Renal Failure

1
Chapter 18

• Renal Failure

2

• Section I .
• Introduction

3
Kidneys are the principal excretive organs
Not only excrete waste metabolic products
to remove various harmful substances,

• But also regulate a variety of material in
  plasma
• to maintain the homeostasis of internal
  environment
• (osmolality and acid-base balance)

Besides, kidneys also produce some bioactive
substances renin, prostaglandins
(regulation of blood pressure)
erythropoietin (formation of matured RBCs)
active vitamin D (metabolism of calcium and
phosphorus)
4
Kidneys are the principal excretive organs
Not only excrete waste metabolic products
to remove various harmful substances,

• But also regulate a variety of material in
  plasma
• to maintain the homeostasis of internal
  environment
• (osmolality and acid-base balance)

Besides, kidneys also produce some bioactive
substances renin, prostaglandins
(regulation of blood pressure)
erythropoietin (formation of matured RBCs)
active vitamin D (metabolism of calcium and
phosphorus)
5
The following pathologic process is termed
''renal failure''
Various causes
Severely impair renal function

• Glomerular filteration rate?
• Retention of metabolic wastes, Disturbanc of
  internal environment

a serial of clinical manifestations
Renal Failure Acute renal failure (ARF)
(CRF) Cronic renal failure
Uremia
6

• 1. Causes of renal dysfunction
• (1) Primary renal disease
• (2) Renal injury secondary to systemic diseases.

7

• 1. Causes of renal dysfunction
• (1) Primary renal disease
• (2) Renal injury secondary to systemic diseases.

1) Glomerular disease 2) Renal tubular
disease 3) Interstitial nephritis 4)
Others
glomerulonephritis nephrotic syndrome
renal
glucosuria aminoaciduria, renal tubular
acidosis
acute or chronic interstitial inflammation
renal injury, tumor, calculus obstructive
nephropathy vascular nephropathy
8

• 1. Causes of renal dysfunction
• (1) Primary renal disease
• (2) Renal injury secondary to systemic diseases
  
• .

1) Circulatory system diseases 2) Auto-immune
and connective tissue diseases 3) Metabolic
diseases 4) Hematological diseases 5)
Others
Shock, AS, thrombosis, etc.
Lupus nephritis, renal injury by rheumatoid
arthritis, etc
Nephropathy caused by amyloidosis,
diabetic or
hyperuricemia
Renal injury by plasmacyte disease, multiple
myeloma or leukemia
Heart failure, hepatic disease, endocrine disease
and malignant tumors
9
2. The basic manifestation of RF

• The anatomic and functional unit of kidney is
  nephron, which
• consists of glomerulus and renal tubule. Each
  human kidney
• has approximately 1 million nephrons. The
  glomerular function
• is to form original urine by filtration, while
  the tubule perform
• reabsorption and secretion. The basic
  presentation of RF include

(l) Dysfunction of glomerule (2) Dysfunction
of renal tubules (3) Dysfunction of renal
endocrine
10
(l) Dysfunction of glomerule
20 of CI

• Renal blood flow?
• Effective filtration pressure of the
  glomerule ?
• Kf (LP?A, permeability and total filtration
  area) ?

Alteration of urinary quantity
GFR ?
125ml/min 180L/day
Permeability ?? (of glomerular
filtration membrane)
99
Abnormality of urinary quality
(hematuria proteinuria)
1.5L/day
11
(2) Dysfunction of renal tubules
The secretion and reabsorption function are
very important for maintain the homeostasis of
internal environment

• l ) Principal influencing factors
• ? Renal tubular EC (may impaired by
  ischemia,
• 
  hypoxia, infection and toxins)
• ? Neuro-humoral factors
• (Aldosterone, ADH, ANP, PTH etc.)
• ? Concentration and flow rate of the
  initial urine
• (ANP atrium natriuretic peptide PTH
  parathyroid hormone)

180L/d
99
1.5L/d
12
2) Types of renal tubular dysfunction

• ? Dysfunction of reabsorption
• Proximal convoluted tubule
  glucosuria, phosphuria,
• aminoaciduria, Na and H2O retention,
  renal tubular acidosis

? Dysfunction of concentration and dilution
Henles (medullary) loop and collecting tubule
polyuria, Isosthenuria (isotonic),
Hyposthenuria (hypotonic)
? Acid-base Disturbances Proximal tubule
(secrete H, NH4, NH3 reabsorb HCO3)
Medullary loop (reabsorb b HCO3 and NH3)
Distal tubule (secrete H)
13

• (3) Dysfunction of renal endocrine
• ? Increased secretion of rennin
  Renin ?

? Declined Kallikrein-kinin system (KKS)
Kinin ?
? Increased secretion of endothelin
ET ?
? Inadequate synthesis of prostaglandins
from arachidonic acid
PGE2 , I2 ?
Renal Hypertension
14

• ? Decreased eryhropoietin
• 
  
• ? Decreased 1-a-hydroxylase
• ? Weakened inactivation to PTH
• ? Weakened inactivation to gastrin
  
  

EPO ?
(90 formed in kidney)
Renal aneamia
1,25-(OH)2- D3 ? PTH ?
Renal osteodystrophy
HCI ?
Ulceration
15

• Section 2.
• Acute Renal Failure

16
Various causes

• Rapidly and severely decline of GFR
• Kidneys fail to excretion and regulation in
  hours to days

Oliguria or anuria Retention of nitrogenous
wastes (azotemia) water/electrolyte acid-base
disturbance
Oliguria is usually emphasized in the past, but
in some cases, patients have high level BUN
(azotemia) while urine volume does not change.
It is called non-oliguria ARF
17
l. Causes and classification

• Acute renal failure (ARF) may result from a
  wide variety of
• diseases (shock, heart failure, severe infection,
  hepatic diseases),
• trauma, surgical procedures, drugs, renal toxins
  and urinary
• tract obstruction.
• According to causes, ARF may be divided into
  three main
• categories Prerenal
• Intrarenal acute renal
  failure
• Postrenal

18

• ( l ) Prerenal failure (functional RF or prerenal
  azotemia)
• (2) Intrarenal failure (parenchymal RF)
• (3) Postrenal failure (Obstructive RF, Postrenal
  azotemia)

caused by any disorder external to the kidneys
that rapidly and severely decreases the blood
supply to the nephron.
caused by disease of the renal tissue itself,
affecting the blood vessels, glomeruli or
tubules.
caused by obstructive disorders (uretal or
urethral) that can block or partially block urine
flow, while the kidney's blood supply and other
functions are initially normal.
19
( l ) Prerenal failure
Hypovolemia, Acute heart failure Expanded
vascular bed volume (Hepatorenal
syndrome Anaphylactic shock, etc. ) Renal
vascular blockage or auto-regulation disturbances
Sudden decrease of renal
perfusion

GFR? Na, H2O
reabsorption?
Azotemia(urinary Cr/plasma Cr gt 40 ) Oliguna
(lt400ml/day) Urinary Nalt20 mmol/L
Urine gravity gt 1.020 No
RBC, WBC or cast in urine
20
 (2) Intrarenal failure
Causes intrinsic (parenchymal) renal diseases
1. Renal tubular diseases
2. Glomerular diseases
3. Renal interstitial diseases
4. Renal blood vessel diseases
Acute renal ischemia
Acute renal poisoning
Acute Tubular Necrosis (most
common)

Renal tubule blocked by Hb or Mb
Glomerulonephritis, pye1onephritis, etc
Severe infection, drug allergy, etc
Thrombosis, DIC, etc
21

• Clinical features
• 1. Oliguria or Non-oliguria
• 2. Isothenuria
• the specific gravity of urine become fixed
  at 1.010 or 0.285 mOsm / L (equal to the osmotic
  concentration of plasma), implying an inability
  of the kidney to concentration or dilute the
  urine.
• 3. Urinary Na gt40mmo l/L (ability to reabsorb
  Na ?)
• 4. Hematuria.
• 5. Azotemia(urinary Cr/plasma Cr lt 20)

22
(3) Postrenal failure

• Stone or tumor ?Bilateral Obstruction

Renal pelvises hydropsy increased renal
interstitial pressure
increased intracapsular pressure ?GFR??
suddenly anuria and azotemia
23
2. Pathogenesis

• There are three major factors may account
• for the development of ARF(ATN)
• 1. Renal hemodynamic factors
• 2. Nephronal factors
• 3. Filtration area and permeability

1. Alteration of renal hemodynamics
2. Renal tubule injury
3. Decreased ultrafiltration coefficient (Kf) of
glomeruli
24
2. Pathogenesis
1. Alteration of renal hemodynamics
2. Renal tubule injury
3. Decreased ultrafiltration coefficient (Kf) of
glomeruli
25
(l ) Alteration of renal hemodynamics

• The decreased renal perfusion caused by
  renal vasoconstriction is the principal
  pathogenesis of ARF.
• Effective filtration pressure, FF Kf ?
• There are many factors may associated
  with renal
• vasoconstriction.

Oliguria or anuria
GFR?
Renin-Angiotensin System
Catecholamine Prostaglandins, etc.
26
1) Renin-angiotension system
Toxin , Ischemia

• Impairing
• proximal convoluted tube and
• ascending limb of medullary lope

vasoconstriction
Reabsorption of Na ?
Renal perfusion pressure ?
Na in distal convoluted tube?
stimulating juxtaglomerular cells in
afferent arteriole
(T-G feedback)
Stimulating macula densa of juxtaglomerular
apparatus
Activating RAS
27

• 2) Catecholamine (CA)
• 3) Prostaglandins (PG)
• 4) Endothelin (ET)
• 5) Others

Effective circulating blood flow? or toxin
? excitation of sympathetic-adrenomedullary
system ? CA??vasoconstriction
of renal cortex
especially of afferent arteriole
Decreased synthesis of PG ? PGI2/TXA2?
? renal
vasoconstriction
Renal diseases may stimulate blood vessel EC
to secrete ET. During ARF the level of plasma ET
and the ability of ET-R to combine ET are all
increased, which will directly or indirectly
lead to renal vasoconstriction
NO synthesis?, ADH, PAF and TNF?and ischemia-
reperfusion injury ? promote ATN
All these go into a vicious circle
and cause increasingly severe damage
28
(2) Renal tubule injury
1) Renal tubule obstruction
Cast formation
2) Renal tubule backflow of original urine
Loss of tubule integrity
29
Renal tubule injury

• Renal tubule EC necrosis Basement membrane
  broken down

Loss of tubule integrity
Dead and detached ECs
Filtered protein (HB or MB)
Backleak of original urine into renal
interstitium
Interstitial edema formation
Cast formation
Oppressing Oppression
renal tubule renal capillary 
Tubule obstruction
Intracapsular pressure ?
Aggravate Aggravate tubule
obstruction renal ischemia
Effective filtration p ?
GFR ?
Oliguria
30
(3) Decreased ultrafiltration coefficient (Kf)
of renal glomeruli

• Decreased filter
  area?
• structural destruction of filter
  membrane
• Ultrafiltration
  Coefficient?

31
3. Clinical course and manifestation

• (l) Oliguria type of ARF
• (2) Nonoliguria type of ARF

32
(l) Oliguria type of ARF

• When various diseases lead to destruction of
  the tubular
• cells of the nephron (as typically occurs in
  cases of ATN),
• a characteristic response pattern is noted.

It usually develops in three stages
? diuresis phase
? recovery phase
Oliguria phase
33

• Oliguria
• Urine volume lt 400 ml / day, or lt50ml / day
  (anuria)
• It usually occurs in one day after renal damage
  and lasting l-2
• weeks. The longer the time last, the worse
  the prognosis is
• A duration more than one month indicates that
  the necrosis of
• tubule is very severe.

l) Oliguria phase
34

• As the urine formation rapidly diminished, the
  wastes of
• protein metabolism and water, electrolytes
  accumulate in
• extracellular fluid, which is often characterized
  by

1. Azotemia Progressive elevation of NPN
(Urea, creatinine, etc.)
2. Hyperkalemia May lead to ventricular
fibrillation and cardiac arrest
(No.1 cause of
death)
3. Metabolic acidosis May depress CNS and
heart, aggravate hyperkalemia
4. Retention of water and sodium Edema,
hyponatremia and even water intoxication
would occur if there is water and
salts overload
35
2. Hyperkalemia
2. Hyperkalemia
3. Metabolic acidosis
Death Triangle
4. Edema, hyponatremia and Water
intoxication
36
Differences between functional and parenchymal
ARF

• INDEXES F - ARF
  P - ARF
• Urine specific gravity gt l .020
  lt l .0l 5
• Urine osmolality gt 500 mmol / L
  lt 350 mmol / L
• Urine Na lt 20 mmol / L
  gt 40 mmol / L
• Urine Cr / Plasma Cr gt 40
  lt 20
• Renal failure index (RFI) lt l
  gt 2
• FENa lt l
  gt2
• Urinary sediment Normal
  Proteins, cells, casts 

urine Na
urine Na /serum Na urine Cr/plasma Cr
urine Cr/plasma Cr
RFI
FENa
37

• 2) Diuresis phase
• If the patient pass through the oliguria
  phase safely, the tubular
• EC may regenerate and the renal function would
  recover gradually.
• An increasing urine volume is a signal of
  renal EC healing, and
• suggests the start-up of diuresis phase if it is
  more than 400 ml per
• day. After then, the urine volume increasing
  doubly up to 3-5L/day
• and may last about one month.

38

• The mechanisms for diuresis including
• a) The RBF GFR recovered gradually while the
  reabsorption function of regenerating immature
  tubules keep on abnormal.
• b) The high level of metabolic products retained
  during the oliguria phase resulted in a
  hyperosmolarity diuretic effect.
• c) The tubular integrity recovered, interstitial
  edema subsided, the casts to be washed out and
  the tubular obstruction relieved.

39

• During this stage, the excretion of urea and
  other nitrogenous
• compounds lags behind that of salt and water as
  reflected by the
• continual rise in the concentrations of these
  substances for
• several days after the onset of the diuresis.
• The reason is the incomplete recovery of GFR.
  Nevertheless,
• the tubular function also not well recovered, the
  kidney still
• work as a simple filter. Salt and water loss
  could occur and lead
• to dehydration, hypokalemia and hyponatremia.

40

• Therefore, this stage is also considered to be
  a critical phase,
• and it has been pointed out that approximately 25
  percent of the
• deaths in ARF occurred following the onset of the
  diuresis.

41
3) Recovery phase

• The improvement of renal function leads to
  a gradual reduction of BUN and correction of
  water, electrolytes and acid-base imbalance. The
  full recovery is depends on the healing of
  tubular ECs.
• This process may take up three months to
  one year. Unfortunately, not all individuals are
  restored to health and may become chronic renal
  failure due to serious damage of the renal
  tubular EC and the fibrosis of renal tissue.

42
(2) Nonoliguric type of ARF

• While oliguria is a hallmark of ARF, some
  patients will develop
• an acute lose of renal function without
  oliguria. The common
• cause of this type is renal toxic substances,
  especially the
• aminoglycoside antibiotics and radiography
  contrast agents.

It is suggested that in such cases, GFR has
not been reduced severely and might remain
partial tubule function, but its ability of
concentration is impaired. The urine volume may
be more (about 400-1000ml / day) and the
concentration of Na in urine may be lower,
while azotemia is still existed.
43

• The prognosis of which is better than that of
  oliguria type. It
• might be related to either a milder renal injury
  or fewer
• complications because of better water/
  electrolyte and acid-base
• balance. However, both types may transform each
  other, the
• nonoliguria type will become oliguria type if
  having not pay
• attention and treat properly.

44
4. Principles of prevention and treatment

• (l) Etiologic treatment (shock, infection,
  DIC, kidney disease,
• recover renal perfusion, eliminate
  tubule obstruction, etc.)
• (2) Diuresis (osmolar diuretic improving
  perfusion,
• excreting toxin and
  alleviating tubular obstruction)
• (3) Maintaining water and electrolytes
  balance,
• correcting hyperkalemia.
• (4) Dialysis (peritoneal dialysis or
  hemodialysis)

45
Various causes
Summary for ARF

• Rapidly and severely decline of GFR
• Kidneys fail to excretion and regulation in
  hours to days

Oliguria or anuria Retention of nitrogenous
wastes (azotemia) water/electrolyte acid-base
disturbance
Acute Renal Failure
Prerenal failure (functional RF)
Intrarenal failure (parenchymal RF)
Postrenal failure (Obstructive RF)
Acute Tubular Necrosis
46
Pathogenesis
Summary for ARF
Toxin , Ischemia
renal tubule injury
Renal hemodynamic alteration
Backleak of original urine into renal
interstitium
renal vasoconstriction
renal perfusion ?
Tubule obstruction
effective filtration pressure
Oliguria
GFR??
glomerular Kf ?
47
Clinical course and manifestation
Summary for ARF

• (l) Oliguria type of ARF

phase ? phase
? phase
diuresis
recovery
Oliguria
hyperkalemia
Metabolic acidosis water intoxication
Differences between functional and parenchymal
ARF (
)
Urine specific gravity, osmolality, Na, Cr
, sediment
(2) Nonoliguric type of ARF
GFR has not been reduced severely and might
remain partial tubule function, but its ability
of concentration is impaired
48
Todays question

• (l) What are the primary causes of death in
  oliguria type of ARF?

Hyperkalemia metabolic acidosis water
intoxication

(2) How to differentiate the functional and
parenchymal ARF


INDEXES F - ARF
P - ARF Urine specific gravity
Urine Na Urine Cr / Plasma Cr Urinary
sediment
gt l .020 lt l .0l5
lt 20 mmol / L gt 40 mmol / L
gt 40 lt 20
Normal Proteins, cells, casts
49

• Section 3.
• Chronic Renal failure

50

• CRF is characterized by progressive and
  irreversible loss
• of large numbers of functioning nephrons, which
  lead to a very
• significant reduction in GFR. The remnant nephron
  fail to
• excrete waste metabolic product and keep the
  constancy of
• internal environment.

Various diseases (kidney or kidney-related
diseases)
progressive irreversible destruction of nephron
Retention of waste metabolic products Water/elect
rolyte and acid-base imbalance Disturbance of
renal endocrine
CRF
51

• A wide variety of renal disorders, including
  disorders of
• the blood vessels, glomeruli, tubules, renal
  interstitium
• and lower urinary tract, can cause CRF.
• Common causes
• Primary--Chronic glomerulonephritis,
  interstitial nephritis
• Secondary--diabetic or hypertensive
  nephropathy
• (The incidence of secondary CRF is
  increasing recently, about 36 and 30 of CRF
  caused by diabetes and hypertension respectively
  in USA.)
• CRF is the ultimate common outcome of various
  kidney or
• kidney-related diseases and have been called
• End-stage renal disease (ESRD).

52
1. Process of disease

• The general course of progressive renal failure
  may be divided into 4 stages
• 
  GFR BUN BCr
  
• Stages
  (ml/min) (mmol/L) (umol/L)
• Compensatory Stage gt50
  lt9 lt178
• Decompensatory Stage 2550
  920 178445
• (renal insufficiency)
• Renal failure lt25
  2028 451707
• Uremia lt10
  gt28.6 gt707
• BCr blood level of
  creatinine

53
Clinical manifestation
Uremic stage
(1)
Renal failure stage
Compensatory Stage
Decompensatory stage
Asymptomatic
Compensatory stage
of normal clearance rate of Cr
CCr GFR BUN BCr ()
(ml/min) (mmol/L) (umol/L) gt30 gt50
lt9 lt178

• Clinical
• Asymptomatic

54
Clinical manifestation
Uremic stage
(2)
Renal failure stage
Decompensatory Stage
Decompensatory stage
Asymptomatic
Compensatory stage
of normal clearance rate of Cr
CCr GFR BUN BCr ()
(ml/min) (mmol/L) (umol/L) 2530 2550
920 178445

• Clinical
• Lassitude, Mild anemia, Nocturia,
• Alimental tract discomfort

55
Clinical manifestation
Uremic stage
(3)
Renal failure stage
Renal failure Stage
Decompensatory stage
Asymptomatic
Compensatory stage
of normal clearance rate of Cr
CCr GFR BUN BCr ()
(ml/min) (mmol/L) (umol/L) 2025 lt25
2028 451707

• Clinical
• Anemia, Acidosis, Cl-?, Na?
• Hypocalcemia, Hyperphosphatemia

56
Clinical manifestation
Uremic stage
(4)
Renal failure stage
Uremic Stage
Decompensatory stage
Asymptomatic
Compensatory stage
of normal clearance rate of Cr
CCr GFR BUN BCr ()
(ml/min) (mmol/L) (umol/L) lt20 lt10
gt28.6 gt707

• Clinical
• Various uremic symptoms

57
2. Pathogenesis

• Despite primary causes, the pathogenesis of
  CRF is a process
• in which
• the nephrons to be damaged continually
• the renal function to be declined
  progressively until failed.

The remnant nephrons (so called intact
nephrons) are compensatory hypertrophy, but
their number decreasing day by day and finally
become decompensatory.
The degree of renal dysfunction depends on the
number of intact nephron
58

• There are two principal types of nephron injury
• (1)   Glomerulosclerosis
• (2)   Tubulointerstitial injury

1) Alteration of glomerular basement membrane
permeability 2) Hemodynamic alterations of
intact nephrone
2) Hemodynamic alterations of intact nephrone
Injuries ? basement membrane
permeability? ?
? Mesangial
cells overload and damaged Proteinuria
?
? Mesangial cells
proliferation and increased Cast formation
production of extracellular matrix
Tubule blocked
? ?

Glomerulosclerosis
59

• There are two principal types of nephron injury
• (1)   Glomerulosclerosis
• (2)   Tubulointerstitial injury

1) Alteration of glomerular basement membrane
permeability 2) Hemodynamic alterations of
intact nephrone
The number of nephron decreasing day by day

? pressure and flow in glomerular capillary of
remnant nephron?
? glomerular hyperfiltration ? further glomerular
injury
60

• There are two principal types of nephron injury
• (1)   Glomerulosclerosis
• (2)   Tubulointerstitial injury

Compensatory hypertrophy in remnant nephron
metabolism ?
oxygen
consumption ? free radical production ?

Tubulointerstitial injury
61

• There are two principal types of nephron injury
• (1)   Glomerulosclerosis
• (2)   Tubulointerstitial injury

Compensatory hypertrophy in remnant nephron
metabolism ?
oxygen
consumption ? free radical production ?

Inflammatory response fibrin
deposition in tubules and surrounding
interstitium
Tubulointerstitial injury
62

• There are two principal types of nephron injury
• (1)   Glomerulosclerosis
• (2)   Tubulointerstitial injury

Loss of some nephrons leads to compensatory
hyperfunction of others, increasing their
vulnerability to damage and going to a vicious
cyclethe nephrons to be continuously lost and
the GFR progressively decreased until the renal
function failed.
63
3. Alteration of function and metabolism

• (1) Disturbance of water, electrolyte and
  acid-base balance
• (2) Azotemia
• (3) Renal hypertension
• (4) Hematologic disorders
• 1) Renal anemia 2) Tendency of bleeding
• (5) Renal Osteodystrophy

64
Disturbance of water, electrolyte and acid-base
balance
l) Water disturbance Alteration of urine
volume Changes in urine osmotic pressure 2)
Electrolyte disturbance Natrium
Potassium Calcium Phosphorus 3) Metabolic
acidosis
65
l) Water disturbance Alteration of urine
volume Changes in urine osmotic pressure

• a) Nocturia (urine volume night gt daytime, or gt
  750 ml)
• b) Polyuria (gt2000 ml per day in adult)
• Mechanisms ? Increased blood flow and rapid
  flow rate of primary urine in the remnant
  nephrons ? Hyperosmolarity diuretic effect ?
  Decreased ability of urine concentration caused
  by destruction of osmolar gradient in medulla.
• c) Oliguria (lt 400 ml per day in adult) when
  extremely few of functional nephrons
  (GFRlt510ml/min).

66
l) Water disturbance Alteration of urine
volume Changes in urine osmotic pressure

• Hyposthenuria
• urine specific gravity lt 1.020 (nomal
  1.002 1.035)
• Isosthenuria
• urine specific gravity fixed at 1.010 or
  0.285 mOsm / L
• (equal to the osmotic concentration of
  plasma, implying
• inability of the kidney to concentration
  or dilute the urine)

67

• 2) Electrolyte disturbance
• Natrium
• Regulation ability?, may maintain normal at
  compensatory stage but tend to depletion or
  retention at late stage.
• Potassium
• May maintain normal as long as the urine
  volume is not
• decreased, although the regulation ability
  has been impaired.
• Hyperkalemia may occur when oliguria,
  acidosis at late stage.

68

• Calcium Phosphorus
• a) Hyperphosphatemia
• GFR??excretion of P?? ? P??Ca?? PTH?
  

Inhibiting reabsorption of phosphorus by tubule?
phosphorus release from bone?
Early stage (GFRgt30ml/min) ? ? ? P remain
normal
Late stage (GFRlt30ml/min) ? lt ? ? P? ? ?
P??
69

• b) Hypocalcemia
• ? Ingestion and absorption of Ca2 inadequacy
• ? P??Ca?to maintain CaP constant
• ? phosphorus excreting through
  intestine
• ?
  interfering absorption of Ca2
• ? 1-hydroxylase?? 1,25-(OH)2-D3?
• ?
• 
  intestinal absorption of Ca2 ?
• ?
• ? Inactivation ? ? PTH?

70

• 3) Metabolic acidosis
• when GFRlt20ml/min, metabolic acidosis will
  occur
• ? Decreased ability of tubule to excrete
  acidic products
• (HPO42, SO42, etc.)
  AG?, Cl-normal
• ? Decreased ability of tubule to
• conserve HCO3-
  AG normal, Cl-?
• ? Decreased ability to secrete H
  
  

interstitial nephritis
71
(2) Azotemia

• Non-protein nitrogen (NPN) gt 28.6 mmol/L (40
  mg/dl).
• Urea, creatinine, uric acid
• 1) Blood urea nitrogen (BUN)
• BUN is not a ideal index for renal function
• It is just increasing if the decrease of GFR
  more than 50.
• It may influenced by exogenous urea (protein
  intake) or
• endogenous urea (infection, alimentary tract
  bleeding)

72

• 2) Creatinine (Cr)
• Cr is end-product of creatine and
  phosphocreatine metabolism.
• Although Cr is rarely influenced by protein
  intake, it is also not
• sensitive during early stage of CRF.
• However, the clearance rate of Cr (CCr ) is
  closely related to
• GFR, as it can be filtrated through glomerulus
  freely but can not
• be reabsorbed by tubule, and only small amount
  may be secreted
• by proximal tubule.
• CCr UV/ P 
• (U urinary level of Cr, V urine volume per
  min, P plasma level of Cr)

73
(3) Renal hypertension

• 1) Sodium and H2O retention
• 
  (sodium-dependent hypertension)
• 2) Increased activity of renin-angiotensin system
• 
  (renin-dependent hypertension)
• 3) Decreased anti-hypertension agents secreted by
  kidney
• 
  (Kallikrein-kinin system and PG system)

74
(3) Renal hypertension

• 1) Sodium and H2O retention
• 
  (sodium-dependent hypertension)
• 2) Increased activity of renin-angiotensin system
• 
  (renin-dependent hypertension)
• 3) Decreased anti-hypertension agents secreted by
  kidney
• 
  (Kallikrein-kinin system and PG system)

Ability of excreting Na, H2O?? Na, H2O
retention ? blood volume?? cardiac
output?? hypertension ?more sensitive
of blood wall ? vasoconstriction ?
75
(3) Renal hypertension

• 1) Sodium and H2O retention
• 
  (sodium-dependent hypertension)
• 2) Increased activity of renin-angiotensin system
• 
  (renin-dependent hypertension)
• 3) Decreased anti-hypertension agents secreted by
  kidney
• 
  (Kallikrein-kinin system and PG system)

Disorder of renal circulation ? hypoxia ?
activating RAA ?AII?? vasoconstriction ?
peripheral resistance? ?

? Aldosterone ?? Na, H2O retention ?
hypertension
76
(3) Renal hypertension

• 1) Sodium and H2O retention
• 
  (sodium-dependent hypertension)
• 2) Increased activity of renin-angiotensin system
• 
  (renin-dependent hypertension)
• 3) Decreased anti-hypertension agents secreted by
  kidney
• 
  (Kallikrein-kinin system and PG system)

Renal dysfunction Renal hypertension
(vicious circle)
77
(4) Hematologic disorders

• 1) Renal anemia (97)
• Decreased production of RBC
• ? Synthesis of erythropoietin?
• ? Deficiency of hematopoietic material (iron,
  folic acid)
• ? RBC-inhibiting factors inhibit RBC
  production
  
• ? Aluminium toxication (inhibiting synthesis
  of hematin,
• interfering iron transfer and stem
  cells proliferation)
• Increased destroy or loss of RBC
• ? Hemolysis, Hypersplenism
• ? Bleeding
•  

(Toxic substances Guanidines, Amines, Phenols,
PTH, Al, etc.)
78

• 2) Tendency of bleeding (17-20)
• The main cause is the abnormality of platelet
  quality rather than its quantity.
• Uremia
  CRF
• Uremic toxins
  TXA2 ? ,PGI2 ?
• (guanidines, phenol)
  Vasopressin receptor ?
• Platele
  dysfunction
• Decreased adherence, aggregative function and
  release of PF3

79
(5) Renal Osteodystrophy (renal osteopathy)

• 1)  Disorder of Vitamin D metabolism
• 2) Disorder of Calcium and phosphorus
  metabolism and
• secondly hyperparathyroidism
•   3)  Aluminium accumulation
• 4)  Acidosis

80

• Chronic RF (dysfunction of excretion and
  endocrine of kidney)
• 
  Excretion of P?

Renal osteodystrophy
81

• Section 4.
• Uremia

82

•   End-Stage of ARF or CRF

Retention of metabolic end-product and endogenous
toxin Disturbance of water/electrolyte and
acid-base balance Disorder of endocrine function
a series of auto-toxic symptoms
Uremia
83
1. Pathogenesis

• (1) Uremic toxin (more than 100)
• (2) PTH
• (3) Aluminium

84

• (1) Uremic toxin (more than 100)
• Urea Guanidines Amine and
  phenol
• Middle molecular weight toxins
• 1) Urea -principal end product of protein
  metabolism
• May lead to headache, Anorexia, nausea,
  vomiting,
• glucose
  tolerance? bleeding

85

• 2) Guanidines second abundant nitrogenous
  matter
• The only confirmed pathway for guanidines
  synthesis is

Arginine
(Normal pathway)
(RF)
Methyl guanidine Guanidino succinic acid
Guanidino acetic acid
Excretion
Creatinine
Both with strong toxicity May induce almost
symptoms of uremia.
86

• 3) Amine and phenol
• Produced by enteric germs, mainly toxic to
  nerve system
• 4) Middle molecular weight toxins (500-5000
  Dalton)
• Can removed by peritoneal dialysis but not
  hemodialysis
• May lead to peripheral or central nerve
  disorder, RBC and
• platelet injury, cellular immune and
  endocrine dysfunction, etc.

87
(2) PTH

• 1)  Mechanism
• ? hypocalcemia ? stimulating thyroid
  proliferation ?
• secondly hyperparathyroidism ? PTH?
• ? decreased elimination and degradation of
  PTH by kidney

88

• 2) Toxicity of PTH
• ? Inducing renal osteodystrophy
• ? Neural toxicity (decreasing neural
  transmission)
• ? Anemia and bleeding
• (inhibiting RBC production and
  Platelet aggregation)
• ? Infection
• (inhibiting WBC migrating,
  phagocytosis and Ab production)
• ? Myocardium injury, vasodilation and B.P.?
• ? Soft tissue necrosis
• ? Increasing protein catabolism? nitrogenous
  substances?
• ? Increasing serum cholesterol and
  triglyceride

89
(3) Aluminium
1)  Mechanism 95 of Al combined with
transferrin in plasma, thus difficult to remove
by dialysis

• 2) Toxicity
• Inhibiting enzymes, toxicity to cell nuclear
• May induce dialytic encephalopathy,
• osteomalacia and
  small-cell anemia.

90
2. Functional and metabolic alterations

• System Altered function
  Manifestation
• Nerve system Increase in metabolic
  Uremic encephalopathy
• products (urea,
  guanidine) Peripheral neuropathy
• Cardiavascular Activation RAS
  Hypertension
• system Excess ECF
  Congestive heart failure
• Elevated BUN
  Uremic pericarditis
• Respiratory Acidosis
  Kussmauls respiration
• system Heart failure,
• Na/H2O retention
  Pulmonary edema
• Hypoalbuminemia
• Urea stimulation
  Uremic pleuritis

91

• System Altered function
  Manifestation
• Digestive Urea ? ammonia
  Anorexia, nausea,
• system
  Vomiting, diarrhea
• gastrin ?HCl?
  Ulceration
• Endocrine Ability of hormone
  Disorder of endocrine
• system secretion or elimination?
  Sexual function impaired
• Skin Ca2, urea deposition
  Itch, urea cream
• Immune Impaired cellular immunity
  Infection
• Metabolism
  Glucose tolerance?
• 
  Hypoproteinemia
• 
  Hypertriglyceridemia

92
3. Principles of prevention and treatment

• (1) Preventing further renal
• injury
• (2) Dialysis (hemodialysis
• or peritoneal dialysis)
• (3) Renal transplantation
•  

93
Summary for CRF
1. A pathologic process of retention of waste
metabolic products, water/electrolyte and
acid-base imbalance, disturbance of renal
endocrine caused by progressive irreversible
destruction of nephrons in kidney or
kidney-related diseases is called chronic renal
failure. It usually go through 4 stages
compensatory stage, decompensatory stage, renal
failure stage and uremia stage.
94
Summary for CRF
nephrons in kidney or kidney-related diseases is
called chronic renal failure. It usually go
through 4 stages compensatory stage, decompensato
ry stage, renal failure stage and uremia
stage. 2. The pathogenesis of CRF include 2
types of nephron injury glumerulosclerosis
and tubulointerstitial injury. The functional
and metabolic alterations in CFR primarily
include
, ,
, hematologic
disorders ( ,
), and
.
water, electrolyte and acid-base imbalance
azotemia
renal hypertension
renal anemia
bleeding tendency
renal osteodystrophy
95
Summary for CRF
electrolyte and acid-base imbalance, azotemia,
Renal hypertension, hematologic disorders(Renal
anemia, bleeding tendency), and renal
osteodystrophy 3. A series of auto-toxic
symptoms at end-stage of RF caused by retention
of metabolic waste and endogenous toxin,
disturbance of water/electrolyte and acid-base
balance, disorder of endocrine function are
called uremia. The pathogenesis include uremic
toxins ( , , ,
. ), and
. Besides the symptomes of
CRF, functional and metabolic alterations in most
organ systems may occur.
urea
guanidines
amine and phenol
middle molecular
weight toxins
PTH
aluminium
96
The End
Back to cover
97

• A.  Definition of terms (15)
• B.  Fill in the blanks with suitable words (20)
• C. Answer questions (40)
• D. Case Presentation (25)