Nephrology & UrologyNephrology & UrologyArcher Online USMLE ReviewsArcher Online USMLE Reviews

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Archer Slides are intended for use with Archer USMLE step 3 Archer Slides are intended for use with Archer USMLE step 3 video lectures. Hence, most slides are very brief summaries of video lectures. Hence, most slides are very brief summaries of

the concepts which will be addressed in a detailed way with the concepts which will be addressed in a detailed way with focus on High-yield concepts in the Video lectures. focus on High-yield concepts in the Video lectures.

These slides are only SAMPLESThese slides are only SAMPLES

Renal FailureRenal Failure Acute Vs. ChronicAcute Vs. Chronic Acute : Pre-Renal, Renal, Post –renal, Glomerular, Acute : Pre-Renal, Renal, Post –renal, Glomerular,

tubular, intersititialtubular, intersititial Indicators : BUN/CREA, FeNA, Urine Spgravity, Indicators : BUN/CREA, FeNA, Urine Spgravity,

serum Sodium, serum osmolality, urine output.serum Sodium, serum osmolality, urine output. Chronic – stages Chronic – stages elective hemodialysis Stage V, elective hemodialysis Stage V,

Emergent hemodialysis indications Emergent hemodialysis indications Acute tubular necrosis : toxic, pigment induced, Acute tubular necrosis : toxic, pigment induced,

IschemicIschemic Evaluating renal function : urinalysis - ? Protein, ?rbc , ? Evaluating renal function : urinalysis - ? Protein, ?rbc , ?

Wbc, ? Casts , ? Crystals, ? Bacteria, ? Nitrite, ? Wbc, ? Casts , ? Crystals, ? Bacteria, ? Nitrite, ? Cytology , ? Leucoesterase, Cytology , ? Leucoesterase,

- Creatinine clearance, Renal ultrasound, Renal biopsy- Creatinine clearance, Renal ultrasound, Renal biopsy

RENAL BIOPSYRENAL BIOPSY

Indications: Indications: Nephrotic syndromeNephrotic syndrome

Glomerular diseaseGlomerular disease

Unexplained renal failureUnexplained renal failure Contraindications: single kidney, bleeding, Contraindications: single kidney, bleeding,

severe hypertension. obesity and uncooperative severe hypertension. obesity and uncooperative patientpatient

DEFINITION OF ARFDEFINITION OF ARF

PPCrCr > 0.5mg/dL if baseline < 3.0mg/dL > 0.5mg/dL if baseline < 3.0mg/dL

PPCrCr > 1.0 mg/dL if baseline > 3.0 mg/dL > 1.0 mg/dL if baseline > 3.0 mg/dL Urine Output : Urine Output : TOTAL ANURIA 0 ccTOTAL ANURIA 0 ccANURIA < 100 ccANURIA < 100 ccOLIGURIA 100-400 ccOLIGURIA 100-400 ccNON OLIGURIA 400-1000ccNON OLIGURIA 400-1000ccPOLYURIA > 1000ccPOLYURIA > 1000cc

CAUSES OF NONOLIGURIC PRE CAUSES OF NONOLIGURIC PRE RENAL ARFRENAL ARF

DiureticsDiuretics Osmotic diuresisOsmotic diuresis HypercalcemiaHypercalcemia Protein malnourishedProtein malnourished Post obstructive diuresisPost obstructive diuresis Diabetes InsipidusDiabetes Insipidus

NSAID ARFNSAID ARF

Form of pre renalForm of pre renal Occurs in states where RBF decreased and thus Occurs in states where RBF decreased and thus

prostaglandin dependentprostaglandin dependent Nonselective and selective NSAID’s inhibit Nonselective and selective NSAID’s inhibit

compensatory afferent arteriolar vasodilationcompensatory afferent arteriolar vasodilation Volume contraction, CHF, cirrhosis, CKD, Volume contraction, CHF, cirrhosis, CKD,

vascular disease and elderly – increases risk.vascular disease and elderly – increases risk. COX-2 inhibitors have similar effectCOX-2 inhibitors have similar effect Allergic interstitial nephritis can also occurAllergic interstitial nephritis can also occur

ACE INHIBITOR ARFACE INHIBITOR ARF

Rapidly reversible ARFRapidly reversible ARF Increase SIncrease SCr > Cr > 0.5Mg/dL if < 2.0 mg/dL or increase S0.5Mg/dL if < 2.0 mg/dL or increase SCr > Cr >

1.0 mg/dL if > 2.0 mg/dL1.0 mg/dL if > 2.0 mg/dL Bilateral renal artery stenosis, unilateral stenosis in Bilateral renal artery stenosis, unilateral stenosis in

solitary kidney, small vessel disease and decreased RBF: solitary kidney, small vessel disease and decreased RBF: CHF, cirrhosis, decreased ECFCHF, cirrhosis, decreased ECF

Inhibition of A-II efferent arteriole vasoconstriction Inhibition of A-II efferent arteriole vasoconstriction leads to decrease Pleads to decrease PGC GC and GFR and GFR

Age, diuretics, diabetes, NSAID’s, cyclosporine and Age, diuretics, diabetes, NSAID’s, cyclosporine and CKD are risk factorsCKD are risk factors

ARB’s pose similar riskARB’s pose similar risk

POST RENAL ARFPOST RENAL ARF

Caused by anatomic obstruction of urine flowCaused by anatomic obstruction of urine flow Accounts for 5-10% of ARFAccounts for 5-10% of ARF Patients are often asymptomatic and thus should always Patients are often asymptomatic and thus should always

be consideredbe considered Ultrasound useful, but can have 10-20% false negativesUltrasound useful, but can have 10-20% false negatives Patients are often oligo-anuric, but any pattern of urine Patients are often oligo-anuric, but any pattern of urine

output may occuroutput may occur Intraureteric obstruction, Extraureteric obstruction, Intraureteric obstruction, Extraureteric obstruction,

Urethral obstructionUrethral obstruction

INTRARENAL ARFINTRARENAL ARF Renal parenchymal diseasesRenal parenchymal diseases

GlomerularGlomerular

VascularVascular

TubularTubular

InterstitialInterstitial Acute tubular necrosis – most commonAcute tubular necrosis – most common

Glomerular syndromes –Glomerular syndromes –Nephrotic Vs Nephritic SyndromesNephrotic Vs Nephritic Syndromes

NEPHROTIC SYNDROMENEPHROTIC SYNDROME Urinary albumin > 3.0 – 3.5 Urinary albumin > 3.0 – 3.5

gm/24 hoursgm/24 hours HypoalbimunemiaHypoalbimunemia EdemaEdema HyperlipidemiaHyperlipidemia LipiduriaLipiduriaFSGN ( HIV), MGN( SLE, hepb, FSGN ( HIV), MGN( SLE, hepb,

Cancer – solid tumors ), Minimal Cancer – solid tumors ), Minimal ( children), MPGN ( HepC)( children), MPGN ( HepC)

FSGN – Rx High dose steroids, FSGN – Rx High dose steroids, cyclosporinecyclosporine

MGN – Methylprednisolone pulse, MGN – Methylprednisolone pulse, cyclosporincyclosporin

Others : DM, Malignancy, Others : DM, Malignancy, vasulitis, amyloidosisvasulitis, amyloidosis

Nephritic SyndromeNephritic Syndrome Hematuria/ RBC CastsHematuria/ RBC Casts OliguriaOliguria HypertensionHypertension Decreased GFRDecreased GFR Proteinuria +/-Proteinuria +/- Focal glomerulonephritisFocal glomerulonephritis

IgA nephropathyIgA nephropathy Focal SLE ( Type III )Focal SLE ( Type III )

Diffuse glomerulonephritisDiffuse glomerulonephritis Post infectiousPost infectious Diffuse SLE ( Type IV )Diffuse SLE ( Type IV )

IgA nephropathy : most common IgA nephropathy : most common presentation asymptomatic presentation asymptomatic microhematuria with mild microhematuria with mild proteinuria proteinuria

RAPIDLY PROGRESSIVE RAPIDLY PROGRESSIVE GLOMERULONEPHRITISGLOMERULONEPHRITIS

Characterized by > 50% decrease in GFR over days to weeksCharacterized by > 50% decrease in GFR over days to weeks Characterized pathologically by crescent formation and clinically Characterized pathologically by crescent formation and clinically

by progression to ESRD in untreated patients within weeks by progression to ESRD in untreated patients within weeks Related to the degree of crescent formationRelated to the degree of crescent formation Present with active urine sediment, hypertension and oliguric Present with active urine sediment, hypertension and oliguric

ARFARF Nephrologic emergencyNephrologic emergency

Classification of RPGN:Classification of RPGN: Type 1: Anti GBMType 1: Anti GBM Type 2: Immune complexType 2: Immune complex Type 3: Pauci-immune ( p-ANCA )Type 3: Pauci-immune ( p-ANCA )

Early evaluation and biopsyEarly evaluation and biopsy

Proteinuria - MicroalbuminuriaProteinuria - Microalbuminuria Normal: 150 mg/dayNormal: 150 mg/day Albumin 30 mgAlbumin 30 mg

Plasma proteins 60 mgPlasma proteins 60 mg Tubular protein 60 mgTubular protein 60 mg

Dipstick test detects (-) Dipstick test detects (-) charge charge

Does not detect light chainsDoes not detect light chains Function of urine Function of urine

concentrationconcentration Total Protein : creatinine Total Protein : creatinine

ratio estimates 24 hour urine ratio estimates 24 hour urine collectioncollection

Microalbuminuria Microalbuminuria

Albumin excretion rate > 15 Albumin excretion rate > 15 ugm/min = 30 mg/dayugm/min = 30 mg/day

Predictor of early diabetic Predictor of early diabetic nephropathy and CVDnephropathy and CVD

Urine albumin: urine Urine albumin: urine creatinine < 0.03creatinine < 0.03

Positive in exercise, fever, Positive in exercise, fever, stress, CHFstress, CHF

Repeat urinalysis in 3-6 Repeat urinalysis in 3-6 months if u think its months if u think its transient proteinuriatransient proteinuria

ACE Inhibitor *****ACE Inhibitor *****

ATNATN Ischemic (50%)Ischemic (50%) Toxic: Toxic: EXOGENOUS TOXIN ATN :EXOGENOUS TOXIN ATN :

-Antibiotics, Radiocontrast, Non steroidals, -Antibiotics, Radiocontrast, Non steroidals, Anesthetics, Chemotherapeutics, Heavy metals/ Anesthetics, Chemotherapeutics, Heavy metals/ solventssolvents

ENDOGENOUS TOXIN ATN :ENDOGENOUS TOXIN ATN :

Pigment Nephropathy Pigment Nephropathy Myoglobin, Hemoglobin Myoglobin, Hemoglobin

Crystal Nephropathy Crystal Nephropathy Uric acid , Calcium, Uric acid , Calcium, Oxalate Oxalate

RADIOCONTRAST ATNRADIOCONTRAST ATN Risk factors: CRF especially diabetic, CHF, elderly and multiple Risk factors: CRF especially diabetic, CHF, elderly and multiple

myelomamyeloma ATN begins abruptly and SATN begins abruptly and SCr Cr peaks in 3-5 dayspeaks in 3-5 days Usually reversible, but some have prolonged renal damageUsually reversible, but some have prolonged renal damage Usually nonoliguric, but oliguria can be seen and FE Usually nonoliguric, but oliguria can be seen and FE NaNa decreased decreased Prevention : Consider non contrast study if high riskPrevention : Consider non contrast study if high risk D/C NSAID’s, ACE inhibitors. ARB’s etcD/C NSAID’s, ACE inhibitors. ARB’s etc Ensure optimal volume status and RBFEnsure optimal volume status and RBF

0.9% saline @ 1cc/kg/hr for 6 hours prior0.9% saline @ 1cc/kg/hr for 6 hours prior DD55W + 3 amps NaHCO3 @ 3.5 cc/kg/hr for 1 hour and W + 3 amps NaHCO3 @ 3.5 cc/kg/hr for 1 hour and

then 1 cc/kg/hour for 6 hours afterthen 1 cc/kg/hour for 6 hours after N-acetylcysteine 600mg bid pre and day of studyN-acetylcysteine 600mg bid pre and day of study Minimize amount of contrast and consider iso-osmolar agentMinimize amount of contrast and consider iso-osmolar agent - -

nonionic and/or isosmolar contrast are less nonionic and/or isosmolar contrast are less nephrotoxicnephrotoxic

ATHEROEMBOLIC ARFATHEROEMBOLIC ARF Results from cholesterol emboli to small renal Results from cholesterol emboli to small renal

arteries and arteriolesarteries and arterioles Livedo reticularis – A clue!!!Livedo reticularis – A clue!!! Aortic surgery, trauma, angiography, fibrinolytic Aortic surgery, trauma, angiography, fibrinolytic

therapy or spontaneouslytherapy or spontaneously Eosinophilia, eosinophiluria, leukocytosis and Eosinophilia, eosinophiluria, leukocytosis and

complement activationcomplement activation Retinal, peripheral and abdominal vesselsRetinal, peripheral and abdominal vessels

MYOGLOBINURIC ARFMYOGLOBINURIC ARF

Rhabdomyolysis: trauma,alcohol, cocaine, seizures, Rhabdomyolysis: trauma,alcohol, cocaine, seizures, hypokalemia, hypophosphatemiahypokalemia, hypophosphatemia

ECF volume depletionECF volume depletion Heme (+) urine without RBC’s, hyperkalemia, Heme (+) urine without RBC’s, hyperkalemia,

hyperuricemia, hyperphosphatemia and hypocalcemiahyperuricemia, hyperphosphatemia and hypocalcemia Decreased FE Decreased FE NaNa

ECF volume repletion, ?mannitol, and ?alkaline diuresisECF volume repletion, ?mannitol, and ?alkaline diuresis Hypercalcemia during recoveryHypercalcemia during recovery

ACUTE INTERSTITIAL ACUTE INTERSTITIAL NEPHRITISNEPHRITIS

Fever, rash, eosinophila, eosinophiluria and Fever, rash, eosinophila, eosinophiluria and active urine sedimentactive urine sediment

Occurs 10-15 days after exposure to usually new Occurs 10-15 days after exposure to usually new medicationmedication

NSAID induced associated with NSAID induced associated with nephrotic nephrotic syndromesyndrome

? Renal biopsy? Renal biopsy Rx: Stop the agent and ?steroidsRx: Stop the agent and ?steroids

CRYSTAL INDUCED ARFCRYSTAL INDUCED ARF

Uric acidUric acid Calcium oxalateCalcium oxalate MethotrexateMethotrexate SulfonamidesSulfonamides AcyclovirAcyclovir IndinavirIndinavir

DIAGNOSTIC MANAGEMENT DIAGNOSTIC MANAGEMENT ARFARF

History / Chart reviewHistory / Chart review Physical examPhysical exam UrinalysisUrinalysis Urine indicesUrine indices Radiologic studiesRadiologic studies Miscellaneous studiesMiscellaneous studies

NON DIALYTIC MANAGEMENT NON DIALYTIC MANAGEMENT ARFARF

Preventive measuresPreventive measures Fluid balanceFluid balance Acid base balanceAcid base balance Electrolyte balanceElectrolyte balance Nutritional balanceNutritional balance Drug managementDrug management Management of uremiaManagement of uremia

INDICATIONS FOR Emergency INDICATIONS FOR Emergency DIALYSISDIALYSIS

REFRACTORYREFRACTORY

HyperkalemiaHyperkalemia AcidemiaAcidemia Hypoxemia/ volume overloadHypoxemia/ volume overload Uremia - manifestationsUremia - manifestations ? Prophylactic when BUN > 60-100 mg/dL? Prophylactic when BUN > 60-100 mg/dL

Chronic Tubulo-Interstitial DiseasesChronic Tubulo-Interstitial Diseases Chronic issues :Chronic issues : Toxins: Analgesics, Heavy metals, Chinese herbs, Lithium, Toxins: Analgesics, Heavy metals, Chinese herbs, Lithium,

Cyclosporine, Radiation, CisplatinCyclosporine, Radiation, Cisplatin Hematologic diseases: MyelomaHematologic diseases: Myeloma Immunologic: Sjogren’s syndrome, Transplant rejectionImmunologic: Sjogren’s syndrome, Transplant rejection Infection: Bacterial pyelonephritis, Tuberculosis, SarcoidInfection: Bacterial pyelonephritis, Tuberculosis, Sarcoid Anatomic: Obstruction, RefluxAnatomic: Obstruction, Reflux Metabolic disorders: Gout, Oxalosis, Hypercalcemia, Metabolic disorders: Gout, Oxalosis, Hypercalcemia,

Hypokalemia, CystinosisHypokalemia, Cystinosis Hereditary: ADPKD, MCDHereditary: ADPKD, MCD Vascular : Nephrosclerosis, Ischemic nephropathy, Vascular : Nephrosclerosis, Ischemic nephropathy,

Atheroembolic diseaseAtheroembolic disease Acute cases : check urine eosinophil count, peripheral eosinophiliaAcute cases : check urine eosinophil count, peripheral eosinophilia

Oxalate NephropathyOxalate Nephropathy

Precipitation of calcium oxalate can cause Precipitation of calcium oxalate can cause interstitial and intratubular crystals leading to interstitial and intratubular crystals leading to inflammation and fibrosisinflammation and fibrosis

Primary hyperoxaluria leads to ESRDPrimary hyperoxaluria leads to ESRD Ethylene glycol, methoxyflurane, excessive Ethylene glycol, methoxyflurane, excessive

intake ascorbic acidintake ascorbic acid Increase intestinal absorption: Ileal bypass, short Increase intestinal absorption: Ileal bypass, short

bowel syndrome and Crohn’s diseasebowel syndrome and Crohn’s disease

Chronic Urate NephropathyChronic Urate Nephropathy

Related to deposition of sodium urate in the Related to deposition of sodium urate in the medullary interstitiummedullary interstitium

Secondary inflammation and interstitial fibrosis Secondary inflammation and interstitial fibrosis and CRFand CRF

Hypertension, bland urinalysis and hyperuriceniaHypertension, bland urinalysis and hyperuricenia Associated with tophaceous gout or an increase Associated with tophaceous gout or an increase

in uric acid out of proportion to degree of CRF in uric acid out of proportion to degree of CRF

Analgesic NephropathyAnalgesic Nephropathy

NSAID induced interstitial nephritis ( associated NSAID induced interstitial nephritis ( associated with nephrotic syndrome with nephrotic syndrome proteinuria) proteinuria)

NSAID induced vasomotor renal insufficiencyNSAID induced vasomotor renal insufficiency

Hepatorenal SyndromeHepatorenal Syndrome The diagnosis of HRS iS The diagnosis of HRS iS of exclusionof exclusion and depends mainly on serum creatinine level, as no specific tests establish the and depends mainly on serum creatinine level, as no specific tests establish the

diagnosis of HRS. diagnosis of HRS. Serum creatinine level is a poor marker of renal function in patients with cirrhosis. But no other reliable noninvasive Serum creatinine level is a poor marker of renal function in patients with cirrhosis. But no other reliable noninvasive

markers exist for monitoring renal function in these patients. markers exist for monitoring renal function in these patients.

Diagnosis of HRS depends on the presence of a reduced GFR in the absence of other causes of renal failure in patients Diagnosis of HRS depends on the presence of a reduced GFR in the absence of other causes of renal failure in patients with chronic liver disease. with chronic liver disease.

Major criteria (Major criteria (All All major criteria are required to diagnose HRSmajor criteria are required to diagnose HRS.) .) Low GFR, indicated by a serum creatinine level higher than 1.5 mg/dL or 24-hour creatinine clearance Low GFR, indicated by a serum creatinine level higher than 1.5 mg/dL or 24-hour creatinine clearance

lower than 40 mL/min lower than 40 mL/min Absence of shock, ongoing bacterial infection and fluid losses, and current treatment with nephrotoxic Absence of shock, ongoing bacterial infection and fluid losses, and current treatment with nephrotoxic

medications medications No sustained improvement in renal function (decrease in serum creatinine to <1.5 mg/dL or increase in No sustained improvement in renal function (decrease in serum creatinine to <1.5 mg/dL or increase in

creatinine clearance to >40 mL/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L creatinine clearance to >40 mL/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L of plasma expander of plasma expander

Proteinuria less than 500 mg/d and Proteinuria less than 500 mg/d and nono ultrasonographic evidence of obstructive uropathy or intrinsic ultrasonographic evidence of obstructive uropathy or intrinsic parenchymal diseaseparenchymal disease

Additional criteria (Additional criteria are not necessary for the diagnosis but provide supportive evidence.) Additional criteria (Additional criteria are not necessary for the diagnosis but provide supportive evidence.) Urine volume less than 500 mL/d Urine volume less than 500 mL/d Urine sodium level Urine sodium level less than 10 mEq/Lless than 10 mEq/L Urine osmolality greater than plasma osmolality , Urine red blood cell count of less than 50 per high-power Urine osmolality greater than plasma osmolality , Urine red blood cell count of less than 50 per high-power

field & Serum sodium concentration greater than 130 mEq/Lfield & Serum sodium concentration greater than 130 mEq/L Urinary indices are not considered major criteria because Urinary indices are not considered major criteria because a subset of patients with HRS may have high urine a subset of patients with HRS may have high urine

sodium levels and low urine osmolalitysodium levels and low urine osmolality (similar to acute tubular necrosis [ATN]), while other patients with (similar to acute tubular necrosis [ATN]), while other patients with cirrhosis and ATN may have low urine sodium levelscirrhosis and ATN may have low urine sodium levels and high urine osmolality. and high urine osmolality.

Case StudiesCase Studies ) A 25 y/o male comes to your office with complaints of dark red colored urine and ) A 25 y/o male comes to your office with complaints of dark red colored urine and

pain in the legs that started this morning. He has been working out at the local gym pain in the legs that started this morning. He has been working out at the local gym excessively for the past three days. He does consume alcohol on weekends but reports excessively for the past three days. He does consume alcohol on weekends but reports having involved in a binge drinking episode that included 10 beers yesterday. On having involved in a binge drinking episode that included 10 beers yesterday. On physical examination, he weighs 70kg and he has some tenderness in his calf muscles physical examination, he weighs 70kg and he has some tenderness in his calf muscles which he attributes to the excessive squats he performed yesterday. Urine dipstick which he attributes to the excessive squats he performed yesterday. Urine dipstick reveals large blood. If this patient develops acute renal failure , the most likely reveals large blood. If this patient develops acute renal failure , the most likely mechanism would be: mechanism would be:

A) Interstitial nephritis due to pigment A) Interstitial nephritis due to pigment B) Glomerulonephritis B) Glomerulonephritis C) Acute Tubular necrosis due to pigment deposition C) Acute Tubular necrosis due to pigment deposition D) Acute Tubular Necrosis due to Ischemia D) Acute Tubular Necrosis due to Ischemia E) Alcohol related direct toxic injury E) Alcohol related direct toxic injury

1b) Lab studies revealed normal electrolytes and normal creatinine but a CPK of 1b) Lab studies revealed normal electrolytes and normal creatinine but a CPK of 50,000. His Urine output has been at 70 ml/hr for the past 6 hours. Your first step in 50,000. His Urine output has been at 70 ml/hr for the past 6 hours. Your first step in the management to prevent development of patient's Acute Renal Faliure : the management to prevent development of patient's Acute Renal Faliure :

A) Intravenos Fluids A) Intravenos Fluids B) Furosemide B) Furosemide C) Calcium Gluconate C) Calcium Gluconate D) No treatment because serum creatinine is normal D) No treatment because serum creatinine is normal D) Sodium Bicarbonate D) Sodium Bicarbonate

Case StudyCase Study A 7-year-old boy is brought to the emergency department by his mother A 7-year-old boy is brought to the emergency department by his mother

because of "tea-colored urine" for the last several days. He has also had some because of "tea-colored urine" for the last several days. He has also had some nausea and vomiting, and his eyes appear swollen when he wakes up in the nausea and vomiting, and his eyes appear swollen when he wakes up in the morning. The eye swelling tends to resolve over the course of the day. He is morning. The eye swelling tends to resolve over the course of the day. He is generally very healthy and there is no family history of any chronic diseases. generally very healthy and there is no family history of any chronic diseases. His temperature is 36.7 C (98.0 F), blood pressure is 130/90 mm Hg, pulse is His temperature is 36.7 C (98.0 F), blood pressure is 130/90 mm Hg, pulse is 96/min, and respiratory rate is 16/min. Physical examination is unremarkable. 96/min, and respiratory rate is 16/min. Physical examination is unremarkable. A urinalysis shows red cell casts. At this time the most appropriate study to A urinalysis shows red cell casts. At this time the most appropriate study to confirm your diagnosis is confirm your diagnosis is

A. antinuclear antibodyA. antinuclear antibodyB. antistreptolysin O antibodyB. antistreptolysin O antibodyC. renal biopsyC. renal biopsyD. renal ultrasoundD. renal ultrasoundE. urine culture E. urine culture

Case studies contd…Case studies contd… 1c) The above patient has been adequately treated but his repeat CPK after 2 1c) The above patient has been adequately treated but his repeat CPK after 2

days is still elevated at 48,000. He complains of increasing pain in his left leg days is still elevated at 48,000. He complains of increasing pain in his left leg and some tingling and pricking sensations. On examination his left leg was and some tingling and pricking sensations. On examination his left leg was mildly swollen and there was pain on passive stretching of the leg muscles. mildly swollen and there was pain on passive stretching of the leg muscles. Dorsalis pedis and posterior tibial pulses are intact. The most likely diagnosis Dorsalis pedis and posterior tibial pulses are intact. The most likely diagnosis at this time: at this time:

A) Deep Vein Thrombosis A) Deep Vein Thrombosis B) Cellulitis B) Cellulitis C) Compartment Syndrome C) Compartment Syndrome D) Edema due to renal failure D) Edema due to renal failure E) Congestive Heart Failure E) Congestive Heart Failure

1d) The immediate course of treatment in this condition would be : 1d) The immediate course of treatment in this condition would be :

A) Anticoagulation with Heparin A) Anticoagulation with Heparin B) Antibiotics B) Antibiotics C) Emergency Fasciotomy C) Emergency Fasciotomy D) Loop diuretics D) Loop diuretics E) Elevation of the leg E) Elevation of the leg

Case Study 2Case Study 2 Q1) A 12 y/o boy is brought to you by his mother for skin rash and complaints of intermittent Q1) A 12 y/o boy is brought to you by his mother for skin rash and complaints of intermittent

abdominal pain, joint pains for past 2 days. He did have an upper respiratory infection about 2 days abdominal pain, joint pains for past 2 days. He did have an upper respiratory infection about 2 days ago. On physical exam, his vitals are normal. Abdomen is benign with out any tenderness or rigidity. ago. On physical exam, his vitals are normal. Abdomen is benign with out any tenderness or rigidity. However, you notice patchy purple discolorations on his extremities and the back. Lab studies are However, you notice patchy purple discolorations on his extremities and the back. Lab studies are obtained that revealed obtained that revealed

WBC: 6.6 , HGB: 15.3 , MCV: 88 , Platelets: 290,000 ( normal 180k to 400k) WBC: 6.6 , HGB: 15.3 , MCV: 88 , Platelets: 290,000 ( normal 180k to 400k) BUN: 11 , Creatinine : 0.6 ( normal) , Anti streptolysin O titer : negative BUN: 11 , Creatinine : 0.6 ( normal) , Anti streptolysin O titer : negative Streptozyme : negative ,Urine dipstick : normal without any blood Streptozyme : negative ,Urine dipstick : normal without any blood Urinalysis : normal/ no rbcs/ no protein Urinalysis : normal/ no rbcs/ no protein

The mother is very anxious and asks about the long term prognosis of her son. Your response : The mother is very anxious and asks about the long term prognosis of her son. Your response :

A) Reassure the mother that boys disorder is self limiting and does not require any follow up A) Reassure the mother that boys disorder is self limiting and does not require any follow up B) Tell her the boy needs to be admitted and treated vigorously to prevent renal failure B) Tell her the boy needs to be admitted and treated vigorously to prevent renal failure C) Tell her that renal failure develops 100% of such cases and hence needs very cautious follow up C) Tell her that renal failure develops 100% of such cases and hence needs very cautious follow up D) Tell her that 50% of such cases progress to end stage renal disease. D) Tell her that 50% of such cases progress to end stage renal disease. E) Tell her that the boy requires follow up monthly urinalysis for at least 3 months in order to make E) Tell her that the boy requires follow up monthly urinalysis for at least 3 months in order to make sure there is no heamaturia/ renal dysfunction. sure there is no heamaturia/ renal dysfunction.

If the boy presented with Renal failure in the above case, the most likely underlying pathology If the boy presented with Renal failure in the above case, the most likely underlying pathology would be : would be : A) IgA mediated vasculitis A) IgA mediated vasculitis B) Post streptococcal glomerulonephritis B) Post streptococcal glomerulonephritis C) Anti GBM disease C) Anti GBM disease D) Acute tubular necrosis D) Acute tubular necrosis E) Interstitial Nephritis. E) Interstitial Nephritis.

ADPKDADPKD Autosomal Dominant Polycystic Kidney DiseaseAutosomal Dominant Polycystic Kidney Disease Clinical featuresClinical features AssociationsAssociations PrognosisPrognosis Screening for Berry Aneurysms:Screening for Berry Aneurysms:

MRA of head – recommended screening test to detect berry MRA of head – recommended screening test to detect berry aneurysmsaneurysms

Screen Screen only if only if family history of subarachnoid hemorrhage ( Family hx of a family history of subarachnoid hemorrhage ( Family hx of a

ruptured berry aneurysm) ruptured berry aneurysm) not justnot just a family history of berry a family history of berry aneurysm. aneurysm.

Patients with with high risk jobs (pilots/ bus-drivers) - an Patients with with high risk jobs (pilots/ bus-drivers) - an event during such a job is a risk to other’s safety as well. event during such a job is a risk to other’s safety as well.

Patients with symptoms suggestive of a berry aneurysm Patients with symptoms suggestive of a berry aneurysm

( severe headache, focal neurological deficits)( severe headache, focal neurological deficits)

QQ A 46 y/o woman who is a school bus driver by occupation presents to your office for A 46 y/o woman who is a school bus driver by occupation presents to your office for

regular follow up. She has a history of ADPKD. Her blood pressure is well controlled regular follow up. She has a history of ADPKD. Her blood pressure is well controlled at 120/70 on enalapril. She has no other problems. She denies any headache. There is at 120/70 on enalapril. She has no other problems. She denies any headache. There is no family history of intracranial or subarachnoid hemorrhage. However, she is no family history of intracranial or subarachnoid hemorrhage. However, she is concerned that her head might explode because her sister who also has ADPKD was concerned that her head might explode because her sister who also has ADPKD was recently diagnosed of having a berry aneurysm. She wants to be screened for berry recently diagnosed of having a berry aneurysm. She wants to be screened for berry aneurysm as soon as possible. Her physical examination is benign and does not reveal aneurysm as soon as possible. Her physical examination is benign and does not reveal any focal neurological deficits. Which of the following suggests the necessity for any focal neurological deficits. Which of the following suggests the necessity for screening in her case?screening in her case?

A. Family history of berry aneurysmA. Family history of berry aneurysmB. Polycystic kidneysB. Polycystic kidneysC. School bus drivingC. School bus drivingD. Cysts in the liverD. Cysts in the liverE. No screening necessary in her caseE. No screening necessary in her case

Copy right: ArcherCopy right: Archer

Ans. CAns. C

High risk jobs ( pilot, bus driver etc) is one of the High risk jobs ( pilot, bus driver etc) is one of the indications to screen for berry aneurysm in indications to screen for berry aneurysm in asymptomatic ADPKD patients.asymptomatic ADPKD patients.

Family hx of berry aneurysm alone does not warrant Family hx of berry aneurysm alone does not warrant screening for berry aneurysm in asymptomatic ADPKD screening for berry aneurysm in asymptomatic ADPKD patients. Asymptomatic ADPKD patients must be patients. Asymptomatic ADPKD patients must be screened if there is a family history of “screened if there is a family history of “Ruptured” Ruptured” berry berry aneurysm ( history of SAH in the family etc)aneurysm ( history of SAH in the family etc)

E. is not the answer because this patient is a school bus E. is not the answer because this patient is a school bus driver by occupation and needs to be screeneddriver by occupation and needs to be screened

UTIsUTIs

CASE STUDYCASE STUDY

A 76 YO DEBILITATED MALE, In extended care facility , A 76 YO DEBILITATED MALE, In extended care facility , develops every 6 months mild fever, frequency of micturation develops every 6 months mild fever, frequency of micturation with urinary incontinence. USUALLY E.COLI count is with urinary incontinence. USUALLY E.COLI count is >100,000.>100,000.

What is the appropriate treatment?What is the appropriate treatment?

A. CYSTOSCOPY and IVPA. CYSTOSCOPY and IVPB. Continuous low dose antibioticsB. Continuous low dose antibioticsC. Catheterize and irrigate the Bladder dailyC. Catheterize and irrigate the Bladder dailyD. Treat only the acute episode of infection D. Treat only the acute episode of infection E. No need of treatment as this is colonizationE. No need of treatment as this is colonization

Symptomatic complicated UTI should be Symptomatic complicated UTI should be treated. Number of UTI are less than 2 in 6 treated. Number of UTI are less than 2 in 6 mos- no need for continuous Abx. mos- no need for continuous Abx.

His Symptoms are associated with UTI and are His Symptoms are associated with UTI and are not persistent. So just treat the acute episodenot persistent. So just treat the acute episode

REMEMBER THE INDICATIONS FOR REMEMBER THE INDICATIONS FOR TREATING “ASYMPTOMATIC “ TREATING “ASYMPTOMATIC “ BACTERIURIA.BACTERIURIA.

Recurrent UTIsRecurrent UTIs

DEFINED AS 2 OR MORE EPISODES IN DEFINED AS 2 OR MORE EPISODES IN PAST 6 MONTHS OR 3 OR MORE PAST 6 MONTHS OR 3 OR MORE EPISODES IN PAST ONE YEAR. EPISODES IN PAST ONE YEAR.

Use Bactrim DS post sexual activity for women Use Bactrim DS post sexual activity for women with hx of recurrent UTIs related to sexual with hx of recurrent UTIs related to sexual activity. activity.

Use daily bactrim for people withj no relation to Use daily bactrim for people withj no relation to sex activity. sex activity.

OTHER ISSUESOTHER ISSUES

Evaluating painless hematuria elderlyEvaluating painless hematuria elderly Painful hematuriaPainful hematuria Treating asymptomatic bacteriuriaTreating asymptomatic bacteriuria Pyelonephritis – pyonephric abscessPyelonephritis – pyonephric abscess When to admit and when to order imaging When to admit and when to order imaging

studies in pyelonephritis?studies in pyelonephritis?

HematuriaHematuria

•Painless ( Asymptomatic) HematuriaPainless ( Asymptomatic) Hematuria•Painful HematuriaPainful Hematuria•Gross HematuriaGross Hematuria

•Microscopic HematuriaMicroscopic Hematuria

HematuriaHematuria ““Not every red urine needs to be a Hematuria”Not every red urine needs to be a Hematuria” A reddish discoloration of urine can occur with out a A reddish discoloration of urine can occur with out a

positive dipstick or urine microscopy . positive dipstick or urine microscopy . Causes of “Red” urine but negative dipstick testCauses of “Red” urine but negative dipstick test

Ingestion of red pigmented foods ( eg: beets, berries, rhubarbs, paprika)Ingestion of red pigmented foods ( eg: beets, berries, rhubarbs, paprika) Drugs like Drugs like RifampinRifampin or Phenazopyridine derivatives or Phenazopyridine derivatives

( remember these drugs only cause reddish urine but ( remember these drugs only cause reddish urine but NOTNOT a positive dipstick) a positive dipstick) Diseases such as “Diseases such as “Porphyria”Porphyria”

Causes of a Positive Dipstick but no true HematuriaCauses of a Positive Dipstick but no true Hematuria: Here : Here Dipstick stains positive for blood but no RBCs in the urine:Dipstick stains positive for blood but no RBCs in the urine: Myoglobinuria ( Rhabdomyolysis, vigorous exercise)Myoglobinuria ( Rhabdomyolysis, vigorous exercise) Hemoglobinuria ( Intravascular hemolysis)Hemoglobinuria ( Intravascular hemolysis)

HematuriaHematuria Screening test for hematuria is urine dipstick. Screening test for hematuria is urine dipstick. Dipstick :Dipstick :

Dipstick is highly sensitive but not specific. False negatives Dipstick is highly sensitive but not specific. False negatives are very rare but false positives are common.are very rare but false positives are common.

Dipstick detects “blood" but it does not say whether this Dipstick detects “blood" but it does not say whether this "blood" is an RBC or a Pigment. "blood" is an RBC or a Pigment.

Pigments such as myoglobin ( as in rhabdomyolysis) or Pigments such as myoglobin ( as in rhabdomyolysis) or Hemoglobin ( as in hemoglobinuria, Black water fever) can Hemoglobin ( as in hemoglobinuria, Black water fever) can stain as "Blood" on dipstick but there are no RBCs on stain as "Blood" on dipstick but there are no RBCs on urine microscopy. urine microscopy.

So, a dipstick positivity should be confirmed always with So, a dipstick positivity should be confirmed always with “urine microscopy” before calling it a hematuria. “urine microscopy” before calling it a hematuria.

HematuriaHematuria ““Painful” vs. “Painless” HematuriaPainful” vs. “Painless” Hematuria

The distinction is important so that you can consider the The distinction is important so that you can consider the relevant differential diagnosis and choose appropriate relevant differential diagnosis and choose appropriate investigations. investigations.

Painful hematuria is often associated with urolithiasis ( renal Painful hematuria is often associated with urolithiasis ( renal calculi) or inflammation/ infection of the bladder ( Cystitis).calculi) or inflammation/ infection of the bladder ( Cystitis).

Painless or Asymptomatic hematuria is often seen with Painless or Asymptomatic hematuria is often seen with tumors of the urinary tract, bladder cancer, tumors of the urinary tract, bladder cancer, glomerulonephritis and benign prostatic hypertrophy. glomerulonephritis and benign prostatic hypertrophy.

A hematuria accompanied by a classic flank pain should A hematuria accompanied by a classic flank pain should raise a suspicion of renal calculus and the next investigation raise a suspicion of renal calculus and the next investigation in such a scenario should be a Non-Contrast CT scan. in such a scenario should be a Non-Contrast CT scan.

Approach to painless hematuria depends on the risk profile Approach to painless hematuria depends on the risk profile of the patient ( i.e; risk of having a renal/ urological disease)of the patient ( i.e; risk of having a renal/ urological disease)

Gross HematuriaGross Hematuria Grossly Reddish or Tea colored urine, dipstick positive for blood and Grossly Reddish or Tea colored urine, dipstick positive for blood and

urine microscopy shows RBCs. urine microscopy shows RBCs.

Any patient with gross hematuria should Any patient with gross hematuria should alwaysalways be referred for be referred for urological evaluation unless this is secondary to an infectionurological evaluation unless this is secondary to an infection. . If a woman has gross hematuria but the urine dipstick also reveals leucoesterase If a woman has gross hematuria but the urine dipstick also reveals leucoesterase

or nitrite or if the woman has symptoms of UTI ( dysuria etc) or if the cultures or nitrite or if the woman has symptoms of UTI ( dysuria etc) or if the cultures are growing bacteria, this can be treated as UTI ( cystitis) with antibiotics with are growing bacteria, this can be treated as UTI ( cystitis) with antibiotics with out referring for further evaluation. A repeat urinalysis should be obtained after out referring for further evaluation. A repeat urinalysis should be obtained after resolution of the infection. Even in this setting of infection, if there are risk resolution of the infection. Even in this setting of infection, if there are risk factors for urological malignancy the patient should still be referred for further factors for urological malignancy the patient should still be referred for further evaluation ( since hematuria from cancer can also be intermittent).evaluation ( since hematuria from cancer can also be intermittent).

Runner's hematuria or March hematuria is another benign condition that presents Runner's hematuria or March hematuria is another benign condition that presents as gross hematuria after a severe physical activity. In such cases, patients may be as gross hematuria after a severe physical activity. In such cases, patients may be observed for resolution. However, if the hematuria is persistent or if the patient observed for resolution. However, if the hematuria is persistent or if the patient has any risk factors for having a urological malignancy, must be referred to a has any risk factors for having a urological malignancy, must be referred to a urologisturologist

Microscopic HematuriaMicroscopic Hematuria Microscopic hematuria is defined as Microscopic hematuria is defined as three orthree or more red blood more red blood

cells per high-power fieldcells per high-power field on microscopic evaluation of on microscopic evaluation of urinary sediment from urinary sediment from two of threetwo of three properly collected properly collected urinalysis specimens. ( >3rbc/hpf on 2 or more occassions). urinalysis specimens. ( >3rbc/hpf on 2 or more occassions).

Always confirm on repeat testing. Always confirm on repeat testing. Repeat urinalyses to Repeat urinalyses to establish whether significant hematuria is present must establish whether significant hematuria is present must be done within 3 to 6 months of the initial test. be done within 3 to 6 months of the initial test.

Look for glomerular origin of hematuria – If urinalysis Look for glomerular origin of hematuria – If urinalysis reveals Red cell casts/ dysmorphic RBCs or Renal function is reveals Red cell casts/ dysmorphic RBCs or Renal function is compromised/ new onset HTN, combined with mild compromised/ new onset HTN, combined with mild proteinuria proteinuria consider glomerulonephritis or renal consider glomerulonephritis or renal parenchymal diseaseparenchymal disease in such cases, next step is referral to a in such cases, next step is referral to a nephrologist and renal biopsy.nephrologist and renal biopsy.

Microscopic HematuriaMicroscopic Hematuria Rule out benign causes first. Rule out benign causes first. Some benign causes of Microhematuria :Some benign causes of Microhematuria :

A) ExerciseA) ExerciseB) Sexual activityB) Sexual activityC) MenstruationC) MenstruationD) UTID) UTIIf UTI is present ( symptoms and dipstick for leucoesterase are clues If UTI is present ( symptoms and dipstick for leucoesterase are clues that point towards infection) - treat it with antibiotics and repeat that point towards infection) - treat it with antibiotics and repeat urinalysis after the infection has cleared.urinalysis after the infection has cleared.E) Benign Prostatic HypertrophyE) Benign Prostatic HypertrophyF) ProstatitisF) Prostatitis

Recurrent painless Hematuria Recurrent painless Hematuria consider IgA nephropathy consider IgA nephropathy Other cluesOther clues 1. Consider strongly CA.Bladder in the elderly and in smokers1. Consider strongly CA.Bladder in the elderly and in smokers 2. R/O benign causes like BPH ( Ask for symptoms of BPH)2. R/O benign causes like BPH ( Ask for symptoms of BPH) 3. R/O Prostate Ca in the elderly and in those with family history3. R/O Prostate Ca in the elderly and in those with family historyDO NOT NEGLECT POSSIBILITY OF BLADDER CA IN Patients DO NOT NEGLECT POSSIBILITY OF BLADDER CA IN Patients

WITH HEMATURIAWITH HEMATURIA

Microscopic HematuriaMicroscopic Hematuria Symptomatic Microhematuria : If the microhematuria is associated Symptomatic Microhematuria : If the microhematuria is associated

with classic flank pain with classic flank pain next step is Non Contrast CT scan to next step is Non Contrast CT scan to rule out renal calculus. In pregnant women rule out renal calculus. In pregnant women do ultrasound to do ultrasound to avoid radiation. avoid radiation.

Asymptomatic MicroHematuria : Patients without the Asymptomatic MicroHematuria : Patients without the classic flank pain of urolithiasis should be evaluated classic flank pain of urolithiasis should be evaluated extensively. Once benign causes such as infection and the extensively. Once benign causes such as infection and the kidney ( glomerular) origin are ruled out, further approach kidney ( glomerular) origin are ruled out, further approach should be defined based on the patient's risk profile. should be defined based on the patient's risk profile.

For patients with low risk of urological disease, a less extensive work-up For patients with low risk of urological disease, a less extensive work-up may be appropriate ( First do may be appropriate ( First do upper tract imagingupper tract imaging and if this is negative, and if this is negative, add urine cytology+cystoscopy). add urine cytology+cystoscopy).

If the patient is a high risk of having a urological malignancy, extensive If the patient is a high risk of having a urological malignancy, extensive work-up is needed ( see the risk factors below) --> work-up is needed ( see the risk factors below) --> Upper tract imaging Upper tract imaging + cystoscopy+ urine cytology + cystoscopy+ urine cytology all are needed. Urine cytology should be all are needed. Urine cytology should be obtained in all patients with asymptomatic hematuria since it is an easy obtained in all patients with asymptomatic hematuria since it is an easy and non invasive step. Sensitivity of urine cytology is only 48% but and non invasive step. Sensitivity of urine cytology is only 48% but remember that if it is positive it is highly specific for urological cancer remember that if it is positive it is highly specific for urological cancer ( 94% specificity)( 94% specificity)

Painless HematuriaPainless HematuriaRisk Factors for Significant Disease in Patients with Microscopic Risk Factors for Significant Disease in Patients with Microscopic

HematuriaHematuria : : Smoking history Smoking history Occupational exposure to chemicals or dyes (benzenes or aromatic Occupational exposure to chemicals or dyes (benzenes or aromatic

amines) amines) History of gross hematuria History of gross hematuria Age >40 years Age >40 years History of urologic disorder or disease History of urologic disorder or disease History of irritative voiding symptoms History of irritative voiding symptoms History of urinary tract infection History of urinary tract infection Analgesic abuse Analgesic abuse History of pelvic irradiationHistory of pelvic irradiation Previous use of Cyclophosphamide ( increases the risk of bladder cancer Previous use of Cyclophosphamide ( increases the risk of bladder cancer

where as ongoing use often causes hemorrhagic cystitis as a adverse where as ongoing use often causes hemorrhagic cystitis as a adverse effect)effect)

These high-risk patients require aggressive work up with CT Urogram + These high-risk patients require aggressive work up with CT Urogram + Cystoscopy + Urine Cytology!Cystoscopy + Urine Cytology!

What Imaging Studies?What Imaging Studies?What imaging studies should be done as initial step in evaluating What imaging studies should be done as initial step in evaluating

Asymptomatic Hematuria?Asymptomatic Hematuria? For both high risk and low risk patients, For both high risk and low risk patients, upper tract imagingupper tract imaging must be must be

performed as an initial step. performed as an initial step. For upper tract imaging, For upper tract imaging, CT urographyCT urography ( i.e; non-contrast CT followed by ( i.e; non-contrast CT followed by

contrast CT imaging from kidney to bladder) is best recommended initial contrast CT imaging from kidney to bladder) is best recommended initial test now to evaluate asymptomatic hematuria. CT urography is less affected test now to evaluate asymptomatic hematuria. CT urography is less affected by overlying bowel gas and is more sensitive for detecting small tumors and by overlying bowel gas and is more sensitive for detecting small tumors and calculi than the IVP. calculi than the IVP.

IVP used to be the best preferred test for upper tract imaging in hematuria IVP used to be the best preferred test for upper tract imaging in hematuria evaluation but now CT urogram is becoming the preferred method. IVP and evaluation but now CT urogram is becoming the preferred method. IVP and ultrasound are good to image the urinary tract but they do not completely ultrasound are good to image the urinary tract but they do not completely assess the renal parenchyma. If you order an IVP, you may eventually need assess the renal parenchyma. If you order an IVP, you may eventually need to order a CT urogram again to image the parenchyma better - so, in order to order a CT urogram again to image the parenchyma better - so, in order to avoid ordering multiple studies, CT urogram is recommended as the best to avoid ordering multiple studies, CT urogram is recommended as the best initial test.initial test.

Upper tract imaging – preferred modality is Helical CT or CT Urogram ( If Upper tract imaging – preferred modality is Helical CT or CT Urogram ( If you do not find CT Urogram in the choices or if you want to reduce radiation you do not find CT Urogram in the choices or if you want to reduce radiation exposure such as in pregnant women, you can choose IVP+renal exposure such as in pregnant women, you can choose IVP+renal ultrasound for upper tract imaging ultrasound for upper tract imaging remember IVP is more invasive and we remember IVP is more invasive and we are not using now. So, where available, CT urogram is first choice for imaging are not using now. So, where available, CT urogram is first choice for imaging the upper tract. But if IVP is used it must be combined with renal ultrasound the upper tract. But if IVP is used it must be combined with renal ultrasound because IVP only images the tract but does not look at the kidney itself). because IVP only images the tract but does not look at the kidney itself).

In patients with high risk of bladder ca, Helical CT followed by urine cytology In patients with high risk of bladder ca, Helical CT followed by urine cytology and cystoscopy must all be performed. and cystoscopy must all be performed.

In patients with low risk for bladder ca, you may choose step-wise approach. In patients with low risk for bladder ca, you may choose step-wise approach. First step then is upper tract imaging. Then urine cytology or cystoscopy. First step then is upper tract imaging. Then urine cytology or cystoscopy.

Bladder CaBladder Ca

Most common histology is Transitional Cell caMost common histology is Transitional Cell ca Routine screening in all patients for bladder ca with Routine screening in all patients for bladder ca with

either urinalysis or cytology is either urinalysis or cytology is notnot recommended recommended Screening for bladder cancer in high risk individuals Screening for bladder cancer in high risk individuals

( those exposed to dyes/ leather, smokers) is ( those exposed to dyes/ leather, smokers) is controversial controversial no clear recommendations. no clear recommendations.

High risk History : Smoking history, Occupational High risk History : Smoking history, Occupational exposure to dyes, rubber, or leather, exposure to dyes, rubber, or leather, previous previous exposure to Cyclophosphamideexposure to Cyclophosphamide

Bladder CaBladder Ca Do not routinely screen but however, if you find Do not routinely screen but however, if you find

Hematuria ( even microscopic) on routine Hematuria ( even microscopic) on routine urinalysis that was done for another purpose urinalysis that was done for another purpose do not neglect this finding. ABNORMAL LAB do not neglect this finding. ABNORMAL LAB always need to be addressed always need to be addressed pursue further pursue further w/u for this hematuria ( BPH, Ca.Bladder, w/u for this hematuria ( BPH, Ca.Bladder, ca.prostate, cystitis, r/o glomerulonephritis)ca.prostate, cystitis, r/o glomerulonephritis)

Remember Micro-HEMATURIA is the Remember Micro-HEMATURIA is the most most commoncommon manifestation of bladder cancer. manifestation of bladder cancer.

Clinical Symps/ SignsClinical Symps/ Signs

Hematuria Hematuria Urinary frequency or dysuria Urinary frequency or dysuria Flank or suprapubic pain Flank or suprapubic pain Constitutional symptoms, such as weight lossConstitutional symptoms, such as weight loss Weight loss Weight loss Adenopathy Adenopathy Palpable suprapubic mass Palpable suprapubic mass Organomegaly Organomegaly BLADDER CA CAN BE TOTALLY BLADDER CA CAN BE TOTALLY

ASYMPTOMATICASYMPTOMATIC

IMPORTANTIMPORTANT

Refer all patients ( especially those at Refer all patients ( especially those at high risk) presenting with unexplained high risk) presenting with unexplained hematuria for cystoscopy, even if their hematuria for cystoscopy, even if their

hematuria is hematuria is intermittentintermittent, and regardless , and regardless of the findings on history and physical of the findings on history and physical

exam. exam.

Bladder Ca - DiagnosisBladder Ca - Diagnosis

Freshly voided urine sample for cytology Freshly voided urine sample for cytology Imaging of the urinary tract Imaging of the urinary tract Cystoscopy and exam under anesthesia with Cystoscopy and exam under anesthesia with

biopsies biopsies Additional diagnostic evaluations, based on Additional diagnostic evaluations, based on

findings from the cystoscopy and pathologic findings from the cystoscopy and pathologic evaluation of the tumor, to assess the upper evaluation of the tumor, to assess the upper urinary tract or to look for metastatic disease urinary tract or to look for metastatic disease lfts, ivp, cxr, ct scan of abd/pelvis, bone scan.lfts, ivp, cxr, ct scan of abd/pelvis, bone scan.

Bladder Ca - RxBladder Ca - Rx Surgical resection for non invasive bladder ca. Surgical resection for non invasive bladder ca. Radical Cystectomy – Rx of choice for muscle-invasive Radical Cystectomy – Rx of choice for muscle-invasive

bladder ca. bladder ca. Adjuvant Intravesical therapy with BCG/ mitomycin-c Adjuvant Intravesical therapy with BCG/ mitomycin-c

for for Cis, T1 tumors, tumor > 5cm size. Cis, T1 tumors, tumor > 5cm size. Adjuvant chemotherapy on case-by case basis Adjuvant chemotherapy on case-by case basis

gemcitabine+cisplatin or methotrexategemcitabine+cisplatin or methotrexate Local side effects of BCG include: Cystitis (90% of Local side effects of BCG include: Cystitis (90% of

patients) , Hematuria (30%) , Contracted bladder , patients) , Hematuria (30%) , Contracted bladder , Ureteral obstruction, Inflammation (prostatitis, Ureteral obstruction, Inflammation (prostatitis, epididymitis, epididymoorchitis) epididymitis, epididymoorchitis)

Systemic side effects of BCG, which should resolve in Systemic side effects of BCG, which should resolve in 48 hours, include: Flu-like symptoms , Arthralgias , 48 hours, include: Flu-like symptoms , Arthralgias , Rash Rash

Bladder Ca Bladder Ca

Post – radical cystectomy requires urinary Post – radical cystectomy requires urinary diversion diversion

External diversions include conduits, usually External diversions include conduits, usually composed of a section of bowel (ileum or composed of a section of bowel (ileum or colon). colon).

Internal conduits include those that require a Internal conduits include those that require a stoma to empty the reservoir (Kock pouch and stoma to empty the reservoir (Kock pouch and Indiana pouch) and orthotopic replacements Indiana pouch) and orthotopic replacements (e.g., Le Bag, Mainz pouch, (e.g., Le Bag, Mainz pouch,

Complications – Urinary diversionComplications – Urinary diversion

Watch for the following after urinary diversion: Watch for the following after urinary diversion: Bleeding , Infection , Hernias , Necrosis , Reflux, Bleeding , Infection , Hernias , Necrosis , Reflux,

Incontinence , Obstruction of conduit, upper tract, or Incontinence , Obstruction of conduit, upper tract, or intestines and Recurrent cancer intestines and Recurrent cancer

Monitor for bacteremia, treat patients with Monitor for bacteremia, treat patients with ProteusProteus or or PseudomonasPseudomonas sp., and observe patients with other sp., and observe patients with other organisms if they are asymptomatic. organisms if they are asymptomatic.

Monitor closely: Monitor closely: Vitamin B12 levels , Acid/base status , Electrolyte levels and Vitamin B12 levels , Acid/base status , Electrolyte levels and

Bone mineralizationBone mineralization

Painful HematuriaPainful Hematuria

UTI/ Cystitis/ PyelonephritisUTI/ Cystitis/ Pyelonephritis Renal CalculiRenal CalculiIMAGING CHOICES: IMAGING CHOICES: Computed tomography ( NON CONTRAST) is the Computed tomography ( NON CONTRAST) is the

best imaging modality for the evaluation of urinary best imaging modality for the evaluation of urinary stones, renal and perirenal infections, and associated stones, renal and perirenal infections, and associated complications complications

Ultrasound : Excellent for detection and Ultrasound : Excellent for detection and characterization of renal cysts (Limitations in detection characterization of renal cysts (Limitations in detection of small solid lesions (<3 cm)) of small solid lesions (<3 cm)) Also, used for stones Also, used for stones eval in pregnancy. eval in pregnancy.

Prostate DisordersProstate Disorders•Benign Prostate HypertrophyBenign Prostate Hypertrophy•Prostatitis – Acute & ChronicProstatitis – Acute & Chronic

•Carcinoma of ProstateCarcinoma of Prostate•Chemoprophylaxis of Prostate cancerChemoprophylaxis of Prostate cancer

•Utility of PSA ( see Oncology)Utility of PSA ( see Oncology)

ElectrolytesElectrolytes

HypernatremiaHypernatremia

HypernatremiaHypernatremia

Defined as serum sodium > 145 meq/LDefined as serum sodium > 145 meq/L Hospital acquired in >80% of patientsHospital acquired in >80% of patients Requires defect in renal concentrating ability and Requires defect in renal concentrating ability and

defect in thirst mechanismdefect in thirst mechanism Normal patients do not become hypernatremicNormal patients do not become hypernatremic Hypernatremia occurs in very young and very Hypernatremia occurs in very young and very

old with a defect in thirstold with a defect in thirst Isovolemic, Hypovolemic & HypervolemicIsovolemic, Hypovolemic & Hypervolemic

Isovolemic Hypernatremia : Usually hemodynaically Isovolemic Hypernatremia : Usually hemodynaically stable unless serum sodium > 170 meq/Lstable unless serum sodium > 170 meq/L

Causes:Causes: HypodipsiaHypodipsia Increases insensible lossesIncreases insensible losses Nephrogenic diabetes insipidus – congenital, Nephrogenic diabetes insipidus – congenital,

acquired acquired CRF, Hypokalemia, Hypercalcemia, Sickle cell CRF, Hypokalemia, Hypercalcemia, Sickle cell disease Amyloidosis, Obstruction, Alcohol, Lithium, disease Amyloidosis, Obstruction, Alcohol, Lithium, Demeclocycline, Glyburide, AmphotericinDemeclocycline, Glyburide, Amphotericin

Essential hypernatremiaEssential hypernatremia Central Diabetes Insipidus : Granulomas, Histiocytosis, Central Diabetes Insipidus : Granulomas, Histiocytosis,

Infections, CVA, Postpartum necrosis, Pregnancy, Head Infections, CVA, Postpartum necrosis, Pregnancy, Head traumaPost hypophysectomy, Suprasellar masses, Intrasellar traumaPost hypophysectomy, Suprasellar masses, Intrasellar massesmasses

PolyuriaPolyuria

? Water or solute diuresis? Water or solute diuresis Water diuresis i.e. diabetes insipidus vs Water diuresis i.e. diabetes insipidus vs

polydipsia ( Upolydipsia ( Uosmosm < 150 mOsm ) < 150 mOsm )

Solute diuresis i.e. electrolyte vs non electrolyte ( Solute diuresis i.e. electrolyte vs non electrolyte ( UUosm osm 300 - 400 mOsm )300 - 400 mOsm )

Diagnostics: Urinalysis, urine osmolality, and Diagnostics: Urinalysis, urine osmolality, and urine electrolytesurine electrolytes

Hypovolemic Hypernatremia Causes Hypovolemic Hypernatremia Causes Renal causesRenal causes Loop diureticsLoop diuretics Osmotic diuresisOsmotic diuresis

Gastrointestinal causesGastrointestinal causes Vomiting / nasogastric drainageVomiting / nasogastric drainage Diarrhea / catharticsDiarrhea / cathartics

Water loss into cellsWater loss into cells Exercise / seizuresExercise / seizures

Cuteaneous causesCuteaneous causes Burns / excessive sweatingBurns / excessive sweating

Hypervolemic HypernatremiaHypervolemic HypernatremiaCauses :Causes :

Hypertonic sodium solutionsHypertonic sodium solutions Hypertonic feedingsHypertonic feedings Ingestion of sea waterIngestion of sea water Hypertonic dialysisHypertonic dialysis Primary aldosteronismPrimary aldosteronism Cushing’s syndromeCushing’s syndrome

Signs and Symptoms HypernatremiaSigns and Symptoms Hypernatremia

Depend on rate, degree and duration Depend on rate, degree and duration Depressed sensoriumDepressed sensorium IrritabilityIrritability Focal neurologic deficits / seizuresFocal neurologic deficits / seizures Muscle spasmsMuscle spasms Nausea/vomitingNausea/vomiting Thirst / feverThirst / fever Volume depletion / hyperglycemiaVolume depletion / hyperglycemia

Therapy of HypernatremiaTherapy of Hypernatremia Hemodynamic or osmolal problem?Hemodynamic or osmolal problem? Acute or chronic problem?Acute or chronic problem? Prior losses and present losses?Prior losses and present losses? Rate of correction?Rate of correction?

Acute: 1-1.5 meq/L/hour reductionAcute: 1-1.5 meq/L/hour reduction Chronic: 0.5 meq/L/hour reduction or 50% within first 24hoursChronic: 0.5 meq/L/hour reduction or 50% within first 24hours

-- WHICH FLUID ? WHICH FLUID ? IsovolemicIsovolemic

water: PO or intravenouswater: PO or intravenous Water deficit = 0.6 (BWWater deficit = 0.6 (BWKgKg) x (P) x (Pnana/140 -1)/140 -1)

Hypovolemic – unstable pt????Hypovolemic – unstable pt???? Correct volume problem i.e. normal salineCorrect volume problem i.e. normal saline Correct osmolal problemCorrect osmolal problem

HypervolemicHypervolemic Salt removal with loop diuretics and free waterSalt removal with loop diuretics and free water

CASE STUDYCASE STUDY

HypercalcemiaHypercalcemia EtiologyEtiology Clinical features : bones, moans, stones, groansClinical features : bones, moans, stones, groans Investigations: Ca, Phos, EKG, PTH, Urinary calcium excretion ( R/o familial Investigations: Ca, Phos, EKG, PTH, Urinary calcium excretion ( R/o familial

hypocalciuric hypercalcemia)hypocalciuric hypercalcemia) Management:Management: Criteria for surgery in primary hyperparathyroidismCriteria for surgery in primary hyperparathyroidism Sestamibi scan only if surgery is planned/indicatedSestamibi scan only if surgery is planned/indicated Hypercalcemic crisis management – ivf + lasix after volume repletion onlyHypercalcemic crisis management – ivf + lasix after volume repletion only Indications for corticosteroids : are useful for treating Indications for corticosteroids : are useful for treating hypercalcemiahypercalcemia caused caused

by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases sarcoidosis, and other granulomatous diseases

Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium gland to extracellular calcium. Also results in concomitant serum calcium decrease decrease Indicated for Indicated for hypercalcemiahypercalcemia with parathyroid carcinoma. with parathyroid carcinoma.

Do not lower Calcium too much Do not lower Calcium too much Serum calcium reduction may cause lowered Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; seizure threshold, paresthesia, myalgia, cramping, and tetany;

Criteria for Surgery – Primary Criteria for Surgery – Primary hyperparathyroidismhyperparathyroidism

Serum total calcium level >12 mg per dL (3 mmol per L) at any time Serum total calcium level >12 mg per dL (3 mmol per L) at any time Hyperparathyroid crisis (discrete episode of life-threatening Hyperparathyroid crisis (discrete episode of life-threatening

hypercalcemiahypercalcemia) ) Marked hypercalciuria (urinary calcium excretion more than 400 mg Marked hypercalciuria (urinary calcium excretion more than 400 mg

per day) per day) Nephrolithiasis Nephrolithiasis Impaired renal function Impaired renal function Osteitis fibrosa cystica Osteitis fibrosa cystica Reduced cortical bone density (measure with dual x-ray Reduced cortical bone density (measure with dual x-ray

absorptiometry or similar technique) absorptiometry or similar technique) Bone mass more than two standard deviations below age-matched controls (Z Bone mass more than two standard deviations below age-matched controls (Z

score less than 2) score less than 2) Classic neuromuscular symptoms Classic neuromuscular symptoms Proximal muscle weakness and atrophy, Proximal muscle weakness and atrophy, hyperreflexiahyperreflexia, and gait , and gait

disturbance disturbance Age younger than 50Age younger than 50

Hypercalcemia – Breast CancerHypercalcemia – Breast Cancer

Management: Management: Principal Rx : Bisphosphonates for moderate to severe Principal Rx : Bisphosphonates for moderate to severe

hypercalcemia ( Aridia, Zolendronic acid) ( and also hypercalcemia ( Aridia, Zolendronic acid) ( and also prevent osteoporosis) ( esply pts on Aromatase prevent osteoporosis) ( esply pts on Aromatase inhibitors are even prone to osteoporosis)inhibitors are even prone to osteoporosis)

Manage hypercalcemic crises as in all other cases ( IV Manage hypercalcemic crises as in all other cases ( IV Fluids and only after complete hydration, then Fluids and only after complete hydration, then furosemide)furosemide)

HyponatremiaHyponatremia

Classify – Hypotonic, Isotonic and HypertonicClassify – Hypotonic, Isotonic and Hypertonic Classify – hypovolemic or euvolemicClassify – hypovolemic or euvolemic Hypovolemic Hyponatremia – Diarrhea, Vomiting, Hypovolemic Hyponatremia – Diarrhea, Vomiting,

early excess diuresisearly excess diuresis Euvolemic Hyponatremia Euvolemic Hyponatremia SIADH SIADH Isotonic Hyponatremia Isotonic Hyponatremia Pseudohyponatremia Pseudohyponatremia

( Hyperglycemia, Hypertriglyceridemia, does not occur ( Hyperglycemia, Hypertriglyceridemia, does not occur with uremia)with uremia)

Rx Rx Correct volume and then osmolal problem Correct volume and then osmolal problem Volume problem Volume problem Isotonic saline always !!!!!!!!!! Isotonic saline always !!!!!!!!!! Asymptomatic Asymptomatic fluid restriction fluid restriction CNS symptoms CNS symptoms 3% Saline 3% Saline

HyperkalemiaHyperkalemia

Several causes : Medication interaction is a Several causes : Medication interaction is a common one ( ACEI+Spironolactone+beta common one ( ACEI+Spironolactone+beta blocker, HEPARIN), renal failure, Addisons blocker, HEPARIN), renal failure, Addisons disease, Rhabdomyolysis, Metabolic acidosis, disease, Rhabdomyolysis, Metabolic acidosis, Hyperglycemic states. Hyperglycemic states.

Effects : arrhythmias, Can lead to tall tented t-Effects : arrhythmias, Can lead to tall tented t-waves on EKG waves on EKG

Ekg- HyperkalemiaEkg- Hyperkalemia

The following changes may be seen in hyperkalaemiaThe following changes may be seen in hyperkalaemia small or absent P waves small or absent P waves atrial fibrillation atrial fibrillation wide QRS wide QRS shortened or absent ST segment shortened or absent ST segment wide, tall and tented T waves wide, tall and tented T waves ventricular fibrillation ventricular fibrillation

58 year old man on haemodialysis presents with profound weakness after a weekend fishing trip.

The man’s K was 9.6The man’s K was 9.6

Next Step Next Step IV CALCIUM CHLORIDE IV CALCIUM CHLORIDE ( CALCIUM GLUCONATE AN ( CALCIUM GLUCONATE AN

ALTERNATIVE)ALTERNATIVE)

30 y/o woman evaluated in the emergency department for a 2-day history of muscle weakness. An electrocardiogram taken in the emergency department is shown.

Which of the following is the best immediate treatment option?

( A ) Hemodialysis ( B ) 50% glucose, 50 mL, intravenously ( C ) Calcium gluconate, 10 mL ( D ) Sodium polystyrene sulfonate (Kayexalate), 50 g, in

sorbitol, rectally ( E ) Peritoneal dialysis

Hyperkalemia - TreatmentHyperkalemia - Treatment

MNEMONIC – CBIGKDropMNEMONIC – CBIGKDrop Check the EKG Check the EKG If EKG changes, calcium If EKG changes, calcium

gluconate IVgluconate IV B – BICARBONATE/ Beta agonistsB – BICARBONATE/ Beta agonists I – INSULINI – INSULIN G – DEXTROSEG – DEXTROSE K – KAYEXALATE If total body potassium is K – KAYEXALATE If total body potassium is

an issuean issue D – Hemodialysis for refractory HyperkalemiaD – Hemodialysis for refractory Hyperkalemia

HYPOKALEMIA - EKGHYPOKALEMIA - EKG

The following changes may be seen in The following changes may be seen in hypokalaemia.hypokalaemia.

small or absent T waves small or absent T waves prominent U waves prominent U waves first or second degree AV block first or second degree AV block slight depression of the ST segment slight depression of the ST segment

Acid Base DisordersAcid Base Disorders

Formulas, Case studies and Formulas, Case studies and ManagementManagement

Acid Base DisordersAcid Base Disorders

Metabolic AlkalosisMetabolic Alkalosis Respiratory AlkalosisRespiratory Alkalosis Metabolic AcidosisMetabolic Acidosis Respiratory AcidosisRespiratory Acidosis Mixed DisordersMixed Disorders

Acid Base DisordersAcid Base Disorders

Common clinical problemsCommon clinical problems Associated with life threatening conditionsAssociated with life threatening conditions Often misdiagnosedOften misdiagnosed Demands an understanding of physiology and Demands an understanding of physiology and

pathophysiologypathophysiology pH is a major determinant of enzymatic reactions pH is a major determinant of enzymatic reactions

– Acedemia denatures the enzymes, decreases – Acedemia denatures the enzymes, decreases threshold for ventricular fibrillation and increases threshold for ventricular fibrillation and increases respiratory drive. Alkalemia suppresses respiratory respiratory drive. Alkalemia suppresses respiratory drive, can cause myocardial ischemia, coronary drive, can cause myocardial ischemia, coronary vasospasm etcvasospasm etc

Acid Base DisordersAcid Base Disorders- CARBONIC ACID - BICARBONATE - CARBONIC ACID - BICARBONATE

SYSTEM : H + HCOSYSTEM : H + HCO33 ↔↔ H H22COCO33 ↔ ↔ H H22O + O +

COCO22

- HENDERSON-HASSELBACHHENDERSON-HASSELBACHEQUATION : pH = pKEQUATION : pH = pKa a + log HCO+ log HCO33 / H2CO / H2CO33

- PLASMA ACIDITYPLASMA ACIDITY : determined by : : determined by :

Balance between concentration of plasma Balance between concentration of plasma

bicarbonate and pCO2bicarbonate and pCO2

Measured as pH or H ion concentrationMeasured as pH or H ion concentration

Acid Base DisordersAcid Base Disorders1. Factors affecting plasma Bicarbonate :1. Factors affecting plasma Bicarbonate : Rate of H ion inputRate of H ion input Rate of H ion excretion via kidneysRate of H ion excretion via kidneys Rate of H ion or bicarbonate loss via GI tractRate of H ion or bicarbonate loss via GI tract Availability of non bicarbonate buffersAvailability of non bicarbonate buffers Volume of distribution of bicarbonateVolume of distribution of bicarbonate2. Factors affecting pCO2 2. Factors affecting pCO2 Rate of CO2 excretion via alveolar ventilationRate of CO2 excretion via alveolar ventilation Rate of CO2 productionRate of CO2 production

ACIDEMIA-ALKALEMIAACIDEMIA-ALKALEMIA Refers to plasma acidityRefers to plasma acidity Acidemia: pH < 7.36Acidemia: pH < 7.36 Alkalemia: pH > 7.44Alkalemia: pH > 7.44

Metabolic Disorder: Metabolic Disorder: - Acid-base disorder caused by primary - Acid-base disorder caused by primary

change in plasma bicarbonatechange in plasma bicarbonate - Plasma bicarbonate = 24-28 meq/L- Plasma bicarbonate = 24-28 meq/L Respiratory DisorderRespiratory Disorder- Acid-base disorder caused by primary - Acid-base disorder caused by primary

change in pCO2change in pCO2- pCO2 = 36 - 44 mmHgpCO2 = 36 - 44 mmHgCompensatory Mechanisms : Compensatory Mechanisms :

Appropriate proportional physiologic Appropriate proportional physiologic responses responses which tend to restore pH which tend to restore pH toward, but not to normaltoward, but not to normal

Terms “over” and “under” Terms “over” and “under” compensation should be avoidedcompensation should be avoided – – INSTEAD USE “ MIXED “ INSTEAD USE “ MIXED “ DISORDER!!!DISORDER!!!

Metabolic AcidosisMetabolic Acidosis Calculate Anion Gap : Na - (Cl + HCOCalculate Anion Gap : Na - (Cl + HCO33) - Normal 3 - 10 ) - Normal 3 - 10

meq/Lmeq/L Given entirely by Unmeasured anions are related to (-) charge Given entirely by Unmeasured anions are related to (-) charge

on albumin on albumin One gram albumin = 2.5 meq/L anion One gram albumin = 2.5 meq/L anioni.e.i.e. Albumin of 4 gm/L, baseline anion gap would be 10 Albumin of 4 gm/L, baseline anion gap would be 10 meq/L which is Normal. Correct Gap for Albumin!!! meq/L which is Normal. Correct Gap for Albumin!!! If If albumin is 2gm%, the baseline anion gap should be 5 in albumin is 2gm%, the baseline anion gap should be 5 in which case 10 should be assumed as increased Anion gap.which case 10 should be assumed as increased Anion gap.

Delta Gap : Delta AG / Delta HCO3:Delta Gap : Delta AG / Delta HCO3: 1:1 = Anion gap acidosis1:1 = Anion gap acidosis

>1 = Anion gap acidosis plus metabolic alkalosis >1 = Anion gap acidosis plus metabolic alkalosis < 1 = Increased Anion gap acidosis plus normal < 1 = Increased Anion gap acidosis plus normal

anion gap acidosisanion gap acidosis Classify Metabolic Acidosis Classify Metabolic Acidosis – – Increased GapIncreased Gap - Normal Anion gap- Normal Anion gap - Mixed : Gap + non gap- Mixed : Gap + non gap

Calculate CompensationCalculate Compensation Compensation Metabolic AcidosisCompensation Metabolic Acidosis Occurs in 12-24 hours and limit PCO2 10 Occurs in 12-24 hours and limit PCO2 10

mmHg :mmHg :Expected Expected pCO2 = 1.5x HCO3 + 8 +/- 2pCO2 = 1.5x HCO3 + 8 +/- 2pCO2 = last 2 digits pHpCO2 = last 2 digits pHpCO2 = HCO3 + 15pCO2 = HCO3 + 15

If measured Pco2 is less than expected pco2 as If measured Pco2 is less than expected pco2 as calculated by this equation – suspect a primary calculated by this equation – suspect a primary respiratory alkalosis. If it is more than expected respiratory alkalosis. If it is more than expected suspect primary respiratory acidosis. This is how suspect primary respiratory acidosis. This is how you diagnose mixed disorders!!!you diagnose mixed disorders!!!

ExampleExample 65 y/o man with CAD 65 y/o man with CAD and then and then

cardiogenic shock. Ph 7.26. PCo2 40 HCO3- cardiogenic shock. Ph 7.26. PCo2 40 HCO3- 10 Na+ 136 Cl- 110 Albumin 2.010 Na+ 136 Cl- 110 Albumin 2.0

2.2. What's the Anion Gap?What's the Anion Gap?3.3. Corrected Anion Gap ? {gap + 2.5(measured Corrected Anion Gap ? {gap + 2.5(measured

albumin)}albumin)}4.4. Delta Anion Gap?Delta Anion Gap?5.5. Delta Hco3-? ( 24 – bicarb)Delta Hco3-? ( 24 – bicarb)6.6. Delta Gap?Delta Gap?7.7. Adequately Compensated or mixed ?Adequately Compensated or mixed ?8.8. Name the disorder ? Name the disorder ?

Normal Anion-Gap Metabolic AcidosisNormal Anion-Gap Metabolic AcidosisGastrointestinal Loss of BicarbonateGastrointestinal Loss of Bicarbonate DiarrheaDiarrhea Urinary diversionUrinary diversion Small bowel, pancreatic, or bile drainage ( fistulas, surgical Small bowel, pancreatic, or bile drainage ( fistulas, surgical

drains )drains ) CholestiramineCholestiramine

Renal Loss of Bicarbonate ( or Bicarbonate equivalent )Renal Loss of Bicarbonate ( or Bicarbonate equivalent ) Renal tubular acidosisRenal tubular acidosis Recovery phase of KetoacidosisRecovery phase of Ketoacidosis Renal InsufficiencyRenal Insufficiency Acidifying Substances- HCl, NH4Cl, Arginine HCl, Lysine HCl, Acidifying Substances- HCl, NH4Cl, Arginine HCl, Lysine HCl,

Sulfur Sulfur

To differentiate calculate Urinary Anion Gap = Urine (Na + k) – To differentiate calculate Urinary Anion Gap = Urine (Na + k) – (cl-). Normal is from +10 to -10. If UAG > +10 (cl-). Normal is from +10 to -10. If UAG > +10 Renal loss. Renal loss. If UAG < -10 or more negative If UAG < -10 or more negative GI Causes ( neGUTive) GI Causes ( neGUTive)

Increased Anion Gap AcidosisIncreased Anion Gap Acidosis

Ketoacidosis - diabetic, alcoholic, starvationKetoacidosis - diabetic, alcoholic, starvation Lactic acidosisLactic acidosis UremiaUremia Toxins - Ethylene glycol, methanol, salicylate, Toxins - Ethylene glycol, methanol, salicylate,

paraldehyde paraldehyde Osmolar Gap = Measured Osmolarity – Osmolar Gap = Measured Osmolarity –

Calculated OsmolarityCalculated Osmolarity Calculated SerumCalculated Serumosmosm = 2(Na) + Glucose/18 = 2(Na) + Glucose/18

+BUN/2.8 ( + ethylalcohol/4.5)+BUN/2.8 ( + ethylalcohol/4.5)

Plasma Level v. OsmolalityPlasma Level v. Osmolality

Ethanol ÷ 4.6Ethanol ÷ 4.6

Methanol ÷ 3.2Methanol ÷ 3.2

Ethylene glycol ÷ 6.2 Ethylene glycol ÷ 6.2

Isopropanol ÷ 6.1Isopropanol ÷ 6.1

For example, a blood ethanol level of 100mg/dL For example, a blood ethanol level of 100mg/dL would increase plasma osmolality 100/4.6 or 22 would increase plasma osmolality 100/4.6 or 22 mOsm/LmOsm/L

Case StudyCase Study Sam is a 35 y/o alcoholic who is brought to the ER in a comatose state. Sam’s Sam is a 35 y/o alcoholic who is brought to the ER in a comatose state. Sam’s

wife tells you that she had an argument in the evening about 5 hrs ago over wife tells you that she had an argument in the evening about 5 hrs ago over Sam’s alcohol habits. Sam apparently got mad over the discussion, drove his Sam’s alcohol habits. Sam apparently got mad over the discussion, drove his car and returned an hour ago in a very intoxicated state. Wife called the EMS car and returned an hour ago in a very intoxicated state. Wife called the EMS and rushed him to the ER. On examination Sam is disoriented and and rushed him to the ER. On examination Sam is disoriented and hallucinating , Pulse 120 Tm 99, RR 26 BP 126/76. The rest of the physical hallucinating , Pulse 120 Tm 99, RR 26 BP 126/76. The rest of the physical exam is normal except for stuporos state and alcohol smell. Lab studies exam is normal except for stuporos state and alcohol smell. Lab studies revealed Na 130 k 3.4 cl- 95 Hco3 16, Glucose 90 Creatinine 1.6 BUN 45. revealed Na 130 k 3.4 cl- 95 Hco3 16, Glucose 90 Creatinine 1.6 BUN 45. Blood Ethylalcohol level was 180. Serum osmolarity was 360mg%. ABGs Blood Ethylalcohol level was 180. Serum osmolarity was 360mg%. ABGs revealed 7.28, Pco2 28, Po2 76 Sao2 93. The next best step in management ?revealed 7.28, Pco2 28, Po2 76 Sao2 93. The next best step in management ?

A) Endotracheal intubation in view of severe acidosisA) Endotracheal intubation in view of severe acidosis B) Hemodialysis because this is an acute renal failure causing acidosisB) Hemodialysis because this is an acute renal failure causing acidosis C) Fomepizole because of suspicion of ethylene glycol intoxicationC) Fomepizole because of suspicion of ethylene glycol intoxication D) Supportive treatment for now because this is an ethylalcohol induced D) Supportive treatment for now because this is an ethylalcohol induced

lactic acidosislactic acidosis E) Bicarbonate drip to reverse the acidosis because this is renal tubular E) Bicarbonate drip to reverse the acidosis because this is renal tubular

acidosisacidosis

Ethylene Glycol PoisoningEthylene Glycol Poisoning Envelope shaped crystals Envelope shaped crystals

Treatment : Consider Antidote Treatment : Consider Antidote ( Fomepizole or Ethanol ) if Level > ( Fomepizole or Ethanol ) if Level > 20mg% or if you suspect ethylene 20mg% or if you suspect ethylene glycol intake with 2 or more – a) glycol intake with 2 or more – a) arterial ph < 7.3, Hco3 <20, osmolar arterial ph < 7.3, Hco3 <20, osmolar gap>10, calcium oxalate crystals in gap>10, calcium oxalate crystals in urine.urine.

Antidote blocks Alcohol Antidote blocks Alcohol dehydrogenase and prevents the dehydrogenase and prevents the Glycolic acid formation. In case of Glycolic acid formation. In case of methanol, toxic meatbolite is formic methanol, toxic meatbolite is formic acidacid

Ethylene glycol found in Ethylene glycol found in antifreeze and de-icerantifreeze and de-icer

Toxicity results at doses >1.0 Toxicity results at doses >1.0 ml/kg ml/kg Ethylene glycol causes CNS Ethylene glycol causes CNS

depression , converts to depression , converts to Glycolic AcidGlycolic Acid (metabolite) (metabolite) effects effects Metabolic AcidosisMetabolic Acidosis & &Renal FailureRenal Failure

Oxalic acid (metabolite) Oxalic acid (metabolite) effects effects Calcium oxalate Calcium oxalate crystal depositioncrystal deposition

C/F: C/F: Confusion, Ataxia, Confusion, Ataxia, Slurred speech Slurred speech ,Hallucination, ,Hallucination, TetanyTetany SeizureSeizures (s (HypocalcemiaHypocalcemia) )

HypertensionHypertension Tachycardia Tachycardia

Increased Osmolal GapIncreased Osmolal Gap

EthanolEthanol MethanolMethanol Ethylene GlycolEthylene Glycol FormaldehydeFormaldehyde Paraldehyde Paraldehyde Lactic AcidosisLactic Acidosis ESRDESRD KetoacidosisKetoacidosis

MannitolMannitol Isopropyl alcoholIsopropyl alcohol HyperlipidemiaHyperlipidemia HyperproteinemiaHyperproteinemia Diethyl etherDiethyl ether

Isopropanol IngestionIsopropanol Ingestion

Present with CNS depression, hypotension, Present with CNS depression, hypotension, arrhytmias and gastritisarrhytmias and gastritis

Acetest reaction positiveAcetest reaction positive Increased osmolal gapIncreased osmolal gap No metabolic acidosisNo metabolic acidosis Anion gap normalAnion gap normal

Renal Tubular AcidosisRenal Tubular Acidosis

Type 1 ( distal)Type 1 ( distal) Type 2 (proximal)Type 2 (proximal) Type 4 (hyporeninemic hypoaldosteronism)Type 4 (hyporeninemic hypoaldosteronism)

Type I RTA (Distal)Type I RTA (Distal)

Causes: autoimmune diseases, hyperglobinemia Causes: autoimmune diseases, hyperglobinemia states and hereditarystates and hereditary

Present with normal anion gap acidosis, urine pH Present with normal anion gap acidosis, urine pH >5.5, hypokalemia, hypercalciuria, >5.5, hypokalemia, hypercalciuria, nephrocalcinosis and stonesnephrocalcinosis and stones

Treatment: alkali i.e. K citrateTreatment: alkali i.e. K citrate

Type II RTA (Proximal)Type II RTA (Proximal)

Isolated defect or associated with generalized proximal Isolated defect or associated with generalized proximal dysfunction i.e. Fanconi syndromedysfunction i.e. Fanconi syndrome

Failure to reclaim filtered bicarbonateFailure to reclaim filtered bicarbonate Increase FEIncrease FEHCO3HCO3

Urine pH > 5.5, but may be < 5.5 once HCOUrine pH > 5.5, but may be < 5.5 once HCO33 < 16 < 16 meq/Lmeq/L

Causes: Causes: Multiple myelomaMultiple myeloma AcetozolamideAcetozolamide Ifosfamide Ifosfamide Lead, cadmium, copperLead, cadmium, copper

Type 4 RTAType 4 RTA

Hypoaldosteronism or aldosterone resistanceHypoaldosteronism or aldosterone resistance Causes: diabetes mellitus, HIV and tubulo-Causes: diabetes mellitus, HIV and tubulo-

interstitial diseaseinterstitial disease Present with hyperkalemia, normal anion gap Present with hyperkalemia, normal anion gap

acidosis and normal urine pH acidosis and normal urine pH

Metabolic AlkalosisMetabolic Alkalosis

Calculate compensation Calculate compensation

PCO2= ( 0.7 x HCO3 ) + 21 . If measured Pco2 PCO2= ( 0.7 x HCO3 ) + 21 . If measured Pco2 is more than this then there is concomitant is more than this then there is concomitant respiratory acidosis. If less than this then respiratory acidosis. If less than this then concomitant respiratory akalosis.concomitant respiratory akalosis.

Delta Gap to r/o mixed disorder – metabolic Delta Gap to r/o mixed disorder – metabolic acidosis + metabolic alkalosis if delta gap >1acidosis + metabolic alkalosis if delta gap >1

Causes of Metabolic AlkalosisCauses of Metabolic Alkalosis Saline responsive : ECF depleted ( contraction alkalosis ), Urine Saline responsive : ECF depleted ( contraction alkalosis ), Urine

chloride < 10 meq/L, do not go by urine sodium in assessing chloride < 10 meq/L, do not go by urine sodium in assessing volume statusvolume status

Gastrointestinal Loss eg : Surreptious vomiting, NG tube Gastrointestinal Loss eg : Surreptious vomiting, NG tube suctions,Villous adenoma, Chloride diarrhea, Diuretics (late),Post suctions,Villous adenoma, Chloride diarrhea, Diuretics (late),Post hypercapneahypercapnea

Saline resistant : Saline Resistant Metabolic AlkalosisSaline resistant : Saline Resistant Metabolic Alkalosis , , Increased Increased mineralocorticoid effect,Urine Cl > 20 meq/Lmineralocorticoid effect,Urine Cl > 20 meq/L

Hypertensive causes:Primary aldosteronismCushing’s syndrome, Hypertensive causes:Primary aldosteronismCushing’s syndrome, 11 or 17 hydroxylase deficiency, Licorice / carbenoxolone, 11 or 17 hydroxylase deficiency, Licorice / carbenoxolone, Liddle’s syndrome, SteroidsLiddle’s syndrome, Steroids

Normotensive causes: Bartter’s syndrome ( thiazide), Gitelman’s Normotensive causes: Bartter’s syndrome ( thiazide), Gitelman’s syndrome ( like loop diuretic), Diuretics (present), Severe syndrome ( like loop diuretic), Diuretics (present), Severe potassium depletion, Severe magnesium depletionpotassium depletion, Severe magnesium depletion

Metabolic Alkalosis - TreatmentMetabolic Alkalosis - Treatment

Saline responsiveSaline responsive Normal saline to volume repleteNormal saline to volume replete KClKCl

Saline resistantSaline resistant Inhibit or remove excess mineralocorticoid effectInhibit or remove excess mineralocorticoid effect

MiscellaneousMiscellaneous Acetazolamide, HCl, NH4ClAcetazolamide, HCl, NH4Cl Hemodialysis Hemodialysis

Case StudyCase Study A 26 year old woman presents to the ER with generalized weakness associated with

perioral numbness. She is moderately built and looks slightly depressed. On physical exam, she has mild pallor. She denies use of any medications. BP 120/88 mmHg and physical exam is normal. Lab data: Cr 1.2mg/dL, BUN 15mg/dLNa 136 , K 2.8 , Cl 88 , HCO3 38. Urine Na 45 meq/L, Urine K 35 meq/L, Urine Cl 8 meq/L, Urine specific gravity 1.010, Urine pH 7

The most likely diagnosis is :D) Laxative AbuseE) Surreptious vomitingF) Licorice abuseG) Malabsorption SyndromeH) Hyporeninemic Hypoaldosteronism

Treatment : K) IV normal salineL) SpronolactoneM) AmilorideN) Psychiatry consultO) Reassurance because this is self limiting