Systemic Lupus Erythematosus

Today we discussed an unfortunate patient with multisystem disease, a positive ANA (as depicted here) and a new diagnosis of SLE.

SLE appears on the differential in many medical conditions due to the multiple organs it can involve (and the multiple manifestations required for diagnosis).

The diagnositic criteria for SLE can be found at this site.

A pathophysiologic review, with a table of the classic rhematologic antibody assays is published in NEJM here.

Have a great weekend!

Congestive Heart Failure

Today, in addition to piloting another format to morning report, we discussed congestive heart failure. Management issues surrounding associated acute renal failure and atrial fibrillation were also reviewed. Here is a brief summary:

ARF

This can make management difficult. When the renal failure is secondary to poor perfusion pressure, this sometimes improves with diuresis. ACE/ARBs are vital to the management of CHF and should be continued whenever possible.

Atrial Fibrillation

This is a classic "chicken or the egg" scenario in that did the AFib push the patient into failure, or did the "atrial stretch" from fluid overload cause the patient to go into Afib? In any case, diuresis is paramount. If needed, rate controlling agents (Digoxin, Amiodarone, intravenous magnesium) can all be used to slow the patient down, but all will be ineffective without diuresis.

In both scenarios above, a trial of BiPaP can go a long way in stabilizing the patient (decreases afterload, increases preload and increases CO) while you are awaiting the effects of diuresis.

Here is a recent review on CHF from NEJM. Also, here is an interesting article on using intravenous iron therapy for iron deficient patients in heart failure.

The Adrenal Incidentaloma

Today we had a great discussion on the approach to an incidentally discovered adrenal mass.

An adrenal incidentaloma is defined as an adrenal mass (>1cm) that is discovered serindipitously on abdominal imaging designed to look for something else. These are common with an estimated frequency of 6% of the general population.

Imaging characteristics
Many radiographic findings can help determine the malignant potential of a lesion. These include size (>4cm), contrast washout time, density, and border contour of the lesion.

Biochemical Workup
The basic principle is to determine whether the lesion(s) is functional or impairing the function of the gland. See Table 2 in the linked article for some guidelines on workup.

Role of Biopsy
The role of fine needle aspiration in an adrenal mass is primarily useful in determining adrenal from non-adrenal tissue (r/o mets or infection). Actual tissue architecture is required to determine if the lesion is a primary adrenocortial carcinoma. Always remember to r/o a pheochromocytoma (24h urine metanephrines) before asking someone to put a needle into these lesions (hypertensive crisis)

There is an excellent NEJM review here.

Aortic Stenosis

This afternoon, physical exam rounds focused on Aortic Stenosis.

This topic was blogged about by Dr. Dave Frost (Last year's CMR) in a previous post. Here is the link.

Enjoy your weekends!

Renal Failure

Today we had a fantastic discussion regarding causes of renal failure secondary to multiple myeloma.

To summarize:
Hypercalcemia
Hypercalcemia (as a consequence of bone destruction) can predispose a patient to renal failure in 3 ways. First, high calcium levels lead to a diuretic effect, reducing the effective circulating volume. Second, calcium can deposit into the kidney itself (nephrocalcinosis). Finally, the high calcium levels can precipitate in the collecting system leading to stone disease.

Stones
In addition to calcium based stones, the high cell turnover also predisposes the patient to form uric acid stone (gouty nephropathy). This can also be nephrotoxic.

Cast Nephropathy
Filtration of toxic light chains leads to both tubular injury and intratubular cast formation (and obstruction). The light chains bind avidly to the normal tubule mucoprotein (Tamm-Horsfall) and lead to obstruction. As the tubule becomes damaged, adult onset Fanconi Syndrome, a proximal type 2 RTA, can develop (loss of amino acids, glucose and ability to acidify the urine).

Light Chain Deposition Disease
Excess monoclonal light chains deposit in the kidney (without forming fibrils) and can lead to a nephrotic type syndrome.

Amyloid
Circulating light chains are taken up by macrophages where they are partially processed, then excreted as Congo-red positive, beta-pleated fibrils. These are nephrotoxic.

Recurrent Infections
Both systemic overwhelming infections (sepsis) and recurrent urologic infections are more common in myeloma patients which put them at risk for renal failure.

NSAIDS
Bone pain hurts. Patients often turn to NSAIDS to help manage the pain and this can lead to renal failure in a number of ways (will be discussed in a future blog).

Renal Vein Thrombosis
MM is a hypercoagulable state (loss of anti-thrombin 3 in the urine). The renal vein is susceptible to thrombosis and subsequent renal failure.

The "anti-kidney" antibody
Multiple antibodies against various "kidney-ness" have been described (evil-humors?) and associated with renal failure.

Cord Compression
Plasmacytoma love the spinal cord and as a consequence, cord compression can develop. A real emergency!

Pretty impressive list. If I missed something, add it to the comment section. Also, check out this article from JASN.

Listeriosis

Today we discussed the interesting case of Listeriosis.

L. monocytogenes is a facultatively anaerobic, nonsporulating, gram-positive rod that grows over a broad temperature range, including refrigeration temperatures. (making small lapses in sanitation at food processing centres an even more dangerous event).

Here is a brief overview of some of the clinical manifestations.

Gastroenteritis
Usually develops within 48 hours of ingestion of a large inoculum of bacteria in contaminated foods (milk, deli meats, soft cheeses and salads). Manifestations include fever, diarrhea, headache, and constitutional symptoms. Unless in a high risk group (see below) no treatment is usually required.

Meningitis/Encephalitis
L. monocytogenes causes ~5–10% of all cases of community-acquired bacterial meningitis in adults in the United States. Case-fatality rates are reported to be 15–26%. This is usually a more sub-acute presentation with a predominance in chronically ill patients or at the extremes of age.
L. monocytogenes can directly invade the brain parenchyma, producing either cerebritis or focal abscess.

Infection in Pregnancy (Nothing makes an internist more uncomfortable than a pregnant patient - except maybe kids).
The usual presentation in pregnancy is a nonspecific acute or subacute febrile illness with myalgias, arthralgias, backache, and headache. Preterm delivery is a common complication. Prepartum treatment of bacteremic women enhances the chances of delivery of a healthy infant. Women usually do well after delivery: maternal deaths are very rare, even when the diagnosis is made late in pregnancy or postpartum. Overall mortality rates for fetuses infected in utero approach 50% in some series; among live-born neonates treated with antibiotics, mortality rates are much lower (~20%). Granulomatosis infantiseptica is an overwhelming listerial fetal infection a feared complication.

Treatment
High dose Ampicillin (2g q4h) or Pen G (4MU q4h) is the recommended therapy for serious Listeria infections. In penacillin allergic patients, desensitization is always an option, although good results have been demonstrated with Septra.

For more information, check out this review.

Hyponatremia

Today we discussed hyponatremia and its management:

Some take home points - rapid correction of hyponatremia is often not required unless it is clear that the patient is acutely symptomatic from their hyponatremia - if you do need to give hypertonic saline (often in marathon runners, ecstasy overdose, etc.) it is often given as 3%NS with a 100cc bolus, then reassessment for further doses. The patient should be in a monitored setting and have frequent repeat electrolytes sent.

Consulting nephrology is never a bad idea for these patients.

We also discussed "BEER POTOMANIA" (apparently potomania is: An intense and persistent desire to drink alcohol to excess).

Malnourished patients (low-protein, high water intake diets) often do noy have enough solute excretion to deal with their water intake . Beer and other primary carbohydrates meals have little solute, however their CHO content suppresses endogenous protein catabolism/urea production.

Example:
Normal subject - 600 mosm/day of solute intake (and output). If they are hyponatremic and make a maximally dilute urine of 60 mosm/L (assume the kidneys cannot make a more dilute urine), their solute load allows a maximum of 10L of urine/day i.e. - their free H2O intake would have to exceed 10L for them to get more hyponatremic.

In malnourished patients - their solute intake/output can be 240 mosm/day. Therefore with a maximally dilute urine of 60 mosm/L (the kidneys cant make it more dilute) then their maximum urine output will be 4L/day. If their intake of fluid is >4L (>11 beers)/ day they will worsen their hyponatremia.

Other tips:
When seeing hyponatremia in the ER:

First rule out acute hyponatremia that needs acute correction.

Recheck the lytes if they were done several hours previously- the patient has possibly received intravenous fluids in the ER that may have significantly altered the sodium concentration - especially if the stimulus (often ECF volume depletion) for ADH secretion has been removed. Following the urine output may help to identify this (although recording can be an issue outside of the ICU) as a brisk, dilute diuresis can be bad sign.

Further tips from a nephrologist who attends on GIM are posted here, as well as an article about the use of DDAVP to prevent overly rapid sodium correction.

End of Life Care

Many people have strong beliefs regarding feeding and end of life care. It is imperative to examine the goals of care with patients when making end of life care decisions and to remember that there will be a number of social, cultural and religious factors to be considered. Enlisting help from palliative care physicians, chaplaincy and other professionals with experience in helping make these decisions is often very important.

An article that examines some important points surrounding the use of feeding tubes in severe dementia is posted here. We often dont focus on promoting oral intake in hospital, but it is important to consider strategies to address this as well.

An article reviewing artificial nutrition and hydration at the end of life can be found here (Pub med abstract) or here (if logged through the university libraries)

COPD Physical Exam

A summary of the physical exam for COPD is posted here

AECOPD

Some interesting articles about morning report:

The Matrix article

The Pimping article

Points about COPD

Definition: (WHO)"Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases."

NOTE THAT COPD IS NOT AN ISOLATED LUNG DISEASE BUT HAS SYSTEMIC EFFECTS

Diagnosis: symptoms compatible with COPD, airflow obstruction (FEV1/FVC ratio less than 0.70 with no alternative cause.

Severity based on FEV1

Mild: FEV1 over 80% of predicted, with or without symptoms

Moderate COPD -FEV1 50-80% predicted

Severe COPD- FEV1 30-50%

Etiologies of exacerbations:

Majority are infection-related (80%) - H. Flu; S. Pneumo; M. Catarrhalis; P. Aeruginosa (5-10%); Rhinoviruses (20-25%).

15-20% are from other causes (inhaled irritants, air pollution)

Treatment consists of

1) Bronchodilators

2) Systemic steroids

3) ABx

4) Ventilatory support if needed (including BiPAP)

Abx - NOT needed for all exacerbations. Some advocate using only if increased sputum purulence. Classically used in all exacerbations requiring assisted ventilation (possible mortality benefit) or when there are 2 or more of increased dyspnea, sputum production or sputum purulence. One of the earlier papers to address that is referenced here.

Steroids: Trials have demonstrated benefit of systemic steroids for vs. placebo. No mortality benefit, but shorter length of stay, PFT improvement, and symptomatic improvement.

Original trial used Solumedrol 125mg IV q8h; no advantage to this high dose over Prednisone 40-60mg PO x 5-7d. No need for taper of this duration.

A NEJM paper from 2002 reviewing AECOPD is here

DKA/HONK

A prior post on this topic with some good references is posted here

FUO

The classic definition of FUO from the early 1960s was: fever greater than 38 degrees Celsius on several occasions over a 3 week period of time with week worth of hospital investigations. With changes in our healthcare system, it is now generally accepted that the definition applies if only 2-3 weeks have past and there have been initial investigations performed (the list of which tests varies)

When thinking about FUO remember the 4 major categories
Inflammatory, Infectious, Malignancy and up to 50% do not end up with a diagnosis (and generally have a good prognosis)

A prospective study from the Netherlands illustrates this

A proposed algorithm based on existing evidence was created by a Toronto internist and published in Archives of Internal Medicine. Dont forget that investigations should be tailored/expanded based on a comprehensive history and physical.

Today we discussed the antiphospolipid antibody syndrome and thromboembolic disease.

A NEJM images in clinical medicine case of phlegmasia cerulea dolens is posted here
Phlegmasia cerulea dolens:

• massive proximal DVT of the leg
  
• complications include severe pain , swelling, cyanosis, edema, venous gangrene, compartment syndrome, and arterial compromise, often followed by circulatory collapse and shock
• one of the few reasons to consider thrombolysis (genearlly catheter directed) or thrombectomy for lower limb DVT

APLA syndrome:

• Recurrent positive testing for an antiphospholipid antibody (>2x >3 months apart)
• Clinical sequlae - usually arterial and/or venous thrombosis or pregnancy loss (either recurrent early loss or single late loss, without other cause)
  

Notes on the lupus anticoagulant:

• causes prolonged aPTT (not always present), the dilute Russell viper venom time (dRVVT), the kaolin clotting time
• prolongation is not reversed during a 50:50 mix test
• patients with this dont always have SLE
  
• the term anticoagulant refers to invitro phenomenon - in vivo these patients are prone to thrombosis
  

Interstitial Lung Disease

A case of interstitial lung disease that covers alot of the issues discussed in morning report can be found here

Another article about exacerbations of IPF can be found here

From a public health point of view, an article about Canada's export of asbestos despite it being classified as a hazardous substance in Canada can be found here

FASTENS
The mnemonic for upper lobe intersitial pattern:
F - farmer's lung (hypersensitivity pneumonitis
A - Ank spond.
S - Sarcoid
T - TB
E - Eosinophilic Granulomatosis
N- Neurofibromatosis
S - silicosis

Sugar, sugar

We started today by discussing an approach to weight loss. A very useful classification is to divide causes with decreased appetite from those with increased appetite. Remember also the big categories: cancer, endocrine, psychological/psychiatric and access to food. CMAJ has a great review of weight loss in the elderly from our local experts.

We also touched on the criteria for Hyperosmolar Hyperglycemic State (calling in HONK is becoming passe). Though decreased level of consciousness is common (seen in over 50%) it is not always seen.

Finally we talked about the evidence for preventing --or delaying-- diabetes in persons with IGT/IFG. Check out the landmark Diabetes Prevention Program (DPP) study to learn more about it. The lifestyle modification arm showed a 60% reduction in progression to diabetes after 3 years, compared to a 30% reducation in those receiving metformin. Now if we could all just find the time to exercise....

Hypercalcemia

Some points about Hypercalcemia

Corrected Calcium:
The physiologically important calcium (Ca2+) is ionized calcium. This can be measured in the lab, however, total calcium is the value most commonly reported.

Calcium is bound to serum proteins, most importantly albumin. Therefore, in patients with low serum albumin concentration, the fraction of total serum Ca2+ that exists as ionized Ca2+ will be higher. When we are correcting calcium it is not because of a lab error, but rather to help us put the measured lab value into proper physiologic context in terms of possible causes, associated symptoms and need for treatment

It is important to know the serum albumin when interpreting total serum calcium levels. A correction for total serum calcium can be made using the following formula (alternatively ionized Ca2+ could be measured):

Ca = SerumCa + 0.02 * (NormalAlbumin - PatientAlbumin) (SI UNITS) - basically means that for every decrease of albumin by 10, add 0.2 to the total calcium.

Pseudohypercalcemia can occur when patients are hyperalbuminemic or have a multiple myeloma with a paraprotein that binds calcium (rare) - in these cases total CA2+ will be high, but ionized CA2+ will be normal.

DIFFERENTIAL DIAGNOSIS:
Most commonly either HyperPTH or Malignancy related. Malignancy related often presents with higher calcium levels, more symptoms and a more acute rise in calcium level (if previous values are known.
Other causes are out there - look them up if in doubt

Treatment:
TREATMENT
FLUIDS!!!!!!!!

Infusion rate depends on volume status, heart function, etc, but should target 100-150 cc urine output/hr - do not need to hydrate beyond euvolemia.

If severe/symptomatic consider: Bisphosphonates (IV) - will not take effect for 48-72 hrs, but will help maintain normal calcium when achieved.

Calcitonin - subQ is also very effective.

If hyperCa2+ is from sarcoid or lymphoma consider steroids (20-40 mg/day) - this works by decreasing calcitriol production from activated mononuclear cells in the lung and lymph nodes. Trying to get tissue before giving steroids if hypercalcemia not overly severe/symptomatic is a good idea.

AVOID LASIX since most patients are profoundly volume depleted initially and once replete can cause hypokalemia, hypomagnesemia, and lead to recurrence of volume depletion. A recent Annals of Internal Medicine article reviews the use/concerns regarding Lasix in hypercalcemia. If Lasix is need for pulmonary edema etc., it can certainly be given, just monitor lytes and volume status.

Dialysis should be considered if the above fail/can't be done because of renal failure or heart failure.

RENAL CELL CARCINOMA and PARANEOPLASTIC SYNDROMES

Hypercalcemia - from lytic bone mets, PTHrP or increased production of prostaglandins that promote bone resorption.

Polycythemia - from EPO overproduction

Hepaitc Dysfunction - "Stauffer syndrome" - in the abscence of mets, increased ALP (+/- fever, wt.loss, fatigue), often improves after nephrectomy

Fever, cacheixa

DKA and HONK

Prior Blog about the management of DKA can be found
here. Be sure to monitor closely both clinically and with charting of lab values.

Dont forget to look for the cause of DKA.
Prior blog about the common precipitants can be found here

Another point regarding phosphate:
Generally not recommended as may lower Ca and Mg levels. Replace if respiratory depression, cardiac dysfunction, hemolytic anemia or PO4 <0.32.

A CMAJ article about the management of diagnosis and treatment of HONK and DKA is posted here.

Another recent article on the issue can be found here.

Phenytoin (Dilantin) toxicity

Yesterday we discussed dilantin toxicity. Dilantin is an anticonvulsant that can cause a number of drug reactions of different types:

Pharmacology:
Phenytoin binds to and inhibits sodium channels in neurons and in cardiac tissue

It is cleared by the liver via the CYP450 system.

An important clinical point about phenytoin pharmacokinetics is that it exhibits "zero-order" kinetics. This means that only a fixed amount (not proportion) of drug is metabolized after a certain point (which is unknown for a given patient). If this threshold is crossed, a very small increase in dose can cause a big increase in level and toxicity. Increase doses slowly and by small increments (e.g. 25-50mg/d at a time, checking levels).

There are many drugs that can increase and decrease phenytoin levels via CYP450 interections. Click here for a complete list.

Phenytoin toxicity ("poisoning")
The earliest sign is nystagmus (usually horizontal) and unsteady gait. More severe toxicity causes slurred speech, lethargy, confusion, and eventually coma.
It can rarely cause cardiac arrhythmias (mainly bradycardia, AV blocks, sinus arrest)
There is no specific antidote for phenytoin; treatment is supportive.

Chronic effects/toxicity
Neurological involvement as above, gingival hyperplasia

Idiosyncratic reactions
These are non-dose related effects.

Drug hypersenitivity syndrome
Characterized by fever, rash (with or without mucosal involvement), and internal organ involvement. Sometimes also called "DRESS" or "drug reaction with eosinophilia and systemic symptoms". Dilantin is a rare, but very well described culprit, along with sulfonamides, allopurinol, dapsone, and many others. Timeframe is 2-8 wks after initiation.

Stevens-Johnson's, Toxic Epidermal Necrolysis
Desquamating skin and mucosal involvement; organ failure. Distinguished by surface area involved. Less than 30% BSA = SJS. More than 50% = TEN; overlap = between. Dilantin is a well described culprit. Tx: supportive (inc. burn unit), possible role for steroids, IVIG.

Drug-induced lupus
Clinically, mainly arthritis, serositis, wt loss. 95% have anti-histone AB, negative anti dsDNA, normal complements.

Others
Isolated hepatitis
Leukopenia, thromboctyopenia, agranulocytosis

Lymphadenopathy
IV preparation can cause hypotension during infusion (treatment is fluid)

Links
Click here for a good overview of idiosyncratic drug reactions

Click here for a summary of phenytoin kinetics

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Hepatic encephalopathy

Today we discussed hepatic encephalopathy and its triggers. Some points that came up:

In the context of stable chronic liver disease, the triggers of hepatic encephalopathy are:
1) non-adherence to diuretics/lactulose/nadolol, etc.
2) psychoactive meds (narcotics, benzos)
3) volume overload (usu insufficient diuretics/NaCl excess)
4) new hepatic insult: hepatitis, HCC, PV thrombosis, Budd Chiari
5) infection: esp SBP
6) GI bleed/protein load
7) hypokalemia/alkalosis

Approach is to control encephalopathy and rule out/in precipitating causes:
1) All cirrhotics with ascites and worsening encephalopathy must be tapped. Also rule out other causes of infection
2) Lactulose 30cc BID, qid PRN for 2-3 loose BMs.
3) Diurese if needed, but consider holding if intravascularly depleted
4) D/C all meds that could contribute
5) Continue/start nadolol
6) Decide on ABx from clinical picture and preliminary tap cell count
7) Consider U/S with dopplers to r/o PV thrombosis, HCC, etc
8) If suspicion of GIB, possible OGD
9) Low salt diet. Fluid restrict.

Click here for the 2004 guidelines for cirrhosis managment from Hepatology

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Subclinical hyperthyroidism

Today we discussed subclinical hyperthyroidism

This is defined as
1) Low (usually undetectable) TSH
2) Normal T3 and T4
3) no symptoms of hyperthyroidism

The causes of subclinical hyperthyroidism mirror the causes of overt hyperthyroidism:
1) Exogenous T4
2) Toxic adenoma or multinodular goiter
3) Subacute thyroiditis
4) Graves' disease
5) Amiodarone
Others...

Differential of a low TSH with normal T3/T4 besides subclinical hyperthyroidism:
1) "Sick euthyroid"- stress causing decreased peripheral conversion to T3 (i.e. low), normal T4, low TSH.
2) Glucocorticoids, dopamine
3) Autonomous thyroid nodule producing enough T3/T4 to suppress TSH but not cause high T3/T4 levels

Workup consists of same as overt hyperthyroidism: radioactive iodine uptake and scan, possibly thyroid-stimulating antibodies.

Concerns in subclinical hyperthyroidism
1) Atrial fibrillation
2) Osteoporosis
3) Risk of progression to overt hyperthyroidism
4) Neuropsychiatric effects, diastolic dysfunction (softer evidence)

Natural history: Depends on underlying cause; ~2-5%/yr progress to overt hyperthyroidism

Whom to treat?

Controversial! Very little evidence.

This structured review from JAMA suggests considering treatment for patients who are older than 60 years and for those with or at increased risk for heart disease, osteopenia, or osteoporosis, or for those with subclinical Graves disease or nodular thyroid disease

Therapy consists of ablative therapy (i.e. radioactive iodine) with replacement or medications (PTU or methimazole) with goal to normalize TSH.

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Inhalational injury

Today we discussed inhalational injury.

This is suggested by:
-soot in the upper airway, including mouth and nares
-singed eyebrows, nares
-persistent cough, stridor, wheezing
-hoarseness

Some principles of managment:
1) Consider early intubation; peak of airway edema is 48-72h after injury, and may make intubation extremely difficult. ARDS is also common following thermal injury
2) Look for carbon monoxide poisoning (more below)
3) Bronchoscopy should be performed initially then frequently to assess the extent of the injury and to clear sloughed airway epithelium
4) Look for cyanide poisoning (from plastics and fabrics burning). This presents as a triad of altered mental status, cardiovascular collapse, and lactic acidosis
5) Ophthalmology should see patients with inhalational injuries to exclude ocular injury, since they often go together

A few points about carbon monoxide poisoning:
Presentation
-Notoriously difficult to diagnose
-Common presenting symptoms are altered mental status, headache
-Physical exam may show a "cherry red hue" but this is unreliable

Labs
-Oxygen saturation is normal! (oximeter reads carboxygemoglobin as oxygen-bound)
-ABG tends to be normal (PO2 is dissolved oxygen, which is not changed by CO)
-Need to do co-oximetry on ABG sample to detect carboxyhemoglobin (reported as a percentage)

Management
-100% oxygen by non-rebreather mask for everyone (decreases the halflife of carboxyHgb from 300 to 100 min)
-Hyperbaric oxygen therapy decreases the halflife to 30 min. Generally recommended for any of 1) Carboxyhemoglobin level over 25% (although some sources suggest 4o%) 2) Signs of ongoing organ ischemia (lactic acidosis, myocardial ischemia, etc) 3) Loss of consciousness, 4) Pregnancy with a level over 20% or fetal distress

Links
Click here for a Cochrane review of hyperbaric oxygen in CO poisoning by Toronto investigators (including this hospital!)
Click here for a website from the University of Utah outlining burn management

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Psychosis: medical causes

Today we discussed the approach to the psychotic patient from a medical standpoint (i.e. causes other than primary psychiatric disease)

See this post for a general approach to dementia.

In terms of psychosis (i.e. hallucinations or delusions) from a medical cause, things to think about include:

Delirium
Hallmark is attention problems. Also cognitive problems, simple hallucinations (often visual), fluctuating course, underlying medical condition
General causes:
Infection, intoxication (esp. anticholinergic; 'mad as a hatter'), medications (e.g. benzos, opiates), substance withdrawal (esp. alcohol), metabolic derangements (Na, Ca, hepatic encephalopathy, uremia), trauma, CNS pathology, hypoxia, deficiencies, endocrine (e.g. hyper or hypothyroidism, hypoglycemia), vascular (e.g. vasculitis, hypertensive emergencies)

With more elaborate hallucinations/delusions, other medical possibilities that are well known to present with psychosis include
-Seizures (especially temporal lobe)
-Encephalitis (especially HSV encephalitis)
-Brain tumor / bleed involving the temporal lobe
-Lewy Body dementia (classically non-bizzare delusions, worsens with neuroleptics)
-Neurosyphillis
-Wilson's disease
-Hyperthyroidism
-Neuropsychiatric lupus
-Carbon monoxide poisoning
-Charles Bonnet syndrome
(complex visual hallucinations with insight in pts with visual impairment that reverse with visual correction)
-"megaloblastic madness" from B12 or folate deficiency
-Porphyria

Link:
Click here for a summary of medical causes of psychosis to consider.

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Hypoglycemia practical management

Today we discussed hypoglycemia in the context of medications.

For a discussion of the differential diagnosis of hypoglycemia, see

this post

Some considerations for dealing with hypoglycemia on the wards:

2 issues: 1. Increase blood glucose. 2. Determine reason

Gucose is below 4: If patient is awake, not NPO,

1. Need 15g carbohydrate (in the form of glucose tabs, 3 packs table sugar in water, 3/4 cup of juice or regular soft drink, 6 life savers)If BG is below 2, need at least 20g glucose.

2. Check glucose q 15 min until above 5, and repeat 15g CHO as needed

3. If over 1h until next meal, snack (e.g. 1/2 sandwich)

4. Look for cause, address.

5. Do not stop insulin in a type 1 diabetic

Pt NPO:
1. 25g CHO in form of D50 (50mL amp) push or D10 500cc. May also give glucagon 1mg sc/im if delay.

2. Check glucose q15 min until it is over 5 and give more D50 or D10 as needed

3. Pt may need ongoing glucose infusion after (e.g. D5 or 2/3+1/3 or D10)

4. Look for cause

5. Do not stop insulin in a type 1 diabetic

Reasons: Insulin or sulfonylurea excess or decreased PO intake.

NB- in sulfonylurea-induced hypoglycemia, consider octreotide as reviewed

here

Pulmonary hypertension

Today we discussed pulmonary hypertension (or, we at least had a "tangent"... on it.)
This is an important clinical entitiy to have an approach to both in terms of physical findings and the workup required to determine the etiology. Some considerations:

Defined as mean PA pressure over 25mmHg at rest with mean LA or wedge pressure below 15 (i.e. no LV dysfunction)

May be primary (idiopathic) or secondary.

May occur from disease anywhere in the following circuit:
PA, lungs, PV, LA, MV, LV

1) Pulmonary artery- luminal (PE), mural (PPH), extramural (tumor)
Clinically and patologically indistinguishible from primary pulm HTN are cases associated with the following: anorexigens (diet pills), cocaine, HIV, rheumatologic diseases (esp CREST/scleroderma), portal HTN

2) Lungs- chronic obstructive and restrictive diseases can cause PHTN through hypoxic vasoconstriction. Interstitial lung disease can also cause destructive changes to pulmonary vasculature, leading to PHTN and cor pulmonale.

3) PV- veno-occlusive disease

4) Cardiac- L CHF- usually causes relatively minor PHTN. Mitral stenosis can cause severe PHTN. Shunts (ASD, VSD) cause higher R-sided pressures. Increased PA flows cause changes in PA structure and subsequent reversal of flow (Eisenmenger's)

Clinical features:

Hx: Sx of heart or lung disease, HIV RFs, Sx suggestive of CTD, esp scleroderma, anorexigens, PE symptoms, Fhx (in 5% of pphtn), snoring/OSA, rheumatic heart disease

P: Loud P2, RV lift (L parasternal), R-sided S4, TR murmur (holosystolic, louder on inspiration), edema, high JVP. A murmur of pulmonic insufficiency called the "Graham Steell murmur" is described (early diastolic, decrescendo, increased on inspiration). Look for findings suggestive of secondary causes including scleroderma, HIV, primary lung disease, etc.

Investigations:
ECG- RAE, RVH with strain (i.e. tall R and small S with R/S over 1 in V1)
CXR- enlarged R hilum, dilated PA (over 14mm in females, over16mm in males)
Echo- RVSP (approximaes PA systolic). Should be less than 40.
PFT/ABG
High resolution CT +/- VQ scan
Possible R heart cath to determine pressures directly

Link:
Click here for an excellent JAMA "grand rounds" discussion on pulmonary HTN

Essential thrombocytosis

Today we discussed essential thrombocytosis (AKA essential thrombocythemia). Some points about this condition:

Thrombocytosis
Majority of cases are reactive. Common causes: Post-op, infection, post-splenectomy, Fe deficiency, malignancy (non-hematologic)

Non-reactive causes include ET, polycythemia vera, myelofibrosis, CML, MDS

ET:
Concerns are
1)Thrombosis risk
2)Bleeding risk (platelets are numerous, but often dysfunctional, and patients can have acquired von willebrand's disease)
3)Potential for transformation to AML

Epidemiology:
median age at dx is 60. F:M is 2:1.
Clinical: ~1/3 asymptomatic. ~1/3 have "vasomotor" sx: Syncope/presyncope, H/A, paresthesias, visual dist, non-exertional c/p. ~1/3 have sx consistent with thrombotic/bleeding events- major or minor

Diagnosis:
PLT consistently above 600, no explanation for reactive cause. May see megakaryocyte hyperplasia on BMBx if done, -ve BCR-ABL, iron replete, no evidence of MDS. JAK2 is a mutation found in over 95% of patients with polycythemia rubra vera, and 50-60% of patients with ET. It can be detected in peripheral blood

Bleeding risk
This paper by Tefferi et al from the Mayo Clinic found a 4% 10-year risk of major hemorrhage. Bleeding risk was directly proportional to PLT level, with over 1500 (i.e. 1.5 million) highest.

Thrombosis Risk
Arterial and venous thrombosis may occur. Typical events are similar to those in PRV: stroke, TIA, ACS, retinal art occ, digital ischemia, pregnancy loss. Less commonly, DVT/PE, PV thromb/Budd-Chiari.
Incidence of major events (MI, stroke, PE) is ~4% at 10 years. There is conflicting data on whether PLT level correlates with thrombosis risk

Antiplatelet therapy
The ECLAP study (RCT) looked at low dose ASA in patients with no other indication for ASA and PRV (which carries similar thrombosis risk)
RR of composite outcome of MI, stroke, PE, CV death was 0.4 on ASA 100mg. No significant mortality benefit. No significant difference in bleeding. It also has demonstrated effect on vasomotor sx of ET.

Cytoreductive therapy in high risk pts
In those meeting high risk criteria (i.e. over 60 or history of thrombosis). this RCT by Cortelazzo et al, evaluated the use of hydroxyurea to bring PLT count to below 600 vs. placebo in patients on antiplatelet therapy. 2 year risk of significant thrombosis was 3.6% on HU, 24% on placebo (NNT 5) Therefore, hydroxyurea to reduce the platelet count to below 600 should be considered in high risk patients. Specific platelet reducing agent (Anagrelide) was evaluated in RCT vs. HU, and showed much higher thrombosis risk



The risk of conversion to AML is reported at 2-5% at 15 years from dx. This is the lowest risk of any of the myeloproliferative disorders