patoloji-ders-notlari

Title

Serdar Balcı

Pulmonary Circulation Disorders

Serdar BALCI, MD

PTE, HEMORRHAGE, INFARCTION

Pulmonary Embolism

• Blood clots occlude the large pulmonary arteries almost always embolic
• >95% of all pulmonary emboli arise from large deep veins of the lower legs
  • popliteal vein and larger veins above it
• Can be small and clinically silent
• Among hospitalized patients autopsy data 1-30%
  • Severe burns, trauma, or fractures

Venous thrombosis predisposing factors

• Prolonged bedrest
  • With immobilization of the legs
• Surgery
  • Orthopedic surgery, of knee and hip
• Severe trauma
  • Burns, multiple fractures
• Congestive heart failure
• In women, the period around parturition or oral contraception using birth control pills with high estrogen content
• Disseminated cancer
• Primary disorders of hypercoagulability
  • Factor V Leiden

Two important consequences of PTE

• Increase in pulmonary artery pressure
  • From blockage of flow
  • Vasospasm caused by neurogenic mechanisms
  • Release of mediators
    • Thromboxane A2, serotonin
• ischemia of the downstream pulmonary parenchyma

Pulmonary Thromboembolism

• Sudden increase in pulmonary artery pressure
• Diminished cardiac output
• Right-sided heart failure
  • Acute cor pulmonale
• Death

Hypoxemia develops in PTE

• Perfusion of lung zones that have become atelectatic
  • Alveolar collapse occurs in the ischemic areas
  • Reduction in surfactant production
  • Pain leads to reduced movement of the chest wall
  • Pulmonary blood flow is redirected through areas of the lung that normally are hypoventilated
• Decrease in cardiac output
  • Widening of the difference in arterial-venous oxygen saturation
• Right-to-left shunting of blood
  • Patent foramen ovale, present in 30% of normal persons

Ischemic necrosis in PTE

• Ischemic necrosis (infarction) occur in 10% in PTE
  • compromise in cardiac function or bronchial circulation
  • that area is underventilated as a result of underlying pulmonary disease

saddle embolus at the main left and right pulmonary arteries

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

PTE

60-80% of emboli are clinically silent

5% cause acute cor pulmonale, shock, or death

Pulmonary infarction

• Emboli usually resolve after the initial acute event
  • Contract
  • Endogenous fibrinolytic activity
  • Total lysis of the thrombus
• Risk of recurrence is high
  • 30% chance of developing a second

Infarction

• Compromised cardiovascular status
  • Congestive heart failure
• The more peripheral the embolic occlusion, the higher the risk of infarction
• 3/4 lower lobes
• >1/2 are multiple
• Wedge-shaped
  • Base at the pleural surface and the apex pointing toward the hilus

A small, roughly wedge-shaped hemorrhagic pulmonary infarct of recent occurrence

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Hemorrhagic infarcts

Lungs have dual circulation

Raised, red-blue areas in the early stages

Adjacent pleural surface covered by a fibrinous exudate

Occluded vessel is found near the apex of the infarcted area

• Red cells begin to lyse within 48 hours
• Infarct pales
• Red-brown
  • Hemosiderin
• Fibrous replacement begins at the margins
  • Gray-white peripheral zone
  • Converts the infarct into a scar
• Hallmark of fresh infarcts is coagulative necrosis of the lung parenchyma and hemorrhage

Nonthrombotic forms of pulmonary embolism

• Air, fat, and amniotic fluid embolism
• Bone marrow embolism
  • Massive trauma
  • Bone infarction secondary to sickle cell anemia
• Foreign body embolism
  • Intravenous drug abuse
• Magnesium trisilicate (talc) → granulomatous response

Talc Granulomas

Talc in interstitium → fibrosis

Talc in pulmonary arteries → Pulmonary hypertension

Talc crystals can be demonstrated by polarized light

PULMONARY HYPERTENSION

Pulmonary Hypertension

Mean pulmonary pressures reach one fourth or more of systemic levels

Most often secondary to a decrease in the cross-sectional area of the pulmonary vascular bed

Increased pulmonary vascular blood flow

Secondary pulmonary hypertension

• Chronic obstructive or interstitial lung disease
  • Destruction of lung parenchyma
  • Consequent reduction in alveolar capillaries
  • Increased pulmonary arterial resistance
  • Elevated arterial pressure
• Recurrent pulmonary emboli
  • Reduction in the functional cross-sectional area
  • Increased vascular resistance
• Antecedent heart disease
  • Mitral stenosis
  • Increases left atrial pressure
  • Higher pulmonary venous pressures
  • Pulmonary arterial hypertension
• Congenital left-to-right shunts

Primary, idiopathic, pulmonary arterial hypertension

Most cases are sporadic

6% are familial with an autosomal dominant mode of inheritance

Secondary pulmonary hypertension

• Endothelial cell dysfunction
  • Due to the underlying disorder
  • Mechanical injury due to increased blood flow in left-to-right shunts
  • Biochemical injury produced by fibrin in recurrent thromboembolism
• Reduced production of vasodilatory agents
  • Nitric oxide, prostacyclin
• Increasing synthesis of vasoconstrictive mediators
  • Endothelin
• Production of growth factors and cytokines
  • Induce the migration and replication of vascular smooth muscle
  • Elaboration of extracellular matrix

Primary pulmonary hypertension

• Uncommon familial form
• TGF-β signaling pathway
  • Key mediator of endothelial and smooth muscle dysfunction
  • Germline mutations of bone morphogenetic protein receptor type 2 (BMPR-2)
• The BMPR2 gene product
  • a cell surface molecule that binds to a variety of TGF-β pathway ligands
  • inhibits proliferation
  • When mutated → abnormal vascular endothelial and pulmonary smooth muscle proliferation
• Possible role for the serotonin transporter gene (5HTT)
  • Pulmonary smooth muscle cells increased proliferation on exposure to serotonin

Vascular alterations in all forms of pulmonary hypertension

• Involve the entire arterial tree
• In the main elastic arteries
  • Atheromas
• In medium-sized muscular arteries
  • Proliferation of myointimal cells and smooth muscle cells
  • Cause thickening of the intima and media
  • Narrowing of the lumina
• In smaller arteries and arterioles
  • Thickening, medial hypertrophy, and reduplication of the internal and external elastic membranes
• The wall thickness may exceed the diameter of the lumen
  • Point of near-obliteration

Robbins Basic Pathology

B: Marked medial hypertrophy.

Robbins Basic Pathology

Idiopathic pulmonary arterial hypertension

Characteristic plexiform lesions

Endothelial proliferation forms multiple lumina within small arteries

Robbins Basic Pathology

Pulmonary hypertension

• Secondary pulmonary hypertension may develop at any age
• Primary pulmonary hypertension
  • Young adults
  • More commonly women
  • Marked by fatigue, syncope (particularly on exercise), dyspnea on exertion, and sometimes chest pain
  • Severe respiratory insufficiency and cyanosis
  • Right-sided heart failure (decompensated cor pulmonale)

DIFFUSE ALVEOLAR HEMORRHAGE SYNDROMES

Pulmonary hemorrhage

• Secondary causes of pulmonary hemorrhage
  • Necrotizing bacterial pneumonia
  • Passive venous congestion
  • Bleeding diathesis
• Diffuse alveolar hemorrhage syndromes
  • Primary
  • Immune-mediated diseases
  • Triad of hemoptysis, anemia, and diffuse pulmonary infiltrates

Goodpasture Syndrome

Proliferative, rapidly progressive glomerulonephritis

Hemorrhagic interstitial pneumonitis

Antibodies targeted against the noncollagenous domain of the α3 chain of collagen IV

These antibodies can be detected in the serum of more than 90% of persons with Goodpasture syndrome

• Lungs are heavy
• Red-brown consolidation
  • Diffuse alveolar hemorrhage
• Focal necrosis of alveolar walls
• Intra-alveolar hemorrhages
• Fibrous thickening of the septa
• Hypertrophic type II pneumocytes
• Hemosiderin, both within macrophages and extracellularly
  • Earlier episodes of hemorrhage
• Characteristic linear pattern of immunoglobulin deposition
  • Usually IgG, sometimes IgA or IgM
  • Hallmark diagnostic finding in renal biopsy specimens
  • May be seen along the alveolar septa

Plasmapheresis

Immunosuppressive therapy

Renal transplantation

Diffuse alveolar hemorrhage syndrome

Large numbers of intra-alveolar hemosiderin-laden macrophages on a background of thickened fibrous septa

Robbins Basic Pathology

Robbins Basic Pathology

Idiopathic Pulmonary Hemosiderosis

• Rare disease of uncertain etiology
• Pulmonary manifestations and histologic features similar to those of Goodpasture syndrome
  • No associated renal disease
  • No circulating anti-basement membrane antibody
• Most cases occur in children
  • Reported in adults as well, who have a better prognosis
• Steroid and immunosuppressive therapy
  • Survival has markedly improved from the historical 2.5 years
  • An immune-mediated etiology is postulated

Pulmonary Angiitis and Granulomatosis

Wegener Granulomatosis

80% develop upper respiratory or pulmonary manifestations

PR3-ANCAs are present in close to 95% of cases

• Lung lesions
• Combination of necrotizing vasculitis
  • Angiitis
• Parenchymal necrotizing granulomatous inflammation
• Upper respiratory symptoms
  • Chronic sinusitis, epistaxis, nasal perforation
• Pulmonary signs and symptoms
  • Cough, hemoptysis, chest pain