chronic renal failure. general introduction etiology pathogenesis clinical findings ...

Chronic Renal Failure

General introduction Etiology Pathogenesis Clinical findings Complications Diagnosis &D.D. Treatment

Chronic Renal Failure

General introduction

1. CRF is defined as a progressive and irreversible loss of renal function. It is a serious stage of renal insufficiency.

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.

General introduction

stage GFR Scr BUN CM

(ml/min) （ umol/L ） （ mmol/L ） （ mg/dl ） （ mg/dl ）

CompensatoryCompensatory stagestage diminished renal reserve

AzotemiaAzotemiaearly renal failure

UremiaUremialate RF

end-stage RF

primary

50 178(2) 9 （ 20 ） diseases

25-50 178 （ 2 ） 9 （ 20 ） GIT symptoms

< 445 （ < 5 ） <20 （ <55 ） anemia

25 445 （ 5 ） 20 （ 55 ） uremic

10 707 symptoms

Etiology

Any urinary system disease that can impair the structure and function of the kidney may cause CRF.

Causes

Primary GNPrimary GNSecondary nephropathy Secondary nephropathy Obstructive renal diseasesObstructive renal diseasesChronic interstitial nephropathyChronic interstitial nephropathyRenal vascular diseasesRenal vascular diseasesCongenital or genetic renal diseasesCongenital or genetic renal diseasesUnknown reasonUnknown reason

China Primary CGN Obstructive nephropat

hy Diabetic nephropathy Lupus nephritis Hypertensive nephrop

athy Policystic disease

Western Diabetic nephropathy Hypertensive nephrop

athy Primary CGN Policystic disease

Causes

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

Intact nephron hypothesis The “trade off” hypothesis Glomerular hyperfiltration hypothesis Tubular hypertrophy hypothesis Others:lipid disorder,Coagulation disor

der,etc.

PathogenesisProgressive deterioration of renal function

Pathogenesis

Intact nephron hypothesis considerable amount of nephrons has b

een 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.

Progressive deterioration of renal function

   The “trade off” hypothesis

PathogenesisProgressive deterioration of renal function

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.

GFR

PathogenesisProgressive deterioration of renal function

   The “trade off” hypothesis example

serum phosphate

serum phosphate normal

(phosphate rising corrected)

PTH

harmful

regulation

Metastatic calcification

Nervous diseases

Impotence

Myopathy

And so on

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.

PathogenesisProgressive deterioration of renal function

Glomerular hyperfiltration hypothesis

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.

PathogenesisProgressive deterioration of renal function

Others lipid disorder Coagulation disorder etc.

PathogenesisProgressive deterioration of renal function

PathogenesisMechanism 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

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.

Symptoms and signs

Organ/system symptoms signs

General fatigue weakness Sallow-appearing chronically illSkin 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 isosthenuriaNeuromuscular restless legs numbness

and cramps in legsNeurologic generalized irritability stupor asterixis myoclonus

and inability to concentrate peripheral neuropathy

decreased libido

GFR

years

Reversible causes

corrected

Urinary tract infections

Obstruction

Extracellular volume depletion

Nephrotoxins

Hypertension

Congestive HF

Hypercalcemia

Pregnancy

e.t.c.

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 Laboratory findings

The findings of small echogenic kidneys bilaterally(<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.

Clinical findings imaging

Complications Water,electrolyte disorder Acid-base disorder Cardiovascular complications Hematologic complications Gastrointestinal complications Musculo-skeletal problems Skin Endocrine Metabolic disorder Immune system

Water retention or dehydration hyponatremia or hypernatremia Hyperkalemia or hypokalemia Hypocalcemia Hyperphosphatemia magnesium

Water,electrolyte disorder

Hyperkalemia Risk of hyperkalemia (NR 3.5~5.5mmol/L) cardiac conduction system inhibition bradycardia,AVB,escape rhythm,heart arre

st

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.

Water,electrolyte disorder

Decreased potassium excretion Acidosis. Blood transfusion. Increased potassium intake. Drugs---spironolactone

Hyperkalemia (normal distridution )

Water,electrolyte disorder

case58ys 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:

ECG:junctional escape rhythm Serum K:6.8mmol/L,Na:125mmol/L HCO3:11mmol/L

Emergency!Emergency!

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

Hyperkalemia Hyperkalemia TreatmentTreatment

Acid-base disorder Acid-base disorder (death rate)(death rate)

Filtration of titratable acid decreased Tubular H+ secretion decreased NH4

+ formation decreased

Osteodystrophy Hyperkalemia Uremic symptoms(GIT,cardiovascular,pulm

onary…)

Deep breath(kussmaul’s breath),bad appetite vomit ,weakness,coma, HF, BP decrease

PH ,CO2CP & HCO3-

Acid-base disorderAcid-base disorder

TreatmentHCO3

- should be maintained at 18~20mmol/l

Sodium bicarbonate ivdrip or po

Cardiovascular complicationsCardiovascular complications

Hypertension Pericarditis Congestive heart failure Others:atherosclerosis

Hypertension Most common complication of ESRD m

ust be properly controlled.

due to Salt and water retention Hyperreninemic states(RAS)

Cardiovascular complicationsCardiovascular complications

TreatmentA.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.

Cardiovascular complicationsCardiovascular complications

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 changesCr

600

400

200

2 yearshospitalization

BP 200/140

BP140/90

BP138/85

Main treatment:BP control

Diet & Six drugs were takencase

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 hospitalizationIgnore her desease, Drugs withdrawal 1.5 year later,back to hospital again,complained ab

out 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 Failure to control BP can accelerate the progression of accelerate the progression of renal damage.renal damage.

Cardiovascular complications hypertension

retention of fluid

uremic cardiomyopathy

Heart failure

treatment Water & salt intake (oliguria auria)

Dialysis(remove excess water)

Diuretics

DigoxinACEI (is proved to be efficient)

retention of metabolic toxins prolonged bleeding time; declined functio

n 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.

Cardiovascular complicationsPericarditis

Pulmonary effectsPulmonary effects

A. pulmonary edema. B. Pneumonitis. C. Pleuritis. Dialysis is needed.

Hematologic Hematologic complicationscomplications

Anemia

Bleeding

WBC dysfunction

Normochromic and normocytic anemia

decreased erythropoietin production Iron intake decreased Bleeding RBC life span shortened BM suppression

Hematologic Hematologic complicationscomplicationsanemiaanemia

Hematologic Hematologic complicationscomplicationsanemiaanemia

Iron, folic acid, VitB12

BM RBC formation

EPOEPO needed

Spleen old RBC disrupted

ingestion

RBC life span 120days

GIT disorder

EPO decreased

BM suppression

RBC 80days

bleeding

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 Hematologic complicationscomplicationsAnemia treatment Anemia treatment

BleedingBleeding Bruising,epistaxis,menorrhagia,hemorrh

agic pericardial effusion. It is mainly caused by platelet dysfunctio

n. Treatment:dialysis

WBC dysfunction WBC dysfunction prone to infection

Hematologic Hematologic complicationscomplications

Gastrointestinal effectsGastrointestinal effects

Gastrointestinal disturbances are among the earliest and 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-Neuro-MuscularMuscular manifestations manifestations

Early manifestations: weakness insomnia concentration dysorder

Late :character changes,bad memory, dumps,cramp,jerk,delirium,convulsion, coma

osteodystrophyosteodystrophy

Osteitis fibrosa Osteomalacia Osteoporosis Osteosclerosis

Active VitD3 deficiency

Secondary PTH Malnutrition others

Active VitD3 Osteitis fibrosa myopathy

0.25-1.0µg/d

Surgery Osteomalacia Osteoporosis

Osteosclerosis

parathyroid

osteodystrophyosteodystrophytreatmenttreatment

skinskin Pruritus. Yellow pigmentation.

Endocrine abnormalitiesEndocrine abnormalitiesA. Plasma renin concentration is normal or

increased.

B. EPO is decreased.

C. 1,25-(OH)2VitD3 is decreased.

D. Insulin, parathyroid hormone and glucagon are increased.

E.  Hypogonadism.

Metabolic disordersMetabolic disorders A. low temperature. B. Abnormality of glucose metabolism. a. Fasting blood sugar is high in some

cases, because peripheral insulin resistance is increased.

b. Diabetes patients have a decrease in their insulin requirements.

C. Hyperuricemia.

Infection immune system Infection immune system

Prone to infection

Dysfunction of WBC Lower amount of WBC Decreased immune function

Diagnosis Diagnosis and differential diagnosisand differential diagnosis

chronic renal failure(stage) chronic renal failure(stage) Primary diseasePrimary disease Risk factors(reversible)Risk factors(reversible) complicationscomplications

CRF or not?

stage?

early azotemia late ESRD

Risk factors

causes

complications

Diagnostic routeDiagnostic route

TreatmentTreatment Primary diseases and risk factors. Dietary treatment -keto acid use BP control Complications Cautious about the side effect of drugs. Dialysis Renal transplantation

Causes

Primary GNPrimary GNSecondary nephropathy Secondary nephropathy Obstructive renal diseasesObstructive renal diseasesChronic interstitial nephropathyChronic interstitial nephropathyRenal vascular diseasesRenal vascular diseasesCongenital or genetic renal diseasesCongenital or genetic renal diseasesUnknown reasonUnknown reason

China Primary CGN Obstructive nephropat

hy Diabetic nephropathy Lupus nephritis Hypertensive nephrop

athy Policystic disease

Western Diabetic nephropathy Hypertensive nephrop

athy Primary CGN Policystic disease

Causes

GFR

years

Reversible causes

corrected

infections

Obstruction

Extracellular volume depletion

Nephrotoxins

Hypertension

Congestive HF

Hypercalcemia

Pregnancy

e.t.c.

Risk factorsRisk factors

Dietary treatmentDietary treatment

A.   Dietary protein restriction It can decrease BUN, plasma phosphate

concentration and relieve acidosis. But if protein intake is too low, malnutration may occur. Generally, dietary protein should be restricted properly when GFR is lower than 50ml/min.

Pr amount : 0.6g/kg high quality Pr(animal Pr)

B. Diet must consist of enough calories and plenty of VitB, VitC and   lactate.

C. Water and sodium must be restricted if patients have edema, HP, heat failure or oliguria;

D. potassium must be restricted when urine volume is less than 1L/d and phosphate should be restricted at azemia stage.

Dietary treatmentDietary treatment

-keto acid use-keto acid use

-keto acid can combine with nitrogen to form EAA and EAA can combine with urea to synthesize protein, so, using -keto acid can decrease BUN.

BP controlBP control

Systamic BP control Intraglomerular pressure control

relieve hyperfiltration ACEI or ARB

SCr>350umol/L cautious

complicationscomplications

TreatmentTreatment

Dialysis

GFR<10ml/min

SCr>707umol/L

peritoneum D, haemodialysis

Renal transplantation

什么是血液透析什么是血液透析

血液透析需要每周进行 2-3 次，每次 3－ 5个小时。

血液透析是利用血透机来净化血液，机器上有一个特殊的滤器，叫做透析器，它就相当于一个人工肾脏，清除身体里的废物和多余的水分。

血液经过一条塑料管子被引流到透析器里接受净化，净化后的血液再通过另一条塑料管子回流到身体里。

由于一般的静脉不够粗、管壁不够厚，不能满足血透治疗对血流量的要求，所以进行血液透析前必需手术建立一条永久血管通路，最常用的是前臂动静脉瘘。

静脉端穿刺针动脉端穿刺针

动脉化静脉动脉

内瘘处静脉

内瘘处动脉

血液透析是如何进行的？血液透析是如何进行的？

含有废物的血液进入透析器

透析器

经过净化的血液输回身体里

什么是腹膜透析？什么是腹膜透析？

腹膜透析与血液透析一样可以净化血液，不同的是它不需要使用透析机和透析器。它利用你腹部内部的一个空腔—腹腔来进行透析治疗。

开始腹透治疗前，首先需要建立一个安全的通路来进行换液。做一个外科小手术，把一条被称为“腹透管”的柔软、可弯曲的管子插入腹腔。管子的一端留在腹腔里，中间一段埋在皮下，另一端留在腹壁外面。你一定要保护好这条腹透管，这就是你的生命线！

新的肾脏放在哪里？新的肾脏放在哪里？

原来的肾脏移植的肾脏

case58ys 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:

ECG:junctional escape rythum Serum K:6.8mmol/L,Na:125mmol/L HCO3:11mmol/L

Emergency!Emergency!

Case 1: Hu fenlan, female, 68ys

Edema for 30ys, fatigue and anorexia for 2Ms

30ys ago, edema on legs was found when she was in pregnancy.10ys ago, HP was found. Nocturnal urine output has been increased for 3ys. 2Ms ago, suffered fatigue, anorexia, nausea and vomiting. Pruritus and arthralgia occurred.

Physical examination: p,92/min, uremic face,the cardiac dullness distending to the left, systolic murmurs heard on mitral area,percussion pain on right renal area.

Lab tests: renal function:BUN 27.8mmol/l, CRE 766mol/l

blood gas: acidosis electrolytes: plasma Na+, k+, Cl-, Ca2+ decr

eased. x rays: left ventricle enlarged abnormalities of bone

Case 2: zhang tao, femal/ 34ys

Fatigue, anorexia and menorrhagia for 4Ms. 4Ms ago, felt fatigue and dizziness accompanied

by menorrhagia. And then, palpitation , dyspnea, anorexia and nausea occurred gradually. One week ago, Bp 170/110mmHg , BUN 22.6mmol/l, Cre 835 mol/l.

Physical examination: the positivfindings were same as case 1.

Lab tests: plasma k+ P + high, RBC and Hb low.