Nephrology & Nephrology & UrologyUrology

Archer Online USMLE Archer Online USMLE ReviewsReviews

www.ccsworkshop.com All rights reservedAll rights reserved

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

Glomerular, tubular, intersititialGlomerular, tubular, intersititial Indicators : BUN/CREA, FeNA, Urine Indicators : BUN/CREA, FeNA, Urine

Spgravity, serum Sodium, serum osmolality, Spgravity, serum Sodium, serum osmolality, urine output.urine output.

Chronic – stages Chronic – stages elective hemodialysis elective hemodialysis Stage V, Emergent hemodialysis indications Stage V, Emergent hemodialysis indications

Acute tubular necrosis : toxic, pigment Acute tubular necrosis : toxic, pigment induced, Ischemicinduced, Ischemic

Evaluating renal function : urinalysis - ? Evaluating renal function : urinalysis - ? Protein, ?rbc , ? Wbc, ? Casts , ? Crystals, ? Protein, ?rbc , ? Wbc, ? Casts , ? Crystals, ? Bacteria, ? Nitrite, ? Cytology , ? Bacteria, ? Nitrite, ? Cytology , ? Leucoesterase, Leucoesterase,

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

RENAL BIOPSYRENAL BIOPSY

Indications: Indications: Nephrotic syndromeNephrotic syndrome

Glomerular diseaseGlomerular disease

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

bleeding, severe hypertension. bleeding, severe hypertension. obesity and uncooperative patientobesity and uncooperative patient

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 CAUSES OF NONOLIGURIC PRE RENAL ARFPRE RENAL 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 Occurs in states where RBF decreased and

thus prostaglandin dependentthus prostaglandin dependent Nonselective and selective NSAID’s inhibit Nonselective and selective NSAID’s inhibit

compensatory afferent arteriolar compensatory afferent arteriolar vasodilationvasodilation

Volume contraction, CHF, cirrhosis, CKD, Volume contraction, CHF, cirrhosis, CKD, vascular disease and elderly – increases vascular disease and elderly – increases risk.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 0.5Mg/dL if < 2.0 mg/dL or

increase Sincrease SCr > Cr > 1.0 mg/dL if > 2.0 mg/dL1.0 mg/dL if > 2.0 mg/dL Bilateral renal artery stenosis, unilateral Bilateral renal artery stenosis, unilateral

stenosis in solitary kidney, small vessel disease stenosis in solitary kidney, small vessel disease and decreased RBF: CHF, cirrhosis, decreased and decreased RBF: CHF, cirrhosis, decreased ECFECF

Inhibition of A-II efferent arteriole Inhibition of A-II efferent arteriole vasoconstriction leads to decrease Pvasoconstriction leads to decrease PGC GC and and GFRGFR

Age, diuretics, diabetes, NSAID’s, cyclosporine Age, diuretics, diabetes, NSAID’s, cyclosporine and CKD are risk factorsand CKD 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 Patients are often asymptomatic and thus

should always be consideredshould always be considered Ultrasound useful, but can have 10-20% false Ultrasound useful, but can have 10-20% false

negativesnegatives Patients are often oligo-anuric, but any Patients are often oligo-anuric, but any

pattern of urine output may occurpattern of urine output may occur Intraureteric obstruction, Extraureteric Intraureteric obstruction, Extraureteric

obstruction, Urethral obstructionobstruction, Urethral obstruction

INTRARENAL ARFINTRARENAL ARF Renal parenchymal diseasesRenal parenchymal diseases

GlomerularGlomerular

VascularVascular

TubularTubular

InterstitialInterstitial Acute tubular necrosis – most Acute tubular necrosis – most

commoncommon

Glomerular syndromes –Glomerular syndromes –Nephrotic Vs Nephritic Nephrotic Vs Nephritic

SyndromesSyndromes 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 MGN – Methylprednisolone pulse, cyclosporinpulse, cyclosporin

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

RAPIDLY PROGRESSIVE RAPIDLY PROGRESSIVE GLOMERULONEPHRITISGLOMERULONEPHRITIS

Characterized by > 50% decrease in GFR over Characterized by > 50% decrease in GFR over days to weeksdays to weeks

Characterized pathologically by crescent Characterized pathologically by crescent formation and clinically by progression to ESRD formation and clinically by progression to ESRD in untreated patients within weeks in untreated patients within weeks

Related to the degree of crescent formationRelated to the degree of crescent formation Present with active urine sediment, hypertension Present with active urine sediment, hypertension

and oliguric ARFand oliguric ARF 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 - Proteinuria - MicroalbuminuriaMicroalbuminuria

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 Anesthetics, Chemotherapeutics, Heavy metals/ solventsmetals/ solvents

ENDOGENOUS TOXIN ATN :ENDOGENOUS TOXIN ATN :

Pigment Nephropathy Pigment Nephropathy Myoglobin, Myoglobin, HemoglobinHemoglobin

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

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

and multiple myelomaand multiple myeloma 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 Usually reversible, but some have prolonged renal

damagedamage Usually nonoliguric, but oliguria can be seen and Usually nonoliguric, but oliguria can be seen and

FE 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 W + 3 amps NaHCO3 @ 3.5 cc/kg/hr for 1 hour

and then 1 cc/kg/hour for 6 hours afterand then 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-Minimize amount of contrast and consider iso-

osmolar agentosmolar agent - nonionic and/or isosmolar - nonionic and/or isosmolar contrast are less nephrotoxiccontrast are less nephrotoxic

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

small renal arteries and arteriolessmall renal arteries and arterioles Livedo reticularis – A clue!!!Livedo reticularis – A clue!!! Aortic surgery, trauma, angiography, Aortic surgery, trauma, angiography,

fibrinolytic therapy or spontaneouslyfibrinolytic therapy or spontaneously Eosinophilia, eosinophiluria, Eosinophilia, eosinophiluria,

leukocytosis and complement activationleukocytosis and complement activation Retinal, peripheral and abdominal Retinal, peripheral and abdominal

vesselsvessels

MYOGLOBINURIC ARFMYOGLOBINURIC ARF

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

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

hyperkalemia, hyperuricemia, hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemiahyperphosphatemia and hypocalcemia

Decreased FE Decreased FE NaNa

ECF volume repletion, ?mannitol, and ?ECF volume repletion, ?mannitol, and ?alkaline diuresisalkaline diuresis

Hypercalcemia during recoveryHypercalcemia during recovery

ACUTE INTERSTITIAL ACUTE INTERSTITIAL NEPHRITISNEPHRITIS

Fever, rash, eosinophila, Fever, rash, eosinophila, eosinophiluria and active urine eosinophiluria and active urine sedimentsediment

Occurs 10-15 days after exposure to Occurs 10-15 days after exposure to usually new medicationusually new medication

NSAID induced associated with NSAID induced associated with nephrotic syndromenephrotic syndrome

? 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 DIAGNOSTIC MANAGEMENT ARFMANAGEMENT ARF

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

NON DIALYTIC NON DIALYTIC MANAGEMENT ARFMANAGEMENT ARF

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 INDICATIONS FOR Emergency DIALYSISEmergency DIALYSIS

REFRACTORYREFRACTORY

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

mg/dLmg/dL

Chronic Tubulo-Interstitial Chronic Tubulo-Interstitial DiseasesDiseases Chronic issues :Chronic issues :

Toxins: Analgesics, Heavy metals, Chinese herbs, Toxins: Analgesics, Heavy metals, Chinese herbs, Lithium, Cyclosporine, Radiation, CisplatinLithium, Cyclosporine, Radiation, Cisplatin

Hematologic diseases: MyelomaHematologic diseases: Myeloma Immunologic: Sjogren’s syndrome, Transplant Immunologic: Sjogren’s syndrome, Transplant

rejectionrejection Infection: Bacterial pyelonephritis, Tuberculosis, Infection: Bacterial pyelonephritis, Tuberculosis,

SarcoidSarcoid Anatomic: Obstruction, RefluxAnatomic: Obstruction, Reflux Metabolic disorders: Gout, Oxalosis, Metabolic disorders: Gout, Oxalosis,

Hypercalcemia, Hypokalemia, CystinosisHypercalcemia, Hypokalemia, Cystinosis Hereditary: ADPKD, MCDHereditary: ADPKD, MCD Vascular : Nephrosclerosis, Ischemic Vascular : Nephrosclerosis, Ischemic

nephropathy, Atheroembolic diseasenephropathy, Atheroembolic disease Acute cases : check urine eosinophil count, peripheral Acute cases : check urine eosinophil count, peripheral

eosinophiliaeosinophilia

Oxalate NephropathyOxalate Nephropathy

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

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

excessive intake ascorbic acidexcessive intake ascorbic acid Increase intestinal absorption: Ileal Increase intestinal absorption: Ileal

bypass, short bowel syndrome and bypass, short bowel syndrome and Crohn’s diseaseCrohn’s disease

Chronic Urate Chronic Urate NephropathyNephropathy

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

Secondary inflammation and Secondary inflammation and interstitial fibrosis and CRFinterstitial fibrosis and CRF

Hypertension, bland urinalysis and Hypertension, bland urinalysis and hyperuriceniahyperuricenia

Associated with tophaceous gout or Associated with tophaceous gout or an increase in uric acid out of an increase in uric acid out of proportion to degree of CRF proportion to degree of CRF

Analgesic NephropathyAnalgesic Nephropathy

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

NSAID induced vasomotor renal NSAID induced vasomotor renal insufficiencyinsufficiency

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 and depends mainly on serum creatinine level, as no

specific tests establish the diagnosis of HRS. specific tests establish the diagnosis of HRS. Serum creatinine level is a poor marker of renal function in patients with cirrhosis. But no 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. other reliable noninvasive 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 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. causes of renal failure in patients 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 Low GFR, indicated by a serum creatinine level higher than 1.5 mg/dL or 24-hour

creatinine clearance lower than 40 mL/min creatinine clearance lower than 40 mL/min Absence of shock, ongoing bacterial infection and fluid losses, and current Absence of shock, ongoing bacterial infection and fluid losses, and current

treatment with nephrotoxic medications treatment with nephrotoxic medications No sustained improvement in renal function (decrease in serum creatinine to <1.5 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 mg/dL or increase in creatinine clearance to >40 mL/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L of plasma expander withdrawal and expansion of plasma volume with 1.5 L of plasma expander

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

Additional criteria (Additional criteria are not necessary for the diagnosis but provide Additional criteria (Additional criteria are not necessary for the diagnosis but provide supportive evidence.) 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 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 less than 50 per high-power field & Serum sodium concentration greater than 130 mEq/LmEq/L

Urinary indices are not considered major criteria because Urinary indices are not considered major criteria because a subset of patients with a subset of patients with HRS may have high urine sodium levels and low urine osmolalityHRS may have high urine sodium levels and low urine osmolality (similar to acute (similar to acute tubular necrosis [ATN]), while other patients with tubular necrosis [ATN]), while other patients with cirrhosis and ATN may have low cirrhosis and ATN may have low urine sodium levelsurine 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 ) 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 and 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 local gym excessively for the past three days. He does consume alcohol on weekends but reports having involved in a binge drinking episode that included weekends but reports having involved in a binge drinking episode that included 10 beers yesterday. On physical examination, he weighs 70kg and he has some 10 beers yesterday. On physical examination, he weighs 70kg and he has some tenderness in his calf muscles which he attributes to the excessive squats he tenderness in his calf muscles which he attributes to the excessive squats he performed yesterday. Urine dipstick reveals large blood. If this patient develops performed yesterday. Urine dipstick reveals large blood. If this patient develops acute renal failure , the most likely mechanism would be: acute renal failure , the most likely 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 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 step in the management to prevent development of patient's Acute Renal Faliure : 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 A 7-year-old boy is brought to the emergency department by

his mother because of "tea-colored urine" for the last his mother because of "tea-colored urine" for the last several days. He has also had some nausea and vomiting, several days. He has also had some nausea and vomiting, and his eyes appear swollen when he wakes up in the and his eyes appear swollen when he wakes up in the morning. The eye swelling tends to resolve over the course morning. The eye swelling tends to resolve over the course of the day. He is generally very healthy and there is no of the day. He is generally very healthy and there is no family history of any chronic diseases. His temperature is family history of any chronic diseases. His temperature is 36.7 C (98.0 F), blood pressure is 130/90 mm Hg, pulse 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 96/min, and respiratory rate is 16/min. Physical examination is unremarkable. A urinalysis shows red cell casts. At this is unremarkable. A urinalysis shows red cell casts. At this time the most appropriate study to confirm your diagnosis is time the most appropriate study to 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 1c) The above patient has been adequately treated but his repeat CPK after 2 days is still elevated at 48,000. He repeat CPK after 2 days is still elevated at 48,000. He complains of increasing pain in his left leg and some tingling complains of increasing pain in his left leg and some tingling and pricking sensations. On examination his left leg was and pricking sensations. On examination his left leg was mildly swollen and there was pain on passive stretching of the mildly swollen and there was pain on passive stretching of the leg muscles. Dorsalis pedis and posterior tibial pulses are leg muscles. Dorsalis pedis and posterior tibial pulses are intact. The most likely diagnosis at this time: intact. The most likely diagnosis 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 1d) The immediate course of treatment in this condition would be : 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 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 intermittent 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. respiratory infection about 2 days ago. On physical exam, his vitals are normal. Abdomen is benign with out any tenderness or rigidity. However, you notice Abdomen is benign with out any tenderness or rigidity. However, you notice patchy purple discolorations on his extremities and the back. Lab studies are 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. The mother is very anxious and asks about the long term prognosis of her son. Your response : Your response :

A) Reassure the mother that boys disorder is self limiting and does not require A) Reassure the mother that boys disorder is self limiting and does not require any follow up any follow up B) Tell her the boy needs to be admitted and treated vigorously to prevent renal B) Tell her the boy needs to be admitted and treated vigorously to prevent renal failure failure C) Tell her that renal failure develops 100% of such cases and hence needs very C) Tell her that renal failure develops 100% of such cases and hence needs very cautious follow up 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 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. months in order to make sure there is no heamaturia/ renal dysfunction.

If the boy presented with Renal failure in the above case, the most likely If the boy presented with Renal failure in the above case, the most likely underlying pathology would be : underlying pathology 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.

UTIsUTIs

CASE STUDYCASE STUDY A 76 YO DEBILITATED MALE, In extended care A 76 YO DEBILITATED MALE, In extended care

facility , develops every 6 months mild fever, facility , develops every 6 months mild fever, frequency of micturation with urinary frequency of micturation with urinary incontinence. USUALLY E.COLI count is 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 treated. Number of UTI are less than 2 in 6 mos- no need for continuous Abx. in 6 mos- no need for continuous Abx.

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

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

Recurrent UTIsRecurrent UTIs

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

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

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

OTHER ISSUESOTHER ISSUES

Evaluating painless hematuria Evaluating painless hematuria elderlyelderly

Painful hematuriaPainful hematuria Treating asymptomatic bacteriuriaTreating asymptomatic bacteriuria Pyelonephritis – pyonephric abscessPyelonephritis – pyonephric abscess When to admit and when to order When to admit and when to order

imaging studies in pyelonephritis?imaging studies in pyelonephritis?

Painless HematuriaPainless Hematuria The recommended definition of microscopic hematuria is The recommended definition of microscopic hematuria is

three orthree or more red blood cells per high-power field on more red blood cells per high-power field on microscopic evaluation of urinary sediment from microscopic evaluation of urinary sediment from two of two of threethree properly collected urinalysis specimens. properly collected urinalysis specimens.

Always confirm on repeat testingAlways confirm on repeat testing If Red cell casts/ dysmorphic RBCs or Renal function is If 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. consider glomerulonephritis.

Recurrent painless Hematuria Recurrent painless Hematuria consider IgA consider IgA nephropathynephropathy

Other causes : 1. Consider strongly CA.Bladder in the Other causes : 1. Consider strongly CA.Bladder in the elderly and in smokerselderly and in smokers

2. R/O benign causes like BPH ( Ask for 2. R/O benign causes like BPH ( Ask for symptoms of BPH)symptoms of BPH)

3. R/O Prostate Ca in the elderly and in 3. R/O Prostate Ca in the elderly and in those with family historythose with family history

DO NOT NEGLECT POSSIBILITY OF BLADDER CA IN PTS DO NOT NEGLECT POSSIBILITY OF BLADDER CA IN PTS WITH HEMATURIAWITH HEMATURIA

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

Microscopic Hematuria : Microscopic Hematuria : Smoking history Smoking history Occupational exposure to chemicals or dyes Occupational exposure to chemicals or dyes

(benzenes or aromatic amines) (benzenes or aromatic 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 The presence of significant proteinuria, red cell casts or The presence of significant proteinuria, red cell casts or

renal insufficiency, or a predominance of dysmorphic renal insufficiency, or a predominance of dysmorphic red blood cells in the urine should prompt an red blood cells in the urine should prompt an evaluation for renal parenchymal disease or referral evaluation for renal parenchymal disease or referral to a nephrologist.to a nephrologist.

Bladder CaBladder Ca Most common histology is Transitional Cell caMost common histology is Transitional Cell ca Routine screening in all patients for bladder ca Routine screening in all patients for bladder ca

with either urinalysis or cytology is with either urinalysis or cytology is notnot recommendedrecommended

Screening for bladder cancer in high risk Screening for bladder cancer in high risk individuals ( those exposed to dyes/ leather, individuals ( those exposed to dyes/ leather, smokers) is controversial smokers) is controversial no clear no clear recommendations. 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 Do not routinely screen but however, if

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

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

hematuria is hematuria is intermittentintermittent, and , and regardless of the findings on regardless of the findings on history and physical exam. history and physical 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 Cystoscopy and exam under anesthesia

with biopsies with biopsies Additional diagnostic evaluations, based Additional diagnostic evaluations, based

on findings from the cystoscopy and on findings from the cystoscopy and pathologic evaluation of the tumor, to pathologic evaluation of the tumor, to assess the upper urinary tract or to look assess the upper urinary tract or to look for metastatic disease for metastatic disease lfts, ivp, cxr, ct lfts, ivp, cxr, ct scan of abd/pelvis, bone scan.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-Radical Cystectomy – Rx of choice for muscle-

invasive bladder ca. invasive bladder ca. Adjuvant Intravesical therapy with BCG/ Adjuvant Intravesical therapy with BCG/

mitomycin-c for mitomycin-c for Cis, T1 tumors, tumor > Cis, T1 tumors, tumor > 5cm size. 5cm size.

Adjuvant chemotherapy on case-by case basis Adjuvant chemotherapy on case-by case basis gemcitabine+cisplatin or methotrexate gemcitabine+cisplatin or methotrexate

Local side effects of BCG include: Cystitis Local side effects of BCG include: Cystitis (90% of patients) , Hematuria (30%) , (90% of patients) , Hematuria (30%) , Contracted bladder , Ureteral obstruction, Contracted bladder , Ureteral obstruction, Inflammation (prostatitis, epididymitis, Inflammation (prostatitis, epididymitis, epididymoorchitis) epididymoorchitis)

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

Bladder Ca Bladder Ca

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

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

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

Complications – Urinary Complications – Urinary diversiondiversion

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

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

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

levels and Bone mineralizationlevels and Bone mineralization

Painful HematuriaPainful Hematuria UTI/ Cystitis/ PyelonephritisUTI/ Cystitis/ Pyelonephritis Renal CalculiRenal CalculiIMAGING CHOICES: IMAGING CHOICES: Computed tomography ( NON Computed tomography ( NON

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

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

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 Requires defect in renal concentrating

ability and defect in thirst mechanismability and defect in thirst mechanism Normal patients do not become Normal patients do not become

hypernatremichypernatremic Hypernatremia occurs in very young and Hypernatremia occurs in very young and

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

Isovolemic Hypernatremia : Usually Isovolemic Hypernatremia : Usually hemodynaically stable unless serum sodium > hemodynaically stable unless serum sodium > 170 meq/L170 meq/L

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

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

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

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

PolyuriaPolyuria

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

vs polydipsia ( Uvs polydipsia ( Uosmosm < 150 mOsm ) < 150 mOsm ) Solute diuresis i.e. electrolyte vs non Solute diuresis i.e. electrolyte vs non

electrolyte ( Uelectrolyte ( Uosm osm 300 - 400 mOsm )300 - 400 mOsm ) Diagnostics: Urinalysis, urine Diagnostics: Urinalysis, urine

osmolality, and urine electrolytesosmolality, and urine 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 Signs and Symptoms HypernatremiaHypernatremia

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 Therapy of HypernatremiaHypernatremia 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 Chronic: 0.5 meq/L/hour reduction or 50% within first

24hours24hours

-- 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 Investigations: Ca, Phos, EKG, PTH, Urinary calcium

excretion ( R/o familial hypocalciuric hypercalcemia)excretion ( R/o familial 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 Hypercalcemic crisis management – ivf + lasix after volume

repletion onlyrepletion only Indications for corticosteroids : are useful for treating Indications for corticosteroids : are useful for treating

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

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

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

Criteria for Surgery – Criteria for Surgery – Primary Primary

hyperparathyroidismhyperparathyroidism Serum total calcium level >12 mg per dL (3 mmol per Serum total calcium level >12 mg per dL (3 mmol per L) at any time L) at any time

Hyperparathyroid crisis (discrete episode of life-Hyperparathyroid crisis (discrete episode of life-threatening threatening hypercalcemiahypercalcemia) )

Marked hypercalciuria (urinary calcium excretion Marked hypercalciuria (urinary calcium excretion more than 400 mg per day) more than 400 mg per day)

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

ray absorptiometry or similar technique) ray absorptiometry or similar technique) Bone mass more than two standard deviations below age-Bone mass more than two standard deviations below age-

matched controls (Z score less than 2) matched controls (Z score less than 2) Classic neuromuscular symptoms Classic neuromuscular symptoms Proximal muscle weakness and atrophy, Proximal muscle weakness and atrophy,

hyperreflexiahyperreflexia, and gait disturbance , and gait disturbance Age younger than 50Age younger than 50

Hypercalcemia – Breast Hypercalcemia – Breast CancerCancer

Management: Management: Principal Rx : Bisphosphonates for Principal Rx : Bisphosphonates for

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

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

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

Vomiting, early excess diuresisVomiting, early excess diuresis Euvolemic Hyponatremia Euvolemic Hyponatremia SIADH SIADH Isotonic Hyponatremia Isotonic Hyponatremia

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

Rx Rx Correct volume and then osmolal Correct volume and then osmolal problemproblem

Volume problem Volume problem Isotonic saline Isotonic saline always !!!!!!!!!!always !!!!!!!!!!

Asymptomatic Asymptomatic fluid restriction fluid restriction CNS symptoms CNS symptoms 3% Saline 3% Saline

HyperkalemiaHyperkalemia

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

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

Ekg- HyperkalemiaEkg- Hyperkalemia

The following changes may be seen in The following changes may be seen in hyperkalaemiahyperkalaemia

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 The man’s K was 9.69.6

Next Step Next Step IV CALCIUM IV CALCIUM CHLORIDE ( CALCIUM CHLORIDE ( CALCIUM

GLUCONATE AN ALTERNATIVE)GLUCONATE AN 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 - Hyperkalemia - TreatmentTreatment

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

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

potassium is an issuepotassium is an issue D – Hemodialysis for refractory D – Hemodialysis for refractory

HyperkalemiaHyperkalemia

HYPOKALEMIA - EKGHYPOKALEMIA - EKG

The following changes may be The following changes may be seen in hypokalaemia.seen in 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 slight depression of the ST

segment segment

Acid Base Acid Base DisordersDisorders

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 Associated with life threatening

conditionsconditions Often misdiagnosedOften misdiagnosed Demands an understanding of physiology Demands an understanding of physiology

and pathophysiologyand pathophysiology pH is a major determinant of enzymatic pH is a major determinant of enzymatic

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

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

SYSTEM : H + HCOSYSTEM : H + HCO33 ↔↔ H H22COCO33 ↔ ↔ H H22O O + CO+ CO22

- HENDERSON-HASSELBACHHENDERSON-HASSELBACHEQUATION : pH = pKEQUATION : pH = pKa a + log HCO+ log HCO33 / / H2COH2CO33

- 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 Rate of H ion or bicarbonate loss via GI

tracttract 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 Rate of CO2 excretion via alveolar

ventilationventilation 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 - Acid-base disorder caused by

primary change in plasma primary change in plasma bicarbonatebicarbonate

- Plasma bicarbonate = 24-28 - Plasma bicarbonate = 24-28 meq/Lmeq/L

Respiratory DisorderRespiratory Disorder- Acid-base disorder caused by - Acid-base disorder caused by

primary change in pCO2primary change in pCO2- pCO2 = 36 - 44 mmHgpCO2 = 36 - 44 mmHgCompensatory Mechanisms : Compensatory Mechanisms :

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

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

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

10 meq/L10 meq/L Given entirely by Unmeasured anions are related to (-) Given entirely by Unmeasured anions are related to (-)

charge on albumin charge on albumin One gram albumin = 2.5 meq/L One gram albumin = 2.5 meq/L anionanioni.e.i.e. Albumin of 4 gm/L, baseline anion gap would be Albumin of 4 gm/L, baseline anion gap would be 10 meq/L which is Normal. Correct Gap for 10 meq/L which is Normal. Correct Gap for Albumin!!! Albumin!!! If albumin is 2gm%, the baseline anion If albumin is 2gm%, the baseline anion gap should be 5 in which case 10 should be assumed gap should be 5 in which case 10 should be assumed as increased Anion gap.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 >1 = Anion gap acidosis plus metabolic alkalosis alkalosis

< 1 = Increased Anion gap acidosis plus < 1 = Increased Anion gap acidosis plus normal anion gap acidosisnormal anion 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 pCO2 = 1.5x HCO3 + 8

+/- 2+/- 2pCO2 = last 2 digits pHpCO2 = last 2 digits pHpCO2 = HCO3 + 15pCO2 = HCO3 + 15

If measured Pco2 is less than expected If measured Pco2 is less than expected pco2 as calculated by this equation – pco2 as calculated by this equation – suspect a primary respiratory alkalosis. If suspect a primary respiratory alkalosis. If it is more than expected suspect primary it is more than expected suspect primary respiratory acidosis. This is how you respiratory acidosis. This is how you diagnose mixed disorders!!!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 cardiogenic shock. Ph 7.26. PCo2 40 HCO3- 10 Na+ 136 Cl- 110 Albumin HCO3- 10 Na+ 136 Cl- 110 Albumin 2.02.0

1.1. What's the Anion Gap?What's the Anion Gap?2.2. Corrected Anion Gap ? {gap + Corrected Anion Gap ? {gap +

2.5(measured albumin)}2.5(measured albumin)}3.3. Delta Anion Gap?Delta Anion Gap?4.4. Delta Hco3-? ( 24 – bicarb)Delta Hco3-? ( 24 – bicarb)5.5. Delta Gap?Delta Gap?6.6. Adequately Compensated or mixed ?Adequately Compensated or mixed ?7.7. Name the disorder ? Name the disorder ?

Normal Anion-Gap Metabolic Normal Anion-Gap Metabolic AcidosisAcidosis

Gastrointestinal Loss of BicarbonateGastrointestinal Loss of Bicarbonate DiarrheaDiarrhea Urinary diversionUrinary diversion Small bowel, pancreatic, or bile drainage Small bowel, pancreatic, or bile drainage

( fistulas, surgical drains )( fistulas, surgical drains ) CholestiramineCholestiramine

Renal Loss of Bicarbonate ( or Bicarbonate Renal Loss of Bicarbonate ( or Bicarbonate equivalent )equivalent )

Renal tubular acidosisRenal tubular acidosis Recovery phase of KetoacidosisRecovery phase of Ketoacidosis Renal InsufficiencyRenal Insufficiency Acidifying Substances- HCl, NH4Cl, Arginine Acidifying Substances- HCl, NH4Cl, Arginine

HCl, Lysine HCl, Sulfur HCl, Lysine HCl, Sulfur

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

Increased Anion Gap Increased Anion Gap AcidosisAcidosis

Ketoacidosis - diabetic, alcoholic, Ketoacidosis - diabetic, alcoholic, starvationstarvation

Lactic acidosisLactic acidosis UremiaUremia Toxins - Ethylene glycol, methanol, Toxins - Ethylene glycol, methanol,

salicylate, paraldehyde salicylate, 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. Plasma Level v. OsmolalityOsmolality

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

Case StudyCase Study Sam is a 35 y/o alcoholic who is brought to the ER in a 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 comatose state. Sam’s wife tells you that she had an argument in the evening about 5 hrs ago over Sam’s argument in the evening about 5 hrs ago over Sam’s alcohol habits. Sam apparently got mad over the alcohol habits. Sam apparently got mad over the discussion, drove his car and returned an hour ago in a discussion, drove his car and returned an hour ago in a very intoxicated state. Wife called the EMS and rushed him very intoxicated state. Wife called the EMS and rushed him to the ER. On examination Sam is disoriented and to the ER. On examination Sam is disoriented and hallucinating , Pulse 120 Tm 99, RR 26 BP 126/76. The rest hallucinating , Pulse 120 Tm 99, RR 26 BP 126/76. The rest of the physical exam is normal except for stuporos state of the physical exam is normal except for stuporos state and alcohol smell. Lab studies revealed Na 130 k 3.4 cl- 95 and alcohol smell. Lab studies revealed Na 130 k 3.4 cl- 95 Hco3 16, Glucose 90 Creatinine 1.6 BUN 45. Blood Hco3 16, Glucose 90 Creatinine 1.6 BUN 45. Blood Ethylalcohol level was 180. Serum osmolarity was 360mgEthylalcohol level was 180. Serum osmolarity was 360mg%. ABGs revealed 7.28, Pco2 28, Po2 76 Sao2 93. The next %. ABGs revealed 7.28, Pco2 28, Po2 76 Sao2 93. The next best step in management ?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 B) Hemodialysis because this is an acute renal failure

causing acidosiscausing acidosis C) Fomepizole because of suspicion of ethylene glycol C) Fomepizole because of suspicion of ethylene glycol

intoxicationintoxication D) Supportive treatment for now because this is an D) Supportive treatment for now because this is an

ethylalcohol induced lactic acidosisethylalcohol induced lactic acidosis E) Bicarbonate drip to reverse the acidosis because this is E) Bicarbonate drip to reverse the acidosis because this is

renal tubular acidosisrenal tubular acidosis

Ethylene Glycol Ethylene Glycol PoisoningPoisoning Envelope shaped crystals Envelope shaped crystals

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

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

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

Toxicity results at doses Toxicity results at doses >1.0 ml/kg >1.0 ml/kg

Ethylene glycol causes Ethylene glycol causes CNS depression , CNS depression , converts to converts to Glycolic Acid (metabolite) effects (metabolite) effects M t ol Me ab ic c

os sid i & &Renal Failure

Oxalic acid (metabolite) Oxalic acid (metabolite) effects effects Calcium Calcium oxalate crystal oxalate crystal depositiondeposition

C/F: C/F: Confusion, Ataxia, Confusion, Ataxia, Slurred Slurred speech ,Hallucination, speech ,Hallucination, Tetany Seizures (s (Hypocalcemia) )

Hypertension 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, Present with CNS depression, hypotension, arrhytmias and hypotension, arrhytmias and gastritisgastritis

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 Type 4 (hyporeninemic

hypoaldosteronism)hypoaldosteronism)

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

Causes: autoimmune diseases, Causes: autoimmune diseases, hyperglobinemia states and hyperglobinemia states and hereditaryhereditary

Present with normal anion gap Present with normal anion gap acidosis, urine pH >5.5, acidosis, urine pH >5.5, hypokalemia, hypercalciuria, 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 Isolated defect or associated with

generalized proximal dysfunction i.e. generalized proximal dysfunction i.e. Fanconi syndromeFanconi syndrome

Failure to reclaim filtered bicarbonateFailure to reclaim filtered bicarbonate Increase FEIncrease FEHCO3HCO3 Urine pH > 5.5, but may be < 5.5 once Urine pH > 5.5, but may be < 5.5 once

HCOHCO33 < 16 meq/L < 16 meq/L Causes: Causes:

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

Type 4 RTAType 4 RTA

Hypoaldosteronism or aldosterone Hypoaldosteronism or aldosterone resistanceresistance

Causes: diabetes mellitus, HIV and Causes: diabetes mellitus, HIV and tubulo-tubulo-

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

anion gap acidosis and normal urine anion gap acidosis and normal urine pH pH

Metabolic AlkalosisMetabolic Alkalosis

Calculate compensation Calculate compensation

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

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

Causes of Metabolic Causes of Metabolic AlkalosisAlkalosis

Saline responsive : ECF depleted ( contraction Saline responsive : ECF depleted ( contraction alkalosis ), Urine chloride < 10 meq/L, do not go by alkalosis ), Urine chloride < 10 meq/L, do not go by urine sodium in assessing volume statusurine sodium in assessing volume status

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

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

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

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

Metabolic Alkalosis - Metabolic Alkalosis - TreatmentTreatment

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

Saline resistantSaline resistant Inhibit or remove excess Inhibit or remove excess

mineralocorticoid effectmineralocorticoid 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 :A) Laxative AbuseB) Surreptious vomitingC) Licorice abuseD) Malabsorption SyndromeE) Hyporeninemic Hypoaldosteronism

Treatment : A) IV normal salineB) SpronolactoneC) AmilorideD) Psychiatry consultE) Reassurance because this is self limiting