A 60-year-old rock musician presents to the office because he has been feeling increasingly tired for the past 6 months. He has a history of intravenous drug use and alcohol abuse. He states that he feels quite tired, but he otherwise has no complaints. Physical examination is noncontributory. His laboratory values are normal other than moderately elevated liver enzymes. Which of the following additional tests should you order first?

Hepatitis E virus-specific IgM antibodies

Hepatitis D virus-specific IgG antibody

Hepatitis A virus-specific IgM antibodies

A 53-year-old diabetic man with cellulitis of the right lower limb presents to the emergency department because of symptoms of fever and chills. His pulse is 122/min, the blood pressure is 76/50 mm Hg, the respirations are 26/min, and the temperature is 40.0°C (104.0°F). His urine output is < 0.5mL/kg/h. He has warm peripheral extremities. The hemodynamic status of the patient is not improving in spite of the initiation of adequate fluid resuscitation. He is admitted to the hospital. Which of the following is the most likely laboratory profile?

WBC count: 16,670/mm3; low CVP; blood culture: gram-negative bacteremia; blood lactate level: 2.2 mmol/L

WBC count: 11,670/mm3; low CVP; blood culture: gram-negative bacteremia; blood lactate level: 0.9 mmol/L

WBC count: 1234/mm3; high CVP; blood culture: gram-negative bacteremia; blood lactate level: 1.6 mmol/L

WBC count: 6670/mm3; low CVP; blood culture: gram-positive bacteremia; blood lactate level: 1.1 mmol/L

WBC count: 8880/mm3; high CVP; blood culture: gram-positive bacteremia; blood lactate level: 2.1 mmol/L

A 70-year-old woman is on hospital day 2 in the medical intensive care unit. She was admitted from the emergency department for a 2-day history of shortness of breath and fever. In the emergency department, her temperature is 39.4°C (103.0°F), the pulse is 120/min, the blood pressure is 94/54 mm Hg, the respiratory rate is 36/min, and oxygen saturation was 82% while on 4L of oxygen via a non-rebreather mask. Chest X-ray shows a right lower lobe consolidation. She was intubated, sedated, and started on broad-spectrum antibiotics for sepsis of pulmonary origin and intravenous norepinephrine for blood pressure support. Since then, her clinical condition has been stable, though her vasopressor and oxygen requirements have not improved. Today, her physician is called to the bedside because her nurse noted some slow bleeding from her intravenous line sites and around her urinary catheter. Which of the following most likely represents the results of coagulation studies for this patient?

D-dimer: elevated, fibrinogen level: low, platelet count: low

D-dimer: negative, fibrinogen level: low, platelet count: low

D-dimer: elevated, fibrinogen level: normal, platelet count: normal

D-dimer: negative, fibrinogen level: elevated, platelet count: elevated

D-dimer: negative, fibrinogen level: normal, platelet count: normal

A 28-year-old man presents to the office with complaints of malaise, anorexia, and vomiting for the past 2 weeks. He also says that his urine is dark. The past medical history is unremarkable. The temperature is 36.8°C (98.2°F), the pulse is 72/min, the blood pressure is 118/63 mm Hg, and the respiratory rate is 15/min. The physical examination reveals a slightly enlarged, tender liver. No edema or spider angiomata are noted. Laboratory testing showed the following: HBsAg Positive IgM anti-HBc < 1:1,000 Anti-HBs Negative HBeAg Positive Anti-HBe Negative HBV DNA 2.65 × 10⁹ IU/L Alpha-fetoprotein 125 ng/mL What is the most likely cause of this patient's condition?

Acute exacerbation of chronic HBV infection

Resolved HBV infection (innate immunity)

A 3-day-old female newborn is brought to the emergency department because of fever, poor feeding, and irritability for 6 hours. She was delivered at home at 39 weeks' gestation and delivery was uncomplicated. The mother had no prenatal care. Her temperature is 39.8°C (103.6°F), pulse is 172/min, respirations are 58/min, and blood pressure is 74/45 mm Hg. She appears lethargic. Physical examination shows expiratory grunting and nasal flaring. Serum studies show elevated levels of interleukin-6. Which of the following is the most likely effect of this laboratory finding?

Increased release of fibrinogen

Decreased synthesis of hepcidin

Decreased expression of MHC class II

Increased classical activation of macrophages

A 73-year-old man comes to the physician because of progressive fatigue and shortness of breath on exertion for 3 weeks. He has swelling of his legs. He has not had nausea or vomiting. His symptoms began shortly after he returned from a trip to Cambodia. He occasionally takes ibuprofen for chronic back pain. He has a history of arterial hypertension and osteoarthritis of both knees. He had an episode of pneumonia 4 months ago. His current medications include lisinopril and hydrochlorothiazide. He has no history of drinking or smoking. His temperature is 37°C (98.6°F), pulse is 101/min, and blood pressure is 135/76 mm Hg. Examination shows pitting edema of the upper and lower extremities. Laboratory studies show: Hemoglobin 14.1 g/dL Leukocyte count 6,800/mm3 Platelet count 216,000/mm3 Serum Urea nitrogen 26 mg/dL Creatinine 2.9 mg/dL Albumin 1.6 g/dL Urine Blood negative Protein 4+ Glucose negative Renal biopsy with Congo red stain shows apple-green birefringence under polarized light. Further evaluation of this patient is most likely to show which of the following findings?

Rouleaux formation on peripheral smear

Positive interferon-γ release assay

Elevated anti-citrullinated peptide antibodies

Systemic effects of inflammation — USMLE Lesson

Fever - The Body's Furnace

Mechanism: A regulated rise in body temperature orchestrated by the hypothalamus in response to pyrogens. The pathway involves:
- Exogenous pyrogens (e.g., LPS) stimulate immune cells.
- Immune cells release endogenous pyrogens (IL-1, TNF).
- These cytokines increase cyclooxygenase (COX) activity in the hypothalamus.
- This leads to elevated prostaglandin E₂ ($PGE₂$), which raises the thermoregulatory set point.

Fever Pathophysiology: Pyrogens to Hypothalamic Set Point

⭐ High-Yield: NSAIDs (e.g., aspirin) achieve their antipyretic (fever-reducing) effect by inhibiting COX enzymes, thus blocking the synthesis of prostaglandins that elevate the hypothalamic set point.

Acute-Phase Response - Liver's Protein Party

Systemic reaction to inflammation where pro-inflammatory cytokines (IL-1, IL-6, TNF-α) stimulate hepatic protein synthesis.
Positive APPs: Plasma concentration ↑ by >25%.
Negative APPs: Plasma concentration ↓ by >25% to conserve amino acids for positive APP production.

Protein	Core Function	Trend
C-Reactive Protein (CRP)	Opsonin; activates complement	↑
Fibrinogen	Coagulation; basis for ESR	↑
Hepcidin	↓ Iron absorption & release	↑
Ferritin	Binds & sequesters iron	↑
Serum Amyloid A (SAA)	Recruits immune cells	↑
Albumin	Maintains oncotic pressure	↓
Transferrin	Transports iron	↓

📌 Mnemonic (Positive APPs): Can Fierce Hepatocytes Feel Sick? (CRP, Fibrinogen, Hepcidin, Ferritin, SAA)

Leukocytosis & ESR - Cellular Shake-Up

Leukocytosis: Systemic inflammation triggers a ↑ in white blood cells.
- Mechanism: Cytokines, primarily IL-1 and TNF, accelerate the release of leukocytes from the bone marrow's post-mitotic pool.
- Neutrophilia with 'Left Shift': A hallmark of acute bacterial infection, characterized by the release of immature neutrophils (e.g., band cells) into the blood.
Erythrocyte Sedimentation Rate (ESR): An indirect measure of inflammation.
- Mechanism: ↑ plasma fibrinogen (an acute-phase reactant) coats RBCs, neutralizing their negative surface charge.
- This promotes RBC aggregation into stacks (Rouleaux formation), which sediment faster than individual cells.

Rouleaux formation and ESR in inflammation

⭐ High-Yield: ESR is significantly elevated (>100 mm/hr) in conditions like giant cell arteritis, polymyalgia rheumatica, and multiple myeloma. However, it can be falsely low in sickle cell anemia (due to abnormal RBC shape) and polycythemia.

Sepsis - The Cytokine Storm

Pathophysiology: A dysregulated host response to infection, driven by a "cytokine storm" (TNF-α, IL-1, IL-6). This leads to systemic vasodilation, ↑ vascular permeability, and a procoagulant state, potentially causing Disseminated Intravascular Coagulation (DIC).
Progression & Definitions:

SIRS Criteria (≥2): Temp >38°C or <36°C; HR >90; RR >20; WBC >12,000 or <4,000.

Pathophysiology of Septic Shock

⭐ Early septic shock ("warm shock") is characterized by high cardiac output and low systemic vascular resistance (SVR) due to vasodilation. Late-stage "cold shock" involves ↓ cardiac output from myocardial depression.

Fever: Mediated by IL-1 and TNF which increase PGE₂ in the hypothalamus, raising the temperature set point.

Leukocytosis: IL-1/TNF stimulate neutrophil release from bone marrow, causing a "left shift".

Acute-Phase Reactants: Synthesized by the liver (stimulated by IL-6); includes CRP and fibrinogen.

Elevated ESR: Caused by fibrinogen promoting RBC rouleaux formation.

Chronic Inflammation Risks: Secondary (AA) amyloidosis from SAA and anemia of chronic disease from hepcidin.

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