Hypertension and kidney Dr.Suresh Kumar

Introduction

Essential Hypertension is mainly due to abnormal retention of sodium There is also genetic predisposition to HTN and progress has been

made to identify the genes responsible for HTN A number of studies also showed low birth weight causes deficient

number of nephrons which in turn causes HTN Obesity per se if not superimposed by low birth weight may be the

cause for HTN Recent development of devices to disrupt the plexus of renal

sympathetic nerves in the adventitia of renal arteries has also become a point of interest in Rx of HTN

Hypertension and kidney The driving force for Glomerular filtration is the blood pressure

and kidneys with inbuilt mechanisms to maintain blood pressure offer a survival advantage

Blood pressure is the product of cardiac output and peripheral resistance

Cardiac output largely depends on the blood volume which is mainly salt and water , the peripheral resistance is determined by the state of tone in resistance vessels

Vasoconstriction is the immediate response to hypotension , but all vasoconstrictor stimuli also initiate mechanisms to retain salt and water So long term maintanence of blood pressure is mainly dependant on

blood volume.

Ancient man has discovered SALT as a preservative and an ingredient as food , and now its use has become excess that body could not handle it

The only way excess salt can be excreted is to shut off the pathways for reabsorption

The most effective tool for excretion is pressure natriuresis High blood pressure in arterioles is transmitted to renal peritubular

capillaries and interstitium and inhibits re absorption of sodium and water by proximal tubule leading to natriuresis

As juxta medullary glomerular arterioles are less capable of constriction in response to HTN vasa recta and medullary interstitium even have high pressure

Increased sheer stress in vasa recta causes release of NO which inhibits sodium transporters in Medullary tubules.

Pressure Natriuresis limits sodium retention and returns BP to baseline

Genetic

There is strong genetic predisposition to HTN Having one Hypertensive in a family increases the risk of other members of having

HTN Inheritance of HTN is a dominant trait A genetic predisposition to HTN coupled with a excessive salt intake leads to HTN and

what we call essential HTN is salt related in susceptible individuals It is clear that incidence of salt sensitive HTN increases with Age Age is associated with stiffening of arteries and arterioles , it is likely that such

senescent arterioles interfere with pressure natriuresis and it causes increased incidence of HTN

The KIDNEY is therefore the cause of the most ESSENTIAL HTN even when renal function is quite normal

In addition most renal diseases are associated with either sodium retention or with over action of RENIN angiotensin system or both and are the major cause of Secondary HTN.

Developmental origins of health and disease

It has been found that low birth weight predispose to HTN in adult hood., particularly if those people become over weight later.

Infants with LBW Or SGA have smaller number of nephrons than those with normal birth weight

When fetal nutrition's is compromised the brain and heart receive more nutrients than kidney

Nephron number has been found reduced in LBW infants Every KILOGRAM of birth weight corresponds to 2,57,426 Glomeruli. Low nephron numbers are associated with large glomeruli and single

nephron Hyper filtration so total glomerular filtration is normal but hyperfiltration progressively damages kidney and leads to CKD.

These kidneys with deficient number are unable to excrete the excessive quantities of Sodium

The Blood pressure Natriuresis set point is reset ever higher and leading to Hypertension

This is a significant cause of HTN especially in developing countries

Obesity and HTN Many factors have been described like

Significantly Hyperactivity of Renin Angiotensin System Sympathetic System Hyperinsulinemia Vasoconstriction and Sodium Retention Pro Inflammatory Cytokines and Oxidative Stress

endothelial Dysfunction and Increase arterial stiffness Sleep apnea also causes release of such cytokines ,

inflammation and HTN Leptins

Renal sympathetic System

The kidney is well supplied with sensory nerves that transmit both chemical and mechanical information to the autonomic nervous system through a post – ganglionic sympathetic plexus in renal arterial adeventitia

The composition of the interstitial fluid and its hydrostatic pressure are both monitored and its alterations influence the Hypothalamus create pain senstations and promote sympathetic outflow to HEART and Kidney

Sympathetic stimulations raises BP by increased renal vascular resistance , stimulating renin release from Juxta glomerular cells and increasing tubular sodium reabsorption

In healthy individuals stimulation of afferent nerves modulate sympathetic nerve outflow both to ipsilateral and contralateral kidneys, reducing vasoconstriction , and sodium reabsorption thereby reducing HTN

But in many renal diseases this effect is lost and leading to vasoconstriction and retention of water and salt Increased Blood Pressure

Increased afferent nerve stimulation could also act on Hypothalamus to release vasopressin and cause HTN and water retention.

Under normal circumstances , sympathetic system has little effect on kidneys however when anxiety and stress exists renal vascular resistance increases and salt, water retention increases causing HTN

Effect of hypertension on the kidney

Benign arteriolar nephrosclerosis predominantly affects the arterioles leading to their thickening and reduction of lumen consequent ischemic changes in glomeruli renal failure develops slowly

Malignant HTN : overhelms renal auto regulation and pressure is transmitted to the glomeruli before arteriosclerosis can occur to protect them Fibrinoid necrosis dominates the picture , hematuria and

Proteinuria can be marked and renal failure develops rapidly

Diuretics for Essential HTN

Since salt retention is the major factor in causing essential HTN , the obvious first choice of therapy is DIURETIC

Hyponatremia is the common side effect of it However MILD hyponatremia ( Sr.Na+ : 130-135 mEqL ) is not such a

harmless condition It causes instability of gait Attention deficit Confusion Increased chances of FALL Increased fractures Osteoporosis

Gout : as diuretics are excreted by organic anion transporters which also transport URIC ACID and diuretics compete with URIC ACID Hyper Uricemia GOUT

Torsemide have the greatest effect Though they cause this effect only in susceptible individuals :

high serum uric acid causes endothelia dysfunction , inflammation and oxidative stress and stimulates RES

Net result is glomerular Hyper filtration and renal interstitial fibrosis and Faster progression of Renal Failure

Precautions

Most anti-hypertensives act by inhibitory compensating mechanisms that should raise BP when we assume in ERECT posture

So we should make it a point in monitoring BP in both LYING and ERECT posture in every patient who is on treatment

The target blood pressure should be 140/90 mmhg in all hypertensives 130/80 in all patients with renal failure

Monitor urine protein and Renal Function test at regular intervals of time

Thank You