21 May 2010

Hyponatremia and Hypernatremia



Hyponatremia and Hypernatremia
By:Conor Gough, HO – III

Hyponatremia
* Defined as sodium concentration < 135 mEq/L * Generally considered a disorder of water as opposed to disorder of salt * Results from increased water retention * Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia * Thus, in most cases, some impairment of renal excretion of water is present Causes * Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level * Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels * Causes of Hyponatremia can be classified based on either volume status or ADH level o Hypovolemic, Euvolemic or Hypervolemic o ADH inappropriately elevated or appropriately suppressed ADH suppresion ADH elevation
First step in Assessment: Are symptoms present?
* Hyponatremia can be asymptomatic and found by routine lab testing
* It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy
* Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

Presentation determines if immediate action is needed
* If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline
* If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia
* Oral fluid restriction is good first step as it will prevent further drop in sodium
* NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

WHAT NEXT?
* With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause
* Hypovolemic – urine output, dry mucous membranes, sunken eyes
* Euvolemic – normal appearing
* Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF)

Volume status helps predict cause
* Hypovolemia
o True Volume Depletion
o Adrenal insufficiency
o Thiazide overdose
o Exercised induced hyponatremia
* Euvolemia
o SIADH
o Primary Polydipsia
* Hypervolemia
o Cirrhosis and CHF

Workup for Hyponatremia
How to interpret the tests?
* Serum Osmolality
o Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia
* Urine Osmolality
o Can differentiate between primary polydipsia and impaired free water excretion
* Urine Sodium concentration
o Can differentiate between hypovolemia hyponatremia and SIADH

Additional Tests
* TSH – high in hypothyroidism
* Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm
* Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia
* Iatrogenic infusion of hypotonic fluids (“Surgeon sign”)
* Ecstasy use – increased water intake with inappropriate ADH secretion
* Underlying infections
* NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels
* Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

SIADH: Important concept to understand
Main diagnostic criteria for SIADH
Treatment is based on symptoms
Severe symptoms present
What if little to no symptoms are present?
Formulas that may help: How much sodium does the patient need?
* Sodium deficit = Total body water x (desired Na – actual Na)
* Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

How about an example:
What if the sodium increases too fast?
Risk Factors for demyelination
Treatment Options
Summary of Hyponatremia
Moving on to Hypernatremia
Causes of Hypernatremia
Symptoms of Hypernatremia
Diagnosis of Hypernatremia
Treatment of Hypernatremia
Summary of Hypernatremia

Hyponatremia and Hypernatremia.ppt

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Monocyte / Macrophage Disorders



Monocyte / Macrophage Disorders
Northeast Regional Medical Center/KCOM

Granuloma Annulare
* Localized
* Generalized
* Macular
* Deep
* Perforating
* In HIV
* In Lymphoma
* Common, Idiopathic, all races
* 50% patients IgM and C3 in vessels
* LCV changes sometimes seen
* Suggests Ab mediated vasculitis
* Common in HIV patients
* EBV sometimes found
* Occurs in resolved lesions Zoster

GA - Histology
Interstitial GA
* Upper dermis
* “Skip areas”
* Mucin
* Deep dermis, subQ
* No “skip” areas
* No mucin

Localized GA
* Young adults
* Acral
* Annular, scalloped
* White or pink flat topped papules spread peripherally
* 75% clear in 2 yrs
* 25% last 8 yrs
Diffuse GA
Subcutaneous GA
Perforating GA
GA in HIV disease
GA and Lymphoma
GA- Treatment
Annular Elastolytic Giant Cell Granuloma of Meischer/Actinic Granuloma of O’Brien
Photoexacerbated GA
Granuloma Mulitforme of Leiker
Sarcoidosis
* Multisystem Disease
* Lungs, lymph nodes, skin and eyes MC.
* 10x more frequent in blacks in US
* Women under age 40
* Irish, African, Afro-Caribbean.
* Presence inversely proportional to the incidence of TB and/or Leprosy.
* Etiology unknown
* HLA-A1 – Lofgren’s syndrome
* HLA-B13 – Chronic & Persistent form
* HLA-B8
* HLA-DR3
* Final common pathway is granuloma formation
“NAKED” GRANULOMAS
“NAKED” meanse a sparse rather than a dense infiltrate. Lymphocytes, macrophages & fibroblasts may occur
Sarcoid Skin Involvement
Sarcoid – like syphillis, mimics many other dz’s
Papular Sarcoid
Annular Sarcoidosis
Hypopigmented Sarcoid
Lupus
Pernio
Punched-Out Lytic lesions, Bone Cysts
Ulcerative Sarcoidosis
Lupus Pernio
Darier-Roussy Sarcoid
Scar Sarcoid
Erythrodermic Sarcoid
Ichthyosiform Sarcoid
Alopecia
Morpheaform Sarcoid
Mucosal Sarcoid
Erythema Nodosum in Sarcoid
Systemic Sarcoidosis
Heerfort’s Syndrome
Mikulicz’s Syndrome
CXR- Hilar Adenopathy
Sarcoidosis in Fingers
Candle-wax drippings – granulomatous uveitis
Sarcoid - Treatment
Non-X Histocytoses
* Juvenile Xanthogranuloma
* Benign Cephalic Histiocytosis
* Solitary/Multicentric Reticulohistiocytosis
* Generalized Eruptive Histiocytoma
* Necrobiotic Xanthogranuloma
* Xanthoma Disseminatum
* Papular Xanthoma
* Indeterminate Cell Histiocytosis
* Progressive Nodular Histiocytoma
* Hereditary Progressive Mucinous Histiocytosis
* Rosai-Dorfman Disease
* Sea-Blue Histiocytosis
Juvenile Xanthogranuloma (JXG)
JXG Histopathology
Reticulohistiocytosis
Reticulohistiocytic Granuloma
Multicentric Reticulohistiocytosis
“Coral Bead” Paronychia
Tx: Multicentric Reticulohisticytosis
Generalized Eruptive Histiocytoma
Necrobiotic Xanthogranuloma (NXG)
NXG and Malignancy
Xanthoma Disseminatum
XD - Pathology
Papular Xanthoma
Indeterminate Cell Histiocytosis
Progressive Nodular Histiocytosis
Hereditary Progressive Mucinous Histiocytosis in Women
Rosai-Dorfman Disease
Rosai-Dorfman Disease – LN Biopsy
RDD - Emperipolesis – Histiocytes engulf plasma cells and lymphocytes
RDD - Treatment
Sea-Blue Histiocytosis
Sea-Blue Histiocytosis – Bone Marrow
X-type Histiocytoses
Hashimoto-Pritzker
Hashimoto-Pritzker Before and After
H-P MANAGEMENT
Histiocytosis X
Histiocytosis X - TX

Monocyte / Macrophage Disorders.ppt

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30 April 2010

The BioArtificial Liver



The BioArtificial Liver
By:Susana Candia
Jahi Gist
Hashim Mehter
Priya Sateesha
Roxanne Wadia

Biology of the Liver
Left lobe
Right lobe
Kidneys
Gallbladder
Falciform Ligament
Inferior Vena Cava
Abdominal Aorta

What does the Liver do?
Among the most important liver functions are:
* Removing and excreting body wastes and hormones as well as drugs and other foreign substances
* Synthesizing plasma proteins, including those necessary for blood clotting
* Producing immune factors and removing bacteria, helping the body fight infection

Other important but less immediate functions include:
* Producing bile to aid in digestion
* Excretion of bilirubin
* Storing certain vitamins, minerals, and sugars
* Processing nutrients absorbed from digestive tract

Why would someone need a BioArtificial Liver?
Liver Transplantation Now
* Patients are in waiting list ranked according to severity of disease and life expectancy among other variables.
* Can be from a cadaveric donor or from a live donor.
* Involves heavy use of immunosuppressants during and after surgery.
* The risk of rejecion is always present.

What does a BioArtificial Liver need to do?
* Cellular components must be purified and every component in it must be clearly identified.
* The cellular preparation must be clearly shown to not transmit any infectious diseases of any kind.
* The cellular component must stay viable and active
* The synthetic component must be fully biocompatible, integrity of the material and parts must also be demonstrated
* The device must be able to introduce the therapeutic and regulatory molecules that a healthy liver provides, and it must also filter substances from the blood the way that the normal liver does.
* Must be immunocompatible.
* Blood must perfuse properly through system

Enabling Technologies
* Hemodialysis/hemofiltration hollow fibers- controlled interaction of cells and circulating fluids
* Maintenance and creation of a cell line
* Immortalizing cells
* Encapsulation-envelopment of hepatocytes in a polymeric matrix.
* Microcarriers- polymeric particles containing cells

Works in Progress: Points to Consider
Bioreactor designs/Membrane configurations
Cellular vs. Acellular system
Porcine vs. Human hepatocytes
Point in Development
Liver Dialysis Unit
* FDA approved in 1994
* Plate dialyzer with blood on one side, dialysate is a mixture of sorbents, activated charcoal being the essential component.
* For a substance to be removed, must be dialyzable and able to bind to charcoal.
* “Bridge to recovery” for treat acute hepatic encephalopathy and overdoses of drugs
* Post-market trials have shown the LDU to be effective in improving physiological and neurological status.

MARS®
* Limited to investigational use in US.
* Hollow fiber membrane hemodialyzer.
* Blood on one side, human albumin on other.
* Albumin recycled through circuit containing another dialyzer and carbon and anion exchanger adsorption columns.
* Removes both water-soluble and protein bound substances
* Keep valuable proteins
* Trial have found it safe and associated with clinical improvement

ELAD®
* Uses cultured human hepatocytes express normal liver-specific metabolic pathways. hollow fiber dialyzer.
* Dialyzer cartridge connected to continuous hemodialysis machines, like those used for renal therapy.
* Blood separated into a cellular component and a plasma component.
* Plasma through dialyzer, hepatocytes on outside of hollow fibers.
* Currently involved in a phase 2 clinical trial to evaluate the safety and efficiency.
BLSS
* Extracorporeal hemofiltration hollow fiber membrane bioreactor with 100 grams of primary porcine hepatocytes
* Whole blood is filtered
* Contains blood pump, heat exchanger, oxygenator to control oxygenation and pH, and hollow fiber bioreactor
* Currently undergoing phase I/II clinical trials
* Patients show some improvement

HepAssist 2000 System
* Four components: a hollow fiber bioreactor containing porcine hepatocytes, two charcoal filters, a membrane oxygenator, and a pump.
* Must be used in conjunction with a commercially available plasma separation machine
* Blood separated; plasma processed through charcoal filters to remove particulates, bacteria, then enters bioreactor
* Hepatocytes must be heated and oxygenated
* FDA mandated full Phase III trials
LIVERx2000
* Hollow fiber cartridge
* Primary porcine hepatocytes suspended in a cold collagen solution and injected inside fibers
* Blood circulates outside the hollow fibers
* Designed to treat both acute and chronic liver failure
* Phase I/II clinical trials are underway to test the safety of efficacy of this device
* Anyone treated with the LIVERx2000 will be monitored for PERV
MELS
* Parallel plate design
* Human hepatocytes attached to semipermeable membranes on parallel plate
* Plasma separator, then plasma passes into the bioreactor
* In the bioreactor, the plasma flows over the semipermeable membrane where the hepatocytes are adhered.
* Current trials in Europe show promise

Demographics and Cost
* Market for liver support is estimated to be substantial: $700 million in the United States and $1.4 billion worldwide.
* Liver transplants have more than doubled in the past ten years, with the transplant waitlist growing in a similar fashion

Current and Future Challenges
* GOAL: To produce a fully implantable bioartificial liver.

Problems:
Cell viability
Fibrosis around implanted capsules
Proteins greater than pore size cannot be released

To achieve density of cells needed to replace liver, an estimated 1000m of hollow fibers would be needed

The BioArtificial Liver.ppt

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