Hypertension Overview Quiz

BMS 200 - Vascular Pathology

• Hypertension:
  • Extremely common, affecting over 1 billion people, prevalence in those over 60 is over 60%.
  • A major risk factor for ischemic heart disease, congestive heart failure, peripheral arterial disease, dementia, stroke, and chronic kidney disease.
  • Antihypertensive therapy reduces risk of these complications, however, over half of cases are untreated or inadequately treated.
  • A complex interaction between many organ systems is involved.

Pathogenesis of Hypertension

• Complex interactions:
  • Central and peripheral nervous systems
  • Endocrine system
  • Kidneys
  • Vascular system
  • Digestive system
  • Immune system
  • Microbiome
  • Diet
  • Altered redox signaling/oxidative stress is present.
  • Genetic factors are significant.
  • Sodium intake/storage is important.
  • Sympathetic activation is relevant.

Primary Hypertension - Basic Pathogenesis

• Heterogenous condition:
  • Over 90% of cases have no single clear abnormality.
  • Multiple factors are involved that impact each other.
  • Traditional models include:
    • Arteriolar vasoconstriction and altered endothelial function.
    • Increased blood volume.
    • Increased sodium retention and increased renin secretion.
    • Increased activation of the sympathetic nervous system.

Importance of Arteriolar Tone in Hypertension

• Increased resistance:
  • Increased tone in resistance vessels, even with maximal dilation, is found in hypertension.
  • Reduced lumen size is a factor.
  • The resistance is inversely proportional to the fourth power of the lumen radius.

Anatomical Site of Blood Pressure Control

• Arterioles:
  • The primary site where total peripheral resistance is regulated.
  • Vascular tone is under hormonal, neural, and local endothelial control. Factors like NO (vasodilator), and SNS/epi (vasoconstriction), are involved.

Vascular Factors in Primary Hypertension

• Remodeling:
  • Arteriolar walls thicken over time.
  • Increased smooth muscle cellular hypertrophy and hyperplasia occurs
  • Extracellular matrix deposition occurs
  • This is termed arteriolosclerosis.
  • Vasodilatory substances (i.e., NO) decrease in hypertensive patients.
  • Larger vessels may remodel and stiffen.

Vascular Remodeling in Hypertension

• Changes in small arteries and arterioles:
  • Particularly prominent in the kidneys.
  • Smooth muscle cell hypertrophy and hyperreactivity.
  • Artery remodeling can contribute to hyperreactivity to vasoactive stimuli.

Hypertension and Intravascular Volume

• Renal sodium handling:
  • Sodium intake exceeding kidney excretory ability increases blood volume.
  • Increased blood volume results in increased mean arterial pressure.
  • Autoregulation in arterioles, constricting to reduce flow to capillary beds, is in response to high pressure.

Hypertension and the Autonomic Nervous System

• Increased sympathetic outflow:
  • A likely contributor to hypertension.
  • Baroreceptor resetting within the brainstem may cause sympathetic activation.
  • A given blood pressure level may elicit a higher sympathetic nervous system activation compared to a normotensive individual. This likely contributes to vasoconstriction, increasing ADH release (increasing water retention), and increased renin and AT2 release.

Hypertension and the RAAS

• RAAS (Renin-Angiotensin-Aldosterone System):
  • Subtle abnormalities are commonly observed.
  • Overactivation of the sympathetic nervous system is often more evident in cases of hypertension.
  • Aldosterone receptors outside the kidneys are also implicated in abnormal vascular function contributing to hypertension by increasing sodium reabsorption.

Hypertension and Inflammation

• Leukocyte migration:
  • Increased leukocyte migration into the kidneys and vascular walls is observed in hypertensive patients.
  • Th17 cells and ILC3 are likely involved in vascular remodeling, possibly influenced by increased extracellular sodium.
  • Inflammation is potentially a significant contributor to hypertension

Hypertension - Other Factors

• Insulin resistance and obesity:
  • Linked to impaired vasodilatory function in the blood vessel endothelium.
  • Weight loss and improved insulin sensitivity can improve hypertension.
  • Renal sodium-glucose cotransporters are closely integrated with sodium handling in the kidney.
  • Hypertension is a key risk factor for atherosclerosis, and if renal arteries have atherosclerosis it can worsen hypertension. Reduced renal blood flow due to atherosclerosis increases renin secretion, vasoconstriction, and sodium retention.

Major Causes of Secondary Hypertension

• Causes impact kidneys or sympathetic nervous system:
  • Accounts for less than 10% of hypertension cases but can be severe.
  • Renal pathologies such as kidney disease, renal tumors, and renovascular disease are common.

Secondary Causes of Hypertension (Table)

• Renal: Cystic kidney disease, renal tumors, and chronic kidney disease.
• Renovascular: Atherosclerosis and conditions causing renal artery narrowing.
• Obstructive sleep apnea: (see individual category for more details).
• Endocrine: Hyper-/hypothyroidism, acromegaly, pheochromocytoma, Conn's or Cushing's syndromes, coarctation of the aorta.
• Congenital: Certain genetic defects (not considered in detail here).
• Medications/Substances: Decongestants, amphetamines, cocaine, and some other agents or medications.

Pathogenesis of Secondary Hypertension (Diagram)

• Diagram illustrating the relationship between various factors and their impact on blood pressure regulation.
• Factors like sympathetic activity, renin-angiotensin-aldosterone activity, renal sodium retention, and cardiac output all contribute.
• Polygenic factors and autoregulation are also shown.

Diagnosis of Hypertension (Canadian Guidelines)

• Multiple visits may be needed for diagnosis:
  • Particularly if mild or moderate hypertension is present.
  • 180/110 mm Hg is considered severe and would warrant immediate hypertension diagnosis.
  • Home measurements, automated measurements, and 24-hour measurements are superior to clinical office visit measurements.
  • Mean awake automated SBP of 135 mmHg or diastolic BP of 85 mmHg is considered hypertension. Lower thresholds may apply for patients with diabetes.

Hypertension Canada Guidelines (FYI, Flowchart)

• Diagnostic flowchart summarizing the diagnostic process according to Canadian guidelines.
• The flowchart shows the considerations in BP measurement and diagnostic approaches (office vs. out-of-office).

Hypertensive Urgencies and Emergencies

• Hypertensive urgency:
  • Very high blood pressure that warrants immediate treatment to prevent end-organ damage.
  • Defined by systolic pressure of over 180 mmHg or diastolic over 120 mmHg.
• Hypertensive emergency:
  • Indicates symptoms/signs of end-organ damage due to the elevated pressure, like stroke.

Malignant Hypertension

• Rapid increases in blood pressure (180/120 mmHg):
  • End-organ damage is likely present.
  • Possible causes include insults such as certain illnesses and discontinuation of antihypertensives.
• Pathological finding: Severe remodeling of arterioles is termed hyperplastic or malignant arteriolosclerosis.

Antihypertensive Medications

• Calcium channel blockers:

  • Inhibit calcium influx.
  • Produce coronary and peripheral vasodilation.
  • Side effects can include negative dromotropic and chronotropic effects that may worsen existing heart problems.

• ACE Inhibitors:

  • Block the conversion of angiotensin I to angiotensin II, preventing vasoconstriction reducing peripheral resistance.
  • Fewer sodium retention effects.
  • Bradykinin is not blocked and vasodilation is possible.

• ARB Inhibitors (Angiotensin II Receptor Blockers): - Blocks AT1 receptors inhibiting vasoconstriction. - Reduces aldosterone secretion.

• Alpha-receptor blockers:

  • Block alpha-1 adrenoreceptors which reduces peripheral vascular resistance and lowers blood pressure.
  • Minimal impact on heart output. Side effects can include; reflex tachycardia, postural hypotension.

The Vasculitis Syndromes

• Vasculitis:
  • Inflammation and necrosis of blood vessels.
• Primary vasculitis: Not caused by another disorder.
• Secondary vasculitis: Caused by other disorders like medications, infections, or autoimmune diseases. (Lupus, Rheumatoid arthritis).
• Types of involved vessels:
  • Large arteries like temporal arteries, Takayasu arteritis,
  • Small and medium-sized arteries like polyarteritis nodosa, thromboangiitis obliterans,
  • Small and medium-sized arteries and veins including granulomatosis with polyangiitis, Churg-Strauss syndrome, Behcet disease.

Why Does Vasculitis Happen?

• T-lymphocyte activation and granuloma formation:
  • Poorly understood processes.
• Immune complex formation (Type III hypersensitivity):
  • Important in some vasculitides, particularly those associated with autoimmune disorders.
• ANCA (Anti-neutrophil cytoplasmic antibodies):
  • Antibodies produced against neutrophil proteins, such as proteinase 3 and myeloperoxidase, leading to
  • neutrophil activation,
  • increased leukocyte release,
  • recruitment, and
  • endothelial damage.

ANCA and Vasculitis

• Neutrophil activation in inflammatory conditions:
  • ANCA binds to ANCA antigens on neutrophil surfaces
  • Neutrophil degranulation occurs releasing toxic factors including
    • reactive oxygen species,
    • PR3 and,
    • myeloperoxidase. This damage to endothelial cells is a contributing factor to some types of vasculitis.

Temporal Arteritis

• Patchy granulomatous inflammation:
  • Primarily affects larger arteries, including branches of the carotid, frequently affecting the temporal arteries.
  • Symptoms include headache with tender scalp, jaw claudication, visual loss, and possibly fever and fatigue.
• Etiology unclear, likely linked to HLA-DR4:
  • More common in women over 50 years of age.
  • Often accompanied by or associated with polymyalgia rheumatica.
  • Treated with glucocorticoids.

Polyarteritis Nodosa

• Necrotizing vasculitis: Affects small and medium-sized muscular arteries.
• Wide range of organs affected, rarely the lungs:
  • Including GI tract, heart, kidneys, testes/ovaries, peripheral and central nervous system; skin, joints, and muscles.
• Etiology unclear but related to hepatitis B:
  • Pathological findings include patchy vessel involvement, early neutrophil invasion, and fibrinoid necrosis.
• Severe inflammation and possible organ damage with high morbidity/mortality:
  • Diagnosis relies on imaging, labs, and clinical features. Treatment necessitates immunosuppression.

Thromboangiitis Obliterans

• Vasculitis of medium and smaller arteries in distal arms/legs:
  • Frequently found in smokers.
  • Results in occlusion of vessels leading to ischemia.
  • Thrombophlebitis can also result from associated venous involvement.

Granulomatosis with Polyangiitis

• Necrotizing vasculitis of small arteries/veins:
  • Often involves the upper and lower respiratory tracts, kidneys, and possibly other organs.
  • Granulomas (often 5cm or more) may be a key finding, particularly in the lung.
• Clinical diagnosis combined with c-ANCA testing and biopsy:
  • Often characterized by marked inflammation, fatigue, weight loss.
  • Significant damage can occur, high morbidity and mortality.

Raynaud's Phenomenon/Disease

• Intermittent, bilateral, patchy ischemia (cold sensitivity):
  • Resulting from vasospasm in the hands and feet vessels.
  • Common in isolation or with associated diseases such as lupus, or systemic sclerosis.

Test your knowledge on the pathophysiology, complications, and treatment of hypertension. This quiz covers key aspects of hypertension, including its impact on various organ systems and common treatment strategies. Perfect for medical students or anyone interested in health sciences.