A 34-year-old woman comes to the physician a week after noticing a lump in her left breast. Three months ago, she was discharged from the hospital after treatment of multiple injuries sustained in a motor vehicle collision. Her only medication is an oral contraceptive. Her mother died of ovarian cancer. Examination shows a 2.5-cm, nontender mass in the upper outer quadrant of the left breast. Mammography shows a circumscribed radiolucent lesion with a rim of peripheral calcification. A photomicrograph of tissue from a biopsy of the mass is shown. Which of the following is the most likely cause of the breast swelling?
Q12
An 8-month-old boy presents with poor feeding. The patient’s mother says that he has refused to eat since yesterday morning. She also noticed that he has had trouble keeping his head up and appears floppy. She had breastfed him exclusively and just recently introduced him to pureed foods. His last bowel movement was 3 days ago which was normal. Past medical history is significant for recent otitis media. No current medications except for herbal supplements administered by his parents. Patient is not immunized due to the parent’s religious beliefs. The vital signs include: temperature 37.0°C (98.6°F), blood pressure 85/45 mm Hg, pulse 140/min, respiratory rate 31/min, and oxygen saturation 99% on room air. On physical examination, the patient is lethargic and drooling. Flaccid muscle tone present in all extremities. There is bilateral ptosis with sluggish pupillary reflexes. Which of the following best describes the pathophysiology of this patient’s condition?
Q13
A 56-year-old woman presents to the clinic complaining of fatigue and nausea. She was recently diagnosed with metastatic ovarian cancer and subsequently started treatment with an alkylating agent. The patient reports recent weight loss, malaise, and drowsiness, but denies fever, headaches, palpitations, shortness of breath, or genitourinary symptoms. Physical exam was unremarkable. Laboratory tests are shown below.
Serum:
Na+: 137 mEq/L
Cl-: 101 mEq/L
K+: 4.8 mEq/L
HCO3-: 25 mEq/L
BUN: 8.5 mg/dL
Glucose: 117 mg/dL
Creatinine: 2.1 mg/dL
Thyroid-stimulating hormone: 1.8 µU/mL
Ca2+: 9.6 mg/dL
AST: 8 U/L
ALT: 11 U/L
What findings on urinalysis are most specific to this patient’s diagnosis?
Q14
A biology student is studying apoptosis pathways. One of the experiments conducted involves the binding of a ligand to a CD95 receptor. A defect of this pathway will most likely cause which of the conditions listed below?
Q15
A 68-year-old man is brought to the physician by his wife because she is concerned about his speech being irregular. Specifically, she says that over the last 8 months, her husband has been saying increasingly nonsensical statements at home. In addition, he is no longer able to perform basic verbal tasks such as ordering from a menu or giving directions even though he was an English teacher prior to retirement. She also reports that he has recently started attempting to kiss strangers and urinate in public. Finally, she has also noticed that he has been frequently binge eating sweets even though he was previously very conscientious about his health. When asked about these activities, the patient does not have insight into his symptoms. Which of the following would most likely be seen in this patient?
Q16
A 29-year-old woman presents with a 2-hour history of sudden onset of severe mid-epigastric pain. The pain radiates to the back, and is not relieved by over-the-counter antacids. The patient also complains of profuse vomiting. The patient’s medical history is negative for similar symptoms. She consumes 3–4 alcoholic drinks daily. The blood pressure is 80/40 mm Hg and the heart rate is 105/min. Examination of the lungs reveals bibasilar crackles. Abdominal examination reveals diffuse tenderness involving the entire abdomen, marked guarding, rigidity, and reduced bowel sounds. The chest X-ray is normal. However, the abdominal CT scan reveals peritoneal fluid collection and diffuse pancreatic enlargement. The laboratory findings include:
Aspartate aminotransferase 63 IU/L
Alkaline phosphatase 204 IU/L
Alanine aminotransferase 32 IU/L
Serum amylase 500 IU/L (Normal: 25-125 IU/L)
Serum lipase 1,140 IU/L (Normal: 0-160 IU/L)
Serum calcium 2 mmol/L
Which of the following cellular changes are most likely, based on the clinical and laboratory findings?
Q17
A 65-year-old man presents with generalized edema and dyspnea on exertion. He also complains of easy bruising and nasal bleeding. Past medical history is significant for a right-sided myocardial infarction 4 years ago. Current medications are metoprolol, aspirin, and rosuvastatin. His vital signs are as follows: blood pressure 140/90 mm Hg, heart rate 78/min, respiratory rate 17/min, and temperature 36.5℃ (97.7℉). On physical examination, the patient is pale and acrocyanotic with cold extremities. Cardiac examination shows the right displacement of the apical beat, decreased heart sounds, and the presence of an S3. Abdominal percussion reveals ascites and hepatomegaly. Which of the following hepatic cell types is most sensitive to ischemia?
Q18
An 84-year-old man is brought to the physician by the staff of a group home where he resides because of worsening confusion and decreased urinary output. His nurse reports that the patient has not been drinking much for the last 3 days. Examination shows a decreased skin turgor and dry oral mucosa. His pulse is 105/min and blood pressure is 100/65 mm Hg. His serum creatinine is 3.1 mg/dL and a urea nitrogen is 42 mg/dL. Urine studies show multiple brownish granular casts. Which of the following processes is most likely involved in the pathogenesis of this patient's condition?
Q19
A 37-year-old man presents to the clinic because of painful, severe blistering over his buttocks for the past week. About a year ago, he noticed a similar outbreak on his inner thighs, but it receded within a few days on its own. Physical examination shows the blisters are tense, and rubbing the affected skin does not result in ‘popping’ of the blisters. A biopsy shows the entire epidermis lifting away from the basal lamina with extensive inflammatory infiltrates abundant with eosinophils. Immunofluorescence shows a linear pattern of immune complex deposits. Which of the following cellular structures, if defective, is most likely involved in the formation of these blisters?
Q20
A 48-year-old man has smoked approximately 3 packs of cigarettes per day for the past 12 years. Which of the following pathologic changes is most likely to occur in his bronchial epithelium?
Cell injury US Medical PG Practice Questions and MCQs
Question 11: A 34-year-old woman comes to the physician a week after noticing a lump in her left breast. Three months ago, she was discharged from the hospital after treatment of multiple injuries sustained in a motor vehicle collision. Her only medication is an oral contraceptive. Her mother died of ovarian cancer. Examination shows a 2.5-cm, nontender mass in the upper outer quadrant of the left breast. Mammography shows a circumscribed radiolucent lesion with a rim of peripheral calcification. A photomicrograph of tissue from a biopsy of the mass is shown. Which of the following is the most likely cause of the breast swelling?
A. Defect in DNA repair
B. Obstruction of lactiferous ducts
C. Stimulation of estrogen receptors
D. Thrombophlebitis of subcutaneous veins
E. Release of cytoplasmic triglycerides (Correct Answer)
Explanation: ***Release of cytoplasmic triglycerides***
- This patient's history of **trauma** followed by a new breast lump and mammographic findings of a **circumscribed radiolucent lesion with peripheral calcification** are classic for **fat necrosis**. The image shows necrotic fat cells, inflammatory infiltrates, and foamy macrophages, consistent with fat necrosis.
- Fat necrosis occurs when **adipocytes** are damaged, causing the release of **triglycerides** and free fatty acids. These then incite an inflammatory response, followed by calcification and fibrosis.
*Defect in DNA repair*
- A defect in DNA repair is associated with an increased risk of **malignancy**, such as breast cancer, especially given the family history of ovarian cancer (BRCA gene mutations). However, the histologic image and the description of a **radiolucent lesion with rim calcification** are not characteristic of malignancy.
- While the family history is relevant for cancer risk, the clinical and histological findings point away from a primary malignancy and towards a benign reactive process.
*Obstruction of lactiferous ducts*
- Obstruction of lactiferous ducts typically leads to conditions like **mastitis**, **duct ectasia**, or **galactocele**. These would present with different radiographic features, often with inflammation or fluid-filled cysts, and different histological patterns.
- The image does not show features of ductal obstruction, such as dilated ducts, inspissated secretions, or periductal inflammation characteristic of duct ectasia.
*Stimulation of estrogen receptors*
- Stimulation of estrogen receptors is relevant in conditions like **fibroadenoma**, **fibrocystic changes**, or certain types of **breast cancer**. While the patient is on oral contraceptives (estrogenic), the clinical picture and biopsy findings are not consistent with these estrogen-mediated conditions.
- Fibroadenomas often appear as well-defined masses on mammography but histologically consist of glandular and stromal proliferation, which is not seen here. Fibrocystic changes involve cysts and fibrosis.
*Thrombophlebitis of subcutaneous veins*
- Thrombophlebitis of subcutaneous veins, also known as **Mondor's disease**, presents as a palpable cord-like structure with pain and tenderness localized along the affected vein. It typically resolves spontaneously.
- This condition is unlikely given the description of a **2.5-cm, nontender mass** and the specific histological findings of necrotic fat and inflammation, which are not characteristic of venous thrombosis.
Question 12: An 8-month-old boy presents with poor feeding. The patient’s mother says that he has refused to eat since yesterday morning. She also noticed that he has had trouble keeping his head up and appears floppy. She had breastfed him exclusively and just recently introduced him to pureed foods. His last bowel movement was 3 days ago which was normal. Past medical history is significant for recent otitis media. No current medications except for herbal supplements administered by his parents. Patient is not immunized due to the parent’s religious beliefs. The vital signs include: temperature 37.0°C (98.6°F), blood pressure 85/45 mm Hg, pulse 140/min, respiratory rate 31/min, and oxygen saturation 99% on room air. On physical examination, the patient is lethargic and drooling. Flaccid muscle tone present in all extremities. There is bilateral ptosis with sluggish pupillary reflexes. Which of the following best describes the pathophysiology of this patient’s condition?
A. Haemophilus influenzae infection
B. Bacterial infection of the meninges
C. Post-viral ascending demyelinating polyneuropathy
D. Ingestion of spores with in vivo toxin production (Correct Answer)
E. Autoantibodies against acetylcholine receptors
Explanation: ***Ingestion of spores with in vivo toxin production***
- The patient's history of introducing **pureed foods** (especially honey or home-canned foods), combined with symptoms like **flaccid paralysis**, **ptosis**, **sluggish pupillary reflexes**, **constipation**, and **poor feeding**, is highly suggestive of **infant botulism**.
- **Infant botulism** is caused by the ingestion of *Clostridium botulinum* **spores**, which **germinate in the intestine** and produce **neurotoxin in vivo** that blocks acetylcholine release at the neuromuscular junction.
- This differs from foodborne botulism in adults where **preformed toxin** is ingested.
- The **descending paralysis** pattern (cranial nerves first, then trunk and extremities) and **autonomic dysfunction** (constipation, poor feeding) are characteristic features.
*Haemophilus influenzae infection*
- While *Haemophilus influenzae* can cause various infections (meningitis, epiglottitis) in unimmunized children, it does not typically present with **descending flaccid paralysis** and **autonomic dysfunction** seen here.
- Would expect fever and more acute systemic illness with H. influenzae infection.
*Bacterial infection of the meninges*
- Meningitis would typically present with symptoms such as **fever**, **nuchal rigidity**, **altered mental status**, and potentially **seizures**.
- The **flaccid tone** and **bilateral ptosis with pupillary abnormalities** are inconsistent with meningitis.
- Meningitis would show increased (not decreased) muscle tone.
*Post-viral ascending demyelinating polyneuropathy*
- This describes **Guillain-Barré syndrome (GBS)**, which typically presents with **ascending paralysis** (starts in legs, moves upward) and often follows viral infections.
- GBS is rare in infants this young, and the **descending pattern** (cranial nerves affected first) points away from this diagnosis.
- GBS typically has **areflexia**, not just sluggish reflexes, and pupillary involvement is uncommon.
*Autoantibodies against acetylcholine receptors*
- This mechanism is characteristic of **myasthenia gravis**, which can present with muscle weakness, ptosis, and feeding difficulties.
- However, myasthenia gravis is extremely rare in infants of this age and typically has a more chronic, fluctuating course rather than acute onset.
- **Pupillary reflexes are typically spared** in myasthenia gravis, whereas they are affected in botulism.
- The severe constipation and autonomic features point strongly to botulism rather than myasthenia gravis.
Question 13: A 56-year-old woman presents to the clinic complaining of fatigue and nausea. She was recently diagnosed with metastatic ovarian cancer and subsequently started treatment with an alkylating agent. The patient reports recent weight loss, malaise, and drowsiness, but denies fever, headaches, palpitations, shortness of breath, or genitourinary symptoms. Physical exam was unremarkable. Laboratory tests are shown below.
Serum:
Na+: 137 mEq/L
Cl-: 101 mEq/L
K+: 4.8 mEq/L
HCO3-: 25 mEq/L
BUN: 8.5 mg/dL
Glucose: 117 mg/dL
Creatinine: 2.1 mg/dL
Thyroid-stimulating hormone: 1.8 µU/mL
Ca2+: 9.6 mg/dL
AST: 8 U/L
ALT: 11 U/L
What findings on urinalysis are most specific to this patient’s diagnosis?
A. Granular casts (Correct Answer)
B. Normal findings
C. RBC casts
D. WBC casts
E. Elevated protein
Explanation: ***Granular casts***
- The patient's elevated **creatinine (2.1 mg/dL)** suggests **acute kidney injury (AKI)**, likely due to the **alkylating agent** used for her ovarian cancer. **Granular casts** are a hallmark of **acute tubular necrosis (ATN)**, a common cause of AKI, due to damaged renal tubular epithelial cells.
- The presence of **fatigue, nausea, weight loss, malaise, and drowsiness** further supports a diagnosis of AKI, consistent with systemic effects of renal impairment.
*Normal findings*
- This option is incorrect because the patient's elevated **creatinine** indicates significant renal dysfunction that would manifest in abnormal urinalysis findings, suggesting an underlying pathology.
- A **normal urinalysis** would be inconsistent with the clinical picture and lab values showing compromised kidney function.
*RBC casts*
- **Red blood cell (RBC) casts** are indicative of **glomerulonephritis**, vasculitis, or severe kidney injury with glomerular involvement.
- While AKI is present, there are no other symptoms or lab findings (e.g., hematuria) to suggest glomerular disease as the primary pathology.
*WBC casts*
- **White blood cell (WBC) casts** are highly suggestive of **pyelonephritis** (kidney infection) or **interstitial nephritis**.
- The patient has no signs of infection (e.g., fever, flank pain) or specific drug-induced interstitial nephritis, making this less likely.
*Elevated protein*
- Elevated protein in the urine (**proteinuria**) is a non-specific finding that can be seen in various kidney diseases, including glomerular damage, tubular dysfunction, and overflow proteinuria.
- While proteinuria may be present due to kidney injury, **granular casts** are more specific to the diagnosis of **acute tubular necrosis**, which is the most probable cause of AKI in this context of chemotherapy.
Question 14: A biology student is studying apoptosis pathways. One of the experiments conducted involves the binding of a ligand to a CD95 receptor. A defect of this pathway will most likely cause which of the conditions listed below?
A. Chronic granulomatous disease
B. Chédiak-Higashi syndrome
C. Follicular lymphoma
D. Autoimmune lymphoproliferative syndrome (Correct Answer)
E. Leukocyte adhesion deficiency
Explanation: ***Autoimmune lymphoproliferative syndrome***
- A defect in the **CD95 (Fas) receptor pathway** impairs the normal **apoptotic deletion of self-reactive lymphocytes**, leading to their accumulation.
- This accumulation results in **lymphadenopathy, splenomegaly, and autoimmune manifestations** due to uncontrolled lymphocyte proliferation.
*Chronic granulomatous disease*
- This condition is characterized by a defect in **NADPH oxidase**, leading to recurrent infections and granuloma formation due to the inability of phagocytes to produce **reactive oxygen species**.
- It does not primarily involve the CD95 apoptosis pathway.
*Chédiak-Higashi syndrome*
- This is an **autosomal recessive disorder** involving a defect in lysosomal trafficking, leading to impaired function of phagocytes, melanocytes, and platelets.
- Symptoms include **recurrent pyogenic infections, partial albinism, and neurological abnormalities**, not directly linked to the CD95 pathway.
*Follicular lymphoma*
- This is a type of non-Hodgkin lymphoma characterized by a **t(14;18) translocation**, which causes overexpression of the **BCL2 gene**, an anti-apoptotic protein.
- While it involves impaired apoptosis, the primary defect is not in the CD95 receptor itself but rather in the regulation of apoptosis through BCL2.
*Leukocyte adhesion deficiency*
- This is a rare **immunodeficiency disorder** characterized by defects in **leukocyte adhesion molecules (integrins)**, impairing the ability of white blood cells to adhere to endothelial surfaces and migrate to sites of infection.
- It results in **recurrent bacterial infections and impaired wound healing**, unrelated to the CD95 apoptosis pathway.
Question 15: A 68-year-old man is brought to the physician by his wife because she is concerned about his speech being irregular. Specifically, she says that over the last 8 months, her husband has been saying increasingly nonsensical statements at home. In addition, he is no longer able to perform basic verbal tasks such as ordering from a menu or giving directions even though he was an English teacher prior to retirement. She also reports that he has recently started attempting to kiss strangers and urinate in public. Finally, she has also noticed that he has been frequently binge eating sweets even though he was previously very conscientious about his health. When asked about these activities, the patient does not have insight into his symptoms. Which of the following would most likely be seen in this patient?
A. Intracellular hyperphosphorylated tau proteins
B. Alpha-synuclein
C. Large intracellular vacuoles
D. Perivascular inflammation
E. Hyperphosphorylated tau inclusion bodies (Correct Answer)
Explanation: ***Hyperphosphorylated tau inclusion bodies***
- The patient's symptoms of **disinhibition** (kissing strangers, public urination), **personality changes** (binge eating sweets), and **progressive language dysfunction** are characteristic of **frontotemporal dementia (FTD)**.
- FTD has heterogeneous pathology: approximately **40-50% of cases** involve **tau pathology** (forming Pick bodies and neurofibrillary tangles), while 50-60% show **TDP-43 pathology**.
- The term **"inclusion bodies"** specifically refers to the aggregated, pathological deposits visible microscopically, making this the most precise answer.
- Tau pathology is particularly associated with **Pick's disease**, a subtype of FTD characterized by **Pick bodies** (spherical tau inclusions).
*Intracellular hyperphosphorylated tau proteins*
- This describes the **same pathological process** as the correct answer but is **less specific**.
- While technically accurate for tau-positive FTD cases, the term lacks the specificity of "inclusion bodies," which denotes the characteristic aggregated form seen on microscopy.
- In pathology, precision matters: stating "inclusion bodies" indicates you recognize the specific morphological finding.
*Alpha-synuclein*
- **Alpha-synuclein** aggregates (Lewy bodies) are characteristic of **Lewy body dementia** and **Parkinson's disease dementia**.
- These conditions typically present with **fluctuating cognition**, **visual hallucinations**, **parkinsonism**, and **REM sleep behavior disorder**.
- The prominent behavioral disinhibition and language dysfunction without parkinsonian features point away from synucleinopathies.
*Large intracellular vacuoles*
- **Spongiform change** (vacuolation) with prion protein accumulation is pathognomonic for **Creutzfeldt-Jakob disease (CJD)**.
- CJD presents with **rapidly progressive dementia** (weeks to months), **myoclonus**, **ataxia**, and periodic sharp waves on EEG.
- The **gradual 8-month progression** and absence of myoclonus make prion disease unlikely.
*Perivascular inflammation*
- **Perivascular lymphocytic infiltration** indicates **inflammatory or infectious CNS disease**, such as **vasculitis** or **viral encephalitis**.
- This patient's **chronic, insidious progression** over 8 months without acute features argues against an inflammatory process.
Question 16: A 29-year-old woman presents with a 2-hour history of sudden onset of severe mid-epigastric pain. The pain radiates to the back, and is not relieved by over-the-counter antacids. The patient also complains of profuse vomiting. The patient’s medical history is negative for similar symptoms. She consumes 3–4 alcoholic drinks daily. The blood pressure is 80/40 mm Hg and the heart rate is 105/min. Examination of the lungs reveals bibasilar crackles. Abdominal examination reveals diffuse tenderness involving the entire abdomen, marked guarding, rigidity, and reduced bowel sounds. The chest X-ray is normal. However, the abdominal CT scan reveals peritoneal fluid collection and diffuse pancreatic enlargement. The laboratory findings include:
Aspartate aminotransferase 63 IU/L
Alkaline phosphatase 204 IU/L
Alanine aminotransferase 32 IU/L
Serum amylase 500 IU/L (Normal: 25-125 IU/L)
Serum lipase 1,140 IU/L (Normal: 0-160 IU/L)
Serum calcium 2 mmol/L
Which of the following cellular changes are most likely, based on the clinical and laboratory findings?
A. Liquefactive necrosis
B. Dry gangrene
C. Caseous necrosis
D. Coagulative necrosis
E. Fat necrosis (Correct Answer)
Explanation: ***Fat necrosis***
- The patient's presentation with severe epigastric pain radiating to the back, elevated serum amylase and lipase, **alcohol abuse**, and diffuse pancreatic enlargement indicates **acute pancreatitis**.
- **Fat necrosis** is a characteristic pathologic finding in acute pancreatitis, resulting from the release of activated pancreatic enzymes (like lipase) into the surrounding adipose tissue, causing **FFA (free fatty acid)** formation that complexes with calcium (saponification).
*Liquefactive necrosis*
- This type of necrosis is characterized by the complete digestion of dead cells, resulting in a **viscous liquid mass**.
- It is typically seen in **bacterial infections** or **cerebral infarcts**, not primarily in pancreatitis.
*Dry gangrene*
- **Dry gangrene** involves ischemic necrosis, usually affecting the extremities, where the tissue becomes **dry, shrunken, and black**.
- It is caused by **lack of blood supply** and does not fit the clinical picture of acute pancreatitis.
*Caseous necrosis*
- **Caseous necrosis** is a distinct form of coagulative necrosis, characterized by a **cheese-like appearance** of the necrotic tissue.
- It is most commonly associated with **tuberculosis** and certain fungal infections, not acute pancreatitis.
*Coagulative necrosis*
- **Coagulative necrosis** is characterized by the preservation of the cell shape and tissue architecture for several days after cell death, often due to **ischemia** (e.g., myocardial infarction).
- While pancreatic cells can undergo coagulative necrosis in severe ischemia, **fat necrosis** is specifically and prominently associated with the enzymatic destruction in acute pancreatitis.
Question 17: A 65-year-old man presents with generalized edema and dyspnea on exertion. He also complains of easy bruising and nasal bleeding. Past medical history is significant for a right-sided myocardial infarction 4 years ago. Current medications are metoprolol, aspirin, and rosuvastatin. His vital signs are as follows: blood pressure 140/90 mm Hg, heart rate 78/min, respiratory rate 17/min, and temperature 36.5℃ (97.7℉). On physical examination, the patient is pale and acrocyanotic with cold extremities. Cardiac examination shows the right displacement of the apical beat, decreased heart sounds, and the presence of an S3. Abdominal percussion reveals ascites and hepatomegaly. Which of the following hepatic cell types is most sensitive to ischemia?
A. Pericentral hepatocytes (Correct Answer)
B. Ito cells
C. Ductal cells
D. Periportal hepatocytes
E. Sinusoidal endothelial cells
Explanation: ***Pericentral hepatocytes***
- **Pericentral hepatocytes** (Zone 3) are located furthest from the hepatic arterial and portal venule blood supply, making them most vulnerable to **ischemic injury**.
- This region is primarily responsible for drug metabolism and detoxification, processes that require high oxygen demand.
*Ito cells*
- **Ito cells**, or hepatic stellate cells, are located in the **space of Disse** and are primarily involved in vitamin A storage and fibrosis upon activation.
- While important for liver function, they are not the cells most sensitive to acute ischemia.
*Ductal cells*
- **Ductal cells** line the bile ducts and are involved in bile modification and transport.
- They are generally more resistant to ischemia compared to hepatocytes.
*Periportal hepatocytes*
- **Periportal hepatocytes** (Zone 1) are closest to the incoming arterial and portal blood supply, making them the most oxygenated and last to be affected by ischemia.
- These cells are important for oxidative metabolism and gluconeogenesis, and are more vulnerable to toxicity than ischemia.
*Sinusoidal endothelial cells*
- **Sinusoidal endothelial cells** form the lining of the hepatic sinusoids and are involved in exchange between blood and hepatocytes.
- Although damage to these cells can contribute to overall liver dysfunction, they are not the primary cell type most sensitive to ischemia compared to pericentral hepatocytes.
Question 18: An 84-year-old man is brought to the physician by the staff of a group home where he resides because of worsening confusion and decreased urinary output. His nurse reports that the patient has not been drinking much for the last 3 days. Examination shows a decreased skin turgor and dry oral mucosa. His pulse is 105/min and blood pressure is 100/65 mm Hg. His serum creatinine is 3.1 mg/dL and a urea nitrogen is 42 mg/dL. Urine studies show multiple brownish granular casts. Which of the following processes is most likely involved in the pathogenesis of this patient's condition?
A. Immune complex deposition in mesangium
B. Leukocytic infiltration of renal interstitium
C. Necrosis of renal papillae
D. Necrosis of tubular epithelial cells (Correct Answer)
E. Disruption of glomerular podocytes
Explanation: ***Necrosis of tubular epithelial cells***
- The patient presents with classic signs of **acute kidney injury (AKI)**, including confusion, decreased urinary output, decreased skin turgor, dry oral mucosa, tachycardia, hypotension, elevated creatinine (3.1 mg/dL), and urea nitrogen (42 mg/dL).
- The presence of **brownish granular casts** in the urine is highly suggestive of **acute tubular necrosis (ATN)**, secondary to ischemia caused by severe dehydration and hypoperfusion.
*Immune complex deposition in mesangium*
- This typically points to a **glomerular pathology**, such as IgA nephropathy or post-infectious glomerulonephritis.
- These conditions would usually present with **hematuria** and **proteinuria**, not necessarily brownish granular casts or the acute dehydration found here.
*Leukocytic infiltration of renal interstitium*
- This finding is characteristic of **acute interstitial nephritis**, which is often caused by drug hypersensitivity or infection.
- The clinical presentation with dehydration and granular casts is not typical for acute interstitial nephritis.
*Necrosis of renal papillae*
- **Renal papillary necrosis** is often associated with analgesic abuse, sickle cell disease, diabetes, or obstruction.
- While it can cause AKI, it typically presents with **flank pain** and **hematuria**, and the urine sediment would show ghost cells or fragments of necrotic papillae, not specifically brownish granular casts.
*Disruption of glomerular podocytes*
- **Podocyte disruption** is seen in primary glomerular diseases like minimal change disease or focal segmental glomerulosclerosis.
- These conditions primarily cause **nephrotic syndrome** (heavy proteinuria, edema), which is not the main presentation here.
Question 19: A 37-year-old man presents to the clinic because of painful, severe blistering over his buttocks for the past week. About a year ago, he noticed a similar outbreak on his inner thighs, but it receded within a few days on its own. Physical examination shows the blisters are tense, and rubbing the affected skin does not result in ‘popping’ of the blisters. A biopsy shows the entire epidermis lifting away from the basal lamina with extensive inflammatory infiltrates abundant with eosinophils. Immunofluorescence shows a linear pattern of immune complex deposits. Which of the following cellular structures, if defective, is most likely involved in the formation of these blisters?
A. Gap junctions
B. Hemidesmosomes (Correct Answer)
C. Lamellar bodies
D. Zonula occludens
E. Macula adherens
Explanation: ***Hemidesmosomes***
- The clinical picture of **tense blisters** that do not pop with rubbing (**negative Nikolsky sign**), along with the histological finding of the **entire epidermis lifting away from the basal lamina** (subepidermal blistering), strongly suggests **bullous pemphigoid**.
- **Immunofluorescence showing linear deposits** along the basement membrane zone is characteristic of bullous pemphigoid, which is caused by autoantibodies targeting proteins within the hemidesmosomes.
*Gap junctions*
- **Gap junctions** are involved in **intercellular communication** and the passage of small molecules between cells.
- Defects in gap junctions do not typically lead to blistering skin disorders.
*Lamellar bodies*
- **Lamellar bodies** are organelles in **keratinocytes** that release lipids to form the **skin barrier**.
- Defects in lamellar bodies are associated with disorders like **ichthyosis**, not blistering as described.
*Zonula occludens*
- **Zonula occludens**, also known as **tight junctions**, are crucial for forming a **seal between epithelial cells**, regulating paracellular transport.
- Dysfunctional tight junctions can lead to increased permeability but are not directly involved in the formation of subepidermal blisters.
*Macula adherens*
- **Macula adherens**, or **desmosomes**, are cell-to-cell adhesion structures that provide strong mechanical attachments between keratinocytes.
- Defects in desmosomes are associated with **pemphigus vulgaris** and **pemphigus foliaceus**, which typically present with **flaccid blisters** that show a **positive Nikolsky sign** and involve intraepidermal cleavage.
Question 20: A 48-year-old man has smoked approximately 3 packs of cigarettes per day for the past 12 years. Which of the following pathologic changes is most likely to occur in his bronchial epithelium?
A. Metaplasia (Correct Answer)
B. Hyperplasia
C. Hypertrophy
D. Dysplasia
E. Atrophy
Explanation: ***Metaplasia***
- Chronic irritation from **cigarette smoking** can cause the **bronchial epithelium** to change from ciliated columnar to stratified squamous, a process known as **metaplasia**.
- This adaptation makes the tissue more resistant to injury but results in the loss of important protective functions like **mucociliary clearance**.
*Hyperplasia*
- **Hyperplasia** involves an increase in the number of cells in a tissue or organ, often in response to increased demand or chronic stimulation.
- While smoking can cause hyperplasia of goblet cells and mucous glands in the bronchi, the direct epithelial change in response to chronic irritation is more specifically **metaplasia**.
*Hypertrophy*
- **Hypertrophy** is an increase in the size of individual cells, leading to an increase in the size of the organ or tissue.
- This is not the primary adaptive change seen in the bronchial epithelium in response to chronic smoking; instead, cells change their type.
*Dysplasia*
- **Dysplasia** refers to disorderly cell growth, often characterized by variations in cell size, shape, and organization; it is considered a precursor to cancer.
- While chronic smoking can eventually lead to dysplasia and then carcinoma, the initial and most common adaptive change in the bronchial epithelium is **metaplasia**.
*Atrophy*
- **Atrophy** is a decrease in cell size or number, leading to a reduction in the size of an organ or tissue, usually due to decreased workload, nutrition, or blood supply.
- This is not a typical response of the bronchial epithelium to chronic irritation from smoking, which tends to induce proliferative or adaptive changes.