Chapter 13 Renal Failure

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Chapter 13 Renal Failure
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1 Concept Introduction

• Kidney structure Nephron (Glomerulus Tubules)
  ,/ Renal interstitium
• ,/ Kidney blood vessels, / Urinary tract
  outside kidney( Ureters bladder )
• Many pysiologecal function?Excretory function
  ?Regulatory function ?Endocrine and metabolic
  function

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• Excretory function Endocrine function
• Excretory function

Reabsorption and secretion In tubules
Filtration function in glomerulus
GFR (125ml/min)
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Urine (1.52L / d )
Removal of waste products,drug and toxic
substances Maintenance of water, electrolyte and
acid-base balance Maintenance of volume and
composition in urine
RF
Azotemia,Hyperkalemia,Metabolic acidosis, Water
intoxication,Oliguria,Anuria/Non-oliguria,
Alteration of composition in urine
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• Endocrine functions
• Renin (R) ?? Renal
  hypertension
• Prostaglandins(PG) ?? Renal hypertension
• Kallikrein Kinin ?? Renal
  hypertension
• Erythropoietin(EOP) ??Renal anemia
• 1,25-(OH)2-D3 ??Renal
  osteodystrophy
• 
  hyperphosphatemia
• 
  hypocalcemia
• Intrarenal R-A system
• Intrarenal K-K-P system
• Intrarenal ET-NO/NOS system
• Acute renal failure, Chronic renal failure,
  Uremia

RF
RF
RF
RF
RF
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2 Acute Renal Failure (ARF)

• Concept
• ARF is a complex pathophysiologic process and
  is an important clinical syndrome. It is
  characterized by sudden decline in renal
  excretory function over a period and usually
  associated with oliguria, anuria / non-oliguria,
  Alteration of composition in urine, azotemia,
  hyperkalemia, metabolic acidosis and water
• intoxication.
• Causes
• (1) Prerenal causes(renal hypoperfusion)
  ?Prerenal ARF
• Blood supply to nephron?----CO?,/ Bp ?,/
  BV ?,/ Constriction
• of kidney blood vessels.

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• Alterations of volume and composition in urine

Oliguria (lt400ml/d) or Anuria
(lt100ml/d) Urinary Na ?(lt20mmol/L ) Urine
specific gravity ?(gt1.020) Urine osmolality
?(gt400mosm/L) Ucr / Pcr ?(gt401) RFI lt 1 FENa
lt1 Urine sedimentary assay (-)
Prerenal causes
Renal perfusion ?
GFR?
ADH?,ADS?
RFIUrinary Na/ Ucr/Pcr
FENaUrinary Na/blood Na/ Ucr/Pcr
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• (2) Intrarenal causes (intrinsic renal injury)
• ? Intrarenal ARF
• Injury of renal tissue itself (glomerulus,/
  tubules,/ blood vessels)
• 1) Diseases of glomerulus--- Acute
  poststreptococcal
• glomerulonephritis,/ Vasculitis
• 2) Acute tubular necrosis (ATN)---Severe renal
  ischemia ,/ Renal poisoning (Heavy metals,/
  ethylene glycol ,/ Insecticide
• ,/ Poisonous mushrooms, / Carbon tetrachloride
  )
• A number of chemical agents can selectively
  and critically destroy renal tubular cells.
• 3)Renal vessel injury--- Embolism of renal
  artery,/ DIC
• 4)Renal interstitial injury---Acute interstitial
  nephritis,/ Bilatenal pyelonephritis

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• Alteration of volume and composition in urine

Oliguria,Anuria or Non-oliguria (
1000ml/d) Urinary Na ?(gt40mmol/L ) Urine
specific gravity ?(lt1.015) Urine osmollarit?
(lt350mOsm/L) Ucr / Pcr ?(lt201) RFI gt1 FENa
gt2 Urine sedimentary assay Proteinuria,
Cylindruria,Blood urine.
Severe renal ischemia Renal poisoinig
Renal perfusion ?
GFR ?
ATN
(3)Postrenal causes?Postrenal ARF Obstructive
disorders in urinary tract--- large stone,/
Blood clots,/ Scarring of injury or surgery.
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3.Pathogenesis of ARF

• 1.Renal hemodynamic alterations
  (Vasomotor theory) ? GFR?
• (1)Decrease of renal perfusion pressure
• arterial blood pressure?? Renal blood
  pressure?
• (2)Renal vasoconstriction
• Renin-angiotensin system ??AT??
• Sympathetic adrenergic system?? Catecholamine?,
• Prostacyclin?,Endothelin(ET)?,Nitric
  oxide(NO)?,
• 3)Renal vascular endothelial swelling
• Hemodynamic factors play an important role
  predominatly during the initiation of the acute
  renal insult.

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• (4)Ischemia-reperfusion injury of Kidney
• . Calcium overload(Calcium paradox) / Active
  xanthine oxydase (XO) ?Oxygen flee radicals?
  obstruct renal capillary and cause tubular
  necrosis
• 2.Renal glomerular injury
• Acute glomerulonephritis,lupus
  nephritis?glomerular membrane damage? filtration
  area??GFR?
• 3. Renal tubular injury
• (1)Passive backflow (Back-Leakage theory)
• (2)Tubule obstruction (Tubule obstruction theory)
• 4.Renal cell injury(endothelial?mesangial cells
  etc.)

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• Renal ischemia,renal poisons
• Injury of renal tubular
  cells
• Loss of Tubule Integrity
  Cellular Debris
• Back-leakage of crude urine Tubular
  Obstruction
• ? Effective Filtration
  pressure
• ?Glomerular filtration
  rate
• Oliguria

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4.Alterations of metabolism and
function

• Oliguric Acute Renal Failure
• 1.Oliguric phase
• (1) Urinous alterrations Oliguria / Anuria,
  Alteration of composition in urine. ?as following
• (2) Azotemia ---an abnormally high level of
  nitrogenous wastes (blood urea nitrogen, uric
  acid, serum creatinine)
• ? Autotoxication Syndrome
• (3) Water intoxication
  
  ?Diluted hyponatremia?Cerebral edema,
  Pulmonary edema, Cardiac insufficiency
• (4) Hyperkalemia
• ?Myocardial poisoning
• (5) Metabolic acidosis
• ?Hyperkalemia, Disfunction of CNS

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• 2.Diuretic phase
• Urine volumegt400ml/d, ? gt3000ml/d.
• In the early pase, BUN, serum creatinine,
  potassium, and phosphate may remain elevated or
  continue to rise even though urine output is
  increased. In the late phase, dehydration,hypokale
  mia,hypernatremia are easy to occur.
• 3. Recovery phase

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Nonoliguric ARF is another type of ARF,in which
renal pathological changes And clinical
presentations are relatively slight, so the
disease is shorter, and Prognosis is better. Its
main characters include ? urine output not
decrease (4001000ml/d) ? special gravity of
urine is low and fixed, and urinous
sodium Content is low ? existence of azotemia.
The mechanism for this type of ARF is
Not understood currently.
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3 Chronic Renal Failure(CRF)

• Concept
• CRF a complex pathophysiologic process and is an
  
• important clinical syndrome It is characterized
  by progressive
• and irreversible destruction of renal tissue.The
  Consequences of
• renal destruction express in progressive
  deterioration of the
• filtration,reabsorptive functions and endocrine
  functions of the
• kidney, damage usually proceeds slowly,
  terminating in death
• when a sufficient number of nephrons have been
  destroyed.
• The end stage of CRF is uremia.

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• 2. Causes
• Any disorder that permanently destroys nephrons
  may result in CRF (glomeruli, tubules, renal
• interstitium, blood vessels ,lower urinary
  tract,)
• (1)Glomerular diseases---Chronic
  glomerulonephritis , Systemic erythematosus
  (SLE), Antiglomerular basement nephritis.
• (2)Tubular-interstitium diseases---?vascular
  causes as arteriolar nephrosclerosis,?infectious
  causes as chronic pyelonephritis,?toxic causes as
  chronic analgesic nephritis,
• ?obstructive causes as stones, clots, tumor,
  ureteral or urethral strictures and enlargement
  of the prostate gland.
• (3)Diabetic nephropathy, Hypertensive
  nephrosclerosis

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2. Causes Any disorder that permanently destroys
nephrons may result in CRF ( by glomeruli,
tubules, renal interstitium, blood vessels ,lower
urinary tract,) Exemplum 1) Chronic
glomerulonephritis---by destruction of
glomeruli. 2) Chronic pyelonephritis---by
fibrosis of renal pelvis and medulla. 3)
Hypertension nephropathy---by narrowing of renal
arteries. 4) Renal calculi, urethral or ureteral
stricture---by damage to the nephrons
caused by fluid back-pressure secondary to
obstruction.
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• 3.Clinical Course of CRF
• Stage of decreased renal reserve(Silent stage)
• Ccrgt30, BUN and serum creatinine(Cr)
  nomal, Renal reserve ?.
• Clearance creatinineUcr x V / Pcr GFR
• (2)Stage of renal insufficiency
• Ccr2530, BUN and Cr ?, Polyuria,
  Nocturia,
• Mild anemia and acidosis.
• (3)Stage of renal failure
• Ccr2025,Marked anemia, severe acidosis,
  hypocalcemia,
• hyperphosphatemia, BUN and Cr??.
• (4)Stage of uremia
• Ccrlt20,A series of uremic symptoms, The uremic
  syndrome
• affects every system in the body.
• .

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• 4.Pathogenesis of CRF
• Intact nephron hypothesois
• Intact nephron hypertrophy (filtration?reabsorpti
  on?)
• Destroyed nephron (filtration?reabsorption?)
• (2) Trade-off hypothesis
• Trade off refers a process that organism
  develops a new
• lesion by Correcting an old damage
• AS the nephrons are progressively destroyed,
  increased blood concentration of some solutes
  stimulates secretion of some related regulatory
  factors (such as hormones) in order to maintain
  the excretion function. At the same time,
  however, high blood levels of the regulatory
  factors will result in further metabolic
  disorder. It is termed trade-off.

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GFR??filtration of phosphate??plasma
phosphate?and plasma calcium??PTH??plasma
phosphate(N) GFR???Plasma phosphate???PTH???bre
akdown of bone ?hyperphosphatemia and renal
osteodystrophy
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• (3)Glomerular hyperfiltration hypothesis
• In the single nephron compensatory
  intraglomerular hyperfusion and hyperfiltration,
  together with intraglomerular hypertension result
  in progressive glomerular sclerosis and eventual
  glomerular death
• Several hormones, growth factor,
  biologically active lipids cytokines
  (AT?,TGF-ß,IL-1, TNF ) influence mesangial and
  interstitial cell proliferation and
• extracellular matrix deposition
• ? nephrons?? vicious circle ? CRF
• (4)Lesion of tubular and interstitial cells

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• 5.Alterations of metabolism add function
• (1)Disturbance of water, electrolyte and
  acid-base
• ?Disorders of water balance
• Nocturia (the urine volume in night time is
  about 23
• times in day time, or more
  than 750ml )
• at GFRlt40ml/min
• Polyuria (gt2000ml/d) at GFRlt30ml/min
• Oliguria (lt400ml/d) at GFR510ml/min
• Hyposthenuria(lt1.020), Isostheuria(1.010,
  285mOsm/L)
• Proteinuria ,Cylindruria
• .
• .

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• ?Disorders of electrolyte metabolism
• Disorders of sodium metabolism
• Hyponatremia ( when polyuria)
• ?
• hypernatremia (When oliguria)
• Disorders of potassium metablism
• Serum potassium concentration is usually
  maintained normal range until GFRlt25.
• Polyuria in early CRF?hypokalemia.
• Oliguria in end-stage CRF?hyperkalimia.

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• Disordrs of calcium-phosphate balance
• Hyperphosphatemia
• GFR??filtration of phosphate??plasma
  phosphate?and
• plasma calcium??PTH??plasma phosphate(N)
• GFR???Plasma phosphate???PTH???breakdown of
• bone?hyperphosphatemia.
• Hypocalcemia
• hyperphosphatemia / vitaminD3 metabolism
  dysfunction/
• PTH?calcitonin secretion ? / some toxic
  substances damage GI to reduce Ca2absorption.
• Metabolic acidosis
• Impaired ability of the kidney to excrete, H/
  NH4 excretion
• is decreased
  
• GFR??retention of phosphate,sulfate and other
  organic
• anions

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• (2) Azotemia
• Non-protein nitrogens( NPN)gt28.6mmol/L or
  gt40mg/dl
• Blood urea nitrogen( BUN)gt3.757.14mmol/L or
  gt1020mg/dl
• Plasma creatinine (Scr)gt0.91.8mg/dl
• Creance clearanceUcr x V(ml/min) / Pcr GFR
  .
• Blood uric acid gt35mg/dl
• (3)Renal hypertension
• Sodium-dependent hypertension
• Renin-dependent hypertension
• PGE2?,PGI2?and KK-K??hypotension

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• (4)Renal osteodystrophy
• which includes renal rickets (for
  children),adult
• osteomalacia, osteitis fibrosa,osteoporosis

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• Chronic renal
  Failure
• 
  GFR?
• 1,25(OH)2Vit.D3? Elimination of phosphate
  ? Acidosis
• 
  Plasma phosphate?
• Deposition of Gastrointestinal
• Calcium in bone? absorption of calcium?
• 
  Hypocalcemia
• Secondary
  hyperparathyroidism
• Renal
  osteodystrophy

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(5) Renal anemia Mechanism Reducing
erythropoiten / Cumulating of toxic substances in
body / Bleeding / Toxic substances destroy RBCs
/ Reducing absorption or utilization of iron
and protein (6)Tendency to hemorrhage Mechanism
by inhibiting role of the cumulating renal
poisons (such as urea, Carbamidine,etc.) on
function of platelet
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4 Uremia

• 1.Concept of uremia
• Uremia is the most severe stage of acute or
  chronic Renal
• failure .Besides disorders of water and
  electrolyte metabolism
• and acid-base imbalance, and renal endocrine
  function, the
• patients with uremia will manifest a series of
  autotoxication
• syndroms caused by accumulation of endogenous
  poisons.
• 2.Clinical manifestation of uremia
• (1)Nenrological signs
• (2)Cardiovascular signs
• (3)Respiratory signs
• (4)Gastrointestinal signs
• (5)Endocrine signs
• (6)Signs of skin
• (7)Immunity signs
• (8)Disorders of metabolism

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• 3.Pathogenesis of uremia
• Uremic Toxins
• ?Urea
• ?Guanidine compound
• ?Amines and phenols
• ?Middle molecules(mol.wt.5005000D)
• (2) Parathyroid hormone (PTH)
• (3)Aluminum

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Pathophysiological basis of prevention and
treatment For the treated of ARF are as
following 1.To maintain fluid and electrolyte,
acid-base, and solute homeostasis, such as
treating hyperkalemia and correcting
metabolic acidosis 2.To control the level of
blood nonprotein nitrogen. 3.To prevent
subsequent infection. 4.To promote healing and
renal recovery. 5.To permit other support
measures, such as nutrition to proceed
without limitation. 6.Renal replacement therapy
may be provided by peritoneal dialysis or
intermittent hemodialysis. For the treated of CRF
and uremia are as following 1.To treat the
primary renal disease. 2.To treat reversible
aggravating factor. 3.To prevent or slow the
progression of real disease. 4.To prevent and
treat end stage renal failure. 5.Other treatment.