December 22nd - MHH - Hematuria

The two cases presented at Morning Report today were related to hematuria - one case is a patient with Acute Promyelocytic Leukemia (APL), the other was one in which the patient had metastatic Renal Cell Carcinoma.  See a prior post for details on APL. Here is some information about workup and other details regarding hematuria

Definition:  The Prescence of 3 erythryocytes/hpf on a urinalysis that is centrifuged. Some references say that this should be repeated to confirm the presence of RBCs. 


Causes: There are many to know, but here is a semi-exhaustive list of the causes. 
Nephrolithiasis
Benign Prostatic Hypertrophy
Prostatitis/UTI
Schistosoma haematobium infection
Renal Cell Carcinoma/Ureteral Malignancy/Bladder Carcinoma/Prostate Cancer
Strictures
Coagulopathy (and it's various causes)
Excessive Exercise
Injury/Trauma (including Foley placement)
von Hippel-Lindau disease
Polycystic Kidney Disease
Sickle Cell Disease and Trait
IgA Nephropathy and Thin Basement Membrane Disease
Any of the various causes of glomerulonephritis (i.e. SLE, PIGN, MPGN, Goodpasture's Syndrome, Anti-GBM Disease, Hemolytic Uremic Syndrome etc)

Other things to consider: Remember, some medications (such as rifampin, dilantin and chloroquine) can cause a false positive test for blood on the urine dipstick, but there will be no RBCs. Similarly, remember that in rhabdomyolysis, Blood is reported as +, but RBCs are absent. These should be considered in all cases of hematuria. Some foods cause the urine to turn red with a completely normal urinalysis - including beets, berries and food coloring.

Basic Workup:

All patients with hematuria should have a metabolic panel (to evaluate renal function), CBC and coagulation studies performed. 

As far as determining the specific cause, one should first do a Urinalysis with microscopy to determine if there is a glomerular vs nonglomerular cause.  Remember that glomerular causes will have RBCs casts and/or dysmorphic Red Blood Cells.  If there is indeed a glomerular cause, then workup includes determining the amount and quantity of protein present.  Some will then send serum complements (esp C3) to divide the causes into those with normal and those with low Complement levels.  Without an evident cause based on the serum workup, renal biopsy may be necessary for the glomerular causes.

If the clinical history is suggestive of infection, then urine culture can be sent. However, some causes of a positive urine culture must be considered in this category besides UTI (i.e. prostatitis, PCKD, and some malignancies!)

If the clinical history is suggestive of nephrolithiasis, one can do a helical CT scan. 

If the patient has risk factors for bladder malignancy (i.e. Age>50, smoking history, pelvic irradiation, analgesic abuse) - cystoscopy is warranted as the next step.  Urologists actually like three studies done - Urine Cytology, Cystoscopy and CT imaging of the abdomen/pelvis. 

December 21st - LBJ - Colorectal Carcinoma/Familial Cancer Syndromes

Today at LBJ morning report our first case was of a 37 year old African American Male with Rectal Carcinoma and multiple polyps on colonoscopy. Also, he had multiple hyperpigmented macules scattered throughout his body.  This brings up a good point to discuss the various inherited colorectal cancer syndromes that you'll need to know for boards. All together these inherited syndromes are responsible for approximately 10% of cases of Colorectal Cancer in the US (the other 90% are from sporadic polyp formation)

Familial Adenomatous Polyposis (FAP):

-Most cases are autosomal dominant, and result from a mutation in the APC gene on Chromosome 5

-By the age of 14-15 patients start developing polyps throughout the colon, and most patients get colorectal cancer from these polyps by the age of 35-40.  At this time, in most patients, thousands of polyps are present in the colon. There is a form of FAP that is inherited in an AR fashion, and they have less polyps by this age- only in the hundreds

- Patients also get desmoid tumors scattered thoughout their GI tract - leading to obstructive/compressive symptoms. 
- Cancer of the ampulla of Vater occurs in about 10% of patients. Other malignancies seen
   in patients with FAP include thyroid, pancreatic and gastric cancer.

 - Another finding is retinal epithelial hyperpigmentation. (This is a favorite one-liner for
    boards!)
- Patients need surveillance sigmoidoscopy/colonoscopy starting at age 10-12, and most
   patients undergo prophylactic colectomy by the age of 30.
- All Patients need Genetic Counseling and screening. Surveillance
   EGDs and thyroid U/S are recommended

Variants of FAP:

Gardner's Syndrome - Skull/Mandible Osteomas, Supernumary Teeth, Epidermoid Cysts and/or Lipomas along with polyps/colorectal cancer. + high incidence of retinal epithelial hyperpigmentation. (and a picture of what epidermoid cysts look like to the left)

Turcot's Syndrome - Polyps/Colorectal Cancer combined with CNS Dz (esp meduloblastoma/glioblastoma)

Lynch Syndrome/Hereditary Non-Polyposis Coli Syndrome

Autosomal Dominant Inheritance. Patients have about an 80% lifetime risk of developing colorectal cancer.  2/3rds of colorectal cancers occur in the region proximal to the splenic flexure (unlike most malignancies in the US - which are predominantly left-Sided) Patients develop colon cancer in their 40's. Other malignancies seen in patients with HNPCC include ovarian, endometrial, gastric and a slew of other rare cancers.

The most recent Amsterdam Criteria establishes the guidelines for suspicion/diagnosis of HNPCC:
One or more of the HNPCC-related cancers diagnosed younger than 50 years
Two successive affected generations
Three or more family members with HNPCC-related cancers
 
So if your patient fits this criteria, or has synchronous or metachronous colorectal cancer along with any other cancer that is seen in patients with HNPCC - be suspicious that this is occuring!!! 
 
Family members need to be screened, and they have to get colonoscopies starting at age 25. Females get aggressive screening for endometrial cancer, and some clinicians send CA-125 regularly. 

Peutz-Jehgers Syndrome

This is more of a disease of "adolescents", but just to know because it is fair game on the boards:

- Hyperpigmented macules on the lips/mucosa

- Multiple hamartomatous polyps in the small intestine, large
  intestine and stomach.  These have low malignancy
  potential, and usually causes symptoms such as
  hematochezia and even intussusception

- Patients still have an overall increased risk of colorectal
   adenocarcinoma, and other malignancies such as
   breast, gastric, pancreatic, lung, and many others.

December 18th - LBJ - AML and Quick Leukemia Info

Today at LBJ a case of AML was presented.  Here is some more detailed info about AML, all you'll need for boards...

We see the leukemias very often in morning report, so I will post more details on other leukemias as we have cases in MR. 

However, from a clinical/ board recognition standpoint - I have put the salient clinical and lab features of the other leukemias. Especially the labs! This is how you can tell on boards, clinically and in MR which is which!!!



AML
Epidemiology: By far, the majority of acute leukemias are AML (>80%)

Risk Factors: Radiation Exposure, Chemotherapy, Benzene Exposure, Genetic Diseases (i.e. Downs, Bloom Syndrome) and Preexisting Heme Diseases such as MDS, Myeloproliferative disorders, PNH

Patients present with: Constitutional symptoms, bone/testicular pain, gum infiltration, splenomegaly, LAD
NOTE: Since platelets and hemoglobin are usually decreased on diagnosis - patients can present with these findings (i.e. pallor, fatigue and petechiae)  Also, a leukostasis syndrome can be present in patients with WBC Counts that are >100,000: Hypoxia, pulmonary infiltrates, retinal hemorrhage, priapism, CVA, Myocardial infarction, etc. 

Labs/Workup:

Patients with AML on presentation are invariably anemic and thrombocytopenic.  Most patients will actually have severe thrombocytopenia (<50,000).  So what about the white count?? Well, it can be down, slightly elevated or very high. So AML can have pancytopenia OR a modest to very high WBC count with anemia and thromboctyopenia.  Remember This!!!!

The Blood Smear/Differential will have >20 Blasts in most cases. The Auer rod is diagnostic that the cell line is myeloid in nature (see picture!)

and represents AML.  Heme Path docs can tell this is the case by special stains.

Bone Marrow is done for cytogenetics in order to tell prognosis, and to guide treatment.  Favorable types include t(15;17), t(8;21) and inv(16).  Poor cytogenetic profiles include inv(3), del 5 and del 7

There are 8 subtypes of AML by the WHO - you'll probably have to only know about acute promyelocytic leukemia - M3 - has translocation (15;17) - can present with DIC.  Treat with high dose ATRA (all trans-retinoic acid)

Treatment:
The patient undergoes "Induction" and "Consolidation" in a "7" + "3" method
Induction: Given 7 days of IV Cytarabine (Ara-C) plus 3 days of bolus Anthracysline (Idarubicin or Daunorubicin are used) - after this induction, patient will be severely pancytopenic. 
Then the consolidation phase:  Patients are usually given either high dose Ara-C or undergo Bone Marrow Transplant at this stage.  Allogeneic Bone Marrow Transplant or Autologous stem cell transplant  is usually reserved for patients with high-risk/poor prognostic cytogenetics. 

Treatment of patients with the leukostasis syndrome is with hydroxyurea and/or leukopheresis

CLL:  Patients are usually asymptomatic at time of diagnosis.  Constitutional symptoms are rare.  1/3rd will have significant LAD and/or organomegaly. Some patients may have signs/symptoms of anemia.
Labs with CLL:  Patients usually have modestly elevated WBC counts.  Patients will usually be anemic.  The WBC Count Rarely gets highly elevated (i.e. >30,000) and Thrombocytopenia is uncommon.
Smear with mature lymphocytes and smudge cells. 

CML:  Patients can present exactly like CLL - meaning they rarely have constitutional symptoms.  Lymphadenopathy is RARE with CML (as compared to CLL) but patients usually have organomegaly (especially splenomegaly). In fact, abdominal pain/fullness or early satiety are the common presenting symptoms (both on boards and I've seen in patients) due to splenomegaly.  They can also have a leukostasis syndrome like in AML, but this is rare unless the blast count is very high.  Remember that CML is a MYELOPROLIFERATIVE Disorder.  That being said: The WBC count is always high.  This is always the case.   The Hemoglobin can be low, normal or high. The platelet count is either normal or high. 
Smear with immature cells - promyelocytes, metamyelocyes and myelocytes.  Patients can have increased basophils and/or eosinophils as well. 

ALL: Rare in adults compared to other leukemias.   What you'll need to know, for the most part - can present just like AML - lymphadenopathy, organomegaly, etc.  Can also get leukostasis syndrome as the WBC count can get very high.... but can also have a low WBC count. Just like AML:  Pancytopenia OR a modest to very high WBC count with anemia and thromboctyopenia. However, since it is a disease of lymphoid lineage - unlike AML - the smear will show predominantly lymphoblasts.   

December 15th - MHH - Pulmonary Carcinoid

Today at MHH morning report a case of pulmonary carcinoid was presented.

For quick board-type "pointers, " here are some key Learning Points about carcinoid in general:



Locations/Sites:
Most commonly affected areas are the GI Tract (especially Stomach, Small Intestine, appendix and rectal) and the Bronchial location. Other sites involved, although rare, include ovaries, pancreas, gallbladder and testes

Symptoms:
For Pulmonary Lesions:
1) Local Effect - Obstruction, persistant pneumonia, atelectasis, bleeding from irritation,  
     dyspnea, wheezing

2) Systemic -
     -About 15% get the "carcinoid syndrome": Diarrhea, Flushing, Tachycardia,  
       Bronchoconstriction, hemodynamic instability - all from excess serotonin. Since these are
       excreted directly into the systemic circulation, patients do NOT have to have metastatic
       disease to the liver to get this syndrome.
     -The flushing usually is on the upper torso and face and lasts 10-30 minutes
     -Episodes of Diarrhea can number even >15x a day
     -Patients can get tricuspid and pulmonary disease (esp stenosis) due to fibrosis caused by
       serotonin. The other valves are not affected because the lungs degrade serotonin
     -Patients can also get a secondary pellagra from niacin deficiency
     -Wheezing and asthma are present in >25% of patients
     -About 1% get Cushings Syndrome from ectopic ACTH production

For GI Lesions:
1) Local - Anemia, abdominal pain, weight loss
2) Systemic - The carcinoid syndrome as above can occur, but lesions from the GI tract have
     to metastasize to the liver before getting this constellation of findings.

Diagnosis of Carcinoid:
1) Urine 5-Hydroxyindoleacetic acid (5-HIAA) - A metabolite of serotonin.  Elevated in 75% of patients.The patient has to be on a strict diet, as certain foods (like caffeine, wine, cheese) can falsely elevate the results.  In addition, medications like INH and Acetaminophen can also elevate the results. 

2) Serum Chromogranin A is elevated in 90% of patients, but only suggests that a neuroendocrine tumor is present

3) Radionucleotide scan with Indium-111 scan has a high sensitivity and specificity to help localize the lesion

4) For Pulmonary Tumors - Imaging will show a lesion in greater than 75% of patients - Then need Biopsy.  Same for GI Tract - can image with colonoscopy (rectal lesions) or CT to better visualize other locations.  Then biopsy


Treatment:
Subcutaneous Octreotide helps relieve the symptoms of the carcinoid syndrome in all tumor types.

Pulmonary Carcinoid is usually treated with surgery +/- Chemotherapy with Streptozotocin/5-FU

GI Carcinoids are also treated with surgery, and various chemotherapy regimens are used

December 15th - LBJ - Ascites

Our Second Case at LBJ Today was a patient with 3-4 weeks of abdominal distention (in this case, ascites).  The diagnosis ending up being Alcoholic Hepatitis/Cirrhosis. 

Just as a review, an Approach to a patient with ascites includes a differentiation based on the serum Albumin-Ascitic Gradient. This has a published accuracy of >97%!





If >1.1 - Consider Liver Disease/Portal Hypertension.
This can be broken into causes based on location:

Pre-Hepatic Causes
Portal Vein Thrombosis
Schistosomiasis (in Egypt!)

Intrahepatic Causes (i.e "Cirrhosis)
Alcohol Abuse
Viral Hepatitis
NASH/NAFLD (i.e. obesity, dyslipidemia, insulin resistance)

Post-Hepatic Causes (i.e. "Congestion")
Constrictive Pericarditis
Budd-Chiari Syndrome
Tricupsid Regurgitation
Right-Sided CHF

If <1.1: Think Low-Albumin States and non-portal hypertensive causes:
Nephrotic Syndrome
Malabsorption/Protein-Losing Enteropathy
Infectious Peritonitis (TB and some fungal diseases)
Malignancy (Peritoneal Carcinomatosis, Ovarian Cancer, HCC, Psedomyxoma peritonii)
Hypothyroidism

All you'll ever need to know about Ascites actually comes from the AASLD - it includes where to do your paracentesis, how to analyze fluid (including SBP and variants) and treatment:
AASLD Practice Guidelines for Cirrhosis and Ascites

December 15th - LBJ - Young Blebs

Of Blebs and Bullae

Today at LBJ a case was presented of a previously healthy 33 year old African American Male who presented to the ER with dyspnea.  He was found to have a large left-sided pleural effusion, was given IV azithromycin by the ED, and left Against Medical Advice.  He was readmitted to the medicine service with the same chief complaint - imaging revealed this large pleural effusion and multiple bullae located in various portions of the lung.  He did have a smoking history, but no history of chronic lung disease or prior pulmonary pathology.

These are some of the various causes of bullous disease in young patients:
1) "Normal" - The journal Chest published a review that 6% of healthy young adults can have bullous disease adjacent to the pleura - usually in those with low BMIs that have a positive smoking history.   This was postulated to be due to reduced pleural adipose tissue.

2) Connective Tissue Diseases - Marfan's Syndrome and Ehlers-Danos Syndrome are the most common in the literature.

3) Chronic Cocaine and Marijuana use - both have been linked to formation of bullae

4) Alpha-1-antitrypsin deficiency - Panacinar involvement and usually involves the lower lobes more than the upper lobes.  Emphysema usually develops in smokers around the age of 40, and in non-smokers in the mid 50s.  Depending on the genetic mutation, however, some patients can have emphysema by the age of 30.    

5) Sarcoidosis - Bullous disease can occur anytime during the course of the disease, and is sometimes a presenting finding or can precede the diagnosis by years. 

6) Pulmonary Langerhans Cell Histiocytosis - An Interstitial lung disease found almost exclusively in young male smokers.  Patients can have constitutional symptoms, or present with cough/dyspnea.  The bullae are usually upper-lobe predominant, and 25% of patients develop spontaneous pneumothorax.  Interestingly, 10-15% of patients are completely asymptomatic and the disease is found during "other reasons" to do lung imaging.  15% of patients have "extrapulmonary" involvement including bone pain from cysts, diabetes inspidus or rash.  Pulmonary cysts are usually visualized on CT Scans. Soking cessation usually leads to resolution of symptoms, although some patients are treated with corticosteroids. 

7) Lymphangioleiomyomatosis (LAM) affects pre-menopausal females.  Patients have multiple thin-walled cysts, lymphadenopathy,  diffuse interstitial infiltrates and eventual fibrosis.  They also have a tendancy to form recurrent chylous pleural effusions.  There is a disease association with  angiomyolipomas and tuberous sclerosis.  Patients with LAM are instructed to prevent pregnancy or not take estrogens, as there is evidence that hormones play a role in the pathogenesis of the disease.  Treatment involves general care and relieving symptoms of effusions. Some patients are put on bronchodilators.  Some have used medroxyprogesterone in the past - but the evidence supporting its use is lacking.  Experimental agents, such as chemotherapeutic drugs, are being investigated.  Some patients may need lung transplant.

Of note:  Centriacinar emphysema is the "classic" pattern seen in smokers, and predominantly affects the upper lobes. There is also a more rare variant called distal acinar emphysema/paraseptal emphysema which causes scattered bullous disease without airflow obstruction.  However, it would be RARE in a 33 year old - as it takes at least 20 cigarettes a day for 20 years to form the changes of chronic lung disease.

Some "board review" notes on pleural fluid (as the patient as a pleural effusion)

Light's Criteria (any of these present = exudate)
1. Pleural fluid protein/serum protein >0.5
2. Pleural fluid LDH/serum LDH > 0.6
3. Pleural fluid LDH > 2/3 upper limit of normal

Chest did an analysis of pleural fluid and found that any of the following characteristics are also consistent with "exudates":
1.Pleural fluid protein >2.9 g/dL
2.Pleural fluid cholesterol > 45 mg/dL
3.Pleural fluid LDH > 60 percent of upper limit for serum

Causes of Transudative Effusions:
Congestive Heart Failure (usually bilateral and small, but can be unilateral)
Cirrhosis
Nephrotic Syndrome
Pancreatitis (left sided)
Pulmonary Embolism

Causes of Exudative Effustions
Malignancy (Lung, Breast and Lymphoma)
Mesothelioma (usually bloody fluid)
Infectious (both bacterial and viral)
Esophageal perforation
Pulmonary Embolism
Rheumatic diseases (Rheumatoid arthritis, SLE)
Transudative causes that turn exudative secondary to diuresis
    (This occurs in less than 20% of these patients - to be sure/better classify - if the difference between serum protein and the pleural fluid protein is greater than 3.1 g/dL - the effusion is transudative.  Alternatively, a serum albumin-effusion albumin gradient greater than 1.2 g/dL is also suggestive that effusion is most likely a true transudate)

Other notes:
WBC >10,000 = parapneumonic
WBC >100,000 = empyema (this will be obvious as the fluid will be purulent)
High Eosinophil Count (10% of total) = Mesothelioma, parasites/fungal and drug reaction
High Lymphocye Count (>50% of total) = Malignancy or TB
High Amylase - Esophageal Rupture and sometimes malignancy
Glucose <60 = Malignancy or Infection. An even lower glucose can be see with rheum Dx
pH<7.2 (when collected quickly) - can see with infection and some malignant cases.  When
       seen in the face of infection, it is an indication for chest tube drainage
Pleural Fluid ADA>45 has a PPV of about 80%
High ANA Titers (>1:160) - SLE and drug-induced Lupus
TG>115 = chylous effusions (can be caused by cancer!)