Thursday, October 11, 2012

Today we spoke about some interesting cases that were admitted over night, here is a synopsis of the different cases we discussed:

1) Does this patient have septic arthritis?

  • Identifiable risk factors and arthrocentesis are most useful for predicting septic arthritis. Physical examination and clinical history are less helpful due to non-specific symptoms and signs. 
    • Age 80+y (LR 3.5)
    • Hx rheumatoid arthritis (LR 2.5)
    • Hx DMII (LR 2.7)
    • Recent join Sx (LR 6.9)
    • Prosthetic hip/knee (LR 3.1)
    • Overlying skin infection and prosthetic joint (LR 15)
    • WBC in synovial fluid: >25, 000 (LR 2.9), >50, 000 (LR7.7), >100,000 (LR28)
    • Percentage PMN in synovial fluid >90% (LR 3.4)
    • Not helpful: presence/absence of fever, ESR/CRP, peripheral WBC
  • Imaging
    • Ultrasound can be used to identify an effusion
    • MRI best for looking for: fractures not seen on radiograph, signs of osteomyelitis, early signs of AVN and for effusions.
  • Management issues:
    • Joint destruction can occur within 48 hrs of septic arthritis. Therefore, should get orthopedics involved early as drainage of purulent synovial fluid is important to prevent joint destruction.

Does this patient have septic arthritis - JAMA

2) What is minute ventilation?

  • Tidal volume: Quantity of air moved into and out of lungs during a normal breath (normal is 500cc)
  • Minute ventilation: Quantity of air moved into and out of lungs during 1 minute (normal is 5-6L)
  • Therefore, the maximal L/min of O2 that can be delivered by NP is 6L/min, beyond that, you are not giving any more O2 to the patient, this is approximately equal to FiO2 of 40%
  • Delivery of oxygen is limitted by the entrainment of ambient room air (FiO2 of 21%). To increase the amount of O2 delivered you must control to amount of entrained air
  • Non-rebreather masks draw oxygen from a reservoir with a one way valve that directs exhaled air out of the mask, thereby limiting the amount of entrained air. These can deliver up to 100% FiO2.

3) Pulmonary Aspergillosis

  • Aspergillus is a fungus that is basically ubiquitous, found in both outdoor and indoor environments
  • There are 4 classic presentations:
    • Allergic bronchopulmonary aspergillosis (ABPA) - common in ashtmatics and CF patients
    • Chronic necrotizing pulmonary aspergillosis (CNPA) - common in immunocompromised patients or patients with underlying lung disease
    • Aspergilloma: a fungus ball that can grow in pre-existing cavities ie. from previous TB, emphysema, PCP
    • Invasive pulmonary aspergillosis (IPA) - occurs in severely immunocompromised hosts with neutropenia or post HSCT
Invasive Pulmonary Aspergillosis

  • Diagnosis:
    • Aspergillus can be a colonizer, so diagnosis is not made solely on the basis of sputum cultures
    • The diagnosis of IPA is based on histopathologic evidence of aspergillus invading lung tissue
    • Diagnostic criteria for ABPA:
      • Hx of asthma, immediate skin sensitivity to aspergillus Ag, aspergillus precipitins, Elevated specific IgG, E, A to aspergillus, central bronchiectasis, serum IgE >1000ng/ml, elevated eosinophils >500/mm, lung infiltrates on CXR
  • Treatment
    • For IPA, tx should be initiated as soon as there is a clinical suspicion and while confirmatory testing is done.
    • Tx depends on the degree of infection. For IPA/CNPA, voriconazole/itraconazole is first line, can use IV liposomal amphotericin b or IV voriconazole for severe infections
    • First line treatment of ABPA is corticosteroids, can use itra or vori as steroid sparing agent

Review of Pulmonary aspergillosis

Wednesday, October 10, 2012

Pituitary Macroadenoma

Approach to Pituitary Macroadenoma

  • Pituitary adenomas are classified based on size and function:
    • Macroadenoma vs Microadenoma
    • Functioning vs non-functioning
  • Causes problems by:
    • Hypersecretion: Most common are gonadotroph secreting adenomas, but they are hardest to recognize as they secrete inefficiently and the effects are not easily noticed; prolactin (PRL), responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone (GH), responsible for acromegaly; adrenocorticotropic hormone (ACTH), responsible for Cushing's disease; thyroid-stinulating hormone (TSH), responsible for hyperthyroidism. 
    • Depressed secretion of hormones: Hypopituitarism, in the order of: GH, LH/FSH, TSH, ACTH, PRL (aka Go Look For The Adenoma Please)
    • Mechanical compression
      • Expansion of dura causes headaches
      • Superior invasion: affects optic chiasm and causes bitemporal hemianopsia
      • Inferior invasion: Through cribriform plate into sphenoid sinus causing CSF rhinorrea and risk of meningitis
      • Lateral invasion: Cavernous sinus/internal carotid artery and cranial nerves 3, 4, 6, 5 (V1/V2)
  • Investigation:
    • Mechanical compression/extension: 
      • Assessed by MRI
      • Also can do visual field testing
    • Hormone secretion:
      • GH: is normally secreted in a diurnal pattern and is suppressed by glucose load. Tested by doing an oral glucose tolerance test. Also can test IGF-1 which does not change hour by hour and reflects integrated GH secretion during the previous 24hrs. Also can test response to OGTT, as patients have insulin resistance.
      • TSH/T3/T4
      • Cortisol: Screening tests: 24 UFC, late night salivary cortisol, 1mg Dex suppression test
      • Prolactin: Prolactin level
    • Hormone suppression:
      • GH, LH/FSH/Testosterone, TSH, AM cortisol, prolactin
    • Comorbidities:
      • If patient found to have GH secreting adenoma should look for visceral organ effects:
        • Colonoscopy to look for polyps/colon ca
        • ECHO to look for cardiomyopathy
        • BP to look for HTN
        • Fasting BG, OGTT to screen for diabetes
        • Screen for obstructive sleep apnea
  • Management:
    • Surgical indications:
      • A visual field deficit due to the lesion or other visual abN
      • Adenoma abutting the optic chiasm on MRI
      • Pituitary apoplexy with visual disturbance
      • Hypersecreting tumour other than prolactinoma
    • Specific situations
      • GH secreting adenoma: First line is surgery. Medical therapies include somatostatin analogues (octreotide/lanreotide) and dopamine agonist (cabergoline) and GH receptor antagonists (Pegvisomant). Can also use radiation (fractionated or by Gamma knife).
      • ACTH secreting tumour: primary therapy is surgery
      • Prolactinoma: Can use medical therapy with DA agonist.
    • Micro-incidentalomas
      • Follow-up MRI in 1 yr and then Q1-2 y thereafter
      • If grows significantly (in proportion to original size) then consider surgery
    • Macro-incidentalomas
      • Follow up MRI in 6 months then Q1yr
      • Evaluate for hypopituitarism and evaluate the visual fields
      • If there is tumour growth, VF abN or hypopit consider surgery

See the Endocrine Society Practice Guidelines for an Approach to Pituitary Incidentaloma

Tuesday, September 25, 2012

Fever in a Returning Traveler

Approach to fever in the returning traveler:

1) History:
  • Detailed travel hx with dates (to calculate incubation period)
  • Exposure history (mosquito bites, water, food)
  • Visiting friends and relatives vs staying in tourist areas
  • associated signs and symptoms
  • Duration and pattern of fever
  • immunizations tatus
  • Use and adherence to antimalarial chemoprophylaxis
2) Differential Diagnosis (not an exhaustive list!)
  • Must rule out MALARIA
    • Incubation period: anywhere from 2 wks to a year.
    • Plasmodium falciparum: must be immediately ruled out as can be rapidly fatal
    • Non-falciparum (P. vivax, P. ovale, P. malariae, P. knowlesi) cause febrile illness but are rarely fatal
    • Must keep malaria on the differential, even if on chemoprophylaxis due to resistance
    • "hectic" fever +/- headache, cough, GI problems.
    • Invx: thick and thin smears x 3, rapid antigen testing, CBC (thrombocytopenia without leukocytosis is characteristic, may have anemia from hemolysis), bili, liver enzymes
    • Complications: altered LOC, seizures, acidosis, ARDS, liver failure, severe hemolysis, renal failure, cerebral malaria
    • Must start antimalarials parenterally if severe infection or if levels exceed 4% of visible erthrocytes
  • Dengue
    •  Caused by a mosquito-borne flavivirus in tropical and subtropical areas
    • Incubation period of 4-7 days
    • Clinical Sx: lymphadenopathy, erythema/nonspecific maculpapular rash, leukopenia and thrombocytopenia
    • Serious infection: dengue shock and dengue hemorrhagic fever
    • Clinical diagnosis + confirmed with serum antibody titers
  • Rickettsia
    • Triad of fever + headache + myalgia
    • Examples: African tick typhus, Mediterranean tick typhus, scrub typhus
    • Transmitted by arthropods (painless eschar at inoculation site) in grassy areas
  • Leptospirosis
    • History of exposure to fresh water
    • fever+ myalgia + headache + rash (Conjunctival suffusion is a diagnostic sign)
  • Typhoid
    •  Causal agent: Salmonella enterica. Fecal oral transmission
    • Sx of fever+abdo distension + constipation+lymphadenopathy
    • Invx: Leukopenia +thrombocytopneia. Dx by blood C+S.
    • Treated with fluoroquinolone/3rd gen cephalosporin
See the following article for further details: Illness after international Travel 

Wednesday, September 19, 2012


Today we talked about an interesting patient with thyrotoxicosis, here are some things we discussed

1) Thyrotoxicosis vs Hyperthyroidism

  • Thyrotoxicosis implies symptomatic excess thyroid hormone, without referring to an etiology
  • Hyperthyroidism implies excess intra-thyroidal production of hormone
  • Causes for thyrotoxicosis can be divided into 1) Disorders associated with normal or high radioiodine uptake or 2) Disorders associated with low or absence radioiodine uptake
2) Normal or High radioiodine uptake
  • Graves disease
  • Toxic multinodular goiter
  • Toxic adenoma
  • Iodine induced hyperthyroidism: i.e. CT contrast or amiodarone (iodine uptake may be low in this case if exogenous iodine has a long half-life or continues to be given, as it will dilute the radioactive tracer)
  • Trophoblastic disease/germ cell tumours: mediated by beta-HCG which cross reacts with TSH receptors. Examples include: hydatidiform moles/choriocarcinoma in females and testicular germ cell tumours.
  • Secondary hyperthyroidism from a functioning pituitary adenoma
3) Low or absent radioiodine uptake
  •  Thyroiditis:
    • Pyogenic thyroiditis
    • Viral thyroiditis
    • Hashimoto's thyroiditis
    • Postpartum thyroiditis (a form of Hashimoto's occuring postpartum)
    • Radiation thyroiditis
    • Palpation thyroiditis (after a surgical excision on the thyroid from it vascular bed)
    • Drug induced: amiodarone, lithium

Liver abscess

Types of Liver abscess:
1) Bacterial aka pyogenic
2) Parasitic (amoebic)
3) Fungal

1) Ascension of bacteria from biliary tree (40-50% of cases)
2) Portal vein spread (from intra-abdo source i.e. diverticulitis, appendicitis)
3) Hematogenous spread
4) Direct inoculation from trauma or surgical procedure
5) Cryptogenic

Risk factors
1) Diabetes
2) Hepatobiliary/pancreatic disease
3) Malignancy
4) Liver transplant
5) Immunocompromised: HIV/AIDS

Bugs commonly involved: mostly polymicrobia aerobes + anearobes
1) Gram positives: Staph, microaerophilic Strep, Strep milleri (abscessogenic), enterococcus
2) Gram negatives: Klebsiella, enterbacteriacea coli
3) Anaerobic: fusobacterium, bacteroides (may not be grown on culture)
4)  Fungus
5) Hydatiform cyst echinococcus: from dogs
6) Amoebic liver abscess: entamoeba histiolytica (fecal oral route)

Treatment of pyogenic liver abscess:
1) Abx to cover gram+/-/anaerobes (a penicillin, aminoglycoside/cephalosporin and metronidazole)
4) Source control: perc drainage

See the following article for more about liver abscesses Liver abscesses and Hydatid disease

Thursday, September 13, 2012


This is my catch-up blog about empyema, which we discussed on Tuesday!

1) Thoracic empyema

  • Defined as pus in the pleural fluid (high PMN count) and or pH  less than 7.20. Also has high LDH due to lysis of PMNs. Progression to an empyema occurs over time and patients present subacutely with a long hx of SOB, cough etc. A dense layer of fibrin can deposit on the visceral and parietal pleurae, leading loculation and worse prognosis. This anaerobic environment leads to the proliferation of anaerobes and other bacteria.
  • Common symptoms include pleuritic chest pain, dyspnea and sputum production. Those with aspiration risk, underlying lung disease, diabetics and immunocompromised are at higher risk.
  • Physical exam reveals dullness to percussion, decreased breath sounds, decreased fremitus and a loss of egophony.
  • Common bacteriology:
    • Prevalent bacteria include: Streptococcus milleri, Staphylococcus aureus, enterobacteriaceae, strep pneumonia, GAS, CNST
    • Diabetics are at increased risk of Klebsiella pneumonia
    • MRSA can cause a necrotizing pneumonia that leads to complicated parapneumonic effusions. 
    • The lack of anaerobic bacteria in culture does not exclude the presence of anaerobes, espcially if the fluid has a putrid odor. Empiric coverage for anaerobes should be initiatied. Common bugs include Peptostreptococcus, Fusobacterium and occasionally Bacteroides fragilus
    • Don't forget tuberculous empyema, characterized by large mounts of pleural PMNs. 
  • Treatment:
    • Antibiotics: Should target the likely underlying cause of the pneumonia. Options for empiric therapy that cover anaerobes as well as gram + and -  include clindamycin, amoxi-clav or piperacillin tazobactam and carbapenems. 
    • Sterilization of the empyema should occur within at least 4-6 wks of therapy, but therapy should be continued if there are persistent symptoms or persistent effusion as seen on imaging.
    • All complicated parapneumonic effusions and empyemas should be managed with complete pleural fluid drainage. This can be done with a pig-tail or tube thoracostomy (preferred for thick loculated empyema)
    • Progress should be assessed by repeat CT imaging
    • Chest tubes are typically left in place until the drainage rate is less than 50mL/day and empyema cavity has closed
    • If Unsuccessful, thoracics may need to be involved for a VATS (video assisted thorascopic surgery) for debridement / decortication
    • Fibrinolytic agents can also be used to improve drainage of loculated effusions/empyemas. 

Tuesday, September 11, 2012

Cerebellar Exam


Yesterday we learned about how to do a neurologic exam of the cerebellum. Here is a recap for those of you unable to attend:

1) The Cerebellum 
  • Coordination of volitional movements: adjusting the rate, range, force and sequence
  • Motor deficits from the cerebellum are ipsilateral to the lesion, while deficits to the motor cortex of the cerebral cortex are contralateral to the lesion.
  • Clinical localization in the cerebellum: The cerebellum can be divided sagitally for purposes of localization of function
    • Midline: concerned with posture, locomotion, position of head relative to trunk. Midline cerebellar disease presents with disorders of stance/gait, truncal postural disturbances.
    • Intermediate: Paravermal region of cerebellum. Concerned with velocity, force of volitional movements.
    • Lateral: Concerned with planning of volitional movements in connection with the Rolandic region of the cerebral cortex.
2) Cardinal Signs of Cerebellar Dysfunction:
  • Hypotonia
  • Ataxia: defective timing of contraction of antagonistic/agonistic muscles, results in a disurbance of the smooth performance of voluntary movements.
  • Dysarthria
  • Abnormal ocular movements
  • Tremor
3) Inspection
  • Level of Consciousness
    • Acute cerebellar strokes can cause raised ICP that can impair LOC
  • Tone:
    • Hypotonia can occur with acute cerebellar infarcts
4) Gait
  • Have patient walk normally, then heel to toe (tandem gait)
  • Walk is wide based, staggering, lurching.
  • Lesions of the lateral cerebellum result in Patients falling towards the ipsilateral side of the lesion
  • Lesions of the midline result in movements in all directions.
  • Ataxia secondary to vestibular disease may appear similar (patients fall towards the affected vestibular apparatus)
5) Test of Station
  • Romberg Test - Not positive in cerebellar disease (positive Romberg = patient falls). With eyes open and closed patient has a sway (towards ipsilateral side of there is a lateral lesion of the cerebellum. Visual orientation does not improve the ataxia.
6) Cranial Nerves
  • Test for any bulbar abnormalities which may accompany a cerebellar stroke
7) Nystagmus
  • Midline lesions: Gaze evoked nystagmus, up beat, opticokinetic, rebound nystagmus. Opsoclonus - multivectorial, fast, involuntary eye movements.
  • Lateral lesions: unidirectional with fast phase towards the affected side
  • Non-fatiguable
8) Speech
  • Scanning, staccato, explosive speech. Unable to control volume.
  • Ask the patient to take a deep breath and say "ahhhh". This tests for control of the expiratory muscles and vocal cords 
  • Ask the patient to say "la, la, la" and "me, me, me" to test for rapid alternating movements of the tongue and lips.
  • Ask patient to say the ABC's to assess the meter and volume of speech
9) Ataxia of the extremities:
  • Ask patient to extend arms out in front and observe for tremor. Sharply tap the arms proximally and observe for oscillations of the arm as they return to baseline. The affected side has more violent oscillations.
  • Test for Rebound: Ask the patient to flex their arm against your resistance, place an arm on their shoulder to protect their face. Suddenly let go of the flexed arm and observe if the patient is able to arrest the rebound of the flexed arm. Patients with Cerebellar dysfunction will be unable to do this.
  • Dysmetria: abnormal excursions of movement, frequently undershooting or overshooting the target
    • Tested by finger to nose testing. Must extend arm completely.
  • Dysdiadochokinesia: Difficulty with rapid alternating movements
    • Test with hand tapping on thigh or foot tapping
    • Test with alternating fingers touching the opposing thumb.
10) Reflexes:
  • Test for Pendullar reflexes with excessive sway
For more information refer to: Cerebellar exam

Friday, September 7, 2012

Nephrotic Syndrome

Today we had an excellent discussion about a 61 yo Female who presented with an acute onset of anasarca and nephrotic range proteinuria with a normal serum creatinine.

There are three major causes of nephrotic syndrome:
1) Minimal Change Disease
  • Epidemiology: Most common in children, but has bimodal distribution. 
  • Clinical presentation: sudden onset (days to weeks) of nephrotic syndrome. Can also have microscopic hematuria. Usually have normal serum creatinine. In elderly, often present with hypertension.
  • Etiology:
    • Idiopathic
    • Drugs: NSAIDS (most common), antibicrobials (ampicillin, rifampicin, cephalosporins), Lithium, Penicillamine, sulfasalazine, Trimethadione, gamma interferon
    • Neoplasms: Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia
  • Diagnosis:
    • Given the high prevalence of MCD in children, a diagnosis can often be made without a renal biopsy. 
    • In adults, often a renal biopsy is needed to distinguish from other causes of nephrotic syndrome.
  • Treatment:
    • Very steroid responsive, 80-90% achieve complete remission. Takes longer in adults than children. up to 75% respond within 6months.
    • Relapses are harder to treat, and may require cyclosporin.
    • In conjuction with: Low salt diet, diuretic, ACEi
2) Focal Sclerosing Glomerular Sclerosis:
  • Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
  • Etiology:
    • Primary FSGS: idiopathic cause of nephrotic syndrome (mediated through circulating permeability factors, increasing the permeability of the glomeruli to albumin). 
    • Secondary: Viruses (HIV, Parvovirus B19, hepatitis C, EBV, CMV), drugs (IV pamidronate, anabolic steroids, interferon), obesity, lupus, reflux nephropathy, hypertensive nephrosclerosis.
  • Diagnosis:
    • Biopsy shows Segmental areas of mesangial collapse and sclerosis. Collapsing FSGS (HIV, iv pamidronate) characterized by collapse and sclerosis of entire glomerular tuft.
  • Treatment:
    • Responds to steroids, but is less responsive to steroids than MCD. For steroid resistant or relapsing disease, cyclosporine is commonly used.
3) Membranous Disease:
  • Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
  • Etiology: Solid organ tumours, lupus - class V lupus nephritis (does not need to be accompanied by other disease manifestations of lupus), infections (Hepatitis B, syphilis), Drugs (penicillamine, gold, NSAIDS)
  • Diagnosis: 
    • ANA, C3/4, Hepatitis serology, 
    • Biopsy shows: Thickening of the glomerular basement membrane, in absence of hypercellularity.
  • Treatment
    • Control BP, ACEi, diuretic
    • Prednisone +/- cyclophosphamide or cyclosporin
For more information refer to the following great articles on Nephrotic syndrome:

Thursday, September 6, 2012

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea here are some pearls:
1) Definition:

  • Bloody Diarrhea = Colitis
  • Triad of bloody diarrhea, lower abdominal pain and fever = "Dyssentry"
2) Etiology:
  • Infectious: Salmonella, Shigella, Yersinia, Campylobacter, C. difficile (though rare), E. coli (enterohemorrhagic O157:H7), CMV in immunocompromised hosts. The most common causes in Toronto would be campylobacter
  • Ischemic: Embolic (a. fib, cardiogenic emboli), mesenteric vein thrombosis, aortoiliac bypass, cardiopulmonary bypass.
  • Inflammatory: Inflammatory bowel disease, vasculitis of the gut
  • Radiation colitis
3) History:
  • Exposure history: 
    • Travel/sick contacts
    • Food: raw beef, pork, poultry, alfalfa sprouts (E.coli), rice (B. cereus), unpasteurized dairy
    • Timing of onset: less than 6hrs likely from pre-formed toxin, 8-16h think clostridium, more than 16hrs think viral or bacterial infection, if starts as diarrhea and progresses to h/a, myalgias, think listeria (especially in pregnant women)
    • Medications: recent abx
    • Recent hospitalizations
    • Hx of IBD, radiation, immunosuppression
    • Extra-intestinal manifestations of IBD
    • Sexual hx
4) Diagnosis:
  • Stool C + S, C. diff PCR - very sensitive and specific
  • Stool O + P - not very cost effective, but reasonable in immunocompromised patients, community outbreaks of giardia or cryptosporidium, chronic diarrhea.
  • Stool leukocytes - not very helpful
5) Treatment:
  • Supportive!
  • IV hydration, replete electrolytes (patients often have Non-Anion Gap Metabolic Acidosis initially)
  • Should you treat with Antibiotics?
    • Impact is modest: Decreases duration of symptoms by several days
    • Consider treatment in people at risk for complications: elderly, diabetics, cirrhotics, immunocompromised
    • Antibiotics are indicated for ETEC (fluoroquinolone), C. diff (metronidazole), Salmonella (flouroquinolone). Abx can also be used for severe campylobacter (macrolides or flouroquinolone)
    • See the following link for Utility of antibiotics in diarrhea
    • HUS: caused by the shiga toxin from E.coli O157:H7 characterized by bloody diarrhea, MAHA, thrombocytopenia, acute renal failure +/- neurologic symptoms. Antibiotics have been shown to prolong diarrhea and lead to worse outcomes. Prognosis is better than TTP.

Thursday, August 30, 2012

Does my butt look firm... or inflammed?

Complications of Polymethylmethacrylate injections

1) What is it?
PMMA is a synthetic material that was first synthesized in 1902 and patented as Plexiglas in 1928. It was initially used in the medical field as bone cement but has gone on to have multiple different uses, including intra-ocular lenses and vertebroplasty. Given its smooth surface, chemical innertness and biocompatibility it has become popular as a dermal filler in cosmetic procedures. There are many commercial fillers containing PMMA, differing in terms of the size of the PMMA spheres and the suspension.

2) How does it work?
PMMA is injected into the dermis. Initially after implantation there is an acute macrophage mediated inflammatory reaction. Permanent results occur when macrophages convert into epitheliod cells that replace the suspension material with fibrin and eventually collagen. However, in a small percentage of cases (pharmaceuticals state less than 2.5%) a nodular granulomatous reaction can occur.

3) Complications:
A study out of the University of Sao Paulo documented and described 32 cases of complications due to PMMA.

  • Tissue necrosis: can occur immediately. Caused by disruption of the vascular supply, by injection or compression on vessels.
  • Delayed type sensitivity to bovine collagen plus PMMA, has been documented 6-24 mo post injection.
  • Granulomas: occurred 6 months - 1 year post injection. Characterized by localized pain and nodules at the site of injection.
  • Chronic inflammation: 1-10yr post injection. Characterized by cyclic pain and swelling.
  • Local infection: can occur immediately and has been documented up to 1 yr post injection.
Some food for thought next time you consider joining a PMMA party...

Thursday, August 23, 2012

Autoimmune Polyglandular Syndrome

Yesterday we talked about an interesting case of a young male with a history of Type I DM and Celiac disease who presented with severe hyperkalemia (8mmol/L), hyponatremia, hypotension and non specific abdominal complaints.

With that degree of hyperkalemia and his history of multiple autoimmune diseases, the working diagnosis was primary adrenal insufficiency and possibly Polyglandular Autoimmune Syndrome type II.

1) Autoimmune Polyglandular Syndrome type I (AKA Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy APECED)

  • Hypoparathyroidism
  • Chronic mucocutaneous candidiasis
  • Primary adrenal insufficiency (Addison's disease)
  • hypogonadism
  • Malabsorption and other gastrointestinal disorders
2) Polyglandular Autoimmune Syndrome type II (much more common)
  • Type I DM
  • Autoimmune thyroiditis, occasionally Graves disease
  • Primary adrenal insufficiency
  • Secondary adrenal insufficiency from autoimmune hypophysitis
  • Hypogonadism
  • Non-endocrine autoimmune phenomenon (vitiligo, myasthenia gravis, TTP)
  • Schmidt's syndrome: primary adrenal insufficiency and autoimmune thyroid disease

Tuesday, August 21, 2012

Fever in the Immunosuppressed Patient

Today we talked about fever in a patient with a history of AML after completion of chemotherapy. We spoke about the importance of maintaining our natural barriers (mucosal, skin, nails) in defence of pathogens. Here are some important points we touched on:

1) Types of immunity:
  • Innate: 
    • Parts of the immune system able to respond to insults immediately, not reliant on antibodies or other acquired mechanisms
  • Acquired:
    • Cellular: Mediated largely by T cells. Important for intracellular pathogens (mycobacterium, fungal infection, viruses, some bacteria, parasites)
    • Humoral: immunologic responses mediated by antibodies (from B-cells and T helper cells) Important for defence against encapsulated bacteria
  • Our patient had AML with post chemotherapy bone marrow suppression and severe neutropenia. Therefore she had suppression of both her innate and acquired immune system.
2) Mucositis/Esophagitis
  • Bacterial translocation: 
    • Gram positives: Strep viridans and milleri. The S. milleri group can survive under low oxygen tension and is "abcessogenic"
    • Anaerobes: Fusobacterium (associated with internal jugular thrombophlebitis AKA Lemierre's syndrome)
    • Gram negatives: institutionalized/sick patients may develop colonisation of the Upper GI tract with lower GI tract commensals, putting them at risk of gram negative bacteremia. Consider Pseudomonas aeruginosa, Enterobacteriacea, Enterococcus.
  • Fungal
    • Candida
    • Fluconazole: activity limited to yeasts and some endemic fungi (histoplasma, blastoomyces, coccidioides and paracoccidioides). Excellent activity against Candida albicans, but less against non-albicans.
    • Itraconazoel: Broader spectrum than fulconazole. Including endemic fungi, sporothrix schenckii and aspergilus.
    • Voriconazole: enhanced activity against aspergillus and other hyalohyphomycoses. Superior to fluconazole resistent C. glabrata dn C. krusei.
    • Posaconazole: expanded spectrum with activity against mucorales, yeasts and molds.

    • Viral
      • HSV, CMV

    3) Aspergillosis
    • Invasive aspergillosis: Diagnosis based on culture of aspergillosus with histopathologic evidence of invasive hyphae or culture from a normally sterile site. Galactomannan or Beta D glucan assay can also be used to determine invasive aspergillosis.
    • Chronic pulmonary aspergillosis: Four types: aspergilloma, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis.

    Thursday, August 16, 2012

    Internal Medicine Potpourri!

    Today we heard about a potpourri of Internal Medicine cases. Here are a few highlights:

    1) Diabetic foot infections:
    • IDSA Classification: Grade 1 = colonisation, no evidence of infx (clean based ulcer with granulation tissue, no purulence or cellulitis); Grade 2 = At least two signs of infection (erythema, purulence, pain, warmth, induration) and less than 2cm of surrounding cellulitis; Grade 3 = 2+ cm surrounding cellulitis, involvement of bone, tendon or deep fascia but no systemic toxicity; Grade 4= systemic toxicity.
    • Microbiology: Grade 1-2 : usually gram + organisms (MSSA, Strep group A, B, C, G, enterococcus). Grade 3+ Polymicrobial: MRSA, staph, strep, gram negative bacilli (e. coli, proteus, klebsiella, ESBL, pseudomonas) and anaerobes (peptococcus, peptostreptococcus, bacteroides, fusobacterium). Risks for resistance: chronic wounds, prior hospitalization and previous abx therapy.
    • Treatment
    • Non pharmacologic: decrease pressure on wounds, good wound care.  
    • Pharmacologic: (suggested regimens only, check with institution specific resistance profiles) Grade 1-2: Abx with good Gram + coverage (Cloxacillin, Cephalexin, Amoxi-clav), if MRSA possible add Septra or Vancomycin. Grade 3: Add aerobic Gram - coverage and anaerobic coverage (Cipro + Clinda, moxifloxicin, cephalosporin + Clinda). Grade 4: consider Pipericillin/tazobactam or a carbapenem. 
    • See the following article for a review on the microbiology and treatment of Diabetic foot infections: Diabetic foot infections
    2) NSAIDS and PUD
    • The risk of causing GI bleeding is nto equal amongst all NSAIDS. A meta-analysis of controlled trials   of commonly prescribed non-selective NSAIDs found that the risk of highest in indomethacin (RR 2.25), then naproxen (RR1.83), diclofenac (RR1.73), ibuprofen (1.43) and meloxicam (RR 1.24).
    • The latest trend is to prescribe an NSAID with a PPI (ie. Vimovo has naphroxen and esomeprazole) However, there is evidence for worsening NSAID induced small bowel injury, due to the changes in small bowel micro-flora with PPI use. So ultimately, NSAID use should still be limited in patients at risk of GI complications.
    3) DKA
    • While serum K+ may be normal, patients have low total K+. Must treat K+ and maintain greater than 4. Best way is orally (may need to place NG tube)
    • Insulin IV to treat the Anion Gap
    • Fluids to treat the hyperglycemia
    • Patients are usually phosphate deficient, however trials looking at repletion of phosphate in DKA showed no difference in duration of DKA, rate of AG improvement or morbidity/mortality. Hypophosphatemia of less than 0.32mmol/L can cause hemolysis, rhabdomyolysis, myoglobinuria (but is rare). Therefore consider treating only if Phosphate is less than 0.3.

    Wednesday, August 15, 2012

    Unusual Causes of Upper GI Bleed

    Today we talked about UGIB with Dr. Ho Ping Kong. Here are some key points we talked about:

    1) Most common causes of UGIB:

    • Peptic Ulcer disease - 55%
    • Variceal - 14%
    • Arterial, venous and other vascular malformations - 11%
    • Mallory Weiss - 5% (although Dr. HPK would disagree)
    • Erosions - 4%
    • Malignancy - 4$
    • Other - 11%
    2) Unusual causes of UGIB:
    Watermelon Stomach
    • Dieulafoy's lesion: Dilated submucosal vessel that is usually located in the antrum of the stomach, but can be found in the esophagus and duodenum. Thought to be congenital. As the artery is not surrounded by stomach muscle, it can become dilated. The artery can bleed (triggered by NSAIDs?) resulting in profuse bleeding, that is often self limited.
    • Gastric Antral Vascular Ectasia (GAVE): AKA Watermelon stomach. Characterized by longitudinal rows of ectatic/sacculated mucosal vessels running from the antrum to the pylorus. Can be idiopathic, but also associated with cirrhosis and systemic sclerosis. Most common presentation is that of slow, chronic blood loss and iron deficiency anemia. 
    • Vascular anomalies: Osler-Weber-Rendu or Hereditary Hemorrhagic Telangiectasia, Ehrlos Danlos, CREST, Klippel-Trenaunay-Weber syndrome.
    • Portal Hypertensive Gastropathy: Occurs in patients with cirrhosis and portal hypertension. Mucosa has a snakeskin like appearance with a fine white reticular pattern and areas of pink mucosa.
    • Hemobilia: Bleeding from the hepatobiliary tract. Usually occuring after hepatobiliary instrumentation.
    • Hemosuccus Pancreaticus: Bleeding from the pacreatic duct. Usually occurs with pancreatic pseudocysts or tumours that erode into adjacent arteries.
    • Aortoenteric Fistulas: Usually secondary to ulcers/tumours. Arteries affected include aorta, gastroduodenal artery.
    • Cameron lesions: Ulcers in a hiatus hernia
    • Tumours: Lymphoma, Kaposi's sarcoma
    • Secondary Angiodysplasia: End stage renal disease, aortic stenosis and Heyde's syndrome
    3) Unusual causes of PUD:
    • H. Pylori (~61% of DU and ~63% GU) and NSAIDs account for the majority of peptic ulcer disease.
    • Gastrinoma: Zollinger-Ellison Syndrome: Non-beta cell islet tumour of the pancreas associated with acid hypersecretion and multiple peptic ulcers. Can occur sporadically or in association with MEN I (hyperparathyroidism, pancreatic tumours and anterior pituitary tumors).
    • Systemic mastocytosis: Secondary to increased circulating histamine
    • Carcinoid tumours: Also secondary to increased circulating histamine
    • Other infections: HSV-1, CMV
    • Stress ulceration: Hospitalized/critically ill ICU patients
    • Sarcoidosis
    • Crohn's Disease
    4) HPK Classic (Couldn't leave this out)
    Bob Marley leads to Rastafari leads to Rasmussen's Aneurysm 

    Rasmussen's Aneurysm: A pulmonary artery aneurysm adjacent to or within a tuberculous cavity. Can cause fatal hemoptysis

    Saturday, August 11, 2012


    Syncope is one of the most common problems encountered in the emergency department. The greatest challenge is determining who should be admitted for inpatient investigations and who can be investigated as an outpatient. 

    1) What is it: Transient, self limited, loss of consciousness.
    2) How is it classified:
     3) Approach to Diagnosis:

    • The cause of a syncopal event is often in the HISTORY
    • The history should focus on the following:
      • Circumstances surrounding episode: Position (supine, sitting, upright); activity (micturition, defecation, unpleasant experience, exertion); predisposing factors (warm, crowded etc.)
      • Prodromal symptoms: Nausea, vomitting, diaphoresis, aura, palpitations or lack of prodorome
      • Eye witnesses: Abnormal posturing, movements of limbs, incontinence etc.
      • After the event: New weakness, confusion, level of consciousness
      • History: Previous events, family hx of sudden cardiac death, hx of coronary artery disease, structural heart disease.
    •  Historical features worrisome for cardiac syncope:
      • Lack of prodromal symptoms, syncope with exertion or supine. Syncope associated with palpitations.
      • Hx of structural cardiac disease
      • Abnormal ECG (sinus bradycardia, Mobitz II or 3rd degree, intraventricular conduction delay (QRS >0.12sec)
    •  Boston Syncope Criteria: Patients meeting any one of the following criteria should be admitted for further investigation:
      • Signs and symptoms of ACS
      • Worrisome cardiac history (hx of CAD, CHF, hx VT/Vfib, pacemaker/ICD, antiarrhythmic medications)
      • Family hx of sudden death
      • Valvular heart disease on hx of exam
      • Signs of conduction disease
      • Volume depletion
      • Perisistent abnormal vital signs in the ED
      • Primary CNS event.
    4) Investigations:
    •  Cardiac investigations:
      • Telemetry
      • ECHO
      • Exercise test
      • Ischemia evaluation
      • If the above is normal, consider the following tests as an outpatient: 
        • If symptoms are frequent Holter monitor 24-48hr
        • If symptoms are infrequent consider Implantable loop recorder
        • Tilt table testing if hx suggestive of neurocardiogenic syncope
    See the following for more information:
    Boston Syncope Criteria
    European Heart Journal guidelines on treatment of syncope

    Thursday, August 9, 2012

    Delirium Tremens

    CIWA protocol

    Delirium Tremens
    Last night we had, as Dr. McNeely put it, "a tsunami of alcoholics". Here are some pearls on Delirium Tremens or the "Rum Fits"

    1)What is it: It is a state of severe psychomotor agitation and sympathetic overdrive in chronic alcoholics who have been abstinent for ~ greater than48-96hrs, but can occur up to 7-10 days since the last drink. It also happens to be the name of a brand of Belgian golden ale as seen above!

    2) When to suspect it:
    • Prolonged daily alcohol consumption
    • Symptoms of withdrawal even while serum etOH levels are still elevated
    • Prolonged period of abstinence
    • Comorbidities
    • Increasing age
    • History of DTs

    3) What to expect:
    • Psychomotor agitation: anxiety, delirium, tremor, hallucinations, seizures,
    • Autonomic dysfunction: hyperthermia, hypertension, tachycardia, tachypnea, diaphoresis, midriasis
    • Seizures: Alcohol withdrawal seizures can occur within 12-48 hours of the last drink, and can occur without DTs. They are tonic clonic, and occur as a single seizure or a brief flurry of seizure activity. If seizures are prolonged or continue for >6 hr period other causes of seizures should be investigated (i.e. intracerebral hemorrhage). 
    4) How to Treat:
    • Benzodiazepines are the mainstay of treatment
    • For patients in the acute phase of alcohol withdrawal treat with diazepam. 
      • Diazepam 10-20 mg PO Q1H x 3
      • If unable to tolerate PO Diazepam IV 2-5mg Q5-10 min until appropriate level of sedation is achieved.
    • Rather than keeping patients sedated it is better to practice symptom based treatment with the CIWA protocol
      • When to start CIWA: For any patient at risk of alcohol withdrawal who has been abstinent for <12 hrs="hrs" li="li">
      • When to stop CIWA: For any patient with a CIWA of less than 10 x 3 consecutive evaluations
    • Hallucinations
      •  Can treat with Haloperidol (watch the QTc)
    • Metabolic disturbance
      • Treat electrolyte abnormalities, Mg, Phos, K+
      • Treat malnutrition: Thiamine 100mg IV daily x 3 and folate
      • IV rehydration
    • Patients can have arrhythmias and should be on telemetry
    • Refer to the following link regarding treatment of alcohol withdrawal: CIWA protocol

    Tuesday, August 7, 2012


    Hyponatremia is the most common electrolyte abnormality encountered in the hospital. It primarily signifies a problem with water, not salt.

    Etiology: Net gain of electrolyte free water relative to the body's stores of Na and K. This can occur in three volume states:

    1) Hypovelemic State: ADH is appropriately released resulting in the retention of water in the kidneys. There is relatively more water retention than sodium retention resulting in hyponatremia. The urine osmolality will be high and urine sodium will be low. Thiazide diuretics are also common culprits of chronic hyponatremia.

    2) Euvolemic State:
    • SIADH: ADH is inappropriately released by many mechanisms including pain response, nausea/vomitting, CNS disturbance, pulmonary disease, medications (anti-depressants, anti-convulsants, MDMA/ectsasy)
    • Tumour producing ADH
    • Endocrine abN (hypothyroidism, adrenal insufficiency)
    • Low solute diet (tea and toast, beer potomania)
    • Psychogenic polydipsia.
    3) Hypervolemic State: Low effective circulating volume i.e. cirrhosis, heart failure.

    The degree of severity is inversely proportional to the serum Na and the time frame over which the change occurred. The risk of hyponatremia is inversely proportional to the Serum Na, with serum Na less than 120mmol/L considered severe. Symptoms are non-specific, including lethargy, headache, confusion, seizures and decreased LOC. Patients with seizures and decreased LOC, secondary to low Na, should have their serum Na corrected quickly (see treatment below). However patients with chronically low serum Na, do not need to be corrected quickly and may in fact be harmed by over correction.

    Patients with chronically low serum [Na] develop shifts in the intracerebral osmoles to coompensate for the chronically low serum [Na]. Therefore, if a rapid correction of serum [Na] occurs, this can result in a sudden shift of water extracellularly, putting patients at risk of osmotic demyelinating syndrome (ODS) or cerebral pontine myelinolysis (CPM). Patients who are elderly, malnourished and hypokalemic are at the highest risk. In the case of rapid correction (8mmol/day or more), the serum Na must be decreased quickly to prevent the development of ODS/CPM. Treatment includes administering hypotonic IV fluids and giving DDAVP to increase serum ADH.

    1) Start by confirming hyponatremic hyponatremia by doing a serum osmolality. Rule out hypertonic hyponatremia caused by other osmoles (hyperglycemia, mannitol)

    2) Assess volume status: hypervolemic, hypovolemic, euvolemic

    3) Confirm volume status with urine lytes:

    • Hypovolemic: High urine osmolality greater than 300mOsm. Low excretion of urine Na less than 20. 
    • Euvolemic: Normal urine Na, normal urine osmolality.
    • Keep in mind if pt is on Lasix, urine Na may be high!
    Treatment of Hyponatremia:
    1) Severe Hypo Na: Treat with hypertonic saline 3% (513 mOsm). Give 100cc 3%NS over 10 minutes, this should increase serum [Na] by 2meq. This can be repeated twice every 10 minutes. Pateints should be treated until symptoms resolve (i.e. seizures). Furosemide can be given reduce volume expansion and prevent shutting off of ADH and diuresis.

    2) Non-severe hypovolemic HypoNa: A safe range for improving sodium is 6-8mEq/24 hrs. Patients should be monitored for urine output, repeat serum lytes and urine lytes Q4hr as they receive IV fluids. A sign of aquaresis is the sudden production of large amounts of dilute urine. If this occurs, to prevent rapid correction of serum [Na], DDAVP can be given 2-4mcg IV. Some insititutions advocate for giving DDAVP up front, however as long as close care is taken to detect aquaresis early, giving up front DDAVP can be avoided.

    3) SIADH = restrict fluid to less than 1.5L per day, and consider salt tabs.

    Please refer to the following recently published article on Hyponatremia in JASN:

    Wednesday, August 1, 2012

    Nephrotic Syndrome

    Today we talked about a patient presenting with bilateral leg edema and proteinuria. This brought up the topic of Nephrotic syndrome:
    1) Nephrotic Syndrome:
    • Characterized by nephrotic range proteinuria (usually more than 3 g/day), edema and hypoalbuminemia (<3g also="also" and="and" associated="associated" g--="g--" hypercoagulable="hypercoagulable" hyperlipidemia="hyperlipidemia" state.="state." with="with">
    • Hyperlipidemia: Triglyceride rich lipoproteins increased in nephrotic syndrome due to decreased catabolism. This is likely due to decreased binding of lipoprotein lipase (LPL) to endothelial cells secondary to the reduced oncotic pressure.
    • Hypercoagulable state: Likely secondary to an imbalance between naturally occuring pro-coagulant/pro-thrombotic factors and anti-coagulant and anti-thrombotic factors. Likely multifactorial, related to increased urinary losses of anti-thrombin, Protein C, Protein S and increased levels of fibrinogen. See this paper for a review of hypercoagulability and nephrotic syndrome
    • Increased susceptibility to infections: unclear etiology, but may be related to urinary losses of IgG.
    2) Etiology
    • Focal segmental glomerulosclerosis: common cause of idiopathic nephrotic syndrome in adults
      • Reflux nephropathy
      • Nephron loss: surgical or congenital
      • Intraglomerular hypertension from primary renal vasodilation: Diabetes, sickle cell disease
      • Obesity
      • Interferon
    • Minimal change disease: Most common cause in children, also occurs in adults.
      • Drugs: NSAIDs, antimicrobials (ampicllin, rifampin), penicillamine, lithium, sulfasalazine
      • Paraneoplastic phenomena: Hodgkin's lymphoma, NHL, leukemia, rarely solid tumors
      • Infectons: TB, syphilis, Hep C, HIV, erlichiosis, mycoplasma, echinococcus
      • Systemic diseases: Diabetes, SLE, PCKD, HIV
      • Allergy
    • Membranous nephropathy
      • Malignancy, typically solid tumor (GI, prostate, lung) and less frequently heme malignancy
      • Infections: Hepatitis B/Hepatitis C, schistosomiasis, malaria, syphilis
      • Autoimmune disease: SLE (lupus nephritis type V)
      • Drugs: NSAIDs, penicillamine, 
    • Amyloidosis
      • AL/primary amyloid: Light chain dyscrasia where fragments of monoclonal light chains form amyloid fibrils.
      • AA/ Secondary amyloid: Secondary to chronic inflammation where the acute phase reactant serum amyloid A forms amyloid fibrils. Occurs for example in Rheumatoid Arthritis or osteomyelitis.
      • In this case, urine dipstick will be negative and serum albumin is normal.

    Tuesday, July 31, 2012

    Today we talked about a case of acute hypoxia in an elderly gentlemen with a history of dysphagia, stroke, seizures and dementia.We covered the differential for acute hypoxia and then identified that the most likely cause in our patient was aspiration pneumonia, with pulmonary embolus on the differential.

    1) Causes of Acute Hypoxia: The differential for hypoxia is extensive, but the differential for sudden onset severe hypoxia is not as long.

    • Pulmonary embolus
    • Pneumothorax
    • Pulmonary edema (cardiogenic/non-cardiogenic)
    • Pulmonary hemmorhage
    • Aspiration pneumonia
    • Bacterial pneumonia
    • Mucous plugging
    2) Aspiration: Defined as misdirection of oropharyngeal or gastric contents into the larynx and lower respiratory tract. There are two entities: Aspiration pneumonitis and pneumonia. Aspiration pneumonitis can lead to ARDS and carries a high mortality (up to 12%). It can present with fever and hypoxia. Treatment is supportive. Use of glucocorticoids is controversial and animal studies have shown variable results.

    Half of healthy adults aspirate during their sleep, but are protected from developing aspiration pneumonia by the following mechanisms: low virulent bacterial load in orophargyngeal/gastric contents, active ciliary transport, normal cough reflex, cellular and humoral immune system to help clear infection.

    • Risk factors for aspiration include
      • Decreased LOC caused by drugs or toxins (i.e. EtOH)
      • Stroke/neurologic injury causing dysphagia/impaired cough reflex
      • Seizure disorder
      • Degenerative CNS disease: dementia, Parkinson's, ALS
      • Dysphagia: esophageal stricutre, diverticulum etc.
      • Recent anesthetic
      • ETT/Trach/NG tube
      • Frequent reflux/vomitting/gastric outlet obstruction
    • Risk factors for developing aspiration pneumonia:
      • Poor dentition
      • Treatment with PPI
      • Underlying lung disease
      • Immunosuppression/decreased cellular immunity
      • Colonization of oropharynx with s. aureus, GNB (Klebsiella pneumonia, Escherichia coli)
    • Common bacterial pathogens:
      • Oral anaerobes: Fusobacterium, Bacteroids, Peptostreptococcus
      • Gram negative bacilli: Klebsiella, E. coli
      • S. aureus
    • Management:
      • Swallowing assessment: by SLP +/- Video Fluoroscopic Swallowing Study (VFSS)
      • Dysphagia diet
      • Antibiotics
        • When anaerobic bacteria is the most likely pathogen: consider Clindamycin
        • Other regimens that also cover CAP: 
          • Amoxicillin-Clavulanate
          • Moxifloxacin
          • Flagyl plus Amoxicillin or Penicillin
        • For nosocomial pneumonia and pt is unwell and coverage for both aerobic and anaerobic bacteria is important: 
          • Pipericillin-tazobactam
          • Carbapenems
      • Management of dysphagia:
        • Studies have looked at using dopamine agonists and ACEi to increase substance P, which enhances swallowing and the cough refelx.
        • Percutaneous feeding/PEG tube has not been shown to increase survival, quality of life or decreased aspiration events
    The following is a systematic review of the evaluation and management of dysphagia due to dementia in the elderly:

    Friday, July 20, 2012

    Today Dr. Okrainec took us through a very interesting case of an unstable patient with an UGIB.
    The medical students, R1s and R2s did a great job of stabilizing the patient and eventually saving his life! Here are some key points that came out of this morning's session.

    1) Approach to the unstable patient:

    • Always remember your ABC's
      • Be cognisant of changes from a patient's baseline, a drop of more than 20mmHg from the baseline BP is significant, even if the absolute value is not in and of itself alarming.
      • Does the patient look sick? Sweating, clammy, cold extremities
      • Always reassess vitals when there is a change in pt's status and Q2-5 minutes
      • Call for help: when needed you can call a code blue to get a 1) monitor 2) ICU nurse 3) RT/anesthesia 4) crash cart
      • Gather as much information as possible: delegate a member on your team to collect information such as: meds, last blood work, past medical history, major things to look at are last creatinine, INR, hgb, wbc
      • Do a focused physical exam
      • Always plan ahead: Check that you have adequate IV access, inform the ICU of a sick patient, will you likely need blood (do you have an up to date group&screen in the lab?)
    2) Approach to UGIB
    • ABCs
      • Start with getting 2 large bore (16-18G) IVs 
      • Start with fluid resuscitation
      • Get blood: Uncross matched if pt is hemodynamically unstable and low likelihood of having alloantibodies.
    • Initial Management:
      • Start Pantoloc 80mg IV bolus followed by 8mg/hr infusion
      • If hx or risk factors for liver disease and varices start octreotide
      • Consider NG tube, but careful if pt has known esophageal varices
      • Optimize clot formation:
        • Reverse INR: Octreotide + Vit K
        • Platelets: should be above 50
        • Uremia: can give DDAVP to help platelet function
    • Definitive management:
      • Call GI: for early endoscopic treatment
      • Call ICU: for possible intubation
      • If pt has liver disease and ascites consider prophylaxis for subacute bacterial peritonitis (SBP)

    Thursday, July 19, 2012

    Today we had a great discussion on bread and butter Internal Medicine cases from the night before. Here is a tasting menu of the issues that came up in this morning's "Grand Morning Report"

    1) Proton Pump Inhibitors - potential side effects

    • Proton pump inhibitors have revolutionized the treatment of UGIB. An acidic environment inhibits   platelet aggregation and promotes fibrinolysis of formed clot by the enzyme pepsin. Bringing the gastric pH to above 6 is thought to promote clot formation. Studies have shown that treatment with a PPI signficantly reduces recurrent bleeding secondary to PUD. 
    • PPIs are often started for various reasons, i.e. to promote healing of peptic and duodenal ulcers, symptom relief from GERD etc. They are very effective, however many forget to reassess the need to continue on PPI therapy and patients may continue them indefinitely. This has led to long term complications of PPI use.
    • Nutritional:
      • Protein bound dietary Vitamin B12 requires acid and pepsin for its initial absorption. Vitamin B12 then binds to haptocorrin, found in the saliva. It is then liberated in the higher pH environment of the duodenum, where it binds to intrinsic factor and is absorbed in the terminal ileum.This may be more important for people who have low Vit B12 intake (i.e. Vegans) or the elderly. Therefore it may be reasonable to measure Vit B12 levels in these populations of people who are on PPIs.
      • There is a theoretical possibility of iron deficiency, as gastric acid is needed to reduce non heme iron (Ferric iron) to the more soluble Ferrous iron.
      • Osteoporosis: Gastric acid secretion is important for dietary calcium absorption.
    • Infections:
      • Pneumonia: By changing the gastric flora and seeding of the lungs from the upper alimentary tract.
      • C. difficile and other enteric infections: Also due to changes in the gastric flora 
    • Cancer:
      • Theoretically the hypergastrinemia resulting from chronic acid suppression can lead to hyperplasia of the gastric enterochromaffin-like cells and lead to gastric carcinoid tumours. Gastrin is also trophic for colonic mucosa, and may also lead to colorectal carcinoma.
    2) Treatment of bacteriuria in the Elderly
    • There is no evidence for treatment of asymptomatic bacteriuria in the elderly. The only cases where asymptomatic bacteriuria should be treated is in pregnant patients and prior to urologic procedures.
    • Bottom line, a positive urinalysis in an obtunded elderly patient does not mean the patient has urosepsis! Look for other signs of infection: Fever, white blood cell count, imaging findings of pyelonephritis, lower urinary tract symptoms.
    3) When to suspect Legionella?
    • Fever >39C
    • Neurologic findings, confusion
    • Gastrointestinal findings: Nausea/Vomiting/Diarrhea
    • Transaminitis
    • Leukocytosis, thrombocytopenia
    • Hematuria
    • Hyponatremia
    • Failure to respond to beta-lactams or aminoglycocide
    • CXR: can show anything from lobar consolidation to interstitial pulmonary inflitrates

    Friday, July 13, 2012

    Paroxysmal Nocturnal Hemoglobinuria

    Today we talked about Paroxysmal Nocturnal Hemoglobinuria, an interesting cause of intravascular hemolysis and thrombosis.

    1) Pathogenesis:

    • Defect in the PIG-A gene that encodes the cell membrane anchor glycophosphatidylinositol (GPI). Glycophosphatidylinositol is necessary for binding proteins to the RBC membrane.
    • Defect in the GPI anchor leads to the absence of GPI linked proteins. Two important proteins that are missing include CD55 and CD59, which are involved in the down regulation of the complement system.
    • The complement system is part of our innate immunity and is composed of a cascade of enzymatic reactions that culminate in the creation of a membrane attack complex (MAC) that results in cell lysis and destruction. There are two forms of the complement system, the classical pathway that is initiated by IgG/IgM antibodies and the surveillance system that does not require antibodies to become activated. It is this latter system that affects RBCs. 
    • CD55 and CD59 act to accelerate decay of the complement system and protect against lysis, respectively, thereby preventing the formation of the deadly MAC. Patients with PNH who lack CD55/CD59 suffer from episodic intravascular hemolysis, the severity of which depends on the degree of absence of GPI linked proteins.
      • PNH III: complete absence
      • PNH II: partial absence
      • PNH I: normal

    2) Symptoms
    • Hemolysis: Episodic hemolysis, the severity of which depends on the degree of expression of CD55/59. The hemolysis is intravascular and therefore characterized by hemoglobinuria, hemoglobinemia and hemosiderin in the urine. Hemolysis in PNH can happen at any time, not necessary at night as the name implies. However, it is thought that hemolysis increases at night due to intestinal absorption of lipopolysaccharides that enhance the complement system. 
    • Nitric Oxide sequestration: Free hemoglobin is a NO scavenger. Nitric Oxide is important in relaxing smooth muscle, therefore depletion of NO as a result of hemolysis results in smooth muscle dysfunction. This manifests as esophageal dysmotility with dysphagia and abdominal cramping.
    • Renal dysfunction: Acute hemolysis results in hemoglobinuria that can cause acute kidney injury. Also over time, chronic renal dysfunction occurs due to hemosiderin deposition.
    • Prothrombotic state: Patient with PNH have a higher propensity for both venous and, to a lesser extent, arterial thrombosis. The etiology is not well known but thought to be secondary to an abnormal  line of platelets. Patients present with thrombosis of hepatic veins, intra-abdominal veins and even cerebral veins.
    • Diminished hematopoiesis: May progress to aplastic anemia
    • Hematologic malignancies: May lead to myelodysplastic syndrome and acute leukemia.
    3) Treatment
    • The treatment of PNH has been revolutionized by the introduction of eculizumab, a humanized monoclonal antibody against C5. This stops terminal complement activation. See this link to the TRIUMPH study a double blind randomized multicenter control study looking at use of eculizumab compared to placebo for PNH. TRIUMPH
    • Supportive therapy includes intermittent transfusions as needed and iron/folate supplementation. Be careful of patients developing iron overload due to repeated blood transfusions!
    • Anticoagulation is initiated for those with a history of thrombosis. Prophylactic anticoagulation may also be used in those with a large percentage of abnormal granulocyte clones.

    Wednesday, July 11, 2012

    Today we discussed an interesting case of a 21 year old male with a non-healing ulcer on his shin. Interestingly he had been recently diagnosed with ulcerative colitis. While, the diagnosis of pyoderma gangrenosum seemed most obvious, the biopsy in fact showed evidence of leukocytoclastic vasculitis and the patient was found to have high peripheral eosinophils and was P-ANCA positive. Talk about a curve ball!

    Here are some interesting questions that arose from our discussion:

    1) Differential Diagnosis of ulcerative lesion:
    Refer to the following NEJM article for an interesting discussion of skin ulcers misdiagnosed as pyoderma gangrenosum. This article gives a great differential diagnosis for ulcerative skin lesions. The key is to have a broad differential and to do a biopsy! The treatment for pyoderma gangrenosum is not benign (steroids and other immunosuppressants) so be sure of the diagnosis before you treat.

    2) Leukocytoclastic vasculitis is not a diagnosis in and of itself but a pathologic term describing neutrophilic small vessel vasculitis. It is an indication of small-vessel vasculitis. This can occur in the following settings:

    • ANCA associated small vessel vasculitis:  
      • Granulomatosis with polyangiitis (formerly known as Wegener's vasculitis)
      • Churg-Strauss vasculitis
      • Microscopic Polyangiitis
    • Immune Complex associated small vessel vasculitis:
      • Hepatitis C with cryoglobulinemia
      • Henoch-Schonlein pupura (HSP)
      • Connective tissue disease-associated vasculitis:
        • RA
        • SLE
        • Sjogren's Syndrome
      • Endocarditis
    • Hypersensitivy vasculitis:
      • Penicillin, ASA, amphetamines, thiazides
    • Viral infections:
      • Strep throat
      • bacterial endocarditis
      • TB
      • hepatitis
      • Staphylococcal infections
      • Foreign proteins (serum sickness)
    3) Differential for non-vasculitic P-ANCA positivity:

    • Infectious: HIV, mycobacterial infections, severe pneumonia, bacterial endocarditis
    • Chronic: Rheumaotid arthritis, IBD, Sweet's syndrome, eosinophilia-myalgia syndrome, Goodpasture's syndrome
    • Neoplasms: Atrial myxoma, small cell lung cancer, NHL, myelodysplasia, colon carcinoma

    4) Differential for Eosinophillia:
    • Infectious: Parasitic infection, fungal infection (aspergillosis)
    • Hematologic/neoplastic: Hypereosinophilic syndromes, leukemia, lymphoma
    • Allergic disorders: atopic dermatitis, asthma, rhinitis, medications
    • Rheumatic disease: Churg Strauss
    • Miscellaneous: Adrenal insufficiency, cholesterol embolization

    Tuesday, July 10, 2012

    This morning we discussed an interesting case of an 84 year old male who presented with falls and change in mental status. Dr Nadjafi took us through an approach to delirium (see blog from July 5th for approach to delirium). After thorough investigations it was discovered that the patient's Calcium was 3.98mmol/L! Here is a quick approach to hypercalcemia:

    1) Diagnosis:
    - Serum Calcium: 40-50% of calcium in serum is bound to protein (mainly albumin). It is the ionized (or "free") calcium that is physiologically important. Therefore, hypo- or hyper-albuminemia can affect the serum ionized calcium. The following calculation helps you determine ionized calcium from measured calcium.

    Ionized Calcium = measured Ca + 0.2(40-measured albumin)

    - Degree of hypercalcemia: Mild hypercalcemia (<2.75mmol/L) usually seen in hyperparathyroidism. Severe hypercalcemia (>3.25mmol/L) usually indicates malignancy associated hypercalcemia.

    2) Symptoms:
    Anxiety, depression, cognitive dysfunction
    In severe cases lethargy and confusion
    Abdominal pain, nausea, anorexia and constipation
    - Diabetes insipidis: Inability to concentrate urine, polyuria/polydipsia
    - Nephrolithiasis: RTA type I: Rare
    - Nephrocalcinosis from long standing hyperCa: Necrosis of tubular cells and interstitial fibrosis
    - Bony pain (from primary cause ie. Cancer or hyperparathyroidism

    "Moans, groans, stones, and psychic overtones"

    3) Etiology:

    a) PTH Mediated:
    • Primary: Sporadic
    • Secondary: Renal disease and decreased production of 1,25-dihydroxyvitamin D. Adynamic bone disease results in reduced bone turnover. The reduced uptake of calcium into bones after a calcium load leads to hypercalcemia.
    • Tertiary: Prolonged hyperphosphatemia and hypocalcemia leads to hypertrophy of the parathyroid glands and unregulated release of PTH. Occurs in patients post renal transplant.
    • Familial: MENI and IIa, familial hypercalciuric hypercalcemia
    b) Non-PTH mediated
    • Malignancy:
      • Osteolytic: Bone mets resulting in induction of local osteolysis by tumor cells and release of osteoclast activating factors in multiple myeloma
      • PTHrp: some tumors produce PTH related peptide that mimics PTH. These include squamous cell carcinomas (lung and H+N), breast, bladder, ovarian
      • Ectopic PTH secreting tumor
    • Granulomatous disease
      •  Activation of extra-renal 1-aOH leading in macrophages and/or lymphocytes. Leading to PTH-independent production of 1,25-dihydroxy Vitamin D
    • Drugs:
      • Lithium
      • Thiazides
    • Increased Vitamin D intake
    • Miscellaneous:
      • Immobility
      • Hyperthyroidism
      • Pheochromocytoma
      • Adrenal insufficiency
      • Milk alkali syndrome: excessive ingestion of Calcium supplements
      • Paget's disease
    4) Treatment:
    • The cornerstone of treatment is: FLUIDS, FLUIDS, FLUIDS
      • Patients are often quitet hypovolemic secondary to their inability to concentrate urine and nephrogenic diabetes insipidus
      • The kidneys should be able to excrete the majority of excess calcium
    • Also consider:
      • Calcitonin: 4u/kg IM/SC rapid reduction in serum Ca by 1-2mmol/L. Works in 4-6 hrs.
      • Bisphosphonates: Pamidronate 30mg, 60mg, 90mg IV. More sustained reduction in Ca, takes 1-2 days to start working.
      • Steroids: Prednisone 20-40mg/day. Decreases conversion of 25 hydroxyvitamin D to 1,25-dihydroxyvitamin D
      • Lasix: Caution as this can cause worsening hypercalcemia. Only used of pt is showing signs of volume overload from fluid resuscitation. see article from Annals of Internal Medicine: Furosemide fro Hypercalcemia: An unproven yet common practice

    Monday, July 9, 2012

    On Friday we spoke about a case of fever of unknown origin or FUO.
    The original definition of FUO as proposed by Petersdorf and Beeson in 1961 required the following criteria:
    (1) Fever of >38.3 on more than one occasion
    (2) Fever for more than or equal to 3 weeks
    (3) No etiology discovered after at least 1 week of inpatient investigations

    However, the definition has evolved with the increasing population of patients with HIV and neutropenia and the ability to perform investigations in an outpatient setting. The following is a new definition proposed in 1991 by Durack and Street:

    Hayakawa et al. Am J Med Sci. April 3. 2012 Epub ahead of date

    A thorough history, including onset, duration and nature of the fever, is crucial. While the pattern of fever has not been found to correlate significantly to the etiology, two patterns have been described: (1)Pel-Ebstein (fever for 3-10 days on, then 3-10 days off, typical of Hodgkin's lymphoma) (2) Typhus inversus: reversal of normal diurnal pattern seen in TB.

    In many cases the etiology can be narrowed down based on the patient's social history. Including the patient's country of origin, vaccination status, recent travel history (where exactly), animal or insect exposure, recreational activities (gardening or swimming in fresh water), sexual activity, use of recreational drugs. The most at risk population for acquiring an travel related infectious disease, are those who immigrated long ago and return to their country of origin to "visit friends and relatives" (VFR), as these people tend to be the population who take the least precautions.

    The following is a table of common causes of FUO:

    Hayakawa et al. Am J Med Sci. April 3. 2012 Epub ahead of date

    For a comprehensive approach to FUO refer to the following interesting articles: