HTN - Pathophys

Define HTN

Persistently elevated arterial BP

(usually asymptomatic)

How is HTN diagnosed?

An elevated value from the average of 2 or more measurements, present during 2 or more clinical encounters

What is the most significant risk factor for CVD?

HTN

Prevalence of HTN in Canada

1 in 4 Canadians aged 18 or older

Does HTN typically occur earlier in life in men or women?

Men (but overall incidence is similar)

What is “essential” HTN? (AKA primary HTN)

When we do not know the cause of the HTN (this type cann only be controlled, not cured)

Which type of HTN can potentially be “cured”?

Secondary HTN

What genetic defects can contribute to HTN?

Defects related to:

• sodium imbalance

• nitric oxide release

• aldosterone excretion

• angiotensin physiology

(+ others)

Since we can’t identify the genetic defect to guide our therapy, what can be used to guide our choice of therapy?

Population studies

• (e.g., stroke is the most important complication among black patients; CHD is more prevalent among Europeans and Americans)

Why are ACEi not recommended as first line therapy for black patients (according to Canadian guidelines)?

Renin is thought to be less active in black patients, so ACEi are believed to be less effective (although mixed results in systematic review)

What % of HTN cases are considered to be 2° HTN?

~10% (either disease or drug or combination cause elevation in BP)

What common OTC medication can lead to secondary HTN?

NSAIDs (always need to ask about their use)

Drugs/substances that can lead to 2° HTN

• NSAIDs

• OCPs

• Corticosteroids

• licorice root

• SSRIs and SNRIs

• cocaine (and other stimulants)

• alcohol

• sodium

• St. John’s wart

(and others)

Withdrawal from which drugs can lead to 2° HTN?

• beta blockers

• centrally acting alpha agonists (clonidine, methyldopa)

• cocaine

• nicotine

What is systolic BP?

Pressure when the heart is contracting

What is diastolic BP?

Pressure when the heart is relaxed

How is MAP calculated?

MAP = (1/3 SBP) + (2/3 DBP)

(since heart spends only 1/3 of the time in systole)

When is MAP used clinically?

During hypertensive emergency

What is pulse pressure?

Difference between SBP and DBP (measure of arterial wall TENSION)

When is pulse pressure used clinically?

For isolated HTN (when only systolic is elevated)

How is BP calculated?

BP = CO x TPR

__ is mainly determined by cardiac output

Systolic BP

__ is mainly determined by total peripheral resistance (TPR)

Diastolic BP

What is cardiac output a function of?

• Stroke volume

• HR

What is stroke volume?

Amount of blood that is pushed out after systole

What is TPR determined by?

• functional vascular constriction

• structural vascular hypertrophy

What can lead to increased cardiac output?

• increased fluid volume (excess sodium intake or reabsorption by kidneys)

• venous constriction due to excess RAAS or SNS activity (means more coming back to the heart)

How does BP change with circadian rhythm?

• lowest while sleeping

• rises sharply a few hours before waking

• highest in midmorning

How is BP classified?

What is believed to be the cause of isolated systolic HTN?

Changes in the arterial vasculature consistent with aging

Why does isolated systolic HTN indicate increased risk of CV morbidity and mortality?

• higher pulse pressure = increased arterial stiffness

• higher pulse pressure directly correlated with risk of CV mortality in those with isolated systolic HTN

Malfunctions in which mechanisms can lead to essential HTN?

• humoral mechanism

  • RAAS

  • Natriuretic hormone

  • Insulin resistance

• neuronal mechanisms

• peripheral autoregulation

• vascular endothelial mechanisms

• disturbances in electrolytes (Na, Ca, K)

What is the most important regulator of BP?

RAAS

Where is renin stored?

In juxtaglomerular cells in afferent arterioles of the kidney

What do juxtaglomerular cells do?

They are baroreceptors

How is renin release regulated?

Intra-renal factors:

• renal perfusion pressure

• level of catecholamines

• angiotensin II levels

Extra-renal factors:

• levels of Na, Cl, and K (affect macula densa)

What are the different angiotensin II receptors?

1. AT-1 (brain, kidney, myocardium, peripheral vasculature, adrenal glands)

2. AT-2 (adrenal medullary tissue, uterus, brain)

What is the target of natriuretic hormone?

Na/K-ATPase

Effects of natriuretic hormone

• reduce Na and water in the system (decreases BP)

• but also interfere with sodium transport out of arteriolar smooth muscle cells, which leads to increased intracellular sodium and calcium which increases vascular tone (increases BP)

How does insulin resistance lead to HTN?

• increased insulin = increased renal sodium retention and sympathomimetic effects

• has growth-hormone effects = hypertrophy of vascular walls = increased TPR

How does the baroreceptor reflex work?

• baroreceptors are nerve endings in the walls of large arteries (like carotids and aortic arch)

• stimulated by changes in BP and send signals to brain stem to maintain homeostasis

What effect does decreased BP have on the baroreceptor reflex?

Causes reflex vasoconstriction and increased HR

What effect does increased BP have on the baroreceptor reflex?

Causes reflex vasodilation and decreased HR

In what age group is the baroreceptor reflex less effective?

Elderly

What is caused by a defect in any part of the baroreceptor reflex?

HTN

How do the kidneys sense changes in BP?

Sense oxygen level in local arterial bed

(low oxygen = low BP)

What is secreted in vasculature to cause vasodilation?

• NO

• Prostacyclin

• Bradykinin

What is secreted in vasculature to cause vasoconstriction?

• Angiotensin II

• Endothelin I

Why could calcium supplementation theoretically decrease BP?

• When dietary Ca is decreased, intracellular Ca increases (cells try to hold on to Ca)

• This increases BP by increasing peripheral vascular resistance

Increasing potassium intake ___ sodium levels

Decreases (increases the excretion of sodium)

Starting at 115/75, risk of CVD increases with every ____ mmHg increase

20/10

What are the major predictors of CHD in patients 60+?

SBP and pulse pressure

What is the major predictor of CHD in patients <50 yrs?

Diastolic blood pressure

What seems to be the most important clinical BP parameter for most patients?

Systolic BP

CV risk factors

• age

  • 55 or older for men

  • 65 or older for women

• DM

• Dyslipidemia

• Albuminuria

• Family hx of premature CV

  • <55 yrs in dad

  • <65 yrs in mom

• Obesity (BMI 30 or higher)

• Physical inactivity

• Tobacco use

Patient preparation before taking a BP reading

• avoid nicotine, caffeine, food, and extraneous effort for at least 30 min before (Wasem said 60 min in class)

• remove all clothing that covers cuff placement

• sitting comfortably with legs uncrossed, back and arm supported

• middle of cuff on upper arm at level of right atrium (mid-point of sternum)

• lower part of cuff 3 cm above the elbow

• patient should not be talking

What is AOBP?

Automated office blood pressure

What time intervals does AOBP measure BP?

1 or 2 minute intervals

How should a blood pressure cuff fit if measuring by auscultation (non-AOBP)?

• bladder width ~40% of arm circumference

• bladder length should cover 80-100% of arm circumference

How is non-AOBP performed?

• increase pressure rapidly to 30 mmHg above the level at which the radial pulse is extinguished

• open control valve with rate of deflation of 2 mmgHg per heart beat

• read systolic (first appearance of clear tapping sound)

• read diastolic (point at which sounds disappear

• perform 3 tests on same arm at least 2 minutes apart (discard first reading and average the rest)

• repeat on other arm and use the higher reading arm for later visits

What is ABPM?

Ambulatory BP monitoring

How does ABPM work?

• at least 24 hrs with a frequency of one measurement q 20-30 min during the day and q 30-60 min at night

Note: threshold for 24-hr mean is lower than for other tests

What technique can be used to measure BP in patients with office-induced increased BP

ABPM

How do all BP-measuring techniques compare?

Non-AOBP is slightly higher, all others are similar

What is considered a hypertensive crisis?

180/120 or higher

Differentiate between hypertensive urgency and hypertensive emergency

Urgency = no target organ damage

Emergency = evidence of acute or progressive end organ damage (CNS, eyes, heart, kidneys)

Examples of end organ damage that would indicate hypertensive emergency if BP 180/120 or higher

• hypertensive encephalopathy

• acute aortic dissection

• acute left ventricular failure

• acute myocardial ischemia

What matters more than BP values in hypertensive crises?

The rate of BP increase

How does treatment strategy change between hypertensive urgency and emergency?

Urgency: reduce BP over several hours to days and give oral therapy

Emergency: immediate reduction of BP within hours and give parenteral therapy

Risk factors for hypertensive crises

• medication non-adherence

• cocaine use

• drug interactionsø

Options for IV meds in hypertensive emergency

• labetalol

• nitroglycerin

• nitroprusside

Options for PO meds for hypertensive urgency

• clonidine

• labetalol

• captopril

Goal BP reductions for hypertensive emergencies

• initially reduced by 25%

• then to target of 160/100 within next 2 hrs

• gradually reduce to normal BP within next 24 hrs

Goal BP reductions for hypertensive urgency

Gradual reduction to normal BP within 24-48 hrs

What routine tests should be done for investigation of all patients with HTN ?

• urinalysis (look for albuminuria)

• blood chemistry (K, Na, Cr)

• FPG and/or A1c

• Lipid panel

• standard 12-lead ECG

True or false. All treated hypertensive pts should be monitored according to the current Diabetes Canada guidelines for the new appearance of diabetes.

True (grade B recommendation)