Tag Archives: Ask the Expert

Electrolyte & Acid–Base Disturbances in Patients with Diabetes Mellitus

Our own master of electrolytes and kidney specialist, Dr. Biff Palmer, recently published an excellent review article in New England Journal of Medicine titled “Electrolyte and Acid–Base Disturbances in Patients with Diabetes Mellitus.” These frequently encountered clinical scenarios pose problems both in the inpatient and outpatient settings and it is important for physicians of all specialties to become familiar with common presentations and approach to workup and management.

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Lower the room temperature, I’m trying to lose weight!

This week at morning report, Dr. Biff Palmer who is a professor of internal medicine at UT Southwestern in the nephrology division, talked with the housestaff about recent research that has shed light on brown adipose tissue and “beige cells” and their role in metabolism and weight loss. This has gained recent coverage in the media, which many news services have referred to as the “polar vortex diet”. But is there any actual science to this?

YES! Long story short, brown adipose tissue in adults is associated with weight loss as it takes calories from normal fat and burns it. Brown fat plays a key role in thermogenesis and has been a target for weight loss. Scientists have shown that with cold exposure, brown adipose tissue become more metabolically active and may potentially lead to weight loss. White adipose tissue on the other hand functions to store energy as scientists have looked for ways to convert white adipose tissue to brown to enhance metabolism and weight loss. Thus, a third subtype of adipose tissue has been identified called “beige adipocytes” which are white fat cells that express similar genes as brown fat cells, particularly under cold exposure and beta-adrenergic stimulation, and may lead to weight loss. Dr. Ajay Chawla from UCSF recently published a paper in Cell, determining that interleukin 4 and interleukin 13 recruit macrophages to fat leading to catecholamine production and the browning of white fat in mouse models. Studies like this has made this an active area of research for potential targets to treat obesity and maintain weight.

Dr. Palmer recently co-authored a paper looking at the effect of Roux-en-Y gastric bypass on browning in gonadal adipose tissue of female mice and may help offer further insight as to why this surgery leads to weight loss and remediation of type-2-diabetes.The study showed that upregulation of Nppb, Npr1, Npr2, and Beta-3 adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased browning which may lead to those beneficial effects. Check out the study co-authored by Dr. Palmer below as well as a great summary about brown and beige fat cells by Nature by clicking on the links below!

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en- Y gastric bypass is associated with gonadal adipose tissues browning (Molecular Metabolism)

Brown and beige fat: development, function, and therapeutic potential (Nature Medicine)

Photo (AP Photo/Mark Lennihan)

Fever of Unknown Origin

“The mark of a good ID clinician is not how many antibiotics he or she starts but how many he or she stops.” — Brad Cutrell

Definitions

  • “Classic” definition of FUO
    • Fever > 38.3 C
    • Duration > 3 weeks
    • Unknown etiology after > 1 week hospital evaluation
  • Revised Classification: proposed revisions decreased duration and removed inpt evaluation criteria
    • šClassic Definition: temperature higher than 38.0 °C (100.4 °F) for more than 3 weeks and either more than 3 days of hospital investigation or more than two outpatient visits without determination of the cause.š
    • Health care–associated FUO: temperature higher than 38.0 °C (100.4 °F) for more than 3 days in a hospitalized patient receiving acute care with infection not present or incubating on admission.
    • šImmune-deficient (neutropenic) FUO: štemperature higher than 38.0 °C (100.4 °F) in a patient in with ANC < 500 in whom the diagnosis remains uncertain after more than 3 days despite appropriate investigation, including at least 48 hours’ incubation of microbiologic cultures.
    • šHIV-related FUO: temperature higher than 38.0 °C (100.4 °F) in a patient with confirmed HIV infection for more than 3 weeks in outpatients or more than 3 days in inpatients.

Epidemiology

  • Classic FUO etiologies fall into 5 major categories: Infection, Malignancy, Inflammatory, Miscellaneous, Unknown
  • Distribution depends on decade, patient age, geography, and type of practice
  • Classic FUO Epid
  • Classic FUO Epi Trends

Etiology

  • Infections
    • Tuberculosis (extrapulmonary, miliary, IC hosts)
    • Occult abscess (abd/pelvic)
    • Complicated UTI
    • Osteomyelitis
    • Culture-negative endocarditis
    • Malaria
    • Typhoid fever
    • Visceral Leishmaniasis
  • Malignancies
    • Lymphoma (esp. NHL)
    • Leukemia
    • Renal Cell carcinoma
    • Hepatocellular carcinoma or liver metastases
  • Inflammatory Disorders
    • Adult-onset Still’s Disease
    • RA
    • SLE
    • Temporal arteritis (Giant Cell arteritis)
    • Polymyalgia rheumatica
  • Miscellaneous
    • Drug Fever (abx, anti-seizure meds, NSAIDs, anti-arrhythmics)
    • Alcoholic hepatitis
    • Venous thromboembolic disease
    • Endocrine disease (hyperT, adrenal insufficiency, pheo)
    • Disordered heat homeostasis (“central fever”)
    • Factitious Fever (Munchausen)
  • Special Populations
    •  Pediatrics
      • Infectious most often, particularly viral and respiratory
      • CTD: Kawasaki in younger, AOSD in older children
    •  Geriatrics
      • CTD (GCA and PMR) and malignancy more common than in < 65 age group
    • Returning Traveler
      • Malaria, typhoid fever, amebic liver abscess, acute HIV

Diagnostic Evaluation

  • History and Physical!
    • Recent prospective Dutch series found average of 10.5 potential diagnostic clues per pt from history/exam and only 3 per pt from lab testing (81% misleading)
    • Dx
  • Laboratory Testing
    • Best guided by history/exam clues, not “shotgun” approach
    • Laboratory testing yields diagnosis in 25% of cases
    • Labs
  •  Imaging
    • CXR and CT abdomen/pelvis part of initial tests
    • MRI/MRA good for CNS, spine, and vasculitis evaluation
    • Older nuclear tagged scans and Gallium scans have been largely replaced by FDG-PET scans
    • Recent meta-analysis showed pooled sens. 98% and spec. 86% for FDG-PET, arguing for role if initial w/u negative
  • Invasive Testing
    • BM evaluation useful, especially if abnormal CBC or immunocompromised host
    • Biopsy of sites with suspected involvement in select cases

Management and Prognosis

  • Management
    • Therapeutic trials of abx generally not recommended
    • “Non-specific Rx rarely cures FUO but may delay Dx.”
    • Exceptions: empiric steroids for suspected GCA or empiric abx in neutropenic patients
  • Prognosis
    • Depends on age and etiology of FUO (worse with elderly and malignancy as etiology)
    • Most without Dx after extensive evaluation have good prognosis with low mortality and fever resolution
  • Remember: The cause is more likely a common diagnosis presenting in an atypical fashion than a rare disease presenting in a typical fashion.
  • FTMO

Ask the expert – Lithium Toxicity

Introducing our newest section, “Ask the Expert.” Questions from morning report are posed to an expert in the field – they able to provide us with salient information to enhance our understanding of the topic. After discussing Lithium toxicity in morning report, Dr. Palmer had the following to add: 

  • Lithium is handled very much like Na, As a result with volume depletion there is increased proximal reabsorption. 
  • This why a lithium treated patient placed on diuretics or who develops gastroenteritis can suddenly get lithium toxic on a previously stable dose. 
  • Lithium is also reabsorbed like Na in the collecting duct through the ENaC channel.  Once in the cell it disrupts AVP signaling and therefore accounts for the concentrating defect that can arise. 
  • This also forms the basis for amiloride to counteract the toxicity of Li since this drug blocks the ENaC channel. 
  • Over the long term accumulation of Li in the distal nephron can rarely cause permananet injury resulting in permanent concentrating defect and even tubulointerstitial fibrosis.  
  • Li can cause increased K by blocking ENaC, thereby interfering in the luminal negative charge which drives K secretion. 
  • Lastly, Li can cause increased Ca as it alters the PTH vitamin D axis. 

Big thanks to Dr. Palmer – looking forward to seeing him at potpourri!