1 chapter 18 renal failure. 2 section i. introduction

1

Chapter 18

Renal Failure

2

Section I .

Introduction

3

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

Kidneys are the principal excretive organs

Not only excrete waste metabolic products

to remove various harmful substances,

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)

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

Kidneys are the principal excretive organs

Not only excrete waste metabolic products

to remove various harmful substances,

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'':

Glomerular filteration rate↓ Retention of metabolic wastes, Disturbanc of internal environment

Uremia

Renal Failure Acute renal failure (ARF) (CRF) Cronic renal failure

a serial of clinical manifestations

Various causes

Severely impair renal function

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1. Causes of renal dysfunction

(1) Primary renal disease (2) Renal injury secondary to systemic diseases.

7


(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 inflammationrenal injury, tumor, calculus; obstructive nephropathy; vascular nephropathy

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(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

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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:

2. The basic manifestation of RF

(l) Dysfunction of glomerule

(2) Dysfunction of renal tubules

(3) Dysfunction of renal endocrine

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Renal blood flow Effective filtration pressure of the glomerule Kf (LPA, permeability and total filtration area)

125ml/min180L/day

1.5L/day

99%

20% of CI

Abnormality of urinary quality

Alteration of urinary quantity

(l) Dysfunction of glomerule

Permeability (of glomerular filtration membrane)

GFR

(hematuria & proteinuria)

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(2) Dysfunction of renal tubules

The secretion and reabsorption function are very important for maintain the homeostasis of internal environment

l ) Principal influencing factors

① Renal tubular EC (may impaired by ischemia,

hypoxia, infection and toxins)

② Neuro-humoral factors (Aldosterone, ADH, ANP, PTH etc.)

③ Concentration and flow rate of the initial urine

(ANP: atrium natriuretic peptide; PTH: parathyroid hormone)

180L/d

99%

1.5L/d

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① Dysfunction of reabsorption

Proximal convoluted tubule: glucosuria, phosphuria,

aminoaciduria, Na+ and H2O retention, renal tubular acidosis

③ Acid-base Disturbances

Proximal tubule (secrete H+, NH4+, NH3 ; reabsorb HCO3

–);

Medullary loop (reabsorb b HCO3– and NH3)

Distal tubule (secrete H+)

② Dysfunction of concentration and dilution

Henle’s (medullary) loop and collecting tubule: polyuria, Isosthenuria (isotonic), Hyposthenuria (hypotonic)

2) Types of renal tubular dysfunction

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Renal Hypertension

(3) Dysfunction of renal endocrine

① Increased secretion of rennin Renin

③ Increased secretion of endothelin ET

② Declined Kallikrein-kinin system (KKS) Kinin

④ Inadequate synthesis of prostaglandins from arachidonic acid PGE2 , I2

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EPO

HCI

1,25-(OH)2- D3 PTH

Renal aneamia

Ulceration

Renal osteodystrophy

⑤ Decreased eryhropoietin

⑥ Decreased 1-hydroxylase ⑦Weakened inactivation to PTH

⑧Weakened inactivation to gastrin

(90% formed in kidney)

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Section 2.

Acute Renal Failure

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Oliguria or anuria Retention of nitrogenous wastes (azotemia)

water/electrolyte acid-base disturbance

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

Various causes

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

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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

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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 canblock or partially block urine flow, while the kidney's blood supply and other functions are initially normal.

( l ) Prerenal failure (functional RF or prerenal azotemia)

(2) Intrarenal failure (parenchymal RF)

(3) Postrenal failure (Obstructive RF, Postrenal azotemia)

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Sudden decrease of renal perfusion

Hypovolemia, Acute heart failure

Expanded vascular bed volume (Hepatorenal syndrome

Anaphylactic shock, etc. )

Renal vascular blockage or auto-regulation disturbances

( l ) Prerenal failure

Azotemia(urinary Cr/plasma Cr > 40 ) Oliguna (<400ml/day) Urinary Na+<20 mmol/L Urine gravity > 1.020 No RBC, WBC or cast in urine

GFR↓Na+, H2O reabsorption↑

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(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 Tubular Necrosis (most common)

Acute renal ischemia Acute renal poisoningRenal tubule blocked by Hb or Mb

Glomerulonephritis, pye1onephritis, etc

Severe infection, drug allergy, etc

Thrombosis, DIC, etc

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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+ >40mmo l/L (ability to reabsorb Na + )

4. Hematuria.

5. Azotemia(urinary Cr/plasma Cr < 20)

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increased intracapsular pressure →GFR↓↓

Renal pelvises hydropsy

increased renal interstitial pressure

suddenly anuria and azotemia

Stone or tumor →Bilateral Obstruction

(3) Postrenal failure

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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

2. Pathogenesis

1. Alteration of renal hemodynamics

2. Renal tubule injury

3. Decreased ultrafiltration coefficient (Kf) of glomeruli

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2. Pathogenesis

1. Alteration of renal hemodynamics

2. Renal tubule injury

3. Decreased ultrafiltration coefficient (Kf) of glomeruli

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Oliguria or anuriaGFR

(l ) Alteration of renal hemodynamics

The decreased renal perfusion caused by renal vaso

constriction is the principal pathogenesis of ARF.

Effective filtration pressure, FF & Kf

There are many factors may associated with renal vasoconstriction:.

Renin-Angiotensin System

Catecholamine Prostaglandins, etc.

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Impairing proximal convoluted tube and ascending limb of medullary lope

stimulating juxtaglomerular cells in afferent arteriole

1) Renin-angiotension system

Toxin , Ischemia

Activating RAS

Renal perfusion pressure

Stimulating macula densa of juxtaglomerular apparatus

Reabsorption of Na+ vasoconstriction

(T-G feedback)

Na+ in distal convoluted tube

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2) Catecholamine (CA)

3) Prostaglandins (PG)

4) Endothelin (ET)

5) Others:

NO synthesis↓, ADH, PAF and TNF↑and ischemia- reperfusion injury → promote ATN

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

All these go into a vicious circle and cause increasingly severe damage

Decreased synthesis of PG → PGI2/TXA2↓

→ renal vasoconstriction

Effective circulating blood flow↓ or toxin → excitation of sympathetic-adrenomedullary system → CA↑→vasoconstriction of renal cortex especially of afferent arteriole

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(2) Renal tubule injury

Cast formation

1) Renal tubule obstruction

2) Renal tubule backflow of original urine

Loss of tubule integrity

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Renal tubule EC necrosis Basement membrane broken down

Oliguria

Oppressing Oppression renal tubule renal capillary

Interstitial edema formation

Backleak of original urine into renal interstitium

Loss of tubule integrity

Dead and detached ECs

Filtered protein (HB or MB)

Cast formation

Tubule obstruction

Intracapsular pressure

GFR

Renal tubule injury

Effective filtration p Aggravate Aggravate

tubule obstruction renal ischemia

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(3) Decreased ultrafiltration coefficient (Kf) of renal glomeruli

Decreased filter area↓

structural destruction of filter membrane

Ultrafiltration Coefficient↓

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3. Clinical course and manifestation

(l) Oliguria type of ARF

(2) Nonoliguria type of ARF

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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 phaseOliguria phase


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Oliguria:

Urine volume < 400 ml / day, or <50ml / 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

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

4. Retention of water and sodium Edema, hyponatremia and even water intoxication would occur if there is water and salts overload

3. Metabolic acidosis

May depress CNS and heart, aggravate hyperkalemia

2. Hyperkalemia May lead to ventricular fibrillation and cardiac arrest (No.1 cause of death)

1. Azotemia Progressive elevation of NPN (Urea, creatinine, etc.)

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4. Edema, hyponatremia and Water intoxication

3. Metabolic acidosis

2. Hyperkalemia

Death Triangle

2. Hyperkalemia

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urine Na+ urine Na+ /serum Na+

urine Cr/plasma Cr; urine Cr/plasma Cr

Differences between functional and parenchymal ARF

RFI = FENa =

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

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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/da

y

and may last about one month.

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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.

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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.

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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.

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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.

3) Recovery phase

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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.

(2) Nonoliguric type of ARF

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.

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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.

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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)

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

Various causes



Prerenal failure

(functional RF) Intrarenal failure (parenchymal RF)

Postrenal failure (Obstructive RF)

Acute Tubular Necrosis

Acute Renal Failure

Summary for ARF



Acute Renal Failure

Acute Renal FailureIntrarenal failure (parenchymal RF)

Acute Tubular Necrosis

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renal tubule injury Renal hemodynamic alteration

Oliguria GFR

renal perfusion Tubule obstruction

Toxin , Ischemia

Summary for ARF

Pathogenesis

glomerular Kf

renal vasoconstrictionBackleak of original urine

into renal interstitium

effective filtration pressure

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Clinical course and manifestation


phase phase phase

hyperkalemia Metabolic acidosis water intoxication

Differences between functional and parenchymal ARF ( )

(2) Nonoliguric type of ARF

Summary for ARF

GFR has not been reduced severely and might remain partial tubule function, but its ability of concentration is impaired

Oliguria diuresis recovery

Urine specific gravity, osmolality, Na+, Cr , sediment

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(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 - ARFUrine specific gravity Urine Na+

Urine Cr / Plasma CrUrinary sediment

Today’s question

Normal Proteins, cells, casts> 40 < 20

< 20 mmol / L > 40 mmol / L

> l .020 < l .0l5

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Section 3.

Chronic Renal failure

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CRF is characterized by progressive and irreversible lossof 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.

Retention of waste metabolic productsWater/electrolyte and acid-base imbalance Disturbance of renal endocrine

progressive irreversible destruction of nephron

Various diseases (kidney or kidney-related diseases)

CRF

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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).

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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 >50 <9 <178

Decompensatory Stage 25~50 9~20 178~445 (renal insufficiency)

Renal failure <25 20~28 451~707

Uremia <10 >28.6 >707

BCr = blood level of creatinine

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Decompensatory stage

Compensatory stage

Renal failure stage

Uremic stage

Clinical

manifestation

Asym

ptomatic

% of normal clearance rate of Cr

Clinical

Asymptomatic

CCr GFR BUN BCr (%) (ml/min) (mmol/L) (umol/L)

>30 >50 <9 <178

CompensatoryStage

(1)

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Compensatory stage

Renal failure stage

Uremic stage

Clinical

manifestation

Asym

ptomatic


Clinical

Lassitude, Mild anemia, Nocturia, Alimental tract discomfort


25~30 25~50 9~20 178~445

DecompensatoryStage

(2)

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Compensatory stage

Renal failure stage

Uremic stage

Clinical

manifestation

Asym

ptomatic


Clinical

Anemia, Acidosis, Cl －↑ , Na+↓ Hypocalcemia, Hyperphosphatemia


20~25 <25 20~28 451~707

Renal failure Stage

(3)

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Compensatory stage

Renal failure stage

Uremic stage

Clinical

manifestation

Asym

ptomatic


Clinical

Various uremic symptoms


<20 <10 >28.6 >707

Uremic Stage

(4)

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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 degree of renal dysfunction depends on the number of intact nephron

The remnant nephrons (so called intact nephrons) are compensatory hypertrophy, but their number decreasing day by day and finally become decompensatory.

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Injuries → basement membrane permeability↑ Mesangial cells overload and damaged Proteinuria Mesangial cells proliferation and increased Cast formation production of extracellular matrix Tubule blocked Glomerulosclerosis

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

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The number of nephron decreasing day by day

→ glomerular hyperfiltration

→ further glomerular injury

→ pressure and flow in glomerular capillary of remnant nephron↑

1) Alteration of glomerular basement membrane permeability

2) Hemodynamic alterations of intact nephrone

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Compensatory hypertrophy in remnant nephron

metabolism

oxygen consumption

free radical production Tubulointerstitial injury

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Compensatory hypertrophy in remnant nephron

metabolism

oxygen consumption

free radical production Tubulointerstitial injury

Inflammatory response

fibrin deposition in tubules and

surrounding interstitium

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Loss of some nephrons leads to compensatory

hyperfunction of others, increasing their vulnerability

to damage and going to a vicious cycle—the nephrons

to be continuously lost and the GFR progressively

decreased until the renal function failed.

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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

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(1) 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

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a) Nocturia (urine volume night > daytime, or > 750 ml)

b) Polyuria (>2000 ml per day in adult)

Mechanisms: Increased blood flow and rapid flow rate of ①primary urine in the remnant nephrons; Hyperosmolarity d②iuretic effect; Decreased ability of urine concentration cau③sed by destruction of osmolar gradient in medulla.

c) Oliguria (< 400 ml per day in adult) when extremely few of f

unctional nephrons (GFR<5~10ml/min).


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Hyposthenuria:

urine specific gravity < 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)


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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.

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Calcium & Phosphorus:

a) Hyperphosphatemia

GFR↓→excretion of P↓① → [P]↑→[Ca]↓→ PTH↑

Late stage (GFR<30ml/min): ② ＜ ① → [P]↑+ → [P]↑↑③

Early stage (GFR>30ml/min): ≥ → [P] remain normal② ①

Inhibiting reabsorption of phosphorus by tubule②

phosphorus release from bone③

20

5

15

L

②

①100

10

40

70

30 30

N E

①

②

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b) Hypocalcemia

① Ingestion and absorption of Ca2+ inadequacy

② [P]↑→[Ca]↓to maintain [Ca][P] constant

↘ phosphorus excreting through intestine

→ interfering absorption of Ca2+

③ 1-hydroxylase↓→ 1,25-(OH)2-D3↓ ↘ intestinal absorption of Ca2+ ↓

↗ ④ Inactivation ↓ → PTH↑

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3) Metabolic acidosis

when GFR<20ml/min, metabolic acidosis will occur

① Decreased ability of tubule to excrete acidic products

(HPO42+, SO4

2+, etc.) AG↑, Cl － normal

② Decreased ability of tubule to

conserve HCO3－ AG normal, Cl －↑

③ Decreased ability to secrete H+

interstitial nephritis

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(2) Azotemia

Non-protein nitrogen (NPN) > 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)

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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)

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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)

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Ability of excreting Na+, H2O↓→ Na+, H2O retention

→ blood volume↑→ cardiac output↑→ hypertension

↘more sensitive of blood wall → vasoconstriction ↗


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Disorder of renal circulation → hypoxia → activating RAA →AII↑→ vasoconstriction → peripheral resistance↑ ↘ ↘ Aldosterone ↑→ Na+, H2O retention → hypertension

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Renal dysfunction Renal hypertension

(vicious circle)

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(4) Hematologic disorders

1) Renal anemia (97%) Decreased production of RBC ① Synthesis of erythropoietin↓; ② Deficiency of hematopoietic material (iron, folic acid) ③ RBC-inhibiting factors inhibit RBC production;

④ Aluminium toxication (inhibiting synthesis of hematin, interfering iron transfer and stem cells proliferation) Increased destroy or loss of RBC ⑤ Hemolysis, Hypersplenism ⑥ Bleeding

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

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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

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(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

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Renal osteodystrophy

Chronic RF (dysfunction of excretion and endocrine of kidney)

Excretion of P↓

③Aluminium accumulation

↓absorption of Ca2+

②

Secondly hyperparathyroid

PTH↑

hypocalcemia

Hyperphosphatemia

④

Ca2+ in bone↓

bone lysis

Acidosis①

↓1,25-(OH)2-D3

Calcification of bone↓

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Section 4.

Uremia

82

Uremia

Retention of metabolic end-product and endogenous toxin Disturbance of water/electrolyte and acid-base balance

Disorder of endocrine function

End-Stage of ARF or CRF

a series of auto-toxic symptoms

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1. Pathogenesis

(1) Uremic toxin: (more than 100)

(2) PTH

(3) Aluminium

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(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

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2) Guanidines –second abundant nitrogenous matter

The only confirmed pathway for guanidines synthesis is:

Both with strong toxicity May induce almost symptoms of uremia.

Methyl guanidine Guanidino succinic acid

(Normal pathway) (RF)

Guanidino acetic acid

Excretion

Arginine

Creatinine

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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

1) Mechanism:

① hypocalcemia stimulating thyroid proliferation secondly hyperparathyroidism PTH↑

② decreased elimination and degradation of PTH by kidney

(2) PTH

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2) Toxicity of PTH:

① Inducing renal osteodystrophy

② Neural toxicity (decreasing neural transmission)

③ Anemia and bleeding (inhibiting RBC production and Platelet aggregation)

④ Infection (inhibiting WBC migrating, phagocytosis and Ab production)

⑤Myocardium injury, vasodilation and B.P.↓

⑥ Soft tissue necrosis

⑦ Increasing protein catabolism nitrogenous substances↑

⑧ Increasing serum cholesterol and triglyceride

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2) Toxicity

Inhibiting enzymes, toxicity to cell nuclear

May induce dialytic encephalopathy,

osteomalacia and small-cell anemia.

(3) Aluminium

1) Mechanism:

95% of Al combined with transferrin in plasma, thus difficult to remove by dialysis

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 Kussmaul’s respiration system Heart failure, Na+/H2O retention Pulmonary edema Hypoalbuminemia Urea stimulation Uremic pleuritis

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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

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(1) Preventing further renal injury

(2) Dialysis (hemodialysis or peritoneal dialysis)

(3) Renal transplantation

3. Principles of prevention and treatment

93

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.

Summary for CRF

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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.

2. The pathogenesis of CRF include 2 types of nephron injury:

glumerulosclerosis and tubulointerstitial injury.

The functional and metabolic alterations in CFR primarily incl

ude , ,

, hematologic disorders ( ,

), and .

Summary for CRF

water, electrolyte and acid-base imbalance azotemia

renal hypertension renal anemia

bleeding tendency renal osteodystrophy

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electrolyte and acid-base imbalance, azotemia, Renal hypertensio

n, hematologic disorders(Renal anemia, bleeding tendency), and r

enal 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.

Summary for CRF

urea guanidines amine and phenol middle molecular

weight toxins PTH aluminium

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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%)

1 chapter 18 renal failure. 2 section i. introduction

Documents

renal dysfunction

renal failure slide

renal function slide

primary renal disease

renal tubular disease

dysfunction of renal

renal injury secondary

hyperuricemia renal