Monday, November 30, 2009

Hypertensive emergency

Today we discussed hypertensive emergencies. Some important points:

Some of the confusing terminology in this area:
"Urgency": SBP over ~180 or DBP over ~110 without end-organ damage- needs correction over days with oral agents
"Emergency": Above, but with acute end-organ damage, needing urgent lowering, usually with IV medications in a monitored setting.
"Malignant": Old term referring to HTN with encephalopathy or renal involvement
"crisis", "accelerated"- largely abandoned, and replaced with "emergency"

End organ complications and specific treatments:
1) Aorta- dissection (B-blockade, nitroprusside after B-bl. No pure vasodilators)
2) Brain- encephalopathy- sz, coma (avoid centrally acting agents); cerebral hemorrhage/infarction, raised ICP
3) Heart- MI, CHF (acute diastolic dysfunction leading to pulmonary edema)- careful with B-bl. May use nitro infusion
4) Kidney- renal failure- careful diuresis, calcium antagonists useful
5) Placenta (pre-eclampsia)- hydralazine, labetalol, delivery
6) Hemolysis (can look just like TTP with MAHA, fragments)

Emergency pts should go to ICU, and have art line. Generally, most extra-cerebral damage benefit from rapid lowering.

Aim for MAP decrease by no more than 20-25% within 2h or to DBP 100-110 over minutes to hours. Exceptions include aortic dissection, where more rapid decrease may be needed, and stoke, where less rapid lowering may be needed.

Special circumstances:
Cocaine- phentolamine or labetalol (avoid unopposed alpha-agonism)
Pheochromocytoma- phentolamine/phenoxybenzamine (as above)

Drugs for acute lowering:
Labetalol 10-20mg bolus then infusion
Hydralazine- 10-20mg bolus (causes reflex tachycardia)
Nitroglycerine 5-100mcg/min
Na nitroprusside- arterial vasodilator
Phentolamine -alpha antagonist

Available in some centres:
Enalaprilat (IV ACE-I)
Fendolapam (arterial vasodilator)


Click here for a good review on this topic from Chest

Sunday, November 29, 2009


We discussed Thrombotic Thrombocytopenic Purpura (TTP), a very important condition to recognize and institute treatement because of its 90% untreated mortality.

Classic pentad:
1) Thrombocytopenia
2) Microangiopathic hemolytic anemia (MAHA; recognized by hemolysis with RBC fragments-shown above)
3) Neurological signs/symptoms
4) Renal failure
5) Fever

the full pentad is seen late in the course. Thrombocytopenia and MAHA without another cause is generally enough to start therapy

Pathologically, thrombin/platelet depositions in organs.

Pathogenesis: ADAMTS13 is a metalloproteinase which degrades von Willebrand's factor. Loss of this enzyme (acquired or genetic) causes large multimers of vWF to accumulate, activating platelets and causing microvascular clotting.

Causes of acquired TTP:
Infection: E.Coli 0157:H7, which causes colonic vascular injury and may induce TTP.
Drugs: ticlopidine, clopidogrel, cyclosporin
Cancer: TTP is assoc with Br, GI, pancreatic, prostate
Autoimmune disease: SLE (most common), RA, dermatomyositis, others.

Plasma exchange: Deficiency in ADAMTS13 is corrected, and antibody against it is removed. Done daily until LDH and PLT normalize. Large volumes of FFP may be transfused until transfer to a PLEX centre

Steroids- prednisone 1mg/kg/d PO or solumedrol 125mg IV BID as adjunct to PLEX.

PLT transfusion- not recommended unless life-threatening bleeding


Click here for the NEJM paper from Ottawa first showing the substantial benefit of PLEX

Click here for a NEJM review article on TTP

Thursday, November 26, 2009

Tricuspid Regurgitation

For sportscar connaisseurs, the iconic Ferrari 512TR

Today we discussed tricuspid regurgitation at physical exam rounds. Some points:

There are generally 2 classes of TR: 1) High pressure, usually secondary to L-heart disease (high RVSP), and 2) low pressure, usually from bacterial endocarditis.

In general, only the high pressure variety is detectable on physical exam because a significant pressure gradient between the RV and RA is required to generate the findings listed below.

The JVP:
-Elevated JVP: Seen in 90% of patients. Its absence strongly argues against high pressure TR
-CV waves: a systolic impulse of the neck veins is seen in about 50-80% of patients. You normally expect to see a descent in the JVP (the X' descent) during early systole (i.e. during and right after S1). If you do not see a descent, the patient probably has a CV wave.

Precordial palpation:
-If the RV is dilated, it may occupy the space where the LV normally lies (i.e. the apex). In this situation, you may see and palpate a systolic retraction of the apex with an outward movement of the L or R lower sternal borders (where the dilated RA lies), which is described as a "rocking" motion

-The murmur of TR is holosystolic. In 75% of patients, it becomes louder with inspiration (called Carvallo's sign). It is usually loudest at the L lower sternal border, but if the RV is dilated enough may be loudest at the apex. The LR+ for a typical murmur is 14.6. However, the lack of a typical murmur does not rule out TR (negative LR 0.8 for mild, 0.4 for severe).

-Pulsatile liver may be palpated (wide range of sensitivities reported). It is not 100% specific for TR (constrictive pericarditis and hepatic AVMs may also cause it), but by far the most common cause. Its presence argues that the TR is moderate to severe.
-Edema, ascites: 90% of patients have edema or ascites (or both)

There is no JAMA RCE specifically for TR; most of above is taken from
Evidence-Based Physical Diagnosis (McKee)

Tuesday, November 24, 2009

Inflammatory bowel disease

Today we discussed inflammatory bowel disease. Some important points:

Extraintestinal manifestations of IBD:
Eyes- uveitis
pyoderma gangrenosum, erythema nodosum

GI- PSC (esp UC)
Renal (stones- affects oxalate metabolism by unabsorbed bile salts binding Ca, allowing oxalate absorption)
Arthritis- Sero-ve, large joint asymmetric. Either peripheral, which parallels IBD or independent (axial)

Extent of UC (treatment):
pancolitis (oral meds), L sided (enemas), sigmoiditis/proctitis (suppositories)

UC- bleeding, colon ca, toxic megacolon
Crohn's- aphthous ulcers, malabsorption, fistulae, abscess, strictures
Both: At higher risk for C. Diff, relatively hypercoagulable

Toxic megacolon: Non-obstructing dilation of the colon.
NB- TM can be from infectious causes as well.
Clinical: tachy, hypotension, fever, volume depletion, altered sensorium.
AXR: over 6cm at transverse, thumbprinting (big haustra), pneumatosis coli. Shown in above picture.

Flare treatment:
NPO (bowel rest)
fluid resuscitation (esp attention to phos, K, Mg, albumin)
Possible antibiotics (esp. Crohn's) -cipro, flagyl, possibly vanco
IV steroids (e.g. Solumedrol 30mg IV bid)
DVT prophylaxis
Possible c-scope, although mucosa is very friable; may be deferred until inflammation settles.


Click here for a recent BMJ review of Crohn's disease

Click here for a Lancet review of new therapies for IBD

Monday, November 23, 2009

Pneumocystis jirovecii pneumonia

PCP (now PJP) is an opportunistic infection commonly seen in HIV positive patients with CD4 counts below 200. Ubiquitous in the environment, but it is very uncommon for immunocompetent patients to be infected.

Besides HIV, the other major risk factor is steroid use. In general, after 2 weeks of corticosteroid use at 20mg or more, PCP prophylaxis is indicated.

The classic clinical presentation is subacute onset dyspnea and dry cough. Other signs may include fever, tachycardia, and tachypnea. The chest exam is variable - there may be crackles, but in up to 50% of cases, the respiratory exam is normal.

The chest X-ray often reveals bilateral interstitial infiltrates, but virtually any abnormality may be seen.

Remember that PCP is a classic example of "CXR-negative pneumonia", where the immune reaction necessary to generate an infiltrate is absent. Pneumothorax may complicate PCP (the c is for cysts, which may rupture into the pleural space). Click here for a CXR showing this

Confirmation of diagnosis:
Silver staining of induced sputum (if possible) or BAL specimen (gold standard). PCR is under investigation.


1) TMP-SMX in high doses. In the event of sulfa allergy (interestingly more common in the HIV population), other agents can be used, such as pentamidine, dapsone, or atovaquone.
With high-dose TMP-SMX, look out for hyperkalemia, renal failure, hypoglycemia

2) Steroids for PO2 of 70 or lower or A-a gradient of 35 or higher.

Regimen is a 21-day oral taper of prednisone. The research showing the benefit of steroids in PCP comes from Toronto, and Toronto Western was part of the trial.

Other links:
Click here for the paper discussed by Marrie et al on "atypical pneumonia" and how clinical features do not reliably distinguish "typical" from "atypical" organisms.


Please click here for a Globe and Mail article about our very own Dr. Ho Ping Kong and his legendary morning report!

Thursday, November 19, 2009

Obstructive lung disease

At physical exam rounds, we discussed the diagnosis of obstructive lung disease.

There are many potential findings, outlined below, and 3 major papers on the evidence-based diagnosis of obstructive lung disease.

Possible findings:

General inspection:
Signs of respiratory distress (accessory muscle use, indrawing, paradoxical abdominal movement), pursed lip breathing, barrel chest, signs of malnutrition, look for clubbing (not expected in COPD), asterixis from CO2 retention, cyanosis, elevated JVP from cor pulmonale, many other possibilities...

Pulsus paradoxus

Subxiphoid cardiac impulse, palpable P2 from pulmonary HTN

Decreased diaphragmatic excursion
Decreased cardiac dullness


Special manouevers:
Forced expiratory time (Patient takes a deep breath and exhales forcefully with open mouth, and examiner listens over lower trachea)
Laryngeal height- measure the maximum distance between the sternal notch and the thyroid cartilage. Less than 4cm is significant.


From JAMA Rational Clinical exam (1995):

Most sensitive tests (i.e. rule out if not present)- no single test sensitive enough
Most specific tests (i.e. rule in if present)
Wheezing (LR 36)
Barrel chest (LR 10)
Decreased cardiac dullness (LR 10)
Match test (patient unable to blow out match held 10cm in front with open mouth) (LR 7.1)
Forced exp time over 9 seconds
Other less useful tests to rule in, but positive LR's: Forced exp time 6-9s, subxiphoid impulse, pulsus paradoxus over 15, decreased breath sounds.

From JGIM- Straus et al, 2002
Took 161 pts with varying disease severity (known, suspected, or no COPD), did spirometry on all, looked at components of history and physical that predicted FEV1 5th percentile.

Key point here is combining findings is powerful in ruling in or ruling out.

Forced exp time over 9 seconds - LR 6.7
Wheezing - LR 4.0
Self-reported COPD LR 5.6

If all 3, LR 59 (rules in). If none, LR 0.3 (i.e. good for ruling out)

Other significant features: Over 40 pack-year smoker: LR 3.3

From JAMA- Straus et al (2000)- primary study, not Rational Clinical Exam

History of smoking over 40 pack-years: LR 8.3
Self-reported COPD: LR 7.3
Maximum laryngeal height less than 4cm LR: 2.8
Age over 45 LR 1.3

If all 4, LR is over 200
If none, LR- is 0.13


For JAMA Rational Clinical Exam abstract click here

For Straus et al JAMA paper click here

For Straus et al JGIM paper click here

Tuesday, November 17, 2009


Today we discussed glomerulonephritis

GN is suggested by hematuria, proteinuria, HTN, edema. The hallmark is RBC casts on urinalysis

First division of GN is primary vs. secondary.

Secondary is suggested by associated symptoms and signs: fever, arthritis, rash
bloodwork for secondary causes includes ANA, complements, dsDNA, ANCA, HBV, HCV, HIV, SPEP, cryoglobulins, rheumatoid factor

Primary GN is divided into proliferative and non-proliferative.

Non-proliferative means no extra cells in glomerulus; presents as nephrotic end of spectrum.
These are generally less aggressive diseases:

1) Minimal change 2) Membranous 3) FSGS

Minimal change- mainly children, but seen in adults too. Rapid onset and offset of nephrotic syndrome. Tx is prednisone

Membranous- Most common primary GN in white males. Gradual onset of nephrotic syndrome. Associated with solid tumors in males over 60. Treatment is controversial.

FSGS- second most common primary GN ~40% respond to high dose prednisone

Proliferative GN- Means increased cells in glomerulus. Prominent RBC casts, hematuria, 'nephritic' presentation. Generally requires more aggressive immunosuppressive treatment

IgA nephropathy:
usually asymptomatic. Sometimes presents as post-URTI hematuria (within 1-5d). Rarely, rapidly progressive. 20% will progress; becomes relatively common reason for ESRD. Treatment is controversial; steroids, fish oil, ACE, ARB

Post-infectious (AKA post-streptococcal). Follows infection by 10-21d. Tx is supportive; usually self-limited. Possible in adults, but less common than children

may be called "rapidly progressive GN" (although other types of GN can progress rapidly)
Divided by immunofluorescence findings:
1) pauci-immune (means ANCA +ve Wegener's, Churg-Strauss, others).
2) immune complex (vasculitis, endocarditis, SLE)
3) linear (Goodpasture's or anti-GBM)
Tx here is aggressive, intensive immunotherapy. PLEX for anti-GBM.

Post-infectious complications of streptococcal infection
Acute rheumatic fever
Reactive arthritis
Erythema nodosum


Click here for a review article on IgA nephropathy from the Toronto Nephrology Rounds series

Click here for a NEJM clinical pathological conference addressing a practical approach to renal failure

Sunday, November 15, 2009

Febrile neutropenia

Febrile neutropenia is a common condition that requires an organized approach and awareness of how this situation differs from fever in the immunocompetent patient.

Textbook definition of neutropenia as absolute neutrophil count (ANC) below 1000. A more practical definition is below 500, because this is when risk of serious infection increases significantly. At below 100, there is a high risk of invasive infections and spontaneous bacteremias.

Single oral temperature of 38.3 or higher, or multiple readings of 38.0 or higher.

Clinical consequences of febrile neutropenia are dictated by
1) severity of neutropenia
2) duration

A source of infection is found in only 30-40% of cases. When a source is found, the most common sites are
1) Skin (mucosal or perianal)
2) Bacteremia (line-related or spontaneous)
3) Pulmonary

This leads to the following usual culprit organisms:
GP- (staph aureus, coag-neg staph, strep viridans, enterococcus). NB- GPs more likely if pt was on FN prophyaxis (usu. fluoroquinolone). These usually originate from skin/lines
GN- aerobes (e. coli, enterobacter, pseudomonas, klebsiella). These usually originate from GI/hospital env't
NB- FN pts are not at higher risk for anaerobes, encapsulated, or intracellular organsms.

Candida- albicans, others; aspergillus- usu with prolonged neutropenia; mucor

Not at particular risk because intracellular; HSV may reactivate, but this is more from "stress" than neutropenia.

Tx: 1) cover common organisms 2) modify regimen for suspected source or specific deficits (eg. add vanco if suspected line infection; add anaerobic coverage if suspect c. diff, typhlitis, sinusitis or periodontal, perirectal; add azith/levo if pneumonia, acyclovir, nystatin or fluco for mucositis)

Possible initial regimens: Pip-tazo alone; cefazolin + tobra; carbapenems, others...

Some guidelines on duration of therapy
If patient is afebrile in 3-5d, treat for usual duration for source identified.
If ANC is over 500 for 48h, consider stopping Abx if source not found
If patient remains febrile and neutropenic for over 3-5d, consider broadening antibiotics (if applicable) and / or adding antifungal empirically

Low risk FN
If all of these conditions are met, may treat orally at home with close followup:
1) hemodynamically stable
2) normal CXR
3) no medical comorbidities
4) normal mental status
5) expected duration of neutropenia less than 10d.
6) access to medical care 24/7
7) not weekend
8) no focus of infection identified

Oral regimen: Amoxicillin-clavulin and ciprofloxacin PO

Click here for IDSA febrile neutropenia guidelines
Click here for evidence behind low risk outpatient treatment described above

Thursday, November 12, 2009


Today we discussed a case of stroke. Some points:

Differential diagnosis of stroke:
Any structural abnormality, seizure, migraine (esp migraine sensory aura- ascending paresthesias over minutes), MS, hypoglycemia, TIA, dissection (esp young), vasculitis, venous sinus thrombosis. Any underlying brain abnormality with something that can cause delirium can cause focal sx.

20% hemorrhagic: HTN (basal ganglia, thalamus, cerebellum, internal capsule); AVM; aneurysm (SAH), amyloid angiopathy (large, lobar)
80% ischemic: Embolic (cardio-embolic: a-fib, valves, akenesis; artery to artery- carotid stenosis), thrombotic (in-situ thrombosis), lacunar (same as HTN areas- lipohyalinosis).

Hemorrhagic conversion of ischemic also occurs.

Stroke syndromes
MCA dominant (usu. means left, where speech function is)
inferiolat frontal lobe: R hemiparesis (arm greater than leg), expressive language.
superior temporal: word-finding
inf. parietal: receptive aphasia, homonymous hemianopsia
MCA non-dominant: L hemiparesis (arm greater than leg), apraxia, sensory neglect, visuospatial
ACA dominant: R hemiparesis (leg greater than arm), verbal problem-solving
ACA non-dominant: L hemiparesis (leg greater than arm), apraxia, lack of insight
PCA: Occipetal lobe- hemianopsia, post. parietal- sensory changes, basal ganglia, cerebellar findings
PICA: (Wallenberg)- Lat. medulla. 1) Ataxia/vertigo from inf. cerebellar peduncle (pt falls towards affected side), 2) ipsilateral loss of pain/temp on face, 3) contralat loss of pain/temp on body (STT). Possible Horners syndrome. Possible contralateral weakness of extremities, ipsilateral facial if 7th nerve nucleus involved. Also associated with dysphagia, hiccups...

Lacunar: subcortical, internal capsule (face=arm=leg weakness), basal gangla involvement (variable)

Cortical vs. subcortical:
Important from etiological standpoint; cortical more likely to be embolic; subcortical more commonly lacunar. Some cortical signs: aphasia, visual field loss, apraxia, neglect.

Small vessel (Lacunar)- recurrence risk is ~3%/ yr
Cardioembolic: 10-15% /yr.
Carotid: 30% recurrence risk/yr, all front-loaded. This is why carotid dopplers are often done prior to discharge decision. NNT for endarterectomy is 3 in first 2 weeks. Patients often await surgery admitted to hospital, sometimes on heparin infusion.

Some references
Click here for ABCD2 TIA score
Click here for original paper describing ABCD2 score
Click here for the NASCET trial of carotid endarterectomy in carotid stenosis

Wednesday, November 11, 2009

Epidural abscess

Today we discussed spinal epidural abscess. This is a very serious and comonly missed diagnosis, requiring a high index of suspicion.

Some points:

Predisposing conditions
1) Immunocompromise - DM2, EtOH, HIV
2) Spinal abnormality/intervention - degenerative disk disease, trauma, surgery, catheters
3) Local or systemic source of infection - skin, osteomyelitis, UTI, sepsis, catheter

Contiguous spread in a third, bacteremia in half, rest not identified.

1) St. aureus (MSSA or MRSA) in over half of cases
2) St. epidermidis (with devices/hardware)
3) GNs (e.coli, pseudomonas)
Rare: anaerobes, TB, fungal, parasitic

1) cord compression
2) cord ischemia
3) osteomyelitis
4) endocarditis
5) psoas abscess

Staging of symptoms
1) back pain
2) nerve root pain
3) motor weakness, sensory deficit, bowel/bladder
4) paralysis

Tempo of progression is variable; may be hours to days.

Location: more common in posterior, thoracic, lumbar areas (more fat). Occasionally, pan-spinal.
MRI with gad and myelography then CT are methods of choice (MRI best). Bacteremia in 60%.

Surgical if neurological impairment and less than 24-36h of symptoms, and not panspinal infection (tx is laminectomy, drainage)
Abx: Empric coverage of staph (usu vanco), gram negatives, (ceftriaxone or pseudomonas coverage if high risk) Best to have microbiologic diagnosis prior to abx; aspirate may be needed if BC are negative.


Click here for a good NEJM review on paraspinal abscess

Friday, November 6, 2009

Cavitary lung lesion

Today we discussed the approach to a cavitary lung lesion. Some points:

Lucent areas within the lung that may or may not contain an air-fluid level, that is surrounded by a wall, which may be of varied thickness. They can be thought of as "holes" in the lung with various changes in the surrounding parenchyma.

Generally results from necrosis of lung parenchyma or central necrosis of an existing nodule or mass.

Useful imaging characteristics to help with differential
1) Surrounding lung parenchyma- within consolidation suggests abscess
2) Wall thickness ( if less than 1mm, almost always benign, if over 15mm almost always malignant
3) Contour- nodular or irregular suggest malignancy; smooth suggests infection or inflammation

Differential diagnosis and predisposing factors

1) Necrotizing infections:
Bacterial: Anaerobes (seizures, decreased LOC, poor dentition, other risk of aspiration), Aerobes (necrotizing pneumonia; St. aureus, st. pneumo, legionella, pseudomonas, others)
Mycobacterial: Tuberculous and non-tuberculous
Fungal: Aspergillus, mucormycosis, endemic mycoses (blasto, coccidio, histo)

2) Malignancy
2-10% of bronchogenic carcinomas have cavitation on CXR.
Germ cell tumors
Metastases (rarely)

3) Inflammatory
Vasculitis, especially Wegener's granulomatosis, can present with cavitary lesions.
Rheumatoid arthritis
There is a cavitating variant of sarcoidosis

4) Others:
Bronchiectasis, bullae or cysts with air-fluid level, pulmonary embolism with infarction.

History and physical are targeted to this differential. Useful investigations include CT chest, bronchoscopy with cultures and cytology, and lung biopsy if etiology still unclear.

Some links:
Click here for a NEJM clinical pathological case on cavitary lesions
Click here for a good radiology textbook chapter on cavitary lesions