Renal Failure

Urine Formation and Micturition;

Plays an important role in
maintaining homeostasis

kidney

ureter

bladder
 Review of normal
renal function
Introduction
Renal insufficiency

Causes
Acute renal failure
Contents (ARF) Pathogenesis
Chronic renal failure
(CRF) Alteration of
metabolism and
function
Uremia
Review of normal renal function
 renal
corpuscle
Nephron is the
basic functional
unit of the kidney
 Nephron: functional unit of the kidney

Renal tubule

glomerulus

Bowman’s capsule

Renal corpuscle
Excretory Function of the kidney

Three steps of urine formation

• Glomerular filtration
 Filtration of waste-laden blood in the
glomerulus (crude urine,180L/day)
• Tubular reabsorption
 Reabsorb substances needed
to maintain the constancy of the
homeostasis into the
bloodstream
• Tubular secretion
 Secrete unneeded materials
into the tubule for elimination
(terminal urine 1~2L/day)
 Endocrine Function of the kidney
• The renin-Angiotensin-Aldosterone System
 Plays
important part in regulation of blood pressure
• Prostaglandins Regulates vasomotion
• Erythropoietin
Regulates the differentiation of red blood cells in bone
marrow
• 1- hydroxylase(activation of Vit D)
 Increases calcium absorption
 Helps regulate calcium deposition in bone
 Normal renal function
• Excretory function:
metabolic wastes, poisons, drugs etc.
• Regulative function:
to regulate the balance in water, electrolytes,
acid-base-----maintenance of homeostasis
and to regulate BP.
• Endocrine function:
to secrete renin, prostaglandins, Epo, 1,25 (OH)2VitD3,
and to inactivate PTH, pepsin.
 Retention of metabolic
wastes, poisons, drugs
in the body.

Excretion↓ Disorders of water,

electrolytes, and
acid-base,BP
Various Renal Regulation↓
diseases insufficiency

Endocrine↓

Endocrine dysfunction:
Renin, Epo, PG; Vit D3
Renal anemia,
rarefaction of bone.
Bone fracture
 Renal insufficiency
Renal failure is the late phase of renal insufficiency

• Definition
A condition in which the kidneys fail to
remove metabolic wastes from the body and
fail to regulate the fluid, electrolyte, and pH
balance of the extra-cellular fluids, finally fail
to maintain the homeostasis.
• Underlying causes
 Renal diseases
(Glomerulonephritis, ATN, Renal tumor, Polycystic
kidneys …)
 Extrarenal diseases
(systemtic diseases:circulatory, autoimmune, metabolic,
diseases of urinary track …)
 Renal insufficiency

Clincal manifestation
Local Extrarenal
manifestation manifestation

• Oliguria/anuria • Edema
• Polyuria/nocturia • Hypertension
• Proteinuria • Renal osteodystrophy
• Hematuria • Anemia
• Ache of renal region
• urinary tract infection
symptoms (urgency,
frequent micturition,
odynuria)
 §Renal Failure

• Acute renal failure

 The kidneys abruptly stop working
 Often is reversible if recognized early and
treated properly
• Chronic renal failure
 lose their functions gradually
 It develops slowly, usually over the course
of a number of years
Ⅰ. Acute renal failure（ ARF）
Ⅰ. Acute renal failure（ ARF）

1.Concept of ARF
ARF is a pathological process that the
kidneys lose the functions abruptly (within hours
to days) and thus leads to disturbance of
internal homeostasis.
Usually the disoders often manifest as overhydration,
azotemia(accumulation in the blood of nitrogenous
waste products,e.g.BUN.Scr ), hyperkalemia, and
metabolic acidosis.
2.Classification of ARF

1.According to urine volume:

 Oliguric type of ARF (<400ml/day)

 Non-oliguric type of ARF (>400ml/day)
Prerenal Classification of ARF
2.According to the anatomical
locations of causes

Prerenal ARF (70% of cases)

Intrarenal Intrarenal ARF ( 25% of cases)

Postrenal Postrenal ARF (< 5% of cases)

Prerenal Classification of ARF
2.According to the anatomical
locations of causes

Prerenal ARF (70% of cases)

Intrarenal Intrarenal ARF ( 25% of cases)

Postrenal Postrenal ARF (< 5% of cases)

 Prerenal
 Prerenal ARF
Causes:
• Hypovolemia: various shocks
• Reduced cardiac output : heart failure
• Vascular obstruction: renal arteriole embolism or
thrombosis
• Decreased renal perfusion due to vasoactive mediators,
drugs, diagnostic agents

Mechanism：
Renal blood flow↓→ Hypoperfusion →GFR↓
 Prerenal factors

ADH Effective circulatory blood volume Aldosterone 

BP↓ sympathetic nerve

system
Renal perfusion pressure Renal arterioles constriction

Renal blood flow 

glomerular effective filtration pressure

Stimulates reabsorption of
water in distal tubules, GFR↓ Reabsorption of water
and sodium ↑
and concentrates urine.
Urine volume 
  Intrarenal ARF
Intrarenal
Causes:
• Acute tubular necrosis (ATN)
• Prolonged renal ischemia
• Exposure to nephrotoxic drugs (aminoglycoside antibiotics) ,
metallic elements (plumbum, hydrargyrum) , organic
solvents (methyl benzene)
• Intratubular obstruction resulting from hemoglobin,
myoglobin
• Acute inflammatory disease: vasculitis, glomerulonephritis
These factors damage nephrons directly or
secondarily →GFR↓
  Postrenal ARF

Postrenal
Causes:
• Postrenal urinary tract obstruction
e.g.ureteral calculus, bladder tumor

• Extra-urethral oppression
e.g.prostatic hyperplasia, Pelvic tumor

Mechanism：
obstruction→urine retention→intra-tubular pressure↑
→ glomerular effective filtration pressure→GFR↓
 The key link in ARF

Sudden & Dramatic Decrease in GFR

GFR
3.Pathogenesis of ARF
one of the main clinical manifestations is
reduced urine volume

 Vascular theories
 Tubular theories
  Vascular theories
(1) Renal perfusion pressure ↓
Only when the renal perfusion pressure falls
below 80 mmHg(the lowest limit of
autoregulation),the ability of renal blood flow
autoregulation is lost, and then the renal
blood flow and GFR fall rapidly.
(2)Renal vasoconstriction
(3)Renal hemodynamic alteration
(4)Glomeruli injury
 (1)Renal perfusion pressure ↓
Severe reduced cardiac output
Heart failure

Low blood pressure

Diminished blood volume
Trauma,
Hemorrhage
Low blood pressure

Is not restored promptly

reduced renal perfusion ARF
 (2)Renal vasoconstriction
①
BP↓ SNS（+） Catecholamine, CA↑
Renin-
②
Renal hypoperfusion and ischemia angiotensin-
aldosterone
system RAAS(+)
Glomerular Tubular
endothelial cell epithelial cells
injury injury Angiotensin II,
④
AngII ↑
③ Prostaglandin
E2 (PGE2)↓
Endothelin, ET ↑、 Renal afferent arteriole
Nitrogen monoxidum, constriction
NO ↓
GFR↓ ARF
 (3) Renal hemodynamic alteration

 Ischemia and ischemic-reperfusion damage the kidneys

 the Kidneys are sensitive to ischemic injury, its reperfusion
will produce calcium overload and oxidative stress, Ca2+ and
oxygen free radical damage vaso-endothelial cells
→ swelling 、necrosis , white blood cell aggregation.
 The injury of vaso-endothelial cells activates endogenic
clotting mechanism, and forms microthrombus in renal
vessels.

The above causes → obstruction in renal vessels lumen →

renal blood flow ↓ → GFR↓
 (4)Glomeruli injury

Acute glomerulonephritis ---- acute streptococcus infection

----Ag-Ab complex(an insoluble immune complex)

entrapped or deposited in the glomeruli, and damage the
tissue, stimulate mesangial proliferation.
----Blocked most of the glomeruli : glomerular filtration
membrane area↓, membrane permeability↓→GFR↓
Pathogenisis of ARF —Vascular theories

(1) Renal perfusion pressure ↓

(2)Renal vasoconstriction
(3)Renal hemodynamic alteration
(4)Glomeruli injury
 Tubular theories
(1)Tubulo-glomerular feedback mechanism
Prolonged hypoxia,
→ ATN →Na+ reabsorption↓
poisons
→ RAAS (+)→AngⅡ↑ →constrict afferent arteriole
→ renal blood flow↓ → GFR ↓
(2)Tubular obstruction

Severe renal ischemia, renal toxin, trauma or hemolysis

Precipitation of nephrotoxins (uric acid, myoglobin,

hemoglobin or oxalate) or congealed protein in the
form of cast , sloughed cells or cellular debris.

Plug the tubules

Intratubular pressure↑

Bowman’s space pressure↑

Decrease net filtration pressure, GFR↓

(3)Tubular backleak of ultrafiltrate
Acute renal ischemia or renal poisoning

tubular epithelial cells, basement membranes

are damaged
Functional integrity of tubular wall is lost,

Passive backflow of ultrafiltrates to

the interstitium

Interstitial edema
Oppresses tubule and increases the pressure
in Bowman's space

GFR↓
Tubular backleak mechanism：

Tubular epithelial cell

Tubular basement
membrane

Renal poisons

Urine

Sloughed tubular epithelial

cells and debris
4.Alterations of Metabolism and Functions
of ARF

Oliguric type of ARF

1. Oliguria stage
three stages 2. Polyuria stage

3. Recovery stage
4.Alterations of Metabolism and Functions
of ARF

Oliguric type of ARF

1. Oliguria stage
three stages 2. Polyuria stage

3. Recovery stage
Oliguric type of ARF
1.Oliguria stage
Urine volume < 400ml/d,
most dangerous stage,
Urinary abnormality

Disturbance of homeostasis
 Oliguria stage
Often persists 7～14 days (determines the prognosis)

Urinary abnormality(volume and component)

Oliguria：urinary volume is less than 400ml/day
Anuria： <100ml/day
Urinary sediment(Urine microscopic examination) may
contain RBC, WBC, epithelial cells or various casts
(granular, hyaline, cellular)
Urine protein (proteinuria)
Urinary Na+
Urinary specific gravity and osmolarity
 Differentiation of functional from parenchymal ARF
urine Functional Parenchymal
(Prerenal , Postrenal) （intrarenal,ATN）

Sediment may contain

microscopic RBC, WBC, epithelial cells
Non-significant
urinalysis or various casts (granular,
hyaline, etc)
protein （—）or small ＋～＋＋＋＋
UNa (mmol/L) <20 >30
osmotic
pressure (mmol/L)
>700 <250
specific gravity >1.020 <1.015
Functional ARF---the renal tubules are not impaired ;
Parenchymal ARF--- both glomerular dysfunction and renal tubular dysfunction
 Acute renal failure

1.Oliguria stage
Disorders of internal homeostasis
 Water intoxication
 Metabolic acidosis
 Hyperkalemia
 Azotemia: progressive increase in BUN and
serum creatinine
 Acute renal failure

2.Polyuria stage

---Urine volume is increased gradually.

(This is a good sign : renal function begins to recover!)
---lasts about 2 weeks.
At early stage，GFR↑, but less than the normal, so
azotemia, hyperkalemia and acidosis still exist (400ml/d
< urine < 1500ml/d)
At late stage, urine ↑↑markedly (even ＞3000ml/d),
dehydration,hypokalemia and hyponatremia may occur.
 Acute renal failure

Polyuria stage

Mechanisms of diuresis:
 Causes removed →GFR↑→ urine volume↑
 the new regenerated tubular epithelial cells(urinary
concentration function is not sound)
 Cumulation of wastes during oliguric phase
(leads to osmotic diuresis)
 Relieve of tubular obstruction and interstitial edema
 Acute renal failure

3.Recovery stage

Urine volume recovers to normal level,

metabolic disorders begin to disappear, and
renal function progressively recovers, but
the full recovery may take several
months , even one year, often lasts for a
long time.
 Principles of
Prevention and Treatment to ARF
 Treatment of the primary diseases (Etiological treatments)；
 Treatment against symptoms (Symptomatic treatments)；
 Correct hyperkalemia, acidosis and azotemia；
 Hemodialysis is highly recommended.

Dialysis :
separation of substances in solution by
means of their unequal diffusion through
semipermeable membranes
hemodialysis
 peritoneum

dialysate

Dyalysis by means
of the patient’s
peritoneum
duct

abdominal cavity

dialysate

excreta,waste products peritoneal dialysis

Ⅱ. Chronic renal failure（ CRF）
 Ⅱ Chronic Renal Failure,CRF

Concept
It is a process that the nephrons are progressively
and irreversibly impaired. The remaining nephrons
can not fully excrete metabolic wastes and maintain
the internal homeostasis. It leads to both the disorder
of homeostasis and dysfunction of the renal endocrine.
Clinical Progression of CRF

1. Stage of decreased renal reserve

2. Stage of renal insufficiency
3. Stage of renal failure
4. Stage of uremia
• Stage of decreased renal reserve
 Kidneys have tremendous functional reserve, even if 50% of
nephrons are lost , patients have no evidence of
functional impairment. But over load (e.g.infection) on the
kidney may promote or aggravate renal failure
• Stage of renal insufficiency
 GFR↓, 25~50% of the normal. Renal regulating function is
quite limited. Internal homeostasis disorders begin to occur.

• Stage of renal failure

 GFR↓↓, 10~25% of the normal. Symptoms of CRF are
increased 、aggravated and marked.
• Stage of uremia
 GFR↓↓↓, less than 10% of the normal . Serum
creatinine and BUN levels rise very sharply. Patients begin to
suffer from severe Symptoms.
CRF----Pathogenesis
1. Intact nephron hypothesis

compensation → decompensation
 Remaining nephrons Comp
adapt by increasing GFR, ensa-
tubular resorption and tory
excretion. stage
early stage

Neprons
Chronic renal are
diseases destroyed

late stage
de-
Intact nephrons go on compens
decreasing to a certain atory
degree stage
 2. Glomerular hyperfiltration hypothesis
primary diseases
destroy nephron
perfusion in remaining nephron↑
pressure in glomerular capillary vessels↑

Hyperpressure,
GFR↑
Hyperperfusion,
Hyperfiltration overload
(remaining nephrons)
Try to maintain renal
function---compensatory Glomerular sclerosis
 3. Trade-off hypothesis

As the nephrons are progressively destroyed,

increaed blood concentration of some solutes
stimulate over-secretion of some related regulatory
factors (such as hormones) in order to increase the
excretion function . At the same time , however,
high blood levels of the regulatory factors will result
in some other metabolic disorders, this mechanism is
called trade-off hypothesis.
 Chronic renal failure（ CRF）

Alterations of Metabolism and Functions

1. urinary abnormality
2. Disorders of internal homeostasis

(1) Azotemia
(2) Acidosis
(3) Disorders in electrolytes metabolism
3. extrarenal menifestations
Renal hypertension
Renal Osteodystrophy
Renal anemia
 Uremia
Uremia is the end-stage of ARF and CRF.
It is a syndrome characterized by
Cumulation of metabolic and endogenous toxins ( uremic toxins);
sever imbalance in water, electrolytes, acid-base metabolism;
and severe deregulation in endocrine system.
Treatments:
Dialysis treatments, Kidney transplantation
 Key points
1.Master the conception of Renal insufficiency , ARFand
CRF
2. Master classification of ARF
3. The key link of ARF is reduced GFR.
4. Be familiar with pathogenesis of ARF
5. What is the three phases of oliguric ARF
6. Master differentiation of functional from parenchymal
ARF according to urine abnormalities
7. Know about the principles of prevention and treatment to
ARF
8. What are the four stages of clinical progression of CRF?
9. Conception of Uremia
 What have we learnt in Pathophysiology?
 Introduction and Conspectus of Disease

 Fundamental Pathological Processes:

Water and electrolytes imbalance, edema,
acid and base disturbance,
stress, fever, hypoxia ,shock

Organic pathophysiology:
heart, lung, liver, kidney
 renal
corpuscle

GEFP= intraglomerular capillary pressure

—plasma colloid pressure
—hydrostatic pressure in Bowman's space