Lab 3: Inflammation and Repair
Definitions:
Friable material is easily crumbled.
A "shift to the left" indicates an increased ratio of immature PMNs ("bands") to mature PMNs ("segs").
Hematemesis is the vomiting of blood.
Obtunded patients will open their eyes and focus on people, but they act confused and are slow to respond. They may also display decreased interest in their environment.
Recanalization is the process of the forming of channels through an organized thrombus so that blood flow is restored.
Questions & Answers:
Appendix: Acute Appendicitis
What is the difference between a transudate and an exudate?
A transudate has a specific gravity of less than 1.012, a low protein content, and few if any cells.
An exudate has a specific gravity of greater than 1.020, a high protein content, and usually contains leukocytes.
What is the friable, granular, grayish-red material present on the surface of the appendix in this case and where did it come from?
Fibrinopurulent exudate. Acute inflammation causes increased vascular permeability which leads to formation of protein rich exudate (fibrinous exudate). Leukocytes are also recruited to the area (purulent exudate).
What are some of the chemoattractants that are involved in recruiting inflammatory cells to this appendix?
Exogenous leukocyte attractants: bacterial products.
Endogenous leukocyte attractants: primarily consist of complement C5a, leukotriene B4, and cytokines--especially IL-8.
Which molecules are responsible for causing pain and fever?
Fever: IL-1, IL-6, TNF, prostaglandins.
Pain: prostaglandins and bradykinins.
Lung: Lobar Pneumonia
What is the likely etiology of pneumonia in this case?
Aspiration of gastric contents. Lobar pneumonia is usually caused by Streptococcus pneumoniae.
What makes up the alveolar exudate and what eventually happens to that exudate?
The exudate is mainly composed of PMNs and fibrin. The exudate undergoes progressive enzymatic digestion to produce a granular, semi-fluid material that is reabsorbed, phagocytosed by macrophages, and/or coughed up.
How well does the lung heal after lobar pneumonia?
Often there is complete resolution with no scarring.
Lung: Bronchopneumonia
What does it mean to have a "shift to the left"?
A "shift to the left" indicates an increased ratio of immature PMNs ("bands") to mature PMNs ("segs") within the peripheral circulation.
Is there destruction of lung parenchyma in bronchopneumonia?
Yes, there is usually destruction of alveoli and, in this case, there are abscesses containing bacteria.
How would this lung have healed if the patient had survived?
Scar tissue would form in the areas of tissue destruction (abscesses).
Lymph Node: Sarcoidosis
What is sarcoidosis?
The exact cause of sarcoidosis is unknown. Sarcoidosis is characterized by non-caseating granulomas in many tissues and organs.
What is the characteristic phenotype of sarcoid granulomas?
The typical characteristic of a sarcoid granuloma is a non-caseating granuloma which consists of an aggregate of tightly-clustered epitheliod cells, often with Langhans’ or multinucleated giant cells. Occasionally, asteroid bodies may be seen.
What are asteroid bodies and are they pathognomonic for sarcoid or are they seen in other diseases?
Asteroid bodies are stellate inclusions within giant cells. They are not pathognomonic for sarcoid; they can be seen in other granulomatous disease processes (e.g., berylliosis).
Lung: Tuberculosis
Does everyone with a positive PPD test have TB?
No, it just indicates exposure to Mycobacterium tuberculosis.
How does this lesion differ from the lesions seen in sarcoid?
These are caseating granulomas with a central region of caseation necrosis and macrophages and lymphocytes around the periphery. Multinucleated, primarily Langhans’ type, giant cells are present within these nodules.
What are epithelioid cells?
Epitheliod cells are tissue macrophages that have an epithelium-like appearance.
Lung: Foreign Body Granuloma
Compare and contrast the tissue reactions to carbon (anthracosis), talc, and silica. What factors are important in the pathogenesis of tissue injury due to these foreign materials?
Carbon is relatively inert and leads to little if any tissue damage.
Talc results in foreign body granulomas but these lesions are mild.
Silica can lead to severe fibrosis of tissues, especially the lung.
Factors important in tissue injury include:
· size of particles (for airborne particles the small size lets them get deep into the lung),
· solubility of material,
· cytotoxicity of material (e.g. silica reacts with free radicals and other chemical groups to cause membrane damage), and finally
· whether the materials can be phagocytosed and removed from the body or whether they damage leukocytes and cause the release of inflammatory mediators.
What are the birefringent particles seen in the nodules adjacent to the vessels and how did they get there?
· The material is talc, which is often used to "cut" street drugs. Intravenous injection of talc leads to some talc being deposited in tissues and initiating an inflammatory response.
Heart: Fibrinous Pericarditis
What is the etiology of the fibrinous pericarditis that developed in this patient with renal failure?
Azotemia (an excess of nitrogen in the blood) is believed to be the cause of fibrinous pericarditis but the exact mechanism is unknown.
What are some other possible causes for pericarditis?
· Infection--viral, bacterial (especially TB), or fungal;
· Rheumatic fever
· Systemic lupus erythematosus;
· Scleroderma;
· Myocardial infarction;
· Trauma; and
· Neoplasia.
From where does the fibrin come that produces fibrinous pericarditis?
· Fibrinogen leaks out of the blood vessels as part of the inflammatory reaction. It is then converted to fibrin. A fibrinous exudate develops when the vascular leaks are large enough or there is a procoagulant stimulus (e.g., pericarditis).
What are the possible outcomes of this condition (fibrinous pericarditis)?
· The inflammatory reaction can progress and lead to tamponade (rare).
· The inflammatory reaction could subside and the fibrin would be lysed via the fibrinolytic system (most likely outcome).
· The fibrin could become organized and result in a fibrous connective tissue scar which could restrict cardiac function.
Stomach: Chronic Peptic Ulcer
What types of factors may predispose to peptic ulcer formation?
Alcoholic cirrhosis, chronic obstructive airway disease, chronic renal disease, and hyperparathyroidism or any condition which leads to hypercalcemia (calcium stimulates gastrin production).
Why is infection with Helicobacter pylori considered to be a significant risk factor for development of peptic ulcers?
H. pylori is found in 90-100% of cases. It is thought that the H. pylori produce urease, leading to ammonia production and that they also produce a protease that breaks down glycoproteins in the mucus which forms the protective coat on the gastric mucosa.
What cells make of the inflammatory reaction at the base of this chronic ulcer?
The base of this chronic ulcer has a granulomatous inflammatory reaction composed of lymphocytes, macrophages, fibroblasts, and endothelial cells. This is in contrast to the acute inflammatory reaction at the surface of the ulcer due to irritation from the acid and gastric contents.
Brain: Healed Infarction
What is the most common cause of stroke?
Thrombotic occlusion of cerebral arteries due to atherosclerosis. The carotid arteries, the origin of the middle cerebral artery, and either end of the basilar artery are the most common sites of thrombus.
What is the likely cause of stroke in this patient?
Infarction resulting from thrombotic material from the prosthetic heart valve.
Heart: Acute Myocardial Infarction
Are the serum enzyme results consistent with the time course of this clinical history?
The infarct occurred approximately 4 days prior to death. His CPK-MB levels would be expected to have gone down by now. His AST is slightly elevated and his LDH is moderately elevated with a high LDH1:LDH2 ratio. These findings are consistent with the clinical history.
Why do mural thrombi often form in infarcted hearts?
The endocardium is usually the most severely damaged after an arterial occlusion since it is at the end of the circulation of the heart. Thus, with the infarcted tissue in the endocardium there is an acute inflammatory reaction which initiates coagulation and thrombus formation.
What is the primary cell type in this inflammatory reaction?
At this stage it is primarily neutrophils, but there area a few macrophages. Usually, neutrophils enter an infarct by 12-24 hours and macrophages enter the lesion by 72 hours post-MI. By 3-7 days the lesion is primarily macrophages and by 10 days there are macrophages, fibroblasts, and endothelial cells (granulation tissue). The healing reaction in this patient may have been slower than normal because of his poor condition.
Heart: Healed Myocardial Infarction
Why does this 37-year-old woman have such severe coronary atherosclerosis?
Diabetes mellitus is a major risk factor for developing premature atherosclerosis.
Why are there areas of acute myocardial injury in the section of myocardium from the patient with the old healed myocardial infarction?
This finding is very common in areas adjacent to an old infarction. If you remember from previous cases, there were areas of vacuolar change adjacent to the acute infarct. The areas adjacent to an infarct may still be alive but they will be at risk for additional ischemic insult. In this current case, the patient had several serious medical problems which may have caused hypotension and poor perfusion to the heart. Thus, the areas of risk could have been damaged leading to acute myocardial necrosis.
What is the time course of the normal inflammatory response after a myocardial infarction?
Few morphologic changes occur in the heart until approximately 6 to 12 hours after coronary occlusion. Subtle changes such as hypereosinophilia, coagulation necrosis and wavy fiber change can be seen during this early time period. If there is reperfusion of the myocardium there may be contraction band necrosis as well.
By two to three days there is an acute inflammatory cell infiltrate comprising primarily neutrophils.
At 5 to 10 days macrophages come in to phagocytose the necrotic myocardial tissue. As the dead tissue is being phagocytosed by macrophages, fibroblasts and blood vessels begin to grow into the area of infarction and form granulation tissue.
Fibroblasts lay down collagen and by two to three months the infarct is replaced by matured collagenous "scar" tissue.