08 October 2009

Differential diagnosis of the flu-like illness

The sepsis syndrome: Differential diagnosis of the flu-like illness
By:Divya Ahuja, M.D.

Med Micro 2008 Clinical Correlations #5
Traditional definitions

* Bacteremia (or fungemia): presence of microorganisms in the blood
* Sepsis: Harmful consequences of microbes or their toxins in blood or tissues
* Septicemia (or bloodstream infection): bacteremia with clinical manifestations
* Septic shock: shock due to sepsis, often with bloodstream infection

Revised definitions
* Systemic inflammatory response syndrome (SIRS)
* Sepsis
* Severe sepsis
* Septic shock

Systemic Inflammatory Response Syndrome (SIRS)
* Two or more of the following
o temperature > 38 degrees C (100.4 F)
o respirations > 20/minute
o Heart rate > 90 beats per minute
o leukocyte count > 12,000/cmm or < 4000/cmm or with > 10% band forms

Sepsis and Severe Sepsis
* Sepsis: SIRS plus a documented infection (culture proven or identified by visual inspection)
* Severe sepsis: Sepsis associated with organ dysfunction, abnormalities due to hypoperfusion (such as lactic acidosis, oliguria, or acute alteration in mental status), ARDS, DIC, low platelets

Septic shock
* Definition: Sepsis-induced hypotension despite fluid resuscitation and/or inotropic support, plus hypoperfusion abnormalities
* The hallmark of septic shock is low systemic vascular resistance, which distinguishes it from hemorrhagic shock and cardiogenic shock.

Multiple Organ Failure
* Some physiologic descriptors
o Serum creatinine
o Platelet count
o pO2/FiO2 ratio
o Serum bilirubin
o Glasgow coma score

* Sepsis has a 20-50% mortality
* Severity has increased recently
* Hospital case-fatality has declined
* Incidence is greatest in winter
* Risk factors for sepsis
o Bacteremia
o Advanced age
o Impaired immune system
o Community acquired pneumonia

Continuum of severity
* Incidence of positive blood cultures increases along the continuum
* Increased mortality rate
* Severe organ dysfunction manifested as
o Acute respiratory distress syndrome
o Acute renal failure
o Disseminated intravascular coagulation

Disseminated intravascular coagulopathy
Case #1
* 20-year-old college student in ER
* General malaise, low-grade fever, and rapid development of purplish discoloration on his face. (from when he left his house to the time he arrived at the emergency room).
* Blood cultures were drawn and he was admitted to the intensive care unit

* Febrile, tachycardic, systolic BP-70
* Creatinine- 3.6, poor urine output
* Platelets-46000
* INR- 2.6
* Obtunded mental status
* Needing maximum ventilatory support
* Meningococcemia with Waterhouse-Friderichsen Syndrome and DIC
* Treat with penicillin, ceftriaxone or chloramphenicol.
* Family members and hospital employees in contact with respiratory secretions should receive prophylaxis. Attack rates for household contacts is 0.3-1%, 300-1000 times the rate in the general population (rifampin x 4 doses or cipro x 1 dose)

Epidemiology of meningococcal disease

Evaluation of blood cultures
* True-positive versus false-positive (contamination; pseudobacteremia)
* Transient versus intermittent versus continuous
* Polymicrobial versus unimicrobial
* Primary versus secondary

Clues to contamination
* Microorganisms that are usually not pathogenic, unless isolated from multiple cultures (e.g., coagulase-negative staphylococci; Bacillus species)
* < 2 positive cultures and/or delayed growth and/or < 1 cfu/ml
* Doesn’t “fit” the clinical picture

Patterns of bacteremia
* Transient: caused by manipulation of a flora-containing body surface
* Intermittent: typical of most infections giving rise to positive blood cultures
* Sustained (or continuous): characteristic of intravascular infections--endocarditis, endarteritis, suppurative thrombophlebitis, infected AV fistula

Number of microorganisms
* Unimicrobial (or “monomicrobial”) bacteremia: one isolate
* Polymicrobial bacteremia: more than one microorganism; typical of complicated situations often with surgical implications

Epidemiology of sepsis
* Contributes to > 100,000 deaths in the United States each year.
* Annual incidence is probably between 300,000 and 500,000 cases.
* About 2/3rds of cases occur in patients hospitalized for another illness (nosocomial infection).

Risk factors for nosocomial sepsis
* Gram-negative bacilli: diabetes mellitus; tumors; cirrhosis; burns; invasive procedures; neutropenia
* Gram-positive cocci: vascular access lines, devices
* Fungi: immunosuppression; broad-spectrum antibiotic therapy

Host factors in sepsis
* Mortality is directly related to severity of underlying disease: rapidly-fatal> ultimately fatal (i.e., within 5 years)>nonfatal.
* Elderly have increased mortality.
* Mortality is higher in patients with subnormal temperatures than in those with fever.

Clinical findings in sepsis
* Early: apprehension, hyperventilation, altered mental status
* Complications: hypotension, bleeding, leukopenia, thrombocytopenia, organ failure
* Lungs: cyanosis, acidosis, full-blown ARDS
* Kidneys: oliguria, anuria, tubular necrosis
* Liver: jaundice and transaminitis
* Heart: heart failure, stunned myocardium
* Gastrointestinal: nausea, vomiting, diarrhea, stress ulceration
* Systemic: lactic acidosis
* Petechiae early in course: suspect especially meningococcemia, RMSF
* Ecthyma gangrenosum: Ps. aeruginosa
* Generalized erythroderma: Toxic Shock Syndrome

Ecthyema gangrenosum

Skin lesions in septicemias (1)
* Neisseria meningitidis: erythematous macules or petechiae and purpura
* Rocky Mountain spotted fever: petechiae, purpura
* Staphylococcus aureus: “purulent purpura”
* Pseudomonas aeruginosa: ecthyma gangrenosum
* Salmonella typhi: “Rose spots”
* Hemophilus influenzae: cellulitis
* Endocarditis: petechiae; Osler’s nodes (painful lesions of finger and toe pads); Janeway lesions (painless lesions of palms or soles)
* Anthrax: papules-->vesicles-->eschar
* Fungemias

A 50 yo man presents to emergency room with severe pain and swelling of LLE. On exam, temperature is 40.0 ºC, pulse rate is 135/min, respiration rate is 35/min, and blood pressure is 80/40

Which of the following is the most appropriate initial therapy?
* LLE elevation
* X-ray of LLE
* Surgical consultation
* Oral antibiotics

Necrotizing fasciitis
* Necrotizing fasciitis usually results from an initial break in skin (trauma or surgery)
* It is deep: may involve the fascial and/or muscle compartments
* The initial presentation is that of cellulitis

Necrotizing fasciitis: Red flags
* Severe pain (out of proportion of skin findings)
* Bullae (due to occlusion of deep blood vessels)
* Skin necrosis or ecchymosis
* Gas in soft tissue (palpation or imaging)
* Systemic toxicity
* Rapid spread during antibiotic therapy

Necrotizing fasciitis
* Monomicrobial: S. pyogenes, S. aureus, anaerobic streptococci,…. Most are community acquired and present in the limbs in patients with DM or vascular insufficiency

* Polymicrobial: aerobic and anaerobic (bowel flora), Usually associated with abdominal surgical procedures, decubitus ulcer, perianal ulcer, bartholin abscess, IV drug injection

Staphylococcal bacteremia
* Complications: endocarditis; metastatic infection; sepsis syndrome
* Staphylococci adhere avidly to endothelial cells and bind through adhesin-receptor interactions
* Fulminant onset; high fever, erythematous rash with subsequent desquamation, and multiorgan damage
* DDx: Rocky Mountain spotted fever, streptococcal scarlet fever, leptospirosis

Streptococcal toxic shock syndrome
* Early onset of shock and organ failure associated with isolation of group A streptococci
* Necrotizing fasciitis present in about 50% of cases
* Early symptoms: Myalgias, malaise, chills, fever, nausea, vomiting, diarrhea
* Pain at minor trauma site may be first symptom

Sepsis in the asplenic patient

* Frequently fulminant with massive bacteremia
* Streptococcus pneumoniae accounts for 50% to 90% of infections and 60% of deaths
* Other pathogens: Haemophilus influenzae, Neisseria meningitidis, Capnocytophaga canimorsus (after dog bites),
Babesia microti (babesiosis)

64 year old WM
* Presents with fever, hypotension, cellulitis with bullous skin lesions
* PMH: cirrhosis
* SH: recently returned from New Orleans, likes oysters

Vibrio vulnificus sepsis
* Organism found in warm seawater and in shellfish (90% of deaths due to seafood in U.S.)
* Cirrhosis a major risk factor to sepsis, with rapid onset
* Chills, fever, characteristic skin lesions (bullae with hemorrhagic fluid; necrotizing fasciitis, other)
* Also causes wound infection after exposure to salt water

41 year old WM
* Fever, “worst headache ever,” myalgias, rash
* Returned from family camping trip in Smoky Mountain National Park 1 week PTA

Rocky Mountain spotted fever
* Generalized infection of vascular endothelium
* Headache typically severe. Fever may be low-grade and rash may be absent (“spotless fever”) when patient first seen
* Suspect with flu-like illness and severe headache in endemic areas!

65 year old woman
* PMH diabetes
* During influenza epidemic, presents with fever, chills, aching all over (myalgia)
* PE: bibasilar rales; no murmur
* Admitted to hospital for treatment of heart failure

Infective endocarditis: definitions

* Septic vegetations of the endocardium usually involving the heart valves or other areas of turbulent flow
* Acute endocarditis occurs on normal heart valves, is caused by highly virulent bacteria and leads to death in < 6 weeks
* Subacute endocarditis is caused by less virulent bacteria and has a more indolent course.

Pathogenesis of endocarditis
* Sterile vegetations arise downstream of high-flow areas of the heart
* Damaged endothelium and foreign bodies increase turbulent flow
* Microorganisms implant on the sterile vegetations during transient bacteremia
* Septic vegetations become a source of infection elsewhere

Diagnosis of endocarditis
* Revised Duke Criteria : positive blood cultures plus echocardiography with or without minor criteria
* Heart murmurs (especially regurgitant)
* Splinter hemorrhages (nail beds)
* Osler nodes (finger pulps; painful)
* Petechiae; “pustular purpura” (Staph)
* Roth spots (fundi)

Etiologies of endocarditis
* Viridans streptococci most common (30-40%)
* Other streptococci include enterococci and Streptococcus bovis
* Staphylococci cause 20-30%)
* Less common: aerobic gram-negative rods; HACEK organisms; fungi; anaerobic bacteria; Brucella; Coxiella burnetti; Chlamydia psittaci
* “Culture-negative” (<5% to 24%)

* 42 year male
* Previously healthy, non smoker
* 2 week history of progressive cough, dyspnea, fever
* Intubated within 48 hours of admission

Hamman-Rich syndrome
* Also known as acute interstitial pneumonia, is a rare, severe lung disease which usually affects otherwise healthy individuals
* Cough, fever, dyspnea
* Hamman-Rich syndrome progresses rapidly, with hospitalization and mechanical ventilation within days to weeks after initial symptoms

* Look at the host (age, immunedeficiency,-HIV, cancer, steroids, cirrhosis, dialysis,
* Clinical assessment for MOD (vitals, perfusion, mental status, urine output)
* Lab parameters-platelets, creatinine, coags, leukocytosis vs. leukopenia
* Hemodyanamic, ventilatory support, antibiotics
* Hit hard and hit early and then deescalate based on emerging microbiological data

The sepsis syndrome: Differential diagnosis of the flu-like illness.ppt


Emerging Infections and Medical Procedures

Emerging Infections and Medical Procedures

Parasitic Infections: Clinical Manifestations, Diagnosis and Treatment
By:Lennox K. Archibald, MD, PhD, FRCP, DTM&H
Hospital Epidemiologist
University of Florida

The Reality
* 1.3 billion persons infected with Ascaris (1: 4 persons on earth)
* 300 million with schistosomiasis
* 100 million new malaria cases/yr
* At UCLA, 38% of pediatric and dental clinic children harbored intestinal parasites

* 42-yr-old previously healthy, UF professor
* 6-week history of intermittent diarrhea, flatus and abdominal cramps
* Diarrhea: x8/day; pale; no blood or mucus
* No tenesmus
* Illness began slowly during camping trip to Colorado with loose stools
* Spontaneously remission for 5-6 days at a time, then recur
* His 8-yr-old son had had a mild course of watery diarrhea—ascribed to viral gastroenteritis by general practitioner
* Stool smear—no pus cells
* However, wet preps showed…

Giardiasis (G. lamblia)
* Should be suspected in prolonged diarrhea
* Contaminated water often implicated—outbreaks
* Campers who fail to sterilize mountain stream water
* Person-person in day care centers
* Symptoms usually resolve spontaneously in 4-6 weeks

Giardiasis Tests of choice
* Examination of concentrated stools for cysts (90% yield after 3 samples)
o Usually no PMNs
* Stool ELISA, IF Antigen (up to 98% sensitive/90-100% specific)
* Consider aspiration of duodenal contents--trophozoites
* Treatment: Metronidazole for 5-7 days

Case 2
* 40 y/o male vicar returned from 2 years of missionary work in South Africa
* Excellent health throughout stay there
* 3 months after returning to U.S.
o Suddenly ill with abdominal distension
o Fever
o Periumbilical pain
o Vomiting
o Blood-tinged diarrheal stools
* Denied arthritis /known exposure to parasites
* Family history of “inflammatory bowel disease”
* Physical examination:
o Acutely ill
o Distended abdomen
o No hepatomegaly or splenomegaly
o Decreased bowel sounds
o Stool exam
+ Gross blood present
+ No pus cells
+ Negative for O&P, one negative C&S

Sigmoidoscopy revealed…
* Multiple punctate bleeding sites at 7 to 15 cm with normal appearing mucosa between sites
* This mucosa easily denuded when pressure applied to it, leaving large areas of bleeding submucosa
* Diagnosed with ulcerative colitis
* Started on corticosteroids
* Temperature rose to 40°C
* Abdomen distension increased and worsening of symptoms
* Emergency laparotomy for toxic megacolon

Entamoeba histolytica
* One of 7 amoebae commonly found in humans
* Only one that causes significant disease
* Causes intestinal (diarrhea and dysentery) and extraintestinal (liver primarily) disease
* In US
o Institutionalized patients
o Tourists returning from developing countries
o Patients with depressed cell mediated immunity

Trophozoites with ingested RBC
Trophozoites in colon tissue (H & E stain)
Cyst (wet mount)

Amoebiasis: Clinical Manifestations
* Symptoms depend on degree of bowel invasion
o Superficial: watery diarrhea and nonspecific GI complaints
o Invasive: gradual onset (1-3 weeks) of abdominal pain, bloody diarrhea, tenesmus
* Fever is seen in minority of patients
* Can be mistaken for ulcerative colitis
* Steroids can dramatically worsen and precipitate toxic megacolon
* Amebic liver abscesses
o RUQ pain, pain referred to right shoulder
o High fever
o Hepatomegaly (50%)

Amoebic abscess—remember…
* Can occur in lung, brain, spleen
Amoebic Abscess
* Liquefaction of liver cells
* Do not contain pus
* Anchovy paste sauce
* Culture of contents usually sterile
* Liver affected:
o 53%-right lobe
o 8%-left lobe

* That stool is merely a convenient vehicle passing by
* Amoebae live the bowel wall
* Direct observation preferable to mere examination of stool
* Trophozoites best seen in direct scrapings of ulcers

Amoebiasis Treatment
* Most respond to metronidazole
* Open surgical drainage should be avoided, if at all possible

Case 3
* Previously healthy 3-year-old girl
* Attends day-care center
* 7 day history of watery diarrhea
* Nausea
* Vomiting
* Abdominal cramps
* Low-grade fever

Case 4
* 34 year-old AIDS patient
* Debilitating, cholera-like diarrhea
* Severe abdominal cramps
* Malaise
* Low-grade fever
* Weight loss
* Anorexia

Diagnosis? Case 3 & 4

Three cysts stained pale red are seen in the center with this acid fast stain
Modified acid-fast stain of stool showing red oocysts of Cryptosporidium parvum against the blue background of coliforms and debris

Cryptosporidium parvum
* Causes secretory diarrhea: 10 liter/day
* Significant cause of death in HIV/AIDS
* Animal reservoirs
* Incubation period: 5-10 days

Cryptosporidium parvum
* Infants & young children in day-care
* Unfiltered or untreated drinking water
* Farming practices: lambing, calving, and muck-spreading
* Sexual practices: oral contact with stool of an infected individual
* Nosocomial setting with other infected patients or health-care employees
* Veterinarians: contact with farm animals
* Travelers to areas with untreated water
* Living in densely populated urban areas
* Owners of infected household pets (rare)

Diagnosis and Treatment
* Best diagnosed by stool exam
* No known effective treatment
* Nitazoxamide shortens duration of diarrhea

Case 5
* Mr. & Mrs. R. were sailing with their 3 children in Jamaica
* Living primarily on the boat with several day trips to a small coastal island
* On island, ate several types of tropical fruit
* Both became suddenly ill with fevers, chills, muscle aches, and loss of appetite.
* Sought treatment locally, and were diagnosed with hepatitis, likely due to ingestion of toxic fruit

Case 5
* Two days later, Mr. R. became jaundiced and passed dark urine
* He progressively worsened, became comatose and died
* In the meantime, Mrs. R. was transferred to SUF for liver transplant
* None of the children were sick despite having eaten the same fruits and other foods.
* The family had taken chloroquine prophylaxis against malaria, but the parents stopped the medicine 2 weeks prior to becoming ill because of side effects.

Falciparum vs. Vivax
* Location: Falciparum confined to tropics and subtropics; vivax more temperate
* Falciparum infects RBC of any age; others like reticulocytes
* Falciparum-infected RBCs stick to vascular endothelium causing capillary blockage

Malaria: Genetic susceptibility
* Two genetic traits associated with decreased susceptibility to malaria
* Absence of Duffy blood group antigen blocks invasion of Plasmodium vivax
o Significant number of Africans
* Persons with sickle cell hemoglobin are resistant to P. falciparum
* Sickle cell disease and trait

Malaria: Clinical manifestations
* Non-specific, flu-like illness
* Incubation
o P. falciparum: 9-40 days
o Non-P. falciparum: may be prolonged
+ P. vivax: 6-12 months
+ P. malariae and ovale: years
* Fever is the hallmark of malaria
o Classically, 2-3 day intervals in P. vivax and malariae
o More irregular pattern in P. falciparum
* Fever occurs after the lysis of RBCs and release of merozoites

Malaria: Clinical manifestations
* Febrile paroxysms have 3 classic stages
o Cold stage
+ Pt feels cold and has shaking chills
+ 15-60 mins. prior to fever
o Hot stage
+ 39-41°C
+ Lassitude, loss of appetite, bone and joint aches
+ Tachycardia, hypotension, cough, HA, back pain, N/V, diarrhea, abdo pain, altered consciousness
o Sweating stage
+ Marked diaphoresis followed by resolution of fever, profound fatigue, and sleepiness
+ 2-6 hours after onset of hot stage
* Other symptoms depend on malaria strain
* P. vivax, ovale and malariae: few other sxs
* P. falciparum:
o Dependent upon host immune status
o No prior immunity/splenectomy  high levels of parasitemia  profound hemolysis
o Vascular obstruction and hypoxia
+ Kidneys: renal failure
+ Brain: (CNS) ― hypoxia, coma, seizures
+ Lungs: pulmonary edema
o Jaundice & hemoglobinuria (blackwater fever)
* Always suspect malaria in travelers from developing countries who present with:
o Influenza-like illness
o Jaundice
o Confusion or obtundation

* Giemsa-stained blood smear
o Thick and thin smears
* P. falciparum:
o Best just after fever peak
* Others:
o Smears can be performed at any time
* Examine blood on 3-4 successive days

Differences in strains
* P. falciparum
o No dormant phase in liver
o Multiple signet ring trophs per cell
o High percentage (>5%) parasitized RBCs considered severe

Differences in strains
* P. vivax and ovale
o Dormant liver phase
o Single signet ring trophs per cell
o Schuffner’s dots in cytoplasm
o Low percent (< 5%) of parasitized RBCs
* P. malariae
o No dormant stage
o Single signet ring trophs per cell
o Very low parasitemia

* P. falciparum malaria can be fatal if not promptly diagnosed and treated
* Non- P. falciparum malaria rarely requires hospitalization

Uncomplicated malaria
* P. vivax, ovale, malariae, chloroquine-susceptible falciparum
o Chloroquine
o Primaquine for dormant liver forms
* Chloroquine-resistant falciparum
o Quinine plus doxycycline
o Mefloquine
o Atovaquone plus proguanil (AP)
o Artemisins (common in SE Asia due to multi-drug resistance)

Treatment Severe malaria
* Drug options
o Quinidine gluconate—only approved parenteral agent in US
o Artemisin
* Mefloquine
* Doxycycline
* Nets
* 30-35% DEET
* Permethrin spray for clothing and nets

And don’t forget baggage malaria!
Case 5
* Mrs. R. was treated with IV quinidine and improved rapidly.
* In retrospect, Mr. R. had died from untreated blackwater fever
o Few parasites in peripheral blood
o Acute renal failure

Case 6
* A 24-year-old white male army officer
* Referred to the VA ID clinic with a 3-month history of a lesion on his right leg, developing approximately 2 weeks after returning from Iraq
* Recent travel history: 1 month in Kuwait and 2 months traveling between Kuwait and Iraq
* Recalled being bitten numerous times by small flying insects and other nasty “bugs”

Physical examination essentially normal except for:
* Non-tender (20 × 15 mm) scaly erythematous plaque with a moist central erosion of the left popliteal area.
* There was no lymphadenopathy and no mucosal lesions were noted

An intact macrophage practically filled with amastigotes (arrows),

* Tropical areas where phlebotomine sandfly is common: South America, India, Bangladesh, Middle East, East Africa
* Sandfly introduces flagellated promastigote into human  ingested by macrophages  develops into nonflagellated amastigote
* Cutaneous
o Most common among farmers, settlers, troops and tourists in Mid East (L. major and tropica), Central and South America (L. mexicana, braziliensis, amazonensis, and panamensis)
o L. mexicana reported in Texas
* Visceral (kala azar)
o Anemia, leukopenia, thrombocytopenia, hypergammaglobulinemia common

Leishmaniasis: Diagnosis
* Biopsy and Giemsa stain with amastigotes
* Species most prevalent in different places
# L. donovani – India
# L. infantum – Mid East
# L. chagasi – Latin America
# L. amazonensis -- Brazil

Visceral Leishmaniasis
* Dissemination of amastigotes throughout the reticulendothelial system of the body
o Spleen
o Bone marrow
o Lymph nodes
* Opportunistic infection in AIDS patients
* Ineffective humeral response

Splenic aspirate
* Most satisfactory method
* Spleen must be at least 3cm below LCM
* Aspirate stained with Giemsa

Leishmaniasis: treatment
* Only drug approved in US is Amphotericin B
* Treatment of cutaneous disease depends on anatomic location
* Many spontaneously heal and do not require treatment

* The factors determining the form of leishmaniasis:
o Leishmanial species
o Geographic location
o Immune response of the host

Case 7
* 38-year-old businessman
* Previously fit
* 2-week history of fever since returning from Brazil business trip
* Flu-like symptoms and myalgia
* Had consumed steak tartare in Brazil
* Results all unremarkable---normal WBC and ESR; negative smears; CXR and urine OK
* Continued to have fever, tachycardia and myalgia

Case 8
* A 29-yr-old man with AIDS (CD4 count=59) presents with a 2 week history of headache, fevers and new onset seizures
* He had not been taking any antiretroviral medications

Cases 7 & 8
What parasite could
cause this picture?
AIDS Patient
Toxoplasma gondii cyst in brain tissue with H & E stain (100x)
For the businessman…
* Toxoplasma serology was positive at a very high titer
* Responded to treatment with sulphonamide + pyrimethamine
* No relapse

* Eating oocysts excreted by cats harboring sexual stages of parasite
* Outbreaks traced to inadequately cooked meat of herbivores (raw beef)
* Mutton

Toxoplasma gondii
* Worldwide distribution
* Human infection
o Ingestion of cysts in undercooked meat of herbivores
o Water/food contaminated with oocysts
o Congenitally
o Infected organs, blood (less common)
* Prevalence of latent infection in US about 10%; France about 75%
o Generally higher in less-developed world
o 50% in AIDS patients; up to 90% of AIDS patients in developing world

Toxoplasma gondii: Immunocompetent hosts
* Latent infection (persistence of cysts) is generally asymptomatic
* Cervical lymphadenopathy (10-20%)
* Mono-like presentation (<1% of all mono-like illnesses)
* Chorioretinitis
* Very rare: myocarditis, myositis

Toxoplasma gondii: Immunocompromised hosts
* Often life-threatening
* Almost always reactivation of latent infection
o Encephalitis most common manifestation
o Usually subacute onset/focal (if CD4< 200)
o Mental status changes, seizures, weakness, cranial nerve abnormalities, cerebellar signs,
o Can present as acute hemiparesis/language deficit
o Usually multiple ring-enhancing lesions on CT/MRI
* Pneumonitis
* Chorioretinitis

Toxoplasma gondii: Clinical manifestations
* Immunocompromised hosts
o Non-AIDS (transplants, hematologic malignancies)
+ CNS 75%
+ Myocardial 40%
+ Pulmonary 25%

Toxoplasma gondii: Clinical manifestations
* Congenital
* Acute infection asymptomatic in mother
* Clinical manifestations range: no sequelae to sequelae that develop at various times after birth
o Chorioretinitis
o Strabismus
o Blindness
o Epilepsy, mental retardation, pneumonitis, microcephaly, hydrocephalus, spontaneous abortion, stillbirth

Toxoplasma gondii: diagnosis
* Clinical suspicion crucial
* Serology is primary method of diagnosis
o IgM, IgG
* Histopathology
o Tachyzoites in tissue sections or body fluid (difficult to stain)
o Multiple cysts near necrotic, inflammatory lesions

Toxoplasma gondii: Treatment
* Immunocompetent adults are usually not treated unless visceral disease is overt or symptoms are severe and persistent
* Immunodeficient patients
o Latent disease: not treated
o Active disease: pyrimethamine + sulfadiazone + folinic acid

Toxoplasma gondii: Treatment
* Congenital:
o Treatment of acute infected pregnant women decreases but does not eliminate transmission
+ Spiramycin
o If fetal infection is documented, treat with pyrimethamine + sulfadiazone + folinic acid
o Postnatal treatment: pyrimethamine + sulfadiazone + folinic acid
Case 22
* 25-year-old Caucasian woman presented with 1-week history of fever, chills, sweating, myalgias, fatigue
* No travel abroad
* Had gone cranberry picking in Massachusetts approx 3 weeks earlier
* PE: anemic, hepatosplenomegaly
* Blood workup: hemolytic anemia, reduced platelets

Thick smear
Thin smear
Maltese cross
* Babesiosis caused by hemoprotozoan parasites of the genus Babesia
* >100 species reported
* Few actually cause human infection
* Babesia microti
* Life cycle involves two hosts:
o Deer tick, Ixodes dammini, (definitive host) introduces sporozoites into white-footed mouse
* Once ingested by an appropriate tick gametes unite and undergo a sporogonic cycle resulting in sporozoites
* Humans enter cycle when bitten by infected ticks
Deer are the hosts upon which the adult ticks feed and are indirectly part of the Babesia cycle as they influence the tick population
* Clindamycin* plus quinine
* Atovaquone* plus azithromycin*
* Exchange transfusion in severely ill patients with high parasitemia
* Approved by FDA

Case 9
* 6-year-old son of seasonal farm worker
* Presents with cough and fever, wheeze
* CXR reveals a lobar pneumonia
* Admitted for initial therapy
* After 2 days of antibiotics, with good defervescence, a worm is found in his bed
* Stool exam reveals …

Ascaris lumbricoides
* In GI tract, few symptoms in light infections
o Nausea
o Vomiting
o Obstruction of small bowel or common bile duct.
* Pulmonary: symptoms due to migration
o Alveoli (verminous pneumonia)—cough, fever wheeze, dyspnea, X-ray changes, eosinophilia
Effects of Adult Ascaris Worms
* Depends on worm load
* Effects
o Mechanical: obstruction, volvulus, intussusception, appendicitis, obstructive jaundice, liver abscesses, pancreatitis, asphyxia
* Toxic and Metabolic
o Malnutrition (complex)

Ascaris lumbricoides Diagnosis
* Characteristic eggs on direct smear examination
* If treating mixed infections, treat Ascaris first
o Mebendazole
o Pyrantel
* Control:
o Periodic mass treatment of children, health education, environmental sanitation
Case 10
* 11-year-old female
* Doing poorly in school
* Not sleeping well
* Anorectic
* Complains of itching in rectal region throughout the day
* A Scotch-tape test reveals…
Enterobius (Pinworm)
* 18 million infections in U.S.
* Incidence higher in whites
* Preschool and elementary school most often
* Mostly asymptomatic
* Nocturnal anal pruritis cardinal feature due to migration and eggs
* May have insomnia, possible emotional symptoms
* DS-eggs or adults on perineum {scotch tape}
* Mebendazole 100 mg. Repeat in 2 weeks. Pyrantel pamoate 11 mg/kg; repeat 2 weeks
* 69-year-old male was admitted to VA Hospital
* Far East Prisoner of War (FEPOW)
* COPD--steroids for 3 years
* 2-month history of nausea, vomiting and anorexia
* 25 pounds weight loss

Case 11
On the day of admission…

* Fever, confusion, and not able to get out of bed---transported to the hospital
* Initial blood work:
o Elevated WBC
o Raised eosinophil count 4 times normal
* Underwent UGI endoscopy
* Duodenal biopsy obtained

Strongyloides: Crucial Aspects of Life Cycle
* Infection acquired through penetration of intact skin
* Infection may persist for many years via autoinfection
* In immunocompromised patients, there is risk of dissemination or hyperinfection
o Hyperinfection syndrome

Disseminated Strongyloidiasis
* High mortality75%
* Penetration of gut wall by infective larvae
* Gut organisms carried on the surface of larvae results in polymicrobial sepsis, meningitis
* Larvae disseminate into all parts of body: CNS, lungs, bladder, peritoneum

Summary—Clinical Findings
* Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?)
* Gl symptoms in about two-thirds:
o Abdominal pain
o Bloating
o Diarrhea
o Constipation
* Wheezing, SOB, hemoptysis

Summary—Clinical Findings
* Skin rash or pruritis in ~ one-third
o Larva currens (racing larva)
o Intensely pruritic
o Linear or serpiginous urticaria with flare that moves 5-15 cm/hr
o Usually buttocks, groin, and trunk
o In dissemination, diffuse petechiae and purpura

Summary-Clinical Findings
* Eosinophilia 60-95%
* Less if on steroids

Case 12
* 57 year old farmer from Dixie County
* Presents with profound SOB
* Physical examination: anemic otherwise unremarkable
* Laboratory examination reveals a profound anemia (hct 24) with aniso and poikilocytosis
* Remainder of laboratory examination normal.

* Hookworm responsible for development of USPHS
* Caused by two different species (North American and Old World)
* Very similar to strongyloides in life cycle
* Attaches to duodenum, feeds on blood
* Elaborates anticoagulant, attaches and reattaches many times
* Loss of around 0.1 ml/d of blood per worm

Case 13
* 8-yr-old schoolgirl visiting the U.S. from Malaysia
* 1 week history of epigastric pain, flatulence, anorexia, bloody diarrhea
* No eosinophilia noted
* Clinical diagnosis of amoebic dysentery made
* However, microscopy of stool prep…

Trichuris trichiura (Whipworm)
* Common in Southeast U.S.
* Frequently coexists with ascaris
* Entirely intraluminal life cycle—eggs are ingested
* Frequently asymptomatic
* Severe infections: diarrhea, abdominal pain and tenesmus
* Rectal prolapse in children
* DS-eggs in stool
* Mebendazole 100 mg bid x 3 days

Case 14
* 18-year-old trailer park handyman seen in ER
* Worked under trailers wearing shorts and no shirt
* Developed intensely pruritic skin rash
* Unable to sleep
* WBC 18,000
* 65% eosinophils.

Case 15
* An 8 year old boy
* Presents with skin lesions and itching after spending the summer at a beach condo in St. Augustine with his family (mother, father, younger sister, dog and cat).
* Legs show several raised, reddened, serpiginous lesions that are intensely pruritic.

Diagnosis ?
Cutaneous Larva Migrans
* Caused by filariform larvae of dog or cat hookworm (Ancylostoma braziliense or Ancylostoma duodenale
* Common in Southeast U.S.
* Red papule at entry with serpiginous tunnel
* Intense pruritis
* Self limiting condition
* Diagnosis clinical
* Topical or oral thiabendazole 25 mg/kg bid for 3-5 days
* May use ethyl chloride topically

Cutaneous larva migrans (creeping eruption)
* More common in children
o Larvae penetrate skin and cause tingling followed by intense itching.
* Eggs shed from dog and cat bowels develop into infectious larvae outside the body in places protected from desiccation and extremes of temperature
* Shady, sandy areas under houses, at beach, etc.
Usually not associated with systemic symptoms

Cutaneous larva migrans (creeping eruption)
* Diagnosis and treatment
* Skin lesions are readily recognized
* Usually diagnosed clinically
* Generally do not require biopsy
# Reveal eosinophilia inflammatory infiltrate
# Migrating parasite is generally not seen
* Stool smear will reveal eggs

Visceral Larva Migrans
* Infection with dog or cat round worms
* Toxocara canis; Toxocara catis
* Underdiagnosed based on seroprevalence surveys
* Heavy infections associated with fever, cough, nausea, vomiting, hepatomegaly, and eosinophilia
* Uncommon in adults
* Ocular type more common in adults
* Diagnosis-ELISA
* Thiabendazole: 25 mg/kg bid X 5 days

Case 17
* A 34 yr-old woman from Saudi Arabia
* Radiation and cyclophosphamide, adriamycin, vincristine and prednisone for diffuse large B cell lymphoma of the neck.
* Mild eosinophilia (AEC=500) at the time of diagnosis
* 4 months after initiation of chemo, c/o intermittent diffuse abdominal pain, bloating, constipation and occasional rectal bleeding.
* Absolute eosinophil count: 1000
* No evidence of lymphoma found on re-staging
* Completed chemo, was deemed to be in complete remission, but had persistence of GI complaints.
* Upper endoscopy was unrevealing.
* Colonoscopy and biopsy revealed granulomatous inflammation, prominent eosinophilic infiltrate, surrounding a collection of eggs.

Chronic intestinal schistosomiasis
* The patient was treated with praziquantel and did not have relapse of symptoms at 2-year follow-up
* AEC=250

Schistosomiasis: Epidemiology and life cycle
* Cercariae in fresh water penetrate human skin.
* Cercariae mature to schistosomulae, which enter the bloodstream, liver and lung.
* Mature worms migrate to the venous system of the small intestine (S. japonicum), large intestine (S. mansoni) or bladder venous plexus (S. haematobium).

Schistosomiasis: Epidemiology and life cycle
* Worms release eggs for many years into stool or urine, resulting in fresh water contamination.
* Freshwater snails are infected by miracidia and are necessary for the production of cercariae and human infection.
* S. mansoni
o South America, Caribbean, Africa, Mid East
* S. japonicum
o China and Philippines
* S. haematobium
o Africa, Mid East

Schistosomiasis: Clinical manifestations
* Three stages of disease, corresponding to life cycle within human hosts
* Swimmer’s itch
o Within 24 hours of cercariae penetration
* Serum sickness syndrome (Katayama fever)
o 4 to 8 weeks later when worms mature and release eggs
+ Fever, headache, cough, chills, sweating, lymphadenopathy, hepatosplenomegaly  usually resolves spontaneously
+ Elevated IgE and eosinophils
+ Most common with S. japonicum

Chronic Schistosomiasis
* Granulomatous reaction to egg deposition in intestine, liver, bladder, lungs
* S. mansoni, japonicum
o Chronic diarrhea, abdominal pain, blood loss, portal hypertension, hepatosplenomegaly, pulmonary hypertension
o Eosinophilia is common
o Liver function tests are usually normal
* S. Haematobium
o Hematuria, bladder obstruction, hydronephrosis, recurrent UTIs, bladder cancer

Diagnosis and Treatment

* Detection of characteristic eggs in stool, urine or tissue biopsy is diagnostic
o Urine is best between 12N and 2Pm, passed through 10 µm filter to concentrate eggs
* Antibody tests are available, but limited by sensitivity, specificity
* Praziquantel is the drug of choice

S. mansoni
S. haematobium
S. japonicum

Case 18
* 15-yr-old girl
* Fever, rash, swelling around the eye and hands, severe headaches
* Fatigue, aching muscles and joints
* Swollen lymph nodes on the back of neck
* Weight loss
* Progressive confusion, personality changes
* Sleeping for long periods of the day
* Insomnia
* Had been on a safari with parents to West Africa
* Dusky red lesion developed within 1 week
* Vaguely remembered being bitten by a fly

* Blood films
* Lumbar puncture

Blood smear
African trypanosomiasis
Trypanosoma brucei gambiense
Tsetse fly
* Suramin
* Melasoprol

Case 19
* 6-yr-old boy recently arrived from Brazil
* Swelling around the eye
* Conjunctivitis
* Fever
* Enlarged lymph nodes
* Hepatosplenomegaly
* Had stayed in a hotel—adobe style with thatched roof

Blood smear
Reduviid bug (assassin bug)
Chagas disease:
Clinical manifestations
* Local edema is followed by fever, malaise, anorexia
o More rarely: myocarditis, encephalitis
* Years later: chronic Chagas Disease (10-30%)
o Heart: primary target
+ Cardiomyopathy associated with CHF, emboli, arrythmias
o GI tract: mega-esophagus, megacolon

Chagas disease: Diagnosis and treatment
* Acute disease is diagnosed by seeing trypomastigotes on peripheral blood smear
* Chronic disease is diagnosed by ELISA detecting IgG antibody to T. cruzi
* Treatment slows the progression of heart disease

Chagas Disease
* Public health implications in the US
* Chronic
o Cardiomyopathy
o Megaesophagus
o Megacolon
* Blood transfusion
* Transplant
o Solid organ
o Musculoskeletal allograft tissue

Case 20
* 20-yr-old male
* Abdominal pain and nausea for several months
* More common in the morning
* Relieved by eating small amounts of food
* Some diarrhea and irritability
* Weight loss
* Pruritus ani
* Passage of white “bits”

Taenia saginata
* Ingestion of raw or poorly cooked beef
* Cows infected via the ingestion of human waste containing the eggs of the parasite
* Cows contain viable cysticercus larvae in the muscle
* Humans act as the host only to the adult tapeworms
* Up to 25 meters in the lumen of intestine
* Found all over the world, including the U.S.

Beef Tapeworm
* Praziquantel
* Albendazole
* Niclosamide
Tapeworms (Cestodes)
* Adult worms inhabit GI tract of definitive vertebrate host
* Larvae inhabit tissues of intermediate host
* Humans
o Definitive for T. saginata
o Intermediate for Echinococcus granulosus (hydatid)
o Both definitive and intermediate for T. solium
* Adult worms shed egg-containing segments in stool ingested by intermediate host larval form in tissues

Case 21
* A 33 year-old Indian man was admitted with a grand mal seizure
* 2 yrs PTA, he had vertigo and CT revealed an enhancing calcified lesion in left temporal-parietal region
* FHx: Brother had grand mal seizure several years earlier
* Throughout his life, he has eaten a diet heavy in pork
* Difficulty speaking and loss of consciousness while on the phone
* Co-workers noticed generalized tonic-clonic seizures lasting 10 minutes.
* CT revealed new localized edema around the previously identified lesion and a second contiguous ring enhancing lesion.
* He received phenytoin (Dilantin, an antiseizure med) and 5 days of corticosteroids.

Case 21
* ELISA titer was positive for antibodies against Taenia solium.
* The neurosurgeons tell you that resection is impossible because of the extent and location of the lesion

* Human infected with the larval stage of Taenia solium
* Humans can serve as definitive or intermediate host
* Eggs are ingested, or possibly get to stomach by reverse peristalsis
* Probably much more common than is reported, since most infections are asymptomatic
* Symptoms depend on location of cysts, but frequently include motor spasms, seizures, confusion, irritability, and personality change
* In the eye, often subretinal or in vitreous. Movement may be seen by the patient. Pain, amaurosis, and loss of vision may occur.
* Clinical manifestations
o Adult worms rarely cause sxs
o Larvae penetrate intestine, enter blood, and eventually encyst in the brain.
+ Cerebral ventircles  hydrocephalus
+ Spinal cord  compression, paraplegia
+ Subarachnoid space  chronic meningitis
+ Cerebral cortex  seizures
o Cysts may remain asymptomatic for years, and become clinically apparent when larvae die
o Larvae may encyst in other organs, but are rarely symptomatic

* Diagnosis
o CT and MRI preferred studies
+ Discrete cysts that may enhance
+ Usually multiple lesions
# Single lesions especially common in cases from India
+ Older lesions may calcify
+ Lymphs or eos, low glucose, elevated protein
o Serology
+ Especially in cases with multiple cysts
* Treatment
o Complex and controversial
o Praziquantel and albendazole may kill cysts, but death of larvae can increase inflammation, edema and exacerbate sxs
o When possible, surgical resection of symptomatic cyst is preferred
o Corticosteroids vs. edema and inflammation; antiseizure meds

Case 21

* He was not treated with praziquantel or albendazole
* He continued to receive dilantin for seizures and was treated with corticosteroids for edema

Classification of Parasitic Diseases
* Protozoa: amoeba; flagellates; ciliates
* Metazoa (two phyla)
o Helminths (worms)
+ Nematodes
# Intestinal
# Extra-intestinal
+ Flatworms (platyhelminths)
# Cestodes (tapeworms)
# Trematodes (flukes)
o Arthopods (ectoparasites): scabies, lice, fly larvae

General rules of treatment
* Protozoa: require species-specific treatment
* Metozoa: species-specific

General rules of treatment of metazoa
Mebendazole or Albendazole
Ivermectin, doxycycline
Praziquantel, Albendazole, Niclosamide

Emerging Infections and Medical Procedures.ppt


Differentiating Babesia from Malaria

Differentiating Babesia from Malaria
By:Devak Desai

Case Presentation
* Middle aged hypertensive and asplenic man presented with a pruritic rash on his right buttock accompanied by flu-like symptoms.
* 1010, arthralgias, myalgias, some nausea, and general malaise, and decreased appetite.
* Reports walking through a wooded area on Martha’s Vineyard, an island off the coast of Mass.
* PE shows a well nourished man with no significant findings other than an erythmatous oropharynx without exudate.

Laboratory Data
* Normal WBC differential
* Blood smear: numerous intraerythrocytes involving 2.7% of RBCs
* Direct Combs test was negative
* Positive serologic test for Lyme Disease

Peripheral Blood Smear
* Numerous erythrocytes are infected with the predominantly ring or pear-shaped form of Babesia microti.
* Pleomorphic rings with 1-3 chromotin dots per parasite.
* 3 dots is unique for Babesia.

Host Infection Cycle
* Infection begins when sporozoites are released from the deer tick’s salivary gland during a blood meal.
* Sporozoites replicate directly in RBCs.
* Attachment and adsorption seems mediated through the C3b receptor.
* During invagination a clear vacuole appears.
* Babesia divided by asynchronous budding.
* The replicating structures are now called trophozoites.
* This is an asynchronous process with varying degrees of hemolysis.

Life cycle of Babesia spp. in the tick and vertebrate hosts
High Power
* Ring shaped trophozites
* The intraerythrocytic trophozoites multiply by binary fission or schizogony, forming two to four separate merozoites.
* White eccentric “food vacuole” in a ring form.
* Very transient stage in Malaria. Very rarely seen.

the famous Maltese Cross
* Presence of 4 daughter merozoites in a tetrad is pathomnemonic.
* However, rarely seen.
* Never seen in malaria.

Multiply infected RBCs
* RBCs can be infected with multiple organisms at the same time. Up to 12 parasites may infect a single RBC.
* Plasmodium has up to 3 parasites/RBC.
* Unremarkable RBCs.

Other Sightings
* Parasite with a peripheral nuclear band
* Basket cell
* Syncytium of extracellular parasites
* Far more common in Babesia infections

Malaria Review
* There are >100 specicies of this intracellular parasite.
* Babesia microti is the predominant human pathogen, endemic to the NE and Midwest.
* 10-20% of adults are seropositive in endemic areas
* Natural parasite reservoir is rodents
* Carried by the hard-bodied Ixodes Deer tick.
* Also carries agents for Lyme Disease, and Ehrlichoisis.
* Can also be transferred transplacentally and through blood transfusion.

Clinical presentation
* Ranges from asymptomatic infection to fatal illness (rare)
* No direct correlation between parasitemia and severity.
* More severe infection tends to occur in immunnocompromised, elderly, and the very young.
* The extreme end of the spectrum is often described as a malaria-like infection; symptoms may include malaise, chills, mylagia, anemia, fatigue, and fever (as high as 1040).
* Some cases also described emesis, night sweats, weight loss, and hematuria.

Special Case – Splenectomy
* Most important risk factor for infection, esp. severe.
* Illness appears suddenly, with hemoglobinuria as the presenting symptom followed by jaundice due to severe hemolysis.
* Parasitemia can reach 80% of RBCs
* Can be a medical emergency.
* In the most severe cases, patients develop a shock-like picture, with renal failure and pulmonary edema.
* Chronic disease with many relapses over months to years may occur if not treated.

* It is estimated from serologic surveys that as many as 13% of Lyme disease patients in babesia-endemic areas are coinfected with B. microti
* The initial symptoms of both babesiosis and Lyme disease overlap significantly.
* Like babesiosis, Lyme disease also presents with nonspecific symptoms of fever,fatigue, and other flu-like symptoms.
* Patients coinfected with B. microti and B. burgdorferi experience more severe symptoms, but does not increase the duration of Babesia parisitemia.
* Doxycycline will not kill Babesia.

* Diagnosis is based on clinical suspicion and history of exposure.
* Thick and thin smears remain most clinically used
* However, it is necessary to examine 200 to 300 oil immersion fields before declaring a specimen negative.
* Various PCR detection assays are available for detection of B microtic and other species.
* More sensitive but also more time consuming and expensive.
* Indirect fluorescent antibody test can also be used as a confirmatory test.
* Can have false negatives (HIV) or false pos (autoimmune)

* Current treatment is Quinine plus Clindamycin
* Better alternative treatment is Atovaquone plus Azithromycin
* This combo is almost as effective with fewer side effects.
* 72% receiving quinine and clindamycin had side effects attributed to the drugs—diarrhea, tinnitus, or vertigo
* 15% receiving atovaquone plus azithromycin experienced side effects (usually diarrhea or rash).
* For severe cases (asplenic) with high levels of parasitemia, RBC exchange transfusions may also be necessary.

* History: check for recent travel
* Symptoms: Babesia is milder and tends not to be cyclic.
* Smear: Babesia has no schizonts, gametocyes, or ameboid trophozoites.
* Lab tests: PCR or indirect antibody test.

* Major deterrents to the diagnosis of babesiosis include the low index of suspicion by physicians (except in endemic areas), non-specific flu-like signs, and the use of automated cell readers that cannot detect merozoites in erythrocytes
* Disease is increasing in prevalence due to more people living in rural tick infested areas and as the number of immunocompromised in increasing.
* Also environmental such as the exponential rise in deer populations.
* Blood transfusion risk becoming an increasing problem.

Differentiating Babesia from Malaria.ppt


06 October 2009


By :
James Yost, MD, MS, MBA
Emory Family Medicine

* Definition
* Epidemiology
* Physiology
* Pathophysiology
* Types
* Clinical Manifestations
* Diagnosis
* Treatment

* Definition:
o Commonly defined as a serum sodium concentration 135 meq/L
o Hyponatremia represents a relative excess of water in relation to sodium.
* Epidemiology:
o Frequency
+ Hyponatremia is the most common electrolyte disorder
+ incidence of approximately 1%
+ prevalence of approximately 2.5%
+ surgical ward, approximately 4.4%
+ 30% of patients treated in the intensive care unit
o Mortality/Morbidity
+ Acute hyponatremia (developing over 48 h or less) are subject to more severe degrees of cerebral edema
# sodium level is less than 105 mEq/L, the mortality is over 50%
+ Chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema
# Brainstem herniation has not been observed in patients with chronic hyponatremia
o Age
+ Infants
# fed tap water in an effort to treat symptoms of gastroenteritis
# Infants fed dilute formula in attempt to ration
+ Elderly patients with diminished sense of thirst, especially when physical infirmity limits independent access to food and drink
* Physiology
o Serum sodium concentration regulation:
+ stimulation of thirst
+ secretion of ADH
+ feedback mechanisms of the renin-angiotensin-aldosterone system
+ renal handling of filtered sodium
o Stimulation of thirst
+ Osmolality increases
# Main driving force
# Only requires an increase of 2% - 3%
+ Blood volume or pressure is reduced
# Requires a decrease of 10% - 15%
+ Thirst center is located in the anteriolateral center of the hypothalamus
# Respond to NaCL and angiotensin II
o Secretion of ADH
+ Synthesized by the neuroendocrine cells in the supraoptic and paraventricular nuclei of the hypothalamus
+ Triggeres:
# Osmolality of body fluids
* A change of about 1%
# Volume and pressure of the vascular system
+ Increases the permeability of the collecting duct to water and urea
o renin-angiotensin-aldosterone
+ Renin
# Stemuli are perfusion pressure, sympathetic activity, and NaCl delivery to the macula densa
# Increase in NaCl delivery to the macula decreases the GFR by decrease in the renin secretion
+ Aldosterone
# Reduces NaCl excretion by stimulating it’s resorption
* Ascending loop of Henle
* Distal tubule
* Collecting duct
o extracellular-fluid and intracellular-fluid compartments make up 40 percent and 60 percent of total body water
o renal handling of water is sufficient to excrete as much as 15-20 L of free water per day
o sodium is the predominant osmole in the extracellular fluid (ECF) compartment and serum

* Pathophysiology
o hyponatremia can only occur when some condition impairs normal free water excretion
o acute drop in the serum osmolality:
+ neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space
+ Swelling of the brain cells elicits 2 responses for osmoregulation, as follows:
# It inhibits ADH secretion and hypothalamic thirst center
# immediate cellular adaptation
* Types
o Hypovolemic hyponatremia
o Euvolemic hyponatremia
o Hypervolemic hyponatremia
o Redistributive hyponatremia
o Pseudohyponatremia
Hypovolemic hyponatremia
* develops as sodium and free water are lost and/or replaced by inappropriately hypotonic fluids
* Sodium can be lost through renal or non-renal routes
* Nonrenal loss
o GI losses
+ Vomiting, Diarrhea, fistulas, pancreatitis
o Excessive sweating
o Third spacing of fluids
+ ascites, peritonitis, pancreatitis, and burns
o Cerebral salt-wasting syndrome
+ traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial surgery
+ Must distinguish from SIADH
* Renal Loss
o Acute or chronic renal insufficiency
o Diuretics

Euvolemic hyponatremia
* Normal sodium stores and a total body excess of free water
o Psychogenic polydipsia, often in psychiatric patients
o Administration of hypotonic intravenous or irrigation fluids in the immediate postoperative period
o administration of hypotonic maintenance intravenous fluids
o Infants who may have been given inappropriate amounts of free water
o bowel preparation before colonoscopy or colorectal surgery
o downward resetting of the osmostat
o Pulmonary Disease
+ Small cell, pneumonia, TB, sarcoidosis
o Cerebral Diseases
+ CVA, Temporal arteritis, meningitis, encephalitis
o Medications
+ SSRI, Antipsychotics, Opiates, Depakote, Tegratol

* Total body sodium increases, and TBW increases to a greater extent.
* Can be renal or non-renal
o acute or chronic renal failure
+ dysfunctional kidneys are unable to excrete the ingested sodium load
o cirrhosis, congestive heart failure, or nephrotic syndrome

Redistributive hyponatremia
o Water shifts from the intracellular to the extracellular compartment, with a resultant dilution of sodium. The TBW and total body sodium are unchanged.
+ This condition occurs with hyperglycemia
+ Administration of mannitol
* Pseudohyponatremia
o The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged.
+ hypertriglyceridemia
+ multiple myeloma
* Clinical Manifestations
o most patients with a serum sodium concentration exceeding 125 mEq/L are asymptomatic
o Patients with acutely developing hyponatremia are typically symptomatic at a level of approximately 120 mEq/L
o Most abnormal findings on physical examination are characteristically neurologic in origin
o patients may exhibit signs of hypovolemia or hypervolemia
* Diagnosis
o CT head, EKG, CXR if symptomatic
o Repeat Na level
o Correct for hyperglycemia
o Laboratory tests provide important initial information in the differential diagnosis of hyponatremia
+ Plasma osmolality
+ Urine osmolality
+ Urine sodium concentration
+ Uric acid level
+ FeNa
o Plasma osmolality
+ normally ranges from 275 to 290 mosmol/kg
+ If >290 mosmol/kg :
# Hyperglycemia or administration of mannitol
+ If 275 – 290 mosmol/kg :
# hyperlipidemia or hyperproteinemia
+ If <275 mosmol/kg :
# Eval volume status
o Plasma osmolality < 275 mosmol/kg
+ Increased volume:
# CHF, cirrhosis, nephrotic syndrome
+ Euvolemic
# SIADH, hypothyroidism, psychogenic polydipsia, beer potomania, postoperative states
+ Decreased volume
# GI loss, skin, 3rd spacing, diuretics
o Urine osmolality
+ Normal value is > 100 mosmol/kg
+ Normal to high:
# Hyperlipidemia, hyperproteinemia, hyperglycemia, SIADH
+ < 100 mosmol/kg
# hypoosmolar hyponatremia
* Excessive sweating
* Burns
* Vomiting
* Diarrhea
* Urinary loss
o Urine Sodium
+ >20 mEq/L
# SIADH, diuretics
+ <20 mEq/L
# cirrhosis, nephrosis, congestive heart failure, GI loss, skin, 3rd spacing, psychogenic polydipsya
o Uric Acid Level
+ < 4 mg/dl consider SIADH
o FeNa
+ Help to determine pre-renal from renal causes
* Treatment
o four issues must be addressed
+ Asyptomatic vs. symptomatic
+ acute (within 48 hours)
+ chronic (>48 hours)
+ Volume status
o 1st step is to calculate the total body water
+ total body water (TBW) = 0.6 × body weight
o next decide what our desired correction rate should be
o Symptomatic
+ immediate increase in serum Na level by 8 to 10 meq/L in 4 to 6 hours with hypertonic saline is recommended
o acute hyponatremia
+ more rapid correction may be possible
# 8 to 10 meq/L in 4 to 8 hours
o chronic hyponatremia
+ slower rates of correction
# 12 meq/L in 24 hours

* Symptomatic or Acute
o Treatment Cont. - Here comes the Math!!!
+ estimate SNa change on the basis of the amount of Na in the infusate
+ ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
# ΔSNa is a change in SNa
# [Na + K]inf is infusate Na and K concentration in 1 liter of solution
o OH MY GOD, what did he just say!!!!!!!!!!!!!!!!!!

* IV Fluids
o One liter of Lactated Ringer's Solution contains:
+ 130 mEq of sodium ion = 130 mmol/L
+ 109 mEq of chloride ion = 109 mmol/L
+ 28 mEq of lactate = 28 mmol/L
+ 4 mEq of potassium ion = 4 mmol/L
+ 3 mEq of calcium ion = 1.5 mmol/L
o One liter of Normal Saline contains:
+ 154 mEq/L of Na+ and Cl−
o One liter of 3% saline contains:
+ 514 mEq/L of Na+ and Cl−

* Example:
o a 60 kg women with a plasma sodium of 110 meq/L
o Formula:
+ ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
o What is the TBW?
o How high will 1 liter of normal saline raise the plasma sodium?
* Answer:
o TBW is 30 L
o Serum sodium will increase by approximately 1.4 meq/L for a total SNa of 111.4 meq/L

* Example:
o a 90 kg man with a plasma sodium of 110 meq/L
o Formula:
+ ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
o What is the TBW?
o How high will 1 liter of 3% saline raise the plasma sodium?
* Answer:
o TBW is 54 L
o Serum sodium will increase by approximately 7.3 meq/L for a total SNa of 117.3 meq/L

* Asymptomatic or Chronic
+ response to isotonic saline is different in the SIADH
+ In hypovolemia both the sodium and water are retained
+ sodium handling is intact in SIADH
+ administered sodium will be excreted in the urine, while some of the water may be retained
# possible worsening the hyponatremia


* Asypmtomatic or Chronic
+ Water restriction
# 0.5-1 liter/day
+ Salt tablets
+ Demeclocycline
# Inhibits the effects of ADH
# Onset of action may require up to one week

* Example:
+ 85 y/o male with weakness and head ache
+ SNa is 118 mEq/L
+ Plasma osmolality is 254 mosmol/kg
+ Urine osmolality is 130 mosmol/kg
+ Urine sodium >20 mEq/L
+ Uric acid is 3mg/dl
o What type of hyponatremia does this patient have?
o What additional labs/studies would you want?

* Example Cont.:
o Noncontrast CT Head:
* Tx
o Call Neurology and neurosurgery
o Free water restriction

* Example:
o 63 y/o female at 75 Kg with N/V/D for 4 days
o SNa is 108 mEq/L
o She has had one seizure in the ambulance
# Plasma osmolality is 251 mosmol/kg
# Urine osmolality is 47 mosmol/kg
# Uric acid is 6mg/dl
o What type of hyponatremia does this patient have?
o What additional labs/studies would you want?
* How will you Tx her?
o Calculate the total body water
+ 0.5 x weight = 37.5 L
o What rate of correction do you want?
+ 8 to 10 mEq/L in 6 to 8 hours
o What fluid will you use?
+ 3% Saline
o How will you calculate the amount of sodium to give her?
+ ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
o How will her sodium increase after 1 liter of 3% saline?
+ By 10.8 mEq/L to 118.8 mEq/L

* What other medication will she need?
o Lasix and a foley
* Her sodium increases to 118.8 mEq/L over the next 8-10 hours. How will you continue to correct her hyponatremia?
o ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)
o ΔSNa = 154mEq/L – 118.8mEq/L ÷ 38.5L = 0.9 mEq/L
* So 2 liters of normal saline over the next 14 hours



Fluid, Electrolyte & Acid-Base Balance

Fluid, Electrolyte & Acid-Base Balance

Body Fluids
* Your body is 66% water
* Not evenly distributed – separated into compartments
* Able to move back and forth thru the cell membranes to maintain an equilibrium

Fluid Compartments
* Intracellular fluid – fluid inside cells [ICF]
* Extracellular fluid – fluid outside cells and all other body fluids --- ž is plasma [intravascular fluid], remaining ū is interstitial fluid. Small amount is localized as CSF, serous fluid, synovial fluid, humors of eye & endo/perilymph of ears

* Condition in which fluid accumulates in the interstitial compartment. Sometimes due to blockage of lymphatic vessels or by a lack of plasma proteins or sodium retention

Fluid Balance
* Amount in = amount out
* Average daily intake is 2500 ml [ fluids, food and metabolic water]
* Average daily output is 2500 ml [ urine, feces, perspiration, insensible perspiration]
* What can throw off these numbers?

Electrolyte Balance
* Def: - concentration of individual electrolytes in the body fluid compartments is normal and remains relatively constant.
* Electrolytes are dissolved in body fluids
* Sodium predominant extracellular cation, and chloride is predominant extracellular anion. Bicarbonate also in extracellular spaces
* Potassium is the predominant intracellular cation and phosphates are the predominant intracellular anion
* Cations are actively reabsorbed, anions passively follow by electrochemical attraction
* Aldosterone works at kidney tubules to regulate sodium & potassium levels
* Because of sodium and potassium influence, water will move between compartments
* Example: if high [sodium], then water will move from intracellular space to extracellular space due to osmotic pressure

Balance of other Electrolytes
* Calcium – hypercalcemia / hypocalcemia
* Magnesium – hypermagnesemia/ hypomagnesemia
* Phosphate – hyperphosphatemia/ hypophosphatemia
* Chloride – hyperchloremia/ hypochloremia
Acid - Base Balance
* Blood - normal pH of 7.2 – 7.45
* < 7.2 = acidosis > 7.45 = alkalosis
* 3 buffer systems to maintain normal blood pH
* Buffers
* Removal of CO2 by lungs
* Removal of H+ ions by kidneys
* Protein Buffer Systems
* Amino Acid buffers
* Hemoglobin buffers
* Plasma Protein buffers
* Phosphate Buffer Systems
* Carbonic Acid – Bicarbonate Buffer System
Maintenance of Acid-Base Balance
* Respiratory System: removal of CO2 by lungs – stabilizes the ECF, has direct effect on Carbonic Acid – Bicarbonate Buffer System

* Urinary System: removal of H+ ions by kidneys

Disturbances to Acid-Base Balance
* Respiratory Acidosis
* Respiratory Alkalosis
* Metabolic Acidosis [ lactic acidosis, ketoacidosis]
* Metabolic Alkalosis

Fluid, Electrolyte & Acid-Base Balance.ppt


Evaluation of Laboratory Data in Nutrition Assessment

Evaluation of Laboratory Data in Nutrition Assessment
By:Cinda S. Chima, MS, RD

Laboratory Data and the NCP
* Used in nutrition assessment (a clinical sign supporting nutrition diagnosis)
* Used in Monitoring and Evaluation of the patient response to nutritional intervention

Specimen Types
* Serum: the fluid from blood after blood cells and clot removed
* Plasma: fluid from blood centrifuged with anticoagulants
* Erythrocytes: red blood cells
* Leukocytes: white blood cells
* Other tissues: scrapings and biopsy samples
* Urine: random samples or timed collections
* Feces: random samples or timed collections
* Less common: saliva, nails, hair, sweat

Interpretation of Routine Medical Laboratory Tests
* Clinical Chemistry Panels
o Basic metabolic panel
o Comprehensive metabolic panel
* Complete blood count
* Urinalysis
* Hydration status

Clinical Chemistry Panels: Basic Metabolic Panel (BMP)
Also called Chem 7
o Electrolytes: Na+, K+, Cl-, HCO3 or total CO2
o Glucose
o Creatinine
Basic Metabolic Panel Charting Shorthand
Clinical Chemistry Panels: Comprehensive Metabolic Panel
* BMP except CO2
* Albumin
* Serum enzymes (alkaline phosphatase, AST [SGOT], ALT [SGPT]
* Total bilirubin
* Total calcium
Phosphorus, total cholesterol and triglycerides often ordered with the CMP

Clinical Chemistry Panels:
Complete Blood Count (CBC)
* Red blood cells
* Hemoglobin concentration
* Hematocrit
* Mean cell volume (MCV)
* Mean cell hemoglobin (MCH)
* Mean cell hemoglobin concentration (MCHC)
* White blood cell count (WBC)
* Differential: indicates percentages of different kinds of WBC

Clinical Chemistry Panels: Urinalysis
Leukocyte esterage
0.1-1 units/dl
Not detected
Not detected
2-8 mg/dl
6-8 (normal diet)
1.010-1.025 mg/ml
Specific gravity
Types of Assays
* Static assays: measures the actual level of the nutrient in the specimen (serum iron, white blood cell ascorbic acid)
* Functional Assays: measure a biochemical or physiological activity that depends on the nutrient of interest (serum ferritin, TIBC)
o (Functional assays are not always specific to the nutrient)

Assessment of Nutrient Pool
Assessment of Hydration Status
* Dehydration: a state of negative fluid balance caused by decreased intake, increased losses, or fluid shifts
* Overhydration or edema: increase in extracellular fluid volume; fluid shifts from extracellular compartment to interstitial tissues
o Caused by increase in capillary hydrostatic pressure or permeability
o Decrease in colloid osmotic pressure
o Physical inactivity
* Use laboratory and clinical data to evaluate pt

Isotonic fluid loss from the extracellular space caused by
* Fluid loss (bleeding, fistulas, nasogastric drainage, excessive diuresis, vomiting and diarrhea)
* Reduced fluid intake
* Third space fluid shift, when fluid moves out of the intravascular space but not into intracellular space (abdominal cavity, pleural cavity, pericardial sac) caused by increased permeability of the capillary membrane or decrease on plasma colloid osmotic pressure

Symptoms of Hypovolemia
* Orthostatic Hypotension (caused by change in position)
* Central venous and pulmonary pressures 
* Increased heart rate
* Rapid weight loss
* Decreased urinary output
* Patient cool, clammy
* Decreased cardiac output
* Ask the medical team!!
Treatment of Hypovolemia
* Replace lost fluids with fluids of similar concentration
* Restores blood volume and blood pressure
* Usually isotonic fluid like normal saline or lactated Ringer’s solution given IV
* Excess of isotonic fluid (water and sodium) in the extracellular compartment
* Osmolality is usually not affected since fluid and solutes are gained in equal proportion
* Elderly and those with renal and cardiac failure are at risk

Causes of Hypervolemia
* Results from retention or excessive intake of fluid or sodium or shift in fluid from interstitial space into the intravascular space
* Fluid retention: renal failure, CHF, cirrhosis of the liver, corticosteroid therapy, hyperaldosteronism
* Excessive intake: IV replacement tx using normal saline or Lactated Ringer’s, blood or plasma replacement, excessive salt intake
* Fluid shifts into vasculature caused by remobilization of fluids after burn tx, administration of hypertonic fluids, use of colloid oncotic fluids such as albumin

Symptoms of Hypervolemia
* No single diagnostic test, so signs and symptoms are key
* Cardiac output increases
* Pulse rapid and bounding
* BP, CVP, PAP and pulmonary artery wedge pressure rise
* As the heart fails, BP and cardiac output drop
* Distended veins in hands and neck
* Anasarca: severe, generalized edema
* Pitting edema: leaves depression in skin when touched
* Pulmonary edema: crackles on auscultation
* Patient SOB and tachypneic
* Labs: low hematocrit, normal serum sodium, lower K+ and BUN (or if high, may mean renal failure)
* ABG: low O2 level, PaCO2 may be low, causing drop in pH and respiratory alkalosis

Treatment of Hypervolemia
* Restriction of sodium and fluid intake
* Diuretics to promote fluid loss; morphine and nitroglycerine to relieve air hunger and dilate blood vessels; digoxin to strengthen heart
* Hemodialysis or CAVH

* Excessive loss of free water
* Loss of fluids causes an increase in the concentration of solutes in the blood (increased osmolality)
* Water shifts out of the cells into the blood
* Causes: prolonged fever, watery diarrhea, failure to respond to thirst, highly concentrated feedings, including TF

Symptoms of Dehydration
* Thirst
* Fever
* Dry skin and mucus membranes, poor skin turgor, sunken eyeballs
* Decreased urine output
* Increased heart rate with falling blood pressure
* Elevated serum osmolality; elevated serum sodium; high urine specific gravity
* Use hypotonic IV solutions such as D5W
* Offer oral fluids
* Rehydrate gradually

Laboratory Values and Hydration: BUN
Low: inadequate dietary protein, severe liver failure
High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy
Creatinine will also rise in severe hypovolemia
Normal: 10-20 mg/dl
Other factors influencing result
Lab Test
Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.
Laboratory Values and Hydration Status: BUN:Creatinine Ratio
Low: inadequate dietary protein, severe liver failure
High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy
BUN: creatinine ratio
Normal: 10-15:1
Other factors influencing result
Lab Test
Laboratory Values and Hydration: HCT
Low: anemia, hemorrhage with subsequent hemodilution (occurring after approximately 12-24 hours)
High: chronic hypoxia (chronic pulmonary disease, living at high altitude, heavy smoking, recent transfusion)
Laboratory Values and Hydration: Alb, Na+
Serum sodium generally reflects fluid status and not sodium balance Serum albumin
Other factors influencing result
Lab Test
Laboratory Values and Hydration Status
Low: diuresis, hyponatremia, sickle cell anemia
High: SIADH, azotemia,
Urine osmolality (200-1200 mosm/kg)
Urine sp. Gravity
Serum osmolality
(285-295 mosm/kg)
Other factors influencing result
Serum sodium
Low: malnutrition; acute phase response, liver failure
High: rare except in hemoconcentration
Serum albumin
Other factors influencing result
Lab Test
Hypokalemia (K+< 3.5 mEq/L)
* ↑ renal losses (diuresis)
* ↑ GI losses (diarrhea, vomiting, fistula)
* K+ wasting meds (thiazide and loop diuretics, etc)
* Shift into cells (anabolism, refeeding, correction of glucosuria or DKA)
* Inadequate intake
Hyperkalemia (K+>5.0 mEq/L)
* Decreased renal excretion as in acute or chronic renal failure
* Medications, e.g. potassium sparing diuretics, beta blockers, ACE inhibitors
* Shift out of cells (acidosis, tissue necrosis, GI hemorrhage, hemolysis)

Serum Calcium
* Normal serum 9.0-10.5 mg/dL (includes ionized calcium and calcium bound to protein, primarily albumin, and ions)
* Ionized calcium: 4.5-5.6 mg/dL
* Normal levels maintained by hormonal regulation using skeletal reserves
* Ionized calcium is more accurate, especially in pt with hypoalbuminemia; evaluate before repleting Ca+
Hypocalcemia (serum calcium <9.0 mg/dL; ionized Ca+ <4.5 mg/dL)
* Hypoalbuminemia
* Hypoparathyroidism
* Hypomagnesemia
* Renal failure, renal tubular necrosis
* Vitamin D deficiency or impaired metabolism

Hypercalcemia (serum calcium >10.5 mg/dL; ionized Ca+ >5.6 mg/dL)
* Hyperparathyroidism
* Some malignancies, especially breast, lung, kidney; multiple myeloma, leukemia, lymphoma
* Medications: thiazide diuretics, lithium, vitamin A toxicity
* Immobilization
* Hyperthyroidism
Serum Phosphorus (normal 3.0-4.5 mg/dL)

* Serum phos a poor reflection of body stores because <1% is in ECF
* Bones serve as a reservoir
Hypophosphatemia (<3.0 mg/dL)

* Impaired absorption (diarrhea, Vitamin D deficiency, impaired metabolism)
* Medications: phosphate binding antacids, sucralfate, insulin, steroids)
* Alcoholism, especially during withdrawal
* Intracellular shifts in alkalosis, anabolism, neoplasms
* Refeeding syndrome
* Increased losses: hyperparathyroidism, renal tubular defects, DKA recovery, hypomagnesemia, diuretic phase of ATN

Charney and Malone, 2004, p. 93

Hyperphosphatemia (>4.5 mg/dL)

* Decreased renal excretion: acute or chronic renal failure (GFR<20-25 mL/min); hypoparathyroidism
* Increased cellular release: tissue necrosis, tumor lysis syndrome
* Increased exogenous phosphorus load or absorption, phosphorus containing laxatives or enemas, vitamin D excess
* Acidosis
Hypomagnesemia <1.3 mEq/L (normal 1.3-2.1 mEq/L)
* Decreased absorption: prolonged diarrhea, intestinal or biliary fistula, intestinal resection or bypass, steatorrhea, ulcerative colitis; upper GI fluid loss, gastric suctioning, vomiting
* Renal losses: osmotic diuresis, DM with glucosuria, correction of DKA, renal disease with magnesium wasting, hypophosphatemia, hypercalcemia, hyperthyroidism
* Alcoholism
* Inadequate intake: malnutrition
* Medications
* Intracellular shift: acute pancreatitis
* Refeeding syndrome
Hypermagnesemia (>2.1 mEq/L)
* Acute or chronic renal failure
Assessment for Protein-Calorie Malnutrition
* Hormonal and cell-mediated response
to stress
o Negative acute-phase respondents
o Positive acute-phase respondents
* Nitrogen balance
Assessment for Protein-Calorie Malnutrition–cont’d
* Hepatic transport proteins
o Albumin
o Transferrin
o Prealbumin
o Retinol-binding protein
o C-reactive protein
o Creatinine
* Immunocompetence
Hormonal and Cell-Mediated Response to Inflammatory Stress
* Acute illness or trauma causes inflammatory stress
* Cytokines (interleukin-1, interleukin-6 and tumor necrosis factor) reorient hepatic synthesis of plasma proteins
* Although protein-energy malnutrition can occur simultaneously, interpretation of plasma proteins is problematic

Hormonal and Cell-Mediated Response to Inflammatory Stress
* Negative acute-phase respondents (albumin, transthyretin or prealbumin, transferrin, retinol-binding protein) decrease
* Positive acute-phase reactants (C-reactive protein, orosomucoid, fibrinogen) increase
* The change in these proteins is proportional to the physiological insult

Nitrogen Balance Studies
* Oldest biochemical technique for assessment protein status
* Based on the fact that 16% of protein is nitrogen
* Nitrogen intake is compared to nitrogen output, adjusted for insensible losses (skin, hair loss, sweat)
* Nitrogen balance in healthy adults is 0
* Nitrogen balance is positive in growing children, pregnant women, adults gaining weight or recovering from illness or injury
* Nitrogen balance is negative during starvation, catabolism, PEM
* Nitrogen balance = nitrogen intake (g/24 hours) –(urinary nitrogen [g/24 hours) + 2 g/24 hours
* Use correction of 4 g/24 hours if urinary urea nitrogen is used
* Nitrogen intake = (grams protein/24 hours)/6.25
Nitrogen Balance Challenges
* Urea nitrogen is highly variable as a percent of total nitrogen excreted
* It is nearly impossible to capture an accurate nitrogen intake for patients taking food po
* Most useful in evaluating the appropriateness of defined feedings, e.g. enteral and parenteral feedings

Visceral Proteins:
Serum Albumin
* Reference range: 3.5-5.2 g/dl
* Abundant in serum, stable (half-life 3 weeks)
* Preserved in the presence of starvation (marasmus)
* Negative acute phase reactant (declines with the inflammatory process)
* Large extravascular pool (leaves and returns to the circulation, making levels difficult to interpret)
* Therefore, albumin is a mediocre indicator of nutritional status, but a very good predictor of morbidity and mortality
Visceral Proteins: Plasma Transferrin

* Reference range: 200-400 mg/dl
* Half-life: 1 week
* Negative acute phase respondent
* Increases when iron stores are depleted so affected by iron status as well as protein-energy status
* Responds too slowly to be useful in an acute setting
Visceral Proteins: Transthyretin (Prealbumin)
* Reference range: 19-43 mg/dl
* Half-life: 2 days
* Negative acute-phase reactant
* Zinc deficiency reduces levels
* Due to short half-life, it is useful in monitoring improvements in protein-energy status if baseline value is obtained near the nadir as inflammatory response wanes
Visceral Proteins: Retinol-Binding Protein
* Reference range: 2.1-6.4 mg/dl
* Half-life: 12 hours
* Negative acute-phase protein
* Unreliable when vitamin A (retinol) status is compromised
* Elevated in the presence of renal failure, regardless of PEM status

Visceral Proteins: C-Reactive Protein
* Positive acute-phase reactant
* Increases within 4-6 hours of injury or illness
* Can be used to monitor the progress of the stress reaction so aggressive nutrition support can be implemented when reaction is subsiding
* Mildly elevated CRP may be a marker for increased risk for cardiovascular disease
* hs-CRP
* Homocysteine

Urinary Creatinine
* Formed from creatine, produced in muscle tissue
* The body’s muscle protein pool is directly proportional to creatinine excretion
* Skeletal muscle mass (kg) = 4.1 = 18.9 x 24-hour creatinine excretion (g/day)
* Confounded by meat in diet
* Requires 24-hour urine collection, which is difficult
Markers of Malabsorption
* Fecal fat
* Fat-soluble vitamins
* Vitamin D
Lipid Indices of Cardiovascular Risk
* Total cholesterol
* HDL: HDL2a, HDL2b, HDL2c, HDL3a, HDLdb
* Lp(a)
Nutrition Diagnoses and Laboratory Indices
* Nutrition-related labs can be used either as diagnostic labels or a clinical sign
Examples of Nutrition Diagnostic Statements Related to Lab Values
* Altered nutrition-related lab values (NC-2.2) related to excessive intake of saturated fat and cholesterol and genetic factors as evidenced by diet history and client history.
* Inappropriate intake of food fats (saturated fat and cholesterol) (NI-5.6.3) related to frequent use of baked goods and fried foods as evidenced by diet history and elevated LDL and TC
Examples of Nutrition Diagnostic Statements Related to Lab Values

* Excessive carbohydrate intake related to evening visits to Coldstone Creamery as evidenced by HS blood glucose and diet history

Evaluation of Laboratory Data in Nutrition Assessment.ppt


HIV/AIDS 2008 Update

HIV/AIDS 2008 Update
By:David H. Spach, MD
Clinical Director, NWAETC
Professor of Medicine
Division of Infectious Diseases
University of Washington, Seattle

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries
* In August 2008, the CDC reported their use of new epidemiologic methods that has led to significant revisions in the estimates of HIV incidence in the United States.

In this recent report, which one of the following statements is TRUE regarding HIV infections in the United States in 2006?

* The number of estimated new infections in 2006 has been revised to a lower number (now 32,000 instead of 40,000)
* The rate (per 100,000 persons) of new infections in blacks was 7x whites
* Heterosexual sex has replaced male-to-male sex as the leading transmission category for new infections
* The number of new infections in women was greater than men
* “Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300.”
* “... the level of new HIV infections in the United States is higher than had previously been known, in fact approximately 40% higher than early estimates…”
Kevin Fenton, MD, PhD
Centers for Disease Control & Prevention.
HIV Rapid Testing*
Rapid HIV Tests
* In the June 18, 2008 issue of the MMWR, the NY City Department of Health and the CDC reported a problem with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test.

What was the reported problem with the OraQuick rapid HIV test?
* Contamination of test kits with mold
* Kits were shipped too close to the expiration date
* Failure of external Kit Controls to validate the assay
* Increased numbers of False-Positive results with oral fluid samples

Persons NOT Infected with HIV
OraQuick Rapid ORAL HIV Test
Confirmatory HIV Test (EIA/WB)
Oral Fluid
Possible Revised Approach: Rapid HIV Testing
OraQuick Rapid HIV Tests
Confirmatory HIV Test (EIA & WB)
Oral Fluid
EXAMPLE: Specificity of HIV Antibody Test
Persons NOT Infected with HIV (N = 15)
EXAMPLE: Specificity of HIV Antibody Test
Antibody Test Result: Persons NOT Infected with HIV
EXAMPLE: Specificity of HIV Antibody Test
HIV Antibody Testing in Low Prevalence Setting
HIV Test Specificity
HIV Antibody Testing in Low Prevalence Setting
DHHS ARV Guidelines
Initiating Antiretroviral Therapy
* As a group, make a list of at least 5 recommendations regarding initiating antiretroviral therapy that are new/different in current 2008 guidelines when compared with guidelines that existed one year ago at this time (at that time October 2006 most recent updated version).
Initiating Antiretroviral Therapy
1. New CD4 threshold (350 cells/mm3 in 2008 instead of 200)
2. New indications for starting ARV (chronic HBV, HIVAN) in 2008
3. Less impact of HIV RNA level in 2008
4. Zidovudine-lamivudine removed from preferred list in 2008
5. Abacavir-lamivudine added to preferred list in 2008
6. Do HLA-B5701 testing if considering using abacavir
Initiating Antiretroviral Therapy January 2008 DHHS Guidelines
*Initiate Antiretroviral Therapy
Consider Antiretroviral Therapy
Construct Regimen by choosing one component from Column A and one component from Column B
Recent Concerns Regarding Abacavir
Antiretroviral Therapy New Information in 2008
Host Cellular Receptors
Extracellular Space
Intracellular Space
Entry Inhibitor: Maraviroc (Selzentry)
Host Cell Membrane
CD4 Receptor
Extracellular Space
Intracellular Space
HIV Co-Receptor Tropism Assay Monogram Biosciences Trofile Assay
HIV-1 Tropism Assay
What is the major difference in the new ENHANCED Trofile assay when compared with the older Trofile assay?

* The new assay has a lower limit of detection of minor species (<1% compared with previous lower limit of 10%)
* Results can be obtained in 7 days with the new assay
* The new assay is accurate with very low HIV RNA levels (accurate down to 100 copies/ml)
* The new assay detects CCR5 mutants resistant to Maraviroc

HIV Co-Receptor Tropism Assay Monogram Biosciences ENHANCED Trofile Assay
Tenofovir + Lamivudine + Efavirenz (n = 38)
- HIV-infected
- Treatment Naive
- HIV RNA > 5,000 copies/ml
- CD4 count > 100 cells/mm3
- Randomized, double-blind
Tenofovir + Lamivudine +
Raltegravir* (n = 160)
Virologic Response: Week 24
* Background
- N = 368
- ARV-naīve
- HIV RNA > 5,000 copies/ml
- Randomized, double-blind
* Regimens (all include 2 NRTIs*)
- Efavirenz: 600 mg qd
- Rilpivirine: 25 mg qd
- Rilpivirine: 75 mg qd
- Rilpivirine: 150 mg qd
New Scientific Discoveries
A Cure for HIV?
* In July 2008, our patients starting coming in asking about the news reports regarding the newly discovered cure for HIV. The report that came out in July 2008 was related to HIV gp120 (envelope).

What new therapeutic strategy was discovered?

* A CD4 coating molecule that is an inhibitor of gp120-CD4 binding
* Use of Abzymes to destroy a critical region of gp120
* A new enzyme that cause gp120 to separate from gp41
* A new particle that destroys the human co-receptor CCR5 and thus prevents gp120-CCR5 binding

HIV: Basic Structure
HIV: Envelope
- Antibodies with enzymatic activity
- Can break down thousands of virus particles per molecule of abzyme

HIV: gp120
HIV gp120: Abzyme Interaction .........

HIV/AIDS 2008 Update: Summary

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries

HIV/AIDS 2008 Update.ppt

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