The Wolf Boy

• a childe that was carried away in the

Forest of Ardenne by Wolves, and
nourished by them. This child having
conversed with them divers years, was at
last apprehended, but could neither speak
nor walk upright, nor eat any thing except
raw flesh, till by a new education among
other children, his bestial nature was quite
abolished
Renal Failure

Zhao Mingyao
BMC. ZZU
2006.05
Functions of kidney

Excretion
maintain
Regulation
homeostasis
Endocrine
renal failure?

renal failure
Excretion
Regulation Homeostasis
Endocrine disorder
 Three types of RF
Nephron damage

ARF End stage

uremia

Body self
CRF intoxication

Intact nephron loss

Part 1 basic pathological taches
for renal failure
1. Dysfunction of GF:
blood flow, pressure, filtration, permeability of filtration
2. Renal tubular Dysfunction:
proximal, henle`s loop, distal tubule
3. Renal endocrine dysfunction:
RAAS, EPO, active vitamin D, Kallikrein-kinin-
prostaglandin-system, PTH, gastrin
 Part 2 Acute renal failure
• Sudden and severe decrease in kidney
function that is short term.
Section 1 etiology and
classification

calyces

pelvis

urethra.
Causes of ARF in hospitalized pts
• 45% ATN
Ischemia, Nephrotoxins
• 21% Prerenal
CHF, volume depletion, sepsis
• 10% Urinary obstruction
• 4% Glomerulonephritis or vasculitis
• 2% AIN( acuteinterstitial nephritis )
• 1% Atheroemboli
 classification of ARF
1.urinary volume
oliguric ~
nonoliguric
2. structure states
functional
parenchyma
3.Damaged site
prerenal
intrarenal
postrenal
Section 2 pathogenesis o f ARF
 1.renal hemodynamic alteration
(1)renal perfusion pressure ↓
(2)renal vasoconstriction
(3)renal vascular endothelial swelling
(4)intrarenal DIC
2.renal glomerular injury
renal glomerular injury
 3.renal tubular injury

(1) renal tubular occlusion: cast obstruction,

interstitial edema
(2) Back-leakage of the glomerular filtration
urine backflow
(3) tubulo-glomerular feedback (TGF)
[Na+] macula densa( Juxtaglomerular
Apparatus ) afferent A GFR
 4. Renal cell injury and its
mechanism
• （ 1) cell injury
tubular cell
vascular endothelia
mesangial
 (2) Mechanism of cell damage
• 1) ATP and ion pump
• 2)OFR
• 3)glutothine
• 4)phospholipase
• 5)cytoskeletal structure
• 6)neautrophil and inflammation
• 7)apoptosis
What are these?
 Section 3 alteration of
metabolism and function
• Three stages
• Oliguric ~ 75% of mortality

• Polyuric ~ 25% of mortality

• Recovery ~
 1.Oliguric stage
• (1) urinary alteration
volume: oliguria and anuria
specific gravity: hyposthenuria and
isosthenuria
component: Na+, Pro, cell debris, cast
 (2)water intoxication

• Endogenous Water
• Water intake
• Renal excretion
 (3) hyperkalemia

• Excreting K
• [K+]c release
• Acidosis
• Hyponatremia: Na+-K+↓
• K+ origin: storage blood, food
 （ 4 ） metabolic acidosis
• GFR
• Excreting H+, NH3 and reabsorbing
NaHCO3-
• Catabolism
 (5)azotemia
• BUN 10~15mg%
• NPN > normal level
 Brief summary
• (1) urinary alteration
• (2) water intoxication
• (3) hyperkalemia
• (4) metabolic acidosis
• (5) azotemia
 2.Polyuric stage
Mechanism of polyuria
1. reperfusion of damaged nephron
2. tubular obstruction released : Interstitial
edema faded and casts rushed out
3. the function of neonatalrenal tubule is
incomplete
4.osmotic diuresis of urea
 3. Recovery stage
• Most normal
• Tubular function recovery in end
• Few convert CRF
Why does not urinary volume
decrease in some ARF?
 Comparison between normal person and nonoliguria RF

plasma filtration L /d reabsorption % end urine/d

Normal 180 99 1.8

Nonoliguria 90 98 1.8

9 80 1.8
 Section 4 Prevention and
treatment
• Treatment of primary disease
• Protect nephrons
• Treatment according to symptoms
• dialysis
Part 3 chronic renal failure(CRF)
Section 1 etiology and clinical
courses
• Chronic renal failure and ESRD affect more than
2 out of 1,000 people in the U.S.
• Diabetes and hypertension (high blood pressure)
are the two most common causes and account
for approximately two-thirds of the cases of
CRF. Other major causes include the following:
• Glomerulonephritis of any type (one of the
most common causes)
• Polycystic kidney disease
 1.Etiology of CRF
(1)prerenal
(2)intrarenal: chronic
glomerulonephritis(50~60%) before;
diabetic nephropathy and hypertensive
nephrosclerosis
(3)postrenal
 2. Clinical courses
(1) silent (compensatory):GFR
>50ml/min
(2)renal insufficiency: GFR25 ~50 /min
(3) renal failure:GFR5 ~25 /min
(4)end stage renal failure (uremia):GFR
<5 /min
 Course of CRF

　　　 Staging 　　　　　 GFR 　　　 　　　 Manifestation 　　　 Scr(um

　　 Compensation 　　　 50%~80% 　　　　　 Asymptom 　　　　 Normal
　　 Azotemia 　　　　 25% ~50% 　　　 asymptom/symptom 　　 178~ 450
　 Renal insufficiency 　 10%~25% 　　　　　 Asymptom 　　　　　 450~ 70
　　　　 Uremia 　　　　﹤ 10% 　　　　 Uremic symptom 　　　　﹥ 707
Stag
GFR Description Treatment stage
e

1 90+ Normal kidney function but Observation, control of

urine or other abnormalities blood pressure
point to kidney disease
2 60-89 Mildly reduced kidney Blood pressure control,
disease monitoring, find out why.

3 30-59 Moderately reduced More of the above, and

probably diagnosis, if not
already made.
4 15-29 Severely reduced Planning for endstage renal
failure - more info.

5 14 or Very severe See treatment choices for

less endstage renal failure.
 Section 2 pathogenesis o f
CRF
• 1.mechanism of compensation
(1)reserve capacity of kidney
(2)adaptation of renal function
(3)renal hypertrophy
(4)autoregulation of renal blood flow
 2. mechanism of
decompensation
• (1)intact nephron hypothesis
• (2)trade off hypothesis
• (3)glomerular hyperfiltration hypothesis
• (4)lesion of tubular and interstitial cells
(1)intact nephron hypothesis
(2)trade off hypothesis
(3)glomerular hyperfiltration
hypothesis
(4)lesion of tubular and
interstitial cells
 Section 3 Alteration of
metabolism and function
 1.alteration of urine
• Polyuria
①flow velocity ↑of original urine
②Osmotic diuresis
③Urinary concentration↓
• Nocturia
• Proteinuria
 2.azotemia
NPN= BUN + PCr + Uric acid
•
CCR: creatinine clearance rate

CCR= Ucr × Vu= 90~140ml/min

Pcr

Ucr: urinary creatinine

concentration
Vu ： urinary vol per min
Pcr ： plasma creatinine
concentration
•BUN or PCr is not a early sensitive index to CRF
 3.water, electrolytes and acid-
base imbalance
• Na+, H2O,
• K+, Mg2+
• Ca2+ and Phosphorus ?
• Acidosis ?
 Hyperphosphatemia and
hypocalcemia
• P
GFR urinary P
PTH bone salt dissolved
Ca2+
P X Ca2+=40
1,25-(OH)2-D3
unsoluble Ca2+ phosphate in gut
gut inhibited by toxin
 4.renal hypertension
•
Renin dependent

Na+ dependent

Renal-deprived vaso-dilating
substances↓
 5.renal osteodystrophy

calcium & phosphate imbalance and PTH ↑

hypocalcemia: 1,25- (OH)2-D3 ↓

acidosis
 6.hemorrhagic tendency
• Plt amount nor, function
 7.renal anemia

erythropoietin ↓

bone marrow inhibited

formation ↓
hematopoietic precursor
RBC ↓ damage↑ substance ↓

loss↑
 Section 3 Alteration of
metabolism and function
• 1.alteration of urine
• 2.azotemia
• 3.water, electrolytes and acid-base
imbalance
• 4.renal hyper tension
• 5.renal osteodystrophy
• 6.hemorrhagic tendancy
• 7.renal anemia
 Section 4 prevention and

 
treatment
• See in uremia

                                  

                   
 Part 4 Uremia
• End stage renal disease

• urine in the blood

• Many toxins
 Section 1 pathogenesis o f
uremia
• 200 metabolites and toxin uremia toxin
• （ PTH （ guanidine compound ）
urea amines ）
 Uremic toxins
• Protein control in the diet
• Dialysis relief
• Uremic plasma cellular toxicity
(1)retained metabolic products
Asymmetric dimethylarginine
(ADMA)
(2)overproduction of counter-regulation
hormone
(3)underproduction of renal hormone
 Section 2 functional and
metabolic alteration
• (1)nervous system
major manifestation
homeostasis disorder
denaturalization of nerve cell
brain edema
Central neurologic system Lethargy, irritability, frank encephalopathy,
asterixis, and seizures
Peripheral neurologic system
Symmetric sensory neuropathy in a glove-and-stocking distribution
• (2)digestive system
the earliest symptom
observed easily
uretic fetor

• Anorexia, nausea, vomiting and weight loss, which improve

after dialysis is initiated.
• Gastritis, peptic ulceration and arterio-venous malformations
→ gastrointerstinal bleeding
• (3)cardiovascular system
pericarditis
pericardial friction rub
pericardial tamponade
(4)respiratory ~
Kussmaul breath (deep and big
Breath)
named for Adolph Kussmaul, the 19th
century German doctor who first noted it.
Also called "air hunger."
 (5)immune

Cellular immune
T cell
NP chemotaxis
infection
 (6)skin changes(dermatologic
abnormalities)
• Pallor
• Pruritus and excoriation
• Uretic frost
• Gray discoloration
• Ecchymosis and hematomas
 (7) metabolic disorders
• glucose
glucose tolerance
• Protein
Negative nitrogen balance
• Fat
triglyceride hyperlipidemia
 Section 3 prevention and
treatment
• 1.treat primary disease
• 2.control and prevent aggravating factors
• 3.dialysis
• 4.other treatment
( end )