Hypertension Pathophysiology

Question 1

Risk factors for HTN

Answer 1

• unavoidable: family history/genetics, age, sex, race, diabetes (type 2)
• life style: salt intake, obesity, alcohol, smoking, exercise, stress

Question 2

Classification of HTN

Answer 2

• noramal: 160 or >100

Question 3

BP with increasing age

Answer 3

• systolic & pulse pressures steady increase after 40
• diastolic increase after 30, peak at 55 then decrease
• mean arterial pressure increase after 35 and plateau about 65

Question 4

Classification of HTN based on etiology

Answer 4

• essential HTN: 90-95% of all HTN, unknown etiology; polygenetic disorder, altered regulation of arterial pressure
• secondary HTN: 5-10%, kidney disease, cushings syndrome, coarctation of aorta, obesity, obstructive sleep apnea, parathyroid disease, pheochromocytoma

Question 5

Genetics of HTN

Answer 5

• genes affect renal-sodium & water reabsorption
• enhanced mineralcorticoid (aldosterone) activity: low renin activity, familial hyperaldosteronism type 1 & 2, pseudohypoaldosteronism type III

Question 6

Liddle syndrome

Answer 6

• mutation in epithelial ENaC w/ increase in Na retention & HTN

Question 7

Bartter & Gitelman Syndromes

Answer 7

• reduced Na+ retention & hypotension

Question 8

Polygenic HTN

Answer 8

• 55% of HTN accounted by genetic factors
• GWAS identified 53 single nucleotide polymorphisms (SNPs)
• difficult to identify specific gene products w/ SNPs

Question 9

SNPs associated with what

Answer 9

• renin angiotensin aldosterone system (RAAS)
• 11beta hydroxylase and enzymes of cortisol biosynthesis
• some forms of pheochromocytoma

Question 10

Monogenic HTN

Answer 10

• 1% of patients
• about 25 genes identified
• affect renal-sodium & water retention
• little syndrome, bartter & gitelman syndrome

Question 11

Secondary HTN - Renal Tumors

Answer 11

• adrenal cortex: increase mineralcorticosteroids (hyperaldosteronism), increased blood volume
• adrenal medulla: pheochromocytoms, increased epinephrine (vasoconstriction)

Question 12

Secondary HTN - Renal artery stenosis

Answer 12

• increased renin release

- increased angiotensin II

Question 13

Factors contributing to HTN

Answer 13

• impaired homeostasis
• imbalance in fluid retention
• neurogenic or psychogenic
• vascular defect
• multifactorial

Question 14

MAP & CO

Answer 14

• mean arterial pressure
• MAP = CO x TPR
• CO = heart rate x stroke volume

Question 15

Normal HR, CO, SV

Answer 15

• HR: 70 beats/min
• CO: 5-6 L/min
• SV: 70 mL/beat

Question 16

Determinants of CO

Answer 16

• SV: ventricular filling pressure (blood volume, venous return) & myocardial contractility
• HR: neural control

Question 17

Determinants of TPR

Answer 17

• peripheral resistance: vascular tone (neural control, neurohumoral factors, angiotensis II)

Question 18

Neural control of BP

Answer 18

• ARTERIAL BARORECEPTORS, arterial chemoreceptors, muscle metaboreceptors
• leads to PNS output on heart and SNS output on heart, vessels, & kidney

Question 19

Time dependent activation of BP control mechanisms

Answer 19

• seconds: 1. baroreceptors 2. chemoreceptors 3. CNS ischemic response
• hours: renal body fluid

Question 20

Altered baroreceptor function in HTN

Answer 20

• HTN leads to baroreceptor resetting

Question 21

Abnormal baroreceptor function

Answer 21

• loss of afferent function: oxygen radicals, atherosclerosis, less distensible
• central defect: angiotensin II, loss of baroreceptor pathways, emotional or reactive stress

Question 22

Plasma renin levels in HTN

Answer 22

• 15% high renin levels
• 25 % low renin
• 60% normal renin

Question 23

Role of vasopressin(ADH), aldosterone, catecholamines

Answer 23

• increase CO & peripheral vascular resistance

- affect Na & fluid retention

Question 24

Angiotensin II effects

Answer 24

• AT2: vasodilation, decreased baroreflex, cell differentiation, anti mitogenesis
  A1: vasoconstriction (RAPID RESPONSE), adosterone (SLOW RESPONSE), mitogenesis (vascular/cardiac hypertrophy)

Question 25

Bradykinin metabolism

Answer 25

• kininogen: converted to bradykinin via kallikrein
• bradykinin: B1=inflammation, B2=vasodilation
• bradykinin broken down via kininase, which is an ACE

Question 26

Endothelial derived vasodilators

Answer 26

• nitric oxide: formed from L-arginine by NO synthase, activates guanylyl cyclase to produce cGMP
• prostacyclin: formed from AA by COX and PGI2 synthase, activates adenylyl cyclase to produce cAMP

Question 27

Abnormal vascular function in CV disease

Answer 27

• abnormal endothelial function

- abnormal smooth muscle function: intracellular Ca2+ concentration, calcium sensitivity of contractile proteins

Question 28

Endothelial derived vasoconstrictors

Answer 28

• endothelin: produced by endothelin converting enzyme, receptors:ETa contriction, ETb dilation
• thromboxane: produced from AA
• angiotensin II: vascular ACE

Question 29

Management of HTN: diet modification - initial strategy

Answer 29

• body weight reduction
• restrict sodium intake: decrease Na-decreases MAP, increases effectiveness of other antiHTN drugs
• restrict fat intake
• decrease alcohol consumption

Question 30

Sodium balance

Answer 30

• excess sodium increases vascular resistance: promotes intracellular Ca2+, increases basal tone of VSM, increased response to NE & angiotensin II, increased vessel stiffness, increased fluid retention, increased release of NE or EPI

Question 31

Body weight & HTN

Answer 31

• incidence of HTN higher in obese
• sleep apnea higher in obese
• mechanism: insulin dependent increase in Na+ reabsorption or increase in central mediated vasoconstriction
• exercise and diet reduce MAP without change in Na+

Question 32

Therapeutic approach to treatment of HTN

Answer 32

• life style management: diet, weight, reduce stress, exercise, smoking
• antihypertensive agents

Question 33

Hypertension long term censequences

Answer 33

• cardiovascular disease: 50%
• renal disease/failure: 10-15%
• stroke: 33%
• retinal disease