ICL 3.6: Pathology of Pulmonary Vascular Diseases Flashcards
eosinophilia in the context of pulmonary diseases
- asthma
- sarcoidosis
- Churg-Strauss
hypertrophy of smooth muscles
asthma
bronchi are constricted
blue bloated
chronic bronchitis
cyanosis around the mouth and nails
spontaneous pneumothorax
paraseptal emphysema
usually in young males who develop sudden sharp chest pain
cirrosis and emphysema in young patient
alpha-one antitrypsin deficiency with PZZ phenotype
panacinar emphysema
insulation industry
asbestos
can cause pulmonary fibrosis, cancer, pleural plugs, mesothelioma etc.
sand balsting
silicosis
egg shell calcification in the mediastinum
silicosis
pleural plug
asbestos
Caplan syndrome
RA and any pneumoconosis
serositis
associated with SLE
inflammation of a serous membrane
alveolitis
**it’s the pathogenesis of restrictive lung disease
smoking
- chronic bronchitis
2. emphysema
constipation and hypercalcemia
sarcoidosis
paniculitis in the legs/inflammation of subcutaneous fat
erythema nodosum
sarcoidosis
infertility
Kartageners
65 year old male smoker with a known history of hypertension and hyperlipidemia presents to the ER with severe shortness of breath and productive cough with frothy sputum PE reveals bilateral basal crackles in the lungs.
Tests: His BNP is 500
diagnosis?
pathogenesis?
pulmonary edema due to CHF!!
frothy sputum = water + air together = water and air in the alveoli!
crackles = alveoli
risk factors = HTN, hyperlipidemia, smoker
what are some of the things that can cause pulmonary edema?
- increased hydrostatic pressure
- decreased oncotic pressure
- lymphatic obstruction
- microvascular injury
- undetermined origin
what can cause pulmonary edema due to increased hydrostatic pressure?
- increased pulmonary venous pressure like in CHF*
- volume overload
- pulmonary vein obstruction
what can cause pulmonary edema due to decreased oncotic pressure?
- hypoalbuminemia
- nephrotic syndome*
- liver disease
- protein losing enteropathies
what can cause pulmonary edema due to microvascular injury?
- infections: pneumonia, septicemia*
- inhaled gases: oxygen, smoke
- liquid aspiration: gastric contents, near-drowning
- drugs and chemicals: chemotherapeutic agents (bleomycin), other medications (amphotericin B), heroin, kerosene, paraquat
- shock, trauma*
- transfusion related (TRALI)*
why are we worried about pulmonary edema due to microvascular injury?
this is what causes ARDS!!!
there is leakage of fibrin from the capillaries due to the damage which cements the walls of the alveoli so that they can’t diffuse gas and they become really hypoxic and giving oxygen doesn’t even help
what can cause pulmonary edema due to undetermined origin?
- high altitude
2. neurogenic (CNS trauma)
what are the gross changes seen in pulmonary edema?
- heavy, wet lungs and frothy blood tinged fluid
- fluid accumulates in the lower lobes where hydrostatic pressure is greater
changes lead to impaired function (interstitial edema) and predisposes one to infections (intra-alveolar edema)
what are the microscopic changes seen in pulmonary edema?
- intra-alveolar granular pink (eosinophilic) precipitate
- alveolar microhemorrhages and hemosiderin-laden macrophages (“heart-failure cells”) present in chronic cases
with long-standing chronic passive congestion (e.g. mitral stenosis), lungs become visibly brown and firm due to numerous hemosiderin-laden macrophages and interstitial fibrosis which is termed “brown induration”***
This thirty-four year old white male collapsed suddenly while waiting for his baggage at the airport after arriving from a business trip to Tokyo on a non-stop, private charter flight. CPR was begun at the airport and continued until his arrival at the ER. At that time, he was found to have electromechanical dissociation and, in spite of all efforts, he could not be resuscitated.
His family history was positive for early death from heart disease, and he had been warned about his elevated cholesterol. He had sustained a recent fracture to his right tibia while skiing, and his right lower leg was in a walking cast.
diagnosis?
pulmonary embolism
was on the plane not moving for a super long time
electromechanical dissociation = pulsus paradoxicus associated with cardiac tamponade
recent fracture to tibia = immobilization
what is a pulmonary embolism?
blood clots that occlude the large pulmonary artieres
most common cause is DVTs in the legs
what are the predisposing factors for developing a PE?
Virchow’s triad:
1. immobilization
- hypercoagulable states
- factor V bleeder
- contraceptive pills (especially estrogen)
- SLE - endothelial injury
what are the consequences of having a PE?
depends on the size of the embolus
large emboli may occlude main pulmonary artery, major branches or lodge at the bifurcation –> if it’s at the bifurcation it’s called a saddle embolus and this is what kills people most often
if it’s small the emboli may travel to more peripheral vessels and may or may not cause infarction
what are the outcomes of a PE?
- most of the time they’re clinically silent because they’re so small so there is none! one (~60-80% are clinically silent)
- hemorrhage (~10-15%): tissue viability sustained by collateral blood flow
- transient chest pain and cough
- only 10% develop infarction if they have inadequate collateral blood flow; often coexisting heart and lung disease is present
- acute right heart failure, cardiovascular collapse and sudden death
- pulmonary hypertension caused by multiple emboli over time; can cause chronic right heart straight and hypertrophy
- secondary embolus (30% chance)
what is the morphology of a PE?
- embolus:
red cells, platelets and fibrin (lines of zahn) fill arterial lumen adhering to endothelial surface
may dissolve or organize and recanalize
- hemorrhage
blood in alveoli and interstitium, preserved architecture
what are Lines of Zahn?
characteristic feature of premoretem clots; not seen postmortem
they are intermingled areas of pale pink platelets and fibrin mixed with red areas of RBCs which form the Lines of Zahn
what is an infarct due to a PE?
usually wedge-shaped and peripheral, with embolus at apex–> the apex points to hilum
sharp pain due to irritation of the pleura
¾ infarcts are in the lower lobe
in over 50% of cases there are multiple pulmonary infarcts
- acute (recent) infarct
coagulative necrosis with hemorrhage (“red infarct”); overlying pleura with fibrinous pleuritis
- remote (old) infarct
Inflammatory response followed by regeneration and fibrosis (scar); often with hemosiderin macrophages
45 year old male falls while skiing and he factures his femur, he goes to the ER his fracture is realigned and he gets a cast 24 hours after he develops severe dyspnea and reports back to the ER.
What happened?
What would you see if you had lung tissue to examination under the microscope?
fat embolus
you’ll see fat droplets in his lungs
what are fat embolisms?
most common form of clinically significant embolism second to thromboembolism
occurs generally as a result of fracture of a long bone, most typically the femur
histological examination shows fat globules in the capillaries and small vessels of the lung
A 14 year old 2 months gestation goes to a friends house to get rid of the pregnancy because she is afraid to tell her Mom. Her friend inject air and insert wire rod through her cervix. The girl develops vaginal bleeding and she goes home but 4 hours later she develops severe dyspnea and is rushed to the ER.
What happened?
air embolism
what is an air embolism?
can be caused by rauma, surgery, intravenous injections, obstetrical procedures, criminal abortion
may cause sudden death
frothy blood is present in the right ventricle and pulmonary artery at autopsy
on histological examination, empty spaces resembling fat emboli are seen
what is a septic embolism?
infected (bacteria or fungus) fragments of venous thrombi or tricuspid valve vegetations that travel to the lungs
“Septic infarct” made of neutrophils and organisms can convert to abscess
Postmortem examination of a 41 year old male who collapsed while hiking reveals bone marrow emboli in the lung vessels.
How did this happen?
bone marrow emboli in the lungs are an incidental finding at autopsy in patients who have undergone CPR
what is an amniotic fluid embolism?
embolus usually at time of delivery
can cause shock and diffuse alveolar damage in severe cases
what are starch or talc particle emboli?
contained in drug solutions injected by addicts
injections are mixed with talc powder
what is the clinical presentation of a large PE?
- chest pain
- dyspnea
- shock
- fever
- elevated (LDH3**)
- mimics MI
what is the clinical presentation of a small PE?
- transient chest pain or cough
- dyspnea
- tachypnea
- chest pain
- hemoptysis
how do you diagnose a PE?
- spiral computed tomographic angiography
dangerous because it could mobilize the clot but it’s the most accurate
- D-dimer
what is D-dimer?
a product of the degradation of fibrin when a blood clot is degraded by fibrinolysis it has 2 cross-linked D-fragments of the fibrin protein which is what is called D-dimer
usually elevated in patients with a PE
how do you prevent PE?
- early post-surgical and postpartum ambulation
- elastic stockings and leg exercises for the bedridden
- anticoagulation for high risk patients
- filter in inferior vena cava
what is pulmonary HTN?
mean pulmonary pressures reach 1/4 of the systemic levels
how is pulmonary HTN classified?
- primary
idiopathic;rare
- secondary
structural cardiopulmonary conditions which increase pulmonary blood flow or pressure, pulmonary vascular resistance, or left heart resistance to blood flow
what are some of the causes of secondary pulmonary HTN?
- chronic obstructive or interstitial lung diseases
- antecedent congenital or acquired heart disease
- recurrent thromboemboli due to scarring
- autoimmune disorders (progressive systemic sclerosis, scleroderma, NOT SLE)
what does elevated LDH3 indicated?
pulmonary infarction
LDH1 = heart and RBC
LDH5 = liver
LDH2 and 4 = nonspecific
electromechanical dissociation in the context of the lungs?
PE
in the heart, it’s cardiac tamponade
brown induration
severe mitral stenosis causing severe congestion of the lungs
fracture femur
fat emoblism
criminal abortion
air embolism
lines of Zahn
premortum blood clot
uremia
causes pulmonary edema = uremic pneumonitis
25 year old female with progressive dyspnea, leg edema and hemoptysis
discomfort in right upper quadrant. no CHF or autoimmune disease or work in the mines, insulation, etc.
primary HTN
what is primary pulmonary HTN?
aka idiopathic pulmonary HTN
usually in females: 24 – 40 yrs; occasionally young children
presenting features: dyspnea, fatigue common. Some patients angina
leads to right ventricular hypertrophy
80% die in 2-5 years of cor pulmonale, often with superimposed thromboembolism & pneumonia
what is the pathogenesis of primary pulmonary HTN?
mutation/inactivation of BMPR2 = bone morphogenetic protein
linkage to BMPR2 locus on 2q33 gene rearrangement deletions can also be found
BMPR2 mutation in the vascular smooth muscles causes:
- embryogenesis
- cell proliferation and differentiation
- apoptosis
normally BMPR2 results in inhibition of proliferation so without it there is proliferation of smooth muscles
what is the morphology of pulmonary HTN?
- atheromatous plaques in the main elastic arteries –> secondary PH
- medial hypertrophy, intimal proliferation and fibrosis in the small arteries and arterioles –> primary PH
- plexogenic pulmonary arteriopathy = capillary tuft formation (“plexiform lesion”**) which indicates severe and irreversible hypertension
this is the classic change in primary PH
what are the microscopic changes seen in pulmonary HTN?
mainly affects arterioles and small arteries (40 -300 mm in diameter)
medial thickness, intimal fibrosis, and narrowing of the lumen
which syndromes are diffuse pulmonary hemorrhage syndromes?
- Goodpasture syndrome
- idiopathic pulmonary hemosiderosis
- vasculitis-associated hemorrhage
what is Goodpasture syndrome?
simultaneous renal and pulmonary disease associated with antibasement membrane antibodies
patients have necrotizing hemorrhagic interstitial pneumonitis
they also have rapidly progressive glomerulonephritis
immunofluorescence shows linear deposits of immunoglobulins and complement on the glomerular basement membrane and in the alveolar septa = type II hypersensitivity reaction
what is idiopathic pulmonary hemosiderosis?
pulmonary hemorrhage due to capillary dilation and breakage and release of blood that gets metabolized to hemosiderin which is then taken up by alveolar macrophages
presents in children and young adults as cough, hemoptysis, anemia, weight loss
we have no idea why it happens
no kidney involvement; no antibodies
what is vasculitis-associated hemorrhage
hypersensitivity angiitis
granulomatous polyangiitis = Wegner syndrome
lupus erythematosus
plexiform lesions
primary pulmonary HTN
anti GBM
Goodpasture syndrome
BMPR2 mutation
primary pulmonary HTN
