Hypertension - Wollak

Question 1

What is the Windkessel effect?

Answer 1

The method of using arterial elasticity and stiffness to convert high velocity pulsatile flow from the aorta to low velocity steady flow in the capillaries.

More elastic arteries expand and store blood as they are filled. Thus there is some delivery during diastole and blood output can be continuous.

More elastic vessels means higher pulse pressure and more healthy blood pressure.

Question 2

What are the effects of the pressure wave reflection at the heart?

Answer 2

Like a wave of pressure that bounces back off of stiff arteries to increase the original artery pressure.

First central pulse pressure is increased (increased max height).

Second, increased LV load, increased risk of LV hypertrophy (increased area under pressure-time curve during systole).

Third, decreased coronary artery perfusion pressure in diastole (from decreased blood storage). Decreased diastolic blood flow at central artery causes ischemia.

Question 3

Mechanism of endothelial dilation of arteries

Answer 3

Via NO through eNOS enzyme in the endothelium

cGMP causes relaxation and vasodilation of vascular smooth muscle

In smooth endothelium: sheer blood flow acts with extracellular Ca2+ (note: cytosolic Ca causes vasoconstriction) to increase eNOS –> NO –> enters smooth muscle and activates cGMP –> vasodilation

Flow mediated dilation

NO and prostacyclin cause vasodilation, antithrombosis, antiinflammation and growth inhibition.
Ang II and Endothelin cause constriction, prothrombosis, proinflammation and growth promotion.

Question 4

How does urinary sodium respond to specific low and high levels of arterial pressure?

Answer 4

Arterial pressure<50mmHg- urinary sodium falls to zero

Arterial pressure=200mmHg- urinary sodium increase six fold to eight fold

In impaired natriuresis/hypertension, as intake of sodium increases, MAP gets higher at any level. Theory of aldosterone effecting mutations.

Question 5

Causes of secondary hypertension

Answer 5

Renal disease

Parenchyma disease
-alteration in renal secretion and sodium absorption

 Renovascular disease

• Unilateral or bilateral
• Atherosclerosis, fibrous dysplasia, renal artery aneurism, vasculitis (Takayasu), cyts or tumors, coarctation of aorta, etc.

Adrenal disease -
Pheochromocytoma
-Pain, perspiration or palpitations needed to diagnose

Primary hyperaldosteronism

• Most common cause of secondary HTN
• adenoma
• low renin
• LVH d/t direct aldosterone effect on the heart

        Cushing’s syndrome  -low renin and aldosterone d/t cortisol activating MC receptor

Sleep apnea syndrome (increased sympathetic tone)

Hypothyroidism, hyperthyroidism, and hyperparathyroidism, acromegaly

Oral contraceptives

Drugs –amphetamins,NSAID,steroids

Question 6

Mechanism of unilateral and bilateral stenosis

Answer 6

Unilateral:

Decreased blood flow to one kidney –> decreased renin by JGA of stenosed kidney –> increased aldosterone and Ang II –> hypertension –> mild elevation in sodium retention and vasoconstriction with increased PR.
Hypertrophy of healthy kidney.
RAS mediated hypertension (more than volume).
High AngII and Aldosterone
Increased target organ damage, LVH.
Hypokalemia

Bilateral:

Decreased blood flow to both kidneys –> impaired natriuresis –> increased blood volume –> decreased or normal aldosterone, renin, and Ang II –> hypertension –> sodium retension and increased blood volume with impaired excretion.
Voume mediated hypertension (ACEi contraindicated).

Existence of extensive atherosclerotic disease
Smoking
Flush pulmonary edema (ER from a little salt)
Impaired renal function (only in bilateral)
Elevation of creatinine after blocking the RAS
Abdominal bruit
Increased sympathetic activity
Increased blood pressure variability
Autonomic instability- flushing
Malignant hypertension

Question 7

Wet vs. Dry Hypertension

Answer 7

Wet:

Main mechanism = volume overload
Low renin:
Low renin essentioal hypertension
Bilateral renal artery hypertension
Primary hyperaldesteronisim
Tx: aldactone (aldosterone antagonist), reacts to diuretics

Dry

Main mechanism is vasoconstriction
High renin:
High renin essential hypertension
Unilateral renal artery stenosis
Mostly increase in systolic pressure

Question 8

Which medications are best used for hypertension?

Answer 8

First line: diuretics + Ca channel blockers. ACEi may be most beneficial. Combination therapy reduces toxicity with lower doses of each drug.

ABCD:
ACEi/Angiotensin II Blockade
Beta blockers (not really)
Ca channel blockeres
Diuretics/ Direct Renin Inhibitors

Diuretics:

1. Thiazides
2. If hypokalemic: give Potassium-sparing diuretics
3. Loop diuretics (furosemide)

ACE Inhibitors:
Increase bradykinin to vasodilate and cause cough (switch to ARBs)
Decrease aldosterone release
Used liberally to improve atherosclerosis with other conditions

Direct Renin Inhibitors:
Improve endothelial function and are organ protective

Decreasers of Peripheral resistance:

Calcium channel blockers (add ACEi to protect kidney from proteinuria):
Dihydropyridines (cause vasodilation)
Nondihydropyridines (rarely used, more action on heart and less vasodilation)

Second line:

Beta blockers:
Goal: block beta-1 receptors
Reduce catecholamine effect
Decrease plasma renin
More effect on the heart, not so potent in vasodilation

Alpha blockers:
Lability of blood pressure, no constant effect

Question 9

What hypertension drug combinations are risky?

Which are good

Answer 9

Beta blockers and ACE inhibitors

Beta blockers and thiazides have adverse metabolic effects

ACEi and ARBs can cause renal failure and increased cancer risk

ACEi or ARBs and Ca channel blockers good

Diuretics with ACE/ARB good