---

Cardialgia: Classification, Differential Diagnosis & Clinical Management (Questions 83–99)

---

83. Classification of Cardialgia Depending on Their Origin

I. Cardiogenic (Cardiac) Pain

1. Ischemic — due to myocardial oxygen supply/demand mismatch
   • Stable angina pectoris
   • Unstable angina
   • Acute myocardial infarction (AMI)
   • Prinzmetal (vasospastic) angina
2. Inflammatory
   • Pericarditis
   • Myocarditis
3. Structural/Mechanical
   • Hypertrophic cardiomyopathy (HCM)
   • Aortic stenosis
   • Mitral valve prolapse
4. Vascular
   • Aortic dissection

II. Non-Cardiogenic (Extra-Cardiac) Pain

1. Pulmonary — pleurisy, pneumonia, pneumothorax, pulmonary embolism, pulmonary hypertension
2. Gastrointestinal — GERD, esophageal spasm, peptic ulcer, cholecystitis, pancreatitis
3. Musculoskeletal — costochondritis, osteochondrosis, rib fracture
4. Neurological/Psychiatric — intercostal neuralgia, herpes zoster, neurocirculatory dystonia (NCD), panic disorder
5. Other — Tietze syndrome, breast pathology

---

84. Differential Diagnosis of Cardiogenic vs. Non-Cardiogenic Chest Pain

Rosen's Emergency Medicine: "Substernal chest pain is the main symptom in 80–90% of patients with ischemic disease. Although certain features of the chest pain history serve to increase or decrease the likelihood of ACS, none is strong enough alone to establish or exclude the diagnosis."

---

85. Differences in Clinical Picture: Cardiogenic vs. Non-Cardiogenic Chest Pain

Cardiogenic Pain — Clinical Picture

• Onset: Often sudden, during exertion or at rest (AMI)
• Quality: "Crushing," "elephant on chest," "pressure," "tightness" — not sharp
• Site: Substernal or precordial; radiation to left arm (ulnar aspect), jaw, neck, both arms
• Associated: Diaphoresis, pallor, nausea, vomiting, dyspnea, anxiety, palpitations
• Posture: Not affected by body position or respiration (unlike pericarditis)
• ECG: ST elevation/depression, T-wave changes, arrhythmias
• Key sign: Pain not reproducible on palpation; not pleuritic

Non-Cardiogenic Pain — Clinical Picture

• Musculoskeletal: Reproduced on chest wall palpation; worsened by movement
• Pleuritic (pulmonary): Sharp, worsened by deep breathing/cough; relieved by shallow breathing
• Esophageal/GI: Burning, retrosternal, worsened after meals, lying down; relieved by antacids
• Neurological/Dermatomal: Follows nerve distribution; burning; hyperesthesia of skin
• NCD/Anxiety: Stabbing, brief, left inframammary; associated with sighing, palpitations, dizziness, without ECG changes

---

86. Classification of Coronary Heart Disease (IHD) According to WHO

1. Angina Pectoris
   • Stable angina (exertional)
   • Unstable angina (includes new-onset, rest, and crescendo angina)
   • Prinzmetal (variant/vasospastic) angina
2. Acute Myocardial Infarction (AMI)
   • STEMI (ST-elevation MI)
   • NSTEMI (Non-ST-elevation MI)
3. Post-Myocardial Infarction (old MI / cardiosclerosis)
4. Heart Failure (as a consequence of IHD)
5. Cardiac Arrhythmias (as a consequence of IHD)
6. Sudden Cardiac Death (primary cardiac arrest)
7. Silent (Painless) Myocardial Ischemia

---

87. Characteristics of Pain Syndrome in Ischemic Heart Disease

• Location: Substernal, precordial; may be right-sided or bilateral
• Character: Tightening, squeezing, pressure, heaviness, fullness, burning — not a sharp stabbing pain
• Radiation: Neck, jaw, shoulders, arms (ulnar aspect); either or both arms may be involved
• Duration:
  • Stable angina: 2–10 min, typically resolves with rest or nitrates
  • Unstable angina: >10–20 min, may occur at rest
  • AMI: >20–30 min, not relieved by nitrates
• Precipitating factors: Physical exertion, emotional stress, cold weather, large meals
• Relieving factors: Rest (stable angina), sublingual nitroglycerin
• Associated symptoms: Dyspnea, diaphoresis, nausea/vomiting, palpitations, syncope, extreme fatigue
• Anginal equivalents: Dyspnea, diaphoresis, nausea, or fatigue without chest pain — particularly common in elderly and diabetic patients

---

88. Differential Diagnosis of Angina Pectoris vs. Myocardial Infarction

---

89. Main Symptoms of Cardiogenic Pain in Pericarditis

• Character: Sharp, pleuritic, stabbing — this is the KEY distinction from ischemic pain
• Location: Precordial, may radiate to the trapezius ridge (pathognomonic) and shoulder
• Duration: Can last hours to days (unlike angina)
• Positional: Worsened by lying supine (or leaning back); relieved by sitting forward / leaning forward
• Respiratory: Worsened by deep inspiration, cough
• Pericardial friction rub: Triphasic scratching sound on auscultation
• Associated: Fever, malaise (infectious pericarditis); may follow AMI (Dressler syndrome)
• ECG: Diffuse saddle-shaped ST elevation in multiple leads; PR depression (early finding)
• Key distinction from AMI: Pain is positional, pleuritic, lasts days, no Q waves, no reciprocal ST changes, diffuse (not localized) ECG changes

---

90. Role of Hypertrophic Cardiomyopathy (HCM) in Development of Cardialgia

• Mechanism: In HCM, massive myocardial hypertrophy increases oxygen demand while simultaneously compressing intramural coronary vessels, causing supply-demand mismatch — mimicking ischemic pain even with normal epicardial coronaries
• Pain character: Similar to angina — exertional chest tightness/pressure
• Additional mechanisms:
  • Dynamic left ventricular outflow tract (LVOT) obstruction → increased wall stress
  • Diastolic dysfunction → elevated filling pressures → subendocardial ischemia
  • Microvascular disease in hypertrophied myocardium
• Associated symptoms: Syncope (especially exertional), palpitations, dyspnea — exertional syncope is a red flag
• Key finding: Crescendo-decrescendo systolic murmur that increases with Valsalva and standing (decreases with squatting and lying down)
• ECG: LVH pattern, deep Q waves in lateral leads, T-wave abnormalities
• Diagnosis: Echocardiography shows asymmetric septal hypertrophy (septum ≥15 mm), LVOT obstruction with systolic anterior motion (SAM) of mitral valve

---

91. Principles of Treatment of Cardiogenic Chest Pain in Acute Conditions

STEMI/AMI (Acute Coronary Syndrome)

• Immediate: MONA protocol historically — Morphine (pain relief, venodilation), Oxygen (if SpO₂ <90%), Nitroglycerin (sublingual/IV — reduces preload), Aspirin (300 mg loading dose — antiplatelet)
• Antiplatelet therapy: Aspirin + P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel)
• Anticoagulation: Heparin (UFH or LMWH) or fondaparinux
• Reperfusion (definitive):
  • Primary PCI (percutaneous coronary intervention) — preferred if available within 90–120 min
  • Thrombolysis (fibrinolytics) — if PCI not available within 2 hours
• Beta-blockers: Reduce myocardial oxygen demand; given early if no contraindications
• ACE inhibitors: Started within 24 hours (if no contraindications)
• Statins: High-intensity statin early

Stable Angina (acute episode)

• Rest + sublingual nitroglycerin (repeat every 5 min × 3; if no relief → call emergency services)

Pericarditis

• NSAIDs (first-line: ibuprofen or aspirin) + colchicine (reduces recurrence)
• Restrict physical activity; avoid anticoagulants if hemorrhagic pericarditis

---

92. Classification of Non-Cardiogenic Chest Pain

1. Pulmonary/Pleural
   • Pneumothorax, pneumonia, pleuritis, pulmonary embolism, pulmonary hypertension, malignancy
2. Gastrointestinal/Esophageal
   • GERD, esophageal spasm, esophagitis, peptic ulcer disease, gastritis, Boerhaave syndrome, cholecystitis, pancreatitis, Mallory-Weiss syndrome
3. Musculoskeletal
   • Costochondritis (Tietze syndrome), rib fracture, muscle strain, fibromyalgia
4. Neurological/Neuropathic
   • Intercostal neuralgia, herpes zoster, osteochondrosis (radiculopathy), brachial plexus entrapment
5. Psychiatric/Functional
   • Neurocirculatory dystonia (NCD), panic disorder, anxiety, somatization, hyperventilation syndrome
6. Vascular (non-cardiac)
   • Aortic dissection (may overlap), subclavian steal
7. Miscellaneous
   • Breast pathology, mediastinitis, phrenic nerve irritation

---

93. Causes of Non-Cardiogenic Chest Pain Associated with Lung Diseases

---

94. Nature of Pain in Acute GI Diseases

---

95. Signs and Symptoms of Non-Cardiogenic Chest Pain in Neurological Pathologies

Intercostal Neuralgia

• Pain: Unilateral, sharp, burning or shooting along intercostal space
• Distribution: Follows dermatome (radiates circumferentially around chest)
• Triggers: Movement, deep breathing, touch (hyperesthesia/allodynia)
• Exam: Tenderness along intercostal nerve; positive Tinel's sign at nerve exit point

Herpes Zoster (Shingles)

• Pre-rash phase: Burning, stabbing unilateral chest pain before rash (prodrome 2–3 days)
• Rash phase: Dermatomal vesicular eruption — pain and rash do NOT cross midline
• Post-herpetic neuralgia: Persistent burning pain after rash resolves

Radiculopathy (Cervicothoracic/Thoracic Spine)

• C7–T1 radiculopathy: Pain radiating down arm, mimicking cardiac radiation
• T2–T6 radiculopathy: Pain across chest wall in dermatomal band
• Features: Aggravated by neck/spine movement; may have paresthesias

Neurocirculatory Dystonia (see Q97)

• Stabbing left inframammary pain, brief, unrelated to exertion

---

96. Role of Osteochondrosis in Non-Cardiogenic Chest Pain

1. Nerve root compression (radiculopathy):
   • Cervical (C4–C8) osteochondrosis → referred pain to precordium, arm, shoulder
   • Thoracic (T1–T6) osteochondrosis → chest wall pain in dermatomal distribution
2. Vertebral artery syndrome (cervical): Dizziness, neck pain, occipital headache
3. Clinical features distinguishing from cardiac pain:
   • Pain provoked by neck/trunk movement, not exertion
   • Reproduced by palpation of spinous processes/paravertebral muscles
   • Pain changes with posture (worse bending, twisting)
   • May have associated paresthesias/numbness in arm
   • No ECG changes; no troponin elevation
   • Normal stress test
4. Diagnosis: Cervical/thoracic spine X-ray or MRI showing disc degeneration, osteophytes, narrowed foramen

---

97. Neurocirculatory Dystonia (NCD) — Laboratory and Instrumental Diagnostics

Clinical Features

• Chest pain: Sharp, stabbing, left inframammary ("at the apex") — brief, seconds; not provoked by exertion
• Palpitations, tachycardia (especially at rest), sinus arrhythmia
• Dyspnea: "Sighing respirations," sensation of incomplete breath
• Fatigue, weakness, exercise intolerance disproportionate to findings
• Vegetative symptoms: Cold extremities, pallor, hyperhidrosis, lightheadedness
• Neurotic features: Anxiety, sleep disturbance, emotional lability

Laboratory Diagnostics

• CBC, biochemistry — normal
• Thyroid hormones (TSH, T3, T4) — to exclude hyperthyroidism
• Electrolytes — normal
• Troponin, CK-MB — normal (no myocardial damage)
• Lipid profile — may be requested

Instrumental Diagnostics

Diagnosis

---

98. Treatment of Non-Cardiogenic Chest Pain in Gastroesophageal Reflux Disease (GERD)

Lifestyle Modifications (first-line)

• Elevate head of bed 15–20 cm
• Avoid lying down within 2–3 hours of eating
• Reduce trigger foods: citrus, tomatoes, chocolate, coffee, alcohol, fatty/spicy foods
• Weight loss (if overweight)
• Quit smoking

Pharmacological Treatment

For Esophageal Hypersensitivity/Functional Chest Pain

• Low-dose tricyclic antidepressants (amitriptyline, imipramine 10–25 mg/night) — reduce visceral hypersensitivity
• SSRIs/SNRIs — for anxiety-related functional chest pain
• Cognitive behavioral therapy (CBT) — significant evidence for functional chest pain

Monitoring

• PPI therapeutic trial: 4–8 weeks of high-dose PPI — if chest pain resolves, GERD confirmed as cause (PPI test)
• 24-hour pH monitoring — gold standard for GERD diagnosis if diagnosis is uncertain

---

99. Diagnostic Methods for Cardiogenic and Non-Cardiogenic Chest Pain

Primary/Emergency Assessment (All Patients)

1. Detailed history: Character, location, radiation, duration, onset, precipitating/relieving factors, associated symptoms
2. Physical examination: BP (both arms), auscultation, palpation (chest wall tenderness)

Instrumental Diagnostics

Laboratory Diagnostics

Specialized Tests

• Upper endoscopy (EGD): For esophageal/gastric causes
• 24-hour esophageal pH monitoring: GERD confirmation
• Esophageal manometry: Esophageal spasm, motility disorders
• Spine X-ray/MRI: Osteochondrosis
• Pharmacological tests: Nitroglycerin test (ischemia?); PPI test (GERD?); orthostatic/potassium test (NCD?)

---

Key References: Rosen's Emergency Medicine (9th ed.) — Table 64.2 Differential Diagnosis of Chest Pain; Yamada's Textbook of Gastroenterology (7th ed.) — Noncardiac Chest Pain; Sleisenger & Fordtran's Gastrointestinal and Liver Disease — Esophageal Chest Pain; Tintinalli's Emergency Medicine — Acute Chest Pain Classification.

---

Questions 100–110: Myocardial Infarction & Arterial Hypertension

---

100. Laboratory Diagnostics of Myocardial Infarction

Gold Standard: Cardiac Biomarkers

The Universal Definition of MI (4th edition)

• Rise and/or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit (URL)
• Plus at least one of: symptoms, ECG changes, imaging evidence, or coronary thrombus

Serial Measurement Protocol

• Draw troponin at 0 h, 3 h, and 6 h (or 0 h and 1–2 h with high-sensitivity assay)
• A delta change of ≥20% rise or fall increases sensitivity for AMI

Additional Lab Tests

---

101. Instrumental Diagnostics of Myocardial Infarction — ECG Signs

12-Lead ECG — Mandatory First Test (obtain within 10 min)

Stages of ECG Changes in AMI:

• Tall, peaked ("hyperacute") T-waves
• Subtle ST-segment straightening

• ST-segment elevation (injury current) — the defining ECG change of STEMI
  • STEMI criteria: ≥1 mm ST elevation in ≥2 contiguous limb leads OR ≥2 mm in ≥2 contiguous precordial leads (V1–V4)
  • New LBBB in appropriate clinical context = STEMI equivalent
• Reciprocal ST depression in opposite leads (confirms true STEMI)

• T-wave inversion (symmetrical, deep) — ischemia pattern
• ST elevation begins to resolve
• Pathological Q waves begin to form: width >0.04 sec (1 small square), depth >25% of R-wave height

• Persistent Q waves (permanent marker of necrosis)
• T-waves may normalize or remain inverted

Localization of AMI by ECG Leads:

NSTEMI / Unstable Angina ECG Changes

• No ST elevation
• ST depression (horizontal or downsloping) in ≥2 leads
• Symmetrical T-wave inversion
• Normal ECG does NOT exclude NSTEMI

Other Instrumental Methods

---

102. Principles of Treatment of Acute Myocardial Infarction

Immediate (First 10–30 minutes — Emergency)

1. Oxygen — if SpO₂ <90%; avoid routine oxygen in normoxic patients (may cause vasoconstriction)
2. Aspirin 300–325 mg (loading dose, chewed) — immediate antiplatelet effect
3. Sublingual nitroglycerin — pain relief, vasodilation (contraindicated if hypotension, RV infarction, PDE5 inhibitor use)
4. IV morphine — analgesia and anxiolysis (use with caution — some evidence of worse outcomes)
5. 12-lead ECG and troponin — simultaneously with above

Reperfusion Therapy (Definitive — for STEMI)

Primary PCI is preferred over fibrinolysis when achievable within 90–120 minutes (door-to-balloon time)

Primary PCI (Percutaneous Coronary Intervention)

• Preferred strategy: Door-to-balloon time ≤90 min at PCI-capable hospital
• Indicated for: All STEMI within 12 h of onset; cardiogenic shock regardless of time
• Results in higher TIMI-3 flow, lower re-infarction rate, less intracranial hemorrhage vs. fibrinolysis

Fibrinolytic Therapy (Thrombolysis)

• When PCI not available within 120 minutes of first medical contact
• Agents: Tenecteplase (TNK), alteplase (tPA), streptokinase
• Contraindications: Prior ICH, ischemic stroke <3 months, active bleeding, aortic dissection, uncontrolled HTN

Antiplatelet & Anticoagulation

Medical Therapy (Started in Acute Phase)

Management of Complications

• Arrhythmias: Defibrillation for VF; lidocaine or amiodarone for VT; temporary pacing for complete heart block
• Cardiogenic shock: Inotropes (dopamine, dobutamine), IABP, consider emergency PCI
• Acute heart failure: Diuretics (furosemide IV), nitrates, non-invasive ventilation
• Mechanical complications: Emergency surgical repair for VSR, papillary muscle rupture, free wall rupture

Secondary Prevention (Post-AMI)

• Aspirin + P2Y12 inhibitor (12 months DAPT)
• ACE inhibitor/ARB lifelong
• Beta-blocker lifelong (especially if reduced EF)
• High-intensity statin lifelong
• Cardiac rehabilitation
• Lifestyle: smoking cessation, diet, exercise

---

103. Modern Classification of Arterial Hypertension

ISH 2020 Classification (International Society of Hypertension)

Diagnostic Thresholds by Measurement Method (ISH 2020)

ACC/AHA 2017 Classification (American)

Special Categories

• Isolated systolic hypertension: SBP ≥140 + DBP <90 (common in elderly — arteriosclerosis)
• Isolated diastolic hypertension: DBP ≥90 + SBP <140 (less common; younger patients)
• White coat hypertension: Elevated office BP but normal ambulatory/home readings
• Masked hypertension: Normal office BP but elevated ambulatory readings
• Resistant hypertension: BP remains >140/90 despite ≥3 antihypertensives at maximum tolerated doses (including a diuretic)
• Hypertensive urgency/emergency: SBP >180 or DBP >120; emergency if target organ damage present

By Etiology

• Primary (essential) hypertension: ~90–95% of cases; no identifiable cause; polygenic + environmental
• Secondary hypertension: ~5–10%; identifiable, treatable cause (see Q104)

---

104. Differential Diagnosis of Primary vs. Secondary Arterial Hypertension

When to Suspect Secondary Hypertension

• Onset before age 30 (especially without family history)
• Sudden onset or rapid worsening in previously controlled patient
• Resistant to ≥3 antihypertensive drugs
• Severe or malignant hypertension
• Specific clinical clues (see below)

Primary (Essential) Hypertension

• Age of onset: Typically 40–65 years
• Family history: Positive
• Onset: Gradual
• BP pattern: Responds to standard therapy
• Labs: Normal unless complications (renal, cardiac)
• Etiology: Genetic predisposition + lifestyle factors (salt, obesity, sedentary, stress)

Secondary Hypertension — Causes & Distinguishing Features

---

105. Diagnostic Criteria for Hypertension

Standard Office Blood Pressure

• Hypertension = office BP ≥140/90 mmHg on ≥2 separate occasions, confirmed on ≥2 visits
• Measured after 5 minutes of rest, seated, using validated device, appropriate cuff size
• Use average of ≥2 readings per visit

Confirmatory Measurements

1. Office BP: ≥140/90 mmHg on repeated measurement
2. 24-hour ABPM average: ≥130/80 mmHg
3. Home BP monitoring (HBPM): Average ≥135/85 mmHg (measured over ≥3 days, morning and evening)

Conditions for Measurement

• Sitting quietly for 5 minutes
• No caffeine, tobacco, or exercise within 30 minutes
• Back supported, feet flat on floor, arm at heart level
• Appropriate cuff size (cuff bladder encircles ≥80% of arm circumference)
• Two measurements ≥1–2 minutes apart; average both

Special Diagnostic Situations

• White coat effect: Confirmed by ABPM or HBPM — treat as lower risk than sustained HTN
• Masked HTN: Normal office but elevated home/ambulatory → treat as sustained HTN
• Isolated systolic HTN: SBP ≥140 + DBP <90 — particularly in elderly
• Isolated diastolic HTN: DBP ≥90 + SBP <140

---

106. Risk Factors for Hypertension

Non-Modifiable

• Age: Risk increases progressively; >65 years → isolated systolic HTN
• Sex: Males at higher risk until age 55; after menopause, women catch up
• Family history/genetics: Strongest predictor of essential HTN; heritability 30–50%
• Race/ethnicity: African descent — higher prevalence, earlier onset, more severe, more salt-sensitive

Modifiable (Lifestyle)

Metabolic Risk Factors

• Diabetes mellitus: Insulin resistance → RAAS activation, sympathetic activation, renal retention of sodium
• Dyslipidemia: Promotes atherosclerosis, reduces vascular compliance
• Hyperuricemia: Associated with HTN; uric acid reduces NO bioavailability
• Obstructive sleep apnea: Intermittent hypoxia → sympathetic activation; major reversible cause

---

107. Target Organ Damage in Hypertension — Clinical Manifestations

1. Heart (Hypertensive Heart Disease)

• Left ventricular hypertrophy (LVH): Adaptive response to increased afterload → diastolic dysfunction → eventually systolic dysfunction
• Coronary artery disease (CAD): Accelerated atherosclerosis → angina, MI
• Heart failure: HFpEF (preserved EF — due to LVH/diastolic dysfunction) or HFrEF
• Atrial fibrillation: LVH → atrial dilatation → AF
• Clinical signs: S4 gallop (stiff LV), displaced apex beat (LVH), crackles (pulmonary edema)

2. Brain (Hypertensive Cerebrovascular Disease)

• Ischemic stroke: Most common complication
• Hemorrhagic stroke: Intraparenchymal hemorrhage (especially in small perforating vessels — basal ganglia, internal capsule, pons, cerebellum)
• Hypertensive encephalopathy: Severe HTN → breakthrough of cerebral autoregulation → cerebral edema → confusion, headache, seizures, visual disturbances (PRES)
• Lacunar infarcts: Small vessel disease → cognitive impairment, vascular dementia
• Clinical signs: Focal neurological deficits, papilledema (severe), retinal changes

3. Kidneys (Hypertensive Nephrosclerosis)

• Benign nephrosclerosis: Arteriolar hyalinosis → reduced GFR → proteinuria (microalbuminuria is earliest sign)
• Malignant nephrosclerosis: Fibrinoid necrosis of arterioles → rapidly progressive renal failure
• Clinical signs: Microalbuminuria → proteinuria → elevated creatinine → CKD
• Laboratory: Microalbuminuria (30–300 mg/g creatinine) is the earliest marker

4. Eyes (Hypertensive Retinopathy)

• Grade I: Arterial narrowing, increased light reflex ("silver wiring")
• Grade II: AV nicking (arteriovenous crossing changes)
• Grade III: Flame hemorrhages, cotton wool spots (nerve fiber layer infarcts), exudates
• Grade IV: Papilledema (malignant hypertension — emergency)

5. Peripheral Vasculature

• Arteriosclerosis: Arterial stiffening → increased pulse pressure
• Peripheral artery disease (PAD): Claudication, reduced ankle-brachial index
• Aortic aneurysm/dissection: Chronic HTN is strongest risk factor for aortic dissection

6. Metabolic

• Insulin resistance, dyslipidemia (clustering = metabolic syndrome)

---

108. Main Pathophysiological Mechanisms of Development of Hypertension

1. Renin-Angiotensin-Aldosterone System (RAAS) Overactivation

• Renin (kidney) → cleaves angiotensinogen → Angiotensin I → ACE → Angiotensin II
• Effects of Ang II: Potent vasoconstriction (↑ PVR), aldosterone release (Na⁺/H₂O retention → ↑ CO), sympathetic activation, vascular remodeling
• Result: Increased BP through both mechanisms

2. Sympathetic Nervous System (SNS) Overactivity

• Increased catecholamines (norepinephrine, epinephrine) → alpha-1 adrenergic receptors → vasoconstriction (↑ PVR)
• Beta-1 adrenergic → increased heart rate and contractility (↑ CO)
• Triggers: Stress, obesity, sleep apnea, insulin resistance
• Also stimulates RAAS

3. Renal Sodium and Water Retention (Volume Expansion)

• Reduced renal excretion of sodium → expanded plasma volume → ↑ CO
• Mechanisms: High dietary sodium, reduced nephron mass (CKD), aldosterone excess, insulin resistance (promotes tubular Na⁺ reabsorption)
• Guyton's pressure-natriuresis concept: Normal kidney excretes excess sodium when BP rises; in HTN, this set-point is reset upward

4. Endothelial Dysfunction

• Reduced nitric oxide (NO) production → impaired vasodilation
• Increased endothelin-1 → vasoconstriction
• Increased reactive oxygen species (ROS) → oxidative inactivation of NO
• Vascular inflammation → structural remodeling (hypertrophy, stiffening)

5. Vascular Structural Changes (Remodeling)

• Hypertrophic remodeling: Increased wall-to-lumen ratio → increased PVR
• Arteriosclerosis: Reduced arterial compliance → elevated systolic BP and pulse pressure
• Rarefaction: Loss of microvascular density → increased PVR

6. Insulin Resistance and Hyperinsulinemia

• Promotes renal sodium retention
• Activates SNS
• Stimulates vascular smooth muscle growth
• Impairs endothelial NO production
• Part of metabolic syndrome (central obesity + HTN + dyslipidemia + hyperglycemia)

7. Genetic Factors

• Polymorphisms in RAAS genes, sodium transporter genes (ENaC, WNK kinases), adrenergic receptors
• Monogenic forms: Liddle syndrome (gain-of-function ENaC), glucocorticoid-remediable aldosteronism, Gordon syndrome

---

109. Influence of Kidney Diseases on Development of Arterial Hypertension

Mechanisms by Which Kidney Disease Causes Hypertension:

1. Sodium and Water Retention (Volume-Dependent HTN)

• Reduced GFR → impaired sodium excretion → expanded extracellular volume → increased CO → HTN
• Seen in: Acute GN, CKD, nephrotic syndrome
• Often responds to dietary sodium restriction and diuretics

2. RAAS Activation

• Ischemia of renal parenchyma (stenosis, nephrosclerosis) → increased renin secretion → Ang II → aldosterone → vasoconstriction + Na retention
• Seen prominently in: Renovascular HTN (renal artery stenosis), CKD

3. Reduced Production of Vasodilatory Substances

• Damaged kidney parenchyma → reduced prostaglandins (PGI₂, PGE₂) and kinin production → net vasoconstriction
• Reduced erythropoietin production (anemia) → compensatory cardiac output increase

4. Sympathetic Nervous System Activation

• Afferent renal nerves from ischemic/diseased kidney → increased central sympathetic outflow
• Denervation of the transplanted kidney partially reverses this

Specific Renal Diseases and HTN:

Vicious Cycle: HTN ↔ CKD

---

110. Influence of Endocrine Diseases on Development of Symptomatic (Secondary) Hypertension

1. Primary Hyperaldosteronism (Conn's Syndrome)

• Prevalence: 5–10% of all hypertension; most common endocrine cause
• Mechanism: Autonomous aldosterone secretion → excessive Na⁺/H₂O retention (↑ CO) + K⁺ excretion (hypokalemia) + direct vascular effects of aldosterone
• Clinical features: Hypertension (often refractory), hypokalemia (muscle weakness, cramps, polyuria), alkalosis; bilateral adrenal hyperplasia or unilateral adenoma
• Diagnosis: Elevated aldosterone/renin ratio (ARR ≥30); CT adrenal; adrenal vein sampling (lateralization)
• Treatment: Aldosteronoma → adrenalectomy; bilateral hyperplasia → spironolactone or eplerenone

2. Pheochromocytoma / Paraganglioma

• Mechanism: Catecholamine excess (epinephrine, norepinephrine) → alpha-1 (vasoconstriction ↑ PVR) and beta-1 (↑ HR, ↑ CO) activation
• Clinical features: "Rule of 10s" — 10% malignant, 10% bilateral, 10% extra-adrenal, 10% hereditary; episodic triad: severe headache + diaphoresis + palpitations; labile hypertension; pallor (not flushing)
• Diagnosis: Plasma free metanephrines (most sensitive) or 24-h urine metanephrines/catecholamines; CT/MRI adrenal; ¹²³I-MIBG scan for extra-adrenal
• Treatment: Alpha-blocker (phenoxybenzamine or doxazosin) FIRST, then beta-blocker, then surgical resection
• Danger: Never start beta-blocker first — causes unopposed alpha-stimulation → hypertensive crisis

3. Cushing's Syndrome (Glucocorticoid Excess)

• Mechanism: Cortisol excess → activation of mineralocorticoid receptors → Na⁺ retention + volume expansion; also increases sensitivity to catecholamines; reduces vasodilatory prostaglandins
• Clinical features: Central obesity, moon face, buffalo hump, purple abdominal striae, proximal muscle weakness, osteoporosis, DM, acne, hirsutism, depression; HTN in 80%
• Causes: Pituitary adenoma (Cushing's disease, most common), adrenal adenoma/carcinoma, ectopic ACTH (small cell lung cancer)
• Diagnosis: 24-h urine cortisol; overnight 1-mg dexamethasone suppression test; late-night salivary cortisol; ACTH level; MRI pituitary
• Treatment: Transsphenoidal surgery (pituitary); adrenalectomy (adrenal); ketoconazole/metyrapone (medical)

4. Hyperthyroidism

• Mechanism: Excess thyroid hormone → increased beta-adrenergic sensitivity → increased heart rate and contractility (↑ CO) → elevated systolic BP; also direct vasodilatory effect → reflex sympathetic activation
• BP pattern: Isolated systolic hypertension with wide pulse pressure; tachycardia
• Clinical features: Weight loss, heat intolerance, tremor, palpitations, exophthalmos (Graves'), goiter
• Diagnosis: Suppressed TSH + elevated free T4
• Treatment: Antithyroid drugs (methimazole, propylthiouracil), radioiodine, thyroidectomy; beta-blockers for symptom control

5. Hypothyroidism

• Mechanism: Reduced thyroid hormone → decreased cardiac output; increased peripheral vascular resistance (impaired vascular relaxation); reduced baroreceptor sensitivity; decreased renal Na⁺ excretion
• BP pattern: Predominantly elevated diastolic BP (increased PVR)
• Clinical features: Bradycardia, weight gain, cold intolerance, constipation, myxedema, depression
• Diagnosis: Elevated TSH + low free T4
• Treatment: Levothyroxine replacement → BP normalizes

6. Hyperparathyroidism

• Mechanism: PTH → increased intracellular calcium in vascular smooth muscle → vasoconstriction; hypercalcemia → vasoconstriction; also activates RAAS
• Clinical features: "Bones, stones, groans, and psychic moans" — bone pain, kidney stones, abdominal pain, depression; HTN in ~50%
• Diagnosis: Elevated serum calcium + elevated PTH; imaging of parathyroid glands
• Treatment: Parathyroidectomy

7. Acromegaly (GH excess)

• Mechanism: Excess GH → IGF-1 → increased renal Na⁺/H₂O retention; sleep apnea (common in acromegaly → sympathetic activation); insulin resistance
• Clinical features: Enlarged hands/feet/jaw, coarse facial features, macroglossia, carpal tunnel, HTN in 30–40%
• Diagnosis: IGF-1 level (elevated); failure of GH suppression after oral glucose tolerance test
• Treatment: Transsphenoidal surgery; somatostatin analogues (octreotide)

---

Key References: Goldman-Cecil Medicine, 26th ed. — STEMI Management; Comprehensive Clinical Nephrology, 7th ed. — ISH 2020 Hypertension Classification (Table 34-4); Brenner & Rector's The Kidney — Secondary Hypertension and Renal Causes; Harrison's Principles of Internal Medicine, 22nd ed. — Hypertension and Target Organ Damage.