First_Aid_for_the_USMLE_Step_1_2023_Compressed_-451-849

["680 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Embryology ` \u2009R E S P I R AT O R Y \u2014 E MB R Y O LO G Y Lung development Occurs in five stages. Begins with the formation of lung bud from distal end of respiratory diverticulum during week 4 of development. Every pulmonologist can see alveoli. STAGE STRUCTURAL DEVELOPMENT NOTES Embryonic (weeks 4\u20137) Lung bud \u008e\u00a0trachea \u008e\u00a0bronchial buds Errors at this stage can lead to \u008e\u00a0mainstem bronchi \u008e\u00a0secondary (lobar) tracheoesophageal fistula. Pseudoglandular bronchi \u008e\u00a0tertiary (segmental) bronchi. (weeks 5\u201317) Canalicular Endodermal tubules \u008e\u00a0terminal bronchioles. Respiration impossible, incompatible with life. (weeks 16\u201325) Surrounded by modest capillary network. Saccular Terminal bronchioles \u008e\u00a0respiratory bronchioles Airways increase in diameter. Pneumocytes (week 24\u2013birth) \u008e\u00a0alveolar ducts. Surrounded by prominent develop starting at week 20. Respiration Alveolar capillary network. capable at week 25. (week 36\u20138 years) Alveolar ducts \u008e\u00a0terminal sacs. Terminal sacs separated by 1\u00b0 septae. Terminal sacs \u008e\u00a0adult alveoli (due to 2\u00b0 In utero, \u201cbreathing\u201d occurs via aspiration and septation). expulsion of amniotic fluid \u008e\u00a0\u008f\u00a0pulmonary vascular resistance through gestation. At birth, air replaces fluid \u008e\u00a0\u0090\u00a0pulmonary vascular resistance. Embryonic Fetal Postnatal period period period Saccular Alveolar BIRTH Canalicular Pseudoglandular Surfactant Embryonic 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 2 4 6 8 Respiration Weeks Years capable L R Choanal atresia Blockage of posterior nasal opening. Often Often part of multiple malformation syndromes, associated with bony abnormalities of the such as CHARGE syndrome: midface. Most often unilateral. When \u0083\t Coloboma of eye bilateral, represents an emergency and \u0083\t Heart defects presents with upper airway obstruction, noisy \u0083\t Atresia of choanae breathing, and\/or cyanosis that worsens during \u0083\t Restricted growth and development feeding and improves with crying. Diagnosed \u0083\t Genitourinary defects by failure to pass nasopharyngeal tube and \u0083\t Ear defects confirmed with CT scan.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Embryology SEC TION III 681 Lung malformations Poorly developed bronchial tree with abnormal histology. Associated with congenital diaphragmatic Pulmonary hypoplasia hernia (usually left-sided), bilateral renal agenesis (Potter sequence). Bronchogenic cysts Caused by abnormal budding of the foregut and dilation of terminal or large bronchi. Discrete, round, sharply defined, fluid-filled densities on CXR (air-filled if infected). Generally asymptomatic but can drain poorly \u008e\u00a0airway compression, recurrent respiratory infections. Club cells Nonciliated; low columnar\/cuboidal with secretory granules. Located in bronchioles. Degrade toxins via cytochrome P-450; secrete component of surfactant; progenitor cells for club and ciliated cells. Alveolar cell types Squamous. 97% of alveolar surfaces. Thinly line Pores of Kohn\u2014anatomical communications Type I pneumocytes the alveoli A for optimal gas exchange. between alveoli that allow for passing of air, Type II pneumocytes fluid, phagocytes, and bacteria (in pneumonia). Cuboidal and clustered B . 2 functions: Alveolar macrophages 1.\t Serve as stem cell precursors for 2 cell Surfactant\u2014\u0090\u00a0alveolar surface tension, \u0090\u00a0alveolar types (type I and type II pneumocytes); collapse, \u0090\u00a0lung recoil, and \u008f\u00a0compliance. proliferate during lung damage. Composed of multiple lecithins, mainly 2.\t Secrete surfactant from lamellar bodies dipalmitoylphosphatidylcholine (DPPC). (arrowheads in B ). Synthesis begins ~20 weeks of gestation and achieves mature levels ~35 weeks of gestation. Application of Law of Laplace in alveoli\u2013alveoli Glucocorticoids important for fetal surfactant have \u008f\u00a0tendency to collapse on expiration as synthesis and lung development. radius \u0090. Collapsing pressure = 2 (surface tension)\/radius Phagocytose foreign materials; release cytokines and alveolar proteases. Hemosiderin-laden macrophages may be found (eg, pulmonary edema, alveolar hemorrhage). A Type II pneumocyte B Type I pneumocyte Type II pneumocyte Type I Alveolar macrophage Capillary Neonatal respiratory Surfactant deficiency \u008e \u008f surface tension Screening tests for fetal lung maturity: lecithin- distress syndrome \u008e\u00a0alveolar collapse (\u201cground-glass\u201d appearance of lung fields) A . sphingomyelin (L\/S) ratio in amniotic fluid A Risk factors: prematurity, diabetes during (\u2265\u00a02 is healthy; < 1.5 predictive of NRDS), foam pregnancy (due to \u008f\u00a0fetal insulin), C-section delivery (\u0090\u00a0release of fetal glucocorticoids; less stability index, surfactant-albumin ratio. stressful than vaginal delivery). Persistently low O2 tension \u008e\u00a0risk of PDA. Treatment: maternal glucocorticoids before birth; exogenous surfactant for infant. Mature L\/S age 3 15 At risk L\/S age 2 Therapeutic supplemental O2 can result in Concentration (mg %) Retinopathy of prematurity, Intraventricular Lecithin hemorrhage, Bronchopulmonary dysplasia (RIB). L\/S ratio 10 1.5 5 L\/S ratio Sphingomyelin 1 20 26 30 35 40 Gestational age (weeks) uploaded by medbooksvn","682 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Anatomy ` \u2009R E S P I R AT O R Y \u2014 A N AT O M Y Respiratory tree Large airways consist of nose, pharynx, larynx, trachea, and bronchi. Airway resistance highest in Conducting zone the large- to medium-sized bronchi. Small airways consist of bronchioles that further divide into terminal bronchioles (large numbers in parallel \u008e least airway resistance). Respiratory zone Warms, humidifies, and filters air but does not participate in gas exchange \u008e \u201canatomic dead space.\u201d Cartilage and goblet cells extend to the end of bronchi. Pseudostratified ciliated columnar cells primarily make up epithelium of bronchus and extend to beginning of terminal bronchioles, then transition to cuboidal cells. Clear mucus and debris from lungs (mucociliary escalator). Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond this point). Lung parenchyma; consists of respiratory bronchioles, alveolar ducts, and alveoli. Participates in gas exchange. Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli. Cilia terminate in respiratory bronchioles. Alveolar macrophages clear debris and participate in immune response. Conducting zone Trachea Goblet cell Basal cell Ciliated cell Bronchi Pseudostrati\ufb01ed ciliated columnar epithelium Smooth muscle Cartilage Club cell Ciliated cell Bronchioles Cuboidal Simple ciliated ciliated cells columnar epithelium Terminal bronchioles Smooth muscle Respiratory zone Club cell Respiratory Simple ciliated bronchioles cuboidal epithelium Alveolar sacs Smooth muscle Cuboidal Club cell Squamous cell cells Simple cuboidal and squamous epithelium Smooth muscle (sparse) Type I pneumocyte Type II pneumocyte Alveolar macrophage Capillary","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Anatomy SEC TION III 683 Lung anatomy Right lung has 3 lobes; Left has less lobes (2) and lingula (homolog of right middle lobe). Instead of Trachea a middle lobe, left lung has a space occupied by the heart A . Relation of the pulmonary artery to the bUrpopenrclohbue s at each lung hilum is described by RALS\u2014Right Anterior; LHeofrtizSountpalerior. Carina is posterior to ascending aorta and anteromedial to descending aorta B . Right lung is a\ufb01mssuorere common site for iOnbhliqaulee d\ufb01ssfuorreeign bodies because right main stem bronchus is wider, more vertical, and shorter than the left. If you aspirate a peanut: Carina \u0083\t While sMuidpdilenleo\u2014be usually enters superiorLinsgeuglament of right lower lobe. \u0083\t While lying on right side\u2014usually entLeorwserright upper lobe. \u0083\t While Iunfperrioigr lhobt\u2014e usually enters right lowloebre lobe. Lower lobe Right Left RL LR bronchus bronchus Anterior view Posterior view Clavicle Anterior view Posterior view Midclavicular line RUL C7 Horizontal \ufb01ssure ICS1 1 LUL LUL 1 T1 RUL ICS2 2 Oblique 2 RML ICS3 3 Oblique \ufb01ssure 3 Horizontal Oblique \ufb01ssure ICS4 4 LLL \ufb01ssure 4 \ufb01ssure ICS5 5 LLL 5 T5 RML RLL 6 6 7 Oblique \ufb01ssure Pleura 8 T8 RLL 9 T9 ICS = intercostal space Lingula 7 10 8 11 9 T12 10 12 11 L1 AB RUL LUL AAo SVC PA RML LLL RLL DAo \u2002\u2002\u2002\u2002 Carina Diaphragm structures Structures perforating diaphragm: Number of letters = T level: T8: vena cava (IVC) Inferior vena Central tendon \u0083\t At T8: IVC, right phrenic nerve T10: (O)esophagus cava (T8) \u0083\t At T10: esophagus, vagus (CN 10; 2 trunks) T12: aortic hiatus Esophagus \u0083\t At T12: aorta (red), thoracic duct (white), (T10) I ate (8) ten eggs at twelve. azygos vein (blue) (\u201cAt T-1-2 it\u2019s the red, C3, 4, 5 keeps the diaphragm alive. Other bifurcations: white, and blue\u201d) \u0083\t The Common Carotid bifourcates at C4. Diaphragm innervated by C3-5 (phrenic). Pain \u0083\t The Trachea bifourcates at T4. Rib Aorta from diaphragm irritation can be referred \u0083\t The abdominal aorta bifourcates at L4. (T12) to shoulder (C5) and trapezius ridge (C3, 4). Vertebra Phrenic nerve injury causes elevation of the Inferior view ipsilateral hemidiaphragm on x-ray. uploaded by medbooksvn","684 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology ` \u2009R E S P I R AT O R Y \u2014 P H Y S I O LO G Y Lung volumes and Note: a capacity is a sum of \u2265 2 physiologic volumes. There are 4 volumes and 4 capacities. capacities Tidal volume Air that moves into lung with each quiet Lung volumes (LITER) Lung capacities inspiration, 6\u20138 mL\/kg, typically ~500 mL. 6.0 Inspiratory reserve IRV volume Air that can still be breathed in after normal Volume Expiratory reserve inspiration VT (L) IC VC TLC volume ERV Residual volume Air that can still be breathed out after normal 2.7 expiration RV 2.2 Inspiratory capacity Air in lung after maximal expiration; RV and IRV = inspiratory reserve volume 1.2 FRC Functional residual any lung capacity that includes RV cannot be VT = tidal volume capacity measured by spirometry ERV = expiratory reserve volume 0 RV = residual volume IC = inspiratory capacity Vital capacity IRV + VT FRC = functional residual capacity Air that can be breathed in after normal VC = vital capacity Total lung capacity TLC = total lung capacity exhalation RV + ERV Volume of gas in lungs after normal expiration; outward pulling force of chest wall is balanced with inward collapsing force of lungs IRV + VT + ERV Maximum volume of gas that can be expired after a maximal inspiration IRV + VT + ERV + RV = VC + RV Volume of gas present in lungs after a maximal inspiration Work of breathing Refers to the energy expended or O2 consumed by respiratory muscles to produce the ventilation needed to meet the body\u2019s metabolic demand. Comprises the work needed to overcome both elastic recoil and airway resistance (ie, work = force \u00d7 distance = pressure \u00d7 volume). Minimized by optimizing respiratory rate (RR) and VT. \u008f in restrictive diseases (\u008f work to overcome elastic recoil achieved with \u008f RR and \u0090 VT) and obstructive diseases (\u008f work to overcome airway resistance achieved with \u0090 RR and \u008f VT). Determination of \tVD\t= V\tT \u00d7 \tPaco2 \u2013 Peco2\t Physiologic dead space\u2014approximately physiologic dead Paco2 equivalent to anatomic dead space in normal space VD = physiologic dead space = anatomic dead lungs. May be greater than anatomic dead space in lung diseases with ventilation\/ space of conducting airways plus alveolar dead perfusion mismatch. space; apex of healthy lung is largest contributor of alveolar dead space. VD = volume of inspired air that does not take part in gas exchange. Paco2 = arterial Pco2. Peco2 = expired air Pco2.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology SEC TION III 685 Ventilation Abbreviated as VE. Total volume of gas entering Normal values: Minute ventilation lungs per minute. \u0083\t RR = 12\u201320 breaths\/min \u0083\t VT = 500 mL\/breath Alveolar ventilation VE = VT \u00d7 RR \u0083\t VD = 150 mL\/breath Abbreviated as VA. Volume of gas that reaches alveoli each minute. VA = (VT \u2212 VD) \u00d7 RR Lung and chest wall Because of historical reasons and small pressures, Lung 0.5 Inspiration Expiration VT properties pulmonary pressures are always presented in Elastic recoil cm H2O. volume (L) Compliance Tendency for lungs to collapse inward and chest 0.0 FRC wall to spring outward. +2 Hysteresis At FRC, airway and alveolar pressures equal Alveolar 0 atmospheric pressure (PB; called zero), and pressure intrapleural pressure is negative (preventing atelectasis). The inward pull of the lung is (cm H O) -2 balanced by the outward pull of the chest wall. System pressure is atmospheric. Pulmonary -4 vascular resistance (PVR) is at a minimum. Intrapleural -6 Change in lung volume for a change in pressure pressure -8 (\u0394V\/\u0394P). Inversely proportional to wall stiffness (cm H O) -10 and increased by surfactant. \u0083\t \u008f compliance = lung easier to fill (eg, 6 TLCVolume (L) ysema emphysema, older adults) Emph \u0083\t \u0090\u00a0compliance = lung more difficult to fill 4 brosis Lung-chest (eg, pulmonary fibrosis, pneumonia, ARDS, Fi wall system pulmonary edema) FRC (net compliance) 2 Lung inflation follows a different pressure- volume curve than lung deflation due to need 0 -10 0 10 20 30 40 to overcome surface tension forces in inflation. -20 Transpulmonary static pressure (cm H\u2082O) uploaded by medbooksvn","686 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology Pulmonary circulation Normally a low-resistance, high-compliance Chronic hypoxic vasoconstriction may lead to system. A \u0090 in Pao2 causes hypoxic vasoconstriction that shifts blood away from pulmonary hypertension +\/\u2013 cor pulmonale. poorly ventilated regions of lung to well- ventilated regions of lung. Diffusion (J) = A \u00d7 Dk \u00d7 P1 \u2013 P2 where \t \u0394x Perfusion limited\u2014O2 (normal health), CO2, N2O. Gas equilibrates early along the length of A = area, \u0394\u2009x = alveolar wall thickness, the capillary. Exchange can be \u008f only if blood Dk = diffusion coefficient of gas, flow \u008f. P1 \u2013 P2 =\u00a0difference in partial pressures. \u0083\t A \u0090 in emphysema. Diffusion limited\u2014O2 (emphysema, fibrosis), CO. Gas does not equilibrate by the time \u0083\t \u0394\u2009x \u008f\u00a0in pulmonary fibrosis. blood reaches the end of the capillary. DLCO is the extent to which CO passes from O2 diffuses slowly, while CO2 diffuses very air sacs of lungs into blood. rapidly across the alveolar membrane. Disease states that lead to diffusion limitation (eg, Partial pressure Equilibration pulmonary fibrosis) are more likely to cause early hypoxia than hypercapnia. PAO\u2082 Perfusion limited PaO\u2082 PaO\u2082 Fibrosis (di usion limited) PACO\u2082 PaCO\u2082 Perfusion limited PaCO Di usion limited 0 Length along pulmonary capillary Pa = partial pressure of gas in pulmonary capillary blood PA = partial pressure of gas in alveolar air Pulmonary vascular P\u2002V\u2002\u2002R\u2002=\u2002P\u2002p\u2003ul\u2003m\u2003arterQy\u02d9\u2013 PL atrium Ppulm artery = pressure in pulmonary artery resistance PL atrium \u2248 pulmonary artery occlusion pressure Remember: \u0394P = Q\u02d9 \u00d7 R, so R = \u0394P \/ Q\u02d9 R = 8\u03b7l (also called pulmonary capillary wedge pressure) \u03c0r4 Q\u02d9 = cardiac output (mL\/min) R = resistance \u03b7 = viscosity of blood (\u201cstickiness\u201d) l = vessel length r = vessel radius","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology SEC TION III 687 Ventilation\/perfusion Ideally, ventilation (V) is matched to perfusion (Q) per minute (ie, ratio = 1) for adequate gas mismatch exchange. Lung zones: \u0083\t at apex of lung = 3 (wasted ventilation) \u0083\t at base of lung = 0.6 (wasted perfusion) Both ventilation and perfusion are greater at the base of the lung than at the apex of the lung. With exercise (\u008f cardiac output), there is vasodilation of apical capillaries \u008e\u00a0 ratio approaches 1. Certain organisms that thrive in high O2 (eg, TB) flourish in the apex. = 0 = \u201coirway\u201d obstruction (shunt). In shunt, 100% O2 does not improve Pao2 (eg, foreign body aspiration). = \u221e = blood flow obstruction (physiologic dead space). Assuming < 100% dead space, 100% O2 improves Pao2 (eg, pulmonary embolus). PA Pv Zone 1 \uf090\uf090\uf090V\u02d9Q\u02d9 \uf08e \uf08fV\u02d9\/Q\u02d9 Pa PA \u2265 Pa > Pv PA Zone 2 V\u02d9\/Q\u02d9 ~ 1 Pa Pv Pa > PA > Pv PA Zone 3 \uf08f\uf08f\uf08fV\u02d9Q\u02d9 \uf08e \uf090V\u02d9\/Q\u02d9 Pa Pv Pa > Pv > PA Alveolar gas equation Pao2 = PIo2 \u2013 Paco2 Pao2 = alveolar Po2 (mm\u00a0Hg) RQ PIO2 = Po2 in inspired air (mm\u00a0Hg) Paco2 = arterial Pco2 (mm\u00a0Hg) \t\t\t\t\t\u2248 150 mm\u00a0Hga \u2013 \u200aP\u200a 0a.c8o2 RQ = respiratory quotient = CO2 produced\/ aAt sea level breathing room air O2\u00a0consumed A-a gradient = Pao2 \u2013 Pao2. Normal A-a gradient estimated as (age\/4) + 4 (eg, for a person < 40 years old, gradient should be < 14). uploaded by medbooksvn","688 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology Carbon dioxide CO2 is transported from tissues to lungs in 3 forms: transport 1 \u2002\u0007HCO3\u2212 (70%). HCO3\u2212\/Cl\u2212 transporter on RBC membrane allows HCO3\u2212 to diffuse out to plasma and Cl\u2212 to diffuse into RBC (chloride shift) via facilitated diffusion countertransport 2 \u2002\u0007Carbaminohemoglobin or HbCO2 (21\u201325%). CO2 bound to Hb at N-terminus of globin (not heme). CO2 favors deoxygenated form (O2 unloaded). 3 \u2002\u0007Dissolved CO2 (5\u20139%). In lungs, oxygenation of Hb promotes dissociation of H+ from Hb. This shifts equilibrium toward CO2 formation; therefore, CO2 is released from RBCs (Haldane effect). Majority of blood CO2 is carried as HCO3\u2212 in the plasma. Tissue Capillary wall Plasma Cl\u2013 HCO3\u2013 1 RBC CO2 enters RBC and is converted to HCO3\u2013 Carbonic CO2 CO2 + H2O anhydrase H2CO3 H+ + HCO3\u2013 HHb H+ + Hb\u2013 CO2 + Hb HbCO2 2 Dissolved CO2 3 Hypoxia and hypoxemia Hypoxia \u0090 O2 delivery to tissues. Commonly due to \u0090\u00a0cardiac output, hypoxemia (insufficient oxygenation of blood with \u0090\u00a0PaO2), ischemia, anemia, CO\/ cyanide poisoning. inspired oxygen tension (PIO2) Hypoventilation (due to PaCO2) PIO2 = FIO2, \u00d7 (PB \u2013 PH2O): most commonly PAO2 = PIO2 - PaCO2 \/ RQ (eg, CNS depression due to PB in high altitude from opiate overdose, obesity hypoventilation syndrome, neuromuscular Normal A-a gradient weakness) Increased A-a gradient Right-to-left shunt (the extreme of V\u02d9\/Q\u02d9 Di usion limitation (eg, \ufb01brosis) mismatch) Normal perfusion in areas of no ventilation. Can be anatomic (eg, intracardiac shunt) or physiologic (eg, perfusion of nonventilated alveoli in ARDS) V\u02d9\/Q\u02d9 mismatch Normal perfusion in areas of ventilation (eg, COPD, pulmonary edema, pulmonary embolism) Hypoxemia Insufficient oxygenation of blood (\u0090 PaO2).","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology SEC TION III 689 Hemoglobin Normal adult hemoglobin (Hb) is composed The protein component of hemoglobin acts as \u03b22 of 4 polypeptide subunits (2 \u03b1 and 2 \u03b2) that buffer for H+ ions. \u03b12 \u03b21 each bind one O2 molecule. Hb is an allosteric Myoglobin is composed of a single polypeptide protein that exhibits positive cooperativity chain associated with one heme moiety. when binding to O2, such that: Higher affinity for oxygen than Hb. Heme \u0083\t Oxygenated Hb has high affinity for O2 (300\u00d7). \u03b11 \u0083\t Deoxygenated Hb has low affinity for O2\u00a0\u008e\u00a0promotes release\/unloading of O2. Oxygen content of O2 content = (O2 bound to hemoglobin) + (O2 solubilized in plasma) = (1.34 \u00d7 Hb \u00d7 SaO2) + (0.003 blood \u00d7 PaO2). SaO2 = percent saturation of arterial blood with O2. 0.003 = solubility constant of O2; PaO2 = partial pressure of O2 in arterial blood. Normally 1 g Hb can bind 1.34 mL O2; normal Hb amount in blood is 15 g\/dL. O2 binding (carrying) capacity \u2248 20 mL O2\/dL of blood. With \u0090\u00a0Hb there is \u0090\u00a0O2 content of arterial blood, but no change in O2 saturation and Pao2. O2 delivery to tissues = cardiac output \u00d7 O2 content of blood. CO poisoning Hb CONCENTRATION SaO2 PaO2 TOTAL O2 CONTENT Anemia Normal \u0090 (CO competes with O2) Normal \u0090 \u0090 Normal Normal \u0090 Polycythemia \u008f Normal Normal \u008f Methemoglobinemia Normal \u0090 (Fe3+ poor at binding O2) Normal \u0090 Normal Cyanide toxicity Normal Normal Normal Oxyhemoglobin Shifts in oxyhemoglobin dissociation curve 100 Hemoglobin dissociation curve (ODC) reflect local tissue oxygen needs. Can be helpful (meets metabolic needs) or harmful 90 oglobin (in toxicities, pathophysiologic situations). 80 Hb saturation (%) Right shift in ODC reflects \u0090 Hb affinity for 70 O2 \u008e \u008f O2 unloading at tissue. Physiologically Left RightMy occurs with \u008f O2 needs: exercise, \u0090 pH, \u008f\u00a0temperature\/fever, hypoxia (\u008f 2,3-BPG); at 60 (\u2193 P50) (\u2191 P50) the cellular level, caused by \u008f H+ and \u008f\u00a0CO2 created by tissue metabolism (Bohr effect). 50 P50 40 Left shift in ODC reflects \u008f Hb affinity for O2 \u008e \u0090\u00a0O2 unloading at tissue. Physiologically 30 occurs with \u0090 O2 needs (\u0090 temperature) and pregnancy (fetal Hb has higher O2 affinity 20 than adult Hb, and \u008f O2 binding due to \u0090 affinity for 2,3-BPG \u008e\u00a0left shift, driving O2 10 Venous blood Arterial blood across placenta to fetus). Pathologically occurs with \u008f CO, \u008f\u00a0MetHb, genetic mutation (\u0090 2,3- (deoxygenated) (oxygenated) BPG). Left is lower. 0 0 10 20 30 40 50 60 70 80 90 100 PO2 (mm Hg) ODC has sigmoidal shape due to positive cooperativity (ie, tetrameric Hb molecule can Mbfoirnydoeag4clohObsi2unmbissoelmqecuouenlnoetmsOaen2rdimchoaalnesdchutihlgeuhbseorduoanfefdsin).ity not show positive cooperativity; curve lacks sigmoidal appearance. uploaded by medbooksvn","690 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology Response to high Constant FIO2 but \u0090 PB \u008e \u0090 atmospheric oxygen (PIO2)\u008e \u0090 Pao2 \u008e \u008f ventilation \u008e \u0090 Paco2 altitude \u008e\u00a0respiratory alkalosis \u008e\u00a0altitude sickness (headaches, nausea, fatigue, lightheadedness, sleep disturbance). Chronic \u008f in ventilation. \u008f erythropoietin \u008e \u008f Hct and Hb (due to chronic hypoxia). \u008f 2,3-BPG (binds to Hb \u008e\u00a0rightward shift of oxyhemoglobin dissociation curve \u008e \u008f\u00a0O2 release). Cellular changes (\u008f mitochondria). \u008f renal excretion of HCO3\u2212 to compensate for respiratory alkalosis (can augment with acetazolamide). Chronic hypoxic pulmonary vasoconstriction \u008e \u008f pulmonary vascular resistance \u008e pulmonary hypertension, right ventricular hypertrophy (RVH). Response to exercise \u008f HR and \u008f SV \u008e \u008f Q\u02d9 \u008e \u008f pulmonary blood flow \u008e \u008f ratio from base to apex (becoming more uniform). \u008f cellular respiration \u008e \u008f CO2 production and \u0090 pH at tissues \u008e right shift of ODC \u008e tissue offloading of more O2 \u008e \u008f O2 consumption. \u008f RR to meet \u008f O2 demand and remove excess CO2\u00a0\u008e\u00a0\u008f\u00a0pulmonary blood flow. PaO2 and PaCO2 are maintained by homeostatic mechanisms. \u0090 P O2 due to \u008f O2 consumption. \u008f P CO2 due to \u008f CO2 production. Methemoglobin Iron in Hb is normally in a reduced state (ferrous Dapsone, local anesthetics (eg, benzocaine), Fe2+; \u201cjust the 2 of us\u201d). Oxidized form of Hb and nitrites (eg, from dietary intake or polluted (ferric, Fe3+) does not bind O2 as readily as Fe2+, water sources) cause poisoning by oxidizing but has \u008f\u00a0affinity for cyanide \u008e\u00a0tissue hypoxia Fe2+ to Fe3+. from \u0090\u00a0O2 saturation and \u0090\u00a0O2 content. Methemoglobinemia can be treated with This Fe3+ form is called methemoglobinemia. methylene blue and vitamin C. While typical concentrations are 1\u20132%, methemoglobinemia will occur at higher levels and may present with cyanosis (does not improve with supplemental O2) and with chocolate-colored blood.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Physiology SEC TION III 691 Cyanide vs carbon Both inhibit aerobic metabolism via inhibition of complex IV of ETC (cytochrome c oxidase) monoxide poisoning \u008e\u00a0hypoxia that does not fully correct with supplemental O2 and \u008f\u00a0anaerobic metabolism. EXPOSURE Cyanide Carbon monoxide PRESENTATION Synthetic product combustion, amygdalin Motor exhaust, gas heaters, fire victims. LABS ingestion (found in apricot seeds), cyanide A ingestion (eg, in suicide attempts), fire victims. Headache, dyspnea, drowsiness, seizure, coma. Headache, vomiting, confusion, visual Skin may appear flushed (\u201ccherry red\u201d). disturbances, coma. May have cherry-red skin Venules in retina appear bright red. Breath with bullous skin lesions. Multiple victims may may have bitter almond odor. be involved (eg, family due to faulty furnace). Normal PaO2. Elevated lactate \u008e\u00a0anion gap Normal PaO2. Elevated carboxyhemoglobin on metabolic acidosis. co-oximetry. Classically associated with bilateral globus pallidus lesions on MRI A , although can rarely be seen with cyanide toxicity. EFFECT ON OXYGEN-HEMOGLOBIN Curve normal. Oxygen saturation may appear Left shift in ODC \u008e\u00a0\u008f\u00a0affinity for O2 \u008e\u00a0\u0090\u00a0O2 CURVE normal initially. Despite ample O2 supply, it unloading in tissues. cannot be used due to ineffective oxidative TREATMENT phosphorylation. Binds competitively to Hb with > 200\u00d7 greater affinity than O2 to form carboxyhemoglobin Decontamination (eg, remove clothing). \u008e\u00a0\u0090\u00a0%O2 saturation of Hb. Hydroxocobalamin (binds cyanide 100% O2. \u008e\u00a0cyanocobalamin \u008e\u00a0renal excretion). Hyperbaric oxygen if severe. Nitrites (oxidize Hb \u008e\u00a0methemoglobin \u008e\u00a0binds cyanide \u008e\u00a0cyanomethemoglobin \u008e\u00a0\u0090\u00a0toxicity). Sodium thiosulfate (\u008f\u00a0cyanide conversion to thiocyanate \u008e\u00a0renal excretion). 20 Normal (100% Hb) O2 bound to Hb (mL O2 \/100 mL) 16 12 50% CO Hb 8 50% Hb (anemia) 4 00 20 40 60 80 100 PaO2 (mm Hg) uploaded by medbooksvn","692 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology ` \u2009R E S P I R AT O R Y \u2014 PAT H O LO G Y Rhinosinusitis Obstruction of sinus drainage into nasal cavity \u008e inflammation and pain over affected area. A Typically affects maxillary sinuses, which drain against gravity due to ostia located superomedially (red arrow points to fluid-filled right maxillary sinus in A ). Orbit Superior meatus\u2014drains posterior ethmoid; middle meatus\u2014drains frontal, maxillary, and anterior Max ethmoid; inferior meatus\u2014drains nasolacrimal duct. Acute rhinosinusitis is most commonly caused by viruses (eg, rhinovirus); may lead to superimposed bacterial infection, most commonly nontypeable H influenzae, S pneumoniae, M catarrhalis. Paranasal sinus infections may extend to the orbits, cavernous sinus, and brain, causing complications (eg, orbital cellulitis, cavernous sinus syndrome, meningitis). Epistaxis Nose bleed. Most commonly occurs in anterior Kiesselbach drives his Lexus with his LEGS: segment of nostril (Kiesselbach plexus). Life- superior Labial artery, anterior and posterior threatening hemorrhages occur in posterior Ethmoidal arteries, Greater palatine artery, segment (sphenopalatine artery, a branch of Sphenopalatine artery. maxillary artery). Common causes include foreign body, trauma, allergic rhinitis, and Anterior ethmoid artery nasal angiofibromas (common in adolescent males). Posterior ethmoid artery Sphenopalatine artery Kiesselbach Greater palatine plexus artery Superior labial artery Head and neck cancer Mostly squamous cell carcinoma. Risk factors include tobacco, alcohol, HPV-16 (oropharyngeal), EBV (nasopharyngeal). Field cancerization: carcinogen damages wide mucosal area \u008e\u00a0multiple tumors that develop independently after exposure. Nasopharyngeal carcinoma may present with unilateral nasal obstruction, discharge, epistaxis. Eustachian tube obstruction may lead to otitis media +\/\u2013 effusion, hearing loss. Laryngeal papillomatosis\u2014also called recurrent respiratory papillomatosis. Benign laryngeal tumor, commonly affecting areas of stratified squamous epithelium such as the true vocal cords, especially in children. Associated with HPV-6 and HPV-11. Deep venous Blood clot within a deep vein \u008e\u00a0swelling, d-dimer test may be used clinically to rule out thrombosis redness A , warmth, pain. Predisposed by DVT if disease probability is low or moderate Virchow triad (SHE): (high sensitivity, low specificity). A \u0083\t Stasis (eg, post-op, long drive\/flight) \u0083\t Hypercoagulability (eg, defect in Imaging test of choice is compression ultrasound coagulation cascade proteins, such as with Doppler. factor\u00a0V Leiden; oral contraceptive use; pregnancy) Use unfractionated heparin or low-molecular \u0083\t Endothelial damage (exposed collagen weight heparins (eg, enoxaparin) for triggers clotting cascade) prophylaxis and acute management. Most pulmonary emboli arise from proximal Use direct anticoagulants (eg, rivaroxaban, deep veins of lower extremity (iliac, femoral, apixaban) for treatment and long-term popliteal veins). prevention.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 693 Pulmonary emboli Obstruction of the pulmonary artery or its branches by foreign material (usually thrombus) that originated elsewhere. Affected alveoli are ventilated but not perfused ( mismatch). May present with sudden-onset dyspnea, pleuritic chest pain, tachypnea, tachycardia, hypoxemia, respiratory alkalosis. Large emboli or saddle embolus (red arrows show filling defects in A ) may cause sudden death due to clot preventing blood from filling LV and increased RV size further compromising LV filling (obstructive shock). CT pulmonary angiography is imaging test of choice for PE (look for filling defects) B . ECG may show sinus tachycardia or, less commonly, S1Q3T3 abnormality. Lines of Zahn C are interdigitating areas of pink (platelets, fibrin) and red (RBCs) found only in thrombi formed before death; help distinguish pre- and postmortem thrombi. Treatment: anticoagulation (eg, heparin, direct thrombin\/factor Xa inhibitors), IVC filter (if anticoagulation is contraindicated). Types: Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor. An embolus moves like a FAT BAT. Fat emboli\u2014associated with long bone fractures and liposuction; classic triad of hypoxemia, neurologic abnormalities, petechial rash. Air emboli\u2014nitrogen bubbles precipitate in ascending divers (caisson disease\/decompression sickness); treat with hyperbaric O2; or, can be iatrogenic 2\u00b0 to invasive procedures (eg, central line placement). Amniotic fl id emboli\u2014typically occurs during labor or postpartum, but can be due to uterine trauma. Can lead to DIC. Rare, but high mortality. ABC Mediastinal pathology Normal mediastinum contains heart, thymus, lymph nodes, esophagus, and aorta. Mediastinal masses Some pathologies (eg, lymphoma, lung cancer, abscess) can occur in any compartment, but there Mediastinitis are common associations: \u0083\t Anterior\u20144 T\u2019s: thyroid (substernal goiter), thymic neoplasm, teratoma, \u201cterrible\u201d lymphoma. Pneumomediastinum \u0083\t Middle\u2014metastases, hiatal hernia, bronchogenic cysts. \u0083\t Posterior\u2014esophageal cancer (may present as mass in, or spread to, middle mediastinum), neurogenic tumor (eg, neurofibroma), multiple myeloma. Inflammation of mediastinal tissues. Commonly due to postoperative complications of cardiothoracic procedures (\u2264\u00a014\u00a0days), esophageal perforation, or contiguous spread of odontogenic\/retropharyngeal infection. Chronic mediastinitis\u2014also called fibrosing mediastinitis; due to \u008f\u00a0proliferation of connective tissue in mediastinum. Histoplasma capsulatum is common cause. Clinical features: fever, tachycardia, leukocytosis, chest pain, and sternal wound drainage. Presence of gas (usually air) in the mediastinum. Can either be spontaneous (due to rupture of pulmonary bleb) or 2\u00b0 (eg, trauma, iatrogenic, Boerhaave syndrome). Ruptured alveoli allow tracking of air into the mediastinum via peribronchial and perivascular sheaths. Clinical features: chest pain, dyspnea, voice change, subcutaneous emphysema, \u2295 Hamman sign (crepitus on cardiac auscultation). uploaded by medbooksvn","694 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Flow-volume loops Normal Obstructive lung disease Restrictive lung disease \u008f \u0090 FLOW-VOLUME PARAMETER >80% predicted \u008f RV >80% predicted \u008f \u0090 FRC >70% \u0090\u0090 TLC \u0090 \u0090 FEV1 \u0090 FVC FEV1 decreased more than \u0090 FEV1\/FVC FVC \u0090 NORMAL InspirationFlow (L\/sec) Expiration Normal or \u008f 8 OBSTRUCTIVE FEV1 decreased proportionately 4 Loop shifts to the left 8 to FVC 4 RESTRICTIVE Loop shifts to the right 86420 8 4 4 8 86 4 2 0 86420 Volume (L) 4 RV 4 8 VC 8 TLC Obstructive lung Obstruction of air flow (\u0090\u0090\u00a0FEV1, \u0090\u00a0FVC \u0090\u00a0FEV1\/FVC ratio) \u008e\u00a0air trapping in lungs (\u008f\u00a0RV, diseases \u008e\u008f\u00a0FRC and \u008f\u00a0TLC) due to premature airway closure at high lung volumes. Includes COPD Chronic obstructive (chronic bronchitis and emphysema), asthma, and bronchiectasis. pulmonary disease Often due to tobacco use (most important risk factor), pollutants, or allergens. Includes chronic Chronic bronchitis bronchitis and emphysema, which often co-exist. Exacerbation: acute worsening of symptoms, often associated with viral or bacterial upper respiratory tract infection. DIAGNOSIS Clinical diagnosis. Criteria: productive cough for \u2265 3 months in a year for > 2 consecutive years. MECHANISMS May also have dyspnea, wheezes, crackles (due to mucus), cyanosis (hypoxemia due to shunting), NOTES 2\u00b0\u00a0polycythemia. Leads to metaplasia of pseudostratified ciliated columnar epithelium into Emphysema stratified squamous epithelium. Hypertrophy and hyperplasia of mucus-secreting glands in bronchi. DIAGNOSIS \u008f\u00a0Reid index (thickness of mucosal gland layer to thickness of wall between epithelium and MECHANISMS cartilage) > 50%. Radiologic or biopsy diagnosis. CXR: barrel chest, \u008f\u00a0AP diameter (best seen in lateral A ), flattened diaphragm, \u008f\u00a0lung field lucency. Alveolar wall destruction B \u008e\u00a0\u008f\u00a0compliance of lung, \u0090\u00a0recoil, and damage to alveolar capillary membrane \u008e\u00a0\u0090\u00a0DLCO; results in \u008f\u00a0air space. Centriacinar\u2014spares distal alveoli, frequently in upper lobes. Associated with tobacco smoking C D . Panacinar\u2014affects respiratory bronchioles and alveoli, frequently in lower lobes. Associated with \u03b11-antitrypsin deficiency.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 695 Obstructive lung diseases (continued) NOTES Mediated by oxidative stress, chronic inflammation (CD8+ T cells, neutrophils, and macrophages), and imbalance of proteases and antiproteases (\u008f\u00a0elastase activity \u008e\u00a0\u008f\u00a0loss of elastic fibers \u008e\u00a0alveolar destruction). Defect\/deficiency\/absence of \u03b11-antitrypsin (antiprotease that inhibits neutrophil elastase( leads to unopposed elastase activity Asthma Intermittent obstructive lung disease often triggered by allergens, viral URIs, stress. Associated with atopy. NSAID- or aspirin-exacerbated respiratory disease\u2014asthma, nasal polyps, and COX-inhibitor sensitivity (leukotriene overproduction \u008e\u00a0airway constriction) (Samter\u2019s triad). DIAGNOSIS Clinical diagnosis. Intermittent episodes of dyspnea, coughing, wheezing, tachypnea. Diagnosis supported by spirometry (obstructive pattern with bronchodilator response, but may be normal when not in exacerbation) +\/\u2013 methacholine challenge. MECHANISMS Type I hypersensitivity reaction \u008e\u00a0smooth muscle hypertrophy and hyperplasia. Hyperresponsive bronchi \u008e\u00a0reversible bronchoconstriction. Mucus plugging E . OTHER Curschmann spirals F \u2014shed epithelium forms whorled mucus plugs. Charcot-Leyden crystals G \u2014eosinophilic, hexagonal, double-pointed crystals formed from breakdown of eosinophils in sputum. Bronchiectasis Obstructive lung disease. Most commonly associated with cystic fibrosis. DIAGNOSIS Characterized by chronic cough and daily purulent sputum production. Often have recurrent pulmonary infections. Confirmed by imaging demonstrating airway dilation and bronchial thickening. Supported by obstructive PFT pattern. PATHOPHYSIOLOGY Initial insult of pulmonary infection combined with obstruction or impaired clearance \u008e\u00a0dysregulated host response \u008e\u00a0bronchial inflammation \u008e\u00a0permanently dilated airways. NOTES Many etiologies, including airway obstruction (eg, foreign body aspiration, mass), poor ciliary motility (eg, tobacco smoking, Kartagener syndrome), cystic fibrosis ( H shows a coughed up inspissated mucus plug), allergic bronchopulmonary aspergillosis, pulmonary infections (eg,\u00a0Mycobacterium avium). A BC D E FG H uploaded by medbooksvn","696 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Restrictive lung May lead to \u0090 lung volumes (\u0090 FVC and TLC). PFTs: normal or \u008f\u00a0FEV1\/FVC ratio. Patient diseases presents with short, shallow breaths. Types: \u0083\t Altered respiratory mechanics (extrapulmonary, normal DLCO, normal A-a gradient): \u0083\t Respiratory muscle weakness\u2014polio, myasthenia gravis, Guillain-Barr\u00e9 syndrome, ALS \u0083\t Chest wall abnormalities\u2014scoliosis, severe obesity \u0083\t Diffuse parenchymal lung diseases, also called interstitial lung diseases (pulmonary, \u0090\u00a0DLCO, \u008f A-a gradient): \u0083\t Pneumoconioses (eg, coal workers\u2019 pneumoconiosis, silicosis, asbestosis) \u0083\t Sarcoidosis: bilateral hilar lymphadenopathy, noncaseating granulomas; \u008f ACE and Ca2+ \u0083\t Idiopathic pulmonary fibrosis \u0083\t Granulomatosis with polyangiitis \u0083\t Pulmonary Langerhans cell histiocytosis (eosinophilic granuloma) \u0083\t Hypersensitivity pneumonitis \u0083\t Drug toxicity (eg, bleomycin, busulfan, amiodarone, methotrexate) \u0083\t Acute respiratory distress syndrome \u0083\t Radiation-induced lung injury\u2014associated with proinflammatory cytokine release (eg, TNF-\u03b1, IL-1, IL-6). May be asymptomatic but most common symptoms are dry cough and dyspnea +\/\u2013 low-grade fever. Acute radiation pneumonitis develops within 3\u201312 weeks (exudative phase); radiation fibrosis may develop after 6\u201312 months. Idiopathic pulmonary Progressive fibrotic lung disease of unknown etiology. May involve multiple cycles of lung injury, fib osis inflammation, and fibrosis. Associated with tobacco smoking, environmental pollutants, genetic defects. Findings: progressive dyspnea, fatigue, nonproductive cough, crackles, clubbing. Imaging shows peripheral reticular opacities with traction bronchiectasis +\/\u2013 \u201choneycomb\u201d appearance of lung (advanced disease). Histologic pattern: usual interstitial pneumonia. \u0090\u00a0type 1 pneumocytes, \u008f\u00a0type 2 pneumocytes, \u008f\u00a0fibroblasts. Complications: pulmonary hypertension, right heart failure, arrhythmias, coronary artery disease, respiratory failure, lung cancer. Hypersensitivity Mixed type III\/IV hypersensitivity reaction to environmental antigens such as thermophilic pneumonitis Actinomyces and Aspergillus. Often seen in farmers and bird-fanciers. Acutely, causes dyspnea, cough, chest tightness, fever, headache. Often self-limiting if stimulus is removed. Chronically, leads to irreversible fibrosis with noncaseating granuloma, alveolar septal thickening, traction bronchiectasis.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 697 Sarcoidosis Characterized by immune-mediated, widespread noncaseating granulomas \u2009A , elevated serum ACE levels, and elevated CD4\/CD8 ratio in bronchoalveolar lavage fluid. More common in Black females. Often asymptomatic except for enlarged lymph nodes. CXR shows bilateral adenopathy and coarse reticular opacities B ; CT of the chest better demonstrates the extensive hilar and mediastinal adenopathy C . Associated with Bell palsy, parotid enlargement, granulomas (noncaseating epithelioid, containing microscopic Schaumann and Asteroid bodies), Rheumatoid arthritis\u2013like arthropathy, \u008f Calcium, Ocular uveitis, Interstitial fibrosis, vitamin D activation (due to \u008f 1\u03b1-hydroxylase in macrophages), Skin changes (eg, lupus pernio, erythema nodosum) (SARCOIDS). Treatment: glucocorticoids (if symptomatic). A BC Liver Sp Inhalation injury and Complication of inhalation of noxious stimuli A B sequelae (eg, smoke). Caused by heat, particulates (<\u00a01\u00a0\u00b5m diameter), or irritants (eg, NH3) \u008e\u00a0chemical tracheobronchitis, edema, pneumonia, ARDS. Many patients present 2\u00b0 to burns, CO\u00a0inhalation, cyanide poisoning, or arsenic poisoning. Singed nasal hairs or soot in oropharynx common on exam. Bronchoscopy shows severe edema, congestion of bronchus, and soot deposition ( A , 18 hours after inhalation injury; B , resolution at 11 days after injury). Mesothelioma Malignancy of the pleura associated with Histology may show psammoma bodies. asbestosis. May result in hemorrhagic pleural EM may show polygonal tumor cells with effusion (exudative), pleural thickening. microvilli, desmosomes, tonofilaments. Calretinin and cytokeratin 5\/6 \u2295 in almost all mesotheliomas, \u229d in most carcinomas. Tobacco smoking is not a risk factor. uploaded by medbooksvn","698 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Pneumoconioses Asbestos is from the roof (was common in insulation), but affects the base (lower lobes). Asbestos-related Silica, coal, and berries are from the base (earth), but affect the roof (upper lobes). disease Asbestos causes asbestosis (pulmonary fibrosis), Affects lower lobes. Berylliosis pleural disease, malignancies. Associated with Asbestos (ferruginous) bodies are golden-brown shipbuilding, roofing, plumbing. \u201cIvory white,\u201d Coal workers\u2019 calcified, supradiaphragmatic and pleural A fusiform rods resembling dumbbells, found pneumoconiosis plaques are pathognomonic. in alveolar sputum sample, visualized using Silicosis Prussian blue stain B , often obtained by Risk of bronchogenic carcinoma > risk of bronchoalveolar lavage. mesothelioma. \u008f\u00a0risk of Caplan syndrome \u008f\u00a0risk of pleural effusions. (rheumatoid arthritis and pneumoconioses with intrapulmonary nodules). Associated with exposure to beryllium in Affects upper lobes. aerospace and manufacturing industries. Granulomatous (noncaseating) C on histology and therefore occasionally responsive to glucocorticoids. \u008f\u00a0risk of cancer and cor pulmonale. Prolonged coal dust exposure \u008e macrophages Affects upper lobes. laden with carbon \u008e inflammation and Small, rounded nodular opacities seen on fibrosis. imaging. Also called black lung disease. \u008f\u00a0risk of Caplan Anthracosis\u2014asymptomatic condition found in syndrome. many urban dwellers exposed to sooty air. Associated with sandblasting, foundries, Affects upper lobes. mines. Macrophages respond to silica \u201cEggshell\u201d calcification of hilar lymph nodes on and release fibrogenic factors, leading to fibrosis. It is thought that silica may disrupt CXR. phagolysosomes and impair macrophages, The silly egg sandwich I found is mine! increasing susceptibility to TB. \u008f\u00a0risk of cancer, cor pulmonale, and Caplan syndrome. AB C","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 699 Acute respiratory distress syndrome PATHOPHYSIOLOGY Alveolar insult \u008e\u00a0release of pro-inflammatory cytokines \u008e\u00a0neutrophil recruitment, activation, and release of toxic mediators (eg, reactive oxygen species, proteases, etc) \u008e\u00a0capillary endothelial damage and \u008f\u00a0vessel permeability \u008e\u00a0leakage of protein-rich fluid into alveoli \u008e\u00a0formation of intra-alveolar hyaline membranes (arrows in A ) and noncardiogenic pulmonary edema (normal PCWP) \u008e \u0090 compliance and mismatch \u008e hypoxic vasoconstriction \u008e \u008f pulmonary vascular resistance. Loss of surfactant also contributes to alveolar collapse (eg, preterm infants, drowning). CAUSES Sepsis (most common), aspiration pneumonia, burns, trauma, pancreatitis, drowning injuries. DIAGNOSIS Diagnosis of exclusion with the following criteria (ARDS): \u0083\t Abnormal chest X-ray (bilateral lung opacities) B \u0083\t Respiratory failure within 1 week of alveolar insult \u0083\t Decreased PaO2\/FIO2 (ratio < 300, hypoxemia due to \u008f\u00a0intrapulmonary shunting and diffusion abnormalities) \u0083\t Symptoms of respiratory failure are not due to HF\/fluid overload CONSEQUENCES Impaired gas exchange, \u0090\u00a0lung compliance; pulmonary hypertension. MANAGEMENT Treat the underlying cause. Mechanical ventilation: \u0090\u00a0tidal volume, \u008f\u00a0PEEP (keeps alveoli open during expiration). AB Endotracheal tube Right internal jugular line Diffuse opacities Diffuse opacities Sleep apnea Repeated cessation of breathing > 10 seconds during sleep \u008e disrupted sleep \u008e daytime somnolence. Diagnosis confirmed by sleep study. Obstructive sleep apnea Nocturnal hypoxia \u008e\u00a0systemic and pulmonary hypertension, arrhythmias (atrial fibrillation\/flutter), sudden death. Central sleep apnea Hypoxia \u008e \u008f EPO release \u008e \u008f erythropoiesis. Obesity hypoventilation Respiratory effort against airway obstruction. Pao2 is usually normal during the day. Associated with syndrome obesity, loud snoring, daytime sleepiness. Usually caused by excess parapharyngeal\/oropharyngeal tissue in adults, adenotonsillar hypertrophy in children. Treatment: weight loss, CPAP, dental devices, hypoglossal nerve stimulation, upper airway surgery. Impaired respiratory effort due to CNS injury\/toxicity, Congestive HF, opioids. May be associated with Cheyne-Stokes respirations (oscillations between apnea and hyperpnea). Treatment: positive airway pressure. Also called Pickwickian syndrome. Obesity (BMI \u2265 30 kg\/m2) \u008e hypoventilation \u008e\u00a0\u008f\u00a0Paco2 during waking hours (retention); \u0090\u00a0Pao2 and \u008f\u00a0Paco2 during sleep. Treatment: weight loss, positive airway pressure. uploaded by medbooksvn","700 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Pulmonary Elevated mean pulmonary artery pressure (> 20 mm Hg) at rest. Results in arteriosclerosis, medial hypertension hypertrophy, intimal fibrosis of pulmonary arteries, plexiform lesions. \u008f\u00a0pulmonary vascular resistance \u008e\u00a0\u008f\u00a0RV pressure \u008e\u00a0RVH (parasternal heave on examination), RV failure. ETIOLOGIES Often idiopathic. Females > males. Heritable PAH can be due to an inactivating mutation Pulmonary arterial in BMPR2 gene (normally inhibits vascular smooth muscle proliferation); poor prognosis. hypertension Pulmonary vasculature endothelial dysfunction results in \u008f\u00a0vasoconstrictors (eg, endothelin) and (group 1) \u0090\u00a0vasodilators (eg, NO and prostacyclins). Left heart disease Other causes include drugs (eg, amphetamines, cocaine), connective tissue disease, HIV infection, (group 2) portal hypertension, congenital heart disease, schistosomiasis. Lung diseases or hypoxia (group 3) Causes include systolic\/diastolic dysfunction and valvular disease. Chronic thromboembolic Destruction of lung parenchyma (eg, COPD), lung inflammation\/fibrosis (eg, interstitial lung (group 4) diseases), hypoxemic vasoconstriction (eg, obstructive sleep apnea, living in high altitude). Multifactorial (group 5) Recurrent microthrombi \u008e\u00a0\u0090\u00a0cross-sectional area of pulmonary vascular bed. Causes include hematologic, systemic, and metabolic disorders, along with compression of the pulmonary vasculature by a tumor. Physical finding in select lung diseases ABNORMALITY BREATH SOUNDS PERCUSSION FREMITUS TRACHEAL DEVIATION Pleural effusion \u0090 Dull \u0090 None if small Away from side of lesion Atelectasis \u0090 Dull \u0090 \u0090 Hyperresonant \u0090 if large Simple pneumothorax \u0090 Hyperresonant \u0090 Toward side of lesion None Tension Bronchial breath sounds; Dull \u008f Away from side of lesion pneumothorax late inspiratory crackles, egophony, whispered None Consolidation pectoriloquy (lobar pneumonia, pulmonary edema) Digital clubbing Increased angle between nail bed and nail plate (> 180\u00b0) A . Pathophysiology not well understood; A in patients with intrapulmonary shunt, platelets and megakaryocytes become lodged in digital vasculature \u008e\u00a0local release of PDGF and VEGF. Can be hereditary or acquired. Causes include respiratory diseases (eg, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis, lung cancer), cardiovascular diseases (eg, cyanotic congenital heart disease), infections (eg, lung abscess, TB), and others (eg, IBD). Not typically associated with COPD or asthma.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 701 Atelectasis Alveolar collapse (right upper lobe collapse against mediastinum in A ). Multiple causes: A \u0083\t Obstructive\u2014airway obstruction prevents new air from reaching distal airways, old air is resorbed (eg, foreign body, mucous plug, tumor) \u0083\t Compressive\u2014external compression on lung decreases lung volumes (eg, space-occupying lesion, pleural effusion) \u0083\t Contraction (cicatrization)\u2014scarring of lung parenchyma that distorts alveoli (eg, sarcoidosis) \u0083\t Adhesive\u2014due to lack of surfactant (eg, NRDS in premature infants) Decreased via incentive spirometry or \u008f\u00a0PEEP during mechanical ventilation. Obstruction Pleura Lung parenchyma Pleural e usion, Scarring Contraction Adhesive air, tumor Compressive Obstructive Pleural effusion Excess accumulation of fluid A between pleural layers \u008e\u00a0restricted lung expansion during inspiration. Can be treated with thoracentesis to remove\/reduce fluid B . Based on the Light\u2019s Exudate criteria, fluid is consistent with an exudate if pleural fluid protein\/serum protein > 0.5, pleural Transudate fluid LDH\/serum LDH\u00a0>\u00a00.6, or pleural fluid LDH > 2\/3 upper limit of normal serum LDH. Cloudy fluid (cellular). Due to infection (eg, pneumonia, tuberculosis), malignancy, connective tissue disease, lymphatic (chylothorax), trauma. Often requires drainage due to \u008f risk of infection. Clear fluid (hypocellular). Due to \u008f\u00a0hydrostatic pressure (eg, HF, Na+ retention) and\/or \u0090\u00a0oncotic pressure (eg, nephrotic syndrome, cirrhosis). Normal Exudate Transudate Increased hydrostatic pressure Plasma Fluid, in\ufb02ammatory cells, Vascular Fluid leakage Decreased colloid proteins and protein leakage permeability oncotic pressure AB Pretreatment Pretreatment Post-treatment Post-treatment uploaded by medbooksvn","702 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Pneumothorax Accumulation of air in pleural space A . Dyspnea, uneven chest expansion. Chest pain, \u0090\u00a0tactile fremitus, hyperresonance, and diminished breath sounds, all on the affected side. Primary spontaneous pneumothorax Due to rupture of apical subpleural bleb or cysts. Occurs most frequently in tall, thin, young males. Secondary Associated with tobacco smoking. spontaneous pneumothorax Due to diseased lung (eg, bullae in emphysema, Marfan syndrome, infections), mechanical Traumatic ventilation with use of high pressures \u008e\u00a0barotrauma. pneumothorax Tension Caused by blunt (eg, rib fracture), penetrating (eg, gunshot), or iatrogenic (eg, central line pneumothorax placement, lung biopsy, barotrauma due to mechanical ventilation) trauma. Can be from any of the above. Air enters pleural space but cannot exit. Increasing trapped air \u008e\u00a0tension pneumothorax. Trachea deviates away from affected lung B . May lead to increased intrathoracic pressure \u008e\u00a0mediastinal displacement \u008e\u00a0kinking of IVC \u008e\u00a0\u0090\u00a0venous return \u008e\u00a0\u0090\u00a0cardiac output, obstructive shock (hypotension, tachycardia), jugular venous distention. Needs immediate needle decompression and chest tube placement. AB Air in pleural Tracheal space deviation Partially Collapsed collapsed lung lung","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 703 Pneumonia TYPICAL ORGANISMS CHARACTERISTICS TYPE S pneumoniae (most common), Legionella, Intra-alveolar exudate \u008e consolidation A ; may Klebsiella involve entire lobe or the whole lung. Lobar pneumonia A Bronchopneumonia S pneumoniae, S aureus, H influenzae, Acute inflammatory infiltrates from bronchioles Klebsiella into adjacent alveoli; patchy distribution Interstitial (atypical) involving \u2265 1 lobe. pneumonia Mycoplasma, Chlamydophila pneumoniae, B Chlamydophila psittaci, Legionella, Coxiella Diffuse patchy inflammation localized to burnetii, viruses (RSV, CMV, influenza, interstitial areas at alveolar walls; CXR shows adenovirus) bilateral multifocal opacities\u00a0 B . Generally follows a more indolent course (\u201cwalking\u201d pneumonia). Cryptogenic Etiology unknown. \u229d\u00a0sputum and blood Formerly called bronchiolitis obliterans organizing cultures, often responds to glucocorticoids but organizing pneumonia (BOOP). Noninfectious pneumonia not to antibiotics. pneumonia characterized by inflammation of bronchioles and surrounding structure. Aspiration pneumonia Aspiration of oropharyngeal or gastric contents \u008e pulmonary infection. Presents days after aspiration event in dependent lung segment. More common in RLL if sitting Risk factors: altered mental status (\u0090 cough up and RUL if lying down due to bronchial re\ufb02ex or glottic closure), dysphagia, neurologic anatomy. Can progress to abscess. disorders (eg, stroke), invasive tubes (eg, nasogastric tube). Aspiration (chemical) pneumonitis\u2014presents hours after aspiration event. Due to gastric acid\u2013 mediated inflammation. Presents with infiltrates in lower lobe(s) and resolves with supportive treatment. uploaded by medbooksvn","704 SEC TION III Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology Natural history of lobar pneumonia Congestion Red hepatization Gray hepatization Resolution DAYS 1\u20132 3\u20134 5\u20137 8+ FINDINGS Red-purple, partial Red-brown consolidation Uniformly gray Enzymatic digestion consolidation of Exudate with fibrin, Exudate full of WBCs, of exudate by parenchyma macrophages bacteria, RBCs, WBCs lysed RBCs, and Exudate with mostly Reversible fibrin bacteria Healthy Healthy Healthy Healthy Healthy alveolus alveolus alveolus alveolus alveolus MacrophMagaecrophagMeacrophageMacrophaMgeacrophage Lysed ELxRuyBsdeRFCadiBtbeCrinExuLdRyaBsFteCeidbrinExudLRaytBseeCd ExuLRydBsaeCted Exudate CapillaryCapillary CapillaBraycteCriaapBilalacrtyeriCaapBillaacrtyeria Bacteria Bacteria FRiBRbCBriCn WBC WBC WBECxudate WExBuCdate WEBxuCdateRBC ExudRaFBtiCebrinExudFRaibBterCin Normal Congestion Red hepatization Gray hepatization Resolution Lung abscess Localized collection of pus within parenchyma. Lung abscess 2\u00b0 to aspiration is most often found A Caused by aspiration of oropharyngeal contents in right lung. Location depends on patient\u2019s (especially in patients predisposed to loss of position during aspiration: RLL if upright, consciousness [eg, alcohol overuse, epilepsy]) RUL or RML if recumbent. or bronchial obstruction (eg, cancer). Air-fluid levels A often seen on CXR; presence suggests cavitation. Due to anaerobes (eg, Bacteroides, Fusobacterium, Peptostreptococcus) or S aureus. Treatment: antibiotics, drainage, or surgery.","Respiratory\u2003 \uf07d\u2009RESPIRATORY\u2014Pathology SEC TION III 705 Lung cancer Leading cause of cancer death. SPHERE of complications: Superior vena cava\/ Presentation: cough, hemoptysis, bronchial TYPE thoracic outlet syndromes, Pancoast tumor, Horner obstruction, wheezing, pneumonic \u201ccoin\u201d syndrome, Endocrine (paraneoplastic), Recurrent Small cell lesion on CXR or noncalcified nodule on CT. laryngeal nerve compression (hoarseness), Small cell (oat cell) Effusions (pleural or pericardial). carcinoma Sites of metastases from lung cancer: liver Risk factors include tobacco smoking, secondhand (jaundice, hepatomegaly), adrenals, bone smoke, radiation, environmental exposures (eg, Non\u2013small cell (pathologic fracture), brain; \u201cLung \u2018mets\u2019 radon, asbestos), pulmonary fibrosis, family history. Adenocarcinoma Love affective boneheads and brainiacs.\u201d Squamous and small cell carcinomas are sentral (central) and often caused by tobacco smoking. Squamous cell In the lung, metastases (usually multiple Hamartomas are found incidentally on imaging, carcinoma lesions) are more common than 1\u00b0 appearing as well-circumscribed mass. Large cell neoplasms. Most often from breast, colon, carcinoma prostate, and bladder cancer. Bronchial carcinoid tumor LOCATION CHARACTERISTICS HISTOLOGY A Central Undifferentiated \u008e very aggressive. Neoplasm of May cause neurologic paraneoplastic syndromes (eg, neuroendocrine Lambert-Eaton myasthenic syndrome, paraneoplastic Kulchitsky cells \u008e small dark blue cells A . myelitis, encephalitis, subacute cerebellar degeneration) and endocrine paraneoplastic syndromes (Cushing Chromogranin\u00a0A\u00a0\u2295, syndrome, SIADH). Amplification of myc oncogenes neuron-specific common. Managed with chemotherapy +\/\u2013 radiation. enolase\u00a0\u2295, synaptophysin \u2295. Peripheral Most common 1\u00b0 lung cancer. Most common subtype Glandular pattern, often in people who do not smoke. More common in females stains mucin \u2295 B . Central Peripheral than males. Activating mutations include KRAS, EGFR, Bronchioloalveolar subtype: grows along alveolar septa Central or and ALK. Associated with hypertrophic osteoarthropathy \u008e\u00a0apparent \u201cthickening\u201d peripheral of alveolar walls. Tall, B (clubbing). columnar cells containing Bronchioloalveolar subtype (adenocarcinoma in situ): mucus. CXR often shows hazy infiltrates similar to pneumonia; better prognosis. Hilar mass C arising from bronchus; cavitation; cigarettes; Keratin pearls D and hypercalcemia (produces PTHrP). intercellular bridges (desmosomes). Highly anaplastic undifferentiated tumor. Strong Pleomorphic giant association with tobacco smoking. May produce hCG cells E . \u008e\u00a0gynecomastia (enlarged breasts). Less responsive to chemotherapy; removed surgically. Poor prognosis. Excellent prognosis; metastasis rare. Symptoms due to mass Nests of neuroendocrine effect (wheezing) or carcinoid syndrome (flushing, diarrhea). cells; chromogranin A\u00a0\u2295. CD E uploaded by medbooksvn","706 SEC TION III Respiratory\u2003 \uf07d\u2009respiratory\u2014pharmacology Pancoast tumor Also called superior sulcus tumor. Carcinoma that occurs in the apex of lung A may cause A Pancoast syndrome by invading\/compressing local structures. 1st rib Compression of locoregional structures may cause array of findings: Mass \u0083\t Recurrent laryngeal nerve \u008e\u00a0hoarseness \u0083\t Stellate ganglion \u008e\u00a0Horner syndrome (ipsilateral ptosis, miosis, anhidrosis) \u0083\t Superior vena cava \u008e\u00a0SVC syndrome \u0083\t Brachiocephalic vein \u008e\u00a0brachiocephalic syndrome (unilateral symptoms) \u0083\t Brachial plexus \u008e\u00a0shoulder pain, sensorimotor deficits (eg, atrophy of intrinsic muscles of the hand) \u0083\t Phrenic nerve \u008e\u00a0hemidiaphragm paralysis (hemidiaphragm elevation on CXR) Superior vena cava Obstruction of the SVC (eg, thrombus, Jugular venous syndrome tumor) impairs blood drainage from the distention head (\u201cfacial plethora\u201d; note blanching after A fingertip pressure in A ), neck (jugular venous Upper extremity distension, laryngeal\/pharyngeal edema), and venous distention upper extremities (edema). Commonly caused Thrombus\/ by malignancy (eg, mediastinal mass, Pancoast obstruction tumor) and thrombosis from indwelling catheters. Medical emergency. Can raise intracranial pressure (if obstruction is severe) \u008e\u00a0headaches, dizziness, \u008f risk of aneurysm\/ rupture of intracranial arteries. ` \u2009R E S P I R AT O R Y \u2014 P H A R M A C O LO G Y H1-blockers Also called antihistamines. Reversible inhibitors of H1 histamine receptors. May function as neutral First generation antagonists or inverse agonists. CLINICAL USE Diphenhydramine, dimenhydrinate, Names usually contain \u201c-en\/-ine\u201d or \u201c-en\/-ate.\u201d chlorpheniramine, doxylamine. ADVERSE EFFECTS Allergy, motion sickness, vomiting in pregnancy, Second generation sleep aid. CLINICAL USE Sedation, antimuscarinic, anti-\u03b1-adrenergic. ADVERSE EFFECTS Loratadine, fexofenadine, desloratadine, Names usually end in \u201c-adine.\u201d Setirizine cetirizine. (cetirizine) is second-generation agent. Allergy. Far less sedating than 1st generation because of \u0090 entry into CNS. Dextromethorphan Antitussive (antagonizes NMDA glutamate receptors). Synthetic codeine analog. Has mild opioid effect when used in excess. Naloxone can be given for overdose. Mild abuse potential. May cause serotonin syndrome if combined with other serotonergic agents.","Respiratory\u2003 \uf07d\u2009respiratory\u2014pharmacology SEC TION III 707 Pseudoephedrine, phenylephrine MECHANISM Activation of \u03b1-adrenergic receptors in nasal mucosa \u008e\u00a0local vasoconstriction. CLINICAL USE Reduce hyperemia, edema (used as nasal decongestants); open obstructed eustachian tubes. ADVERSE EFFECTS Hypertension. Rebound congestion (rhinitis medicamentosa) if used more than 4\u20136 days. Associated with tachyphylaxis. Can also cause CNS stimulation\/anxiety (pseudoephedrine). Pulmonary hypertension drugs DRUG MECHANISM CLINICAL NOTES Endothelin receptor Competitively antagonizes endothelin-1 Hepatotoxic (monitor LFTs). antagonists receptors \u008e\u00a0\u0090\u00a0pulmonary vascular resistance. Example: bosentan. PDE-5 inhibitors Inhibits PDE-5 \u008e\u00a0\u008f\u00a0cGMP \u008e\u00a0prolonged Also used to treat erectile dysfunction. vasodilatory effect of NO. Contraindicated when taking nitroglycerin or other nitrates (due to risk of severe Prostacyclin analogs PGI2 (prostacyclin) with direct vasodilatory hypotension). effects on pulmonary and systemic arterial vascular beds. Inhibits platelet aggregation. Example: sildenafil. Adverse effects: flushing, jaw pain. Examples: epoprostenol, iloprost. Endothelin pathway Nitric oxide pathway Prostacyclin pathway Endothelium Proendothelin L-arginine Arachadonic acid L-citrulline Endothelin-1 Nitric oxide Prostacyclin Prostacyclin Basement Endothelin Nitrates PDE-5 inhibitors analogs membrane receptor antagonist cAMP Endothelin receptor PIP\u2082 IP\u2083 cGMP GTP \uf068 Ca2+ Smooth muscle Vasoconstriction and Vasodilation and \uf068 proliferation \uf069 proliferation uploaded by medbooksvn","708 SEC TION III Respiratory\u2003 \uf07d\u2009respiratory\u2014pharmacology Asthma drugs Bronchoconstriction is mediated by (1) inflammatory processes and (2) parasympathetic tone; therapy is directed at these 2 pathways. Inhaled \u03b22-agonists Albuterol, salmeterol, formoterol\u2014relax bronchial smooth muscle. Can cause tremor, Inhaled arrhythmia. Albuterol is short-acting, used for acute symptoms. Salmeterol and formoterol are glucocorticoids long-acting. Muscarinic Fluticasone, budesonide\u2014inhibit the synthesis of virtually all cytokines. Inactivate NF-\u03baB, the antagonists transcription factor that induces production of TNF-\u03b1 and other inflammatory agents. 1st-line Antileukotrienes therapy for chronic asthma. Use a spacer or rinse mouth after use to prevent oral thrush. Anti-IgE monoclonal Tiotropium, ipratropium\u2014competitively block muscarinic receptors, preventing therapy bronchoconstriction. Also used for COPD. Tiotropium is long acting. Methylxanthines Montelukast, zafirlukast\u2014block leukotriene receptors (CysLT1). Especially good for aspirin- PDE-4 Inhibitors induced and exercise-induced asthma. Chromones Zileuton\u20145-lipoxygenase inhibitor. \u0090 conversion of arachidonic acid to leukotrienes. Hepatotoxic. Anti-IL-5 monoclonal therapy Omalizumab\u2014binds mostly unbound serum IgE and blocks binding to Fc\u03b5RI. Used in allergic asthma with \u008f\u00a0IgE levels resistant to inhaled glucocorticoids and long-acting \u03b22-agonists. Theophylline\u2014likely causes bronchodilation by inhibiting phosphodiesterase \u008e \u008f cAMP levels due to \u0090 cAMP hydrolysis. Limited use due to narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by cytochrome P-450. Blocks actions of adenosine. Roflumilast\u2014inhibits phosphodiesterase \u008e \u008f cAMP \u008e bronchodilation, \u0090 airway inflammation. Used in COPD to reduce exacerbations. Cromolyn\u2014prevents mast cell degranulation. Prevents acute asthma symptoms. Rarely used. Prevents eosinophil differentiation, maturation, activation, and survival mediated by IL-5 stimulation. For maintenance therapy in severe eosinophilic asthma. Mepolizumab, reslizumab\u2014against IL-5. Benralizumab\u2014against IL-5 receptor \u03b1. Avoidance Exposure to allergen (eg, dust, pollen) Allergen- speci\ufb01c IgE Th2 cell Fc receptor for IgE Mepolizumab Glucocorticoids Anti-IgE monoclonal therapy Reslizumab Fluticasone Omalizumab Budesonide Chromones IL-5 Mast cell Cromolyn IL-5R\u00b0 degranulation Benralizumab Eosinophil Proin\ufb02ammatory mediators (eg, leukotrienes, histamine, interleukins) ACUTE RESPONSE (bronchoconstriction) CHRONIC RESPONSE (in\ufb02ammation) ATP \u02dc \u2082-agonists AMP Muscarinic antagonists Proin\ufb02ammatory cytokines AC Tiotropium PDE Methylxanthines Adenosine Ipratropium Bronchodilation Theophylline ACh cAMP PDE-4 inhibitors Ro\ufb02umilast (COPD only) Bronchial tone Bronchoconstriction Mucous secretion CysLT1 Antileukotrienes Phospholipase A\u2082 Glucocorticoids Plasma exudation receptor Montelukast Arachidonic acid Fluticasone Eosinophil recruitment Za\ufb01rlukast Budesonide Antileukotrienes 5-Lipoxygenase COX1\/COX2 Prostaglandins Zileuton Prostacyclin Thromboxane Leukotrienes","HIGH-YIELD SYSTEMS Rapid Review \u201cStudy without thought is vain: thought without study is dangerous.\u201d `\tPathophysiology of \u2014Confucius Important Diseases \t 710 \u201cIt is better, of course, to know useless things than to know nothing.\u201d `\tClassic 722 \u2014Lucius Annaeus Seneca Presentations \t \u201cFor every complex problem there is an answer that is clear, simple, and `\tClassic Labs\/ 728 wrong.\u201d Findings\t \u2014H. L. Mencken `\tKey Associations\t 732 The following tables represent a collection of high-yield associations `\tEquation Review\t 737 between diseases and their clinical findings, treatments, and key associations. They can be quickly reviewed in the days before the exam. `\tEasily Confused 739 Medications\t We have added a high-yield Pathophysiology of Important Diseases section for review of disease mechanisms and removed the Classic\/ Relevant Treatments section to accommodate the change in focus of the USMLE from pharmacology to pathophysiology. 709 uploaded by medbooksvn","710 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs `\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASES CONDITION MECHANISM PAGE Lesch-Nyhan syndrome Absent HGPRT \u008e\u00a0\u008f\u00a0de novo purine synthesis \u008e\u00a0\u008f\u00a0uric acid production 35 \u03b2-thalassemia Mutation at splice site or promoter sequences \u008e\u00a0retained intron in mRNA 38, 425 Lynch syndrome Failure of mismatch repair during the S phase \u008e\u00a0microsatellite instability 37, 395 I-cell disease N-acetylglucosaminyl-1-phosphotransferase defect \u008e\u00a0Golgi mediated 45 mannose residues phosphorylation failure (\u0090\u00a0mannose-6-phosphate) Osteogenesis imperfecta \u008e\u00a0\u008f\u00a0cellular debris in lysosomes 49 Menkes disease 49 Type 1 collagen defect due to inability to form triple helices Marfan syndrome 50 Defective ATP7A protein \u008e\u00a0impaired copper absorption and transport Prader-Willi syndrome \u008e\u00a0\u0090\u00a0lysyl oxidase activity \u008e\u00a0\u0090\u00a0collagen cross-linking 56 Angelman syndrome FBN1 mutation on chromosome 15 \u008e\u00a0defective fibrillin (normally forms 56 sheath around elastin) Cystic fibrosis 58 Uniparental disomy or imprinting leading to silencing of maternal gene. Duchenne muscular dystrophy Disease expressed when paternal allele deleted or mutated 59 Myotonic dystrophy Silenced gene leading to mutation, lack of expression, or deletion of UBE3A 59 on maternal chromosome 15 Fragile X syndrome 60 Bitot spots in vitamin A deficiency Autosomal recessive \u0394F508 deletion in CFTR gene on chromosome 7 64 \u008e\u00a0impaired ATP-gated Cl\u2212 channel (secretes Cl\u2212 in lungs and GI tract and Wernicke encephalopathy in alcoholic reabsorbs Cl\u2212 in sweat glands) 64 patient given glucose Dystrophin gene frameshift mutations \u008e\u00a0loss of anchoring protein to ECM 65 Pellagra in malignant carcinoid (dystrophin) \u008e\u00a0myonecrosis syndrome 69 CTG trinucleotide repeat expansion in DMPK gene \u008e\u00a0abnormal expression Kwashiorkor of myotonin protein kinase \u008e\u00a0myotonia 70 Lactic acidosis, fasting hypoglycemia, Trinucleotide repeat in FMR1 gene \u008e\u00a0hypermethylation \u008e\u00a0\u0090\u00a0expression 76 hepatic steatosis in alcoholism \u0090\u00a0differentiation of epithelial cells into specialized tissue \u008e\u00a0squamous 78 Aspirin-induced hyperthermia metaplasia 78 Hereditary fructose intolerance Thiamine deficiency \u008e\u00a0impaired glucose breakdown \u008e\u00a0ATP depletion worsened by glucose infusion Classic galactosemia Tryptophan is diverted towards serotonin synthesis \u008e B3 deficiency (B3 is derived from tryptophan) Protein malnutrition \u008e\u00a0\u0090\u00a0oncotic pressure (\u008e\u00a0edema), \u0090\u00a0apolipoprotein synthesis (\u008e\u00a0liver fatty change) \u008f\u00a0NADH\/NAD+ ratio due to ethanol metabolism \u008f\u00a0permeability of mitochondrial membrane \u008e\u00a0\u0090\u00a0proton [H+] gradient and \u008f\u00a0O2 consumption \u008e\u00a0uncoupling Aldolase B deficiency \u008e\u00a0Fructose-1-phosphate accumulates \u008e\u00a0\u0090\u00a0available phosphate \u008e\u00a0inhibition of glycogenolysis and gluconeogenesis Galactose-1-phosphate uridyltransferase deficiency \u008e\u00a0accumulation of toxic substances (eg, galactitol in eyes)","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 711 CONDITION MECHANISM PAGE Cataracts, retinopathy, peripheral Lens, retina, Schwann cells lack sorbitol dehydrogenase \u008e\u00a0intracellular 79 neuropathy in DM sorbitol accumulation \u008e\u00a0osmotic damage 105 Recurrent Neisseria bacteremia Terminal complement deficiencies (C5\u2013C9) \u008e\u00a0failure of MAC formation 105 Hereditary angioedema C1 esterase inhibitor deficiency \u008e\u00a0unregulated activation of kallikrein 105 Paroxysmal nocturnal hemoglobinuria \u008e\u00a0\u008f\u00a0bradykinin 110 Type I hypersensitivity PIGA gene mutation \u008e\u00a0\u0090\u00a0GPI anchors for complement inhibitors (DAF\/ CD55, MIRL\/CD59) \u008e\u00a0complement-mediated intravascular hemolysis 110 Type II hypersensitivity Immediate (minutes): antigen cross links IgE on mast cells \u008e\u00a0degranulation 111 Type III hypersensitivity \u008e\u00a0release of histamine and tryptase 111 Type IV hypersensitivity Late (hours): mast cells secrete chemokines (attract eosinophils) and 112 Acute hemolytic transfusion reaction leukotrienes \u008e\u00a0inflammation, tissue damage 114 X-linked (Bruton) Antibodies bind to cell-surface antigens \u008e\u00a0cellular destruction, 114 agammaglobulinemia inflammation, cellular dysfunction DiGeorge syndrome 115 Antigen-antibody complexes \u008e\u00a0activate complement \u008e\u00a0attracts neutrophils 115 Hyper-IgM syndrome Leukocyte adhesion deficiency (type\u00a01) T cell-mediated (no antibodies involved). CD8+ directly kills target cells, 115 CD4+ releases cytokines Ch\u00e9diak-Higashi syndrome 115 Type II hypersensitivity reaction against donor RBCs (usually ABO antigens) 116 Chronic granulomatous disease Candida infection in Defect in BTK gene (tyrosine kinase) \u008e\u00a0no B-cell maturation \u008e\u00a0absent 117 B\u00a0cells in peripheral blood, \u0090\u00a0Ig of all classes 126 immunodeficiency Graft-versus-host disease 22q11 microdeletion \u008e\u00a0failure to develop 3rd and 4th branchial (pharyngeal) 130 Recurrent S aureus, Serratia, B\u00a0cepacia pouches 130 infections in CGD Defective CD40L on Th cells \u008e\u00a0class switching defect 130 Hemolytic uremic syndrome 131 Tetanus LFA-1 integrin (CD18) defect \u008e\u00a0impaired phagocyte migration and chemotaxis 131 Botulism Gas gangrene LYST mutation \u008e\u00a0microtubule dysfunction \u008e\u00a0phagosome-lysosome fusion defect Toxic shock syndrome, scarlet fever NADPH oxidase defect \u008e\u00a0\u0090\u00a0ROS, \u0090\u00a0respiratory burst in neutrophils \u0090\u00a0granulocytes (systemic), \u0090\u00a0T cells (local) Type IV HSR; HLA mismatch \u008e\u00a0donor T cells attack host cells Catalase \u2295 organisms degrade H2O2 before it can be converted to microbicidal products by the myeloperoxidase system Shiga\/Shiga-like toxins inactivate 60S ribosome \u008e\u00a0\u008f\u00a0cytokine release Tetanospasmin prevents release of inhibitory neurotransmitters (GABA and glycine) from Renshaw cells Toxin (protease) cleaves SNARE \u008e\u00a0\u0090\u00a0neurotransmitter (ACh) release at NMJ Alpha toxin (phospholipase\/lecithinase) degrades phospholipids \u008e\u00a0myonecrosis TSST-1 and erythrogenic exotoxin A (scarlet) cross-link \u03b2\u00a0region of TCR to MHC class II on APCs outside of antigen binding site\u00a0\u008e\u00a0\u008f\u008f\u00a0IL-1, IL-2, IFN-\u03b3, TNF-\u03b1 uploaded by medbooksvn","712 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs CONDITION MECHANISM PAGE Shock and DIC by gram \u229d bacteria Lipid A of LPS \u008e\u00a0macrophage activation (TLR4\/CD14), complement 131 activation, tissue factor activation 126, Prosthetic device infection by Biofilm production 133 S\u00a0epidermidis 126, 134 Endocarditis 2\u00b0 to S\u00a0sanguinis Dextrans (biofilm) production that bind to fibrin-platelet aggregates on 136 damaged heart valves 137 Pseudomembranous colitis 2\u00b0 to Toxins A and B damage enterocytes \u008e\u00a0watery diarrhea 138 C\u00a0difficile Exotoxin inhibits protein synthesis via ADP-ribosylation of EF-2 139 Diphtheria 140 143 Virulence of M\u00a0tuberculosis Cord factor activates macrophages (promoting granuloma formation), 143 Tuberculoid leprosy induces release of TNF-\u03b1; sulfatides (surface glycolipids) inhibit phagolysosomal fusion 146 Th1 immune response \u008e\u00a0mild 166 166 No effective vaccine for N\u00a0gonorrhoeae Antigenic variation of pilus proteins 169 173 Cystitis and pyelonephritis by E\u00a0coli Fimbriae (P pili) K capsule 213 Pneumonia, neonatal meningitis by E\u00a0coli Lack of classic peptidoglycan (reduced muramic acid) 217 Chlamydiae resistance to \u03b2-lactam RNA segment reassortment \u008e\u00a0antigenic shift 217 antibiotics Mutations in hemagglutinin, neuraminidase \u008e\u00a0antigenic drift Binds to ACh receptors \u008e\u00a0retrograde transport (dynein) 302 Influenza pandemics 302 302 Influenza epidemics 303 CNS invasion by rabies 305 HIV infection Virus binds CD4 along with CCR5 on macrophages (early), or CXCR4 on T cells (late) Granuloma Macrophages present antigens to CD4+ and secrete IL-12 \u008e\u00a0CD4+ differentiation into Th1 which secrete IFN-\u03b3 \u008e\u00a0macrophage activation Limitless replicative potential of cancer cells Reactivation of telomerase \u008e\u00a0maintains and lengthens telomeres \u008e\u00a0prevention of chromosome shortening and aging Tissue invasion by cancer \u0090\u00a0E-cadherin function \u008e\u00a0\u0090\u00a0intercellular junctions \u008e\u00a0basement membrane Persistent truncus arteriosus and ECM degradation by metalloproteinases \u008e\u00a0cell attachment to ECM proteins (laminin, fibronectin) \u008e\u00a0locomotion \u008e\u00a0vascular dissemination Failure of aorticopulmonary septum formation D-transposition of great arteries Failure of the aorticopulmonary septum to spiral Tet spells in tetralogy of Fallot Crying, fever, exercise \u008e\u00a0\u008f\u00a0RV outflow obstruction \u008e\u00a0\u008f\u00a0right-to-left flow Eisenmenger syndrome across VSD; Squatting \u008e\u00a0\u008f\u00a0SVR \u008e\u00a0\u0090\u00a0right-to-left shunt \u008e\u00a0\u0090\u00a0cyanosis Atherosclerosis Uncorrected left-to-right shunt \u008e\u00a0\u008f\u00a0pulmonary blood flow \u008e\u00a0remodeling of vasculature \u008e\u00a0pulmonary hypertension \u008e\u00a0RVH \u008e\u00a0right to left shunting Endothelial cell dysfunction \u008e\u00a0macrophage and LDL accumulation \u008e\u00a0foam cell formation \u008e\u00a0fatty streaks \u008e\u00a0smooth muscle cell migration, extracellular matrix deposition \u008e\u00a0fibrous plaque \u008e\u00a0complex atheromas","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 713 CONDITION MECHANISM PAGE Thoracic aortic aneurysm Cystic medial degeneration 306 Myocardial infarction 308 Non\u2013ST-segment elevation MI Rupture of coronary artery atherosclerotic plaque \u008e\u00a0acute thrombosis 308 ST-segment elevation MI Subendocardial infarcts (subendocardium vulnerable to ischemia) 308 Death within 0-24 hours post MI Transmural infarcts 309, Ventricular arrhythmia 314 Death or shock within 3-14 days post 309, MI Macrophage-mediated ruptures: papillary muscle (2-7 days), interventricular 314 septum (3-5 days), free wall (5-14 days) 311 Wolff-Parkinson-White Abnormal accessory pathway from atria to ventricle bypasses the AV node 315 Hypertrophic obstructive \u008e\u00a0ventricles begin to partially depolarize earlier \u008e\u00a0delta wave. Reentrant cardiomyopathy circuit \u008e\u00a0supraventricular tachycardia. 315 Syncope, dyspnea in HOCM Sarcomeric proteins gene mutations (myosin binding protein C and 317 \u03b2-myosin heavy chain) \u008e\u00a0concentric hypertrophy (sarcomeres added in 317 Hypovolemic shock parallel). Death due to arrhythmia 317 Cardiogenic shock 319 Distributive shock Asymmetric septal hypertrophy, systolic anterior motion of mitral valve 339 Rheumatic fever \u008e\u00a0outflow obstruction Most common form of congenital 344 \u0090\u00a0preload \u008e\u00a0\u0090\u00a0CO adrenal hyperplasia \u0090\u00a0CO due to left heart dysfunction Heat intolerance, weight loss in \u0090\u00a0SVR (afterload) hyperthyroidism Antibodies against M protein cross react with self antigens; type II HSR Myxedema in hypothyroidism Graves ophthalmopathy 21-hydroxylase deficiency\u008e\u00a0\u0090\u00a0mineralocorticoids, \u0090\u00a0cortisol, \u008f\u00a0sex hormones, \u008f\u00a017-hydroxyprogesterone 1\u00b0 hyperparathyroidism 2\u00b0 hyperparathyroidism \u008f\u00a0Na+-K+ ATPase \u008e\u00a0\u008f\u00a0basal metabolic rate \u008e\u00a0\u008f\u00a0calorigenesis Euvolemic hyponatremia in SIADH \u008f\u00a0CAGs in interstitial space 344 Small\/large vessel disease in DM 346 Diabetic ketoacidosis Lymphocytic infiltration, fibroblast secretion of GAGs \u008e\u00a0\u008f\u00a0osmotic muscle swelling, inflammation 349 Hyperosmolar hyperglycemic state 349 Zollinger-Ellison syndrome Parathyroid adenoma or hyperplasia \u008e\u00a0\u008f\u00a0PTH 342 Duodenal atresia \u0090\u00a0Ca2+ and\/or \u008f\u00a0PO43\u2013 \u008e\u00a0parathyroid hyperplasia \u008e\u00a0\u008f\u00a0PTH, \u008f\u00a0ALP 350 Jejunal\/ileal atresia \u008f\u00a0ADH \u008e\u00a0water retention \u008e\u00a0\u0090\u00a0aldosterone, \u008f\u00a0ANB, \u008f BNP \u008e\u00a0\u008f\u00a0urinary Na+ 351 secretion 351 357 Nonenzymatic glycation of proteins 366 \u0090\u00a0Insulin or \u008f\u00a0insulin requirement \u008e\u00a0\u008f\u00a0fat breakdown \u008e\u00a0\u008f\u00a0free fatty acids 366 \u008e\u00a0\u008f\u00a0ketogenesis Hyperglycemia \u008e\u00a0\u008f\u00a0serum osmolality, excessive osmotic diuresis Gastrin-secreting tumor (gastrinoma) of pancreas or duodenum \u008e\u00a0recurrent ulcers in duodenum\/jejunum and malabsorption Failure to recanalize Disruption of SMA \u008e\u00a0ischemic necrosis of fetal intestine uploaded by medbooksvn","714 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs CONDITION MECHANISM PAGE Superior mesenteric artery syndrome Compression of transverse (third) portion of duodenum by SMA and aorta 370 Achalasia 383 Loss of postganglionic inhibitory neurons (contain NO and VIP) in Barrett esophagus myenteric plexus \u008e\u00a0failure of LES relaxation 385 Acute gastritis 2\u00b0 to NSAIDs Replacement (metaplasia) of nonkeratinized stratified squamous epithelium 386 Celiac disease with intestinal epithelium (nonciliated columnar with goblet cells) 388 Fistula formation in Crohn \u0090\u00a0PGE2 \u008e\u00a0\u0090\u00a0gastric protection 389 Meckel diverticulum Autoimmune-mediated intolerance of gliadin (found in wheat) 391 Hirschsprung disease 391 \u008e\u00a0malabsorption (distal duodenum, proximal jejunum), steatorrhea Adenoma-carcinoma sequence in 395 colorectal cancer Transmural inflammation 396 Fibrosis in cirrhosis Persistence of the vitelline (omphalomesenteric) duct 397 Reye syndrome 398 Hepatic encephalopathy Loss of function mutation in RET \u008e\u00a0failure of neural crest migration \u008e\u00a0lack 400 \u03b11-antitrypsin deficiency of ganglion cells\/enteric nervous plexuses in distal colon Wilson disease 402 Loss of APC (\u0090\u00a0intercellular adhesion, \u008f\u00a0proliferation) \u008e\u00a0KRAS mutation Hemochromatosis (unregulated intracellular signaling) \u008e\u00a0loss of tumor suppressor genes 402 (TP53, DCC) Gallstone ileus 403 Stellate cells Acute cholangitis 403 Acute pancreatitis Aspirin \u0090\u00a0\u03b2-oxidation by reversible inhibition of mitochondrial enzymes 404 Rh hemolytic disease of the newborn 411 Cirrhosis \u008e\u00a0portosystemic shunts \u008e\u00a0\u0090\u00a0NH3 metabolism Anemia in lead poisoning Misfolded proteins aggregate in hepatocellular ER \u008e\u00a0cirrhosis. In lungs, 425 Anemia of chronic disease \u0090\u00a0\u03b11-antitrypsin \u008e\u00a0uninhibited elastase in alveoli \u008e\u00a0panacinar emphysema 427 Mutated hepatocyte copper-transporting ATPase (ATP7B on chromosome G6PD deficiency 428 13) \u008e\u00a0\u0090\u00a0copper incorporation into apoceruloplasmin, excretion into bile Sickle cell anemia \u008e\u00a0\u0090\u00a0serum ceruloplasmin, \u008f\u00a0copper in tissues and urine 428 Bernard-Soulier syndrome HFE mutation on chromosome 6 \u0090\u00a0hepcidin production, \u008f\u00a0intestinal 432 absorption \u008e iron overload (\u008f\u00a0ferritin,\u008f\u00a0iron, \u0090\u00a0TIBC \u008e\u00a0\u008f\u00a0transferrin saturation) Fistula between gallbladder and GI tract \u008e\u00a0stone enters GI lumen \u008e\u00a0obstructing ileocecal valve (narrowest point) Biliary tree obstruction \u008e\u00a0stasis\/bacterial overgrowth Autodigestion of pancreas by pancreatic enzymes Rh \u229d mother form antibodies (maternal anti-D IgG) against RBCs of Rh \u2295 fetus Lead inhibits ferrochelatase and ALA dehydratase \u008e\u00a0\u0090\u00a0heme synthesis, \u008f\u00a0RBC protoporphyrin. Inflammation \u008e\u00a0\u008f\u00a0hepcidin \u008e\u00a0\u0090\u00a0release of iron from macrophages, \u0090\u00a0iron absorption from gut Defect in G6PD \u008e\u00a0\u0090\u00a0NADPH \u008e\u00a0\u0090\u00a0reduced glutathione \u008e\u00a0\u008f\u00a0RBC susceptibility to oxidant stress Point mutation \u008e\u00a0substitution of glutamic acid with valine in \u03b2 chain \u008e\u00a0low O2, high altitude, acidosis precipitates sickling (deoxygenated HbS polymerizes) \u008e\u00a0anemia, vaso-occlusive disease \u0090\u00a0GpIb \u008e\u00a0\u0090\u00a0platelet-to-vWF adhesion","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 715 CONDITION MECHANISM PAGE Glanzmann thrombasthenia \u0090\u00a0GpIIb\/IIIa \u008e\u00a0\u0090\u00a0platelet-to-platelet aggregation, defective platelet plug 432 formation 432 Thrombotic thrombocytopenic 433 purpura \u0090\u00a0ADAMTS13 (a vWF metalloprotease) \u008e\u00a0\u0090\u00a0degradation of vWF multimers 433 \u008e\u00a0\u008f\u00a0platelet adhesion and aggregation (microthrombi formation) 450 von Willebrand disease 450 \u0090\u00a0vWF \u008e\u00a0\u0090\u00a0platelet-to-vWF adhesion, possibly \u008f\u00a0PTT (vWF protects factor Factor V Leiden VIII) 450 Axillary nerve injury Mutant factor V (Arg506Gln) that is resistant to degradation by protein C 450 Radial nerve injury (\u201cSaturday night palsy\u201d) Fractured surgical neck or anterior dislocation of humerus \u008e\u00a0flattened 452 deltoid 452 Median nerve injury (Ape\u2019s hand\/ 452 Pope\u2019s blessing) Compression of axilla (use of crutches), midshaft humerus fracture, 457 repetitive pronation\/supination of forearm \u008e\u00a0wrist\/finger drop, decreased 457 Ulnar nerve injury grip strength 457 466 Erb palsy (waiter\u2019s tip) Proximal lesion: supracondylar fracture \u008e\u00a0loss of sensation over thenar 466 Klumpke palsy eminence, dorsal and palmar aspect of lateral 3\u00bd fingers Winged scapula 467 Common peroneal nerve injury Distal lesion: carpal tunnel syndrome 467 Superior gluteal nerve injury 468 Pudendal nerve injury Proximal lesion: fractured medial epicondyle \u008e\u00a0radial deviation of wrist on Radial head subluxation flexion 468 Slipped capital femoral epiphysis Distal lesion: fractured hook of hamate \u008e\u00a0ulnar claw on digital extension Achondroplasia Osteoporosis Traction\/tear of C5-C6 roots during delivery on the neck of the infant, and Osteopetrosis due to trauma in adults Osteitis deformans Traction\/tear of C8-T1 roots during delivery on the arm of the infant, and on trying to grab a branch in adults Injury to long thoracic nerve (C5-C7), like on axillary node dissection during mastectomy Trauma on lateral aspect of leg or fracture of fibular neck \u008e\u00a0foot drop with steppage gait Iatrogenic injury during IM injection at gluteal region \u008e\u00a0Trendelenburg sign: lesion contralateral to side of hip that drops due to adductor weakness Injury during horseback riding or prolonged cycling; can be blocked during delivery at the ischial spine Nursemaid\u2019s elbow; due to sudden pull on arm (in children) Obese young adolescent with hip\/knee pain. Increased axial force on femoral head \u008e\u00a0epiphysis displaces relative to femoral neck like a scoop of ice cream slips off a cone Constitutive activation of FGFR3 \u008e\u00a0\u0090\u00a0chondrocyte proliferation \u008e\u00a0failure of endochondral ossification \u008e\u00a0short limbs \u008f\u00a0osteoclast activity leading to \u008f\u00a0bone resorption secondary to \u0090\u00a0estrogen levels and old age. Carbonic anhydrase II mutations \u008e\u00a0\u0090\u00a0ability of osteoclasts to generate acidic environment \u008e\u00a0\u0090\u00a0bone resorption leading to dense bones prone to fracture, pancytopenia (\u0090\u00a0marrow space) \u008f\u00a0osteoclast activity followed by \u008f\u00a0osteoblast activity \u008e\u00a0poor quality bone formed that is prone to fractures. uploaded by medbooksvn","716 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs CONDITION MECHANISM PAGE Osteoarthritis Mechanical degeneration of articular cartilage causing inflammation with 472 inadequate repair and osteophyte formation. 472 Rheumatoid arthritis 474 Autoimmune inflammation due to HLA-DR4 causing pannus formation. 476 Sjogren syndrome Type III Hypersensitivity reaction. 478 Systemic lupus erythematosus Autoimmune Type IV hypersensitivity reaction leading to lymphocyte 480 mediated damage of exocrine glands. 480 Blindness in giant cell (temporal) 484 arteritis Predominantly a Type III hypersensitivity reaction with decreased 484 clearance of immune complexes. Hematologic manifestations are a type II 485 Myasthenia gravis hypersensitivity reaction. Lambert-Eaton myasthenic syndrome 485 Albinism Ophthalmic artery occlusion Vitiligo 485 Atopic dermatitis Autoantibodies to postsynaptic nicotinic (ACh) receptors 489 Allergic contact dermatitis Autoantibodies to presynaptic calcium channels \u008e\u00a0\u0090\u00a0ACh release 489 Psoriasis Normal melanocyte number, \u0090\u00a0melanin production 501 501 Pemphigus vulgaris Autoimmune destruction of melanocytes 501 Bullous pemphigoid Epidermal barrier dysfunction, genetic factors (ie, loss-of-function mutations 501 in the filaggrin [FLG] gene), immune dysregulation, altered skin 502 Spina bifida occulta, meningocele, microbiome, environmental triggers of inflammation 502 myelomeningocele, myeloschisis 502 Type IV HSR. During the sensitization phase, Allergen activates Th1 cells Anencephaly \u008e\u00a0memory CD4+ cells and CD8+ form. Upon reexposure \u008e\u00a0CD4+ cells Holoprosencephaly release cytokines and Cd8+ cells kill targeted cells Lissencephaly Disrupted skin barrier \u008e\u00a0activation of dendritic cells via inflammatory Chiari I malformation cytokines (IL-1B, IL-6, TNF) \u008e\u00a0activated dendritic cells release IL-23 Chiari II malformation \u008e\u00a0Naive T cells form Th1 (IL-12) and Th17 (IL-23) cells that secrete IFN-y and IL-17A\/IL-22 respectively \u008e\u00a0Acanthosis, parakeratosis, hypogranulosis Dandy-Walker malformation Type II HSR. IgG autoantibodies form against desmoglein 1 and 3 in desmosomes \u008e\u00a0separation of keratinocytes in stratum spinosum from stratum basale Type II HSR. IgG autoantibodies against hemidesmosomes \u008e\u00a0separation of epidermis from dermis Failure of caudal neuropore to fuse by 4th week of development Failure of rostral neuropore to close \u008e\u00a0no forebrain, open calvarium Failure of the forebrain (prosencephalon) to divide into 2 cerebral hemispheres; developmental field defect typically occurring at weeks 3-4 of development; associated with SHH mutations Failure of neuronal migration \u008e\u00a0smooth brain surface lacking sulci and gyri Downward displacement of cerebellar tonsils inferior to foramen magnum Herniation of cerebellum (vermis and tonsils) and medulla through foramen magnum \u008e noncommunicating hydrocephalus Agenesis of cerebellar vermis \u008e\u00a0cystic enlargement of 4th ventricle that fills the enlarged posterior fossa; associated with noncommunicating hydrocephalus","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 717 CONDITION MECHANISM PAGE Syringomyelia Fluid-filled, gliosis-lined cavity within spinal cord, associated with Chiari I 502 malformation (low-lying cerebellar tonsils), less commonly with infections, Gerstmann syndrome tumors, trauma 526 Hemispatial neglect syndrome 526 Kl\u00fcver-Bucy syndrome Lesion in the dominant parietal cortex \u008e\u00a0agraphia, acalculia, finger agnosia, 526 Parinaud syndrome (inability to move left-right disorientation 526 527 eyes up and down) Lesion in the nondominant parietal cortex Cerebral edema 528, Bilateral lesions in the amygdala; seen in HSV-1 encephalitis 531 Aphasia \u008e\u00a0disinhibition, including hyperphagia, hypersexuality, hyperorality 528 528 Locked-in syndrome (loss of horizontal, Lesion in the dorsal midbrain; often due to pineal gland tumors 529 but not vertical, eye movements) 529 Fluid accumulation in the brain parenchyma \u008e\u00a0\u008f\u00a0ICP; may be cytotoxic 529 Lateral pontine syndrome (intracellular fluid accumulation due to osmotic shift; associated with early Lateral medullary (Wallenberg) ischemia, hyperammonemia, SIADH) or vasogenic (extracellular fluid 530 accumulation due to increased permeability of BBB; associated with late 530 syndrome ischemia, trauma, hemorrhage, inflammation, tumors) Medial medullary syndrome 530 Neonatal intraventricular hemorrhage Stroke in dominant (usually left) hemisphere, in either the superior temporal 530 gyrus of temporal lobe (Wernicke; receptive aphasia) or inferior frontal Epidural hematoma gyrus of frontal lobe (Broca; expressive aphasia) 531 Subdural hematoma Stroke of the basilar artery 531 Subarachnoid hemorrhage Intraparenchymal hemorrhage Stroke of the anterior inferior cerebellar artery Phantom limb pain Stroke of the posterior inferior cerebellar artery Diffuse axonal injury Stroke of the anterior spinal artery Reduced glial fiber support and impaired autoregulation of BP in premature infants \u008e\u00a0bleeding into the ventricles, originating in the germinal matrix (a highly vascularized layer within the subventricular zone) Rupture of middle meningeal artery, often secondary to skull fracture involving the pterion Rupture of bridging veins; acute (traumatic, high-energy impact, sudden deceleration injury) or chronic (mild trauma, cerebral atrophy, \u008f\u00a0age, chronic alcohol overuse, shaken baby syndrome) Trauma, rupture of aneurysm (such as a saccular aneurysm), or arteriovenous malformation \u008e\u00a0bleeding Systemic hypertension (most often occur in the putamen of basal ganglia, thalamus, pons, and cerebellum), amyloid angiopathy, arteriovenous malformation, vasculitis, neoplasm, or secondary to reperfusion injury in ischemic stroke \u008e\u00a0bleeding Most commonly following amputation \u008e\u00a0reorganization of primary somatosensory cortex \u008e\u00a0sensation of pain in a limb that is no longer present Traumatic shearing of white matter tracts during rapid acceleration and\/or deceleration of the brain (eg, motor vehicle accident) \u008e\u00a0multiple punctate hemorrhages involving white matter tracts \u008e\u00a0neurologic injury, often causing coma or persistent vegetative state uploaded by medbooksvn","718 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs CONDITION MECHANISM PAGE Conduction aphasia Damage to the arcuate fasciculus 531 Global aphasia 531 Heat stroke Damage to both Broca (inferior frontal gyrus of frontal lobe) and Wernicke 532 Migraine (superior temporal gyrus of temporal lobe) areas 534 Parkinson disease 536 Huntington disease Inability of body to dissipate heat (eg, exertion) \u008e\u00a0CNS dysfunction 536 (eg,\u00a0confusion), rhabdomyolysis, acute kidney injury, ARDS, DIC Alzheimer disease 536 Irritation of CN V, meninges, or blood vessels (release of vasoactive Frontotemporal dementia neuropeptides [eg, substance P, calcitonin gene-related peptide]) 536 Vascular dementia 537 HIV-associated dementia Loss of dopaminergic neurons of substantia nigra pars compacta 537 Idiopathic intracranial hypertension 538 Communicating hydrocephalus Trinucleotide (CAG) repeat expansion in huntingtin (HTT) gene on 538 Normal pressure hydrocephalus chromosome 4 \u008e\u00a0toxic gain of function \u008e\u00a0atrophy of caudate and putamen 538 Noncommunicating hydrocephalus with ex vacuo ventriculomegaly \u008e\u00a0\u008f\u00a0dopamine, \u0090\u00a0GABA, \u0090\u00a0ACh in brain 538 Ex vacuo ventriculomegaly \u008e\u00a0neuronal death via glutamate excitotoxicity 538 Multiple sclerosis 539 Osmotic demyelination syndrome Widespread cortical atrophy, narrowing of gyri and widening of sulci; 540 senile plaques in gray matter composed of beta-amyloid core (formed by Acute inflammatory demyelinating cleavage of amyloid precursor protein); neurofibrillary tangles composed of 540 polyneuropathy (subtype of Guillain- intracellular, hyperphosphorylated tau protein; Hirano bodies (intracellular Barr\u00e9 syndrome) eosinophilic proteinaceous rods in hippocampus) 540 540 Charcot-Marie-Tooth disease Frontotemporal lobe degeneration \u008e\u00a0\u0090\u00a0executive function and behavioral Progressive multifocal inhibition leukoencephalopathy Multiple arterial infarcts and\/or chronic ischemia Secondary to diffuse gray matter and subcortical atrophy Increased ICP, associated with dural venous sinus stenosis; impaired optic nerve axoplasmic flow \u008e\u00a0papilledema Reduced CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis) \u008e\u00a0\u008f\u00a0ICP, papilledema, herniation Idiopathic, CSF pressure elevated only episodically, no \u008f\u00a0subarachnoid space volume; expansion of ventricles distorts the fibers of the corona radiata Structural blockage of CSF circulation within ventricular system (eg,\u00a0stenosis of aqueduct of Sylvius, colloid cyst blocking foramen of Monro, tumor) Decreased brain tissue and neuronal atrophy \u008e\u00a0appearance of increased CSF on imaging Autoimmune inflammation and demyelination of CNS (brain and spinal cord) \u008e\u00a0axonal damage Rapid osmotic changes, most commonly iatrogenic correction of hyponatremia but also rapid shifts of other osmolytes (eg, glucose) \u008e\u00a0massive axonal demyelination in pontine white matter Autoimmune destruction of Schwann cells via inflammation and demyelination of motor and sensory fibers and peripheral nerves; likely facilitated by molecular mimicry and triggered by inoculations or stress Defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath Destruction of oligodendrocytes secondary to reactivation of latent JC virus infection \u008e\u00a0demyelination of CNS","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 719 CONDITION MECHANISM PAGE Sturge-Weber syndrome Somatic mosaicism of an activating mutation in one copy of the GNAQ 541 gene \u008e\u00a0congenital anomaly of neural crest derivatives \u008e\u00a0capillary vascular Pituitary adenoma malformation, ipsilateral leptomeningeal angioma with calcifications, 542 Spinal muscular atrophy episcleral hemangioma 546 Amyotrophic lateral sclerosis 546 Tabes dorsalis Hyperplasia of only one type of endocrine cells found in pituitary (most 546 Poliomyelitis commonly from lactotrophs, producing prolactin) 546 Friedreich ataxia Congenital degeneration of anterior horns 547 Noise-induced hearing loss Can be caused by defect in superoxide dismutase 1 550 Presbycusis Degeneration\/demyelination of dorsal columns and roots \u008e\u00a0progressive 550 sensory ataxia (impaired proprioception \u008e\u00a0poor coordination) Cholesteatoma 550 M\u00e9ni\u00e8re disease Poliovirus infection spreads from lymphoid tissue of oropharynx to small 550 Hyperopia intestine and then to CNS via bloodstream \u008e\u00a0destruction of cells in 551 Myopia anterior horn of spinal cord (LMN death) 551 Astigmatism 551 Presbyopia Trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes 552 Glaucoma frataxin (iron-binding protein) \u008e\u00a0impairment in mitochondrial functioning 553 Open-angle glaucoma \u008e\u00a0degeneration of lateral corticospinal tract, spinocerebellar tract, dorsal 553 Angle-closure glaucoma columns, and dorsal root ganglia 553 Damage to stereociliated cells in organ of Corti \u008e\u00a0loss of high-frequency hearing first; sudden extremely loud noises can lead to tympanic membrane rupture \u008e\u00a0hearing loss Destruction of hair cells at the cochlear base (preserved low-frequency hearing at apex) \u008e\u00a0aging-related progressive bilateral\/symmetric sensorineural hearing loss (often of higher frequencies) Abnormal growth of keratinized squamous epithelium in middle ear Increased endolymph in inner ear \u008e\u00a0vertigo, hearing loss, tinnitus and ear fullness Eye too short for refractive power of cornea and lens \u008e\u00a0light focused behind retina Eye too long for refractive power of cornea and lens \u008e\u00a0light focused in front of retina Abnormal curvature of cornea \u008e\u00a0different refractive power at different axes Aging-related impaired accommodation, primarily due to \u0090\u00a0lens elasticity Optic neuropathy causing progressive vision loss (peripheral \u008e\u00a0central), usually accompanied by increased intraocular pressure Associated with increased resistance to aqueous humor drainage through trabecular meshwork Anterior chamber angle is narrowed or closed; associated with anatomic abnormalities (eg, anteriorly displaced lens resting against central iris) \u008e\u00a0\u0090\u00a0aqueous flow through pupil \u008e\u00a0\u008f\u00a0pressure in posterior chamber \u008e\u00a0peripheral iris pushed against cornea \u008e\u00a0obstruction of drainage pathways by the iris uploaded by medbooksvn","720 SEC TION III Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs CONDITION MECHANISM PAGE Diabetic retinopathy Chronic hyperglycemia \u008e\u00a0\u008f\u00a0permeability and occlusion of retinal 554 vessels \u008e\u00a0microaneurysms, hemorrhages (nonproliferative); retinal Hypertensive retinopathy neovascularization due to chronic hypoxia (proliferative) 554 Retinal artery occlusion 554 Chronic hypertension \u008e\u00a0spasm, sclerosis, and fibrinoid necrosis of retinal Retinal vein occlusion vessels 554 Retinal detachment Blockage of central or branch retinal artery usually due to embolism (carotid 554 artery atherosclerosis > cardiogenic); less commonly due to giant cell Retinitis pigmentosa arteritis 554 Papilledema 554 Relative afferent pupillary defect Primary thrombosis \u008e\u00a0central retinal vein occlusion; secondary thrombosis 556 Horner syndrome at arteriovenous crossings (sclerotic arteriole compresses adjacent venule 557 causing turbulent blood flow) \u008e\u00a0branch retinal vein occlusion Cavernous sinus syndrome 559 Separation of neurosensory retina from underlying retinal pigment Delirium epithelium \u008e\u00a0loss of choroidal blood supply \u008e\u00a0hypoxia and degeneration 577 Schizophrenia of photoreceptors; due to retinal tears (rhegmatogenous) or tractional or 579 Distal RTA (type 1) exudative (fluid accumulation) (nonrhegmatogenous) 613 Proximal RTA (type 2) 613 Hyperkalemic tubular acidosis (type\u00a04) Progressive degeneration of photoreceptors and retinal pigment epithelium 613 Nephritic syndrome 615 Nephrotic syndrome \u008f\u00a0ICP (eg, secondary to mass effect) \u008e\u00a0impaired axoplasmic flow in optic 615 Nephritic-nephrotic syndrome nerve \u008e\u00a0optic disc swelling (usually bilateral) 615 Unilateral or asymmetric lesions of afferent limb of pupillary reflex (eg,\u00a0retina, optic nerve) Lesions along the sympathetic chain: 1st neuron (pontine hemorrhage, lateral medullary syndrome, spinal cord lesion above T1 like Brown- Sequard syndrome or late-stage syringomyelia); 2nd neuron (stellate ganglion compression by Pancoast tumor); 3rd neuron (carotid dissection) Secondary to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection (spreads due to lack of valves in dural venous sinuses) Usually secondary to illnesses (eg, CNS disease, infection, trauma, substance use), or medications (eg, anticholinergics) Altered dopaminergic activity, \u008f\u00a0serotonergic activity, \u0090\u00a0dendritic activity Inability of \u03b1-intercalated cells to secrete H+ \u008e\u00a0no new HCO3\u2013 generated \u008e\u00a0metabolic acidosis Defective PCT HCO3\u2013 reabsorption \u008e\u00a0\u008f\u00a0excretion of HCO3\u2013 in urine \u008e\u00a0metabolic acidosis Hypoaldosteronism\/aldosterone resistance \u008e\u00a0\u008f\u00a0K+ \u008e\u00a0NH3 synthesis in PCT\u00a0\u008e\u00a0\u0090\u00a0NH4+ excretion Glomerular inflammation \u008e\u00a0GBM damage \u008e\u00a0loss of RBCs in urine \u008e\u00a0dysmorphic RBCs, hematuria Podocyte damage \u008e\u00a0impaired charge barrier \u008e\u00a0proteinuria Severe GBM damage \u008e\u00a0loss of RBCs in urine + impaired charge barrier \u008e\u00a0hematuria + proteinuria","Rapid Review\u2003 \uf07d\u2009PATHOPHYSIOLOGY OF IMPORTANT DISEASEs SEC TION III 721 CONDITION MECHANISM PAGE Infection-associated Type III HSR with consumptive hypocomplementemia 616 glomerulonephritis 617 Type IV collagen mutation (X-linked dominant) \u008e\u00a0irregular thinning and 620 Alport syndrome thickening and splitting of GBM \u008e\u00a0nephritic syndrome 620 Stress incontinence 620 Urge incontinence Outlet incompetence (urethral hypermobility\/intrinsic sphincter deficiency) 622 Overflow incontinence \u008e\u00a0leak on \u008f\u00a0intraabdominal pressure 622 Prerenal azotemia 622 Intrinsic renal failure Detrusor overactivity \u008e\u00a0leak with urge to void 645 Postrenal azotemia Adnexal torsion Incomplete emptying (detrusor underactivity or outlet obstruction) \u008e\u00a0leak 662 with overfilling 663 Preeclampsia 665 Supine hypotensive syndrome \u0090\u00a0RBF \u008e\u00a0\u0090\u00a0GFR \u008e\u00a0\u008f\u00a0reabsorption of Na+\/H2O and urea 665 Functional hypothalamic amenorrhea Patchy necrosis \u008e\u00a0debris obstructing tubules and fluid backflow \u008e\u00a0\u0090\u00a0GFR Polycystic ovarian syndrome 671 Outflow obstruction (bilateral) 690 Varicocele 692 Methemoglobin Twisting of ovary\/fallopian tube around infundibulopelvic ligament 697 Deep venous thrombosis and ovarian ligament \u008e\u00a0venous\/lymphatic blockage \u008e\u00a0arterial inflow 699 Sarcoidosis associated hypercalcemia continued \u008e\u00a0edema \u008e\u00a0blockade of arterial inflow \u008e\u00a0necrosis Acute respiratory distress syndrome 699 Abnormal placental spiral arteries \u008e\u00a0endothelial dysfunction, Sleep apnea vasoconstriction, ischemia \u008e\u00a0new-onset HTN with proteinuria Supine position \u008e compressed abdominal aorta and IVC by gravid uterus \u008e\u00a0\u0090\u00a0placental perfusion and \u0090\u00a0venous return Severe caloric restriction, \u008f\u00a0energy expenditure, and\/or stress \u008e\u00a0altered pulsatile GnRH secretion \u008e\u00a0\u0090\u00a0LH, FSH, estrogen Hyperinsulinemia and\/or insulin resistance \u008e\u00a0altered hypothalamic feedback response \u008e\u00a0\u008f\u00a0LH:FSH, \u008f\u00a0androgens, \u0090\u00a0rate of follicular maturation \u008e\u00a0unruptured follicles (cysts) + anovulation Dilated veins in pampiniform plexus due to \u008f\u00a0venous pressure \u008e\u00a0enlarged scrotum Oxidized Hb secondary to dapsone, local anesthetics, nitrites \u008e\u00a0Hb oxidization (Fe2+) \u008e\u00a0\u0090\u00a0O2 binding but \u008f\u00a0cyanide affinity \u008e\u00a0tissue hypoxia Stasis, hypercoagulability, endothelial damage (Virchow triad) \u008e\u00a0blood clot within deep vein Noncaseating granulomas \u008e \u008f\u00a0macrophage activity \u008e \u008f\u00a01\u03b1-hydroxylase activity in macrophage \u008e\u00a0vitamin D activation \u008e \u008f\u00a0Ca2+ Alveolar injury \u008e\u00a0inflammation \u008e\u00a0capillary endothelial damage and \u008f\u00a0vessel permeability \u008e\u00a0leakage of protein-rich fluid into alveoli \u008e\u00a0intra-alveolar hyaline membranes and noncardiogenic pulmonary edema \u008e\u00a0\u0090\u00a0compliance and V\/Q mismatch \u008e\u00a0hypoxic vasoconstriction \u008e\u00a0\u008f\u00a0pulmonary vascular resistance Respiratory effort against airway obstruction (obstructive); impaired respiratory effort due to CNS injury\/toxicity, CHF, opioids (central); obesity \u008e\u00a0hypoventilation \u008e\u00a0\u008f\u00a0PaCO2 during waking hours uploaded by medbooksvn","722 SEC TION III Rapid Review\u2003 \uf07d\u2009Classic Presentations `\u2009CLASSIC PRESENTATIONS CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Gout, intellectual disability, self-mutilating behavior in a Lesch-Nyhan syndrome (HGPRT deficiency, X-linked 35 boy recessive) 47 49 Situs inversus, chronic ear infections, sinusitis, Primary ciliary dyskinesia (Kartagener syndrome) 49 bronchiectasis, infertility 50 Osteogenesis imperfecta (type I collagen defect) 50 Blue sclera, multiple fractures, dental problems, 55 conductive hearing loss Ehlers-Danlos syndrome (type V collagen defect, type III collagen defect seen in vascular subtype of ED) 58 Elastic skin, hypermobility of joints, \u008f\u00a0bleeding tendency Marfan syndrome (fibrillin defect) 59 Arachnodactyly, lens dislocation (upward and temporal), aortic dissection, hyperflexible joints Homocystinuria (autosomal recessive) 59 59 Arachnodactyly, pectus deformity, lens dislocation McCune-Albright syndrome (Gs-protein activating 61 (downward) mutation) 61 61 Caf\u00e9-au-lait spots (unilateral), polyostotic fibrous Cystic fibrosis (CFTR gene defect, chromosome 7, \u2206F508) 62 dysplasia, precocious puberty, multiple endocrine 64 abnormalities Muscular dystrophy (most commonly Duchenne, due to 64 X-linked recessive frameshift mutation of dystrophin 65 Meconium ileus in neonate, recurrent pulmonary gene) 65 infections, nasal polyps, pancreatic insufficiency, 67 infertility\/subfertility Duchenne muscular dystrophy (Gowers sign) 68 Becker muscular dystrophy (X-linked non-frameshift 69 Calf pseudohypertrophy deletions in dystrophin; less severe than Duchenne) Child uses arms to stand up from squat Patau syndrome (trisomy 13) Slow, progressive muscle weakness in boys Edwards syndrome (trisomy 18) Infant with cleft lip\/palate, microcephaly or holoprosencephaly, polydactyly, cutis aplasia Down syndrome Cri-du-chat (cry of the cat) syndrome Infant with microcephaly, rocker-bottom feet, clenched Wernicke encephalopathy (add confabulation\/memory hands, and structural heart defect loss for Korsakoff syndrome) Single palmar crease, intellectual disability Wet beriberi (thiamine [vitamin B1] deficiency) Microcephaly, high-pitched cry, intellectual disability Confusion, ophthalmoplegia\/nystagmus, ataxia Vitamin B5 deficiency Pellagra (niacin [vitamin B3] deficiency) Dilated cardiomyopathy\/high-output heart failure, Scurvy (vitamin C deficiency: can\u2019t hydroxylate proline\/ edema, alcoholism or malnutrition lysine for collagen synthesis); tea and toast diet Burning feet syndrome Rickets (children), osteomalacia (adults); vitamin D Dermatitis, dementia, diarrhea Swollen gums, mucosal bleeding, poor wound healing, deficiency Vitamin K deficiency petechiae, corkscrew hairs, perifollicular hemorrhages Bowlegs (children), bone pain, and muscle weakness Hemorrhagic disease of newborn with \u008f\u00a0PT, \u008f\u00a0aPTT","Rapid Review\u2003 \uf07d\u2009Classic Presentations SEC TION III 723 CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Intellectual disability, musty body odor, hypopigmented Phenylketonuria 82 skin, eczema Alkaptonuria (homogentisate oxidase deficiency; 82 Bluish-black connective tissue, ear cartilage, sclerae; ochronosis) urine turns black on prolonged exposure to air 85 Cori disease (debranching enzyme deficiency) or von Infant with hypoglycemia, hepatomegaly, cardiomyopathy Gierke disease (glucose-6-phosphatase deficiency, more 85 severe) Chronic exercise intolerance with myalgia, fatigue, 86, painful cramps, myoglobinuria McArdle disease (skeletal muscle glycogen phosphorylase 554 deficiency) \u201cCherry-red spots\u201d on macula 86 Tay-Sachs (ganglioside accumulation; no Hepatosplenomegaly, pancytopenia, osteoporosis, hepatosplenomegaly); Niemann-Pick disease 92 avascular necrosis of femoral head, bone crises (sphingomyelin accumulation; hepatosplenomegaly); 114 central retinal artery occlusion 114 Achilles tendon xanthoma 114 Male child, recurrent infections, no mature B cells Gaucher disease (glucocerebrosidase [\u03b2-glucosidase] Anaphylaxis following blood transfusion deficiency) 115 Recurrent cold (noninflamed) abscesses, eczema, high Familial hypercholesterolemia (\u0090 LDL receptor signaling) 115 serum IgE, \uf08f eosinophils Bruton disease (X-linked agammaglobulinemia) Late separation (>30 days) of umbilical cord, no pus, IgA deficiency 133 Hyper-IgE syndrome (Job syndrome: neutrophil recurrent skin and mucosal bacterial infections 134, Recurrent infections and granulomas with catalase \u2295 chemotaxis abnormality) 478 Leukocyte adhesion deficiency (type 1; defective LFA-1 135 organisms 136 Fever, vomiting, diarrhea, desquamating rash following integrin) 136 Chronic granulomatous disease (defect of NADPH use of nasal pack or tampon 137 \u201cStrawberry tongue\u201d oxidase) 138 140, Colon cancer associated with infective endocarditis Staphylococcal toxic shock syndrome 353 Flaccid paralysis in newborn after ingestion of honey 143 Abdominal pain, diarrhea, leukocytosis, recent antibiotic Scarlet fever (sandpaper rash); Kawasaki disease (lymphadenopathy, high fever for 5 days) 144 use Tonsillar pseudomembrane with \u201cbull\u2019s neck\u201d appearance Streptococcus bovis 144 Back pain, fever, night sweats Clostridium botulinum infection (floppy baby syndrome) Adrenal insufficiency, fever, bilateral adrenal hemorrhage Clostridioides difficile infection Corynebacterium diphtheria infection Pott disease (vertebral TB) Waterhouse-Friderichsen syndrome (meningococcemia) Red \u201ccurrant jelly\u201d sputum in patients with alcohol Klebsiella pneumoniae pneumonia overuse or diabetes Jarisch-Herxheimer reaction (due to host response to Fever, chills, headache, myalgia following antibiotic sudden release of bacterial antigens) treatment for syphilis Erythema migrans from Ixodes tick bite (Lyme disease: Large rash with bull\u2019s-eye appearance Borrelia) uploaded by medbooksvn","724 SEC TION III Rapid Review\u2003 \uf07d\u2009Classic Presentations CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Ulcerated genital lesion Nonpainful, indurated: chancre (1\u00b0 syphilis, Treponema 145, pallidum) 180 Painful, with exudate: chancroid (Haemophilus ducreyi) 145 145 Smooth, moist, painless, wartlike white lesions on genitals Condylomata lata (2\u00b0 syphilis) 147 Pupil accommodates but doesn\u2019t react to light Neurosyphilis (Argyll Robertson pupil) 148 Dog or cat bite resulting in infection (cellulitis, Pasteurella multocida (cellulitis at inoculation site) 148 osteomyelitis) 150 Atypical \\\"walking pneumonia\\\" with x-ray looking worse Mycoplasma pneumoniae infection 153 than the patient 156 161 Rash on palms and soles Coxsackie A, 2\u00b0 syphilis, Rocky Mountain spotted fever 167 Black eschar on face of patient with diabetic ketoacidosis Mucor or Rhizopus fungal infection 167 and\/or neutropenia 296 Chorioretinitis, hydrocephalus, intracranial calcifications Congenital toxoplasmosis 296 Pruritus, serpiginous rash after walking barefoot Hookworm (Ancylostoma spp, Necator americanus) 296 Child with fever later develops red rash on face that Erythema infectiosum\/fifth disease (\u201cslapped cheeks\u201d spreads to body appearance, caused by parvovirus B19) 308 Fever, cough, conjunctivitis, coryza, diffuse rash Measles 308 314 Small, irregular red spots on buccal\/lingual mucosa with Koplik spots (measles [rubeola] virus) blue-white centers 317 318 Bounding pulses, wide pulse pressure, diastolic heart Aortic regurgitation murmur, head bobbing 318 Systolic ejection murmur (crescendo-decrescendo), Aortic stenosis 318 narrow pulse pressure, pulsus parvus et tardus 318 320 Continuous \u201cmachinelike\u201d heart murmur PDA (close with indomethacin; keep open with PGE analogs) 342 Chest pain on exertion Angina (stable: with moderate exertion; unstable: with minimal exertion or at rest) Chest pain with ST depressions on ECG Angina (\u229d troponins) or NSTEMI (\u2295 troponins) Chest pain, pericardial effusion\/friction rub, persistent Postcardiac injury syndrome (autoimmune-mediated fever following MI post-MI fibrinous pericarditis, 2 weeks to several months after acute episode) Distant heart sounds, distended neck veins, hypotension Beck triad of cardiac tamponade Painful, raised red lesions on pads of fingers\/toes Osler nodes (infective endocarditis, immune complex deposition) Painless erythematous lesions on palms and soles Janeway lesions (infective endocarditis, septic emboli\/ microabscesses) Splinter hemorrhages in fingernails Infective endocarditis Retinal hemorrhages with pale centers Roth spots (infective endocarditis) Telangiectasias, recurrent epistaxis, skin discoloration, Hereditary hemorrhagic telangiectasia (Osler-Weber- arteriovenous malformations, GI bleeding, hematuria Rendu syndrome) Polyuria, polydipsia Primary polydipsia, diabetes insipidus (central, nephrogenic)","Rapid Review\u2003 \uf07d\u2009Classic Presentations SEC TION III 725 CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE No lactation postpartum, absent menstruation, cold Sheehan syndrome (severe postpartum hemorrhage 343 intolerance leading to pituitary infarction) 344 Heat intolerance, weight loss, palpitations Hyperthyroidism 344 Cold intolerance, weight gain, brittle hair Hypothyroidism 344 Cutaneous\/dermal edema due to deposition of Myxedema (caused by hypothyroidism or 348 mucopolysaccharides in connective tissue hyperthyroidism [Graves disease]) 348 Facial muscle spasm upon tapping Chvostek sign (hypocalcemia) 351 Carpal spasm upon inflation of BP cuff Trousseau sign (hypocalcemia) 353 Rapid, deep, labored breathing\/hyperventilation Diabetic ketoacidosis (Kussmaul respirations) Skin hyperpigmentation, orthostatic hypotension, fatigue, Chronic 1\u00b0 adrenal insufficiency (Addison disease) \uf08e 353 weakness, muscle aches, weight loss, GI disturbances \u008f ACTH, \u008f MSH 356 Shock, altered mental status, vomiting, abdominal pain, Acute adrenal insufficiency (adrenal crisis) 356 weakness, fatigue in patient under glucocorticoid MEN1 (autosomal dominant MEN1 mutation) 356 therapy MEN2A (autosomal dominant RET mutation) Pancreatic, pituitary, parathyroid tumors 357 Medullary thyroid carcinoma, parathyroid hyperplasia, MEN2B (autosomal dominant RET mutation) pheochromocytoma 375, Medullary thyroid carcinoma, pheochromocytoma, Carcinoid syndrome (\u008f\u00a0urinary 5-HIAA); indicates 405 mucosal neuromas, marfanoid habitus systemic dissemination (eg, post liver metastases) 384 Cutaneous flushing, diarrhea, bronchospasm, heart murmur Courvoisier sign (distal malignant obstruction of biliary 384 Jaundice, palpable distended non-tender gallbladder tree) 386 Vomiting blood following gastroesophageal lacerations Mallory-Weiss syndrome (alcohol use disorder, bulimia 387 nervosa) 387 Dysphagia (esophageal webs), glossitis, iron deficiency 388 anemia Plummer-Vinson syndrome (may progress to esophageal 390 squamous cell carcinoma) 390 Enlarged, hard left supraclavicular node 394 Hematemesis, melena Virchow node (metastasis from abdominal malignancy) Hematochezia Upper GI bleeding (eg, peptic ulcer disease) 394 Arthralgias, cardiac and neurological symptoms, diarrhea Lower GI bleeding (eg, colonic diverticulosis) Severe RLQ pain with palpation of LLQ Whipple disease (Tropheryma whipplei) 401 Severe RLQ pain with deep tenderness Rovsing sign (acute appendicitis) Hamartomatous GI polyps, hyperpigmented macules on McBurney sign (acute appendicitis) 402 Peutz-Jeghers syndrome (inherited, benign polyposis can mouth, feet, hands, genitalia Multiple colon polyps, osteomas\/soft tissue tumors, cause bowel obstruction; \u008f breast\/GI cancer risk) Gardner syndrome (subtype of FAP) impacted\/supernumerary teeth Severe jaundice in neonate Crigler-Najjar syndrome (congenital unconjugated hyperbilirubinemia) Golden brown rings around peripheral cornea Wilson disease (Kayser-Fleischer rings due to copper accumulation) uploaded by medbooksvn","726 SEC TION III Rapid Review\u2003 \uf07d\u2009Classic Presentations CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Female, fat (obese), fertile (multiparity), forty, fair Cholelithiasis (gallstones) 403 Painless jaundice with enlarged gallbladder Cancer of pancreatic head obstructing the bile duct 405 Bluish line on gingiva Burton line (lead poisoning) 425 Short stature, caf\u00e9-au-lait spots, thumb\/radial defects, Fanconi anemia (genetic loss of DNA crosslink repair; 427 \u008f\u00a0incidence of tumors\/leukemia, aplastic anemia often progresses to AML) 428 Red\/pink urine, fragile RBCs Paroxysmal nocturnal hemoglobinuria 429 Painful blue fingers\/toes, hemolytic anemia Cold agglutinin disease (autoimmune hemolytic 432 Petechiae, mucosal bleeding, prolonged bleeding time anemia caused by Mycoplasma pneumoniae, infectious mononucleosis, CLL) 434 Fever, night sweats, weight loss Platelet disorders (eg, Glanzmann thrombasthenia, 435 Skin patches\/plaques, Pautrier microabscesses, atypical Bernard Soulier, HUS, TTP, ITP, uremic platelet dysfunction) 452 T\u00a0cells B symptoms of malignancy Mycosis fungoides (cutaneous T-cell lymphoma) or 455 Neonate with arm paralysis following difficult birth, arm S\u00e9zary syndrome (mycosis fungoides + malignant 468 in \u201cwaiter\u2019s tip\u201d position T\u00a0cells in blood) Erb-Duchenne palsy (superior trunk [C5\u2013C6] brachial 472 Anterior drawer sign \u2295 plexus injury) Bone pain, bone enlargement, long bone chalk-stick Anterior cruciate ligament injury 473 Osteitis deformans (Paget disease of bone, \u008f osteoblastic 474 fractures and osteoclastic activity) Swollen, hard, painful finger joints in an elderly Osteoarthritis (osteophytes on PIP [Bouchard nodes], DIP 475 [Heberden nodes]) 476 individual, pain worse with activity Gout\/podagra (hyperuricemia) Sudden swollen\/painful big toe joint, tophi Sj\u00f6gren syndrome (autoimmune destruction of exocrine 478 Dry eyes, dry mouth, arthritis glands) Reactive arthritis associated with HLA-B27 479 Urethritis, conjunctivitis, arthritis in a male Systemic lupus erythematosus \u201cButterfly\u201d facial rash, arthritis, cytopenia, and fever in a 480 Kawasaki disease (mucocutaneous lymph node syndrome, young female treat with IVIG and aspirin) 486 Cervical lymphadenopathy, desquamating rash, coronary 491 Immunoglobulin A vasculitis (Henoch-Sch\u00f6nlein aneurysms, red conjunctivae and tongue, hand-foot purpura, affects skin and kidneys) 525, changes 545 Palpable purpura on buttocks\/legs, joint pain, abdominal Raynaud phenomenon (vasospasm in extremities) 526 pain (child), hematuria Painful fingers\/toes changing color from white to blue to Kaposi sarcoma, associated with HHV-8 red with cold or stress Lichen planus Dark purple skin\/mouth nodules in a patient with AIDS Pruritic, purple, polygonal planar papules and plaques Babinski sign (UMN lesion) (6\u00a0P\u2019s) Dorsiflexion of large toe with fanning of other toes upon Cerebellar lesion (lateral affects voluntary movement of plantar scrape extremities; medial affects axial and proximal movement) Truncal ataxia, nystagmus, head tilting, fall towards injured side","Rapid Review\u2003 \uf07d\u2009Classic Presentations SEC TION III 727 CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Hyperphagia, hypersexuality, hyperorality Kl\u00fcver-Bucy syndrome (bilateral amygdala lesion) 526 Resting tremor, athetosis, chorea Basal ganglia lesion 526 Dysphagia, hoarseness, \u0090 gag reflex, nystagmus, ipsilateral Lateral medullary (Wallenberg) syndrome (posterior 529 Horner syndrome inferior cerebellar artery lesion) 530 Lucid interval after traumatic brain injury Epidural hematoma (middle meningeal artery 530 \u201cWorst headache of my life\u201d rupture; branch of maxillary artery) 536 Resting tremor, rigidity, akinesia, postural instability, Subarachnoid hemorrhage Parkinson disease (loss of dopaminergic neurons in 536 shuffling gait, micrographia Chorea, dementia, caudate degeneration substantia nigra pars compacta) 538 Huntington disease (autosomal dominant CAG repeat 539 Urinary incontinence, gait apraxia, cognitive dysfunction Relapsing and remitting nystagmus, intention tremor, expansion) 540 Normal pressure hydrocephalus scanning speech, bilateral internuclear ophthalmoplegia Multiple sclerosis 541 Rapidly progressive limb weakness that ascends following Guillain-Barr\u00e9 syndrome (acute inflammatory 541 GI\/upper respiratory infection demyelinating polyneuropathy) Caf\u00e9-au-lait spots, Lisch nodules (iris hamartoma), 541 Neurofibromatosis type I cutaneous neurofibromas, pheochromocytomas, optic 541 gliomas Nevus flammeus (benign, but associated with Sturge- 545 Vascular birthmark (port-wine stain) of the face Weber syndrome) 545 547 Renal cell carcinoma (bilateral), hemangioblastomas, von Hippel-Lindau disease (deletion of VHL on angiomatosis, pheochromocytoma chromosome 3p) 548 Bilateral vestibular schwannomas Neurofibromatosis type II 550 Hyperreflexia, hypertonia, Babinski sign present UMN damage 557 Hyporeflexia, hypotonia, atrophy, fasciculations LMN damage 560 Staggering gait, frequent falls, nystagmus, hammer toes, Friedreich ataxia 577 diabetes mellitus, hypertrophic cardiomyopathy LMN facial nerve (CN VII) palsy; UMN lesions spare the Unilateral facial drooping involving forehead forehead 606 Episodic vertigo, tinnitus, sensorineural hearing loss M\u00e9ni\u00e8re disease 615 Ptosis, miosis, anhidrosis Horner syndrome (sympathetic chain lesion) Conjugate horizontal gaze palsy, horizontal diplopia Internuclear ophthalmoplegia (damage to MLF; may be 617 \u201cWaxing and waning\u201d level of consciousness (acute unilateral or bilateral) onset), \u0090 attention span, \u0090 level of arousal Delirium (usually 2\u00b0 to other cause) Polyuria, renal tubular acidosis type II, growth retardation, Fanconi syndrome (multiple combined dysfunction of the electrolyte imbalances, hypophosphatemic rickets proximal convoluted tubule) Periorbital and\/or peripheral edema, proteinuria (> 3.5 g\/ Nephrotic syndrome day), hypoalbuminemia, hypercholesterolemia Alport syndrome (mutation in type IV collagen) Hereditary nephritis, sensorineural hearing loss, retinopathy, anterior lenticonus uploaded by medbooksvn","728 SEC TION III Rapid Review\u2003 \uf07d\u2009Classic Labs\/Findings CLINICAL PRESENTATION DIAGNOSIS\/DISEASE PAGE Wilms tumor, macroglossia, organomegaly, Beckwith-Wiedemann syndrome (WT2 mutation) 626 hemihyperplasia, omphalocele Turner syndrome (45,XO) 657 Streak ovaries, congenital heart disease, horseshoe kidney, cystic hygroma, short stature, webbed neck, lymphedema Meigs syndrome 667 Paget disease of the breast (sign of underlying neoplasm) 670 Ovarian fibroma, ascites, pleural effusion Peyronie disease (connective tissue disorder) 671 Red, itchy, swollen rash of nipple\/areola Fibrous plaques in tunica albuginea of penis with Emphysema (\u201cpink puffer,\u201d centriacinar [tobacco 694 smoking] or panacinar [\u03b11-antitrypsin deficiency]) abnormal curvature 695 Pink complexion, dyspnea, hyperventilation Chronic bronchitis (hypertrophy and hyperplasia of mucus-secreting glands, \u201cblue bloater\u201d) 697 Hypoxemia, polycythemia, hypercapnia Sarcoidosis (noncaseating granulomas) Bilateral hilar adenopathy, uveitis `\u2009CLASSIC LABS\/FINDINGS LAB\/DIAGNOSTIC FINDING DIAGNOSIS\/DISEASE PAGE Colonies of Pseudomonas in lungs Cystic fibrosis (autosomal recessive mutation in CFTR 58 gene \u008e\u00a0fat-soluble vitamin deficiency and mucous plugs) \u0090 AFP on second trimester screening 61 \u008f \u03b2-hCG, \u0090 PAPP-A on first trimester screening Down syndrome, Edwards syndrome 61 \u008f serum homocysteine, \u008f methylmalonic acid, \u0090 folate Down syndrome 67 Anti-histone antibodies Vitamin B12 deficiency 113 \u0090 T cells, \u0090 PTH, \u0090 Ca2+, absent thymic shadow on CXR Drug-induced lupus 114 Thymic aplasia (DiGeorge syndrome, velocardiofacial Recurrent infections, eczema, thrombocytopenia 115 Large granules in phagocytes, immunodeficiency syndrome) 115 Wiskott-Aldrich syndrome Optochin sensitivity Ch\u00e9diak-Higashi disease (congenital failure of 132 Novobiocin response phagolysosome formation) 132 Bacitracin response Sensitive: S pneumoniae; resistant: viridans streptococci 132 Branching gram \u2295 rods with sulfur granules (S\u00a0mutans, S sanguis) 137 Hilar lymphadenopathy, peripheral granulomatous lesion Sensitive: S epidermidis; resistant: S saprophyticus 138 Sensitive: S pyogenes (group A); resistant: S agalactiae in middle or lower lung lobes (can calcify) 140 \u201cThumb sign\u201d on lateral neck x-ray (group B) 147 Bacteria-covered vaginal epithelial cells, \u2295 whiff test Actinomyces israelii 153, Ring-enhancing brain lesion on CT\/MRI in AIDS 174 Ghon complex (1\u00b0 TB: Mycobacterium bacilli) Epiglottitis (Haemophilus influenzae) \u201cClue cells\u201d (Gardnerella vaginalis) Toxoplasma gondii (multiple), CNS lymphoma (may be solitary)","Rapid Review\u2003 \uf07d\u2009Classic Labs\/Findings SEC TION III 729 LAB\/DIAGNOSTIC FINDING DIAGNOSIS\/DISEASE PAGE Dilated cardiomyopathy with apical atrophy, megacolon, Chagas disease (Trypanosoma cruzi) 155 megaesophagus Infectious mononucleosis (EBV infection) 162 Atypical lymphocytes, heterophile antibodies Croup (parainfluenza virus) 167 Narrowing of upper trachea and subglottis (Steeple sign) Negri bodies of rabies 169 on x-ray Eosinophilic inclusion bodies in cytoplasm of Meningiomas, papillary thyroid carcinoma, 207 mesothelioma, papillary serous carcinoma of the hippocampal and cerebellar neurons endometrium and ovary 302 Psammoma bodies 304 Tetralogy of Fallot (due to RVH) 311 \u201cBoot-shaped\u201d heart on x-ray Coarctation of the aorta Rib notching (inferior surface, on x-ray) Wolff-Parkinson-White syndrome (bundle of Kent 317 \u201cDelta wave\u201d on ECG, short PR interval, supraventricular 319 bypasses AV node) 347 tachycardia Cardiac tamponade Electrical alternans (alternating amplitude on ECG) Aschoff bodies (rheumatic fever) 349, Granuloma with giant cells after pharyngeal infection \u201cOrphan Annie\u201d eyes nuclei (papillary carcinoma of the 469 Empty-appearing nuclei with central clearing of thyroid 354 thyroid) 386 cells Hyperparathyroidism or osteitis fibrosa cystica (deposited 388 \u201cBrown\u201d tumor of bone hemosiderin from hemorrhage gives brown color) 389 Hypertension, hypokalemia, metabolic alkalosis 1\u00b0 hyperaldosteronism (eg, Conn syndrome) 389 Mucin-filled cell with peripheral nucleus \u201cSignet ring\u201d cells (diffuse gastric carcinoma) 394 Anti-transglutaminase\/anti-gliadin\/anti-endomysial Celiac disease (diarrhea, weight loss) 395 antibodies \u201cString sign\u201d (Crohn disease) 398 Narrowing of bowel lumen on barium x-ray Ulcerative colitis (loss of haustra) 398 \u201cLead pipe\u201d appearance of colon on abdominal imaging Familial adenomatous polyposis (autosomal dominant, 398 Thousands of polyps on colonoscopy mutation of APC gene) 399 \u201cApple core\u201d lesion on barium enema x-ray Colorectal cancer (usually left-sided) Eosinophilic cytoplasmic inclusion in liver cell Mallory body (alcoholic liver disease) 402 Triglyceride accumulation in liver cell vacuoles Fatty liver disease (alcoholic or metabolic syndrome) Anti-smooth muscle antibodies (ASMAs), anti-liver\/ Autoimmune hepatitis 402 kidney microsomal-1 (anti-LKM1) antibodies Chronic passive congestion of liver due to right heart 405 \u201cNutmeg\u201d appearance of liver failure or Budd-Chiari syndrome 421, Antimitochondrial antibodies (AMAs) 1\u00b0 biliary cholangitis (female, cholestasis, portal 426 hypertension) Low serum ceruloplasmin Wilson disease (hepatolenticular degeneration; Kayser- Migratory thrombophlebitis (leading to migrating DVTs Fleischer rings due to copper accumulation) and vasculitis) Trousseau syndrome (adenocarcinoma of pancreas) Hypersegmented neutrophils Megaloblastic anemia (vitamin B12 deficiency: neurologic symptoms; folate deficiency: no neurologic symptoms) uploaded by medbooksvn"]