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?

Hyperlipidemia, thrombocytopenia

Nephrotoxicity, gingival hyperplasia

Cytokine release syndrome, hypersensitivity reaction

A 24-year-old male with cystic fibrosis is brought to the emergency room by his mother after he had difficulty breathing. He previously received a lung transplant 6 months ago and was able to recover quickly from the operation. He is compliant with all of his medications and had been doing well with no major complaints until 2 weeks ago when he began to experience shortness of breath. Exam reveals a decreased FEV1/FVC ratio and biopsy reveals lymphocytic infiltration. Which of the following components is present in the airway zone characteristically affected by the most likely cause of this patient's symptoms?

Pseudostratified columnar cells

An investigator studying immune-mediated pulmonary damage performs an autopsy on a bilateral lung transplant recipient who died of hypercapnic respiratory failure. The patient underwent lung transplantation for idiopathic pulmonary fibrosis. Microscopic examination of the lung shows diffuse eosinophilic scarring of the terminal and respiratory bronchioles and near-complete luminal obliteration by polypoidal plugs of granulation tissue. Examination of the skin shows no abnormalities. The findings in this patient are most consistent with which of the following conditions?

Transfusion-related acute lung injury

Acute graft-versus-host disease

In which of the following pathological states would the oxygen content of the trachea resemble the oxygen content in the affected alveoli?

Foreign body obstruction distal to the trachea

A 66-year-old man is transferred from another hospital after 3 days of progressively severe headache, vomiting, low-grade fever, and confusion. According to his partner, the patient has been dealing with some memory loss and complaining about headaches for the past 2 weeks. He has a history of interstitial pulmonary disease that required lung transplantation 2 years ago. Upon admission, he is found with a blood pressure of 160/100 mm Hg, a pulse of 58/min, a respiratory rate of 15/min, and a body temperature of 36°C (97°F). During the examination, he is found with oral thrush and symmetric and reactive pupils; there are no focal neurological signs or papilledema. A lumbar puncture is performed. Which of the following features would be expected to be found in this case?

Aspect: clear, opening pressure: ↑, cell count: ↑ lymphocytes, protein: ↑, glucose: ↓

Aspect: clear, opening pressure: normal, cell count: < 5 cells/µL, protein: normal, glucose: normal

Aspect: clear, opening pressure: normal, cell count: ↑ lymphocytes, protein: normal, glucose: normal

Aspect: cloudy, opening pressure: ↑, cell count: ↑ neutrophils, protein: ↑, glucose: ↓

Aspect: xanthochromic, opening pressure: normal, cell count: ↑ red blood cells, protein: normal, glucose: normal

A 38-year-old kidney transplant recipient maintained on tacrolimus presents with a 2-week history of progressive confusion, ataxia, and visual disturbances. MRI shows multifocal white matter lesions without mass effect or enhancement. CSF analysis reveals mild pleocytosis with elevated protein. JC virus DNA is detected in CSF by PCR. Serum tacrolimus level is therapeutic at 8 ng/mL. Apply knowledge of this condition to determine the appropriate management strategy.

Significantly reduce or discontinue immunosuppression and provide supportive care

Switch from tacrolimus to sirolimus to preserve graft while treating infection

Continue current immunosuppression and administer IVIG therapy

Maintain immunosuppression and start cidofovir antiviral therapy

Reduce tacrolimus by 50% and start high-dose corticosteroids

Lung transplantation for USMLE Step 2 CK: High-Yield Surgery Lessons

Indications & Contraindications - Who Gets New Lungs?

Indications (End-Stage Disease)	Absolute Contraindications
* COPD (Chronic Obstructive Pulmonary Disease)	* Active or recent malignancy (<5 years)
* Idiopathic Pulmonary Fibrosis (IPF)	* Untreatable, severe extrapulmonary organ dysfunction
* Cystic Fibrosis (CF)	* Active infection (esp. Burkholderia cenocepacia)
* Pulmonary Arterial Hypertension (PAH)	* Active substance abuse or psychiatric non-adherence
* Alpha-1-antitrypsin deficiency	* Significant chest wall or spinal deformity

⭐ The Lung Allocation Score (LAS) is a numerical value (0-100) that predicts survival benefit. It prioritizes candidates based on medical urgency and likelihood of success, not just waiting time.

Pre-Op & Surgery - The Lung Swap

Donor-Recipient Matching: ABO compatibility, Human Leukocyte Antigen (HLA) typing, and size matching (Total Lung Capacity) are paramount.
Surgical Approach: Anterolateral or posterolateral thoracotomy, or clamshell incision. Cardiopulmonary bypass (CPB) may be used, especially in bilateral transplants or with pulmonary hypertension.

Lung Transplant Anastomoses

Anastomosis Order: Typically 1) Bronchus, 2) Pulmonary Artery, 3) Pulmonary Veins (atrial cuff).

⭐ The donor lung's bronchial circulation is not re-established. The airway anastomosis relies on retrograde blood flow from the low-pressure pulmonary circulation, making it vulnerable to ischemia and dehiscence.

Immunosuppression - Taming the Defenses

Post-transplant therapy aims to prevent rejection while minimizing drug toxicity and infection risk. A typical triple-drug regimen includes a calcineurin inhibitor, an antiproliferative agent, and corticosteroids. Lifelong therapy is required.

Class	Drug(s)	Mechanism of Action (MOA)	Key Side Effect(s)
Calcineurin Inhibitors	Tacrolimus, Cyclosporine	Block IL-2 synthesis by inhibiting calcineurin	Nephrotoxicity, neurotoxicity, hypertension
Antiproliferatives	Mycophenolate, Azathioprine	Inhibit purine synthesis, ↓ lymphocyte proliferation	GI intolerance (Mycophenolate), myelosuppression
mTOR Inhibitors	Sirolimus, Everolimus	Block IL-2 signaling via mTOR pathway	Impaired wound healing, stomatitis, pneumonitis
Corticosteroids	Prednisone	Broad anti-inflammatory, inhibit cytokine genes	Hyperglycemia, osteoporosis, Cushing's

Rejection & Risks - When Good Lungs Go Bad

Primary risks involve rejection and opportunistic infections due to immunosuppression. Chronic rejection is the main long-term challenge.

Rejection Type	Timing	Pathophysiology & Key Features
Hyperacute	Minutes-Hours	Pre-formed anti-donor antibodies (ABO/HLA). Leads to thrombosis, ischemia. Rare due to cross-matching.
Acute	Weeks-Months	T-cell mediated response against graft HLA antigens. Presents with cough, dyspnea, low-grade fever, infiltrates. Reversible.
Chronic	Months-Years	Bronchiolitis Obliterans Syndrome (BOS): Progressive inflammation and fibrosis of small airways. Results in irreversible airflow obstruction (↓FEV1).

⭐ Bronchiolitis Obliterans Syndrome (BOS) is the leading cause of late mortality. It manifests as a progressive, irreversible decline in FEV1, often termed the "popcorn lung" appearance on imaging.

Indications: Most commonly for end-stage COPD, idiopathic pulmonary fibrosis (IPF), and cystic fibrosis.

Chronic Rejection: The leading long-term complication is chronic lung allograft dysfunction (CLAD), most often presenting as bronchiolitis obliterans syndrome (BOS) with obstructive physiology.

Infections: High risk for opportunistic pathogens, especially CMV, Aspergillus, and Pneumocystis jirovecii; antimicrobial prophylaxis is crucial.

Acute Rejection: Typically occurs within the first 6-12 months; diagnosed via transbronchial biopsy showing perivascular lymphocytic infiltrates.

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