Chapter 13 Renal Failure
§1 Concept & Introduction
• Kidney structure: Nephron (Glomerulus & Tubules) ,/ Renal interstitium
,/ Kidney blood vessels, / Urinary tract outside kidney( Ureters & bladder )
•
Many pysiologecal function:⑴Excretory function ⑵Regulatory function
⑶Endocrine and metabolic function
Excretory function & Endocrine function
• Excretory function
Reabsorption and secretion
Filtration function
in glomerulus
In tubules
GFR (125ml/min)
99%
Urine (1.5~2L / 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
Endocrine functions:
•
•
•
•
•
Renin (R)
Prostaglandins(PG)
Kallikrein & Kinin
Erythropoietin(EOP)
1,25-(OH)2-D3
RF
RF
RF
RF
RF
↑ Renal hypertension
↓ Renal hypertension
↓ Renal hypertension
↓Renal anemia
↓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
§2 Acute Renal Failure (ARF)
1. 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.
2. Causes
(1) Prerenal causes(renal hypoperfusion) Prerenal ARF
Blood supply to nephron↓----CO↓,/ Bp ↓,/ BV ↓,/ Constriction
of kidney blood vessels.
Alterations of volume and composition in urine:
Prerenal
causes
Renal perfusion ↓
GFR↓
ADH↑,ADS↑
Oliguria (<400ml/d) or
Anuria (<100ml/d)
Urinary Na+ ↓(<20mmol/L )
Urine specific gravity ↑(>1.020)
Urine osmolality ↑(>400mosm/L)
Ucr / Pcr ↑(>40:1)
RFI < 1
FENa <1
Urine sedimentary assay: (-)
RFI=Urinary Na+∕ Ucr/Pcr
FENa=Urinary Na+/blood Na+/ Ucr/Pcr
(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
Alteration of volume and composition in urine:
Oliguria,Anuria or
Non-oliguria ( ≈1000ml/d)
Urinary Na+ ↑(>40mmol/L )
Severe renal ischemia
Renal poisoinig
Renal perfusion ↓
GFR ↓
ATN
Urine specific gravity ↓(<1.015)
Urine osmollarit↓ (<350mOsm/L)
Ucr / Pcr ↓(<20:1)
RFI >1
FENa >2
(3)Postrenal causesPostrenal
Urine sedimentary assay:
Proteinuria, Cylindruria,Blood
ARFurine.
Obstructive disorders in urinary tract--- large stone,/
Blood clots,/ Scarring of injury or surgery.
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 ↑ATⅡ↑
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.
(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.)
Renal ischemia,renal poisons
Injury of renal tubular cells
Loss of Tubule Integrity
Back-leakage of crude urine
Cellular Debris
Tubular Obstruction
↓ Effective Filtration pressure
↓Glomerular filtration rate
Oliguria
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
2.Diuretic phase
Urine volume>400ml/d, → >3000ml/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,hypokalemia,hypernatremia are
easy to occur.
3. Recovery phase
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 ① urine output not
decrease (400～1000ml/d); ② special gravity
of urine is low and fixed, and urinous sodium
Content is low; ③ existence of azotemia.
The mechanism for this type of ARF is Not
understood currently.
§3 Chronic Renal Failure(CRF)
1. 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.
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.
3.Clinical Course of CRF
(1) Stage of decreased renal reserve(Silent stage)
Ccr>30%,
BUN and serum creatinine(Cr) = nomal,
Renal reserve ↓.
[ Clearance creatinine=Ucr x V / Pcr ≈ GFR ]
(2)Stage of renal insufficiency
Ccr=25~30%, BUN and Cr ↑, Polyuria, Nocturia,
Mild anemia and acidosis.
(3)Stage of renal failure
Ccr=20~25%,Marked anemia, severe acidosis, hypocalcemia,
hyperphosphatemia, BUN and Cr↑↑.
(4)Stage of uremia
Ccr<20%,A series of uremic symptoms, The uremic syndrome
affects every system in the body.
.
4.Pathogenesis of CRF
(1) Intact nephron hypothesois
Intact nephron hypertrophy (filtration↑reabsorption↑)
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”.
GFR↓→filtration of phosphate↓→plasma phosphate↑and
plasma calcium↓→PTH↑→plasma phosphate(N)…
GFR↓↓→Plasma phosphate↑↑→PTH↑↑→breakdown of
bone
→hyperphosphatemia and renal osteodystrophy
(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 (ATⅡ,TGF-β,IL-1, TNF ) influence
mesangial and interstitial cell proliferation and
extracellular matrix deposition
→ nephrons↓→ vicious circle → CRF
(4)Lesion of tubular and interstitial cells
5.Alterations of metabolism add function
(1)Disturbance of water, electrolyte and acid-base
①Disorders of water balance
Nocturia (the urine volume in night time is about 2~3
times in day time, or more than 750ml )
at GFR<40ml/min
Polyuria (>2000ml/d) at GFR<30ml/min
Oliguria (<400ml/d) at GFR=5~10ml/min
Hyposthenuria(<1.020), Isostheuria(1.010, 285mOsm/L)
Proteinuria ,Cylindruria
.
.
②Disorders 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 GFR<25%.
Polyuria in early CRF→hypokalemia.
Oliguria in end-stage CRF→hyperkalimia.
• 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 Ca2+absorption.
• Metabolic acidosis
Impaired ability of the kidney to excrete, H+/ NH4+ excretion
is decreased
GFR↓→retention of phosphate,sulfate and other organic
anions
(2) Azotemia
Non-protein nitrogens( NPN)>28.6mmol/L or
>40mg/dl
Blood urea nitrogen( BUN)>3.75~7.14mmol/L or
>10~20mg/dl
Plasma creatinine (Scr)>0.9~1.8mg/dl
[ Creance clearance=Ucr x V(ml/min) / Pcr ≈GFR .]
Blood uric acid >3~5mg/dl
(3)Renal hypertension
Sodium-dependent hypertension
Renin-dependent hypertension
PGE2↓,PGI2↓and KK-K↓→hypotension
(4)Renal osteodystrophy
which includes renal rickets (for children),adult
osteomalacia, osteitis fibrosa,osteoporosis
Chronic renal Failure
GFR↓
1,25(OH)2Vit.D3↓
Elimination of phosphate ↓
Plasma phosphate↑
Deposition of
Calcium in bone↓
Gastrointestinal
absorption of calcium↓
Hypocalcemia
Secondary hyperparathyroidism
Renal osteodystrophy
Acidosis
(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
§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
3.Pathogenesis of uremia
(1) Uremic Toxins
①Urea
②Guanidine compound
③Amines and phenols
④Middle molecules(mol.wt.500~5000D)
(2) Parathyroid hormone (PTH)
(3)Aluminum
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.