Inflammation

Inflammation US Medical PG Question 1: A 56-year-old postmenopausal woman comes to the physician because of a 6-month history of worsening pain and swelling in her left knee. She has a history of peptic ulcer disease for which she takes cimetidine. Examination shows palpable crepitus and limited range of motion of the left knee. Which of the following is the most appropriate pharmacotherapy for this patient’s symptoms?

• A. Acetylsalicylic acid
• B. Diclofenac
• C. Meloxicam
• D. Celecoxib (Correct Answer)
• E. Ketorolac

Inflammation Explanation: ***Celecoxib*** - This patient suffers from **osteoarthritis** (evidenced by her age, postmenopausal status, knee pain, crepitus, and limited range of motion) and has a history of **peptic ulcer disease (PUD)**. **Celecoxib** is a **COX-2 selective NSAID**, which reduces the risk of gastrointestinal side effects compared to non-selective NSAIDs. - Given her history of PUD, a COX-2 selective NSAID is the most appropriate choice to manage her pain while minimizing the risk of a PUD exacerbation or bleed. *Acetylsalicylic acid* - **Aspirin** (acetylsalicylic acid) is a non-selective NSAID and would pose a significant risk of **gastrointestinal bleeding** or ulcer exacerbation in a patient with a history of **peptic ulcer disease**. - While it has anti-inflammatory properties, its adverse effect profile makes it unsuitable for this patient's chronic pain management. *Diclofenac* - **Diclofenac** is a **non-selective NSAID**, meaning it inhibits both COX-1 and COX-2 enzymes. - Due to its inhibition of COX-1, it carries an increased risk of **gastric ulcers** and bleeding, making it less safe for a patient with a history of **peptic ulcer disease**. *Meloxicam* - **Meloxicam** is a partially COX-2 selective NSAID, but it still has some affinity for COX-1 at higher doses, conferring a risk for **gastrointestinal adverse effects**. - Although it may have a slightly better GI safety profile than non-selective NSAIDs, **celecoxib** offers superior GI protection. *Ketorolac* - **Ketorolac** is a potent **non-selective NSAID** primarily used for short-term management of moderate to severe acute pain, often administered parenterally. - Its use is associated with a high risk of **gastrointestinal toxicity** and renal impairment, making it inappropriate for chronic pain management in a patient with **peptic ulcer disease**.

Inflammation US Medical PG Question 2: A 31-year-old female receives a kidney transplant for autosomal dominant polycystic kidney disease (ADPKD). Three weeks later, the patient experiences acute, T-cell mediated rejection of the allograft and is given sirolimus. Which of the following are side effects of this medication?

• A. Nephrotoxicity, hypertension
• B. Hyperlipidemia, thrombocytopenia (Correct Answer)
• C. Nephrotoxicity, gingival hyperplasia
• D. Pancreatitis
• E. Cytokine release syndrome, hypersensitivity reaction

Inflammation Explanation: ***Hyperlipidemia, thrombocytopenia*** - **Sirolimus** (rapamycin) is an **mTOR inhibitor** commonly used in transplant immunology, which frequently causes **hyperlipidemia** (elevated cholesterol and triglycerides) and **thrombocytopenia** (low platelet count). - Other common side effects include **myelosuppression** (leukopenia, anemia), **mouth ulcers**, and **impaired wound healing**. *Nephrotoxicity, hypertension* - **Nephrotoxicity** and **hypertension** are more characteristic side effects of **calcineurin inhibitors** like **tacrolimus** and **cyclosporine**, which are also used in transplant immunosuppression but have a different mechanism of action than sirolimus. - While sirolimus can indirectly affect kidney function, it is generally considered less nephrotoxic than calcineurin inhibitors. *Nephrotoxicity, gingival hyperplasia* - **Gingival hyperplasia** is a hallmark side effect of **cyclosporine**, a calcineurin inhibitor, along with **hirsutism** and **nephrotoxicity**. - Sirolimus does not typically cause gingival hyperplasia. *Pancreatitis* - While some immunosuppressants can rarely cause pancreatitis, it is not a common or characteristic side effect of **sirolimus**. - **Azathioprine** is more frequently associated with pancreatitis among immunosuppressive agents. *Cytokine release syndrome, hypersensitivity reaction* - **Cytokine release syndrome** and acute **hypersensitivity reactions** are more often associated with **monoclonal antibodies** (e.g., **basiliximab**, **daclizumab**) used for induction therapy or treatment of acute rejection, particularly within hours or days of administration. - Sirolimus is less likely to cause these immediate severe reactions.

Inflammation US Medical PG Question 3: An 18-year-old woman presents to the emergency department with a complaint of severe abdominal pain for the past 6 hours. She is anorexic and nauseous and has vomited twice since last night. She also states that her pain initially began in the epigastric region, then migrated to the right iliac fossa. Her vital signs include a respiratory rate of 14/min, blood pressure of 130/90 mm Hg, pulse of 110/min, and temperature of 38.5°C (101.3°F). On abdominal examination, there is superficial tenderness in her right iliac fossa, rebound tenderness, rigidity, and abdominal guarding. A complete blood count shows neutrophilic leukocytosis and a shift to the left. Laparoscopic surgery is performed and the inflamed appendix, which is partly covered by a yellow exudate, is excised. Microscopic examination of the appendix demonstrates a neutrophil infiltrate of the mucosal and muscular layers with extension into the lumen. Which of the following chemical mediators is responsible for pain in this patient?

• A. IgG and complement C3b
• B. Bradykinin and prostaglandin (Correct Answer)
• C. 5- hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene A4
• D. Serotonin and histamine
• E. Tumor necrosis factor and interleukin-1

Inflammation Explanation: ***Bradykinin and prostaglandin*** - **Bradykinin** and **prostaglandins** are key inflammatory mediators that directly stimulate **nociceptors**, leading to the sensation of pain. Prostaglandins are also responsible for inducing fever. - The patient's symptoms, including **severe abdominal pain**, fever, and local tenderness, are consistent with acute inflammation (appendicitis), where these mediators play a central role. *IgG and complement C3b* - **IgG** is an antibody involved in the adaptive immune response, primarily responsible for pathogen neutralization and opsonization. - **Complement C3b** is a component of the complement system involved in opsonization and forming the membrane attack complex, but neither directly mediates pain. *5- hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene A4* - **5-HPETE** is an unstable intermediate in the lipoxygenase pathway, leading to the formation of leukotrienes. - **Leukotriene A4** is a precursor to other leukotrienes (e.g., LTB4, LTC4, LTD4) that are potent **chemotactic agents** and **bronchoconstrictors**, but they are not primary pain mediators. *Serotonin and histamine* - **Serotonin** is primarily involved in smooth muscle contraction, vasoconstriction, and neurotransmission; while it can modulate pain, it is not a direct primary mediator in acute appendicitis. - **Histamine** is released by mast cells and basophils, causing vasodilation and increased vascular permeability (contributing to edema), but its role in direct pain mediation in this context is less significant than bradykinin or prostaglandins. *Tumor necrosis factor and interleukin-1* - **Tumor necrosis factor (TNF)** and **interleukin-1 (IL-1)** are **pro-inflammatory cytokines** that are crucial in initiating and amplifying the inflammatory response. - While they contribute to fever and systemic symptoms of inflammation, their primary role is in cell signaling and immune cell activation rather than direct pain sensation.

Inflammation US Medical PG Question 4: A 55-year-old woman with diabetes presents to the emergency department due to swelling of her left leg, fever, and chills for the past 2 days. The woman’s maximum recorded temperature at home was 38.3°C (101.0°F). Her left leg is red and swollen from her ankle to the calf, with an ill-defined edge. Her vital signs include: blood pressure 120/78 mm Hg, pulse rate 94/min, temperature 38.3°C (101.0°F), and respiratory rate 16/min. On physical examination, her left leg shows marked tenderness and warmth compared with her right leg. The left inguinal lymph node is enlarged to 3 x 3 cm. Which of the following chemical mediators is the most likely cause of the woman’s fever?

• A. Bradykinin
• B. Histamine
• C. PGE2 (Correct Answer)
• D. Arachidonic acid
• E. LTB4

Inflammation Explanation: ***PGE2*** - **Prostaglandin E2 (PGE2)** is a potent **pyrogen** that acts on the **hypothalamus** to reset the body's thermoregulatory set point, leading to fever. - In infections like **cellulitis**, inflammatory mediators stimulate the production of PGE2, causing the systemic symptom of fever. *Bradykinin* - **Bradykinin** primarily mediates **pain** and **vasodilation** at the site of inflammation. - While it contributes to local signs of inflammation, it is not a direct mediator of systemic fever. *Histamine* - **Histamine** is a key mediator in immediate **hypersensitivity reactions** and local inflammation, causing **vasodilation** and increased **vascular permeability**. - It does not directly induce fever by acting on the thermoregulatory center. *Arachidonic acid* - **Arachidonic acid** is a **precursor** molecule derived from membrane phospholipids, which is metabolized to various inflammatory mediators like prostaglandins and leukotrienes. - It is not a direct chemical mediator of fever itself; rather, its downstream products such as PGE2 are. *LTB4* - **Leukotriene B4 (LTB4)** is a potent **chemotactic agent** for neutrophils, playing a role in immune cell recruitment to the site of inflammation. - While involved in inflammation, LTB4 does not directly cause fever.

Inflammation US Medical PG Question 5: Which of the following patient presentations would be expected in an infant with defective LFA-1 integrin (CD18) protein on phagocytes, in addition to recurrent bacterial infections?

• A. Cardiac defects, hypoparathyroidism, palatal defects, and learning disabilities
• B. Chronic diarrhea, oral candidiasis, severe infections since birth, absent thymic shadow
• C. Progressive neurological impairment and cutaneous telangiectasia
• D. Skin infections with absent pus formation, delayed umbilicus separation (Correct Answer)
• E. Eczema and thrombocytopenia

Inflammation Explanation: ***Skin infections with absent pus formation, delayed umbilicus separation*** - A defect in **LFA-1 integrin (CD18)** prevents phagocytes from adhering to endothelial cells and migrating to sites of infection, leading to **absent pus formation** despite severe infections. - **Delayed umbilical cord separation** (typically >30 days) is a classic sign due to impaired neutrophil recruitment at the site of cord detachment. *Cardiac defects, hypoparathyroidism, palatal defects, and learning disabilities* - This constellation of symptoms is characteristic of **DiGeorge syndrome**, which involves a defect in T-cell development due to thymic aplasia/hypoplasia. - These specific defects are not directly caused by LFA-1 integrin deficiency. *Chronic diarrhea, oral candidiasis, severe infections since birth, absent thymic shadow* - These symptoms are highly suggestive of **Severe Combined Immunodeficiency (SCID)**, which involves a profound defect in both B and T cell immunity. - SCID presents with a broader spectrum of opportunistic infections and developmental issues not directly related to integrin function. *Progressive neurological impairment and cutaneous telangiectasia* - These are hallmark features of **Ataxia-Telangiectasia**, a genetic disorder affecting DNA repair and leading to immune deficiencies and cerebellar degeneration. - This condition primarily involves T-cell dysfunction and increased cancer risk, not LFA-1 integrin deficiency. *Eczema and thrombocytopenia* - The combination of **eczema** (dermatitis) and **thrombocytopenia** (low platelet count), along with recurrent infections, is characteristic of **Wiskott-Aldrich syndrome**. - This syndrome is caused by a defect in the WASP protein, affecting immune cell function and platelet formation, distinct from LFA-1 integrin deficiency.

Inflammation US Medical PG Question 6: During a clinical study evaluating the effects of exercise on muscle perfusion, 15 healthy individuals perform a 20-minute treadmill run at submaximal effort. Before and after the treadmill session, perfusion of the quadriceps muscle is evaluated with contrast-enhanced magnetic resonance imaging. The study shows a significant increase in muscle blood flow per unit of tissue mass. Which of the following local changes is most likely involved in the observed change in perfusion?

• A. Increase in adenosine (Correct Answer)
• B. Decrease in potassium
• C. Increase in thromboxane A2
• D. Increase in endothelin
• E. Decrease in prostacyclin

Inflammation Explanation: ***Increase in adenosine*** - **Adenosine** is a potent **vasodilator** released by metabolically active tissues, particularly in response to increased oxygen demand and ATP hydrolysis during exercise. - Its accumulation leads to relaxation of vascular smooth muscle, increasing blood flow to meet the muscles' elevated metabolic needs. *Decrease in potassium* - An increase in **extracellular potassium** (not a decrease) generally causes vasodilation in skeletal muscle by hyperpolarizing smooth muscle cells. - A decrease in potassium outside the cell would not be expected to cause vasodilation and increased perfusion during exercise. *Increase in thromboxane A2* - **Thromboxane A2** is primarily a **vasoconstrictor** and platelet aggregator, mainly involved in hemostasis and inflammation. - Increased levels would lead to reduced blood flow, not the observed increase in perfusion during exercise. *Increase in endothelin* - **Endothelin** is one of the most potent **vasoconstrictors** known, primarily released from endothelial cells. - An increase in endothelin would severely constrict blood vessels and decrease muscle perfusion, counteracting the effects of exercise. *Decrease in prostacyclin* - **Prostacyclin (PGI2)** is a potent **vasodilator** and inhibitor of platelet aggregation. - A decrease in prostacyclin would lead to vasoconstriction and reduced blood flow, which is contrary to the increased perfusion seen during exercise.

Inflammation US Medical PG Question 7: A 31-year-old woman scrapes her finger on an exposed nail and sustains a minor laceration. Five minutes later, her finger is red, swollen, and painful. She has no past medical history and does not take any medications. She drinks socially with her friends and does not smoke. The inflammatory cell type most likely to be prominent in this patient's finger has which of the following characteristics?

• A. Segmented nuclei (Correct Answer)
• B. Dramatically expanded endoplasmic reticulum
• C. Large cell with amoeboid movement
• D. Multiple peripheral processes
• E. Dark histamine containing granules

Inflammation Explanation: ***Segmented nuclei*** - This scenario describes **acute inflammation** following a minor injury, with classic signs of **redness, swelling, and pain** within minutes. - **Neutrophils** are the primary inflammatory cells in acute inflammation and are characterized by their **segmented (multi-lobed) nuclei.** *Dramatically expanded endoplasmic reticulum* - An expanded endoplasmic reticulum is characteristic of cells highly active in protein synthesis and secretion, such as **plasma cells** producing antibodies. - Plasma cells are typically involved in **chronic inflammation** and adaptive immune responses, not rapid acute inflammation. *Large cell with amoeboid movement* - This describes **macrophages**, which are phagocytic cells important in both acute and chronic inflammation, and in cleaning up debris. - While macrophages are present, **neutrophils** are the predominant early responders in acute bacterial infections and tissue injury. *Multiple peripheral processes* - This description is characteristic of **dendritic cells**, which are antigen-presenting cells that initiate adaptive immune responses. - Dendritic cells play a role in linking innate and adaptive immunity but are not the primary inflammatory cell type in the immediate acute response. *Dark histamine containing granules* - This description applies to **mast cells** and **basophils**, which release histamine and other mediators in allergic reactions and acute inflammation. - While mast cells are involved in the immediate response by releasing mediators, **neutrophils** are the main cellular players migrating to the site of injury.

Inflammation US Medical PG Question 8: A 59-year-old male with a 1-year history of bilateral knee arthritis presents with epigastric pain that intensifies with meals. He has been self-medicating with aspirin, taking up to 2,000 mg per day for the past six months. Which of the following medications, if taken instead of aspirin, could have minimized his risk of experiencing this epigastric pain?

• A. Naproxen
• B. Celecoxib (Correct Answer)
• C. Indomethacin
• D. Ibuprofen
• E. Ketorolac

Inflammation Explanation: ***Celecoxib*** - **Celecoxib** is a selective **COX-2 inhibitor**, which preferentially inhibits the COX-2 enzyme responsible for inflammation and pain, while largely sparing COX-1. - Sparing **COX-1** reduces the inhibition of **prostaglandins** that protect the gastric mucosa, thereby lowering the risk of GI side effects like epigastric pain and ulcers compared to non-selective NSAIDs. *Naproxen* - **Naproxen** is a **non-selective NSAID** that inhibits both COX-1 and COX-2 enzymes. - Inhibition of **COX-1** interferes with the production of protective prostaglandins in the stomach, increasing the risk of gastrointestinal adverse effects such as epigastric pain, ulcers, and bleeding, similar to aspirin. *Indomethacin* - **Indomethacin** is a potent **non-selective NSAID** with significant inhibition of both COX-1 and COX-2. - Its strong **COX-1 inhibition** makes it particularly prone to causing gastrointestinal side effects including severe epigastric pain, nausea, and dyspepsia. *Ibuprofen* - **Ibuprofen** is a **non-selective NSAID** commonly used for pain and inflammation that inhibits both COX-1 and COX-2 enzymes. - Although generally better tolerated than indomethacin or high-dose aspirin, it still carries a dose-dependent risk of **GI adverse effects** due to COX-1 inhibition. *Ketorolac* - **Ketorolac** is a potent **non-selective NSAID** primarily used for short-term management of acute moderate to severe pain. - It has a high risk of **gastrointestinal complications**, including gastric ulcers and bleeding, making it unsuitable for long-term use and not a safer alternative to aspirin in terms of GI risk.

Inflammation US Medical PG Question 9: You are seeing a 4-year-old boy in clinic who is presenting with concern for a primary immune deficiency. He has an unremarkable birth history, but since the age of 6 months he has had recurrent otitis media, bacterial pneumonia, as well as two episodes of sinusitis, and four episodes of conjunctivitis. He has a maternal uncle who died from sepsis secondary to H. influenza pneumonia. If you drew blood work for diagnostic testing, which of the following would you expect to find?

• A. Abnormally low number of T cells
• B. Abnormally high number of B cells
• C. Elevated immunoglobulin levels
• D. Abnormally low number of B cells (Correct Answer)
• E. Abnormally high number of T cells

Inflammation Explanation: ***Abnormally low number of B cells*** - The recurrent bacterial infections (otitis media, pneumonia, sinusitis, conjunctivitis) and the family history of death from *H. influenza* pneumonia suggest a **primary B-cell immunodeficiency**, such as **X-linked agammaglobulinemia (XLA)**. - In XLA, there is a block in B-cell development, leading to a profound absence of mature B cells and immunoglobulins. *Abnormally low number of T cells* - This would point towards a **T-cell immunodeficiency** or a **combined immunodeficiency**, typically presenting with opportunistic infections, viral, or fungal infections, rather than predominantly bacterial infections. - Examples include **Severe Combined Immunodeficiency (SCID)**, which often presents earlier and more severely. *Abnormally high number of B cells* - This is not characteristic of a primary immunodeficiency with recurrent bacterial infections; rather, it might be seen in certain autoimmune conditions or lymphoproliferative disorders. - **High B cell counts** generally imply a functioning humoral immune system, which contradicts the infectious history. *Elevated immunoglobulin levels* - This finding would generally indicate a **functioning humoral immune response**, possibly due to chronic infection or an inflammatory process, but not a primary B-cell immunodeficiency causing recurrent bacterial infections. - In conditions like **Common Variable Immunodeficiency (CVID)**, some immunoglobulin levels might be normal, but often key classes (like IgG, IgA, or IgM) are low. *Abnormally high number of T cells* - This finding is generally not associated with the pattern of recurrent bacterial infections described, which strongly points to a **humoral (antibody) deficiency**. - **Elevated T cells** could be seen in some autoimmune conditions or certain viral infections, but not typically in a primary immunodeficiency characterized by recurrent bacterial infections.

Inflammation US Medical PG Question 10: A 47-year-old man presents as a new patient at an outpatient clinic. He has never seen a physician before, but was motivated by his 40-year-old brother's recent heart attack and seeks to optimize his health. In particular, he read that uncontrolled atherosclerosis can lead to a heart attack. Which molecule is downregulated in response to the advent of atherosclerosis?

• A. Tumor necrosis factor
• B. Serotonin
• C. Nitric oxide (Correct Answer)
• D. Interleukin 1
• E. Thromboxane A2

Inflammation Explanation: ***Nitric oxide*** - **Nitric oxide (NO)** is a potent **vasodilator** and **anti-inflammatory** molecule produced by endothelial cells. In atherosclerosis, endothelial dysfunction leads to reduced NO bioavailability. - Decreased NO production contributes to vasoconstriction, increased platelet aggregation, and enhanced smooth muscle cell proliferation, all of which promote **atherosclerotic plaque formation** and progression. *Tumor necrosis factor* - **Tumor necrosis factor-alpha (TNF-α)** is a **pro-inflammatory cytokine** that plays a significant role in the pathogenesis of atherosclerosis. - It is **upregulated** in response to atherosclerotic plaque formation, contributing to endothelial activation, leukocyte recruitment, and smooth muscle cell proliferation. *Serotonin* - **Serotonin (5-hydroxytryptamine)** is primarily known for its role as a neurotransmitter but also acts as a **vasoconstrictor** and promotes platelet aggregation. - While it can be released from activated platelets in the context of vascular injury, it is not consistently **downregulated** in atherosclerosis; rather, its effects can contribute to disease progression. *Interleukin 1* - **Interleukin-1 (IL-1)**, particularly IL-1β, is a major **pro-inflammatory cytokine** critically involved in the immune response in atherosclerosis. - It is **upregulated** in atherosclerotic plaques, contributing to systemic inflammation, endothelial dysfunction, and vascular smooth muscle cell activation. *Thromboxane A2* - **Thromboxane A2 (TXA2)** is a potent **vasoconstrictor** and **platelet aggregator** produced by activated platelets. - Its levels are **increased** in atherosclerosis, contributing to hypercoagulability and increased risk of thrombotic events like myocardial infarction.

Inflammation Flashcard 1 of 10

Question: Are acute phase reactants produced by liver in acute or chronic inflammatory states?_____

Answer: Both

Inflammation Flashcard 2 of 10

Question: What acute phase reactant is upregulated during inflammation that correlates with ESR_____

Answer: Fibrinogen

Inflammation Flashcard 3 of 10

Question: Inhibition of _____ (ie: immunosuppresion, drugs) results inlack of granuloma formation and resultant reactivation of tuberculosis

Answer: TNF-a

Inflammation Flashcard 4 of 10

Question: Acute inflammation is characterized by the presence of edema and _____ in tissue

Answer: neutrophils (cell type)

Inflammation Flashcard 5 of 10

Question: The _____ is a cytoplasmic protein complex that recognizes products of dead cells, microbial products, and crystals

Answer: inflammasome

Inflammation Flashcard 6 of 10

Question: Leukocyte adhesion deficiency type _____ is due to a defect in Sialyl-Lewisx

Answer: 2

Inflammation Flashcard 7 of 10

Question: One cardinal sign of inflammation is _____, or loss of function

Answer: Functio laesa

Inflammation Flashcard 8 of 10

Question: One cardinal sign of inflammation is _____, or warmth

Answer: calor

Inflammation Flashcard 9 of 10

Question: Lymph node biopsy in cat scratch disease reveals _____ resembling those seen in sarcoidosis

Answer: stellate granulomas

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Inflammation Flashcard 10 of 10

Question: Diffuse proliferative glomerulonephritis is characterized by "_____" of capillaries on light microscopy

Answer: wire looping

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