Jad Skaf, MD

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Chiefs Rounds with Lawrence S. Weisberg, MD
Professor of Medicine. Head of Nephrology

• Jad Skaf, MD
• 11/16/09

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Case 1

• WF is a 66 year old male brought in by EMS after
  being found unresponsive at home.
• He had been feeling ill for approximately two
  weeks, according to his family, complaining of
  severe epigastric pain.
• PMH
• Alcohol use
• Erosive esophagitis
• Gout
• HTN
• Reactive airways disease
• Known serum creatinine 6 months earlier 1.0
  mg/dl

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History, contd

• Social Hx
• Cigarettes 25 p-y,
• EtOH 1 pint of vodka every 2-3 days
• Meds
• Folate 1 mg daily,
• Pantoprazole 40 mg BID,
• Thiamine 100 mg daily,
• Trazodone HCL 100 mg PO daily,

4
12.3
144
83
69
8.8
305
98
2.9
39
6.7
37.7
Calcium 18.6 8.5-10.5 Magnesium 3.7 1.6-2.6
Phosphorus 3.9 CK 36
Initial labs
iCa 6.7 4.20-5.00 pH 7.47 7.35-7.45
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What are the problems?

• Hypercalcemia
• Acute kidney injury
• Metabolic alkalosis

Are they related?
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Regulation of systemic calcium homeostasis
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Dysregulation of systemic calcium homeostasis ?
hypercalcemia

• 1 hyperparathyroidism
• Lithium

• Humoral Hypercalcemia of Malignancy (PTHrP, TNF
  a)
• Immobilization
• Paget Ds.
• Thyrotoxicosis
• Vit A intoxication

• Excessive Vit D ingestion
• Lymphomas
• Granulomatous Dss.

Familial hypocalciuric hypercalcemia

• Excessive Ca ingestion?

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Hypercalcemia
48
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Hyperparathyroidism
Malignancy
.Chronic Granulomatous ds. .Vit D
intoxication .Meds (lithium, theophylline..) .Hype
rthyroidism .Acromegaly .Adrenal
Insufficiency .Immobilization .TPN .Milk-Alkali Sd
lt 11
gt 13
Lafferty FW. J Bone Miner Res 1991 Oct6 Suppl
2S51-9 Burtis WJ Wu TL Insogna KL Stewart AF.
Ann Intern Med 1988 Mar108(3)454-7. Ratcliffe
WA Hutchesson AC Bundred NJ Ratcliffe
JG-Lancet 1992 Jan 18339(8786)164-7.
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More lab results

• suppressed

• PTHrP negative
• SPEP and UPEP negative
• TSH normal
• 25(OH)-vitamin D 11 (20-100)

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?
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More history

• When the patient woke up, he admitted to treating
  his epigastric pain, over a week or so, with
• Aspirin 1300 mg q 4 h
• Calcium carbonate 1000 mg q 4 h

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12.3
144
83
69
8.8
305
98
2.9
39
6.7
37.7
Calcium 18.6 8.5-10.5 Magnesium 3.7 1.6-2.6
Phosphorus 3.9 CK 36

• Hypercalcemia
• Metabolic alkalosis
• Acute kidney injury

iCa 6.7 4.20-5.00 pH 7.47 7.35-7.45
Milk alkali syndrome
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Milk-Alkali SyndromeA Historical Perspective
1912 Dr. Sippy regimen for peptic ulcer
treatment hourly milk and Sippy
Powders (Calcium carbonate, sodium bicarbonate,
magnesium oxide, and bismuth subcarbonate)
Hardt, L.L. and Rivers, A.B. Toxic manifestations
following the alkalic treatment of peptic ulcer.
Arch. Int. Med.- 31171-180, 1923
Cope, C.L. Base changes in the alkalosis produced
by the treatment of gastric ulcer with alkalies.
Clin. Sci. 2287-300, 1935-1936.
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Prolonged Excessive Intake of Milk and
Alkali Hypercalcemia, azotemia, proteinuria,
alkalosis and calcinosis.
.Band Keratopathy .CNS Calcifications .Lymph
Nodes .Vascular System .Subcutaneous
tissues .Nephrocalcinosis
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Classical Presentation
Acute after approximately 1 week of treatment.
The symptoms are those of acute
hypercalcemia nausea, vomiting, weakness, and
mental changes with psychosis or depressed
sensorium. There is also severe metabolic
alkalosis, a normal to elevated plasma phosphate
concentration, and acute renal insufficiency. Ch
ronic (Burnett's syndrome), long history of
high milk/alkali intake. Symptoms of chronic
hypercalcemia, such as polyuria, polydipsia,
muscle aches, and pruritus . There was evidence
of mestastatic calcifications. Subacute or
intermediate (Cope's syndrome), therapy with
milk and alkali had been taken intermittently for
years. Affected patients had symptoms of both
acute and chronic hypercalcemia and responded to
medication withdrawal with gradual improvement.
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Schematic incidence over time
CaCO3 Vitamin D suppl.
Sippy regimen
H2 blockers PPIs
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Modern Presentation
Since 1990, approximately 40 patients have been
reported. Calcium Carbonate was the
predominant source of calcium and alkali intake
in all patients, supplemented with milk in 43 .

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40 Modern Cases (since 1990)- Patient
Characteristics

• 50 had an acute presentation
• Calcium concentration varied widely
• Renal insufficiency was moderate in most cases
• Bicarbonate concentration usually ranged from 28
  to 40 meq/L
• Mild hypophosphatemia was seen in approximately
  40 percent
• Intact PTH was measured in 12 cases.

• Milk-alkali syndrome associated with calcium
  carbonate consumption. Report of 7 patients with
  parathyroid hormone levels and an estimate of
  prevalence among patients hospitalized with
  hypercalcemia. Beall DP Scofield RH.Medicine
  (Baltimore) 1995 Mar74(2)89-96.
• Milk alkali syndrome. McGuinness B Logan JI.
  Ulster Med J 2002 Nov 71(2)132-5.
• Milk-alkali syndrome in pregnancy. Picolos MK
  Sims CR Mastrobattista JM Carroll MA Lavis VR.
  Obstet Gynecol 2004 Nov104(5 Pt 2)1201-4.

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125 non ESRD patients hospitalized
with hypercalcemia 72.7 women
Milk-Alkali Syndrome 8.8
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1,25 dihydroxy-vitamin D

Alkalosis
Volume depletion -Vomiting -Hypokalemia -Pre-exis
ting renal dz
NaHCO3 Reabsorption
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? Ca
Ca
Ca
AKI
X
COXi
NaCl Ca
NaHCO3
H2O H
? NaHCO3
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12.3
144
83
69
8.8
305
98
2.9
39
6.7
37.7
Calcium 18.6 8.5-10.5 Magnesium 3.7 1.6-2.6
Phosphorus 3.9 CK 36

• Hypercalcemia
• Metabolic alkalosis
• Acute kidney injury

iCa 6.7 4.20-5.00 pH 7.47 7.35-7.45
Milk alkali syndrome
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Milk-Alkali Syndrome
Hypercalcemia
Kidney Failure
Alkalosis Volume Depl
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Renal Failure in MAS
PTH
Volume Depletion
Alkalosis
Hypercalcemia
GFR
Nephrocalcinosis
27
What remains unexplained is the difference in
sensitivity of individuals to increased intake of
calcium and alkali.
Role of Calcitriol Suppression ?
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Modern Risk Factors

• Ingestion of Calcium Carbonate
• Concurrent therapy with vitamin D
• renal insufficiency
• Volume contraction
• Thiazide diuretics
• COX inhibitors!!

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Reducing daily calcium intake or close monitoring
may be prudent in patients taking thiazides,
patients who have preexisting renal failure, or
those who experience concurrent vomiting (bulimia
or hyperemesis of pregnancy)
Muldowney WP, Mazbar SA. Rolaids-yogurt syndrome
a 1990s version of milk-alkali syndrome. Am J
Kidney Dis. 199627(2)270-272. Described a
patient with bulimia who developed MAS by taking
about 1.7 g of calcium daily. Patients with
bulimia seem to be particularly vulnerable
because of the frequent combination of vomiting,
diuretic use, and deviant eating habits.
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Back to our patient

• Calcium carbonate was stopped and the patient was
  started on saline infusion. His K was
  replenished.

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Calcium over time
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Creatinine over time
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Case 1

• ?

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Case 2

• 46 y.o. man sent to ED by his nursing home staff
• for diminished urine output for several days
• PMH
• Psych disorder COPD
• Sz disorder
• CKD SCr 1.5 mg/dL one year PTA
• Meds
• valproic acid lansoprazole olanzapine
• SHx
• Institutionalized for years
• gt 50 p.y. h/o cigarettes

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Physical Examination

• BP 100/60, HR 102 at rest, RR 8, afebrile
• Poor dentition
• Diminished breath sounds throughout the chest
• Normal heart exam
• Diminished bowel sounds, soft abdomen, non tender
  to palpation
• No peripheral edema
• Lethargic, uncooperative with the history and
  examination

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13.1
139
73
67
Calcium 9.6 8.5-10.5
8.6
280
104
2.6
39
4.2
36.7
ABG pH 7.64, pCO2 66, pO2 45, HCO3 72
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Causes of metabolic alkalosis

• Intravascular volume depletion, absolute or
  effective
• Gastrointestinal acid loss
• Vomiting or nasogastric suction
• Villous adenoma
• Chloride diarrhea
• Renal acid loss
• Diuretics (loop, thiazide)
• Bartter syndrome
• Gitelman syndrome
• Magnesium depletion
• Post-hypercapnic state
• Congestive heart failure
• Hepatic cirrhosis/ascites
• Intravascular volume expansion
• High renin, high aldosterone
• Renal artery stenosis
• Severe hypertension
• Renin-secreting tumor
• Low renin, high aldosterone

Palmer BF, Alpern RJ. J Am Soc Nephrol 1997
81462-1469
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What is the most useful initial lab test to
narrow the DDx of metabolic alkalosis?

1. spot urine K concentration
2. spot urine Cl concentration
3. fractional excretion of K
4. spot urine Na concentration

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Diagnosis of metabolic alkalosis
UCl
gt 10 mEq/L
lt 10 mEq/L
UK
lt 20 mEq/L
gt20 mEq/L

• current diuretics
• Bartter or Gitelman
• SAME
• primary aldosteronism
• Cushing
• exogenous mineralocorticoid
• secondary aldosteronism
• Liddle syndrome

• vomiting / NG suction
• prior diuretics
• prior hypercapnea
• villous adenoma
• chloridorrhea

• laxative use
• clay pica

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More labs
Ca 9.6
139 lt 50 67 / 4.2
2.6 73 104
ABG pH 7.64, pCO2 66, pO2 45, HCO3 72
UNa 84 mmol/L UCl lt10 mmol/L UK 74 mmol/L
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Diagnosis of metabolic alkalosis
UCl
gt 10 mEq/L
lt 10 mEq/L
UK
lt 20 mEq/L
gt20 mEq/L

• current diuretics
• Bartter or Gitelman
• SAME
• primary aldosteronism
• Cushing
• exogenous mineralocorticoid
• secondary aldosteronism
• Liddle syndrome

• vomiting / NG suction
• prior diuretics
• prior hypercapnea
• villous adenoma
• chloridorrhea

• laxative use
• clay pica

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139
73
67
104
2.6
39
4.2
Anion gap 27
ABG pH 7.64, pCO2 66, pO2 45, HCO3 72
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Why does he have a high anion gap?

• Its an artifact
• It has something to do with albumin
• He probably has a lactic acidosis

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high anion gap in alkalemia
Na
AG
HCO3-
Cl-
H
OH-
Na
45
high anion gap in alkalemia
Na
AG
HCO3-
Cl-
Na
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Metabolic consequences of Alkalemia
Alkalemia
hypoventilation
vasoconstriction
Bohr effect
hypoxemia
Decreased tissue O2 delivery
lactic acidosis
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How should the patient be treated?

• normal saline solution IV
• NSS IV plus KCl
• hydrochloric acid IV plus KCl
• acetazolamide
• KCl alone

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Hydrochloric acid infusion for treatment of
metabolic alkalosis

• Method
• 0.1-0.25N HCl IV to deliver about 20 mmol HCl per
  hour (adults)
• e.g. 0.1N HCl at 200 ml/h
• Duration 6-12 hours
• Risks
• Venous sclerosis, extravasation
• Reserve for refractory cases
• Requires central venous delivery

Brimioulle et al. Crit Care Med 198513738-42
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Hospital Course
0.1N HCl _at_ 200 ml/h
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Role of hypokalemia in maintenance of metabolic
alkalosis
HCO3- ?
NH3-
H
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Hospital Course
0.1N HCl _at_ 200 ml/h
Hospitalization No.1
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Thank you