QUESTION 26
A pathologist is examining a resected appendix from a patient who presented with abdominal pain that had been on-going for three days. Infiltrating the wall and occluding the lumen of the appendix are innumerable neutrophils. Examination of some of the neutrophils reveals a fragmented nucleus. Of the following, which mediator played the greatest role in the development of the nuclear changes in the neutrophils?
A. Histamine
B. CD31
C. LFA-1
D. Bcl-2
E. Caspases
Answer For Question 26
Answer: E (caspases)
Explanation: given that the inflammatory process has been going on for around three days, some of the neutrophils should be at the end of their life expectancy, and will be undergoing apoptosis. Nuclear fragmentation is characteristic of apoptosis. Histamine, CD31, and LFA-1 play a role in the inflammatory process, vasodilation, transmigration (diapedesis), and leukocyte adhesion respectively, but do not play a direct role in apoptosis. Bcl-2 inhibits apoptosis. Caspases are activated in apoptosis, by either the release of cytochrome c or through adaptor proteins activated by Fas-FasLigand binding. Caspases activate endonucleases (among other enzymes), resulting in nuclear fragmentation.
QUESTION 27
A pathologist is examining a biopsy of the colon obtained from an individual with chronic diarrhea. In the depths of some crypts, the pathologist identifies cells that are shrunken and have fragmented nuclei. No neutrophils are identified in the adjacent tissue. Of the following, which molecular is expressed on the surface of these shrunken cells and plays a direct role in the process observed by the pathologist?
A. Phosphatidylserine
B. Phosphatidylcholine
C. Phosphatidylinositol
D. Phospholipase A
E. Phospholipase C
Answer for Question 27
Answer: A (phosphatidylserine).
Explanation: the description of the cells fits that of apoptosis (i.e, shrunken cells with fragmented nuclei, and with no associated adjacent neutrophilic infiltrate). Apoptotic cells express phosphatidylserine on their surface as a signal to phagocytic cells that they should be engulfed and removed, and thus, do not trigger an acute inflammatory reaction. The other answers are incorrect.
QUESTION 28
A pharmaceutical company wants to develop a drug that will allow for better survival of cells after exposure to radiation. Of the following, which mechanism would best accomplish this task?
A. Lysis of BH3 proteins
B. Bcl-2 antagonists
C. FAS agonists
D. FAS antagonists
E. Phosphatidylserine binding
Answer for Question 28
Answer: A (lysis of BH3 proteins)
Explanation: cells exposed to radiation develop DNA damage and can undergo apoptosis. The mitochondrial pathway of apoptosis is one of two pathways by which apoptosis can occur, but is the pathway most commonly utilized, including by radiation induced damage. Cell injury, including DNA damage, activates BH3 sensors, which promotes Bax and Bak, which lead to release of cytochrome C from the mitochondria and subsequent activation of caspases. Lysis of BH3 proteins would directly inhibit apoptosis. Bcl-2 inhibits apoptosis, so antagonists would block this negative influence, and better allow for apoptosis to occur. While FAS ligand binding to FAS promotes apoptosis through the death receptor pathway, and an antagonist should inhibit this pathway, the death receptor pathway is not as commonly used as the mitochondrial pathway. Binding to phosphatidylserine, depending upon its effects, could inhibit or promote the cleaning up of cells that have undergone apoptosis, but it would not affect whether or not a cell became apoptotic. Apoptosis is an important mechanism by which the body can remove dead or damaged cells. In the case of radiation induced DNA damage, hindering apoptosis to allow for the survival of the cells would not necessarily be a good idea.
QUESTION 29
A 71-year-old male with a 50-pack-year smoking history combined with treated essential hypertension develops pain in his right lower extremity whenever he walks more than five blocks. Imaging studies reveal a 85% stenosis of his right femoral artery. Walking less than five blocks does not elicit pain. Of the following, which molecular change in his skeletal muscle best allows for him to be pain free with lesser exertion?
A. Increased numbers of mitochondria
B. Increased activity of cytochrome C
C. Production of hypoxia-inducible factor 1 (HIF-1)
D. Down-regulation of VEGF
E. Inhibition of glucokinase
Answer for Question 29
Answer: C (production of hypoxia-inducible factor 1 (HIF-1))
Explanation: stenosis of the femoral artery would lead to ischemia of the lower extremity. To adapt to ischemia, the skeletal muscle cells would produce hypoxia-inducible factor 1, which would then induce several changes to lead to increased blood flow, including the up-regulation of VEGF, to promote develop of new vasculature. HIF-1 would also inhibit oxidative phosphorylation and promote aerobic glycolysis.
QUESTION 30
A 53-year-old male with a long history of treated essential hypertension and a 35-pack-year smoking history develops chest pain while working outside. His wife calls an ambulance and he is transported to the hospital where clot-lysing medication is given. The time from the start of the chest pain to the use of the clot lysing medication was about 45 minutes. Laboratory testing reveals a small increase in troponin I. Of the following mechanisms, which would best explain an increase in tissue damage following lysis of his clot?
A. Increased production of hypoxia-inducible factor I
B. Inhibition of bcl-2
C. Release of FAS ligand by inflammatory cells
D. Increased production of reactive oxygen species
E. Impaired glycolysis
Answer for Question 30
Answer: D (increased production of reactive oxygen species)
Explanation: the patient has sustained a myocardial infarct. Following lysis of the clot, blood will flow to the damaged tissue; however, because the tissue is damaged, an increased number of reactive oxygen species may be generated, potentially from dysfunction of the electron transport chain, or through increased infiltration with inflammatory cells. This process is termed reperfusion injury. The release of troponin I indicates necrosis has occurred, with release of enzymes from the cell. Inhibition of bcl-2 and release of FAS ligand would increase apoptosis, which may play a role, but would be less significant, if they occurred, than the increased production of reactive oxygen species.
QUESTION 31
A pathologist is examining a microscopic section of the heart from a 68-year-old male and identifies a finely stippled yellow-brown pigment in most of the cells and which is centered around the nucleus. Of the following, which chemical or mediator contributed the most to these changes?
Prostacyclin
Catalase
Superoxide
Glucokinase
Ionized calcium
Answer for Question 31
Answer: C (superoxide)
Explanation: the description is consistent with lipofuscin. Lipofuscin, a finely stippled yellow-brown pigment, also called wear and tear pigment, is commonly found in the heart of older individuals and in a perinuclear distribution. Lipofuscin derives from lipid peroxidation of membranes, which is caused by oxygen-derived free radicals, including superoxide.
QUESTION 32
A pathologist is reviewing old autopsy slides from the file of the hospital at which he works. One of the slides includes a section of liver and gallbladder from a person who was exposed to carbon tetrachloride at the dry cleaning store he worked at. At which of the following locations will the pathologist identify the greatest amount of cellular injury?
A. Mucosa of the gallbladder
B. Muscularis of the gallbladder
C. Periportal hepatocytes
D. Centrilobular hepatocytes
E. Portal arteries
Answer for Question 32
Answer: D (centrilobular hepatocytes)
Explanation: toxins affecting the body can be either direct acting or latent. Direct acting toxins are those which themselves exert the deleterious effect on the body (e.g., mercuric chloride). Latent toxins are those which first have to be modified by the body (often the cytochrome p-450 system) before they exert effects. Carbon tetrachloride is an example of a latent toxin. Carbon tetrachloride is converted to a free radical, which is toxic to the liver (as the liver is the organ the alters the carbon tetrachloride, that it is the organ most affected first is understandable). When blood enters the liver, it flows from the portal tract through the hepatic sinusoids to the central veins. Thus, when carbon tetrachloride enters the liver, it is non-toxic, but, as it is metabolized, it becomes toxic, so, the centrilobular hepatocytes would be expected to sustain the majority of the injury. Acetaminophen functions in the same way, becoming toxic when metabolized by the liver.
QUESTION 33
A 71-year-old male with dementia is autopsied at the request of his family to determine the exact cause of his dementia. Microscopic examination of the brain reveals a prominent number of neurofibrillary tangles in the neocortex, consistent with the diagnosis of Alzheimer’s disease. Immunohistochemical stains reveal tau protein. Of the following mechanisms, which could most likely contribute to the microscopic findings?
A. Decreased production of chaperones
B. Increased production of chaperones
C. Decreased production of hypoxia-inducible factor 1
D. Increased production of hypoxia-inducible factor 1
Answer for Question 33
Answer: A (decreased production of chaperones)
Explanation: chaperones guide proteins through the endoplasmic reticulum. A decreased number of chaperones could contribute to an increase in the amount of misfolded protein, and therefore, the accumulation of tau protein tangles in neurons. The brain is very sensitive to hypoxia and not capable of significant adaptation to hypoxia. The production of hypoxia-inducible factor 1 would play little role in the development of neurofibrillary tangles.
QUESTION 34
A 23-year-old male suddenly develops a pressure sensation in his chest that is accompanied by shortness of breath. His friends rush him to the emergency room where he is diagnosed with an acute myocardial infarct. Laboratory testing reveals a LDL of 756 mg/dL. Of the following, what was the mechanism most likely responsible for his underlying disease process?
A. Overproduction of phagocyte oxidase
B. Hyper-reactive IL-1
C. Misfolded protein
D. Failure of protein synthesis
E. Viral infection
Answer for Question 34
Answer: C (misfolded protein)
Explanation: the patient has family hypercholesterolemia. Familial hypercholesterolemia occurs due to a loss of the LDL receptor (which impairs LDL from being removed from the blood). This loss is due to misfolding of the LDL receptor protein.
QUESTION 35
A researcher is examining multiple different proteins for the effects of cross-linking induced by free radical damage in tissue during acute inflammation. Proteins rich in which of the following amino acids are likely to be the most affected?
A. Glycine
B. Cysteine
C. Phenylalanine
D. Serine
E. Histidine
Answer for Question 35
Answer: B (cysteine)
Explanation: free radicals cause protein cross-linking through sulfhydryl groups. Of the amino acids listed, only cysteine has a sulfhydryl group.