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