Hemoptysis Case 1

A 28-year-old man is evacuated by ambulance from his work to the emergency department of a local hospital after he abruptly develops massive hemoptysis. When seen in the emergency department, he is already hypotensive and requires transfusion to maintain blood
pressure. Emergency department personnel perform intubation with assisted ventilation to maintain his respiratory function. A chest x-ray film shows diffuse bilateral alveolar infiltrates. According to the patient's wife, the man had a number of minor episodes of hemoptysis with blood- tinged sputum during the past year, but discounted them and refused to seek medical attention.

Q 1
Which of the following is the most likely diagnosis?
/ A. Bronchogenic carcinoma
/ B. Goodpasture syndrome
/ C. Idiopathic pulmonary fibrosis
/ D. Pneumonia
/ E. Tuberculosis

Q2

The man is admitted to the hospitaI, and during his hospitalization, is also found to have hematuria, proteinuria, red cell casts in the urine, and rising serum creatinine. A hematoxylin and eosin stained section of a renal biopsy is shown above. Which of the following is the most likely diagnosis?

/ A. End-stage renal disease
/ B. Glomerulonephritis
/ C. Kimmelstiel-Wilson nodules
/ D. Pyelonephritis
/ E. Tubulointerstitial nephritis

Q3

A second section from the renal biopsy was stained with immunofluorescent antibodies to human lgG (and human complement) with the result shown. Which of the following is most likely the antigen against which the lgG antibody is directed?
/ A. Collagen
/ B. EIastin
/ C. Fibronectin
/ D. Laminin
/ E. Vitronectin

Q 4
The antigenic determinant against which the lgG is specifically directed is located in the C-terminal domain of one peptide chain of the
molecule. The nucleotide sequence encoding this region is known, and a small portion of the intron (Iower case) and exon (UPPER CASE)
sequence of this region is shown below:
c a t t a g G A A C T C T T G
How many amino acids of the this antigen are translated from the in-frame sequence shown?
/ A. 1
/ B. 2
/ C. 3
/ D. 4
/ E. 5

Q 5
Which of the following would be the most appropriate pharmacotherapy for this patient?
/ A. Erythropoietin
/ B. Famciclovir
/ C. Foscarnet
/ D. Isoniazid
/ E. Methylprednisolone

Q 6
Over the next six months, the patient is treated with repeated plasmapheresis. Which of the following is the rationale of this therapy for this patient?
/ A. Decrease blood clotting factors
/ B. Increase hematocrit
/ C. Increase platelets
/ D. Protect against infection
/ E. Reduce circulating autoantibodies

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Hemoptysis Case 1 Answers

A1
The correct answer is B. Goodpasture syndrome is a hypersensitivity disorder of unknown cause that can cause hemoptysis and dyspnea secondary to bleeding from the alveolar capillary bed. The pulmonary hemorrhage may be mild to massive. Most patients, as in this case, are young men.
Bronchogenic carcinoma (choice A) and tuberculosis (choice E) can cause pulmonary hemorrhage, which is usually not massive, but can be excluded because a mass lesion was not seen on chest x-ray.
Idiopathic pulmonary fibrosis (choice C) and pneumonia (choice D) could both cause diffuse pulmonary changes visible on x-ray, but would be unlikely to cause massive hemoptysis.

A2

The correct answer is B. In addition to lung involvement, Goodpasture syndrome is also characterized by severe renal involvement which may precede, coexist with, or follow lung involvement. Renal biopsy characteristically shows rapidly progressive glomerulonephritis with crescent formation in Bowman's spaces.
End-stage renal disease (choice A) with marked scarring of the renal cortex and loss of glomeruli can be seen after many years of kidney disease of many types.
Kimmelstiel-Wilson nodules (choice C) are characteristic of diabetic nephropathy.
Pyelonephritis (choice D) is an infection of the kidney, and can complicate a urinary tract infection or be due to hematogenous dissemination of bacteria.
Tubulointerstitial nephritis (choice E) can be seen with drug reactions and toxins.

A3
The correct answer is A. The photomicrograph shows the linear immunofluorescence characteristic of Goodpasture syndrome. The antigenic determinant in Goodpasture syndrome is on the alpha-3 chain of type IV (basement membrane type) collagen.
Elastin (choice B), fibronectin (choice C), laminin (choice D) and vitronectin (choice E) are all found in the extracellular matrix. These molecules could conceivably be antigenic, but have not been implicated in Goodpasture syndrome.

A4

The correct answer is C. The intron sequence (lower case) is a non-coding region between exons. Therefore, the intron portion of the sequence above (cattag) does not encode any amino acids in the Goodpasture antigen. The 9 nucleotides of the in-frame exon sequence shown (UPPER CASE) would be translated into 3 amino acids (3 nucleotides/amino acid) of the Goodpasture antigen. None of the 3 codons shown (GAA, CTC, TTG) is a stop codon.
If all the nucleotides shown were part of an exon, the sequence would code for only 1 amino acid (choice A) because the second triplet (tag) is a stop codon.

A5

The correct answer is E. Corticosteroids and cyclophosphamide are used to prevent the formation of new antibodies and control the inflammatory response in Goodpasture syndrome. Intravenous administration of corticosteroids, such as methylprednisolone or prednisone, or immunosuppressive therapy with cyclophosphamide is usually carried out for several days.
Erythropoietin (choice A) is a glycoprotein, normally produced in the kidneys, that stimulates red blood cell production. It is indicated for treatment of anemia associated with chronic renal failure, zidovudine therapy in HIV-infected patients, and for cancer patients on chemotherapy. It is contraindicated in patients with uncontrolled hypertension and hypersensitivity to mammalian cell-derived products or to human albumin.
Famciclovir (choice B) is a synthetic acyclic purine nucleoside analog that interferes with DNA synthesis in herpes simplex virus (types 1 and 2) and varicella zoster virus. It is used in the treatment of genital herpes in patients who are not immunocompromised.
Foscarnet (choice C) is an agent that inhibits the replication of all known herpes viruses, including cytomegalovirus, herpes simplex virus (types 1 and 2), human herpesvirus 6, Epstein-Barr virus and varicella zoster virus. This agent is indicated for the treatment of cytomegalovirus (CMV) retinitis, mucocutaneous herpes simplex virus (HSV), and acyclovir-resistant HSV in immunocompromised patients.
Isoniazid (choice D) is an agent indicated for the treatment of all forms of tuberculosis (TB) as well as the prophylaxis of tuberculosis. This agent is associated with the development of severe and sometimes fatal hepatitis. Peripheral neuropathy is the most common side effect seen with isoniazid therapy and is associated with a symmetrical numbness and tingling of the extremities. Pyridoxine administration can treat/prevent this condition.

A6

The correct answer is E. In plasmapheresis, the patient's blood is removed (in small amounts over time). The blood cells are collected and the plasma is discarded, and then the blood cells are resuspended in someone else's plasma before being returned to the patient's body. Plasmapheresis is a very effective, albeit expensive, way of washing autoantibody out of the patient's body, and together with pharmacologic immunosuppression has markedly changed the formerly dismal prognosis of Goodpasture syndrome. Surviving patients often stop producing clinically significant amounts of autoantibody within 12 to 18 months, although some patients may require longer-term immunosuppressive therapy.