Respiratory Path IIIDr Rotimi Adigun

Hemodynamics, Vascular disturbances

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

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.

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

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.

ALI, Early ARDS

ARDS morphology

Endotheliumnecrosis

Type I alveolarcells necrosis

Fibrin

Edema

Waxy Hyalinemembranes

Diffuse Alveolar Injury

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.

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

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

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

Pulmonary Infarction

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

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.

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.

Figure 15-28 Pathogenesis of primary pulmonary hypertension. See text for details.

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

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.

Morphology of pulmonaryhypertension

• Plexiform changes in severevarieties only (primary)

• Necrosis of wall (fibrinoid)• Thrombosis

• Rupture, bleed• Dilation lesions, angiomatoid

lesions

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