PATHOLOGY Flashcards
(204 cards)
1
Q
What are the hallmark features of acute inflammation?
A
- Increased blood flow (vasodilation)
- Increased vascular permeability
- Neutrophil immigration into tissues
2
Q
What is the role of macrophages in acute inflammation?
A
- Macrophages initiate the inflammatory response by recognizing DAMPs and PAMPs.
- They secrete cytokines to recruit neutrophils and other immune cells.
3
Q
Describe the process of neutrophil extravasation.
A
- Margination and rolling: WBC adhere loosely to endothelial cells.
- Adhesion: WBC - endothelial cells tight binding
- Transmigration: WBC travels between endothelial cells and exits blood vessel
- Migration: WBC travels through interstitium to site of injury or infection guided by chemotactic signals
4
Q
What are the potential outcomes of acute inflammation?
A
- Resolution and healing (IL-10, TGF-β)
- Persistent acute inflammation (IL-8)
- Abscess (acute inflammation walled off by fibrosis)
- Chronic inflammation (antigen presentation by macrophages and other APCs activation of CD4+ Th cells)
- Scarring
5
Q
What distinguishes chronic inflammation from acute inflammation?
A
- Chronic inflammation lasts longer and involves simultaneous tissue destruction and repair.
- It is characterized by mononuclear cell infiltration, primarily macrophages and lymphocytes.
6
Q
What causes chronic inflammation?
A
- Persistent infections (e.g., tuberculosis)
- Autoimmune diseases
- Prolonged exposure to irritants (e.g., silica)
7
Q
What are the two types of macrophages in chronic inflammation?
A
- M1 Macrophages: Activated via the classical pathway, involved in microbial killing and inflammation.
- M2 Macrophages: Activated via the alternative pathway, focused on tissue repair and anti-inflammatory responses.
8
Q
How do M1 macrophages contribute to tissue damage?
A
They generate reactive oxygen species and secrete pro-inflammatory cytokines, leading to tissue destruction.
9
Q
What are the potential consequences of chronic inflammation?
A
- Scarring (e.g., cirrhosis)
- Secondary amyloidosis
- Increased risk of malignancy (e.g., chronic hepatitis leading to liver cancer)
10
Q
What is the significance of Toll-like receptors (TLRs) in inflammation?
A
TLRs on macrophages recognize DAMPs and PAMPs, triggering the inflammatory response.
11
Q
A 45-year-old man presents to the emergency department with fever, chills, and a painful red swelling on his leg. Laboratory tests show an elevated white blood cell count with a predominance of neutrophils. Which of the following best describes the primary function of neutrophils during acute inflammation?
A) Antigen presentation
B) Phagocytosis of pathogens
C) Secretion of antibodies
D) Activation of the complement system
A
Correct Answer: B
Explanation: Neutrophils are the primary cells involved in phagocytosis during acute inflammation, rapidly responding to tissue injury and infection.
12
Q
A researcher is studying the role of macrophages in the inflammatory response. Which of the following features is characteristic of M1 macrophages?
A) Promote tissue repair
B) Release anti-inflammatory cytokines
C) Produce reactive oxygen species
D) Inhibit the activation of T cells
A
Correct Answer: C
Explanation: M1 macrophages are involved in the destruction of pathogens and produce reactive oxygen species as part of their inflammatory response.
13
Q
patient develops chronic inflammation due to an autoimmune disease. Which of the following cell types would be predominantly observed in this patient’s affected tissues?
A) Neutrophils
B) Eosinophils
C) Lymphocytes and macrophages
D) Basophils
A
Correct Answer: C
Explanation: Chronic inflammation is characterized by the presence of mononuclear cells, primarily lymphocytes and macrophages, rather than neutrophils.
14
Q
A patient presents with a long-standing infection that has led to the formation of granulomas. Which of the following processes is most likely involved in the pathogenesis of this condition?
A) Acute neutrophilic inflammation
B) Type I hypersensitivity reaction
C) Chronic inflammation with tissue repair
D) Activation of the inflammasome
A
Correct Answer: C
Explanation: Granulomas are a result of chronic inflammation, where there is ongoing tissue damage and repair, typically seen in infections like tuberculosis.
15
Q
A 30-year-old woman with a history of hepatitis B presents with abdominal swelling and fatigue. Liver biopsy reveals extensive fibrosis. What is the most likely outcome of her chronic inflammation?
A) Complete resolution
B) Scarring and cirrhosis
C) Formation of granulomas
D) Acute inflammatory response
A
Correct Answer: B
Explanation: Chronic inflammation from hepatitis B can lead to scarring (fibrosis) and ultimately cirrhosis of the liver.
16
Q
What are the primary cells involved in acute inflammation?
A
Neutrophils
17
Q
Name three major chemical mediators of acute inflammation.
A
Histamine
Prostaglandins
Bradykinin
18
Q
What are the main cells involved in chronic inflammation?
A
Macrophages,
Lymphocytes
Plasma cells.
19
Q
What type of chronic inflammation is characterized by granuloma formation, and what cells are involved?
A
Granulomatous inflammation is characterized by epithelioid macrophages and multinucleated giant cells.
20
Q
What are the three key features of chronic inflammation?
A
Tissue destruction
Fibrosis
Angiogenesis
21
Q
Which cytokines are responsible for the fever and systemic effects of inflammation?
A
IL-1
IL-6
TNF-α
22
Q
What is the role of IFN-γ in chronic inflammation?
A
Activates macrophages
23
Q
A 25-year-old man presents to the emergency department after falling off his bike. He has abrasions and swelling around his knee, with localized redness and pain. Which of the following mediators is primarily responsible for the pain he is experiencing?
(A) Histamine
(B) Prostaglandins
(C) Interleukin-1 (IL-1)
(D) Nitric oxide
(E) Tumor necrosis factor-alpha (TNF-α)
A
(B) Prostaglandins
24
Q
A 30-year-old man presents to the emergency department with a 2-day history of high fever, chills, and muscle aches. He recently returned from a trip abroad where he developed gastrointestinal symptoms. His temperature is 39.0°C (102.2°F), blood pressure is 120/80 mm Hg, and pulse is 105/min. Laboratory findings reveal elevated white blood cells and positive blood cultures for Gram-negative bacilli. Pyrogens from the Gram-negative bacteria have triggered the release of cytokines, leading to his fever.
Which of the following molecules is directly responsible for the increase in temperature set point in this patient?
(A) Cyclooxygenase (COX)
(B) Prostaglandin E2 (PGE2)
(C) Tumor necrosis factor-alpha (TNF-α)
(D) Interleukin-1 (IL-1)
(E) Lipopolysaccharide (LPS)
A
Correct Answer: (B) Prostaglandin E2 (PGE2)
Explanation:
In this case, the patient has a fever caused by pyrogens, such as lipopolysaccharide (LPS), from Gram-negative bacteria. Pyrogens stimulate macrophages to release IL-1 and TNF-α, which then act on the hypothalamus. These cytokines increase cyclooxygenase (COX) activity in the perivascular cells of the anterior hypothalamus, leading to increased production of prostaglandin E2 (PGE2). PGE2 is the direct mediator that raises the temperature set point, leading to fever.
25
A 60-year-old man with a long history of untreated rheumatoid arthritis presents with joint pain and swelling in his hands and knees. Which of the following cells plays the most important role in the chronic inflammatory response observed in his joints?
(A) Neutrophils
(B) Macrophages
(C) Eosinophils
(D) Mast cells
(E) Platelets
(B) Macrophages
26
Which of the following statements best differentiates chronic inflammation from acute inflammation?
(A) Acute inflammation is mediated by macrophages, while chronic inflammation is mediated by neutrophils.
(B) Chronic inflammation is characterized by angiogenesis and fibrosis, while acute inflammation is characterized by neutrophil infiltration.
(C) Acute inflammation is a long-lasting process, while chronic inflammation is short-term.
(D) Chronic inflammation is primarily mediated by prostaglandins and histamine.
(E) Acute inflammation is driven by lymphocytes and plasma cells.
(B) Chronic inflammation is characterized by angiogenesis and fibrosis, while acute inflammation is characterized by neutrophil infiltration.
27
A 35-year-old woman presents with shortness of breath, non-productive cough, and fatigue. A chest X-ray shows bilateral hilar lymphadenopathy. A biopsy of her lung reveals non-caseating granulomas. Which of the following conditions is most likely responsible for her symptoms?
(A) Tuberculosis
(B) Sarcoidosis
(C) Rheumatoid arthritis
(D) Systemic lupus erythematosus (SLE)
(E) Rheumatic fever
(B) Sarcoidosis
28
A 45-year-old man with a history of liver cirrhosis presents with a fever of 38.7°C (101.7°F) and shaking chills. His laboratory results show elevated C-reactive protein (CRP). Which of the following cytokines is most responsible for stimulating the acute phase response and production of CRP?
(A) Interleukin-4 (IL-4)
(B) Interleukin-6 (IL-6)
(C) Interleukin-12 (IL-12)
(D) Tumor necrosis factor-alpha (TNF-α)
(E) Interferon-gamma (IFN-γ)
The correct answer is (B) Interleukin-6 (IL-6).
Explanation:
Interleukin-6 (IL-6) is the primary cytokine responsible for stimulating the acute phase response, including the production of C-reactive protein (CRP), which is synthesized by the liver. IL-6 is released by macrophages and other immune cells in response to infection or tissue injury and plays a central role in mediating inflammation.
29
A 30-year-old woman presents with a red, swollen, and painful left ankle after twisting it while running. Which of the following vascular changes is responsible for the swelling she is experiencing?
(A) Increased vascular permeability
(B) Decreased vascular resistance
(C) Increased smooth muscle contraction
(D) Decreased capillary hydrostatic pressure
(E) Increased arterial resistance
(A) Increased vascular permeability
30
A 40-year-old man presents with a chronic cough and night sweats. His chest X-ray reveals cavitations in the upper lobes. A biopsy of his lung tissue shows caseating granulomas. Which of the following cell types is most important in the formation of the granulomas seen in this patient?
(A) B cells
(B) Epithelioid macrophages
(C) Neutrophils
(D) Mast cells
(E) Platelets
(B) Epithelioid macrophages
31
A 52-year-old woman with a 15-year history of untreated Crohn’s disease presents with abdominal pain, diarrhea, and weight loss. Which of the following cytokines is most likely responsible for the activation of macrophages in this patient’s chronic inflammation?
(A) Interferon-gamma (IFN-γ)
(B) Tumor necrosis factor-alpha (TNF-α)
(C) Interleukin-4 (IL-4)
(D) Interleukin-10 (IL-10)
(E) Interleukin-2 (IL-2)
(A) Interferon-gamma (IFN-γ)
- Th1 cells secrete IFN-γ macrophage classical activation (proinflammatory)
- Th2 cells secrete IL-4 and IL-13macrophage alternative activation (repair and anti-
inflammatory)
32
A 35-year-old woman presents to the clinic with abdominal pain, fatigue, and peripheral neuropathy. Laboratory tests reveal microcytic anemia, elevated blood lead levels, and basophilic stippling of erythrocytes. Which of the following pathophysiological mechanisms best explains the neurological symptoms observed in this patient?
(A) Inhibition of heme synthesis leading to decreased neurotransmitter production
(B) Direct neurotoxic effects causing demyelination of peripheral nerves
(C) Disruption of calcium signaling in neurons leading to synaptic dysfunction
(D) Formation of reactive oxygen species resulting in neuronal apoptosis
(E) Impaired release of acetylcholine at neuromuscular junctions due to decreased calcium availability
(B) Direct neurotoxic effects causing demyelination of peripheral nerves
Explanation:
(A) Inhibition of heme synthesis primarily affects erythropoiesis and does not directly cause neurological symptoms.
(B) Lead is known to have neurotoxic effects, particularly leading to demyelination of peripheral nerves, which aligns with the patient's neurological symptoms.
(C) While lead exposure can disrupt calcium signaling, the primary neurological impact is due to demyelination rather than synaptic dysfunction.
(D) Lead can contribute to oxidative stress, but the primary mechanism for the observed symptoms relates to demyelination.
(E) Although lead can affect neuromuscular function, the symptoms in this case are more closely linked to peripheral neuropathy rather than acetylcholine release impairment.
33
A 53-year-old woman presents to her primary care physician with a 4-month history of progressive fatigue, low-grade fever, and unintentional weight loss. She also reports joint pain in her hands and wrists, particularly in the morning. On physical examination, she has mild scleral icterus, tender, swollen metacarpophalangeal joints, and mild splenomegaly. Laboratory studies reveal:
Hemoglobin: 9.8 g/dL
Platelets: 180,000/µL
White blood cell count: 7,200/µL
Bilirubin, total: 3.1 mg/dL
Bilirubin, direct: 0.5 mg/dL
C-reactive protein: Elevated
Rheumatoid factor: Positive
Direct Coombs test: Positive for IgG antibodies
Peripheral blood smear: Shows spherocytes and no schistocytes
A liver biopsy is performed, and the histological findings demonstrate focal periportal lymphocytic infiltration, with piecemeal necrosis and interface hepatitis.
Which of the following is the most likely underlying cause of this patient’s symptoms?
(A) Autoimmune hemolytic anemia with warm antibodies
(B) Granulomatous inflammation involving the liver
(C) Chronic inflammatory process with immune complex deposition
(D) Granulocyte-macrophage colony-stimulating factor (GM-CSF) overproduction
(E) Antibody-mediated platelet destruction
(C) Chronic inflammatory process with immune complex deposition.
34
What is hypertrophy and in which types of cells does it occur?
Increase in cell size in response to stress.
It occurs in non-dividing cells like skeletal muscle and cardiac muscle
35
What is hyperplasia and how does it differ from hypertrophy?
Increase in the number of cells in a tissue, typically in response to hormonal stimulation.
It differs from hypertrophy, which involves an increase in cell size without an increase in cell number.
36
What are the common causes of atrophy?
- Decreased workload
- Loss of innervation
- Diminished blood supply
- Inadequate nutrition
- Aging
- Hormonal withdrawal
37
What is metaplasia and provide a classic example.
Metaplasia is the reversible change of one differentiated cell type to another.
An example is Barrett’s esophagus, where squamous epithelium is replaced by columnar epithelium in response to chronic acid reflux.
38
What is dysplasia and why is it clinically significant?
Disordered cell growth
Precancerous condition
39
What causes cellular swelling in reversible cell injury?
Failure of ion pumps (e.g., Na+/K+ ATPase) due to ATP depletion
40
In which organ is fatty change commonly seen during reversible cell injury?
Liver
## Footnote
due to metabolic dysfunction.
41
What are the key features of irreversible cell injury?
* Membrane damage
* Mitochondrial dysfunction
* Release of cytochrome c (triggering apoptosis)
* Nuclear changes (karyolysis, pyknosis, and karyorrhexis)
42
What is necrosis and how does it differ from apoptosis?
Necrosis is unregulated cell death caused by injury, characterized by inflammation and cell rupture.
Apoptosis is a regulated, programmed form of cell death without inflammation.
43
What are the main types of necrosis and give examples?
* Coagulative necrosis: Common in ischemic injuries (e.g., myocardial infarction).
* Liquefactive necrosis: Seen in brain infarcts and abscesses.
* Caseous necrosis: Typical in tuberculosis.
* Fat necrosis: Seen in acute pancreatitis.
* Fibrinoid necrosis: Associated with immune-mediated vasculitis.
44
What are the two main pathways leading to apoptosis?
* Intrinsic pathway (triggered by mitochondrial release of cytochrome c)
* Extrinsic pathway (triggered by death receptors like Fas and TNF receptors).
45
What causes oxidative stress and how does it lead to cell injury?
Accumulation of reactive oxygen species (ROS), which damage lipids (lipid peroxidation), proteins, and DNA, leading to cell injury.
46
What is reperfusion injury and what causes it?
Reperfusion injury occurs when blood supply returns to ischemic tissues, leading to a burst of ROS and further tissue damage.
47
How does mitochondrial damage lead to cell death?
Mitochondrial damage leads to ATP depletion and the release of cytochrome c, which triggers apoptosis.
48
In which type of tissue injury is coagulative necrosis typically seen?
Ischemic tissue injury (e.g., myocardial infarction, except in the brain).
49
Where is liquefactive necrosis most commonly found?
Brain infarcts and abscesses, where tissue is digested by enzymes.
50
Which infection is most commonly associated with caseous necrosis?
Tuberculosis.
51
Why is metaplasia clinically significant?
Increases the risk of dysplasia and cancer if the underlying stress persists.
52
A 58-year-old man with a long-standing history of hypertension presents for a routine follow-up. An echocardiogram reveals left ventricular hypertrophy. Which of the following molecular changes is most likely responsible for the hypertrophy observed in his cardiac myocytes?
(A) Decreased synthesis of actin and myosin
(B) Increased production of angiogenic factors
(C) Activation of growth factor receptors and increased protein synthesis
(D) Accumulation of misfolded proteins in the endoplasmic reticulum
(E) Increased cell division and mitotic activity
(C) Activation of growth factor receptors and increased protein synthesis
53
A 52-year-old man presents with chronic cough and increasing shortness of breath. He has a 30-year history of smoking one pack of cigarettes per day. A biopsy of his bronchi reveals stratified squamous epithelium replacing the normal pseudostratified columnar epithelium. Which of the following changes is this patient at risk for if the smoking persists?
(A) Chronic atrophic gastritis
(B) Barrett’s esophagus
(C) Adenocarcinoma of the esophagus
(D) Squamous cell carcinoma of the lung
(E) Transitional cell carcinoma of the bladder
(D) Squamous cell carcinoma of the lung
54
A 63-year-old man is brought to the emergency department after suffering an acute myocardial infarction. He undergoes successful thrombolytic therapy with tissue plasminogen activator (tPA). However, over the next 24 hours, his troponin levels continue to rise, and his condition deteriorates. Which of the following mechanisms most likely explains the continued tissue damage?
(A) Persistent coronary artery occlusion
(B) Reactive oxygen species formation
(C) Myocardial apoptosis
(D) Activation of the intrinsic coagulation cascade
(E) Activation of complement by immune complexes
(B) Reactive oxygen species formation
55
A 34-year-old woman presents with abdominal pain and nausea. She is diagnosed with acute pancreatitis. A biopsy of her pancreas shows enzymatic fat necrosis. Which of the following best describes a distinguishing feature of necrosis, in contrast to apoptosis?
(A) DNA fragmentation into nucleosome-sized fragments
(B) Cell membrane rupture and leakage of cellular contents
(C) Formation of apoptotic bodies
(D) Phagocytosis of apoptotic cells by neighboring cells
(E) Caspase activation leading to cell death
(B) Cell membrane rupture and leakage of cellular contents
56
A 45-year-old man presents with fatigue, jaundice, and dark-colored urine. He was recently treated with sulfa antibiotics for a urinary tract infection. His peripheral blood smear shows Heinz bodies and bite cells. A deficiency of which of the following enzymes is most likely responsible for this patient’s symptoms?
(A) Catalase
(B) Glutathione peroxidase
(C) Glucose-6-phosphate dehydrogenase
(D) Superoxide dismutase
(E) Xanthine oxidase
(C) Glucose-6-phosphate dehydrogenase
57
A 72-year-old man with a history of coronary artery disease and a recent myocardial infarction is found dead at home. An autopsy reveals a well-demarcated area of coagulative necrosis in the left ventricle. Which of the following best describes the characteristic feature of coagulative necrosis?
(A) Lysis of dead cells with formation of cystic spaces
(B) Enzymatic digestion of dead cells and tissue liquefaction
(C) Preservation of cellular architecture with loss of nuclei
(D) Deposition of fibrin-like material in the tissue
(E) Granulomatous inflammation with caseous necrosis
(C) Preservation of cellular architecture with loss of nuclei
58
A 39-year-old woman presents with severe epigastric pain that radiates to her back. Laboratory studies reveal elevated serum lipase and amylase levels. An abdominal CT scan shows an inflamed and swollen pancreas. During surgery, chalky-white lesions are found in the peripancreatic fat. Which of the following best explains the pathogenesis of the fat necrosis observed in this patient?
(A) Ischemic damage to adipocytes
(B) Activation of pancreatic enzymes leading to hydrolysis of triglycerides
(C) Accumulation of immune complexes in fat tissue
(D) Trauma-induced rupture of adipocytes
(E) Peroxidation of lipids due to oxidative stress
(B) Activation of pancreatic enzymes leading to hydrolysis of triglycerides
59
A 56-year-old woman with a history of hepatitis C and cirrhosis undergoes a liver biopsy. The biopsy reveals extensive hepatocyte apoptosis. Which of the following molecular events initiates the intrinsic pathway of apoptosis in this patient?
(A) Activation of Fas receptor
(B) Binding of TNF-α to TNF receptor
(C) Release of cytochrome c from mitochondria
(D) Activation of caspase-8
(E) Inhibition of p53 tumor suppressor protein
(C) Release of cytochrome c from mitochondri
60
A 45-year-old woman with a long-standing history of systemic hypertension presents for a routine follow-up. Physical examination reveals an elevated blood pressure. A cardiac biopsy is performed and shows an increase in myocyte size but no increase in the number of cells. Which of the following best explains the cardiac changes observed in this patient?
(A) Metaplasia
(B) Hyperplasia
(C) Dysplasia
(D) Hypertrophy
(E) Atrophy
(D) Hypertrophy
61
A 70-year-old man is brought to the hospital after a sudden onset of right-sided weakness and slurred speech. A CT scan of the brain reveals a large infarct in the left middle cerebral artery territory. Two weeks later, the infarcted area is characterized by liquefactive necrosis. Which of the following enzymes is primarily responsible for this type of necrosis in the brain?
(A) Caspases
(B) Pancreatic lipase
(C) Lysosomal enzymes
(D) Cytochrome c
(E) Perforin
(C) Lysosomal enzymes
62
A 64-year-old retired shipyard worker has been experiencing shortness of breath, a cough, and chest pain for 5 months. In that time he has lost 14.5 kg (32 lb). He develops progressive ascites, and ultimately dies due to a pulmonary embolus. Autopsy results are shown in the image. Exposure to which substance is a risk factor for this patient’s disorder?
(A) Aflatoxin B
(B) Asbestos
(C) Benzene
D) Cadmium
(E) Silica
(B) Asbestos
63
Golden-brown fusiform rods resembling dumbbells in alveolar sputum, visualized with Prussian blue stain
Diagnosis?
Asbestosis
64
“Ivory white,” calcified, supradiaphragmatic and pleural A plaques are pathognomonic of
Asbestosis
65
Disease associated with: shipbuilding, roofing, plumbing.
Asbestosis
66
A 37-year-old HIV-positive man presents for evaluation of anogenital lesions. He states that the lesions have been present for years, but have recently grown in size and become pruritic and tender. On examination he is circumcised and has multiple hyperkeratotic papules on his penis shaft, perineum, and anal area. He also has a palpable rectal mass with guaiac- positive stool and conjunctival pallor. On further questioning, he admits to recent unintentional weight loss, constipation, and bloating. His CD4+ cell count is 150/mm3 and his he- matocrit is 26%. CT scan of the abdomen shows a 3 × 4-cm rectal mass with multiple metastatic lesions in his liver. What tumor-suppressor protein is targeted by the virus causing this patient’s rectal cancer?
(A) APC
(B) BRCA1
(C) MSH2
(D) NF1
(E) p53
**(E) p53**
HPV produces E6 and E7 proteins, which inactivate the p53 and Rb tumor-suppressor proteins, respectively.
67
Cancer association with HPV 16 and 18:
* Cervical and penile/anal carcinoma
* Head and neck cancer
68
Cancer association with Schistosoma haematobium
Squamous cell bladder cancer
69
Cancer association with EBV:
* Burkitt lymphoma
* Hodgkin lymphoma
* Nasopharyngeal carcinoma
* 1° CNS lymphoma (in immunocompromised patients)
70
What is the structure of human papillomavirus (HPV)?
HPV is a non-enveloped, double-stranded DNA virus belonging to the Papillomaviridae family.
71
Which HPV types are considered high risk for causing cancer?
HPV types 16 and 18
72
How do HPV contribute to carcinogenesis?
E6 degrades p53, and E7 inactivates Rb (retinoblastoma protein), leading to uncontrolled cell growth and increased risk of cancer.
73
Which HPV types are associated with benign lesions such as genital warts?
HPV types 6 and 11 are low risk and cause genital warts (condylomata acuminata) and laryngeal papillomatosis.
74
A 66-year-old woman has an autosomal recessive disease with multiple sequelae, including diabetes mellitus and arthritis. Physical examination reveals hepatomegaly and skin hyper-pigmentation. A biopsy of her liver is shown in the image. What is the most likely explanation for her health problems?
A) Chronic ingestion of alcohol
(B) Genetic deficiency in the synthesis of
β-globin chains
(C) Inappropriately high iron absorption (D) Mutation in RBC membrane protein
75
Multiple blood transfusions or hereditary HFE mutation (can result in heart failure, “bronze diabetes,” andrisk of hepatocellular carcinoma)
Diagnosis?
Hemochromatosis
76
How is the interpretation of iron studies on hemochromatosis?
Increased serum iron
Decreased transferrina or TIBIC
Increased Ferritin
Increased % transferrin saturation (serum iron/TIBC)
77
What are de genetic features of hereditary hemochromatosis?
Autosomal recessive. Mutation in HFE gene, located on chromosome 6
78
Hemochromatosis triad
Cirrhosis
Diabetes mellitus
Skin pigmentation
(“bronze diabetes”)
79
A patient with AIDS and a CD4+ cell count <50/mm3 is suffering from an infection that af- fects his lungs, eyes, gastrointestinal tract, and central nervous system. Results of a biopsy are shown in the image. With what is the patient most likely infected?
(A) Candida albicans
(B) Cryptococcus neoformans
(C) Cytomegalovirus
(D) Herpes simplex virus
(E) Mycobacterium avium (F) Pneumocystis jiroveci
80
Mechanism of Fever Induction
Pyrogens (e.g., LPS) stimulate macrophages to release IL-1 and TNF-α.
IL-1 and TNF-α enhance COX activity in the perivascular cells of the anterior hypothalamus.
This increase leads to the production of PGE2 (prostaglandin E2).
PGE2 raises the temperature set point in the hypothalamus, resulting in fever.
81
Lead poisoning peripheral blood smear shows:
Basophilic stippling
82
Lead poisoning bone marrow shows:
Ringed sideroblasts
83
Examples of diseases with immune complex deposition:
Rheumatoid arthritis (RA): A chronic autoimmune disease where immune complexes deposit in the joints, causing inflammation, synovitis, and joint damage. Immune complexes can also deposit in other organs, contributing to systemic symptoms like vasculitis, pericarditis, and glomerulonephritis.
Systemic lupus erythematosus (SLE): Another autoimmune disease where immune complexes deposit in multiple organs, including the kidneys (causing lupus nephritis), skin, and brain. This leads to chronic inflammation and organ dysfunction.
Post-streptococcal glomerulonephritis: Following a streptococcal infection, immune complexes form and deposit in the kidneys, leading to inflammation and glomerular injury.
84
What are the four components of Tetralogy of Fallot (TOF)?
Pulmonary stenosis
Right ventricular hypertrophy
Overriding aorta
Ventricular septal defect (VSD)
85
What classic sign is seen on a chest X-ray in Tetralogy of Fallot?
A boot-shaped heart due to right ventricular hypertrophy.
86
What causes "Tet spells" in Tetralogy of Fallot, and what relieves them?
"Tet spells" are caused by an increase in right-to-left shunting, leading to cyanosis. Squatting increases systemic vascular resistance, reducing the shunt and improving oxygenation.
87
What is the key feature of Transposition of the Great Arteries (TGA)?
Back: The aorta and pulmonary artery are switched (aorta arises from the right ventricle and pulmonary artery from the left ventricle), resulting in two separate circulatory systems. This causes cyanosis immediately after birth.
88
What is the characteristic chest X-ray finding in Transposition of the Great Arteries (TGA)?
Back: An "egg on a string" appearance, due to a narrow mediastinum and abnormal positioning of the great vessels.
89
What is required for survival in Transposition of the Great Arteries?
Back: Survival depends on mixing of oxygenated and deoxygenated blood, which can occur through a patent ductus arteriosus (PDA), patent foramen ovale (PFO), or ventricular septal defect (VSD). Prostaglandin E1 can be given to keep the ductus arteriosus open.
90
What is Truncus Arteriosus?
Back: Truncus Arteriosus is a congenital defect where a single arterial trunk arises from both ventricles, supplying both the systemic and pulmonary circulations. This results in mixed oxygenated and deoxygenated blood.
91
What is the pathophysiology of Tricuspid Atresia?
Back: In Tricuspid Atresia, there is an absence of the tricuspid valve, preventing blood flow from the right atrium to the right ventricle. For survival, a patent foramen ovale (PFO) or atrial septal defect (ASD) is required to allow blood to reach the lungs.
92
What is Total Anomalous Pulmonary Venous Return (TAPVR)?
Back: In TAPVR, the pulmonary veins drain into the right atrium (or veins associated with it) instead of the left atrium. This causes mixed oxygenated and deoxygenated blood and leads to cyanosis.
93
What are the clinical features common to all right-to-left shunts?
Back:
Cyanosis (bluish skin due to low oxygen levels)
Polycythemia (increased red blood cells as a compensatory response to low oxygen)
Clubbing of fingers and toes
Risk of paradoxical emboli (due to blood bypassing the lungs)
94
A 3-week-old infant presents to the emergency department with severe cyanosis and difficulty breathing. Echocardiography reveals a large ventricular septal defect and an overriding aorta. The pulmonary valve is significantly stenotic, and the right ventricle is hypertrophied. Which of the following hemodynamic changes would most likely explain the patient's acute cyanotic episodes?
(A) Increased systemic vascular resistance
(B) Decreased right ventricular pressure
(C) Increased right-to-left shunt
(D) Decreased pulmonary vascular resistance
(E) Increased left-to-right shunt
(C) Increased right-to-left shunt
95
A 1-day-old newborn is evaluated for severe cyanosis and poor feeding. His oxygen saturation is 75% in both the upper and lower extremities. Echocardiography reveals the pulmonary artery arising from the left ventricle and the aorta arising from the right ventricle. The foramen ovale is patent, and there is a small ventricular septal defect. Which of the following pharmacologic interventions is essential to maintain the newborn's survival until surgery can be performed?
(A) Indomethacin
(B) Furosemide
(C) Prostaglandin E1
(D) Sildenafil
(E) Digoxin
(C) Prostaglandin E1
96
Ebstein anomaly is associated with an intra utero exposure:
Lithium
97
What is Ebstein anomaly?
Back: Ebstein anomaly is a congenital heart defect characterized by the downward displacement of the tricuspid valve into the right ventricle, leading to atrialization of part of the right ventricle and tricuspid regurgitation
98
What are the key features of Ebstein anomaly?
Back:
Downward displacement of the tricuspid valve.
Atrialization of the right ventricle.
Tricuspid regurgitation.
Associated right-to-left shunt through ASD or PFO, leading to cyanosis.
Risk of arrhythmias, including Wolff-Parkinson-White syndrome.
99
What are the common clinical presentations of Ebstein anomaly?
Back:
Cyanosis (due to right-to-left shunt)
Heart failure symptoms (fatigue, dyspnea)
Palpitations or arrhythmias (such as supraventricular tachycardia)
100
What congenital heart defect is commonly associated with Ebstein anomaly?
Back: An atrial septal defect (ASD) or patent foramen ovale (PFO) is commonly associated, which can lead to a right-to-left shunt and cyanosis.
101
What are the celular injury adaptations?
- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia
- Dysplasia
102
What is apoptosis?
Back: Apoptosis is an ATP-dependent programmed cell death that is tightly regulated and does not cause inflammation.
103
What are the key features of apoptosis on histology?
Cell shrinkage
Deeply eosinophilic cytoplasm with basophilic nucleus
Nuclear changes: pyknosis (nuclear shrinkage) and karyorrhexis (nuclear fragmentation)
Formation of apoptotic bodies
No inflammation
104
What is DNA laddering, and why is it significant?
Back: DNA laddering refers to the cleavage of DNA into fragments of approximately 180 base pairs, which is a hallmark of apoptosis and a sensitive indicator of this process.
105
What is the intrinsic pathway of apoptosis?
The intrinsic pathway occurs when a regulating factor is withdrawn (e.g., IL-2 after an immune response) or after exposure to injurious stimuli (e.g., radiation, toxins, hypoxia) and is regulated by the Bcl-2 family of proteins.
Bax and Bak promote apoptosis by forming pores in the mitochondrial membrane, allowing the release of cytochrome c which activates caspases.
106
What are the triggers of intrinsic pathway of apoptosis?
When a regulating factor is withdrawn (e.g., IL-2 after an immune response) or after exposure to injurious stimuli (e.g., radiation, toxins, hypoxia)
107
How does the intrinsic pathway of apoptosis is regulated?
By Bcl-2 family proteins
Pro-apoptotic: Bax and Bak form pores in the mitochondrial membrane, leading to cytochrome c release and caspase activation.
Anti-apoptotic: Bcl-2 and Bcl-xL maintain mitochondrial membrane integrity, preventing cytochrome c release and apoptosis.
108
What is the extrinsic pathway of apoptosis?
The extrinsic pathway is initiated by the binding of death ligands (e.g., FasL or TNF-α) to death receptors (e.g., Fas/CD95 or TNFR). This leads to the formation of the death-inducing signaling complex (DISC) and the activation of caspase-8, which activates downstream caspases, leading to cell death.
109
What is the perforin/granzyme B pathway in apoptosis?
Back: This pathway is used by cytotoxic T-cells and NK cells. Perforin forms pores in the target cell membrane, allowing granzyme B to enter the cell and activate caspases, triggering apoptosis.
110
What is the role of caspases in apoptosis?
Back: Caspases are proteases that orchestrate the cell's destruction during apoptosis. They exist in inactive forms and are activated by both intrinsic and extrinsic pathways. Initiator caspases (e.g., caspase-8 and -9) activate executioner caspases (e.g., caspase-3, -6, -7), which degrade cellular components.
111
What is the importance of the Fas-FasL interaction in apoptosis for auto-immunity prevention?
This interaction is crucial for thymic medullary negative selection, where self-reactive T-cells are eliminated
112
How does p53 induce apoptosis?
p53 is a tumor suppressor protein that induces apoptosis in response to severe DNA damage. It increases the expression of pro-apoptotic proteins like Bax, leading to cytochrome c release and activation of the intrinsic apoptosis pathway.
113
What is the difference between apoptosis and necrosis?
Back:
Apoptosis: Programmed, energy-dependent, no inflammation, membrane remains intact, and involves DNA fragmentation (laddering).
Necrosis: Uncontrolled, energy-independent, causes inflammation, membrane rupture, and random DNA fragmentation (smearing).
114
What is Autoimmune Lymphoproliferative Syndrome (ALPS)?
Defective Fas-FasL interaction leads to failure of clonal deletion, resulting in an increased number of self-reacting lymphocytes, causing lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias.
115
What are the cellular changes in the apoptosis?
Cell shrinkage, chromatin condensation, membrane blebbing, and the formation of apoptotic bodies, which are phagocytosed without triggering inflammation.
116
A 54-year-old man is diagnosed with follicular lymphoma. Cytogenetic analysis reveals a translocation t(14;18), which leads to overexpression of a protein. Which of the following proteins is most likely overexpressed in this patient?
(A) p53
(B) Bcl-2
(C) Bax
(D) Fas
(E) Caspase-9
Correct answer: (B) Bcl-2
Explanation: Follicular lymphoma is characterized by the t(14;18) translocation, which results in the overexpression of Bcl-2, an anti-apoptotic protein. This prevents apoptosis of B cells, contributing to lymphoma development.
117
A 24-year-old woman is evaluated for fatigue, weight loss, and easy bruising. Laboratory studies show leukocytosis with an abnormal population of immature lymphocytes. Further testing reveals a defect in the Fas-FasL interaction. Which of the following best describes the role of the Fas-FasL interaction in the immune system?
(A) It promotes positive selection of lymphocytes in the thymus.
(B) It induces apoptosis of self-reactive lymphocytes during negative selection in the thymus.
(C) It stimulates the differentiation of lymphocytes in response to infection.
(D) It mediates cell division in response to growth factors.
(E) It is responsible for DNA repair in lymphocytes.
Correct answer: (B) It induces apoptosis of self-reactive lymphocytes during negative selection in the thymus.
Explanation: Fas-FasL interaction is crucial for negative selection in the thymus, ensuring the elimination of self-reactive T-cells to prevent autoimmunity.
118
A 7-year-old boy with a history of recurrent infections is found to have an elevated white blood cell count and generalized lymphadenopathy. Genetic testing reveals a mutation affecting the Fas receptor. Which of the following is the most likely diagnosis?
(A) Autoimmune Lymphoproliferative Syndrome (ALPS)
(B) Severe Combined Immunodeficiency (SCID)
(C) X-linked agammaglobulinemia
(D) Chronic Granulomatous Disease
(E) Ataxia-telangiectasia
Correct answer: (A) Autoimmune Lymphoproliferative Syndrome (ALPS)
Explanation: ALPS is caused by mutations affecting the Fas receptor, leading to impaired apoptosis of lymphocytes and resulting in lymphoproliferation and autoimmune manifestations.
119
A researcher is studying the mechanisms of apoptosis in cancer cells. She identifies a protein that forms pores in the mitochondrial membrane, allowing the release of cytochrome c. Once in the cytosol, cytochrome c activates a cascade of proteolytic enzymes. Which of the following proteins is most likely responsible for pore formation?
(A) Bcl-2
(B) Bcl-xL
(C) Bax
(D) Fas
(E) Granzyme B
Correct answer: (C) Bax
Explanation: Bax is a pro-apoptotic member of the Bcl-2 family that forms pores in the mitochondrial membrane, leading to the release of cytochrome c and the activation of the intrinsic apoptotic pathway.
120
A 3-year-old boy with a genetic mutation in the p53 gene is at an increased risk of developing multiple types of cancers. Which of the following best explains why p53 mutations lead to cancer?
(A) Loss of p53 inhibits DNA replication.
(B) Mutated p53 promotes cell cycle progression despite DNA damage.
(C) Loss of p53 enhances immune surveillance of cancer cells.
(D) Mutated p53 increases cellular differentiation.
(E) Loss of p53 increases susceptibility to infections.
Correct answer: (B) Mutated p53 promotes cell cycle progression despite DNA damage.
Explanation: p53 is a tumor suppressor that promotes apoptosis in response to DNA damage. Mutations in p53 allow cells with damaged DNA to continue dividing, contributing to cancer development.
121
A 48-year-old man undergoes chemotherapy for treatment of lymphoma. The chemotherapy induces apoptosis in the cancer cells by damaging their DNA. Which of the following proteins is most likely activated to initiate the intrinsic pathway of apoptosis?
(A) Caspase-8
(B) Fas
(C) Bax
(D) Granzyme B
(E) TNF-α
Correct answer: (C) Bax
Explanation: Bax is activated in response to DNA damage and forms pores in the mitochondrial membrane, allowing cytochrome c release and triggering the intrinsic pathway of apoptosis.
122
A 5-year-old girl has a rare genetic disorder in which she is unable to mount an effective cytotoxic immune response. Her T-cells are capable of recognizing and binding to target cells, but they cannot induce apoptosis of the infected or cancerous cells. Which of the following pathways is most likely defective in this patient?
(A) Intrinsic mitochondrial pathway
(B) Fas-FasL pathway
(C) Granzyme-perforin pathway
(D) TNF-α pathway
(E) DNA laddering pathway
Correct answer: (C) Granzyme-perforin pathway
Explanation: The granzyme-perforin pathway is essential for the cytotoxic activity of T-cells and NK cells. Defects in this pathway prevent the induction of apoptosis in infected or cancerous cells.
123
A 50-year-old woman with systemic lupus erythematosus presents with joint pain and fatigue. The dysregulation of apoptosis in self-reactive lymphocytes is thought to contribute to the pathogenesis of her disease. Which of the following apoptosis-related defects is most likely involved in this patient?
(A) Excessive activation of pro-apoptotic proteins
(B) Overexpression of anti-apoptotic proteins
(C) Failure of Fas-mediated apoptosis of self-reactive lymphocytes
(D) Increased activity of caspase-3
(E) Loss of cytochrome c release from the mitochondria
Correct answer: (C) Failure of Fas-mediated apoptosis of self-reactive lymphocytes
Explanation: In systemic lupus erythematosus, dysregulation of apoptosis often involves a failure of Fas-mediated apoptosis, leading to the survival of self-reactive lymphocytes that attack the body's own tissues.
124
A 45-year-old man presents with exertional chest pain that has progressively worsened over the past few months. Coronary angiography reveals a 75% occlusion of the left anterior descending artery due to atherosclerosis. Which of the following cells is most likely responsible for producing the fibrous cap seen in atherosclerotic plaques?
A. Neutrophils
B. Smooth muscle cells
C. Endothelial cells
D. Macrophages
E. Lymphocytes
125
A 6-month-old male presents with recurrent infections, hepatosplenomegaly, and developmental delay. Genetic analysis reveals a deficiency of the enzyme glucocerebrosidase. Accumulation of glucocerebroside in macrophages is most likely to be observed in which of the following diseases?
A. Niemann-Pick disease
B. Tay-Sachs disease
C. Gaucher disease
D. Fabry disease
E. Hurler syndrome
126
A 55-year-old female presents with a 3-month history of fatigue, weight loss, and night sweats. A peripheral blood smear shows numerous smudge cells. Flow cytometry reveals the presence of CD5 and CD20 positive cells. What is the most likely diagnosis?
A. Acute myelogenous leukemia
B. Chronic lymphocytic leukemia
C. Acute lymphoblastic leukemia
D. Hairy cell leukemia
E. Hodgkin lymphoma
127
A 60-year-old male presents with difficulty urinating and lower back pain. His prostate-specific antigen (PSA) level is elevated. A biopsy of his prostate gland shows small glands with prominent nucleoli and loss of basal cells. What is the most likely diagnosis?
A. Benign prostatic hyperplasia
B. Acute prostatitis
C. Chronic prostatitis
D. Prostate adenocarcinoma
E. Transitional cell carcinoma
128
35-year-old female presents with fever, weight loss, and a 3 cm mass in her neck. A biopsy of the mass reveals large, binucleate cells with prominent nucleoli (Reed-Sternberg cells) in a background of lymphocytes and eosinophils. What is the most likely diagnosis?
A. Follicular lymphoma
B. Burkitt lymphoma
C. Hodgkin lymphoma
D. Diffuse large B-cell lymphoma
E. Mantle cell lymphoma
129
A 40-year-old male presents with difficulty swallowing and chronic heartburn. Endoscopy reveals a stricture and a biopsy of the esophagus shows intestinal metaplasia with goblet cells. Which of the following is the most likely underlying condition?
A. Achalasia
B. Barrett esophagus
C. Squamous cell carcinoma
D. Peptic ulcer disease
E. Esophageal varices
130
A 65-year-old male presents with a 3-month history of fatigue, generalized edema, and foamy urine. Urinalysis reveals 4+ proteinuria, but no red blood cells or casts. Renal biopsy shows effacement of podocyte foot processes on electron microscopy. What is the most likely diagnosis?
A. Membranous nephropathy
B. Focal segmental glomerulosclerosis
C. Minimal change disease
D. Diabetic nephropathy
E. IgA nephropathy
131
A 28-year-old woman presents with a 2-week history of fever, arthritis, and a malar rash. Laboratory studies show a positive anti-nuclear antibody (ANA) and anti-double-stranded DNA antibodies. Which of the following is the most likely renal complication of this disease?
A. Poststreptococcal glomerulonephritis
B. Alport syndrome
C. Lupus nephritis
D. Goodpasture syndrome
E. Berger disease
132
A 40-year-old woman with a history of multiple blood transfusions presents with jaundice and dark urine. Laboratory tests show elevated indirect bilirubin and a positive direct Coombs test. Which of the following is the most likely underlying mechanism of this patient's anemia?
A. Hereditary spherocytosis
B. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
C. Autoimmune hemolytic anemia
D. Sickle cell disease
E. Pyruvate kinase deficiency
133
A 55-year-old male presents with fatigue, weight loss, and night sweats. A peripheral blood smear reveals granulocytes at all stages of differentiation, and a markedly elevated white blood cell count. Genetic analysis reveals a t(9;22) translocation. Which of the following is the most likely diagnosis?
A. Acute lymphoblastic leukemia
B. Acute myelogenous leukemia
C. Chronic myelogenous leukemia
D. Myelodysplastic syndrome
E. Hairy cell leukemia
134
A 65-year-old man presents to the emergency department with crushing substernal chest pain radiating to his left arm. He is diagnosed with a myocardial infarction. Which of the following histologic changes would most likely be seen 24 hours after the onset of the myocardial infarction?
A. Coagulative necrosis with neutrophil infiltration
B. Granulation tissue and neovascularization
C. Dense collagenous scar
D. Wavy fibers with no inflammatory infiltrate
E. Macrophages and fibroblasts
135
A 50-year-old woman with a history of hypertension presents with severe chest pain that radiates to her back. Chest x-ray reveals a widened mediastinum. What is the most likely underlying cause of this patient's condition?
A. Aortic dissection
B. Acute pericarditis
C. Pulmonary embolism
D. Myocardial infarction
E. Pneumothorax
136
A 60-year-old man presents with progressive dyspnea and lower extremity swelling. Physical examination reveals jugular venous distension and a positive hepatojugular reflux. Echocardiography shows thickening of the ventricular walls and impaired diastolic filling. Which of the following is the most likely diagnosis?
A. Dilated cardiomyopathy
B. Restrictive cardiomyopathy
C. Hypertrophic cardiomyopathy
D. Constrictive pericarditis
E. Cardiac tamponade
137
A 5-year-old boy presents with fever, rash, and bilateral conjunctivitis. He is also noted to have a swollen tongue with prominent papillae (strawberry tongue). Which of the following is the most serious complication of this disease?
A. Aortic aneurysm
B. Coronary artery aneurysm
C. Pericardial effusion
D. Pulmonary hypertension
E. Mitral valve prolapse
138
A 70-year-old man presents with syncope while walking up the stairs. On physical examination, a harsh systolic ejection murmur is heard at the right second intercostal space that radiates to the carotids. What is the most likely diagnosis?
A. Aortic stenosis
B. Mitral regurgitation
C. Aortic regurgitation
D. Mitral stenosis
E. Tricuspid regurgitation
139
A 55-year-old woman presents with a sudden onset of sharp chest pain that worsens with inspiration and improves when leaning forward. An ECG reveals diffuse ST-segment elevations. Which of the following is the most likely cause of her symptoms?
A. Myocardial infarction
B. Aortic dissection
C. Acute pericarditis
D. Pulmonary embolism
E. Tension pneumothorax
140
A 75-year-old man with a history of hypertension and smoking presents with a pulsatile abdominal mass. A CT scan confirms the presence of an abdominal aortic aneurysm (AAA). What is the most significant risk factor for the development of this condition?
A. Hyperlipidemia
B. Diabetes mellitus
C. Smoking
D. Family history of cardiovascular disease
E. Physical inactivity
141
A 35-year-old man presents to the emergency department with fever, new-onset hA 45-year-old woman with a history of systemic lupus erythematosus (SLE) presents with fatigue, dyspnea, and bilateral leg swelling. Echocardiography reveals a dilated left ventricle with poor contractility. Which of the following is the most likely underlying mechanism?
A. Viral myocarditis
B. Alcoholic cardiomyopathy
C. Rheumatic heart disease
D. Dilated cardiomyopathy secondary to SLE
E. Hypertrophic obstructive cardiomyopathyeart murmur, and Janeway lesions on the palms and soles. Blood cultures reveal Streptococcus viridans. What is the most likely underlying condition?
A. Rheumatic fever
B. Infective endocarditis
C. Pericarditis
D. Myocarditis
E. Libman-Sacks endocarditis
142
A 60-year-old male presents with a history of severe lower extremity pain, particularly after walking. He has diminished pulses in his legs and feet, and an ankle-brachial index of 0.6. What is the most likely underlying pathology?
A. Atherosclerosis
B. Deep vein thrombosis
C. Varicose veins
D. Buerger disease
E. Raynaud phenomenon
143
A 65-year-old man presents with resting tremor, bradykinesia, and cogwheel rigidity. MRI of the brain reveals loss of dopaminergic neurons in the substantia nigra. Which of the following findings is most likely to be seen on histopathology?
A. Neurofibrillary tangles
B. Lewy bodies
C. Amyloid plaques
D. Pick bodies
E. Negri bodies
144
A 30-year-old woman presents with episodes of diplopia, muscle weakness, and numbness that have occurred intermittently over the past 2 years. MRI shows multiple white matter lesions in different areas of the brain and spinal cord. What is the most likely diagnosis?
A. Guillain-Barré syndrome
B. Multiple sclerosis
C. Myasthenia gravis
D. Amyotrophic lateral sclerosis
E. Lambert-Eaton myasthenic syndrome
145
A 55-year-old man presents with progressive difficulty walking and frequent falls. His family history is significant for similar symptoms in his father. On physical examination, he has a high-stepping gait and a positive Romberg sign. Genetic testing reveals a GAA trinucleotide repeat expansion. Which of the following is the most likely diagnosis?
A. Amyotrophic lateral sclerosis
B. Huntington disease
C. Friedreich ataxia
D. Duchenne muscular dystrophy
E. Myotonic dystrophy
146
A 75-year-old man presents with rapidly progressive dementia and myoclonus. MRI shows areas of hyperintensity in the basal ganglia and thalamus. A brain biopsy reveals spongiform changes in the gray matter without inflammatory infiltrate. What is the most likely diagnosis?
A. Alzheimer disease
B. Creutzfeldt-Jakob disease
C. Parkinson disease
D. Lewy body dementia
E. Pick disease
147
A 45-year-old woman presents with worsening headaches and difficulty concentrating. MRI of the brain reveals a 4 cm extra-axial mass attached to the dura with a dural tail sign. Histology shows whorled cell clusters and psammoma bodies. What is the most likely diagnosis?
A. Glioblastoma multiforme
B. Meningioma
C. Schwannoma
D. Medulloblastoma
E. Ependymoma
148
A 68-year-old man presents with sudden onset of weakness in his right arm and leg, as well as difficulty speaking. His symptoms began 2 hours ago. CT of the brain shows no hemorrhage. What is the best initial management for this patient?
A. Heparin
B. Aspirin
C. Tissue plasminogen activator (tPA)
D. Warfarin
E. Clopidogrel
149
A 25-year-old woman presents with episodes of severe, throbbing headaches associated with nausea, photophobia, and visual auras. The patient’s symptoms typically last for several hours. What is the most likely diagnosis?
A. Cluster headache
B. Tension headache
C. Migraine headache
D. Trigeminal neuralgia
E. Temporal arteritis
150
A 7-year-old boy presents with morning headaches, vomiting, and ataxia. MRI rA 32-year-old woman presents with weakness, fatigue, and difficulty chewing that worsens throughout the day. Physical exam reveals ptosis and diplopia. Edrophonium (Tensilon) test transiently improves her symptoms. What is the most likely underlying cause?
A. Autoantibodies against acetylcholine receptors
B. Autoantibodies against voltage-gated calcium channels
C. Demyelination of peripheral nerves
D. Loss of dopaminergic neurons in the substantia nigra
E. Trinucleotide repeat expansioneveals a mass in the cerebellum. A biopsy shows small blue cells that are densely packed and Homer-Wright rosettes. What is the most likely diagnosis?
A. Pilocytic astrocytoma
B. Medulloblastoma
C. Ependymoma
D. Craniopharyngioma
E. Glioblastoma multiforme
151
A 68-year-old woman presents with progressively worsening memory loss, confusion, and difficulty performing daily activities over the past 2 years. MRI reveals cortical atrophy, particularly in the hippocampus. Histologic analysis shows extracellular amyloid plaques and intracellular neurofibrillary tangles. What is the most likely diagnosis?
A. Vascular dementia
B. Lewy body dementia
C. Frontotemporal dementia
D. Alzheimer disease
E. Normal pressure hydrocephalus
152
What is the classic histologic finding in rheumatic heart disease?
Back: Aschoff bodies (granulomatous nodules with giant cells) and Anitschkow cells (enlarged macrophages with wavy nuclei).
153
What is the most common cause of infective endocarditis?
Back: Staphylococcus aureus is the most common cause of acute infective endocarditis, especially in IV drug users. Streptococcus viridans is the most common cause of subacute infective endocarditis.
154
What are Janeway lesions and Osler nodes?
Back: Both are signs of infective endocarditis.
Janeway lesions: Painless, erythematous macules on palms and soles.
Osler nodes: Painful nodules on finger and toe pads.
155
What are the pathological changes seen in myocarditis?
Back: Myocarditis is inflammation of the myocardium, often viral in origin (e.g., Coxsackievirus), with lymphocytic infiltrate and focal necrosis of myocardial cells.
156
What are the most common complications after a myocardial infarction?
Back: Complications include arrhythmias, ventricular rupture, papillary muscle rupture, heart failure, and Dressler syndrome (autoimmune pericarditis).
157
What are the histologic changes 12-24 hours post-myocardial infarction (MI)?
Back: Early coagulative necrosis, with the presence of wavy fibers and neutrophilic infiltration
158
What gross and microscopic changes occur 1-3 days after MI?
Back:
Gross: Hyperemia (increased redness).
Microscopic: Extensive coagulative necrosis, with acute inflammation and neutrophils.
159
What is Dressler syndrome?
Autoimmune-mediated post-myocardial infarction pericarditis occurring weeks to months after MI, presenting with fever, pleuritic pain, and pericardial effusion.
160
What is the most common type of congenital heart defect?
Ventricular septal defect (VSD) is the most common congenital heart defect.
161
What are the three main phases of wound healing and their effector cells?
- Inflammatory (up to 3 days after wound): Platelets, neutrophils, macrophages
- Proliferative (day 3–weeks after wound): Fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages
- Remodeling (1 week–6+ months after wound): Fibroblasts
162
What are the key growth factors involved in wound healing, and what roles do they play?
- VEGF: Stimulates angiogenesis (new blood vessels), important in scar formation and tumor growth.
- FGF: Attracts fibroblasts and stimulates angiogenesis and collagen production.
- TGF-beta: Promotes collagen production and has anti-inflammatory properties.
- PDGF: Stimulates fibroblast growth, migration, and collagen synthesis.
163
What types of collagen are involved in scar formation, and how do they change during wound healing?
- Type III Collagen: Initially deposited during early scar formation.
- Type I Collagen: Replaces type III collagen during the maturation phase to form a stronger scar.
164
What role do metalloproteinases and lysyl oxidase play in wound healing?
- Metalloproteinases: Zinc-dependent enzymes that degrade type III collagen, essential for scar remodeling.
- Lysyl Oxidase: Copper-dependent enzyme that cross-links collagen, making the scar stronger.
165
What is the difference between a keloid and a hypertrophic scar?
- Keloid: Raised scar that extends beyond the borders of the original wound. Contains type I and III collagen in a disorganized manner.
- Hypertrophic Scar: Raised scar that remains within the wound borders. Contains mostly type III collagen in an organized pattern.
166
What phase of wound healing is happening up to 3 days after wound and what are the key features?
Inflammatory phase:
- Clot formation
- Increase vessel permeability
- Neutrophil migration into tissue
- Macrophages clear debris 2 days later
167
What phase of wound healing is happening after 3 days to weeks after wound and what are the key features?
Proliferative phase:
- Deposition of granulation tissue and type
III collagen
- Angiogenesis
- Epithelial cell proliferation
- Dissolution of clot
- Wound contraction (mediated by myofibroblasts)
168
What phase of wound healing is happening after 1 week to 6 months after wound and what are the key features?
Remodeling:
- Type III collagen replaced by type I collagen
- Increase of tensile strength of tissue
- Collagenases (require zinc to function) break down type III collagen
169
What cause delayed second phase of wound healing?
Vitamin C and copper deficiency
170
What cause delayed third phase of wound healing?
Zinc deficiency
171
What is the Warburg effect, and how do cancer cells generate energy? A: The Warburg effect is the process by which cancer cells prefer aerobic glycolysis (converting glucose to lactate) for ATP production, even in the presence of oxygen. This results in increased glucose uptake by cancer cells.
172
What is the difference between dysplasia and carcinoma in situ? A: Dysplasia refers to disordered, non-neoplastic tissue growth, which can precede cancer. Carcinoma in situ is dysplasia involving the entire epithelial layer without basement membrane invasion.
173
What is anaplasia, and what does it signify in cancer prognosis? A: Anaplasia refers to undifferentiated cell growth where cells lose resemblance to their tissue of origin. It is associated with aggressive, poorly differentiated tumors and a poor prognosis.
174
What are the hallmarks of malignant cells (cancer)? A: The hallmarks are:
Autonomous growth
Evasion of cell death
Immortality (unlimited replication)
Angiogenesis
Invasion and metastasis
175
How does telomerase contribute to the immortality of cancer cells? A: Telomerase prevents the shortening of telomeres during cell division, enabling cancer cells to divide indefinitely without undergoing replicative senescence.
176
How is tumor grade determined, and what does it indicate? A: Tumor grade refers to the degree of differentiation of the tumor cells. It is determined by biopsy. Low-grade tumors are well-differentiated and generally have a better prognosis, while high-grade tumors are poorly differentiated (anaplastic) and more aggressive.
177
What does tumor stage represent, and how is it determined? A: Tumor stage represents the extent of tumor spread. It is determined by imaging studies, such as CT scans. Early-stage tumors are confined to the tissue of origin, while advanced-stage tumors have spread to lymph nodes or distant sites.
178
What are hamartomas and choristomas? A:
Hamartomas: Disorganized masses of mature cells within their correct tissue (e.g., lung hamartomas).
Choristomas: Well-differentiated tissue located in an abnormal site (e.g., gastric tissue in the ileum in Meckel’s diverticulum).
179
How do sarcomas and carcinomas typically spread? A:
Sarcomas: Spread through the bloodstream (hematogenous spread), often via veins.
Carcinomas: Usually spread via lymphatics, except for choriocarcinoma, renal cell carcinoma, hepatocellular carcinoma, and follicular thyroid carcinoma, which spread through the bloodstream.
180
What are the four exceptions of carcinomas that spread by hematogenous way rather than lymphatic way?
Choriocarcinoma
Hepatocellular carcinoma
Follicular Thyroid carcinoma
Renal Carcinoma
181
What are tumor suppressor genes, and what mutation is required for cancer to develop? A: Tumor suppressor genes normally inhibit cell division. For cancer to develop, both alleles of the tumor suppressor gene must be mutated (e.g., p53, RB).
182
What is carcinogenesis, and what are the two main types of genes involved? A: Carcinogenesis is the process by which cancer develops due to non-lethal DNA damage. The two main types of genes involved are:
Tumor suppressor genes: Normally limit cell growth (e.g., p53, RB).
Oncogenes: Promote uncontrolled cell growth when mutated.
183
What are Concentrically laminated calcified spherules?
Psammoma bodies
184
What are Psammoma bodies?
Concentrically laminated calcified spherules
185
In what tumors are generally psammoma bodies seen?
Papillary Thyroid Carcinoma
Meningioma
Serous Ovarian Carcinoma
Mesothelioma
Prolactinoma ("Milk")
"Please, MOM Milk"
186
What are the differences between Distrophic calcifications and Metastatic Calcifications?
Distrophic Calcifications
- Localized
- Previous necrosis
- Normal blood Ca++ and PO
Metastatic Calcifications
- Spread
- Hyperphosphatemia and/or hypercalcemia
- Normal tissues
187
What is amyloidosis?
A: A group of diseases characterized by the extracellular deposition of misfolded proteins that form amyloid fibrils, disrupting normal tissue function.
188
What is Primary (AL) Amyloidosis associated with?
A: Immunoglobulin light chain deposition, often linked to plasma cell dyscrasias (e.g., multiple myeloma).
189
What causes Secondary (AA) Amyloidosis?
A: Deposition of serum amyloid A (SAA), associated with chronic inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease.
190
What are the key organs commonly affected by systemic amyloidosis?
A: Kidneys (nephrotic syndrome), heart (restrictive cardiomyopathy), liver (hepatomegaly), nervous system, and GI tract.
191
What stain is used to identify amyloid deposits, and what is the characteristic finding?
A: Congo Red Stain; shows apple-green birefringence under polarized light.
192
What is the hallmark of amyloid deposition on H&E stain?
A: Eosinophilic, amorphous deposits in tissues.
193
What is Dialysis-related Amyloidosis caused by, and where does it often deposit?
A: Caused by β2-microglobulin deposition, often in joints (e.g., carpal tunnel syndrome).
194
What is Senile (Age-related) Amyloidosis?
A: Amyloid deposition of wild-type transthyretin (TTR) in the heart, leading to restrictive cardiomyopathy in elderly patients.
195
Which types of amyloidosis are associated with transthyretin (TTR) mutations?
A: Familial Amyloid Cardiomyopathy and Senile Amyloidosis.
196
What is the role of β-amyloid in amyloidosis?
A: β-amyloid is implicated in Alzheimer's disease, where it forms amyloid plaques in the brain.
197
A 58-year-old man with a history of chronic rheumatoid arthritis presents with progressive fatigue, swollen ankles, and decreased urine output. His blood pressure is 145/90 mmHg. Laboratory results show:
Creatinine: 2.5 mg/dL
Total protein: 8.2 g/dL
Albumin: 2.4 g/dL
Urinalysis: 4+ protein, no blood
A biopsy of the kidney shows eosinophilic, amorphous material in the glomeruli that stains with Congo Red and demonstrates apple-green birefringence under polarized light. Which of the following is the most likely protein deposited in his tissues?
A) β2-microglobulin
B) Immunoglobulin light chains
C) Transthyretin
D) Serum amyloid A (SAA)
E) β-amyloid
198
A 72-year-old man presents with increasing shortness of breath and difficulty climbing stairs over the last 6 months. Physical examination reveals jugular venous distension, crackles at the lung bases, and pitting edema in both legs. An echocardiogram shows thickened ventricular walls and a low ejection fraction. A biopsy of the myocardium shows pink, amorphous material that stains positive with Congo Red. Serum calcium and phosphate levels are normal. The patient has no history of chronic inflammatory diseases or malignancy.
Which of the following is the most likely cause of his condition?
A) Transthyretin deposition
B) Immunoglobulin light chain deposition
C) β2-microglobulin deposition
D) Serum amyloid A (SAA) deposition
E) β-amyloid deposition
199
A 40-year-old man with a history of chronic hemodialysis presents with pain and weakness in both wrists. He reports difficulty gripping objects and numbness in his fingers. Physical examination reveals bilateral positive Tinel and Phalen signs, consistent with carpal tunnel syndrome. An X-ray of his hands shows periarticular calcifications but no erosions. His serum calcium and phosphate levels are normal. A biopsy of the tissue around the wrist shows deposits of amyloid.
Which of the following proteins is most likely to be involved in this patient's condition?
A) Immunoglobulin light chains
B) Transthyretin
C) β2-microglobulin
D) Serum amyloid A (SAA)
E) β-amyloid
200
A 33-year-old woman presents with recurrent episodes of abdominal pain, diarrhea, and unintentional weight loss. She has a 10-year history of Crohn’s disease. Physical examination shows mild pallor and pedal edema. Laboratory findings reveal:
Total protein: 7.5 g/dL
Albumin: 2.1 g/dL
Urinalysis: 3+ protein
A biopsy of the rectum shows pink, amorphous material in the submucosa that stains positive with Congo Red and shows apple-green birefringence under polarized light. Which of the following is the most likely diagnosis?
A) Primary AL amyloidosis
B) Dialysis-related amyloidosis
C) Secondary (AA) amyloidosis
D) Familial Mediterranean fever
E) Senile systemic amyloidosis
201
A 68-year-old woman presents with progressive memory loss and confusion over the past year. Her family reports that she has had difficulty remembering recent events and performing daily activities. She has a family history of dementia in her mother. On physical examination, there are no focal neurological deficits. A brain biopsy shows extracellular plaques composed of amorphous material that stain with Congo Red and show apple-green birefringence under polarized light.
Which of the following proteins is most likely involved in the pathogenesis of this patient's condition?
A) β-amyloid
B) Serum amyloid A (SAA)
C) β2-microglobulin
D) Immunoglobulin light chains
E) Transthyretin
202
A 45-year-old man with no significant past medical history presents with a 6-month history of fatigue, swelling in his legs, and foamy urine. Laboratory findings reveal:
Serum creatinine: 3.1 mg/dL
Albumin: 2.2 g/dL
Urinalysis: 4+ protein A renal biopsy shows eosinophilic deposits in the glomeruli that stain with Congo Red. Serum protein electrophoresis shows a monoclonal spike.
Which of the following is the most likely diagnosis?
A) Primary AL amyloidosis
B) Secondary AA amyloidosis
C) Dialysis-related amyloidosis
D) Familial Mediterranean fever
E) Senile systemic amyloidosis
203
A 30-year-old woman presents with recurrent fevers, abdominal pain, and joint pain that have been ongoing for several years. She was diagnosed with familial Mediterranean fever at age 15. Physical examination reveals hepatosplenomegaly and 2+ pitting edema in both legs. Laboratory studies show:
Total protein: 8.0 g/dL
Albumin: 2.0 g/dL
Urinalysis: 3+ protein A biopsy of her kidney reveals Congo Red-positive deposits in the glomeruli. What is the most likely protein responsible for her condition?
A) β2-microglobulin
B) Immunoglobulin light chains
C) Transthyretin
D) Serum amyloid A (SAA)
E) β-amyloid
204
A 66-year-old man presents with progressive dyspnea, fatigue, and lower extremity edema. Echocardiogram shows a thickened left ventricular wall with a normal ejection fraction. A biopsy of the heart reveals amorphous eosinophilic deposits in the myocardium that are Congo Red-positive with apple-green birefringence under polarized light. Genetic testing reveals a mutation in the transthyretin gene.
What is the most likely diagnosis?
A) Primary AL amyloidosis
B) Secondary AA amyloidosis
C) Familial amyloid cardiomyopathy
D) Dialysis-related amyloidosis
E) Senile systemic amyloidosis
