Renal Insufficiency

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Renal Insufficiency
2
To be a great champion you must believe you are
the best. If youre not, pretend you are.!
Muhammad Ali
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TOPICS

• Introduction
• Acute renal failure
• Chronic renal failure
• Uremia

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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.

5

• 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.

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Functions of the Kidney

• Waste excretion
• Electrolyte balance
• Fluid balance
• pH
• Osmolality
• Hormone production

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Anatomy of Kidney
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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

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??VitD3?????

• ??? 25-??? 1a-???
• 7-????? VitD3 25-(OH)VitD3
  1,25-(OH) 2VitD3
• (??) (????)
  (????)

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Acute Renal Failure, ARF
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• Definition
• Etiology classification
• Prerenal failure
• Intrinsic renal failure
• Post(obstructive) renal failure
• Pathogenesis
• Clinical manifestation
• Therapy

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Definition

• Acute renal failure (ARF) is defined as a
  precipitous and significant (gt50) decrease in
  glomerular filtration rate (GFR) over a period of
  hours to days, with an accompany-ing accumulation
  of nitrogenous wastes in the body.

14
??????????

•  ???????(acute renal failure,ARF)?????????????????
  ???????,?????????????????????????
• ??????????GFR????,???????????????????????????????
  ??
• ???????????????,?????(????????400ml)?????(????????
  400ml)?????????????,?????,??????,?????

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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 (lt5 of cases)
• resulting from obstruction of urinary
  flow between the kidney and urinary meatus.

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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)

17
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• 
  ?????
• ?????(??????????????
• ??????)???(?????)
•  
• ADH? ???????
  Ald?
•  
• 
  ????
• ?????
  ?????
•  
  ?????
•   ?????????
•  
  GFR?
•  
• 
  ????

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• 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

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• 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.

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Causes of ARF in tertiary care hospital setting
21
????????????

• ???ARF (??????ARF )
• ??????????????????????ARF??????? ?
• ??ARF(?????ARF)
• ?????????????????(acute tubular
  necrosis,ATN)????????????ARF??,??ARF?7580 ?
• ???ARF
• ??????????,????????????????

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Pathogenesis of ARF
I. Renal hemodynamics factors

• Decreased renal blood flow
• Renal hypoperfusion
• Vasoconstriction
• Vascular obstruction
• Redistribution of renal blood flow

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II. Nephronal factors

• Tubule injury
• Tubule obstruction
• Passive backflow

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Acute Renal Failure, IntrinsicAcute 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

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Acute Tubular NecrosisNephrotoxic Agents

• Exogenous
• Antibiotics
• Contrast
• Diuretics
• Chemotherapeutics
• Analgesics
• Solvents, metals, chemicals

• HIV meds
• Antiulcer meds
• Anesthetics
• Endogenous
• Pigment nephropathy
• Crystal deposition
• Tumor-specific syndromes

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Acute Tubular Necrosis
Cell Hypoxia
Depletion of ATP
Hypoxanthine
Impaired function Of plasma membranes And ATPases
Ca imbalance
Na-K imbalance
Cell Swelling
Disrupt cytoskeleton Activate phospholipases Forma
tion of xanthine oxidase Uncoupling of oxidative
phosphorylation
Disrupt lipid bilayer
Reperfusion injury Free radicals
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Acute Tubular Necrosis

• Leads to
• Loss of cell polarity
• Brush border loss
• Impaired cell-cell adhesion
• Impaired tight junction

• End results
• Impaired solute and water transport
• Sloughing of tubule cells ? obstruction
• Back leakage of filtrate

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????????????

• ??????????????GFR????
• ? ????????
• ???????
• ?????? ????? ?????
• ???????
• ? ?????
• ?????
• ????
• ? ?????????

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Characteristics clinical courses

• Oliguric phase
• Diuretic phase
• Recovery phase

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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

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Urinary Indices in ARF
Prerenal ARF ATN
Urinary Na, mEq/L lt20 gt40
Urine to plasma Cr gt40 lt20
Urine osmolality gt500 lt400
Urine specific gravity gt1.020 lt1.015
Renal Failure Index lt1 gt1
FENa lt1 gt1
Response to IVF Good Poor
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???????????(ATN)???

• ?????
  ?????
• ????
• ???
• ????
• ??
• ???/???
• ???
• ?????

gt1.020 lt1.015
gt500mOsm/L lt400mOsm/L
lt20mmol/L gt40mmol/L
gt40 lt20
?? ??????????????
???????? ???????? ??????,GFR?
????
??? ?????? ??????
??????
???????
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Muddy Brown Cast
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Red Cell Cast
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White Cell Casts
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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
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ARF??????????????

• ? ???
• 1. ?????
• 2. ???????????,??GFR??,?????????????????????
  ?,?????????????(gt28.6mmol/L,?gt40mg/dl)?
• 3. ???????????????,???????,???????????,??????
  ???,?????????????????????ARF??,??????????
• 4. ??????GFR????????????,????????????????????
  ??????????,?????????????????????????????????ARF???
  ???????????
• 5. ?????????GFR??????????????????????????????
  ???????

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• ? ???
• ??????,???????400ml,????????????????????????
  ??????????????,GFR??????,????????????????????????,
  ??????????????,????????????????????,??????????????
  ?????????????,???????????????,?????????????
• ? ???
• ????????,?????????????????????,????????????
  ?

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Nonoliguric acute renal failure

• ????ARF??????????????????????????????????????????
  ????????? ???????????,??????????????????????
  ???????????????????????? ??????????????,?????????
  ,???????????,?4001000 ml/d???????ARF????ARF??????
  ?,??????????,??????????????????????ARF?????,??????
  ??ARF?

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Management

• Renal Diet
• Acidosis
• Hyperuricemia
• Hypertension
• Volume overload
• Protein Load
• Newer AgentsANF
• Dialysis
• Kidney Transplantation
• Hospital inpatients with ARF 50 mortality rate

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Dialysis indications

• I. Serum abnormalities unresponsive to medical
  therapy
• Severe Acidosis
• Severe Hyperkalemia
• II. Uremia
• Mental status changes (usually delirium)
• Nausea and vomiting
• Pericarditis (pericardial friction rub)
• III. Volume Overload

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Peritoneal Dialysis
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Hemodialysis

• Blood is circulated through artificial cellophane
  membrane that permits a similar passage of water
  and solutes

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Chronic Renal Failure, CRF
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• Definition
• Etiology
• Pathogenesis
• Clinical manifestation
• Therapy

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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.

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• 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.

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49
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• ??????????????????????????,???????????????????????
  ??????????????????????????????????????????,???????
  ?????,??????????,???????????????????
• ??????????????,?????????????,????????????,????????
  ????????,?????????????????????????????????

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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

51
??????????

• ???????????????,??????????????????????????,??C
  RF?5060?
• (1)???????????????????????????????????
• (2)????????????????
• (3)??????????????????
• (4)??????????????
• (5)??????????

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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.

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Stages of Chronic Kidney Disease

54
???????????????

• ??????? ????
  ????
• (ml/min)
• ??? gt50
  ? ????????????
• 
  ??????????
• ????
• ?????? 20-50 ????
  ??????????
•  
• ?????? 10-20 ??
  ???????????? ?? ????
• ???? lt10 ??
  ????????,???
• ??????

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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
  Tubulointerstitial cell injury
• Trade-off hypothesis

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Intact Nephron Hypothesis

• Nephrons functioning in diseased kidneys maintain
  glomerulo-tubular balance. That is, filtration
  and net excretion of various substances are
  coordinated. (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).

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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. That is, nephrons can magnify their
  excretion of a given solute. (e.g. tubular
  creatinine excretion is lt 10 with normal renal
  function. In CRF it may increase to 30).

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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.

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????????????

• ??????????
• ????
• ??? - ????

60
?????????

• ??????
•  
• ????
•  
• 
  GFR? GFR?? VitD3?
  
• ???
• 
  ???? ????? ???
• ????
• 
  ??????? ????
•   ???????? PTH?
  ????
• (?????)
• ???
  ?? ???????
•   ??
  ??

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??? ? ??/?
???????Ccr
???
???90-140ml/min ?????2-3????? ??????????lt40g/
?,???,???????
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Clinical manifestations of CRF

• Loss of nephrons 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

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Anemia

• Anemia is universal as GFR falls below
  25 ml/min. in certain disorders it may occur
  with mild renal insufficiency. Several factors
  contribute 
• a. 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.
• b. Red cell survival is shortened with a mild to
  moderate decrease in red cell life span, possible
  due to a uremic toxin.
• c. Blood loss is common in uremic patients,
  possibly secondary to abnormal coagulation due to
  decreased platelet function.
• d. Marrow space fibrosis occurs with osteitis
  fibrosa of secondary hyperparathyroidism
  resulting in decreased erythropoiesis.

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Hypertension

•   Hypertension occurs in 80 to 90 of
  patients with renal insufficiency. Several
  factors contribute
• a. Expansion of extracellular fluid volume this
  may arise because of reduced ability of the
  kidney to excrete ingested sodium.
• b. 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.
• c. Dysfunction of the autonomic nervous system
  occurs with insensitive baroreceptor sensitive
  and with increased sympathetic tone.
• d. Possible diminished presence of vasodilators
  there may be decreased renal generation of
  prostaglandins or of factors in the
  kallikrein-kinin system.

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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.

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??????????????

• 1.??????
• ?????????????????
• ????????????????????
• ??????????????????????????
• 2.????
• 3.????????????
• ???????????????,????????????????????????,?????
  ?????
• 4.?????(renal hypertension)
• 5.????(renal anemia)
• 6.????
• 7.???????

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???????????????

• ????
•  
• GFR? ???????
  ?????
•  
• ????? ?????
•  
• ???? Ald? ?????II?
  ?????
• 
  
  PGA2?PGE2???
• ???? ?????
•  
• ????? ???
•  

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????????????

•   ???????
•  
• 1,25-(OH)2VitD3
  GFR?
•  
• ????? ???
•  
• ???? ????
  ???
•  
• ?????? PTH???
•  
  ????? ????
•  
  ???????
•  

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Uremia
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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.

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Uremia

• Definition symptomatic azotemia
• Acidosis ( tachypnea)
• Mental Status changes
• Hypervolemia / Hypertension
• Hyperkalemia
• Pericarditis

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???

• ????????????,???????????????,?????????,???????
  ??????,?????????????,?????(uremia)????????????????
  ?????????

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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.

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• 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

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Principles of treatment for CRF Uremia

• Conservative management
• Dialysis
• Peritoneal dialysis
• Hemodialysis
• Renal transplantation

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case

• ?8??????????????,???????,??5??,??3?????100ml/d,???
  ???????480µmol/L(????lt178µmol/L),??
  100mmol/L(????lt20mmol/L),????? 1.008?????????????
  ??????,????????,??????????????????????????????????
  ????????????????????????????

77
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.

78

• Azotemia - elevated blood urea nitrogen (BUN
  gt28mg/dL) and creatinine (Crgt1.5mg/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 gt3 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

79
The End
80
??????(glomerural filtration rate,GFR)

• ???????
• ????????
• ????????? ??????? ??????
• ????

81
Glomerular Filtration Rate
GFR Kf (Pgc-PB) - (?gc-?B) Kf (?P-??) Kf
glomerular ultrafiltration coefficient Pgc
glomerular capillary hydraulic pressure PB
Bowmans space hydraulic pressure ?gc
glomerular colloid osmotic pressure ?B Bowmans
space colloid osmotic pressure
82
Estimates of GFR

• Inulin neither secreted or reabsorbed
• Clearance of inulin approximates GFR
• Uinulin V
• Pinulin
• Creatine is secreted, so Cr clearance
  overestimates GFR

GFR
83
Estimates of GFR
Urinary Estimate Ucr V Pcr
Cockcroft Gault Estimate 140-age
(yr)body wt (kg) 72Pcr
CrCl
CrCl
84
Glomerulus
85
(No Transcript)
86
Filtration Membrane Electron Micro.
Capillary Space
GBM
Endothelium
Urinary Space
Podocyte
87
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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