Hypertension may be primary (idiopathic) or less commonly secondary to an identifiable underlying condition. In close to 95% of cases hypertension is idiopathic or “essential”. Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing (renovascular hypertension), or adrenal disorders (
Table 10.2 ). Essential hypertension is compatible with long life unless a myocardial infarction, stroke, or other complication supervenes. Prognosis of secondary hypertension depends on adequate treatment of the underlying cause. Several relatively rare single-gene disorders cause hypertension (and hypotension) by affecting renal sodium resorption. Such disorders include the following: • Gene defects in enzymes involved in aldosterone metabolism (e.g., aldosterone synthase, 11β-hydroxylase, 17α
Table 10.2 Types and Causes of Hypertension (Systolic and Diastolic)
Adrenocorticalhyperfunction(Cushingsyndrome,primaryaldosteronism,congenitaladrenalhyperplasia,licoriceingestion)
Exogenoushormones(glucocorticoids,estrogen[includingpregnancy-inducedandoralcontraceptives],sympathomimeticsandtyraminecontainingfoods,monoamineoxidaseinhibitors)
PsychogenicIncreasedintracranialpressureSleepapneaAcutestress,includingsurgery hydroxylase), leading to increased aldosterone secretion, increased salt and water resorption, and plasma volume expansion • Mutations in proteins that affect sodium resorption (as in Liddle syndrome, which is caused by mutations that prevent the normal degradation of the ENaC sodium channel, leading to increased distal tubular resorption of sodium)
Although the specific triggers are unknown, it appears that both altered renal sodium handling and increased vascular resistance contribute to essential hypertension.
Reduced renal sodium excretion in the presence of normal arterial pressure probably is a key pathogenic feature; indeed, this is a common etiologic factor in most forms of hypertension. Decreased sodium excretion causes an obligatory increase in fluid volume and increased cardiac output, thereby elevating blood pressure (see
Fig. 10.3 ). At the new higher blood pressure, the kidneys excrete additional sodium. Thus, a new steady state of sodium excretion is achieved, but at the expense of an elevated blood pressure.
Increased vascular resistance may stem from vasoconstriction or structural changes in vessel walls. These are not necessarily independent factors, as chronic vasoconstriction may result in permanent thickening of the walls of affected vessels.
Genetic factors play an important role in determining blood pressure, as shown by familial clustering of hypertension and by studies of monozygotic and dizygotic twins. In a small proportion of cases of essential hypertension there is linkage to specific angiotensinogen polymorphisms and angiotensin II receptor variants; polymorphisms of the renin-angiotensin system also may contribute to the known racial differences in blood pressure regulation. Susceptibility genes for essential hypertension in the vast majority of cases are currently unknown but probably include those that influence renal sodium resorption, the production of endogenous pressors, and SMC growth.
Environmental factors, such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants. Evidence linking dietary sodium intake with the prevalence of hypertension is particularly strong.
MORPHOLOGYHypertensionnotonlyacceleratesatherogenesisbutalsocausesdegenerativechangesinthewallsoflarge-andmedium-sizedarteriesthatcanleadtoaorticdissectionandcerebrovascularhemorrhage.Threeformsofsmallbloodvesseldiseasearehypertension-related(