renal physiology, electrolytes and renal failure daniel shoskes md, frcs(c) professor of...

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Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland Clinic

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Page 1: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Renal Physiology, Electrolytes and Renal Failure

Daniel Shoskes MD, FRCS(C)

Professor of Surgery/Urology

Glickman Urological and Kidney Institute

Cleveland Clinic

Page 2: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

What you need to know:

• Renal anatomy• Control of vascular

tone• Tubular function• Handling Na+/water• Handling K, Cl• Handling acid• Pathophysiology of

renal failure

• Electrolyte disorders

• Acid-Base disorders

• Water disorders

• Conduit/pouch effects

• Obstruction effects

• Stones/RTA

• Diuretic effects

Page 3: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Basic Anatomy

Page 4: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Renal Architecture

Page 5: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland
Page 6: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Renal Hemodynamic Definitions

• Renal Blood Flow (RBF)– blood to kidneys per minute (1200 ml/min)

• Renal Plasma Flow (RPF)– plasma flow to kidneys per minute (670 ml/min)

• Glomerular Filtration Rate (GFR)– volume of plasma filtered per minute by the

glomeruli (125 ml/min males, 100 ml/min females)

• Filtration Fraction (FF)– GFR:RPF (about .18-.22)

Page 7: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

GFR

• balance of hydrostatic and oncotic pressures

• hydrostatic pressure controlled by relative tonicity of pre-

and post-glomerular arterioles

• hyper-renin state will maintain GFR by post-glomerular

arteriolar constriction

• GFR may be approximated by creatinine clearance,

since Cr filtered, not resorbed and minimally secreted

Page 8: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland
Page 9: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Equations we Hate (1)

Creatinine Clearance (ml/min) =

(140-age) x lean body weight (kg)-------------------------------------------

72 x plasma creatinine

(In women, above x 0.85)

urine Cr x urine vol= ----------------------------

serum creatinine

A.

B.

(total creatinine should be 1 mg/kg/hror else inadequate collection)

Page 10: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

GFR and Plasma Creatinine

GFR(ml/min)

plasma creatinine (mg/dl)

100

50

25

12

6

0.5 1.0 2.0 4.0 8.0

RULE OF THUMB

everytime PCr doubles, GFR drops by 50%

Page 11: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

MDRD Formula

Glomerular Filtration Rate (ml/min/1.73m2) =

186 x (PCr) -1.154 x (age) -0.203 x (0.742 if female) x (1.210 if African American)

More accurate than Cockcroft Gault in pts with renal impairment. Obviously can't ask you to calculate in exam, but know the variables

Page 12: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Renin-Angiotensin System

Page 13: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Tubular Function

• maintain appropriate water, acid and electrolyte balance using passive and active mechanisms

• reabsorb selectively up to 99% of the glomerular filtrate

• respond to endocrine signals to make necessary changes

Page 14: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Tubular Organization

Page 15: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Proximal Tubule

• resorbs 100% of glucose and amino acids, 90%

of bicarbonate and 80-90% of inorganic

phosphate and water

• solutes active, water passive

• Na reabsorption through Na-H and Na-solute

active transporters

• HCO3 generated in cell and absorbed with Na

• ammonium secretion

Page 16: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Loop of Henle

• early water and urea permeability, filtrate

becomes hypertonic

• later Na-Cl permeability

• final, Na-Cl actively transported, filtrate

hypotonic

• creates high interstitial osmolality which

permits urinary concentration

Page 17: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Thick Ascending Limb

• the "diluting" segment

• active transport of NH3 and Na

• aldosterone and ADH augment Na

reabsorption

Page 18: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Countercurrent Mechanism

Page 19: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Collecting Duct

• provides final touches to Na, HCO3 and K

• Na absorbed, K secreted (stimulated by

aldosterone)

• H secreted based on blood pH

• NH3 secreted into lumen and can trap H to

make NH4

• If ADH present, permeable to water and water

is drawn by hypertonic medulla

Page 20: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Thiazide Diuretics

• HCTZ, chlorthalidone, metolazone

• inhibit Na and Cl reabsorption in distal

convoluted tubule

• reduce GFR and Renal Blood Flow

• decrease urinary calcium

Page 21: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Loop Diuretics

• furosemide, ethacrinic acid, bumetanide

• inhibit Na/K/Cl cotransporter

• increased diuresis and excretion of Na, K, Cl,

Ca and Mg

• reduce medullary solute content and impair

urinary concentrating and diluting capacity

Page 22: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Disorders of Water/Sodium

• Primary goals:

– maintain blood pressure

– excrete wastes

• Mechanisms

– thirst

– ADH

– aldosterone

Page 23: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Equations we Hate (2)

Osmolality:

Posm = 2 x plasma [Na] + [glucose]/18 + [BUN]/2.8

Page 24: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Osmolality Changes

Page 25: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Response to Water Loss

Page 26: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

How Water Disorders Develop

Page 27: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hyponatremia Evaluation

Page 28: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hyponatremia Therapy

Page 29: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Equations we Hate (3)

Sodium Deficit

Na deficit = voldist x body weight (kg) x

(125 - plasma [Na])

voldist: men = 0.5 women = 0.6

Page 30: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hypernatremia Evaluation

Page 31: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hypernatremia Therapy

Page 32: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Secretion of Acid

• Active Na-H pump

• Glomerular filtration of buffers

– HCO3, HPO4

• Ammonia (NH3) secreted in tubule combines

to form non-diffusible NH4 (ammonium ion)

Page 33: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland
Page 34: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Acid-Base Disorders

• normal arterial blood pH ranges from 7.37 to 7.43, maintained by lungs (PCO2) and kidneys (HCO3)

• sudden changes tempered by buffers in blood• first determine primary disorder, then check

compensation• if compensation not appropriate, suspect mixed

disorder• check anion gap in metabolic acidosis

(Na-(Cl+HCO3)) looking for "extra" anions (normal is 10-12)

Page 35: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Simple Acid-Base Disorders

Metabolic AcidosisExpected pCO2 = 1.5 x [HCO3-] + 8 ± 2

Alkalosis Expected pCO2 = 6 mmHg per 10 mEq/L  in HCO3

Respiratory Acidosis  Acute Expected HCO3 =1 mEq/L for each 10 mm pCO2Chronic Expected HCO3 =3.5mEq/L for each 10 mmHg pCO2

Alkalosis  Acute Expected HCO3 =2 mEq/L for each 10 mm Hg pCO2Chronic Expected HCO3- =5 mEq/L for each 10 mmHg pCO2

BUT: Nowadays most people use nomograms

Page 36: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland
Page 37: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Metabolic Disorders

Page 38: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Primary Disorder

• pH=7.18, pCO2=14, HCO3=14, Na=140, Cl=104– pH is low therefore acidemia– bicarb is low therefore metabolic acidosis– pCO2 is low, expected compensation– predicted pCO2 compensation 1.5*4+8=14– anion gap 140-(104+14) = 22 (elevated)

• Therefore anion gap metabolic acidosis with appropriate compensation

Page 39: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Respiratory Disorders

• Respiratory Acidosis

– insufficient respiration

– consider central,

mechanical and

obstructive causes

– headache and

drowsiness lead to

coma and death

• Respiratory Alkalosis

– hyperventilation

– anxiety, fever, pain,

septicemia, iatrogenic

(ventilator settings)

– may have tetany,

parasthesia

Page 40: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Renal Tubular Acidosis

• syndromes of metabolic acidosis from defects in tubular H secretion and urinary acidification

• Type 1 (Distal, includes old 3,collecting duct)– hypo K, hypo Cl, non-anion gap met acidosis– urinary pH > 6.0 (inappropriate)– 75% of these patients get stones

• Type 2 (Proximal)– same features but can acidify urine– HCO3 wasting from inability to absorb

• Type 4 (Generalized Distal)– hyper K, hyper Cl– aldosterone deficiency or resistance

Page 41: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

RTA Type 1

• Most common form

• Stones usually Ca phosphate

– high urine pH, Ca and low urine citrate

• Diagnose by urine pH>5.5, if no met acidosis,

provoke with ammonium chloride test

• Treat by oral alkalinization and citrate,

monitor for low K during therapy

Page 42: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Other RTA Forms

• Type 2– more common in children– normal citrate, no stones– growth retardation, met bone disease

– treat with NaHCO3

• Type 4– often have azotemia and hypertension– treatment aimed to reduce K

Page 43: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Disorders of Potassium

• Mostly intracellular

• Serum levels do not reflect total body content

in disease states

• K driven into cells by insulin, bicarb, beta-

agonists

• Changes in dietary intake handled by

intracellular stores and urinary excretion

• Excretion promoted by aldosterone, high

distal Na load, chronic acidosis

Page 44: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Cellular K Shift

Page 45: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hypokalemia

• Usually increased loss (GI, urine) or

intracellular shift (aLKylosis = Low K)

• Iatrogenic common

– diuretics, laxatives, amphotericin, theophylline

• hyperaldosterone states, Cushing syndrome

• tachycardia, heart block, ST depression

• treat underlying cause, replace K (40 mEq/hr

max IV)

Page 46: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

EKG Changes in Hypokalemia

Page 47: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Hyperkalemia

• usually reflects decreased renal excretion or shift out of cells (acidosis)

• GI bleed, hemolysis will often exacerbate• RTA type 4, K sparing diuretics, ACE

inhibitors, beta blockers• usually asymptomatic until cardiac changes

– short QT, peaked T waves, ventricular arryth

• mild increase, reverse predisposing cause• moderate, use binding agents (Kayexalate)• severe, give Ca/insulin/glucose drip; dialysis

Page 48: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

EKG Changes in Hyperkalemia

Page 49: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Treatment of Hyperkalemia

Page 50: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Calcium Distribution

Page 51: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Tubular Handling of Calcium

Page 52: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Response to Hypocalcemia

Page 53: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Effects of Urinary Diversion

• Dependent on bowel segment, length used, time of exposure, solute concentration, renal function, urine pH

• Stomach– hypo Cl, hypo K, met alkalosis

• Jejunum– hypo Na, hypo Cl, hyper K, met acidosis

– rehydrate with NaCl and NaHCO3

Page 54: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Ileum and Colon Diversions

• hyperchloremic met acidosis

• predisposed by impaired renal function

• ammonium absorption with Cl is exchanged for Na and HCO3

• inability to secrete acid as ammonium depletes buffers

• Treat with Na bicarb and/or nicotinic acid (Cl transport inhibitor)

Page 55: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Postobstructive Diuresis

• requires bilateral obstruction or obstruction of solitary unit

• mechanisms– Na leak, urea osmotic diuretic, loss of

concentrating ability from urea washout in medulla

• mild form can be corrected by oral intake• severe requires partial IV replacement and

electrolyte monitoring

Page 56: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Case #1

• 25 yo male presenting with recurrent renal stones has the following serum electrolytes:

1. What further investigations are required?

2. How would you approach this problem?

• Na 137 mmol/l• K 3.5 mmol/l• Cl- 112 mmol/l

• HCO3-16 mmol/l

• creatinine 1.0 mg/dl• BUN 14 mg/dl• albumin 41 g/l

pH blood 7.31

pH urine 6.3

Page 57: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Approach to Metabolic Acidosis

anion gap

normal

inability to secrete H+

• RTA type 1• RTA type 4

elevated

loss of HCO3-

• RTA type 2• diarrhea• ureteral diversion

excess acid generation

Page 58: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Case #1

in this case…

• blood pH 7.31 (acidemic)

• HCO3- 16 (low)

metabolic acidosis

• anion gap 9 (normal)

normal anion gap metabolic acidosis

• urine pH high (> 5.5)

distal RTA (type 1)

Page 59: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Case #2

• 70 yo male post op nephrectomy for RCC• diabetes, hypertension, CAD• renal transplant 3 yrs ago

• bloodwork reveals:• Na 136 mmol/l• K 6.2 mmol/l• HCO3

- 18 mmol/l• creatinine 1.8 mg/dl• glucose 144 mg/dl

• how would you manage the hyperkalemia?

Page 60: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Approach to Hyperkalemia

true hyper K

renal excretion cellular shift

hypoaldosteronism• age• diabetes• drugs

excess intake

tubular defects• drugs

distal delivery of salt and water

(renal failure)

Page 61: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Case #2

• look for excess intake• supplements (po or IV, salt substitutes)

• look for DRUGS• ACE inhibitors and ARBs

• calcineurin inhibitors (cyclosporine, tacrolimus)

• potassium sparing diuretics (amiloride, triamterene)

• aldosterone antagonists (spironolactone, eplerenone)

• others (NSAIDs, heparin, trimethaprim)

Page 62: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Case #2

• prevent recurrence • low K diet • drug adjustments

• reduce total body stores • diuretics • binding resins • hemodialysis (if ESRF)

• intracellular shift • glucose/insulin, agonist• NaHCO3

• stabilize myocardium • calcium gluconate IV (*with EKG changes)

< 6.0 6.0-6.5 6.5-7.0 > 7.0 *

Serum K

Page 63: Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland

Internet File Location

• ftp://ftp.dshoskes.com