Chronic Renal Failure • General introduction • Etiology • Pathogenesis • Clinical findings • Complications • Diagnosis &D.D. • Treatment
General introduction • 1. CRF is defined as a progressive and irreversible loss of renal function. It is a serious stage of renal insufficiency.
General introduction • Eliminate wastes and excess water • maintain water,electrolyte and acid-base balance----homeostasis • strong bone • RBC formation(erythropoietin) • control blood pressure(RAAS)
General introduction Renal function declines • retention of metabolite • imbalance of fluid • electrolyte and acid-base disorder • harms to other organs(almost every system)
General introduction • CRF is artificially divided into 3 stages according to glomerular filtration rate (GFR NR 80~120ml/min). Serum creatinine , BUN may reflect GFR in some extent.
Etiology • Any urinary system disease that can impair the structure and function of the kidney may cause CRF.
Causes Primary GN Secondary nephropathy Obstructive renal diseases Chronic interstitial nephropathy Renal vascular diseases Congenital or genetic renal diseases Unknown reason
China Primary CGN Obstructive nephropathy Diabetic nephropathy Lupus nephritis Hypertensive nephropathy Policystic disease Western Diabetic nephropathy Hypertensive nephropathy Primary CGN Policystic disease Causes
Pathogenesis • Progressive deterioration of renal function chronic renal disease is rarely reversable and leads to progressive decline in renal function.this occur even after an inciting event has been removed. • Mechanism of uremic symptoms
Pathogenesis Progressive deterioration of renal function • Intact nephron hypothesis • The “trade off” hypothesis • Glomerular hyperfiltration hypothesis • Tubular hypertrophy hypothesis • Others:lipid disorder,Coagulation disorder,etc.
Pathogenesis Progressive deterioration of renal function Intact nephron hypothesis considerable amount of nephrons has been impaired,remaining nephrons still work,but reduction in renal mass leads to hypertrophy of the remaining nephrons to meet the body’s need. Unfortunately these adaptations place a burden on the remaining nephrons and leads to progressive glomerular sclerosis and interstitial fibrosis.
Pathogenesis Progressive deterioration of renal function The “trade off” hypothesis The “trade off” hypothesis is to be considered together with the intact nephron hypothesis,i.e,the concept that adaptations arising in chronic renal failure may control one abnormality,but only in such a way as to produce other changes characteristic of the uremic syndrome.
Pathogenesis Progressive deterioration of renal function The “trade off” hypothesisexample GFR serum phosphate Metastatic calcification Nervous diseases Impotence Myopathy And so on regulation PTH harmful serum phosphate normal (phosphate rising corrected)
Pathogenesis Progressive deterioration of renal function hypertrophy of the remaining nephrons high filtration, high perfusion and high pressure in glomeruli which will lead to glomerular sclerosis and injure the remaining nephrons. • Glomerular hyperfiltration hypothesis
Pathogenesis Progressive deterioration of renal function Tubular hypertrophy hypothesis although this adaptive mechanism can be beneficial in maintaining fluid, electrolyte and acid-base balance, long term consequence is perpetuation of tubular damage. Tubular hypertrophy is usually associated with increased energy expenditure and high metabolism.
Pathogenesis Progressive deterioration of renal function Others • lipid disorder • Coagulation disorder • etc.
Pathogenesis Mechanism of uremic symptoms Water electrolyte disorder Acid-base imbalance Uremic toxins Uremic symptoms Uremic toxins Decreased depletion of metabolic products. Urea,creatinine,phosphate,sulphate,guanidines,products of nucleic acid metabolism(UA,cAMP…),phenol compounds,hormones(PTH…),middle molecules
Clinical findings Symptoms and signs • The symptoms of CRF often develop slowly and are nonspecific.Individuals can remain asymptomatic until renal failure is far-advanced.(GFR<10~15ml/min ) • In any patient with renal failure,it is important to identify and correct all reversible causes.
Organ/system symptoms signs General fatigue weakness Sallow-appearing chronically ill Skin pruritus easy bruisability pallor ecchymoses excoriations edema xerosis ENT pale conjuctiva Pulmonary shortness of breath rales pleural effusion Cardiovascular dyspnea on exertion hypertension cardiomegaly pain on inspiration friction rub Genitourinary nocturia impotence isosthenuria Neuromuscular restless legs numbness and cramps in legs Neurologic generalized irritability stupor asterixis myoclonus and inability to concentrate peripheral neuropathy decreased libido
GFR corrected years Reversible causes Nephrotoxins Hypertension Congestive HF Hypercalcemia Pregnancy e.t.c. Urinary tract infections Obstruction Extracellular volume depletion
Clinical findings Laboratory findings • Urinalysis early in the course of chronic renal failure provide valuable information,but late in renal failure urinary abnormalities are less conspicuous.
Clinical findings Laboratory findings • Proteinuria • Red cells • Casts red cell casts granular and hyaline casts large “chronic RF cast”(wax) • glycosuria
Clinical findings imaging • The findings ofsmallechogenic kidneysbilaterally(<10cm) by UCG supports a diagnosis of CRF; • Though normal or even large kidneys can be seen with CRF caused by adult polycystic kidney disease,DN,multiple myeloma,amyloidosis and obstructive uropathy. • Radiologic evidence of renal osteodystrophy is another helpful findings.
Complications • Water,electrolyte disorder • Acid-base disorder • Cardiovascular complications • Hematologic complications • Gastrointestinal complications • Musculo-skeletal problems • Skin • Endocrine • Metabolic disorder • Immune system
Water,electrolyte disorder • Water retention or dehydration • hyponatremia or hypernatremia • Hyperkalemia or hypokalemia • Hypocalcemia • Hyperphosphatemia • magnesium
Hyperkalemia Water,electrolyte disorder • Risk of hyperkalemia (NR 3.5~5.5mmol/L) cardiac conduction system inhibition bradycardia,AVB,escape rhythm,heart arrest • Potassium balance generally remains intact in CRF until GFR is less than 10ml/min.However,certain states pose an increased risk of hyperkalemia at higher GFRs.
Hyperkalemia (normal distridution ) Water,electrolyte disorder • Decreased potassium excretion • Acidosis. • Blood transfusion. • Increased potassium intake. • Drugs---spironolactone
case 58ys Female,DM for 15ys ,BP for 5 ys severe edema ,urine output decreased for 2Ms Diagnosis: DM DN CRF(uremia) Refuse to accept dialysis Conservative treatment, symptom not released Felt weakness HR:45bpm,BP:90/40mmHg Cardiac monitor:
Emergency! • ECG:junctional escape rhythm • Serum K:6.8mmol/L,Na:125mmol/L • HCO3:11mmol/L
Hyperkalemia Treatment • Cardiac monitoring, decrease K intake • 1.Correct acidosis: • 2.Calcium chloride (act against the inhibition on cardiac conduction system) • 3.Insulin administration with glucose • 4.An orally or rectally administered ion exchange resin(sodium potassium exchange) • 5.!K+>6.5mmol/L urgent dialysis
Acid-base disorder (death rate) • Filtration of titratable acid decreased • Tubular H+ secretion decreased • NH4+ formation decreased • Osteodystrophy • Hyperkalemia • Uremic symptoms(GIT,cardiovascular,pulmonary…)
Acid-base disorder • Deep breath(kussmaul’s breath),bad appetite vomit ,weakness,coma, HF, BP decrease • PH ,CO2CP & HCO3- Treatment HCO3- should be maintained at 18~20mmol/l Sodium bicarbonate ivdrip or po
Cardiovascular complications • Hypertension • Pericarditis • Congestive heart failure • Others:atherosclerosis
Cardiovascular complications Hypertension • Most common complication of ESRD must be properly controlled. due to • Salt and water retention • Hyperreninemic states(RAS)
Cardiovascular complications Treatment A.salt & water restriction(case) a mildly decreased salt diet(4~6g/d) if hypertension persists, reduced to 2g/d B.Drug therapy ACE inhibitors & ARB are the first recommendation if serum potassium and GFR permit. CCB agents,diuretics,and β-blocking agents. adjunctive drugs that are often needed reflect the difficulty of achieving and maintaining hypertensive control in these patients.
28ys,female,headache for 2 months ,GIT disorder Hypertension found,200/130~140mmHg, Family history:negative urine test : blood 2+, Pr 2+ ;blood test : Hb 88g/L serum test: Cr 596umol/L Kidney image:length 88mm & 92mm;echo changes Cr 600 400 200 case BP 200/140 Main treatment:BP control Diet & Six drugs were taken BP140/90 BP138/85 2 years hospitalization
32ys, female,found hypertension in pregnancy urine Pr3+,blood 3+,gave birth after 8Ms pregnancy (infant died right after delivery) suffer ARF,got recovery,but renal lesion still exited. SCr 200umol/L,drugs taken for BP controlling. After hospitalization Ignore her desease, Drugs withdrawal 1.5 year later,back to hospital again,complained about anorexia,vomitting,fatigue,bad memory,cramp occasionally BP 170/100mmHg Tests:Hb 54g/L,BUN 55mmol/L,SCr 1002umol/L, K+ 5.6mmol/L,Na+128mmol/L,Ca2+ 1.7mmol/L,HCO3- 12mmol/L. case
Failure to control BP can accelerate the progression of renal damage.
Cardiovascular complications Heart failure hypertension retention of fluid uremic cardiomyopathy treatment Water & salt intake (oliguria auria) Dialysis(remove excess water) Diuretics Digoxin ACEI (is proved to be efficient)
Cardiovascular complications Pericarditis • retention of metabolic toxins • prolonged bleeding time; declined function of platelet and decreased amount of platelet. • Chest pain,fever,signs of poor cardiac output; a friction rub may be auscultated, X-ray,UCG • Pericarditis is an absolute indication for initiation of hemodialysis.
Pulmonary effects • A. pulmonary edema. • B. Pneumonitis. • C. Pleuritis. • Dialysis is needed.
Hematologic complications • Anemia • Bleeding • WBC dysfunction
Hematologic complications anemia • Normochromic and normocytic anemia • decreased erythropoietin production • Iron intake decreased • Bleeding • RBC life span shortened • BM suppression
Hematologic complications anemia Iron, folic acid, VitB12 ingestion GIT disorder RBC life span 120days Spleen old RBC disrupted BM RBC formation EPO needed RBC 80days bleeding EPO decreased BM suppression
Hematologic complications Anemia treatment • Recombinant EPO is used in patients 20~50units/kg(1000~4000u/dose) subcutaneously injection or iv. three times a week. • Iron stores must be adequate to ensure response.(folic acid,VitB12)
Hematologic complications • Bleeding • Bruising,epistaxis,menorrhagia,hemorrhagic pericardial effusion. • It is mainly caused by platelet dysfunction. • Treatment:dialysis • WBC dysfunction prone to infection
Gastrointestinal effects • Gastrointestinal disturbances are among the earliestand most common signs of the uremic syndrome. • metabolic taste and loss of appetite; Later, nausea and intermittent vomiting, even gastrointestinal bleeding may occur. Gastritis, peptic ulcer.
Neuro-Muscular manifestations • Early manifestations: weakness insomnia concentration dysorder • Late :character changes,bad memory, dumps,cramp,jerk,delirium,convulsion, coma