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Slide 1 [WebScope][ImageScope]
Liver: Steatosis (“fatty infiltration,” etc.)
This slide is from the liver of a 54-year-old alcoholic who died of heart failure. At autopsy, the liver was enlarged (2800 gm, as compared to the expected normal of 1700 gm), and had a paler than usual color, almost uniformly throughout the organ. Look at the lighter staining area on the right side of the slide and note all of the apparent empty spaces in the cells [example], which are lipid inclusions caused by dysfunction and injury to the liver cells. In many places, the liver cells are so engorged with lipid [example] that they almost look like adipocytes, and, indeed, there probably are some true adipocytes mixed in but DO NOT worry about trying to tell them apart --the point about this slide is just to show lipid inclusions.
Review questions:
The lighter staining area on the right side of the slide is relatively free of inflammation. However, the darker region on the lower left side of the slide is much more inflamed, and presence of high numbers of lymphocytes suggests long-standing, or chronic, inflammation. In the setting of this chronic inflammation, what is MOST LIKELY to happen to the injured liver tissue?
- regeneration via activation of stem cells
- regeneration by proliferation of any remaining viable hepatocytes
- formation of granulomas
- replacement of injured tissue by a fibrotic scar
Note that within the inflamed area there aren't very many hepatocytes, meaning that the hepatocytes that were there have died. Did they die via necrosis or via apoptosis? How can you tell?
What general features would you expect to see in hepatocytes dying via apoptosis?
- nuclear fragmentation
- activation of caspases
- cell shrinkage
- ALL of the above
Whereas this particular slide shows changes in the liver that occur due to cellular stress, recall that the patient also had heart disease (specifically, heart failure). Which of the following is the MOST LIKELY change you would expect to see in the heart muscle tissue in this patient?
- proliferation of cardiomyocytes
- hypertrophy of cardiomyocytes
- dystrophic calcification
- widespread necrosis
Slide 42 [WebScope][ImageScope]
Lung: Early Chronic Passive Congestion - Hemosiderin pigment
This specimen of lung was obtained from a 66-year-old patient who had been in congestive cardiac failure prior to death. In this condition, the heart does not pump blood out very efficiently, so it starts to back up in the lungs and peripheral tissues. In the lungs in particular, blood starts to spill out of the capillaries and into surrounding tissues. Resident macrophages then ingest the red blood cells and break down the hemoglobin into hemosiderin, which is evident as rather large, glassy-brown granules. In fact, the macrophages are so engorged with hemosiderin that it may be difficult to even see their nuclei except in few instances where they are sectioned just right and/or they haven't quite stuffed themselves so much [example].
Review question:
As you might expect, much of the lung is occupied by empty air spaces surrounded by delicate tissue in a honeycomb fashion. If you look closely within the tissue, you will see the engorged blood vessels, and you should note the presence of quite a few inflammatory cells as shown here. Judging from the type of cells present, about how long would you estimate this inflammation has been ongoing?
- less than 12 hours
- about 1 day
- about 1 week
- several weeks
Slide 12 [WebScope][ImageScope]
Artery: Atherosclerosis - lipid inclusions and dystrophic calcification
These sections of arteries came from a 62-year-old hypertensive diabetic who had generalized lesions of this sort.
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We haven't studied the detailed morphology of blood vessels yet, so it is probably easiest to focus on the section on the right side of the slide [example] since it's easier to make out what's left of the original lumen of the vessel, which is lined by a simple squamous endothelium [example].
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About 2/3 of the original lumen has been taken up an athersclerotic plaque, within which you can see "foam cells" [example] that have ingested cholesterol.
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The cholesterol accumulation is so great that it also collects extracellularly as large, elliptical "crystals" (also called cholesterol clefts) --of course, since they are lipid, they are extracted with tissue processing, so they appear as empty spaces.
- Within the plaque, you may also see amorphous, basophilic debris [example], which are examples of dystrophic calcification.
Slide 8 [WebScope][ImageScope]
Kidney: Infarction - Coagulative necrosis and Acute Inflammation
This specimen of kidney was obtained from a patient that had a small clot in the aorta that broke loose and lodged into a small branch of a renal artery causing the infarction of a triangle-shaped wedge of tissue. The healthy tissue is on the right side of the slide and should be examined first. We haven't studied the histology of the kidney, so don't worry about the particulars, but note the tangles of capillary loops called "glomeruli" [example] where blood is initally filtered and all of the tubules lined by simple cuboidal epithelium modify the filtrate (mostly by resorbtion) to produce urine.
Then, move over to the infarcted area [example], and note that the general structure of the cells is preserved, hence the term "coagulative", but there are no nuclei, so the tissue is most definitely dead.
Review question:
Judging from the appearance of the necrotic tissue, how much time had MOST LIKELY elapsed between time of the insult and the time this particular sample was collected?
- less than 12 hours
- about 1 day
- about 1 week
- about 1 month
Slide 2 [WebScope][ImageScope]
Heart: Lipofuscin pigment, Coagulative Necrosis, and Acute Inflammation (myocardial infarct)
This 63-year-old patient was admitted to the hospital for a “heart attack.” He was stabilized and transferred to the intensive care unit but then died shortly thereafter. The immediate cause of his death was an irreversible cardiac arrhythmia.
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First, we'll focus on an area of healthy myocardium [example]. Be sure you can identify it as cardiac muscle. Then, zoom in to notice the granules of brownish-yellow pigment (particularly around the nuclei) which is lipofuscin or "wear and tear" pigment consisting of peroxidized phospolipids.
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Next, we'll move into the area of the infarct [example], which is a bit darker staining. The increased eosinophilia is due to protein coagulation within the dead cardiomyocytes. The areas of basophilia are streams of neutrophils coming in as part of the acute inflammatory process. Zoom in on an area [example] and note that the general structure of the cardiomyocytes is preserved, hence the term "coagulative" necrosis. The nuclei in the necrotic cells are faded or completely absent (karyolysis) and the cytoplasm is markedly more eosinophilic compared to normal cardiomyocytes [example] and the extracellular space around the necrotic cells is filled with neutrophils, a hallmark of acute inflammation.
Review questions:
Judging from the appearance of the necrotic tissue, how much time had MOST LIKELY elapsed between time of the insult and the time this particular sample was collected?
- less than 12 hours
- about 1 day
- about 1 week
- about 1 month
Can you predict in general histologic terms what would have happened to this tissue over time had this patient survived? (Slide 49 [WebScope][ImageScope] illustrates some of this.)
Slide 15 [WebScope][ImageScope]
Appendicitis: Suppurative Inflammation with Liquefactive Necrosis
This slide shows the appendix that was removed from 16-year-old with appendicitis. The slide contains one more-or-less longitudinal section and two cross-sections of the appendix. The lower left cross section [example] is from a relatively uninflamed area (this is near the area where the surgeons cut to remove the appendix) that shows the normal architecture of the appendix. Being a GI organ, the layers are similar that which you've seen in Webslide 0032 of the ileum [ImageScope] [WebScope]. Starting from the lumen of the appendix, the layers consist of:
- simple columnar epithelium
- loose, cellular connective tissue with lots of lymphocytes
- a thin layer of smooth muscle
- a layer of dense, irregular connective tissue with large blood vessels
- a layer smooth muscle (actually 2 layers --one is circularly arranged and the other is longitudinal)
- finally, an outer layer of connective tissue covered by a simple squamous mesothelium [example]
The lower right cross section shows inflamed tissue [example] consisting mostly of neutrophils, thus allowing you to classify this generally as acute inflammation. As to further classifying the morphological type of acute inflammation seen in this particular area, we would say that it is suppurative or purulent because of the purulent exudate consisting of cell debris and neutrophils (pus).
The inflammatatory response is so great that it has caused necrosis of the epithelial tissue and the underlying loose connective tissue, which has been completely obliterated and all that is left is a mass of eosinophilic cell debris [example] (the slight basophilic tinge seen here are actually masses of bacteria that pick up the hemotoxylin stain because of the DNA in them). As to the specific type of necrosis, we would say this is liquefactive.
In the outer layer of connective tissue, a slightly different kind of acute inflammation is seen [example]. Masses of neutrophils are present, so the inflammation is "purulent", but we can also amorphous tangles of fibrin [example] that have leaked out of the nearby blood vessels, so it also somewhat "fibrinous," or, putting the terms together, "fibrinopurulent."
The point here is not to get hung up so much on nomencalture but to realize that the processes can occur together and have different clinical consequences: the suppurative element weakens the wall of the appendix leading to the risk of rupture, which would be disastrous. The fibrinous element may lead to "organization" or fibrosis in the outer wall and possible attachment to other parts of the bowel or body cavity lining and could cause an obstruction, which would be equally problematic.
Review question:
Based on the primary inflammatory cell type(s) present, would you characterize this as acute or chronic inflammation?
Slide 3 [WebScope][ImageScope]
Spleen: Granulomatous Inflammation with Caseous Necrosis
This spleen is from a 28-year-old patient who died of a systemic tuberculosis infection.
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Scan this section under the lowest power of your microscope. You’ll quickly spot the basophilic lymphocytes clustered around small vessels which is the normal histologic arrangement of the spleen, which we haven't studied yet, so don't worry about trying to make too much sense of the overall architecture. However, scattered amongst the normal splenic tissue are pale, pink foci [example], each surrounded by a light-staining cellular halo. Under higher power you’ll note that the pale areas consist largely of granular cell debris -- a mix of cytoplasmic “crumbs,” karyorrhectic particles, and disintegrating cells. Grossly visible masses of this dead material appear cheesy, hence this form of necrosis is called caseous.
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The halo of pale staining cells around each caseous area consists of so-called "epithelioid" cells which are actually activated macrophages --they are called "epithelioid" because they appear layered and have flattened nuclei [example]. Their main function is to wall off the foci, which at their core contain tuberculosis bacteria thus trying to prevent spread of the infection to surrounding areas. Around some of the foci are occasional multinucleated giant cells (derived from macrophages) [example]. So, what we have here are balls of granular material surrounded by a shell of epithelioid macrophages and occasional giant cells, commonly refered to as "granulomas," thus qualifying this particular type of inflammation as “granulomatous.”
Review question:
Based on the primary inflammatory cell type(s) present, would you characterize this as acute or chronic inflammation?
Slide 0143 [WebScope] [ImageScope]
Breast: foreign body reaction / chronic inflammation
This slide was obtained from breast tissue in which a silicon implant ruptured thus initiating a persistent foreign body reaction and therefore further demonstrates some of the features of chronic inflammation. Rather than polymorphonuclear neutrophils, the primary inflammatory cells are mononuclear (monocytes and lymphocytes). The monocytes differentiate into macrophages which then fuse into multi-nucleated giant cells [example] in an attempt to deal with the implant material. The lymphocytes may be seen scattered amongst the surrounding connective tissue [example]. Recall that lymphocytes are characterized by small, dark, round nuclei.
Review question:
The list below contains links to blood cell types that may be found in a peripheral blood smear. The multi-nucleated giant cells shown in this particular case are derived from which type of peripheral blood cell?
- blood cell A
- blood cell B
- blood cell C
- blood cell D
- blood cell E
Slide 68 [WebScope] [ImageScope]
Lung: Chronic Inflammation associated with asthma
This slide is of lung tissue from a 24 year old who died due to complications associated with asthma. We haven't yet studied lung tissue in detail, so don't worry about trying to identify any of the particular structures. Instead, just focus on the epithelial lining of the two large airways shown in the slide (the airways are surrounded by plates of hyaline cartilage which you should be able to identify). One of the airways is relatively clear of debris [example] whereas the other is filled with a fibrinous exudate [example]. Zoom in on the epithelium lining the airway, and you should be able to recognize the pseudostratified, ciliated columnar epithelium, although it is not quite in as good a shape as the normal trachea (UMich Slide 40 - [ImageScope] [WebScope]) that you studied in the Epithelium lab.
Look deep to the epithelium in the underlying loose connective tissue, and note the massive infiltration of eosinophils [example] which is often observed in many chronic inflammatory conditions affecting the GI and respiratory tract.
Review question:
Patients with chronic respiratory inflammation such as asthma or chronic obstructive pulmonary disease often take oral inhaled steroids as part of the their treatment regimen. These agents provide effective therapy primarily by:
- directly inducing regeneration of damaged tissue
- inhibting proliferation of neutrophils
- blocking synthesis of histamine
- blocking synthesis of prostaglandins
- ALL of the above
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