Lecture 27: Overview of HTN epidemiology and consequences

Question 1

What is hypertension?

Answer 1

A disorder of regulation of Systemic Vascular Resistance
A syndrome that encompasses a large group of disorders
-systemic arterial pressure is regulated at a sustained abnormally increased level
Abnormal fibrosis (deposition of collagen) in tissues
End product of heredity, environment and behavior

Question 2

What are the two groups of HTN?

Answer 2

1. Primary (essential) hypertension
   
   • resistance hypertension
   • compliance hypertension (stiff pipes)
2. Secondary hypertension

Question 3

What is the vicious cycle of HTN?

Answer 3

Increases systolic pressure (LV hypertrophy and fibrosis of myocardium)
Elastic arteries are subjected to increased stress due to increased systolic pressure
Increased stress = atherosclerosis and aneurysms more SVR
Arterioles then go obliterative destructive process, particularly in kidney
Renal failure = further increase in systolic BP

Question 4

What are the clinical consequences of HTN?

Answer 4

1. cardiac dysfunction secondary to progressive LV hypertrophy and myocardial fibrosis
2. Accelerated disease of large and small systemic arteries
   
   • leads to MI, stroke and aneurysms
3. Renal dysfunction secondary to progressive renal destruction due to disease of arteries from HTN

Question 5

What happens to SBP and DBP with age?

Answer 5

SBP increases but DBP decreases (since you have less compliance and therefore less blood that is stored in the elastic arteries to maintain diastolic BP)
Thus pulse pressure increases

Question 6

What are the two definitions of HTN?

Answer 6

1. epedimiological definition
   2 morbidity based definition
   Hard to define HTN because BPO varies with gender, age and race

Question 7

What are the challenges for the epidemiologic definition of HTN?

Answer 7

Continuum of BP values in the population
Disorder is so prevalent that HTN may appear to be normal
Tendency for BP to increase with age

Question 8

What are the challenges of the morbidity based definition?

Answer 8

Continuum of frequency of morbidity with BP

But Lower is usually better

Question 9

What is the physiological significance of hypertension?

Answer 9

i. Left ventricle: generates higher pressure, leads to higher wall stress, left ventricular hypertrophy, fibrosis of myocardium
ii. The arterial system: must contain the increased pressure, increases wall stress, aneurysms, atherosclerosis, destruction of systemic arterioles
iii. The kidney: destruction of the kidney due to arteriolar destruction, decrease ability to excrete sodium
Leads to MI, stroke and aneurysms

Question 10

What’s the correlation between coronary heart disease and systolic/diastolic pressure?

Answer 10

Higher the pressure = higher risk of coronary heart disease

Question 11

Why is HTN the silent killer?

Answer 11

You have no symptoms until you have end organ failure

Question 12

What is the etiology of hypertension?

Answer 12

1. secondary (caused by one of the arterial pressure regulatory mechanisms)
   
   • kideny, adrenal, CNS disease or drug intake
2. primary (no identifiable cause)

Question 13

What is BP determined by?

Answer 13

BP = CO x SVR

Question 14

What are the mechanisms that should prevent the development of hypertension?

Answer 14

1. baroreceptor reflex
2. pressure-natriuresis
3. RAA system
   When these mechanisms go wrong, you get hypertension

Question 15

How can HTN override the baroreceptor reflex?

Answer 15

If you have sustained HTN, the baroreceptor is reset and will not signal afferent nerves to decrease systolic BP

Question 16

What are the epidemiologic correlates of HTN?

Answer 16

African Americans
Africans in the UK
Asians
Familial aggregation
Aggregation in monozygotic twins

Question 17

What is the genetic correlate of hypertension?

Answer 17

There is a clear-cut genetic component that predisposes one to HTN
Some people who eat a lot of salt have no HTN
Some people who eat a lot of salt do have HTN
Demonstrated by Dahl’s “R” and “S” rats, the former are normotensive while the latter is hypertensive

Question 18

What is pressure-natriuresis curve?

Answer 18

An intrinsic renal mechanism
Increase in renal artery = increased urine/sodium excretion
Individuals with sustained hypertension must have defective renal-natriuresis or a renal pressure/natriuresis curve that is reset
Those who excrete more sodium when they intake more are the ones who are most resistant to HTN

Question 19

What is the mechanism for “R” rats to stay normotensive?

Answer 19

The higher the inflow pressure in the kidney the higher sodium is excreted in comparison to the “S” rats

Question 20

What are behavior correlates of hypertension?

Answer 20

More salty foods = HTN
Obesity (no exercise)
Sedentary lifestyle
Alcohol consumption

Question 21

What are the characteristics of individuals genetically predisposed to HTN?

Answer 21

Excrete less Na

More pronounced vasoconstrictive response to stress than normal

Question 22

What is resistance hypertension?

Answer 22

Fundamental abnormality is abnormal regulation of vascular resistance
SVR is elevated as well as SBP, DBP and MAP
Pulse pressure not as elevated
Typical BP = 150/100
regulation by baroreceptor, RAAS and pressure/natruiresis

Question 23

What is compliance hypertension?

Answer 23

Fundamental abnormality is the presence of decreased great vessel compliance
SVR is normal or modestly elevated
Systolic pressure is elevated by diastolic pressure is low/normal
Pulse pressure is greatly elevated (due to pulse wave velocity bouncing back faster)
Typical BP = 170/60

Question 24

What are the consequences of compliance hypertension?

Answer 24

1. Severe left ventricular pressure overload
   
   • diastolic heart failure (ie HCM)
2. Accelerated vascular disease

Question 25

What is the “Vicious cycle” in hypertension?

Answer 25

1. underlying causes
   
   • genetic predisposition, sodium intake, other behavioral traits
2. Initial effects
   
   • increased total body sodium
   • increased SVR
3. Subsequent effects
   
   • destruction of systemic arterioles
   • loss of functioning renal mass tissue fibrosis
4. Consequences
   
   • progressive increase in SVR
     - Progressive loss of renal function and ability to excrete sodium
     - Increased CV load
     - Changes in left ventricular systolic and diastolic properties

Question 26

What are the main etiologies of essential hypertension?

Answer 26

1. heredity
2. environmental factors
3. sodium relationship

Question 27

What is the natriuretic hormone?

Answer 27

Something we are still looking for lol
Believed to be a Na/K inhibitor that will allow kidney to excrete more
Maybe binds to the “oubain” receptors?

Question 28

Do diet and behavior matter in hypertension (ala Blumenthal et al study)?

Answer 28

Yes

Weight loss and increased oxygen delivery

Question 29

How does the kidney play a role in the pathogenesis of HTN?

Answer 29

Patients with hypertension have increased afferent and increased efferent renal sympathetic nerve activity
Hypothetically can be targeted for treatment
Example: Catheter based renal denervation (in trial stage)

Question 30

What are the types of receptors responsible for efferent adrenergic activity?

Answer 30

Alpha1 receptor in renal arteriole
Alpha1 receptor in renal tubular cell
Beta1 receptor in JG granular cell
Activation of all these will increase HTN by
i. decreasing renal blood flow and GFR
ii. activates N/K ATPase and increased Na and H20 reabsorption
iii. increase renin secretion
If you have selective beta blockers to renal function, you may get better HTN