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Should understand why it is so important for MAP to be homeostatically regulated. Physiological variables in MAP regulation are CO and TPR each of which is affected by many factors. Additionally there are physical factors which also contribute to MAP such as blood volume and arterial compliance. For the acute regulation of MAP the baroreceptors are of paramount importance. Understand where the baroreceptors are located how they function and what they control. These are shown in Figures 28-8, 28-9, 28-10 and 28-13. Stretch of baroreceptors as occurs in elevated MAP increases afferent firing which inhibits the vasoconstriction centre in the medulla and decreases sympathetic efferent output. The reverse is also true. Carotid baroreceptors respond more to rates of changes in MAP than steady state change compared to baroreceptors in the aortic arch.
1. Role of kidney in blood pressure regulation
a. Renin Angiotensin system
The mechanisms of renal control of MAP were discussed. The structure of the JGA is shown in F 40-4. The important parts of the JGA include the macula densa which is on the ascending limb of the nephron and the granular cells of the afferent and efferent arterioles in this area. The granular cells secrete renin which controls the amounts of angiotensin II and thus aldosterone. AT II is a potent vasoconstrictor and regulator of aldosterone secretion which regulates natriuresis. You should already be familar with these processes in some detail.
Renin secretion from the granulosa or granular cells is increased in response to:
increased sympathetic discharge. This also decreases GFR which increases PV.
decreased arteriole pressure in the JGA. Renin release decreases with increased [Ca2+] in the granular cell which is caused by increased stretch of the afferent and efferent arterioles due to increased MAP. In response to decreased MAP, there is less stretch of granular cells, lower [Ca2+] and increased renin release.
reduced [Na] in the ascending limb of the nephron tubule (as detected by the macula densa).
b. Pressure diuresis
Kidneys show pressure diuresis - increased MAP results in increased diuresis which decreases plasma volume over time, decreasing EDV, decreasing CO, decreasing MAP. Plasma volume is a balance between this diuresis and water/salt intake. Look at Figure 2 (Figure 19-4 from Guyton).
2. Non-renal factors
atrial natriuretic peptide (ANP). Stretch of atrial walls releases ANP from atria. ANP causes diuresis and natriuresis by acting on the kidneys. Also causes vasodilation thus ANP serves to decrease TPR and plasma volume both of which decrease blood pressure. Increased diuresis is caused by increasing GFR, inhibiting the effects of aldosterone and ADH, and inhibiting Na reabsorption - resulting in increased Na and water excretion.
antidiuretic hormone (ADH) - nine aa peptide AKA vasopressin. See pp 719-722 and Figure 42-3. Secreted from from posterior pituitary in response to elevated osmolarity (as detected by osmoreceptors in the hypothalamus) primarily and to decrease in plasma volume as detected by baroreceptors. ADH increases water permeability in the collected ducts of the nephrons through the actions of PKA which increase the number of water channels in membrane. The effect of this is to increase water reabsorption - increasing plasma volume. Also increases thirst. ADH secretion is also affected by other hormones previously discussed: angiotensin II (+) and ANP (-).
shifts in Starling equilibrium at the level of the capillaries due to changes in MAP
II. Hypertension
A. Effects
cardiac concentric hypertrophy (left ventricle for systemic hypertension and right ventricle for pulmonary hypertension). Concentric hypertrophy means increased wall thickness and is a reflection of increased myocyte thickness - sarcomeres added in parallel. From epidemiological studies we know that LV hypertrophy can be a strong predictor of premature death from CV failure.
atherosclerosis. Hypertension causes increased wall stress on the blood vessel wall - triggering plaque formation.
aneurysms
organ failure
B. Etiology
renal hypertension. Accounts for only ~10% of cases. If renal artery is occluded then afferent arteriole pressure decreases even if MAP is normal. This will result in increased renin secretion and hypertension.
essential (idiopathic, primary) hypertension. Although it accounts for ~90% of cases, etiology is not well understood. Probably due to increased TPR that may occur for a variety of reasons or chronic increase in volume which can cause increased TPR secondarily. A chronic volume overload can lead eventually to an increase in TPR due to autoregulation (increased myogenic tone in some vascular beds) and eventually hypertension.
C. Treatment
a. Pharmacological
diuretics - Increase diuresis, decrease plasma volume, decrease CO, decrease MAP
Calcium antagonists- blockers of L-type Ca channel in VSM mostly and ventricular myocytes to a lesser degree. Inhibit contraction in VSM, vasodilate, decrease TPR, decrease MAP. Because of the effect on ventricles will also decrease contractility, decrease CO and decrease MAP. Recently very controversial
b blockers - antagonists of the b adrenergic receptor which decrease contractility, decrease CO, decrease MAP
ACE inhibitors - decrease angiotensin II (AT II) levels in blood decreasing vasoconstriction (decrease TPR) and decreasing aldosterone secretion (decrease plasma volume)
AT II type I receptor blockers - decrease AT II function as above
b. Lifestyle
change in diet (i.e. reduce Na intake)
increase activity - aerobic exercise
stop smoking