Hypertension
Objectives
The student will be expected to know
and understand:
1. The definition of hypertension
2. The prevalence
of hypertension
3. The major
causes of hypertension; primary vs secondary hypertension
4. Natural history
of hypertension and the complications related thereto, i.e. target organ damage
5. The physiological determinants of systemic blood pressure
a. cardiac ourput/blood flow
b. vascular resistance
c. circulatory compliance
d. blood volume
e. blood viscosity
6. Neurohumoral control of the circulation and blood pressure
a. role of the autonomic nervous system
b. role of the renin-angiotensin-aldosterone system
c. the potential role of other humoral factors including:
1) arginine vasopressin (AVP)
2) prostaglandins and other eicosanoids
3) kallikrein-kinin system
4) atrial natriurettc peptide
5) endothelium derived relaxing factors (EDRFS)
6) endothelin and ocher endothelium derived vasoconstricting factors
(EDVCS)
7. Guyton's Hypothesis: The
dominant role of the kidney in long-term BP control via the influence of
systemic blood pressure on renal excretion of sodium and water.
8. Pathogenesis and pathophysiology of hypertension secondary to excess
mineralocorticosteroid and the mechanism of the "escape" phenomenon.
9. Pathogenesis and pathophysiology of hypertension secondary to renal
parenchymal disease and the renal microcirculatory adaptation to a decrease in
the number of functioning nephrons.
a. hypertension associated with acute glomerulonephritis
b. hypertension associated with chronic renal failure
10. Pathogenesis and pathophysiology of hypertension secondary to renal
artery
stenosis
(Goldblatt Hypertension) including:
a. physiology of the renin-angiotensin-aldosterone system
1) regulation of renin secretion
2) effects of angiotensin II on vascular smooth muscle, the adrenal
cortex and the kidney
b. responses to a sustained infusion of angiotensin II
c. effect of unilateral renal artery constriction on renin secretion, renal
function and system blood pressure
d. effect of bilateral renal artery constriction on renin secretion,
renal function and systemic blood pressure
11. Pathogenesis
and pathophysiology of essential hypertension including:
a. definition of essential hypertension
b. role of dietary factors: Na+, K+, Mg++,
Ca++, calories
c. role of genetic factors
d. role of the sympathetic nervous system
e. role of the renin-angiotensin-aldosterone system
f. role of other humoral factors
CLASSIFICATION OF
HYPERTENSION
I. Systolic
Hypertension (only the systolic blood pressure is raised).
A. Increased stroke output of the left
ventricle (e.g. complete heart block, aortic regurgitation, AV fistula,
thyrotoxicosis, Paget's disease of bone).
B. Increased rigidity of the aorta due to
degenerative disease.
II. Hypertension in which
diastolic blood pressure is raised with or without elevation of systolic blood
pressure.
A. Primary or essential hypertension.
B. Secondary hypertension (hypertension
occurring as a manifestation of a recognized
disease).
I. Diseases of the kidneys.
a. Acute and chronic glomerulonephritis.
b. Chronic pyelonephritis and other forms of chronic
interstitial nephritis.
c. Renal artery stenosis and other forms of renovascular
disease.
d. Polycystic kidney disease.
2. Coarctation of the aorta.
3. Pheochromocytoma.
4. Cushing's Syndrome.
5. Primary hyperaldosteronism.
6. Pre-eclamptic toxemia of pregnancy.
7. Various CNS disorders.
EFFECTS OF ENDOTHELIN
Direct:
Vasoconstriction
Proliferation
Indirect:
Release of ANF
Release of
aldosterone and catecholamines from adrenal gland
Inhibition of renin from JG cells
Positive inotropic
and chronotropic effects
Modulation of
renal sodium excretion
SUBSETS
OF PRIMARY HYPERALDOSTERONISM
1. Primary hyperaldosteronism secondary to unilateral
adrenal cortical adenoma.
2. Primary adrenal hyperplasia.
3. Idiopathic hyperaldosteronism (no apparent anatomic
defect; incomplete autonomy).
4. Adrenalcortical carcinoma with aldosteronism excess.
5. Glucocorticosteroid remediable hyperaldosteronism
UNUSUAL, FORMS OF MINERALOCORTICOID HYPERTENSION
1. Adrenal tumors that produce excessive quantities of
deoxycorticosterone.
2. Congenital adrenal hyperplasia.
a. 11b-hydroxylase deficiency:decreased production
of cortisol, increased secretion of ACTH which stimulates increased production
of DOC and androgens causing hypertension and virilization.
b. 17a-hydroxylase deficiency syndrome:autosomal
recessive disorder characterized by mineralocorticoid hypertension without
virilization.
3. Liddle's Syndrome: autosomal dominant hereditary
hypertensive disorder characterized by a primary increase in collecting tubule
sodium reabsorption due to a genetic defect involving the beta and gamma
subunit of the luminal membrane sodium channel. The hormonal profile includes
low aldosterone, low renin, normal cortisol.
4. Syndrome of apparent mineralocorticoid excess:deficiency of 11b-hydroxysteroid
dehydrogenase.
a. Congenital
b. Acquired
1) Licorice-induced (glycyrrhizic acid)
2) Glucocorticosteroid excess ....
DAY 1: GFR = 50 nl/min x (2 x 106) = 100 ml/min.
DAY 2: GFR = 50
nl/min x (1 x 106) = 50 ml/min.
DAY 3: GFR = 60
nl/min x (1 x 106) = 60 ml/min.
DAY 90:GFR= 70
nl/min x (1 x 1106) = 70 ml/min.
MECHANISM OF SNGFR
Positive sodium balance leads to
1) decreased renal
sympathetic tone
2) inhibition of
the rennin- angiotensin- aldosterone system
3) inhibition of
endothelin secretion
4) stimulation of
nitric oxide synthesis
5) stimulation of
atrial natriuretic peptide synthesis and secretion
6) stimulation
ofvasodilator prostaglandin synthesis
7) stimulation of
“natriuretic hormone" synthesis and secretion
8) increased
systemic arterial pressure
9) glomerular
hypertrophy with an increase in the filtration surface area
