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Cardiovascular System > Hypertension > Flashcards

Flashcards in Hypertension Deck (64):
1

What is the arterial pressure equation?

Arterial Pressure = CO X TPR

2

How can arterial pressure increase?

  1. Constricting almost all arterioles of the body, which increases total peripheral resistance
  2. Increasing blood volume which increases venous return and cardiac output
  3. Constricting large vessels of the circulation, thereby increasing venous return and cardiac output
  4. Directly increasing cardiac output by increasing heart rate and contractility

3

What class of drugs affects vascular tone?

Vasodilators

4

What are the levels of vascular resistance regulation?

  • Neural controls
  • Local controls
  • Humoral controls

5

List the vasoconstrictors and vasodilators at each level of vascular resistance regulation:

  • Neural controls 
    1. Vasoconstrictors - Sympathetic system
    2. Vasodilators - Parasympathetic system
  • Local controls 
    1. Vasoconstrictors - Myogenic response
    2. Vasodilators - PO2 reduction; K+, CO2, H+ osmolality; NO; Adenosine
  • Humoral controls​ 
    1. Vasoconstrictors - NE; AngII; Vasopressin; Endothelin; Thromboxanes
    2. Vasodilators - EpinephrineANP; Bradykinin; Histamine; Prostaglandins

6

How does the nervous system globally regulate circulation?

  1. Redistribution of blood flow to different areas
  2. Affects heart rate and pumping activity of the heart
  3. Essential for the very rapid control of arterial pressure.

7

Be able to describe the signal transduction that modulate calcium in vascular smooth muscle:

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8

What are areas of the brain that play important roles in the nervous regulation of the circulation?

  1. Reticular substance:
    • lateral and superior portions ~ excitation
    • medial and inferior portions ~ inhibition
  2. Hypothalamus:
    • posterior-lateral portions cause mainly excitation
    • anterior portion can cause mild excitation or inhibition
  3. Motor cortex:
    • excitation or inhibition depending on region stimulated

9

Where is the vasomotor center?

Located bilaterally in the reticular substance of the medulla and lower third of the pons

10

Describe the specific task of each vasomotor center area:

  1. Vasoconstrictor area “C-1” anterolateral upper medulla:
    • sympathetic discharge
  2. Vasodilator area “A-1” anterolateral lower medulla:
    • inhibits C-1 area
  3. Sensory area “A-2” bilateral in nucleus tractus solitarii:
    • receive sensory signals from vagus and glossopharyngeal from baroreceptors
    • Control C-1 and A-1 areas
  4. Cardiac center
    • heart rate and contractility

11

  • What does the sympathetic nervous system innervate? 
  • How is the parasympathetic nervous system involved?

Sympathetic nerve fibers:

  • Innervate all vessels except capillaries and precapillary sphincters and some meta arterioles
  • Innervation of small arteries and arterioles allow sympathetic nerves to increase vascular resistance
  • Large veins and the heart are also sympathetically innervated

Parasympathetic nervous system

  • mainly important in control of heart rate via the vagus nerve

12

What is responsible of vasomotor tone?

Sympathetics are responsible for “vasomotor tone”

13

What is the function of α1 and α2 adrenergic receptors?

  • α1:
    • vasoconstriction (vascular smooth muscle)
  • α2:
    • inhibit NE release (increase venous tone)

14

What do adrenergic receptor agonists activate?

Signal transduction pathways

15

What is the function of the β1 adrenergic receptor? 

↑ HR and contractility

16

Where are α and β adrenergic receptors generally located?

  1. α:
    • α1: vascular smooth muscle 
    • ​α2: sympathetic neuron
  2. β:
    • β1: myocardium

17

Where are baroreceptors located? 

How are the signals transferred between each baroreceptor?

  • Baroreceptors are located in the walls of the carotid bifurcation called the carotid sinus and in the walls of the aortic arch
  • Signals from the carotid sinus are transmitted by the Hering’s nerve to the glossopharyngeal nerves and then to the nucleus tractus solitarii (NTS) of the medulla
  • Signals from the arch of the aorta are transmitted through the vagus into the NTS

18

What type of feedback is the baroreceptor system?

Negative feedback control system

19

What is feedback gain (G)?

“Feedback gain” (G) represents the strength of the feedback

G = Correction of error signal / Error (abnormality still remaining)

20

How does the baroreceptor system respond to a fall in carotid sinus pressure?

Constrict Common Carotids → ↓ Pressure at Carotid Sinuses → ↑ Arterial Pressure

21

Baroreceptors respond to:

Arterial Pressure Changes

22

As pressure increases, the number of impulses from carotid sinus increases; this results in:

  1. inhibition of the vasoconstrictor
  2. activation of the vagal center

23

At what pressure are the baroreceptors most sensitive?

100 mmHg

24

What happened to arterial pressure after the baroreceptors were denervated in a dog?

Extreme fluctuations in arterial pressure

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25

Why are baroreceptors reset?

  • thought to prevent the reflex from functioning as a control system for changes in pressure that last more than a day
    • However, resetting is not complete

26

Describe the RAA system:

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27

What is the role of ACE?

  • Activates: Ang1 to Ang2
  • Inactivates: Bradykinin

28

How do NO and ROS affect the vasculature in hypertension?

  • NO: can lead to endothelial dysfunction
  • ROS: can lead to medial wall hypertrophy

29

How can ROS potentially be involved in HTN?

ROS can affect:

  1. Heart, Vessels
    • Increased GSSG, H2O2, O2- 
    • Lipid peroxidation
    • ↑ levels of Ang II/Aldosterone

  2. Kidney
    • Activation of the RAA system
    • ↑ production/ release of vasoactive neurotransmitters
    • ↑ release of aldosterone

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30

How does HTN impact the population?

  • Essential hypertension (EH) affects 972 (26.4%) of the world adult population
    • 90% cause of all HTN
  • 67 millions Americans affected
  • Controlled in only about one-half of US population

31

How do blood pressures correlate with mortality?

Mortality increases exponentially with increasing age and BP

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32

Classification of HTN:

  • Normal:
  • Pre-HTN:
  • Stage 1 HTN:
  • Stage 2 HTN:

  • Normal:
    • Systolic: < 120 mmHG and
    • Diastolic: < 80 mmHG
  • Pre-HTN:
    • Systolic: 120 - 139 mmHg or
    • Diastolic: 80-89 mmHg
  • Stage 1 HTN:
    • Systolic: 140 - 159 mmHg or
    • Diastolic: 90-99 mmHg
  • Stage 2 HTN:
    • Systolic: ≥ 160 mmHg or
    • Diastolic: ≥ 100 mmHg

33

Since blood pressures can widely vary, what is the best guideline for evaluation?

  • A single accurate measurement is a good start but not enough:
    • Measure blood pressure twice and take the average
    • Running average is more important than individual readings.
  • 2-3-4 rule:
    • Hypertension is diagnosed if the average of at least 2 readings per visit obtained at 3 separate visits each 2 to 4 weeks apart is 140 mm Hg or greater systolic and 90 mm Hg or greater diastolic

34

At what age does systolic BP usually begin to greatly increase (both males and females)?

Ages 50-59

35

How does race factor into HTN?

  • Prevalence of HTN is highest in blacks of non-hispanic origin (44%).
  • Blacks are 4.2 times more likely to develop ESRD
  • 2007: death from HTN related complications were 15.7% for white males, 49.2 for black males, 14.3 for white females, and 37.0 for black females

36

What is the risk of doing nothing about HTN?

  • Hypertension is closely associated with heart disease, stroke and renal disease
  • For every 20 mmHg systolic or 10 mmHg diastolic increase in BP, there is 2X mortality from both ischemic heart disease and stroke (JNC, 7th Report)
  • Hypertension is the 2nd leading cause of ESRD
    • “High normal” BP (130-139 / 85-89 mmHg) is associated with ~ 3-fold greater risk of future development of ESRD

37

Risks: 

  • Gender: 
  • Age: 
  • Race: 

  • Gender:
    • Age-specific associations of ischemic heart disease (IHD) with BP is slightly greater for women than men 
  • Elderly:
    • Systolic BP rises progressively with age and elderly people with hypertension are at greater risk for CV disease 
  • Race:
    • Blacks tend to have higher levels of BP (compared to non-Blacks), and overall hypertension 

38

Causes of essential HTN are both __________ and ___________.

Causes of essential HTN are both polygenic and multifactorial.

39

What are exogenous causes of HTN?

  • Oral contraceptives
  • Nonsteroidal anti-inflammatory drugs
  • Cocaine, ethanol, amphetamines, decongestants
  • Glucocorticoids
  • Cyslosporin
  • Erythropoietin

40

Match the exogenous causes with the following results:

  1. Na retention:
  2. ↑ sympathetic activity:
  3. ↑ blood viscosity:

  1. Na retention:
    • Oral contraceptives
    • Glucocorticoids
    • Cyclosporin
  2. ↑ sympathetic activity:
    • Cocaine, ethanol, amphetamines, decongestants
  3. ↑ blood viscosity:
    • Erythropoietin

41

What is the most common cause of HTN?  What are the clues?

 

  • Most common cause: Essential HTN
  • Clinical Clues:
    1. Age of onset: 20-50 years
    2. Family History of HTN
    3. Normal serum K+; urinalysis

42

What are the primary genetic forms of HTN?

  • Rare Mendelian forms (Bartter’s syndrome; Liddle’s syndrome)
  • Essential hypertension (genes + environment; complex polygenic disease) ~ 90%

43

What are the secondary forms of HTN?

  • Renovascular (1%)
  • Renal parenchymal disease (2-4%)
  • Pheochromocytoma (0.2%)
  • Cushing’s syndrome (0.1%)
  • Coarctation of aorta (0.1%)

44

What are the comorbidities of HTN?

  • Atherosclerosis
  • Coronary artery disease
  • Myocardial infarction
  • Stroke
  • Congestive heart failure
  • Peripheral vascular disease
  • Chronic kidney disease
  • Obesity
  • Diabetes
  • Metabolic syndrome
  • Obstructive sleep apnea
  • Cognitive impairment

45

Why is the kidney important in HTN?

Mass balance

  • The kidney makes the cardiovascular system open
    • Can affect how much Na/H2O comes in or goes out

46

How is “mass balance” of sodium/water achieved? 

  • ↑ Na/H2O intake → ↑ Blood volume
  • Reflex and hormonal responses:
    • ↓ Sympathetic activity
    • ↓ ADH, Renin-Angiotensin II, Aldosterone
    • ↑ ANP
    • ↑ Prostaglandins
  • ↑ Na/H2O excretion

47

What is the role of pressure-natriuresis in regulation of BP?

Negative feedback to return pressure to control levels

48

General determinants of the pressure-natriuresis relationship:

  1. Vascular resistance
  2. GFR
  3. Tubular reabsorption

49

What are the intrinsic factors and extrinsic factors that determine the relationship between pressure and sodium excretion?

Intrinsic factors:

  1. Physical factors
  2. Angiotensin II
  3. Prostaglandins
  4. Kinins
  5. ROS (O2-, H2O2, NO)
  6. 20-Hete

Extrinsic factors:

  1. Angiotensin II
  2. CNS Sympathetic
  3. Aldosterone
  4. Vasopressin
  5. Atrial Natriuretic Peptide
  6. Endothelin
  7. Other

50

How will increased Ang II affect renal perfusion? 

How will this affect the pressure-natriuresis curve?

  • ↑ angiotensin II levels → ↑ renal perfusion pressure
    • to achieve sodium and water balance
  • reduce the slope of the pressure-natriuresis relationship

51

What was the conclusion from the experiment of the infusion of Ang II and the servocontroller on the dog’s renal arteries?

with increased Ang II, a rise of renal perfusion pressure is required to achieve Na+ and H2O balance 

52

What will happen if the renal arteries are uncontrolled and there is an increased infused Ang II or norepinephrine?

BP will rise to hypertensive levels

53

When will there be a rise in TPR (in relation to HTN)?

Secondary to HTN

54

What else will rise with an increased arterial pressure?

  1. ECF
  2. Blood volume
  3. CO

55

What happens with CO and TPR as age increases?

  • ↓ CO
  • ↑ TPR

56

Forms of Hypertension:

  • Hereditary
  • Secondary 

  • Hereditary
    • Human
    • SHR
    • Dahl S
    • TGR
  • Secondary
    • Ang II
    • Goldblatt
    • RRM + salt
    • adrenergic
    • Aldo/DOCA salt
    • L-NAME

57

What is the relationship between HTN and salt-sensitivity?

Salt sensitivity greatly increases mortality in patients with HTN (increases in normotensive as well)

58

What are the human forms of salt-sensitive HTN?

  • salt-sensitive, insulin resistant, hyperlipidemic
  • low renin form of hypertension
  • proteinuria and glomerosclerosis
  • medullary interstitial fibrosis
  • early-stage renal failure

59

What is the main effect in the renal tubules in a patient with salt-sensitive HTN?

excess Na+ reabsorption

60

What are the α2 Na+ pumps?  What do they affect?

  • Type-1 Na/Ca exchangers
  • Receptor operated- and store-operated Ca2+ channels
  • Affect:
    1. CO and TPR
    2. Oubain

61

What happens with ↑ RPP?

  • Release:
    • Cytokines
    • Angiotensin II
    • Inflammation
    • Fibrosis
    • Glomerular sclerosis
    • Proteinuria
  • T-cell infiltration

62

What are the effects of prolonged high NaCl intake?

  • arterial pressure
  • Heart:
  • Blood vessels:
  • Kidneys:

  • ↑ arterial pressure
  • Heart:
    • Cardiac hypertrophy
    • Diastolic dysfunction
    • Systolic dysfunction
  • Blood vessels:
    • Oxidative stress
    • Endothelial dysfunction
    • Fibrosis
    • ↓ vascular elasticity
  • Kidney:
    • Glomerular injury
    • Renal failure

63

What do all rare extreme outliers in families with monogenic (Mendelian) mutations affect?

All affect the kidneys

  • Affect renal Na+ reabsoprtion

64

What are the major consequences of arterial HTN?

  1. Heart failure
  2. Myocardial ischemia & infarction
  3. Aortic aneurysm & dissection → stroke
  4. Nephroscelrosis & renal failure
  5. Retinopathy