An Overview of the Clinical Pathophysiology of Hypertension, its Interpretation According to Tibb Philosophy and its Relationship with Temperament- Investigating whether a trend exists between blood pressure readings and patient temperament and its responsive to the respective Tibb medications.

ABSTRACT According to Tibb philosophy, hypertension results from either hot and moist or as cold and dry excess. Therefore, those with a dominant or subdominant Sanguinous or Melancholic temperament respectively are more susceptible to the development of hypertension. Sanguinous hypertension conventionally correlates with primary or essential hypertension and would present with both high systolic and diastolic blood pressure readings, whereas the melancholic hypertension which is clinically seen as secondary hypertension presents with a high systolic and a normal or slightly elevated diastolic. The aim of this research was to evaluate and interpret the clinical pathophysiology according to Tibb philosophy and to assess whether a relationship between blood pressure readings and temperament exist. Our results found that most patients who suffered with hypertension for which there was no known clinical cause had a Sanguinous Dominant or subdominant temperament, the interpreted hypothesized pathophysiology concurs with Tibb philosophy, however the blood pressure readings recorded presented with no particular trend and were across the board according to the clinical classification stages of blood pressure readings. Only a small sample of melancholic patients were assessed, where 50% presented with isolated systolic hypertension which results from excess dryness, and the other half had not known the cause of their hypertension. The interpreted pathophysiology did not support that secondary hypertension results from excess melancholic humour as there are many secondary causes with multi-factoral pathologies. The onset of raised blood pressure in secondary hypertension results either from increase cardiac output (hot and moist) or increase systemic vascular resistance (cold and dry) or both.

Definition and classification of hypertension Hypertension is defined as an abnormal elevation in diastolic pressure and/or systolic pressure.

Hemodynamic Basis of Hypertension Increase in arterial blood pressure is caused by either an increase in systemic vascular resistance (SVR) determined by the vascular tone (i.e., state of constriction) of systemic resistance vessels an increase in cardiac output (CO) determined by heart rate and stroke volume

Categories of Hypertension Primary Hypertension-idiopathic Secondary Hypertension-identifiable cause According to Tibb Sanguinous Hypertension = primary hypertension Melancholic hypertension = secondary hypertension

Primary Hypertension Pathogenesis Early elevations of blood volume and cardiac output initiates changes in systemic vasculature (increased resistance). Inability of the kidneys to regulate sodium ↑ Na retention = ↑ blood volume Chronic long-standing hypertension Blood volume and cardiac output are normal ↑↑ systemic vascular resistance ∵ thickening of the walls and reduction in lumen diameter. ↑ vascular tone ∵ enhanced sympathetic activity or ↑ angiotensin II ↓ nitric oxide is produced and vascular smooth muscle is less senstive to the action of this vasodilator. ↑ endothelin production- enhance vasoconstrictor tone

Interpretation According to Tibb Philosophy Sanguinous Hypertension Later oxidation leads to ↑ dryness C & D Hypertension

Secondary Hypertension

Renal Artery Stenosis

Chronic Renal Disease ∵ diabetic nephropathy; glomerulonephritis etc. Damage caused to the nephrons Impaired excretion of sodium → sodium retention and ↑ blood volume → ↑ cardiac output by Frank Starling mechanism May also result in ↑ release of renin

Primary Aldosteronism

Stress Activation of sympathetic nervous system → ↑ norepinephrine in heart and blood vessels → ↑ cardiac output and ↑ systemic vascular resistance Adrenal medulla secretes catecholamines (epinephrine and norepinephrine) ↑ angiotensin II, aldosterone and vasopressin Cardiac and vascular hypertrophy = sustained ↑ blood pressure

Sleep Apnea Higher incidence of hypertension The mechanism of hypertension may be related to sympathetic activation and hormonal changes associated with repeated periods of apnea-induced hypoxia and hypercapnea, and from stress associated with the loss of sleep.

Hyper- or hypothyroidism Excessive thyroid hormone induces systemic vasoconstriction, an ↑ blood volume, and ↑ cardiac activity, all of which can lead to hypertension. Hypothyroidism unclear may be related to ↓ tissue metabolism reducing the release of vasodilator metabolites, thereby producing vasoconstriction and increased systemic vascular resistance.

Pheochromocytoma ↑↑ catecholamines (both epinephrine and norepinephrine) This leads to alpha-adrenoceptor mediated systemic vasoconstriction and beta-adrenoceptor mediated cardiac stimulation → ↑↑ arterial pressure.

Pre-eclampsia 3rd trimester of pregnancy ↑ blood volume and tachycardia The former increases cardiac output by the Frank- Starling mechanism

Aortic coarctation Elevated pressures proximal to the coarctation (i.e., elevated arterial pressures in the head and arms) Distal pressures are not necessarily reduced Reduced systemic blood flow and reduced renal blood flow → ↑ renin and an activation of the renin-angiotensin- aldosterone system → ↑ blood volume and arterial pressure Baroreceptor reflex in blunted due to structural changes in the walls of vessels where the baroreceptors are located Baroreceptors become desensitized to chronic elevation in pressure and become "reset" to the higher pressure

Isolated Systolic Hypertension Defined as SBP ≥ 140mmHG and DBP ≤ 90mmHG 60% of hypertensives > 80 years old From age 35/40 many people have elevated systolic or diastolic pressure and this elevation leads to the widening and stiffening of the aorta ↓ elasticity and ↓ compliance of the large blood vessels → ↑ SBP and ↓ DBP

Interpretation according to Tibb Philosophy Renal Artery Stenosis- ↑ cardiac output and ↑ vascular resistance Multifactoral Pt and temperament specific Chronic renal disease- impaired salt homeostasis Sanguinous Primary aldosteronism - ↑ blood volume Sanguinous

Continued… Stress - ↑ cardiac output and ↑ systemic vascular resistance Pt and temperament specific Sleep apnea – more prevalent in obese pt Phlegmatic or sanguinous Hyperthyroidism Bilious Hypothyroidism Phlegmatic

Continued… Pheochromocytoma- ↑ systemic vascular constriction and ↑ cardiac output Pt and temperament specific Pre-eclampsia- ↑ blood volume and tachycardia → ↑ cardiac output Aortic coarctation Associated with moistness Congenital condition in children Isolated systolic hypertension- increased resistance of large arteries Elderly pt melancholic

Blood pressure relationship with Temperament AgeSexDominantSubdominantinitial BPsynthetic medication 65FMelancholicPhlegmatic170/100N 45MSanguinousPhlegmatic160/120Y 74FMelancholicBilious140/76Y 45MSanguinousBilious140/90Y 61FSanguinousBilious180/110N 72FMelancholicPhlegmatic200/80N 49FSanguinousPhlegmatic130/100N 43MSanguinousPhlegmatic160/110N 44MSanguinousBilious140/96N

Continued…. 57FSanguinousBilious160/90Y 55FPhlegmaticSanguinous160/98Y 54FSanguinousPhlegmatic119/78Y 53FSanguinousPhlegmatic164/90Y 54MPhlegmaticSanguinous140/90Y 49FPhlegmaticSanguinous170/110Y 52FPhlegmaticSanguinous140/100N 35MPhlegmaticSanguinous130/95N 22FPhlegmaticSanguinous150/100N 68FSanguinousBilious160/90Y 30FMelancholicBilious150/110N 50FBiliousSanguinous200/100Y/N

Sanguinous dominant or sub- dominant pts AgeSexDominantSubdominantinitial BPsynthetic medication 45MSanguinousPhlegmatic160/120Y 45MSanguinousBilious140/90Y 61FSanguinousBilious180/110N 49FSanguinousPhlegmatic130/100N 43MSanguinousPhlegmatic160/110N 44MSanguinousBilious140/96N 57FSanguinousBilious160/90Y 55FPhlegmaticSanguinous160/98Y

Continued… 54FSanguinousPhlegmatic119/78Y 53FSanguinousPhlegmatic164/90Y 54MPhlegmaticSanguinous140/90Y 49FPhlegmaticSanguinous170/110Y 52FPhlegmaticSanguinous140/100N 35MPhlegmaticSanguinous130/95N 22FPhlegmaticSanguinous150/100N 68FSanguinousBilious160/90Y 50FBiliousSanguinous200/100Y/N

Melancholic pts AgeSexDominantSubdominantinitial BPsynthetic medication 65FMelancholicPhlegmatic170/100N 74FMelancholicBilious140/76Y 72FMelancholicPhlegmatic200/80N 30FMelancholicBilious150/110N

SB case studies 21 total pt 17 pt sanguinous dominant or subdominant 81% 4 pt melancholic dominant or subdominant 19% Sanguinous/dominant subdominant pt 15 ↑↑ SBP and ↑↑ DBP 88% years old 1 Normal BP- using synthetic medications 1 normal SBP and ↑↑ DBP Melancholic dominant/subdominant pt 2 ↑↑ SBP and normal DBP 50% Age > 70years 2 ↑↑ SBP and ↑↑ DBP 30 and 65 years old

Dr. Andreas Kefaldelis Research Project AgeSexDominantSubdominantBPsynthetic medication 37FSanguinousPhlegmatic136/95N 46FPhlegmaticSanguinous148/110N 35MSanguinousPhlegmatic168/117N 55FSanguinousBilious144/93N 23FSanguinousPhlegmatic139/92N 49FPhlegmaticSanguinous181/102Y 56FPhlegmaticSanguinous193/92N 33FSanguinousPhlegmatic149/105Y 43MPhlegmaticSanguinous187/152Y/N 64MSanguinousBilious210/110N

Continued… 31FSanguinousPhlegmatic150/114N 52FSanguinousPhlegmatic205/155Y 64FPhlegmaticSanguinous210/160Y/N 47FSanguinousBilious165/115Y 29FSanguinousPhlegmatic134/105N 47FPhlegmaticSanguinous145/116N 62FPhlegmaticSanguinous160/129N 27MSanguinousPhlegmatic140/100Y 51FSanguinousBilious192/111N 49MSanguinousPhlegmatic167/67N 55fSanguinousPhlegmatic154/99Y

Continued… 41MSanguinousPhlegmatic162/102N 35FPhlegmaticSanguinous145/89N 58FSanguinousPhlegmatic160/93N 36MSanguinousPhlegmatic157/85N 50MPhlegmaticSanguinous172/118N 57MSanguinousPhlegmatic182/112N 35MSanguinousBilious135/91N 53FSanguinousBilious134/84N 40FSanguinousPhlegmatic158/102N 27MSanguinousPhlegmatic148/95N 75MSanguinousPhlegmatic202/105Y

Continued… 57MSanguinousBilious167/120Y 24FSanguinousPhlegmatic130/96N 27MSanguinousBilious151/100N 24FPhlegmaticSanguinous153/94N 50MSanguinousPhlegmatic178/112N 53FSanguinousPhlegmatic163/100Y 52FPhlegmaticSanguinous156/102N 51MPhlegmaticSanguinous151/103N 40FSanguinousPhlegmatic148/113N 21FSanguinousPhlegmatic138/91N 49MPhlegmaticSanguinous145/97Y 53MSanguinousPhlegmatic184/118N 49FPhlegmaticSanguinous148/94N 38FSanguinousPhlegmatic147/102N

Dr. Andreas Kefaldelis Research Project 46 total pts 100% dominant/subdominant sanguinous temperament 36 pts ↑↑ SBP and ↑↑ DBP 78% years old 6 pts ↑↑ DBP 13% years old 3 pts ↑↑ SBP 7% years old 1 pt had wide pulse pressure 1 pt prehypertension

Effects of synthetic medication on blood pressure readings Prehypertension Stage 1Stage 2mixed 134/84 N 144/93 N168/117 N136/95 N 154/99 Y181/102 Y148/110 N 148/95 N187/152139/92 N 153/94 N210/110 N193/92 N 145/97 Y205/155 Y149/105 Y 148/94210/160134/105 N 140/90 Y165/115Y145/116 N 140/96 N160/129 N140/100 Y 140/90 Y192/111 N167/67

172/118 N145/89 N 182/112 N160/93 N 202/105 Y157/87 N 178/112 N135/91 N 163/100 Y158/ /118 N130/96 N 160/120 Y151/100 N 180/110 N156/102 N 170/110 N151/103 N 200/100148/113

o 138/91 147/ /100 N 160/90 Y 160/98 164/90 Y 140/100 N 130/95 N 150/100 N 160/90 Y

Prehypertension Stage 1Stage 2Mixed 1 N 4 N10 N18 N 4 Y6 Y5 Y 1 non compliant3 non compliant6 non compliant

Stages of blood pressure readings on mixed BP measurements Stage 1/Stage 2 12 patients 2 hypotensive medication 7 no medication 3 non compliant Stage 2/Stage 1 6 patients 3 hypotensive medication 2 no medication 1 non compliant Prehypertension/stage 1 or 2 8 patients 7 no medication 1 non compliant Stage 1 or 2/prehypertension 3 patients 2 no medication 1 non compliant

90-95% pts suffer with primary hypertension 91% of total pts in this study Sanguinous dominant/subdominant temperament Concludes primary hypertension = sanguinous hypertension No relationship exists between the blood pressure reading and the quality of hypertension Synthetic medication did not affect the overall results as most patients were not using any hypotensive agents

Elderly melancholic pts are more susceptible to developing isolated systolic hypertension Research suggests that obese pt have higher cardiac outputs BUT lower total peripheral vascular resistance compared to lean patients More research on melancholic patients with hypertension is needed

Response to Tibb medication Most patients responded positively when given a combination of pressure eeze and pressure eeze forte Pathogenesis generally complex and multi-factoral Combination therapy combats both ↑ cardiac output (pressure eeze forte) and ↑ systemic vascular resistance (pressure eeze) 1 elderly isolated SBP pt had no response to Rx 1 elderly isolated SBP pt responded well to pressure eeze alone 1 sanguinous pt had ↓ DBP but an ↑ SBP 2 sanguinous pt had no response when given pressure eeze in isolation but responded positively with combination Rx 1 sanguinous pt had no response to both pressure eeze and pressure eeze forte 1 sanguinous pt had ↓ SBP but no response in diastolic blood pressure

Considerations Compliancy to lifestyle factors were not considered in this study White coat hypertension- anxiety in dr’s office may ↑ BP by 26mmHg Small sample- findings not absolute Effects of other chronic disease on hypertension Dyslipidaemia Hyperinsulinaemia and hyperglycaemia (type II diabetes) endothelial dysfunction Free radical damage ↓ nitric oxide bioavailability

References 1. cardiovascular physiology, 2. isolated systolic hypertension: an update, low diastolic ambulatory blood pressure is associated with greater all cause mortality in older patients with hypertension, hypercholesterolaemia and its potential role in the presentation and exacerbation of hypertension, 5. white coat effect and white coat hypertension: what do they mean?, the relationship between body weight and the prevalence of isolated systolic hypertension in older subjects, To assess the relationship between the qualities associated with chronic disorders and the temperament of the person affected. By Dr Andreas Kefaladelis