# Clinical Cases: Blood Pressure Regulation

## Case 1: Pheochromocytoma - Paroxysmal Hypertension

### Patient Presentation
**Demographics:** 38-year-old female

**Chief Complaint:** Episodic severe headaches with palpitations and sweating

**History of Present Illness:**
A 38-year-old female presents with a 6-month history of episodic severe headaches, palpitations, and profuse sweating. Episodes occur 2-3 times weekly, lasting 20-30 minutes, and are accompanied by a sense of impending doom. During episodes, she has measured her blood pressure at home as high as 220/130 mmHg. Between episodes, her BP is 145/92 mmHg. She also reports unintentional 15-pound weight loss and anxiety.

**Physical Examination (during episode):**
- Vital Signs: BP 235/140 mmHg, HR 130 bpm, RR 22/min, SpO2 99%, Temp 37.8°C
- General: Diaphoretic, anxious, tremulous, pale
- Cardiovascular: Tachycardic, regular rhythm, S4 gallop
- Pupils: Dilated
- Skin: Cool, pale, diaphoretic (not flushed)

### Workup
- **Labs (24-hour urine collection):**
  - Metanephrines: 2,850 μg/24h (markedly elevated, normal <400)
  - Normetanephrines: 3,200 μg/24h (markedly elevated)
  - VMA (vanillylmandelic acid): 18 mg/24h (elevated)
  - Plasma metanephrines: 4.2 nmol/L (elevated)
- **CT Abdomen:** 4.5 cm right adrenal mass with heterogeneous enhancement
- **MIBG scan:** Intense uptake in right adrenal gland confirming pheochromocytoma
- **Echocardiogram:** Concentric LVH, EF 60%
- **Genetic testing:** RET mutation negative, VHL negative

### Diagnosis
**Pheochromocytoma with episodic catecholamine-mediated hypertensive crises**

*Blood Pressure Regulation Correlation:*

**Classic triad:** Headache, palpitations, diaphoresis (present in 50% of cases)

**Catecholamine effects on BP:**
- **Norepinephrine (α1):** Vasoconstriction → ↑ SVR → ↑ BP
- **Epinephrine (β1):** ↑ HR, ↑ contractility → ↑ CO
- **Net effect:** Severe hypertension from both ↑CO and ↑SVR

**Why episodic?**
- Tumor releases catecholamines in bursts
- Triggers: Physical activity, tumor manipulation, certain foods (tyramine), anesthesia, medications

**Baroreceptor response:**
- Normally high BP activates baroreceptors → ↓ sympathetic tone
- In pheochromocytoma, the catecholamine surge overwhelms this reflex
- Chronic exposure may reset baroreceptor sensitivity

**Pale (not flushed):** Due to α1-mediated cutaneous vasoconstriction

### Treatment
1. **Alpha-blockade first:** Phenoxybenzamine (irreversible) or doxazosin (selective α1)
   - Must block alpha before beta to prevent unopposed α-mediated vasoconstriction
2. **Beta-blockade second:** Add after adequate alpha-blockade (propranolol or metoprolol)
3. **Preoperative preparation:** 10-14 days of alpha-blockade, high-salt diet, IV fluids
4. **Surgical resection:** Laparoscopic adrenalectomy (definitive treatment)
5. **Intraoperative management:** Have nitroprusside and phentolamine ready for hypertensive surges

### Clinical Image
![Pheochromocytoma CT](case_01_image.jpg)

**Image Description:** CT scan of the abdomen showing a right adrenal mass (pheochromocytoma) appearing as a heterogeneous, well-circumscribed mass superior to the kidney with areas of necrosis or hemorrhage.

**Source:** Radiopaedia - Pheochromocytoma
**License:** CC BY-NC-SA 3.0
**URL:** https://radiopaedia.org/cases/phaeochromocytoma-3

---

## Case 2: Renovascular Hypertension - Renal Artery Stenosis

### Patient Presentation
**Demographics:** 62-year-old male

**Chief Complaint:** Difficult-to-control hypertension

**History of Present Illness:**
A 62-year-old male with 15-year history of hypertension, diabetes, and hyperlipidemia presents for evaluation of refractory hypertension. Despite taking lisinopril 40 mg, amlodipine 10 mg, and hydrochlorothiazide 25 mg, his BP remains 175/105 mmHg. He has had progressive decline in kidney function over the past year. He reports a recent episode of acute pulmonary edema ("flash pulmonary edema") that resolved with diuresis. Heavy smoker (50 pack-years).

**Physical Examination:**
- Vital Signs: BP 178/108 mmHg (both arms equal), HR 72 bpm, RR 16/min
- General: Obese male, appears older than stated age
- Cardiovascular: Regular rhythm, S4 gallop, abdominal bruit (right periumbilical)
- Peripheral vascular: Diminished femoral pulses, ABI 0.7 bilateral
- Fundoscopy: Arteriovenous nicking, copper wiring (hypertensive retinopathy)

### Workup
- **Labs:**
  - Creatinine: 2.1 mg/dL (was 1.3 one year ago)
  - Potassium: 3.2 mEq/L (low - secondary hyperaldosteronism)
  - BUN: 38 mg/dL
  - Plasma renin activity: 12 ng/mL/hr (elevated)
  - Aldosterone: 28 ng/dL (elevated)
- **Renal Doppler ultrasound:** Right kidney 8.5 cm (small), left 11 cm; elevated resistive indices
- **CT angiography:** 85% stenosis of right renal artery, moderate left renal artery stenosis (60%)
- **Renal artery duplex:** Peak systolic velocity 380 cm/s in right renal artery (normal <180)

### Diagnosis
**Atherosclerotic bilateral renal artery stenosis with secondary renovascular hypertension**

*Blood Pressure Regulation Correlation:*

**RAAS Activation in Renal Artery Stenosis:**
1. Stenosis → ↓ renal perfusion pressure
2. Juxtaglomerular cells sense low pressure → ↑ renin secretion
3. Renin converts angiotensinogen → angiotensin I
4. ACE converts angiotensin I → angiotensin II
5. Angiotensin II effects:
   - Vasoconstriction → ↑ SVR → ↑ BP
   - Aldosterone release → Na+/H2O retention → ↑ volume → ↑ BP
   - ADH release → H2O retention
   - Sympathetic activation

**Flash pulmonary edema:** Sudden volume and pressure overload overwhelms cardiac reserve

**Hypokalemia:** Due to secondary hyperaldosteronism (aldosterone promotes K+ excretion)

**ACE inhibitor caution:** Can cause acute kidney injury in bilateral RAS (removes angiotensin II-mediated efferent arteriolar constriction that maintains GFR)

### Treatment
1. **Medical optimization:**
   - Continue calcium channel blocker (amlodipine)
   - Add/continue diuretic
   - Caution with ACE-I/ARB in bilateral disease
   - Statin for atherosclerosis
2. **Revascularization options:**
   - Renal artery stenting (angioplasty with stent)
   - Surgical revascularization (bypass)
   - Indicated for: flash pulmonary edema, progressive CKD, refractory hypertension
3. **Risk factor modification:**
   - Smoking cessation (critical)
   - Diabetes control
   - Lipid management

### Clinical Image
![Renal Artery Stenosis Angiogram](case_02_image.jpg)

**Image Description:** Renal angiogram demonstrating severe stenosis of the renal artery with characteristic narrowing and post-stenotic dilation. The stenosis is typically located at the ostium or proximal segment in atherosclerotic disease.

**Source:** Wikimedia Commons - Renal artery stenosis
**License:** CC BY-SA 3.0
**URL:** https://commons.wikimedia.org/wiki/File:Renal_artery_stenosis.jpg

---

## Case 3: Orthostatic Hypotension - Autonomic Dysfunction

### Patient Presentation
**Demographics:** 75-year-old male

**Chief Complaint:** Dizziness and falls when standing

**History of Present Illness:**
A 75-year-old male with Parkinson's disease (diagnosed 8 years ago) presents with 6 months of progressive dizziness and near-syncope upon standing. He has had 4 falls in the past month, all occurring shortly after standing up. Symptoms are worse in the morning and after meals. He also reports constipation, urinary hesitancy, and decreased sweating. Current medications include carbidopa-levodopa and pramipexole.

**Physical Examination:**
- Vital Signs:
  - **Supine:** BP 145/85 mmHg, HR 70 bpm (after 5 min supine)
  - **Standing (1 min):** BP 98/60 mmHg, HR 74 bpm
  - **Standing (3 min):** BP 85/55 mmHg, HR 76 bpm
- General: Masked facies, resting tremor, shuffling gait
- Cardiovascular: Regular rhythm, no murmurs
- Neurologic: Bradykinesia, rigidity, postural instability

### Workup
- **Orthostatic BP testing:** Systolic BP drop >40 mmHg with minimal HR increase
- **Head-up tilt table test:** Reproduced orthostatic hypotension without vasovagal features
- **Labs:** Basic metabolic panel normal, hemoglobin 13.5 g/dL, cortisol normal
- **Autonomic function testing:**
  - Heart rate variability: Reduced
  - Valsalva ratio: Blunted (indicates parasympathetic dysfunction)
  - Sweat testing: Anhidrosis in lower extremities
- **Cardiac autonomic testing:** Blunted HR response to deep breathing

### Diagnosis
**Neurogenic orthostatic hypotension secondary to Parkinson's disease with autonomic dysfunction**

*Blood Pressure Regulation Correlation:*

**Normal standing response:**
1. Standing → blood pools in lower extremities (500-800 mL)
2. ↓ Venous return → ↓ CO → ↓ BP
3. Baroreceptors detect ↓ BP → activate sympathetic response:
   - ↑ HR (normally increases 10-25 bpm)
   - Vasoconstriction (↑ SVR)
   - Venoconstriction (↑ venous return)
4. Result: BP maintained within 10-20 mmHg of baseline

**In autonomic failure:**
- Efferent sympathetic pathways damaged → cannot increase HR or vasoconstrict
- α-synuclein deposits in autonomic ganglia (Parkinson's, MSA, Lewy body dementia)
- Baroreceptor reflex arc disrupted
- Result: Uncompensated BP drop, minimal HR response

**Criteria for orthostatic hypotension:**
- Systolic BP drop ≥20 mmHg OR
- Diastolic BP drop ≥10 mmHg
- Within 3 minutes of standing

**Neurogenic vs. non-neurogenic:** Minimal HR increase (<15 bpm) suggests neurogenic cause

### Treatment
1. **Non-pharmacologic measures:**
   - Rise slowly from sitting/lying
   - Compression stockings (waist-high)
   - Abdominal binder
   - Increase salt and fluid intake (2-3 L/day, 6-10 g sodium)
   - Elevate head of bed 10-20°
   - Avoid large meals, alcohol, hot environments
2. **Medication review:**
   - Reduce/eliminate offending agents (may need to adjust Parkinson's meds)
3. **Pharmacologic treatment:**
   - Midodrine (α1 agonist): 5-10 mg TID before meals
   - Fludrocortisone (mineralocorticoid): 0.1-0.2 mg daily (volume expansion)
   - Droxidopa (norepinephrine prodrug): For neurogenic OH

### Clinical Image
![Orthostatic Hypotension Mechanism](case_03_image.jpg)

**Image Description:** Diagram illustrating the pathophysiology of orthostatic hypotension, showing blood pooling in lower extremities upon standing and the normal baroreceptor-mediated compensatory response that fails in autonomic dysfunction.

**Source:** Wikimedia Commons - Orthostatic hypotension
**License:** CC BY-SA 4.0
**URL:** https://commons.wikimedia.org/wiki/File:Orthostatic_hypotension.svg