Pathology
Lecture 37 Diseases of Vascular Origin
1) To understand Starling’s Law of capillary/interstitial fluid exchange.
The net outward forces minus the net inward forces predict the movement of fluid.
Vessel → Interstitium: capillary hydrostatic pressure, interstitial oncotic pressure.
Interstitium → Vessel: capillary oncotic pressure, interstitial hydrostatic pressure.
2) To know the causes of pulmonary edema.
Type
Hemodynamic
pulmonary edema
Subtype
Hydrostatic
Oncotic
Permeability
pulmonary edema
Lymphatic obstructive
Injury to vascular and
alveolar epithelium
Defuse alveolar
Disease process
Left-sided CHF, mitral stenosis, volume overload, pulmonary
vein obstruction
Hypoproteinemia of cirrhosis, nephrotic syndrome, and
malnutrition
Neoplasm
Infections, inhaled gases, aspiration, drowning, shock, drugs,
toxins, radiation.
Leads to ARDS
3) To become familiar with causes and sequence of events that result in Adult
Respiratory Distress Syndrome, ARDS. Central to the causation of ARDS is
diffuse damage to the alveolar capillary walls; this is followed by a series of
morphologic and physiologic alterations leading to respiratory failure.
a. Cytokines such as IL-8, IL-1, and TNF sequester neutrophils into the alveolar
space, where they undergo activation.
b. Neutrophils release leukotrienes, oxidants, proteases, and PAF, which leads to
local tissue damage, accumulation of fluid, surfactant inactivation, and hyaline
membrane formation.
c. Macrophage inhibitory factor (MIS) sustains the ongoing Pro inflammatory
response.
d. The release of macrophage derived fibrogenic cytokines such as TGF-β and
PDGF stimulate fibroblast growth in collagen deposition.
4) To be aware of clinical settings, and physiologic and pathologic consequences of
pulmonary emboli.
Clinical Settings: pulmonary embolism is the sole or major contributing cause of
death and about 10% of adults who die acutely and hospitals. It is a complication
principally in patients who are already suffering from some underlying disorder, such
as cardiac disease or cancer, or who are immobilized for several days or weeks, those
with hip fracture being at high risk. Hypercoagulable states, either primary
(hyperhomocysteinemia, factor V Leiden, antiphospholipid syndrome, etc.) or
secondary (obesity, recent surgery, oral contraceptive use, pregnancy, etc.).
Physiologic and Pathologic Consequences: depend on extent of obstruction, size of
vessels, number of emboli, cardiovascular health, and release of vasoactive factors
from platelets at the site of thrombus. Two main consequences: respiratory
compromise (ventilated but not perfused) and hemodynamic compromise (pulmonary
hypertension in the acute right-sided heart failure).
5) To be familiar with pulmonary hypertension, and understand the terms of
primary and secondary pulmonary hypertension.
Pulmonary hypertension: mean pulmonary pressure reaches 25% of systemic arterial
pressure. Usually a secondary process with known cause or uncommonly (5%)
primary of unknown etiology.
6) To be aware of the disease Wegener’s granulomatosis. Wegener 's granulomatosis
is an immunologically mediated disease were anti-neutrophil cytoplasmic antibodies
(ANCA) in serum correlate with disease activity and may protect proteases from
inactivation by binding to their natural inhibitors. It presents as nodular densities on
chest x-ray, hemoptysis, chest pain, fever, dyspnea, chronic sinusitis, and evidence of
renal disease. Acute necrotizing granulomas of upper respiratory tract and lungs,
focal necrotizing vasculitis of lungs, and necrotizing glomerulitis.
7) To answer all questions posed in the Directed Reading.
1. According to Starling’s Law of capillary interstitial fluid exchange, which forces
move fluid out of the vessel into the interstitial space, and which forces move
fluid from the interstitial space into the vessel?
Vessel → Interstitium: capillary hydrostatic pressure, interstitial oncotic pressure
Interstitium → Vessel: capillary oncotic pressure, interstitial hydrostatic pressure
2. Name the most common hemodynamic cause of pulmonary edema, and three
other causes.
Hydrostatic (left-sided CHF). Other causes: mitral stenosis, volume overload,
pulmonary vein obstruction.
3. Describe the histologic appearance of pulmonary edema.
Alveolar capillaries are engorged, and an intra-alveolar granular pink
precipitate is seen. Alveolar microhemorrhages and hemosiderin-laden
macrophages ("heart failure" cells) may be present.
4. In long-standing pulmonary congestion, which cells are responsible for the brown
discoloration of the lungs?
Hemosiderin-laden macrophages.
5. What is the initial injury in course of events which lead to ARDS?
Diffuse alveolar capillary damage.
6. What is the most common source of pulmonary thromboemboli?
95% rise from deep veins of the legs and pelvis.
7. What is the mechanism of sudden death associated with large pulmonary emboli
such as saddle emboli?
Sudden-death, right heart failure (cor pulmonale), or cardiovascular collapse
occurs with 60% or more of the pulmonary circulation is obstructed with emboli.
8. Describe the gross histologic appearances of an acute pulmonary infarct.
Acute pulmonary infarcts extend to the periphery of the lung substance as a
wedge with the apex pointing toward the hilus of the lung. It is classically
hemorrhagic and appears as a raised, red-blue area in the early stages. The
opposed pleural surface is covered by a fibrinous exudate the red cells begin to
lyse within 48 hours, and the infarct becomes paler and eventually red-brown as
hemosiderin is produced. Fibrous replacement begins at the margins as graywhite peripheral zone and eventually converts the infarct to a contracted scar.
9. What two factors determine the clinical significance of pulmonary infarct?
The size of the embolic mass and the general state of the circulation.
10. What substances other than thrombi may embolize to the lung?
Air, bone marrow (after trauma and bone marrow necrosis in sickle cell patients),
fat (trauma and surgery), amniotic fluid (during parturition), and foreign bodies
(in IV drug abusers).
11. Name at least one cause of secondary pulmonary hypertension that act by each of
the following mechanisms?
a) Increased pulmonary blood flow: left to right shunt associated with congenital
heart disease.
b) Increased resistance: vasospasm, mechanical obstruction, and destruction of
vascular bed.
c) increased pulmonary venous pressure: left heart failure, acquired heart
diseases, mitral stenosis.
12. What mechanism is currently thought to cause primary pulmonary hypertension?
Molecular studies have shown mutation in bone morphogenic protein receptor
type 2 gene (BMPR2) in 50% of familial and 26% of sporadic cases. Normal
BMPR2 signaling causes inhibition of proliferation and favors apoptosis of
vascular smooth muscle. Loss of signaling promotes proliferation. Additional
genetic or environmental insults are required to produce disease.
13. What changes are seen in the main elastic pulmonary arteries with pulmonary
hypertension?
Presence of many organizing or recanalized thrombi favors recurrent pulmonary
emboli as the cause, and the coexistence of diffuse pulmonary fibrosis, or severe
emphysema and chronic bronchitis, points to chronic hypoxia as the initiating
event.
14. In which form of pulmonary hypertension are plexiform arterial lesions present?
Plexogenic pulmonary arteriopathy occurs in primary pulmonary hypertension or
congenital heart disease with left to right shunts, the name comes from a tuft of
capillary formations producing a network, or Web, that spans the lumens of
dilated thin walled, small, arteries.
15. What is Wegener's granulomatosis?
An autoimmune disease most often involving the upper respiratory tract and/or
the lungs, with hemoptysis being the most common presenting symptom.
16. What organs are involved in Goodpasture syndrome?
The kidneys and the lungs.