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Respiratory Path IIIDr Rotimi Adigun
Hemodynamics, Vascular disturbances
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Topics Covered In ThisLecture1.Pulmonary Edema
2.Acute respiratory distresssyndrome (ARDS)3.SARS (Severe acuterespiratory syndrome)4.Pulmonary Embolism5.Pulmonary Hypertension
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Alveolar wall microscopy
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Case History
• 72 yr old extremely pleasantCaucasian male with a past medicalhistory of CABG and multiple stents,unstable angina and myelodysplasticsyndrome, presented with left armpain
• He was admitted, but died within 24hours• A post mortem was performed.
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Post mortem findings
• Right lung weighed 1,100 g and theleft lung weighed 750 g• Severe coronary atherosclerosis wasnoted• There was evidence of acutemyocardial infarction and massivepulmonary edema
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Causes of PulmonaryEdema
• Hemodynamic disturbances- Increased hydrostatic pressure
• Left sided congestive heart failure
– Heavy wet lungs (basal regions of lower lobes)- Alveolar capillaries engorged
- Intra-alveolar granular pink precipitate- Heart failure cells; brown discoloration- Impairs pulmonary function and predisposesto infection
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Pulmonary Edema- Causes
HemodynamicIncreased hydrostatic pressure• Left ventricular failure (common)• Excess IV fluids, Excess blood transfusion.Decreased oncotic pressure• Severe hypoproteinemia, Liver disease,Nephrotic syndrome
Other• Lymphatic obstruction (carcinoma, rare)
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Pulmonary edema--Causes
Microvascular Injury• Damage to vascular endothelium• Leakage of fluid and proteins intointerstitium and lumen• Diffuse edema is a contributor to
acute respiratory distress syndrome
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Microvascular injury
• Infections: Pneumonia, septicemia• Inhaled gases: Oxygen, smoke• Liquid aspiration: Gastric contents• Drugs and chemicals:Chemotherapyagents, heroin, cocaine, paraquatpoisoning• Shock, trauma• Radiation• Transfusion related
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Adult(Acute) RespiratoryDistress Syndrome (ARDS)
Syn. Shock Lung Syndrome, Diffusealveolar damage (DAD), Acute lunginjury (ALI)
(cf. RDS in neonates due todeficiency of surfactant)
Clinical syndrome caused by diffusealveolar damage
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Mechanism of ARDS
• Imbalance between pro-inflammatoryand anti inflammatory cytokines• Toll like receptors activate NF-kB, atranscription factor controllingexpression of pro-inflammatorygenesUltimately pro-inflamatory mediators such as IL-1,IL-8,TNF and thrombin are produced inExcess compared to the production of anti-Inflammatory mediators such as IL-10.Neutrophils play a major role in this process.
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ALI, Early ARDS
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ARDS morphology
Endotheliumnecrosis
Type I alveolarcells necrosis
Fibrin
Edema
Waxy Hyalinemembranes
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Diffuse Alveolar Injury
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Shock lung
• Endothelial damage, damage to type 1pneumocytes• Exudate, impaired gas exchange• Hyaline membrane (necrotic debris from
epithelial cells plus edema fluid coagulate)• Type II pneumocyte necrosis=>loss
of surfactant-=>microatelectasis
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What Causes ARDS?
• Infections*• Sepsis*• Head injuries*• Gastric aspiration*• Pancreatitis• Burns• Trauma
• Fractures with fat embolismInfection, sepsis, head injuries and gastric aspirationAccount for more than 50 %of cases.
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Clinical features
• Serious disorder• Respiratory difficulty- acute• Gasping for breath
• Severe hypoxemia, cyanosis, unresponsive tooxygen(Diffusion defect-intrapulmonary shunt)• Bilateral infiltrates on chest X-ray• Absence of clinical features of LVF• High mortality: 40% in 190,000 ARDS cases/yr• Patchy distribution
• Healing may result in diffuse interstitial fibrosis
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Phases of ARDS
• Exudation- 0-7 days• Proliferation - 1-3 weeks
macrophages phagocytose deadcells and hyaline membrane, typeII pneumonocytes proliferatemature in to type I cells
• Fibrosis- TGF-β, PDGF
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SARS(Severe acute respiratory syndrome)
• First appeared in China in Nov 2002; last case 2004• Cause -- Corona virus; 8000 cases; 774 deaths• 2-10 day incubation period;begins with dry cough,
malaise, myalgia, fever, chills• 1/3rd fight infection, but 2/3rd progress to severe
respiratory disease, shortness of breath, tachypnea,and pleurisy• 10% of patients die from illness
• First transmitted through wild masked palm civets• Patho-physiology unknown; how virus moved from
animals to humans unknown
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Wild masked palm civet
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Pulmonary embolismPulmonary Infarction
• Causes more than 50,000 US deaths/year• Large pulmonary embolus is a cause of sudden instantaneous death• Blood clots that occlude large pulmonaryvessels are embolic arising mainly from the
deep veins of the leg
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Pulmonary embolism
• 95% from deep leg veins• Sick, bedridden patients with
pulmonary, cardiovasculardisease, atherosclerosis ,OCP use
• BIG embolus -> bifurcation of PA, sudden
death from acute right heartfailure - no time to develop anychanges in lungs
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Pulmonary embolism
• MEDIUM -> hemorrhage, infarctiononly if circulatory status alreadycompromized
• SMALL -> usually no infarct becauseof dual supply, resolve ( lysis),
- if recurrent- pulmonary hypertension
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Saddle embolism
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Pulmonary Infarction
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Infarction
• Clinically resembles myocardialinfarction - chest pain, dyspnea,shock
• Gross: Wedge shaped, hemorrhagicinfarct, may be multiple
• Micro: coagulation necrosis
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Pulmonary hypertension• When pulmonary pressure reaches
1/4thof systemic levels(usually not more than 1/8 of Systemic
Five distinct groups.• Pulmonary arterial hypertension• PH with left heart disease• PH with lung disease• PH with chronic thrombotic or embolic disease• Miscellaneous
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Pulmonary hypertension Underlying pathogenetic mechanism usually related
to any of• Increased pulmonary blood flow/pressure• Increased pulmonary vascular resistance• Increased left heart resistance to blood flow.Common etiologic factors includes: COPD or
interstitial lung disease, Congenital heart disease, Recurrent thrombo-embolism, Connective tissue disease, obstructive sleep apnea.
Idiopathic pulmonary arterial hypertension is a rare cause of pulmonary hypertension.
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Pulmonary hypertension• Idiopathic pulmonary arterial hypertension/Primary PH•Familial PH - BMPR2 locus mutations
• Rare, young women,recurrentdyspnea ,syncope
• Raynaud’s phenomenon (vasopasmof peripheral vessels)
Characterised by obstruction to the lumen of Pulmonary vessels caused by proliferation of Endothelial cells,smooth muscle and intimal fibrosis.
••
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BMPR2
• bone morphogenetic protein receptor, type 2 (BMPR2)
• a cell surface molecule that binds to a variety of TGF-β pathway ligands
• It is normally inhibitory to vascular proliferation.• Hence Loss of function mutation affecting the
gene would lead to excessive vascular proliferation.
• Implicated in 50 % of cases of Primary pulmonary hypertension.
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Figure 15-28 Pathogenesis of primary pulmonary hypertension. See text for details.
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Primary pulmonary hypertension-clinical
• Symptoms appear late• Fatigue, dyspnoea• Syncope on exercise• Chest pain• Respiratory insufficiency, cyanosis• Cor pulmonale
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Pulmonary hypertension
• Secondary PH-endothelia dysfunction due to• COPD - Chronic bronchitis,
emphysema, diffuse fibrosis• Congenital L-R shunts- VSD• Recurrent pulmonary
Thrombo-embolism in small sizedvessels•Drugs-appetite suppressant(aminorex)•Crotalaria spectabilis(Bush tea)
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Pulmonary hypertension
Morphology:• Irrespepective of etiology, all PH have the
following morphologic changes in common:-Medial hypertrophy affecting muscular and
elastic arteries-Atheromas of pulmonary artery-Right ventricular hypertrophy
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Pulmonary hypertension
Mild -
ElasticNormalpulmonaryartery
Severe –Medial hypertrophy,intimal fibrosis
duplication
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Pulmonary hypertension
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Plexiform lesions
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Plexiform Lesions
Extreme changes. Seen in:• Idiopathic and Primary PH• Drug use• HIV Characterised by the presence of a tuft of
capillaries producing a web like network that spans the lumina of dilated arteries.
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Morphology of pulmonaryhypertension
• Plexiform changes in severevarieties only (primary)
• Necrosis of wall (fibrinoid)• Thrombosis
• Rupture, bleed• Dilation lesions, angiomatoid
lesions
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