Hypertension PATHO Flashcards
Primary Hypertension
Definition, prevalence, risk Factors
Primary HTN
Essential HTN
Idiopathic HTN
Elevated BP with no identifiable cause
95% HTN
Risk factors
- old age
- obesity
- smoking
- alcoholism
- sedentary lifestyle
- Gender (men > women before 55; women > men after 55)
- african
- indigenous
- low SES
- high dietary sodium
- low dietary potassium, calcium, mangesium
- glucose intolerance
Secondary HTN
Definition, prevalence, risk factors
Secondary HTN
elevated BP with known cause
treat cause, reverse HTN
10% HTN
younger people
Risk Factors
- Renal disease
- coartication aorta
- OSA
- pheochromocytoma
- aldosteronism
- cushings syndrome
- hyperthyroid (high SBP), hypothyroid (High DBP)
- drug induced (NSAIDS, corticosteroids, immunosupressants, oral contraceptives, stimulants (amphetamines, cocaine), alcohol, smoking, SNRIs, lithium)
- Food induced (licorice, ginsing)
Risk Factors for HTN
- Lack of exercise (< 150 min per week moderate intensity)
- Diet ( < 5 servings fruit/vegetables per day, > 2000mg sodium, low potassium/calcium/magnesium)
- obesity ( BMI > 25, waist > 102/88cm)
- DIABETES
- KIDNEY DISEASE (GFR < 60mL/min)
- ALCOHOL (abstain)
Long term effect of HTN
- Microvascular 2. Macrovascular damage –> End organ damage
HTN -> damages capillaries, endothelial lining –> scaring –> atheroscelersosis –> narrowing –> ischemia
- Heart
- high BP increases afterload of heart
- high BP decreases RBP and increases RAAS and SNS
- collectively angiotensin II, aldosterone, SNS result in vascular and cardiac remodelling (increase ECM and fibrosis, increase atheroscelerosis, hypertrophy)
- vessel damage results in atheroscelerosis
- Increase demand for oxygen due to workload
- ischemia
–> CAD, angina, MI, HFrEF, LV hypertrophy - Kidney
- high BP reduces RBP
- reduction of GFR
- activation RAAS and SNS
- results in angiotensin II, aldosterone (cardiovascular remodelling; and SNS stimulation) –> + HTN
- reduced RBP ischemia
- ATN; increase intratubular pressure; damage glomerular basement membrane
- proteinuria - Brain
- high BP damages endothelial lining
- atheroscelerosis, narrowing, ischemia
- TIA, strokes, dementia - Eyes
- high BP damages capillaries
- flare hemorrhages, cotton wool spots, retinal scelerosis - Peripheral arteries
- intermittent claudication due to ischemia from atheroscelerosis
- gangrene due to ischemia
Pathophysiology
SNS and RAAS = HTN
SNS
1. Vascular/cardiac remodeling
2. insulin resistance
3. vascular resistance
4. coagulation
= HTN
- Heart
- beta 1 adrenergic receptors: HR, conduction, contraction = increase BP - Pancreas
- SNS inhibits release insulin, increase release glucagon, increase BP = endothelial dysfunction, inflammation, atheroscelerosis, narrowing = BP
- cortisol increases insulin resistance (released by adrenal medulla from SNS stimulation)
- epinephrine increases blood glucose (released by adrenal medulla from angiotensin II stimulation) - Kidney
- beta 1 receptors juxtaglomerular cells release renin
- high BP decreases RBP releases renin (+)
- RAAS pathway
- angiotensin II 1. vascular remodelling (narrowing, increase BP 2. cardiac remodelling (hypertrophy, HF) 3. vasoconstriction direct (BP) 4. release cortisol, aldosterone, epinephrine (insulin resistance, BP, cardiac remodeling) - Coagulation factors
- increase circulation of coagulation factors
Function of Natriuretic peptides
ANP/BNP
- atrial natriuretic peptide
- bone natriuretic peptide
- released from atrium/ventricle during stretch
- prevent kidney from reabsorbing sodium
- diuresis of water
CNP and urodilantin
- CNP released from vasculature
- urodilantin released from collecting duct
- during stretch
- promote dilation of renal arteriole
- promote GF and diuresis
*Dysfunction natriuretic peptides result in hypertension
Inflammation and HTN
Pro-inflammatory states
- hyperglycemia
- hypoglycemia (proinflammation, procoagulation)
- obesity
Inflammation = endothelial cell dysfunction
- doesn’t produce NO for vasodilation
- vaosoconstriction
- narrowing, atheroscelerosis, and HTN
Obesity and HTN
Obesity
- adipokines proinflammatory
- activation SNS (vasoconstriction ; release cortisol and NE)
- NE binds beta 1 adrenergic receptors on heart; increase HR, conduction, contractility; increase BP
- NE binds beta 1 adrenergic receptors on kidney; increase renin release; RAAS activation; increase BP
- cortisol increases blood glucose; inflammation; atheroscelerosis; narrowing; BP
- SNS inhibits insulin release from pancreas, increases glucagon release; increase BG; increase inflammation, atheroscelerosis, narrowing: BP
Insulin Resistance and HTN
Insulin Resistance
- Obesity is the driver for insulin resistance MSK
- increase BG
- damages blood vessels
- atheroscelerosis, narrowing
- obesity adipokines also damage beta cells resulting in dysfunction
- decrease insulin and amylin release
- increase gulcagon release; increase BG, inflammation, atheroscelerosis, narrowing
Shift in pressure-natriuresis relationship
HTN
- SNS
- RAAS
- dysfunction natriuretic peptides
- insulin resistance
- obesity
- diet
- glomerular and tubular inflammation
- endothelial dysfunction
- genetics
*retention sodium and water
HTN
HTN
Treatment Goals based on Risk Stratification
High Risk
- Diabetes (>130/80mmHg)
- >/= 75 years
- >/= 50 years with SBP > 130mmHg and:
- CVRF > 15%
- CKD (GFR < 60mL/min)
- CVD
Diabetes HTN: > 130/80
Goal: < 130/80
Other HTN: >130
Goal: < 120
Moderate - High Risk
- CVRF > 10%
- TOD present
- HTN: >140/90
- Goal: < 140/90
Low risk
- CVRF none
- TOD none
- HTN > 160/100
- Goal < 140/90
Pharmacological Treatment
Diabetes
with microalbuminuria, CVD, CV risk factors, renal disease
First line:
ACEi/ARB (nephroprotective, cardioprotective)
Combination:
ACEi/ARB + CCB dihydropyridine
Pharmacological Treatment
Diabetes
without TOD
First line:
ACEi/ARB/CCB/Thiazide diuretic
Combination therapy:
ACEi/ARB + CCB dihydropyridine
Pharmacological treatment
Non-Diabetic CKD / proteinuria
First Line:
ACEi/ARB
Combination:
ACEi/ARB + Diuretic
Pharmacological treatment
Past stroke/TIA
First Line:
ACEi + Thiazide Diuretic
Ex. Perindopril + Indapamide (reduce stroke 4 years)
Pharmacologial treatment
Coronary Artery Disease
First line:
ACEi/ARB
CAD with stable angina
First line:
Beta blocker/CCB
Combination therapy:
ACEi/CCB added
Pharmacological treatment
Recent MI
HF LEF < 40%
First line:
Beta blocker + ACEi
OR
CCB + ARB
Addition:
Aldosterone antagonist (elevated BNP, hospitalization, acute MI, HF symptoms II-IV)
Thiazide diuretic
HTN
Candian Prevalence
Increases with age
> 70 years 70%
Men = Women
< 40 years
untreated, silent, undermanaged
Goal of HTN Treatment
Prevent TOD
- microvascular and macrovascular changes
1. heart 2. kidney 3. eyes 4. peripheral arteries 5. brain
Pathophysiology HTN
BP = CO x PVR
HTN =
1. increase CO
2. increase peripheral resistance
3. BOTH
Increase CO
- CO = Stroke volume x HR
- SNS
- RAAS
PVR
- Diameter
- Vascular compliance
- blood viscosity
SNS and HTN
SNS activation releases NE, E, cortisol
- heart
increase HR, CO, conduction = increase BP - kidney
release renin
RAAS pathway
reabsorption water, sodium = BP
angiotensin II = vasoconstriction, + SNS, remodeling heart, VSM, release aldosterone
aldosterone = reabsorption sodium, water, remodellig heart, prevent NE degredation + SNS, baroreceptor setpoint higher - pancreas
- inhibtion insulin release, increase glucoagon release, BG, inflammation
- SNS insulin resistance periphery
- obesity inflammation pancreatic beta cell dysfunciton decrease insulin - pro-coagulation
virchow triad: endothelial dysfunction, inflammation, increased blood viscosity = increase thrombosis - Endothelial dysfunction
Accurately diagnosing HTN
Measurement Techniques
- sitting
- rest for 5 minutes before start
- back supported
- arm supported
- cuff at heart level
- cuff 40% diameter, 80-100% length
- 3 cm above elbow
- no talking, moving
- feet flat
- legs uncrossed
- measurements 1-2 minutes apart
- provider out of room
- arm with higher blood pressure used
- automated, provider out of room preferred
Diagnosis cut offs in office/out of office HTN
HTN
BP > 180/110mmHg ==> Hypertention
AOBP >/= 135/85mmHg
OBPM >/= 140/90mmHg (*in room)
diabetics >/= 130/80mmHg
*3 readings average second two
*3-5 office visits if ABPM or HBPM is not available
*probable HTN suspected then you proceed to out of office measurements
ABPM >/= 135/85mmHg (daytime average)
>/= 130/80mmHg (24 hour average)
*readings are taken every 20-30 minutes for 24 hours?
HBPM >/= 135/85mmHg (7 days, 2x AM 2x PM, discard first day)
Diagnostic and laboratory investigations
Suspected HTN
- urinalysis (Proteinuria, hematuria, glucosuria)
- ECG
- lipid pannel
- A1C and FPG (r/o pre-diabetes, diabetes)
- lytes (sodium, potassium, calcium, magnesium)
- kidney function (BUN, creatinine)
- liver function
- pregnancy screen
*
r/o secondary causes
- TSH, free T3, free T4
- 24 hour urine corticosteroids
- Drugs etc.
Approach to treatment of HTN
Stratify based on RISK
Framingham risk Score
- age
- gender
- SBP
- smoking status
- HDL
- TC
High risk > 15%
moderate risk 10-15%
low risk < 10%
*High risk and moderate will also start statin therapy for lipids
Lifestyle modifications
HTN
Exercise
> 150minutes / week moderate-intense
Diet
< 2000mg/ day sodium
increase potassium, calcium, magnesium
DASH
> 5x fruits, vegetables, fibres, low fat, whole grain, plant protien
Weight loss
BMI < 25
waist circumference < 102cmm < 88cm women
Abstain alcohol and smoking
< 2 drinks per day
Stress management
CBT and relaxation
Pharmacotherapy
Things to remember
- long acting thiazide diuretics > short acting
- beta blockers should not be used as monotherapy OR >/= 60 years of age
- RAAS drugs (ACEi , ARBs) are teratogenic 2nd and 3rd trimester
- Do not combine ACEi or ARBs
- Caution combining beta blockers and CCB (cardiosupression toxic as same mechanism for non-dihydropyridines)
- beta blockers and ACEi together have limited therapeutic effect (preferrable is CCB)
- single pill combinations are preferred
- ACEi + CCB
- ACEi/ARB + thiazide diruetics
- low dose multiple drugs > one drug high dose (less SE)
- > 3 drugs, uncontrolled, referral
Pregnancy
HTN pharmacotherapy
First line: Beta blockers
labetalol (third generation beta blocker, block beta 1, 2 and alpha 1)
acebutolol
metoprolol
pindolol
propranolol
Others:
long acting nifedipine
methyldopa ( Brainstem, supression SNS)
Additive:
Thiazide diuretic
R/O before resistant HTN
- white coat syndrome
- non adherence medication / lifestyle
- secondary hypertension
- inadequate drug/combination
Poor response to HTN therapy
causes
- inaccurate measurement
- inappropriate treatment
- dosage
- combination drugs
- poor adherence diet, exercise, medication
- Drugs that cause HTN
- Undiagnosed secondary conditions
Follow up HTN
pharmacological and lifestyle management
Follow up
1-2 months until BP in target
2 consecutive visits below target
3-6 month intervals
Lifestyle modification and adherence
3-6 month visits
not in target 1-2 months
Pathophysiology of
HTN baroreceptor reflex
High baroreceptor reflex in HTN
keeps BP high
- sense low BP, carotid arch, and aorta baroreceptors
- signal brain
- activation SNS
- beta 1 receptors increase HR, conduciton, contraciton
- beta 1 receptors kidney, release renin (RAAS pathway)
- alpha 1 receptors vasoconstriction peripheral arteries/veins
- increase BP to higher set point
MOA
Thiazide diuretics
- prevention Na/K/Cl reabsorption at the early distal tubules
- promotion vascular muscle relaxation / vasodilation
Can you cure HTN?
No
Therapy is life long
lifestyle +/- drug therapy
Why start low and go slow with dosing?
Everyone has different sensitivity (receptors)
prevents triggering baroreceptor reflex
resets the setpoint
Benefit of multiple drug therapy
Lower dosage of each drug needed
lower SE profiles
Treatment considerations African American
First line: diuretic
Do not use beta blocker / ACEi monotherapy
*exception is risk profile
Why don’t we use beta blockers with older people >/= 60 years?
blunt the baroreceptor reflex
results in orthostatic hypotension and falls
HTN in pregnancy
10% pregnancies
Screen all pregnancies
High risk pre-eclampsia
Treat 160/110
Risk
- placental abruption
- fetal malformation and growth restrictions
- premature delivery
- death
Pre-eclampsia
Pathophysiology, diagnosis, treatment
HTN > 140/90
proteinuria
eclampsia = seizures
after 20 weeks gestation
6 weeks after pregnancy
Pathophysiology
- hyperperfused placenta (narrowing spiral arteries)
- pro-inflammatory proteins released from placenta
- endothelial cells dysfunctional in mom
- kidney retain salt
- arteries narrow
Risk factors
- HTN
- diabetes
- black
- first pregnancy
- family history
- > 35 years
- obesity
Complications
- Seizures “eclampsia”
- Renal failure - damaged glomerulus
- Damage retina - blurred vision
- Liver damage - RUQ pain (cardinal symptom)
- Third spacing fluid - edema, legs, face, hands, pulmonary, cerebral edema (HA, seizures)
- stroke - micro-thrombi, hemolysis (HELP syndrome)
- placental abruption, intrauterine growth restriction
- HELP - hemolysis, elevated liver, low platelets
Treatment
- delivery baby and placenta (source of dysfunction)
HTN follow up
1-2 months uncontrolled
3-6 months controlled
HTN uncontrolled - reassess what?
pharm adherence
non pharm adherence
correct measurement
secondary factors - refer out
