Clubbing

Today's physical exam rounds were on clubbing. Some points:

Etiologies (not meant to be exhaustive!)

1) Pulmonary- neoplastic, suppurative (i.e. abscess, empyema), bronchiectasis, inflammatory (e.g. fibrosis), pulmonary AVMs (as in HHT)
2) Cardiac- cyanotic heart disease, endocarditis
3) GI- cirrhosis (often non-alcohol related, as in PBC), celiac, IBD
Others: alpha-1 antitrypsin deficiency, sarcoma, hyperthyroidism

Classically first appears on 4th finger on non-dominant hand

Physical examination for clubbing:

May see obvious changes of terminal phalanges

Nailfold angles
1) Profile angle (AKA Lovibond's angle): Between skin proximal to cuticle and "takeoff" of nail; should be less than 180 degrees
2) Hyponychial angle: between skin proximal to cuticle and distal nail; should be less than 192 degrees.

Phalangeal depth ratio
Ratio of the distal phalangeal depth (i.e. vertical height of the finger at the middle of the distal phanynx) to the interphalangeal depth (i.e. vertical height of the finger at the DIP joint). Interphanangeal depth is normally greater than distal phanangeal depth. This is reversed in clubbing.

Schamroth sign
Diamond-shaped opening when dorsal distal phalanges are opposed

Palpation:
May have "boggy" nailbed, where proximal edge of nail is felt, and may be able to rock the nail back and forth using nailbed as a fulcrum

Evidence:
Based on the JAMA Rational Clinical Exam article on clubbing,
the lack of an accepted gold standard makes sensitivity and specificty determinations difficult. Their literature review showed that 'normals' are very unlikely to have profile angle over 176 degrees, hyponychial angle over 192 degrees, or phalangeal depth ratio over 1.0. Patients are more likely to have IBD or lung cancer if clubbing is present, and the phalangeal depth ratio was the best test for this purpose.

The poisoned patient

Today we discussed an approach to the poisoned patient. Some points:

Detective work is often required in these situations, and history from witnesses / bystanders / family members / paramedics, etc. often provides a key clue

Always ask about

1) Details of what was found near the patient and events (including number of pills left in bottles- gives the "worst case scenario" in terms of amount of a substance taken)

2) Timing of ingestion

3) History of what medications the patient was taking, including possibly from pharmacy directly
4) Medications/substances the patient would have had access to (including family members' medications)

5) History of previous intoxications, psychiatric history

In many cases, collateral history is not possible, and even the most thorough searching does not reveal the substance taken. In these cases, the physical exam often reveals a "toxidrome" that can point to the substance and guide therapy.

Toxidromes (and some mnemonics)

Sympathomimetic
febrile, flushed, tachycardic, hypertensive (more than anticholinergic), mydriasis, diaphoretic (distinction from above)
Examples: cocaine, amphetamines, pseudoephedrine
Treatment: Benzodiazepines, supportive

Narcotic
dec. LOC, hypotension, dec. respiratory rate, miosis. Response to naloxone
Examples: Morphine, other opiates
Treatment: Naloxone

Anticholinergic
hot as a hare, dry as a bone, red as a beet, mad as a hatter, blind as a bat febrile, flushed, tachy, mydriasis, dry mucosa, decreased bowel sounds, urinary retention, hallucinations Examples: Benadryl (or other antihistamines), Gravol, tricyclic antidepressants, antiparkinsonians
Treatment: Acetylcholinesterase inhibitor (e.g. physostigmine)

Cholinergic:
"SLUDGE and the killer B's": salivation, lacrimation, urination, diaphoresis, gi (diarrhea), emesis. Killers: bradycardia, bronchorrhea
Examples: Organophosphate insecticides, donepezil, rivastigmine, galantamine
Treatment: Atropine

Sedative / hypnotic:
dec. LOC, dec. respiratory rate, slurred speech, ataxia, nystagmus
No response to naloxone
Examples: Phenobarbital, alcohols, benzodiazepines
Treament: No specific antidote for phenobarbital; flumazenil for benzo; EtOH or fomepizole for MeOH

Managing the poisoned patient:

1) ABC- may need definitive airway management, supportive care

2) Try to identify agent or toxidrome as above
Always remember co-ingestions! Ways to identify these are by the anion gap, osmolal gap, ECG (looking for signs of cardiac toxicity), and serum + urine toxicology screens

3) Administer "universal antidotes" where appropriate- oxygen, glucose, naloxone, thiamine

4) Think about preventing absorption
Activated charcoal or whole bowel irrigation
Charcoal: If less than 4h from ingestion (preferably less than 2h). Want 10:1 ratio of charcoal to substance. Not for caustics, metals (Li, Fe), hydrocarbons. Repeated charcoal with drugs with enterohepatic circulation- theophylline, phenytoin, carbamazepine
Whole bowel irrigation: Enteral PEG-LYTE administration until rectal effluent is clear. It is effective with drug packets, extended release preparations, substances not well adsorbed by activated charcoal. Dose 2L per hour PO or NG until clear.

5) Think about a specific antidote if one exists

6) Think about enhancing elimination
(e.g. by dialysis or alkalinization of urine)

7) Always call poison control!

Dialyzable drugs:
Salicylates, alcohols, Li, phenobarb, valproate, theophylline, carbamazepine

Links:

Click here for a NEJM clinical case outlining approach to the poisoned patient

Click here for a review of a new potential antidote to lipophilic drug intoxicatios, a lipid emulsion- "Intralipid"

Aortic insufficiency

Today's physical exam rounds were on aortic insufficiency. Some key points:

May be caused by disease involving aortic leaflets or root.

Valvular: Calcific (some element of AI in 75% or pts with AS); endocarditis, trauma (ascending aortic tear), rheumatic disease.
Root: Age-related, cystic medial necrosis (isolated or with Marfan's), bicuspid valve, syphilis, ank spond, Behcet's, psoriatic, UC

Regardless of etiology, AI causes dilation and hypertrophy of LV +/- LA.
Compensation is by increased LVEDV (and therefore pressure, to decrease regurgitant volume, and also by tachycardia because it reduces diastolic time (and regurgitant volume)

Exam:
1) Peripheral: deMusset (head bobbing), Quinke's (capillary pulsations), Muller's (uvula), many others...
2) Vitals: High pulse pressure. With more severe disease, peripheral vasoconstriction can cause increase in diastolic pressure. Tachycardia may be present (compensatory). May see A-fib because of LA enlargement.
3) Pulses: "water hammer": abrupt distension and quick collapse (Corrigan's), esp radial with arm elevated. Traube's (pistol shot femorals- booming systolic sound over femoral), Duroziez (systolic murmur over femoral when proximally constricted and diastolic when distally)
4) JVP: No specific findings except possible A-fib from dilation (no a-wave in this case)
5) Palpation: apical impulse is diffuse and hyperdynamic. It is laterally and inferiorly displaced. May feel ventricular filling wave at apex
6) Heart sounds: S1 may be soft because of long PR. A2 may be normal or loud if root; soft if valve. S3 may be present from dilation
7) Murmurs: high frequency right after A2. Best heard with diaphragm with pt sitting up and leaning forward in end-expiration. If root/aorta, heard at RSB. If valve, LSB 3rd or 4th ICS (classically). Mid and late diastolic murmur (apical rumble) is Austin Flint. Caused by flow across mitral and reflux. MS murmur is different because OS is present and S1 is usually loud.

Evidence:

From JAMA "Does this Patient have Aortic Regurgitation?"

Most sensitive test (i.e. good for ruling out if absent):
Early diastolic murmur

Most specific test (i.e. good for ruling in if present):
Early diastolic murmur if heard by an expert (!)

None of the peripheral signs described above are very powerful in ruling in or out AI.
Of all of them, Hill's sign (SBP over 20mmHg higher in legs than arms) has highest positive LR and lowest negative LR.

Dermatologic manifestations of malignancy

Yesterday we discussed some of the skin findings associated with internal malignancy.

Some of these are:

1) Acanthosis nigricans (shown above)
Hyperpigmented areas mainly on flexural surfaces. Associated with intraabdominal malignancy, most often gastric carcinoma

2) Dermatomyositis
May see Gottron's papules, heliotrope rash, shawl sign
~30% of cases are associated with underlying malignancy

3) The sign of "Leser-Trelat"
Acute onset of multiple seborrheic keratoses (often on the back) associated with GI adenocarimonas, lung, breast, and urinary tract cancers

4) Pyoderma gangrenosum
Classically occurs on extremities and is associated with IBD. Purulent ulcers, sometimes with cyanotic borders. Occasionally associated with multiple myeloma, non-Hodgkin's lymhoma, or solid tumors

5) Extramammary Paget's disease
Often affects anogenital area and sxillary skin; red, scaly plaques, often pruritic. 12% have internal malignancy, interestingly often physically close to area of Paget's (i.e. perianal is oten rectal ca; genital is often uterine/bladder/vaginal/prostate ca)

6) Sweet Syndrome
Erythematous, tender papules or plaques; may be diffuse (erythroderma). May be associated with hematologic malignancy (most often AML), or less commonly solid tumors

7) Carcinoid syndrome
75% of cases include facial flushing (other parts of the syndrome include dyspnea, wheezing, diarrhea). Most originate in GI tract, often appendiceal.

8) Inherited cancer syndromes

Cowden's disease- multiple hamartomas
Neurofibromatosis- cafe au lait spots; associated with optic gliomas, astrocytomas, acoustic neuromas

Click here for a good review on this topic

Staph aureus bacteremia

Today we discussed staph aureus bacteremia. This is an important and serious internal medicine problem, and needs to be recognized promptly and treated effectively to prevent poor outcomes.

A few points:

-Colonization is either nasal or skin; of pts with SAB, 80% have exact same organism colonizing nose, but only ~1% of colonized people get SAB in 5 years.

-Remember that initially, you will not know whether it's staph aureus causing the gram +ve cocci on the gram stain. GPC in clusters may be any of St. aureus (MRSA or MSSA), St. epidermidis, E. faecalis. Safest to assume it's the worst and start vanco empirically e.g. 1g IV x 1 then reassess (unless very likely to be contaminant)

Major questions:
1) Is this endocarditis?
2) Is this "complicated"?
Uncomplicated SAB = removable focus (e.g. line, abscess). Complicated implies bone, joint or valve focus.

Predictors of complicated SAB:
1) community acquired
2) failure to defervesce at 72h
3) +ve BC at 72h on treatment
4) skin lesions

MSSA responds better to cephalosporins than vancomycin, so switch as soon as you know sensitivities.

Duration of therapy:
If no foreign bodies, catheters, valvular abnormalities, 14d IV minimum
If deep focus/endocarditis/peristent bacteremia despite treatment, 4-6 wks IV minimum

Most common "metastatic" sites of St. aureus:
1) Bone and joint
2) Kidney
3) Endocarditis
4) Spleen
5) Lung

Final pearl: If you see St. aureus in a urine culture, it probably came from the blood (never a contaminant), so take seriously!

Some links:

Click here for an epidemiological study on the outcomes of MRSA and MSSA bacteremias
Click here for a study on risk factors for persistent staph aureus bacteremia

Adrenal insufficiency

Today we discussed adrenal insufficiency. Some of the main points:

From the 1849 original description of Thomas Addison, which describes most of the key clinical features:

"The leading and characteristic features of the morbid state to which I would direct attention, are, anæmia, general languor and debility, remarkable feebleness of the heart’s action, irritability of the stomach, and a peculiar change of colour in the skin, occurring in connexion with a diseased condition of the supra-renal capsules."

Adrenal insufficiency may be primary (i.e. an adrenal problem) or secondary (i.e. a pituitary problem).

Causes of primary insufficiency (not exhaustive!)
1) Autoimmune (sometimes associated with polyglandular autoimmune syndromes- I or II)
2) Granulomatous (TB, histoplasmosis, coccidiomycosis, cryptococcosis, sarcoidosis)
3) Other infections (meningococcemia, CMV, HIV, MAI)
4) Medications (ketoconazole, etomidate, phenytoin, rifampin...)
5) Bilateral hemorrhage
6) Adrenal metastases
7) Congenital (e.g. adrenoleukodystropy)

Common clinical manifestations
Weakness, hyperpigmentation, weight loss, anorexia, nausea, vomiting, BP below 110/70

A word on the hyperpigmentation:
diffuse, brown, tan, or bronze darkening of creases, elbows, and normally more pigmented areas (areolae, perineum). Also may see bluish-black patches on mucous membranes.

Lab findings:
May see hyponatremia, hyperkalemia, lymphocytosis, eosinophilia, mild hypercalcemia, hypoglycemia.
In primary, low cortisol, high ACTH. May have normal random cortisol, so stimulation test is more sensitive.

Primary vs. secondary:
May see associated pituitary hormone deficiency manifestations or signs of compression from pituitary mass in secondary. Hyperpigmentation does not occur in secondary. Hyponatremia, but not hyperkalemia, occurs in secondary (no mineralocorticoid deficiency).

Treatment:
Acutely, hydrocortisone 100mg IV q8h +/- fludrocortisone (usually not needed acutely because hydrocortisone has minaralocorticoid effect). Maintenance doses as soon as patient is over crisis. Supportive care otherwise (fluid resuscitation, etc.).
Chronically, may start with doses like hydrocortisone 20mg qAM, 10mg qPM
fluorinef 0.1mg PO OD

Some links:

Click here for a recent NEJM review article

Click here for Addison's original description from 1849

Fever

Today we discussed fever and some of its nuances. Some points:

The definition of a fever depends where you look; Sapira's textbook uses oral temperature of 37.9 as a cutoff; definitions of febrile neutropenia use multiple readings of 38.0 or single reading of 38.3. Fever of unknown origin definitions typically use 38.3

Some classic fever patterns (use with caution; most patients do not obey these "rules"!)

Relapsing (hours or days of fever, then days without): Hodgkin's, TB, malaria, familial mediterranian fever

Pel-Ebstein: seen in 16% of Hodgkin's- hours to days with then days to weeks without

Tertian- recurs q48h (3rd day)- P. vivax, P. ovale

Quartian- q72h (4th day)- P. malariae

Some diagnostic possibilities with a very high fever (over ~40)

1) Drug reactions (including neuroleptic malignant syndrome and hypersensitivity reactions)
2) Causes of "normal" fever with superimposed autonomic dysfunction as in diabetic autonomic neuropathy
3) "Heat stroke" (overwhelming activity with impaired cooling mechanisms)
4) Infections (classically CNS infections, malaria, and deep-seated abscesses- esp. empyema, hepatic, etc)
5) Intoxications (amphetamines, ecstasy overdoses causing serotonin syndrome)

Fever of unknown origin

Usually defined as fever (as defined above) for 3 weeks or more with uncertain etiology after investigations (used to specify 1 week hospitalization, but this definition is now challenged since more tests can be done as outpatient)

Major categories for FUO:

1) infection (massive list...)
2) inflammatory (temporal arteritis, adult Still's, RA, SLE, IBD, sarcoid, FMF...)
3) malignancy (lymphoma, leukemia, RCC, HCC, pheo)
4) drugs (NMS, serotonin syndrome, EtOH withdrawal, etc)
5) necrosis (PE, MI, massive stroke)
6) hyperthyroidism
7) hepatic (any process including viral hepatitis, infiltration, etc)
8) hemolysis

Based on this study from local investigators, there is evidence for
-applying Duke's criteria for endocarditis
-CT abdomen
-liver diopsy
-nuclear medicine scan to detect inflammation or malignancy
-temporal artery biopsy in elderly patients

Click here for a study from the Netherlands proposing a graded diagnostic algorithm for evaluating FUO

Leukocytoclastic vasculitis and PAN

Today we discussed leukocytoclastic vasculitis, and one of its causes, polyarteritis nodosa (although LCV is not the most typical skin involvement; livedo reticularis is more common). A few points:

Leukocytoclastic vasculitis = palpable purpura, usually lower extremity.
This is not a diagnosis; it is associated with many potential etiologies

Differential diagnosis of this presentation: A useful mnemonic is VASCULITIS (courtesy of Dr. Scott Walsh)

V- viral (Hep C, Hep B, HIV)
A- autoimmune (SLE, RA, Sjogren's, Henoch-Schonlein purpura)
S- staph, strep infections
C- cryoglobulinemia (e.g. from Hep C, RA)
U- ulcerative colitis, crohn's
L- lymphoproliferative disorders (esp. hairy cell leukemia)
I- infection- endocarditis, meningococcemia
T- thiazides, NSAIDS
I- immune complex (e.g. from endocarditis)
S- septra, b-lactam antibiotics

Polyarteritis nodosa

Medium or small vessel vasculitis typically presenting as multisystem disease, fever, abdominal pain, renal involvement, hypertension, and skin lesions.

The ACR criteria include weight loss skin lesions, testicular pain, myalgias, HTN, renal involvement, neuropathy, HBV infection, angiographic findings, and biopsy findings.

Hep B surface antigen is present in 15%; there is also an association with HCV, but less commonly. p-ANCA is sometimes positive, but is not a criterion.

Diagnosis is clinical, but strongly supported by tissue (usually either a nerve- usually sural nerve, skin, or kidney biopsy depending on organ involvement), or angiographic findings.

Treatment is immunosuppression (steroids +/- cytotoxic agents)

Some links:

Click here for a NEJM clinical pathological case of PAN

Click here for a previous blog post on general approach to vasculitis

Shock

Today we discussed an approach to hypotension and shock. A few important points:

Hypotension and shock are not synonymous; shock is tissue hypoperfusion.
e.g.
1) A patient with a baseline sBP of 180 whose sBP falls to 110 because of sepsis. If there are signs of hypoperfusion, this relatively low BP for this patient (but not necessarily someone else) means shock.
2) A patient with EF of 20 % might have a baseline sBP of 80 and be perfectly well perfused

How can you tell whether a patient is in shock?
Look for signs of hypoperfusion of different organs:
1) Brain- altered mental status
2) Kidneys- decreased urine output, prerenal failure - this is the most sensitive
3) Skin- cool, clammy, 'clamped down' (although be careful since causes of distributive shock do not do this)
4) Heart- signs of ischemia (unusual unless profound)
5) Liver- elevated liver enzymes (usually post-shock)
6) Lab sign of general tissue hypoxia: elevated lactate (type A lactic acidosis)- look for a high anion gap and a low bicarbonate

Differential diagnosis of shock and what you might find on exam:
1) Hypovolemic / hemorrhagic: usually a cause is apparent; low JVP, clear lungs, peripheral vasoconstriction (cool extremities)
2) Distributive (sepsis, anaphylaxis, neurogenic)- primary problem is uncontrolled peripheral vasodilation. Low JVP, clear lungs, peripheral vasodilation (warm extremities)
3) Cardiogenic- primary problem is low cardiac output. Peripheral vasoconstriction in response, often pulmonary edema, high JVP
4) Obstructive- Cardiac tamponade, tension pneumothorax, massive PE. Primary problem is decreased preload or R heart output. Often high JVP, clear chest, peripheral vasoconstriction

Others:
Tachy/brady arrhythmias, adrenal crisis.
Sepsis is unique in that it causes a combination of many of the above (distributive problem, hypovolemia, myocardial depression)

Special cases:
-Shock / hypotension with high JVP: cardiogenic shock, massive PE, tamponade, tension pneumothorax.
-Shock / hypotension and hypoxemia: cardiogenic shock with pulmonary edema, ARDS, PE, tension pneumothorax

Link: Click here for a previous post on acute UGIB management

Polyuria

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.


Results

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


Bonus:

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

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

Prerenal:

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

Postrenal:

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.

Link:

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

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)

Management:

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.

Idiopathic:
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).

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

Membrane

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

Extracorpuscular

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)

Metabolic:
Renal failure- esp echinocytes
Hepatic failure- esp acanthocytes
Hypophosphatemia
Osmotic hemolysis (dialysis)

Toxins/physical:
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.

Infections:
clostridial sepsis
DIC
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
lymphadenopathy
organomegaly, Murphy's sign

Lab:

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.


Management:

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

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
VDRL
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.

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

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.

Pathophysiology:
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.

Labs:
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.

Management:

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)

Link:

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

Listeriosis

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"

Microbiology:
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
-Coleslaw
-Deli meats
-Smoked fish
-Butter


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

Treatment:

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

Link:

Click here for a recent CMAJ review of listeriosis

Rhabdomyolysis

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
-pyomyositis
-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)

Management:

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.

Link:

Click here for good review from Critical Care

Click here for a paper questioning the use of bicarb and mannitol

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

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

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

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

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

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

Links:

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

Splenomegaly

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.


Evidence:
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

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

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

Hypoglycemia

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)
Insulinoma
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)

Link:

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

Asthma in inpatients

Acute asthma exacerbations are relatively common internal medicine referrals. Some points on managing this potentially life-threatening condition:

Indicators of severity:

Clinical- SILENT CHEST, pulsus paradoxus, acc muscle use, diaphoresis, inability to speak
Peak flow- less than 200 or less than 50% of baseline is severe attack
ABG- hypoxia is rare, and indicates very severe. Hypercapnia or even normal PCO2 is bad; indicates tiring.
CXR- unhelpful usually; may do to exclude pneumothorax (possible complication), pneumonia.

Very important to get a peak flow reading on presentation and then monitor closely q1-2h during therapy to assess progress.

Therapy

1) B-agonist: Mainstay of therapy
Salbutamol 4-6 puffs q1-2h iniitally. Outcomes with inhaler vs. nebulizer are essentially equal assuming proper technique. 1 NEB treatment generally equals 4-6 MDI puffs with a spacer.

2) Ipratroprium: Added if not initially responding or if severe.
Especially recommended for pts with COPD or B-Bl triggered asthma.
Ipratroprium 500mcg NEB q6-8h (can be given with 1st ventolin neb treatment) or MDI 2 puffs of 17mcg each q6h.

3) Steroids:
Consider if:
1) less than 10% increase in PF after 1st dose of B-ag
2) attack in pt on oral steroids before attack
3) PF less than 70% predicted after 1h of treatment
Only difference between PO and IV steroids is onset of action; within 1d for IV vs possibly 2d for PO. Otherwise equivalent. Dose of steroid is not clear. For severe, a commonly studied dose is Solumedrol 125mg IV q6h x 3d. For less severe, consider Solumedrol 30mg IV q8h x 3d then switch to oral.
PO: Prednisone 1-2mg/kg/d divided q 8-12h for 2-4d, then reduce. All pts who received steroids should get oral steroids on discharge; usually prednisone on tapering regimen for 8-10d, but also acceptable if steroid naive to keep on prednisone for 1 week, reassess, and d/c abruptly if less than 10d

4) MgSO4: Some evidence of benefit; blocks SM contraction. 2g IV over 20min. Little toxicity to this dose

5) Epinephrine: last resort; patient will probably need intubation.

6) Final step is rapid sequence induction and intubation by the most skilled person available (there may only be 1 chance), and initiation of inhaled anesthetics (which are bronchodilators). Ketamine is also a bronchodilator.

Little or no role for antibiotics, theophylline, montelukast

Consider admission if:
-peak flow less than 40% of predicted after bronchodilators or less than 25% on arrival
-any hypoxia, distress, etc.

Consider ICU or intubation if:
-Clinically tiring or in respiratory distress
-Hypercapnea or hypoxia
-Worsening on therapy
-PF less than 150

Links:

Click here for acute exacerbation guidelines from 2007

Click here for evidence for magnesium in acute exacerbation

Asthma in outpatients

We had a clerk teaching session on asthma, and I thought I would share some points with everyone:

Diagnosis

Relative increase in FEV1 of 12% post-bronchodil AND over 200cc change. More sensitive test is methylcholine challenge

Steps for therapy: With each, patient education, environmental control

1) SABA prn
2) low dose ICS
3) (low dose ICS + LABA) or medium dose ICS
4) medium dose ICS + LABA
5) high dose ICS + LABA and consider omalizumab for allergic asthma (eosinophilia or symptoms)
6) high dose ICS + LABA + oral steroid and consider omalizumab

Before stepping up treatment, check puffer technique, adherence, environmental control, comorbidity.

Note that LABAs are never used without inhaled steroids; LABA alone increased mortality in trials

Do not step down unless asthma is well controlled for 3 months.

Parameters of control
daytime sx less than 4x/wk night sx less than 1x/wk normal physical activity mild, infrequent exac, no absenteeism B2 agonist use less than 4x/wk peak flow or FEV1 over 90% of best

Some general differences between asthma and COPD

1) reversible vs fixed obstruction
2) steroid responsiveness higher in asthma than COPD
3) small role for anticholinergics in asthma
4) very rarely use abx for exacerbations in asthma
5) dyspnea, tightness, wheeze in asthma vs dyspnea, cough, sputum in copd
6) early vs. late onset

In the non-responding asthmatic, think about:
1) poor compliance
2) poor inhaler technique
3) environment
4) drugs- B-bl, ASA
5) comorbitites- GERD, sinusitis, allergies, CHF
6) complications- ABPA, churg-strauss, chronic eosinophilic pneumonia
7) psychosocial
8) wrong diagnosis- consider vocal cord dysfcn, airway obstruction, CF (adult)

Links:

Click here for the 2007 NIH asthma guidelines

Acknowledgement:

Some of the above is taken from the University of Toronto Department of Respirology resident handbook

Hyponatremia

Today we discussed a common internal medicine problem, hyponatremia.

Acute vs. chronic cutoff is 48h.

Hyponatremia relative excess of free H2O for a given total body Na or ECFV (whether it's hypo/eu/hyper).

Traditional first breakpoint is by serum osmolality:
1) Hyperosmolal: hyperglycemia (10:3 adjustment), mannitol (IV)
2) Euosmolal: hyperproteinemia, hyperlipidemia (both pseudo; not usually an issue with modern lab techniques), bladder irrigation (dilutional)
3) Hypo-osmolal: Most common

Within Hypo-osmolar, divide by volume status:
Hypo: vomiting, diarrhea, DKA, diuretics, hypercalcemia
Eu: post-op, pain, nausea, pregnancy, SIADH (paraneopl from lung/CNS/pancreas/HL/leukemia or non-neoplastic), beer potomania, psychogenic polydipsia, hypothyroidism, adrenal insufficiency
Hyper: CHF, cirrhosis, nephrotic syndrome, renal failure

A word on SIADH:

Drugs that cause it: The "C's":
cyclosporin, cyclophosphamide, carbamazepine, cisplatin, 1st gen sulfonylureas (like chlorpropramide), antipsychotics (like clozapine), SSRI (OK...not a "C")

SIADH criteria
serum osm less than 275
urine osm more than 100
urine na more than 40
euvolemia
no diuretics
normal thyroid and adrenal function

NB- 'SIADH' with low UNa is not inappropriate b/c hypovolemia should turn on ADH.

Rate of correction:

Be very careful with the hypovolemic, hyponatremic patient (which is very common!). Danger is to volume replete and turn off ADH, causing dilute urine excretion, and rapid increase in Na. Consider ddAVP here; e.g. 2-4mcg IV or SC, even possibly before volume resuscitation. Always monitor urine output and serum lytes closely in this setting.

Aim for an increase of less than 8mEq per 24h (truly dangerous range is 12mEq/24h)
Highest CPM risk: malnourished, elderly, EtOH use (i.e. most people who get hyponatremic!)

Acute or severely symptomatic (e.g. sz, coma, cerebral edema):
3% saline at 1-2ml/kg/h
aim for 2mM/h increase
check Na q2h
d/c when symptoms improve

Othewise, fluid restrict and watch carefully.

Links:

Click here for a NEJM review of SIADH

Click here for the evidence for ddAVP in preventing overcorrection

Dementia

Today we discussed dementia, paricularly with a rapidly progressive course

General classification of dementias:

1) Alzheimer's disease: 60-70%- hallmark is early loss of anterograde memory, with loss of functioning. Late loss of languange function.


2) Non-AD: 30-40%

Vascular- hx of CV risk factors, hx of overt stroke. Imaging shows stroke, leukoencephalopathy, ischemic or degenerative changes. Classically step-wise, with steps overnight.


With Parkinsonism:
- Dementia with Lewy bodies and Parkinson's dementia. Difference is whether parkinsonism was present first for over 1yr, which means PDD. DLB is characterized by nonbizarre delusions, neuroleptic sensitivity, REM sleep behaviour disorder (i.e. no paralysis in sleep, acting out violent dreams), autonomic disturbance
- Progressive Supranuclear Palsy (PSP)- upward, then downward, then lateral gaze palsy. Prominent truncal parkinsonism, with severe postural instability. Very high fall risk. Increased tone. Minimal response to L-dopa.
- Cortico-basal degeneration (CBD)- marked laterality of movement disorder. Apraxia, alien limb possible. Minimal response to L-dopa


Frontotemporal dementia (FTD)
- Frontal: personality change, with executive dysfunction, disinhibition, and/or apathy
- Temporal: Memory loss in 25%, language deficits- all anomic, either fluent or non-fluent with circumlocution and word-finding difficulty.
NB- ALS may present this way


Rapidly progressive dementia- a long, but still incomplete list of potential causes

1) Atypical presentation of primary neurodegenerative dementias (FTD, AD, LBD, PSP, etc.)
2) Structural brain disease (tumors, bleeds, collections, NPH)
3) Medications- Li, serotonin syndrome
4) Seizures
5) Infections (HIV, PML, cryptococcal meningitis, syphillis, malaria, TB, bartonella, Whipple's)
6) Psychiatric illness
7) Prion disorder (CJD, vCJD)
8) Autoimmune (Hashimoto's encephalopathy, others)
9) Inflammation (MS, ADEM)
10) Paraneoplastic (limbic, brainstem, etc)
11) Vasculopathy (vasculitis, intravascular lymphoma, CADASIL)
12) Nutritional (B12, folate, niacin, thiamine)
13) Genetic- late presentation of genetic disorder (e.g. hereditary adrenoleukodystrophy, neuronal ceroid lipofuscinosis, etc.)
14) Toxin (cocaine, EtOH, amphetamines, heavy metals, solvents, chemotherapy)
15) Systemic disease (sarcoid, celiac, CNS lupus, Sjogren's, Behcet's)
16) Metabolic (hypothyroidism, hypercalcemia, etc.)

Investigations:

CBC, lytes, liver, renal, glucose, thyroid, B12. CT scan for subdural, NPH. Possible MRI with gadolinium, EEG.
In correct settings, consider HIV, syphillis, depression, CNS vasculitis (h/a, sz, dementia), prion disease

Links:

Click here for NEJM clinical conference on this topic
Click here for CMAJ review of dementia diagnosis