation b. Unable to perform functions, leading to unfavorable remodeling of pulmonary vasculature c. When working normally, inhibits vascular smooth muscle proliferation, promotes survival of vascular epithelium, especially in pulmonary system whenever an insult occurs - ALK1- modify active of BMPR2 - SMAD9 - modify active of BMPR2 - TGFb - modify active of BMPR2 - PPH1- modify active of BMPR2 - **Mutation in BMPR2 + modifier genes + environmental triggers pulmonary vascular thickening and occlusion primary pulmonary hypertension** - Autosomal dominant with \~20% penetrance, mostly in women aged 20-40 - Often dx late -- significant lung damage, HF. Dx with RHC and Echo. - Average life expectancy is 2.8 years after dx c. **Pulmonary Chemical Changes** - Imbalance between factors that increase vascular resistance and those that induce blood vessel relaxation - **Endothelin -1 (vasoconstrictor):** binds to endothelin receptors on vascular SM (increased in vascular smooth muscle amount more receptors) - **Thrombaxane (vasoconstrictor):** induces vasoconstriction and clotting by activating platelets; clotting is a secondary issue w/ PAH - **Prostacyclin 1:** promotes vascular relaxation, there is a deficiency with PAH - **Nitric Oxide (NO):** promotes vascular relaxation - Because there is an increased amount of tissue that can constrict, the normal amounts of Prostacyclin 1 and NO are overpowered d. **S/s:** - Fatigue - Dyspnea, worse on exertion - Dry cough - Syncope - Leg/ankle swelling - Tachycardia/dysrhythmias/palpitations - Angina - Decreased oxygen saturation - Cyanosis - RHF e. **Tx**: anti-coagulants (narrowed lumen makes it easier for blood clots to form), heart/lung transplant, vasodilators (prostaglandin agonists), endothelial-1 antagonists B. **Pulmonary Fibrosis** f. **Pathophysiology** - Common, restrictive lung disease - Progressive disease, with few periods of remission (initiating factor happens years before person is symptomatic; dx is delayed) - Loss of cellular regulation - Lung injury inflammation fibrosis scarring - Injury begins in the alveolar epithelial cells - fibrin deposits in alveolar wall and between pulmonary capillaries, thickening distance for gas exchange - Triggers secretion of profibrous growth factors and inflammation that leads to increased collaged production, interstitial fibrosis with stiffness, decreased O2 diffusion - No inhaled anesthetics -- can impact fibroblast drugs - Can lead to PAH and Cor pulmonale a. **Causes** - Gene environment interaction - Cigarette smoking - Chronic exposure to inhalation irritants - Drugs (amiodarone, bleomycin) - Viral infection - Vaping b. **S/s** - **Early**: gradually increasing dyspnea on exertion, dry cough, fatigue - **Later**: gradual deterioration of lung function, hypoxemia, cyanosis, clubbing C. **Cystic Fibrosis** g. **Pathophysiology** - Caused by mutation in CFTR gene on chromosome 7; autosomal recessive transmission - CF disorder expressed when allele mutations are homozygous or compound heterozygous - Allele may be present in a family for many generation without overt expression - Equally expressed in males and females - Traits first appear in siblings rather than in parents; often skips generations ( - Unaffected carriers of CF gene can transmit the gene and trait to their children - Risk of children of two affected parents to express the disorder is 100% - Two carrier parents can have an affected child with a 25% risk i. The CFTR protein promotes chloride and bicarb, influences sodium transport pathways -- CFTR mutations disrupt these functions to varying degrees (sodium transport disruption is a bigger problem) ii. Most common mutation is deletion of phenylalanine 508 frameshift mutation affecting protein folding iii. Major problem is the formation of thick, sticky mucus in the epithelial cells of the lungs, pancreas, liver, salivary glands, and testes which causes glandular atrophy and reduces organ function over time - When lungs are mostly involved, it is more severe but diagnosed earlier - Most common in Caucasians h. **S/s:** - Diagnosed by sweat chloride analysis - Gene testing performed to determine exact mutation - CFTR direct sequencing testing to establish carrier status, prenatal dx, predicting potential disease severity - Lung and pancreas function affected most - **[Lungs manifestations]** - Mucus plugged airways, reducing airflow - Chronic lower respiratory bacterial infection - Chronic bronchitis - Bronchiectasis - Increased alveolar compliance - Lung abscesses - Pneumothorax - Arterial erosion and hemorrhage - Respiratory failure and death 1. **[Pancreatic manifestations]** - Cyst formation - Reduced exocrine and endocrine function (insulin, glucagon) - Poor protein and fat digestion, malnutrition - Small stature - Fatty diarrhea - Fat-soluble enzyme/vitamin deficiencies - DM (late in disease course) 2. **[Misc. Manifestations]** - Abnormal saliva (dental caries) - Decreased liver function, eventual liver failure - Male infertility (absent vas deferens) - Life expectancy is significantly reduced (\~47 years, pulmonary involvement \~44years) - Considered to have CF if both alleles are mutated and at least one manifestation is present - CF -- resistance to cholera and typhus D. **Lung CA (Bronchogenic Carcinoma) -- restrictive and obstructive disease** i. **Pathophysiology** - **Non-small cell -- more responsive to tx** - Adenocarcinoma - Squamous cell carcinoma - Large cell carcinoma - **Small Cell Carcinoma** - Mesothelioma-asbestos exposure j. **Malignant Transformation** - The process of changing a cell from a normal cell phenotype to a malignant phenotype - Involves cell alterations at the gene level (not usually inherited like breast cancer) - Malignant Cell Characteristics: - Unregulated cell division - Anaplastic morphology (look different from tissue from which they arise) - Large nuclear/cytoplasmic ratio - Loss of differentiated functions - Loosely adherent - Able to migrate k. **Environmental Carcinogens** - 20 -- 30% of cancers caused by tobacco byproducts of combustion (70-85% for lung cancer) found in cigarette some - Multiple (weak) carcinogens, requiring **prolonged** exposures for gene changes to persist to the point cancer develops and is detectable -- long, slow process for a cell to become a tumor l. **Risk Factors/Causes** - Cigarette smoking = 85% of all lung cancer deaths - Passive (2^nd^ hand, 3^rd^ hand smoke -- staying in a room where someone has smoked) - Asbestos, beryllium, chromium - Coal distillates, cobalt, iron oxide - Mustard gas - Radiation, tar, nickel - Vaping m. **S/s:** - Persistent chills, fever, cough - Blood-tinged sputum - Hemoptysis, labored painful bleeding - Pleuritic chest pain - Retractions, accessory muscle use - Flared nares, stridor - Asymmetric diaphragmatic movement - Dyspnea, wheezing, orthopnea - Wasting/weight loss n. **Metastatic Sites** -- adjacent structures, near and distant lymph nodes, brain, bone, and liver **The Gastrointestinal System** A. **[Structure and Function]** a. GI tract (alimentary canal) -- mouth pharynx esophagus stomach small intestine large intestine anus i. Primary Function: Digestion and Absorption b. Accessory organs -- salivary glands, liver, gallbladder, exocrine pancreas ii. The salivary glands empty into the oral cavity, and the liver and pancreas are connected to the small intestine. iii. The exocrine pancreas is responsible for secretion of digestive enzymes, ions and water into the duodenum of the GI tract. iv. Exocrine = emptying into ducts; Endocrine = emptying into blood stream. B. **[Anatomy of the GI Wall ]** c. All segments of the digestive tract consist of four layers: v. **[Mucosa (innermost tunic)]** 1. Consists of mucous epithelium, a loose connective tissue called the lamina propria and a thin smooth muscle layer, the muscular mucosae 2. Villi -- increase SA for absorption vi. **[Submucosa ]** 3. Lies just outside the mucosa 4. Thick layer of loose connective tissue containing nerves, blood vessels, and small glands (glands/ducts cause secretions to come into the intestinal lumen) 5. An extensive network of nerve cell processes form the submucosal plexus (network). Autonomic nerves innervate this plexus (controls involuntary body functions); contributes to mechanical aspect of digestion and absorption vii. **[Muscularis]** 6. Consists of an **inner layer of circular smooth muscle** (contracting movements) and an **outer layer of longitudinal smooth muscle (peristalsis; primary movement to contents from mouth to rectum)** a. A nerve plexus (innervated by the ANS) lies between these two muscle layers 7. Together, the nerve plexuses of submucosa and muscularis compose the enteric nervous system b. This nervous system is extremely important in controlling movement and secretion within the tract viii. **[Serosa (outermost tunic) -- connective tissue layer]** 8. Consists of the peritoneum, which is a smooth epithelial layers and its underlying connective tissue; sits against our organs 9. Double layer of peritoneum comes together to form mesentery 10. Regions not covered by peritoneum are covered by a connective tissue layer called the adventitia 11. When the outermost layer is attached to surrounding tissue, it is called adventitia d. **[Mesentery ]** ix. The mesentery is a fold of membrane that attaches the intestine to the wall around the stomach area and hold it in place. x. Mesenteries are double layers of peritoneum in the abdominal cavity and are continuations of the visceral and parietal peritoneum with the serous membranes adhered back to back so that the outer mesothelium secretes serous fluid into the peritoneal cavity. 12. The decreases the friction between the adjacent visceral surfaces and allows some movement of the organs during digestion xi. The mesentery attaches the intestines to the abdominal wall and also helps storing the fat, and allows the blood, lymph vessels, and nerves supply the intestines xii. The peritoneum is the largest serous membrane of the human body -- consisting of ligaments, the greater and lesser omentum as well as the mesenteries 13. Mesentery fold against itself to create 4 layers called the omentum (4 layers of our peritoneum) e. **[Principles of Motility]** xiii. **[Autonomic Nervous System]** 14. ANS -- is a component of the peripheral nervous system that regulates involuntary physiologic processes including HR, BP, respiration, digestion and sexual arousal. c. **[Parasympathetic ]** i. **CN X (vagus nerve**) -- extensive innervation to esophagus, stomach and pancreas; causes and promotes motility. 1. Other CN that help with swallowing (oropharynx and pharyngeal somatic muscle movement) CN V (trigeminal) and CN IX (oropharyngeal) -- motor and sensory components ii. **Sacral** -- 2^nd^, 3^rd^, and 4^th^ segment of spinal cord passes through pelvic nerves to the distal half of the large intestine down to the anus (sigmoidal, rectal, anal). d. **[Sympathetic ]** iii. Arises from abdominal prevertebral ganglia (Celiac, superior mesenteric, and inferior mesenteric ganglia) iv. **T5 -- L2,** postganglionic fibers that innervate gut, leave spinal cord, enter sympathetic chains that lie lateral to spinal column (celiac ganglion, mesenteric ganglia), spread through postganglionic sympathetic nerves back to gut xiv. **[Enteric Nervous System ]** 15. One of the main divisions of the autonomic nervous system; consists of a mesh-like system of neurons that governs the function of the GI tract. 16. Where the postganglionic neurons of the parasympathetic nervous system are located 17. **[Myenteric plexus (Auerbach's plexus)]** e. Lies between the longitudinal and circular muscle layers f. Controls muscle activity along length of gut g. When it is stimulated, increase tonic contraction of gut wall. Increase intensity, rate, and velocity of contraction of gut wall. 18. **[Submucosal plexus (Meissner's plexus)]** h. Lies in the submucosa i. Controls local conditions, such as luminal surface, glandular secretions, electrolyte/water transport and local blood flow xv. **[Neurotransmitters and Hormones]** 19. **Acetylcholine** -- promotes GI activity j. Moves food through your intestine by contracting intestinal muscles and increasing stomach and intestine secretions 20. **Norepi, Epi** -- inhibits GI activity k. Norepi acts on alpha receptors which results in vasoconstriction, increasing vascular resistance and decreasing blood flow to the intestines 21. CCK -- slows gastric emptying 22. GIP -- slows gastric emptying 23. GLP-1 -- slows gastric emptying by inhibiting peristalsis 24. PPY -- slows gastric emptying; appetite suppressing gut hormone xvi. **[Electrical Excitation]** 25. Resting membrane potential (-50 to -60 mV) l. **Slow waves** -- non-action potential, undulations in resting membrane potential (5-15 mV) that causes intermittent spike potentials v. Generate rhythmic GI movements; NOT muscle contraction-- not strong enough to generate an action potential vi. Interstitial cells of Cajal akin to cardiac pacemaker cells -- cause membrane potential changes m. **Spike potentials** -- true action potentials, occur when resting membrane potential becomes \>-40 mV vii. Further depolarization of a "threshold potential" is stimulated by release of **acetylcholine** from nerves, triggering a **rapid influx of calcium** into the cells, generating a **spike potential** associated with contraction of the muscle cells xvii. **[Functional movements ]** 26. **Propulsion** -- food movement forward at an appropriate to accommodate digestion/absorption is primarily via: n. **Peristalsis** viii. Stimuli -- distension (myogenic reflex), chemical/physical irritation of epithelial lining of gut, strong parasympathetic trigger (vagal response) ix. Myenteric plexus is principally responsible 2. Used atropine and blocked Ach nerve endings -- will not have effectual peristalsis 3. No Ach to prime resting membrane potential to make it more positive to allow action potential to occur 4. Patients who get anti-cholinergic drugs end up with constipation x. Behaves according to "law of the gut" o. **Mixing** xi. Intestinal contents mixed for better chemical digestion/absorption xii. Primarily peristalsis, with local intermittent constrictive contractions C. **[Regions of the GI Tract]** f. **[Pharynx ]** xviii. **Mastication** -- food bolus in the mouth initiates chewing reflex 27. Mechanoreceptors in mouth send sensory information to brainstem, driving reflex oscillatory patterns in pons -- generates rhythm of mastication 28. Reflex inhibition of muscles used to masticate (CN V -- trigeminal) -- allows lower jaw to drop which initiates a stretch reflex which causes rebound contraction that closes your teeth and pulls food bolus against mechanoreceptors xix. **Swallowing** 29. **Voluntary** -- rolling food posteriorly into pharynx 30. **Involuntary** (pharyngeal stage) - stimulation of epithelial swallowing receptor (**tactile tonsillar pillars**), impulses passed to brainstem, to initiate autonomic pharyngeal muscle contractions p. **Pulls soft palate up** q. **Close posterior nares** r. **Vocal cord closes** s. **Larynx gets pulled up, pushing epiglottis down over larynx** 31. **Protection against aspiration (aspiration occurs when swallowing occurs during inspiration)** t. Temporal coordination of close of vocal cords arytenoids epiglottis u. Inhibition of respiration at neural control centers in the brainstem v. Swallowing coordinated during expiration 32. **Saliva ph 6-7 (produce about a liter of day)** w. Serous -- **ptyalin** (primary component of saliva) -- type of **alpha amylase** -- carbohydrate digestion x. Mucus secretion -- lubrication surface protection 33. Secretion controlled by taste/tactile stimuli, CNS, and reflexes of stomach and small intestine (primarily controlled by PSNS) g. **[Esophagus]** xx. Conducts food rapidly from **pharynx to stomach** via peristalsis 34. **Primary** -- continuation of wave that began in pharynx 35. **Secondary** -- when primary fails y. Distension of esophagus itself initiates intrinsic neural circuits in myenteric nervous system 36. Larynx raises to relax upper esophageal sphincter (UES) z. Protect against reflux of food into the airways and prevent entry of air into the digestive tract 37. Function of the lower esophageal sphincter (LES) -- 3cm above junction with stomach, formed by esophageal circular muscle a. **Prevention of acidic stomach contents from eroding esophagus** b. Receptive relaxation via myenteric inhibitory neurons -- as peristaltic swallowing wave passes down esophagus to allow stomach to receive food xiii. If sphincter does not relax, it is a pathology -- esophagitis/erosion 38. **Secretions** -- primarily lubrication of food (simple mucous glands with protection of esophageal wall (compound mucous glands) near gastric junction h. **Stomach (first 80% is body, second 20% is antrum)** xxi. **Stores large quantities of food until it can be further processed** 39. When food stretches stomach, vasovagal reflex reduces muscle tone to accommodate larger amount xxii. **Mixture of food with gastric secretions to make chyme** 40. Presence of food causes peristaltic constrictor waves, "mixing waves" c. Initiated by slow waves, **intensity increases toward antrum to generate action potential** forcing towards pylorus 41. Retropulsion -- reflex contraction d. Propulsion, grinding, and retropulsion continues until the food particles are small enough to pass through the pylorus into the duodenum xxiii. **Slow emptying of chyme into small intestine at a rate appropriate for digestion/absorption** 42. Increasing pressure towards pylorus reflexive contraction 43. Increased volume elicit myenteric reflexes and "pyloric pump" 44. Gastrin -- mild stimulatory motor effects xxiv. **Oxyntic (gastric) gland** -- body (first 80% of stomach) 45. **Chief (peptic) cells** -- pepsinogen; active form pepsin chops up denaturized proteins into polypeptides 46. **Parietal (oxyntic)** -- hydrochloric acid (HCl), intrinsic factor, role in vitamin B12 absorption in ileum; most bacteria won't survive at this low pH xxv. Pyloric gland -- antrum (posterior 20% of stomach) 47. G- cells -- gastric xxvi. BOTH 48. **Mucous neck cells** -- mucus to lubricate food movement and protect stomach from digestion of gastric enzymes -- alkaline gel 49. D- cell -- somatostatin 50. Enterochromaffin cell (ECL cells) -- histamine  i. **Regulation and Production of HCl** xxvii. Regulation -- stimulation of parietal cells occurs via 51. Gastrin which stimulates ECL (enterchrommafin) cells to secrete histamine e. Gastric production is stimulated by protein containing foods reaching the antrum f. High contents of protein in stomach, drives HCl production. 52. Histamine regulates the rate of formation and secretion of HCl (H2 blockers work here) g. **Somatostatin** -- inhibit both gastrin release thus parietal acid secretion (own built in regulator of this process; kicks in when stomach is mostly empty). D. **A[ccessory Organs]** j. **[Exocrine Pancreas]** xxviii. Secretions stimulated by **acetylcholine, hormones (CCK)** -- small intestine releases these **in response to fats/amino acids and secretin (which is in response to high acid levels)** xxix. **Acinar cells (primary functional cell)** contribute enzymes for the breakdown of: 53. **Protein** -- **trypsinogen (when activated will activate the following)**, chymotrypsinogen, carboxypolypeptidase h. **Trypsinogen activation upon entering intestinal cavity via enterokinase**; or autocatalytically activated by trypsin i. Trypsin inhibitor prevents activation prior to entering intestines 54. **Carbohydrates** -- pancreatic amylase -- hydrolyzes starches, glycogen, and most other carbohydrates 55. **Fat** -- pancreatic lipase (more specific to pancreas), cholesterol esterase, phospholipase xxx. **Centeroacinar cells** -- large volumes of sodium bicarbonate; support activation of pancreatic enzymes because it is alkaline. Neutralizes stomach acid before it enters duodenum to prevent erosion. k. **[Liver -- produces bile ]** xxxi. **Purpose of bile** 56. Emulsify large fat particles into minute particles so that pancreatic lipase has a greater surface area to operate j. Aid in absorption of digested fat end products in intestinal mucosal membrane xxxii. **Secretion of bile** 57. Secretion of bile occurs through the **hepatocytes** -- continually secrete large amount of bile acids, cholesterol, lecithin, and bilirubin into bile canaliculi between cells k. Flows toward interlobular septa where it empties into terminal bile ducts common hepatic duct common bile duct xiv. Either directly to duodenum OR diverted for up to hours to cystic duct gallbladder l. **[Gallbladder]** xxxiii. Holds 30-60 mL of bile, however water and electrolytes can be absorbed through the gallbladder mucosa to concentrate up to 5-20 fold 58. Primarily high concentration of bile salts, but also lipids -- cholesterol and lecithin which are well-emulsified l. **Development of gallstones** (too much absorption of water from bile, too much absorption of bile acids from bile, or too much cholesterol in bile -- most gallstones are made from cholesterol) xxxiv. Empties within 30 minutes after a meal, primarily in response to fatty foods within the duodenum, because of CCK stimulus m. **[Small Intestine]** xxxv. **Regulation of stomach emptying** (mostly controlled by duodenum) 59. Inhibitory effect of enterogastric nervous reflexes (inhibition will increase the rate at which the stomach empties) m. **Initiated by**: duodenal distension, irritated duodenal mucosa, acidity of duodenal chyme, osmolarity of chyme, and presence of proteins and fats 60. **Causes**: strong inhibition of "pyloric pump" propulsive contractions and increases in the tone of the pyloric sphincter xxxvi. **Primary site of absorption** xxxvii. **Ileocecal valve** -- prevention of backflow from the colon to small intestine xxxviii. **Mixing contractions** 61. **Segmentation** -- stretching of intestinal wall elicits localized concentric contractions spaced at intervals for short periods of time (driven by slow waves and chopping of chyme) 62. Moves at about 8-9x a min xxxix. **Propulsive contractions** 63. **Peristalsis**, at a very slow pace -- net 1 cm/min n. **Takes about 3-5 hours to travel from pylorus to ileocecal valve** o. Faster at proximal but slower at terminal intestine p. Driven by gastroenteric reflex, initiated by stomach dissension through myenteric plexus, stimulatory hormones (gastric, CCK, motilin and inhibitory hormones secretin) xl. First few centimeters of duodenum **Brunner's glands -- secretion of high amount of alkaline mucus to neutralize gastric acid in response to:** 64. Tactile or irritating stimuli on duodenal mucosa 65. Vagal stimulation 66. GI hormones -- secretin (released in response to highly acidic conditions) xli. Brunner's Glands are **inhibited by sympathetic stimulation (decreases amount of alkaline mucus)** -- the duodenum is where 50% of all peptic ulcers occurs xlii. Between villi are crypts of Lierberkuhn epithelium covered by: 67. **Goblet cells** -- mucus that protects and lubricates mucosal surface 68. **Enterocytes** (high amount) q. **Secrete large quantities of water and electrolytes that are reabsorbed** (up to 2L of fluid), along with end-products of digestion by nearby villi; create like a "river" that will be dispersed within small intestine to allow for absorption. r. **Contain digestive enzymes** (peptidases; sucrase/maltase/isomaltase/lactase; intestinal lipase) becomes active as digestion occurs; this occurs so absorption can occur. xliii. Regulated by local enteric nervous reflexes xliv. Folds of Kerckring villi microvilli increases absorptive area 1000-fold, 250 sq. meters n. **[Large Intestine ]** xlv. Proximal large intestine is where you will have absorption of water and electrolytes from chyme to form solid feces 69. **Mixing movements** -- **"haustrations"** s. Combination of segmentation (circular contractions) with longitudinal movement of **tenia coli** to form outward bulges of baglike sacs t. Sluggish, dug into and rolled over colon mucosal surface so absorption can occur (semifluidsemisolid) over 8-15 hours. 70. **Distal intestine**: Storage of fecal matter until it can be expelled u. **Propulsive movements -- "mass movements" -- will occur if area of colon is distended or irritated; person with UC will have mass movements continuously (will always have urge to go to bathroom)** xv. 1-3 times a day, where it takes over the propulsive role -- constrictive ring, loss of haustrations and contract as a unit 71. **Active transport of sodium into cell** v. Tight junction prevent back-diffusion of ions 72. **Secretion of bicarbonate ions into lumen while absorbing chloride ions in exchange process** w. Bicarbonate helps neutralize acidic end products of bacterial action in large intestine xvi. **Bacterial activity also produces vitamin K**, vitamin B12, thiamine, riboflavin. Byproduct gases are what contribute to flatus (CO2, H2 gas and methane). Feces is brown due to bilirubin. Feces is mostly composed of dead cells. E. **[Miscellaneous ]** o. **Defecation Reflexes** xlvi. **Intrinsic reflex** -- distension of rectal wall initiates afferent signals via myenteric plexus initiating: 73. Peristaltic waves in descending colon rectum 74. Inhibitory signals allowing for internal anal sphincter relaxation x. People with incontinence have poor rectal tone from internal anal sphincter xlvii. **Parasympathetic defecation reflex** -- sacral segments of spinal cord travel through pelvic nerves to descending colon rectum via PSNS fibers in pelvic nerves 75. Works with intrinsic reflex to intensify peristaltic waves and relaxes internal anal sphincter 76. Converts the intrinsic reflex into a powerful process (must have the parasympathetic and intrinsic reflex to have a bowel movement) xlviii. If external anal sphincter is also voluntarily relaxed, defecation occurs xlix. **Defecation can also occur with:** taking a deep breath, closure of glottis, contraction of abdominal wall muscles (can also be purposefully activated) p. **Gastrointestinal Blood Flow** l. 20-25% of cardiac output 77. **80% contributed to mucosa, submucosa** 78. **20% contributed to muscularis** li. When PSNS kicks in, GI blood flow reduces. lii. **Arterial supply:** 79. Thoracic aorta abdominal aorta 80. Celiac trunk (T12) left gastric artery (supplies lower curvature of stomach and lower esophagus) + left gastric artery anastomosis to right gastric artery splenic artery (supplies blood to most of body of stomach, pancreas, and spleen) 81. Common hepatic artery (supplies blood to liver and pylorus of stomach, gallbladder, duodenum) 82. Superior mesenteric artery -- branches off at L1; provides blood to mid gut (jejunum, ileum, cecum, appendix, ascending colon, proximal 2/3 of transverse colon) 83. Inferior mesenteric artery --branches off at L3; covers sigmoid colon, rectum, descending colon liii. **Portal venous system** 84. All venous blood from splenic circulation will dump into portal vein 85. Portal vein branches into right and left portal veins that dump into liver sinusoids through each lobule of the liver -- to detoxify splenic blood before it returns to the RA 86. Azygous vein (collateral) -- part of venous system of esophagus; diverting blood into collaterals esophageal varices. q. **Immune Defenses of the GI Tract** liv. Saliva -- flow washes away pathogenic bacteria; contains thiocyanate ions and lysozymes that attack bacteria lv. HCl in stomach lvi. Central lacteal lymph vessel of small intestine -- example of gut lymph drainage lvii. Appendix -- in the younger person (functions to mature B-lymphocytes) lviii. Gut-associated lymphoid tissue (GALT) -- one of largest systems of lymphoid tissue in the body lix. Kupffer cells -- phagocytic cells of the liver F. **[Alterations and Disease ]** r. **[Nausea and vomiting ]** lx. **Dorsal vagal complex within medulla oblongata generates nausea/vomiting** 87. **Composed of nucleus of solitary tract, dorsal motor nucleus of the vagus, and area postrema** which all lack blood-brain barrier, neurons respond rapidly to systemic stimuli y. Major receptor sites for **enterochromaffin cells**, which synthesize \>90% of body's serotonin (5-HT) and substance P whose receptors are present on vagal afferents initiating N/V xvii. Zofran is a serotonin receptor antagonist. z. Also responsive to visceral afferents, drugs lxi. Most common cause is gastroenteritis s. **[Abdominal pain]** lxii. **Parietal** -- transmitted via A-delta fibers that travel w/ somatic peripheral nerves to spinal cords, corresponds to skin dermatomes T6-L1 88. **Peritoneal signs are possible** -- shake bed and patient would be in extreme pain lxiii. **Visceral** -- transmitted via C fibers that are predominantly unmyelinated, sparse, and multi-segmented; related to organ (bowel stretching, no flatus -- dull/crampy) -- somewhat less intense lxiv. **Referred** -- visceral and somatic converge t. **[Acute abdomen ]** lxv. **Sudden onset, severe abdominal pain** 89. Requires urgent often surgical intervention 90. Diagnosis is clinical -- does not necessitate imaging to confirm diagnosis lxvi. **Acute peritonitis** -- rupture of hollow viscus complication of inflammatory bowel disease, malignancy 91. **Bowel rupture** -- bowel contents will irritate peritoneum; then, you will generate air. (Air from perforated bowel will travel) 92. **Pneumoperitoneum on imaging** lxvii. **Vascular** -- mesenteric ischemia, ruptured abdominal aortic aneurysm lxviii. **Obstetric, gynecological** causes -- ruptured ectopic pregnancy, ovarian torsion lxix. **Urologic** -- ureteral colic, pyelonephritis u. **[Dysphagia ]** lxx. **Swallowing difficulties** 93. **Oropharyngeal** a. Food pushed around remaining in mouth; coughing with intake b. Propulsive (neurogenic or myogenic) or structural xviii. Ex: Zenker's diverticulum -- structural 94. **Esophageal** c. Food not going down, globus sensation or "stuck in my throat" d. Propulsive or structural xix. Ex: Schatzki ring -- structural. Achalasia -- LES cannot reflex. v. **[GERD]** lxxi. GERD is a common condition in which the stomach contents move up into the esophagus lxxii. Can cause **esophagitis** lxxiii. **Etiology**: abnormalities in function of LES (hiatal hernia, achalasia), esophageal motility, gastric motility or emptying 95. Resting tone of LES tends to be lower such that vomiting, coughing, lifting, bending, obesity, pregnancy -- any increases in abdominal pressure will exacerbate 96. Esophageal tissue repeatedly exposed to stomach acid pro-inflammatory cells and cytokines are recruited to area e. Can lead to: asthma/chronic cough, laryngitis, laryngeal and tracheal stenosis, Barret's esophagus (squamous columnar cells are more resistant to acid -- can turn into cancer) lxxiv. **Clinical manifestations**: heartburn and regurgitation lxxv. **Tx**: lifestyle/diet modifications, H2 blocker or PPI is first line w. **[Acute Gastritis]** lxxvi. Inflammation of the gastric mucosa 97. Superficial mucosal ulcers, with or without hemorrhage 98. Etiology f. Drugs -- NSAIDS (inhibit COX-1 inhibits prostaglandin synthesis inhibits secretion of mucus) g. Alcohol, stress h. H. pylori infection 99. **Clinical manifestations** -- abdominal pain, epigastric tenderness, bleeding 100. **Tx**: spontaneously, within a few days -- may use antacids, PPI or H2-blocker to help manage symptoms x. **[Gastroparesis ]** lxxvii. Delayed gastric emptying 101. **Etiology**: common complication of poorly controlled DM due to autonomic neuropathy i. Chronic hyperglycemia leads to neuron damage abnormal myenteric transmission, dysfunctional interstitial cells of Cajal and impaired inhibitory neuronal function fewer contractions of antrum/uncoordinated antro-duodenal contractions and pyloric spasms 102. **Clinical manifestations**: vomiting, postprandial fullness, nausea, bloating, constipation or vomiting y. **[Hiatal Hernia]** lxxviii. Stomach pushes through opening in diaphragm into the chest and compromises the LES 103. **[Classifications: ]** j. **[Type 1]** (sliding type): GEJ (gastroesophageal junction) is displaced upwards towards the hiatus; 95% of patients will have this type k. **[Type 2]** (paraoesophageal): part of the stomach migrates into the mediastinum parallel to the esophagus l. **[Type 3]**: both the GEJ and a portion of the stomach have migrated into the mediastinum m. **[Type 4]**: stomach, with colon, small intestine, or spleen also herniate in chest lxxix. **[Etiology]**: congenital, age, increased abdominal pressure lxxx. **[Clinical manifestations:]** GERD type s/s z. **[Peptic Ulcer Disease]** lxxxi. Typically involves stomach and proximal duodenum lxxxii. **Extension into muscularis layer -- more prone to bleeding as compared to gastritis** lxxxiii. **Clinical presentation**: postprandial epigastric pain \-- 15-30 mins- gastric; 2-3 hours -- duodenal; or if causing complications, GI bleed lxxxiv. **Dx**: EGD (high specificity) lxxxv. Tx: PPI, H2 blockers a. **[Diarrhea]** lxxxvi. **[Acute]**: 3+ loose or watery stools a day for \14 days, typically non-infectious (medications, malabsorption) lxxxviii. Too much secretion or not enough absorption 104. **Osmotic (malabsorptive)** -- high concentration of solutes retaining water in lumen n. Altered motility, altered digestion, damage to enterocytes/surface transporters 105. **Secretory** -- elevated rates of fluid transport out of epithelial cells into lumen 106. **Exudative (inflammatory)** -- damage to epithelial cell layer 107. **Motility** -- elevated transit times in colon lxxxix. **Clinical manifestations**: dependent on patient's subjective experience b. **[Constipation]** xc. Uncomfortable, or subjectively infrequent bowel movements 108. **[Primary constipation]** o. **Normal transit** -- stool at a normal rate through the colon, frequency normal, but patients feel constipated p. Slow transit q. Defecation disorders (low sensation to rectum, structural issues) 109. **[Secondary constipation]** r. Medications -- opioids, antihypertensives, iron, AEDs, anti-Parkinsonian s. Medical conditions t. Lifestyle -- low fiber, dehydration c. **[Appendicitis ]** xci. **Most common cause of acute abdominal pain in their 20s** xcii. Acute inflammation of the vermiform appendix xciii. **Etiology** -- most often obstruction by a fecalith (hardened lump of stool) xciv. **Clinical manifestations**: low grade fever, epigastric/periumbilical pain followed by brief nausea, vomiting and anorexia that progresses to RLQ pain xcv. **Complications**: necrosis, gangrene, and perforation peritonitis xcvi. **Tx**: abx with the quickest surgical approach d. **[Diverticular disease ]** xcvii. **Diverticulosis** -- deformity of colon where mucosa and submucosa herniate through the underlying hypertrophic muscularis 110. Primarily descending, sigmoid colon xcviii. **Etiology**: highly refined, low fiber diets chronic constipation, altered collagen-connective tissue disorder xcix. **Clinical Manifestations**: abdominal pain in LLQ, relieved with passing of flatus/feces c. **Complications**: diverticulitis (most common), diverticular blee ci. Tx: low fiber diet, abx/surgery if abscess of peritoneal signs e. **[Inflammatory bowel disease]** cii. Caused by interaction of genetic and environmental factors 111. Genetic preposition for bacteria to not be well-managed 112. Situation where you have more bad bacteria than good bacteria 113. Humara blocks inflammatory cytokine -- TNF-alpha ciii. **2 main forms** 114. **[Crohn's]** -- transmural, granulomatous in character -- **anywhere along GI tract** u. Manifest with symptoms outside GI tract -- inflammatory disorders such as arthritis, autoimmune hepatitis 115. **[Ulcerative Colitis]** -- superficial, limited to colonic mucosa civ. **Clinical Manifestations**: chronic (months), with exacerbations and remissions, mucopurulent or bloody diarrhea with lack of growth of microbial pathogens, and no improvement with antibiotics; weight loss, abdominal pain, urgency f. **[Colorectal cancer ]** cv. Typically adenocarcinoma, 75% located distal to splenic flexure 116. Adenomatous polyps dysplasia carcinoma v. Etiology: genetics and environmental risk factors w. Risk factors: 1^st^ degree relatives of patients with hx of breast/gyn caner, \>10 year hx of UC or Crohn's cvi. **Clinical Manifestations**: rectal bleeding, altered bowel habits, abdominal/back pain, weight loss g. **[Bowel obstruction]** cvii. Lesion causing obstruction in small or large bowel; partial or complete; **\>3 cm dilation for ileus or bowel obstruction; imaging gives us distinction between ileus and obstruction** cviii. Transition point -- where the dilated bowel changes caliber, from dilated to compressed cix. **[Types of lesions causing obstruction]**: 117. Adhesions 118. Tumor 119. Hernia 120. Intraluminal lesions -- foreign body, gallstones, bezoars 121. Intussusception (most common in small bowel) -- bowel telescoping into bowel 122. Volvulus (most common in large bowel) -- loop of intestine twists around itself and the mesentery that supplies it cx. Ileus -- no peristalsis; low flow states such as sepsis, gastroparesis, gut is being manipulated -- nerves coordinating bowel function are being disrupted h. **[Upper GI Bleed (above ligament of Treitz) ]** cxi. 70% of GIB cxii. Esophagus, stomach, and part of small intestine cxiii. **Clinical Manifestations:** hematemesis (bright red blood clots -- rapid bleed), coffee ground emesis (slower chronic bleed), and/or melena (black, tarry stools, which persists 5-7 days after initial bleed) cxiv. **Mostly caused by peptic ulcers, also esophageal varices and excessive vomiting (which can cause a Mallory-Weiss tear)** i. **[Lower GI Bleed (below ligament of Treitz) ]** cxv. 30% of GIB cxvi. Small intestine and colon cxvii. **Clinical Manifestations**: hematochezia (bright red blood per rectum, clots), melena cxviii. Most caused by colonic bleed/diverticulosis j. **[Acute Pancreatitis ]** cxix. Clinical syndrome of acute inflammation and destructive autodigestion of the pancreas and peripancreatic tissues cxx. Alcohol -- metabolite (acetaldehyde) -- intracellular trypsin activation; increases pancreatic secretions -- forming "protein plugs" cxxi. **Clinical Manifestations**: mild, self-limiting abdominal pain, N/V, fever, ileus to hypovolemic shock k. **[Cholelithiasis]** cxxii. **Cholestasis** -- gallstones -- 80%=cholesterol 123. Female, fat, fertile, forty 124. 70-80% biliary colic cxxiii. **Complications** 125. **Cholecystitis** -- 90% of the time, cholethiasis causing inflammation of the gallbladder 126. **Choledocholithiasis** -- gallstones blocking the common bile duct x. Acute, ascending cholangitis -- inflammation of the biliary tree l. **[Liver Cirrhosis ]** cxxiv. Irreversible distortion of normal liver architecture characterized by hepatic injury, fibrosis, nodular regeneration 127. **Causes:** y. Alcohol -- most common cause in the US z. Non-alcohol fatty liver disease