3. Hemodynamic determinants of
blood pressure (BP)
Arterial BP is the product of cardiac output (CO)
and systemic vascular resistance (SVR).
BP = CO x SVR
(analogous to Ohm law)
Malignant hypertension
is caused by
Increased SVR.
4. Hypertensive crisis
Hypertensive crisis is the turning point in the
course of hypertension in which immediate
management of the elevated BP has a decisive
role in the eventual outcome.
It is a condition of severe and uncontrolled
increase in the BP.
An acute increase in BP can occur
in the absence or presence of acute
or chronic target organ
dysfunction.
5. Target organs affected by
hypertensive crisis
Four organs are the usual target of severely
elevated BP:
Kidneys: acute kidney injury caused by proliferative
endarteritis and fibrinoid necrosis of afferent artery
Brain: hypertensive encephalopathy,
cerebrovascular accidents (CVA)
Eye or retina: retinal hemorrhage or exudates or
papilledema .
Heart: acute coronary syndrome, decompensated
heart failure, aortic dissection, and acute
intravascular hemolysis .
6. Malignant hypertension and
accelerated hypertension
Both are syndromes in which a markedly
elevated BP is associated with hypertensive
neuro retinopathy.
In accelerated hypertension, there may be
Flame hemorrhages or cotton wool
exudates.
Malignant hypertension
Is diagnosed when papilledema occurs
as well.
7. Hypertensive urgency (HU) OR
Non-emergent hypertension (NEH)
When severe hypertension occurs in the
absence of any acute end-organ damage, it is
classified as HU-NEH.
Because the complications from HU are not
immediate, this condition can be treated safely
outside the intensive care unit and hospital with
gentle reduction in BP achieved
over hours to days.
8. Hypertensive encephalopathy
Hypertensive encephalopathy occurs in the
setting of sudden and sustained elevation in
BP.
It occurs in both benign and malignant
hypertension.
The clinical presentation is that of altered
mental status and/or seizures, but focal
neurologic findings are uncommon.
This condition can be difficult to distingui-
sh from a primary neurologic event.
9. Causes of
malignant and accelerated
hypertension
In contrast to ambulatory hypertension (over
90% essential) as many as 50% of patients
with malignant or accelerated hypertension
have secondary causes.
The most important of secondary causes are
medications, chronic kidney disease, and
renal artery stenosis (RAS).
10. The short-term treatment of
hypertension and hypertensive
emergency
The short-term treatment of choice is intravenous
(IV) sodium nitroprusside.
The initial dose is 0.5 mcg/kg/min, and this should
be increased by 0.5 mcg/kg/min every 2 to 3 minutes
until a diastolic BP < I10 mm Hg has been attained.
Further acute decreases in BP should be avoided to
prevent hypoperfusion to vital organ(s) because
Blood flow autoregulation may have been altered
to accommodate chronically elevated BP.
11. Acceptable alternative parenteral drugs for the
short-term treatment of malignant hypertension
include
Labetalol, Nicardipine,Enalaprilat,
or Fenoldopam.
Extreme caution should be taken while using
agents known to cause
or further worsen intravascular volume status
because patients with hypertensive emergency
often present with
Intravascular volume depletion.
12. Outline the typical long-term
antihypertensive regimen after
successful
treatment of malignant
hypertension or hypertensive
crisis.
Because malignant hypertension is mediated by
increased SVR, it is recommended that longterm
therapy include a vasodilator such as
Hydralazine or minoxidil.
13. Vasodilators cause reflex tachycardia and
sodium retention
Therefore it is usually also necessary to
Include a-
p-blocker (labetalol) and a diuretic
agent.
In some cases, long-term BP reduction may be
achieved with less potent vasodilators, such as
Angiotensin-converting enzyme (ACE)
inhibitors or calcium channel blockers.
14. The appropriate short-term treatment
for hypertension in a patient with
pheochromocytoma
Hypertension from pheochromocytomas is
caused by
Vascular smooth muscle a-receptor
activation, which results in
vasoconstriction.
15. Thus the best short-term treatment is IV
administration of the
a1-blocker phentolamine.
Sodium nitroprusside
is also a reasonable choice.
B-Blockers should initially be
avoided because they cause both
unopposed peripheral
a-receptor stimulation and
decreased CO.
16. Describe the short-term treatment of
cocaine-induced hypertensive crisis.
Cocaine-induced hypertensive crisis
falls under
“Catecholamine-associated
hypertension."
Cocaine causes hypertension by inhibiting
catecholamine reuptake at nerve terminals.
Therefore drugs that can block a-receptors
such as labetalol or phentolamine are effective.
17. Selective p-blockers without a1
blockade such as propranolol are not
recommended because of the risk of
unopposed a1 action.
If hypertension is severe, sodium nitroprusside
is the drug of choice.
In the setting of cocaine-related myocardial
ischemia, nitroglycerin and benzodiazepines are
effective against both cocaine-induced hypertension
and vasoconstriction of the coronary arteries.
18. Coca-ethylene :
Is a compound formed in vivo
when cocaine and ethyl alcohol
(EtOH) have been ingested
simultaneously. It produces greater
increases in heart rate, rate-
pressure product, and euphoria
compared with the effects of cocaine
alone.
19. Coca-ethylene :
Therefore the treatment of hypertension tends
to pose greater therapeutic challenge in
patients consuming EtOH as well as cocaine.
Cocaine-induced hypertension
should be treated with extreme caution and
treatment regimens reviewed
with passage of time because the condition
undergoes
Spontaneous resolution when cocaine
is metabolized.
20. How is hypertension treated in the
short term in patients with aortic
dissection?
Aortic dissection begins with a tear in the intima of
the aorta; this is propagated by the aortic pulse
wave (dp/dt).
Myocardial contractility, heart rate,
and BP contribute to
the aortic pulse wave.
The goal of treatment is to decrease
myocardial contractility and heart
rate.
21. This goal has traditionally
been best achieved with
Sodium nitroprusside and
esmolol.
Labetalol alone
is also effective in this
setting.
22. Why is BP elevated in patients
with CVA?
Patients with CVA often have a severe
increase in BP potentially resulting from a
central mechanism and/or
compensatory increase
in response to
Increased intracranial pressure.
23. Stress responses to hospitalization,
headache, urinary retention, or
concomitant infection may lead to
abnormal autonomic activity and
raised levels of circulating
catecholamines.
Greater than 60% .of patients with
CVA will have
An acute hypertensive response.
24. Central mechanism
The primary cause is damage or compression of
specific regions in the brain that mediate autonomic
control.
Increased sympatho-adrenal tone and
subsequent release of renin
Each in isolation or together, can also contribute to
high BPS.
Failure of autoregulation of cerebral blood flow and
response to increased intracranial pressure (ICP)
With acute brain injury
The ability of the brain to autoregulate and
maintain cerebral blood flow is impaired.
25. Autoregulation
Is a mechanism by which the brain can maintain
a constant cerebral blood flow despite a wide
fluctuation in cerebral perfusion pressure (CPP)
(from the range of 60-180 mm Hg).
Cerebral blood flow = CPP/Cerebral vascular
resistance
CPP is the difference between mean arterial
pressure (MAP) and ICP.
26. Under physiologic circumstances cerebral
venous pressure
(backflow in the cerebral venous system)
is the primary determinant of ICP.
In absence of any pathologic condition,
Cerebral venous pressure is zero;
thus the arterial pressure
determines CPP.
When the ICP goes up because of increase
in cerebral venous pressure (as in CVA),
MAP goes up in an attempt to maintain
adequate CPP.
27. How should hypertension be treated
in patients with CVA?
Hypertensive encephalopathy
The goal is gradual and careful reversal of
vasogenic subcortical edema.
MAP should be cautiously reduced by no more
than 15% over a 2- to 3-hour period.
Severe neurologic complications
have occurred
with MAP reductions at 40% or more.
28. Thromboembolic cerebrovascular
disease
The goal is salvation of
ischemic penumbra
For patients thought to be candidates for
reperfusion therapy
{ Thrombolytic therapy }, systolic BP (SBP)
>I85 mm Hg and diastolic BP (DBP) >I10 mm
Hg warrant treatment.
29. For the subset of patients who are
not candidates for reperfusion
therapy, the
expert opinion is to treat SBP >220
mm Hg and DBP >I20 mm Hg
with a goal of 15% to 25% reduction
in MAP over the first 24 hours.
30. Subarachnoid hemorrhage
Poorly controlled BP increases the risk of
rebleeding.
The presence of blood in the subarachnoid
space induces intense vasospasm and
increases the risk of severe ischemia 4 to 12
days after the first bleeding.
The goal is 20% to 25% reduction in BP over a
6- to 12-hour period but not less than 160 to
180/100 mm Hg.
31. Intracerebral hemorrhage
The consensus guidelines on treatment of
intracerebral bleeding:
IV medications should be used to treat SBP > 200
mm Hg or MAP >I50 mm Hg with BP monitoring
done every 5 minutes.
In suspected intracranial hypertension, BP should
be lowered with a parenteral agent if SBP is >I80
mm Hg or MAP >I30 mm Hg while maintaining
CPP above 60 to 80 mm Hg.
32. In the absence of elevated ICP, treat SBP
>I80 mm Hg and MAP > 130 mm Hg with a
target BP of 160/90 mm Hg or a MAP of 110
mm Hg.
The rate of BP reduction should be slowed if
the patient's neurologic status deteriorates.
Oral therapy should be instituted before
parenteral treatment is discontinued.
Clonidine or a-methyldopa
Should be avoided because of the risk of
impaired cerebral function.
33. Describe the short-term treatment of
hypertension in patients with ischemic
heart disease and ongoing angina.
Hypertension can precipitate ischemic chest pain in
patients with severe coronary artery disease.
Alternatively, hypertension can result from chest
pain, which results in marked increases in
catecholamines and secondary reactive
hypertension.
In either setting, hypertension is associated with
an increase in SVR and increases in myocardial
oxygen demand.
34. Describe the short-term
treatment of hypertension in
patients with ischemic heart
disease and ongoing angina.
Hypertension can precipitate ischemic
chest pain in patients with severe
coronary artery disease.
35. Alternatively, hypertension can result
from chest pain, which results in marked
increases in catecholamines and
secondary reactive hypertension.
In either setting, hypertension is
associated with an increase in SVR
and increases in myocardial oxygen
demand.
36. Nitroglycerin and p-blockers
Are the initial agents of choice.
Because nitroprusside
increases heart rate and
myocardial oxygen demand in
this setting
It is considered a secondary
agent.
38. How should hypertension
associated with preeclampsia be
treated?
The traditional treatments of choice are
Hydralazine or a-methyldopa.
If these drugs are ineffective or poorly tolerated,
labetalol
Is a reasonably safe and effective alternative.
39. Medications to be avoided because
of potential teratogenesis
Include
Sodium nitroprusside,
trimethaphan, diazoxide, ACE
inhibitors, p-blockers, and calcium
channel blockers.
Unfortunately, the safety profile of many
antihypertensive drugs during pregnancy is
unknown.
40. Because
Preeclampsia and eclampsia
may be life threatening, sometimes it may
be necessary to prescribe potent
antihypertensive agents
(Sodium nitroprusside or Minoxidil)
with unclear fetal toxicity potential.
41. Causes of RAS
{ Renal artery stenosis }
And how should it be evaluated?
The major causes are fibromuscular dysplasia
(especially in young women) and atherosclerosis (in
those aged >55 years in association with polycystic
kidney disease).
Although Doppler ultrasonography of the renal
vasculature is an excellent noninvasive test to confirm
RAS, it has not been standardized, and magnetic
resonance angiography is recommended.
42. Reactive hypertension
Patients with stage 1 or 2 hypertension that is poorly
controlled with medications can have marked
elevation in BP to stressors such as pain or shortness
of breath.
Increases in catecholamines of stress lead to
severe elevations in BP that should be distinguished
from primary hypertension
because the approaches to therapy differ.
In reactive hypertension it is necessary to treat
the cause of BP, for example, chest pain or
pancreatitis, rather than the elevated BP.
43. Why does lowering of BP potentially result
in a decline in glomerular filtration rate
(GFR) in severe hypertension?
Normally, GFR is maintained despite decreases in
BP by compensatory increases
In efferent arteriolar tone
Two major causes exist of loss of GFR after
reduction of BP in the setting of severe
hypertension:
RAS{ Renal artery stenosis }
Long-standing essential hypertension
44. RAS{ Renal artery stenosis }
In a patient with a fixed
atherosclerotic lesion of the main
renal artery, a drop in BP can cause a
fall in GFR because the fixed lesion
limits afferent arteriolar flow to such
an extent that even maximal
elevation in efferent arteriolar tone
cannot compensate and maintain
GFR.
45. Long-standing essential
hypertension
In this setting, no macrovascular abnormalities
are present; the problem is
Marked sclerosis of the microvasculature of
the kidney, including the afferent artery.
Because of afferent arteriolar sclerosis, the
afferent artery is unable
to vasodilate in response to a drop in BP.
Hence, GFR falls when BP is lowered even with
increases in efferent arteriolar tone that normally
would offset, at least partially, decreases in BP.
47. At initial presentation of malignant
hypertension
(especially if the patient is white,
younger than 30 years, or older
than 50 years of age)
When rapid onset of severe
hypertension occurs within less
than 5 years
48. When an increase in serum
creatinine level occurs after the
initiation of ACE inhibitor treatment
In compliant patients whose BP is
difficult to control after an adequate
trial with a combinationof
Diuretic, p-blocker, and potent
vasodilator
49. Important causes of secondary
hypertension
Secondary hypertension accounts for 5%
of cases of hypertension.
Renal:
Renovascular disease, renal
parenchymal disease, polycystic kidney
disease, Liddle syndrome, syndrome of
apparent mineralocorticoid excess,
hypercalcemia
52. Causes of primary aldosteronism,
and how should they be
distinguished?
The major causes are unilateral aldosterone-
producing adenoma (APA)
And bilateral idiopathic adrenal hyperplasia
(IAH).
Primary aldosteronism should be suspected in a patient with
hypokalemia and hypertension with metabolic alkalosis.
53. Primary aldosteronism should be
suspected in a patient with hypokalemia
and hypertension with metabolic
alkalosis.
It is necessary to first demonstrate renal
potassium wasting (high urine K+ in
association with low serum K+) followed by
a decrease in renin and an elevated
aldosterone level.
The plasma aldosterone/renin ratio (>40)
is often used.
54. The plasma aldosterone/renin ratio
(>40) is often used.
If the ratio is elevated, the aldosterone
response to either NaCl infusion or
fludrocortisone is used and considered
positive if the plasma aldosterone level
remains elevated (> 10 pg/mL).
55. Treatment of APA { aldosterone-producing
adenoma } is surgical adrenalectomy,
whereas mainstays of treatment of IAH {
idiopathic adrenal hyperplasia } are mainly
medical.
Adrenal imaging can sometimes distinguish
between APA and IAH, but it is often
necessary to pursue a more definitive study
to verify the diagnosis of APA.
56. By far, selective adrenal vein
sampling is the most validated
technique used to differentiate
APA from IAH.
