Introduction
Worldwide, an estimate of 1 in 4 adults between 30 to 79 years of age have hypertension. According to the National Heart, Lung, & Blood Institute (NHLBI) of the U.S.A., The standard threshold for clinically significant hypertension is ≥140/90mmHg. However, other factors may affect this threshold.
The NHLBI defines a malignant hypertension as rapidly rising blood pressure in hypertensive patients. Features include: severe hypertension (>200/120mmHg); renal failure; retinal hemorrhages and exudates; with or without papilledema.
Hypertension and Hypotension are two distinct variables that can affect an individual. While hypotension causes tissue hypoperfusion, dysfunction & cell death, hypertension causes atherosclerosis, vessel, and end-organ damage.
Let’s review the morphology and role of the blood vessels, before discussing about hypertension and arteriosclerosis.
The morphology and role of the blood vessel
The human blood vessel consists of arteries and veins with varying thicknesses. This thickness is due to the compositions of the blood vessel walls. Compositions of blood vessel wall include: endothelial cells; smooth muscle cells; extracellular matrix (elastin, collagen, glycosaminoglycans).
The layers of blood vessels & compositions include: intima (single layer endothelial cells); media (smooth muscle cells); adventitia (connective tissues, blood vessels, nerves).
The internal elastic lamina is between the intima and media, while external elastic lamina is btw the media and adventitia. About one third of media receives nourishment from blood vessel lumen. Two-third of media receives nourishment from vasa vasorum (vessels of vesels)
The vascular walls of arteries are thicker than veins. The thickness decreases as the vessels become smaller. The types of arteries include: Large, elastic arteries; medium-sized muscular arteries; small muscular arteries; arterioles.
Types of arteries
The large, elastic arteries contain much elastic fibers within their media, to allow for expansion and recoil. E.g. brachiocephalic artery, subclavian artery, common carotid artery; iliac artery.
The medium-sized muscular arteries contain mainly smooth muscle cells within the media. E.g. coronary arteries, renal arteries.
Small muscular arteries contain less smooth muscle cells within their media with lumen diameter of <2mm. Arterioles contain much lesser smooth muscle cells within their media, with lumen diameter btw 20 to 100µm. They’re closer & immediately supply tissues and organs.
Capillaries are blood vessels which have a single layer of endothelial cells, with no media. They have diameter of about 8µm & are suitable for rapid exchange of permeable substances between tissues and blood.
Predominant smooth muscle cells within muscular arteries contract and relax to control blood flow and pressure. Vasoconstriction and vasodilation of smooth muscles are regulated by the autonomous nervous system, local metabolic factors, & cellular interactions.
The small muscular arteries & arterioles are vessels in which physiologic peripheral resistance occur. Any further changes in their diameter due to structural changes or vasoconstriction would result in negative consequence.
In considering the arterial types, we can conclude that atherosclerosis affects large, elastic & medium-sized muscular arteries. On the other hand, hypertension affects small muscular arteries and arterioles.
HYPERTENSION
There are two types of hypertensions: essential and secondary hypertension.
Essential hypertension
In essential hypertension, the underlying cause of hypertension is unknown, and may be multifactorial.
Genetic predispositions include: Liddle syndrome (Na channel protein mutation) which causes Na+ reabsorption in DCT; reduction in renal Na+ excretion; genetic mutations in enzymes (e.g. aldosterone synthase, 11β hydroxylase) that cause excess aldosterone secretion.
Environmental factors that can increase impact include: smoking; high salt intake; physical inactivity; stress; obesity.
Secondary hypertension
This is a type in which the causes are known. Examples include:
- Cushing syndrome
- primary aldosteronism
- congenital adrenal hyperplasia
- pheochromocytoma
- oral contraceptives
- pregnancy
- exogenous glucocorticopid
- pheochromocytoma
- sympathomimetics
- myxedema
- thyrotoxicosis
- acute glomerulonephritis;
- chronic renal disease
- polycystic kidney disease
- renal artery stenosis
- renin-producing tumors
- acromegaly
- pheochromocytoma
- sleep apnea
- acute stress
- psychogenic
- increased intracranial pressure;
- polyarteritis nodosa
- high intravascular volume; surgery
- Coarctation of the aorta
- Rigidity of the aorta
General regulation of blood pressure
The determinants of blood pressure are cardiac output and peripheral vascular resistance (in arterioles). Cardiac output is dependent on blood volume, while hormonal and neural factors affect vascular peripheral resistance.
In order to avoid hyperperfusion in tissues, arterioles autoregulate by undergoing vasoconstriction.
Blood pressure regulation requires a balance between plasma containing vasoconstriction and vasodilating factors. Vasoconstriction factors (endothelin, angiotensin II, catecholamines, thromboxane). Vasodilating factors (prostaglandin, kinin, and NO). Other factors which may also affect blood pressure are: PH, hypoxia, α & β adrenergic system.
How the kidneys and heart play a role in blood pressure regulation
The renin-angiotensin system is a mechanism to regulate fall in blood pressure by the kidney (e.g. in renal artery stenosis). The juxtaglomerular cells produce renin which converts angiotensinogen to angiotensin I. Angiotensin I to angiotensin II by angiotensin converting enzyme.
Angiotensin II stimulates secretion of aldosterone from renal glands which raises blood volume through Na reabsorption from distal renal tubule. It also acts constricts vascular smooth muscle, thereby increasing peripheral resistance and blood volume. In order to counter the effect of angiotensin II, the kidney also produces prostaglandin, and NO.
In blood volume reduction arising from diuresis and Na excretion, a fall in glomerular filtration rate causes Na reabsorption. Na reabsorption occurs in proximal tubules leading to fluid conservation.
When there is volume overload, the atrial and ventricular myocardium secrete natriuretic peptides. The natriuretic peptides inhibit Na reabsorption in distal tubule, resulting in Na excretion, and diuresis. They also cause peripheral vasodilation.
ARTERIOSCEROSIS
Arteriosclerosis is a general term that describes the thickening of arterial walls and loss of elasticity. Pattern of arteriosclerosis include: arteriolosclerosis; Monckeberg’s medial sclerosis; atherosclerosis.
Arteriolosclerosis
This causes media thickening and luminal narrowing in small muscular arteries and arterioles. The two types include: hyaline and hyperplastic arteriosclerosis. The are both as a result of hypertension.
Hyaline arteriolosclerosis
In hyaline arteriolosclerosis, there is a uniform pink hyaline thickening with narrow lumen. Pink hyaline thickening arises due to: protein leakage after endothelial injury; excess extracellular cell matrix secretion by smooth muscle cells. This condition is seen in diabetic microangiopathy, & nephrosclerosis.
Hyperplastic arteriolosclerosis
Hyperplastic arteriolosclerosis shows onion-skin lesion which features: thick media; luminal narrowing; smooth muscle cells with double basal membranes. This condition is common is severe malignant hypertension.
Monckeberg’s medial sclerosis
This pattern of arteriosclerosis shows calcific deposits in muscular arteries that may undergo bone metaplasia. It is a condition common in people older than 50, and is clinically insignificant.
Atherosclerosis
This is an intimal lesion, with atheroma formation that protrudes into vessel lumen. The lesion arises from chronic inflammatory and healing response of arterial wall endothelial injury.
The atheroma is made of a lipid core (cholesterol with cholesterol esters) and overlying white fibrous cap. The fibrous cap consists of: macrophages, foam cells, ECM, neovascularization).
After endothelial injury, abnormal LDL accumulates within intima and undergoes oxidation. Endothelial cells or macrophages release oxygen free radicals that oxidize LDL. Macrophages engulf oxidized LDL through scavenger receptor and form foam cells.
As a result of chronic inflammatory process, macrophages and endothelial cells produce growth factors. These growth factors promote smooth muscle cell proliferation and ECM synthesis.
Atherosclerosis causes: ischemia; vessel thrombosis (when it ruptures); aneurysm formation (weakens media); coronary artery disease (CAD); myocardial infarction; aortic & carotid atherosclerotic disease; stroke.
The risk factors for CAD consist of modifiable and non-modifiable risk factors.
Non modifiable risk factors
- increasing age
- family history
- male gender
- genetic abnormalities (familial hypercholesterolemia)
Modifiable risk factors
- Hyperlipidemia: hypercholesterolemia from high low-density lipoprotein (LDH), and low high-density lipoprotein (HDL), and abnormal lipoprotein (a) levels.
- Diet: saturated fats rich in cholesterol (egg yolks; animal fats; butter)
- Physical inactivity & excessive alcohol consumption (lower HDL)
- Obesity and smoking (lowers HDL)
- Hypertension
- Cigarette smoking
- C-reactive protein