Pathophys ch. 11-12 test 2

enlarged lymph nodes

“complete response” in that treatment has eliminated all clinically discoverable cancer cells (but it takes 1 trillion or so before a cancer can be found)

Inflammation/infection of the mouth

both the donated tissue and the recipient area lie within the same person.

donor and recipient are different people.

An immature, developing form of blood cell

one of the Herpes viruses. This is the virus that causes acute mononucleosis.

by some means other than through the gastrointestinal tract. (Think “needle.”)

abnormally elevated serum levels of gamma globulins (antibodies or immunoglobulins)

conversion into the state in which a blood test become positive.

inability of immune system to respond to a substance expected to be antigenic (capable of generating an immune response)

a multi-nucleated mass created by the fusion of multiple cells

• ---clinical manifestations and explanations of why they occur--
• 1.Bone marrow suppression (common because normal blood cell precursors “crowded out” by malignant cells) causes
• a.Anemia
• b.Thrombocytopenia—causes bleeding difficulties
• c.Neutropenia

2.Infiltrative manifestations (malignant cells invading solid organs)

peripheral blood smear, bone marrow biopsy, lymph node biopsy

1. Nutrition maintenance—difficult due to anorexia, nausea/vomiting, stomaitis.

a. Colony stimulating factors—can be administered to stimulate development of leukocytes and shorten time of neutropenia.

• a.Donor sample harvest less difficult due to peripheral stem cell transplantation—for either:
• i.Autologous—from patient’s own cells; or
• ii.Allogenic—from a different person’s cells.

b.Anemia—erythropoeitin administration helpful.

c.Thrombocytopenia—may require platelet transfusions.

d.Pain—always a problem

e.Loss of epithelial tissues & appendages—mucous membranes, hair, eyebrows/lashes, etc.

• i. Megakaryocytes—which give rise to platelets
• ii. Red blood cells
• iii. Monocytes—which develop into macrophages (and all the macrophages that carry different names—histiocytes, microglia, Kupffer cells, etc.)
• iv. Granulocytes
• a. Neutrophiles
• b. Eosinophils
• c. Basophils

• i.T-cells (T-lymphocytes)
• ii.B-cells (B-lymphocytes)
• iii.NK cells

• a.Chronic myeloid leukemia (CML)—15% of all leukemia cases in US. Average age of onset 40-50 yo.
• i.Philadelphia chromosome—unique to this disease.
• 1.This balanced translocation causes production of a single oncogene which causes the disease.

ii.Prognosis not usually good—allogenic bone marrow transplant or some newer chemotherapy drugs can be useful.

• i.AML—80% of acute leukemias in adults are AML; 20% in children.
• 1.Outcome worse if P53 & Rb tumor suppressor gene function lost.
• 2.Prognosis best with promyelocytic subtype.

• -if present in bone marrow: called leukemia;
• -if present in lymph nodes, called lymphoma.
• Location is a consequence of stage of disease, rather than cell type.

30% of all leukemias in US.

i.95% have malignant B-cell precursor.

ii.Indolent course, frequently found accidently in CBC blood tests, with no symptoms usually apparent.

iii.Average age of diagnosis 65-70 years; so frequently treatment not necessary (patients more likely to die of another condition than CLL).

iv.Mutation in the variable region of the immunoglobulin gene is associated with a median survival of 24 years; those lacking this mutation have median of 8 years!

80% B cells, remainder T cell precursors.

i.Malignant cells resemble immature lymphocytes, called lymphoblasts.

ii.Most cases present as leukemias, but lymphoblastic lymphomas are thought to be same condition at later stage.

iii.ALL primarily a disease of children—the most common malignancy & the 2nd leading cause of death.

iv.Quite curable in children (5 yr. survival 85%); less so in adults (30-50%).

rare, chronic leukemia, very curable

Malignancy of antibody-secreting matured, monoclonal B-cells (plasma cells), which invade bone and form multiple tumor sites. Exclusively adult.

i.Monoclonal antibodies detectable in blood on serum protein electrophoresis.

ii.Bence Jones protein—are antibody light chains found in urine; can cause kidney damage. (Renal insufficiency develops in 50% of patients.)

iii.Pathologic fractures and the bone pain associated with the bone infiltration are very miserable!

iv.Onset of disease usually slow, with some patients having only excess monoclonal antibodies, but no Bence Jones protein or bone lesions—a condition called monoclonal gammopathy of undetermined significance (MGUS).

The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and the second in those over 55 years old

malignancy of lymph nodes characterized by Reed-Sternberg cells (which originate from B-cells).

i.Epstein-Barr virus—frequently found in genome of these cells.

ii.Disease usually progresses in a predictable step-by-step pattern along lymph node chains.

• iii.Staging (I-IV) includes the letters “A” and “B”
• 1.A—no clinical symptoms
• 2.B—symptoms include: loss of >10% body weight, unexplained fevers, night sweats, pruritus (itching)

iv.Treatment with chemo/radiation; prognosis as good as 90% at 10-years, depending on stage.

i.95% in older adults, common in AIDS patients.

ii.Lifetime risk of developing one of these lymphomas: 1 in 50!

iii.Overall 5-year survival about 50%

• iv.Subtypes to know:
• 1.Burkitt lymphoma—the African variety is caused by Epstein-Barr virus, doubles in size daily!, and actually responds well to treatment.
• 2.T-cell lymphomas in adults are associated with infection by human T-cell leukemia virus, type I (HTLV-1)

RNA retrovirus, contains at least 9 genes. Reverse transcriptase is the enzyme that allows the virus to copy RNA into DNA.

1. once inside the body, HIV binds to cells with receptors called CD4 on their surface: especially T-helper/inducer cells & macrophages (but there are many others).

2. Intially the virus is attracted to macrophages and is called M-tropic. Later the virus becomes either dual tropic and affects both macrophages & T-cells, or T-tropic and affects primarily T-cells.

• 1. T cells are infected before the onset of symptoms. CD4+ T cells are composed of 2 subsets:
• a. T-helper-1 (TH1)—which produces interferon γ and IL-2, and is the subset markedly affected in advanced disease.
• b. T-helper-2 (TH2)—(produces IL-4, IL-6 and IL-10—but don’t memorize).

2. Once in the cytoplasm, a single-stranded DNA copy is made by reverse transcriptase from the viral RNA. DNA polymerase then copies it to make a second DNA strand, and destroys the RNA. The accuracy of DNA transcription is poor, with mutations occurring frequently

3. The DNA migrates into the nucleus, integrase incorporates it into host DNA, then it replicates together with the host DNA during every cell division, as well as being transcribed by viral promoter sequences to form virions between mitoses.

a. Macrophages & T cell numbers are decreased; B-cell numbers are normal. Hypergammaglobulinemia is common, but because B-cells require TH activation to respond to bacterial polysaccharide antigens, their responsiveness is decreased.

b. Huge numbers of viruses are produced every day—overwhelming the immune system. Longer-term survivors produce fewer virions and have strong CD8+ killer T-cell activity.

1. Primary infection—virus enters body, infects cells in blood, mucosa, which drains to lymph nodes & spleen.

2. Infection established in lymphoid tissues—which leads to viremia and symptoms: fever/chills, headaches, nausea/vomiting, fatigue, weakness, arthralgias, sore throat, stiff neck, photophobia, irritability, & rash, etc. platelets decreased, sed rate increased. These symptoms disappear. It is during this period that seroconversion occurs: anti-HIV antibodies appear.

3. Latency—3-12 year period in which antiviral immune activity is ongoing, production of virus continues, symptoms mild if present at all, 2 million or so viruses produced per day.

4. Symptomatic, chronic HIV infection—anergy, syncytium production, oral/genital herpes simplex & candidiasis usually develop, oral hairy leukoplakia, CMV, EBV infections, opportunistic infections.

5. Full-blown AIDS—CD4+ T-cell count < 100, 1 or more opportunistic infections, one or more tumors or cancers, including Kaposi sarcoma, lymphomas, or cancer of rectum/tongue.

6. **To diagnose infection, anti-HIV antibodies are detected, so until seroconversion occurs, infection is not diagnosable.

7. As the CD4+count declines, the patient progresses along the above continuum from HIV+ to full-blown AIDS.

The diagnosis of Pneumocystis carinii pneumonia in a HIV+ patient is enough to diagnose AIDS.