Transcript Renal Insufficiency

Renal Insufficiency
“To be a great champion you must
believe you are the best. If you’re not,
pretend you are….!”
– Muhammad Ali
TOPICS
• Introduction
• Acute renal failure
• Chronic renal failure
• Uremia
Functions of kidney
The kidneys are a pair of small organs that lie on either side of
your spine at about waist level. They act as filters that keep your
blood free of by-products and toxins.
• The kidneys excrete these compounds with water to
make urine.
• They also eliminate excess body water while selectively
reabsorbing useful chemicals and allowing waste to pass
freely into the bladder as urine.
• They allow you to continue to consume a variety of foods,
drugs, vitamins and supplements, additives, and excess
fluids without worry that toxic by-products will build up
to harmful levels.
• The kidneys play an essential role in maintaining
electrolyte and acid-base balance.
• They produce some hormones including renin,
prostaglandins, erythropoietin, and active vitamin D.
• So, they are crucial in the regulation of blood pressure,
formation of matured red blood cells, and metabolism of
calcium and phosphorus.
Functions of the Kidney
• Waste excretion
• Electrolyte balance
• Fluid balance
• pH
• Osmolality
• Hormone production
Anatomy of Kidney
Manifestation of renal dysfunction
Glomerulus
· decreased GFR
· glomerular filtration membrane permeability alteration
Renal tubule
· concentrative function decline (hyposthennuria/isosthennuria)
· water, electrolyte, acid-base disorder
· others
Endocrine disorder
· hypertension · anemia · renal osteodystrophy
· others
体内VitD3的代谢过程
紫外线 25-羟化酶
1α-羟化酶
7-脱氢胆固醇
VitD3
25-(OH)VitD3
1,25-(OH) 2VitD3
（皮肤） （肝微粒体） （肾线粒体）
Acute Renal Failure, ARF
• Definition
• Etiology & classification
Prerenal failure
Intrinsic renal failure
Post(obstructive) renal failure
• Pathogenesis
• Clinical manifestation
• Therapy
Definition
• Acute renal failure (ARF) is defined as a
precipitous and significant (>50%) decrease
in glomerular filtration rate (GFR) over a
period of hours to days, with an accompanying accumulation of nitrogenous wastes in
the body.
急性肾功能衰竭的定义
急性肾功能衰竭（acute renal failure，ARF）是指各种
病因引起双侧肾脏在短期内泌尿功能急剧降低，导致机体内环
境出现严重紊乱的病理过程和临床综合症。
肾泌尿功能障碍表现为GFR迅速下降，出现少尿无尿；内环
境紊乱主要表现为氮质血症、高钾血症和代谢性酸中毒。
急性肾功能衰竭根据尿量减少与否，分为少尿型（成人每
日尿量少于400ml）和非少尿型（成人每日尿量大于400ml）两
种类型。急性肾衰病情凶险，临床较常见，但若及时诊治，预
后较好。
Etiology
Pre-renal (~70% of cases)
resulting from impaired blood flow
to or oxygenation of the kidneys.
Intrinsic-renal (~25% of cases)
resulting from injury to or
malformation of kidney tissues.
Post-renal (<5% of cases)
resulting from obstruction of
urinary flow between the kidney and
urinary meatus.
Causes
• Prerenal failure - Diseases that compromise renal
perfusion
 Decreased effective arterial blood volume - Hypovolemia,
CHF, liver failure, sepsis
 Renal arterial disease - Renal arterial stenosis
(atherosclerotic, fibromuscular dysplasia), embolic disease
(septic, cholesterol)
肾前性因素
休克的原因（失血、失液、感染、急性心衰、
严重过敏反应）和其它（肝肾综合征）
有效循环血量
ADH
Ald
血压降低
肾灌流压
肾血管收缩
肾血流量
肾小球有效滤过压
GFR
尿量
肾前性急性肾功能衰竭的发生机制
• Intrinsic renal failure - Diseases of the renal
parenchyma, specifically involving the renal
tubules, glomeruli, interstitium
 ATN, ischemia, toxins (eg, aminoglycosides, radiocontrast, heme
pigments, cisplatin, myeloma light chains, ethylene glycol)
 Interstitial diseases - Acute interstitial nephritis, drug reactions,
autoimmune diseases (eg, systemic lupus erythematosus [SLE]),
infiltrative disease (sarcoidosis, lymphoma), infectious agents
(Legionnaire disease, hantavirus)
 Acute glomerulonephritis
 Vascular diseases - Hypertensive crisis, polyarteritis nodosa,
vasculitis
• Postrenal failure - Diseases causing urinary
obstruction from the level of the renal tubules to
the urethra
 Tubular obstruction from crystals (eg, uric acid, calcium oxalate,
acyclovir, sulfonamide, methotrexate, myeloma light chains)
 Ureteral obstruction - Retroperitoneal tumor, retroperitoneal
fibrosis (methysergide, propranolol, hydralazine), urolithiasis,
papillary necrosis
 Urethral obstruction - Benign prostatic hypertrophy; prostate,
cervical, bladder, colorectal carcinoma; bladder hematoma; bladder
stone; obstructed Foley catheter; neurogenic bladder.
Causes of ARF in tertiary care hospital setting
急性肾功能衰竭病因与分类
• 肾前性ARF （早期为功能性ARF ）
有效循环血量减少引起肾血流量急剧减少是肾前性
ARF发生的关键因素 。
• 肾性ARF（亦称器质性ARF）
由肾脏实质病变引起。急性肾小管坏死（acute
tubular necrosis，ATN）是临床上最常见、最重要的
ARF类型，约占ARF的75%～80% 。
• 肾后性ARF
因双侧性尿路梗阻引起，如尿路结石、肿瘤、前列
腺疾患等。
Pathogenesis of ARF
I. Renal hemodynamics factors
Decreased renal blood flow
Renal hypoperfusion
Vasoconstriction
Vascular obstruction
Redistribution of renal blood flow
II. Nephronal factors
Tubule injury
Tubule obstruction
Passive backflow
Acute Renal Failure, Intrinsic
Acute Tubular Necrosis
• Renal hypoperfusion/ischemia
• Nephrotoxic agents (both endogenous and
exogenous)
• Mortality 50%
Bronchopulmonary infections, sepsis,
cardiovascular disease, bleeding disorders
• Complete Recovery 25%, Incomplete 20%, No
Recovery 5%
Acute Tubular Necrosis
Nephrotoxic Agents
Exogenous
• Antibiotics
• Contrast
• Diuretics
• Chemotherapeutics
• Analgesics
• Solvents, metals, chemicals
• HIV meds
• Antiulcer meds
• Anesthetics
Endogenous
• Pigment nephropathy
• Crystal deposition
• Tumor-specific syndromes
Acute Tubular Necrosis
Cell Hypoxia
Depletion of ATP
Hypoxanthine
Impaired function
Of plasma membranes
And ATPases
Ca++ imbalance
Disrupt cytoskeleton
Activate phospholipases
Formation of xanthine oxidase
Uncoupling of oxidative phosphorylation
Na-K imbalance
Cell Swelling
Disrupt lipid
bilayer
Reperfusion injury
Free radicals
Acute Tubular Necrosis
Leads to…
End results…
• Loss of cell polarity
• Brush border loss
• Impaired solute and
water transport
• Impaired cell-cell
adhesion
• Sloughing of tubule
cells  obstruction
• Impaired tight
junction
• Back leakage of
filtrate
急性肾功能衰竭的发病机制
急性肾衰发病机制的中心环节是GFR的降低。
一
肾血流动力学异常
肾血流急剧减少
肾灌注压下降
肾内血流重分布
二
肾小管损伤
肾小管阻塞
原尿返流
三
肾小球超滤系数降低
肾血管收缩
肾血管阻塞
Characteristics & clinical courses
• Oliguric phase
• Diuretic phase
• Recovery phase
Oliguric phase
Usually lasting for 1 to 6 weeks,the average
duration is between 7 & 10 days.
• Features of urine: I. Oliguria or Anuria
II. Hematuria and casts
III. Low specific gravity and osmolality
IV. Urinary [Na+] above 20mM
•
•
•
•
•
Azotemia
Metabolic acidosis
Hyperkalemia
Hypervolemia / Hypertension
Others: edema, water intoxication，tachypnea
Urinary Indices in ARF
Prerenal ARF
ATN
Urinary [Na+], mEq/L
<20
>40
Urine to plasma Cr
>40
<20
Urine osmolality
>500
<400
Urine specific gravity
>1.020
<1.015
Renal Failure Index
<1
>1
FENa
<1
>1
Response to IVF
Good
Poor
功能性肾衰和器质性肾衰（ATN）的鉴别
功能性肾衰
器质性肾衰
尿液性质
尿比重
尿渗透压
尿钠
尿肌酐/血肌酐
尿常规
>1.020
<1.015
>500mOsm/L
<20mmol/L
>40
<400mOsm/L
>40mmol/L
<20
正常
蛋白尿、管型、红细胞、白细胞
治疗与反应
补液后
应迅速补充血容量
使肾血流恢复，GFR
需严格控制补液量
量出而入
尿量迅速增多
病情明显好转
尿量持续减少
甚至使病情恶化
Muddy Brown Cast
Red Cell Cast
White Cell Casts
Diuretic phase
As healing begins, improvement is reflected in
the production of more than 400 ml of urine per
day.
• Fluid and electrolyte abnormalities.
• Cr may still rise for 1-2 more days.
Recovery phase
ARF的主要机能代谢变化和临床表现
一 少尿期
1. 少尿、无尿
2. 氮质血症：指肾功能衰竭时，由于GFR下降，含氮的代谢产物
如尿素、肌酐、尿酸等在体内蓄积，引起血中非蛋白氮的含量增加
（＞28.6mmol/L，或＞40mg/dl）。
3. 水中毒：当肾排水功能障碍的情况下，一旦水摄入稍多，就
易造成稀释性低钠血症，大量水份进入细胞内，引起脑水肿、肺水肿、
心力衰竭。因此对少尿期ARF患者，要严格控制摄入水量。
4. 高血钾：主要由GFR降低和肾小管泌钾障碍引起，机体代谢分
解增强使钾释放增多及酸中毒引起细胞内钾向细胞外转移，都能促使
血钾进一步增高。严重高血钾可导致室颤和心跳骤停。高钾血症是
ARF患者第一周死亡的最常见原因。
5. 代谢性酸中毒： 主要由GFR降低、肾小管排酸保碱作用减退、
体内分解代谢加强使固定酸产生过多等原因引起。
二 多尿期
经过少尿期后，当每天尿量大于400ml，说明病人已进入多尿期。
进行性尿量增多是肾功能开始恢复的一个标志。多尿期的早期，GFR仍
较正常为低，主要因肾小管修复再通而修复的肾小管浓缩功能仍很差，
一方面排出代谢产物的能力不足，一方面出现多尿。这时患者仍可存在
氮质血症，也可能存在高钾血症。尿量过多常使患者发生水、电解质紊
乱，主要倾向是脱水、低血钾和低血钠，所以对这些病人要注意预防。
三 恢复期
患者自我感觉好转，逐步能自理生活和进行劳动。尿量逐渐恢复正
常，血尿素氮和肌酐也接近正常。
Nonoliguric acute renal failure
非少尿型ARF近年来有逐渐增多的趋势；这可能与病人医
疗意识加强、医疗诊治手段提高及肾毒性抗生素广泛应用有关。
其机制为：① 不同肾单位受损程度不一，小部分肾单位的肾
血流量和肾小球滤过功能存在；② 肾小管重吸收功能障碍远
较肾小球滤过功能降低为重；③ 肾髓质形成高渗状态的能力
降低，使尿液浓缩功能下降，故发病后尿量无明显降低，在
400～1000 ml/d左右。非少尿型ARF较少尿型ARF病情轻、预后
好，但因症状轻而不太明显，容易延误病人的就诊或引起医生
的漏诊。非少尿型ARF不及时治疗，则会转化为少尿型ARF。
Management
•
•
•
•
•
•
•
•
•
Renal Diet
Acidosis
Hyperuricemia
Hypertension
Volume overload
Protein Load
Newer Agents：ANF
Dialysis
Kidney Transplantation
Hospital inpatients with ARF ~50% mortality rate
Dialysis indications
I. Serum abnormalities unresponsive to medical therapy
a.
Severe Acidosis
b.
Severe Hyperkalemia
II. Uremia
a.
Mental status changes (usually delirium)
b.
Nausea and vomiting
c.
Pericarditis (pericardial friction rub)
III. Volume Overload
Peritoneal Dialysis
Hemodialysis
• Blood is circulated through artificial cellophane
membrane that permits a similar passage of water and
solutes
Chronic Renal Failure, CRF
• Definition
• Etiology
• Pathogenesis
• Clinical manifestation
• Therapy
Definition
• Chronic renal failure (CRF) is defined as a
permanent reduction in glomerular filtration
rate (GFR) sufficient to produce detectable
alterations in well-being and organ function.
This usually occurs at GFR below 25 ml/min.
• CRF is characterized by progressive and
irreversible loss of large numbers of functioning
nephrons. Serious clinical symptoms often do not
occur until the number of functional nephrons falls
to at least 70 per cent below normal. In fact
relatively normal blood concentrations of most
electrolytes and normal body fluid volumes can
still be maintained until the number of functioning
nephrons decreases below 20-30percent of normal.
慢性肾功能衰竭的定义
慢性肾功能衰竭是由于各种肾脏疾病引起肾单位进行性破坏，
以致残存的有功能的肾单位不能充分排出代谢废物和维持内环境恒
定的缓慢发展的一种肾功能损害的病理过程。机体逐渐出现代谢废
物和毒物的潴留，水、电解质与酸碱平衡紊乱，以及肾内分泌功能
障碍，并可伴有全身各系统功能受损的临床症状。
因为肾组织的破坏是逐渐发生的，而且肾脏又有较强的代偿能
力，故慢性肾衰常常是缓慢发展，病程迁延数月、数年以至更长的
时间，最后常导致尿毒症而死亡。尿毒症是指急、慢性肾功能衰竭
最危重的阶段。
Causes of CRF
Any disorder that permanently destroys nephrons
can result in chronic renal failure. Most common
causes of CRF are:
•
•
•
•
•
Diabetic nephropathy
Hypertensive nephrosclerosis
Glomerulonephritis
Interstitial nephritis
Polycystic kidney disease
慢性肾功能衰竭的病因
凡能引起肾实质进行性破坏的疾患，均可引起慢性肾功能衰竭。
其中以慢性肾小球肾炎为最常见，约占CRF的50%～60%。
（1）肾脏疾患：慢性肾小球肾炎、慢性肾盂肾炎、肾结核、肾
肿瘤、全身性红斑狼疮。
（2）肾血管疾患：高血压肾小动脉硬化等。
（3）尿路慢性梗阻：尿路结石、前列腺肥大等。
（4）全身代谢性疾病：糖尿病肾病等。
（5）其他：药物性肾损伤等。
Clinical courses of CRF
Four stages of decreased renal function may be
visualized:
Silent – GFR up to 50 ml/min.
Renal insufficiency – GFR 25 to 50 ml/min.
Renal failure – GFR 5/10 to 25 ml/min
End-stage renal failure (ESRF) – GFR less than
5/10 ml/min.
Stages of Chronic Kidney Disease
Stage
Description
GFR Level
Normal kidney
function
Healthy kidneys
90 mL/min or more
Stage 1
Kidney damage with normal or
high GFR
90 mL/min or more
Stage 2
Kidney damage and mild
decrease in GFR
60 to 89 mL/min
Stage 3
Moderate decrease in GFR
30 to 59 mL/min
Stage 4
Severe decrease in GFR
15 to 29 mL/min
Stage 5
Kidney failure
Less than 15 mL/min or on
dialysis
慢性肾功能衰竭的发展过程和分期
代偿期
内生肌酐清除率
（ml/min）
氮质血症
>50
无
失代偿期
肾功能不全期 20-50
轻、中度
临床表现
无任何症状。但不能负荷额
外的水、电解质和酸碱
轻度消化道症状和贫血
肾功能衰竭期 10-20
较重
明显多尿、夜尿和水、电解
质、 酸碱紊乱
尿毒症期
严重
全身中毒症状明显，各脏器
系统功能障碍
<10
Pathogenesis
• The most intriguing aspect of CRF is that compensatory
mechanisms allow loss of 90% of GFR before manifestations
of the uremic syndrome are evident. Thus a variety of
adaptations compensate for the decreased GFR and allow a
new steady state of external balance to exist, but on the
other hand contribute to the uremic syndrome. In spite of
these adaptations, the hallmark of CRF is the loss of
flexibility in responding to challenges to external load of
solutes and water.
Intact Nephron hypothesis
Trade-off hypothesis
Tubulointerstitial cell injury
Intact Nephron Hypothesis
• Nephrons functioning in diseased kidneys maintain
glomerulo-tubular balance. That is, filtration and
net
excretion
coordinated.
of
various
substances
are
(e.g. with normal renal function,
usually 50-60% of filtered urea is reabsorbed
from the tubules. In CRF it may fall to 30% to
maintain balance).
The Magnification Phenomenon
• although nephrons in diseased kidneys function
homogeneously, they alter their handling of given
solutes as needed to maintain balance of these
solutes.
excretion
That is, nephrons can magnify their
of
a given
solute.
(e.g. tubular
creatinine excretion is < 10% with normal renal
function. In CRF it may increase to 30%).
Trade-off Hypothesis
• The mechanisms that are magnified to maintain individual
solute control may have deleterious effects on other
systems.
This trade-off is seen in the increased
parathyroid hormone (PTH) secretion seen in CRF which
enhances renal phosphorus excretion. PTH has been
implicated in the pathogenesis of many disturbances of
uremia (sleep, sex, bone, disease, anemia, lipidemia, vascular
disease). As renal disease progresses and GFR decreases,
high level PTH no longer maintains the phosphate excretion.
The excessive PTH may result in further side effects, such
as osteomalacia, deposit of calcium phosphate salts into soft
tissue and damage of cardiovascular, neural systems.
慢性肾功能衰竭的发病机制
• 健存肾单位进行性减少
• 矫枉失衡
• 肾小管 - 间质损害
钙磷代谢的矫枉失衡
慢性肾脏疾患
肾单位↓
GFR↓
GFR↓↓
肾排磷↓
肾排磷↓↓
血磷↑、血钙↓
血磷↑↑
VitD3
血磷↓
酸中毒
肾排磷↑
肾小管重吸收磷↓
PTH↑
血钙↓↓
（健存肾单位）
血钙↑
“矫正”
溶骨
肾性骨营养不良
“失衡”
内生肌酐清除率Ccr =
[ 尿肌酐 ]  尿量/分
[ 血肌酐 ]
*正常值：90－140ml/min
*无肌酐饮食2－3天后测定。
*无肌酐饮食：摄入蛋白质<40g/天，禁肉食，避免剧烈运动。
Clinical manifestations of CRF
• Loss of nephron’s function to excrete water and solutes.
Characteristics of urine:
urine volume,osmotic & gravity, urinary sediment
• Effects on body fluids.
water & sodium imbalance
potassium imbalance
metabolic acidosis
phosphate & calcium metabolism dysfunction
azotemia
• Other signs of CRF
cardiovascular abnormalities
anemia & bleeding
renal osteodystrophy
Anemia
a.
b.
c.
d.
Anemia is universal as GFR falls below 25 ml/min.; in
certain disorders it may occur with mild renal insufficiency.
Several factors contribute:
Erythropoiesis is markedly depressed, mainly due to reduced
erythropoietin production; in addition, there may be reduced
end-organ response to erythropoietin with reduced heme
synthesis.
Red cell survival is shortened with a mild to moderate
decrease in red cell life span, possible due to a “uremic”
toxin.
Blood loss is common in uremic patients, possibly secondary
to abnormal coagulation due to decreased platelet function.
Marrow space fibrosis occurs with osteitis fibrosa of
secondary hyperparathyroidism resulting in decreased
erythropoiesis.
Hypertension
a.
b.
c.
d.
Hypertension occurs in 80% to 90% of patients with renal
insufficiency. Several factors contribute:
Expansion of extracellular fluid volume; this may arise
because of reduced ability of the kidney to excrete ingested
sodium.
Increased activity of the renin-angiotensin system is common;
many patients with advanced renal failure have renin levels
that are not completely suppressed by the elevated blood
pressure.
Dysfunction of the autonomic nervous system occurs with
insensitive baroreceptor sensitive and with increased
sympathetic tone.
Possible diminished presence of vasodilators: there may be
decreased renal generation of prostaglandins or of factors
in the kallikrein-kinin system.
Altered Calcium and Phosphorus Metabolism
(Renal Osteodystrophy)
a. As GFR decreases there is a slight retention of phosphorus; this phosphorus
retention can lead to hypocalcemia, which stimulates PTH. The latter causes
phosphaturia, with restoration of serum phosphorus and calcium toward
normal. However, this occurs only at the expense of elevated serum PTH
levels. This cycle repeats itself in progressive renal failure with PTH levels
increasing progressively. Ultimately, the renal tubule can no longer respond
to higher levels of PTH with a further decrease in phosphorus reabsorption.
When this occurs, hyperphosphatemia develops, hypocalcemia may become
prominent and PTH level can increase to very high levels. High PTH levels
cause bone disease with severe osteitis fibrosa.
b. Altered vitamin D metabolism occurs secondary to decreased renal mass or to
phosphate retention, with decreased synthesis of 1,25 (OH)2 D3. This
deficiency leads to: 1. Diminished intestinal absorption of calcium, 2.
decreased calcemic response of the skeleton to PTH, 3. impaired suppression
of PTH secretion for any increase in serum calcium level, and 4. altered
collagen synthesis. With advanced renal failure, these events can lead to
secondary hyperparathyroidism and osteomalacia.
c. Skeletal resistance to the calcemic action of PTH develops; thus an increased
PTH is required to maintain serum calcium at any level.
d. Finally, accumulation of aluminum from aluminum binding antacids may
contribute to the bone disease.
慢性肾功能衰竭的功能代谢变化
1．泌尿功能障碍
尿量的变化：早期：夜尿、多尿；晚期：少尿。
尿渗透压的变化：低渗尿、低比重尿→等渗尿。
尿质的变化：尿中可出现蛋白尿、红细胞、白细胞、管型等。
2．氮质血症
3．水、电解质和酸碱平衡紊乱
机体对水、钠、钾的调节能力下降，并可出现高磷、低钙血症。
由于肾脏排酸保碱功能降低，可发生代谢性酸中毒。
4．肾性高血压（renal hypertension）
5．肾性贫血（renal anemia）
6．出血倾向
7．肾性骨营养不良
慢性肾功能衰竭引起高血压的机制
肾脏疾病
GFR↓
肾血液灌流量↓
钠水排出↓
钠水潴留
肾实质破坏
肾素分泌↑
Ald↑
血管紧张素II↑
血容量↑
外周阻力↑
心输出量↑
高血压
肾髓质细胞
PGA2、PGE2生成↓
肾性骨营养不良的发生机制
慢性肾功能衰竭
GFR↓
1,25-(OH)2VitD3
骨质钙化障碍
肠钙吸收↓
排磷↓
低钙血症
高磷血症
酸中毒
PTH分泌↑
骨盐溶解↑
肾性骨营养不良
骨质脱钙
Uremia
Concept
• Uremia, from the Greek “urine in the blood”, is a
clinical and biochemical syndrome that occurs
either abruptly or gradually as renal function
decreases acutely or chronically. In its extreme
expression as uremic coma, the patient behaves as
if poisoned, hypothermia, intermittent seizures, a
bleeding diathesis,cardiac arrhythmias, vomiting,
and rapid, shallow respirations may appears.
Uremia
a. Definition: symptomatic azotemia
b. Acidosis (± tachypnea)
c. Mental Status changes
d. Hypervolemia / Hypertension
e. Hyperkalemia
f. Pericarditis
尿毒症
急性或慢性肾功能衰竭晚期，病人体
内水电解质、酸碱平衡紊乱，肾脏内分泌
功能失调，大量代谢产物和毒性物质蓄积，
从而引起一系列全身中毒症状，称为尿毒
症（uremia）。尿毒症是急性或慢性肾功
能衰竭的最严重和最后阶段。
Clinical Manifestations
The symptoms and signs which constitute the uremic
syndrome are summarized below:
• Neurological Disorders:
Fatigue, lethargy, sleep
disturbances,
headache,
seizures,
encephalopathy,
peripheral neuropathy including restless leg syndrome,
paraesthesia, motor weakness, paralysis.
• Hematologic Disorders: Anemia, bleeding tendency – due in
part to platelet dysfunction.
• Cardiovascular Disorders:
Pericarditis, hypertension,
congestive heart failure, coronary artery disease,
myocardiopathy.
• Pulmonary Disorders: Pleuritis, uremic lung.
• Gastrointestinal Disorders:
Anorexia, nausea, vomiting
gastroenteritis, GI bleeding, peptic ulcer.
• Metabolic-Endocrine Disorders:
Glucose intolerance,
hyperllipidemia,
hyperuricemia,
malnutrition,
sexual
dysfunction and infertility.
• Bone, Calcium, Phosphorus Disorders: Hyperphosphatemia,
hypocalcemia, tetany, metastatic calcification, secondary
hyperparathyroidism, 1,25-dihydroxy vitamin D deficiency,
osteomalacia, osteitis fibrosa, osteoporosis, osteosclerosis.
• Skin Disorders:
Pruritus, pigmentation, easy bruising,
uremic frost.
• Psychological Disorders:
Depression, anxiety, denial,
psychosis.
• Fluid
and Electrolyte Disorders:
Hyponatremia,
hyperkalemia, hypermagnesemia, metabolic acidosis, volume
expansion or depletion
Principles of treatment for CRF &
Uremia
• Conservative management
• Dialysis
Peritoneal dialysis
Hemodialysis
• Renal transplantation
case
• 某8岁患儿因感染采用磺胺嘧啶治疗，因使用剂量过大，用
药5天后，连续3日尿量少于100ml/d,急诊入院。经查：血肌
酐480μmol/L（正常值为＜178μmol/L），尿钠 100mmol/L
（正常值为＜20mmol/L），尿相对密度 1.008。问：该病
人是否发生了肾功能衰竭？如果是，是急性肾功能衰竭，
还是慢性肾功能衰竭？该病人的尿少是肾前性因素、肾性
因素还是肾后性因素所致？为什么血肌酐、尿钠浓度增高？
为什么尿相对密度降低？
Treatment of end stage renal failure(ESRF)
• When GFR falls below 5 ml/min, the patient usually can
not live without renal replacement therapy. Renal
replacement therapy includes dialysis and kidney
transplantation .
• Various social or medical factors influence decisions
about peritoneal or hemodialysis, and transplantation in
the treatment of end-stage renal failure. It should
also be noted that none of the above are panaceas and
each, modality is associated with complications and
failures.
1.
2.
3.
4.
5.
6.
Azotemia - elevated blood urea nitrogen (BUN
>28mg/dL) and creatinine (Cr>1.5mg/dL)
Uremia - azotemia with symptoms or signs of
renal failure
End Stage Renal Disease (ESRD) - uremia
requiring transplantation or dialysis
Chronic Renal Failure (CRF) - irreversible kidney
dysfunction with azotemia >3 months
Creatinine Clearance (CCr) - the rate of
filtration of creatinine by the kidney (GFR
marker)
Glomerular Filtration Rate (GFR) - the total rate
of filtration of blood by the kidney
The End
肾小球滤过率
（glomerural filtration rate，GFR）
• 肾小球滤过面积
• 肾小球有效滤过压
= 肾小球毛细血管血压 – 血浆胶体渗透压 – 肾小球囊内压
• 肾血流量
Glomerular Filtration Rate
GFR = Kf [(Pgc-PB) - (Πgc-ΠB)] = Kf (ΔP-ΔΠ)
Kf = glomerular ultrafiltration coefficient
Pgc = glomerular capillary hydraulic pressure
PB = Bowman’s space hydraulic pressure
Πgc = glomerular colloid osmotic pressure
ΠB = Bowman’s space colloid osmotic pressure
Estimates of GFR
• Inulin neither secreted or reabsorbed
• Clearance of inulin approximates GFR
GFR =
[U]inulin V
[P]inulin
• Creatine is secreted, so Cr clearance
overestimates GFR
Estimates of GFR
Urinary Estimate
[U]cr V
CrCl =
[P]cr
Cockcroft Gault Estimate
[140-age (yr)][body wt (kg)]
CrCl =
72[Pcr]
Glomerulus
Filtration Membrane
– Electron Micro.
Capillary Space
GBM
Endothelium
Urinary Space
Podocyte
Symptoms of chronic kidney disease
• Fatigue and weakness (from anemia or accumulation of waste
products in the body)
• Loss of appetite, nausea and vomiting
• Need to urinate frequently, especially at night
• Swelling of the legs and puffiness around the eyes (fluid
retention)
• Itching, easy bruising, and pale skin (from anemia)
• Headaches, numbness in the feet or hands (peripheral
neuropathy), disturbed sleep, altered mental status
(encephalopathy from the accumulation of waste products or
uremic poisons), and restless legs
• High blood pressure, chest pain due to pericarditis
(inflammation around the heart)
• Shortness of breath from fluid in lungs
• Bleeding (poor blood clotting)
• Bone pain and fractures
• Decreased sexual interest and erectile dysfunction