Pathophysiology - Chapter 12 HIV/AIDs: Exam 1

CD4+ is wanted kept

HIGH, CD4+ lymphocyte > below 20% is an increased risk for AIDS

HIV resistance is

Major problem fro successful therapy > due to non-compliance

CD4+ decrease signifies

AIDS

HIV must be able to enter

into a whole human celll + interact w/ their DNA so it takes over genetic working of the cell to reproduce

if western blot is done between infection and seroconversion

it will be negative

category 3 HIV

less then 200 - AIDS defining

CRP + ESR are

non-specific will show inflammation but not where

HIV infected cells undergo

viral budding to generate and produce new visions

HIV takes

3 weeks to 6 months to seroconvert

other tests for HIV

> CBC: can detect anemia, neutropenia, thrombocytopenia > chemistry panel/screen > chest radiations >STDs > Hept A,B, C

category 2 HIV

> CD4+ 200-499

AIDS defining

> CD4+ cell count below 200 > one or more opportunistic infections > one or more cancers + tumors > PCP pneumonia > frequent pneumonia

Category 1 HIV

> CD4+ less then 500

AIDS Diagnostic Testing

> ELISA > Western Blot > P24 antigen > Oraquick Rapid HIV-1

Neurological manifestations of HIV

> HIV encephalopathy symptoms > inattentiveness, confusion, forgetfulness, concentration loss > slower verbal response > headache > apathy > inability to complete or perform * can range form forgetfulness to dementia *

Pathogenesis of HIV/AIDS

> HIV infects and kills CD4 T cells > After infection, see rapid depletion of CD4 T cells until immune system mounts a response > Body establishes "set point" with balance between virus and immune system > Person may appear healthy for many years; however, virus continues to replicate and establish infection in lymphoid organs > As a result of continuing CD4 T cell loss, body becomes vulnerable to opportunistic infections and malignancies

Viral Production and Cell Death

> HIV replicates quick from onset > high level of vision turnover (made by converting RNA-DNA and transcribing to make more virus) > high level of CD4+ turnover (death)

Effect on Immune Cells at Cellular Level

> Hallmark of HIV infection: decrease in CD4+ T-helper/inducer lymphocytes > Macrophages become more functionally impaired as infection progresses and also contribute to T-cell decline by increasing CD4+ cell death > B cell changes: overproduction of non-essential antibdodies ineffective to disease, increases apoptosis

in order for viral production,

> Long-term survival need > Low viral load and strong CD8+ killer T-cell activity

pulmonary clinical manifestations of HIV

> PCP = most common: increased incidence with prophylaxis, CD4 below 200, pnenmocytosis activates PCP - dry cough, low surfactant protection, dyspnea, tachypnea, pallor, cyanosis (similar to ARDS) > MAJOR FEATURE: unable to oxygenate, hypoxemia, PaO2 below 60

monitoring HIV progression

> absolute CD4+ count, specifically indicates HIV -- AIDS

renal impairment of HIV

> affects kidneys causing AIDS-associated nephropathhy, drug-induced ischemia, renal failure

hematologic impairment with HIV

> anemia, thrombocytopenia, granulocytopenia (phagocytic WBCs that release granules to fight infections)

successful factors for antiretroviral therapy

> appropriate poly drug therapy > compliance and convince of dosing > early detection of HIV > * low baseline viremia * > * HIGH CD4+ counts

Plasma viral load (PVL)

> checked with CD4+ > indicates amt of viral replication + effectiveness of therapy > helps predict disease progression

PCP is diagnosed via

> chest x-ray > wrist-giemas > stain (sputum) > biopsy > bronchoalvar lavage (scope washes out lungs)

GI clinical manifestations of HIV

> common targeted organ > MAJOR: chronic diarrhea (watery, bloody - treated w/ anti-diuretics/antidiarrheals) > oral canditis > anorexia > nausea / vomiting > museums membrane ulcers > abdominal pain > low serum b12 > restrorenal pain or swallowing

Western blot

> confirmatory test for HIV > used when ELISA is positive > confirms HIV diagnosis > checks antibodies, identifies specific antibodies against HIV protein antigen > uses electrophoresis (expensive) > specific, must wait 1-2 weeks >

Aids diagnosis clinical manifestations (general)

> coughing/SOB > dysphasia (difficulty swallowing) > odyaphagia (painful swallowing) > mental symptoms > severe/persistent diarrhea (GI) > fever > weight loss > nausea/vomiting > abdominal cramps > extreme fatigue > headaches *lots of GI symptoms

Hallmark of HIV

> defective cell-mediated immunity > decrease in CD4+ (helper T cells) lymphocytes

goals for HIV patients

> delay disease progression > avoid drug resistance (multi-drug regimen aimed to attack HIV at all standpoints - different drugs attack different enzymes) > minimize clinical manifestations > prolong survival > drug management evolved to polydrug therapy: AART + HAART

Seroconversion

> enough antibodies detected in blood

Clinical manifestations of primary HIV infection

> flu or mono-like symptoms >CD4+ T cells great then 400 (above 400 is good) >decreased # of WBCs (excepts CD8+) > decreased platelets >elevated ESR > high HIV count in genital fluids

cardiovascular clinical manifestations of HIV

> hyperglycedermia, lipidemia > increased risk for CV + renal disease in HIV pts > immunosuppression/HIV viremia/HAART involved in pathology of CV disease > HIV therapy may help protect from hip-induced CV disease

liver dysfunction of HIV

> increased risk for concumitant Hept C, B > effects caused by multiple HIV drugs

hiv enters and quickly replicates but

> is not detected on normal lab > usually asymptomatic > infectious but doesn't know > is present in blood

systematic clinical manifestations of HIV

> malnutrition/wasting syndrome: unintended involuntary loss of more then 10% body weight > muscle wasting - hyper metabolic state > muscle wasting from malnutrition, inflammation

CRP (C-reactive protein)

> measure of inflammation and infection > increases in a state of infection

opportunistic infection

caused by a pathogen that does not normally produce an illness in healthy humans

Most important for patient success

compliance

What is the biggest factor for progression of HIV?

compliance

RNA must

convert to DNA in order tot replicate and create visions

clinical manifestations of symptomatic, chronic HIV

* Complete Anergy * > severe viral/fungal skin/mucous membrane infections > oral + genital herpes, leukoplaisa (white spots on toungue) > persistent skin rash/flaky skin, memory loss, PID, non-responsive to treatment > opportunistic infections

ESR (erythrocyte sedimentation rate)

> measurement/time of inflammation in the body > the rate in which it takes for RBC's to settle off in an tube

Virions

infectious virus particles

Oroquick rapid HIV-1

> new, rapid fingerstick > results in 20 minutes > positive result MUST be confirmed by western blot > false-negatives can occur * best way to check neonates *

mucocutaneous clinical manifestations of HIV

> occurs late + early in HIV > HIV viral exanthema - usually first symptom > erythematous maculopapular rash (red, fine, small flat papule (bump) rash) on face > self limiting 40-60% get it >Neoplasms: Kaposi Sarcoma -AIDS defining > squamous cell carcinoma, basal cell > AIDS related malignancy: affects skin, mucous membranes, lymphatics, other internal organs

the evolution form mono drug therapy to poly drug therapy has

> produced better viral suppresion > complete viral elimination is not currently possible > continuous therapy provides best results

current recommendations for HIV

> start therapy for AIDS-defining illness or severe symptoms @ any CD4 count to viral load (AART) > all symptomatic HIV-infected w/ CD4+ below 350 (AART) > anyone w/ HIV-associated nephropathy or Hept B virus confection (AART)

anergy/delayed hypersensitivity (type IV) test

> tests fro M. tuberculosis, mumps, measles virus > early HIV: skin test is normal > advanced case = anergy (no response, CD4 below 200)

infection risk increases greatly once

CD4+ drops below 200 > begin use of prophylactic meds to prevent infection

CDC HIV Classification System

CD4+ T-cell counts link with clinical symptomatology > Three CD4+ T-cell categories > Three clinical categories > Mutually exclusive

HIV is an

RNA retrovirus > causing defect in cell mediated immunity which may progress to AIDS

the higher the ESR

increased inflammation

AIDS

acquired immune deficiency syndrome

HIV/AIDS

acquired immunodeficiency disorder that result in defective immune functioning

goal is for patient to

be at undetectable level + have high CD8 levels (40,000 or less)

HIV is transmitted by

blood and body fluids

p24 antigen test

detects p24, a protein in HIV > quick, immediate response > will be positive whether seroconversion happened or not

ELISA test

enzyme-linked immunosorbent assay > a screening test - will not confirm diagnosis > will be positive for HIV id blood or oral mucosal transudate (fluid) of infected person reacts w/ surface antigen of killed HIV virus > HIGHLY sensitive + specific (if +, HIV is likely) > MUST be performed with HIV-1 and HIV-2

Kaposi's sarcoma is one of the

few neoplasms that indicate immune system dysfunction

GI tract is a major site

for HIV replication due to high turnover rate in mucous membrane issues

Primary HIV infection is

highly infectious - even if symptoms go away

HIV

human immunodeficiency virus

Goal of viral load

reduce number with therapy

As CD4 drops,

risk of infection increases

Level of HIV RNA in plasma is the

strongest predictor of outcome over time

Aids is a

syndrome - virus may express itself in multiple ways

Seroconversion of HIV

takes 3 weeks to 6 months

viral load

the number of virus particles circulating in the body > will determine how well treatment is working > want it to be undetected