1. Basic Concepts, Types, Pathogenetic Factors Hypertension

1. Basic concepts, types, pathogenetic factorsHypertension2. Secondary hypertension3. Essential hypertension4. Therapy1.Basic concepts, types, pathogeneticfactorsBasic concepts and definitions:Factors determining blood pressure (Fig. 1)1Regulation of peripheral resistance (Fig. 2)Regulation of circulating volume (Fig. 3)23

Discrimination between “pathologic” and “normal” BP values isarbitrary (Fig. 4)Types of hypertension:Resistance hypertension :In its chronic phase, diastolic pressure is allwaysenhanced, systolic p. as a rule;pressure rise is a consequence of enhanced totalperipheral vascular resistanceOutput (volume) hypertension :Only systolic p. rises, owing to enhanced cardiacoutputElastic hypertensionOwing to loss of great vessels elasticity in old ageRecommended values :Systolic140 mmHg by age 40150 mmHg in 40 - 60160 mmHg since 60Diastolic90 mmHg for all agesEnhanced BP is a sign of underlying condition rather than adisease in itself“Essential” hypertension can be analyzed utilizingconcepts explaining types of secondaryhypertensionTypes of secondary hypertension range from“volume dependency” to “pressor dependency”(Fig. 5)5Damaged endothelium vasoconstrictory effect of varioushumoral factors (Fig. 6)Common pathogenic factors of different types ofhypertensionFamilial load, intracellular Ca2 in SMCStructural changes of the walls of arteries:Hypertrophy of media - substantial pathogeneticfactor for progression and maintainanceof hypertension (esp. essential)genetic& environm.factorsmildunstablerise ofBPmedia hypertrophy precapillaryresistance

2. Secondary hypertensionSecondary causes of hypertension (Tab. 1)Decline of baroreceptor sensitivitystructuralwall changes arterialbaroreceptorsensitivity sympatoadr.reactivity to stress &exercise development & maintainance of hypertensionIt may undermine therapeutic effect of vasodilatorsTab. 1Interplay of pressure/volume hypertension (Fig. 7)Renin-angiotensin system reacts quickly (in minutes)to the renal artery obstruction or to sympaticus activation via angiotensin II resistance hypertension(short-term cardiorenal homeostasis)Volume renin angiotensin systemRAS depresses itself in a long run, as it activatesaldosterone (in hrs or days) volume RASBillateral renal disease loss of nephrocytes RASDiuretics RAS!(Fig. 7)7Pathogenesis of secondary hypertension (Tab. 2)Overproduction of adrenal hormonesCushing s syndromeGlucocorticoids have specific hypertensionproducing effect, too, independent on sympathicus& RAS (receptors in CNS ?)1. Primary hyperaldosteronismAdenoma/hyperplasia (zona glomerulosa) retention of Na & H2O volume paradigmatic volume hypertensionLater, however, autoregulation TPVR resistance hypertensionTab. 2

2. PheochromocytomaTumor of adrenal medulla mixture of catecholamines paradigmatic resistance hypertensionPressure natriuresis & tonization of veins volume orthostatic problems3. Renovascular hypertension (unilateral)Stage 1 - Resistance hypertensionConstriction of art. renalis renin AG II vasoconstriction BPStage 2 AG II aldosterone Na & H2Oretention volume RAS Later, volume autoregulation TPVR resistance hypert.Stage 3 TPVR vascular & parenchymal damageof contralateral kidney state similar torenal-parenchymal hypertension(Tab. 2)Hypertension caused by drugsContraceptivesManifest hypertension in 5% of women, esp. whenother risiko factors of hypertension are present (incl.age!).Estrogen and progesterone component. RAS ?Indomethacine vasodilatory prostaglandines4. Chronic end-stage renal disease (renal-parenchymalhypertension, bilateral renovascular hypertension)Loss of nephrons GFR Na & H2O retention circul. volume venous return CO autoregulation TPVR circul. volum RASLoss of nephrons disruption of BP/Na excretionrelationAutoregulation : CO & ? TPVRIn some patients or with volume supressed bydiuretics RAS (normal absolutely, butenhanced relatively to Na & BP)Evidence of RAS participation: billateralnephrectomy normalization of pressure(excretion being ensured)Tab. 23. Essential hypertensionDefinition:No recognizable organ pathology as a cause. Dg per exclusionemDevelopment of EH (Fig. 9)TPVR normal: CO TPVR MAP TPVR later (due to secondary changes invasculature) :CO TPVR MAP (Fig. 10)8

Etiology of EH is heterogenousThere are several important factors promotingmanifestation of EH, none of them is dominant,however (Fig. 9 and 11)More important, interplay of BP regulating factors isdisruptedFactors may be important differently in individual patients9108Hypothesis :Genetic and environmental factorsGenetic factors about 30 % of BP varianceRacial differencesSome environm. factors sympatoadr. activation- stress (noise, flying personell)- psychosocial factorsNa consumption15 g 6 g NaCl daily BP by 9 mmHg.This is due to salt sensitive individuals(genetically determined).Animals : Cl- important, too !Atrial natriuretic peptide (ANP): no effect on Na/K-ATPase,no role in pathophysiology of hypertension

Overweight hypertensionPlasma volume, RASSympatoadrenal systemPlasma renin activity is not enhanced absolutely in majority of ess. hypertonics, but relatively to BPACE inhibitors therefore BP4. TherapyMay be used to exclude some of the primary causeswhen unsuccessfullTwo strategies for exclusion of secondary hypertensionSingle reading insufficient (“white-coat hypertension”, a.o.)With mild hypertension, observation may be prolonged formonths under recommended change in life-styleChanged way of living first choice therapy- obesity- diet ( Na, K, alcohol; caffeine does not producehypert. itself)- smoking equivocal effect on BP- relaxaton therapyPharmacology- diuretics- sympaticolytics peripheral vasodilators (e.g., Ca2 channel blockers)- ACE inhibitors- AG II receptor antagonistsTherapy should be combined and individualized

(short-term cardiorenal homeostasis) Volume renin angiotensin system RAS depresses itself in a long run, as it activates aldosterone (in hrs or days) volume RAS Billateral renal disease loss of nephrocytes RAS Diuretics RAS! (Fig. 7) 7 Pathogenesis of secondary hypertension (Tab. 2) Tab. 2 Overproduction of adrenal .