February 5th - MHH - Polyuria and Diabetes Insipidus

Today at Morning Report, Endocrine consults presented a patient in her third trimester with polyuria and polydipsia.  Here is a general approach to a patient with polyuria, and info on DI

In general, polyuria is defined as at least 3L of urine a day. The frequency of urination does not matter as much as the total amount.  Patients with polyuria will commonly also have polydipsia (to compensate, as long as their thirst center is intact) and will have nocturia.





The basic causes to know for rotations and the boards are:
Diabetes Mellitus
Diabetes Insipidus (Central and Nephrogenic)  - and their multiple causes
Primary/Psychogenic Polydipsia
Diuretic Use (esp in those using it for weight loss)
Hypercalcemia
Medications (either directly or by causing a nephrogenic DI)
Post-ATN or Post-Obstrutive Uropathy

Your exam in these patients may show signs of dehydration, although this is not as common when the patient has an intact thirst mechanism. A Good neurologic examination is essential with the variety of causes of central DI.  Further examination is directed mostly to other causes of Central/Nephrogenic DI or primary polydipsia (i.e. skin findings with sarcoid, amyloid infiltration, lymph nodes with systemic lymphoma, etc)

For the boards, a key topic is being able to identify and contrast Central Diabetes Insipidus, Nephrogenic Diabetes Insipidus and Primary Polydipsia

Central Diabetes Insipidus occurs from inadequate secretion of vasopressin. 
Causes: There are familial/inherited forms, but this is not as common as other causes - tumors of the CNS (including lymphoma and mets), trauma, granulomatous disease (TB/Sarcoid), infections (meningitis) and Sheenhan Syndrome. 

Nephrogenic Diabetes Insipidus occurs from renal insensitivity to vasopressin. 
Causes: This is commonly an inherited disorder, but can be secondary to medications (esp Lithium, Ampho B), systemic conditions (amyloid, Sjogrens, sickle cell disease, pregnancy), or electrolytes (HyperCA and HypoK)

Primary Polydipsia is simply increased water intake, usually psychogenic in nature (but can also be seen with lesions that affect the thirst center of the brain - sarcoid is a commonly tested one. 

Labs: Basic workup should include ruling out causes listed above, if not already obvious.  The best test to do initially is a BMP and Urine Osmolarity.  Patients will not be hypernatremic if they have an intact thirst mechanism, so don't rule out any of the above three if the patient has access to water, and takes in an amount to offset their urine output.  Undiagnosed DM and secondary osmotic diuresis can be ruled out with the glucose on the chemistry.  The electrolytes are also very important - both Hypercalcemia and Hypokalemia can not only cause polyuria, but in most cases, will make the symptoms worse as they interfere with the kidneys ability to concentrate urine.  Therefore, check these labs and correct as needed. 

Urine Osmolarity will be low in patients with Both forms of DI - generally <200. This is usually also the case with Primary Polydipsia. This is the general first step, although it makes sense because of very dilute urine. 

The other test that is done is the much heard about water deprivation test.  Patients are to be started on this protoco , and are instructed to not drink for about 2 hours before coming to the clinic or hospital for testing. During the time frame, the patient is not given access to fluids -> dehydration -> maximum stimulus for Vasopressin Secretion. Basic labs are drawn, and both Urine Volume/osm are measured every 2 hours. During this time frame, patients with Primary Polydipsia will be able to concentrate their urine. Therefore, in patients with Primary Polydipsia, the Urine osm will rise during the test.  In patients with both Central and Nephrogenic DI, the urine osm does not change much, yet the serum sodium may increase. 

So, now with no change in urine osm, the patient has either Central or Nephrogenic DI. How to tell apart - the patient is given desmopressin and we see what happens to the Urine Osm. Those patients with Central  DI will have at least a 50% increase in the Urine Osm after this medication, whereas patients with nephrogenic DI will have none or a slight increase (<10%) in their urine Osm. In those with primary polydipsis, the urine osm will increase at least 50% as well. 

Of NOTE:  On Boards, some other lab info/approaches may be given to differentiate the conditions.  With a low urine osm, and without the use of the water deprivation test, desmopression may be administered to see what happens to the urine osm.  If it changes >50%, then it is central DI.  Also, on various board review materials, they mention measuring ADH during the deprivation test. This is usually not done much clinically. You should be aware that with the water deprivation test - a rising plasma osm with no change in ADH is Central, and a rising ADH with no change in urine osm is Nephrogenic.  This makes sense, and may be presented on boards - but is not usually the way to diagnose this clinically. 

Treatment:
Central DI: Usually get intranasal Desmopressin lifelong
Nephrogenic DI:  Treat the underlying disorder/change medications.  Treatment is also thiazide Diuretic +/- K-sparing diuretic (The cause voume contraction sensed by the kidneys, and the resulting autoregulatory decrease in GFR will help decrease Urine Output)

Reference:
Image Courtesy of www.operationalmedicine.org

February 2nd - MHH - Mesenteric Ischemia and Ischemic Bowel Disorders

Today at Hermann, a case was presented regarding a patient with post-prandial abdominal pain (and also history of coronary artery disease and PVD).  The diagnosis was Mesenteric Ischemia (aka "Intestinal Angina")

Housestaff frequently interchange the different ischemic diseases of the bowel, and I've hear the term "ischemic colitis" to describe the clinical scenario above. Here is a review of the different ischemic disorders involving the bowel.


There are essentially 4 ischemic disease that affects the mesentery - acute and chronic mesenteric ischemia, mesenteric thrombosis and ischemic colitis. Keep in mind, that each of these has a variety of causes (see below).

Mesenteric Ischemia
In almost all of the causes, the presentation is similar - post prandial abdominal pain, weight loss and "fear of eating." Most of these symptoms occur indolently, yet depending on the cause, this symptoms can present more acutely.  The symptoms simply occur from a supply/demand mismatch, and the SMA is the usual site of involvement.  Overall, these patients DO NOT present with blood in the stool/diarrhea.... that is unless there is another overlapping cause that leads to gut infarction. This overlapping cause is usually caused by severe hypovolemia, cardiogenic shock or sepsis.

On exam, the classic presentation is that the patient's complaint of pain is out of proportion to the exam.  In fact, the way that patients describe pain - one may suspect that they would have peritoneal signs, but they are essentially non-tender during the exam.  (Remember, however, that this would not be the case if there was gut infarction that resulted from an overlapping cause).  In all patients, Auscultation of the abdomen may reveal a bruit. 

   Acute Mesenteric Ischemia - These patients usually present acutely, and are the highest risk of developing infarction of the bowel.  There are a variety of causes, but in all - patients have poor perfusion of the colon - usually at the area of the SMA

Embolic Disease: Common causes of this include atrial fibrillation, or a mural clot post myocardial infarction.This is sometimes seen after vascular surgery as well. Emesis is usually present.

Mesenteric Arterial Thrombosis: Usually causes by rupture of an atherosclerotic plaque. Patients present usually when precipitated by low-flow states.  These cases commonly develop gut infarction/necrosis rapidly. 

Non-occlusive disease: Hypotension from a variety of causes (MI, Sepsis, etc), vasopressors, cocaine and Digoxin

Workup of Acute Mesenteric Ischemia:  CBC (may have elevated white count, and usually hemoconcentration occurs), Amylase usually elevaed.  Can have a lactic acidosis. KUB (to rule out other causes) may have findings later in the disease course (especially c/w SBO). CT may be helpful, but mostly to rule out other causes of abdominal pain.  Diagnosis is usually done via angiography, which is currently preferred over MRA. 

Treatment of Acute Mesenteric Ischemia: This is an emergency, as it can rapidly progress to bowel infarction and gangrene   During angiography, thrombolytics can use used with ischemic disease.  Some may need angioplasty or stents afterwards if there is atherosclerotic disease.  Less emergent cases can be treated with Heparin or LMWH.  If there are any signs of infarction (peritonitis, acidosis, lactic acid up) - then emergent surgery is needed

Chronic Mesenteric Ischemia - Over 90% of patients with this have atherosclerotic disease as the cause.  They usually have more chronic symptoms, and although they rarely get gut infarction, they have a high risk of emboli/thrombosis which can lead to infarction.  Think of this as the cause of abdominal pain in a patient with risk factors for coronary artery disease (esp Smoking, DM, HTN, Dyslipidemia) and/or have a history of CAD/MI/CVA/PVD. 

Workup of Chronic Mesenteric Ischemia: Mostly done to rule out other causes (i.e. liver disease, pancreatitis, biliary disease, nephrolithiasis, etc).  Angiography is the gold standard for diagnosis.

Treament of Chronic Mesenteric Ischemia: Stenting of the SMA.  If this is not possible, endarterectomy or bypass can be performed

Mesenteric Venous Thrombosis -  Usually presents acutely, but can be chronic.  Causes by other things you would think of causing venous thrombosis - hypercoaguable states (esp Factor V Leidin, Protein C/S, PNH), pancreatitis, cirrhosis and sickle cell disease. 

Patients present very similarly to those with mesenteric ischemia - post-prandial abdominal pain, "fear of food" and weight loss. The exam is the same as well - essentially non-tender although the patient complains of a lot of pain.  Bruits are not usually heard. 

Workup: Rule out other causes of abdominal pain.  CT scan is the test of choice. Once imaging shows findings c/w a thrombosis - then workup the cause.

Treatment: Consists of heparin/LMWH then long-term coumading. Thrombolysis for emergent cases. Surgery is signs of infarction/peritonitis develop. 

Ischemic Colitis (aka Colonic Ischemia - confusing huh?)
These Patients have a non-occlusive cause of their disease. Unlike the above causes, which invariably affect the SMA, this disease usually affects the IMA.  Especially involved is the so called "watershed area" of the splenic flexure.  Any area distal from the splenic flexure, however, can be involved. 

There are multiple causes of this - mostly post-operative, low-flow states, hypercoaguable states, vasospastic drugs (cocaine), vasculitis and history of radiation exposure.   Embolism post MI or from Afib is RARELY the cause. 

These patients present very different from mesenteric ischemia.  The presentation is almost always acute, with pain on the left side of the abdomen.  These are the patients that present with a sequence including strong urge to defecate  then diarrhea without blood then diarrhea with blood.  Low grade fever may be present, as well as nausea and emesis.  They are usually very tender on physical exam.

Workup: KUB to r/o other causes, as well as labs to investigate pancreatitis, infectious causes, and other mimics.  Colonoscopy is diagnostic (will show mucosal hemorrhage). 

Treatment: Supportive care - fluids, NPO and antibiotics if severe.  Patients can progress to gangrene of the gut, and will need immediate surgical resection.