hypertension Flashcards

1
Q

what are the 2 types of hypertension?

A

pulmonary hypertension
systemic hypertension

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2
Q

pulmonary hypertension?

A
  • increased blood pressure in the arteries of the lungs
  • right side of the heart has to work harder
  • rare
  • more common in patients with another heart or lung condition
  • usually only diagnosed if severe and symptomatic
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3
Q

causes of pulmonary hypertension?

A
  • can be due to hypoxia
  • endothelial dysfunction
  • genetics
  • blockage/damage to blood vessels
  • side effects of drugs
  • left sided HF
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4
Q

systemic arterial hypertension?

A
  • systemic arterial hypertension is the condition of persistent non-physiological elevation of system blood pressure
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5
Q

value definition for systemic arterial hypertension?

A

systolic >140 mmHg (and/or)
diastolic > 90 mmHg

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6
Q

how is systemic arterial hypertension identified as one of the major casual risk factors for cardiovascular disease?

A

because it is a silent killer that can cause:
- heart attack
- kidney failure
- vision loss
- stroke/dimmentia

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7
Q

hypertension risk factors?

A
  • genetic
  • environmental
  • age
  • weight
  • sex:
    < 60 years more prevalent in males
    >60 years more prevalent in females
  • race:
    african Americans are more effected due to RAAS
  • education status
  • diet
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8
Q

what 2 monitor tests should be done to confirm HT?

A
  • ambulatory blood pressure monitoring (ABPM)
  • home blood pressure monitoring (HBPM)
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9
Q

ambulatory blood pressure monitoring?

A
  • measured twice per hour during waking hours
  • at least 14 measurements to calculate an average
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10
Q

home blood pressure monitoring?

A
  • monitored twice daily (day/night, sitting)
  • 2 recordings, 1 min apart for 7 days (at least 4)
  • all recordings after 1st to calculate an average
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11
Q

who should have their BP measured for HT?
how many readings should be done?

A
  • all adults >40 years
  • < 40 years with a family history of atherosclerosis
  • minimum of 3-4 pairs of readings gathered over 3-4 months
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12
Q

3 classes of hypertension?

A
  • stage 1 hypertension
  • stage 2 hypertension
  • severe hypertension
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13
Q

stage 1 hypertension

A
  • clinical BP is 140/90 mmHg or higher
  • ambulatory or home blood pressure monitoring daytime average is 135/85 mmHg (take 5 off both respectively)
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14
Q

stage 2 hypertension

A
  • clinical BP is 160/100 mmHg or higher
  • ABPM or HBPM daytime average is 150/95 mmHg or higher (take 10 off respectively)
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15
Q

severe hypertension

A
  • clinical systolic BP is 180 mmHg or higher
  • clinical diastolic BP is 110 mmHg or higher
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16
Q

primary hypertension (systemic arterial hypertension)

A
  • “essential” or “idiopathic” hypertension
  • accounts for around 95% of human hypertension
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17
Q

cause of primary hypertension?

A
  • no apparent underling cause
  • weight
  • lifestyle
  • diet:
    sodium intake, lack of excersise, alcohol, smoking
  • genetics
  • organ systems (heart, brain, kidney, vasculature= most effected)
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18
Q

short term control of BP?

A

BP= CO x TPR

CO= stroke volume x HR

  • complex interactions of neurohormonal and local control systems that regulate BP and local tissue flow.
  • but it also involves additional system that regulate circulatory volume in relation to vascular capacitance (long term control)
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19
Q

long term control of BP?

A

effective circulating volume (ECV)
(kidneys)

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20
Q

what are the 3 possible contributions to systemic hypertension?

A

1- increased sympathetic activity/sensitivity
2- renin angiotensin aldosterone system (RAAS)
3- Circulating factors

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21
Q

what interactions does SNS have to control BP?

A
  • blood vessel tone
  • heart rate and force of contraction
  • adrenal gland secretion of adrenaline
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22
Q

how do SNS and PSNS work to control visceral activity?

A

synergistically (often opposite)

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23
Q

describe the sympathetic pathway for norepinephrine release?

A

preganglionic fibre (from CNS) synapses on a ganglion in the periphery
- releasing Ach onto an N2 receptor
- releasing norepinephrine
- binding to alpha and beta adrenoreceptors

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24
Q

describe the sympathetic pathway for epinephrine release?

A

preganglionic fibre (from CNS) synapses on a ganglion in the periphery
- releasing Ach onto an N2 receptor
- releasing adrenaline
- binding to alpha and beta adrenoreceptors

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25
Q

where is adrenaline released from?

A

chromaffin cells not a post ganglionic neurone

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26
Q

describe the parasympathetic pathway of neurotransmission?

A

pregandlionc fibres release Ach
- binds to N2 receptor
- postganglionic fibres release Ach
- this acts on M muscarinic receptors

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27
Q

what effect will binding of noradrenaline have on a1 receptors?

A

vasoconstriction in vascular smooth muscle

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28
Q

what are the alpha and beta receptors bound too?

A

g coupled receptors
- signalling cascade will happen inside

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29
Q

what is the intracellular action of a specific catecholamine determined by?

A

the complement of receptors expressed on the cell surface

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30
Q

what is isoprenaline?

A

synthetic B agonist

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31
Q

how does the sympathetic nervous system contribute to control in blood pressure?

A

increased blood pressure due to:
- increased signalling to vascular smooth muscle cells of blood vessels (a1)
= vasoconstriction and increased TPR

  • increased signalling to pacemaker and contractile cells in heart (B1)
    = increased HR and contraction and increased CO
  • adrenal gland secretion of adrenaline
  • renin secretion of B1 receptors
    = increased angiotensin II, vasoconstriction, increased TPR
  • angiotensin II causes increased sodium and H2O absorption
  • increased ECV
32
Q

what are specific examples of secondary hypertension?

A
33
Q

kidneys?

A
  • functional unit is nephron
  • filters blood and produces urine
  • filters around 180 L of blood/day
  • reabsorption
34
Q

describe what sodium does in the kidney/ the contribution of Na to the maintenance of BP?

A
  • Na is the predominant cation in ECF
  • movement of Na is established by osmotic gradients for H20
  • Na is filtered across the glomerulus, 99% will be reabsorbed (where Na moves, so does water)
  • the kidneys must balance Na intake and excretion
  • this maintains ECF volume and therefore long term BP
  • this is a critical target for anti-hypertensive drugs
35
Q

what is angiotensinogen?

A
  • A2 globulin
  • synthesised by the liver
  • released into circulation
36
Q

what is renin?

A
  • proteolytic enzyme
  • released by granular cells in the juxtamedullary apparatus of the kidney
  • cleaves angiotensinogen to angiotensin I
  • renin is cleared rapidly from the plasma
37
Q

angiotensin I?

A
  • has no biological activity
  • precursor for angiotensin II
38
Q

angiotensin converting enzyme (ACE) ?

A
  • found in vascular endothelium in the lungs and the renal afferent and efferent arterioles
  • converts angiotensin I to angiotensin II
39
Q

angiotensin II?

A
  • binds AT1 receptors
  • potent vasoconstrictor
  • increases TPR
40
Q

when angiotensin II binds to AT1 receptors, what effect does it have on vascular smooth muscle cells of blood vessels?

A
  • vasoconstriction
  • increased TPR
41
Q

when angiotensin II binds to AT1 receptors, what effect does it have on the hypothalamus?

A
  • increased release of vasopressin (ADH)
  • increased reabsorption of H20 in the kidneys
  • increased ECV
42
Q

when angiotensin II binds to AT1 receptors, what effect does it have on renal tubules of the kidneys?

A
  • stimulates increased secretion of aldosterone from adrenal glands
  • increased Na reabsorption in the kidney
  • increased ECV
43
Q

what are the 3 circulating factors?

A

1- endothelin
2- nitric oxide
3- reactive oxygen species

44
Q

describe endothelin?

A
  • this is the most potent vasoconstrictor
  • ## endothelin- 1(ET-1) os the predominant isoform in the cardiovascular system
45
Q

when will you not see circulating concentrations of ET-1?

A

circulating concentrations of ET-1 are NOT commonly increased in primary hypertension
- but they may have local increased levels.

46
Q

what can endothelin bind to and cause?

A
  • bind to ETa receptors on vascular smooth muscle cells and cause vasoconstriction
  • ca bind ETa receptors in cardiomyocytes and increase contractility
47
Q

what happens if endothelin binds to ETb receptor ?

A
  • bind to ETb receptors and cause production of nitric oxide causing vasodilation
  • in the kidneys this promotes Na and H20 excretion (natriuesis and diuresis respectively)
48
Q

describe nitric oxide and its effect as a circulating factor?

A
  • lipophilic gas released from endothelial cells in response to stimuli
  • most potent endogenous vasodilator
  • very short half life:
    (usually only acts in the tissue it is secreted)
  • chronic regulator of renal blood flow ind increases Na excretion
49
Q

descrive reactive oxygen species and its effect as a circulating factor?

A
  • includes superoxide, hydrogen peroxide and peroxynitrate
  • patients with essential hypertension have increased circulating hydrogen peroxide
  • ROS in the vaculatiure may uncoil the enzymes which produce NO
  • chronic treatment with antioxidants does NOT lower pressure
50
Q

the meta-analysis of large scale randomised trial showed what? (when treating systemic hypertension)

A

10/5 mmHg reduction in BP is associated with:
- 15% reduction in all cause mortality
- 35% reduction in stroke
- 40% reduction in heart failure
- 20% reduction in myocardial infection

51
Q

what are the effects of blood pressure on hypertension?

A
  • accounts for 35-50% of BP variance
52
Q

secondary hypertension?

A
  • around 5% o cases
  • identifiable underlying cause
  • often in patients <25
53
Q

renal secondary hypertension ?

A
  • renal parenchymal disease: glomerularnephritis, diabetic nephoropathy, lupus nephritis, polycystic kidney disease
  • renal vascular: renal artery stenosis, vasculitis, fibromuscular dysplasia
54
Q

endocrine secondary hypertension?

A

adrenal gland:
- zona glomerulus (Aldo)- conn’s syndrome
- zona fasiculata (cort) - cushing’s syndrome
- adrenal medulla (E/NE) - pheochromocytoma

55
Q

consequences on the heart of secondary hypertension?

A
  • heart failure:
    pressure overload from increased TPR, left ventricular hypertrophy
  • MI
56
Q

consequences on the kindeys in secondary hypertension?

A
  • continued hypertension
  • albuminuria
  • end stage renal disease
57
Q

consequences on the vasculature in secondary hypertension?

A
  • accelerated atherosclerosis (smaller arteries and arterioles)
  • stroke
  • retinopathy
58
Q

other factors causing secondary hypertension?

A

pregnancy = eclampsia, preeclampsia

coarction of aorta

drugs = contraceptive pill, cocaine, amphetamine, NSAID’s, alcohol

obstructive sleep apnoea

59
Q

(pulmonary hypertension)
What does it cause the heart to do?

When it is more common?

When is it usually diagnosed?

A
  • Pulmonary hypertension causes the right side of the heart to work harder
  • PH is More common in patients with another heart or lung condition
  • It is usually only diagnosed when severe and symptomatic
60
Q

What 4 things is SAH major risk factor for?

A
  • SAH is a major risk factor for:
    1) CV disease and heart attack
    2) Stroke/dementia
    3) Kidney failure
    4) Vision loss
61
Q

What is the diagnosis and treatment for clinic BP and ABMP and HPBM:
* Stage 1 hypertension
* Stage 2 hypertension
* Severe hypertension

A

What is the diagnosis and treatment for clinic BP and ABMP and HPBM:
* Stage 1 hypertension
* Stage 2 hypertension
* Severe hypertension

62
Q

What is the formula for blood pressure?

What is the formula for cardiac output?

What regulates BP and local tissue flow?

A
  • Blood pressure = Cardiac output x Total peripheral resistance (MABP = CO x TPR)
  • Cardiac output (CO) = Stroke volume (SV) x Heart rate (CO – SV x HR)
  • BP and local tissue flow is regulated by complex interactions of neurohormonal and local control systems
  • Additional systems that regulate blood volume in relation also regulate blood pressure
63
Q

What are the Sympathetic and Parasympathetic nervous systems?

What 3 factors can the SNS control that affect blood pressure?

A
  • The Sympathetic and Parasympathetic nervous system are two major efferent pathways controlling targets other than skeletal muscle
  • 3 factors the SNS controls that affect blood pressure:

1) Blood vessel tone (responsible for vasoconstriction – increased blood pressure)

2) Heart rate and contractility (increases both – positive chronotropic and inotropic effects – increased blood pressure)

3) Adrenal gland secretion of adrenaline (increases stroke volume and heart rate, hence increasing cardiac output (CO = SV x HR)

64
Q

What are catecholamines?

What are 3 examples of catecholamines?

What do catecholamines do?

Describe 2 ways the sympathetic nervous system connects to effectors (4 steps each)

A
  • Catecholamines are neurotransmitters in the central and peripheral nervous systems as well as hormones in the endocrine system
  • Catecholamine examples:
    1) Noradrenaline (Norepinephrine)
    2) Adrenaline (epinephrine)
    3) Isoprenaline (synthetic β-agonist)
  • Catecholamines bind adrenoceptors (adrenergic receptors) to elicit their actions
  • How the sympathetic nervous system connects to effectors:
  • Method 1:
    1) Short pre-ganglionic fibre releases acetylcholine (Ach) in sympathetic ganglion
    2) This Ach binds to nicotinic Ach receptors on the post-ganglionic neuron
    3) This long post-ganglionic neuron goes out towards effectors and releases the catecholamine Norepinephrine
    4) Norepinephrine binds to α and β adrenergic receptors on effectors, which can be smooth muscle, cardiac muscle, or glands
  • Method 2:
    1) Short pre-ganglionic fibre releases acetylcholine (Ach) towards a chromaffin cell in the adrenal gland
    2) The Ach binds to nicotinic acetylcholine receptors in the chromaffin cell (adrenal glands acts as a ganglion for syanpse)
    3) This stimulates the release of adrenaline (epinephrine) into the vessels
    4) The adrenaline can travel to effectors, where it binds to α and β adrenergic receptors on effectors
65
Q

What are catecholamines?

What are 3 examples of catecholamines?

What do catecholamines do?

What are the 4 different types of adrenoreceptor?

How do catecholamine interaction with adrenergic receptors (adrenoreceptors) differ?

How is the intracellular action of a specific catecholamine determined?

A
  • Catecholamines are neurotransmitters in the central and peripheral nervous systems as well as hormones in the endocrine system
  • Catecholamine examples:
    1) Noradrenaline (Norepinephrine)
    2) Adrenaline (epinephrine)
    3) Isoprenaline (synthetic β-agonist)
  • Catecholamines bind adrenoceptors to elicit their actions
  • The 4 different types of adrenoreceptor are:
    1) α1
    2) α2
    3) β1
    4) β2
  • Each catecholamine demonstrates different affinities to each receptor
  • Intracellular action of a specific catecholamine is determined by the complement of receptors expressed on the cell surface (GPCR)
66
Q

Describe the effects of Adrenaline, Noradrenaline, and Isoprenaline on α1 and α2 receptor tissues.

What are these 2 receptor tissues?

Which catecholamine has the highest affinity for each receptor?

What effect does affinity have on the effect of the catecholamine on the effectors?

A
  • Effects of Adrenaline, Noradrenaline, and Isoprenaline on α1 and α2 receptor tissues
  • Which catecholamine has the highest affinity for each receptor
  • The greater the affinity of a catecholamine for a receptor on an effector, the lesser the concentration of catecholamine required to achieve maximal effect on the effector
67
Q

Describe the effects of Adrenaline, Noradrenaline, and Isoprenaline on β1 and β2 receptor tissues.

What are these 3 receptor tissues?

Which catecholamine has a higher affinity for each receptor?

A
  • The effects of Adrenaline, Noradrenaline, and Isoprenaline on β1 and β2 receptor tissues.
  • Which catecholamine has the highest affinity for each receptor
68
Q

Describe the 4 pathways of sympathetic contribution to hypertension

A
  • 4 pathways of sympathetic contribution to hypertension:

1) Increased signalling to vascular smooth muscle cells of blood vessels
* Norepinephrine acts on α1 receptors
* Increases vasoconstriction, which increases TPR, which increase BP

2) Increased signalling to pacemaker and contractile cells in heart
* Norepinephrine acts on β1 receptors
* Increases HR and contractility, which increases CO, which increases BP

3) Adrenal gland secretion of adrenaline
* Feeds into the first 2 pathways and has the same effects

4) Renin release
* Renin is released from juxtaglomerular cells of the kidneys in response to the circulating catecholamines that activate β1 adrenoreceptor on the kidneys
* This triggers RAAS pathway, which generates Angiotensin 2
* Angiotensin 2 acts as an AT1 and AT2 receptor agonist

  • Roles of angiotensin 2:

1) Vasoconstriction
* Angiotensin causes vasoconstriction of renal arteries, which increases total peripheral resistance and constricts blood flow via the kidneys

2) Release of aldosterone
* Angiotensin 2 causes the release of aldosterone from the zona glomerulosa (outermost region) of the adrenal glands, which changes the volume of water excreted from the kidney by increasing Na+ and water reabsorption

3) Stimulation of release of ADH (anti-diuretic hormone / vasopressin) from the pituitary
* ADH increases blood volume by increasing water permeability in the renal collecting ducts, which decreases urine production

  • All of these roles of angiotensin 2 lead to an increase in blood pressure
69
Q

What is the nephron?

What is the function of the nephron?

What is Na+ in the blood?

What is the role of Na+ in the kidney?

What must the kidneys balance in relation to water and Na+?

Why is this done?

What is this system a target for?

A
  • The nephron is the functional unit of the kidney
  • The nephron filters blood (180L/day) and produces urine
  • Na+ is the predominant cation in the ECF (Blood compromises 36% of ECF volume – ECF is sum of plasma volume and interstitial fluid volume)
  • Movements of Na+ established osmotic gradients for H2O movement - In the kidneys, wherever the sodium moves, the water will follow
  • Na+ is freely filtered across the glomeruli of the nephron, with 99% being reabsorbed through the long tubule of the nephron back into the blood
  • The kidneys must balance Na+ and water intake with Na+ and water excretion
  • This is done to maintain blood volume that makes up ECF volume, and therefore long-term BP
  • This system is a critical target for anti-hypertensives
70
Q

The RAAS system.

Describe the pathway in which decreased arterial pressure produces angiotensin 2

What vessels and receptors does angiotensin 2 act on?

What are 3 roles of angiotensin 2?

What do all of these roles lead to?

What is the purpose of the RAAS system?

A
  • This full system is the RAAS system
  • The pathway in which decreased arterial pressure produces angiotensin 2
    1) Decreased arterial blood pressure
    2) Leads to renin (enzyme) release from the juxtaglomerular cells of the kidneys
    3) Renin substrate angiotensinogen is released from the liver
    4) Venous blood from the liver and kidneys are mixes together
    5) Renin breaks down angiotensinogen into angiotensin 1
    6) This venous blood then circulates to the heart and then the lungs
    7) Converting enzyme in the lungs converts angiotensin 1 to angiotensin 2 (active for short period of time)
    8) Angiotensin rich blood then comes around the circulation
  • Angiotensin acts on resistance vessels
  • Angiotensin 2 acts as an AT1 and AT2 receptor agonist
  • Role of angiotensin 2:

1) Vasoconstriction
* Angiotensin causes vasoconstriction of renal arteries, which increases total peripheral resistance and constricts blood flow via the kidneys

2) Release of aldosterone
* Angiotensin 2 causes the release of aldosterone from the zona glomerulosa (outermost region) of the adrenal glands, which changes the volume of water excreted from the kidney by increasing Na+ and water reabsorption

3) Stimulation of release of ADH (vasopressin) form the pituitary
* ADH increases blood volume by increasing water permeability in the renal collecting ducts, which decreases urine production

  • All of these roles of angiotensin 2 lead to an increase in blood pressure
  • The role of the RAAS system is to increase MABP
71
Q

When does low renin hypertension occur?

When can it become secondary?

Where is it more prevalent?

How is it diagnosed?

A
  • Low renin hypertension occurs in a subset of patients with hypertension
  • It becomes secondary (caused by another condition) if the cause is known e.g Conn’s syndrome – overproduction of aldosterone
  • It is more prevalent in elder individuals and those of Afro-Caribbean descent
  • Low renin hypertension is diagnosing using a plasma aldosterone: renin ratio tests, where low renin and abnormal aldosterone indicates low renin hypertension
72
Q

What is nitric oxide (NO)?

What is its half-life like?

Where does NO usually act?

What does it regulate?

A
  • Nitric oxide (NO) is lipophilic gas released from endothelial cells in response to stimuli, and acts as the most potent endogenous vasodilator
  • Has a very short half-life
  • NO usually acts in tissues where it is secreted
  • NO is a chronic regulator of renal blood flow and increases Na+ excretion
73
Q

What 3 things do reactive oxygen species (ROS) include?

How does H2O2 concentration relate to hypertension?

How is it linked with NO?

Does chronic treatment with anti-oxidants help to lower blood pressure?

A
  • Including superoxide, hydrogen peroxide (H2O2) and peroxynitrite
  • Patients with essential hypertension have increased circulating H2O2
  • ROS in the vasculature may uncouple the enzymes which produce NO
  • Chronic treatment with antioxidants does not lower pressure
74
Q

What is secondary systemic hypertension?

How many cases of hypertension does it make up?

In what age group does it typically occur in?

What are diseases/situations that cause secondary hypertension?

A
  • Secondary systemic hypertension is high blood pressure that’s caused by another medical condition
  • Makes up about 5% of systemic hypertension cases
  • Secondary hypertension typically occurs in patients <25 years old
  • Diseases/situations that cause secondary hypertension:

1) Renal system diseases

*Renal parenchymal disease:
* Glomerular nephritis,
* Diabetic nephropathy,
* Lupus nephritis,
* Polycystic
* Kidney disease

  • Renal vascular:
  • Renal artery stenosis
  • Vasculitis
  • Fibromuscular dysplasia

2) Endocrine system diseases:
* Adrenal gland:
* Zona glomerulosa (increase aldosterone) – Conn’s syndrome
* Zona fasciculata (increased cortisol) – Cushing’s syndrome
* Adrenal medulla (too much epinephrine/norepinephrine) – Pheochromocytoma

3) Pregnancy - Eclampsia, pre-eclampsia (high blood pressures during/after labour)

4) Coarctation of aorta (narrowing)

5) Drugs - Contraceptive pill, cocaine, amphetamine, NSAIDs, alcohol

6) Obstructive sleep apnoea

75
Q

What are 3 consequences on the heart from systemic hypertension?

What are 4 consequences of the vasculature?

What are 3 consequences of the kidneys?

A
  • Consequences of systemic hypertension:

1) Heart
* Heart failure
* Pressure overload from increased TPR, left ventricular hypertrophy
* Myocardial infarction

2) Vasculature
* Accelerated atherosclerosis
* Smaller arteries and arterioles
* Stroke
* Retinopathy

3) Kidneys
* Continued hypertension
* Albuminuria – too much albumin in urine (sign of kidney disease)
* End stage renal disease

76
Q

Consequences of mild, moderate, and severe hypertension on the heart and blood vessels

A

Consequences of mild, moderate, and severe hypertension on the heart and blood vessels