Ghai Essential Pediatrics8th

blockers (ARB), beta blockers, calcium channel blockers and diuretics (Table 15.23). ACE inhibitors and calcium­ channel blockers are commonly used in children. ACE inhibitors or ARB are preferred in patients with diabetes or chronic kidney disease.

The goal of therapy for pediatric hypertension should be to reduce blood pressure below 95th percentile, except in the presence of chronic kidney disease, diabetes or target organ damage, when the goal is to reduce blood pressure to less than 90th percentile. Pharmacotherapy is done in a stepped-care approach and usually starts with a low dose of a single agent (step 1). If blood pressure control is not achieved, the dose is titrated every two weeks until blood pressure goals are achieved or the maximum dosage for the drug is reached (step 2). If adequate blood pressure control is not achieved with a single agent, a second agent with a complementary mechanism of action should be added and dose titrated until adequate control or dosage limit is reached (step 3). If adequate blood pressure control is not achieved with a

two-drug regime, a third agent from a different drug class should be added as mentioned earlier (step 4).

In the case of hypertensive emergencies, the safest way is to lower blood pressure using an antihypertensive medication that is administered by continuous intravenous infusion in an intensive care unit, where the patient can be monitored appropriately. In general, the pressure should be reduced by up to 25% over the first 8 hr (10% in the first hour), followed by a further gradual reduction in blood pressure over the next 36-48 hr. Too rapid a reduction in blood pressure may lead to cerebral ischemia. Drug choices include labetalol, nicardipine and sodium nitroprusside ofwhichnicardipine is the preferred drug in children due to its efficacy and safety (Table 15.24). Many patients in hypertensive crisis are volume depleted because of a combination of decreased oral intake and pressure natriuresis. Volume repletion in such conditions will helprestoretissueperfusionand prevent a precipitous fall in BP that may occur with intravenous anti­ hypertensive therapy.

Prevention

The prevention of high blood pressure in children can be achieved by preventing childhood obesity. Regular physical activity, consumption of fruits and vegetables, moderation of salt intake, low consumption of processed food items and animal fats and reducing sedentary activities willaidin reducing theprevalenceofhighblood pressure in children and adolescents.

Suggested Reading

National High Blood Pressure Education Program Working Group on High Blood pressure in Children and Adolescents. The fourth re­ port on the diagnosis, evaluation and treatment ofhigh blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report): 555-76

Raj M, Sundaram KR, Paul M, Deepa AS, Kumar RK.,Obesity in chil­ dren - time trends and relationship with hypertension, Natl Med J In­ dia, 2007;20:288-93

PULMONARY ARTERIAL HYPERTENSION

Pulmonaryarterialhypertension (PAH)isdefinedas resting mean pulmonary arterial pressure greater than 25 mm Hg, or mean pulmonaryarterypressure following exercise that exceeds 30 mmHg. PAH occurs inan idiopathic form or in association with other etiologies. The condition is a critical determinantofmorbidityandmortalityin diversepediatric cardiac, lung, hematologic, and other diseases.

Etiology

PAH maybeassociatedwith a number ofcongenitalheart diseases. Idiopathic PAH is rare in children. In a small

proportion mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, the activin receptor-like kinase type 1 (ACVRLl), or endoglin are identified.

Persistent Pulmonary Hypertension of the Newborn (PPHN)

At birth, pulmonary vascular resistance is high, it normally fallsrapidlythroughoutthefirstweekoflife. By6to8 weeks, pulmonary vascular resistance usually has reached a normal adult level of 1 to 3 Wood units. These changes are accompaniedby agradualdilationof the smallerand thenthelargermuscular pulmonaryarteriesanddevelop­ mentofnewarteriesandarterioles. PPHN develops when pulmonary vascular resistance remains elevated after birth, resulting in right-to-left shunting ofbloodthrough fetal circulatory pathways. The common associations include congenital diaphragmatic hernia, meconium aspiration syndrome and perinatal asphyxia. These newbornpatientstypically requiremechanicalventilatory support and those with underlying lung disease may benefit from high-frequency oscillatory ventilation or extracorporeal membrane oxygenation (ECMO). Pul­ monary vasodilators, such as inhaled nitric oxide, improve the outcome and reduce the need for ECMO. Sildenafilis increasingly usedforPPHNas analternative to inhaled nitric oxide.

ClinicalManifestations

The clinical features of PAH are related to the degree of pulmonary hypertension and right ventricular function

and status of the right ventricle. Most common symptom is exertionalbreathlessness due to the inability of the right ventricle to raise cardiac output with exercise. Other symptoms are hemoptysis, atypicalchestpain,congestive heart failure, dizziness or syncope and arrhythmias. Cyanosis and its complications are seen in Eisenmenger patients but not otherwise unless there is a patent foramen ovale. A comprehensive evaluation is advised before a diagnosis of idiopathicPAH is made. It is essential to rule out cardiac (congenital heart disease), respiratory, upper airway obstruction (Down syndrome, adenoids), neurogenic causes (sleep apnea) and liver disease (porto­ pulmonary hypertension).

Management

Supplemental low-flow oxygen alleviates arterial hypoxemia in patients with chronic pulmonary pare­ nchymal disease. Patients with Eisenmenger syndrome or idiopathic PAH do not exhibit resting alveolar hypoxia and do not require oxygen unless significantly hypoxic. Children with severe right ventricular failure and resting hypoxemia may require continuous oxygen therapy.

Diuretics are useful in patients with symptomatic right heart failure. The right ventricle is highly preload dependent, and care should be taken to avoid excessive diuresis since this can lead to a fall in cardiac output and compromise other pharmacologic measures, such as vasodilators. Patients are athigherrisk of thromboembolic events due to sluggish pulmonary circulation and dilated right-sided cardiac chambers. Anticoagulants may have a role in select cases when the risk for thromboembolism outweighs the likelihood of hemoptysis.

The goal of vasodilator therapy for PAH is to reduce pulmonary artery pressure and increase cardiac output without causing systemic arterial hypotension. Sildenafil is an oral phosphodiesterasetype 5 inhibitor that prevents the breakdown of cGMP and potentiates pulmonary vasodilation with inhaled nitric oxide. Symptomatic patientswithPAH,PPHNandpostoperative PAH benefit with sildenafil. Other agents including bosentan, an oral endothelin-receptor antagonist (ERA) and prostacyclin analogs.

Combined heart lung transplantation, or lung trans­ plantation alone has been performed successfully in patientswithPAH.Themajorlimitations to itswidespread use include the limited number of centers with the expertise to perform the procedure and care for patients and the limited availability of suitable donors and signi­ ficant cost.

Prognosis

Prognosis is dictated by the underlying etiology and the right ventricular function. An overall 80% 5 yr survival has been reported in patients with Eisenmenger syndrome compared with a 2-3 yr mean survival after the diagnosis of idiopathic PAH.

Disorders of Cardiovascular System -

Suggested Reading

Abman SH, Ivy DD. Recent progress in understanding pediatric pul­ monary hypertension. Curr Opin Pediatr 2011;23:298-304

Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and as­ sessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:SSS-66

RHYTHM DISORDERS

The recognition of cardiac arrhythmias in children is challenging and requires a high index of suspicion. It is important to arrive at a precise diagnosis since the treatment is dictated by the specific arrhythmia. In some situations, it may be possible to affect a complete cure.

Clinical Features

These are listed in Table 15.25.

Irregular heart rate. The commonest cause of an irregular heart rate is physiological sinus arrhythmia. This can be recognised by an increase in heart rate with inspiration and decrease with expiration. Sinus arrhythmia is usual following afebrile illness and by drugs that increase vagal tone (such as digoxin). It is readily abolished by exercise. Irregularities of rhythm are commonly seen in premature infants especially bradycardia associated with periodic apnoea. Common causes of heart rate irregularity in children include atrial and ventricular premature beats and conduction disturbances (Table 15.26).

Inappropriate heart rate. A heart rate that is inappropriately fast or slow for the clinical condition should arouse the suspicion of an underlying arrhythmia. Inappropriately

Table 15.25: Clinical features in arrhythmias

Irregular heartbeat

Heart rate that is inappropriate for the clinical condition Unexplained heart failure

Syncope, palpitations, chest discomfort

Underlying cardiac anomaly known to be associated with rhythm disorders

Family history of sudden cardiac events

Table 15.26: Causes of irregular heart beat

Sinus arrhythmia

Other common and usually benign causes

Supraventricular (atrial and junctional premature beats) Ventricular premature beats

Transient conduction disturbances (Wenckebach type), atrioventricular and sinoatrial blocks

Transient bradycardia in a premature infant

Uncommon but potentially serious causes

Mobitz type II heart block

Ectopic atrial tachycardia; multifocal atrial tachycardia

Polymorphic ventricular tachycardia and Torsades

Atrial fibrillation, with or without WPW syndrome

Atrial flutter with variable conduction

.

Il

slow heart rate in a child with fatigue, giddiness or syncope should arouse the suspicion of complete heart block. Inappropriately fast rates suggest tachyarrhythmias such as SVT.

Unexplained heart failure. Incessant arrhythmias such as ectopic atrial tachycardia (EAT), permanent junctional re-entrant tachycardia (PJRT) and some forms of ventriculartachycardiacan present as heart failure. At the time of initial evaluation the heart rates may not be inappropriate for the degree of heart failure. Diagnosis may be missed and requires a high index of suspicion. These conditions should be considered in the differential diagnosisofchildhooddilated cardiomyopathy, especially if the heart rate is relatively fixed.

Underlying conditions. A number of congenital and acquired heart diseases and certain systemic conditions are known to be associated with cardiac arrhythmias (Table15.27). Ventricularandsupraventricular arrythmias can follow cardiac surgery for correction of CHO.

10 Operationsresultingin scar formation in the right ventricle such as repair of tetralogy of Fallot are known to be associated with ventricular tachycardia. The Fontan operation for single ventricle physiology or the Senning or Mustard procedure for transposition is known to result in a particularly high incidence of re-entrant atrial arrhy­ thmias. Organophosphate exposure, tricyclic anti­ depressant overdose, digoxin toxicity, antiarrhytrnic drug treatment and substance abuse can be associated with a variety of arrhythmias.

Syncope. The commonest cause of syncope in children is mediated via the autonomic nervous system, known as

Table 15.27: Arrhythmias suggestive of specific congenital heart disease

Sick sinus syndrome

Sinus venosus, atrioventricular canal defect, Holt Oram syndrome with atrial septal defect (ASD)

Narrow QRS tachycardias

Ebstein anomaly; corrected transposition with Ebstein anomaly

Atrioventricular canal, ASD. pulmonic stenosis, total anomalous pulmonary venous connection, tricuspid atresia (older patients)

Atrialfibrillation andflutter

Congenital mitral stenosis, total anomalous pulmonary venous connection, coronary AV fistula

WPW and pre-excitation syndromes

Ebstein anomaly; corrected transposition with Ebstein anomaly

Wide QRS tachycardias

Anomalous left coronary artery from pulmonary artery, coronary AV fistula, arrhythmogenic rightventricle, atrio­ ventricular conduction defects, corrected transposition of great arteries; Ebstein anomaly

Postoperative patients

Supraventricular, ventricular arrhythmias

the neurocardiogenic syncope or vasovagal syncope. A fraction of syncopal episodes result from cardiac arrhythmias. Life threatening ventricular tachycardia (VT), as associated with long QT syndrome characteristically results in syncope. It is important to differentiate them from vasovagal episodes. Vasovagal syncope occurs in specific situations like prolonged standing in a hot environment, sight of blood, painful stimulus, emotional stress or following a recent illness. Syncope secondary to arrhythmia are sudden, unpredictable, paroxysmal and usuallyhave nopredisposingcause orpremonition. Dura­ tion of syncopedependsupon the durationof arrhythmia. Someformsof longQT syndromesand catecholemenergic tachycardia are precipitated by exercise. Ventricular tachycardia secondary to Brugada syndrome may be precipitated during febrile illness.

Palpitations and chest discomfort. Older children may complain of episodic palpitations. Not infrequently, they have a sensation of chest discomfort or pain during tachyarrhythmia.

Basic Electrophysiology Concepts

Arrhythmia that originates at or above the bundle of His has narrow QRS morphology; that below this level (Purkinje fibers, ventricular muscles) have wide QRS morphology. Majority of tachycardia in children are regular. Common irregular tachycardia are ectopic atrial tachycardia, multifocal atrial tachycardia, atrial flutter with varying conduction, atrial fibrillation (rare in children) and ventricular fibrillation. During a regular narrow QRS tachycardia, if a P wave is identified and has normal morphology, axis and 1:1 P and QRS relation, it suggests sinus tachycardia. Absence of any of the three suggests supraventricular tachyarrhythmia.

Re-entrant vs. automatic tachyarrhythmias. Tachyarrhythmia is generally considered to result from one of the three mechanisms: re-entry, increased automaticity and triggered activity. In children, the first two mechanisms accountformostimportantarrhythmias.Clinicaland EKG featurestogetherwithresponsetocertainmedicationsand maneuvres help distinguish re-entrant tachyarrhythmias from those due to increased automaticity. Re-entrant arrhythmias characteristically have a relatively sudden onset and termination. Successful termination with DC cardioversion or overdrive pacing (pacing at rates faster than the arrhythmia rate) strongly suggests a re-entrant mechanism. Automatic arrhythmias characteristically have a relatively slow onset. Gradual acceleration (warm­ up) to the peak rates may be demonstrable at onset and gradual deceleration (cool down) at termination is seen.

Diagnostic Workup of Suspected Arrhythmia

Attemptsshouldbemadetoanswerallthequestionslisted in Table 15.28. This will allow the specific treatment strategy to be initiated. A 12lead EKG should be obtained

Table 15.28: Initial assessment of arrhythmia

Can the clinical condition result from a cardiac arrhythmia? Is there hemodynamic instability?

Is the arrhythmia incessant or episodic?

Is this a re-entrant arrhythmia or does it involve an automatic focus?

Where is the arrhythmic focus or circuit located? Is there an underlying structural heart disease?

and cardiac rhythm monitoring should be initiated as quickly as possible.

Management of Hemodynamic Instability

All tachyarrhythmias and bradyarrhythmias influence hemodynamics adversely, manifesting with no detectable manifestations to circulatory collapse. Extreme hemodynamic instability is relatively rare in childhood arrhythmias, particularly in absence of structural heart disease. Hemodynamicinstability necessitates emergency treatment. Most unstable tachyarrhythmias are broad QRS. Unstable narrow QRS tachycardia are quite uncom­ mon, especially in the absence of structural heart disease. Low energy (0.5-2 J/kg) synchronized DC cardioversion should be performed. If and when possible cardioversion should always be preceded by administration of a short­ acting benzodiazepine such as midazolam (0.1-0.2 mg/ kg/dose). Emergency treatment options for brady­ arrhythmias are shown in Table 15.29.

Diagnosis and Management of Tachyarrhythmia

A combined strategy that simultaneously addresses both diagnosis andtreatment is appropriate. This is determined by the QRS duration on the initial EKG and presence or absence of hemodynamic instability. Based on the QRS duration arrhythmias can be classified as narrow and wide. This is a useful practical classification and serves as an excellent guide to initial treatment.Age specificnormal values for QRS duration are given in Table 15.30. As a preliminary step, sinus tachycardia should be excluded. Rates as high as 240/min can occasionally be recorded during sinus tachycardia. There is always an underlying cause for sinus tachycardia and this is usually apparent during the initial evaluation. Fever, circulatory failure, extreme dehydration, accidental ingestion of drugs and

Disorders of Cardiovascular System

Table 15.30: Normal QRS duration at various age groups

Values represent range (mean)

toxic substances are common examples. Figure 15.48 depicts a useful treatment algorithm.

Narrow QRS tachycardia. Most narrow QRS tachycardias (Table 15.31) are reasonably well tolerated and allow a preliminary diagnostic workup (Table 15.32). If a patient is seen during an episode oftachyarrhythmia, all attempts should be made to obtain quality data before terminating the arrhythmia. Information that should be specifically sought include the P wave morphology and P-QRS relationship.Pwavesthatappearnormalduringthetachy­ arrhythmia suggest sinus tachycardia. Ectopic atrial tachycardia is suggested by abnormal P wave morpho­ logy. Inverted P waves may be seen when atria are acti­ vated in a retrograde fashion as in the case of re-entrant tachyarrhythmias involving accessory pathways (AV re-entrant tachycardia) (Fig. 15.49). Often P waves are not

Stable narrow QRS tachycardia

Adenosine 140 µg/kg bolus

fig. 15.48: Management algorithmfor stable narrowORStachycardia. AVNRT atrioventricular nodal re-entrant tachycardia; AVRT atrioventricular re-entrant tachycardia

Table 15.31: Causes of narrow QRS tachycardia

clearly seen on baseline EKG but are unmasked by adenosine. Evidence of 2:1 AV conduction as suggested by a 2:1 P-QRS ratio during a narrow QRS tachycardia indicates atrial flutter (Fig. 15.50). Evidence of complete AV dissociation (no consistent P-QRS relationship) indicates junctional ectopic tachycardia.

Adenosine administration acts by producing a marked slowing of AV node conduction (Table 15.32). The effect of adenosine lasts for a few seconds. Side effects are short­ lived and include flushing, chest pain and dyspnea.

Adenosine needs to be administered rapidly followed by rapidpushof normal saline as a bolus. Therecommended dose is 50-300 µg/kg. Most re-entranttachycardias,where AV node is a part of the circuit (AV node re-entrant tachy­ cardia, AV re-entrant tachycardia) will be terminated by adenosine. Atrialflutter is seldom terminated by adenosine.

The transient AV block that results from adenosine administration can unmask flutter waves on the EKG thereby confirming the diagnosis (Fig. 15.51). Similarly transient slowing of AV conduction can unmask ectopic atrial tachycardia. If adenosine is not available, vagal maneuvres can be attempted. For infants and young children an ice filled plastic bag placed on the face is the most effective vagal maneuver. Older children can be encouraged to perform the Valsalva maneuver or carotid sinus massage can be attempted. Eyeball pressure is contraindicated in infants.

Wide QRS tachycardia. Wide QRS complex tachycardias usually result from foci or circuits in the ventricles. Some supraventricular tachycardias can also result in a wide QRS configuration. The overall approach is quite similar to narrow QRS tachycardias, with identification of P waves, defining P-QRS relationship and determining the QRS axis configuration (Fig. 15.52).

Demonstrable AV dissociation (inconsistent P-QRS relation) suggests ventricular tachycardia (VT). In most situations, however, it is not easy to distinguish VT from SVT. If the patient is stable, administration of adenosine will terminate or unmask SVT. If there is no response, treatment for VT should be initiated. In stable patients it is better to initiate pharmacologic treatment of VT before considering cardioversion since the response to initial

treatment can help decides longterm therapy. Lignocaine is the initial choice, while procainamide is an effective alternative; othersinclude amiodarone, sotalol,mexeletine and flecanide.

Unstable wide QRS tachycardia. Wide QRS tachycardia with hemodynamic instability is a medical emergency. Synchronised cardioversion (0.5-2 J /kg) should be performed immediately. For pulseless patients, CPR

I I

,....._

fl\

Fig. 15.52. Wide ORS tachycardia resulting from a re-entrant circuit involving an accessory pathway in a patient with right bundle branch block. Surface ECG, can be mistaken for ventricular tachycardia. ECG of the top two rows has been obtained directly from the atrium using postoperative atrial wires as electrodes. The bottom strip is the surface ECG from a monitoring lead. Conversion to sinus rhythm after adenosine is seen in the last four complexes on the right. a artial contraction, Pp wave

should be initiated. Subsequent treatment should follow standard guidelines recommended for pulseless patients with VT (Fig. 15.53).

Irregular wide QRS tachycardia. Sustainedandirregularwide QRS tachycardia is uncommon and usually suggests a diagnosisofWolfParkinsonWhite (WPW)syndromewith atrialfibrillation. Inpresence of hemodynamic instability, synchronised cardioversion (1-2 J/kg) is indicated. If the patient is stable, procainamide infusion may be tried.

Once the arrhythmia has been managed, recurrences need to be prevented. Most childhood arrhythmias warrant evaluationbyapediatriccardiologistforfollowup care and toplan definitive treatment. An echocardiogram, Holter test (24 hr ambulatory EKG recording) and eso­ phageal electrophysiologic study is often required. Invasive intracardiac electrophysiologic study is com­ bined with radiofrequency (RF) ablation. Most accessory pathways are now treated by radiofrequency ablation, especially in older children (>4-yr-old). For younger children RF ablation is reserved for refractory situations.

PREVENTING ADULT CARDIOVASCULAR DISEASE

Major risk factors for cardiovascular disease in adulthood include cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and physical inactivity. Some of these risk factors have genesis in childhood and are

amenable to modification, contributing to primary prevention of cardiovascular disease.

Childhood Obesity

Obesity influences major cardiovascular risk factors such as dyslipidemia, hypertension, glucose intolerance and inflammation. Emerging cardiovascular risk factors like carotid intimamediathickness as well as carotid elasticity has also shown strong association with childhood obesity. Childhood obesity is managed by a combination of increased physical activity and dietary interventions.

Hypertension

Primary or essential hypertension is the most common form of hypertension in older children and adolescents. Childhood obesity is associated with hypertension in children, which often tracks into adulthood.

Dyslipidemia

Screening for dyslipidemia is recommended for children whose parents and/or grandparents required coronary artery bypass-surgery or balloon angioplasty before age 55, those with a family history of myocardial infarction, angina pectoris, peripheral or cerebral vascular disease, or sudden death before age 55 and those whose parents have dyslipidemia. Youth with dyslipidemia are treated with a diet low in total and saturated fats and cholesterol. The intake of complex carbohydrates isincreased, whereas that of simple sugars is decreased. Drug therapy is used in patients with significantly elevated LDL-cholesterol.

Diabetes Mellitus

Diabetes mellitus is associated with cardiovascular complications, which develop early in childhood and adolescence. Endothelial dysfunction seen in both types of diabetes is recognized to aggravate cardiovascular risk in later life. Optimal daily and longterm glycemic control, maintenance of blood pressure and lipid levels in the normal values for age, regular exercise, healthy diet and avoidance of smoking are necessary.

Tobacco Consumption

Mechanisms by which smoking exerts its detrimental effects on cardiovascular system include endothelial dysfunction, increased oxidative stress, increased arterial stiffness, alterations in lipoprotein metabolism and induction of prothrombotic state. School based campaigns to prevent smoking and chewing tobacco are appropriate tools to contain this public health concern. Parents should be role models tochildren byavoiding or quitting smoking and chewing tobacco.

Early atherosclerotic disease has been documented in certain conditions in children. The risk category, group of diseases in each category and the prevention oriented treatment targets are shown Table 15.33.

Suggested Reading

Raj M. Obesity and cardiovascular risk in children and adolescents. Indian J Endocrinol Metab 2012;16:13-19

Raj M, Sundaram KR, Paul M, et al. Obesity in children - time trends and relationship with hypertension. Natl Med J India 2007; 20:288-93

RENAL ANATOMY AND PHYSIOLOGY

Each kidney is composed of approximately a million nephrons, each consisting of a glomerulus and renal tubule. The glomerulus is made of a tuft of capillaries and a central region of mesangium. The capillaries arise from the afferent arteriole andjoin to form theefferentarteriole, the entry and exit being at the hilum of the kidney. The capillary wall consists of fenestrated endothelium, glomerular basement membrane and foot processes (podocytes) of visceral epithelial cells. The basement membrane is made of type IV collagen, laminin and heparan sulfate proteoglycan. The Bowman space leads into the proximal tubule that has an initial convoluted portion, then the straight segment, descending and ascending limbs of theloopof Henleandthedistal tubule. Six to eight distal tubules join to form the collecting ducts that finally enter the renal pelvis.

The renal artery divides into segmental arteries that branch to form interlobar and arcuate arteries. The latter give rise to the intralobar arteries, which provide the afferent arterioles for the glomeruli. The efferent arterioles from theglomeruli forma meshwork of peritubular venous capillaries that empty into intralobar veins. The early part of the distal tubule on its ascent from the medulla to the cortex lies near the glomerulus of the same nephron. The cells of the tubule in contact with the afferent arteriole are denser than the rest and called macula densa. The smooth muscle cells of the afferent arteriole, in this region, contain prominent cytoplasmic granules that are the site of renin activity.Thejuxtaglomerularapparatus CTGA) iscomposed of afferent and efferent arterioles, the macula densa and lacis cells located between these structures. The JGA is involved in systemic blood pressureregulation, electrolyte homeostasis and tubuloglomerular feedback.

Renal Physiology

Glomerular filtration depends upon the higher pressure in afferent arterioles. The filtration barrier is constituted

by the endothelium with slit pores, basement membrane and podocytes of visceral epithelial cells. Filtration of solutes depends upon their molecular size, shape and electrical charge. The filtrate from the glomerular capillaries passes from the Bowman capsule into the proximal convoluted tubule, loop of Henle, distal tubule and collecting ducts. The filtrate contains all the diffusible and ultrafiltrable substances present in plasma. Small quantities of protein are usually present, but are reabsorbed in proximal tubule. Bulk of the glomerular filtrate is reabsorbed into the peritubular capillaries and only 0.5% is excreted as urine.

Tubular Reabsorption

The proximal tubules reabsorb about 80% of the glome­ rular filtrate.Approximately65% of sodium is reabsorbed in the proximal tubule, through several active transport systems. Sodium transport is dependent on the parallel transport of bicarbonate, chloride, amino acids and glucose. Tubular reabsorption of sodium and other permeable solutes is promoted by the phenomenon of solvent drag during transport of water across the tubular epithelium. Figure 16.1 indicates the principal sites of reabsorption of sodium and potassium.

The glomerular filtration rate is regulated by tubulo­ glomerular feedback that depends upon the functional integrity of the JGA. Increased delivery of chloride to the macula densa results in local activation of renin-angio­ tensin mechanism. The renin-angiotensin-aldosterone system, prostaglandins and natriuretic peptides are involved in sodium handling. Potassium is completely reabsorbed in the proximal tubule; the amount seen in urine depends upon its secretion in the distal tubule.

Distal tubules and collecting ducts are responsible for urinary acidification, concentration and regulation of sodium balance. Exchange of potassium or hydrogen ions for sodium takes place in the distal tubules under the regulationof aldosterone.Antidiuretichormone mediates