• Hypertension is a risk factor for coronary artery disease and cerebrovascular accidents
• It is raised pressure in a vascular bed
• It can lead to;
  • Cardiac hypertrophy
  • Heart failure
  • Aortic dissection
  • Renal failure
• Hypertension is defined as a sustained systolic pressure of >140 mm Hg and a sustained diastolic pressure of >90 mm Hg. By these criteria 25% of persons in the general population are hypertensive
• Prevalence increases with age and is higher in African Americans
• Systolic blood pressure is more important that diastolic pressure as a determinant of cardiovascular  except in young individuals

 

Factors controlling blood pressure

• Blood pressure = cardiac output x peripheral resistance
• Cardiac output depends up;
  • Cardiac factors e.g heart rate and contractility
  • Blood volume e.g. sodium, mineralocorticoids
• Peripheral resistance
  • Humoral factors
    • Constrictors;
      • Angiotensin II
      • Catecholamines
      • Thromboxane
      • Leukotrienes
      • Endothelin
    • Dilators
      • Prostaglandins
      • NO
  • Local factors
    • Autoregulation
    • Ionic (pH, hypoxia)
  • Neural factors
    • Constrictors – α- adrenergic
    • Dilators – β-adrenergic

 

Causes

• 95% of cases are idiopathic and termed essential hypertension
• Causes of secondary hypertension;
  • Renal
    • Acute glomerular nephritis
    • Chronic renal disease
    • Renal artery stenosis
    • Renal vasculitis
  • Endocrine
    • Adrenocortical hyperfunction – Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia
    • Exogenous hormones – glucocorticoids, oestrogen, sympathomimetics
    • Pheochromocytoma
    • Acromegaly
    • Hypothyroidism
    • Hyperthyroidism
  • Cardiovascular
    • Coartation of the aorta
    • Vasculitis
    • Increased intravascular volume
    • Increase cardiac output
  • Neurological
    • Increased ICP
    • Sleep apnoea
    • Stress

 

Pathogenesis

• The major factors that determine blood pressure are age, gender, body mass index and diet, particularly sodium intake
• The kidney plays an important role in blood pressure;
  • Via the renin-angiotensin syndrome. Angiotensin II raises BP by increasing peripheral resistance and by increasing blood volume (increasing distal tubular reabsorption of sodium)
  • Produces vascular relaxing substances such as NO and prostaglandins
  • When BP is reduced the GFR falls leading to increased sodium reabsorption and expanding blood vol
  • Natriuretic factors, including those secreted by the atrial and ventricular myocardium act on the distal tubules to cause sodium excretion and diuresis
  • When renal artery excretory function is impaired, the increased arterial pressure is a compensatory mechanism that helps restore fluid and electrolyte balance

 

Mechanisms of essential hypertension

Genetic factors

• Single gene disorders are rare and cause severe forms of hypertension
• Gene defects involved in aldosterone metabolism e.g. aldosterone synthase, 11β-hydroxylase and 17α-hydroxylase. These lead to an increase in aldosterone secretion, increased salt and water reabsorption and therefore plasma volume
• Mutations in proteins that affect sodium reabsorption e.g. Liddle syndrome, caused by a mutation in ENaC leading to increased reabsorption of sodium induced by aldosterone
• There are different hypothesis put forward to explain essential hypertension
• Reduced renal sodium excretion in the presence of normal arterial blood pressure, leading to increased fluid volume, increased cardiac output and peripheral vasoconstriction, thus elevating blood pressure. At this higher setting enough additional sodium could be excreted by the kidneys to equal intake and prevent fluid retention. Thus an altered state of sodium excretion could be achieved but with the expense of a stable increase in blood pressure

An alternative hypothesis is one of vasoconstrictive influences as the primary cause of hypertension. Chronic or repeated vasoconstrictive influences may cause structural thickening of the vessels

Environmental factors;

• Can modify the expression of the genetic determinants of increased pressure
  • Stress
  • Obesity
  • Smoking
  • Physical inactivity
  • Heavy consumption of salt (also augments the disease in secondary hypertension)

 

Vascular pathology in hypetension

• Accelerates atherogenesis
• Causes degenerative changes in the walls of large and medium arteries that potentiate aortic dissection and cerebrovascular haemorrhage
• It is also associated with 2 forms of small vessel disease;
  • Hyaline arteriolosclerosis
  • Hyperplastic arteriolosclerosis

 

Morphology

• Hyaline arteriolosclerosis
  • Homogenous, pink hyaline thickening of the walls of the arterioles with loss of underlying structural detail and with narrowing of the lumen
  • Common in diabetics as part of the characteristic microangiography
  • The lesion reflects leakage of the plasma components across the vascular endothelium and excessive extracellular matrix production by the SMC secondary to the haemodynamic stress of hypertension of the metabolic stress in diabetes that accentuates EC
  • Hyaline arteriolosclerosis is a major morphologic characteristic of benign nephrosclerosis
• Hyperplastic arteriolosclerosis
  • Related to more acute or severe elevations in blood pressure and is a characteristic of malignant hypertension (diastolic >120 mmHg)
  • Onionskin, concentric, laminated thickening of the walls of the arterioles with progressive narrowing of the lumen
  • The laminations consist of SMC and thickened basement membrane
  • In malignant hypertension you can also get necrosis of the vessel walls referred to as necrotising arteriolitis

 

Affects on organs

• Kidney
  • Hyaline arteriosclerosis results in diffuse impairment of renal blood supply, loss of nephrons and renal failure.
  • Arterial changes cause chronic glomerular ischaemia with subsequent glomerulosclerosis, tubular atrophy and scarring (benign nephrosclerosis)
• Brain
  • Hemorrhagic stroke
  • In the extreme reduced oxygen delivery resulting in hypoxic encephalitis. This results in restlessness, stupor and coma.
• Heart
  • Increased afterload leads to left ventricular hypertrophy (with increased pressure, the myocytes increase in cross section but not length of sarcomeres are deposited parallel to the long axis of the cells). This reduces the lumen size and makes to wall stiffer, impairing dystolic filling. This results in LV dilation and LA enlargement. This can result in AF
  • The LV hypertrophy increased the HR and contractility resulting in increased oxygen requirements. Because of the hypertrophy there is also reduced capillary disease and increased intracapillary distance
  • This results in an increased risk of ischaemic heart disease and heart failure
  • Hypertension resulting in atherosclerosis of the coronary vessels can also cause ischaemic heart failure

 

Vascular pathology in benign hypertension

 

Large arteries

Hypertension accelerates atherosclerosis and causes vascular structural changes predisposing to aneurysm formation with an increased risk of vessel rupture.

 

Medium / small arteries – Narrowed lumen & thickened walls due to intimal proliferation & medial hypertrophy.

 

Arterioles – “hyaline arteriolosclerosis”

This results in a narrowed lumen & thickened vessel wall due to endothelial injury with leakage of plasma components into the arteriolar walls and the synthesis of extracellular matrix by smooth muscle cells.

It may result in ischaemia of distal tissues eg. Renal parenchyma (glomerulosclerosis & tubule atrophy).

 

 

Vascular pathology in malignant hypertension

 

Arterioles – “hyperplastic arteriolosclerosis”

This results in a narrowed lumen & thickened wall. There is a concentric “onion skin” thickening of the wall due to reduplication of the basement membrane and smooth muscle proliferation.

There is progressive narrowing of the lumen often accompanied by  fibrinoid necrosis of walls referred to as “necrotising arteriolitis” This results in ischaemia  or haemorrhages within the tissues involved eg. kidney, retina etc.

 

 

This entry was posted on Tuesday, February 5th, 2008 at 4:23 pm and is filed under Cardiovascular. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.