Renal failure

1
Renal failure
2
1 Introduction

• Normal function of the kidney
• Renal insufficiency
• Causes
• Basic manifestation of renal insufficiency

3
Normal function of the kidney
1.Excretion

• Remove waste product from the body
• Regulate electrolyte and acid-base balance.

2. Endocrine
Produce renin?EPO?1,25(OH)2D3 and
prostaglandins Inactivate gastrin?PTH.
4
Renal insufficiency
Dysfunction of excretion and endocrine
Diseases
Symptoms and signs
Edema, hypertension, oliguric, polyuria,
hematuria, proteinuria, anemia, osteodystrophy.
5
Causes

• 1 Primary renal diseases
• Primary glomerular diseases, Primary tubular
  diseases, Interstitial nephritis, et al.
• 2 Secondary renal lesion
• Circulatory system diseases, immunity siseases,
  metabolic diseases, hematopathy, et al.

6
Basic manifestation of renal insufficiency

• 1 Glomerular dysfunction
• 2 Tubular dysfunction
• 3 Endocrine dysfunction

7
1 Glomerular dysfunction

• ?GFR
• ?blood flow
• ?net filtration pressure
• ? Kf
• ? Glomerular permselectivity

8
2 Tubular dysfunction

• ?proximal tubule
• Renal glycosuria, aminoaciduria, renal tubular
  acidosis, hypophosphatemia
• ?loop of Henle
• Hypotonic or isotonic urine, polyuria
• ?distal tubule
• Acid-base and electrolyte disorders, polyuria

9
3 Endocrine dysfunction

• ? Renin
• ?Endothelins
• ?KKS disorders
• ?AA Disequilibrium
• ?EPO
• ? 1,25(OH)2D3

10
2 Acute renal failure
Conception
Diseases

water intoxication,azotemia, hyperkalemia,
metabolic acidosis
11
Section 1 Cause and Classification
Classification
1 causes Prerenal Intrarenal Postrenal
2renallesion functional organic obstructive
3urine volume Oliguric Nonoliguric
12
Causes

• 1 Prerenal factor
• renal blood flow

• Characteristic
• early stage functional late stage organic
• (2) oliguria

13
Mechanism
ECF?
RBF ?
GFR? Reabsorption?
oliguria Impaired hemeostasis
14
2 intrarenal factor

• Causes
• (1) acute tubular necrosis,ATN 2/3
• acute renal ischemia
• acute renal poisoning hemoglobinuria,
  myoglobinuria
• (2) renal disease

• Characteristic
• (1) parenchymal
• (2) oliguric
• nonoliguric

15

• Differentiation between the two RF
• urine functionalRF organic RF
• specific gravity gt 1.020 lt 1.015
• OP(mmol/L) gt 700 lt 250
• Na(mmol/L) lt 20 gt 40
• UrCr/SrCr gt 40 lt 20
• Sediment normal
• Manicol test urine volume urine volume

Necrosis epithelial cells,RBC,casts, albuminuria
16
3 Postrenal factor

• Causes
• Kidney stone, tumor, obstruction of necrosis
  tissue

• Characteristic
• early stage obstructive
• late stage organic

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Mechanism
Bowmans capsule pressure?
Obstruction of the urinary tract
Net filtration pressure?
GRF?
Oliguria, anuria
18
Section 2 Pathogenesis
1 Glomerular factor

• ? RBF
• (1) Net filtration pressure
• BP lt 60mmHg
• CO RBF
• BP (50-70mmHg) GFR (1/2 2/3)
• BP(40mmHg) GFR 0
• Urinary obstruction intracapsular pressure

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(2)renal vessels constriction RBF
sympathetic nerve Shock RAS
afferent arteriole
constriction prostaglandin kallikrein -
kinin syetem
afferent arteriole constriction efferent
arteriole constriction
GFR
ET
20
(3) swelling endothelial cell ischemia
Na - K - ATPase free radical
endothelial cellular injury
(4)alteration of renal hemorheology
fibrinogen Blood viscosity
RBC??????? PLT?? WBC????? ?????
renal DIC
21
? Glomerular lesion
filtration surface area
Glomerular permselectivity
GFR
22
2 Tubular factor
?tuble obstruction ?? ???? ?????? ??
???? GFR ?passive
backflow ???????????? ???? ????? ???
GFR ??
23
3 renal cellular injury and its mechanism

• ? damaged cells
• (1) renal tubular cells
• 1)necrotic lesion
• tubulorrhexic lesion ?????????
• ??????????
• ????????????
• nephrotoxic lesion?????????
• ?????,??????
• ???????

24
2)apoptotic lesion distal tubule
(2) endothelial cell
Tubular ischemia
??????????
clot
endothelial injury
platelet
glomerular endothelial window
GFR
???????????
25
(3)mesangial cell Ang??ADH Gentamicin?adenosine
 
contraction of mesangial cells
resistance of glomerular capillary filtration
area
GFR
26
?mechanism of cell injury (1) production of
ATP and Na - K - ATPase hypoxia
ischemia toxication  
Na - K - ATPase Ca2 - ATPase
Nain,H2O Ca2in
damage of mitochondria
ATP
27
(2)free radical(FR) ischemia GSH
FR clearance reperfusion
FR?? (3)GSH ??????? ,???? (4)phospholipas
e Ca2in phospholipase A2
  cell membrane injury
Cellular injury
28
(5)alteration of cell framework ischemia
ATP toxication (6)apoptosis
alteration of cell framework
29
Section 3 Clinical Course and manifestation
oliguric ARF

• 1 oliguria phase(daysweeks)
• (1)features of urine
• urine volumeoliguria(?400ml/d)or
  anuria(?100ml/d)
• S.G.1.0101.020
• Na tubular reabsorption dysfunction
• urine sedimenterythrocytes, casts,
  proteinuria

30
(2) water toxication

• oliguria
• Catabolism ,???
• Transfuse fluid
• ADH

Hypervolemic hyponatremia
Fluid retention
Cell edema
31
(3) Hyperkalemia

• Urinary excretion of K
• Tissue destruction
• Metabolic acidosis
• Transfuse non-fresh blood, high K diet
• hyponatremia,exchange of Kand Na

Movement of K from cells into ECF
Hyperkalemia
32
(4) Metabolic acidosis
grogressive,difficult to correct

• GFR excretion of acid production
• Secretion of H??NH3? , reabsorption of HCO3
• Catabolism , acid production

Metabolic acidosis
Hyperkalemia
33
(5) Azotemia (NPNgt40 mg/dl)

• Excretion of protein metabolite
• Protein catabolism

??????????????? ??????
34
2 diuresis phase(12W)

• Mechanism
• ???????????????
• ???????????????
• ?????????,?????
• ???????,?????

35
manifestation

• polyuria,gt400 ml/d
• Early stage Hyperkalemia, Azotemia ,
• Metabolic acidosis
• Late stagedehydration, hypokalemia,
  hyponatremia, infection.

3 recovery phase
36
Nonoliguric ARF

• Feaures
• ???????????
  ????
• ???????????
  ???
• ???,???,???????

37
Section 4 Treatment Principle of ARF

• 1. Treat the cause
• ?????????????
• ???????????
• 2. Rescue actively.
• ?????? ????
• ??????????
• ????.

38

• ???,11???????????9?,??3????
• 9?????????,???????,??34?,?????,????,???????,????
  41????????????????????????,????????????,?????3839
  ???,???????5???????????????,???X??????????,??????
  ?,?????1.0g?1/2?0.9????200ml?,????,??????????????
  ?,????33.92mmol/L,???786.76µmol/L,??8.6mmol/L,????
  ???5.83mmol/L, ???????????????????,???????????

39

• ????60?/?,??120?/?,??85/54mmHg????????,????????
  ??????,??????,????,???,????????,?????,???????????
  ???????,?????????4???????0.5cm,????,??????,??120?
  /?,??,?????????,?????,???????5.5cm????1.0cm,?????
  ????????1.5cm,???????????????????????????

40

• ?????Hb84g/L,???3.261012/L,????????0.14,???0.6
  1,????0.03,????0.22,???196109/L???????8.6mmol/
  L,??128mmol/L,???100mmol/L, ??1.98mmol/L,??2.33mmo
  l/L,???????6.73mmol/L,???37.12mmol/L,???804.44µmol
  /L????pH7.17, PCO23.27kPa,HCO-38.6mmol/L,
  SBE-18.3mmol/L?????????,T????

41

• Addition 
• 1. The role of free radical
• ? kinds and concept of free radical
• free radical
• ?????????????????????????

42

• oxygen free radical
• 
  O-2 ?OH
• kinds of (active oxygen
  1O2?H2O2)
• free radical lipid free radical
• 
  L?LO?LOO
• others Cl?CH3?NO

43

• (2) mechanism of increase of oxygen free radical
•  ? formation of oxygen free radical
•  
• nature oxidation of Hb , Adr , Cyt
  C
• O2 O ?2 H2O2
  OH H2O
• 
  H2O
• oxidation of enzyme xanthine
  oxidase(XO)
• O ?2 xanthine
  uric acid
• 
  O2 O ?2
• Mitochondria CoQ
• Cyt P450 (?????)

44

• Xanthine oxidase
  
• Ischemia
  ATP Ca2i
• 
  xanthine
  xanthine
  
• 
  dehydrogenase
  oxidase
• ADP ?AMP
  
• ? increase of adenosine? xanthine
  O?2
• oxygen free O?2 cell membrane
  
• radical LTB
  4
• repiratory
  burst O?2 ?OH
• 
  mitochondria
• hypoxia
  O?2
• 
  sympathetic
• 
  nervous system

45

• (3) damage action of free radical
• ? membrane lipid peroxidation
• cellular membrane permeability
• lipid peroxidation of membrane Ca2
  i
• lipid cross-linked calcium
  overload
•  
• inhibition of Na-pump
• and Ca2-pump Na i ,
  Ca2 i
•  
• membrane lipid phospholipase C PGs ,
  LTs
• peroxidation phospholipase D
  TXA2
• damage of mitochondria membrane ATP

46

•   ? inhibition of protein function
• enzymes , channels , pump , and so on
• ? destruction of nuclear acid
• ?????DNA?? ??????????
•  

47

• 2 Damage mechanism of calcium overload
• ?phospholipase injury of cell
  membrane
• 
  and cell organ 
• ?ATPas ATP
• ?Ca2 phosphate production of ATP
  
• deposition
•  
• ? Ca2 i XO
  free radical
•  
•  

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Chronic Renal Failure
Section 1 Conception

• etiological factors destruct nephron

Dysfunction of excretion and endocrine
waste product , acid-base and electrolyte
disorders , dysfunction of endocrine
49
Section 2 Causes of CRF

• Renal diseases chronic glomerulonephritis et al
• Vascular disordersdiabetes mellitus?hypertensive
  disease?Periarteritis nodosa, et al
• Urinary tract obstructionurinary
  calculus?prostatic hyperplasia et al

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Section 3 Clinical Course of CRF

• compensatory stage
• Renal insufficiency stage
• Renal failure stage
• Uremia stage

51
?? GFR (ml/min) BUN (mmol/L) Cr (umol/L) ????
??? gt50 lt9 lt178 ????,?????
?????? 2550 920 178445 ??,????,?????
?????? lt25 2028 451707 ??,??????,?????????????
???? lt10 gt28.6 gt707 ?????????
52
Section 4 Pathogenesis

• Intact nephron hypothesis
• Glomerular hyperfiltration hypothesis
• Trade-off hypothesis
• Tubulointerstitial injury

53

• Intact nephron hypothesis

causes
Destroy nephron persistently
Progressive reduction in the number of nephrons
Renal compensation insufficiency
Renal failure
54

• Trade-off hypothesis

(??) ????
GFR?
?????(P)?
(????)
???? (??)
???(PTH)?
55
(No Transcript)
56

• Glomerular hyperfiltration hypothesis

Compensatory glomerular hyperfiltration
Glomerulosclerosis
Renal failure
57

• Mechaniasm of nephron dysfunction
• Primary disease
• Secondary progressive glomerulosclerosis
• RAS activation?oxidative stress?proteinuria?aldost
  erone

58
Section 5 Changes of Function and Metabolism
?????? ????? ???????

• 1 characteristics of urine
• volumenocturia?polyuria(gt2000ml/d)or oliguria

specific gravityhypotonic urine (early stage)?
isotonic urine(late stage) sedimentProteinuria?he
maturia?casts
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???????
??
???
???

• ?????

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2 acid-base and electrolyte disorders

• (1)fluidpulmonary and cerebral edema,heart
  failure,dehydration
• (2)Nahyponatremia?Hypernatremia
• (3) Khypokalemia or hyperkalemia
• K diet emesis?diuretic(excrete K )
• K oliguria?Potassium-sparing
  diuretic?acidosis?catabolism ,
  hemolysis?intake K

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(4) Ca P

• P early stage compensation(PTH )
• late stage nephron
  bone dissolve
• Ca P
• Vit D
• calcium phosphate
• Toxic substance damage
• intestinal tract
• (5) Acidosis ?????? ?carbonic anhydrase
  ??NH3 ??H

Absorption of intestine Ca
62
3 azotemia (NPNgt28.6mmol/L)

• BUN is not parallel to renal function
• Plasma creatinine
• endogenous creatinine clearance rate
• ----?????

Ucr Vu
CCR
Pcr
63
4 renal hypertension

• (1) Fluid and sodium retention
• (2) renin
• (3) kinin?PGE2

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5 renal osteodystrophy

• ?????,???????????????????D3???????????????

includebone cystic Fibrosis?Osteomalacia?osteopor
osis and renal rickets
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(2)Vit D3 ???? ,????
(1)P Ca and secondary hyperparathyroidism
(3) acidosisbone mineral lysis,decalcification,
VitD3 ,absorption of intestine Ca

• (4)Al ????????????????????

66

• ???????

GFR?
1,25(OH)2D3???
??
????
??????
?????
???
????
???
PTH???
????? ???
???? ???
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6 hemorrhagic tendency

• Toxic substance inhibite the function of platelet
• PF3 ????????????

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(1) EPO(2) bone marrow(3)bleeding(4)
Erythrocyte life span(5)Fe and Folic acid
deficiency(6)Al
7 Renal anemia
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End-stage renal failure
uremia
ARF CRF
Intoxication symptom
Toxin
70
source 1. Metabolite 2. Ectogenesis
toxin 3. Ectogenesis toxin metabolite
4. Normal activity material
Uremia toxin
71
common urea, guanidine, amines and
phenol,middle molecules?PTH?Al
Uremia toxin
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• PTH
• 1) renal osteodystrophy
• 2) neurotoxicity
• 3)RBC Plt
• 4) Myocardium injury
• 5) Soft Tissues necrosis
• 6) Protein catabolism
• 7) Cholesterol and triglyceride

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1?nervous system ??2?digestive system
?????3?cardiovascular system4?respiratory
system ??5?skin ????6?immune system
Dysfunction 7?Material metabolism
???????????8?endocrine system EPO, somatotropin,
Ins, thyroid function, sex function
change of function and metabolism
74
Treatment principle 1?treatment of the
primary disease 2? dialysis therapy 3?
renal transplantation
75
????
??,?,35?????????????20?,??1??????
???????????6????????,??10??,??4-5?,2000ml/????,BP1
46/100mmHg,Hb40-70g/L,RBC1.3-1.76?1012/L????,RBC?
WBC?????5-7/HP?3???????,???2500-3500ml/?,?????1.01
0????????????,???????????10?????????,???????????
?????????????????????,?????????
T37??R20?/??P120?/??BP150/100mmHg?RBC1.49
?1012/L?Hb47g/L,WBC9.6 ?109/L,??1.9mmol/L,??1.3mmo
l/L????,RBC10-15/Hp,WBC0-2/Hp,??0-2/Hp,????2-3/LP
?X???????,?????,?????????????,?????
??????????????????????????????????????????????
?????????

76

• ??????,???????????????????,??????????
• ??????????,?????????,?????????????????????????????
  ????????????????????,?????????????????????????????
  ???????????????

77

• ????????????????????????????????????????????????8?
  ??,???????16?????16????,4?????K?,12?????L?????????
  ???L???????????????????

78
??????????
79
Thanks