Hypertension Flashcards
1
Q
What is the arterial pressure equation?
A
Arterial Pressure = CO X TPR
2
Q
How can arterial pressure increase?
A
- Constricting almost all arterioles of the body, which increases total peripheral resistance
- Increasing blood volume which increases venous return and cardiac output
- Constricting large vessels of the circulation, thereby increasing venous return and cardiac output
- Directly increasing cardiac output by increasing heart rate and contractility
3
Q
What class of drugs affects vascular tone?
A
Vasodilators
4
Q
What are the levels of vascular resistance regulation?
A
- Neural controls
- Local controls
- Humoral controls
5
Q
List the vasoconstrictors and vasodilators at each level of vascular resistance regulation:
A
-
Neural controls
- Vasoconstrictors - Sympathetic system
- Vasodilators - Parasympathetic system
-
Local controls
- Vasoconstrictors - Myogenic response
- Vasodilators - PO2 reduction; K+, CO2, H+ osmolality; NO; Adenosine
-
Humoral controls
- Vasoconstrictors - NE; AngII; Vasopressin; Endothelin; Thromboxanes
- Vasodilators - Epinephrine; ANP; Bradykinin; Histamine; Prostaglandins
6
Q
How does the nervous system globally regulate circulation?
A
- Redistribution of blood flow to different areas
- Affects heart rate and pumping activity of the heart
- Essential for the very rapid control of arterial pressure.
7
Q
Be able to describe the signal transduction that modulate calcium in vascular smooth muscle:
A
8
Q
What are areas of the brain that play important roles in the nervous regulation of the circulation?
A
-
Reticular substance:
- lateral and superior portions ~ excitation
- medial and inferior portions ~ inhibition
-
Hypothalamus:
- posterior-lateral portions cause mainly excitation
- anterior portion can cause mild excitation or inhibition
-
Motor cortex:
- excitation or inhibition depending on region stimulated
9
Q
Where is the vasomotor center?
A
Located bilaterally in the reticular substance of the medulla and lower third of the pons
10
Q
Describe the specific task of each vasomotor center area:
A
-
Vasoconstrictor area “C-1” anterolateral upper medulla:
- sympathetic discharge
-
Vasodilator area “A-1” anterolateral lower medulla:
- inhibits C-1 area
-
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
-
Cardiac center
- heart rate and contractility
11
Q
- What does the sympathetic nervous system innervate?
- How is the parasympathetic nervous system involved?
A
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
Q
What is responsible of vasomotor tone?
A
Sympathetics are responsible for “vasomotor tone”
13
Q
What is the function of α1 and α2 adrenergic receptors?
A
-
α1:
- vasoconstriction (vascular smooth muscle)
-
α2:
- inhibit NE release (increase venous tone)
14
Q
What do adrenergic receptor agonists activate?
A
Signal transduction pathways
15
Q
What is the function of the β1 adrenergic receptor?
A
↑ HR and contractility
16
Q
Where are α and β adrenergic receptors generally located?
A
-
α:
- α1: vascular smooth muscle
- α2:** **sympathetic neuron
-
β:
- β1: myocardium
17
Q
Where are baroreceptors located?
How are the signals transferred between each baroreceptor?
A
- 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
Q
What type of feedback is the baroreceptor system?
A
Negative feedback control system
19
Q
What is feedback gain (G)?
A
“Feedback gain” (G) represents the strength of the feedback
G = Correction of error signal / Error (abnormality still remaining)
20
Q
How does the baroreceptor system respond to a fall in carotid sinus pressure?
A
Constrict Common Carotids → ↓ Pressure at Carotid Sinuses → ↑ Arterial Pressure
21
Q
Baroreceptors respond to:
A
Arterial Pressure Changes
22
Q
As pressure increases, the number of impulses from carotid sinus increases; this results in:
A
- inhibition of the vasoconstrictor
- activation of the vagal center
23
Q
At what pressure are the baroreceptors most sensitive?
A
100 mmHg
24
Q
What happened to arterial pressure after the baroreceptors were denervated in a dog?
A
Extreme fluctuations in arterial pressure
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:
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
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
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?
## Footnote
* **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
