Renal Physiology, Electrolytes and Renal Failure Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland Clinic
Renal Physiology, Electrolytes and Renal Failure
Daniel Shoskes MD, FRCS(C)
Professor of Surgery/Urology
Glickman Urological and Kidney Institute
Cleveland Clinic
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
Basic Anatomy
Renal Architecture
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)
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
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)
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%
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
Renin-Angiotensin System
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
Tubular Organization
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
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
Thick Ascending Limb
• the "diluting" segment
• active transport of NH3 and Na
• aldosterone and ADH augment Na
reabsorption
Countercurrent Mechanism
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
Thiazide Diuretics
• HCTZ, chlorthalidone, metolazone
• inhibit Na and Cl reabsorption in distal
convoluted tubule
• reduce GFR and Renal Blood Flow
• decrease urinary calcium
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
Disorders of Water/Sodium
• Primary goals:
– maintain blood pressure
– excrete wastes
• Mechanisms
– thirst
– ADH
– aldosterone
Equations we Hate (2)
Osmolality:
Posm = 2 x plasma [Na] + [glucose]/18 + [BUN]/2.8
Osmolality Changes
Response to Water Loss
How Water Disorders Develop
Hyponatremia Evaluation
Hyponatremia Therapy
Equations we Hate (3)
Sodium Deficit
Na deficit = voldist x body weight (kg) x
(125 - plasma [Na])
voldist: men = 0.5 women = 0.6
Hypernatremia Evaluation
Hypernatremia Therapy
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)
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)
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
Metabolic Disorders
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
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
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
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
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
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
Cellular K Shift
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)
EKG Changes in Hypokalemia
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
EKG Changes in Hyperkalemia
Treatment of Hyperkalemia
Calcium Distribution
Tubular Handling of Calcium
Response to Hypocalcemia
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
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)
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
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
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
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)
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?
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)
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)
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
Internet File Location
• ftp://ftp.dshoskes.com