BP Regulation, HTN + HHD

Question 1

What systems respond to changes in BP in:

1. seconds to minutes (4)
2. minutes to hours (5)
3. hours to days

Answer 1

1. baroreceptors (sense MAP, PP, and HR), chemoreceptors, afterload, cerebral-ischemia induced response (and Cushing reaction specifically in high ICP)
2. low pressure receptors (stretch receptors in veins, atria, and ), ANP, capillary fluid transfer, vascular stress relaxation, RAAS
   3.

Question 2

Pulse pressure - what is it and where is it higher/lower?

Answer 2

the difference between the SBP and DBP; highest in muscular arteries (femoral) because they are less compliant than elastic arteries (aorta)

Question 3

What effect does increasing afterload have on CO and SV?

Answer 3

increased afterload will decrease CO and SV, therefore this system is a buffer for increases in aortic pressure

Question 4

RAAS (renin angiotensin aldosterone system)

Answer 4

Decreased arterial pressure is sensed by the kidneys. The juxtaglomerular cells release renin, an enzyme that converts angiotensinogen (protein made by liver, found in circulation) to angiotensin I. In the lungs and kidney, angiotensin converting enzyme (ACE) will convert AT-I to AT-II. AT-II binds the AT-type I receptors in endothelium and causes vasoconstriction. This increases TPR and venous filling pressure, which increases CO so the kidneys won’t be hypoperfused anymore.
AT-II also releases Aldosterone from adrenals, which makes sodium stay and water with it, increasing BV.

Question 5

Renal function curve

Answer 5

Curve that plots renal fluid output (y-axis) and arterial pressure (x-axis). Shows that there must be a big change in fluid output/intake to make a minor change in pressure; this is a good buffer system for changes in pressure. Subject to adjustment to new set point for pressure (shift to the right) or salt-sensitivity (rotate clockwise, become less steep).

Question 6

Things that shift the renal function curve:

• to the right
• to the left

Answer 6

Shift right:
AT-II, ALD, SNS activity, vasopressin, renal disease, obesity
*in experiments, removal of one kidney - just can’t keep up with the amount of output it should be achieving, and so fluid is retained
Shift left:
ANP, NO, PGs, diuretics, B-blockers (basically, vasodilators and things that get rid of BV)

Question 7

Whole body regulation (of BP)

Answer 7

An increase in organ perfusion rate (such as in increased BV or BP) causes an autoregulatory increase in resistance in the vessels feeding the organs. Thus TPR is increased and total flow is decreased.
So in the experiment where 75% of kidneys were removed, the rats got increased BP at first because BV was up, but then the organs were like we don’t need all this blood and they increased TPR, so the CO was forced to slow down. Still end up with a net increase in BP.

Question 8

Relationship between TPR, CO, and MAP

Answer 8

MAP depends on CO and TPR (like BP depends on flow and resistance)
Increase TPR and CO will decrease, so that MAP stays constant. *As long as kidneys work.

Question 9

Diastolic dysfunction

Answer 9

when the ventricle can’t fill up as much as it needs to with blood during diastole due to hypertrophy/decreased compliance of the ventricular wall. This also means that blood stays in the atrium longer and thus the atria dilate.

Question 10

Hypertensive Heart Disease (HHD)

Answer 10

from chronically increased AP/afterload and work, the ventricular wall undergoes concentric hypertrophy. The big, non-compliant wall decreases the ventricle size and causes impaired ventricular filling, hence diastolic dysfunction.

Question 11

Similarities and differences between the 4 major hypertrophic heart diseases:
HHD, HCM, CP, and aortic stenosis

Answer 11

Similarities: common presentations include dyspnea, angina, or SCD; can be chronic
Differences: CP won’t have LVH, only aortic stenosis will reliably produce a murmur and pretty much only presents in males; HCM will present in young people, others are in old people

Question 12

Hypertrophic cardiac myocytes, microscopic appearance

Answer 12

enlarged nuclei (sometimes compared to boxcars) from increased transcription and protein synthesis, expanded cytoplasm from needing more space to work

Question 13

Fibrosis in hypertrophic heart disease

Answer 13

TGF-beta and other cytokines drive interstitial fibrosis; some patients get it and it’s progressive

Question 14

Reentrant ventricular trachycardia

Answer 14

fibrosis, whether from hypertrophy or healed MI, provides a region of abnormal conduction so that the electrical impulse is weird and can be conducted back the way it came, slowly around the fibrotic region, or elsewhere

Question 15

Aortic stenosis

Answer 15

nodular calcifications are deposited in the sinuses of Valsalva (pockets between the cusps of the valve and the aortic wall) and prevent complete opening as well as complete closing of the aortic valve. 3 types/causes: 1) degenerative, associated with age; 2) rheumatic, associated with rheumatic valvulitis; 3) congenital bicuspid aorta with raphe where there should have been a comissure

Question 16

Normal heart: right ventricular wall thickness compared to left

Answer 16

RV wall should be 1/3 the thickness of the LV wall

Question 17

Hypertrophic Cardiomyopathy (HCM)

Answer 17

Group of genetic conditions (deficient structural proteins, AD) that results in larger sarcomeres.
Structural features:
-asymmetric hypertrophy where the septum is thicker than the free; 1/3 of cases have HOCM: septum impinges on aortic outflow tract
-septum hits the mitral valve, see fibrosis of valve and upper septum leading to regurgitation.
-myocyte disarray where cells are out of normal parallel orientation; results in impaired contraction ability.
Treatment: kill/thin part of septum with EtOH infusion.

Question 18

Cor pulmonale (CP)

Answer 18

Right-sided, isolated primary pulmonary HHD; R ventricular pressure overload due to increased pressure in the pulmonary circulation (anywhere between pulmonary valve stenosis and LHF); can be due to lung parenchymal disease like PE, microemboli, COPD, emphysema. Right heart will be hypertrophied if chronic, dilated if acute, hypertrophied and dilated if acute-on chronic. Most patients with CP are compensated.

Question 19

Normal heart: right ventricular wall thickness compared to left

Answer 19

RV wall should be 1/3 the thickness of the LV wall

Question 20

What is BP, normal BP, and HTN?

Answer 20

BP = CO * TPR
CO = SVHR
BP = SVHR * TPR
SV depends on preload and contractility. HR depends on ANS and conduction system. TPR depends on neurohumoral (RAAS, vasopressin), local factors (kinins, PGs, NO).
Normal is 120/80. HTN is >140/90; for >60yrs treatment is initiated at 150/90.

Question 21

Essential HTN

Answer 21

No identifiable cause defines Essential HTN, but there are identifiable contributing behaviors (obesity, salt intake, alcohol). But there is functionally a GOF in pathways that promote vasoconstriction and sodium retention, or LOF in pathways that promote vasodilation and renal sodium excretion.

Question 22

Causes of HTN

Answer 22

Essential HTN (95%) - unknown cause
Secondary causes (5%):
Pheochromocytoma, renal dysfunction/disease, excess mineralocorticoid, pregnancy, neurogenic, endocrine (hyperaldosteronism)

Question 23

Treatment for HTN

Answer 23

• lifestyle changes - weight loss, DASH diet, exercise, no EtOH/tobacco
• drug therapy
• watch out for differential benefit - as risk factors accumulate, benefit of therapy increases, but if there are not that many risk factors then the pt doesn’t stand to benefit very much and treatment may not be indicated

Question 24

3 goals of evaluating a patient with elevated BO

Answer 24

1. Obtain accurate reading - technique, equipment, skill, all data recorded, repeated, timing, concomitant factors (anxiety, drugs, caffeine, etc.)
2. Significance of BP - stratify risk factors (HLD, DM, tobacco, EtOH, etc.), assess for target organ damage (history, physical-EKG, check kidneys-labs/brain/eyes-retina)
3. Identify and treat the identifiable causes of HTN - secondary causes like renal disease, stenosis, hyperaldosteronism, etc.

Question 25

Drug therapy for HTN

Answer 25

First line = ACEIs (-pril), ARBs (-sartan), CCBs (DHPs: -pine, and non-DHP), thiazide diuretics
NOT first line = beta-blockers, alpha-1 blockers, central alpha-2 agonists, direct vasodilators

Question 26

CCBs in treatment of HTN

Answer 26

Reduce TPR to decrease BP.
2 types:
1. dihydropyridines - specific for vasculature, produce relaxation, end in -pine
2. non-dihydropyridines - slow the HR by blocking L-type Ca channels, include verapamil and diltiazem

Question 27

Diuretics in treatment of HTN

Answer 27

longer acting and promote renal loss of sodium, potassium, and magnesium; may worsen BGlu control in diabetics, may produce hyperuricemia; effective as add-on therapy

Question 28

Beta blockers in treatment of HTN

Answer 28

these drugs decrease HR but don’t decrease risk of death/stroke/MI – so don’t use as first-line, but they can be added on to existing therapy to avoid reflex tachycardia

Question 29

Alpha-1 blockers in treatment of HTN

Answer 29

Will cause dilation of skin and splanchnic vessels. Don’t use as first line because they have been associated with increased incidence of HF in patients with HTN.

Question 30

Central alpha-2 agonists in treatment of HTN

Answer 30

Reduces TPR by inhibiting release of NE which vasodilates the skeletal muscle vessels. Watch out for clonidine withdrawal syndrome (severe acute HTN upon withdrawal b/c receptors were up-regulated); clonidine is definitely not a first- or even second-line agent, only used for rapid BP reduction when parenteral treatment not needed. Methyldopa works by same mechanism; sometimes used in pregnancy because of proven safety record.

Question 31

Why not use direct vasodilators to treat HTN?

Answer 31

They cause reflex tachycardia which can worsen/precipitate angina (ischemia) - best to use with a beta-blocker.
Hydralazine can induce lupus, and Minoxidil causes lots of fluid retention with possible pericardial effusion (must use with potent diuretics and beta-blockers).

Question 32

What’s a hypertensive crisis (numbers) and what constitutes an emergency?

Answer 32

“Severely elevated BP” - which is around SBP >180, DBP>120.
Emergency if there is ongoing target organ damage. Must treat promptly but not excessively–only lower BP by 25% within first 2hrs. If BP is brought down too fast may compromise perfusion by activating autoregulatory mechanisms.