Nephrology Review February 19, 2010
RENAL FUNCTION <ul><li>EXCRETORY </li></ul><ul><li>REGULATORY  </li></ul><ul><li>ENDOCRINE & METABOLIC </li></ul>END PRODU...
GFR <ul><li>Inulin clearance </li></ul><ul><li>Cr clearance :  </li></ul><ul><li>UcrV/Pcr  =  50 mg/dl  ×  1500   cc  = cc...
Milutinovic et al. Kidney Int. 1975:8;185-190 inulin iothalamate (CCr+Curea)/2
Na + K + Cl -
Tubular function <ul><li>Absorption </li></ul><ul><li>Na + , Cl - , H 2 O, HCO 3 - , glucose, Ca 2+ , PO 4 , amino acid, u...
การที่มี  BUN  และ  serum creatinine  สูงเกินค่าปกติ   (Normal Cr  ชาย  ≤   1.5,  หญิง   ≤   1.3 mg/dl)  Azotemia
Uremia กลุ่มอาการที่เกิดจากความผิดปกติของการคั่งของของเสีย สารน้ำและเกลือแร่ที่เกิดคู่กับการเสื่อมหน้าที่ของไต - nausea, v...
Azotemia GFR   ปกติ GFR   ต่ำ Acute KI Chronic KD Intrinsic RF Post RF Pre RF Chronic GN Chronic TIN BUN  Cr
Normal GFR <ul><li>   BUN </li></ul><ul><li>Protein load </li></ul><ul><li>high protein diet </li></ul><ul><li>parenteral...
Decrease GFR <ul><li>Normal BUN </li></ul><ul><li>Low protein diet </li></ul><ul><li>Advance chronic liver disease </li></...
Acute Renal Failure (ARF)  Acute Kidney Injury (AKI) <ul><li>Prerenal  </li></ul><ul><li>Renal  </li></ul><ul><li>Post re...
Definition of Acute kidney injury OR 2004 Level of  dysfunciton Outcome
 
Acute Kidney Injury Within 48 hours  serum Cr > 0.3 mg/dL  serum Cr > 50% (1.5 fold) More than 6 hours  urine output < ...
AKIN classification   Baseline serum Cr (48 hr)   urine output Stage 1 (R)  >0.3 mg/dL or   1.5-2 fold  <0.5 mL/kg/hr >6...
 
Decreased circulatory volume Activation of central baroreceptors Norepinephrine Vasopressin Angiotensin II PGE2 / PGI2 Nit...
Renal causes <ul><li>ATN  : ischemic, nephrotoxic </li></ul><ul><li>AIN  : allergy (drugs-betalactam), tumor (lymphoma), i...
Functional & Physiologic change Loss of cell polarity Loss Cell-cell, cell matrix interaction Tight junction  defect ↑  Di...
Pre-renal VS Renal <ul><li>Index   Pre-renal   Renal </li></ul><ul><li>Urine sp.gr.   >1.018 < 1.012 </li></ul><ul><li>Uri...
Na + K + Cl - Medullary ischemia Intermediate syndrome Urine Na low Urine spgr low
Risk of aminoglycosides nephrotoxic  <ul><li>Dose frequency : once daily better </li></ul><ul><li>Cationic amino group (NH...
Amphotericin B <ul><li>Renal vasoconstriction & tubular injury </li></ul><ul><li>Renal complication </li></ul><ul><li>dist...
Cisplatin <ul><li>Tubular injury (low Cl, reactive hydroxyl radical) </li></ul><ul><li>Hypomagnesemia  </li></ul><ul><li>R...
Radiocontrast nephropathy <ul><li>Azotemia within 48 hours after exposure </li></ul><ul><li>High risk : CKD (esp.  DM ) wi...
Acute renal failure <ul><li>Prerenal :  volume depletion, heart failure </li></ul><ul><li>Hx : volume loss, PND, CAD, orth...
Investigation <ul><li>U/S : obstruction, kidney size,  </li></ul><ul><li>doppler, MRA – RAS, renogram (Cr > 3 – 4 can not ...
Management <ul><li>Rx causes </li></ul><ul><li>Stop harmful drugs </li></ul><ul><li>Nutrition  </li></ul><ul><li>Volume st...
 
 
CAUSES OF ANEMIA IN CRF <ul><li>↓   Erythropoietin production </li></ul><ul><li>↓   Erythrocyte survival </li></ul><ul><li...
RENAL OSTEODYSTROPHY <ul><li>High turnover </li></ul><ul><li>Hyperparathyroidism </li></ul><ul><li>Low turnover </li></ul>...
Comprehensive strategy <ul><li>Intervention  Goal </li></ul><ul><li>ACEI or ARB or Both proteinuria < 0.5 g/d </li></ul><u...
RENAL Na +  REABSORPTION HCO 3 - HCO 3 -  + H 2 O+CO 2 CA H +  +HCO 3 - CA Na + glucose PO 4 AA Carbonic anhydrase inhibit...
TAL of Henle Loop diuretics
DISTAL TUBULE Thiazide
CORTICAL COLLECTING TUBULE Na + K + H + spironolactone Amiloride
POLYURIA
DEFINITION <ul><li>Urine volume </li></ul><ul><li>> 3 L/day,  </li></ul><ul><li>> 2 cc/min,  </li></ul><ul><li>> 30 cc/kg/...
What is urine? <ul><li>Clearance of H 2 O + Clearance of solute </li></ul><ul><li>(CH 2 O + Csolute)  </li></ul>
   GFR    salt excretion    H 2 O excretion
Polyuria <ul><li>   CH 2 O     water diuresis </li></ul><ul><li>Diabetes insipidus  :  </li></ul><ul><li>central or neph...
Central DI <ul><li>Sudden onset </li></ul><ul><li>Trauma, pituitary surgery, tumor, hypoxic encephalopathy </li></ul><ul><...
Nephrogenic DI <ul><li>Abnormality of V2 receptor, aquaporin 2, medullary hypertonicity </li></ul><ul><li>Reduce maximal c...
Water reabsorption V2 Medullary Hypertonicity
Approach <ul><li>History </li></ul><ul><li>Nocturia : DI  </li></ul><ul><li>Psychogenic disorders : polydipsia </li></ul><...
Approach <ul><li>Physical examination : </li></ul><ul><li>ECF depletion : salt losing </li></ul><ul><li>CNS lesion : bitem...
Approach <ul><li>Hx :  brain lesion, drugs, electrolytes, intake, ATN </li></ul><ul><li>Volume status </li></ul><ul><li>La...
CAUSES <ul><li>1 patient :  >  1 lesions </li></ul><ul><li>   CH 2 O  </li></ul><ul><li> Csolute </li></ul><ul><li> CH ...
Water diuresis <ul><li>DI </li></ul><ul><li>central </li></ul><ul><li>nephrogenic </li></ul><ul><li>gestational DI </li></...
Gestational DI <ul><li>Vasopressinase from placenta </li></ul><ul><li>(cystine aminopeptidase) </li></ul><ul><li>Resist to...
Primary polydipsia <ul><li>Anxious, middle-aged women </li></ul><ul><li>Psychiatric illness, phenothiazine  </li></ul><ul>...
Water deprivation test <ul><li>ADH stimulation </li></ul><ul><li>ADH response </li></ul><ul><li>(5 u of aq vasopressin SC ...
ADH stimulation Central Nephrogenic Partial Complete
Water Deprivation Test <ul><li>Urine vol, urine osmolality, BW q 1 hr </li></ul><ul><li>Plasma osmolality and Na q 2 hr </...
 
Solute diuresis <ul><li>Electrolytes  </li></ul><ul><li>Diuretics : furosemide, dopamine </li></ul><ul><li>Diuretic ATN, <...
Solute diuresis <ul><li>Electrolytes </li></ul><ul><li>2(U[Na+K])  > 0.6 </li></ul><ul><li>  Uosm </li></ul><ul><li>Nonele...
Fluid therapy
hypotonic isotonic colloid ICF 2/3 ECF 1/3 II 3/4 IV 1/4 TBW  - male : 60%BW, Female 50%BW Elder - male : 50%BW, Female 45...
HYPERTONIC SALINE <ul><li>↑  Intravascular volume > volume infused </li></ul><ul><li>(prehospital use !) </li></ul><ul><li...
Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation.  Cochrane Database of Systematic Reviews 2008, Iss...
Fluid therapy <ul><li>Side effects : coagulopathy (dextran) </li></ul><ul><li>  anaphylaxis (gelatin) </li></ul><ul><li>Go...
SUMMARY <ul><li>Control loss or bleeding </li></ul><ul><li>Prehospital  hypertonic  fluid therapy benefit in head injury <...
Water balance
Hyponatremia  <ul><li>Water retention  +  Na loss </li></ul><ul><li>Why water is retained? </li></ul><ul><li>severe impair...
Management hyponatremia <ul><li>Acute  or chronic : symptoms  </li></ul><ul><li>Chronic or mild : 8 – 12 mEq/day </li></ul...
 
 
 
Potassium
K BALANCE <ul><li>Intake : 40 – 120 mEq/day </li></ul><ul><li>Distribution :  </li></ul><ul><li>intracellular anabolism : ...
50 – 55 mEq/kg 3,000 – 4,000 mEq 65 mEq (2%) Red cell 250 mEq Muscle 2,635 mEq Liver 250 mEq  Bone 300 mEq ICF ECF II IV K...
 
100% 25% 10% 25% 20% <ul><li>Flow </li></ul><ul><li>Aldosterone </li></ul><ul><li>serum K + </li></ul>
HYPOKALEMIA
DEFINITION <ul><li>Serum K +   <  3.5 mEq/L </li></ul>
DIAGNOSIS <ul><li>CLINICAL SIGNS & SYMPTOMS  (rate of   ) </li></ul><ul><li>proximal muscle weakness </li></ul><ul><li>ar...
SIGNS & SYMPTOMS <ul><li>CARDIAC CONDUCTION DEFECTS </li></ul><ul><li>ISCHEMIA </li></ul><ul><li>HEART FAILURE </li></ul><...
ST depress, Peak P, PR prolong Widening QRS
CAUSES <ul><li>Decrease intake  </li></ul><ul><li>Shift  </li></ul><ul><li>Extrarenal loss </li></ul><ul><li>Renal loss </...
Hypokalemia [acid-base, ECF volume, hypertension, urine K + ] Metabolic acidosis urine K +   low    high (urine Na+ > 100 ...
Hypokalemia, Hypertension, Metabolic alkalosis, renal K +  loss (screening test) [plasma renin activity (PRAng/ml/hr), pla...
Algorithm <ul><li>History  :  diarrhea,  </li></ul><ul><li>diuretic uses, vomiting, drugs  </li></ul><ul><li>ECF volume   ...
TTKG <ul><li>Urine Osm CCT  = Urine K + CCT </li></ul><ul><li>Urine Osm Urine K + </li></ul><ul><li>TTKG =  Urine K + CCT ...
Treatment <ul><li>Evaluation : EKG and weakness </li></ul><ul><li>Emergency : arrhythmia, respiratory failure, paralysis <...
Treatment <ul><li>IV K + </li></ul><ul><li>15%KCl  (1cc = K +  2 mEq)  ,  </li></ul><ul><li>8.7%K 2 HPO 4  (1cc = K +  1 m...
HYPERKALEMIA
DIAGNOSIS <ul><li>CLINICAL SIGNS & SYMPTOMS </li></ul><ul><li>proximal muscle weakness </li></ul><ul><li>arrhythmia </li><...
Flat P Prolong PR AV block Widening QRS Sine-wave
CAUSES <ul><li>K +  load  </li></ul><ul><li>Shift  </li></ul><ul><li>Decrease renal K +  excretion </li></ul><ul><li>Decre...
DIAGNOSIS <ul><li>Rule out factitious hyperkalemia </li></ul><ul><li>K +  load </li></ul><ul><li>Cause of shift </li></ul>...
TREATMENT <ul><li>Emergency  </li></ul><ul><li>Abnormal EKG </li></ul><ul><li>Serum K +  > 6.5 (or acute > 6.0) </li></ul>...
TREATMENT <ul><li>SPECIFIC </li></ul><ul><li>ADJUNCTIVE </li></ul><ul><li>CAUSE </li></ul><ul><li>PREVENTION </li></ul>
SPECIFIC TREATMENT <ul><li>Antagonize membrane effect </li></ul><ul><li>Decrease K +  level </li></ul><ul><li>Remove K +  ...
 
Intracellular K +  shift <ul><li>Insulin : most effective and reliable </li></ul><ul><li>Beta2 agonist : modest, tachycard...
Remove K + <ul><li>Hemodialysis : most rapid </li></ul><ul><li>Anion exchange resin + laxative </li></ul><ul><li>Kayexalat...
TREATMENT   mechanism   onset  peak Ca  antagonist   1-5 min   HD  remove   15 min PD  remove   2 h Kay exalate  remove   ...
ADJUNCTIVE TREATMENT <ul><li>Restrict K +  2 g/day </li></ul><ul><li>Stop risk factors </li></ul><ul><li>Diuretics : incre...
Acid-Base Disorders
DEFINITION <ul><li>Acidemia --- Euphemia --- Alkalemia </li></ul><ul><li>(-emia    pH of blood) </li></ul><ul><li>Acidosi...
PCO 2 H + , HCO 3 - HCO 3 - /CO 2 Albumin Bone Proteins PO 4 Buffers
 
REMEMBER <ul><li>Metabolic Acidosis/Alkalosis =  </li></ul><ul><li>disturbances of blood bicarbonate  </li></ul><ul><li>Re...
Normal  meat-based  Diet <ul><li>Carbohydrate and fat  metabolism will generate  20,000 mEq  of acid/day in the form of  C...
KIDNEYS <ul><li>Regulate acid-base by the following mechanisms: </li></ul><ul><li>Reabsorption of filtered HCO 3 ¯  </li><...
COMPENSATORY RESPONSE [ACIDOSIS] <ul><li>Respiratory acidosis </li></ul><ul><li>acute  :  ↑  PCO 2  10  mmHg      ↑  HCO ...
COMPENSATORY RESPONSE [ALKALOSIS] <ul><li>Respiratory alkalosis </li></ul><ul><li>acute  :  ↓  PCO 2  10  mmHg      ↓  HC...
 
ASSESSMENT OF ACID-BASE DISORDER <ul><li>Clinical (history & physical exam) </li></ul><ul><li>correct diagnosis </li></ul>...
Hypoventilation
Hyperventilation
Causes of  metabolic acidosis
H + X -   -> H + X -   ->   CO 2  + NaX   ->  Kidney   ->   + HCO 3 <ul><li>↑  H +  PRODUCTION </li></ul><ul><li>lactic ac...
<ul><li>Measured  ⊕  + Unmeasured  ⊕  = Measured  ⊖  + Unmeasured  ⊖ </li></ul><ul><li>Measured  ⊕  - Measured  ⊖   =  Unm...
H + X -   -> H + X -   ->   CO 2  + NaX   ->  Kidney   -> H + X -   + Na HCO 3 <ul><li>↑  H +  PRODUCTION </li></ul><ul><l...
H + X -   -> H + X -   ->   CO 2  + NaX   ->  Kidney   -> H + X -   + Na HCO 3 <ul><li>↑  H +  PRODUCTION </li></ul><ul><l...
Mixed wide & normal gap acidosis <ul><li>Wide anion gap </li></ul><ul><li>↑ anion gap = ↓HCO 3 - </li></ul><ul><li>∆ anion...
TREATMENT <ul><li>CAUSES   </li></ul><ul><li>ALKALI THERAPY </li></ul><ul><li>chronic loss : RTA </li></ul><ul><li>pH  <  ...
CAUSES OF METABOLIC ALKALOSIS (Generation) <ul><li>H +  LOSS </li></ul><ul><li>GI (gastric content) :  </li></ul><ul><li>v...
Renal HCO 3 -   reabsorption Serum  HCO 3 -   (mEq/l) HCO 3 -   reabsorption 25   50 Volume depletion K +  depletion
Assessment <ul><li>Blood pressure :  </li></ul><ul><li>hypertension     aldosteronism </li></ul><ul><li>Volume status : E...
CAUSES OF METABOLIC ALKALOSIS (Generation) <ul><li>H +  LOSS </li></ul><ul><li>GI (gastric content) :  </li></ul><ul><li>v...
CAUSES OF METABOLIC ALKALOSIS <ul><li>Generation factors </li></ul><ul><li>Maintenance factor </li></ul><ul><li>ECF volume...
TREATMENT <ul><li>CAUSES  (generation factors)   </li></ul><ul><li>Maintenance factors </li></ul><ul><ul><ul><li>Cl -  dep...
Approach to Patients with Glomerular Diseases Suchai Sritippayawan Division of Nephrology , Internal Medicine, Siriraj Hos...
Structure
pore fenestration charge Slit pore
Pathogenesis
JOURNAL OF NEPHROLOGY Vol .  11 No .  4  -  1998  /  177-182
 
Structure Proliferation Expansion  Endocap-proliferation Thinkening : spike, double contour Necrosis Leucocytic infiltrati...
Mesangial : IgMN, IgAN, lupus Subepithelial : membranous Subendothelial : lupus Intra GBM : lupus, MPGN I
Brenner :  Brenner and Rector's The Kidney,  8th ed. Copyright ©  2007 Saunders, An Imprint of Elsevier
Clinical features <ul><li>Proteinuria </li></ul><ul><li>   GFR </li></ul><ul><li>Nephritis  </li></ul><ul><li>Edema  </li...
Clinical syndromes <ul><li>Asymptomatic : hematuria, proteinuria </li></ul><ul><li>Nephrotic </li></ul><ul><li>Nephritis <...
Asymtomatic hematuria  <ul><li>RC > 3/HD, glomerular RC </li></ul><ul><li>No  nephrotic, nephritic, HT, edema, azotemia, o...
>70% of RC are glomerular RC Proteinuria > 1 g/day   or 2+ Indetermine 30–70% Nonglom. <30% acanthocyte ring
Proteinuria <ul><li>Normal : < 200 mg/day of total protein </li></ul><ul><li>Microalbuminuria : 30 – 300 mg/day </li></ul>...
Types of proteinuria (pathophysiology) <ul><li>Glomerular : glomerulonephritis </li></ul><ul><li>Tubular : tubulointerstit...
Asymptomatic proteinuria <ul><li>Transient or orthostatic proteinuria    good prognosis </li></ul><ul><li>diagnosis : sep...
Nephrotic syndrome <ul><li>Proteinuria > 3 g/1.73 m 2 /day </li></ul><ul><li>Edema  </li></ul><ul><li>Hypoalbuminemia </li...
 
Nephrotic syndrome <ul><li>Most common :  </li></ul><ul><li>1 o     IgMN, MCD, membranous GN </li></ul><ul><li>2 o     D...
 
Nephritic syndrome <ul><li>Hematuria :  </li></ul><ul><li>microscopic hematuria </li></ul><ul><li>macroscopic :  IgAN </li...
 
Rapidly progressive GN (RPGN) <ul><li>Clinical diagnosis </li></ul><ul><li>loss of kidney function >50% within weeks to mo...
Telescopic urine sediment
How to approach?
<ul><li>Primary or secondary??? </li></ul><ul><li>clinical features of </li></ul><ul><li>Hypertension </li></ul><ul><li>Ne...
Secondary  glomerular diseases
Secondary  glomerular diseases <ul><li>Metabolic diseases :  DM (most common) </li></ul><ul><li>Autoimmune diseases : SLE,...
Secondary  glomerular diseases <ul><li>Nephrotic </li></ul><ul><li>Diabetic nephropathy </li></ul><ul><li>Ig deposition di...
Metabolic disorders <ul><li>DM Diabetic nehropathy  (Nephrotic) </li></ul><ul><li>Hyperthyroidism membranous GN </li></ul>
Diabetic nephropathy <ul><li>Type 1 </li></ul><ul><li>5 – 10 y :  microalbuminemia </li></ul><ul><li>13 – 20 y :  overt pr...
Diabetic nephropathy <ul><li>Type 2 </li></ul><ul><li>duration : variable  (HT, atherosclerosis) </li></ul><ul><li>50 – 80...
DM & glomerular diseases <ul><li>Diabetic nephropathy </li></ul><ul><li>Hypertensive nephropathy </li></ul><ul><li>Other p...
Collagen vascular diseases autoimmune disease <ul><li>SLE lupus nehritis (nehritic, nephrotic) </li></ul><ul><li>RA membra...
Ig deposition diseases <ul><li>Amyloidosis  </li></ul><ul><li>Light chain deposition diseases </li></ul><ul><li>Heavy chai...
Infections  <ul><li>Viral  </li></ul><ul><li>HBV membranous GN </li></ul><ul><li>HCV mixed cryoglobulinemia </li></ul><ul>...
Drugs <ul><li>NSAID : minimal change disease </li></ul><ul><li>Gold, d-penicillamin : membranous </li></ul>
Malignancy  <ul><li>Hematologic :  </li></ul><ul><li>non Hodgin    membranous </li></ul><ul><li>Hodgin     minimal chang...
Others  <ul><li>Cirrhosis    IgA nephropathy </li></ul>
Primary  glomerular diseases
Primary glomerular diseases <ul><li>Nephrotic </li></ul><ul><li>IgM nephropathy </li></ul><ul><li>Minimal change dis </li>...
Investigations <ul><li>Diagnosis of glomerular diseases  </li></ul><ul><li>blood pressure </li></ul><ul><li>GFR </li></ul>...
Kidney biopsy <ul><li>Indication  </li></ul><ul><li>Diagnosis </li></ul><ul><li>Prognosis </li></ul><ul><li>Method  </li><...
Individual investigations <ul><li>ANA, antiDNA   lupus nephritis </li></ul><ul><li>Complement   inflammatory related </l...
Managements
Managements <ul><li>Primary or secondary </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>most common causes : minim...
Managements <ul><li>Nephrotic syndrome </li></ul><ul><li>most common causes : minimal change disease </li></ul><ul><li>cyc...
Managements <ul><li>Nephritis  </li></ul><ul><li>treatment depends on etiology </li></ul><ul><li>recommend kidney biopsy i...
IgA nephropathy <ul><li>Asymptomatic hematuria    RPGN </li></ul><ul><li>Factors associated with progressive disease (Sir...
Lupus nephritis   :  Siriraj experience <ul><li>ANA +ve 90%,  antiDNA +ve 67% </li></ul><ul><li>Classification </li></ul><...
Lupus nephritis treatment <ul><li>Class II  </li></ul><ul><li>oral prednisolone 0.5 mg/kg/day </li></ul><ul><li>Class IV <...
 
PREGNANCY  &  KIDNEY DISEASE
NORMAL PHYSIOLOGY <ul><li>Systemic hemodynamics </li></ul><ul><li>   blood volume </li></ul><ul><li>   peripheral vascul...
RENAL FUNCTIONS <ul><li>   GFR & RPF 40 – 50% </li></ul><ul><li>Onset : 1 m,  Peak : end of 1st trim. </li></ul><ul><li>...
ELECTROLYTES & ACID-BASE <ul><li>Chronic respiratory alkalosis </li></ul><ul><li>   RC center : progesterone </li></ul><u...
HYPERTENSION <ul><li>PREECLAMSIA </li></ul><ul><li>CHRONIC HYPERTENSION </li></ul><ul><li>GESTATIONAL HYPERTENSION </li></...
DEFINITION <ul><li>>  140/90 mmHg </li></ul><ul><li>mild & moderate  </li></ul><ul><li>(140-169/90-109) </li></ul><ul><li>...
DIFFERENTIAL DIAGNOSIS <ul><li>  Preeclapmsia   RD&CHT   GHT </li></ul><ul><li>Onset >  20 wk   < 20 wk  3 rd  trim </li><...
ACUTE RENAL FAILURE <ul><li>EARLY PREGNANCY </li></ul><ul><li>Prerenal  : hyperemesis gravidarum </li></ul><ul><li>ATN :  ...
  HELLP  acute fatty live HUS,TTP Onset > 20 wk      < 20 wk < 48 hr PPT      > 48 hr PPT Plt        Coag   DIC DIC  ...
ACUTE RENAL FAILURE <ul><li>RENAL CORTICAL NECROSIS </li></ul><ul><li>abruptio placenta, placenta previa, amniotic fluid e...
PREGNANCY    RENAL DIS. <ul><li>Cr < 1.5  :  same outcome </li></ul><ul><li>Cr > 1.5 </li></ul><ul><li>Renal failure :  ...
<ul><li>Azotemia </li></ul><ul><li>Pretermature 6 times </li></ul><ul><li>HYPERTENSION </li></ul><ul><li>fetal death, pret...
TERMINATION OF PREGNANCY <ul><li>Serum Cr > 1.4 or GFR < 70 ml/min </li></ul><ul><li>Uncontrolled HT </li></ul><ul><li>Sev...
TREATMENT <ul><li>Benefit ? : restrict activity, admission </li></ul><ul><li>AntiHT drugs in mild – moderate HT : </li></u...
ANTIHYPERTENSIVE <ul><li>Methy DOPA or labetalol   </li></ul><ul><li>Hydralazine     </li></ul><ul><li>Ca ch blocker   ...
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  • อธิบายเรื่อง ค่า Cr ที่ไม่เท่ากันในแต่ละคนขึ้นกับ Muscle Mass
  • อธิบายเรื่อง ค่า Cr ที่ไม่เท่ากันในแต่ละคนขึ้นกับ Muscle Mass
  • Tutorial national board 2010 Nephrology

    1. 1. Nephrology Review February 19, 2010
    2. 2. RENAL FUNCTION <ul><li>EXCRETORY </li></ul><ul><li>REGULATORY </li></ul><ul><li>ENDOCRINE & METABOLIC </li></ul>END PRODUCTS DRUGS TOXINS FLUID ELECTROLYTES OSMOLARITY ACID-BASE RENIN ERYTHROPOIETIN 1,25(OH) 2 VIT.D3 Briggs JP, Schnermann JB. Primer on KIDNEY DISEASES. 2nd ed. 1998
    3. 3. GFR <ul><li>Inulin clearance </li></ul><ul><li>Cr clearance : </li></ul><ul><li>UcrV/Pcr = 50 mg/dl × 1500 cc = cc/min </li></ul><ul><li> 1.2 mg/dl × 1440 </li></ul><ul><li>Radionucleide : iothalamate, chromium, DTPA </li></ul><ul><li>Renal blood flow : hippurate, MAG3 </li></ul>
    4. 4. Milutinovic et al. Kidney Int. 1975:8;185-190 inulin iothalamate (CCr+Curea)/2
    5. 5. Na + K + Cl -
    6. 6. Tubular function <ul><li>Absorption </li></ul><ul><li>Na + , Cl - , H 2 O, HCO 3 - , glucose, Ca 2+ , PO 4 , amino acid, uric acid, protein, urea </li></ul><ul><li>Secretion </li></ul><ul><li>H + , K + , NH 4 + , organic acid-base </li></ul><ul><li>Metabolism </li></ul><ul><li>drugs, hormones (insulin, calcitriol, EPO) </li></ul>
    7. 7. การที่มี BUN และ serum creatinine สูงเกินค่าปกติ (Normal Cr ชาย ≤ 1.5, หญิง ≤ 1.3 mg/dl) Azotemia
    8. 8. Uremia กลุ่มอาการที่เกิดจากความผิดปกติของการคั่งของของเสีย สารน้ำและเกลือแร่ที่เกิดคู่กับการเสื่อมหน้าที่ของไต - nausea, vomiting - anorexia - weight loss - dyspnea - fatigue - pruritus
    9. 9. Azotemia GFR ปกติ GFR ต่ำ Acute KI Chronic KD Intrinsic RF Post RF Pre RF Chronic GN Chronic TIN BUN Cr
    10. 10. Normal GFR <ul><li> BUN </li></ul><ul><li>Protein load </li></ul><ul><li>high protein diet </li></ul><ul><li>parenteral amino acid </li></ul><ul><li>GI bleed </li></ul><ul><li>hypercatabolism </li></ul><ul><li>BUN  > 30 </li></ul><ul><li>uric  > 2 </li></ul><ul><li>K  > 1 – 2 </li></ul><ul><li>PO 4  > 1 </li></ul><ul><li>Drugs : steroid, tetracycline </li></ul><ul><li> Cr </li></ul><ul><li>Muscle injury </li></ul><ul><li>trauma, rhabdomyolysis </li></ul><ul><li>Inhibit secretion </li></ul><ul><li>cimethidine, trimethoprim </li></ul><ul><li>Interfere assay </li></ul><ul><li>ketone, cefoxitin, methanol </li></ul>
    11. 11. Decrease GFR <ul><li>Normal BUN </li></ul><ul><li>Low protein diet </li></ul><ul><li>Advance chronic liver disease </li></ul><ul><li>Normal Cr </li></ul><ul><li>Low muscle mass </li></ul><ul><li>Advance chronic liver disease </li></ul>
    12. 12. Acute Renal Failure (ARF)  Acute Kidney Injury (AKI) <ul><li>Prerenal </li></ul><ul><li>Renal </li></ul><ul><li>Post renal </li></ul>
    13. 13. Definition of Acute kidney injury OR 2004 Level of dysfunciton Outcome
    14. 15. Acute Kidney Injury Within 48 hours  serum Cr > 0.3 mg/dL  serum Cr > 50% (1.5 fold) More than 6 hours  urine output < 0.5 ml/kg/hr Adequate fluid resuscitation
    15. 16. AKIN classification Baseline serum Cr (48 hr) urine output Stage 1 (R)  >0.3 mg/dL or  1.5-2 fold <0.5 mL/kg/hr >6 hr Stage 2 (I)  2-3 fold <0.5 mL/kg/hr >12 hr Stage 3 (F)  >3 fold or <0.3 mL/kg/hr >24 hr  >0.5 mg/dL if Cr > 4 mg/dL) anuria for 12 hr RRT No GFR criteria
    16. 18. Decreased circulatory volume Activation of central baroreceptors Norepinephrine Vasopressin Angiotensin II PGE2 / PGI2 Nitric oxide Autoregulation (MAP > 70) Vasoconstriction Mesangial contraction Reduced renal blood flow & GFR Prerenal
    17. 19. Renal causes <ul><li>ATN : ischemic, nephrotoxic </li></ul><ul><li>AIN : allergy (drugs-betalactam), tumor (lymphoma), infection, rejection </li></ul><ul><li>Vessels : renal artery or vein thrombosis </li></ul><ul><li>Microvascular : </li></ul><ul><li>HUS, TTP </li></ul><ul><li>RPGN </li></ul><ul><li>scleroderma </li></ul><ul><li>drugs (CSA, amphoB, radiocontrast) malignant HT pregnancy related hyperviscosity (MM) </li></ul>
    18. 20. Functional & Physiologic change Loss of cell polarity Loss Cell-cell, cell matrix interaction Tight junction defect ↑ Distal Na delivery Tubular obstruction Back leak Renal vasoconstriction ↓ GFR Tubuloglomerular feedback Brush border detachment
    19. 21. Pre-renal VS Renal <ul><li>Index Pre-renal Renal </li></ul><ul><li>Urine sp.gr. >1.018 < 1.012 </li></ul><ul><li>Urine Osm > 500 < 350 </li></ul><ul><li>BUN / Cr ratio > 20 < 10 </li></ul><ul><li>U Na (mEq/l) < 10 > 20 </li></ul><ul><li>FE Na (%) < 1 > 1 </li></ul><ul><li>RFI < 1 > 1 </li></ul><ul><li>U / P Cr > 40 < 20 </li></ul>= UNa  PCr  100 PNa  UCr FE Na (%) RFI
    20. 22. Na + K + Cl - Medullary ischemia Intermediate syndrome Urine Na low Urine spgr low
    21. 23. Risk of aminoglycosides nephrotoxic <ul><li>Dose frequency : once daily better </li></ul><ul><li>Cationic amino group (NH3 + ) : </li></ul><ul><li>neomycin - worst, streptomycin – least </li></ul><ul><li>Duration (>1 wk) </li></ul><ul><li>Renal ischemia, other nephrotoxic </li></ul><ul><li>Hypokalemia </li></ul><ul><li>Liver diseases </li></ul><ul><li>Earliest lesion : ↑ lysosomal myeloid bodies </li></ul>
    22. 24. Amphotericin B <ul><li>Renal vasoconstriction & tubular injury </li></ul><ul><li>Renal complication </li></ul><ul><li>distal RTA type I (back leak) </li></ul><ul><li>nephrogenic DI </li></ul><ul><li>hypomagnesemia </li></ul><ul><li>Dose & cumulative dose dependent </li></ul><ul><li>Rx : hydration, liposome? (phospholipid vesicles) </li></ul>
    23. 25. Cisplatin <ul><li>Tubular injury (low Cl, reactive hydroxyl radical) </li></ul><ul><li>Hypomagnesemia </li></ul><ul><li>Rx : hydration </li></ul><ul><li>Cyclosporin </li></ul><ul><li>Renal vasoconstriction </li></ul><ul><li>Hyperkalemia , met acidosis : Cl shunt </li></ul>
    24. 26. Radiocontrast nephropathy <ul><li>Azotemia within 48 hours after exposure </li></ul><ul><li>High risk : CKD (esp. DM ) with eGFR < 60 mL/min/1.73 m 2 , high contrast volume > 100 mL </li></ul><ul><li>Prevention </li></ul><ul><li>nonionic & isoosmolar contrast media </li></ul><ul><li>correct prerenal : effective volume </li></ul><ul><li>NSS 1-1.5 ml/kg/hr 3-12 hr before & 12-24 hr after contrast exposure </li></ul><ul><li> drug : N-acetyl cysteine before & after 24 hrs </li></ul>
    25. 27. Acute renal failure <ul><li>Prerenal : volume depletion, heart failure </li></ul><ul><li>Hx : volume loss, PND, CAD, orthopnea </li></ul><ul><li>PE : JVP, S3 gallop, crepitation </li></ul><ul><li>Renal : Drugs (ACEI, NSAID, radiocontrast, antibiotics) </li></ul><ul><ul><li> RAS : Hx – DM, age, hyperlipidemia, claudication, CAD, stroke </li></ul></ul><ul><ul><li> PE : peripheral pulse, abdominal bruit </li></ul></ul><ul><li>Postrenal : </li></ul><ul><li>common pathway : BPH, CA cervix </li></ul><ul><li>DM  neurogenic bladder </li></ul><ul><li>bilat ureteric obstruction </li></ul><ul><li>single kidney </li></ul><ul><li>Hx : dysuria, pass stone, hesitancy, urine flow&volume </li></ul><ul><li>PE : full bladder, bimanual palpation </li></ul>
    26. 28. Investigation <ul><li>U/S : obstruction, kidney size, </li></ul><ul><li>doppler, MRA – RAS, renogram (Cr > 3 – 4 can not be interpreted) </li></ul><ul><li>Electrolyte acid base, Ca, P </li></ul><ul><li>Glom dis : urine sediments, UPCR, 24h urine proteins, serum albumin, lipid </li></ul><ul><li>Underlying Dis and complication ! </li></ul>
    27. 29. Management <ul><li>Rx causes </li></ul><ul><li>Stop harmful drugs </li></ul><ul><li>Nutrition </li></ul><ul><li>Volume status & urine output </li></ul><ul><li>Electrolytes </li></ul><ul><li>Acid base </li></ul><ul><li>Dialysis </li></ul>
    28. 32. CAUSES OF ANEMIA IN CRF <ul><li>↓ Erythropoietin production </li></ul><ul><li>↓ Erythrocyte survival </li></ul><ul><li>Marrow inhibitors </li></ul><ul><li>Malnutrition </li></ul><ul><li>Blood loss </li></ul>Schrier RW, Gottschalk CW. Diseases of the kidney. 6th ed. Vol.III, 1996. Fe , Folate , B1, B6, B12 Mild hemolysis : ↓ Na-K-ATPase activity sensitive to oxidants , dialysis Factors?, PTH, Al
    29. 33. RENAL OSTEODYSTROPHY <ul><li>High turnover </li></ul><ul><li>Hyperparathyroidism </li></ul><ul><li>Low turnover </li></ul><ul><li>Osteomalacia </li></ul><ul><li>Adynamic bone </li></ul><ul><li>Mixed </li></ul>Hypocalcemia Hyperphosphatemia Low vitamin D Bone resistance
    30. 34. Comprehensive strategy <ul><li>Intervention Goal </li></ul><ul><li>ACEI or ARB or Both proteinuria < 0.5 g/d </li></ul><ul><li>↓ GFR < 2 mL/min/y </li></ul><ul><li>Blood pressure <130/80 proteinuria < 1g/d </li></ul><ul><li><125/75 proteinuria > 1g/d </li></ul><ul><li>Dietary protein restriction 0.6 – 0.8 g/kg/d </li></ul><ul><li>Glycemic control in DM HbA1c < 7.0% </li></ul><ul><li>Lipid lowering Rx LDL < 100 mg/dL </li></ul><ul><li>EPO Rx Hb > 11-12 g/dL </li></ul><ul><li>Na restriction 3 – 5 g/d </li></ul><ul><li>Ca × P product 55 </li></ul><ul><li>iPTH 150-300 </li></ul><ul><li>Smoking cessation, weight control, avoid nephrotoxins </li></ul>Med Clin N Am 89 (2005) 489–509
    31. 35. RENAL Na + REABSORPTION HCO 3 - HCO 3 - + H 2 O+CO 2 CA H + +HCO 3 - CA Na + glucose PO 4 AA Carbonic anhydrase inhibitor H + Na + 3 HCO 3 - Na + 3Na + 2K + 3Na + 2K + 3HCO 3 - Na +
    32. 36. TAL of Henle Loop diuretics
    33. 37. DISTAL TUBULE Thiazide
    34. 38. CORTICAL COLLECTING TUBULE Na + K + H + spironolactone Amiloride
    35. 39. POLYURIA
    36. 40. DEFINITION <ul><li>Urine volume </li></ul><ul><li>> 3 L/day, </li></ul><ul><li>> 2 cc/min, </li></ul><ul><li>> 30 cc/kg/day </li></ul><ul><li>Inappropriate urine output </li></ul>
    37. 41. What is urine? <ul><li>Clearance of H 2 O + Clearance of solute </li></ul><ul><li>(CH 2 O + Csolute) </li></ul>
    38. 42.  GFR  salt excretion  H 2 O excretion
    39. 43. Polyuria <ul><li> CH 2 O  water diuresis </li></ul><ul><li>Diabetes insipidus : </li></ul><ul><li>central or nephrogenic </li></ul><ul><li>Polydipsia </li></ul><ul><li> Csolute  solute diuresis </li></ul><ul><li>salt losing </li></ul><ul><li> salt loading (intake or GFR) </li></ul>
    40. 44. Central DI <ul><li>Sudden onset </li></ul><ul><li>Trauma, pituitary surgery, tumor, hypoxic encephalopathy </li></ul><ul><li>50%  idiopathic </li></ul>
    41. 45. Nephrogenic DI <ul><li>Abnormality of V2 receptor, aquaporin 2, medullary hypertonicity </li></ul><ul><li>Reduce maximal conscentrating ability : common (elderly, renal diseases)  can not produce polyuria </li></ul><ul><li>True polyuria </li></ul><ul><li>X-linked (V2 receptor) </li></ul><ul><li>Li (20%) </li></ul><ul><li>hypercalcemia </li></ul><ul><li>Hypokalemia, amyloidosis, Sjogren </li></ul>
    42. 46. Water reabsorption V2 Medullary Hypertonicity
    43. 47. Approach <ul><li>History </li></ul><ul><li>Nocturia : DI </li></ul><ul><li>Psychogenic disorders : polydipsia </li></ul><ul><li>Onset : acute – central DI </li></ul><ul><li>ATN : diuretic phase, postobstructive </li></ul><ul><li>IV load : solute diuresis </li></ul><ul><li>Drugs : Li–NDI, diuretics, dopamine – solute diuresis </li></ul><ul><li>Pregnancy :  GFR, DI </li></ul><ul><li>Intracranial lesion : surgery, pituitary-DI; </li></ul><ul><li> SAH-cerebral salt losing </li></ul><ul><li>Thirst : cool water – central DI </li></ul>
    44. 48. Approach <ul><li>Physical examination : </li></ul><ul><li>ECF depletion : salt losing </li></ul><ul><li>CNS lesion : bitemporal hemianopia </li></ul><ul><li> subarachnoid hemorrhage </li></ul>
    45. 49. Approach <ul><li>Hx : brain lesion, drugs, electrolytes, intake, ATN </li></ul><ul><li>Volume status </li></ul><ul><li>Lab : </li></ul><ul><li>serum Na + </li></ul><ul><li>low  polydipsia </li></ul><ul><li>high  DI </li></ul><ul><li>urine osmolality </li></ul><ul><li>< 150 :  CH 2 O </li></ul><ul><li>> 300 :  Csolute </li></ul><ul><li>150 – 300 : mixed </li></ul>
    46. 50. CAUSES <ul><li>1 patient : > 1 lesions </li></ul><ul><li>  CH 2 O </li></ul><ul><li> Csolute </li></ul><ul><li> CH 2 O +  Csolute </li></ul><ul><li> CH 2 O +  Csolute </li></ul><ul><li> CH 2 O +  Csolute </li></ul>
    47. 51. Water diuresis <ul><li>DI </li></ul><ul><li>central </li></ul><ul><li>nephrogenic </li></ul><ul><li>gestational DI </li></ul><ul><li>Primary polydipsia </li></ul>
    48. 52. Gestational DI <ul><li>Vasopressinase from placenta </li></ul><ul><li>(cystine aminopeptidase) </li></ul><ul><li>Resist to AVP </li></ul><ul><li>Respond to dDAVP </li></ul>
    49. 53. Primary polydipsia <ul><li>Anxious, middle-aged women </li></ul><ul><li>Psychiatric illness, phenothiazine </li></ul><ul><li>(dry mouth) </li></ul><ul><li>Hypothalamic lesion (thirst center, dipsogenic DI) : infiltrative lesion (granoloma) </li></ul><ul><li>Serum Na < 137 </li></ul>
    50. 54. Water deprivation test <ul><li>ADH stimulation </li></ul><ul><li>ADH response </li></ul><ul><li>(5 u of aq vasopressin SC </li></ul><ul><li>or 10 ug of dDAVP nasal insufflation) </li></ul>
    51. 55. ADH stimulation Central Nephrogenic Partial Complete
    52. 56. Water Deprivation Test <ul><li>Urine vol, urine osmolality, BW q 1 hr </li></ul><ul><li>Plasma osmolality and Na q 2 hr </li></ul><ul><li>End point : </li></ul><ul><li>serum osmolality > 295 mOsm/kg </li></ul><ul><li> urine osmolality < 30 mOsm/kg 2 times </li></ul><ul><li>body weight 3 – 5% </li></ul>
    53. 58. Solute diuresis <ul><li>Electrolytes </li></ul><ul><li>Diuretics : furosemide, dopamine </li></ul><ul><li>Diuretic ATN, </li></ul><ul><li>postobstructive </li></ul><ul><li>Solute load : </li></ul><ul><li>↑ GFR – pregnancy </li></ul><ul><li>↑ intake parenteral </li></ul><ul><li>cerebral salt wasting (subarachnoid hemorrhage) </li></ul><ul><li>Salt losing  NO! </li></ul><ul><li>Non-electrolytes </li></ul><ul><li>Mannitol </li></ul><ul><li>Hyperglycemia </li></ul><ul><li>Urea </li></ul>
    54. 59. Solute diuresis <ul><li>Electrolytes </li></ul><ul><li>2(U[Na+K]) > 0.6 </li></ul><ul><li> Uosm </li></ul><ul><li>Nonelectrolytes </li></ul><ul><li>Urea </li></ul><ul><li>Glucose </li></ul><ul><li>mannitol </li></ul>} > 250 mmol/L
    55. 60. Fluid therapy
    56. 61. hypotonic isotonic colloid ICF 2/3 ECF 1/3 II 3/4 IV 1/4 TBW - male : 60%BW, Female 50%BW Elder - male : 50%BW, Female 45%BW Children : 60%BW
    57. 62. HYPERTONIC SALINE <ul><li>↑ Intravascular volume > volume infused </li></ul><ul><li>(prehospital use !) </li></ul><ul><li>↓ endothelial cell swelling </li></ul><ul><li>↑ cardiac output </li></ul><ul><li>↓ peripheral vascular resistance </li></ul>! Benefit in head injured patients ! Arch Surg 1993;128
    58. 63. Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001319. DOI: 10.1002/14651858.CD001319.pub2. There is no evidence that one colloid solution is more effective or safe than any others (albumin, PPF, dextran, HES, gelatin) There is no evidence from RCTs that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids,in patients with trauma, burns or following surgery. Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD000567. DOI: 10.1002/14651858.CD000567.pub3.
    59. 64. Fluid therapy <ul><li>Side effects : coagulopathy (dextran) </li></ul><ul><li> anaphylaxis (gelatin) </li></ul><ul><li>Goals : ↑ O 2 delivery & microcirculation </li></ul><ul><li>Hb 7 - 9 g/dl </li></ul><ul><li>Monitoring : clinical , CVP, PCWP, echocardiography, gastric tonometry, laser doppler flowmetry </li></ul>
    60. 65. SUMMARY <ul><li>Control loss or bleeding </li></ul><ul><li>Prehospital hypertonic fluid therapy benefit in head injury </li></ul><ul><li>Colloids are not better than crystalloids. </li></ul><ul><li>Human albumin is not better than synthetic colloids </li></ul><ul><li>Fluid warming </li></ul>
    61. 66. Water balance
    62. 67. Hyponatremia <ul><li>Water retention + Na loss </li></ul><ul><li>Why water is retained? </li></ul><ul><li>severe impair GFR? </li></ul><ul><li>low solute excretion? </li></ul><ul><li>ADH effect? </li></ul><ul><li>volume depletion </li></ul><ul><li>SIADH (CNS, lung, drugs, malignancy) </li></ul><ul><li>severe stress, pain </li></ul><ul><li>hypothyroidism, adrenal insuff </li></ul>No corrected formula for any serum glucose level
    63. 68. Management hyponatremia <ul><li>Acute or chronic : symptoms </li></ul><ul><li>Chronic or mild : 8 – 12 mEq/day </li></ul><ul><li>Acute or severe : </li></ul><ul><li>convulsion, coma, brain herniation </li></ul><ul><li>2 mEq/hr 2 – 3 hr </li></ul><ul><li>Complication of Rx </li></ul><ul><li>Central pontine myelinolysis or </li></ul><ul><li>osmotic demyelination syndrome </li></ul>
    64. 72. Potassium
    65. 73. K BALANCE <ul><li>Intake : 40 – 120 mEq/day </li></ul><ul><li>Distribution : </li></ul><ul><li>intracellular anabolism : glucose, insulin, folic, B12 </li></ul><ul><li>cell membrane factor : Na +- K +- ATPase, insulin, adrenergic receptor (  -out,  2- in) </li></ul><ul><li>extracellular factor : acidosis-out, alkalosis-in </li></ul><ul><li>GI : secretion - upper 5 – 15 mEq/L </li></ul><ul><li> lower 90 mEq/L </li></ul><ul><li>Renal excretion </li></ul><ul><li>K depletion  renal K ~ 5-25 mEq/day </li></ul>
    66. 74. 50 – 55 mEq/kg 3,000 – 4,000 mEq 65 mEq (2%) Red cell 250 mEq Muscle 2,635 mEq Liver 250 mEq Bone 300 mEq ICF ECF II IV K 160mEq/l K 4mEq/l 5-10 mEq 5-10 mEq 50-100 mEq 90-95 mEq
    67. 76. 100% 25% 10% 25% 20% <ul><li>Flow </li></ul><ul><li>Aldosterone </li></ul><ul><li>serum K + </li></ul>
    68. 77. HYPOKALEMIA
    69. 78. DEFINITION <ul><li>Serum K + < 3.5 mEq/L </li></ul>
    70. 79. DIAGNOSIS <ul><li>CLINICAL SIGNS & SYMPTOMS (rate of  ) </li></ul><ul><li>proximal muscle weakness </li></ul><ul><li>arrhythmia </li></ul><ul><li>SERUM K + < 3.5 mEq/L </li></ul><ul><li>Exclude : spurious hypokalemia </li></ul><ul><li>WC > 100,000/mm 3 </li></ul>
    71. 80. SIGNS & SYMPTOMS <ul><li>CARDIAC CONDUCTION DEFECTS </li></ul><ul><li>ISCHEMIA </li></ul><ul><li>HEART FAILURE </li></ul><ul><li>LVH </li></ul><ul><li>DIGITALIS </li></ul>
    72. 81. ST depress, Peak P, PR prolong Widening QRS
    73. 82. CAUSES <ul><li>Decrease intake </li></ul><ul><li>Shift </li></ul><ul><li>Extrarenal loss </li></ul><ul><li>Renal loss </li></ul>
    74. 83. Hypokalemia [acid-base, ECF volume, hypertension, urine K + ] Metabolic acidosis urine K + low high (urine Na+ > 100 mEq/day) <ul><li>Lower GI loss </li></ul><ul><li>diarrhea </li></ul><ul><li>laxative abuse </li></ul><ul><li>villous adenoma </li></ul><ul><li>Renal loss </li></ul><ul><li>RTA </li></ul><ul><li>DKA </li></ul><ul><li>acetazolamide </li></ul>Metabolic alkalosis urine K + low high (urine Na + > 100 mEq/day) <ul><li>loss gastric secretion (late) </li></ul><ul><li>(urine pH<5.5, low urine Cl - ) </li></ul><ul><li>remote diuretic use </li></ul><ul><li>(thiazide, loop diuretics) </li></ul><ul><li>laxative abuse </li></ul><ul><li>loss gastric secretion (early) </li></ul><ul><li>(urine pH>7, low urine Cl - ) </li></ul><ul><li>recent diuretic use </li></ul><ul><li>(thiazide, loop diuretics) </li></ul><ul><li>Bartter’s syndrome </li></ul><ul><li>Gitelman’s syndrome </li></ul><ul><li>Mg 2+ depletion </li></ul>normotension hypertension <ul><li>mineralocorticoid </li></ul><ul><li>excess or effects </li></ul>Normal acid-base <ul><li>Intracellular shift </li></ul><ul><li>insulin </li></ul><ul><li>β -agonist </li></ul><ul><li>↑ extracellular pH </li></ul><ul><li>thyrotoxicosis </li></ul><ul><li>periodic paralysis </li></ul><ul><li>↑ cell production </li></ul><ul><li>intoxication </li></ul><ul><li>other drugs (see text) </li></ul>Urine pH < 5.5  diarrhea > 5.5  urine net charge -ve  diarrhea +ve  RTA
    75. 84. Hypokalemia, Hypertension, Metabolic alkalosis, renal K + loss (screening test) [plasma renin activity (PRAng/ml/hr), plasma aldosterone concentration (PAC,ng/dl)] ↑ PRA ↓ PRA (<1) ↓ PRA ↑ PAC ↑ PAC ( > 9) ↓ PAC PAC/PRA ~10 > 50 24 hr urine aldosterone >14  g < 20 exclude <ul><li>Secondary hyperaldosteronism </li></ul><ul><li>renovascular hypertension </li></ul><ul><li>diuretic use </li></ul><ul><li>renin producing tumor </li></ul><ul><li>malignant hypertension </li></ul><ul><li>coarctation of the aorta </li></ul><ul><li>Primary hyperaldosteronism </li></ul><ul><li>GRA </li></ul><ul><li>Mineralocorticoid-like effects </li></ul><ul><li>exogenous (licorice, see text) </li></ul><ul><li>congenital adrenal hyperplasia </li></ul><ul><li>DOC-producing tumor </li></ul><ul><li>cushing’s syndrome </li></ul><ul><li>11-HSD deficiency </li></ul><ul><li>altered aldosterone metabolism </li></ul><ul><li>Liddle’s syndrome </li></ul><ul><li>Confirmatory test </li></ul><ul><li>NaCl loading test </li></ul><ul><li>Fludrocortisone suppression </li></ul><ul><li>test </li></ul>
    76. 85. Algorithm <ul><li>History : diarrhea, </li></ul><ul><li>diuretic uses, vomiting, drugs </li></ul><ul><li>ECF volume : JVP </li></ul><ul><li>Blood pressure : hypertension or orthostatic hypotension </li></ul><ul><li>24 hr urine K or TTKG </li></ul>
    77. 86. TTKG <ul><li>Urine Osm CCT = Urine K + CCT </li></ul><ul><li>Urine Osm Urine K + </li></ul><ul><li>TTKG = Urine K + CCT </li></ul><ul><li>plasma K + </li></ul><ul><li>= Urine K +  plasma Osm </li></ul><ul><li>plasma K +  urine Osm </li></ul><ul><li>K + depletion : TTKG < 2 </li></ul><ul><li>Hyperkalemia : TTKG > 9 </li></ul>
    78. 87. Treatment <ul><li>Evaluation : EKG and weakness </li></ul><ul><li>Emergency : arrhythmia, respiratory failure, paralysis </li></ul><ul><li>IV KCl (1 cc : K + and Cl - 2 mEq) </li></ul><ul><li> 40 – 60 mEq/ IV 1 L without glucose </li></ul><ul><li>rate <10 – 20 mEq/hr </li></ul><ul><li>40 – 60 mEq/day </li></ul><ul><li>Oral : KCl (general) > Kcitrate (RTA) </li></ul><ul><li>Check serum K + q 60 mEq iv replacement </li></ul><ul><li>Causes : Mg 2+ depletion </li></ul>+
    79. 88. Treatment <ul><li>IV K + </li></ul><ul><li>15%KCl (1cc = K + 2 mEq) , </li></ul><ul><li>8.7%K 2 HPO 4 (1cc = K + 1 mEq) </li></ul><ul><li>Oral K + </li></ul><ul><li>KCl : elixir (15 cc  20 mEq) </li></ul><ul><li> tablet (wax matrix, microencapsulated) </li></ul><ul><li>Kcitrate (15 cc  10 mEq) </li></ul>
    80. 89. HYPERKALEMIA
    81. 90. DIAGNOSIS <ul><li>CLINICAL SIGNS & SYMPTOMS </li></ul><ul><li>proximal muscle weakness </li></ul><ul><li>arrhythmia </li></ul><ul><li>SERUM K + > 5.0 mEq/L </li></ul><ul><li>Exclude : spurious hyperkalemia </li></ul><ul><li>WC > 100,000/mm 3 </li></ul><ul><li>Plt > 1,000,000/mm 3 </li></ul><ul><li>Hemolysis </li></ul><ul><li>Clenching </li></ul>
    82. 91. Flat P Prolong PR AV block Widening QRS Sine-wave
    83. 92. CAUSES <ul><li>K + load </li></ul><ul><li>Shift </li></ul><ul><li>Decrease renal K + excretion </li></ul><ul><li>Decrease distal flow </li></ul><ul><li>Decrease aldosterone effect </li></ul><ul><li>Cell defect </li></ul>
    84. 93. DIAGNOSIS <ul><li>Rule out factitious hyperkalemia </li></ul><ul><li>K + load </li></ul><ul><li>Cause of shift </li></ul><ul><li>Decrease renal K + excretion </li></ul><ul><li>advanced renal failure </li></ul><ul><li>decrease aldosterone effect : drugs </li></ul>
    85. 94. TREATMENT <ul><li>Emergency </li></ul><ul><li>Abnormal EKG </li></ul><ul><li>Serum K + > 6.5 (or acute > 6.0) </li></ul><ul><li>Severe paralysis, respiratory failure </li></ul><ul><li>EKG monitoring </li></ul>
    86. 95. TREATMENT <ul><li>SPECIFIC </li></ul><ul><li>ADJUNCTIVE </li></ul><ul><li>CAUSE </li></ul><ul><li>PREVENTION </li></ul>
    87. 96. SPECIFIC TREATMENT <ul><li>Antagonize membrane effect </li></ul><ul><li>Decrease K + level </li></ul><ul><li>Remove K + from the body </li></ul>
    88. 98. Intracellular K + shift <ul><li>Insulin : most effective and reliable </li></ul><ul><li>Beta2 agonist : modest, tachycardia (IV) </li></ul><ul><li>HCO 3 - : ineffective in advanced renal failure, use in metabolic acidosis cases </li></ul>
    89. 99. Remove K + <ul><li>Hemodialysis : most rapid </li></ul><ul><li>Anion exchange resin + laxative </li></ul><ul><li>Kayexalate : Na polystylene sulfonate </li></ul><ul><li>0.6 – 0.7 mEq K + /1 g resin </li></ul><ul><li>15 g + 70%sorbitol 50 ml q 6 hr </li></ul><ul><li>Complication </li></ul><ul><li>intestinal necrosis </li></ul><ul><li>Na + overload </li></ul>
    90. 100. TREATMENT mechanism onset peak Ca antagonist 1-5 min HD remove 15 min PD remove 2 h Kay exalate remove 1-6 h NaHCO 3 shift unreliable Insulin shift 1 0 - 2 0 min 1-2 h B2 agonist shift 1 0 - 20 min 1-2 h
    91. 101. ADJUNCTIVE TREATMENT <ul><li>Restrict K + 2 g/day </li></ul><ul><li>Stop risk factors </li></ul><ul><li>Diuretics : increase ECF </li></ul><ul><li>Fludrocortisone : decrease ICF </li></ul><ul><li>Long term kayexalate with meal </li></ul><ul><li>Avoid fasting without glucose </li></ul>
    92. 102. Acid-Base Disorders
    93. 103. DEFINITION <ul><li>Acidemia --- Euphemia --- Alkalemia </li></ul><ul><li>(-emia  pH of blood) </li></ul><ul><li>Acidosis  Alkalosis OR Mixed </li></ul><ul><li>(-osis : pathologic process causing acid or alkali accumulation) </li></ul><ul><li>Metabolic OR Respiratory OR Mixed </li></ul>Clinical & Arterial blood gas
    94. 104. PCO 2 H + , HCO 3 - HCO 3 - /CO 2 Albumin Bone Proteins PO 4 Buffers
    95. 106. REMEMBER <ul><li>Metabolic Acidosis/Alkalosis = </li></ul><ul><li>disturbances of blood bicarbonate </li></ul><ul><li>Respiratory Acidosis/Alkalosis = </li></ul><ul><li>disturbances of PaCO 2 </li></ul>PCO 2 H + , HCO 3 -
    96. 107. Normal meat-based Diet <ul><li>Carbohydrate and fat metabolism will generate 20,000 mEq of acid/day in the form of CO 2 excreted by the lungs </li></ul><ul><li>Protein catabolism produces 1 mEq/kg (50-60 mEq/day) of inorganic acids (like sulfuric, phosphoric, or hydrochloric acids) which must be excreted by the kidney </li></ul>
    97. 108. KIDNEYS <ul><li>Regulate acid-base by the following mechanisms: </li></ul><ul><li>Reabsorption of filtered HCO 3 ¯ </li></ul><ul><li>Formation of titrable acid </li></ul><ul><li>Excretion of NH 4 + in the urine </li></ul>
    98. 109. COMPENSATORY RESPONSE [ACIDOSIS] <ul><li>Respiratory acidosis </li></ul><ul><li>acute : ↑ PCO 2 10 mmHg  ↑ HCO 3 - 1 mmol/L </li></ul><ul><li>chronic : ↑ PCO 2 10 mmHg  ↑ HCO 3 - 4 mmol/L </li></ul><ul><li>( kidney 3 – 5 days, HCO 3 - > 15 mmol/L ) </li></ul><ul><li>Metabolic acidosis (1hr  12 – 24 hr) </li></ul><ul><li>PCO 2 = 1.5  [HCO 3 - ] + 8 + 2 mmHg </li></ul><ul><li>∆ PCO 2 = 1.2∆[HCO 3 - ] </li></ul>
    99. 110. COMPENSATORY RESPONSE [ALKALOSIS] <ul><li>Respiratory alkalosis </li></ul><ul><li>acute : ↓ PCO 2 10 mmHg  ↓ HCO 3 - 2 mmol/L </li></ul><ul><li>chronic : ↓ PCO 2 10 mmHg  ↓ HCO 3 - 5 mmol/L </li></ul><ul><li>Metabolic alkalosis </li></ul><ul><li>∆ PCO 2 = 0.7∆[HCO 3 - ] </li></ul>
    100. 112. ASSESSMENT OF ACID-BASE DISORDER <ul><li>Clinical (history & physical exam) </li></ul><ul><li>correct diagnosis </li></ul><ul><li>Extracellular </li></ul><ul><li>acute or chronic (pH out of normal range?), </li></ul><ul><li>primary problem (metabolic or respiratory) </li></ul><ul><li>pH  PCO 2 , HCO 3 - </li></ul><ul><li>Compensation </li></ul><ul><li>mixed acid-base disorder ?? </li></ul>
    101. 113. Hypoventilation
    102. 114. Hyperventilation
    103. 115. Causes of metabolic acidosis
    104. 116. H + X - -> H + X - -> CO 2 + NaX -> Kidney -> + HCO 3 <ul><li>↑ H + PRODUCTION </li></ul><ul><li>lactic acidosis </li></ul><ul><li>ketoacidosis </li></ul><ul><li>toxic substances </li></ul><ul><li>renal failure </li></ul><ul><li>HCO 3 - loss </li></ul><ul><li>diarrhea </li></ul><ul><li>proximal RTA </li></ul><ul><li>↓ RENAL H + EXCRETION </li></ul><ul><li>(HCO3 regeneration) </li></ul><ul><li>renal failure </li></ul><ul><li>distal RTA </li></ul>H + : TA, NH 4 + NaX
    105. 117. <ul><li>Measured ⊕ + Unmeasured ⊕ = Measured ⊖ + Unmeasured ⊖ </li></ul><ul><li>Measured ⊕ - Measured ⊖ = Unmeasured ⊖ - Unmeasured ⊕ </li></ul><ul><li>(Na + ) – (Cl- + HCO 3 - ) = Unmeasured ⊖ - Unmeasured ⊕ </li></ul>SERUM ANION GAP ( Albumin , phosphate, sulphate, organic anion) – (K + , Mg 2+ , Ca 2+ ) = 12 HA  H + + A - 1 g/dL = 2.5 - 3 mEq/L
    106. 118. H + X - -> H + X - -> CO 2 + NaX -> Kidney -> H + X - + Na HCO 3 <ul><li>↑ H + PRODUCTION </li></ul><ul><li>lactic acidosis </li></ul><ul><li>ketoacidosis </li></ul><ul><li>toxic substances </li></ul><ul><li>renal failure </li></ul><ul><li>HCO3- loss </li></ul><ul><li>diarrhea </li></ul><ul><li>proximal RTA </li></ul><ul><li>↓ RENAL H + EXCRETION </li></ul><ul><li>renal failure </li></ul><ul><li>distal RTA </li></ul>Wide anion gap Normal anion gap
    107. 119. H + X - -> H + X - -> CO 2 + NaX -> Kidney -> H + X - + Na HCO 3 <ul><li>↑ H + PRODUCTION </li></ul><ul><li>lactic acidosis </li></ul><ul><li>ketoacidosis </li></ul><ul><li>toxic substances </li></ul><ul><li>renal failure </li></ul><ul><li>HCO3- loss </li></ul><ul><li>diarrhea </li></ul><ul><li>proximal RTA </li></ul><ul><li>↓ RENAL H + EXCRETION </li></ul><ul><li>renal failure </li></ul><ul><li>distal RTA </li></ul>Wide anion gap Normal anion gap Poor tissue perfusion  serum lactate > 5 mmol/l DKA, alcolhol  serum ketone Methanol, ethylene glycol  serum osmolol gap > 25 Urine NH 4 +  urine net charge (Na + + K + ) - Cl -
    108. 120. Mixed wide & normal gap acidosis <ul><li>Wide anion gap </li></ul><ul><li>↑ anion gap = ↓HCO 3 - </li></ul><ul><li>∆ anion gap/∆HCO 3 - = 1 </li></ul><ul><li>∆ anion gap/∆HCO 3 - < 1 </li></ul><ul><li>mixed normal and wide anion gap </li></ul>
    109. 121. TREATMENT <ul><li>CAUSES </li></ul><ul><li>ALKALI THERAPY </li></ul><ul><li>chronic loss : RTA </li></ul><ul><li>pH < 7.15 </li></ul><ul><li>Bicarbonate deficit (mEq) = </li></ul><ul><li>LBWx0.5x(Desired HCO 3 ¯ –actual HCO 3 ¯ ) </li></ul>
    110. 122. CAUSES OF METABOLIC ALKALOSIS (Generation) <ul><li>H + LOSS </li></ul><ul><li>GI (gastric content) : </li></ul><ul><li>vomiting, gastric outlet obstruction </li></ul><ul><li>Diuretics </li></ul><ul><li>kidney (aldosterone) </li></ul><ul><li>hyperaldosteronism </li></ul><ul><li>Intracellular shift (hypokalemia) </li></ul><ul><li>HCO 3 - gain </li></ul><ul><li>intake, bone apatite </li></ul><ul><li>CONTRACTION ALKALOSIS </li></ul><ul><li>ECF volume contraction </li></ul>
    111. 123. Renal HCO 3 - reabsorption Serum HCO 3 - (mEq/l) HCO 3 - reabsorption 25 50 Volume depletion K + depletion
    112. 124. Assessment <ul><li>Blood pressure : </li></ul><ul><li>hypertension  aldosteronism </li></ul><ul><li>Volume status : ECF volume loss </li></ul><ul><li>H + , GI loss, Diuretics </li></ul><ul><li>Lab : Urine Cl - (not urine Na + ) : </li></ul><ul><li>ECF volume status </li></ul>
    113. 125. CAUSES OF METABOLIC ALKALOSIS (Generation) <ul><li>H + LOSS </li></ul><ul><li>GI (gastric content) : </li></ul><ul><li>vomiting, gastric outlet obstruction </li></ul><ul><li>Diuretics </li></ul><ul><li>kidney (aldosterone) </li></ul><ul><li>hyperaldosteronism </li></ul><ul><li>Intracellular shift (hypokalemia) </li></ul><ul><li>HCO 3 - gain </li></ul><ul><li>intake, bone apatite </li></ul><ul><li>CONTRACTION ALKALOSIS </li></ul><ul><li>ECF volume contraction </li></ul>Volume depletion, ↓ urine Cl - Hypertension, ↑ urine Cl - Volume depletion, ↓ urine Cl -
    114. 126. CAUSES OF METABOLIC ALKALOSIS <ul><li>Generation factors </li></ul><ul><li>Maintenance factor </li></ul><ul><li>ECF volume (Cl - ) depletion </li></ul><ul><li>hypokalemia </li></ul>Treatment
    115. 127. TREATMENT <ul><li>CAUSES (generation factors) </li></ul><ul><li>Maintenance factors </li></ul><ul><ul><ul><li>Cl - depletion </li></ul></ul></ul><ul><ul><ul><li>K + depletion </li></ul></ul></ul>
    116. 128. Approach to Patients with Glomerular Diseases Suchai Sritippayawan Division of Nephrology , Internal Medicine, Siriraj Hospital, Mahidol University
    117. 129. Structure
    118. 130. pore fenestration charge Slit pore
    119. 131. Pathogenesis
    120. 132. JOURNAL OF NEPHROLOGY Vol . 11 No . 4 - 1998 / 177-182
    121. 134. Structure Proliferation Expansion Endocap-proliferation Thinkening : spike, double contour Necrosis Leucocytic infiltration Extracap-proliferation (crescent) vasculitis
    122. 135. Mesangial : IgMN, IgAN, lupus Subepithelial : membranous Subendothelial : lupus Intra GBM : lupus, MPGN I
    123. 136. Brenner : Brenner and Rector's The Kidney, 8th ed. Copyright © 2007 Saunders, An Imprint of Elsevier
    124. 137. Clinical features <ul><li>Proteinuria </li></ul><ul><li> GFR </li></ul><ul><li>Nephritis </li></ul><ul><li>Edema </li></ul><ul><li>Hypertension </li></ul><ul><li>Foamy urine </li></ul><ul><li>Hematuria </li></ul><ul><li>Lipiduria </li></ul><ul><li>Oliguria </li></ul><ul><li>Kidney failure </li></ul>
    125. 138. Clinical syndromes <ul><li>Asymptomatic : hematuria, proteinuria </li></ul><ul><li>Nephrotic </li></ul><ul><li>Nephritis </li></ul><ul><li>Nephrotic-nephritic </li></ul><ul><li>Rapidly progressive glomerulonephritis (RPGN) </li></ul><ul><li>Chronic kidney failure </li></ul>
    126. 139. Asymtomatic hematuria <ul><li>RC > 3/HD, glomerular RC </li></ul><ul><li>No nephrotic, nephritic, HT, edema, azotemia, oliguria </li></ul><ul><li>If no proteinuria (< 2 g/day)  </li></ul><ul><li><10% from glomerular disease </li></ul><ul><li>Proteinuria < 1 g, serum Cr < 1.5 mg/dL  IgA or thin BM nephropathy </li></ul>
    127. 140. >70% of RC are glomerular RC Proteinuria > 1 g/day or 2+ Indetermine 30–70% Nonglom. <30% acanthocyte ring
    128. 141. Proteinuria <ul><li>Normal : < 200 mg/day of total protein </li></ul><ul><li>Microalbuminuria : 30 – 300 mg/day </li></ul><ul><li>Overt proteinuria : > 300 mg/day </li></ul><ul><li>Albustix : 20 – 300 mg/dL  abuminuria </li></ul><ul><li>turbidometry  total protein </li></ul><ul><li>if –ve albustix but +ve turbidometry </li></ul><ul><li> low MW proteinuria </li></ul><ul><li>Urine protein or albumin/Cr ratio (UPCR) </li></ul><ul><li> 24 h urine protein </li></ul>
    129. 142. Types of proteinuria (pathophysiology) <ul><li>Glomerular : glomerulonephritis </li></ul><ul><li>Tubular : tubulointerstitial dis, drugs, toxin </li></ul><ul><li>Overflow :  protein production (MM) </li></ul><ul><li>Tissue : urinary tract inflammation, tumor </li></ul>
    130. 143. Asymptomatic proteinuria <ul><li>Transient or orthostatic proteinuria  good prognosis </li></ul><ul><li>diagnosis : separate urine collection </li></ul><ul><li>Persistent proteinuria </li></ul><ul><li>if no underlying dis and active urine sediment or azotemia  yearly follow up (proteinuria, BP and kidney function) </li></ul>
    131. 144. Nephrotic syndrome <ul><li>Proteinuria > 3 g/1.73 m 2 /day </li></ul><ul><li>Edema </li></ul><ul><li>Hypoalbuminemia </li></ul><ul><li>Hyperlipidemia & lipiduria </li></ul><ul><li>Hypertension </li></ul><ul><li>Kidney failure </li></ul><ul><li>Complications </li></ul><ul><li>Thromboembolism </li></ul><ul><li>Hyperlipidemia & Atherosclerosis </li></ul><ul><li>Infections </li></ul><ul><li>Malnutrition </li></ul>
    132. 146. Nephrotic syndrome <ul><li>Most common : </li></ul><ul><li>1 o  IgMN, MCD, membranous GN </li></ul><ul><li>2 o  DM, amyloidosis </li></ul>
    133. 148. Nephritic syndrome <ul><li>Hematuria : </li></ul><ul><li>microscopic hematuria </li></ul><ul><li>macroscopic : IgAN </li></ul><ul><li> Postinfectious </li></ul><ul><li> ANCA-GN Hereditary nephritis </li></ul><ul><li>Hypertension </li></ul><ul><li>Kidney failure </li></ul>
    134. 150. Rapidly progressive GN (RPGN) <ul><li>Clinical diagnosis </li></ul><ul><li>loss of kidney function >50% within weeks to months </li></ul><ul><li>Pathological diagnosis </li></ul><ul><li>crestcent > 50% </li></ul><ul><li>Causes : immune complex GN </li></ul><ul><li> antiGBM GN </li></ul><ul><li> Pauci-immune GN (ANCA) </li></ul>
    135. 151. Telescopic urine sediment
    136. 152. How to approach?
    137. 153. <ul><li>Primary or secondary??? </li></ul><ul><li>clinical features of </li></ul><ul><li>Hypertension </li></ul><ul><li>Nephritis </li></ul><ul><li>kidney function </li></ul>
    138. 154. Secondary glomerular diseases
    139. 155. Secondary glomerular diseases <ul><li>Metabolic diseases : DM (most common) </li></ul><ul><li>Autoimmune diseases : SLE, small vessel vasculitis </li></ul><ul><li>Ig deposition diseases </li></ul><ul><li>Infections : postinfectious GN </li></ul><ul><li>Drugs : NSAID, gold, D-penicillamine </li></ul><ul><li>Malignancy : solid or hematologic </li></ul><ul><li>Others : cirrhosis </li></ul>
    140. 156. Secondary glomerular diseases <ul><li>Nephrotic </li></ul><ul><li>Diabetic nephropathy </li></ul><ul><li>Ig deposition disease </li></ul><ul><li>Preeclampsia </li></ul><ul><li>Lupus nephritis V </li></ul><ul><li>Nephritis </li></ul><ul><li>Postinfectious GN </li></ul><ul><li>lupus nephritis III, IV </li></ul><ul><li>Mixed cryoglobulinemia </li></ul><ul><li>ANCA related GN </li></ul><ul><li>AntiGBM GN </li></ul><ul><li>HUS, TTP </li></ul>
    141. 157. Metabolic disorders <ul><li>DM Diabetic nehropathy (Nephrotic) </li></ul><ul><li>Hyperthyroidism membranous GN </li></ul>
    142. 158. Diabetic nephropathy <ul><li>Type 1 </li></ul><ul><li>5 – 10 y : microalbuminemia </li></ul><ul><li>13 – 20 y : overt proteinuria </li></ul><ul><li>then :  GFR 1 ml/min/month </li></ul><ul><li>>90% have retinopathy </li></ul><ul><li>control : blood sugar </li></ul><ul><li> BP (130/80 mmHg), ACEI, protein diet, lipid </li></ul>
    143. 159. Diabetic nephropathy <ul><li>Type 2 </li></ul><ul><li>duration : variable (HT, atherosclerosis) </li></ul><ul><li>50 – 80% have retinopathy </li></ul><ul><li>control : blood sugar </li></ul><ul><li> BP (130/80 mmHg), ARB, protein diet, lipid </li></ul>
    144. 160. DM & glomerular diseases <ul><li>Diabetic nephropathy </li></ul><ul><li>Hypertensive nephropathy </li></ul><ul><li>Other primary or secondary glomerular diseases </li></ul><ul><li>no retinopathy </li></ul><ul><li>hematuria </li></ul><ul><li>rapid  serum Cr </li></ul><ul><li>acute onset </li></ul><ul><li>very low serum albumin (< 2 g/dL) </li></ul>
    145. 161. Collagen vascular diseases autoimmune disease <ul><li>SLE lupus nehritis (nehritic, nephrotic) </li></ul><ul><li>RA membranous GN, amyloidosis </li></ul><ul><li>Polymyositis membranous GN </li></ul><ul><li>AS IgAN </li></ul><ul><li>Psoriasis IgAN </li></ul>
    146. 162. Ig deposition diseases <ul><li>Amyloidosis </li></ul><ul><li>Light chain deposition diseases </li></ul><ul><li>Heavy chain deposition diseases </li></ul><ul><li>Associated with plasma cell dyscrasia </li></ul><ul><li>Investigation : </li></ul><ul><li>CBC, serum immunoelectrophoresis </li></ul><ul><li>serum free light chains :  ,  </li></ul><ul><li>biopsy : skin, rectal, abdominal fat pad, kidney, liver </li></ul>
    147. 163. Infections <ul><li>Viral </li></ul><ul><li>HBV membranous GN </li></ul><ul><li>HCV mixed cryoglobulinemia </li></ul><ul><li>HIV collapsing FSGS </li></ul><ul><li>Bacteria postinfectious GN </li></ul><ul><li>syphilis (2 nd , congenital) </li></ul><ul><li>Fungus </li></ul><ul><li>Parasite : malaria, schistosomiasis </li></ul><ul><li> (membranous GN) </li></ul>
    148. 164. Drugs <ul><li>NSAID : minimal change disease </li></ul><ul><li>Gold, d-penicillamin : membranous </li></ul>
    149. 165. Malignancy <ul><li>Hematologic : </li></ul><ul><li>non Hodgin  membranous </li></ul><ul><li>Hodgin  minimal change dis </li></ul><ul><li>Solid tumor </li></ul><ul><li>membranous nephropathy </li></ul>
    150. 166. Others <ul><li>Cirrhosis  IgA nephropathy </li></ul>
    151. 167. Primary glomerular diseases
    152. 168. Primary glomerular diseases <ul><li>Nephrotic </li></ul><ul><li>IgM nephropathy </li></ul><ul><li>Minimal change dis </li></ul><ul><li>FSGS (or IgM with sclesrosis) </li></ul><ul><li>Membranous GN </li></ul><ul><li>MPGN type1 </li></ul><ul><li>Fibrillary GN </li></ul><ul><li>Nephritis </li></ul><ul><li>IgA nephropathy </li></ul><ul><li>MPGN type2 </li></ul><ul><li>Hereditary nephritis </li></ul><ul><li>Alport syndrome </li></ul><ul><li>TBM dis </li></ul>
    153. 169. Investigations <ul><li>Diagnosis of glomerular diseases </li></ul><ul><li>blood pressure </li></ul><ul><li>GFR </li></ul><ul><li>urine protein excretion </li></ul><ul><li>24h > 2 g/day, UPCR > 2 </li></ul><ul><li>urine sediment : </li></ul><ul><li>oval fat body </li></ul><ul><li>glomerular red cell </li></ul><ul><li>cast – fatty, red cell, cellular </li></ul><ul><li>systemic or extrarenal manifestations </li></ul><ul><li>kidney biopsy </li></ul>
    154. 170. Kidney biopsy <ul><li>Indication </li></ul><ul><li>Diagnosis </li></ul><ul><li>Prognosis </li></ul><ul><li>Method </li></ul><ul><li>Light microsope study : morphology </li></ul><ul><li>Immunofluorescence study : Ig, C3, C4 </li></ul><ul><li>Electron microscope study : deposition & ultrastructure </li></ul>
    155. 171. Individual investigations <ul><li>ANA, antiDNA  lupus nephritis </li></ul><ul><li>Complement  inflammatory related </li></ul><ul><li>ANCA, CXR  pauci-immune : WG, CS, micro.PAN </li></ul><ul><li>antiGBM, CXR  antiGBM dis </li></ul><ul><li>RF, cyroglobulin  mixed cryoglob GN </li></ul><ul><li>ASO, antiDNAase  postinfectious </li></ul><ul><li>HBsAg, antiHCV  hepatitis related NS </li></ul><ul><li>antiHIV  HIVAN </li></ul><ul><li>VDRL  2 nd syphilis, congenital </li></ul><ul><li>CBC, electrophoresis  IgDD </li></ul>
    156. 172. Managements
    157. 173. Managements <ul><li>Primary or secondary </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>most common causes : minimal change disease </li></ul><ul><li>try predinolone 1 mg/kg/day </li></ul><ul><li>(check infection : CXR, stool exam, fever) </li></ul><ul><li>if response : continue 1 mg/kg/day for 1 month and reduced 5 – 10 mg/month </li></ul><ul><li>if not response (16 wks) : </li></ul><ul><li>refer for kidney biopsy </li></ul><ul><li>ACEI or ARB  reduce proteinuria </li></ul>
    158. 174. Managements <ul><li>Nephrotic syndrome </li></ul><ul><li>most common causes : minimal change disease </li></ul><ul><li>cyclophosphamide 1mg/kg/day for 1 month may benefit in </li></ul><ul><li>Steroid dependent (can not stop steroid or relapse within 2 wks after stop steroid) </li></ul><ul><li>frequent relapse ( > 2 times/6 m) </li></ul><ul><li>steroid side effects </li></ul>
    159. 175. Managements <ul><li>Nephritis </li></ul><ul><li>treatment depends on etiology </li></ul><ul><li>recommend kidney biopsy in </li></ul><ul><li>urine protein > 1-2 g/day </li></ul><ul><li>hypertension </li></ul><ul><li> GFR </li></ul>
    160. 176. IgA nephropathy <ul><li>Asymptomatic hematuria  RPGN </li></ul><ul><li>Factors associated with progressive disease (Siriraj experiencea) </li></ul><ul><li>serum Cr > 1.5 mg/dL </li></ul><ul><li>proteinuria > 1 g/day </li></ul><ul><li>Rx with prednisolone 1 mg/kg/day as minimal change disease (Siriraj experience) </li></ul>
    161. 177. Lupus nephritis : Siriraj experience <ul><li>ANA +ve 90%, antiDNA +ve 67% </li></ul><ul><li>Classification </li></ul><ul><li>class I 0.6% </li></ul><ul><li>class II 17.9% </li></ul><ul><li>class III 9.9% </li></ul><ul><li>class IV 58.6% </li></ul><ul><li>class V 12.9% </li></ul><ul><li>Edema, hypertension, nephrotic, nephritis,  GFR </li></ul>
    162. 178. Lupus nephritis treatment <ul><li>Class II </li></ul><ul><li>oral prednisolone 0.5 mg/kg/day </li></ul><ul><li>Class IV </li></ul><ul><li>oral prednisolone 1 mg/kg/day plus cyclophosphamide or mycophinolate mofetil </li></ul><ul><li>Class V </li></ul><ul><li>steroid plus cytotoxic drugs </li></ul>
    163. 180. PREGNANCY & KIDNEY DISEASE
    164. 181. NORMAL PHYSIOLOGY <ul><li>Systemic hemodynamics </li></ul><ul><li> blood volume </li></ul><ul><li> peripheral vascular resistance </li></ul><ul><li>Onset : early preg. Peak : 2nd trim. </li></ul><ul><li>BP  10 mmHg  105/60 mmHg </li></ul><ul><li>Cardiac output  30 – 50% </li></ul><ul><li>PLASMA  30 – 40% </li></ul><ul><li>water :  6 – 8 litrs </li></ul><ul><li>Na+ :  900 – 1,000 mEq </li></ul><ul><li>RC :  250 – 450 ml (24-26wk) </li></ul><ul><li>Nitric oxide </li></ul><ul><li> </li></ul><ul><li>relaxin (ovarian hormone) </li></ul><ul><li>HCG </li></ul>
    165. 182. RENAL FUNCTIONS <ul><li> GFR & RPF 40 – 50% </li></ul><ul><li>Onset : 1 m, Peak : end of 1st trim. </li></ul><ul><li> 20 – 30% : 3rd trim. Normal : PPT 3 m </li></ul><ul><li>Serum Cr 0.4 – 0.5 ( < 0.8) mg/dl </li></ul>
    166. 183. ELECTROLYTES & ACID-BASE <ul><li>Chronic respiratory alkalosis </li></ul><ul><li> RC center : progesterone </li></ul><ul><li>Hyponatremia (  5 mEql) </li></ul><ul><li>relaxin (by HCG) </li></ul><ul><li>normal 1 – 2 m PPT </li></ul><ul><li>Polyuria </li></ul><ul><li>vasopressinase (   4 : placenta),  GFR </li></ul><ul><li>impair secretory reserve or renal response </li></ul><ul><li>normal : 2 – 3 wk PPT </li></ul><ul><li>dDAVP - sensitive </li></ul>Sheehan’s Nephrogenic DI Acute fatty liver (central DI)
    167. 184. HYPERTENSION <ul><li>PREECLAMSIA </li></ul><ul><li>CHRONIC HYPERTENSION </li></ul><ul><li>GESTATIONAL HYPERTENSION </li></ul><ul><li>RENAL DISEASES </li></ul>
    168. 185. DEFINITION <ul><li>> 140/90 mmHg </li></ul><ul><li>mild & moderate </li></ul><ul><li>(140-169/90-109) </li></ul><ul><li>severe : DBP > 110 mmHg </li></ul>
    169. 186. DIFFERENTIAL DIAGNOSIS <ul><li> Preeclapmsia RD&CHT GHT </li></ul><ul><li>Onset > 20 wk < 20 wk 3 rd trim </li></ul><ul><li>Proteinuria + -/+ - </li></ul><ul><li>Sediment - -/+ - </li></ul><ul><li>Serum uric >4  - </li></ul><ul><li>Urine Ca <100 >200 >200 </li></ul>Gradual onset HT Proteinuria edema
    170. 187. ACUTE RENAL FAILURE <ul><li>EARLY PREGNANCY </li></ul><ul><li>Prerenal : hyperemesis gravidarum </li></ul><ul><li>ATN : septic abortion </li></ul>
    171. 188. HELLP acute fatty live HUS,TTP Onset > 20 wk  < 20 wk < 48 hr PPT  > 48 hr PPT Plt    Coag DIC DIC normal Liver dysfn    normal hypoglycemia Renal failure mild    
    172. 189. ACUTE RENAL FAILURE <ul><li>RENAL CORTICAL NECROSIS </li></ul><ul><li>abruptio placenta, placenta previa, amniotic fluid embolism, prolong intrauterine fetal death </li></ul><ul><li>URINARY TRACT OBSTRUCTION </li></ul><ul><li>ACUTE PYELONEPHRITIS </li></ul>
    173. 190. PREGNANCY  RENAL DIS. <ul><li>Cr < 1.5 : same outcome </li></ul><ul><li>Cr > 1.5 </li></ul><ul><li>Renal failure :  40%, 1/3 irreversible, 10% -ESRD </li></ul><ul><li>Proteinuria : ½  </li></ul><ul><li>HT : ¼  </li></ul><ul><li>Lupus nephritis : active if remission < 6 m </li></ul>
    174. 191. <ul><li>Azotemia </li></ul><ul><li>Pretermature 6 times </li></ul><ul><li>HYPERTENSION </li></ul><ul><li>fetal death, preterm labour, </li></ul><ul><li>IUGR, LBW </li></ul>RENAL DIS.  PREGNANCY
    175. 192. TERMINATION OF PREGNANCY <ul><li>Serum Cr > 1.4 or GFR < 70 ml/min </li></ul><ul><li>Uncontrolled HT </li></ul><ul><li>Severe nephrotic or nephritis </li></ul>
    176. 193. TREATMENT <ul><li>Benefit ? : restrict activity, admission </li></ul><ul><li>AntiHT drugs in mild – moderate HT : </li></ul><ul><li>↓ risk of severe HT </li></ul><ul><li>preeclampsia, fetal death, SGA </li></ul><ul><li>Acute severe HT </li></ul><ul><li>IV labetalol, oral nifedipine are better than IV hydralazine </li></ul>
    177. 194. ANTIHYPERTENSIVE <ul><li>Methy DOPA or labetalol  </li></ul><ul><li>Hydralazine  </li></ul><ul><li>Ca ch blocker  </li></ul><ul><li>Beta blocker ? </li></ul><ul><li>Diuretic ? </li></ul><ul><li>ACEI × </li></ul>

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