Presentation on theme: "ANATOMY OF THE KIDNEY The kidney is a retroperitoneal organ occupying the space slightly above the umbilicus. measures 6cm in the term new born and weighs."— Presentation transcript:
ANATOMY OF THE KIDNEY The kidney is a retroperitoneal organ occupying the space slightly above the umbilicus. measures 6cm in the term new born and weighs 24gm. It has an outer layer called the cortex which contains the glomeruli, proximal tubule, convoluted tubule and the collecting ducts, while the medulla contains the straight portion of the tubule, the loops of henle and the terminal loops. Each kidney contains approximately 1m nephron(glomeruli + associated tubule) whose formation is complete at birth. The functional maturation of these occurs later. *NO NEW NEPHRON CAN BE FORMED AFTER BIRTH*
GLOMERULAR FILTRATION The glomeruli network of specialized capillaries serves as the filtering mechanism of the kidney. These capillaries are lined by endothelial cells having thin cytoplasm which contains fenestration. The glomeruli has 3layers: (i) lamina densa (ii) lamina rara interna (iii) Lamina rara externa The visceral epithelial cells cover the capillary projects and the “foot processes”, between the foot processes are the filtration slits. Mesangium lies between the glomerular capillary on the endothelial side of BM forming medial wall of the capillary walls. It serves as a supporting structure for the capillary. It also plays a role in glomerular blood flow, filtration and removal of micro-molecules. The glomerulus is surrounded by the bow- mans capsule. Glomeruli filtration is the net result of opposing forces across the capillary walls and this forces arise from the systemic arterial pressures. The opposing force is the glomerulus capillary oncotic pressure created by plasma protein.
As blood passes through the glomeruli capillaries, plasma is filtered through the capillary walls. The ultra filtrate which is formed by passage of plasma through the glomerulus is cell free. It is collected in the bow-man space from where it enters the tubules while it gets modified according to the need of the body after which it leaves the body as urine. Filtration is modified by glomerula plasma flow,hydrostatic pressure within the bowman space and the glomerula capillary wall permeability. Glomerular filtration begins in utero around the 9 th week, the rate increases until growth ceases towards the end of the second decade of life. GFR in a child does not approximate that of adult till the third year of life. GFR may be estimated by measurement of serum creatinine level. It is of value in the steady state only and this is because the level does not rise above normal till GFR is <70% of normal.
The precise measurement of GFR is achieved by quantitating the clearance of a freely filtered substance across the capillary wall, such a substance is neither reabsorbed nor secreted by the tubules. GFR is 25ml/min/1.73m 2 during the first 2-3days of post natal life in term neonate,it increases 2-3 times during first week of life reaching adult values by 1-2 yrs. eGFR = (140-age)* weight*1.23/scr eGFR = (140-age)* weight*1.23/scr Schwartz formular: k*height (cm)/scr ** k is a constantwhich is age dependent.
CONGENITAL PROBLEMS Renal Agenesis: This means that one of the renal anlarge either the mesonephric duct, and the ureteric bud or the metenephric blastema has failed to differentiate. It is a common cause of prenatal RF. It is seen in 1:1000-5:5000 births There is male preponderance especially in the bilateral. It is sporadic. Familial tendency has been reported. There is male preponderance especially in the bilateral. It is sporadic. Familial tendency has been reported. It may be unilateral or bilateral; when unilateral, the ipsilateral fallopian tubes and other genital tracts structures may be absent. It may be unilateral or bilateral; when unilateral, the ipsilateral fallopian tubes and other genital tracts structures may be absent. Bilateral agenesis reflects a greater supression of structures arising from posterior portion of cloaca, mesonephric and paramesonephric ducts and may thus affect the limbs and spine. In this, the fallopian tubes … are present but the uterus, vagina are absent or abnormal.
Clinical features Oligo hydramnous- due to lack of fetal micturition Postural deformities- due to oligihydramnous Potter facie/syndrome-widely seperated eyes, epicanthics folds, low set ears Prognosis-this is usually poor and affected by : (i) (i) Contralateral renal hypoplasia (ii) (ii) Contralateral nephrolithiasis (iii) (iii) Infection (iv) (iv) Associated anomalies of CVS, CNS and MSS. Death usually occurs in the peri-natal period and the usual cause of death is pulmonary hypoplasia
OTHER CONG ANOMALY Hypoplasia: This refers to small kidneys and this small sized kidneys could arise from: Insufficient amount of metanephric blastema available for kidney production. Insufficient early ducts branching leading to low number of lobes. Reduced nephric induction or a retardation of postnatal tubule glomerular enlargement. the condition may be unilateral or bilateral. The unilateral is a common cause of HT in the first decade of life while bilateral causes CRF and is a leading cause of ESRD. The bilateral has two types vis :
i. Histologically normal Small kidney that may present with polyuria, acidosis, salt wasting and azotemia. ii. Oligomeganephronia/oligonephric hypoplasia usually present in the first or second year of life with polydipsia, polyuria, vomiting, diarrhoea and FTT. They develop renal insufficiency by end of first decade of life. Renal Dysplasia This term refers to an altered structural differentiation of the fetal kidneys. Includes a spectrum of renal defects with certain features in common which may be an abnormally located urethral orifice or urinary tract anomalies which may produce unilateral, bilateral or segmental urinary tract obstruction. May remain asymptomatic if unilateral, many of them are associated with cystic changes. Pathogenesis (THEORIES) i. i. Toxic or physical injury occuring to the interacting ureteric bud and nephrogenic blastema extent of which is dependent on the stage of development. The damaging injury is usually believed to be due to increase HP due to either a complete or partial obstruction of the ureter or bladder outlet. ii. ii. The 2ary injury of the urethral bud and metanephric component occuring during the period of migration. This causes a failure of vascularization leading to ischaemia. iii. iii. Implies an intrinsic deficiency or the inadequate displacement of anlargen from the normal position.
Variants i. i. Multicystic variety -most common type of renal dysplasia (cystic), dies in childhood, may be bilateral or unilateral. Bilateral is more common, seen in 0.02- 0.05 per 100,000 ii. ii. Subtotal: this type is seen in association with megacystic,megaureter PUV, ureterocele Features may be asymptomatic Urinary infection Renal failure, HT, hematuria M x : relief of the associated urinary obstruction. prevention of infection. Surgical : nephrectomy.
Multicystic dysplastic kidney -Has very little kidney tissue -10% of them have uretero- pelvic junction obstruction in the opposite kidney -May also have reflux May suffer HT, recurrent urinary tract infection. Polycystic kidney disorder Renal cysts are abnormal fluid filled sacs arising in the renal parenchyma, may occur in cortex, medulla, or both regions of the kidney and may or may not be associated with other renal or systemic anomaly. they may be hereditary in which case they may be AR, AD, may also be acquired Autosomal polycystic kidney Disorder (ADPKD) Incidence 1:1000, more common form of cystic disorder. It has no sex predelection. It is AD with complete penetrance with variable expression. The abnormal gene has been linked to alpha globin cluster located on chromosome 16 and ADPKD2 on chromosome 4. Types: infantile, neonatal juvenile, perinatal CLINICAL FEATURES. Hypoplastic lungs Hypoplastic lungs Die shortly from RF Die shortly from RF Kidneys are enlarged and function poorly Kidneys are enlarged and function poorly May have an associated hepatic fibrosis May have an associated hepatic fibrosis
PHT (GIT bleeding, hematemesis, melena) PHT (GIT bleeding, hematemesis, melena) RUSS: Enlarged Kidneys, cysts IVP : For the excretory function Prognosis: depends on PHT, renal failure Infantile: Hematuria, HT Hematuria, HT Abdominal pain Abdominal pain Protenuria Protenuria Anaemia in RF due to ADPKD is not as profound as that in other terminal renal d x Juvenile: - nocturia due to poor concentrating ability - abdominal swelling - hematuria IVP: - i. deformity of collecting system RUSS: - ii. Enlarged kidneys with multiple echo free areas CT:- contrast enhancement is prefered. It distinguishes between solid and liquid renal moss. Radioisotopic scanning using Te 99 in labelled inappropriate is used in accessing and comparing renal tubule full, GF
AR polycystic kidney disease Seen in 1:6000-55000 live births Has variable expression Actual genetic defect is not known Affects both the kidney and liver. It is a continuum with different presentations at different stages. Neonatal/Perinatal: - potter syndrome - rapidly fatal - rapidly fatal If they survive, features are like that of the ADPKD. They may have pneumomediastinum, pneumothorax pnuemonia. HT, cardiac hypertrophy, CCF, endocardial fibroelastosis, UTI PHT Renal failure RUSS i. very important which shows enlarged kidney with echogenecity in cortex, medulla. ii. Poor collecting system iii. Fuzzy deliniation of kidney from sorrounding tissues. CT Prenatal screening ----elevated alpha feto-protein.
Posterior Urethral valves Obstructive lesion of the urinary tract can occur at any level. Urinary tract obstruction can be congenital or acquired when it is due to trauma, neoplasia, though most obstructive lesion are due to congenital problems. There are different types and they include the following: bladder outlet and urethra e.g PUV, urethral strictures, phimosis bladder outlet and urethra e.g PUV, urethral strictures, phimosis Uretero- pelvic junction e.g congenital stenosis, calculi, post surgical Uretero- pelvic junction e.g congenital stenosis, calculi, post surgical Ureter e.g congenital obstructive megaureter, uterocele, ureteral valves Ureter e.g congenital obstructive megaureter, uterocele, ureteral valves PUV is the most common type of obstructive uropathy in children. The PUV are membranes with eccentric openings arising from the verumontanum in males. It is an exclusive disease of males. Pathogenesis: With the obstruction, there is dilatation and hypertrophy of the part proximal to the obstruction. There is increased intratubular pressure and renal plasma flow due to vasodilatory effect of prostanglandins, the persistence of this leads to a reduction in renal plasma flow due to increase in the interstitial pressure. The obstruction leads to hydronephrosis as this progresses further without relieve of the obstruction, there is renal parenchyma damage resulting from vesico urethral reflux of varying degrees and in severe cases dysplasia. The urinary stasis in the bladder due to the bladder neck hypertrophy increases the risk of infection and inflammation which will further worsen the obstruction and gives rise to poor stream of urine. With the persistence of obstruction, there is accumulation of toxin FTT, RF. There is reduction in both the concentrating ability of the kidney as well as the excretion of hydrogen ion.
Clinical features Weak or poor stream of urine, flank mass Weak or poor stream of urine, flank mass Features of sepsis Features of sepsis post voiding dribs post voiding dribs FTTPEx: palpable mass due to hydronephrosis FTTPEx: palpable mass due to hydronephrosis Urinary ascites resulting from leakage from of urine due to increased pressure in the intra renal collecting system and rupture calyx into the peritoneal cavity. Urinary ascites resulting from leakage from of urine due to increased pressure in the intra renal collecting system and rupture calyx into the peritoneal cavity.Investigation To make the diagnosis. i. Micturating cysto urethrogram which will show dilatation of the prostatic urethrea and transverse filling defects. ii. RUSS: - evaluate kidney size,hydonephrosis IVP: presence of hydronephrosis, reflux IVP: presence of hydronephrosis, reflux Blood Investigation FBC: - there may be presence of leucocytosis due to infection - Anaemia - Anaemia E, U, Cr: elevated urea and creatinine in presence of renal failure Urinalysis Prenatal diagnosis M x - Surgical: i. Mainly where the ablation of the valves through a tran urethral approach ii. Temporary vesicotomy ii. Temporary vesicotomy iii. Cutaneous pyelostomy in case of suspected dysplasia or irreversible renal damage. iii. Cutaneous pyelostomy in case of suspected dysplasia or irreversible renal damage.
Medical Treat infection. Dialysis when indicated. Complications Urinary incontinence in about 50% from dilation of prostratic urethra, poor bladder compliance and or surgical damage to the sphincter. VUR is present in 2/3 Recurrent UTI Recurrent UTIPrognosis VUR worsens prognosis
URINARY TRACT INFECTION Introduction: Urine is an excellent cultural medium for bacteria and this becomes more important in the presence of UTO with development of residual urine volumes thus allowing for X of organism. It is particularly difficult to diagnose in < 2yrs UTI refers to the inversion of UTI by pathogenic organisms. It is of great significance in childhood due to the formation of scars which could occur within 5yrs of life and could be a major factor contributing to development of HT, renal failure. UTI include cystitis, pyelonephritis. Breast feeding has been associated with reduced risk of UTI in child < 6 months because of the low solutes load on the kidneys and it also inhibit colonization of the gut by coliforms.
EPIDEMIOLOGY Bacteriuria is influenced by the age, sex and method of diagnosis. Incidence: this varies according to the age and sex. NNates:1-4%M>F Infants:1.1-1.2&(2%)M=F 1-7yrs:1.6-7.8%(5%)F>M >7yrs:2.5%F>M Factors Organisms: 60-80% are caused by E-coli Organisms: 60-80% are caused by E-coli Gram -ve: Proteus spp, Klebsiella, Serratia,Pseudomonas Enterobacteris acct for 5-10% Gram -ve: Proteus spp, Klebsiella, Serratia,Pseudomonas Enterobacteris acct for 5-10% Gram +ve: Staph epidermidis Gram +ve: Staph epidermidis Staph aureus Staph aureus Strept Viridans Strept Viridans Fungal: Candida, Cryptococcus,Aspergillus Fungal: Candida, Cryptococcus,Aspergillus Viral: Mumps, Herpes-simplex, Adenovirus. Viral: Mumps, Herpes-simplex, Adenovirus. Risk factors A. Organisms: presence of virulence factors in the E-coli which include the i. mannose sensitive common, pilli which is responsible for anchoring E-coli to the mucus in LI and thereby allowing colonization i. mannose sensitive common, pilli which is responsible for anchoring E-coli to the mucus in LI and thereby allowing colonization ii. P-pilli : Agglutinate human RBC carrying the P-blood group antigen iii. Afrimbial adhesions in the uropathogenic E-coli, these are different from pilli. iii. Afrimbial adhesions in the uropathogenic E-coli, these are different from pilli. iv. Toxins which are lipopolysacharide: They are cytolytic and creates pores in cell membrane causing inflammation and appears to be responsible for symptoms. iv. Toxins which are lipopolysacharide: They are cytolytic and creates pores in cell membrane causing inflammation and appears to be responsible for symptoms. Others include production of siderophores and K+ ag which avoids opsonization. Others include production of siderophores and K+ ag which avoids opsonization.
B. Host factors : i. females are more susceptible than males from the infancy ii. Washing action of urine iii. P blood group iv. Presence of immuno suppressants either from drugs or other illnesses like DM, SCA. v. presence of UTO and other anatomic defects-eg PUV vi. Male sex: uncircumcission is a risk especially in < 1 yrs vii. Hx of prematurity is said to increase the risk of bacteriuria viii. Pin worm infestation ix. Labial fusion x. bubble bath, constipation and encopresis. Pathogenesis : T his can be hematogenous or through an ascending infection via the urethra Hematogenous is commoner in neonates. Once the organisms gains entrance, it adheres thus resisting flushing during voiding and attaches itself through the kag which Φ(inhibit) phagocytosis releasing endotoxin causing inflammation. The formation of intra cellular biofilms in bladder walls also protects bacteria from rupture into bladder lumen thus producing bacteriuria for recurrent infection. With the inflammation there is enlargement of the kidneys due to inflammatory infiltrates in the medulla and pelvis, this may lead to formation of abcess (micro) which could also progress to renal scarring. The risk of renal scarring is greatest with presence of VUR. Clinical types Types: Acute pyelonephrits Chronic pyelonephritis Chronic pyelonephritis
Symptoms May be asymptomatic. Symptoms will include: N-Nates: nonspecific - vomitting, irritability, diarrhoea, poor feeding, failure to thrive infants and toddlers: fever, (>38°C - 40°C) Older children: freq, urgency, dysuria, abdominal pain, enuresis, flank pain, hematuria Signs: ±HT - suprapubic tenderness, renal angle tender (RAT) - dehydration if vomitting is severe. DIAGNOSIS. Confirmation of diagnosis is based on a properly collected specimen with a positive growthInvestigation Urinalysis: Best specimen for this and MCS is the suprapubic aspirate. MSU can also be used. MSU can also be used. - WBC > 5HPF, casts, - WBC > 5HPF, casts, - pH-proteus produces alkaline pH - pH-proteus produces alkaline pH - microscopic hematuria - microscopic hematuria Urine MCS: any colony count following a SPA is diagnostic 100,000 cfil/ml – female 100,000 cfil/ml – female 10,000 cfil/ml - male 10,000 cfil/ml - male Blood MCS: may reveal bacteremia Procalcitonnin level may help to differentiate between upper UTI and lower UTI.
CRP > 20mg/l sensitive but not predictive WBC: leucocytosis RUSS: - size corticomedullary difference, hydronephrosis, calculi - presence or absence of renal, peri -renal abscesses. - presence or absence of renal, peri -renal abscesses. - acute lobar nephronia - acute lobar nephronia DMSA( dimecaptosuccinic acid)- parenchymal filling defect in acute pyelonephritis It is superior to RUSS and IVU MCUG: may be indicated in suspected anatomic anomaly e.g reflux, PUV. IVU: - produces information regarding precise anatomic image - estimate renal function not reliable for detecting renal scarring or pyelonephritis - large dose radiation is required Renal cortical scintigraphy very sensitive in detecting renal cortical defects detects pyelonephritis and renal scarring early little radiation is required CT:- more sensitive in detecting pyelonephritis - but expensive - can change acute lobar nephronia ComplicationBacteremia Renal scarring Renal scarring
HT Acute lobar nephronia represents progression of acute pyelonephritis it is a precursor of renal abscess ESKD ESKD Chronic UTI Treatment:Specific-antibiotics for 14days -CTM, Ceftiaxone, Amoxyl/clavulanic Supportive-hydration, feeding Long term prophylaxis Persistent VUR UTO Underlying voiding dysfunction (dysfunction urine elimination syndrome). Prognosis: Good if discovered and managed properly
PREVENTION Discourage FGM Discourage FGM Male to be circumcised on time Male to be circumcised on time Frequent and prompt change of baby diapers Frequent and prompt change of baby diapers Early detection and repair of obstructive uropathies Early detection and repair of obstructive uropathies Perineal care especially in females. Perineal care especially in females.
NEPHROTIC SYNDROME Introduction: NS is the clinical manifestation of many morphologically distinct glomerular disease. It is also called nephrosis. It is a leading cause of childhood renal disorders. Has diverse etiology with distinct glomerular histopathology and clinical course. It can be congenital or acquired. It can be congenital or acquired. Definition: it is a clinical syndrome characterized by the following 1. Heavy protenuria a. urinalysis 3+ - 4+protein selectivity b. > 50mg/kg/dayIgG/a/b 50mg/kg/dayIgG/a/b <0.2- selective c. > 1gm/m 2 /day d. > 40mg/m2/hr>0.2 non selective e. urinary pr/cr >2 ( 2 (<0.2 normal) 2. Hypo albuminemia < 2.5g/dl 3. Oedema 4. Hyper cholesteronemia >200mg/dl
EPIDEMIOLOGY Incidence 2-7 :100,000 per year Age 2-6years in the caucasians 5-8years in blacks. 5-8years in blacks. Sex M>F in early childhood M=F in adolescent M=F in adolescent
ETIOLOGY CONTD Secondary Secondary Systemic illnesses like goodpasture syndrome Systemic illnesses like goodpasture syndrome Henoch schonlein purpura. Henoch schonlein purpura. Malignancies like burkitts lymphoma,leukemia Malignancies like burkitts lymphoma,leukemia Toxins like bee sting Toxins like bee sting Infections like HBV, CMV,HIVAN Infections like HBV, CMV,HIVAN Metabolic like DM, Metabolic like DM, Miscellaneous massive obesity, SCA, reflux nephropathy Miscellaneous massive obesity, SCA, reflux nephropathy
PATHOGENESIS Albuminuria/hypoalbumenia : There is T-cell dysfunction with alteration of cytokines which leads to loss of the negatively charged glycoprotein producing an increased permeability of the glomerular basement membrane (GBM). The permeability of GBM heavy urinary loss of albumin, with renal loss of albumin catabolism is increased hence the greater tendency of hypoalbuminemia. There is T-cell dysfunction with alteration of cytokines which leads to loss of the negatively charged glycoprotein producing an increased permeability of the glomerular basement membrane (GBM). The permeability of GBM heavy urinary loss of albumin, with renal loss of albumin catabolism is increased hence the greater tendency of hypoalbuminemia. Hepatic synthesis of albumin is also insufficient at this time to keep up with the urinary loss. Hepatic synthesis of albumin is also insufficient at this time to keep up with the urinary loss.
Oedema: There is altered distribution of albumin. Normally about 30-50% (150gm) of albumin is located in the intravascular compartment while the rest is in the interstitial space. When there is hypoalbuminemia, the total exchangeable albumin is reduced. This produces a distruption of renal mechanism of the extracellular fluid which correlates to the severity of oedema. The reduced albumin leads to reduced plasma oncotic pressure modifying transudation of fluid from the IVS into the Is producing hypovolemia which stimulates RAA and the ADH producing Na+, H2O accumulation. This Na and H2O retention further worsens fluid shift due to the low O.P as it exercerbates albuminemia. The hypovolemia reduces GFR ARF
LIPIDEMIA Lipoproteins are responsible for the transportation of lipids hence when there is hypoalbuminemia the lipoprotein level is reduced and the circulating levels of lipids is increased Lipoproteins are responsible for the transportation of lipids hence when there is hypoalbuminemia the lipoprotein level is reduced and the circulating levels of lipids is increased There is also the inhibition of LPL by the circulating plasma factor due to deficiency of Apo C which is lost in the urine. There is also the inhibition of LPL by the circulating plasma factor due to deficiency of Apo C which is lost in the urine. ↑production of VLDL ↑production of VLDL
Clinical Features Symptoms H x Usually a male child Oedema which the mother first notices as fullness of the face especially on waking up which regresses as the day goes by or she notices tightening of clothing. The oedema later progresses to the feet when it is pitting generalized Anorexia Abdominal pain Oliguria Anuria
PE: - darkening around the periorbital - increase weight for age - increase weight for age - muehrcke’s nails (2 horizontal white stripes due to hypoalbuminemia) - muehrcke’s nails (2 horizontal white stripes due to hypoalbuminemia) - pitting pedal oedema ± anarsarca - CVS: PR - small volume, regular features of shock may be found BP -High Or N (25% have HT) RS – respiratory distress in presence of pulmonary oedema – CNS: lethargic, anxious
COMPLICATIONS INFECTIONS. INFECTIONS. Reduced Ig, opsonization of bacteria Reduced Ig, opsonization of bacteria Hypo-complementamia Hypo-complementamia Reduced bactericidal activity of leucocytes Reduced bactericidal activity of leucocytes Reduced splenic function due to ↓perfusion Reduced splenic function due to ↓perfusion Edema fluid is a good medium Edema fluid is a good medium Protein loss →malnutrition Protein loss →malnutrition The most common infection is 1ry peritonitis caused by Strept pneumococcus. Others are septicemia, UTI,cellulitis. Others are septicemia, UTI,cellulitis.
COMPLICATIONS CONTD Thrombosis Thrombosis Due to hypovolemia which cause circulatory sluggishness. Due to hypovolemia which cause circulatory sluggishness. Increased viscocity Increased viscocity ↓plasma antithrombin ↓plasma antithrombin ↑plasma concentration of coagulation factors(5,7,8,10) ↑plasma concentration of coagulation factors(5,7,8,10) Φof fibrnolysis Φof fibrnolysis ↑platelet aggregation ↑platelet aggregation
COMPLICATION CONTD CVA CVA Results from thrombotic phenomenon Results from thrombotic phenomenon Could be fatal Could be fatal Renal failure Due to reduced GFR Due to reduced GFR Low Vit D, T3,Zinc
MCNS This the commonest of the NS This the commonest of the NS Seen in 85% of cases of the idiopathic NS Seen in 85% of cases of the idiopathic NS Also known as lipoid nephrosis Also known as lipoid nephrosis 10% may have microscopic hematuria 10% may have microscopic hematuria C3 level is normal in them C3 level is normal in them Normal GBM on microscopy Normal GBM on microscopy IF shows occasional mesangial deposit IF shows occasional mesangial deposit EM shows effacement of foot process EM shows effacement of foot process
MANAGEMENT Steroid Month 1 -2mg/kg(60mg/m2) Month 2 -2mg/kg alternate day Month 3 -Tapering of steroid over 2-4wks Diuretic Immunosuppressants CPM 2-3mg/kg * 8-12wks Supportive:-daily weight -I/O -BP monitoring -daily urinalysis -Tx of ARF if present -prevention of infection pneumococcal vac malaria prophylaxis Diet salt restriction protein
MANAGEMENT CONTD Steroid responsive Steroid responsive Urinalysis negative for 3days consecutively Urinalysis negative for 3days consecutively Steroid resistant failure to induce remission Steroid resistant failure to induce remission Steroid dependent relapse of features as steroid is being tailed off Steroid dependent relapse of features as steroid is being tailed off Relapse Relapse occurrence of proteinuria with 2 wks discontinuation of steroid occurrence of proteinuria with 2 wks discontinuation of steroid
PROGNOSIS Histologic type Histologic type Frequency of relapse Frequency of relapse Associated complications Associated complications
GlOMERULO NEPHRITIS INTRODUCTION: Disorders of glomerula structures and functions constitute a major problem with the practise of nephrology. It is a disorder of structure and functional anomaly with either or both structural and functional anomaly. The manifestation of glomerular diseases can be grouped according to various combination of cardinal expressions of the injury and these include protenuria, hematuria, ↓GFR, HT, circulatory congestion (alteration of Na excretion). The disorder is characterized by heterogeneous inflammatory changes. It is of an abrupt onset with a tendency to spontaneous recovery. It may be acute or chronic. The chronic type is a common cause of ESKD in children. Hematuria and proteinuria are non specific expression of glomerular disease. Epidemiology organism: group A streptococcus contains 1,2,3,4,12,12,18,25,49,55,57 Host : latent period of 10-14 days (> 3wks in some) genetic susceptibility Age: 5-12 yrs rare before 2yrs Sex:M>F
ETIOLOGY INTRINSIC INTRINSIC Post streptococcal GN Post streptococcal GN Diffuse proliferative GN Diffuse proliferative GN Mesangial proliferative GN Mesangial proliferative GN Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis Membranous glomerulopathy Membranous glomerulopathy Rapidly progressive GN Rapidly progressive GN
PATHOGENESIS In the idiopatic or primary GN. It is mainly an immune mediated disease based on the Ag provocation, genetic predisposition and immune mediated damage to the glomerular. In the immune mediated damage, the presence of circulating anti GBM ab leads to cell mediated injury by neutrophils and macrophages as well as the mediators of inflammation including the complement system, coagulation system, i.e both humoral and cell mediated mechanisms are involved. Humoral in the formation of Ag-Ab complex. There are nephritogenetic Ags which are unknown except for collagen IV and anti GBM. The T cells are activated and the subset Th1 and Th2 are said to generate different immune effectors responses. There is the proliferation of all the mesangial, endothelial and epithelial cells which may sometimes block the lumen
PATHOPHYSIOLOGY The circulating factor increases glomerular permeability from loss of negatively charged glycoprotein and this leads to loss of protein in urine though not as much as NS and it is non selective. The presence of inflammatory changes involving the GBM leads to hematuria which may either be gross or microscopic. There is ↓GFR RAA, ANP →NA +, H 2 0 of the leads to fluid retention and circulatory congestion GFR …↓RPF GFR …↓RPF Urinary concentrating ability is preserved -Na +,Ca 4 excretion are reduced -H +,K + impairment due to ECF volume expansion
C LINICAL FEATURES Hx of passage of dark smoky urine Hx of preceeding sore throat, skin infection Hx facial or pedal oedema, seizure, oliguria, anorexia ** GROSS HEMATURIA, HT,OLIGURIA ARE THE HALL MARK OF DIAGNOSIS P.E - HT, oedema - respiratory distress in presence of severe fluid accumulation - respiratory distress in presence of severe fluid accumulation - seizures, HT - seizures, HT - HT encaphalopathy and may be unconscious - HT encaphalopathy and may be unconscious Urinalysis:- pH-acid - colour-dark smoky urine - red cell casts commonly leucocyte (pyuria) leucocyte (pyuria) - waxy –suggest pre existing nephritis - pr- +,2+ not massive<500mg/dl -non selective pr (>0.2 IgG/alb) -Na +, Ca2 + reduced -FeNa <0.5% -FeNa <0.5%
E&U-↑Cl,.. -↓Na (dilutional), -↓Na (dilutional), -↑K+ especially if there is oliguria Throat Swab- grp A strept organism ASO>200 todds unit often attained 3wks may be negative in cases of early antibiotic therapy for pharyngitis may be normal if GN followed impetigo Streptozyme:-useful screening bcos it combines with several anti streptococcal ab Complement: -C3 low in the early course of disease - return to normal = 8/52 FBC- anaemia dilutional or due to blood loss dilutional or due to blood loss Rx: Rx HT when present : diuretic diuretic anti HT anti HT Diet: normal protein Low salt when there is HT Low salt when there is HT
PREVENTION PREVENTIONPrevention: -Antibiotics-may reduce the incidence with prompt usage in strept infection -improved personal hygiene Complication-HTencephalopathy -renal failure -hyperkalemia -fluid overload -CCF
BIOPSY Indication for Bx -anuria, -prolonged severe oliguria -prolonged severe oliguria -persistent or marked hematuria -persistent protenuria -low C3 for >3 months
DIALYSIS Indication for dialysis: -severe refractive hyperkalemia -pulmonary congestion - persistent and marked hematuria
DIFFERENTIAL DIAGNOSIS Ig A nephropathy Ig A nephropathy ATN ATN Alport syndrome Alport syndrome SCA glomerulopathy SCA glomerulopathy UTI UTI HUS HUS
PROGNOSIS Immediate prognosis is favourable Immediate prognosis is favourable Pointers of poor prognosis Pointers of poor prognosis Persistent proteinuria Persistent proteinuria Cresentric lesion Cresentric lesion Prolonged severe oliguria Prolonged severe oliguria Persistent proteinuria Persistent proteinuria
CHRONIC GLOMERULONEPHRITIS CHRONIC GLOMERULONEPHRITIS A clinical expression of wide variety of glomerular disease with a protracted course. It is often asymptomatic and there is reduction in renal mass and leads to ESKD. It is often asymptomatic and there is reduction in renal mass and leads to ESKD.Pathogenesis - continued activity of the 1° basic lesion - superimposed hypertensive arterionephrosclerosis - hyper lipidemia - hemodynamically mediated glomerular sclerosis - chronic tubulo interstitial injury Clinical features persistent urinary anomaly after PSAGN e.g protenuria, sediments, hermaturia persistent urinary anomaly after PSAGN e.g protenuria, sediments, hermaturia -renal failure, HT Later: biochemical and metabolic derangements. Uremia Uremia
Renal failure Acute renal failure is a significant cause of morbidity and mortality in children. Morbidities like electrolyte derangements, disordered coagulation and endocrine dysfunction are common. Some definitions: Oliguria: reduction in U.O <= 300ml/m 2 or <1ml/kg/hr Anuria: reduction in U.O to < 1ml kg/day Polyuria: urine output > 4ml kg/hr Azotemia: high nitrogeneous waste indicated by high urea Uraemia: symptom complex reflecting organ dysfunction occurring when the kidney fails to regulate body composition The cause of RF may be prerenal, intrinsic renal or post renal. The commonest causes in pediatrics are often pre-renal and are due largely to preventable causes, least common cause is post renal. 50% ARF in children are non oliguric. Definition: defined as a sudden, rapid and progressive deterioration in renal function manifesting as a rise in plasma urea, creatinine and accompanied by oliguria and occasionally polyuria Recently referred to AKI
EPIDEMIOLGY Causes are largely due to preventable M > F 2:1 M > F 2:1 Age: < 5 yrs – 10 yrs Infants and young children are most vulnerable Incidence: true incidence is not known as ARF is often missed in NB. in most cases 2° causes of ARF predominates especially in developing countries, however in other countries 1° causes predominates e.g HUS, AGN. in most cases 2° causes of ARF predominates especially in developing countries, however in other countries 1° causes predominates e.g HUS, AGN. Seen in 5% of ICU admission Mortality 25%
Aetiology Pre renalIntrinsic a. Volume depletionAGN, HUS GE, peripheral vaso septicemia, malaria DIpyelonephritis burnsacute interstatial nephritis Hge nephrotoxic – NSAID NSorganic solvents b. Reduced effective circulatory volume septic shock, perinatal asphyxia post renal Red C.O PUV, PUJ c. Renal vasoconstrictionVUJ neurogenic bladder neurogenic bladder d. Hepatorenal syndrome
pathogenesis ARF evolves in 3 stages Initiation: results from reduced renal perfusion due to reduction in total effective circulating blood volume. At this stage, there is no kidney damage. The reduction in CBV reduces cortical blood flow, GFR. This is reversible if the causes of ↓CBV is addressed fast if this goes beyond a “critical level” renal damages occur. Maintenance: persistently↓ GFR if the disease is not reversed or the cause of renal failure if not intrinsic is not reversed, there comes an alteration in the intrarenal hemodynamics. There is passive backflow across the injured tubular cells into the peritubular capillaries. Recovery: This will depend on the removal of sub lethally injured cells, necrotic cells, casts as well. There is regeneration of renal cells to restore normal renal function. The factors inducing these are not known..
CLINICAL FEATURES Fluid retention Fluid retention Oliguria Oliguria Oedema Oedema Dyspnnea Dyspnnea HT→convulsion HT→convulsion CCF CCF Features of underlying disease Features of underlying disease Pallor Pallor Acidotic breathing Acidotic breathing
INVESTIGATION INVESTIGATION Pre renalRenal Pre renalRenalUrine SG>1.020 1.020<1.020 Osmolality500<350 Na 20 Fe Na 1 Una / Pcr BUN>20 20<20 Blood – Na, ↑K +,↑ urea, ↓HCO 3, PCV ↓Na+ - due to dilution ↓Na+ - due to dilution ↓C 3 AGN ↓C 3 AGN ↓Ca 2+ ↑PO 4 ↓Ca 2+ ↑PO 4 CXR- cardiomegaly and pulmonary congestion RUSS-IVP ECG- ↑K, arrhythmia
MANAGEMENT MANAGEMENT Mx: Fluid and Electrolyte Restriction to previous days output and the insensible loss Restriction to previous days output and the insensible loss GIT bleeding HTSeizures Indication for dialysis Acidosis Elyte anomaly especially..K+ HT Fluid overload, CCF CNS disturbances (symptomatic …..) BleedingPrognosis -Depends on the underlying etiology -mortality-10-60%
CHRONIC RENAL FAILURE - This is an irreversible reduction in GFR - Prevalence at 18 per million - Cause may be congenital or acquired KDQI defines chronic kidney disease (CKD) as a kidney damage GFR of = 3 months. Whatever is the kidney cause, there is irreversible sclerosis and loss of nephrons which leads to ↓GFR 20% of renal function Clinical staging Stage 1- kidney damage with normal GFR > 90ml/nim 2- mild reduction in GFR 60-69 ml/mm/1.73m2 2- mild reduction in GFR 60-69 ml/mm/1.73m2 3- mod reduction in GFR 30-59 ml/mm/1.73m2 3- mod reduction in GFR 30-59 ml/mm/1.73m2 4- severe “ “ “ 15-29 “ “ “ “ 4- severe “ “ “ 15-29 “ “ “ “ 5- kidney failure GFR < 15ml/mm 5- kidney failure GFR < 15ml/mm
AETIOLOGY Age dependent <5yrs commonly from anatomic anomalies > 5yrs. Acquired glomerular dx GN, UTO, REFLUX,CONG ANOM,UTI have been found to be leading causes of CRF across the globe.
PATHOGENESIS Whatever is the cause of unresolved renal failure, the injury progresses despite the removal of the insult. 1- hyperfiltration sets in as a loss of nephron occurs this is to maintain renal function, the other nephrons undergo structural and functional hypertrophy characterised by↑ GBF thereby increasing the driving force of the surviving nephrons. This compensation temporarily relieves total renal function but as the injury progresses, elevated hydrostatic pressure in the capillary wall integrity coupled with protein toxic effect due to increase passage of protein thru the GBM, the surviving nephrons undergo sclerosis resulting in a vicious cycle. 2 - proteinuria also causes a decline in GFR due to a direct toxic effect on the glomerular capillary and recruitment of macrophage promoting sclerosis and interstitial tubulo fibrosis arteriolar nephrosclerosis 3 - ↑ PO4 CA- PO4 deposition in renal interstitium and blood vessel 4 – lipdaemia causes oxidation mediated injury 5 – HT
Pathophysiology - hyper kelemia dvps when GFR is < 25ml/min due to the red K excretion - - Metabolic acidosis: kidneys are unable to produce enough ammonia in proximal tubule to excrete endogeneous acid - - ECF expansion due to Na, H2O retention - - Anaemia: Normochromic, normocytic due to reduced erythropoetin production, reduced dietary intake, reduced RBC survival time, bleeding tendencies from uremia induced platelet dysfunction - - 20 HPTH due to red Ca2+ from the reduction in production of 1,25 dihydro-cholecalciferol + hyperphosphatemia
CLINICAL FEATURES - - Specific and non-specific Non-specific: headache, fatique, lethargy, anorexia, vomiting, growth failure Specific: anaemia, oliguria, anuria, puffiness
Investigation RUSS: small echogenic kidneys in ESRD polycystic kidney in structural anomalies Renal radionucleid scan: Renal artery stenosis may be performed with captopril though unreliable when GFR<30 CT scan: can define presence of cyst MRI: useful in RVT, RAS VCUG: VUR Urine: urinalysis- Pr: glomerular or TI problems WBC: inetrstinal nephritis especially with eosinophiluria Spot urine for total protein : cr 2.0g in glomerular range 3.0-3.5g in nephrotic range 3.0-3.5g in nephrotic range < 2.0g tubulo interstial problem < 2.0g tubulo interstial problem 24 HUP –total protein - CRCL Blood: serum conplements-in case of AGN -anti GBM abodies-suggestive of good pastures syndrome HB, HC, Retroviral screening Serum E,U Na, urea, Cl-, K+, HCO3 Ca red Ca2+ PO4 inc Lipid profile
Treatment A. Goal is to delay progression if possible B. Treatment of pathologic manifestation C. Renal transplantation A. Treatment of underlying condition like UTI, GNtides, control BP, especially ACE inhibitors to delay progression through the reduction of pr excretion control of lipidemia avoid nephrotoxins B. Anaemia-avoid blood Tx do not initiate Tx till PCV is <30% and aim to maintain PCV at 30% Tx Fe def either orally or parenteral Tx Fe def either orally or parenteral Erythropoetin either SC or IV Erythropoetin either SC or IV C. Electrolyte D. Diet – protein restriction K+, Na+,
PROGNOSIS Poor generally Poor generally Survival beta with RRT Survival beta with RRT
RENAL REPLACEMENT THERAPY Refers to alternative way of helping the body get rid of toxins. Refers to alternative way of helping the body get rid of toxins. Consists of dialysis and transplantation. Consists of dialysis and transplantation. Dialysis APD, HD, CPD Dialysis APD, HD, CPD
DIALYSIS This is a form of therapeutic intervention where the body is cleansed of toxins This is a form of therapeutic intervention where the body is cleansed of toxins Careful assessment of co-morbid state is needed before prescribing dialysis Careful assessment of co-morbid state is needed before prescribing dialysis There are different types of dialysis There are different types of dialysis
PERITONEAL DIALYSIS This is often used in neonate and infants This is often used in neonate and infants Peritoneal membrane is used as the filter Peritoneal membrane is used as the filter Types include Types include APD APD CAPD CAPD In peritoneal dialysis an hyper-osmolar fluid/dialysate is infused into the peritoneal cavity In peritoneal dialysis an hyper-osmolar fluid/dialysate is infused into the peritoneal cavity The infused dialysate is allowed to stay for 45’-60’ The infused dialysate is allowed to stay for 45’-60’ The fluid is then drained either manually or a cycler The fluid is then drained either manually or a cycler This removes fluid and electrolyte This removes fluid and electrolyte This is however CI in abdominal disorders. This is however CI in abdominal disorders.
HEMODIALYSIS This is useful for removal of small particles such as urea and electrolytes This is useful for removal of small particles such as urea and electrolytes The ultrafiltration in this is driven by the generation of negative hydaulic pressure on the dialysate on the dialysate side of the dialyser The ultrafiltration in this is driven by the generation of negative hydaulic pressure on the dialysate on the dialysate side of the dialyser Components are Components are artificial kidney or dialyser artificial kidney or dialyser dialysate (the fluid ) dialysate (the fluid ) delivery system ie mechanical device delivery system ie mechanical device The flow of blood and the dialysate are critical determinants of the effectiveness of the procedure The flow of blood and the dialysate are critical determinants of the effectiveness of the procedure
HEMODIALYSIS CTD ADVANTAGES ADVANTAGES reduces neurologic complications reduces neurologic complications inter-dialysis weight gain is less inter-dialysis weight gain is less low inter dialysis solute accumulation low inter dialysis solute accumulation Done thrice a week. Done thrice a week. Types include the intermittent that is useful in patient with stable hemodynamics, removes both fluid and elyte and uses pump driven extracoporeal circuit Types include the intermittent that is useful in patient with stable hemodynamics, removes both fluid and elyte and uses pump driven extracoporeal circuit
CRRT This is another type of hemodialysis This is another type of hemodialysis Used in patient that a unstable hemodynamically in which there is concomitant sepsis and multi organ failure Used in patient that a unstable hemodynamically in which there is concomitant sepsis and multi organ failure Removes fluids, elyte, small and medium solutes continuously Removes fluids, elyte, small and medium solutes continuously There are different types There are different types CVVH –F(filtration) CVVH –F(filtration) CVVH-D(dialysis) CVVH-D(dialysis) CVVH- DF(hemodiafiltration) this is the most effective of all CVVH- DF(hemodiafiltration) this is the most effective of all
Renal transplantation the optimal treatment for children with ESRD is an early RT. RT is not a cure for ESRD. The first successful transplant was done in BOSTON in 1954 between identical twins the optimal treatment for children with ESRD is an early RT. RT is not a cure for ESRD. The first successful transplant was done in BOSTON in 1954 between identical twins Indication:.ESRD 1. Process: involved Donor:- :living related donor ( LRD-RT) cadaveric related donor (CAD-RT) cadaveric related donor (CAD-RT) 2. Tests 2. Tests MHC blood group HB, HC MHC blood group HB, HC 3. Immuno supression azathxopine, cycloproxine, low dose steroid 4. counselling:-Pre Post Post Complication: 1.rejection-acute early< 60/7 -late acute -late acute -chronic -chronic 2. recurrence of some of the dx 2. recurrence of some of the dx 3. surgical Cx 3. surgical Cx 4. lnfx 4. lnfx Acute – red U.O, low BP, fever, pain, tenderness swelling - occuring within 60 days