Pathology Labs – Definitions + Q&A
Lab 10: Fungal Diseases
Definitions:
Epistaxis is bleeding from the nose.
A thoractomy is a surgical procedure in which an opening is made through the chest wall.
Questions & Answers:
Kidney: Candidiasis
What is the significance of seeing yeast and hyphae in these histologic tissue sections?
Candida is the only fungus which grows as
1) a yeast form,
2) pseudohyphae, and
3) true hyphae with septa.
All three of these forms may be present in the same section of tissue.
Who is at risk for developing systemic candidiasis?
Neutropenic patients.
Candida species--especially C. albicans--are part of the normal flora of the skin, mouth, and GI tract, and are the most frequent cause of human fungal infections. These infections vary from superficial lesions in healthy persons to disseminated infections in neutropenic patients.
Severe disseminated candidiasis is associated with neutropenia secondary to chronic granulomatous disease, leukemia, anticancer therapy, or immunosuppression after transplantation.
Candida can be introduced into the bloodstream by intravenous lines, catheters, peritoneal dialysis, cardiac surgery, or intravenous drug abuse.
What types of infections does Candida cause in humans?
Candida infections can occur in the oral cavity (thrush), vagina, and in the skin--especially in warm moist areas (i.e., between the fingers and toes and in inguinal creases, inframammary folds, and the anogenital region).
Candida esophagitis can occur with nasogastric tube placement.
Adrenal Gland: Histoplasmosis
What is the usual route of infection with Histoplasma?
Histoplasma capsulatum infection is usually acquired by inhalation of dust particles from soil contaminated with bird or bat droppings. The droppings contain small spores (microconidia).
What types of infections does Histoplasma produce?
1) A self-limited primary pulmonary involvement which may result in coin lesions on chest x-ray;
2) chronic, progressive, lung disease, which often localizes to the lung apices and causes cough, fever, and night sweats;
3) localized lesions in extrapulmonary sites, including mediastinum, adrenals, liver, or meninges; and
4) a widely disseminated involvement, particularly in immunosuppressed patients.
How do Histoplasma organisms infect cells?
Histoplasma conidia and yeasts bind to the beta-chain of the integrins receptors LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18).
Histoplasma yeasts are phagocytosed by the unstimulated macrophages, multiply within the phagolysosome, and lyse the host cells.
Lung: Cryptococcosis
How is Cryptococcus neoformans usually transmitted to man?
Cryptococcus neoformans is present in the soil and in bird (particularly pigeon) droppings.
The organism infects humans when it is inhaled.
Who is susceptible to infection with C. neoformans?
Normal healthy people can get cryptococcal meningoencephalitis but cryptococcal infections are more common in individuals
(1) who receive high-dose corticosteroids and/or
(2) who have AIDS, leukemia, lymphoma, systemic lupus erythematosus,
Hodgkin’s disease, sarcoidosis, or transplant patients.
What virulence factors facilitate infection by C. neoformans?
Three properties of Cryptococcus neoformans are associated with virulence:
(1) the capsular polysaccharide;
(2) resistance to killing by alveolar macrophages; and
(3) production of phenoloxidase an enzyme that consumes host epinephrine in the synthesis of fungal melanin and thus protects the fungi from the epinephrine oxidative system present in the host nervous system.
It is thought that one reason why Cryptococcus neoformans preferentially infects the brain may be because the CSF lacks alternative pathway complement components (present in serum) that bind to the carbohydrate capsule and facilitate phagocytosis and killing by polymorphonuclear cells.
Lung: Blastomycosis
What is the route of infection of Blastomyces?
Blastomyces is acquired by inhalation of infectious spores from the soil.
Blastomyces has a restricted geographical distribution in the US. What regions are endemic?
In the United States, infection is usually limited to areas along the Mississippi, Ohio, and St. Lawrence Rivers, and along the Great Lakes.
What groups of people are at increased risk for Blastomyces?
Those exposed to dust--construction workers exposed to dust from construction sites, hunters and outdoors people who walk in dusty areas, and farm workers.
What is the usual clinical manifestation of Blastomyces infection?
Most patients get a pyogranulomatous pneumonia. However, Blastomyces can spread outside the lungs to the skin, bones, and prostate.
Carotid Artery: Mucormycosis
How is Mucor spread?
The spores are widespread in dust and air and can be inhaled or ingested. They are ubiquitous contaminants colonizing the normal human skin or gut without causing illness in immunocompetent people.
What are the common sites of infection with Mucor?
Mucor commonly causes vasculitis and thrombosis.
The three primary sites of Mucor invasion are the nasal sinuses, lungs, and gastrointestinal tract.
What special risks of Mucor infection are associated with diabetes?
In diabetics, the fungus may spread from nasal sinuses to the orbit, and subsequently the brain, giving rise to rhinocerebral mucormycosis.
Lab 11: Parasitic Diseases
Definitions:
Tonic-clonic seizures consist of loss of consciousness followed by tonic, then clonic, convulsions.
An elevated erythrocyte sedimentation rate is a non-specific indicator of infection or inflammation.
Questions & Answers:
Malaria
This man had been taking appropriate malaria chemoprophylaxis during his stay in Thailand. Why did the patient get malaria nonetheless?
He could have gotten malaria because some malaria organisms have developed resistance to commonly used antimalarial drugs. Another common cause is noncompliance--travelers forget to take their drugs!
What was the possible mechanism for the dysentery that developed in this patient?
Parasitized red blood cells cause obstruction of small blood vessels in the bowel leading to bowel ischemia. Another possible cause for dysentery in someone just back from a third world country would be intestinal parasites, such as Giardia, Entamoeba, or helminths.
What was the probable cause of the patient's altered mental status?
Patients with very high fever can develop altered metal status, but in this case the likely cause would be malignant cerebral malaria. Parasitized RBCs block small blood vessels in the brain leading to multifocal areas of hypoxia.
Leishmaniasis
How is leishmaniasis transmitted and why was this patient at risk for getting leishmaniasis?
Leishmania parasites are transmitted by the bite of an infected sand fly. Sand flies are common in Central and South America as well as in the Middle East, Southeast Asia, and Africa. Travelers can help prevent infection by using insect repellent--especially at night when sand flies are out biting.
In what host cells do the parasites grow and how do they tolerate this hostile environment?
Leishmania amastigotes grow inside macrophage phagolysosomes. They have special glycoconjugates on their surface which help them resist attach by complement, help them bind to and be phagocytosed by macrophages, and help protect them from free radical damage inside the phagolysosomes. Leishmania amastigotes also have a special proton-transporting ATPase that helps them survive the high acidity of the phagolysosome.
The patient had simple cutaneous leishmaniasis. What other clinical forms of leishmaniasis exist?
Patients can also get mucocutaneous leishmaniasis or visceral leishmaniasis depending on the species of leishmania organism causing the infection.
If the biopsy had shown only a granulomatous inflammatory response but no organisms, what other infectious diseases would be in the differential diagnosis?
Blastomyces, Mycobacterium ulcerans, Sporothrix schenckii.
Ascariasis
Was the original diagnosis of streptococcal pharyngitis in error? Does it relate to the subsequent intestinal obstruction?
The patient did have streptococcal pharyngitis. The high fever produced by the streptococcal infection "upset" the intestinal parasites and made them become more active and possibly contributed to the mass of worms that resulted in the intestinal obstruction.
How is ascariasis transmitted? How does this relate to the multiplicity of parasites identified in this patient's stool specimen?
Ascariasis and the two protozoan parasites seen in this woman are common in countries with poor sanitation. This can include fecal contamination of water, soil and therefore fruits and vegetables that are not washed adequately. After Ascaris eggs are excreted in the feces of the primary host, the eggs must incubate in soil for two weeks before they are infective. After two weeks, ingested embryonated eggs hatch and the larval worms burrow through the wall of the small intestine and enter the blood. They are primarily filtered out in the capillaries of the lung where they burrow into the alveoli, are coughed up and swallowed. They then take up residence in the small intestine. Children who practice geophagia commonly have very high Ascaris loads in areas with promiscuous defecation. The two protozoa form cysts in the colon of patients who do not have severe diarrhea and are infectious as soon as passed. The cysts remain viable in soil and water for weeks to months. The most likely common source for these three organisms would be non-chlorinated water or fruits and vegetables contaminated with soil or water. A food handler with Ascaris is not a public health threat while infection with either of the other organisms is a risk for transmission.
Cysticercosis
How did this patient get this parasite?
Cysticercosis is caused by the cestode parasite, Taenia solium (pig tapeworm). Cysticercosis is contracted by ingesting eggs from the feces of a person infected with an adult Taenia solium. The eggs can survive for several weeks in soil but are also infectious as soon as passed. The larvae migrate through the intestinal wall and are disseminated via the blood stream and can encyst in the brain, heart, skeletal muscle, or skin.
Schistosomiasis
How did the patient acquire schistosomiasis?
Fresh water snails are required intermediate hosts for schistosomal organisms. The snails release cercaria into the water that can penetrate the skin of anyone walking in the water. Since this patient worked on a fish farm, he spent a lot of time in the water.
How do Schistosoma mansoni eggs cause liver pathology?
A substance released from the eggs is a direct hepatotoxin. The eggs incite a chronic granulomatous inflammatory reaction (thought to be mediated by TNFa and T-helper cells). And schistosome eggs stimulate lymphocytes to secrete lymphokines that stimulate periportal fibrosis.
How does the clinical picture of S. haematobium differ from that of the other schistosomes?
S. haematobium leads to granulomatous lesions in the urinary bladder that can erode the surface epithelium and lead to hematuria. Chronic inflammation and fibrosis can lead to obstruction, hydronephrosis and ascending bacterial infections. There is also an increased risk for squamous cell carcinoma of the bladder.
Chagas Disease
How is Chagas’ disease transmitted?
Reduviid bugs (kissing bugs) bite people while they sleep. The bug defecates on the skin and the infected bug feces is rubbed into the wound. Organisms from the infected feces can also enter the body via mucous membranes. These organisms then circulate via the blood stream to infect cells.
This patient had acute Chagas' disease. What would you expect to see in a patient with chronic Chagas' disease?
Chronic Chagas' disease leads to congestive heart failure. These patients commonly have right bundle branch block and/or other arrhythmias. These hearts are dilated and hypertrophied, have areas of fibrosis especially in the apex, and often contain mural thrombi. The myocardium is infiltrated with lymphocytes and macrophages and there is interstitial edema and fibrosis. This inflammatory reaction is most severe around the area of the right bundle branch. Patients may also develop megaesophagus and/or megacolon.
Lab 12: Environmental Pathology
Definitions:
Icterus ishyperbilirubinemia making the patient appear yellow. Also called jaundice.
Spider Angiomata is a focal network of small arteries and arterioles arranged in a radial pattern.
A radical mastectomy involves removal of the breast, underlying pectoralis muscles, and axillary lymph nodes.
A modified mastectomy involves removal of the breast and axillary lymph nodes. The underlying pectoralis muscles are preserved.
Pericardiectomy is the surgical removal of the pericardium.
Cardiac tamponade is compression of the heart by an acute accumulation of fluid within the pericardium.
Parametrectomy is the surgical removal of supporting tissues that surround the uterus.
Questions & Answers
Liver: alcoholic Cirrhosis
How does alcohol cause liver damage?
Initial changes include hepatocellular steatosis. This is caused by altered metabolism with high levels of NADH from lactate dehydrogenase resulting in increased lipid biosynthesis. Mobilization of lipids from peripheral fat stores and decreased lipid acceptor protein synthesis leads to insufficient lipoprotein production.
Alcohol induces free radical production as it is broken down by the microsomal ethanol oxidizing system. Alcohol also impairs microtubular and mitochondrial function and membrane fluidity.
Acetaldehyde, the major ethanol metabolite, can cause lipid peroxidation and acetaldehyde-protein complexes that further inhibit the microtubular system.
Finally, alcohol also induces an immunologic reaction in the liver. This immune-mediated liver damage is thought to result from the expression of neoantigens on hepatocytes possibly due to alcohol-induced alterations in membranes or acetaldehyde binding to proteins leading to neoantigen formation.
Why did this patient have a prolonged prothrombin time?
Since most of the clotting factors are produced by the liver, chronic liver damage with loss of liver parenchyma will lead to a reduction in clotting factors. In addition, this patient had bleeding esophageal varices and ascites which could both use up or sequester clotting factors, respectively.
What causes esophageal varices in a patient with hepatic cirrhosis?
Hepatic cirrhosis with extensive parenchymal damage and fibrosis results in an increased resistance to portal blood flow. The increased portal pressure leads to increased pressure in the coronary veins of the stomach. This results in increased pressure in the esophageal plexus in the terminal portion of the esophagus as the blood travels through this plexus to empty into the azygous vein. The increased pressure and increased flow of blood through this plexus of thin-walled veins leads to dilation and formation of varices. These varices can then rupture and lead to life-threatening hemorrhage as was seen in this case.
Increased portal pressure also leads to increased pressure in the inferior hemorrhoidal veins and can lead to the formation of anorectal varices.
What is the pathogenesis of Wernicke's encephalopathy?
Wernicke's encephalopathy is caused by thiamine (Vitamin B1) deficiency. Chronic alcoholics often have poor diets and alcohol inhibits intestinal absorption of thiamine. Thus, some chronic alcoholics can develop Wernicke's encephalopathy which consists of foci of symmetric discoloration, softening, and punctate hemorrhages in the paraventricular regions of the thalamus and hypothalamus, in the mamillary bodies, around the aqueduct in the midbrain, in the floor of the fourth ventricle and in the anterior cerebellum. There is demyelinization and loss of neuropil. Even after treatment with thiamine, there is significant memory deficit.
Liver: Acetominophen Toxicity
What is the most likely cause for the liver necrosis seen in this patient?
The acetaminophen level on admission was not elevated; however, the patient had been in distress for some time and had not taken any acetaminophen within the previous 12 hours. Upon questioning, the patient admitted that he had continued to take his usual doses of acetaminophen even after his internist put him on new drugs. He was unaware that one of the new drugs he was taking had acetaminophen in it. Thus, he was taking an overdose of acetaminophen and this resulted in hepatic toxicity.
Adverse drug reactions can occur with therapeutic agents, but in this case the most probable cause for liver necrosis was the unintentional overdose of acetaminophen by this patient who was not aware that one of the new drugs he was taking already contained acetaminophen.
Why did this patient develop DIC?
Liver necrosis releases thromboplastin and can initiate the coagulation cascade leading to intravascular coagulation.
Lung: Radiation Fibrosis:
Why is the lung particularly vulnerable to radiation injury?
The lungs are extremely vascular; thus, the radiation changes seen in the vasculature can have a profound effect on the lungs. During the immediate post-irradiation period, endothelial cell swelling and vacuolization can be seen in the alveolar capillaries. The increased vascular permeability may lead to marked pulmonary congestion and edema and the other changes similar to those encountered in adult respiratory distress syndrome.