T2 - Neoplasia 8 And 9 - Pathology Of Aids And Hiv Infection (Moroz) And Hiv/aids From Mushatt

Front 1

define aids and HIV positivity - what cells can HIV invade?

Back 1

a previous diagnosis of HIV infection plus less than 200 CD4 count OR an aids defining illness (including the light ones, like oral candiasis).

HIV can invade CD4 containing cells - t cells, monocytes, microgolial cells, LANGERHANS cells in the mucosa (often first infected), dendridic cells (folicular and tissue). recall that the FDC's are transported to the lymph nodes, where the infection spreads like crazy and can destroy LN's.

Front 2

talk about HIV and its effects on the lymphoreticular system, spleen, lymph nodes, bone marrow, other lymph tissue. don't foreget PGL.

Back 2

HIV infection is a process of DECREASED T-cell activity (immune surveilance) and INCREASED B-cell function, leading to lymphoid hyperplasia, malignant lymphoma, and AUTOIMMUNE problems.

in lymph nodes, get PGL (persistent generalized lymphadenopathy) - two LN's enlarged not in the inguinal area for >3 months. get hepatosplenomegaly, HYPER gamma globulinemia (upped B cells make more Ig's).

in PGL, you see NAKED FOLLICLES, detroyed GERMINAL CENTERS, and LOTS of lymphoid depletion.

so have follicle hyperplasia but germinal center destruction.

Front 3

what do KS, lymphomas, and other carcinomas have to do with HIV infection? talk about histology of NHL.

Back 3

30% of aids patients get NHL. usually has to do with an EBV-driven translocation.

"stary sky" = NHL. lymph nodes are full of macs eating up dead lymphocytes. LCA marker!!! = burkitt's (or burkitt's like)

HHV8 causes KS and BODY CAVITY LYMPHOMA. remember that it's more common in sex transmission, 'cause HHV8 is sex transmitted.

OTHER CARCINOMAS: cervical due to synegistic relationship between HPV and HIV. loss of CD8 cells = less immunosurveilance.

Front 4

what protozoans and viral infections do you have to be worried about? talk about what you see histologically and what stains are used.

Back 4

protozoans:

cryptosporosis: ziel/nielsin stain cysts in poop. diarrhea. see organisms in duodenum.

toxoplasma: intracranial masses, abscesses, tachyzoites/bradyzoites. sometimes big CNS cysts full of the bradyzoites.

they still list PCP, know that it involves SEPTAL inflammation, alveolar spaces full of eosinophilic fluid, and SILVER STAIN

Front 5

what fungal and mycobacterial infections do you have to worry about?

Back 5

candidia, histoplasma, coccoidies, crypotoccus.

Cocciodies - see lung infiltration/invasion, cysts full of endospores.

crypotoccus - THICK CELL WALL = INDIA INK. think meningitis.

mycobacteria: TB and MAC.

TB can show necrotizing granulomas which lead to bloody cough, but remember that in immunosuppressed, may have no ability to make granulomas.

MAC shows multinucleated giant cells.

Front 6

what's pathoneumonic for AIDS dementia complex?

what's PML?

Back 6

Microglial Nodules!

see cortical atrophy/ventricular dilation. Loose myelin and axons.

PML is caused by JC virus, involves demylenation of white matter. SPAGHETTI AND MEAT BALLS.

Front 7

go through the initial infection steps (cells infected)

Back 7

if sex, mucosal cells first - langerhans cells = tissue dendridic cells.

these fuse with CD4 cells that go to the lymphatics, then get big spread to lots of other lymphocytes.

then seed tissues - GALT, brain, etc.

Front 8

what branch of the immune system responds to HIV infection? what's bad about it?

Back 8

both neutralizing antibodies are made, and cell mediated is the most important.

killing off all the HIV infected cells contributes to CD4 depletion.

there's homology between MHC II and HIV's Gp41/120

also get ADCC of your CD4 cells. APOPTOSIS TOO.

Front 9

what do you see in acute disease in terms of CD4 count and viral load? how does it change over time? acute blood tests show what?

Back 9

acute disease sees a big increase in viral load and a rapid depletion of CD4 cells, but these both stop as equilbrium is reached

note that during acute phase, likely to show up negative on antibody screenings, as you haven't built up enough yet.

. spend the chronic, latent phase loosing 80 or so T cells per year, viral load creeping up.

Front 10

where does the virus hide out?

Back 10

1st compartment = circulating CD4 T-cells, this is for about a day

2nd compartment = macs, dendridic cells, protected tissues (hide out for weeks).

3rd compartment - long lived T cells, live here for years. This is where the incurable part comes from - might take 80 years to clear virus.

Front 11

what's the best HIV test?

Back 11

viral load = HIV RNA detection. Early detection (less than two weeks post infection) and highly sensitive/specific.

Front 12

what are the pros and cons of treating early?

Back 12

pros are that you might get out front of possible diseases, alter the "set point," reduce mutations, stop transmission.

risk is that you're dealing with toxicities, see drug resistance earlier, have fewer options when things go wrong later

Front 13

what are the symptoms that pop up first (as in with higher CD4 counts)? what about late and advanced?

Back 13

above 500, get lymphadenopathy regularly.

less than 500, see thrush, herpes, OHL, TB/KS. Usually nothing, though.



late = PCP, other OI's

advanced = PML, dementia.

Front 14

for what diseases do you do prophylaxis and at what CD4's? when do you start haart, for sure?

Back 14

below 200, protect against PCP

below 100, do toxo.

below 50, do MAC

also make sure you do TB is ppd is positive, all the good vaccines, Hep B if not infected, influenza.

start HAART at 350, for sure

Front 15

what resistance should we know about

Back 15

HLA B5701 for Abacovir!!!!

Front 16

review the side effects of the major drug classes:

Back 16

PI's have hyperlipidemia and type II diabetes. loose arm fat, gain it in the trunk, get buffalo hump. Lipoatrophy in the face.

NNRTI's = rashes/hypersensitivity (nevarapine has liver problems too).

NRTI's = mitochondrial toxicity with lactic acidosis, hepatitc steatosis.

Front 17

who gets viral genotyping?

Back 17

everybody now, looking for resistances.

Front 18

what's a possible adverse effect of HAART, generally?

Back 18

IRIS - immune reconstitution inflammatory syndromes. Getting all your T cells back really fast when you still have infections going on, get all sorts of secondary side effects to inflammation. Fever/pain/CNS problems. Latent infections pop up.

Front 19

so why can't we clear the virus? what are some ideas to get around these problems?

Back 19

drugs don't penetrate certain compartments well, and we have over a trillion resting CD4 cells that might be infected. So anatomy + cells.

it might be possible to use histone deacetylases (HDAC) to coax the virus into growth cycle, out of latency. Maybe valproic acid too.

Front 20

what are the last diseases to pop up in HIV?

Back 20

CMV and MAC both indicate having less than 50 cd4 cells. Don't forget that MAC can take weeks to grow up!

note that toxo, crypto, and lymphoma show up at less than 100.

Front 21

if someone has an OI, do you automatically start treatment?

Back 21

no - need to consider how to treat the main infection while not interfering with HIV drugs, if you're going to start them. Also reconstitution syndrome possible.

but sometimes - crypto, PML, KS, the only treatment is HAART.

Front 22

what's one big side effect to remember with AZT?

Back 22

stop producing RBC's as much, so get serious anemias.