7 - Pathophysiology of Hypertension Flashcards

1
Q

Define hypertension

A

A condition of chronically elevated blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do you diagnose hypertension?

A

Hypertension can be only be diagnosed based on 2 or more recordings taken in the seated position at 2 or more office visits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the range of blood pressure to diagnose hypertension

A
Systolic = >140 mmHg
Diastolic = >90 mmHg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe white coat hypertension

A

“White coat hypertension” is a relatively recently defined phenomenon of high blood pressure only in the clinical setting; despite the episodic nature of this elevation in blood pressure, these patients are also at a higher risk for some of the cardiovascular-related events seen in overtly hypertensive patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is one of the main concerns in the treatment of hypertension?

A

The number of patients not achieving blood pressure control despite being treated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What comorbidities are often seen in patients with hypertension?

A
  • Ischemic heart disease
  • Heart failure
  • Atrial fibrillation
  • Stroke

The pathogenesis of these conditions overlaps with hypertension and can create a vicious cycle, as hypertension increases the risk of these conditions and these conditions increase the risk of hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the relationship between increased blood pressure and the risk for MI, stroke and HF

A

The risk for MI, stroke, and HF doubles with a 20 mmHg increase in systolic or 10 mmHg increase in diastolic pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is an uncontrollable risk factor for hypertension?

A

Aging

There is a 90% lifetime risk of developing hypertension in normotensive middle-aged individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the general trend of systolic and diastolic pressure before and after the age of 50

A

Systolic and diastolic blood pressure increase together until about age 50, then diastolic pressure decreases while systolic pressure continues the upward trend

This means that older individuals are more likely to have isolated systolic hypertension than systolic and diastolic hypertension and younger individuals are more likely to have isolated diastolic hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does aging contribute to hypertension?

A

The aging process impairs cardiac function, reducing diastolic pressure, and alters vascular function, increasing systolic pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a controllable risk factor for hypertension?

A

Obesity

As BMI increases, the prevalence of hypertension also increases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What factors underlie the pathogenesis of obesity-related hypertension?

A

Many factors have been proposed to underlie the pathogenesis of obesity-related hypertension…

  • enhanced sympathetic activity/ responsiveness
  • activation of the renin-angiotensin-aldosterone system (RAAS)
  • metabolic disturbances

These factors ultimately change vascular and renal function to increase blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the organ damage that hypertension can lead to

A

Hypertension initiates damage to organs, including vasculopathy, cerebrovascular damage, heart disease, and nephropathy

In addition, secondary processes are activated to exacerbate damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe cardiac remodeling which can result from chronically elevated blood pressure

A
  • Ventricular hypertrophy occurs as the heart responds to the high afterload
  • Hypertrophy increases the risk of cardiovascular incidents including MI, HF and sudden cardiac death from a fatal arrhythmia or embolism
  • Treating hypertension can decrease risks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where else can remodeling occur due to hypertension?

A

In he vasculature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is atherosclerosis?

A

Vascular remodeling and plaque formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What two factors can induce remodeling in the vasculature?

A
  • Sheer stress on the vessels

- Hormonal factors such as Angiotensin II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does Angiotensin II mediate vascular remodeling?

A

Angiotensin II mediates vascular remodeling through activation of intracellular signaling cascades to alter vascular tone directly and gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is another process involved in the pathogenesis of hypertension?

A

Inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is inflammation activated by hypertension?

A

Hypertension can activate a T cell-mediated response and further exacerbate end-organ damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does inflammation contribute to organ damage?

A

Inflammation alters the oxidative capacity in the immune cells and reactive oxygen stress can influence vascular tone and protein expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does RAAS contribute to hypertension?

A

The renin-angiotensin-aldosterone system (RAAS) also contributes to immune activation in hypertension.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the two components of regulating short-term blood pressure?

A

1 - neural reflex arcs

2 - total peripheral resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the purpose of neural reflex arcs?

A

To modulate heart rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are the two major neural reflex arcs?
- baroreflexes | - chemoreflexes
26
Where do baroreceptors exist? What do they detect?
- Carotid sinus - Atria - Pulmonary arteries Baroreceptors detect blood pressure throughout the vascular tree
27
Where do baroreceptors send their signals regarding current blood pressure?
Into the CNS (medulla of brain)
28
What is the purpose of sending this information to the CNS?
Modulation of sympathetic and parasympathetic outflow
29
What can sympathetics and parasympathetics do with the information they receive regarding blood pressure?
Project to areas of the periphery including the heart and vasculature in order to modulate heart rate and total peripheral resistance
30
What are the key steps and components of a reflex arc?
- Stimulus to be detected by a sensory receptor ("detector") - Sensory info is transmitted to an integration center - Integration center compares afferent information from several sites to determine the appropriate effector response - Effector response serves to modulate the initial stimulus, changing the activity of the sensory receptor ("detector")
31
How does the reflex arc and feedback loop work for the arterial baroreflex?
Activation of the reflex results in a reduction of the sensed stimulus, meaning that an increase in BP will cause a decrease in BP and vise versa
32
What type of receptors are baroreceptors? What are they activated by?
baroreceptors are mechanosensitive sensory receptors, activated by the distending pressure in the carotid or atria (stretch receptors) Increased stretch of the wall generates an action potential in the nerve ending
33
Why are baroreceptors not involved in long-term maintenance of BP?
Because they sense both actual stretch and how the stretch is changing with time If the stretch is not changing with time (a period of extended stretch), the baroreceptors will "reset" to the new "normal"
34
What is the main integration center in the brain for sensory information from baroreceptors?
Nucleus of the solitary tract (NST) in the medulla of the brainstem
35
What happens to the sensory information at the NST? Where does the information go from there?
- The sensory information is integrated with information from the hypothalamus before it is projected to other brain regions - These other brain regions are important for modulation of total peripheral resistance, stroke volume, heart rate, parasympathetic tone, vagal tone and sympathetic tone - The projections then flow into the periphery and synapse in the sympathetic chain and parasympathetic ganglia
36
Where are chemoreceptors located?
The effector sensors of the chemoreflex are located in similar locations as the arterial baroreceptors, in the glomus cells of the carotid body and aortic bodies
37
What is the integration site for chemoreceptors?
Same as baroreceptors NTS - Nucleus of the Solitary Tract
38
What happens when chemoreceptors detect low O2, high CO2 or low pH?
Vasoconstriction and bradycardia
39
What accompanies this response?
This intrinsic response is mitigated by changes in ventilation that accompanies this response, as well as the activation of other chemoreceptors, to increase ventilation, which will cause a tachycardia.
40
What is one source of long-term regulation of blood pressure?
Hormones
41
What is a potent vasoactive substance that alters blood pressure?
Angiotensin II
42
What is the role of angiotensin II?
Angiontensin II causes.... - Direct vasoconstriction - Moderate sodium reabsorption - Stimulates aldosterone secretion from the adrenal gland, which promotes even greater sodium reabsorption from the kidney
43
How is angiotensin II produced?
By angiotensinogen released from the liver It then gets to the kidney where renin cleaves it into angiotensin I Once angiotensin I gets to the pulmonary vasculature angiotensin-converting enzyme (ACE) cleaves it into the vasoactive form of angiotensin II
44
What three processes is angiotensin II involved in (think rapid, slow and long-term)?
- Rapid vascular response - Slow renal response - Long-term remodeling
45
What is an organ that plays a predominant role in long-term blood pressure regulation?
Kidney
46
How does the kidney accomplish this?
Through regulating changes in sodium and water excretion | think blood volume
47
What happens when there is low arterial pressure in regards to the kidney?
Renal mechanisms to conserve water and salt are activated
48
What happens when there is high arterial pressure in regards to the kidney?
Renal mechanisms to increase the excretion of salt and water are activated
49
In what other way can changes in pressure alter kidney function?
Changes in pressure alter the filtration capacity of the glomeruli in the kidneys to alter the amount of water filtered
50
What is the effect of high pressure on the filtration capacity in the kidney
High pressure will increase resistance and therefore result in increased sodium excretion (water will follow) leading to a decreased blood volume
51
What is this relationship of filtration regulation referred to as?
Pressure-natriuresis
52
What can we infer about the effects of kidney damage on blood pressure
Any dysfunction of renal sodium and/or water handling will result in abnormal blood pressures
53
What will happen with a reduction in kidney mass or an enhanced tubular reabsorption of sodium?
Decreased glomerular capillary filtration and an inappropriate retention of sodium and water leading to hypertension
54
What is secondary hypertension?
Hypertension is classified based on the underlying pathology, so secondary hypertension is any hypertension resulting from a known cause The known cause (primary) issue results in (secondary) hypertension
55
What is primary hypertension? What else do we call this?
Hypertension in which no one causal factor can be identified AKA essential hypertension
56
What is renovascular disease?
Renovascular disease can result due to plaque formation in the renal artery, other stenotic processes, or vascular dysfunction Pretty much, the RENAL ARTERY is impaired
57
How do renal baroreceptors react to renovascular disease?
They detect a drop in blood pressure and respond by releasing renin in an attempt to increase circulating angiotensin II
58
What does increasing angiotensin II do?
Increases vascular resistance and inhibits natiuresis and diuresis at the level of the nephron (retains water)
59
What is obstuctive sleep apnea and how does it cause secondary hypertension?
OSA is a type of sleep apnea which results in intermittent hypoxic episodes which induce chemoreceptors to signal low oxygen
60
What do the chemoreceptors do during hypoxic states?
Send a sympathoexcitatory reflex which increases sympathetic nerve activity to change ventilation, increase renin secretion The goal is to increase ventilation and heart rate to decrease CO2 and increase O2
61
What factors may contribute to OSA-related hypertension?
- Vascular dysfunction - Obesity - Chronic stress (lack of sleep) - Inflammatory processes
62
How do you treat secondary hypertension?
Treat the primary insult Do NOT treat the hypertension
63
How do you treat a patient with renovascular hypertension?
Correct the vascular lesion via surgery
64
How do you treat a hypertensive patient with renal parenchymal disease?
Replace the kidney
65
How do you treat a hypertensive patient with coarctation of the aorta?
Fix the aorta
66
How do you treat a hypertensive patient with Cushing's disease and pheochromocytoma?
Excise the tumor
67
How do you treat a hypertensive patient with OSA or obstructive sleep apnea?
Open the airway - This is a good strategy theoretically but not clinically effective - This may be due to changes that occur centrally and/or the presence of co-morbidities
68
Do the majority of hypertension patients have primary (essential) or secondary hypertension?
Primary (essential) hypertension where no one factor can be identified
69
What are the general causes of primary (essential) hypertension?
Genetic - renal abnormalities - RAAS mutations - immunity - salt-sensitivity - sympathetic hyperactivity Environmental - stress - high salt intake - drug abuse - alcohol abuse
70
What three organ systems have been shown to be dysfunctional in hypertension
Each play a role - CNS dysfunction - Vascular dysfunction - Renal dysfunction
71
What is the benefit of lowering blood pressure?
Lowering blood pressure is associated with improved outcomes and reduced burden of comorbid factors
72
What is the first line in treating essential hypertension?
Lifestyle modification
73
What are the lifestyle modifications which can be effective?
- Weight reduction *** - DASH eating plan *** - Dietary sodium restriction - Physical activity - Moderate or low alcohol consumption *** two most effective methods
74
When lifestyle modification is ineffective, a medication plan is indicated. What is the typical drug therapy?
- Diuretic is indicated first - Then a combination of a RAAS target, calcium channel blocker or a beta blocker The combination of drugs used depends on the level of blood pressure
75
Why do patients on blood pressure medications need to be closely monitored?
An "escape" mechanism can develop and high blood pressure can recur, even on medication
76
What do medications targeting RAAS accomplish?
Therapeutics aimed at RAAS targets not only reduce resistance and sodium/water retention but also reduce cellular remodeling and are thought to reduce inflammatory processes
77
What is a growing concern in the pharmacological treatment of hypertension?
Resistant or refractory hypertension This means that the blood pressure goal is not reached with 3 or more pharmacological agents
78
What treatments are indicated in the case of resistant or refractory hypertension?
- Carotid sinus stimulator | - Renal denervation therapy
79
What is a carotid sinus stimulator?
- A carotid sinus stimulator is implanted around the carotid sinus and programmed to activate the baroreflex - This reduces blood pressure on the long-term (years) in patients and seems to be well-tolerated
80
What is renal devervation therapy?
- A more controversial therapy - A device ablates the renal nerves and lowers BP by reducing sympathetic outflow from the CNS - While it has been proven to be safe, the BP lowering effect has been mixed