CIRCULATORY DERANGEMENTS I

Slide 41 [WinLab] [Mac] [WinHome]

Lung: Acute Passive Congestion and Edema

This lung came from a 37-year-old man who died with signs and symptoms of sepsis.

• Under the lowest power of your microscope, you can readily identify sectors of fairly normal lung parenchyma. In much of this slide, however, the usually “empty” air spaces are filled with a pale pink, homogenous to slightly granular material which is edema fluid. Most of this fluid has fairly low protein content (and is therefore pale-staining), but in very limited foci there are deposits of fibrin which stain more deeply and have a fibrillar texture.

• In many of the alveolar spaces, there are air bubbles in the edema fluid. How did they come to be there? What are the clinical manifestations associated with this?

• A rather diffuse change associated with the edema is vascular engorgement, i.e., congestion, manifested by an excessive number of erythrocytes in alveolar septa. This is a difficult determination to make microscopically (don’t fret about it!), but grossly the congestion is not subtle. The lung would have had a dusky, purplish hue. Some of the “excess” erythrocytes have been extruded into alveolar spaces reflecting the increased hydrostatic pressure within the lungs, and the delicate structure of the alveolar septa. This so-called “hemorrhage by diapedesis” is often sufficient to produce a gross blood-tinging of the edema fluid.

• Under what circumstances might you encounter pulmonary vascular congestion of an “active” sort, associated with vascular permeability changes? (See Slide 9 [WinLab] [Mac] [WinHome] and Slide 16 [WinLab] [Mac] [WinHome].) The situation in Slide 41 [WinLab] [Mac] [WinHome] is a bit different -- with passive congestion and edema. Under what circumstances would acute passive congestion and edema be encountered? What signs and symptoms would be associated?

• An added feature in this case is the presence of circumscribed foci of inflammation. Most of your slides will show (scan under low power!) clusters of alveoli filled with polymorphonuclear neutrophils, and other areas where actual suppuration has taken place, i.e., where the parenchyma has undergone liquefactive necrosis leaving a puddle of pus. (Localized suppuration = abscess). The rim of fibroblastic proliferation around these lesions indicates that the process is at least several days to a week old. Suppurative lesions usually reflect infection. How can microbial agents reach the lung?

Slide 42 [WinLab] [Mac] [WinHome]

Lung: Early Chronic Passive Congestion

This specimen of lung was obtained from a 66-year-old patient who had been in congestive cardiac failure for some weeks.

• Alveolar septa everywhere in the section are engorged with red cells, reflecting passive congestion. Hemorrhage by diapedesis is prominent.

• A feature which distinguishes this slide from Slide 41 [WinLab] [Mac] [WinHome] is the presence of numerous intra-alveolar clumps of brown pigment, evident even on low power. On higher powers, the clumps are seen to be aggregates of pigment granules, which seem to be intracellular as judged from their smooth circumscription. If you search a bit, you’ll find a nucleus in some of these cells (if cut just right) allowing you to conclude that the cells are macrophages. The pigment granules are quite large, have a sort of “waxy” appearance, and a warm brown color. These features are typical of hemosiderin granules.

• In the lung, you can also encounter macrophages containing variable dirty brown-black granules representing inhaled then phagocytosed crud. This must be distinguished from hemosiderin.

• The most common source of hemosiderin, as in this case, is blood breakdown. (In Slide 13 [WinLab] [Mac] [WinHome] you will see hemosiderin of different origin within cells of the liver.) Generally, you can expect to encounter hemosiderin in areas of hemorrhage that are being mopped up, or in thrombi that are undergoing resolution or organization.

• In the lung that remains congested over a period of time (“chronic passive congestion”), the continuing hemorrhage by diapedesis leads to accumulation of hemosiderin. The pigment-containing macrophages which can also be seen in expectorated sputum, have been called “heart failure cells.” If sufficiently prolonged, the congestion can lead to an increase in interstitial connective tissue. Then, the lung grossly is brown and firm, leading to the old term “brown induration” to describe the chronically congested lung.

• Can you list some cardiac conditions that might lead to a lung of this sort?

Slide 43 [WinLab] [Mac] [WinHome]

Liver: Changes Related to Cardiac Failure

This liver specimen was obtained at autopsy of a 44-year-old woman who died after many months of cardiac dysfunction.

• Under the lowest power of your microscope, you’ll note that this liver has a peculiar pattern of lighter areas alternating with darker areas. (The normal liver would have a fairly homogeneous appearance at this power, i.e., uniformly the darker staining.)

• With higher magnification it can be seen that the lighter areas are characterized by smaller hepatocytes than in the darker areas. The sinusoids are correspondingly widened. (The blood has partly drained during specimen dissection yielding an “empty” appearance.)

• Using the portal tracts (with their bile duct/arterial branch/portal vein branch) for orientation, you’ll be able to discern that the lighter areas are around central veins, i.e., centrilobular, with preservation of normal structure more peripherally. This pattern of centrilobular sinusoidal dilatation and hepatocyte atrophy can be produced by chronic impairment of outflow of blood through central-veins, hepatic veins, and vena cava, and has been classically called chronic passive congestion.

• This chronic passive congestion pattern is frequently found in the livers of patients with “right side” heart failure (usually secondary to “left sided” failure with changes of passive congestion in the lungs). Can you imagine other “non cardiac” circumstances that might produce a similar pattern in the liver?

• Although there are examples of primary right sided heart failure, most often both sides are involved. Therefore, there is frequently an aspect of failure of “forward” flow due to decreased left ventricular output. When this is severe, particularly with hypotension as the cardiac patient is decompensating, arterial perfusion drops, and centrilobular areas in the liver, farthest from the blood supply, begin to undergo ischemic necrosis.

• In many of the central zones in your slide, close inspection will reveal pyknosis and karyolysis in some hepatocytes, occasionally with a few leukocytes clustered about -- reflecting very early ischemic necrosis. Sometimes the combination of poor perfusion and passive congestion results in necrotic centrilobular areas stuffed with blood. This pattern, called “central hemorrhagic necrosis,” is seen only focally in your slide, but can be seen more or less globally in some cases.

• What clinical evidence might there be of the findings in your slide, in a living patient?

Slide 44 [WinLab] [Mac] [WinHome]

Esophagus: Varices

This specimen was obtained from a 56-year-old man who died of a massive upper gastrointestinal hemorrhage.

• Under low power, begin by identifying the esophageal mucosa (“moist type” stratified squamous epithelium), submucosa, and muscularis.

• The most striking feature of this slide is the presence of numerous, markedly dilated veins at all levels of the wall, but particularly in the submucosa. These vessels are engorged with blood, and are associated with extensive hemorrhage into the adjacent tissues. Dilated and tortuous veins are called “varicose veins” or varices (singular-varix).

• Some of these varices contain thrombi particularly evident as masses of fibrin with entrapped blood elements. Some of the thrombi have been around long enough to be organizing, as shown by the ingrowth (from the vessel lining) of fibroblasts and capillaries. In most of your sections, the largest varix, partly thrombosed, is just under the squamous epithelium with an area of erosion. This vessel, or one like it, was probably the source of the massive GI hemorrhage.

• A detail: The mucosa and part of the submucosa in one sector are necrotic, possibly the result of pressure from a device inflated within the esophageal lumen to tamp the bleeding.

• Varices generally result from prolonged engorgement of veins. How can you account for such a condition in esophageal veins? Where else are varices commonly encountered?

Slide 45 [WinLab] [Mac] [WinHome]

Dura: Organizing Subdural Hematoma

This specimen was obtained at autopsy of a 71-year-old man with a history of chronic alcohol abuse. Grossly it appeared as an ovoid mass adherent to the inner dura, impinging on the brain.

• On the slide are two segments of the “shell” of this hematoma. Under the lowest power of your microscope, you’ll note that a dense fibrous membrane forms one margin of each section. This is the dura. Try to visualize a large puddle of blood accumulating beneath the dura, and beginning to organize with the passage of time. The tissue beneath the dura is the capsule that forms around the hematoma. The more central puddle of blood doesn’t really appear in the section, but would have been in continuity with the deep edge of each section.

• Thus, the tissue beneath the dura is the new connective tissue that forms as the hematoma is organized and mopped up from the periphery toward the center. Since the process immediately adjacent to the dura is oldest, there is a change of density and cellularity as one proceeds from the dura to the opposite edge (i.e., toward the center of the hematoma).

• Just under the dura, the connective tissue of the capsule is compact and quite collagenous and contains an inflammatory infiltrate which includes lymphocytes and macrophages (some of which contain hemosiderin). The deeper tissue is not as compact, and appears less collagenous and more vascular. Red cells are scattered through the interstices of this tissue. Hemosiderin-containing macrophages are numerous in this area where red cells are actively being mopped up.

• What would be the ultimate fate of a lesion of this sort, had the patient survived?

• How does the body’s handling of a simple bruise differ from this?

• What symptoms might be associated with a subdural hematoma?

• In this particular case, what is the relationship between the patient’s history and the development of a subdural hematoma?

• In what other situation (other than breakdown of blood) might hemosiderin be encountered?

Slide 46 [WinLab] [Mac] [WinHome]

Soft Tissues of Leg: Organizing Venous Thrombi

These fragments of soft tissue were obtained at autopsy from the left leg of a 73-year-old woman who had died suddenly.

• Within a background of skeletal muscle are large veins, distended with blood. Their distended state immediately suggests that something is wrong. Generally vessels appear more collapsed, as seen in routine sections, unless fixed by perfusion under pressure, or unless something is holding the vessel open.

• In this case, it is blood that appears to be holding the vessels open. If this had been only fluid blood at the time of the patient’s demise, how would it appear in the sections?

• Note that in several of the veins, the blood is not simply a mixture of red cells and leukocytes, but is traversed by bands of fibrin and platelets, trapping the various formed elements. In a post-mortem clot (as opposed to an ante-mortem thrombus) how would the appearance of any fibrin or platelets differ? Karyorrhexis of leukocyte nuclei is also a feature of thrombi.

• Note, also, that in some of the thrombi there is very early ingrowth of capillaries and fibroblasts from the vessel wall, i.e., organization. This, of course, would not happen in a postmortem clot. What does this organization tell you about the age of the thrombus?

• Had the patient survived, how would the histologic picture in these vessels evolve?

• What factors might have led to the formation of these thrombi?

• Can you relate these thrombi to the patient’s demise?