Case #5 HIV Flashcards
Describe the structure of HIV.
Retroviruses
spherical
enveloped
RNA viruses
It encodes RNA-dependent deoxyribonucleic acid polymerase (reverse transcriptase). The envelope surrounds a capsid that contains two identical copies of the positive strand RNA genome. The virion also contain reverse transcriptase and integrase enzyme and two cellular transfer RNA (tRNA).
Describe the replication cycle within the T cell.
https://www.youtube.com/watch?v=eS1GODinO8w
HIV infects cells expressing CD4 and either the CCR5 or the CXCR4 chemokine receptors. This includes CD4 T cells, macrophages, and dendritic cells.After binding to cell surface receptors, the virus fuses its envelope with the cell membrane and delivers the virion contents and genome into the cytoplasm. The positive-strand (+) RNA genome is reverse transcribed into DNA, which integrates into the host chromosome and is then transcribed similar to a very active host gene. mRNA is transcribed, including a full-length +RNA which becomes a new viral genome. The virion assembles on glycoprotein-modified membranes, and then the viral protease cleaves the virion proteins into individual proteins contained within the envelope.
Describe the pathogenesis of HIV infection.
1- HIV is transmitted through blood and genital fluids. Virus-cell fusion and HIV entry subsequently take place. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; other cells such as macrophages create reservoirs for the virus in many tissues. The host reaction against HIV, through neutralizing antibodies and cellular immune responses, can keep the virus suppressed for many years.
2 - Pathogenesis of human immunodeficiency virus (HIV). HIV causes lytic and latent infection of CD4 T cells and persistent infection of monocytes, macrophages, and dendritic cells and disrupts neuron function. The outcomes of these actions are immunodeficiency and acquired immunodeficiency syndrome (AIDS) dementia.
What cells support viral replication?
Human immunodeficiency virus primarily infects CD4 T cells and cells of the myeloid lineage (e.g., monocytes, macrophages, alveolar macrophages of the lung, dendritic cells, and microglial cells of the brain).
What is the time course of untreated infection?
Four stages of untreated infections
- Flu-like (acute HIV Syndrome - seeding of lympoid organs)
- Feeling fine (Clinical latency)
- Falling count (Constitutional symptoms - ARC)
- Final crisis (Opportunistic disease; CD4+ less than 100)
List the common disease of HIV positive adults with CD4+ counts less than 500 cells/mm^3.
Candice put Barton in the Crypt when She learned HE had HPV.
Candida albicans - oral thrush
Bartonella henselae - bacillary aniomatosis
Cryptosporidium spp. - Chronic watery diarrhea
HHV-8 - Kaposi sarcoma
EBV - oral hairy leukoplakia
HPV - squamous cell carcinoma, anus or cervix
What viral drugs are used to treat herpes virus?
VALerie is in the ACYCLOVIR FAMily
HSV1 - Acyclovir, Famciclovir, Valacyclovir
HSV2 - Acyclovir, famciclovir, Valacyclovir
VZV - Acyclovir, famciclovir, Valacyclovir (not for latent)
EBV - weak activity –>Acyclovir, famciclovir, Valacyclovir
CMV - Ganciclovir
HHV-6/HHV-7 - being studied
HHV-8 - being studies
What drugs are used to treat HIV?
HAART (Highly Active Antiretroviral Therapy)combines multiple antiretroviral drugs to limit the potential selection of resistant mutants. The drugs target the reverse transcriptase, integrase, protease, CCR5 co-receptor, or block the fusion event.
Regiman: 3 drugs [2 NRTIs and 1: NNRTI, protease inhibitor OR integrase inhibitor]
What is a representative disease state for metabolic acidosis?
SLAM’D CARD
(Increased Anion Gap)
Starvation
Lactic acidosis
Aspirin poisoning
Methanol poisoning
Diabetes Mellitus
(Normal Anion Gap)
Carbonic Anhydrase Inhibitors
Addison disease
Renal tubular acidosis
Diarrhea
What is a representative disease state for respiratory acidosis?
POEM of Respiratory Acidosis
Pneumonia
Other lung disease
Emphysema
Mental - Brain damage
What is a representative disease for metabolic alkalosis?
MALe VOICE
Metabolic ALkalosis
Vomiting gastric acid
Overuse of diuretics (except Carbonic anhydrase inhibitors)
Increased Base intake
(mineral)Corticoid Excess
What is a representative disease for respiratory alkalosis?
CHAMPS
CNS disease (increses hyperventilation)
Hypoxia (high altitude)
Anxiety
Mech Ventilators
Pulmonary embolism
Salicylates/Sepsis
What is the arterial blood gas for a patient with metabolic acidosis?
pH less than 7.4
HCO3- less than 24 mEq/L
Pco2 less than 40 mmHg
What is the arterial blood gas for a patient with metabolic alkalosis?
pH greater than 7.4
HCO3- >24 mEq/L
Pco2 >40 mmHg
What is the arterial blood gas for a patient with respiratory acidosis?
pH less than 7.4
Pco2 >40mmHg
HCO3- >24 mEq/L (compensation)
What is the arterial blood gas for a patient with respiratory alkalosis?
pH less than 7.4
Pco2 less than 40 mmHg
HCO3- less than 24 mEq/L
Give an example of a NRTI (Nucleoside Reverse Transcriptase Inhibitors).
Have you dined (vudine) with my nuclear (nucleosides) family?
NRTIs
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
LamiVUDINE (3TC)
StaVUDINE(d4T)
Tenofovir (TDF) [nucleoTide]
ZidoVUDINE (ZDV,
formerly AZT)
What is the mechanism of action of NRTIs (Nucleoside Reverse Transcriptase Inhibitors)?
https://www.youtube.com/watch?v=XK52oKGekeA
Competitively inhibit nucleotide binding to
reverse transcriptase and terminate the DNA
chain (lack a 3′ OH group).
What is the toxicity of NRTIs (Nucleoside Reverse Transcriptase Inhibitors)?
Bone marrow suppression (can be reversed
with granulocyte colony-stimulating factor
[G-CSF] and erythropoietin),
peripheral neuropathy
lactic acidosis (nucleosides),
rash (non-nucleosides),
anemia (ZDV),
pancreatitis (didanosine).
Give an example of a NNRTI (Non Nucleoside Reverse Transcriptase Inhibitors).
NEED NNRTI
NEvirapine
Efavirenz
Delavirdine
What is the mechanism of action of NNRTIs (Non Nucleoside Reverse Transcriptase Inhibitors)?
Bind to reverse transcriptase at site different
from NRTIs. Do not require phosphorylation
to be active or compete with nucleotides.
What is the toxicity of NNRTIs (Non Nucleoside Reverse Transcriptase Inhibitors)?
Rash and hepatotoxicity are common to all NNRTIs.
Vivid dreams and CNS symptoms are common with efavirenz.
Delavirdine and efavirenz are contraindicated in pregnancy.
vivid dreams (NooNoo dreams) NNRTI
Give an example of a Protease Inhibitor.
Protease Inhibitors
Navir (never) tease a protease
Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Ritonavir
Saquinavir
What is the mechanism of action of a Protease inhibitor?
Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
What is the toxicity of a Protease Inhibitor?
Hyperglycemia,
GI intolerance (nausea, diarrhea),
lipodystrophy.
Nephropathy,
hematuria (indinavir).
Give the examples of an Integrase Inhibitor.
Raltegravir
What is the mechanism of action of the Integrase Inhibitor, Raltegravir?
Inhibits HIV genome integration into host cell
chromosome by reversibly inhibiting HIV integrase.
What is the toxicity of the Integrase Inhibitor, Raltegravir?
Hypercholesterolemia (2014)
Increased creatine kinase (2015)*
*Note there is a difference in the First Aid books.
Ralt has a grave problem with hypercholesterolemia.
List the common disease of HIV positive adults with CD4+ counts less than 200 cells/mm^3.
Toxoplasma gondii - brain abscesses
HIV - dementia
JC virus - progressive multifocal leukoencephalopathy
Pneumocystis jirovecii - Pneumoncystis pneumonia
List the common disease of HIV positive adults with CD4+ counts less than 100 cells/mm^3.
Candice ASPired to be a bird but HIS CMV & EBV sent eherto the CRYPT.
Aspergillus fumigatus - hemoptysis, pleuritic pain
Cryptococcus neoformans - meningitis
Candida albicans - esophagitis (different presentation)
CMV - Retinitis, esophagitis, colitis, pneumonitis, encephalitis
EBV - B cell lymphoma (Non-Hodgkins and CNS lymphoma)
Histoplasma capsulatum - fever, weight loss, fatigue, cough, dypnea, nausea, vomiting, diarrhea
Mycobacterium avium - nonspecific systemic symptoms (fever, night sweats, weight loss) or foacl lymphadenitis
HIV patients comes in with cavitation or infiltrates on chest imaging. Suspected pathogen?
Aspergillus fumigatus
HIV patients comes in with thickly encapsulated yeast on India ink stain. Suspected pathogen?
Cryptococcus neoformans
(note under 100 cells/mm^3 Cryptococcus)
HIV patients comes in with white plaques on endoscopy, yeast and pseudohyphae on biopsy. Suspected pathogen?
Candida albicans
HIV patients comes in with linear ulers on edoscopy, cotton-wool spots on fundoscopy. Biopsy reveals cells with intranuclear (owl eyes) inclusion bodies. Suspected pathogen?
CMV
Cotton-wool spots
HIV patients developed CNS lymphoma with ring enhancing lesions on MRI. Suspected pathogen?
EBV
ring Enhancing
(can also be toxoplasma)
HIV patients comes in with oval yeast cells within macrophage. Suspected pathogen?
Histoplasma capsulatum
(capsule means someting -yeast- has to be within)
HIV patients comes in with scrabable white plaque with pseudohyphae on microscopy. Suspected pathogen?
Candida albicans
HIV patients comes in with unscrabable white plaque on lateral tongue. Suspected pathogen?
EBV
V looks like a tongue and is on the lateral part of EBV
HIV patient’s biopsy has neutrophilic inflammation. Suspected pathogen?
BartoNElla henselae
NEutraphilic inflammation
HIV patient’s biopsy has lymphocytic inflammation. Suspected pathogen?
HHV-8
Karposi Sarcoma
HIV patients comes in with acid-fast oocysts in stool. Suspected pathogen?
CryptoSporidium spp.
ooCYST
