The following cases and commentary, which address hypertension, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Lupus patient with kidney injury
A 35-year-old woman with a 3-year history of systemic lupus erythematosus is admitted to the hospital with a blood pressure of 180/90 mm Hg and evidence of acute kidney injury. Her last lupus flare was 1 year ago, and she is currently asymptomatic. Five years ago, she developed deep venous thrombosis and pulmonary embolism after an automobile accident. She has had three first-trimester miscarriages. Her only medication is hydroxychloroquine.
On physical examination, temperature is normal, blood pressure is 200/96 mm Hg, pulse rate is 102/min, and respiration rate is 20/min. Cardiopulmonary examination is normal except for an S4 gallop. Abdominal examination is unremarkable. There is no rash, lymphadenopathy, or oral ulcers.
Laboratory studies show hemoglobin 12.3 g/dL (123 g/L); leukocyte count 5300/µL (5.3 × 109/L); platelet count 122,000/µL (122 × 109/L); reticulocyte count 1.9% of erythrocytes; serum creatinine 3.2 mg/dL (244.2 µmol/L); serum complement (C3 and C4) normal; antinuclear antibodies 1:1280 (speckled pattern); anti–double-stranded DNA antibodies negative; IgM-specific anticardiolipin antibodies >100 U/mL; IgG-specific anticardiolipin antibodies >100 U/mL; lupus anticoagulant positive; urinalysis: 2+ protein, 1+ blood, 2-3 leukocytes, 3-5 erythrocytes/hpf; urine protein-creatinine ratio 1.2 mg/mg.
A direct antiglobulin test (Coombs test) is negative. Peripheral blood smear reveals rare schistocytes. Renal ultrasonography reveals normal-sized kidneys with no obstruction or renal vein thrombosis. Renal biopsy shows capillary congestion and intracapillary fibrin thrombi consistent with thrombotic microangiopathy. Immunofluorescence testing reveals deposition of fibrin but not IgG, IgM, or C3.
Which of the following is the most appropriate next step in this patient's treatment?
C. Prednisone plus cyclophosphamide
D. Plasmapheresis plus fresh frozen plasma
Case 2: Explosive headache
A 73-year-old woman is evaluated in the emergency department for the onset of a severe, “explosive” headache 8 hours ago. She initially rested in a dark bedroom after headache onset, but when the pain did not abate, her husband drove her to the hospital. The patient has hypertension controlled with lisinopril. Family medical history is noncontributory.
As assessment in the emergency department begins, she becomes nauseated, vomits, and then becomes rapidly and progressively more obtunded. Intubation and mechanical ventilation are required.
On physical examination, temperature is normal, blood pressure is 188/102 mm Hg, pulse rate is 120/min, and respiration rate is 20/min. The patient exhibits a flaccid quadriplegia, and meningismus is present. Both pupils are 4 mm in diameter and nonreactive; the oculocephalic reflex is absent, and the corneal reflex is absent bilaterally. She has a depressed level of consciousness, with a Glasgow Coma Scale score of 3. Subhyaloid hemorrhages are noted on funduscopy.
Results of a complete blood count (with differential) are normal, as are blood urea nitrogen, serum creatinine, and serum electrolyte levels.
A CT scan of the head shows an extensive acute subarachnoid hemorrhage and mild prominence of the temporal tips of the lateral ventricles.
Which of the following neurologic complications is most likely to have caused this patient's rapid deterioration?
C. Syndrome of inappropriate antidiuretic hormone secretion
Case 3: Incontinence after stroke
A 66-year-old woman, who resides in a nursing home following a stroke, is hospitalized because of loose stools and confusion. On the second hospital day, the patient has two episodes of urinary incontinence. Neither the nursing-home staff nor family members report previous problems with incontinence. Medical history is significant for a cerebrovascular accident with severe aphasia and left hemiparesis, hypertension, and type 2 diabetes mellitus. Current medications are aspirin, dipyridamole, lisinopril, and glipizide.
On physical examination, temperature is 36.8° C (98.2° F), blood pressure is 164/96 mm Hg, pulse rate is 92/min, and respiration rate is 18/min. Arterial oxygen saturation is 98% on ambient air. Results of cardiopulmonary, abdominal, and rectal examinations are normal. On neurologic examination, the patient is not oriented to place or date and she keeps trying to climb out of bed. There is expressive aphasia and moderate weakness of the left arm and leg.
Laboratory studies show a normal complete blood count, calcium 8.6 mg/dL (2.15 mmol/L), creatinine 1.2 mg/dL (106.1 µmol/L), glucose 100 mg/dL (5.55 mmol/L), and normal electrolytes. Urinalysis finds 2+ glucose, moderate protein, 10-20 leukocytes and 3-5 erythrocytes/hpf.
Results of urine and blood cultures are pending. An electrocardiogram and chest radiograph are normal.
Which of the following is the best management for this patient's incontinence?
A. Begin ciprofloxacin
B. Discontinue glipizide
C. Insert an indwelling urinary catheter
D. Schedule a CT scan of the head
Case 4: Chest pain in emergency department
A 62-year-old woman is brought to the emergency department by paramedics for chest pain that has been present for 5 hours. Medical history is notable for type 2 diabetes mellitus, hypertension, and a stroke 1 year ago. Medications include glyburide, lisinopril, atorvastatin, and aspirin.
On physical examination, she appears comfortable. She is afebrile, blood pressure is 190/90 mm Hg, pulse rate is 88/min and respiration rate is 16/min. Cardiac examination shows no murmurs, extra sounds, or rubs. The lungs are clear and pulses are equal bilaterally. Neurologic examination is normal.
The electrocardiogram shows 2-mm ST-segment elevation in leads II, III, and aVF.
A coronary catheterization laboratory is not available, and the nearest hospital with percutaneous intervention capability is 1 hour away.
Which of the following is the best management option for this patient?
A. Aggressive medical therapy without reperfusion attempt
B. Immediate thrombolytic therapy
C. Transfer for coronary artery bypass graft surgery
D. Transfer for percutaneous coronary intervention
Case 5: Dyspnea with history of hypertension
A 72-year-old man is admitted to the hospital with a 3-month history of progressive dyspnea, bilateral lower-extremity edema, and nonradiating pain in the right flank. He has gained 3.2 kg (7 lb). He was diagnosed with benign prostatic hyperplasia 3 years ago. He has a 30-year history of hypertension. Medications are lisinopril and terazosin.
On physical examination, temperature is 36.5° C (97.8° F), blood pressure is 158/92 mm Hg, pulse rate is 82/min, and respiration rate is 12/min. BMI is 31. Jugular venous pressure is normal. Cardiopulmonary examination reveals decreased breath sounds at both lung bases. Abdominal and neurologic examinations are normal.
Laboratory studies show hemoglobin 14.3 g/dL (143 g/L), fasting glucose 85 mg/dL (4.7 mmol/L), serum total cholesterol 320 mg/dL (8.3 mmol/L), blood urea nitrogen 32 mg/dL (11.4 mmol/L), serum creatinine 2.1 mg/dL (185.6 µmol/L). Urinalysis results are 3+ protein, occasional hyaline casts and urine protein-creatinine ratio is 8 mg/mg.
Serum and urine protein electrophoreses are normal. A chest radiograph shows normal heart size and bilateral pleural effusions. On kidney ultrasound, the right kidney is 13.5 cm and the left kidney is 12.0 cm. There is increased echogenicity and no hydronephrosis. Doppler ultrasound shows possible right renal vein thrombosis.
Which of the following is the most likely diagnosis?
A. IgA nephropathy
B. Membranous nephropathy
C. Multiple myeloma
D. Obstructive nephropathy
Answers and commentary
Correct answer: A. Heparin.
This patient has a 3-year history of systemic lupus erythematosus (SLE). Her history of deep venous thrombosis, pulmonary embolism, and three first-trimester miscarriages also is strongly suggestive of the antiphospholipid antibody syndrome (APS). This diagnosis is confirmed by the presence of anticardiolipin antibodies and a lupus anticoagulant. APS is characterized by the presence of at least one type of autoantibody known as an antiphospholipid antibody and at least one recognized clinical feature of this condition, which may include venous or arterial thromboses, recurrent fetal loss, or thrombocytopenia.
This patient now presents with new-onset hypertension, proteinuria, renal failure, and a thrombotic microangiopathy seen on renal biopsy. These findings are most likely caused by her APS, and the most appropriate treatment is heparin. Although corticosteroids, plasmapheresis, and rituximab have been used in patients with catastrophic APS, anticoagulation is considered first-line treatment for APS-related microangiopathy.
Determining whether acute kidney injury in patients with SLE who have antiphospholipid antibodies is associated with inflammation, which would be suggestive of SLE, or thrombosis, which would be suggestive of APS, is critical in order to initiate appropriate treatment. The presence of a thrombotic microangiopathy on renal biopsy in a patient with anticardiolipin antibodies and a lupus anticoagulant suggests that this patient's renal failure is a manifestation of APS and therefore thrombotic in origin. The therapy for APS is the same regardless of whether the disorder is primary or secondary to SLE. Anticoagulation therapy with heparin, followed by warfarin, is indicated in patients with thrombotic-associated manifestations of this condition.
Prednisone and cyclophosphamide are used in the treatment of lupus nephritis. However, this patient currently has no symptoms of active SLE. In addition, her renal biopsy reveals no evidence of inflammation consistent with lupus nephritis, anti–double-stranded DNA antibody assay is negative, and her complement levels are normal.
Plasmapheresis plus fresh frozen plasma is indicated to treat thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS), which may be associated with SLE. Rituximab also has been used to treat this condition. The presentation of TTP-HUS is similar to that of APS-associated thrombotic microangiopathy, and renal biopsy results in patients with TTP-HUS and APS-associated thrombotic microangiopathy can be indistinguishable. However, TTP-HUS would not explain the presence of antiphospholipid antibodies. In addition, patients with TTP-HUS often have fever, mental status changes, and severe thrombocytopenia. The microangiopathic hemolytic anemia associated with TTP-HUS is characterized by numerous schistocytes on peripheral blood smear and usually is associated with a high reticulocyte count, both of which are absent in this patient.
- Anticoagulation therapy with heparin followed by warfarin is indicated in patients who have thrombotic microangiopathy associated with the antiphospholipid antibody syndrome.
Correct answer: B. Rebleeding.
The most likely complication to have caused this patient's rapid deterioration is rebleeding. In the first few hours after an initial hemorrhage, up to 15% of affected patients have a sudden deterioration of consciousness, which strongly suggests rebleeding. In patients who survive the first day, the rebleeding risk is evenly distributed during the next 4 weeks, with a cumulative risk of 40% without surgical or endovascular interventions. Occlusion of the responsible aneurysm is thus the first aim in the management of a subarachnoid hemorrhage and is usually performed by coiling or clipping.
Typically, patients who develop hydrocephalus after having a subarachnoid hemorrhage are initially alert but then experience a gradual reduction in consciousness over the next 24 hours. Downward deviation of the eyes and small, unreactive pupils indicate dilatation of the proximal part of the cerebral aqueduct with dysfunction of the pretectal area. Although this patient may have secondarily developed hydrocephalus, her symptoms and examination findings suggest that the principal reason for her precipitous decline is early rebleeding. On average, one in five patients who sustain subarachnoid hemorrhages will have mildly enlarged ventricles on the initial CT scan but not frank hydrocephalus.
The syndrome of inappropriate antidiuretic hormone secretion is recognized as a potential complication in patients with subarachnoid hemorrhages and other critical care neurologic conditions. Its symptoms and signs are muscle cramps, weakness, altered sensorium, coma, and seizures. This syndrome causes the electrolyte disturbance of hyponatremia. This patient's serum electrolytes were determined to be in the normal range at the time of her evaluation in the emergency department.
Vasospasm-induced cerebral ischemia after a subarachnoid hemorrhage has a more gradual onset than occurred in this patient. It often involves more than the territory of a single cerebral artery. The clinical manifestations evolve gradually over several hours and consist of hemispheric focal deficits, a reduction of consciousness, or both. The peak frequency of vasospasm is from 5 to 14 days after the subarachnoid hemorrhage.
- Rebleeding is the most imminent danger after a subarachnoid hemorrhage.
Correct answer: A. Begin ciprofloxacin.
This patient with new-onset urinary incontinence should first be evaluated for transient, reversible causes, for which the mnemonic DIAPERS may be useful: Drugs, Infection, Atrophic vaginitis, Psychological (depression, delirium, dementia), Endocrine (hyperglycemia, hypercalcemia), Restricted mobility, and Stool impaction. Urinary tract infection is a very common cause of transient incontinence in the elderly, particularly if other contributing factors such as cognitive impairment or impaired mobility are present. The presence of significant pyuria in this setting generally justifies administration of empiric antibiotic therapy pending urine culture results. Therefore, beginning ciprofloxacin is appropriate for this patient.
Although some medications may induce transient incontinence, causative agents are most often diuretics or drugs that affect autonomic nervous system or bladder function. Oral hypoglycemic agents do not typically cause incontinence, and discontinuing these agents in a patient with diabetes mellitus could precipitate hyperglycemia and increased incontinence.
Indwelling catheterization is a treatment of last resort for patients who have chronic incontinence that is unresponsive to other therapy and in whom intermittent catheterization is not feasible.
This patient's confusion is more consistent with delirium in an elderly patient as a generalized response to an acute illness rather than a focal neurologic event. CT scan of the head is typically not helpful in such patients and is unlikely to provide an explanation for this patient's incontinence.
- Empiric antibiotic treatment pending the results of a urine culture may be warranted in elderly patients with new-onset urinary incontinence and pyuria.
Correct answer: D. Transfer for percutaneous coronary intervention.
The patient is experiencing an acute inferior wall ST-elevation myocardial infarction (STEMI). The treatment for an acute STEMI is either revascularization or thrombolytic therapy. Relative contraindications to thrombolytic therapy include pregnancy, poorly controlled hypertension, prior ischemic stroke more than 3 months ago, prolonged cardiopulmonary resuscitation within 3 weeks, recent (within 2 to 4 weeks) internal bleeding, active peptic ulcer disease, and current use of anticoagulants (warfarin).
Absolute contraindications include any prior intracerebral hemorrhage, known cerebrovascular lesion (arteriovenous malformation), ischemic stroke within 3 months, suspected aortic dissection, active bleeding (excluding menses), and significant closed head or facial trauma within 3 months. The patient presented has two relative contraindications for thrombolytic therapy—uncontrolled hypertension and a prior stroke. She is currently hemodynamically stable without cardiogenic shock. Despite the inherent time delays, the best treatment approach would be to transfer her to a nearby facility where percutaneous coronary intervention could be performed. Current data suggest that a time delay of less than 60 minutes is acceptable in transferring patients for percutaneous coronary intervention.
Aggressive medical therapy would not be the correct option for this patient given the electrocardiographic findings, her relatively young age, and the ability to transfer her to a nearby hospital to receive appropriate care.
Transfer for coronary artery bypass graft surgery would not be the correct option given that the patient's coronary anatomy has not yet been defined. Most patients presenting with a STEMI can be treated effectively with percutaneous coronary intervention. Bypass surgery in the setting of an acute infarction is therefore rarely performed.
- Absolute and relative contraindications to thrombolytic therapy should be reviewed in all patients being considered for thrombolytic therapy.
Correct answer: B. Membranous nephropathy.
This patient most likely has membranous nephropathy, which may occur secondary to infection, autoimmune diseases, malignancies, and use of drugs such as NSAIDs. In most patients with malignancy-associated membranous nephropathy, malignancy is already diagnosed or suspected by the time proteinuria is discovered. Patients recently diagnosed with membranous nephropathy should undergo age- and sex-appropriate screening for malignancies; additional screening tests should be guided by the patient's clinical presentation. Many experts also recommend serologic screening for hepatitis B and C virus and syphilis and an antinuclear antibody assay in these patients.
Membranous nephropathy is the most common cause of primary nephrotic syndrome in patients older than 70 years of age. This syndrome may manifest as a urine protein excretion above 3.5 g/24 h (3.5 g/d), edema, hypoalbuminemia, hyperlipidemia, and lipiduria.
Membranous nephropathy is often associated with microscopic hematuria and an increased risk for large-vein thromboses. Renal vein thrombosis in particular may develop in these patients and frequently manifests as flank pain and worsening proteinuria and kidney insufficiency. Renal vein thrombosis also may be associated with pulmonary emboli.
Patients with IgA nephropathy typically have an active nephritic urine sediment and often have gross hematuria; progressive kidney failure is rare in these patients. IgA nephropathy also does not commonly cause renal vein thrombosis.
Multiple myeloma may manifest as kidney insufficiency and proteinuria but is unlikely in a patient with normal results on serum and urine protein electrophoreses.
Patients with benign prostatic hyperplasia have an increased risk for obstructive nephropathy, but the absence of hydronephrosis or an increased postvoid residual volume argues against this diagnosis. Furthermore, obstructive nephropathy secondary to prostatic hyperplasia is not associated with the nephrotic syndrome or renal vein thrombosis.
- Membranous nephropathy may occur secondary to malignancy and is associated with renal vein thrombosis.