Hypertension - includes two AC1 lectures and presentation Flashcards
1
Q
Define hypertension
Define essential hypertension
What are the three stages and parameters associated with them?
A
Hypertension = persistently raised arterial BP.
Essential hypertension defined as blood pressure ≥140/90 mmHg with no secondary cause identified
Three stages:
Stage 1 - clinic BP ≥140/90 or ABP≥135/85
Stage 2- clinic BP ≥160/100 or ABP≥150/95
Stage 3 - clinic BP systolic BP≥180 or diastolic >110
2
Q
What are the different classifications of hypertension?
A
- Essential or primary hypertension
- no clearly identifiable secondary cause
- secondary hypertension
- HBP caused by another condition
- pseudo- resistant
- HBP that seems to resist treatment when other factors e.g. medication/diet are raising BP and making treatment difficult
- resistant or refractory
- HBP that does not respond well to aggressive medical tx - when individaul is taking 3 different blood pressure medications at maximal doses
- isolated systolic hypertension
- when diastolic BP is less than 80 mmHg but systolic BP is 130 mmHg or higher - common in over 65s
- in pregnancy
- chronic prior to pregnancy or diagnosed within 1st 20 weeks
- gestational HTN - diagnosed 2nd trimester
- pre-eclampsia - new HTN with multiorgan involvement
- paediatric
- made when repeated BP measurements greater than 95th percentile
3
Q
What are the complications of HTN?
How is BP distributed and what happens with increasing BP?
what is the prevalence of HTN in the population?
A
- HTN is a major cause of premature vascular disease - leads to cerebrovascular events, ischaemic heart disease and peripheral vascular disease
- BP is normally distributed in the population and mortality rises with increasing BP
- prevalence of HTN is 30-45% of population
4
Q
How does blood pressure vary throughout the day?
A
- Blood pressure is normally lower at night and whilst sleeping
- Blood pressure starts to rise a few hours before you wake up
- It continues to rise throughout the day, peaking in middle afternoon.
5
Q
What is labile HTN?
What is non dipping HTN?
A
Labile hypertension - observed clinical phenomenon characterised by recurrent, sudden and transient rises in BP. Different to physiological rises in BP with time of day/stress/caffiene etc.
Non dipping HTN - describes prolonged hypertension that continues throughout the night - lack of nocturnal dip. Greater risk of CV problems.
6
Q
What are the causes of secondary hypertension?
A
- Primary hyperaldosternism = Conn’s syndrome
- adrenal adenoma
- adrenal bilateral hyperplasia
- Renovascular disease
- fibromuscular dysplasia
- atherosclerotic
- Obstructive sleep apnoea
- chronic kidney disease
- phaeochromocytoma
- aortic coarctation
- cushing’s disease
- hyperparathyroidism
7
Q
Pathophysiology: primary hyperaldosteronism (Conn’s syndrome)
A
- Conns syndrome - cause of 1-5% of secondary hypertension, most common cause of secondary HTN!
- 50% caused by adrenal adenoma, 50% bilateral hyperplasia
- Excessive production of aldosterone by adrenal glands –> results in Na and H2O retention and K+ excretion
- Therefore elevated BP and Hypokalaemia
8
Q
Pathophysiology: Renovascular disease - how does it cause 2ndary HTN?
A
- Any condition that compromises blood flow to kidneys can cause renovascular HTN
- Renovascular hypertension = HBP caused by the kidney’s hormonal response to the narrowing of the renal arteries
- Causes:
- Renal artery stenosis (most common) caused by either fibromuscular dysplasia or atherosclerotic processes.
- extrinsic compression
- renal artery dissection/ infarction
- inflammation - antiphospholipid antibody, takayasu’s arteritis (aortic arch syndrome - large vessel granulomatous vasculitis with intimal fibrosis)
-
Pathophysiology:
- decreased perfusion of kidney, decreased GFR - detected by renal baroreceptors in the afferent arteriole
- Renin secretion stimulated by:
- loss of inhibition on JGA from secreting renin
- low Na+ detected by macula densa
- increase in B adrenergic stimulation
- Activation of RAAS cascade –> Renin converts angiotensinogen (liver) –> converted to AT1, AT1 converted to AT2 by ACE in vascular endothelium of the lungs, AT2:
- arteriolar vascoconstriction
- SNS stimulation –> more renin release and NA action
- secretion aldosterone by adrenal cortex –> Na and H20 retention
- increase thirst response and ADH secretion from posterior lobe pituitary gland –> increase H20 uptake
9
Q
What is fibromuscular dysplasia?
Who does it more commonly affect?
A
- Fibromuscular dysplasia = non atherosclerotic, non inflammatory disease of blood vessels
- causes abnormal growth in wall of an artery - most common arteries affected are renal and carotid arteries
- On angriogram has a “string of beads” look with thickened arterial walls
- Affects younger patients (25-50 yrs) , more common in females, can have a family hx.
10
Q
Main causes of renal artery stenosis?
Who is at risk with the most common cause?
A
- RAS - caused by atherosclerosis (90%) or FMD (10%)
- At risk for atherosclerotic RAS if you have CV risk factors:
- High cholesterol/ BP
- insulin resistance/ diabetes
- overweight/obese - diet high in fat/cholesterol/sodium/sugar
- age
- physical inactivity
- renal artery stenosis occurs in 50% of patients with clinical vascular disease, early risk of vascular death
11
Q
Pathophysiology: Obstructive sleep apnoea
A
- Repeated and intermittent upper airway collapse during sleep - complete= 10 sec pause in breathing, patial = 10 secs and 50% reduction in ventilation
- irregular breathing at night and excessive sleepiness in day —> leads to increased Sympathetic response/activation –> inflammation due to intermittent hypoxia and oxidative stress –> HTN
- patients with obstructive sleep apnea often obese –> increased risk HTN/MI/stroke
12
Q
Pathophysiology: Chronic kidney disease
A
- CKD –> decreased GFR stimulates kidneys to upregulate production of renin and raise BP and renal perfusion
- Fluid overload also contributes –> kidneys fail to excrete volumes required for homeostasis
- Both upregulation of RAAS and fluid overload –> HTN
13
Q
Pathophysiology: Phaeochromocytoma
A
- Tumour arising from catecholamine producing chromaffin cells in adrenal medulla
- Majority of tumours are benign - 10% are malignant
- 90% in adrenal gland, remainder are (10%)extra adrenal in origin - commonly found in head and neck in paraganglion chromaffin tissue.
- 10% bilateral, 10% familial - MEN2a (multiple endocrine neoplasia type 2)
- Phaeochromocytomas synthesise and secrete catecholamines - Adrenaline, NA, & rarely dopamine.
- NA –> Acts via A1/A2 and B1 receptors. Via A1 - vasconstriction, plus positive inotropic effects on cardiomyocytes. B1 stimulation has positive initropic effect and chronotropic effect. PLUS B1 stimlation –> release of renin
- Adrenaline –> stimulates B1 and B2 receptors –> Positive inotropy and chronotropy in heart, B2 increase NA release from sympathetic ganglia.
- Overall increase in CO and vasoconstriction –> HTN
14
Q
Most common symptoms of phaeochromocytoma?
A
Sweats
Headaches
plus/ minus palpitations
paroxysmal HTN
cardiomyopathy
15
Q
Pathophysiology: Aortic coarctation
A
- Coarctation of the aorta –> narrowing of the aorta, often distal to ligamentum arteriosum (coarctation can occur before). This narrowing is often after teh left subclavian artery which leads to increased blood pressure in the arms but decreased blood pressure after this.
- usually hypertension in the upper limbs but weak or absent pulses in the lower limbs
- Decreased renal perfusion due to narrowing which leads to RAAS activation –> HTN
16
Q
Pathophysiology: Cushing’s disease
A
- Excessive production of cortisol by a pituitary or adrenal tumour, or the use of exogenous corticosteroids.
- Enhancement of the HPA - remember Hypothalamus releases CRH –> travels via hypophyseal portal system to anterior pituitary –> ACTH released into bloodstream –> acts on adrenal glands which produce cortisol
Mechanism of HTN:
- cortisol enhances the vasocontrictor effect of catecholamines
- increased action on MR receptor due to excess –> increased renal tubular sodium reabsroption, hypokaleamia, intravascular volume expansion and HTN
- activation of RAAS - cortisol upregulates angiotensin ii receptors
- cortisol enhances the vasocontrictor effect of catecholamines
17
Q
Pathophysiology -
Hyperthyroidism
Hyperparathyroidism
A
Hyperthyroidism - excess thyroxine exacerbates SNS effect –> increasd vascular resistance and CO
Hyperparathyroidism - HTN often noted, mechanism unclear.
18
Q
What could cause pseudoresistant HTN?
A
- White coat HTN
- inaccurate measurement
- poor adherence to treatment
19
Q
Define resistant HTN?
A
- Defined when a patient’s BP is not controlled to recommended BP goals - i.e <140/90 mmHg despite tx with appropriate combination of three drug therapies - A+C+D prescribed at maximum recommended/tolerated doses
- Most resistant HTN is due to systolic HTN
20
Q
What are the common characteristics of patients with resistant HTN?
A
- Older age (>75yrs)
- high basline BP
- chronic uncontrolled HTN
- target organ damage - LVH and/or CKD
- diabetes
- obesity
- atherosclerotic vascular disease
- aortic stiffening
- women
- black african origin
- excessive dietary sodium and alcohol consumption
- drugs
21
Q
What drugs are known to raise BP?
A
- NSAIDS
- estrogen and analogues - COCP and HRT
- methylxanthines
- cyclosporine
- erythropeitin
- cocaine
- nicotine
- phencylidine (angel dust)
- withdrawal - bb, alpha antagonise, opiods, alcohol, calcium antagonists
27
Q
Investigations for HTN:
Bloods?
A
Bloods:
- Hb - anaemia of CKD and polycythaemia may be seen with phaeochromocytoma
- TSH - indicated if signs/sx Hyper or hypo thyroidism
- Fasting metabolic panel with estimated GFR:
- U&E’s - renal function, hypokalemia in Conn’s syndrome (primary hyperaldosteronism) and Cushing’s syndrome (cortisol)
- Note: request calcium - may be raised in hyperparathyroidism
- Liver - LFT’s - baseline and alcohol excess
- Kidney- creatinine and BUN (Blood urea nitrogen), eGFR
- U&E’s - renal function, hypokalemia in Conn’s syndrome (primary hyperaldosteronism) and Cushing’s syndrome (cortisol)
- Fasting Lipid panel - risk of HTN increased if metabolic syndrome - may show elevated LDL/HDL/triglycerides
- Blood glucose - DM
- Aldosterone - Conn’s syndrome and RAAS
- Renin - Conn’s syndrome and RAS, renin often raised in renal artery stenosis
- NOTE: Adrenal vein sampling to compare ratio of renin to aldosterone in each kidney
- Serum Growth hormone/ OGTT —> acromegaly (pituitary produces too much GH)- another cause of HTN. OGTT- if GH remains raised after oral glucose load= diagnostic.
32
Q
What are the therapeutic targets for BP?
A
- Main goal = reduce risk of mortality and cardiovascular/renal morbidity
- 18-59 yrs - Goal = BP < 140/90 mmHg (including those w DM/CKD)
- > 60 yrs - Goal = < 150/90 mmHg
- Not sure where above is from maybe the lecture - NICE guidelines are for over 80 or under 80 yrs
33
Q
Management: therapy for stage 1 HTN?
A
- Stage 1 HTN = clinic BP 140/90 or ABPM 135/85 mmHg
- discuss lifestyle modifications, calculate Qrisk2 score
- Antihypertensive drug treatment in all under 80 with target organ damage/established CVD/renal disease/ Diabetes, estimated CVD risk 10% or more
- Consider antihypertensive tx in under 60 yrs w lower CVD (below 10%)
- STEP1: under 55 yrs –> ACEi
- STEP1: > 55 yrs or black african-african carribean –> offer CCB
34
Q
Management: Stage 2 HTN?
parameters?
Drug therapy?
A
- Stage 2 HTN : 150/95 ABPM or clinic BP 160/100 mmHg
- If HTN not controlled with step 1 - already on ACEi or ARB offer:
- A CCB
- or thiazide diuretic
- If > 55 yrs of black-african or african carribean origin - already on CCB, offer:
- ACEi or ARB or Thiazide diuretic
36
Q
How do we confirm resistant HTN?
How is it managed?
A
- When HTN is still uncontrolled despite taking optimal tolerated doses of all antihypertensive drugs
- confirm resistant with ABPM
- Ax for postural HTN
- Discuss adherence to tx
- Consider adding 4th drug:
- For people with blood potassium level of 4.5 mmol/L or less (less risk of hyperkalaemia) add low dose spironolactone
- monitor blood sodium/potassium/renal function
- blood potassium level greater than 4.5 mmol/L consider alpha blocker or beta blocker
37
Q
Name the thiazide diuretics
MOA
What do they prevent?
What are their adverse effects?
A
- Bendroflumethiazide
- Hydrochlorothiazide
- Indapamide
- Chlortalidone
MOA:
- act at distal convoluted tubule
- inhibit Na/Cl transport from lumen
- increase sodium and water excretion
- increase potassium loss
Prevention of heart attack and stroke: vasodilate by potassium channel activation
Adverse effects:
- high uric acid and gout
- low potassium and sodium
- raise glucose and cholesterol
39
Q
What is the difference between B1 and B2 adrenoreceptors?
A
- Beta 1 –> positive inotropic, chronotropic and conduction velocity effects on cardiomyocytes
- Beta 2 –> mainly found on smooth muscle –> induces SMC relaxation in GI/Vascular/Bronchial/Cililary
41
Q
What is the normal role of calcium channels?
What effect do CCB’S have? (MOA)
A
- Normally calcium channels are found on:
- VSM
- Cardiac myocytes and SAN/AVN
- renal tubules
- regulate influx of calcium into cells
- stimulate smooth muscle and cardiac myocyte contraction
- contribute to pacemaker currents and AP’s
- Therefore calcium channel blockers cause:
- VSM relaxation
- Decreased myocardial force generation
- Decreased heart rate
- natriuresis and diuresis
42
Q
What are the three types of CCB’s?
A
- Verapamil - mostly works on cardiac muscle, slows the AV node and the HR, decreases contractility. Inducses coronary vasodilation same as all others, does reduce SVR. Useful for atrial flutter due to slowing Ca entry in phases 2/3 of cardiac AP.
- Diltiazem - Benzothiazepine
- affects cardiac SM, causing coronary vasodilation, small reduction in SVR (peripheral vasodilatation), slows AV node/HR and SV. Antiarrythmic, may also be used in angina and HTN.
- Dihydropyridines - Nifedipine, Amlodipine –> mostly used to lower SVR (+++) and decrease cardiac workload. Drop in BP can cause a compensatory HR rise.
46
Q
Main role of RAAS?
When is it activated?
Which drugs can be used to Block RAAS activation?
A
- Main role - reduce sodium and water loss, maintain/ increase BP,
- Activated in heart failure and septicaemia/severe blood loss, implicated in HTN
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