Term
| what level of resistance is pulmonary HTN usually? what qualifies as pulmonary HTN? |
|
Definition
| pulm HTN is usually low, around 1/8 systemic BP, and if it rises to 1/4 systemic BP, it becomes pulm HTN (this is why you generally don't see atherosclerosis in the lungs) |
|
|
Term
| is pulm HTN usually primary or secondary |
|
Definition
| pulm HTN is usually secondary to cardiopulmonary diseases that increase pulmonary blood flow and/or pressure, pulmonary vascular resistance or L heart resistance to blood flow. there is however, a rare mutation in the BMPR2 gene that causes primary pulm HTN. |
|
|
Term
| how can chronic obstructive or interstitial lung disease cause pulmonary HTN? |
|
Definition
| hypoxia and destruction of the lung parenchyma, resulting in fewer alveolar capillaries, causing *increased pulmonary arterial resistance and pressure |
|
|
Term
| how can antecedent congenital or acquired heart disease lead to pulmonary HTN? |
|
Definition
| mitral stenosis due to an increase in L atrial pressure can cause an increase in pulmonary venous pressure and pulmonary artery pressure |
|
|
Term
| how can recurrent thromboemboli cause pulm HTN? |
|
Definition
| recurrent thromboemboli can cause a reduction in cross-sectional area of the pulmonary vascular bed due to obstructing emboli and leading to an increase in pulmonary vascular disease |
|
|
Term
| how can autoimmune disorders lead to pulm HTN? |
|
Definition
| autoimmune disorders, especially *systemic sclerosis involve pulmonary vasculature, leading to inflammation, intimal fibrosis medial hypertrophy and pulm HTN |
|
|
Term
| what characterizes primary pulm HTN? |
|
Definition
| primary pulm HTN is uncommon, sporadic and most commonly seen in women between 20-40. it is a dx of exclusion |
|
|
Term
| is there a genetic component to primary pulm HTN? what is the histologic effect of this mutation on the lung tissue? |
|
Definition
| genetically, primary pulm HTN is caused by mutations in the *bone morphogenic protein receptor type 2 (BMPR2) signaling pathway*. histologically, this leads to vascular obstruction of the vascular caused by proliferation of endothelial, smooth muscle, and intimal cells with *concentric laminar intimal fibrosis* (concentric, layerwise narrowing of the vasculature) |
|
|
Term
| what is the bone morphogenic protein receptor type 2? |
|
Definition
| a cell-surface protein which binds TGF-B, bone morphogenic protein (BMP) activin, and inhibin. BMPR2 is important for embryogenesis, apoptosis, cell proliferation and differentiation |
|
|
Term
| what does BMPR2 do in pulm vascular SMCs? what happens if it is missing? |
|
Definition
| BMPR2 causes *inhibition of proliferation and favors apoptosis, in absence of this signaling - smooth muscle proliferation occurs, leading to vascular changes (narrowing and occlusions) (environmental factors may also cause dysfunction of vasoregulatory mechanisms) |
|
|
Term
| how should tx for pulm HTN be approached? |
|
Definition
| by IDing and txing the underlying problem |
|
|
Term
| what is the general pathogenesis of secondary pulm HTN? |
|
Definition
| increased shear and mechanical injury associated with R to L shunts, biochemical injury produced by fibrin in thromboembolism or vasoconstriction (due to decreased elaboration of prostacyclin, decreased NO and increased release of endothelin) |
|
|
Term
| how does decreased prostacyclin and NO affect vasculature, including that in the lungs? |
|
Definition
| decreased prostacyclin and NO promotes platelet adhesion and activation |
|
|
Term
| how does endothelial activation affect vasculature, including that in the lungs? |
|
Definition
| endothelial activation makes endothelial cells thrombogenic and promotes the persistence of fibrin |
|
|
Term
| how does increased production and release of growth factors affect vasculature, including that in the lungs? |
|
Definition
| increased production and release of growth factors induce the migration and replication of vascular SMCs and elaboration of the ECM (narrows blood vessels) |
|
|
Term
| are PEs common causes of pulm HTN? how does this happen? |
|
Definition
| yes, the PE may be only partially broken down, stay in the wall and re-organize - forming occlusive scar tissue. this new tissue formation may recanalize, or form another hole - but this often will not effectively reduce the occlusion |
|
|
Term
| how can COPD and diffuse pulmonary fibrosis commonly cause pulm HTN? |
|
Definition
| COPD and diffuse pulmonary fibrosis commonly cause pulm HTN via chronic hypoxia which leads to breakdown of the vascular walls, decreased oxygenation, and compressed vasculature |
|
|
Term
| what can vascular changes seen in pulm HTN involve? |
|
Definition
| the vascular changes seen in pulm HTN can involve the entire arterial tree from the main pulmonary arteries down to the arterioles |
|
|
Term
| why are there no atherosclerotic lesions usually seen in the lungs? what does it indicate if you see this? |
|
Definition
| there should be no atherosclerotic lesions seen in the lungs b/c the low flow state - but *if there are, think pulm HTN |
|
|
Term
| what does any level of atheromatous deposits found in the pulm artery or its branches indicate? how might this manifest itself? |
|
Definition
| any level of atheromatous deposits found in the pulm artery or its branches indicates pulm HTN and may manifest as thickening of the media or intimal fibrosis |
|
|
Term
| when might you see plexigenic pulmonary arteriopathy in a pt? what is it? |
|
Definition
| if they have primary pulmonary HTN and/or congenital heart disease w/R->L shunts. plexigenic pulm arteriopathy consists of *microscopic capillary formations producing a network of vessels that doesn't efficiently transport blood = HTN |
|
|
Term
| what are some of the clinical presentations associated with primary pulm HTN? |
|
Definition
| dyspnea, fatigue, and sometimes chest pain; as it progresses you may start to see severe respiratory distress, cyanosis, *R ventricular hypertrophy and death from decompensated cor pulmonale w/superimposed thromboembolism (can cause or be caused by HTN) and pnuemonia (decreased blood flow) |
|
|
Term
| what are the diffuse pulmonary hemorrhage syndromes? |
|
Definition
| goodpastures's syndrome, idiopathic pulmonary syndrome, vascultis associated hemorrhage, and wegener granulomatosis |
|
|
Term
| what can help differentiate possible hemorrhage in a histologic slide of pulm tissue? |
|
Definition
|
|
Term
| what is goodpasture syndrome? how may it present? |
|
Definition
| an uncommon autoimmune disease where circulating autoantibodies attack the *noncollagenous domain of collagen IV. antibodies initiate *inflammatory destruction of the BM in both kidney glomeruli and lung alveoli. pts w/this may have hemoptysis and hematuria |
|
|
Term
| is there an HLA association with goodpastures? |
|
Definition
|
|
Term
| how do lungs affected by goodpasture syndrome appear? |
|
Definition
| the lungs are heavy with areas of *red-brown consolidation (hemosiderin) and there is *focal necrosis of alveolar walls associated with *intra-alveolar hemorrhages |
|
|
Term
| why do the lungs of pts w/goodpastures contain hemosiderin-laden macrophages? |
|
Definition
| b/c the macrophages are trying to clean up hemosiderin which is accumulating due to the breakdown of hemoglobin from blood leaking out of the ruputured alveoli |
|
|
Term
| how do lungs in later stages of goodpastures appear histologically? |
|
Definition
| later stages of goodpastures may have *fibrous thickening of the septae, *hypertrophy of type II pneumocytes and *organization of blood in the alveolar spaces |
|
|
Term
| what would you see with IF in lungs affected by goodpastures? |
|
Definition
| immunofluorescence would show *linear deposits along the BM of the septal walls |
|
|
Term
| what do most cases of goodpasture syndrome *begin with? |
|
Definition
| most cases of goodpasture syndrome *begin with respiratory symptoms such as hemoptysis/dyspnea |
|
|
Term
| what is seen on a CXR for a goodpasture syndrome pt? |
|
Definition
| some focal pulmonary consolidation |
|
|
Term
| what happens in the later stages of goodpastures syndrome? |
|
Definition
| glomerulonephritis, which leads to rapidly progressive renal failure. the *common cause of death for these pts is uremia. |
|
|
Term
| what is a good treatment method for pts w/goodpasture syndrome? |
|
Definition
| plasma exchange, which can improve survival by removing circulating anti-basement antibodies |
|
|
Term
| what generally characterizes the effect of goodpasture syndrome and who does it usually affect? |
|
Definition
| goodpasture syndrome, which causes proliferative, usually rapidly *progressive glomerulonephritis and a *necrotizing hemorrhagic interstitial pneumonitis (interstitium) mostly occurs in *teens and *twenties a nd most commonly affects *males |
|
|
Term
| what is idiopathic pulmonary hemosiderosis? how does this appear on CXR? |
|
Definition
| an insidious onset of productive cough, hemoptysis, anemia, and weight loss. on CXR, this will appear as pulmonary infiltrates similar to goodpasture syndrome |
|
|
Term
| who does idiopathic pulmonary hemosiderosis usually affect? |
|
Definition
| children, though there are some rare cases involving adults |
|
|
Term
| how do lungs affected by idiopathic pulmonary hemosiderosis appear grossly? |
|
Definition
| the lungs are moderately increased in weight w/areas of consolidation that are usually red-brown and there is *intermittent* diffuse alveolar hemorrhage |
|
|
Term
| how do lungs affected by idiopathic pulmonary hemosiderosis appear microscopically? what is the clinical course? |
|
Definition
| the *macrophages may contain hemosiderin, there may be *hyperplasia of type II pneumocytes w/varying degrees of *interstitial fibrosis. there is *no vasculitis*, no inflammatory infiltrate, and *no anti-BM antibodies* or renal damage. the disease has a mild to moderate course. |
|
|
Term
| what is thought to be the cause behind idiopathic pulmonary hemosiderosis? |
|
Definition
| since successful treatment has been found using immunosuppression, the disease likely has an immunologic mechanism, which produced the pulmonary capillary damage and associated hemorrhage. long term f/u also indicates that some pts develop other immune disorders. |
|
|
Term
| what % of SLE pts have pulmonary hemorrhage? |
|
Definition
| 2% (hemoptysis may be a presenting symptom) |
|
|
Term
| how many microscopic polyarteritis pts usually have pulm hemorrhage? |
|
Definition
| 1/3 (hemoptysis may be a presenting symptom) |
|
|
Term
| what level of pulm hemorrhage do wegener's granulomatosis pts usually have? |
|
Definition
| mild hemorrhage (hemoptysis may be a presenting symptom) |
|
|
Term
| what is wegener granulomatosis? |
|
Definition
| *acute necrotizing granulomas of the respiratory tract and *granulomatous vasculitis of small to medium-sized vessels especially in the lungs. (the kidney may be affected in the form of focal necrotizing, often cresenteric glomerulitis, and the eye/skin/heart may also be affected) |
|
|
Term
| what characterizes the granulomas seen with wegeners affecting the upper respiratory tract? |
|
Definition
| upper respiratory tract lesions range from *inflammatory sinusitis resulting from mucosal granulomas to *ulcerative lesions of the nose (saddle deformity), palate or pharynx rimmed by *necrotizing granulomoas and accompanying *vasculitis |
|
|
Term
| how do the granulomas associated with wegener granulomatosis appear microscopically? |
|
Definition
| microscopically the granulomas have a *geographic pattern of necrosis, they are surrounded by lymphocytes, plasma cells, macrophages, and variable number of giant cells. there is also necrotizing or granulomatous vasculitis of small and sometimes larger arteries and veins (which can give you hemorrage) |
|
|
Term
| how can wegeners be confused with TB? |
|
Definition
| the granulomas due to wegeners may coalesce to form nodules which may cavitate and can be *confused with TB. these lung lesions may lead to alveolar hemorrhage |
|
|
Term
| what might wegener granulomatosis represent a form of hypersensitivity to? |
|
Definition
| an inhaled infectious or environment agnent |
|
|
Term
| what evidence supports the hypothetical association between wegeners granulomas and immunologic mechanisms? |
|
Definition
| immune complexes have been seen in glomeruli/vessel walls of some pts and pts usually respond to immunotherapy (suggests a cell mediated immunologic mechanism) |
|
|
Term
| who is more commonly affected by wegeners granulomatosis? what is the clinical presentation? |
|
Definition
| males around 40 are more commonly affected. pts with wegeners granulomatosis present with persistent *pnemonitis* w/bilateral nodular and cavitary infiltrates, chronic sinusitis, mucosal ulcerations of the nasopharynx and renal disease. the pts may also present with skin rashes, muscle pains, articular involvement, mononeuritis, polyneuritis, and fever |
|
|
Term
| what is the prognosis for wegeners granulomatosis pts? |
|
Definition
| if untreated, the course of the disease is fatal w/in a year |
|
|
Term
| what is a good marker for disease activity? |
|
Definition
| *c-ANCA, which is present in the serum of most pts w/active generalized disease. during tx, a rising c-ANCA titer suggests a relapse and most pts in remission have a negative test or fall in titers |
|
|
Term
| what is the association between lymphomatoid granulomatosis and wegeners granuloma? |
|
Definition
| lymphomatoid granulomatosis can mimic wegener granulomatosis, and is characterized by *pulmonary nodules of lymphoid and plasmacytoid cells often w/cellular atypia |
|
|
Term
| what is unique about lymphomatoid granulomatosis? |
|
Definition
| lymphomatoid granulomatosis may represent an evolving lymphoproliferative disorder, since up to 50% of pts develop a lymphoid malignancy (most commonly: hodgkin) |
|
|
Term
| where do most pulmonary thromboembolisms originate? |
|
Definition
| most PEs originate in the deep veins of the legs (sometimes the prostatic plexus, pelvic veins, inferior vena cava) |
|
|
Term
| what are pulmonary thromboembolisms often associated with? |
|
Definition
| *bed rest, leg injury, congestive heart failure, oral use of contraceptives (women over 35 that smoke), burns, traumas, fractures, cancer, and indwelling central venous lines (can be a nidus for a R atrial thrombus) |
|
|
Term
| what typifies the origin of blood clots that occlude the large pulmonary arteries? |
|
Definition
| usually, blood clots that occlude the large pulmonary arteries are embolic in origin. large vessel in situ thromboses are rare - but can occur in the setting of pulm HTN, pulm atherosclerosis and heart failure |
|
|
Term
| what is a saddle embolus? |
|
Definition
| an embolus that sticks right at the bifurcation of the pulmonary artery - which can lead to sudden death (no infarct - b/c no time) |
|
|
Term
| what factors can determine how a person responds to a PE? |
|
Definition
| the extent to which the pulmonary blood is obstructed, the size of the occluded vessel, the number of emboli, the overall status of the CV system, and the release of vasoactive factors (such as thromboxane A2 from platelets that accumulate at the site of the thrombus) |
|
|
Term
| what are the two main pathophysiologic consequences of a PE? |
|
Definition
| respiratory compromise: nonperfusion of a lung segment, even though it is ventilated. hemodynamic compromise: due to increased resistance to the pulmonary blood flow produced by embolic obstruction which can lead to *pulmonary HTN* and *acute R-sided heart failure* (SOB, chest pain, dizziness) |
|
|
Term
| can a PE cause acute R sided heart failure (acute cor pulmonale)? |
|
Definition
|
|
Term
| what is the danger with smaller emboli in the lungs? |
|
Definition
| smaller emboli can travel into the more peripheral vessels, where they can cause infarction (this is less common and usually only occurs if there are already circulatory problems or if the pts are elderly) |
|
|
Term
| if there is obstruction to the pulmonary arterial system, how might pts still possibly sustain the lung parenchyma? |
|
Definition
| if the pts still have enough cardiovascular function, the bronchial artery can often sustain the lung parenchyma |
|
|
Term
| can hemorrhage due to a PE still occur even if there is no infarction of the underlying pulmonary parenchyma? |
|
Definition
|
|
Term
| where do most infarcts due to PEs occur? do they usually happen on their own or in multiple? |
|
Definition
| PEs commonly happen in the lower lobes and generally occur in multiple |
|
|
Term
| what shape do PEs form in the pulmonary vasculature? |
|
Definition
| wedge shaped (w/the apex being near the point of occlusion) that extend to the periphery of lung |
|
|
Term
| how do PEs appear in the early stages? after 48 hrs? |
|
Definition
| PEs appear classically as a *raised red-blue area in the early stages, and the opposed pleural surface may be covered in a *fibrinous exudate. the RBCs begin to lyse by 48 hrs and the infarct becomes *paler, eventually red-brown due to hemosiderin formation |
|
|
Term
| if the pt survives a PE, what does the area affected look like? |
|
Definition
| the fibrinous replacement begins at the margins as a gray-white peripheral zone and eventually converts the infarct into a contracted scar (contraction atelectasis) |
|
|
Term
| histologically, what effect does an acute infarct due to a PE have on the lung tissue? |
|
Definition
| the acute infarct will cause *ischemic necrosis of the lung in the areas of hemorrhage, affecting the alveolar walls, bronchioles and vessels |
|
|
Term
| what happens if the PE is infectious (as w/infectious endocarditis)? |
|
Definition
| the infarct will have a more intense neutrophilic exudation and inflammatory infiltrate, which is referred to as a *septic infarct |
|
|
Term
| what is one of the few cases of virtually instantaneous death? |
|
Definition
|
|
Term
| what are the signs and symptoms of a PE similar to? |
|
Definition
| that of an acute MI (chest pain, SOB, shock, elevated temperature, and increased levels of serum lactic dehydrogenase) |
|
|
Term
| how might small emboli present in pts w/normal CV systems? |
|
Definition
| transient chest pain, cough or possibly small pulmonary hemorrhages w/o infarcts |
|
|
Term
| how might a PE appear on a CXR? |
|
Definition
| there may be a pulmonary infarct visible usually 12-36 hrs after the PE, appearing as a wedge-shaped infiltrate |
|
|
Term
| what is the most definitive test for a PE? |
|
Definition
| pulmonary arteriography - however it may pose a greater risk to the pt |
|
|
Term
| how do emboli usually resolve after the initial insult? |
|
Definition
| contraction and fibrinolysis |
|
|
Term
| can unresolved, small PEs contribute to pulmonary HTN, pulmonary vascular sclerosis, and chronic cor pulmonale? |
|
Definition
|
|
Term
| do pts w/a hx of one PT have an increased risk of another? |
|
Definition
| yes, and prevention is a major clinical challenge |
|
|
Term
| what are measures taken to prevent PEs? |
|
Definition
| early ambulation, elastic stockings, and preventitive anticoagulation therapy. in high risk pts, a filter can be inserted into the inferior vena cava |
|
|
