Diseases Test 1 Flashcards
Parvovirus B19
“Fifths Disease”
Genomic organization: ssDNA (-), small non-enveloped, icosahedral
Tropism: Erythroid progenitor cells. Blood group P antigen (some people are group P antigen deficient and therefore innately immune)
Transmitted via respiratory system and replicates in eyrthroid progenitors. Viral protein NS1 induces erythroid apoptosis
Clinical presentation: Macular rash and arthralgia “slapped cheek”
Rx: Supportive care (IVIG for immunocompromised)
Transient aplastic crisis can occur in pts w/: hemolytic disorders.
Can also cause: chronic anemia/ pure red cell aplasia, hydrops fetalis (fetal loss)
X linked lymphoproliferative disease
Recessive disorder of young boys develop a fatal lymphoproliferative disorders after EBV. Present with severe sx of mono.
Most die.
Colorado Tick Fever Virus
Genomic organization: linear DS RNA virus. (uses negative strand for transcription and as a template for replication of positive strand) No envelope. Icosahedral capsid.
Tropism: Erythroid progenitor cells.
Animal vectors: Rocky Mt Wood Tick (small mammal resevoir)
Found in Rockies and West Coast from May to September (peak in june)
Clinical presentation: Fever, chills, body aches, malaise.
Dx by history, viral RNA (RT-PCR), and IGM
Rx: Supportive care
Complicating onset of meningitis and encephalitis (rare)
Epstein Barr Virus
Genomic organization: dsDNA (Gamma-1 Herpes virus) Evoloped virus w/ icosahedral head.
Tropism: lytic cycle in epithelial tissue. Latent infx in B-cells.
Associated malignancies: Burkitt’s lymphoma, Anaplastic nasopharyngeal carcinoma, Hodgkin’s disease, lymphomatoid granulomatosis.
EBV oncogene LMP1 is a homolog of CD40 and LMP2 is a homolog for BCL2.
LMP1 activates epidermal growth factor receptor transcription factors.
LMP2 activates B-cell proliferation/anti-apoptotic.
EBV gains entry to B cells by contact w/ CD21 on the surface of B-cells. Directly on tonsillar regions. Indirectly through contact with epithelial.
EBV oncogene EBNA3C down-regulates p53 transcriptional activity resulting in increased B cell transformation.
Clinical presentation: Classic triad = mild fever (10-14 days) , severe sore throat (3-5 days), and swollen glands (esp. posterior cervical lymph nodes).
VCA-IgM antibody is diagnostic (Viral Capsid Antigen)
Atypical lymphocytes with deformed nuclei and dark rimmed cytoplasm is also diagnostic. (Downey cells)
Severe if X linked lymphoproliferative disease.
Cytomegalovirus
Genomic organization: dsDNA. Enveloped w/ Icosahedral capsid.
Tropism:
Systemic infx: epithelial cells, endothelial cells, smooth muscle cells, macrophages, and neurons.
Latent infx: lifelong latency in pCD34 myeloid progenitor cells.
Tranmitted congenitally and by tranfusion, sexual contact, saliva, urine, or transplant.
Effective at evading host immune response via preventing antigens from being presented on MHC-1
Clincal presentation:
Congenital sx: microcephaly, seizures, deafness, jaundice, and purpura (blueberry muffin) due to thrombocytopenia. Hepatosplenomegaly and mental retardation.
Heterophil-negative mononucleosis: fever, lethargy, abnormal lymphocytes.
Can cause pneumonitis, esophagitis, hepatitis in immunocompromised
Dx w/ ELISA and presence of OWL’s EYEs cells in blood smears.
Rx: supportive care, or ganciclovir (severe/congenital)
HHV 6 and HHV 7
Exanthem subitum, Roseola, or sixth disease.
Genomic organization: dsDNA (beta herpes virus), enveloped w/ icosahedral capsid
Tropism: hematopoetic stem cell, leukocytes, epithelial cells.
Clincal course: Infancy and childhood. Faint pink, nonpruritic morbilliform rash on trunk which develops after a high fever (72hrs.).
Rx: ganciclovir and foscarnet
Can also cause: Adult- mononucleosis, pityriasis rosea.
immunocompromised - encephalitis, pneumonitis, sycytial giant-cell hepatitis, and disseminated disease
Kaposi Sarcoma Virus
HHV - 8
Genomic organization: dsDNA, enveloped w/ icosahedral, capsid.
Malignacies: Kaposi Sarcoma (vFLIP, vBCL-2, and vCyclin are homologs of normal protein that regulates apoptosis. VGPCR is homolog for protein that regulates cell fate.)
People affected immunocompromised.
Tropism: B cells
Rx: Ganciclovir, Cidofovir, and foscarnet. Goal is to attack lytic phase preventing reinfection only.
Acute T-cell lymphoma (ATL)
2-4% or patients infected w/ HTLV develop this malignancy.
Sx: Malaise, Night sweats, Fever, Cachexia, Adenopathy
Human T-cell Lymphotrophic Virus (HTLV-1 and HTLV-2)
Genomic organization: + ssRNA w/ reverse transcriptase. Enveloped w/ icosahedral capsid.
Tropism: T-cells.
HTLV-1 - causes T-cell leukemia, and HTLV-1 associated myelopathy/tropical spastic paraparesis.
HTLV-2 - non pathogenic
HTLV-2 - more common in Carribean, Eastern S. America, Western Africa, and Southern Japan.
HTLV binds host gp46 and fuses w/ host cell membrane –> integrates into DNA –> TAX-induced (affects CREB, CREM, NFKB, and NSF) viral gene transcription and REX induced tranlation or viral mRNA
Malignancies: Acute T-cell lymphoma (ATL) occurs in 2-4% or HTLV-1 Associated Myelopathy/Tropical Spastic Parapesis
HTLV-1 Associated Myelopathy (HAM) or Tropical Spastic Parapesis (TSP)
Pathology: infected T cells lead to astrocytosis and inflammation of gray and white matter of spinal cord resulting in progressive demyelination.
Sx: Gait disturbance, Stiffness/ weakness in legs, back aches, weak bladder, constipation
HIV
Genomic organiztion: Group VI + ssRNA w/ RT. Lentivirus subgroup. Enveloped w/ Icosahedral capsid.
Tropism: CD4+ T cell primarily. Also Macrophages, and dendritic cells. CD4, CCR5, or CXCR4.
HIV-2 has a lower transmissibility and less potential to progress to AIDS (confined to W. Africa).
Cell counts: CD4+ 500-1500 cells/ cubic mm (normal) Below 500 (immunocompromised) Below 200 AIDS
Rx: Zidovudine, efavirenz, raltegrovir, ritonavir, maroviroc
Dx w/ rapid ELISA test. Confirmed w/ Western Blot. Monitor patient’s status w/ CD4 tests and RT PCR viral load tests. `
Ebola
Genomic organization: - RNA virus. Enveloped with helical capsid.
Tropism: monocytes, macrophages, and dendritic cells
Clinical signs: fever (always and before infectious stage), myalgia, and malaise. Initial period followed by flu-like symptoms and sometimes rash, melena, hematemesis, shock, and encephalopathy.
Cause of death is sever organ dysfunction, encephalitis, anuria, seizures, and ultimately death.
Rx: Supportive care especiall replacement of fluid and lytes. Oxygen and vasopressors to maintain adequate bodily bodily function.
Iron-Deficiency Anemia
Things you must know:
- Most important cause: GI bleeding
- Microcytic, hypochromic anemia
- Increased anisoctyosis and poikilocytosis
- Abnormal iron studies
Causes: GI bleed, menses, hemorrhage, pregnancy, poor diet, poor absorption (celiac’s), pregnancy, gastric bypass, crohn’s, H. pylori, PNH
Clinical symptoms: pale, Koilonychia (spoon nails), smooth tongue, pica, reduced work productivity, Angular cheilitis, dsyphagia secondary to esophogeal webs.
Morphology: hypochromic, microcytic anemia, anisocytosis, poikilocytosis, decreased reticulocytes, increased platelets.
Labs: decreased serum iron, increased iron-binding capacity, and decreased ferritin (run first –> if positive = iron deficiency), decreased transferrin saturation, decreased hemoglobin
Bone marrow aspirate w/ prussian blue stain is gold standad.
Rx: Find out why patient is iron-deficient. Then give oral iron.
Megaloblastic Anemia
Retarded DNA synthesis w/ unimpaired RNA synthesis resultin in BIG cells w/ immature nucleus and mature cytoplasm.
Secondary to: B12 deficiency (dietary, lack of intrinsic factor, tapeworm), Folate deficiency (diet, alcoholism)
Morphology: oval macrocytes, hypersegmented neutrophils*
Symptoms: atrophic glossitis
Hemolytic anemia
Both chronic and acute; inherited and acquired.
Signs: Increased RBC destruction (Increased unconjugated/indirect bilirubin (jaundice), Increased LDH, Decreased haptoglobin (binds free hemoglobin in blood, hemoglobinemia/uria.) Increased RBC production (Reticulocytosis, and nucleated red cells in blood)
Labs: Direct Antiglobulin Test, DAT (do this right away. Positive = immune process.)
Morphology: Normochromic, normocytic, spherocytes, other poikilocytes.
Treatment: Acute: treat shock, transfusions w/ caution. Splenectomy may help.
Heriditary Spherocytosis
Things you must know:
- Tons of spherocytes
- Spectrin (or other cytoskeleton) defect
- Splenectomy is currative
Clinical picture: Triad: anemia, jaundice, splenomegaly (don’t need all three).
1 in 5000
Variable age of onset, severity. Crisis often due to parvovirus.
Rx: Splenectomy or RBC transfusion as needed.
Warm Autoimmune Hemolytic Anemia
Things you must know:
- IgG
- Spleen
- Spherocytes
Can be primary or secondary to leukemia/lymphoma, other malignancies, autoimmune disorders, infx, drugs
Pathogenesis: IgG coats red cells (opsonization) –> macrophages engulf (disappear) or nibble on them (spherocytes).
Dx: w/ DAT.
Rx: steroids and splenectomy if necessary.
Cold Autoimmune Hemolytic Anemia
Things you must know:
- IgM, complement
- Some intravascular hemolysis
- Mostly spleen
- Agglutination
Pathogenesis: IgM coats RBCs, falls off in warm body parts. Causes agglutinaiton
Clinical - chronic hemolysis aggravated by cold. Pallor, cyanosis in cold body parts.
Morphology: RBC agglutinates, rare spherocytes.
Dx w/ DAT
Rx: keep patient warm and treat underlying cause (not a huge concern)
Congenital Neutropenia
Lack of GM-CSF
Frequent bacterial infections
Chronic granulomatous disease
Inability to produce hydrogen peroxide and hypochlorous acid.
Inability to kill phagocytosed bacteria
Leukocyte adhesion deficiency (LAD)
Lack of integrin subunit, the common Beta chain.
Inability to recruit innate immune cells to site of inflammation
Increased susceptibility to bacterial, fungal, and viral infxs.
Complement defects (various)
Increased susceptibility to bacterial infxs.
Reduced ability to remove immunocomplexes.
Chediak-Higashi Syndrome
Defect in gene LYST, a lysosomal trafficking gene
Increased susceptibiltiy to bacterial infxs.
B6 deficiency
Slowed heme production resulting in microcytic, hypochromic anemia. (pyridoxal phosphate is needed for heme synthesis)
Isoniazid can casue B6 deficiency resulting in peripheral neuropathy, CNS effects, and anemia. (monitor levels in TB patients)
Consider supplementation in patients in which neuropathy is common.
Lead poisoning
Lead inactivates delta-aminolevulinic acid dehydratase and ferrochelatase.
Results in decreased heme production.
LEAD
Lead Lines on gingivae and epiphyses of long bones on x-ray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops - wrist and foot drop. Dimercaprol and EDTA 1st line of treatment.
Succimer for kids (It sucks to be a kid who eats lead.
Acute prophyrias
Almost always autosomal domminant.
Very very rare.
Sx: Abdominal pain, vomitting, constipation, neurologic problems (pain, paresis, mental sx) No photosensitivity.
Urine darkens w/ time
Characterized by long quiescent periods w/ acute attacks.
If suspect run rapid urine BPG.
Rx: withdraw provoking factor, supportive care. IV hematin.
Heriditary Coproporphyria
Deficiency in coproporphyrinogen
Sx same as acute intermittent porphyria + photosensitivity.
Porphyria Cutanea Tarda
Deficiency of hepatic uroporhyrinogen decarboxylase (URO-D)
Most common porphyria (around 5-25 per 100,000)
There is an acquired form that is often associated (50%) with Hepatitis C.
Sx: Bullous dermatosis, Scarring, hyperpigmentation, and hypertrichosis.
Elevated urine total porphyrins
Rx: Avoid precipitating factors (EtOH), Phlebotomy once a week until remission. Iron chelation if phleb not possible.
Anemia of Chronic Disease (AOCD)
Hypoproliferative anemia secondary to inflammation. Iron stores are increased, but decreased utilization.
Associated w/ chronic nonhematologic conditions:
- infx
- malignant
- immunologic
- ischemic heart disease
- traumatic
Increased inflammatory cytokines result in increased hepcidin and decreased EPO (adaptive response to keep iron away from bacteria that require it for metabolism)
Labs: low serum iron, low transferrin/TIBC, normal/high ferritin, normal serum transferrin saturation. Increased ESR and CRP.
Rx: most is self limited/ tx underlying process. Correct any iron deficiency, EPO if needed.
Heriditary Hemochromatosis
Type 1 - HFE mutation (only one that is important)
autosomal recessive
Mutated protein results in increased hepcidin levels resulting in too much iron abosrbtion. Eventual iron overload.
High prevalence. 3-5/1000 (10-15% = heterozygotes)
Lab tests: Increased serum iron, ferritin, TF saturation, low TIBC/tranferrin, decreased iron storage in macrophages. Normal hemoglobin.
Gold standard is liver biopsy w/ Perl’s stain for hemosiderin.
Severe sx usually not seen until decades after iron loading, so important to catch early to treat. Normal life if caught.
Triad of sx: DM, hepatomegaly, Hyperpigmentaion.
Death is from cirrhosis, hepatocellular carcinoma, CHF.
Rx: If ferritin > 1000 and normal LFTs at dx proceed w/ phelbotomy (1-2 units/week) as long as HCT > 35 (32 in Females). Maintenance phlebotomy to maintain ferritin between 20-50.
If ferritin
Thalassemias
Genetic defect in hemoglobin synthesis. Decreased synthesis of one of two globin chains.
Ranges in severity from asymptomatic to incompatible with life (hydrops fetalis)
Found in people of Africa, Asian, and Mediterranean heritage.
Dx: smear: microcytic/hypochromic, misshapen RBCs, abnormal Hgb electrophoresis, Fe stores elevated.
Rx: RBC transfusions + Fe chelation, stem cell transplants.
Sideroblastic Anemias
Heterogenous grouping of anemias defined by presence of ringed sideroblasts in the BM.
Etiologies:
- Heriditary (rare)
- Myelodysplasia
- EtOH
- Drugs (Isoniazid, Chloramphenicol)
