Fanconi Syndrome

Fanconi syndrome refers to a proximal tubular disorder. This is where amino acids, glucose, uric acid, phosphate, bicarbonate, and also Na, K, and water are primarily reabsorbed. You can imagine if cells get damaged here, an individual will spill glucose, uric acid, and amino acids, and bicarbonate in their urine. These can be measured, and are essential in the diagnosis of this condition. Because bicarbonate is not being fully resorbed, much of it spills over into the urine. This loss of bicarbonate leads to a metabolic acidosis (with a normal anion gap) - hence, there is a Renal Tubular Acidosis, also known as Type 2 or Proximal renal tubular acidosis.

Who gets Fanconi syndrome? Patients with multiple myeloma, amyloidosis, hereditary causes, Wilson's disease, heavy metal poisoning, and medications like tenofovir, aminoglycosides, and some chemotherapeutic agents like cisplatin, ifosfamide, and 6-mercaptopurine.

Here is a good article on the physiology of acid-base balance: http://content.nejm.org/cgi/content/full/339/12/819

Cauda Equina Syndrome

Basically, this is compression of the cauda equina from any cause. This presents classically with low back pain, sensory disturbances in the perineal region, leg weakness, diminished deep tendon reflexes, urinary retention often proceeding to overflow incontinence and decreased rectal tone. This should be confirmed radiologically with CT or MRI of the spine, and our surgical colleagues should be involved as early as possible.

Possible causes include Trauma, Lumbar disc herniation, Metastases (most commonly from breast, prostate, lung), Lumbar stenosis, Infection causing collapse (TB, osteomyelitis) or epidural abscess.

Here is a great review article: http://www.jaaos.org/cgi/content/full/16/8/471

Treatment of Status Epilepticus

This is the treatment of a long seizure that does not remit. How long? Well different sources say different times, but they range between 10 and 30 minutes. Regardless, any prolonged seizure needs to be stopped to prevent catastrophic complications. Drugs of choice...

1. Benzodiazapines: first line. Lorazepam and Diazepam are the most widely used agents. Lorazepam is favoured because it is less lipid soluble and may paradoxically have higher serum levels for a prolonged time. Excellent in breaking most seizures.

2. Phenytoin: this is next on your armamentarium. This is more useful in preventing further seizures than in stopping the current one. You can load a patient IV or PO. Caution with IV - you need cardiac monitoring and can induce a profound hypotension. Infuse slowly. Fosphenytoin is a pro-drug of phenytoin and can be infused much more rapidly.

3. Barbiturates: eg. Phenobarbital. If you are getting to this point, the ICU should be well involved.

4. Propofol: again, this is not for the medicine wards...the ICU will be caring for these patients.

Check out this NEJM article for the evidence behind our choices of treatment: http://content.nejm.org/cgi/content/full/339/12/792

Guillain Barre Syndrome

HoPingKong-isms:
1. "the knee bone is connected to the hip bone, the hip bone is connected to the diaphragm": referring to the progression of Guillain-Barré syndrome where weakness can sometimes ascend to respiratory muscles.

2. "You are only half right": referring to to the Brown-Séquard syndrome - a lateral hemisection of the spinal cord.

3. "I'm a little sad today, and a little cocky": referring to Coxsackie viral infections which can cause pericarditis

Guillain-Barré syndrome:
This is really an umbrella term that encompasses a few related syndromes which are immune-related polyneuropathies. Classically, patients present with bilateral ascending weakness and decreased deep tendon reflexes. Many patients will also have a sensory component (eg. numbness), and autonomic dysfunction as well (eg. tachycardia, hyper/hypotension, urinary retention). One of the major risks is when respiratory muscle function is depressed - patients need ventilatory support in the intensive care unit.

The diagnosis can be confirmed with nerve conduction studies and cerebral spinal fluid analysis. An albuminocytologic dissociation may be seen in the CSF about a week after symptoms start, which shows a normal WBC count but elevated protein.

See the below link for a great BMJ review article: http://www.bmj.com/cgi/content/full/337/jul17_1/a671

Diabetic Ketoacidosis: Precipitants

1. Any major illness: like infections (eg. pneumonia), infarctions (eg. myocardial), ischemia (eg. gut).

2. New onset of DKA: caution if this is new onset in someone older than their teens - there may be another destructive pancreatic process which warrants investigation.

3. Prescribed drugs: may affect glucose metabolism like glucocorticoids, antipsychotic agents.

4. Non-prescribed drugs: Cocaine is an independent risk factor for DKA. (Endocrine Practice 2007 3, 1, :22-9).

5. Poor compliance with insulin regimen: think about eating disorders like anorexia nervosa, other psychiatric conditions.

A great article from CMAJ on the Management of DKA: http://www.cmaj.ca/cgi/content/full/168/7/859

Ascites

There are many complications of liver disease, ascites being one of them. One way we can diagnose the etiology of ascites is with Serum-Ascites Albumin Gradient.

If greater that 11 g/L: think about cirrhosis, EtOH hepatitis, CHF, Budd-Chiari syndrome, or a high burden of liver metastases

If less than 11 g/L: think about pancreatitis, peritoneal carcinomatosis, peritoneal TB, serositis, or low albumin states like nephrotic syndrome.

here is a great article from the NEJM on managing cirrhosis and ascites http://content.nejm.org/cgi/content/full/350/16/1646

Left Bundle Branch Blocks

When are they dangerous? when this is a new finding on ECG (and in the right clinical context), this is suggestive of an acute MI.

What about in asymptomatic patients? In those with known or suspected coronary artery disease, a LBBB is an independent predictor of mortality.

What about left ventricular function? with a LBBB, the LV is often dis-synchronized, and will have a decreased LV ejection fraction.

Anything else? yes, exercise stress testing with a known LBBB is of limited value.

Factoids? rarely you may see a rate-related LBBB. Slow the heart down a bit and it disappears. This may be a predictor for major cardiac events, however there is some controversy over this.

Secondary Hypertension

Who are we worried about?
1. severe hypertension, or hypertension very refractory to treatment
2. onset of hypertension in those less than 30 years old (with no family history or obesity)
3. stable blood pressure values that acutely rise
4. onset of hypertension before puberty

What are some of the secondary causes of hypertension?
-Renal disease: virtually any cause
-Pheochromocytoma:remeber to screen for MEN IIa and IIb
-Hyperaldosteronism: may have associated hypokalemia
-Cushing's syndrome: hypercortisolemia from any source
-Sleep apnea: zzzzzzz
-Medications: OCP, HRT, some NSAIDS, some antidepressants (eg Venlafaxine)
-Coarctation of the aorta
-Hypothyroidism
-Hyperparathyroidism

Canadian Hypertension Guidelines:

http://hypertension.ca/chep/

Stigmata of Endocarditis

HoPingKong-isms:
1. "can you hear me?!!?!?" (speaking loudly): referring to ototoxicity with heavy gentamicin use .
2. "are you a sensitive person?" referring to a desensitization protocol that can be done under close observation with allergies to antibiotics such as penicillin.
3. "let me give you a preamble" referring to the presystolic accentuation of the murmur of mitral stenosis

Peripheral stigmata of infective endocarditis:
(Remember the Duke Criteria for diagnosis).

Vascular phenomena - major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhages, conjunctival hemorrhages, Janeway lesions (not painful, on hands/feet)

Immunologic phenomena - glomerulonephritis, Osler's nodes (painful, on hands/feet), Roth spots, positive rheumatoid factor


















Janeway lesion on the left, and Oslers node on the right.

Lemierre's Syndrome

What is it? a septic thrombus of the jugular vein.

Which bacteria are implicated? usually oral flora, and typically Fusobacterium species.

How does one get it? after a pharyngitis, there may be a small abscess or erosion of the mucosa. Bacteria can then invade the peri-pharyngeal space which houses the carotid sheath (encasing the jugular vein), and neck musculature.

How do patients present? typically younger patients with a prodrome of a sore throat present with fever, and possibly tenderness over the thrombosed vein. Septic emboli frequently spread to the lungs so an element of respiratory distress may be seen.

Treatment? use a beta-lactamase resistant beta-lactam. Surgical exploration may be required. The role of anticoagulation is controversial.

A great reference: http://content.nejm.org/cgi/content/full/350/10/1037

Have a great day.

Hypercalcemia in Cancer

Some mechanisms...

1. Direct metastases to bone: These mets trigger the production of inflammatory cytokines and stimulate ostoclasts. Sometimes osteoclasts are directly stimulated by tumor cells via Osteoclast Activating Factors (eg IL6) in multiple myeloma or lymphoma.

2. PTH related peptide: this is the most common cause of hypercalcemia from non-metastatic solid tumors. Classically in squamous cell lung Ca

3. PTH: this is rare! only a few case reports of PTH being released from tumors

4. Calcitriol: a very common mechanism for hypercalcemia in the lymphomas.

a great article here
http://content.nejm.org/cgi/content/full/352/4/373

TIMI

The TIMI Risk score

Part of our discussion this morning was about the prognosis of those individuals admitted with Acute Coronary Syndromes. This TIMI score came up in conversation. This score estimates mortality of your ACS patient in the next 14 days. Each item is worth a point for a total score out of 7. 0-2 points is low risk with a 14 day mortality of less than 3%. 5 points and above is high risk, with estimated 14 day mortality rates over 12%.

1.Age greater than or equal to 65 years
2. Presence of at least three risk factors for CHD (hypertension, diabetes, dyslipidemia, smoking, or positive family history of early MI)
3. Prior coronary stenosis greater than or equal to 50%
4. ST segment changes on admission ECG
5. Two or more anginal episodes in the preceding 24 hours
6. Elevated serum cardiac biomarkers
7. Use of ASA in the past 7 days

Antman EM, Cohen M, Bernink PJ, et. al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000 Aug 16;284(7):835-42.

Taking a History for Acute Coronary Syndromes:

Below is a link to the JAMA article that discuses which components of the cardiac history are important for Acute Coronary Syndromes:

http://jama.ama-assn.org/cgi/content/full/294/20/2623

Nephrotic Syndrome

Today we discussed some issues about Nephrotic Syndrome. Here are some thoughts....

What is it? proteinuria (albuminuria greater than 3 g per 24 hours), hypoalbuminemia, and peripheral edema. Patients also have a predilection for hyperlipidemia and thrombotic disease.

Etiology: diabetes mellitus, systemic lupus erythematosus, and then primary or secondary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy and amyloidosis.

A brief word about some of these:

Minimal change disease: more common in children. Also seen in Hodgkin's Disease or with NSAID use.

Focal Segmental Glomerulosclerosis: more common in those of African descent. Can be seen with HIV, reflux nephropathy, NSAID use, or obesity.

Membranous nephropathy: often associated with underlying hepatitis B, solid and hematologic malignancies, autoimmune disease, and medications.

See you on the wards,

Isaac

TB Meningitis

HoPingKong-isms

1. “Give me a kernel of knowledge…” referring to Kernig's sign of meningitis – when the hip is bent at 90 degrees there is difficulty extending the knee secondary to pain (and resistance). This is usually coupled with Brudzinski's sign - a supine patient with meningism will flex at the hip and knee when their neck is passively flexed. These signs have very low sensitivity.

2. “Don’t be tense…” referring to tenosynovitis as one of the manifestations of disseminated gonococcal infection.

3. “I’m a megalomaniac today….” referring to megaloblastic anemias, as caused by B12 or Folate deficiencies.

Treatment of TB meningitis
For the first two months (the “intensive phase”) a number of antibiotics are used simultaneously – this is a slow growing organism and there is lots of resistance. Then the regimen can be altered based on the resistance pattern of the organism.

The drugs: INH, Rifampin, Pyrazinamide, and Ethambutol

Anything else I should add? yes, Steroids. Dexamethasone and Prednisone have both been used successfully – eg. 3 weeks of Dex (12 mg/day) then a 3 week taper (N Engl J Med 2004 Oct 21;351(17):1741-51.)


If the strain of TB is fully sensitive, you are now in the “Continuation phase” and treat with INH and Rifampin for 7 – 10 months. Go check out the Infectious Diseases Society of America web page for details (http://www.idsociety.org/)

That's all for now.

Immune Thrombocytopenia Purpura

Immune thrombocytopenic purpura aka Idiopathic thrombocytopenic purpura aka ITP was discussed today. We touched on the differential diagnosis, physical exam, and management of ITP.

A few words on management:

Steroids: first line. typically Prednisone 1mg/kg daily until the platelet count starts to rise, then taper. There are ongoing trials looking at shorter courses of high dose Dexamethasone now.

Intravenous Immunoglubulin: IVIG is frequently used after patients fail steroids. There is no clear time frame that dictates when IVIG should be used....some will initiate it after 4-5 days if there is no response to steroids, others may wait a bit longer.

Splenectomy: very effective for refractory ITP, but a bit invasive.

Rituximab: a very cool drug. It is a monoclonal antibody that binds to cells expressing CD-20 (B cells) and seems to be a promising alternative to splenectomy. Large trials are in the works.

Others: some other drugs that have been used successfully include vincristine, cyclophosphamide, and danazol.

Pimping 101: Accessory Spleen? What? Sometimes after splenectomy patients may still have resistant ITP. What's going on? Rarely a bit of splenic tissue is left behind, but even more rarely there may be an anatomic variant where there is a 'mini spleen' in the neighbourhood of the 'real spleen', about the size of a peanut M&M (See picture below).



























Have a great day,