Presentation on theme: "Pathophysiology of Hypertension Jianzhong Sheng MD, PhD Department of Pathophysiology, School of Medicine."— Presentation transcript:
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. fibersParasympathetic 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 Pressure A.Regulation of Cardiac Output B.Regulation of Peripheral Resistance C.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 Heart Contractability Autoregulation Hypertension = 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.
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 ( O 2 ), hypercapnia ( CO 2 ), & pH changes. BP + Chemoreceptors ++ V.M.C = C.I.C + Sympathetic Vasoconstriction & TPR = Parasympathetic HR Haemorrhage Hypoxia + Adrenal medulla
4. Hormonal Agents: ■ NA vasoconstriction. ■ A vasoconstriction (except in sk. ms.). ■ Angiotensin II vasoconstriction. ■ Vasopressin vasoconstriction.
Regulation of Arterial Blood Pressure C. 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 Adrenal cortex Corticosterone Angiotensinogen (Lungs) renal blood flow &/or Na + ++ Juxtaglomerular apparatus of kidneys (considered volume receptors) Angiotensin I Converting enzymes 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 pressureWashout of medullary solute gradient Superficial nephrons Decreased sodium resorption in proximal tubule Possible thick ascending limb Deep nephrons Decreased sodium resorption in proximal tubule Possible thin descending limb Possible 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 :
Angiotensinogen Angiotensin II Angiotensin I Arenal cortex Kideney CNSIntestine Heart Vascular Smooth muscle Peripheal Nervous system Aldosterone Distal nephron reabsorption Sodium and Water reabsorption Thirst Salt appetite Adrenergic facilitation Sympathetic discharge Vasopression release Contracctility Cardiac output 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 difference Arterioles Low renin (wet vasoconstriction) Higher High Low High Low Yes Peripheral resistance Aldosterone Plasma volume Cardiac output Haematocrit Blood urea Blood viscosity Tissue perfusion Postural hypotension High Low to High High Low High NO Clinical examples High renin essential hypertesion Renovascular and malignant hypertension Low renin essential hypertesion Primary 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 + High VASOCONSTRICTIONVASOCONSTRICTION Malignant hypertension Unilateral renovascular hypertension High renin essential hypertension Pheochromocytoma VOLUMEVOLUME Low Medium Medium-renin essential hypertension Bilateral renovascular hypertension Normal Low Low-renin essential hypertesion Primary hyperaldosteronism High Normal BP = (PRA, plasma renin activity) X (Na + Volume)
Renin- angiotensin Sympathetic nervous system Other (genetic) Episodic hypertension Norepinephrine angiotensin II Peritubular capillary pressure Peritubular capillary flow Capillary damage tubulointerstitial injury Ischaemia NO Adenosine Ang II RSNA Capillary injury Capillary rarefaction Renal vascular Resistance Tubuloglomerular feed back Pressure natriuresis NaCl excretion Salt-dependent hypertension
Na-K ATPase (co-transport) Na fluxes K fluxes Ca binding Ca ATPase others Na-H antiport (Na-Li counter T) Cell Na Cell Ca Cell pH Na retention Contractility Growth Depolarisation
Na + / H + exchange Renal proximal tubule cellsVascular smooth muscle cells Na reabsorption Vascular volume expansion Cell Na and pH Vascular tone Growth Vascular wall thickness Peripheral resistance Hypertension Cai 2+
Acetycholine Ca 2+ Calmodulin NO synthase Arginine +O 2 Citrulline + NO Endothelial cell FeFe Guanyate Cyclase GTP cGMP Relaxation NO Smooth muscle cell
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