Tuesday, August 25, 2009


Today we had a discussion about polyuria, and how to differentiate its different causes.

Polyuria is defined as greater than 3L/d. Always get a urine specific gravity. 1.010 is equivalent to plasma osmolality (~300)

General approach:

1. Solute- mediated: glucose, mannitol, NaCl (saline infusion, diuretics, post-obstructive), urea from high protein feeds.
Labs for solute show urine osm over 300, 24h urine osmoles over 900.
2. Psychogenic- urine osmol less than 300, esp probable if serum Na less than 137
3. Central DI- hypothalamic or pituitary stalk disease- urine osm less than 300. Serum Na usu over 142. May see urine osm over 300 if it is partial central DI and pt is water deprived.
4. Nephrogenic DI- X-linked, Li-induced, hyperCa2+, HypoK+, amyloid, sjogren's. Urine osm less than 300, Serum Na usu over 142. May see urine osm over 300 if it is partial central DI and pt is water deprived.

A word about psychogenic polydipsia and beer potomania:

Minimum achievable urine osmolality is ~50mEq/L (i.e. no ADH). Metabolism of a normal diet yields ~600mOsm/d. This means maximum urine output is ~12L/d.

In primary polydipsia, maximum output is exceeded by free water intake, leading to dilutional hyponatremia despite minimally concentrated, high volume urine output. Result is low (below 100) urine osm, low serum osm, hyponatremia, high urine output.

In beer potomania, protein intake is low, and ~250mOsm/d are produced, leading to a theoretical maximum urine output of 5L/d. If free water intake exceeds this (i.e. in beer), the same situation develops, with low urine osmolality, low serum osmolality, and relatively lower urine output.

Water deprivation test: Used for diagnosis of diabetes insipidus.

Patient is admitted to hospital first thing in AM. Do hourly weights, urine vol, urine lytes, osmol, serum Na, serum osm, ADH. Stop the test if urine osm is over 600. This means psychogenic polydipsia (i.e. kidneys can concentrate urine)
Give DDAVP 2ug sc when 1 of:
over 3% of body wt lost
serum osm over 300 or serum Na over 145
serum osm increasing, but urine osm unchanged x 2-3h

After DDAVP give, collect urine and plasma for 2 more hours.


Complete nephrogenic DI: urine osm lower than 300, no resp to DDAVP
Partial nephrogenic DI: urine osm over 300 pre DDAVP, then no response to DDAVP
Complete central: urine osm never over 300, then over 50% increase after DDAVP
Partial central: urine osm over 300, rises 10-50% post DDAVP

Nephrogenic- fix underlying, salt restrict, thiazides
Central- give ddAVP


Secondary causes of central DI

1) Infection - TB, Whipple's
2) Malignancy- Germ cell tumor, lymphoma
3) Infiltration- Hemochromatosis, amyloidosis
4) Autoimmune- Wegner's, sarcoidosis, lymphocytic infundibulitis
5) Histiocytoses- Langerhans' cell or non-langerhans' cell

Monday, August 24, 2009

Approach to renal failure

Today we discussed acute renal failure. Some important points:

The time-tested approach to acute renal failure (or 'acute kidney injury') is
Prerenal, renal, and post-renal


Hypovolemia: low intake, GI, GU, or insensible losses, hemorrhage, vasodilation)
Low effective circulating volume: CHF, cirrhosis, 'third spacing')
Renal vasoconstrictors: GN sepsis, cyclosporine, NSAIDS, ACE-I/ARB (sort of; different mechanism), hepatorenal syndrome
Characterized by clinical signs of hypovolemia or above problems, bland urine, urine osmol over 450, low urine Na. Responds to fluid replacement

Renal parenchymal:

1) Glomerular
Look for nephritic syndrome: HTN, rbcs, rbc casts, sub-nephrotic proteinuria
or nephrotic syndrome: edema, dyslipidemia, heavy proteinuria (over 3 g/day), hypoalbuminemia, thrombosis
Rapidly Progressive GN AKA 'crescentic' GN: mainly present as nephritic, but sometimes nephrotic (or both!)
1. Immune complexes: (with decreased complement- post strep, endocarditis, SLE, cryoglobulinemia. With normal complement levels- endocarditis, IgA)
2. Linear (Goodpasture's, AGBM)
3. Pauci-immune (Wegener's, Churg-Strauss, microscopic polyangiitis)

Other mainly nephritic: IgA nephropathy (can also be nephrotic), membranoproliferative GN, focal proliferative GN

Mainly nephrotic: minimal change, FSGS, membranous, nodular

2) Tubulointerstitial:
AIN: Drugs: Abx (methicillin classic, also quinolones), NSAID, allopurinol. Infection- pyelo, CMV, legionella. Neoplastic: myeloma, amyloid. May see WBC casts (shown above),
urine eosinophils (Sn ~70%. Sp ~80%)
ATN: ischemic (hypotension, sepsis), toxic: exogenous (meds- aminoglycosides, ampho, cisplatin, contrast) or endogenous (myoglobin, hemoglobin, uric acid eg. from tumor lysis, Ca2+). Hallmark is heme granular
casts. Characterized by high urine Na, low osmolality.

3) Vascular:
Large vessel: RAS RA thrombosis vasculitisrenal v. thrombosis esp. in nephrotic syn
Small vessel: HTN nephrosclerosis, scleroderma renal crisis, cholesterol embolic (livedo reticularis, blue toes, dusky feet, eosinophilia) TTP/HUS, antiphospholipid syndrome, DIC


Lower UT obstruction (prostate, mass, etc) or effective obstruction (e.g. retention from meds), neurogenic bladder, UTI, bladder stones, bilateral stones or stone with 1 kidney, retroperitoneal fibrosis (NB- may have no hydronephrosis here), lymphoma
Usually characterized by bland urine, imaging evidence of obstruction (but not always). Urine output is not
always low.

General approach:

1. Previous creatinine
2. Hx: drugs, volume, systemic disease (lung, joint, skin, fever...)
3. Volume status assessment, assesment for dialysis indications
4. Urinalysis: blood, protein, casts, cells, eosinophils
5. Urine lytes, osmolality
6. U/S of abdo to r/o obstruction
7. Serology: ANA, anti-GBM, ANCA, C3, C4.

Click here for a NEJM CPC that goes over the approach to ARF

Friday, August 21, 2009

Pulmonary embolism

Today we discussed PE in the setting of malignancy. Some points about this common and serious disease:

Clinical presentation:
Notoriously unreliable. May see any or none of

SOB, pleuritic C/P, hemoptysis, palpitations
Tachypnea, tachycardia, desaturation, hypotension

Other possible findings:
ABG- hypoxia, resp alkalosis
CXR- atelectasis, effusion,
Westermarks's (proximal pulm art dist with distal oligemia), Hampton's hump (peripheral density from infarct). This CXR signs are rare; most commonly normal CXR
ECG- RV strain (STD V1-V2, RBBB, RAE, RVH, R axis dev),
S1Q3T3- massive. Usually just sinus tach
Echo- RV stress (hypokinesis, TR, dilation)

Clinical exam is of insufficient Sn/Sp to make diagnosis; it gives a pretest probability.
Non-invasive investigations are also not Sn or Sp alone, although a -ve CTA may be sufficient to withhold anticoagulation

Approach is to
1) Determine pretest probability
2) Determine whether pt has adequate cardiopulmonary reserve (i.e. will another PE kill this pt?)
3) Perform noninvasive or invasive investigations.

Risk stratification:
Clinical findings of DVT- 3
No other more likely dx- 3
Immobilized over 3d or major surgery within 1 mo- 1.5
HR over 100- 1.5
Previous DVT/PE- 1.5
Active Ca- 1
Hemoptysis- 1

Greater than 6: High PTP (78% have PE)
2-6: Int (28% have PE)
Lower than 2: Low (3% have PE)


DVT and PE are treated the same way:
Initially: LMWH (unless renal impairment or need ability to reverse, in which case UFH infusion. Start warfarin; adjust to INR 2-3, then d/c warfarin
Long term:
With reversible/treatable cause for DVT/PE:
Treat underlying, anticoag for 3-6 mo then stop.
Anticoag for 6/12, then decide whether to continue based on:
bleeding risk, pregnancy plans, pt's preference.
Underlying unmodifiable reason:
Lifelong anticoag recommended

EBM points:

VTE in cancer
CLOT trial compared the efficacy and complications of the use of LMWH vs. warfarin in treatment of DVT/PE in cancer pts.
Intervention: Dalteparin 200u/kg SC OD x 5d, followed by coumadin for INR 2.5 or dalteparin alone, 200u/kg for 1 month and 150u/kg for 5 months.
Outcomes: recurrent DVT in 6 months, mortality, bleeding
Results: Recurrent DVT: 17% vs. 9% on LMWH (ARR 8%, NNT 13). Significant bleeding: 4% warf, 6% LMWH. Mortality in 6/12: 39% LMWH, 41% warfarin. Subgroup analysis showed decreased mortality on LMWH in pts presenting with VTE and metastatic ca.

Thrombolysis in PE
Only RCT evidence comes from 2002 NEJM paper comparing alteplase vs. placebo in patients with acute PE and RV dysfunction or pulmonary hypertension. Endpoint was mortality or "clinical deterioration requiring escalation of treatment"; this might include pressors/inotropes, CPR, surgery, intubation, or thrombolysis. There was no mortality difference, but the alteplase group had significantly lower "escalation of care". This is a criticized paper because some argue that it essentially gives the "escalation of care" outcome to 1 group to begin with (i.e. thrombolysis as both an intervention and an outcome is a bit strange).

Thursday, August 20, 2009

Hemolytic anemia

Today we discussed hemolysis. These cases are relatively rare, but can cause impressive anema and can be very challenging to manage (and blog about!). A few points:

Hemolytic anemias account for less than 5% of cases of anemia, and have over 200 causes.

Traditional approach to differential is

1) Intracorpuscular 2) Membrane 3) Extracorpuscular

Intracorpuscular- think of what an RBC contains: Hgb, enzymes.

Inherited hemoglobinopathies:
alpha and beta thalassemia, sickle cell disease (SS and SC), unstable hemoglobins

RBC enzymopathies:
Pyruvate kinase def (N.Europe; shows echinocytes)
G6PD def- in males mainly. Inducers of G6PD deficiency related hemolysis:
dapsone, primaquine, sulfamethoxazole (many other obscure drugs), fava beans


Hereditary spherocytosis: N europe (1/2000). 75% AD. Has spherocytosis, osmotic fragility
Hereditary elliptocytosis


Inherited RBC antigen abnormalities

Immune-mediated hemolysis: Shown in above picture
Autoimm- warm (IgG), cold (IgM or IgG). Associated with autoimmune conditions, immunodeficiency, lymphoproliferative disorders, malignancy, infection (For cold, mycoplasma, EBV, HSV. For warm, CMV).
Alloimmune- active (e.g. transfusion, transplant), passive (e.g. in newborns)

Renal failure- esp echinocytes

Hepatic failure- esp acanthocytes
Osmotic hemolysis (dialysis)

aresnic, lead, Wilson's
valvular disease, vegetations
LVAD, intraaortic balloon pump, cardiac bypass, dehisced mechanical valves,
burns, radiation, trauma (e.g. march hemoglobinuria in soldiers)
Venoms (snake, spider)

Drug- induced hemolysis :
May be hapten, innocent bystader (RBCs adsorbed to IC's), or induce warm autoimmune (bad because remains after drug goes)
Drugs (many!)- Classics are alphamethyldopa, cephalosporins, penicillin, quinine, sulfonamides.

clostridial sepsis
Mycoplasma, EBV, CMV
HSV, syphillis
Parasitic: malaria, babesiosis

Thrombotic microangiopathy
DIC, TTP, HUS, HELLP, acute fatty liver of pregnancy, ticlopidine, plavix, calcineurin inh

Some points on a "hemolysis history"

Age, ethnicity, malaria endemicity
temporal onset (for acquired vs congenital cause)
anemia symptoms
hemolysis symptoms (flank pain, hemoglobinuria, biliary colic)
PMHx (autoimm, rheum, malignancy, infectious, thrombosis)
FHx (hemolysis, splenectomy, pigment stones)
Meds/foods: Drug induced (or 'DIHA' as hematologists call it), TTP instigators, G6PD triggers
Transfusion hx

Focused physical

fever, tachycardia, hypotension
scleral icterus, pallor, jaundice
SLE features
organomegaly, Murphy's sign


1) For hemolysis itself:

Reticulocytosis, blood film changes (fragments, spherocytes, etc), plasma hemoglobinemia, high unfractionated bili, high LDH (nb- AST may be high, not ALT), low haptoglobin (both intra and extravascular). If all RBC production stops, expect Hgb fall of ~10/wk. If faster, probably destruction (e.g. hemolysis) happening

2) For potential causes

CBC, retics, blood film, DIC testing, ABO type and screen (i.e. indirect AT), DAT, cold agglutinin testing
Others: PNH, HB electrophoresis, osmotic fragility, sickle testing, 02 affinity testing, HIT, blood cultures, viral titres.


Depends on reason for hemolysis. If autoimmune, general principles are

1) avoid transfusion unless absolutely necessary, but involve the blood bank . transfusion medicine early- may be extremely difficult or impossible to find appropriate units
2) If cold autoimmune: warm extremities, warm IV fluids, steroids, plasmapheresis
3) If warm autoimmune: steroids, IVIG, plasmapheresis. Splenectomy in refractory cases
4) Try to reverse underlying cause if possible

Some links:

Click here for interesting NEJM case and image on cold agglutinin disease
For the serious connaisseur, click here for a review of autoimmune hemolytic anemias

Tuesday, August 18, 2009

HIV- CNS manifestations

Today we discussed the approach to neurological symptomatology in the setting of HIV.

As a general rule, whenever faced with a new (or worsened) problem in the setting of a pre-existing disease, a useful dichotomy is whether this new problem is related or unrelated to the underlying disease.

A useful way of subdividing this problem is whether or not there are imaging abnormalities (may require enhanced MRI to see), and if so, whether there is mass effect.

CNS lesion with mass effect:
1) Toxoplasma (in CD4 <100). Reactivation from prior infection. Toxo antibodies are supportive. Lesions are multiple, and localized to frontal or parietal lobes, thalamus, basal ganglia. Ring enhancement in 90%. Shown in the above picture. May be mimicked by lymphoma- MRI is best test.
2) Primary CNS lymphoma. May see neuro sx or wasting sx. Solitary and multiple lesions are equally frequent. Corpus callosum lesions or periependymal lesions are more likely lymphoma.
3) Brain abscess (staph, strep, salmonella, aspergillus, listeria, 'gumma' from syphillis) Rarely, tuberculoma or cysticercosis

CNS lesion without mass effect:
1) PML- demyeliniting disease from JC virus (acquired in childhood by 90% of population). Seen in severe immunosuppression. Rapidly progressive focal deficits inc. hemiparesis, field deficits, ataxia, aphasia, cognitive changes. Multifocal demyelination.
2) CMV encephalitis- need CD4<50. delirium, confusion, neurological abnormalities.
3) HSV encephalitis- increased risk in HIV; may see temporal lobe changes on MRI
4) HIV encephalopathy: memory and psychomotor slowing, depression, movement disorders- may see symmetric MRI lesions

No CNS lesion on imaging:
1) Bacterial meningitis- esp S. pneumo, listeria
2) TB meningitis
3) Cryptococcal meningitis- need to send CSF and serum crypto antigen.
4) Neurosyphillis

Brain biopsy is gold standard, and is sometimes required to differentiate above possibilities (esp. lymphoma vs. toxoplasmosis)

Some tests you might order from a lumbar pucture in this setting in addition to routine:
Fungal cultures, AFB staining
PCR for JC virus, HSV, EBV, TB ('AMTD')
Cryptococcal antigen
Check opening pressure; may be high in cryptococcal meningitis. High OP in cryptococcal meningitis carries a poor prognosis, and may require a lumbar drain or shunt.

Click here for a good review of PML from the ID department

Monday, August 17, 2009

Diabetic ketoacidosis

Today we discussed DKA. This potentially life-threatening problem is a relatively common internal medicine referral, and although most cases are straightforward, there are a few points to keep in mind to ensure optimal management.

Requires insulin deficiency and increased counterregulatory hormones. Often triggered by inadequate insulin dosing, surgery, infarction (e.g. MI, mesenteric, etc.), infection, steroids. Always search for the precipitant of DKA!

Points on history:
1) History of hyperglycemia: polydypsia, polyuria, polyphagia, visual blurring
2) History suggestive of DKA itself: abdominal pain is common, tachypnea, nausea
3) History of volume depletion: Presyncope, postural symptoms
4) Search for precipitant: Chest pain, abdominal pain, medications, intoxications, insulin use (ar lack thereof...)

Points on physical:
Physical examination may or may not demonstrate depressed sensorium. Typical findings include tachypnea with Kussmaul’s respiration, tachycardia, frank hypotension or orthostatic blood pressure changes, the odor of acetone on the breath, and signs of volume depletion.

Ordered on most patients would be
Glucose, cbc+diff, lytes, ABGs, serum ketones, urine dipstick, Cr, BUN, tox screen, lactate, troponin, ECG, CXR
Monitors: 2 large bore IVs, ECG, foley, possibly art line.

3 Common errors in DKA management:
1) Mismanagement of K+ is the main reason for mortality in these patients. The K+ may be normal because of shifting out of cells from acidosis and lack of insulin, but patients are total body depleted because of urinary losses from polyuria and increased aldosterone. Starting with normal K+ is concerning, and starting with low K+ is very concerning, and that patient may need ICU for central line to deliver K+

2) The main problem in DKA is not hyperglycemia, it is ketoacidosis. The insulin drip is to treat the anion gap (i.e. the ketoacidosis), not the hyperglycemia. If the patient has a high anion gap and normal glucose, continue the insulin and add glucose.

3) Transition to SC insulin after infusion is an issue. Remember that the halflife of IV insulin is minutes, and you therefore need to overlap SC with IV, usually for several hours (until the effect of the SC insulin) before turning infusion off. Transition to SC when anion gap is normal, glucose is controlled, IV insulin dose is stable, and patient is eating. Remember that SC insulin is half as bioavailable as IV.


Major issues (not necessarily in this order; depends on specific situation) are:
1) volume 2) electrolytes (esp. K+) 3) insulin 4) acid/base status

1. IV fluids: Start with 1L NS wide open. Make sure urine output. General teaching is 1L in 30 min then 1L in 1h. When glucose reaches 12-14, change to D5W with 1/2 NS and decrease insulin to 0.05U/kg/h. Maintain glucose at this level until DKA is resolved and pt is alert. Avoid giving hypotonic solutions because of risk of brain edema (seen more in kids) which comes from shifts in glucose without accmpanying change in Na.

2. K, PO4: If K less than 3.3mM, hold insulin, give 40mM K per liter of IV fluid until K is greater than 3.3. If K is above 5.5, do not give K, but check level q2h. If K is between 3.3 and 5, give 20-40mM K in IV fluid to keep K at 4-5mM, possibly with additional K po. Give K before insulin anticipating fall if it is low to begin with. Remember that phosphate also gets shifted (like K) and if gets very low may cause rhabdo, severe muscle weakness, CHF, etc. Replace it.

3. Insulin (IV): Bolus 0.1u/kg, then 0.1U/kg/h. Check glucose hourly. If it does not fall by 3mM in 1st hour, double insulin dose hourly until steady drop of 3-4mM/h. See above for when glucose=12-14. After resolution, check glucose q4h and start SC insulin. Insulin continues until AG normalizes.

4. Acid/base: In general bicarb not required unless pH is less than 7.0. If so, may give amps or dilute 3 amps NaHCO3 in 850mL D5W, and infuse 150-200mL/h.
Control N/V with IV Gravol

Many people find it convenient to manage DKA by a flowchart updated ~hourly (although not everything needs to be checked hourly). You may want to record:
Time, Vitals, urine output, pH, HCO3, AG, Ket, Glu, K, PO4, IV fluid rate, insulin dose

A couple of extra points:
-Na for anion gap calculation is not adjusted for glucose.
-Expect to see non-anion gap metabolic acidosis after AGMA resolves, because of loss of ketone bodies without H+ (i.e. loss of anion alone)

Click here for a CMAJ review article on DKA that also compares and contrasts with diagnosis and management of HONK

Friday, August 14, 2009


Today we discussed issues related to listeriosis. Some important points:

Listeria monocytogenes is an important cause of bacteremia and CNS infection in high risk groups. Listeria enters the body through the GI tract and then disseminates hematogenously; it is particularly "CNS-tropic"


Aerobic gram positive bacillus that grows in cold temperatures, making it particularly suited to be a "refrigerator-proof" food-borne organism. Effectively cultured from normally sterile sites (e.g. blood, CSF), but not from stool samples.

Some of the implicated foods in outbreaks:
-Soft cheeses
-Deli meats
-Smoked fish

Clinical syndromes
1) Self-limiting GI illness with foodborne ingestion in immunocompetent hosts
2) Bacteremia often without obvious focus. Non-specific presentation of fever, malaise, myalgias, back pain. This is the most common form to complicate pregnancy
3) Neonatal- early onset sepsis syndrome or late onset meningitis at 2 weeks
4) CNS infection (may follow bacteremia)- meningitis, encephalitis, brain abscess, brainstem involvement ("rhombencephalitis"; abrupt onset of asymmetric cranial nerve deficits, cerebellar signs, hemiparesis.
5) Others (rare): endocarditis, septic arthritis

Risk factors for listeriosis in adults
Deficits in cell-mediated immunity:
1) Pregnant women in 2nd or 3rd trimester- 30% of cases
2) HIV with low CD4 count (although Septra prophylaxis covers listeria)
3) Hematologic malignancy
4) Transplant
5) Steroids
6) Kidney or liver disease
7) Age over 60


Ampicillin is the drug of choice; this is why it is included in empiric meningitis treatment regimens in patients with risk factors.

Duration: Minimum 2 weeks IV for invasive infections (i.e. more than then self-limited GI illness); at least 3 weeks for CNS involvement


Click here for a recent CMAJ review of listeriosis

Thursday, August 13, 2009


Today we discussed rhabdomyolysis. Some important points:

There is a distinction between a CK elevation without other sequellae and rhabdomyolysis, which may involve consequences such as weakness, electrolyte disturbances, renal failure, acidosis, etc. True rhabdomyolysis is unlikely if the CK is below 10000.

Rhabdomyolysis is a syndrome of muscle necrosis and release of intracellular contents into circulation.

Clinical manifestations are myalgias, pigmenturia (positive supernatent for blood after spinning).

Weakness is only present in most severe cases with significant muscle necrosis.

Lab hallmark is increased CK; 10000 range, up to 100000. CK is the MM fraction. Myoglobin from muscle is released together with CK, but myoglobin is cleared before CK, so may see CK up, but not myoglobin

Renal failure- usually oliguric ATN, from tubular deposition of heme pigment casts and iron from myoglobin

Lytes- Disturbances in Na (sometimes high), K (high), PO4 (high), Ca (low), HCO3 (low), uric acid (high). Hypocalcemia may be extreme, from hyperphosphatemia and increased Ca/PO4 product from Ca salt deposition in necrotic muscle.

Can see hypernatremia because free water "3rd spaces" to muscle because of all of the metabolites.

May increase Cr out of proportion to GFR because creatine is broken down to creatinine

DDx of major causes: (for complete list see link below)

1) Trauma/compression
-crush injury
-struggle against restraint
-immobilization from coma, fracture
-compartment syndrome
-surgery; positioning and tourniquets

2) Non-traumatic "exertional"
-extreme exertion (RFs are unfit, hyperthermia, impaired sweating)
-hyperkinetic states: T-C Sz, DT, severe agitation, amphetamine OD

3) Drugs / poisonings
-Malignant hyperthermia: fever, rigidity, muscle contraction
-EtOH, narcotics, anything causing coma leads to compression
-Sympathomimmetics- cocaine, ecstasy, amphetamines
-CO poisoning
-Statins (esp with cyp inhibitors)
-NMS: fever, rigidity, autonomic instability, post-dopamine antagonist (antipsychotic), or withdrawal of anti-parkinsonians

4) Infections (do not usually cause 'rhabdo-level' CK elevations)
-generalized sepsis
-viral (HSV, HIV, EBV, Coxsackie, influenza, CMV)

5) Inflammatory (do not usually cause 'rhabdo-level' CK elevations)
-Dermatomyositis, polymyositis, other inflammatory myopathies

6) Metabolic
-hypokalemia, hypophosphatemia: normally, exercise causes shift of K out of cells, which is trigger for pathway leading to muscle hyperemia and increased O2 delivery. If total body K depleted, less shift, less hyperemia, necrosis.
-extreme hypothyroidism
-metabolic myopathies (suspect in recurrent; CPT deficiency most commonly- may present in adulthood)


1) HYDRATION!- even if euvolemic, lots of NS, or possibly 150mM HCO3 (i.e. "normal bicarb")- goal urine pH >6.5
2) Reverse underlying cause if possible
3) Mannitol for osmotic diuresis (this is controversial). Give 0.5-1g/kg then 0.25-0.5g/kg q4-6h, usu 20-200g/24h as 20% solution in D5. Possible alternative is loop diuretic (also controversial) Replace urine losses with appropriate IV solution- do urine lytes.
4) Correct lyte disturbances, except Ca, which is replaced only if clinically hypocalcemic (i.e. paresthesias, tetany, long QT) or hyperkalemic. NB- in extreme cases, may see profound hypernatremia acutely, from free water loss in muscle.

Click here for good review from Critical Care
Click here for a paper questioning the use of bicarb and mannitol

Tuesday, August 11, 2009

A hematology sampler

I couldn't find a unifying theme to morning report today other than all things hematologic. Many big topics were discussed, so to avoid a post that's 12 pages long, here are a few pearls that came up with a bit more detail...

"Leukoerythroblastic picture"
Neutrophilia, nucleated RBCs, few circulating blasts.
Ddx inc severe stress, infection, sepsis.
This with teardrop cells means "myelophthisic" picture
Ddx here includes tumor invasion of marrow, myelofibrosis, granulomatous disease

WBC morphology on blood film
-Normally less than 70% PMN, less than 30% lymphocytes
-PMNs should have no more than 3 lobes. More is megaloblastic (B12, folate, thyroid, valproate, AZT, hydroxyurea, folate antagonists). Bilobed seen in Pelger-Huet (congenital defect of PMN differentiation)
-Infection is suggested by a) toxic granulations, b) bands
-Atypical lymphocyes seen in EBV (means nuclei with nucleoli)
-Auer rod seen in AML. May also see eosinophils
-Eosinophils- drugs, parasites (esp filariasis), Churg-Strauss, HES, cholesterol emboli, many others
-Basophils- adrenal insuff, malignancy
-Monocytosis- seen in MDS
-Smudge cells- seen in CLL
-Marked L shift with preserved morphology- seen in CML before transformation

Myelodysplastic syndrome

Common feature: Ineffective production of normal mature red cells.
MDS implies risk of developing AML; 20-30% of MDS pts progress to AML

Dx is suspected if 1) sx of blood disorder 2) incidental finding of cardial MDS features: a) macrocytosis, b) monocytosis, c) cytopenias in any lineage - combination of these is highly suggestive.
~80% of pts are anemic at diagnosis; 50% have Hb <100. 40% are neutropenic at dx. TCP in 30-45%. Neutropenia or thrombocytopenia may occur without anemia.

Splenomegaly causes by etiology

Massive (i.e. below or across the umbilicus): Thal major
Non-massive: RBC membrane defects, hemoglobinopathies, autoimmune hemolytic anemias

Massive: none
Non-massive: RA (felty), SLE, sarcoidosis

Massive: leishmaniasis, malaria, MAC
Non-massive: viral, bacterial, mycobacterial, fungal, parasitic

Massive: none
Non-massive: cirrhosis, venous thrombosis (portal, hepatic, splenic)

Massive: lymphomas, myeloproliferative, Gaucher's
Non-massive: lymphoma, myeloproliferative, cancer, amyloidosis, Gaucher's, Niemann-Pick, glycogen storage diseases, hemophagocytic syndrome, histiocytosis


Click here for a good review of myelodysplastic syndromes
Click here for a good hematopathology slide site from the University of Utah
Click here for a NEJM CPC of massive splenomegaly

Monday, August 10, 2009


Today at physical exam rounds we discussed splenomegaly.

Some important points:

3 Percussion methods (Castell's is easiest and best):
1. Castell's: Pt supine, percuss lowest ICS L ant axillary line and full insp and exp. +ve is any dullness.
2. Traube's: Pt supine, L arm out of the way. Space is bordered by 6th rib superiorly, midax line laterally, L costal margin inferiorly. Pt breathes normally, and space is percussed. +ve is any dullness
3. Nixon's: Pt in RLD position. Percuss in midpoint of L costal margin (nipple line), and move perpendicular to margin. +ve is dullness over 8cm above costal margin.

3 Palpation methods:
1) Patient supine: Start in RLQ and move up to LUQ; Pt inspires, and feel for spleen tip meeting examiner's stationary hand. If not felt, move 2cm towards LUQ on expiration.
2) Patient in R decubitus: Examiner's L hand is across patient's thorax, lifting the L ribcage anteriorly and medially. R hand is just below costal margin. Pt takes deep breath, and feel for spleen tip. If not felt, move 2cm towards umbilicus to ensure massive spleen not missed.
3) Hooking: Pt lies flat with fist under CVA on L. Examiner is on pt's L side, facing pt's feet, with fingers of both hands under costal margin. Pt takes deep breath, and feel for tip.

In general, percussion is sensitive, and palpation is specific.
When the pre-test probability is low, physical exam cannot reliably rule out or rule in splenomegaly.
Examination is most useful in ruling in splenomegaly when the pre-test probability is high (i.e. if percussion and palpation are both positive, the diagnosis is established).
In high pre-test probability, no method is sensitive enough to exclude; need imaging.

Most sensitive signs (i.e. make it unlikely if not present):
1) Castell's sign (~80% range)
2) Traube's space palpation (~60%)
3) Nixon's method (~60%)
All palpation methods are insensitive (~50-60%)

Most specific signs (i.e. make it likely if present)
Any of the above palpation methods; (~90% specific)

Spleen vs. kidney:
1) upper pole never palpable in spleen
2) respiratory movement with spleen, not kidney
3) notch
4) kidney may be balotable
5) spleen expands towards RLQ; kidney expands vertically

Bruit: heard in splenic hemangioma
Rub: heard in splenic infarct

Click here for JAMA Rational Clinical Exam on splenomegaly (need log-in; ask me how to obtain)


Today we discussed hypoglycemia. Outside context of medications, this is very rare, but must be investigated. Some important points that came up:

A framework for causes (loosely based on Harrison's):

1) Alimentary / postprandial

"Pseudo": normal glucose with symptoms. Possible role for 5h glucose tolerance test
"True": Occurs with rapid gastric emptying (gastrectomy, pyeloroplasty, refeeding, post-vagotomy)

2) Fasting

Decreased supply (i.e. not an insulin problem):

Hormone deficiency (pituitary or adrenal)
Liver failure (late)Starvation (late)
Enzyme deficiency (in childhood/neonate)
EtOH (from decreased NADH)
Medications (sulfa, salicylates, pentamidine, quinolones)

Increased demand (i.e. an insulin problem)

Low insulin- IgF-secreting tumor (sarcoma, RCC, HCC)

High insulin
Exogenous insulin
Insulin secretagogue (e.g. sulfonylurea)
Insulin receptor antibodies (autoimmune)

Pts usually become symptomatic (neuroglycopenic or autonomic symptoms) at BG less than 2.5-3

Need to confirm hypoglycemia (with serum, not capillary glucose), that symptoms are caused by it, and that glucose reverses the symptoms (sometimes referred to as Whipple's triad)

Best test to rule in insulinoma or other neuroendocrine tumor after ruling out medications and adrenal insufficiency is 72h fast

Pts are admitted to hospital, and fasted for up to 72h, allowed to take calorie-free fluids only, and are active during waking hours. Blood for measurement of glucose (serum, not accucheck), insulin, c-peptide are taken q6h, with measurement of insulin and c-peptide when BG less than 3.3mM

Endpoints of the test are any of: 1) BG below 2.5, 2) neuroglycopenic symptoms, 3) 72h elapsed
-Also give 1mg glucagon and measure BG q 20min x 3
-Feed the pt
-Insulin level over 3uU/mL when BG is below 3.0 is highly suggestive of insulinoma.
-C-peptide is measured to differentiate endogenous vs. exogenous insulin (with exogenous insulin, insulin level is high, but c-peptide is undetectable since exogenous insulin does not have c-peptide)

If test is positive, imaging studies: CT/MRI/US

Therapy for insulinoma is surgery; medical management is octreotide or diazoxide.

NB- look for MEN1 if insulinoma (pancreatic endocrine tumors, pituitary tumors, primary hyperparathyroidism)


Click here for 2009 practice guideline for this problem from the Journal of Clinical Endocrinology and Metabolism