Blood pressure variation in the left ventricle (Blue line) & aorta (Red line) showing the cyclic...

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HYPERTENSIONhigh blood pressure

Definition of Hypertension

Chronic elevation of blood pressure.

140/90 mmHg

“Systemic, Arterial Blood Pressure”

Blood pressure variation in the left ventricle (Blue line) & aorta (Red line) showing the cyclic variations of systolic and diastolic pressure

elastic recoil

Etiology of Hypertension

• Primary Hypertension “Essential Hypertension”

• Secondary Hypertension

95%

2ry to another medical condition

No identifiable cause

Pheochromocytoma catecholamine

Cushing syndrome cortisol

Secondary Hypertension

Suprarenal: adenoma

Cushing Syndrome

Suprarenal: adenoma


Suprarenal: adenoma

Cushing Syndrome

Polycystic Kidney


Renal: Tumors


Renal: Renal Artery Stenosis

Coarctation of Aorta


Liquorice 11β-hydroxysteroid dehydrogenase enzyme mineralocorticoid® BP &® K+

Drugs


NSAIDsCOX2 selectiveSteroids

Pregnancy


PIHPreclampsia “EPH gestosis”

Sleeping Disturbance


• Tonsil enlargement

• Postnasal adenoma

• DNS

• Obesity.

Sleeping Disturbance


Management:Mandibular Advancement Splint (MAS), tonsillectomy, adenoidectomy, septoplasty or weight loss.


Hyperthyroidism

Hypothyroidism

Ca

Other Causes:

Rebound hypertension


Withdrawal ofClonidineBBs

Diagnosis of Hypertension

Korotkoff sounds

K1K2K3K4K5

Symptoms & Signso No symptomso Symptoms of 1ry Cause (2ry hypertension)o Headache, Fatigue, Blurred Vision, Epistaxiso Nausea – Vomiting.o Retina : copper or silver wire appearance, exudates, hemorrhages or papilledema.

Complications of Hypertension

vasogenic edema

Metabolic Syndrome

nephrosclerosis

Risk Factors of 1ry Hypertension

Risk Factors

Primary Hypertensionno identifiable reversible cause

o Sedentary lifestyleo Obesityo Insulin resistanceo Metabolic syndromeo Agingo Alcoholo Vitamin-D deficiency

Risk Factors

Primary Hypertension

o Low birth-weighto Family historyo Genetico Na+ sensitivityo Sympathetic overactivityo Renin overactivity

no identifiable reversible cause

Pathophysiology Hypertension

Factors Affecting Arterial Blood Pressure

Management of Hypertension

ResistantHypertension

Failure to reduce blood pressure to the appropriate level after taking a 3-drug regimen including thiazide.

Management of

Hypertension

Prevention

Lifestyle advice (non-pharmacological control)

Should be offered to the patient, before initiation of any drug therapy.

Lifestyle Changes

Healthy Diet

Salt Restriction

DASH diet: (dietary approaches to

stop hypertension)

Rich in fruits & vegetables and low-fat or fat-free dairy foods.

Weight Reduction

More ExerciseExercise

Reduce Stresses

HypertensionManagement

Guidelines

Lifestyle Changes “American & British Guidelines” suggest that:

Lifestyle changes should be explored in all patients who are hypertensive or pre-hypertensive.

Classification of

Hypertension

Classification of Hypertension

Systolic pressure

Diastolic pressure

mmHg mmHg

Normal 90–119 60–79

Pre-hypertension 120–139 80–89

Stage 1 140–159 90–99

Stage 2 ≥160 ≥100

Isolated systolic HT ≥140 <90

&

&

or

oror

STROKEMIHF BY 40%

25%50%

AMERICAN GUIDELINES

UK Hypertension GuidelinesStarting

Treatment threshold

GroupTreatment Target

>160/100 All those with such persisting readings >160/100. <140/90

>140/90

Have established cardiovascular disease, or Have C.V. Risk (>20% per 10 years), or Have evidence end-organ damage without D.M., or Ch. renal dis., without Macroalbuminuria (or D.M.)

<140/90

>130/80 Type-2 Diabetes alone. <130/80

>135/85 Type-1 Diabetes alone. <130/80

>130/80Type-1 or 2 Diabetes with microalbuminuria. Type-1 or 2 Diabetes with renal, eye or CV damage.

<130/80

>130/80 Chronic renal disease with Macroalbuminuria. <125/75

COMPELLINGINDICATIONS

Urine ALB/CR 2

DIABETIC HYPERTENSION

Diabetic Nephropathy with (Microalbuminuria)

ACEIs / ARBs.

Diabetic Nephropathy with (Macroalbuminuria)

ARBs / ACEIs.

Diabetic Hypertension without Nephropathy

ACEIs / ARBs +/- Thiazide +/- CCBs.

Urine ALB/CR 2

Definition: [ GFR 60 ml / min / 1.73 m2 (= serum creatinine 1.5 mg / dL or 1.3 mg / dL )] [Albuminuria 300 mg/day (macroalbuminuria)].

Treatment Goal: Aggressive BP Lowering 125/75

Compelling Drug: ACEIs or ARBs (Diabetic or non-Diabetic Nephropathy). N.B. GFR (serum creatinine) up to 35% from baseline is acceptable , And is NOT a reason to withhold treatment unless hyperkalemia develops.

In Advanced Renal Disease: [= GFR 30 ml / min / 1.73 m2 (serum creatinine 2.5 - 3mg / dL)]:Increasing dose of loop diuretic is usually needed with ARBs or ACEIs)

CHRONIC RENAL DISEASE

HEART FAILURE

Asymptomatic HF ACEIs / ARBs + BBs.

Advanced HF ACEIs / ARBs + BBs + Diuretic.

CEREBRO-VASCULAR STROKE

Risks & Benefits of ACUTE Lowering of BP DURING acute CV Stroke are still unclear.

Control of BP at intermediate levels (approximately 160/100 mmHg) is appropriate until condition is stabilized or improved.

Stroke rates are lowered better by ACEIs / ARBs + Thiazide.

ISCHEMIC HEART DISEASE

Asymptomatic Angina: BBs or CCBsSymptomatic Angina: ACE-Is / ARBs

(ARBs in Patients can’t tolerate ACE-Is)Acute MI (elevated ST segment): ACE-Is / ARBs + BBs

(ARBs in Patients can’t tolerate ACE-Is)

N.B. CCBs if given there should be extreme cautious to avoid heart failure.

AA, aldosterone antagonist; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II-receptor blocker; βB, ß-blocker; CCB, calcium channel blocker; MI, myocardial infarction; CAD, coronary artery disease.

JAMA. 2004;289(19):2560-2572.

The Seventh Report of the Joint National Committee

Compelling Indications Diuretic ßB ACEI ARB CCB AA

Heart failure Post-MI

High CAD risk Diabetes

Chronic kidneydisease

Recurrent stroke

prevention

Difference Between American & British Guidelines

Thiazide

ACE-I ARB CCB BB

BB

ThiazideACE-I ARB CCB

American Guidelines

British Guidelines

AntihypertensiveDrugs

CLASSES OFANTIHYPERTENSIVE

DRUGS

DIURETICS

DIURETICSDrugs used to do forced diuresis.

INDICATIONS:

o Treatment of Heart Failure.o Treatment of Hypertension.o Treatment of Liver cirrhosis.o Treatment of Certain Renal Conditions.o Urine Alkalinization To Treat Aspirin overdose:Acetazolamide ( carbonic anhydase H+ excretion)

The Use of Diuretics Require Electrolyte &

Acid-base Balance Monitoring

DIURETICSTHIAZIDE DIURETIC:

o Antihypertensive independent from its diuretic effect At a dose that causes diuresis. Due to Direct Vasodilator Effect Peripheral Resistance BP Afterload

At dose causing diuresis Blood Volumevenous return Preload

o Compelling Indication in HF

o Least S.E.

DIURETICSAdvantages of thiazide diuretic:

o Least S.E.o Drug of 1st Choice in JNC7.o Causes synergism when combined with any antihypertensive therapy. o Compelling indication in HF.o Also Ca sparing diuretic.

Osmoticmannitol glucose

furosemide

HCTchlortalidone spironolactone

CAIacetazolamide

Loop Diuretics

Lasix

o High Ceiling diuretic: “cause up to 20% increase in Na+ filtration load”

o Safer for Short term use only

Potassium Sparing Diureticso Used mainly to Correct Hypokalaemia “caused by other diuretics or digitalis”.

o Spironolactone AA: A compelling indication in HF.

Adverse Effect Type of Diuretics Example Clinical EffectHypovolemia Loop Diuretic

ThiazideLasixHCT 25 mg/day

HypotensionThirst GFR

Hypokalemia Loop DiureticThiazideCarbonic Anhydrase Inhibitor

LasixHCT 25 mg/dayAcetazolamide

Muscle weaknessCardiac arrhythmia

Hyperkalemia Potassium Sparing Diuretics Spironolactone Muscle CrampsCardiac arrhythmia

Hyponatremia Loop DiureticThiazide

LasixHCT 25 mg/day

Neurological manifestations

Metabolic Alkalosis Loop DiureticThiazide

LasixHCT 25 mg/day

CNS manifestationsCardiac arrhythmia

Metabolic Acidosis Potassium Sparing Diuretics

CAI

Amilorides – triamtereneAcetazolamide

muscle weakness neurological symptomsseizures

Decrease Ca++ Excretion Thiazide HCT Prevents OsteoporosisPrevents Renal calculi

Hyperuricemia Loop Diuretic Lasix Gout

α-blockers

α-adrenergic receptors are present in the smooth muscles e.g. prostate, arteries & veins. α1 -adrenergic stimulation smooth muscles contraction vasoconstriction.α1-adrenergic blockers Relaxing vascular smooth muscles vasodilatation vascular resistance hypotension.α1-adrenergic blockers Relaxing prostate & U.B. neck.

α-blockers(α1 blockers or α1 antagonists)

α-blockers(α1 blockers or α1 antagonists)

Other minor effects:Relaxing cardiac muscle COP hypotension.

Side effects:o Relaxing cardiac muscle Heart Failure.o Appetite obesityo Dryness of moutho Weak antihypertensive

( HF events - ALLHAT)

β-blockers

β-blockers(β-blockers or β-antagonists)

β-adrenergic Receptors Location:o β1-adrenergic receptors mainly in : Heart & kidneys.

o β2-adrenergic receptors mainly in : Smooth muscles, (vascular – bronchial) Liver & Sk. Muscles.o β3-adrenergic receptors : Fat cells.


o β2 : Bronchodilation. Vasodilatation. Affect Glycogen Breakdown in Liver & Skeletal muscles

o β3 : Lipolysis.

Renin Release BP.

Stimulation of β-adrenergic Receptors:o β1 : +ve Chronotropic on heart muscle. +ve Inotropic on heart muscle.


Blocking of β-adrenergic Receptors By β-blockers :o β1 : Stress & Physical exertion effect on heart muscle. HR & Cardiac contractility force. Renin Release BP.

o β2 : Bronchospasm induces asthma Vasospasm BP. NB. (non selective β-blockers induce overall hypotension)

o β3 : Diabetogenic.


( cardiac workload oxygen demand)

o Management of cardiac arrhythmias

( conduction & HR)

o Antihypertensive. ( COP & vascular resistance)

Indications of β-adrenergic blockers:o Cardio-protection after MI


Side Effects of β-blockers :o Bronchospasm & dyspnea.o Diabetogenic Risk: disturbed glucose & lipid metabolism:Recent studies revealed that: Diuretics and β-blockers risk of diabetes ACE inhibitors & ARBs risk of diabetes.

That is why UK clinical guidelines :recommend avoiding diuretics and β-blockers as first-line treatment of hypertension.


Other Side Effects of β-blockers :oHyperkalemia.o Erectile dysfunction.o Bradicardia, heart failure, heart block.o Hypotension, orthostatic hypotension.o Tremors.o Insomnia

Anti-Renin Effect

melatonin.

Calcium Channel-blockers (CCBs)Mode of Action: Disrupt the calcium ions (Ca+2) transport at calcium channels:o In vascular smooth muscles o In cardiac muscle

vascular resistance.

contractility Stroke volume COP.o In cardiac muscle HR

INDICATIONS:o Hypertension o Atrial flutter & AF BBs are better than CCBs

CCBs are better than BBs

o Angina vascular resistance BP contractility

Work load & O2 demand

Calcium Channel-blockers (CCBs)Side effects :o Headache. o Flushing. o Lower limb edema

o At high doses CCBs block the effect of insulin.

Contraindicated in HFo Direct Bradycardia.o Reflex Tachicardia:Direct vasodilatation stimulate baroreceptors HR(That’s why BBs are better in controlling AF)(That’s why CCBs better avoided in MI)

Side effects :o Headache. o Flushing. o Lower limb edema

AnginaAF

Hypertension+ cardiotropic

ACE-Is & ARBs

Renin Angiotensin

Aldosterone

System

Renin Angiotensin

Aldosterone

System

R A AS

Anatomy & PhysiologyOf Renal

Glomerulus

Nephron

GFRIGP

Glomerular Corpuscle

Juxta glomerular cells

macula densa

Afferent arteriole

Efferent arteriole

Distal convoluted tubule

Urinary chamber

Bowman’s capsule

Basement membrane -Podocytes

Proximal convoluted tubule

Urinary excretion: Fluid & electrolyte filtration from capillary side to urinary side through the basement membrane & podocytes to the urinary chamber of the glomerulus.

RENIN

BP

Na

BP

GFR

GFR

Direct Na+ H2O retention

water retention Bl

ood

Bloo

d

Bloo

d

urine

urine

BP

GFR


water retention

Bloo

dBl

ood

Bl

ood

urine

urine

BP

GFR

GFRIGPAfferent vasodilatation

Efferent vasoconstriction

BP

RENIN

Functional & Structural Changes of RAAS Activation


water retention Bl

ood

Bloo

d

Bloo

d

urine

urine

water retention

BP

GFR

BLOOD VOL

GFRIGPAfferent vasodilatation

Efferent vasoconstriction

RENIN

BP

Functional ChangesIn HemodynamicsRenal Hyper-Filtration

Magdi El-ShalakanyMean Arterial Pressure (mm Hg)

Intr

aglo

mer

ular

Pre

ssur

e

Chronic hypertension with chronic

renal disease

Chronic hypertensionNormal

Low

High

80 120 160 18014010060

Renal Autoregulatory Curve

with normal renal function

The Continuum of Diabetic

Nephropathy

Structural Changes of RAAS Activation

RENAL CORPUSCLE

podocytesbasement membrane

Bowman's capsule

PCT

DCT

urinary Space

mesangial tissue

Juxtaglomerular cells

Macula densa

Juxta-Glomerular Apparatus

Renin

smooth muscle

cells

glomerular capillaries

(afferent)(efferent)

RAAS STIMULATION1. Hypertension2. IGP3. Renal Hyperfiltration4. Renal Tissue injury5. Structural & Morphological

Changes :• Mesangial tissue expansion• Basement membrane thickening• Podocyte pedicles’ detachment• Intraglomerular Fibrosis

ACE-I1. BP2. IGP3. Renal t. injury4. GFR5. Bradykinin S.E:• Persist Dry Cough• Inflammation symp• Angio-edema

6. Tolerance

Degradation

RAAS STIMULATION1. Hypertension2. Left Ventricular remodeling (CHF)3. IGP4.Renal Hyper-filtration5.Renal Tissue injury Chronic renal disease6.Structural & Morphological Changes :o Mesangial tissue expansiono Basement membrane thickeningo Podocytes pedicles’ detachmento Intraglomerular Fibrosis

ACE-I EFFECTS1. BP2. sympathetic tone peripheral resistance3. Na+ & water retention blood volume 4. sympathetic tone HR5. COP & Heart work load & O2 consumption

ACE-I INDICATIONS1. Hypertension2. Heart Failure3. Angina4. Post myocardial infarction

Prophylaxis in Acute Coronary Syndrome

ACE-I EFFECTS6. Intra-Glomerular Pressure (IGP)7. Renal Hyper-filtration8. Renal Tissue injury9. Improve functional & structural renal condition10. Structural & Morphological Changes11. micro & macro-albuminuria

ACE-I INDICATIONS5. Diabetic Nephropathy6. Chronic renal disease

Both due to BP & also independent to its Antihypertensive Effect

ACE-I SIDE-EFFECTS1. Bradykinin & inflammatory related S.E:o Persistent Dry Cougho Angio-edemao Rash o Inflammation-related Pain

2. GFR Creatinine Clearance Rate (Ccr or C C) serum Creatinine

GFR (serum creatinine) up to 35% from baseline is acceptable & is NOT a reason to withhold treatment unless hyperkalemia develops.

3. Hyperkalemia

4. Metallic Taste (sulfhydryl part in Captopril molecule)

1. Renal artery stenosis (bilateral)

2. Renal artery stenosis (Unilateral)3. Impaired renal function (ACE-Is may GFR).4. Aortic valve stenosis or cardiac outflow obstruction (ACE-I COP). 5. Hypovolemia or dehydration (ACE-Is diuresis ( fluid volume)

& BP).

6. Pregnancy (category D)

ACE-I ContraindicationsAbsolute Contraindications

Relative Contraindications

ACE-I is Contraindicated in Pregnancy

Why ARBs Are Better than ACE-Is?

(afferent)(efferent)

RAAS STIMULATION1. Hypertension2. IGP3. Renal Hyperfiltration4. Renal Tissue injury5. Structural & Morphological

Changes :• Mesangial tissue expansion• Basement membrane thickening• Podocyte pedicles’ detachment• Intraglomerular Fibrosis

ACE-I1. BP2. IGP3. Renal t. injury4. GFR C Cr5. Bradykinin S.E:• Persist Dry Cough• Inflammatory symptoms• Angio-edema

6. Tolerance

Degradation

ARBs are better than ACE-Is1. No Bradykinin & inflammatory related S.E:

o Persistent Dry Cougho Angio-edemao Rash o Inflammation-related Pain

2. ARBs prevent excessive GFR Creatinine Clearance Rate which serum creatinine.

It Keeps the Drop in GFR & C cr (if occur) 35% from baseline which is acceptable & So No Need to Withhold treatment.

3. No Decline of Anti-Hypertensive Effect

4. No Metallic Taste (sulfhydryl part in Captopril molecule)

Beside All Benefits of ACE-Is

Factors Affecting Arterial Blood Pressure

Diuretics

Diuretics

α-blockers

β-blockers

β-blockers

CCBs

CCBs

CCBs

ACE-Is/ARBs

ACE-Is/ARBsACE-Is/ARBs

ACE-Is/ARBs

ESH 2010: Possible Drug Combinations of Different Classes of Antihypertensive Agents

-blockers

-blockersCalcium

antagonists

AT1-receptorblockers

Diuretics

ACE inhibitors

The most effective and well tolerated combinations are shown as solid lines

ESH Guidelines. J Hypertens. 2007;25:1105-1087. ESH= European Society of Hypertension

THANKYOU

Renal Functions &

Renal Disease

Renal Disease Terminologyo CRD = Chronic Renal Disease.o GFR = Glomerular Filtration Rate.o BUN = Blood Urea Nitrogen = Uremia = Azotemia.o ESRD = End Stage Renal Disease (= Need for Dialysis or Kidney Transplant)

o Plasma concentrations of creatinine and urea (BUN = Blood Urea Nitrogen) are used to measure renal function.

Kidney Function Tests

o Creatinine clearance rate (CCr or CrCl): “A measure for GFR”.

o BUN and serum creatinine will not be raised normal Until 60% of total kidney function is lost.

o Creatinine clearance (CCr or CrCl) is then more accurate to measure suspected renal disease.

Kidney Function Testso Proteinuria (elevated level of protein (albumin) in urine) : It is an important Prognostic marker for renal disease. o Albumin level 30 mg/24 hr urine is diagnostic for chronic kidney disease o Microalbuminuria is a level of 30-300 mg/24 hr urine; (can not be detected by usual urine dipstick methods).o Macroalbuminuria is a level 300 mg/24 hr urine.

KEY MESSAGES OF AMERICAN GUIDELINES AND BRITISH GUIDLINES

KEY MESSAGES OF AMERICAN GUIDELINES “JNC7”

1. In patients 50 yr : SBP ( 140 mmHg) is much more important Risk Factor for CVD than DBP.

2. CVD Risk doubles with each increment of 20/10 mmHg (above normal).

3. Pre-hypertensive patients (SBP 120-139 / DBP 80-89) Require Lifestyle modifications to CV Risk.


4. Thiazide diuretic is drug of First choice for most patients with uncomplicated hypertension.

5. Certain Risk conditions are Compelling Indications For Other Anti-hypertensive Agents (e.g. ACE-Is , ARBs , CCBs , BBs …. etc)

6. Most hypertensive patients will require 2 or more antihypertensive agents to Achieve Treatment Goals:

( 140/90 mmHg, or 130/80 mmHg for Diabetic or Chronic Renal disease patients )

7. If BP is 20/10 mmHg above Goal, consider additional agent therapy, one of which should be thiazide.


8. Empathy & Motivating Patients are very important to reach Treatment Goal.

9. Responsible Physician’s Judgment remains paramount in the presence of these guidelines.

What Are The Main Differences In British

Guidelines?

UK Guidelines Recommendations

1. In hypertensive patients aged 55 or black patients of any age, the first choice for initial therapy should be either a CCB or a thiazide-type diuretic .

2. In hypertensive patients younger than 55, the first choice for initial therapy should be an ACE inhibitor /(ARBs).


3. If initial therapy is a CCB or a thiazide diuretic & a second drug is required, an ACE inhibitor /(ARBs) should be added.

4. If initial therapy was with an ACE-I or a CCB, a thiazide diuretic should be added.


5. If treatment with three drugs is required, the combination of ACE-I /(ARBs) , CCB, and thiazide diuretic should be used.6. If a fourth drug is required, one of the following should be considered:

a- A higher dose thiazide diuretic,

b- Another diuretic (with careful monitoring),

c- β-blockers, d- α-blockers.


8. Beta blockers are not preferred as initial therapy of hypertension.

β-blockers may be considered in young

age, and those with intolerance or

contraindication to ACE inhibitors and ARBs: e.g. women with child-bearing potential.


9. When a β-blockers is withdrawn, dose should be stepped down gradually.

β-blockers should NOT be withdrawn in patients with compelling indications for β-blockers:

e.g. those who have symptomatic angina or who have had myocardial infarction.

Blood pressure variation in the left ventricle (Blue line) & aorta (Red line) showing the cyclic...

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