Hypertension Pathophysiology Flashcards
1
Q
Risk factors for HTN
A
- unavoidable: family history/genetics, age, sex, race, diabetes (type 2)
- life style: salt intake, obesity, alcohol, smoking, exercise, stress
2
Q
Classification of HTN
A
- noramal: 160 or >100
3
Q
BP with increasing age
A
- 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
4
Q
Classification of HTN based on etiology
A
- 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
5
Q
Genetics of HTN
A
- genes affect renal-sodium & water reabsorption
- enhanced mineralcorticoid (aldosterone) activity: low renin activity, familial hyperaldosteronism type 1 & 2, pseudohypoaldosteronism type III
6
Q
Liddle syndrome
A
- mutation in epithelial ENaC w/ increase in Na retention & HTN
7
Q
Bartter & Gitelman Syndromes
A
- reduced Na+ retention & hypotension
8
Q
Polygenic HTN
A
- 55% of HTN accounted by genetic factors
- GWAS identified 53 single nucleotide polymorphisms (SNPs)
- difficult to identify specific gene products w/ SNPs
9
Q
SNPs associated with what
A
- renin angiotensin aldosterone system (RAAS)
- 11beta hydroxylase and enzymes of cortisol biosynthesis
- some forms of pheochromocytoma
10
Q
Monogenic HTN
A
- 1% of patients
- about 25 genes identified
- affect renal-sodium & water retention
- little syndrome, bartter & gitelman syndrome
11
Q
Secondary HTN - Renal Tumors
A
- adrenal cortex: increase mineralcorticosteroids (hyperaldosteronism), increased blood volume
- adrenal medulla: pheochromocytoms, increased epinephrine (vasoconstriction)
12
Q
Secondary HTN - Renal artery stenosis
A
- increased renin release
- increased angiotensin II
13
Q
Factors contributing to HTN
A
- impaired homeostasis
- imbalance in fluid retention
- neurogenic or psychogenic
- vascular defect
- multifactorial
14
Q
MAP & CO
A
- mean arterial pressure
- MAP = CO x TPR
- CO = heart rate x stroke volume
15
Q
Normal HR, CO, SV
A
- HR: 70 beats/min
- CO: 5-6 L/min
- SV: 70 mL/beat
16
Q
Determinants of CO
A
- SV: ventricular filling pressure (blood volume, venous return) & myocardial contractility
- HR: neural control
17
Q
Determinants of TPR
A
- peripheral resistance: vascular tone (neural control, neurohumoral factors, angiotensis II)
18
Q
Neural control of BP
A
- ARTERIAL BARORECEPTORS, arterial chemoreceptors, muscle metaboreceptors
- leads to PNS output on heart and SNS output on heart, vessels, & kidney
19
Q
Time dependent activation of BP control mechanisms
A
- seconds: 1. baroreceptors 2. chemoreceptors 3. CNS ischemic response
- hours: renal body fluid
20
Q
Altered baroreceptor function in HTN
A
- HTN leads to baroreceptor resetting
21
Q
Abnormal baroreceptor function
A
- loss of afferent function: oxygen radicals, atherosclerosis, less distensible
- central defect: angiotensin II, loss of baroreceptor pathways, emotional or reactive stress
22
Q
Plasma renin levels in HTN
A
- 15% high renin levels
- 25 % low renin
- 60% normal renin
23
Q
Role of vasopressin(ADH), aldosterone, catecholamines
A
- increase CO & peripheral vascular resistance
- affect Na & fluid retention
24
Q
Angiotensin II effects
A
- AT2: vasodilation, decreased baroreflex, cell differentiation, anti mitogenesis
A1: vasoconstriction (RAPID RESPONSE), adosterone (SLOW RESPONSE), mitogenesis (vascular/cardiac hypertrophy)
25
Q
Bradykinin metabolism
A
- kininogen: converted to bradykinin via kallikrein
- bradykinin: B1=inflammation, B2=vasodilation
- bradykinin broken down via kininase, which is an ACE
26
Q
Endothelial derived vasodilators
A
- 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
27
Q
Abnormal vascular function in CV disease
A
- abnormal endothelial function
- abnormal smooth muscle function: intracellular Ca2+ concentration, calcium sensitivity of contractile proteins
28
Q
Endothelial derived vasoconstrictors
A
- endothelin: produced by endothelin converting enzyme, receptors:ETa contriction, ETb dilation
- thromboxane: produced from AA
- angiotensin II: vascular ACE
29
Q
Management of HTN: diet modification - initial strategy
A
- body weight reduction
- restrict sodium intake: decrease Na-decreases MAP, increases effectiveness of other antiHTN drugs
- restrict fat intake
- decrease alcohol consumption
30
Q
Sodium balance
A
- 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
31
Q
Body weight & HTN
A
- 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+
32
Q
Therapeutic approach to treatment of HTN
A
- life style management: diet, weight, reduce stress, exercise, smoking
- antihypertensive agents
33
Q
Hypertension long term censequences
A
- cardiovascular disease: 50%
- renal disease/failure: 10-15%
- stroke: 33%
- retinal disease
