Rubin's Chapter 1 Flashcards
Photo of a burst forming unit, recombinant erythropoietin. This colony, committed to the erythrocyte
pathway of differentiation, represents an example of which
of the following physiologic adaptations to transmembrane
signaling?
Hyperplasia – an increase in the number of cells in an organ or tissue, in response to trophic signals or increased functional demand and is commonly a normal process. Erthyrocyte hyperplasia – seen in ppl living at high altitude bc low O2 tension evokes production of erythropoietin, which promotes survival and proliferation of erythroid precursors in bone marrow. Mechanisms responsible for hyperplasia relate to control of cell proliferation/cell cycle.
50 yo alcoholic presents w/ 12 hrs severe abdominal pain, radiating to back and urge to vomit. Lab studies show serum amylase, which morphological changes would be expected in the patient’s peripancreatic tissue?
Fat necrosis: saponification of fat derived from peripancreatic fat cells exposed to pancreatic enzymes is a typical feature of fat necrosis. Acute pancreatitis releases lipase from pancreatic acinar cells, which hydrolyzes fat into fatty acids and glycerol. Free fatty acids bind with calcium to form soaps – soaponification. Calcium entry into injured tissue reduces the level of calcium in blood –so hypocalcium is associated with acute pancreatitis. Acute pancreatitis presents with sudden onset abdominal pain, distention
A 68 yr old man with history of GERD dies from a massive stroke. Esophogus at autopsy: abnormal tissue shows intestine like epithelium composed of goblet cells and surface cells similar to those of incompletely intestinalized gastric mucosa. No evidence of nuclear atypia. What describes the morphological response to persistent injury in the patient’s esophagus?
Glandular metaplasia –the major adaptive responses of cells to sublethal injury are atophy, hypertrophy, hyperplasia, metaplasia, dysplasia and intracellular storage. Metaplasia = the conversion of one differentiated cell pathway to another. In this case, esophageal squamous epithelium is replaced by columnar epithelium as a result of gastroesophageal reflux.
A CT scan of a 43-year old woman with a parathyroid adenoma and hyperparathyroidism revels extensive calcium deposits in the lungs and kidney parenchyma. Which disease mechanism explains these radiologic findings?
Metastatic calcification – associated with hypercalcemia. Increased serum calcium can almost always lead to calcification in the alveolar septa of the lung, renal tubules and blood vessels. This patient had a parathyroid adenoma that produced lots of PTH. Other examples of metastatic calcification: opacities in the cornea of a child given lots of Vit D, partially calficied alveolar septa in lungs of breast cancer metastatic to bone.
75 yo F w. Alzheimers dies of CHF, brain autopsy reveals what response to chronic injury?
Atrophy – dec in organ size/function. Often seen in areas of vascular insufficiency/chronic inflammation/disuse. Atrophy to the brain in Alzheimer is second to extensive cell death.
68 yr old woman with history of smoking and pneumonia presents w/ 2 week ho fever and productive cough. CXR: right lower lobe infiltrate, transbronchial biopsy confirms pneumonia + preneoplastic changes within the bronchial mucosa. What characterizes the morphology of this bronchial mucosal lesion?
Abnormal pattern of cellular maturation. Cells that compose an epithelium exhibit uniformity of size and shape and undergo orderly maturation, Dysplasia = disturbation of this regular apperance by: 1) variations in size and shape of cells 2) enlargement, irregularity and hyperchromatism of the nuclei, and 3) disorderly arragement of the cells within the epithelium. Dysplasia of the bronchial epithelium is a reaction of resp epi to carcinogens in tobacco smoke. It can be reversible if the patient stops smoking but it is preneoplastic and can progress to cancer.
A 64 yr old man with long-standing angina pectoris and arterial hypertension dies of spontaneous intracerebral hemorrhage. At autopsy the heart appears globoid. LV measures 2.8cm. This adaptation to chronic injury was mediated primarily by changes in the intracellular concentration of which component?
mRNA – hypertrophic cardiac myocytes have more cytoplasm and larger nuclei than normal cells. Although the elucidation of the cellular and molecular mechanisms underlying the hypertrophic response is still actively pursuedm the final steps include increases in mRNA, rRNA and protein. Hypertrophy results from transcriptional regulation.
A 24 yo F contracts toxoplasmosis during her pregnancy and delivers a neonate at 37 weeks gestation w/ severe malformation of the CNS. MRI studies of the neonate reveal porencephaly and hydrocephalus. An X-ray film of the head shows irregular densities in the basal ganglia. These x ray results point to what disease mechanism?
Dystrophic calcification – reflects underlying cell injury. Serum levels of calcium are normal and calcium deposits are located in previously damaged tissue. Intrauterine toxoplasmosa infection affects 0.1% of pregnancies.
A 30 yo M with AIDS-dementia develops acute pnemonia and dies of respiratory insufficiency. Autopsy: CNS neurons show hydropic degeneration. This manifestation of sublethal neuronal injury was most likely mediated by impairment of which cellular process?
Plasma membrane sodium transport. Hydropic swelling reflects acute, reversible (sublethal) cell injury, It results from impairment of cellular volume regulation, a process that controls ionic conc in cytoplasm. This regulation for sodium involves: 1-plasma membrane, 2-plasma membrane sodium pump 3-supply of ATP. Injurious agents may interfere with these membrane regulated processes. Accumulation of sodium in the cell leads to an increase in water content to maintain isosmotic conditions, so the cell swells.
62 yo M presents to ED in disoriented state, physical exam: jaundice, splenomegaly and ascites. Serum levels of ALT, AST, alkaline phosphatase and bilirubin are elevated. A liver biopsy demonstrates alcoholic hepatitis with Mallory bodies. These cytoplasmic structures are made of interwoven bundles of what protein?
Intermediate filaments. Hyaline is a term that refers to any material that exhibits a reddish, homogenous appearance when stained with H and E. Alcoholic hyaline/Mallory is composed of cytoskeletal intermediate filaments – cytokeratins.
A 65 yo M dies from a heart attack. Lung exam at autopsy: numerous pigmented nodules scattered in the parenchyma:
Anthracosis – storage of carbon particles in the lung and regional lymph nodes. They accumulate in alveolar macrophages and get transported to hilar and mediastinal lymph nodes, where the indigestible material is stored indefinitely within tissue macrophages. The gross lung appearance of anthracosis is alarming but it’s really no big deal. Coal mine workers get anthracite pmneumocosis/pulmonary fibrosis.
A 32 YO F w/ poorly controlled diabetes mellitus delivers a healthy boy at 38 weeks of gestation. Maternal hyperglycemis during pregnancy → pancreatic islets in the neonate, shows which response to injury?
Hyperplasia: infants of diabetic mothers show 5%-10% incidence of major developmental abnormalities: heart, great vessel anomalies and neural tube defects. The frequency relates to control of maternal diabetes during early gestation. During fetal development, the islet cells of the pancreas have proliferative capacity and respond to increased demand for insulin by undergoing physiologic hyperplasia. Fetuses exposed to hyperglycemia in utero may develop hyperplasma of pancreatic B cells, which secrete insulin and cause hyperglycemia.
59 yo F alcoholic comes to ED w/ fever and bad breath. She develops acute broncho-pneumonia and dies of respiratory insufficiency. A pulmonary abscess is identified at autopsy. Histological exam of the wall of the lesion would demonstrate which pathological change?
Liquefactive necrosis: when the rate of dissolution of the necrotic cells is faster than the rate of repair, the resulting morphologic appearance is termed liquefactive necrosis. The polymorphonuclear leukocytes of the acute inflammatory reaction are endowed with potent hydrolases that are capable of digesting dead cells. A sharply localized collection of these acute inflammatory cells in response to a bacterial infection produces rapid death and dissolution of tissue. This often results in an abscess, defined as a cavity formed by liquefactive necrosis in a solid tissue.
A 20 yo M from China, persistent cough, night sweats, low-grade fever, general malaise. Sputum: acid-fast bacilli. Exam: hilar lymph nodes demonstrate what pathologic changes?
Caseuous necrosis – characteristic of primary TB, in which necrotic cells fail to retain their cellular outlines. They don’t disappear by lysis, that’s liquefactive necrosis.
A 31 yo F complains of increased vaginal discharge for 1 mo. A cervical pap smear is shown in the image, with superficial epithelial cells. Compared to cells from the deeper intermediate layer, the nuclei of the superficial cells exhibit which cytologic feature?
Pyknosis: coagulative necrosis refers to light microscope alterations in dying cells. When stained w/ H&E, the cytoplasm of a necrotic cell is eosinophilic. The nucleus displays an initial clumping of chromatin followed by its redistribution along the nuclear membrane. In pyknosis, the nucleus becomes smaller and stains deeply basophilic as chromatin clumps up.
A 30 yo F suffers a tonic clonic seizure and presents w/ delerium and hydrophobia. She was bitten by a bat a month ago. She dies of respiratory failure. Autopsy: viral particles are found throughout the brainstem and cerebellum. Direct viral cytotoxicity and necrosis of virally infected neurons are mediated by which mechanism?
Humoral and cellular immunity: both humoral and cellular immunity protect against viral infections.
52 yo F loses her right kidney following a car accident. 2 years later, CT scan shows enlargement of left kidney. Renal enlargement is an example of which adaptation?
Hypertrophy: a normal response to trophic signals or increased functional demand. The surviving kidney kypertrophies to accommodate increased demand. The molecular basis of hypertrophy reflects increased expression of growth promotoing genes – protooncogenes – like myc, fas and ras.
An 82 yo M has bleeding from a peptic ulcer and dies of hypovolemic shock. Liver at autopsy: centrilobular necrosis. Compared to viable hepatocytes, the necrotic cells have higher intracellular what?
Calcium: Coagulative necrosis = massive influx of calcium into the cell. Normally the plasma membrane maintains a gradient with calcium conc. 10,000x higher in the interstital fluid than in the cell. Call damage messes up the plasma membrane so it fails to maintain this gradient, allow influx of calcium into the cell.
28 yo F, trauma: compound fracture of the right tibia, it’s immobilized in a cast for 6 weeks. Upon cast removal, right leg is weak and smaller than the left. What’s this called?
Atrophy: reduced functional demand causes muscle cells to atrophy and strength is lost because differentiation gene expression is lost. Atrophied calls can return to normal.
