Dementia Syndromes

1. Alzheimer's disease: A very common form of dementia in elderly patients. Characterized by progressive short term memory loss and cognitive decline. It is a clinical diagnosis, however classic histology reveals amyloid deposition in the brain (in beta-pleated sheets) and neurofibrillary tangles. A great link on AD here.

2. Vascular dementia: Manifested by cognitive decline after a stroke. There is a "stepwise" deterioration in function with subsequent ischemic injuries. Imaging of the brain will reveal ischemic changes.

3. Fronto-Temporal dementia: Atrophy of frontal and temporal lobes, but without histologic evidence of Alzheimer disease. This classically occurs in a slightly younger cohort...50-60 year old males and females. One of the hallmarks of this disease are personality changes - inappropriate personal or social behaviours. Aphasia may also be seen. You may hear of "Pick's Disease", a subset of fronto-temporal dementia with a progressive, non-fluent aphasia component to it.

4. Lewy-Body dementia: manifested by progressive cognitive decline, vivid visual hallucinations, delusions, syncope, and occasionally Parkinson-like symptoms (see below).

5. Dementia associated with Parkinsonism: This is an umbrella term for dementia associated with primary Parkinson's disease, and the Parkinson Plus Syndromes. Note that the Parkinson Plus syndromes typically have a poor response to dopaminergic therapy - that with their individual clinical features, this often helps clinicians distinguish them from primary Parkinson's disease.

• 
  Progressive supranuclear palsy: Parkinsonian symptoms, dementia, syncope, and vertical gaze abnormalities. Many have bulbar symptoms like dysarthria and dysphagia. It is sometimes referred to as the Steele-Richardson-Olszewski syndrome.


• 
  Multisystem Atrophy: A more mild progressive dementia, with mild features of Parkinson's disease (although tremor is mostly absent), and autonomic dysfunction manifested by syncope. You may also hear this condition referred to as the Shy-Drager syndrome. An excellent link here.
  
• 
  Corticobasilar Degeneration: A progressive dementia, with motor features of bradykinesia, rigidity, and postural instability. Patients may have sensory disturbances, apraxia, aphasia, or even alien limb syndrome.

6. Reversible Dementias: these include conditions where we can remove/modify an offending agent. Think about drug/toxin exposure, space occupying lesion, depression, or a metabolic abnormality.

Well's Criteria for DVT/PE

When we are clinically suspecting a deep vein thrombosis or pulmonary embolism we need to use a composite of clinical findings to estimate our pre-test probability of having the event - this is because no single finding is sensitive enough on it's own. As thromboembolic disease can have catestophic results, we want to ensure that the sensitivity of our composite of tests is high. The name "Wells" appears frequently...

Deep Vein Thrombosis: Wells Scoring System
[JAMA 1998; 279: 1094 – 1099]

• Active Cancer (on treatment/within 6 months/palliative): 1
• Paralysis, paresis, or recent plaster immobilization of the lower extremities: 1
• Recently bedridden for >3 days or major surgery within 4 weeks: 1
• Localized tenderness along the distribution of the deep venous system: 1
• Entire leg swelling: 1
• Calf swelling > 3 cm compared to asymptomatic leg (measured 10 cm below tibial tuberosity): 1
• Pitting edema (greater in the symptomatic leg): 1
• Collateral superficial veins (nonvaricose): 1
• Alternative diagnosis as more likely than that of deep vein thrombosis: -2

DVT Clinical Pretest Probability
Is the score...

A. Greater than/equal to 2? DVT Likely
B. Less than 2? DVT unlikely

Pulmonary Embolism: Modified Wells’ criteria
[Ann Intern Med 2001; 135: 98 – 107]

• Clinical findings suggestive of DVT: 3
• No other more likely alternative diagnosis: 3
• Immobilization (bedridden ³ 3 days) or major surgery within past 4 wks: 1.5
• HR > 100: 1.5
• Previous DVT/PE: 1.5
• Active malignancy: 1
• Hemoptysis: 1
  

Simplified Wells Criteria Scoring System [JAMA 2006; 295: 172-179]
Is the score...

A. Greater than 4? PE Likely
B. Less than 4? PE Unlikely

Your choice of investigations will be determined from the above scoring systems - whether thromboembolic disease is "likely" or "unlikely". More on this soon.

It is also important to ask yourself why this person his having thromboembolic disease in the first place?

(Get it? Get it? There's a picture of a well. Well's criteria? Yeah - that's terrible, I know.)

Cirrhosis - etiology

Cirrhosis - what are the causes?

1. Drug/Toxin: Alcohol, prescribed and non-prescribed medications

2. Chronic viral hepatitis - Hep B, C, and D

3. Metabolic diseases: Non-alcoholic fatty liver disease, hemochromatosis, alpha 1 antitrypsin deficiency, Wilsons disease

4. Autoimmune hepatitis

5. Vascular processes: Right sided heart failure, Budd-Chiari Syndrome

6. Diseases of the Biliary Tract: Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis, Tumor

7. Cryptogenic

-Here is a great NEJM article on the management of cirrhosis and ascites
-We discussed the evaluation of Ascites here.
-We looked at peripheral stigmata of liver disease here.

Pneumocystis carinii (or P. jirovecii) pneumonia

PCP is a common respiratory opportunistic infection in HIV+ individuals. Those with a CD4 count less than 200 are at the greatest risk. It is a protozoa, and is found ubiquitously in soil - we are all exposed, but this organism poses few problems to healthy immune systems.

The classic clinical presentation is dyspnea with subacute onset, and a dry cough. Patients may have a low-grade fever, tachycardia, and tachypnea. The chest exam is variable - you may hear crackles...you may have a normal exam (in up to 50% of cases). The Chest X-ray often reveals bilateral interstitial infiltrates, but virtually any abnormality may be seen.

Remember, we can make the diagnosis roughly 90% of the time with history and physical exam alone. Still, it is nice to confirm your diagnosis by politely acknowledging the presence of an organism. Methenamine silver (photo above) or Immunofluorescent (photo below) stains on induced sputum (or bronchoalveolar lavage) has a high sensitivity and specificity.

Treatment: TMP-SMX in high doses. This has some interesting complications associated with it. If people are allergic to sulfa drugs or have complications, other agents can be used, such as TMP-Dapsone, or Atovaquone.

Steroids? Yep. If the PaO2 is less than 70, this is very helpful. Of note, this was a major breakthrough in medicine and was discovered here at the Toronto Western Hospital.

What else? Watch these patients closely. There is often a profound inflammatory reaction to the dying organisms, and patients often get worse on day 2-ish of treatment. That is why the steroids are added in severe disease.

Acid Base Approach...and Metabolic Acidosis

Acid-Base Problems...

Step 1: look at the pH. Whichever side of 7.4 the pH is on will be your Primary abnormality. Eg. if the pH is less than 7.4, you have a primary acidemic issue.

Step 2: find out if this is a metabolic or respiratory disorder (see flow chart below).

normal values:
pH 7.4
HC03 25
pCO2 40

Step 3: Look for “Compensation”
The body’s goal is to attain a pH of 7.4, this is a pH which our enzymes, muscles, nerves, etc. function at their best. The direction of compensation is almost always the same as the primary disorder to help the pH get back to normal.

Eg.1. you have a primary metabolic acidosis (low pH, low HCO3), you would expect your pCO2 to also fall, hence the direction of compensation of pCO2 is in the same direction as the primary disorder, they are both lowered.

Eg.2. if you have a primary respiratory alkalosis (high pH, low pC02), you would expect your HCO3 to fall as well.

Step 4: Look at the magnitude of compensation (discussed below).

What is the mechanism of compensation?
respiratory disorders: the kidneys increase their rate of HCO3 production in response to respiratory acidosis, and decrease their rate of HCO3 production in response to respiratory alkalosis
↑ pCO2 → HCO3↑
↓ pCO2 → HCO3 ↓

metabolic disorders: Patients hyperventilate in response to metabolic acidosis, and hypoventilate in response to metabolic alkalosis.
↓ HCO3 → pCO2 ↓
↑ HCO3 → pCO2 ↑


Metabolic Acidosis

Today we discussed a case of Diabetic Ketoacidosis. We talked about precipitants of DKA earlier and you can read about it here, we have also discussed the management of DKA here. There are some good links on both pages.

Ask yourself a few questions:

1. Firstly: Is this an anion gap, or non-anion gap metabolic acidosis? See below for details.

2. What is the etiology? you can use your “mudpiles,” but I find this a simpler way…you only have to remember 4 things...

1. Lactic acidosis: hypoperfusion of tissue vs Liver disease and cannot metabolize lactate.
2. Ketones: from Diabetes, alcohol, starvation
3. Uremia
4. Poisons/Toxins: ethanol, methanol, ethylene glycol, ASA, isopropyl alcohol, etc.

3. Is there compensation? for each 1 mmol/L fall in HCO3, you would expect a 1 mmHg drop in pCO2

4. Calculate the Anion Gap: AG = Na – [Cl + HCO3], a normal value is 12 or less

Remember to correct for Albumin: for every drop of albumin by 10, add 3 to your AG. So if you calculate your AG to be 12 (seemingly normal), but your albumin is 30, you must add 3 to your AG, making it 15… now start looking for excess anions (see above etiologies).

5. The Delta Delta: Delta what? Not to worry, it's pretty straight forward, and it adds some valuable information. Compare the change in anion gap to the change in HC03. What does this mean? Let’s say our patient has an AG of 20 and a HCO3 of 17. Well, compared to our normal values, the delta AG is 8 (20 – 12), and the delta HCO3 is 8 (25 – 17), so the delta AG is equal to the delta HCO3. We would expect the change in AG and the change in HC03 to be similar in a pure metabolic acidosis. If the delta AG is bigger than the delta HCO3, there is also a concurrent metabolic alkalosis present. If the delta AG is less than the delta HCO3, there is a concurrent AG metabolic acidosis, and non-AG metabolic acidosis.

6. Calculate the Osmolar Gap:

OG = [2x Na] + Urea + Glucose ....Remember "two salts and a sugar-bun"

Measured OG – Calculated OG should be less than 10.

Is this greater than 10? think about EtOH, methanol, ethylene glycol, isopropyl alcohol

Non-AG Metabolic Acidosis? think about diarrhea, and renal tubular acidosis. You can read more about RTA's here.

Respiratory Arrest in Pregnancy

Yikes. We have to be very careful in these situations and consider the heath of both the mother and unborn child. A critical question is if the shortness of breath is pregnancy related, not pregnancy related, or from a pre-existing condition.

Pre-existing conditions/Not pregnancy related:
Think about asthma, pneumonia, COPD, and previous cardiac conditions. The clinical manifestations of valvular abnormalities like mitral or aortic stenosis will be accentuated during pregnancy because of an increased cardiac output - normal physiologic changes. You can read more about valvular abnormalities in pregnancy here.

Pregnancy Related Conditions:
Pulmonary Edema: may be secondary to a few things. Eclampsia or Preeclampsia can cause this. Also, think about Pregnancy Associated Cardiomyopathy - this presents at 8 months gestation up to 5 months post partum. Salient features include a reduced left ventricular ejection fraction (less than 45%), the timing when cardiomyopathy develops, and ruling out other etiologies. Finally, tocolytic therapy may be associated with pulmonary edema.

Pulmonary embolism is about 5 times more common during pregnancy. Why? likely from a combination of venous stasis from the gravid uterus intermittently compressing the inferior vena cava, and from alterations of clotting factors (remember Virchow's Triad). Finally, if severe respiratory symptoms develop during labour and delivery, consider an amniotic fluid embolus - which unfortunately tends to be catastrophic.

ACLS guidelines in pregnancy can be found here.

Rhabdomyolysis

First, think about the underlying etiology:
1. Trauma: this can be overt, like a crush injury or a bit more subtle, like immobilization in an elderly person who falls and is unable to get up for some time. Also think about immobilization in patients with a decreased level of consciousness or during prolonged operation.

2. Physical activity: rhabdo may occur in those who either perform excessive physical activity (eg. marathons), in those who are doing significantly more physical activity than they are used to (eg. couch potato who goes on run for 1st time in 10 years), or in situations where hyperthermia may occur (eg. jogging in the Sahara). Also, don't forget seizures as a common etiology.

3. Drugs/Toxins: as always, we should consider prescribed drugs (eg statins, colchicine), and non-prescribed drugs (eg. alcohol, cocaine, ecstasy). There are always a few cases per year of rhabdomyolysis from wild mushroom poisoning.

4. Infections: many viruses (eg. cytomegalovirus, Coxsackievirus, Epstein-Barr, Influenza, adenovirus, HIV), bacteria (eg. pyomyositis), sepsis, and parasitic (Falciparum malaria).

5. Electrolyte: primarily hypokalemia and hypophosphatemia from any cause.

6. Endocrinopathy: mostly in hypothyroidism, but may also be seen in DKA/HONK - probably from hypophosphatemia.

7. Those who are more prone: people who have myopathies may be more prone to developing rhabomyolysis. Think about those with poly/dermatomyositis, malignant hyperthermia, or rare congenital myopathies

What should I watch out for?
1. Hyperkalemia: lots of potassium can be released from muscle cells. Monitor this and the ECGs closely.
2. Renal failure: watch out. Myoglobin is toxic to the renal tubules and can cause acute tubular necrosis.
3. Other electrolytes: hyperphosphatemia (released from muscle cells), hypocalcemia.

Treatment:
This primarily revolves around finding and reversing precipitants, and aggressive fluid administration to prevent myoglobin-induced ATN. There is debate whether the best fluids are saline or if sodium bicarbonate added to D5W works best. Also, keep a close eye on the potassium.

Some good links:
Here's an interesting case
Here's a strange case of Rhabdo from the CMAJ

Tastes like chicken...

HoPingKong-isms

1."...What was discovered here in Toronto?...don't be nervous...you don't have to sweat here..." Referring to Professor Lap-Chee Tsui, who discovered the Cystic Fibrosis Transmembrane Regulator (CFTR) genetic mutation responsible for Cystic Fibrosis. "Don't sweat" hints towards the Sweat Chloride Test for the diagnosis of Cystic Fibrosis.

2. "...To diagnose amyloidosis, do you go to India? Noooooo, you go to Africa..." Referring to the Congo Red stain that is helpful in the diagnosis of amyloidosis. If amyloid protein is present you will see an apple-green birefringence under polarized light. Check out the picture below of renal amyloidosis stained with Congo Red under polarized light....looks 'apple green' to me.

3. "...There are some genetic causes of liver disease....think about a leader of Germany, no bagels, no doughnuts, no buns..." Hmmm, tricky. There is a Kaiser in Germany, but really he is referring to Keiser-Fleisher rings seen in Wilson's disease. You can see a good picture of these KF rings and read more here.

4. "...A surgical problem? I don't think they will operate...they will probably give you the finger...". Get it? Get it? (I sure didn't). He was referring to Inglefinger's sign, seen in pancreatitis. This is when epigastric pain is diminished when patients sit up and lean forward. You can read more about issues in pancreatitis here.

5. "...Think about a medical liver problem from East Asia...you may get it right, but it may be a fluke..." Okay, sure...we all know he is referring to a liver fluke...but which one? It's Clonorchis sinensis, a cute little tramatode that can cause some serious damage. Those who eat fish are at risk. Adult worms live in the distal biliary ducts for years, and can cause fibrosis, cirrhosis, and cholangiocarcinoma. Check out a glamor shot of one of these worms at the top of the page.

mmmmh....apples.

Approach to Headaches

History and physical examination are vital. Most diagnoses can be made by history. It is important to rule out "red flags" that may indicate a headache secondary to something more ominous.

Red Flags:
1. Neck stiffness: possible meningitis
2. Focal neurologic deficits: mass lesion or infarction
3. Evidence of elevated intracranial pressure: headache worse in AM or on exertion, papilledema
4. Visual changes: think about temporal arteritis or elevated intracranial pressures
5. Constitutional symptoms: is there a malignant, inflammatory, or chronic infection causing this?

Based on History and Physical Exam, try determine whether you are dealing with a Primary or Secondary headache

Primary Headaches:
Migraine
Tension
Cluster

Secondary Headaches:
1. Infectious: think about meningitis, encephalitis, abscess
2. Vascular: hemorrhage (epidural, subdural, subarachnoid, intraparenchymal), arterio-venous malformations, sinus venous thrombosis, unruptured aneurysms
3. Mass effect: such as tumour, abscess, blood
4. Trigeminal neuralgia
5. Temporal Arteritis
6. Other: sinusitis, Temporal-Mandibular Joint pain, hydrocephalus, referred pain,

1. Here is a link to a good rational clinical exam on Meningitis
2. Here's another link written by local talent on the evaluation of headaches

Pleural Effusions: transudate vs exudate

An important part of evaluating a pleural effusion includes categorising the fluid as a Transudate or an Exudate. We use Light's Criteria to guide us here. If one or more of the following is positive, then we are dealing with an exudate:

1. pleural fluid protein/serum protein is greater than 0.5

2. pleural fluid LDH/serum LDH is greater than 0.6

3. Pleural fluid LDH is more than two-thirds of the serum normal upper

Exudate: these include infections (bacterial, viral, tuberculous, fungal and parasitic). Remember tuberculous infectious will have predominantly lymphocytes. Malignancy is an unfortunate cause of an exudative pleural effusion and may be seen in primary lung tumors or metastatic disease such as breast cancer. It is also common in lymphoma. Gastrointestinal causes include pancreatitis and esophageal rupture. Exudative pleural effusions are seen in Connective Tissue Diseases like pleuritis in lupus, rheumatoid pleuracy, and more rarely Churg Strauss syndrome and Wegeners Granulomatosis. A pulmonary embolism can cause an an exudative or transudative effusion however exudative effusions are more common. Other things to consider include chylothorax and drug-induced exudative effusions (amiodarone, nitrofurantoin).

Transudate: These are most commonly seen in in patients with congestive heart failure. Cirrhotic patients often have right-sided transudative effusions. The nephrotic syndrome, pulmonary embolism, and rarely constrictive pericarditis are other causes.

Here is a great diagnositic approach to pleural effusions

A link for complicated pleural effusions - thanks to the CMR at Toronto General Hospital.

Here is the NEJM video on how to perform a thoracentesis

Staphylococcus aureus bacteremia: Complications

This is a dangerous bug. We take it very seriously as there is a high mortality rate associated with infection - upwards of 20% in all comers with bacteremia (in hospital).

Risk factors for complications include a longer duration of bacteremia, the route and site of infection, if there are indwelling devices (prosthesis, lines), and host factors (eg. immunocompromised hosts like HIV,). Metastatic spread of S. aureus is more common in those who acquire the infection in the community rather than in hospital. Also, most patients will have an identifiable source of infection, however those that do not have a greater likelihood of metastatic spread.

How do we predict complications? Good question. There is a greater probability of complications with the following risk factors:

1. If blood cultures are positive over 48 hours after admission.

2. If the patient is still febrile over 72 hours after admission.

3. If skin findings suggestive of acute infection are present.
4. If the infection was community acquired.

If patients have 0/4 of these risk factors then there is about a 15% chance of complications, compared to a 90% chance if 4/4 of these risk factors are positive.

Okay...so what are we worried about? What are the complications?

1. Infective Endocarditis. We will discuss this in detail later, but I have written a bit about it here.

2. Seeding of other sites: S. aureas can go anywhere, but it has a particular predilection for the vertebral column (osteomyelitis), joints (septic arthritis), the spleen (splenic abscesses), skin and soft tissue (can cause myositis or necrotising fasciitis), lungs (in those with right sided endocarditis like IV drug users), veins (septic thrombophlebitis if an IV or other catheter in place), intracardiac hardware (pacemakers, ICD's), and orthopedic hardware.

3. Sepsis

Here is a link to the sentinel paper on this topic

Renal Tubular Acidosis

Oy. These are kind of tricky. Let’s work through it.

Okay…let’s say we have already established that we have a metabolic acidosis, and that the anion gap is not elevated (nor is the osmolar gap). Fine. The next step is to look at the urine anion gap.

Urine Anion Gap (UAG) = [Urine Na + Urine K] – [Urine Cl]

The whole goal of this UAG business is to see how the kidneys are processing NH4+ . The UAG really is a surrogate measurement for NH4+ because we don’t measure it directly. Think about this for a second…if there is lots of NH4+, then we would expect more anions to balance out that positive charge (like more Cl-). So if the UAG is negative, it means we have more Cl than Na and K in the urine and that there is good kidney processing of NH4+. The kidneys are working well here, so think about non-renal causes to your non-anion gap metabolic acidosis – like diarrhea.

Now what if the UAG is positive? Well, then there is a failure of the kidneys to secrete NH4+ in this situation, causing a non-anion gap metabolic acidosis.

Type 1 RTA (distal): usually a more sever metabolic acidocis with HCO3 commonly less than 17 mmol/L from defective H+ secretion. Common etiologies include lupus, Sjogren’s syndrome, multiple myeloma, and medications such as amphotericin.

Type 2 RTA (proximal): less severe acidosis with HCO3 typically above 17 mmol/L. Common etiologies include multiple myeloma, amyloidosis, heavy metal poisoning, and medications like tenofovir, aminoglycosides. You can read more about this here.

Type 4 RTA: this is seen in hypoaldosteronism, and is very common in patients with longstanding diabetes. Hyperkalemia and a mild acidosis is the hallmark.

When you think of Thrombosis....

Think about Virchow's Triad:

1. Stasis: anything that prevents blood flow will be contribute to coagulation eg. venous compression (lymph node, mass), long plane ride, etc.

2. Endothelial Damage: is there damage to the delicate endothelial wall? eg. trauma or instrumentation.

3. Hypercoaguable States: Remeber that there are hereditary and acquired causes.

Hereditary causes include the Factor V Leiden mutation, Prothrombin 20210 mutation, Protein C deficiency, Protein S deficiency, and Antithrombin III deficiency.

Acquired causes include malignancy, surgery/trauma, pregnancy, drugs (eg OCP, HRT), nephrotic syndrome, inflammatory bowel disease, antiphospholipid antibody syndrome, hyperhomocysteinemia, myeloproliferative disorders (like polycythemia rubra vera, essential thrombocytosis), paroxysmal nocturnal hemoglobinurea, and immobility.

Warfarin-Induced Skin Necrosis
This is a rare complication of warfarin that may present within a week after the drug is initiated. Necrotic skin lesions are more commonly seen on the trunk and extremities. Warfarin initially decreases levels of Protein C, causing a hypercoaguable state - the necrosis is from microthrombi in the skin (see picture below). This condition is associated with high doses of warfarin (>10 mg) and Protein C deficiency. Stop the warfarin, and use another anticoagulant.

Alcohol Withdrawal

Symptoms: within the first 6-24 hours after the last drink patients may feel tremulous, diaphoretic, and have palpitations. Seizures can occur within the first 48 hours, and may be tonic-clonic in nature. Hallucinations may occur 12-48 hours after the last drink, and can be tactile, auditory or visual. Finally, onset of the dreaded Delirium Tremens may occur at 2 -6 days. This manifests as agitation, hallucinations, and autonomic instability (tachycardia, hypertension, hyperthermia) - it has a mortality rate of about 5%.

A key point: make sure you are dealing with alcohol withdrawal...rule out other etiologies for behavioural changes/seizures/decreased level of consciousness.

Treatment: revolves around symptoms control. Thiamine administration, multivitamins, and of course, benzodiazepenes. Benzo's should be dosed in a symptom-triggered method with protocols like the Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWAS-Ar). Also, This is a perfect time to get our multidisciplinary team involved to help deal with underlying social issues.

A good review Article: Here

Hypertensive Emergency: end organ damage

1. End organ damage:
eyes: retinal hemmorhages, exudates, and papilledema (see picture below for details)
brain: cerebral edema, ischemia, hemmorhage, seizure, altered mental status
heart: angina, flash pulmonary edema from LV failure
kidney: proteinurea, hematurea
blood and vessels: aortic dissection, hemolytic anemia

2. Mechanism of action:
Normally our arterioles will constrict with increasing blood pressure in order to protect the fragile capillary beds beyond. This autoregulatory process fails with blood pressures well above normal (usually >180 -190 systolic, 110 diastolic), and the resulting high pressure damages distal blood vessels/capillaries. High pressures damage the endothelial wall, causing localized edema - which may obliterate perfusion to that region. This mechanisms accounts for many items on our "end organ damage" list seen above.

3. A good link: Canadian Hypertension Guidelines

Types of Kidney Stones

Calcium: the majority of stones have calcium in them. Calcium oxylate is the most common, but calcium phosphate is seen too. Think about hyperparathyroidism, other causes of hypercalcemia, medulary sponge kidney, low urine volumes, or chronic metabolic acidosis like in distal renal tubule acidosis (aka Type 1).

Uric Acid: Seen primarily in patients with particularly acidic urine, like a pH less than 5.5 where uric acid precipitates out. This is seen most commonly in those with gout, but can be found in anyone with high uric acid production (eg myeloproliferative/lymphoproliferative disorders). Note: Plain X-ray is not helpful in the diagnosis as these stones are radiolucent. Treat with increasing urine volume, urine alkalinization, and allopurinol to lower uric acid production.

Struvite: caused by organisms that produce the enzyme urease (Proteus or Klebsiella). These may form really big stones, called Staghorn stones, and can fill collecting ducts. See the accompanying pictures. Ouch.

Cystine: Usually an autosomal dominant disorder where patients have cystinuria. A hexagonal cystine crystals may be seen on urinalysis. Treatment usually involves increasing fluid intake and alkalinization of the urine with an agent like potassium citrate.

A good review article

Wilson's Disease

What is it? A disease of copper metabolism resulting in copper deposition in tissues. Usually the liver and brain are affected, but virtually any tissue can be.

How does this happen? There is a mutation in ATP7B on chromosome 13, resulting in decreased incorporation of copper into ceruloplasmin. Also, there is significant impairment of copper excretion into bile.

Who gets it? it is mostly an Autosomal Recessive trait, so there are clusters in families. Sporadic cases can occur too. Symptoms can present anywhere from the pre-teens to early mid-life.

What are the Neurologic manifestations? tremors, rigidity, dysphagia, gait abnormalities, subtle changes in personality, delusions, or hallucinations. Classic eye findings include Kayser-Fleischer rings which are visible on slit lamp. Check out the picture above - note the brown copper deposition around the iris.

What are the Hepatic manifestations? patients can have a mild transaminitis to overt cirrhosis. The hepatic manifestations usually occur prior to neurologic disease.

How do I diagnose it? Patients will have a low serum ceruloplasmin and high urine copper levels. These tests have sub-optimal sensitivities and specificities. The gold standard is liver biopsy with copper quantification.

How do we treat the disease? with copper chelation therapy. Common drugs include Penicillamine , Trientine, and Zinc.

HoPingKong-isms Redux

1. "This cup is housing water"...referring to the Waterhouse–Friderichsen Syndrome: bilateral adrenal hemorrhage classically occurring with disseminated Neisseria meningitidis infection, but also with sepsis from any etiology.

2. "You're a big hit here"...referring to Heparin-Induced Thrombocytopenia. The more serious form of this, Type II 'HIT', is an immune mediated hypercoaguable disorder that presents roughly 3-10 days after exposure to the drug. Heparin should be stopped immediately, and patients will require anticoagulation with a non-heparin like compound, such as Lepirudin or Argatroban. Here is a good review.

3. "Your name is Adam, right? I'd change it to Stoke"...referring to Stokes-Adams attacks, aka Cardiac Syncope. Named after Robert Adams and William Stokes.

4. "No man is an island"...referring to the pancreatic Islets of Langerhans. These are clusters of cells which include Alpha cells (glucagon), Beta cells (insulin), and Delta cells (somatostatin). The picture above is a recent British Medical Journal cover showing the Islets of Langerhans....or earth from from outer space.

5. "This is a big question...an obese question"...referring to fat embolism. This is an uncommon condition which can occur after pelvic or long-bone fractures. The symptom triad includes hypoxemia, neurologic changes, and a petichial rash of the face, upper thorax and axilla. Here is a good article

Temporal (or Giant Cell) Arteritis

What is it? A large vessel vasculitis of unknown etiology that affects the temporal artery and it's branches.

Why is it dangerous? It can lead to permanent blindness if not diagnosed and treated expeditiously.

Who gets it? People over the age of 50 (median age = 72), commonly of Northern European descent, and commonly with the HLA-DR4 haplotype. It is much more common in those with Polymyalgia Rheumatica.

What are the symptoms? Classically, this presents subacutely with a localised headache in the temporal region, jaw claudication ("I get a cramping pain when I chew my food"), decreasing visual acuity, or blindness in one or both eyes. Patients may also describe exquisite scalp tenderness ("It really hurts to comb my hair"). It is very closely associated with Polymyalgia Rheumatica - roughly 15% go on to develop temporal arteritis. These patients will typically describe an aching pain in the shoulders, hips, and neck.

What Do you see on Physical Exam? Patients will appear unwell. Feel the temporal artery for tenderness, enlargement, and to see if a pulse is indeed present. An ophthalmologic exam is warranted - looking for ischemic neuropathy (swollen disc +/- blurred margins).

Any pertinent diagnostic tests? By definition, the erythrocyte sedimentation rate (ESR) should be greater than 50 mm/hr, however it is usually over 100. A definitive diagnosis can be made via temporal artery biopsy. This is often a contentious issue for a few reasons (see review article below), and may be difficult to arrange expeditiously. Regardless, you should not delay treatment waiting for biopsy. Interestingly, ultrasonography of the temporal arteries may be helpful . See this NEJM article from 1997 for details.

What about treatment? Prednisone in high doses (like 1mg/kg) initially. Patients will need months and months of therapy with a slow taper guided by their symptoms. Remember bone protection while on steroids - Calcium, Vitamin D, and a Bisphosphonate.

A great review article here on Polymyalgia Rheumatica and Temporal Arteritis from the Annals of Internal Medicine.

Managment of Diabetic Ketoacidosis...a few tips

These patients can be very ill and need close observation - preferably in a step-up unit.

There are a few major principles:

1. Stability: patients will need close monitoring of vitals signs, electrolytes, and volume status

2. Volume: initial fluid resuscitation with normal saline. No need to be stingy here with the fluids...patients are litres (usually 6+) low.

3. Glucose: some give an initial small bolus of IV humulin R, others do not. Then IV insulin should be given at about 0.1 U/kg/hr. Follow the anion gap closely - do not stop IV insulin until the anion gap has normalized. If your patients glucose normalizes, you can add dextrose to the IV, but keep them on insulin to prevent ketone production

4. Lytes: Potassium should be watched very closely and replaced. The values may look normal (or even high), but this is from the shift of K into the extracellular compartment secondary to acidosis - there are actually very low total body stores of potassium. Also remember that potassium levels will drop precipitously when insulin is administered as it will shift back into cells. Hmmmm. A good idea is to add 20 meq/L of K to fluids if the serum potassium is between 3.3 - 5 mmol/L, and 40 meq/L if serum potassium is under 3.3 mmol/L. Don't forget about good 'ol sodium too. You may see artificially low levels secondary to the hyperglycemia.

5. Acidosis: Sometimes sodium bicarbonate is given in situations where the pH is low....like less than 7.

6. Precipitants: Ask yourself why this patient went into this state in the first place....See the blog entry from Sept 23, 2008

Here is a great article on the management of DKA and the Hyperosmolar Non-Ketotic State from the CMAJ.

Approach to Pancytopenia...and a bit about PNH

Pancytopenia: Think about general etiologies...

1. Medications/Toxins: methotrexate (folic acid antagonist), Septra, chemotherapeutic agents, NSAIDs benzene

2. Infections: Sepsis (any cause), HIV, Parvovirus B19, EBV

3. Malignancy: more common with Leukemia or Lymphoma

4. Bone Marrow replacement: think about fibrosis, solid tumors, or granulomatous diseases like TB

5. Nutrition: severe folate or B12 deficiency

6. Myelodysplastic syndromes

7.Autoimmune phenomena: eg. Lupus, Paroxysmal nocturnal hemoglobinuria

8.Radiation

Paroxysmal Nocturnal Hemoglobinurea is a rare, acquired condition manifested by intermittent hemolytic anemia, venous thrombosis, cytopenias, and recurrent bouts of hemoglobinurea (from hemolysis). There is a mutation in the PIG-A gene, resulting in complement being able to damage RBC surface proteins, causing the hemolysis. It can be diagnosed with Ham's test (yes...PIG, HAM...it's not a Kosher disease). More recently, PNH can be diagnosed via flow cytometry on peripheral blood. A great article Here.

Morning Report Tapas

HoPingKong-isms

1. "....Did you go camping this summer in a tent..." referring to tenting, or peaked T waves seen on ECG in hyperkalemia. Take a look at this article for more info on ST and T wave changes in various medical conditions.


2. "....Your ankle bone is connected to your knee bone..." referring to Ancylostoma duodenalis, one of two common species of hookworms that infect humans (the other being Necator americanus). This is very common cause of anemia worldwide with an estimated 800 million people infected. Yes, the adjacent picture is of a hungry hookworm. How can you be angry at a punim like that? (if you don't know what 'punim' is come find me).

3. "...Be quick, give me the answer in a flash..." referring to flash pulmonary edema as seen in mitral stenosis. this may also be associated with acute myocardial infarctions, aortic or mitral regurgitation, and renal artery stenosis.

4. "...Anybody here wearing pants, or are you wearing trousers..." referring to Trousseau's Syndrome, a migratory thrombophlebitis typically seen with underlying malignancies and an associated hypercoaguable state.

5. "...You're lagging behind me..." referring to the lid lag, often seen in Graves Disease. Other features of Graves disease include lid retraction, acropachy, and pretibial myxedema. A great review article on Graves Disease Here

6. "...Think about how you make muffins, bread, and bagels..." referring to baking - a Bakers cyst. This was in reference to creating a differential diagnosis for unilateral leg swelling: deep vein thrombosis, cellulitis, chronic venous insufficiency, Achillies tendon rupture or gastrocnemius muscle injury, ruptured bakers cysts, and lymphatic obstrction (with the example of Filariasis - Wuchereria bancrofti)

A word on Sodium Correction....

In patients who are truly hypo-osmolar and hypovolemic and have symptoms of hyponatremia and/or hypovolemia, a careful correction must be made. These patients must be in a closely supervised setting like an intensive care unit or step-up unit where frequent blood work and monitoring can occur. The rapid correction of sodium can be dangerous - leading to permanent neurologic deficits including central pontine myelinolysis - a spastic quadriplegia and pseudobulbar palsy resulting from pontine demyelination of corticospinal and corticobulbar tracts.

Normal saline can be used to correct hypovolemia in most cases: it will raise the plasma sodium a bit as well as it has 154 mEq of Na in it. Remember, we want to raise the sodium up to a level where patients are not seizing or at risk of seizing. We not targeting normal sodium levels here - essentially, we do not want to raise the serum sodium more than 8 mmol/L per day. Hypovolemic patients will have a lot of ADH released - sucking up every drop of water through the cortical collecting ducts. When volume is restored, the stimulus for ADH will be turned off and patients may start to diurese. This can cause an unintentional and overly rapid correction of serum sodium and can lead to neurologic injury. We can be prevent this overly rapid correction by giving DDAVP (desmopressin, a synthetic version of ADH) back to the patient.

Finally, if patients are profoundly hyponatremic and symtomatic, hypertonic (3%) saline can be administered in emergency situations. This is usually done in an acute setting to stop or prevent seizure activity. Again, these patients will need very close monitoring of their neurologic status and electrolytes - and this is best done in an intensive care unit.

This equation can be used to predict the rise in sodium based on the fluids being administered:

Increase in PNa = (Infusate [Na] - PNa) ÷ (Total Body Water + 1)

(TBW is the estimated by: lean body weight times 0.5 for women, or 0.6 for men)

A great review article HERE

Pericarditis

Clinical presentation: usually a sudden onset of retrosternal chest pain with a pleuritic component to it, often relieved by sitting up. You may hear a pericardial rub - this is classically described as a triphasic, high-pitched sound. The 'tri' refers to 1. atrial systole, 2. ventricular systole, and 3. ventricular diastole. It may be a transient phenomenon so listen again if you don't hear it.

ECG: may show diffuse, concave ST elevations that do not fit any particular vascular territory. PR depression is also seen. Check out the ECG above.

Treatment: In most cases of idiopathic pericarditis, high dose NSAIDS are effective. Steroids and colchicine also may have a role. Interestingly, newer evidence suggests that colchicine may be a good first line agent (http://www.circ.ahajournals.org/cgi/content/full/112/13/2012).

A great review article: http://content.nejm.org/cgi/content/full/351/21/2195

Acute Pancreatitis

The mainstays of treating pancreatitis includes identifying an underlying cause and correcting it (eg. gallstone, hypertriglyceridemia, hypercalcemia, etc.), pain control and fluid resuscitation. Other issues that should be considered are feeding status and preventing infection.

1. Infection: patients are prone to infection by translocation of gut organisms if pancreatic necrosis is present. There is debate in the literature whether prophylactic antibiotics are indicated, and this uncertainty is reflected in guidelines from gastroenterology societies - one recommends it, one does not. Take a look at this Cochrane review and decide for yourself: http://www.cochrane.org/reviews/en/ab002941.html

2. Feeding: The classic teaching was that we do not feed our patients with acute pancreatitis. Newer evidence suggests that early oral feeding is alright if the patient can tolerate it. (http://www.ncbi.nlm.nih.gov/sites/entrez)

Here is a good review article touching on most of these topics: http://content.nejm.org/cgi/content/full/354/20/2142

Stigmata of Liver Disease

HoPingKong-isms:

1. "...does the patient live near the liberty bell?..." referring to the Philadelphia chromosome and the bcr-abl gene in CML.

2. "...this thing is hidden...it's like crypton..." referring to cryptogenic cirrhosis.

3. "...I'm getting colder and colder...and I'm constipated..." referring to hypothyroidism as a rare cause of rhabdomyolysis.

Stigmata of Liver disease:

1) Liver failure
a. Encephalopathy
b. Asterixis
c. Jaundice / icterus of sclera or frenulum
d. Fetor hepaticus
e. Bruising
f. Muscle wasting (Temporalis muscle, interosseous muscles)
g. Clubbing

2) Causes of cirrhosis
a. Duputryen’s contracture (alcohol)
b. Track marks (IV drug use)
c. Keiser Fleischer rings (Wilson’s disease)
d. "Bronzed" complexion of skin (hemachromatosis)

3) High estrogen state
a. Palmar erythema
b. Spider Nevi
c. Gynacomastia
d. Pectoral allopecia and feminization of body hair
e. Testicular atrophy

4) Portal Hypertension
a. Pedal Edema and ascites
b. Distended abdominal veins
c. Caput medusae
d. Splenomegaly

spider angiomas, Dupuytren's contracture, and palmar erythema seen below...