Pathology Labs
Lab 1: Cell Injury and Death
Definitions:
Myocardial infarction is necrosis of myocardial tissue which occurs as a result of a deprivation of blood supply, and thus oxygen, to the heart tissue. Blockage of blood supply to the myocardium is caused by occlusion of a coronary artery.
Atherosclerosis is the deposition of lipid into the intima of arteries, resulting in narrowing of the vessel lumen.
A thrombus is a solid mass resulting from the aggregation of blood constituents within the vascular system.
Palliative surgery provides alleviation but is not curative.
Candidiasis is an infection by the fungus Candida in the oral cavity.
An infiltrate is an accumulation of cells in the lung parenchyma--this is a sign of pneumonia.
Consolidation is the filling of lung air spaces with exudate--this is a sign of pneumonia.
An abscessis a collection of pus (white blood cells) within a cavity formed by disintegrated tissue.
Hematuria is the presence of blood in the urine.
Pyuria is the presence of white blood cells (pus) in the urine.
Sepsis is the presence and persistence of pathogenic microorganisms and their toxins in the blood.
Disseminated tuberculosis refers to the hematogenous spread of tuberculous lesions throughout the body.
Pulmonary congestion is the engorgement of pulmonary vessels with blood. The increased pressure caused by this engorgement leads to transudation of fluid through the capillary walls and into the alveolar and interstitial spaces.
Pulmonary edema refers to the accumulation of fluid in the pulmonary alveolar and tissue spaces as a result of changes in capillary permeability and/or increases in capillary hydrostatic pressure.
Anthracotic pigment is coal dust deposited in the lungs--it is seen in coal miners, city-dwellers, and smokers.
Corpora amylacea are small hyaline masses of degenerated cells and inspissated secretions.
Questions & Answers:
Heart: Myocardial Infarction (Coagulative Necrosis)
What type of necrosis is present in this myocardial tissue?
Coagulative necrosis.
What are the morphologic characteristics of coagulative necrosis?
- Hypereosinophilia
- Coagulation of cellular proteins
- Loss of nuclei (pyknosis, karyolysis, & karyorrhexis)
What causes the vacuolar change seen in the tissue adjacent to this infarct and is this change reversible or irreversible injury?
- The vacuolar change (hydropic change) seen in myocytes at the edge of an infarct is a REVERSIBLE CHANGE caused by CELLULAR EDEMA.
At the edge of an infarct the oxygen tension is low (hypoxia) so there is a decrease in oxidative metabolism and an increase in anaerobic glycolysis. Since anaerobic glycolysis is less efficient than aerobic metabolism there are lower ATP levels which result in impaired osmotic regulation. In addition, metabolic metabolites accumulate which further increases the intracellular osmotic load and leads to cellular edema.
Kidney: Infarction (Coagulative Necrosis)
Why is the infarct triangular and why is the apex of the infarct at the corticomedullary junction?
The shape of the infarct is due to the blood flow distribution of the renal circulation.
Remember that the interlobar arteries branch at 90 degrees to form the arcuate arteries at the level of the corticomedullary junction. This is a good place for thrombi to lodge. Also, the interlobular arteries branch off the arcuate arteries at 90 degrees, another good place for thrombi to lodge.
If an infarct is caused by ischemia, why is there blood in this infarct?
Ischemia means too little blood flow to maintain viability of the tissue. Blood flow can be decreased enough to result in necrosis of a metabolically active tissue like the kidney, but the blood flow does not necessarily have to be completely stopped. Also, blood can seep into an area of infarction through damaged blood vessels at the edge of the infarcted tissue.
Lung: Abscess (Liquefactive Necrosis)
What factors predisposed this patient to pneumonia?
The patient had terminal cancer, had undergone a major surgery, and was on a ventilator. Any of these factors could have predisposed the patient to pneumonia. Also, being a patient in the hospital is itself a risk factor due to nosocomial infections.
What causes abscesses to liquefy?
The proteolytic enzymes released by white blood cells digest the tissue and cause it to liquefy. The presence of bacteria accentuates the inflammatory response and the bacteria themselves can also release enzymes that digest the tissue.
If this patient had lived, could these lesions have resolved?
If the patient had lived, the body could have eventually removed all of the necrotic and liquefied material. However, since there was loss of tissue and disruption of the basement membranes, many of the lesions would heal by scar tissue. So, the lung would never return to its original normal morphology and function.
Pancreas: Fat Necrosis (Enzymatic Necrosis)
What is the definition of enzymatic fat necrosis?
Focal areas of destruction of fat tissue resulting from abnormal release of activated lipases.
Where else can enzymatic fat necrosis occur besides the pancreas?
Salivary gland
What causes the formation of the white, chalky, nodules that are seen in the fat tissue adjacent to the pancreatic tissue?
Injury to the pancreas (infection, toxins, viruses, trauma, ischemia) causes release of activated pancreatic enzymes which liquefy fat cell membranes. The released lipases split the triglyceride esters contained within the fat cells and these released fatty acids combine with calcium to form the grossly visible chalky white nodules characteristic of fat necrosis.
Lung: Tuberculosis (Caseous Necrosis)
From where does the term caseation necrosis originate?
"Caseous" means "cheesy." Grossly, the lesions look white and cheesy.
What makes up the caseous core of the lesion in this case?
Amorphous granular debris composed of fragmented, coagulated cells enclosed within a granuloma.
Prostate: Apoptosis
What is the cause of apoptosis in this case?
The diethylstilbesterol blocks the normal trophic hormone response that controls prostate growth. With loss of trophic influence the prostatic epithelial cells go through apoptosis and this results in atrophy of the gland. This would be an example of pathologic atrophy of a hormone-dependent tissue.
How is apoptosis different than necrosis?
Apoptosis is the result of a gene program that leads to self-destruction of individual cells. The apoptotic cells shrink, there is condensation of the chromatin, formation of cytoplasmic blebs, and fragmentation of the cell to form apoptotic bodies. Apoptotic bodies are membrane-bound fragments of cytoplasmic organelles with or without fragments of chromatin. A hallmark of apoptosis distinguishing it from necrosis is the fact that there is no inflammation associated with apoptotic cell death as compared to other types of cell death (e.g., necrosis).
Lab 2: Cell Adaptations
Definitions:
Pleural effusion is the presence of fluid in the pleural space. Increased hydrostatic pressure in the pulmonary vasculature, as seen in heart failure, is one cause of pleural effusion.
Dysuria is the experience of pain upon urination.
"Cystitis" refers to an infection of the urinary bladder
"Hyperemic" means "engorged with blood."
A renal calculus is a "kidney stone."
A bladder diverticulum is an out-pouching of the bladder wall, usually caused by chronic urethral obstruction.
Hydronephrosis is dilation of the renal pelvis and atrophy of the cortex due to increase pressure from retained urine
Atrophy results from decreased blood flow due to stenosis of the ipsilateral renal artery. The increased pressure in the renal pelvis leads to decreased blood flow to the renal tissues.
Decreased blood flow and increased pressure lead to atrophy (decreased size and number of renal parenchymal cells).Differentiating between atrophy and hypoplasia is often difficult!
With atrophy the parenchymal component of the tissue atrophies while the stroma usually remains intact. Thus, there is an "empty bag" appearance.
With hypoplasia, all components of the tissue are small--parenchyma and stroma.
Questions & Answers:
Heart: Myocardial Hypertrophy
Is this case of myocardial hypertrophy an example of physiologic or pathologic hypertrophy?
Pathologic.
What are some factors that may have been responsible for the "decompensation" of this heart?
The exact mechanism for why hypertrophied hearts go on to develop congestive heart failure is not known. However, some contributing factors may include:
(1)limitation of the vascular supply to the enlarged myocardial fibers,
(2) diminished oxidative capabilities of the mitochondria,
(3) alterations in protein synthesis & degradation, or
(4) alterations in the cytoskeleton.
Prostate: Nodular Hyperplasia
What is the name of the condition in this man's prostate?
This is an example of nodular hyperplasia which is commonly referred to as benign prostatic hyperplasia (BPH). The term BPH is redundant since hyperplasia is always benign.
In what anatomical region of the prostate is nodular hyperplasia most prevalent?
Nodules are most common in the inner peri-urethral region; thus, urethral obstruction is an early and common clinical sign.
In what region of the prostate does prostatic adenocarcinoma usually originate?
Prostatic adenocarcinoma usually arises in the peripheral zone of the gland, usually in a posterior location. Adenocarcinoma nodules are usually palpable by rectal examination.
What is the age-specific incidence of nodular hyperplasia in males?
The incidence of nodular hyperplasia is:
20% in men 40 years of age
30% in men 50 years of age
70% in men 60 years of age
90% in men 70 years of age
Does nodular hyperplasia predispose to adenocarcinoma?
No.
What other conditions can be associated with or result from nodular hyperplasia of the prostate?
Urinary retention, cystitis, bladder distention, hypertrophy, trabeculation, diverticulum formation, renal infections, and hydronephrosis.
Kidney: Squamous metaplasia
What is a neurogenic bladder and what complications may result from this condition?
A neurogenic bladder is any condition or dysfunction of the urinary bladder caused by a lesion of the central or peripheral nervous system. Complications primarily include stasis, infection, and stone formation.
What factors in this case predisposed to nephrolithiasis?
Stasis and infection.
Does this metaplastic process predispose to neoplasia?
Yes.
Testis: Atrophy
What is PSA and how useful is it as a marker of prostatic cancer?
Prostatic Specific Antigen. PSA can be a useful marker for prostatic cancer; however, PSA levels may be elevated for a number of reasons other than cancer.
What is the cause of testicular atrophy in this case?
The cause was HORMONAL.
Prostatic growth is dependent upon testicular androgens. Estrogen therapy leads to inhibition of pituitary gonadotropin and/or ACTH production which causes androgen deprivation. Newer drugs use specific testosterone receptor blocking mechanisms to regress prostate hyperplasia and prostate cancer.
There appears to be an increase in the number of interstitial cells. Is there such a thing as Leydig cell hyperplasia?
No. The Leydig cells appear more prominent due to the paucity of germ cells.
Lung: Metastatic Calcification
Contrast metastatic calcification and dystrophic calcification.
Dystrophic calcification occurs in necrotic tissue with normal serum calcium levels; metastatic calcification occurs in normal tissue and requires elevated serum calcium levels.
What are some causes of hypercalcemia?
*Hyperparathyroidism
*Vitamin D intoxication
*Systemic sarcoidosis
*Milk-alkali syndrome
*Hyperthyroidism
*Addison's disease
*Increased bone catabolism
*Hypercalcemia of malignancy
Fatty Change & Cirrhosis
What substances have accumulated to produce fatty liver?
Triglycerides
What are possible causes of steatosis and which of these may have produced the fatty liver seen in this case?
Steatosis can be caused by:
* toxins
* protein malnutrition
* diabetes mellitus
* obesity
* anoxia
What causes hepatocellular steatosis in an alcoholic?
Alcohol induces hepatic steatosis primarily by:
- the shunting of normal substrates away from catabolism and toward biosynthesis due to generation of excess NADH by alcohol dehydrogenase,
- impaired assembly and secretions of lipoproteins, and
- increased peripheral catabolism of fat.
Many other factors also come into play.
Is the accumulation of fat in this liver a reversible or an irreversible change?
Reversible
Lab 3: Inflammation and Repair
Definitions:
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 substances have accumulated to produce fatty liver?
Triglycerides
What are possible causes of steatosis and which of these may have produced the fatty liver seen in this case?
Steatosis can be caused by:
* toxins
* protein malnutrition
* diabetes mellitus
* obesity
* anoxia
What causes hepatocellular steatosis in an alcoholic?
Alcohol induces hepatic steatosis primarily by:
- the shunting of normal substrates away from catabolism and toward biosynthesis due to generation of excess NADH by alcohol dehydrogenase,
- impaired assembly and secretions of lipoproteins, and
- increased peripheral catabolism of fat.
Many other factors also come into play.
Is the accumulation of fat in this liver a reversible or an irreversible change?
Reversible
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?