ARCHER NOTES

1. Nephrology & Urology
Archer Online USMLE Reviews
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2. Renal Failure
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Acute Vs. Chronic
Acute : Pre-Renal, Renal, Post –renal, Glomerular,
tubular, intersititial
Indicators : BUN/CREA, FeNA, Urine Spgravity,
serum Sodium, serum osmolality, urine output.
Chronic – stages  elective hemodialysis Stage V,
Emergent hemodialysis indications
Acute tubular necrosis : toxic, pigment induced,
Ischemic
Evaluating renal function : urinalysis - ? Protein, ?rbc , ?
Wbc, ? Casts , ? Crystals, ? Bacteria, ? Nitrite, ?
Cytology , ? Leucoesterase,
- Creatinine clearance, Renal ultrasound, Renal biopsy

3. RENAL BIOPSY
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Indications:
Nephrotic syndrome
Glomerular disease
Unexplained renal failure
Contraindications: single kidney, bleeding,
severe hypertension. obesity and uncooperative
patient

4. DEFINITION OF ARF

PCr > 0.5mg/dL if baseline < 3.0mg/dL
PCr > 1.0 mg/dL if baseline > 3.0 mg/dL
 Urine Output :
TOTAL ANURIA
0 cc
ANURIA
< 100 cc
OLIGURIA
100-400 cc
NON OLIGURIA
400-1000cc
POLYURIA
> 1000cc
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5. CAUSES OF NONOLIGURIC PRE
RENAL ARF
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Diuretics
Osmotic diuresis
Hypercalcemia
Protein malnourished
Post obstructive diuresis
Diabetes Insipidus

6. NSAID ARF
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Form of pre renal
Occurs in states where RBF decreased and thus
prostaglandin dependent
Nonselective and selective NSAID’s inhibit
compensatory afferent arteriolar vasodilation
Volume contraction, CHF, cirrhosis, CKD,
vascular disease and elderly – increases risk.
COX-2 inhibitors have similar effect
Allergic interstitial nephritis can also occur

7. ACE INHIBITOR ARF
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Rapidly reversible ARF
Increase SCr > 0.5Mg/dL if < 2.0 mg/dL or increase SCr >
1.0 mg/dL if > 2.0 mg/dL
Bilateral renal artery stenosis, unilateral stenosis in
solitary kidney, small vessel disease and decreased RBF:
CHF, cirrhosis, decreased ECF
Inhibition of A-II efferent arteriole vasoconstriction
leads to decrease PGC and GFR
Age, diuretics, diabetes, NSAID’s, cyclosporine and
CKD are risk factors
ARB’s pose similar risk

8. POST RENAL ARF
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Caused by anatomic obstruction of urine flow
Accounts for 5-10% of ARF
Patients are often asymptomatic and thus should always
be considered
Ultrasound useful, but can have 10-20% false negatives
Patients are often oligo-anuric, but any pattern of urine
output may occur
Intraureteric obstruction, Extraureteric obstruction,
Urethral obstruction

9. INTRARENAL ARF
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Renal parenchymal diseases
Glomerular
Vascular
Tubular
Interstitial
Acute tubular necrosis – most common

10. Glomerular syndromes –
Nephrotic Vs Nephritic Syndromes
NEPHROTIC SYNDROME
 Urinary albumin > 3.0 – 3.5
gm/24 hours
 Hypoalbimunemia
 Edema
 Hyperlipidemia
 Lipiduria
FSGN ( HIV), MGN( SLE, hepb,
Cancer – solid tumors ), Minimal
( children), MPGN ( HepC)
FSGN – Rx High dose steroids,
cyclosporine
MGN – Methylprednisolone pulse,
cyclosporin
Others : DM, Malignancy,
vasulitis, amyloidosis
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Nephritic Syndrome
Hematuria/ RBC Casts
 Oliguria
 Hypertension
 Decreased GFR
 Proteinuria +/ Focal glomerulonephritis
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IgA nephropathy
Focal SLE ( Type III )
 Diffuse glomerulonephritis
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Post infectious
Diffuse SLE ( Type IV )
 IgA nephropathy : most common
presentation asymptomatic
microhematuria with mild
proteinuria

11. RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS
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Characterized by > 50% decrease in GFR over days to weeks
Characterized pathologically by crescent formation and clinically
by progression to ESRD in untreated patients within weeks
Related to the degree of crescent formation
Present with active urine sediment, hypertension and oliguric
ARF
Nephrologic emergency
Classification of RPGN:
 Type 1: Anti GBM
 Type 2: Immune complex
 Type 3: Pauci-immune ( p-ANCA )
Early evaluation and biopsy

12. Proteinuria - Microalbuminuria
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Normal: 150 mg/day
Albumin
30 mg
Plasma proteins 60 mg
Tubular protein 60 mg
Dipstick test detects (-)
charge
Does not detect light chains
Function of urine
concentration
Total Protein : creatinine
ratio estimates 24 hour urine
collection
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Microalbuminuria 
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Albumin excretion rate > 15
ugm/min = 30 mg/day
Predictor of early diabetic
nephropathy and CVD
Urine albumin: urine
creatinine < 0.03
Positive in exercise, fever,
stress, CHF
Repeat urinalysis in 3-6
months if u think its
transient proteinuria
ACE Inhibitor *****
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13. ATN
Ischemic (50%)
 Toxic:
 EXOGENOUS TOXIN ATN :
-Antibiotics, Radiocontrast, Non steroidals,
Anesthetics, Chemotherapeutics, Heavy metals/
solvents
 ENDOGENOUS TOXIN ATN :
Pigment Nephropathy  Myoglobin, Hemoglobin
Crystal Nephropathy  Uric acid , Calcium,
Oxalate
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14. RADIOCONTRAST ATN
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Risk factors: CRF especially diabetic, CHF, elderly and multiple
myeloma
ATN begins abruptly and SCr peaks in 3-5 days
Usually reversible, but some have prolonged renal damage
Usually nonoliguric, but oliguria can be seen and FE Na decreased
Prevention : Consider non contrast study if high risk
D/C NSAID’s, ACE inhibitors. ARB’s etc
Ensure optimal volume status and RBF
 0.9% saline @ 1cc/kg/hr for 6 hours prior
 D W + 3 amps NaHCO3 @ 3.5 cc/kg/hr for 1 hour and
5
then 1 cc/kg/hour for 6 hours after
N-acetylcysteine 600mg bid pre and day of study
Minimize amount of contrast and consider iso-osmolar agent -
nonionic and/or isosmolar contrast are less
nephrotoxic

15. ATHEROEMBOLIC ARF
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Results from cholesterol emboli to small renal
arteries and arterioles
Livedo reticularis – A clue!!!
Aortic surgery, trauma, angiography, fibrinolytic
therapy or spontaneously
Eosinophilia, eosinophiluria, leukocytosis and
complement activation
Retinal, peripheral and abdominal vessels

16. MYOGLOBINURIC ARF
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Rhabdomyolysis: trauma,alcohol, cocaine, seizures,
hypokalemia, hypophosphatemia
ECF volume depletion
Heme (+) urine without RBC’s, hyperkalemia,
hyperuricemia, hyperphosphatemia and hypocalcemia
Decreased FE Na
ECF volume repletion, ?mannitol, and ?alkaline diuresis
Hypercalcemia during recovery

17. ACUTE INTERSTITIAL
NEPHRITIS
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Fever, rash, eosinophila, eosinophiluria and
active urine sediment
Occurs 10-15 days after exposure to usually new
medication
NSAID induced associated with nephrotic
syndrome
? Renal biopsy
Rx: Stop the agent and ?steroids

18. CRYSTAL INDUCED ARF
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Uric acid
Calcium oxalate
Methotrexate
Sulfonamides
Acyclovir
Indinavir

19. DIAGNOSTIC MANAGEMENT
ARF
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History / Chart review
Physical exam
Urinalysis
Urine indices
Radiologic studies
Miscellaneous studies

20. NON DIALYTIC MANAGEMENT
ARF
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Preventive measures
Fluid balance
Acid base balance
Electrolyte balance
Nutritional balance
Drug management
Management of uremia

21. INDICATIONS FOR Emergency
DIALYSIS
REFRACTORY
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Hyperkalemia
Acidemia
Hypoxemia/ volume overload
Uremia - manifestations
? Prophylactic when BUN > 60-100 mg/dL

22. Chronic Tubulo-Interstitial Diseases
Chronic issues :
 Toxins: Analgesics, Heavy metals, Chinese herbs, Lithium,
Cyclosporine, Radiation, Cisplatin
 Hematologic diseases: Myeloma
 Immunologic: Sjogren’s syndrome, Transplant rejection
 Infection: Bacterial pyelonephritis, Tuberculosis, Sarcoid
 Anatomic: Obstruction, Reflux
 Metabolic disorders: Gout, Oxalosis, Hypercalcemia,
Hypokalemia, Cystinosis
 Hereditary: ADPKD, MCD
 Vascular : Nephrosclerosis, Ischemic nephropathy,
Atheroembolic disease
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Acute cases : check urine eosinophil count, peripheral eosinophilia

23. Oxalate Nephropathy
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Precipitation of calcium oxalate can cause
interstitial and intratubular crystals leading to
inflammation and fibrosis
Primary hyperoxaluria leads to ESRD
Ethylene glycol, methoxyflurane, excessive
intake ascorbic acid
Increase intestinal absorption: Ileal bypass, short
bowel syndrome and Crohn’s disease

24. Chronic Urate Nephropathy
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Related to deposition of sodium urate in the
medullary interstitium
Secondary inflammation and interstitial fibrosis
and CRF
Hypertension, bland urinalysis and hyperuricenia
Associated with tophaceous gout or an increase
in uric acid out of proportion to degree of CRF

25. Analgesic Nephropathy
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NSAID induced interstitial nephritis ( associated
with nephrotic syndrome  proteinuria)
NSAID induced vasomotor renal insufficiency

26. Hepatorenal Syndrome
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The diagnosis of HRS iS of exclusion and depends mainly on serum creatinine level, as no specific tests establish the
diagnosis of HRS.
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.
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.
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Major criteria (All major 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
lower than 40 mL/min
 Absence of shock, ongoing bacterial infection and fluid losses, and current treatment with nephrotoxic
medications
 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
of plasma expander
 Proteinuria less than 500 mg/d and no ultrasonographic evidence of obstructive uropathy or intrinsic
parenchymal disease
Additional criteria (Additional criteria are not necessary for the diagnosis but provide supportive evidence.)
 Urine volume less than 500 mL/d
 Urine sodium level less than 10 mEq/L
 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/L
Urinary indices are not considered major criteria because a subset of patients with HRS may have high urine
sodium levels and low urine osmolality (similar to acute tubular necrosis [ATN]), while other patients with
cirrhosis and ATN may have low urine sodium levels and high urine osmolality.

27. 
Case Studies
) 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
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
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
reveals large blood. If this patient develops acute renal failure , the most likely
mechanism would be:
A) Interstitial nephritis due to pigment
B) Glomerulonephritis
C) Acute Tubular necrosis due to pigment deposition
D) Acute Tubular Necrosis due to Ischemia
E) Alcohol related direct toxic injury
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
the management to prevent development of patient's Acute Renal Faliure :
A) Intravenos Fluids
B) Furosemide
C) Calcium Gluconate
D) No treatment because serum creatinine is normal
D) Sodium Bicarbonate

28. Case Study
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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
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
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
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
confirm your diagnosis is
A. antinuclear antibody
B. antistreptolysin O antibody
C. renal biopsy
D. renal ultrasound
E. urine culture

29. 
Case studies contd…
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
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.
Dorsalis pedis and posterior tibial pulses are intact. The most likely diagnosis
at this time:
A) Deep Vein Thrombosis
B) Cellulitis
C) Compartment Syndrome
D) Edema due to renal failure
E) Congestive Heart Failure
1d) The immediate course of treatment in this condition would be :
A) Anticoagulation with Heparin
B) Antibiotics
C) Emergency Fasciotomy
D) Loop diuretics
E) Elevation of the leg

30. 
Case Study 2
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
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
obtained that revealed
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
Streptozyme : negative ,Urine dipstick : normal without any blood
Urinalysis : normal/ no rbcs/ no protein
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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
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
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
sure there is no heamaturia/ renal dysfunction.
If the boy presented with Renal failure in the above case, the most likely underlying pathology
would be :
A) IgA mediated vasculitis
B) Post streptococcal glomerulonephritis
C) Anti GBM disease
D) Acute tubular necrosis
E) Interstitial Nephritis.

31. UTIs

32. CASE STUDY
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A 76 YO DEBILITATED MALE, In extended care facility ,
develops every 6 months mild fever, frequency of micturation
with urinary incontinence. USUALLY E.COLI count is
>100,000.
What is the appropriate treatment?
A. CYSTOSCOPY and IVP
B. Continuous low dose antibiotics
C. Catheterize and irrigate the Bladder daily
D. Treat only the acute episode of infection
E. No need of treatment as this is colonization

33. 
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Symptomatic complicated UTI should be
treated. Number of UTI are less than 2 in 6
mos- no need for continuous Abx.
His Symptoms are associated with UTI and are
not persistent. So just treat the acute episode
REMEMBER THE INDICATIONS FOR
TREATING “ASYMPTOMATIC “
BACTERIURIA.

34. Recurrent UTIs
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DEFINED AS 2 OR MORE EPISODES IN
PAST 6 MONTHS OR 3 OR MORE
EPISODES IN PAST ONE YEAR.
Use Bactrim DS post sexual activity for women
with hx of recurrent UTIs related to sexual
activity.
Use daily bactrim for people withj no relation to
sex activity.

35. OTHER ISSUES
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Evaluating painless hematuria elderly
Painful hematuria
Treating asymptomatic bacteriuria
Pyelonephritis – pyonephric abscess
When to admit and when to order imaging
studies in pyelonephritis?

36. Painless Hematuria
The recommended definition of microscopic hematuria is three or
more red blood cells per high-power field on microscopic evaluation
of urinary sediment from two of three properly collected urinalysis
specimens.
 Always confirm on repeat testing
 If Red cell casts/ dysmorphic RBCs or Renal function is
compromised/ new onset HTN, combined with mild proteinuria 
consider glomerulonephritis.
 Recurrent painless Hematuria  consider IgA nephropathy
 Other causes : 1. Consider strongly CA.Bladder in the elderly and in
smokers
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 history
DO NOT NEGLECT POSSIBILITY OF BLADDER CA IN PTS
WITH HEMATURIA
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37. Painless Hematuria
Risk Factors for Significant Disease in Patients with Microscopic Hematuria :
 Smoking history
 Occupational exposure to chemicals or dyes (benzenes or aromatic
amines)
 History of gross hematuria
 Age >40 years
 History of urologic disorder or disease
 History of irritative voiding symptoms
 History of urinary tract infection
 Analgesic abuse
 History of pelvic irradiation
The presence of significant proteinuria, red cell casts or renal
insufficiency, or a predominance of dysmorphic red blood cells in the
urine should prompt an evaluation for renal parenchymal disease or
referral to a nephrologist.

40. Bladder Ca
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Most common histology is Transitional Cell ca
Routine screening in all patients for bladder ca with
either urinalysis or cytology is not recommended
Screening for bladder cancer in high risk individuals
( those exposed to dyes/ leather, smokers) is
controversial  no clear recommendations.
High risk History : Smoking history, Occupational
exposure to dyes, rubber, or leather, previous
exposure to Cyclophosphamide

41. Bladder Ca

Do not routinely screen but however, if you find
Hematuria ( even microscopic) on routine
urinalysis that was done for another purpose 
do not neglect this finding. ABNORMAL LAB
always need to be addressed  pursue further
w/u for this hematuria ( BPH, Ca.Bladder,
ca.prostate, cystitis, r/o glomerulonephritis)

Remember Micro-HEMATURIA is the most
common manifestation of bladder cancer.

42. Clinical Symps/ Signs
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Hematuria
Urinary frequency or dysuria
Flank or suprapubic pain
Constitutional symptoms, such as weight loss
Weight loss
Adenopathy
Palpable suprapubic mass
Organomegaly
BLADDER CA CAN BE TOTALLY
ASYMPTOMATIC

43. IMPORTANT
Refer all patients ( especially those at
high risk) presenting with unexplained
hematuria for cystoscopy, even if their
hematuria is intermittent, and regardless
of the findings on history and physical
exam.

44. Bladder Ca - Diagnosis
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Freshly voided urine sample for cytology
Imaging of the urinary tract
Cystoscopy and exam under anesthesia with
biopsies
Additional diagnostic evaluations, based on
findings from the cystoscopy and pathologic
evaluation of the tumor, to assess the upper
urinary tract or to look for metastatic disease 
lfts, ivp, cxr, ct scan of abd/pelvis, bone scan.

45. 
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Bladder Ca - Rx
Surgical resection for non invasive bladder ca.
Radical Cystectomy – Rx of choice for muscle-invasive
bladder ca.
Adjuvant Intravesical therapy with BCG/ mitomycin-c
for  Cis, T1 tumors, tumor > 5cm size.
Adjuvant chemotherapy on case-by case basis 
gemcitabine+cisplatin or methotrexate
Local side effects of BCG include: Cystitis (90% of
patients) , Hematuria (30%) , Contracted bladder ,
Ureteral obstruction, Inflammation (prostatitis,
epididymitis, epididymoorchitis)
Systemic side effects of BCG, which should resolve in
48 hours, include: Flu-like symptoms , Arthralgias ,
Rash

46. Bladder Ca
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Post – radical cystectomy requires urinary
diversion
External diversions include conduits, usually
composed of a section of bowel (ileum or
colon).
Internal conduits include those that require a
stoma to empty the reservoir (Kock pouch and
Indiana pouch) and orthotopic replacements
(e.g., Le Bag, Mainz pouch,

47. Complications – Urinary diversion
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Watch for the following after urinary diversion:
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Bleeding , Infection , Hernias , Necrosis , Reflux,
Incontinence , Obstruction of conduit, upper tract, or
intestines and Recurrent cancer
Monitor for bacteremia, treat patients with Proteus or
Pseudomonas sp., and observe patients with other
organisms if they are asymptomatic.
Monitor closely:

Vitamin B12 levels , Acid/base status , Electrolyte levels and
Bone mineralization

48. Painful Hematuria
UTI/ Cystitis/ Pyelonephritis
 Renal Calculi
IMAGING CHOICES:
 Computed tomography ( NON CONTRAST) is the
best imaging modality for the evaluation of urinary
stones, renal and perirenal infections, and associated
complications
 Ultrasound : Excellent for detection and
characterization of renal cysts (Limitations in detection
of small solid lesions (<3 cm))  Also, used for stones
eval in pregnancy.


49. Electrolytes

50. Hypernatremia

51. Hypernatremia
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Defined as serum sodium > 145 meq/L
Hospital acquired in >80% of patients
Requires defect in renal concentrating ability and
defect in thirst mechanism
Normal patients do not become hypernatremic
Hypernatremia occurs in very young and very
old with a defect in thirst
Isovolemic, Hypovolemic & Hypervolemic

52. 

Isovolemic Hypernatremia : Usually hemodynaically
stable unless serum sodium > 170 meq/L
Causes:
 Hypodipsia
 Increases insensible losses
 Nephrogenic diabetes insipidus – congenital,
acquired  CRF, Hypokalemia, Hypercalcemia, Sickle cell
disease Amyloidosis, Obstruction, Alcohol, Lithium,
Demeclocycline, Glyburide, Amphotericin


Essential hypernatremia
Central Diabetes Insipidus : Granulomas, Histiocytosis,
Infections, CVA, Postpartum necrosis, Pregnancy, Head
traumaPost hypophysectomy, Suprasellar masses, Intrasellar
masses

53. Polyuria
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? Water or solute diuresis
Water diuresis i.e. diabetes insipidus vs
polydipsia ( Uosm < 150 mOsm )

Solute diuresis i.e. electrolyte vs non electrolyte (
Uosm 300 - 400 mOsm )

Diagnostics: Urinalysis, urine osmolality, and
urine electrolytes

55. 
Hypovolemic Hypernatremia Causes

Renal causes
 Loop diuretics
 Osmotic diuresis
Gastrointestinal causes
 Vomiting / nasogastric drainage
 Diarrhea / cathartics
Water loss into cells
 Exercise / seizures
Cuteaneous causes
 Burns / excessive sweating
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

56. 
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Hypervolemic Hypernatremia
Causes :
Hypertonic sodium solutions
Hypertonic feedings
Ingestion of sea water
Hypertonic dialysis
Primary aldosteronism
Cushing’s syndrome

57. Signs and Symptoms Hypernatremia
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Depend on rate, degree and duration
Depressed sensorium
Irritability
Focal neurologic deficits / seizures
Muscle spasms
Nausea/vomiting
Thirst / fever
Volume depletion / hyperglycemia

58. 
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Therapy of Hypernatremia
Hemodynamic or osmolal problem?
Acute or chronic problem?
Prior losses and present losses?
Rate of correction?
 Acute: 1-1.5 meq/L/hour reduction
 Chronic: 0.5 meq/L/hour reduction or 50% within first 24hours
- WHICH FLUID ?
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Isovolemic
 water: PO or intravenous
 Water deficit = 0.6 (BW ) x (P /140 -1)
Kg
na
Hypovolemic – unstable pt????
 Correct volume problem i.e. normal saline
 Correct osmolal problem
Hypervolemic
 Salt removal with loop diuretics and free water

59. CASE STUDY

60. Hypercalcemia
Etiology
 Clinical features : bones, moans, stones, groans
 Investigations: Ca, Phos, EKG, PTH, Urinary calcium excretion ( R/o familial
hypocalciuric hypercalcemia)
 Management:
 Criteria for surgery in primary hyperparathyroidism
 Sestamibi scan only if surgery is planned/indicated
 Hypercalcemic crisis management – ivf + lasix after volume repletion only
 Indications for corticosteroids : are useful for treating hypercalcemia caused
by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma),
sarcoidosis, and other granulomatous diseases
 Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by
increasing sensitivity of calcium sensing receptor on chief cell of parathyroid
gland to extracellular calcium. Also results in concomitant serum calcium
decrease  Indicated for hypercalcemia with parathyroid carcinoma.
Do not lower Calcium too much  Serum calcium reduction may cause lowered
seizure threshold, paresthesia, myalgia, cramping, and tetany;


61. 






Criteria for Surgery – Primary
hyperparathyroidism
Serum total calcium level >12 mg per dL (3 mmol per L) at any time
Hyperparathyroid crisis (discrete episode of life-threatening
hypercalcemia)
Marked hypercalciuria (urinary calcium excretion more than 400 mg
per day)
Nephrolithiasis
Impaired renal function
Osteitis fibrosa cystica
Reduced cortical bone density (measure with dual x-ray
absorptiometry or similar technique)




Bone mass more than two standard deviations below age-matched controls (Z
score less than 2)
Classic neuromuscular symptoms
Proximal muscle weakness and atrophy, hyperreflexia, and gait
disturbance
Age younger than 50

62. Hypercalcemia – Breast Cancer
Management:
 Principal Rx : Bisphosphonates for moderate to severe
hypercalcemia ( Aridia, Zolendronic acid) ( and also
prevent osteoporosis) ( esply pts on Aromatase
inhibitors are even prone to osteoporosis)

 Manage hypercalcemic crises as in all other cases ( IV
Fluids and only after complete hydration, then
furosemide)

63. Hyponatremia









Classify – Hypotonic, Isotonic and Hypertonic
Classify – hypovolemic or euvolemic
Hypovolemic Hyponatremia – Diarrhea, Vomiting,
early excess diuresis
Euvolemic Hyponatremia  SIADH
Isotonic Hyponatremia  Pseudohyponatremia
( Hyperglycemia, Hypertriglyceridemia, does not occur
with uremia)
Rx  Correct volume and then osmolal problem
Volume problem  Isotonic saline always !!!!!!!!!!
Asymptomatic  fluid restriction
CNS symptoms  3% Saline

64. Hyperkalemia

Several causes : Medication interaction is a
common one ( ACEI+Spironolactone+beta
blocker, HEPARIN), renal failure, Addisons
disease, Rhabdomyolysis, Metabolic acidosis,
Hyperglycemic states.

Effects : arrhythmias, Can lead to tall tented twaves on EKG

65. Ekg- Hyperkalemia
The following changes may be seen in hyperkalaemia
 small or absent P waves
 atrial fibrillation
 wide QRS
 shortened or absent ST segment
 wide, tall and tented T waves
 ventricular fibrillation

66. 58 year old man on
haemodialysis presents with
profound weakness after a
weekend fishing trip.

67. The man’s K was 9.6
Next Step  IV CALCIUM CHLORIDE
( CALCIUM GLUCONATE AN
ALTERNATIVE)

68. 






30 y/o woman evaluated in the emergency department for a 2day 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

69. Hyperkalemia - Treatment
MNEMONIC – CBIGKDrop
 Check the EKG  If EKG changes, calcium
gluconate IV
 B – BICARBONATE/ Beta agonists
 I – INSULIN
 G – DEXTROSE
 K – KAYEXALATE If total body potassium is
an issue
 D – Hemodialysis for refractory Hyperkalemia

70. HYPOKALEMIA - EKG
The following changes may be seen in
hypokalaemia.
 small or absent T waves
 prominent U waves
 first or second degree AV block
 slight depression of the ST segment

71. Acid Base Disorders
Formulas, Case studies and
Management

72. Acid Base Disorders





Metabolic Alkalosis
Respiratory Alkalosis
Metabolic Acidosis
Respiratory Acidosis
Mixed Disorders

73. Acid Base Disorders





Common clinical problems
Associated with life threatening conditions
Often misdiagnosed
Demands an understanding of physiology and
pathophysiology
pH is a major determinant of enzymatic reactions
– Acedemia denatures the enzymes, decreases
threshold for ventricular fibrillation and increases
respiratory drive. Alkalemia suppresses respiratory
drive, can cause myocardial ischemia, coronary
vasospasm etc

74. Acid Base Disorders
- CARBONIC ACID - BICARBONATE
SYSTEM : H + HCO3 ↔ H2CO3 ↔ H2O +
CO2
-
HENDERSON-HASSELBACH
EQUATION : pH = pKa + log HCO3 / H2CO3
PLASMA ACIDITY : determined by :
Balance between concentration of plasma
bicarbonate and pCO2
Measured as pH or H ion concentration
-

75. Acid Base Disorders
1. Factors affecting plasma Bicarbonate :
 Rate of H ion input
 Rate of H ion excretion via kidneys
 Rate of H ion or bicarbonate loss via GI tract
 Availability of non bicarbonate buffers
 Volume of distribution of bicarbonate
2. Factors affecting pCO2
 Rate of CO2 excretion via alveolar ventilation
 Rate of CO2 production

76. ACIDEMIA-ALKALEMIA



Refers to plasma acidity
Acidemia: pH < 7.36
Alkalemia: pH > 7.44
Metabolic Disorder:
- Acid-base disorder caused by primary
change in plasma bicarbonate
- Plasma bicarbonate = 24-28 meq/L
 Respiratory Disorder
- Acid-base disorder caused by primary
change in pCO2
pCO2 = 36 - 44 mmHg

Compensatory Mechanisms :

Appropriate proportional physiologic
responses which tend to restore pH
toward, but not to normal
Terms “over” and “under”
compensation should be avoided –
INSTEAD USE “ MIXED “
DISORDER!!!

77. Metabolic Acidosis
Calculate Anion Gap : Na - (Cl + HCO3) - Normal 3 - 10
meq/L
Given entirely by Unmeasured anions are related to (-) charge
on albumin  One gram albumin = 2.5 meq/L anion
i.e. Albumin of 4 gm/L, baseline anion gap would be 10
meq/L which is Normal. Correct Gap for Albumin!!!  If
albumin is 2gm%, the baseline anion gap should be 5 in
which case 10 should be assumed as increased Anion gap.

Delta Gap : Delta AG / Delta HCO3:
1:1 = Anion gap acidosis
>1 = Anion gap acidosis plus metabolic alkalosis
< 1 = Increased Anion gap acidosis plus normal
anion gap acidosis
 Classify Metabolic Acidosis
– Increased Gap
- Normal Anion gap


78. Calculate Compensation
Compensation Metabolic Acidosis
Occurs in 12-24 hours and limit PCO2 10
mmHg :
Expected pCO2 = 1.5x HCO3 + 8 +/- 2
pCO2 = last 2 digits pH
pCO2 = HCO3 + 15
 If measured Pco2 is less than expected pco2 as
calculated by this equation – suspect a primary
respiratory alkalosis. If it is more than expected
suspect primary respiratory acidosis. This is how
you diagnose mixed disorders!!!


79. Example

1.
2.
3.
4.
5.
6.
7.
65 y/o man with CAD  and then
cardiogenic shock. Ph 7.26. PCo2 40 HCO310 Na+ 136 Cl- 110 Albumin 2.0
What's the Anion Gap?
Corrected Anion Gap ? {gap + 2.5(measured
albumin)}
Delta Anion Gap?
Delta Hco3-? ( 24 – bicarb)
Delta Gap?
Adequately Compensated or mixed ?
Name the disorder ?

80. Normal Anion-Gap Metabolic Acidosis
Gastrointestinal Loss of Bicarbonate

Diarrhea

Urinary diversion

Small bowel, pancreatic, or bile drainage ( fistulas, surgical
drains )

Cholestiramine
Renal Loss of Bicarbonate ( or Bicarbonate equivalent )

Renal tubular acidosis

Recovery phase of Ketoacidosis

Renal Insufficiency

Acidifying Substances- HCl, NH4Cl, Arginine HCl, Lysine HCl,
Sulfur
To differentiate calculate Urinary Anion Gap = Urine (Na + k) –
(cl-). Normal is from +10 to -10. If UAG > +10  Renal loss.
If UAG < -10 or more negative  GI Causes

81. Increased Anion Gap Acidosis






Ketoacidosis - diabetic, alcoholic, starvation
Lactic acidosis
Uremia
Toxins - Ethylene glycol, methanol, salicylate,
paraldehyde
Osmolar Gap = Measured Osmolarity –
Calculated Osmolarity
Calculated Serumosm = 2(Na) + Glucose/18
+BUN/2.8 ( + ethylalcohol/4.5)

82. Plasma Level v. Osmolality
Ethanol ÷ 4.6
Methanol ÷ 3.2
Ethylene glycol ÷ 6.2
Isopropanol ÷ 6.1
For example, a blood ethanol level of 100mg/dL
would increase plasma osmolality 100/4.6 or 22
mOsm/L

83. Case Study

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
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
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
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.
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 ?

A) Endotracheal intubation in view of severe acidosis
B) Hemodialysis because this is an acute renal failure causing acidosis
C) Fomepizole because of suspicion of ethylene glycol intoxication
D) Supportive treatment for now because this is an ethylalcohol induced
lactic acidosis
E) Bicarbonate drip to reverse the acidosis because this is renal tubular
acidosis





84. 
Ethylene Glycol Poisoning
Envelope shaped crystals




Treatment : Consider Antidote
( Fomepizole or Ethanol ) if Level >
20mg% or if you suspect ethylene
glycol intake with 2 or more – a)
arterial ph < 7.3, Hco3 <20, osmolar
gap>10, calcium oxalate crystals in
urine.
Antidote blocks Alcohol
dehydrogenase and prevents the
Glycolic acid formation. In case of
methanol, toxic meatbolite is formic
acid
Ethylene glycol found in
antifreeze and de-icer
Toxicity results at doses >1.0
ml/kg

Ethylene glycol causes CNS
depression , converts to
Glycolic Acid (metabolite)
effects 
Metabolic Mcido
&Renal Failure

Oxalic acid (metabolite)
effects  Calcium oxalate
crystal deposition



C/F: Confusion, Ataxia,
Slurred speech
,Hallucination, Tetany
Seizures (Hypocalcemia)
Hypertension
Tachycardia

85. Increased Osmolal Gap








Ethanol
Methanol
Ethylene Glycol
Formaldehyde
Paraldehyde
Lactic Acidosis
ESRD
Ketoacidosis





Mannitol
Isopropyl alcohol
Hyperlipidemia
Hyperproteinemia
Diethyl ether

86. Isopropanol Ingestion





Present with CNS depression, hypotension,
arrhytmias and gastritis
Acetest reaction positive
Increased osmolal gap
No metabolic acidosis
Anion gap normal

87. Renal Tubular Acidosis



Type 1 ( distal)
Type 2 (proximal)
Type 4 (hyporeninemic hypoaldosteronism)

88. Type I RTA (Distal)



Causes: autoimmune diseases, hyperglobinemia
states and hereditary
Present with normal anion gap acidosis, urine pH
>5.5, hypokalemia, hypercalciuria,
nephrocalcinosis and stones
Treatment: alkali i.e. K citrate

89. Type II RTA (Proximal)





Isolated defect or associated with generalized proximal
dysfunction i.e. Fanconi syndrome
Failure to reclaim filtered bicarbonate
Increase FEHCO3
Urine pH > 5.5, but may be < 5.5 once HCO3 < 16
meq/L
Causes:




Multiple myeloma
Acetozolamide
Ifosfamide
Lead, cadmium, copper

90. Type 4 RTA



Hypoaldosteronism or aldosterone resistance
Causes: diabetes mellitus, HIV and tubulointerstitial disease
Present with hyperkalemia, normal anion gap
acidosis and normal urine pH

91. Metabolic Alkalosis
Calculate compensation
PCO2= ( 0.7 x HCO3 ) + 21 . If measured Pco2
is more than this then there is concomitant
respiratory acidosis. If less than this then
concomitant respiratory akalosis.
Delta Gap to r/o mixed disorder – metabolic
acidosis + metabolic alkalosis if delta gap >1


92. Causes of Metabolic Alkalosis
Saline responsive : ECF depleted ( contraction alkalosis ), Urine
chloride < 10 meq/L, do not go by urine sodium in assessing
volume status
Gastrointestinal Loss eg : Surreptious vomiting, NG tube
suctions,Villous adenoma, Chloride diarrhea, Diuretics (late),Post
hypercapnea
 Saline resistant : Saline Resistant Metabolic Alkalosis , Increased
mineralocorticoid effect,Urine Cl > 20 meq/L
 Hypertensive causes:Primary aldosteronismCushing’s syndrome,
11 or 17 hydroxylase deficiency, Licorice / carbenoxolone,
Liddle’s syndrome, Steroids
 Normotensive causes: Bartter’s syndrome ( thiazide), Gitelman’s
syndrome ( like loop diuretic), Diuretics (present), Severe
potassium depletion, Severe magnesium depletion


93. Metabolic Alkalosis - Treatment

Saline responsive
Normal saline to volume replete
 KCl


Saline resistant


Inhibit or remove excess mineralocorticoid effect
Miscellaneous
Acetazolamide, HCl, NH4Cl
 Hemodialysis


94. 
Case 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 Abuse
B)
Surreptious vomiting
C)
Licorice abuse
D)
Malabsorption Syndrome
E)
Hyporeninemic Hypoaldosteronism
Treatment :
A)
IV normal saline
B)
Spronolactone
C)
Amiloride
D)
Psychiatry consult
E)
Reassurance because this is self limiting