CBI 3: 52 Year Old Man with Hemoptysis: WEGENER S GRANULOMATOSIS

CBI 3: 52 Year Old Man with Hemoptysis: WEGENER S GRANULOMATOSIS

CBI 3: 52 year old man with hemoptysis: WEGENER’S GRANULOMATOSIS

Initial Case Presentation

Chief Complaint:

Martin Smith is a 52 year old male mechanic who comes to urgent care complaining of coughing up blood since the previous evening.

Diff Dx:

  • TB/Cocci
  • Lung Cancer
  • Mesothelioma
  • PE
  • Vasculitis (Wegener’s)
  • Pneumonia
  • Trauma
  • Goodpasture’s
  • Laryngeal Cancer
  • CHF
  • Lupus

HPI (Pertinent):

  • Bright red blood in small amounts continuously last night and this morning. ½ cup total.
  • Began 10-14 days ago with dyspnea, NPC, and 7 days of blood streaked sputum
  • + night sweats
  • 35 pack/year smoking history
  • X wt loss, chest pain, hematemesis, chest pain, orthopnea, wheezing, easy bruising/bleeding, hematuria.

ROS (Pertinent):

  • Rash on fingers noted 1 month ago
  • Mild myalgias x1 month

Physical (Pertinent):

  • Pulse Ox: 90%
  • RR: 24
  • Crackles over both lung fields, prominent at bases
  • Guiac +

Lab (Pertinent):

  • CXR: Bilateral opacities with alveolar filling patterns
  • Elevated WBC (PMNs) & Platelets
  • Low CO2, PaCO2, PaO2 (mild respiratory alkalosis)
  • Elevated BUN/Creatitine (10:1 intrarenal), ESR (inflammation), CRP
  • Hematuria w/casts (glomerulonephritis), proteinuria

Learning Issues

  • Red rash- Steve
  • Goodpasture’s- Jen
  • Lupus-Karen
  • Wegener’s- Nick
  • Obstructive VS Restrictive Lung Dz (lung function tests and causes)-
  • Summarize quantifying renal function (calculate GFR, renal plasma clearance, afferent and efferent arterioles)-Raji
  • Antibiotics review-Mike

Friday Session-Presentations

Palmar Rash

  • Purpura: RBC’s extravasate into superficial space. Palpable VS non-palpable.
  • Wegner’s skin manifestations: Ulcers, purpura, vesicles, hemorrhage, and papules.
  • Goodpasture’s skin manifestations: None
  • SLE skin manifestations:
  • Malar facial rash
  • Discoid pattern rash
  • Subacute cutaneous: Recurrent (papulosquamous or annular) rashes on extremities on face, extremities, and trunk.

SLE

  • Systemic autoimmune disease seen mostly in young women with higher incidence in African and Hispanic Americans.
  • Etiology: Antibodies to many different self tissues form. HLA DR3 and DR4 predispose people to developing SLE.
  • Pathophysiology: Type III hypersensitivity due to immune complex deposition in the tissues with activation of complement.
  • Clinical Criteria:

  • Malar/discoid rash
  • Photosensitivity
  • Arthritis
  • Hematologic disorders
  • Renal disorder (subendothelial wire-loop lesions, mesangial hyperplasia)
  • Serositis
  • Fever
  • Libman-Sacks endocarditis (mitral vegetations)
  • Cause of Death: Infection and renal failure.

  • Diagnosis: ANA’s-Generic, Anti-DS DNA, Anti-Smith, anti-histone, anti-phospholipid (causes false-positive syphilis test).
  • Tx: Glucocorticoids

Goodpasture’s

  • Autoimmune disease
  • Etiology: Antibodies to 3 chain of type 4 collagen present in the basement membrane
  • Pathogenesis: Type II hypersensitivity due to antibodies that cause destruction of the basement membrane in areas with small capillary beds such as the lung and the glomerulus.
  • Clinical: Episode of progressive glomerulonephritis, pneumonitis (hemoptysis, focal consolidations, restrictive lung disease) with unknown trigger. Cause of death: Uremia.
  • Path:
  • Lung: Hemosiderin laden macrophages and type 2 pneumocyte hypertrophy, fibrous septate thickening.
  • Kidney: Focal proliferative glomerulonephritis with crescentic morphology.
  • Both: Linear deposition of IG along the basement membrane.
  • Diagnosis: Percutaneous renal biopsy
  • Tx: Plasmapheresis or immunosuppression.

Wegner’s Granulomatosis

  • Systemic necrotizing granulomatous vasculitis of small and medium arteries and veins
  • Etiology: Genetic
  • Pathogenesis: Anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for inflammation, granuloma formation,and necrosis of vasculature causing end organ damage associated with the wide variety of symptoms seen.
  • Clinical:
  • Acute/Chronic
  • Upper/lower respiratory
  • Ulceration, septal perforation, saddle nose deformity, sinusitis, pulmonary infiltrates, nodules with cavitation, hemorrhage, obstructive or restrictive lung disease)
  • Renal involvement
  • Crescentic glomerulonephritis with renal insufficiency.
  • Fever
  • Weight loss
  • Myalgias/arthralgias
  • Cutaneous: purpura, ulcers, gangrene
  • Neurologic: peripheral neuropathy, cranial neuropathy, infarction, hemorrhage, seizures
  • GI: Abdominal pain, diarrhea, bleeding, ulcerations, infarction
  • Cardiac: Pericarditis, arteritis, conduction defects, cardiomyopathy
  • GU
  • Diagnosis: Renal biopsy with crescentic GN, granuloma formation, and fibrinoid necrosis. Presence of C-ANCA. + Rheumatoid factor.
  • Tx: Cyclophosphamide, corticosteroids.

Spirometry Interpretations

  • FVC: Forced vital capacity
  • FEV-1: Forced expiratory volume in one second
  • FEF 25-75%: Forced expiratory flows between 25-75% of volume
  • Obstructive
  • Increased resistance within the lung causing decreased flows
  • FVC: Normal
  • FEV-1: Decreases
  • FEV1/FVC: Decreases
  • Restrictive
  • Loss of effective lung volume
  • FVC: Decreases
  • FEV-1: Decreases
  • FEV1/FVC: Normal to increased

Quantifying Renal Function

  • GFR x Pinulin = V x Uinulin GFR = (V x Uinulin) / Pinulin
  • Can also be done using creatinine, but this overestimates GFR because creatinine is secreted from the tubules as well as being filtered.
  • Clearance: Volume of plasma cleared of a substance per unit time
  • If clearance is > Cin the substance is filtered + secreted
  • If clearance is < Cin the substance is filtered + reabsorbed
  • Effective renal plasma flow: (Upah x V)/Ppah
  • RPF: ERPF/.9
  • Renal Blood Flow: ERPF / (1-HCT)
  • FF: GFR/RPF (amount of plasma that flows through the kidney that is filtered by the glom)
  • Fractional Excretion: FEx = (Ux x V) / (Px x GFR)
  • Fractional Reabsorption: FRx = 1- FEx

Antibiotic Review- See Mike’s Presentation 

  1. Identify categories of diseases that result in hemoptysis and specific disease processes in each category.
  • Airway Disease
  • Upper-obstruction, trauma, mucosal ulceration, bronchitis, infection, neoplasm
  • Lower-obstruction, neoplasm, trauma, infection
  • Pulmonary parenchymal disease: PF, ARDS, infection (tuberculosis, coccidiodes), autoimmune disease (lupus, Goodpasture’s, Wegener’s), iatrogenic, cocaine use
  • Pulmonary vascular disease: PE, AVM (osler-weber-rendupresents w/telangiectasia), pulmonary hypertension
  • Cryptogenic
  1. Explain the utility of urinalysis in the diagnosis of renal disease and the particular significance of red blood cell casts.
  • Components of Urinalysis:

  • Color/consistency
  • Protein +/-
  • pH
  • Osmolality/specific gravity
  • Glucose +/-
  • Bacteria +/-
  • Cells
  • Casts

  • The components of a urinalysis, as shown above, are many and varied. There are also a number of specific urine tests that can be ordered that examine for the presence/absence of specific molecules to help evaluate specific disease process (ie porphobilinogen in porphyria). Urinalysis is a helpful tool in evaluating the cause of renal/urinary disease because there are characteristic findings which are strongly suggestive of specific diagnoses.
  • RBC casts indicate glomerulonephritis (glomerular inflammation), and can help differentiate renal disease that presents with hematuria from cystitis that presents with hematuria (which would show RBC’s without casts).
  1. Explain potential pathogenic mechanisms underlying disease processes that produce the syndrome of pulmonary alveolar hemorrhage and acute glomerulonephritis (red cell casts, and renal insufficiency).
  • Post-streptococcal glomerulonephritis: Antibodies to the group b strep M antigen can be cross-reactive with the glomerular basement membrane and cause glomerulonephritis secondary to a streptococcal infection.
  • Goodpasture’s Syndrome:Short-lived circulating of antibodies directed against the -chain of type 4 collagen (found in the basement membrane) attach to the GBM and the alveolar BM inciting inflammation and the classical presentation of glomerulonephritis and hemoptysis. Inciting stimulus is unknown.
  • Lupus: Lupus is an autoimmune disorder in which circulating anti-nuclear antibody complexes deposit in tissues and incite an inflammatory response that causes tissue damage.
  • Wegener’s: Wegener’s is an autoimmune disorder that is the result of antibodies to neutrophil granule proteins that cause release of inflammatory mediators that cause a systemic vascular inflammation. The production of anti-neutrophil cytoplasmic antibodies (ANCAs) is one of the hallmarks of WG.
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