pathophysiology of hypertension
DESCRIPTION
Pathophysiology of Hypertension. Jianzhong Sheng MD, PhD. Department of Pathophysiology, School of Medicine. Regulation of ABP:. ■ Maintaining B.P. is important to ensure a steady blood flow (perfusion) to tissues. ■ BP is regulated neurally through centers in medulla oblongata: - PowerPoint PPT PresentationTRANSCRIPT
Pathophysiology of Hypertension
Jianzhong Sheng MD, PhD
Department of Pathophysiology, School of Medicine
Regulation of ABP:
■ Maintaining B.P. is important to ensure a steady blood flow (perfusion) to tissues.
■ BP is regulated neurally through centers in medulla oblongata: 1. Vasomotor Center (V.M.C.), or (pressor area): Sympathetic fibers. 2. Cardiac Inhibitory Center (C.I.C.), or (depressor area): Parasympathetic fibers (vagus).
cardiac control centers in medulla oblongata
Regulation of ABP (continued)
1. Cardiacaccelerator
center(V.M.C)
2. Cardiacinhibitory
center(C.I.C)
Sympathetic n. fibers Parasympathetic n. fibers Regulatory mechanisms depend on: a. Fast acting reflexes: Concerned by controlling CO (SV, HR), & PR. b. Long-term mechanism:
Concerned mainly by regulating the blood volume.
Regulation of Arterial Blood PressureA. Regulation of Cardiac OutputB. Regulation of Peripheral ResistanceC. Regulation of Blood Volume
Classification of hypertension
1. Essential hypertension
2. Secondary hypertension
Excess sodium intake
Venous constriction
Fluid volume
Reduced nephron number
Decreased filtration surface
Renal sodium
retention
Endothlium derived factors
Obesity
Preload
Hyper- insulinaemia
Cell membrane alteration
Renin angiotensin
excess
Sympathetic nervous over
activity
Genetic alteration
Stress
Blood pressure = Cardiac output X Peripheral resistance
Structural hypertrophy
Functional constriction
HeartContractability
AutoregulationHypertension = Increased CO and/or Increased PR
Some of the factors involved in the control of blood pressure that affect the basic equation: blood pressue = cadiac output x peripheral resistence.
A. Regulation of CO:
■ A fast acting mechanism. ■ CO regulation depends on the regulation of:
a. Stroke volume, & b. Heart rate
Regulation of Arterial Blood Pressure
Mean arterial pressure
Cardiac output = Stroke volume X Heart rate
End Contraction diastolic strength volume (EDV) Stretch
Sympathetic n Parasympathetic n
Frank - Starling
A. Regulation of the CO:
Regulation of Arterial Blood Pressure
B. Regulation of Peripheral Resistance
B. Regulation of Peripheral Resistance (PR):
■ A fast acting mechanism. ■ Controlled by 3 mechanisms: 1. Intrinsic. 2. Extrinsic. 3. Paracrine.
Intrinsic mechanism:Blood vessel tone
Extrinsic mechanism is controlled through several reflex mechanisms, most important:
1. Baroreceptors reflex. 2. Chemoreceptors reflex.
1. Baroreceptors reflex:
■ Baroreceptors are receptors found in carotid sinus & aortic arch.
■ Are stimulated by changes in BP. BP
+ Baroreceptors =
V.M.C
++ C.I.C
=Sympathetic
Vasodilatation & TPR
+Parasympathetic
Slowing of SA node ( HR) & CO
2. Chemoreceptors reflex:■ Chemoreceptors are receptors found in carotid & aortic bodies.■ Are stimulated by chemical changes in blood mainly hypoxia ( O2), hypercapnia ( CO2), & pH changes.
BP
+ Chemoreceptors
++ V.M.C
= C.I.C
+ Sympathetic
Vasoconstriction
& TPR
= Parasympathetic
HR
Haemorrhage
Hypoxia
+ Adrenalmedulla
3. Other Vasomotor Reflexes:
1. Atrial stretch receptor reflex: Venous Return ++ atrial stretch receptors reflex
vasodilatation & BP.2. Thermoreceptors: (in skin/or hypothalamus)
• Exposure to heat vasodilatation.• Exposure to cold vasoconstriction.
3. Pulmonary receptors: Lung inflation vasoconstriction.
4. Hormonal Agents:
■ NA vasoconstriction.■ A vasoconstriction (except in sk. ms.).■ Angiotensin II vasoconstriction.■ Vasopressin vasoconstriction.
Regulation of Arterial Blood PressureC. Regulation of Blood Volume
Regulation of Blood Volume:
■ A long-term regulatory mechanism. ■ Mainly renal: 1. Renin-Angiotensin System. 2. Anti-diuretic hormone (ADH), or vasopressin. 3. Low-pressure volume receptors.
1. Renin-Angiotensin System:
■ Most important mechanism for Na+ retention in order to maintain the blood volume.
■ Any drop of renal blood flow &/or Na+, will stimulate volume receptors found in juxtaglomerular apparatus of the kidneys to secrete Renin which will act on the Angiotensin System leading to production of aldosterone.
Renin
Aldosterone
Adrenalcortex
Corticosterone
Angiotensinogen
(Lungs)
renal blood flow &/or Na+
++ Juxtaglomerular apparatus of kidneys
(considered volume receptors)
Angiotensin I
Convertingenzymes
Angiotensin II(powerful
vasoconstrictor) Angiotensin III
(powerful vasoconstrictor)
• Renin-Angiotensin System:
N.B. Aldosterone is the main regulator of Na+ retention.
2. Anti-diuretic hormone (ADH), or vasopressin:
■ Hypovolemia & dehydration will stimulate the osmoreceptors in the hypothalamus, which will lead to release of ADH from posterior pituitary gland.
■ ADH will cause water reabsorption at kidney tubules.
3. Low-pressure volume receptors:
■ Atrial natriuritic peptide (ANP) hormone, is secreted from the wall of right atrium to regulate Na+ excretion in order to maintain blood volume.
Increased renal perfusion pressure
Increased pressure and flow vasa recta
Increased renal interstitial pressure Washout of medullary solute gradient
Superficial nephronsDecreased sodium resorption in proximal tubule Possible thick ascending limb
Deep nephronsDecreased sodium resorption in proximal tubule Possible thin descending limbPossible thick ascending limb
Proposed mechanism of pressure natriuresis.
Low birth weight and impaired renal development
Reduction in FSA
(Filtration surface area)
Acquired glomerular
sclerosis
Systemic/glomerular hypertension
Fig. 3 :
Na+ ingestionCentral venous volume Venous tone
Kidneys
Na+ excretion
Na+(+Cl + H2O) Plasma volumeretention
[Ca 2+ ]i [Na +]iVenous smooth muscle
[Na +]i [Ca 2+ ]i platelets
Endothelium[Na +]i [Ca 2+ ]i
ADHAdolsteroneReninANPOuabain
Arterial smoothMuscle [Na +]i [Ca 2+ ]i Sympathetic neurons
[Na +]i [Ca 2+ ]i
Blood pressure
Cardiovascularreflex activity
Arterial tone
(-)
CatecholamineRe-uptake
Catecholaminerelease
(-)
(-)
(-)
NO
(-)
(+)
Angiotensinogen
Angiotensin II
Angiotensin I
Arenalcortex Kideney CNSIntestine HeartVascular
Smoothmuscle
PeriphealNervoussystem
Aldosterone
Distal nephronreabsorption
Sodium and Waterreabsorption
Thirst Saltappetite
Adrenergicfacilitation
Sympatheticdischarge
Vasopressionrelease
Contracctility
Cardiacoutput
Maintain or increase ECFV
Total periphral resistance
Vasoconstriction
Renin
Converting enzyme Angiotension III
Angiotensinase A
Macula densa signal
Renal arteriolar pressure
Renal nerve activity
High renin(Dry vasoconstriction)
Pathophysiologic differenceArterioles
Low renin(wet vasoconstriction)
HigherHighLowLowHighHighLowYes
Peripheral resistanceAldosteronePlasma volumeCardiac outputHaematocritBlood ureaBlood viscosityTissue perfusionPostural hypotension
HighLow to HighHighHighLowLowHighNO
Clinical examplesHigh renin essential hypertesionRenovascular and malignant hypertension
Low renin essential hypertesionPrimary aldosteronism
Vascular sequelae(+) Stroke (-)(+) Heart attack (-)(+) Renal damage (-)(+) Retinopathy encephalopathy (-)
Treatments(+) Converting enzyme inhibitors (-)(+) Beta blockers (-)(-) Calcium channel blockers (+) (-) Diuretics (+)(-) Alpha blockers (+)
PRA Body Na+
HighVASOCONSTRICTION
Malignant hypertensionUnilateral renovascular hypertensionHigh renin essential hypertensionPheochromocytoma
VOLUME
Low
Medium Medium-renin essential hypertensionBilateral renovascular hypertension
Normal
LowLow-renin essential hypertesionPrimary hyperaldosteronism
High
Normal BP = (PRA, plasma renin activity) X (Na+ Volume)
Genetics Stress
Resetting ofcadiovascularcenters
Cadiovascularcenters
Increasedsympatheticoutflow
Renin-angiotensionsystem
Increased arterialpressure Increased
vascularresistance
Endothelium derivedrelaxing factors
Endothelium derivedcontracting factors
Endothelium and platelet derived mitogens
Vascularhypertrophy
Renin-angiotensin
Sympatheticnervous system
Other(genetic)
Episodichypertension
Norepinephrineangiotensin II
Peritubular capillarypressure
Peritubular capillaryflow
Capillary damagetubulointerstitial injury
Ischaemia NO Adenosine Ang II RSNA
Capillary injuryCapillary rarefaction Renal vascular Resistance
Tubuloglomerularfeed back
Pressurenatriuresis
NaCl excretion
Salt-dependenthypertension
Na-K ATPase(co-transport)
Na fluxes K fluxes
Ca binding
Ca ATPaseothers
Na-H antiport (Na-Li counter T)
Cell Na
Cell Ca
Cell pH
Na retention
Contractility
Growth
Depolarisation
Na+ / H + exchange
Renal proximal tubule cells Vascular smooth muscle cells
Na reabsorption
Vascular volume expansion
Cell Na and pH
Vascular tone Growth
Vascular wall thickness
Peripheral resistance
Hypertension
Cai2+
Acetycholine
Ca2+ Calmodulin
NO synthase
Arginine +O2 Citrulline + NO
Endothelial cell
Fe
Guanyate Cyclase
GTP cGMP Relaxation
NO
Smooth muscle cell
Type 2 diabetesmellitus
Dyslipidaemia
Obsity + Androgen increased abdominal fat Release of free fatty acids
Peripheralinsulin resistance
Increasedpancreaticinsulin secretion
Decreasedhepatic insulinextraction
Hyperinsulinaemia
Attenuatedvasodilation
Increasedsympatheticnervousactivity
Sodiumretention
Vascularhypertrophy
Hypertension
X
Lipolysis
Normal humaninsulin
Sympatheticactivation
IncreasedBlood pressure
DecreasedBlood pressure
Vasodilation
No increase in blood pressure
Obesity or hypertension insulin
Potentiatedsympatheticactivation
Impaireddepressor action
Augmented Pressure action
ImpairedDepressor action
Elevated blood pressure
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