Unit 4 Study Guide
Below is a list of the specific topics that you should know for exam 4.
1. Know Infectious mononucleosis: patho, clinical manifestations, diagnostics,
treatment & complications. (p 945)
• Benign, acute, self limiting, lymphoproliferative clinical syndrome characterized by acute viral
infection of B lymphocytes (B cells)
• Assoc. with human tumors, such as B- cell and T- cell lymphoma, Hodgkin lymphoma, and
nasopharyngeal carcinoma,
• Linked to posttransplant lymphoproliferative diseases and gastric carcinoma
• Most common cause: EBV; HSV
SYMPTOMS
• Pharyngitis, lymphadenopathy, fever
• Individuals with immunodeficiency the proliferation of infected B Cells may be uncontrolled and can
lead to B Cell lymphomas/those with malaria/HIV increased risk of EBV ass lymphomas, include.
Burkitt lymphoma.
• EBV not documented from environmental sources, HUMANS are major reservoir
• More than 90% of individuals have antibodies to EBV
• 50-85% of children are infected by age 4, usually asymptomatic and provide immunity
• Symptomatic IM usually affects young adults btwn 15-24 yrs old ,males have a later peak 18-24.
• Overall incidence 6-8 cases/1000 persons/yr
• IM uncommon in >40, if does occur, commonly from CMV
TRANSMISSION
• Person to person (virus is shed in salivary secretions at high levels for a prolonged time) viral oral
shedding persists for about 6 months, once infected, virus may be intermittingly shed in oropharynx for
decades
• Breastfeeding
• Sexual transmission
• Virus initially infects the oropharynx, nasopharynx, and salivary epithelial cells with later spread into
lymphoid tissue inro and B cells. Once the virus enters the blood stream, the infection spreads
systemically.
PATHOPHYSIOLOGY
1 1
, • Immunocompetent- unaffected B cells produces antibodies (IgG,IgA,IgM) against the virus. At the
same time, massive activation and proliferation of cytotoxic T cells (CD8) directed against EBV
infected cells. Immune response against EBV infected cells is largely responsible for cellular
proliferation in the lymphoid tissue (lymph nodes, spleen, tonsils, and occasionally liver) Sore throat
and fever are caused by inflammation at the site of initial viral entry and initial infection (mouth and
throat )
CLINICAL MANIFESTATIONS:
• Incubation period for IM 30-50 days
• Early flu like symptoms-h/a, malaise, joint pain, fatigue, may appear during first 3-5 days although
some people are without symptoms
• At the time of diagnosis, commonly present with class group of symptoms:
Fever, sore throat, cervical lymph node enlargement, and fatigue
• Pharyngitis is diffuse with whitish/grayish green thick exudate, can be painful
• Progression: generalized lymphadenopathy, enlarged spleen, atypical activated T lymphocytes
(mononucleosis cells) in the blood
• Self-limiting, recovery occurs in a few weeks; fatigue 1-2 months after resolution
• Splenomegaly clinically evident 50% of the time, rare, but most common cause of death
Complications:
• liver or spleen enlargement, hepatic failure, meningitis, encephalitis, Guillain-Barre syndrome, Bell
palsy, pleural effusion. Eye manifestations, eyelid and periorbital edema, dry eyes, keratitis,
conjunctivitis. Reyes syndrome in children with ebv infection. Pulm and resp failure have been
documented but in immunocompromised.
Diagnostics & treatment:
• based on Hoagland's criteria of at least 50% lymphocytes and at least 10% atypical lymphocytes in the
blood in the presence of fever, pharyngitis, and adenopathy confirmed by a positive serologic test.
Serologic tests are used to determine a heterophile antibody response.
2. Know the leukemias: patho, clinical manifestations, diagnostics, treatment &
complications p. 947
• Clonal malignant disorder of the bone marrow and usually but not always of the blood
2 2
, • Common pathological feature of all forms is uncontrolled proliferation of malignant leukocytes,
causing overcrowding bone marrow and decreased production of and function of normal hematopoietic
cells
• Chromosomal abnormalities and translocations common
• When genes become mutated, they create genomic aberrations that block cell maturation and activate
pro-growth signaling pathways that prevent apoptic cell death
• World Health Organization (WHO) groups lymphoid neoplasms into 5 broad categories, defined by
cell of orgin:
1. Precursor B-cell neoplasms (immature B cells)
2. Peripheral B-cell neoplasms (mature B cells)
3. Precursor T-cell neoplasms (immature T cells)
4. Peripheral T-cell and NK (natural killer)-cell neoplasms(mature T cells and NK Cells)
5. Hodgkin Lymphoma (Reed Sternberg [RS] cell and variants)
• Acute Leukemia characterized by undifferentiated or immature cells, usually a blast cell. Onset
ABRUPT and RAPID. Without tx, short survival time.
• Chronic Leukemia, predominant cell is more differentiated but does not function normally, with
SLOW progression
• Four General Types of Leukemia:
-Acute Lymphocytic (ALL)
-Acute Myelogenous (AML)
-Chronic Lymphocytic (CLL)
-Chronic Myelogenous (CML)
• Leukemia is more common in adults/higher incidence in males
• Rates of induced remission and survival in most types has increased
PATHOPHYSIOLOGY
• Most lymphoid neoplasms arise from B-cell and T-cell differentiation pathways
• Hypothesis of origin for leukemias is “clonal disorders driven by genetically abnormal progenitor cells
or stem like cancer cells (SLCCs) 85-90% of lymphoid neoplasm are of B-cell origin, followed by T-
cell tumors, and rarely NK cell tumors.
• Abnormal immature white blood cells, called leukemic blasts, fill bone marrow and spill into the
blood. They “crowd out” the bone marrow, compete for growth factors and cause cellular proliferation
of the other cell lines to decrease or cease.
3 3
, • Genetic translocations (mitotic errors) are observed in leukemic cells
• most common genetic abnormality is reciprocal translocation between chromosomes 9 and 22 -t (9;22,
the Philadelphia chromosome. First observed in people with CML, present in 95%. A single most
leukemia and lymphoma does not lead to an aggressive malignancy. (p 950)
• In most cases leukemic cells are ejected into the blood where they accumulate, these cells also infiltrate
and accumulate in the liver, spleen, lymph nodes, and other organs, throughout the body. The
presentation of large numbers of leukemic cells in the blood may be one of the indicators of leukemia,
however, leukemia is still a primary disruption of bone marrow
• Environmental factors such as cigarette smoke, benzene, and ionizing radiation may increase risk of
developing leukemia, as well as infections with HIV, hepatitis C virus, or the human T-cell
leukemia/lymphoma virus type 1 (HTLV-1). Also, drugs that cause bone marrow depression may
predispose individuals to leukemia.
ACUTE LEUKEMIAS (p 951)
• 2 types: Acute Lymphocytic leukemia (ALL) /Acute Myelogenous Leukemia (AML)
• ALL disease of the bone marrow, aggressive and fast growing, too many lymphoblasts (immature
lymphocyte with altered morphology) or lymphocytes in the bone marrow and peripheral blood. It is
also called acute lymphoblastic leukemia. Increased rink to ALL link to exposure to x rays before birth,
ionizing radiation, post tx with chemo, certain chemo exposures, paint strippers, and certain genetic
conditions.
• AML is a disease of the bone marrow, an aggressive fast -growing leukemia, highly heterogenous
disease. Malignancy of stem cell precursors of the myeloid lineage re blood cells, platelets, wbcs,
(except b and t cells) characterized by overproductions neoplastic clonal myeloid stem cells or
myeloblasts (there are 6 groups of AML (P. 951) more common in adults.
• People from developed countries and higher socioeconomic classes have increased incidence of ALL
PATHOPHYSIOLOGY
• ALL progress from malignant transformation of immature B or T cell progenitor cells (like a stem cell)
Most cases of ALL occur in children and In first decade. Adult mortality rate HIGHER
• Chromosomal aberations in all disrupt normal B and T cell development by causing dysregulation of
expression and function of transcription factors. Most T ALLS have mutations in NOTCH1 a gene ,
necessary for normal T cell development.
• Many B- ALLs have mutations affecting genes required for differentiation of early precursor cells, such
as PAX5, TCF3, ETV6, RUNX1. By altering these “prime” regulatory factors, the mutations promote
maturation arrest and increased self- renewal creating a stem cell phenotype. the identification of
mutations found in ALL is ongoing and includes mutations that drive cell growth and mutations that
increase tyrosine kinase activity and RAS signaling.
• AML IS MOST COMMON ADULT LEUKEMIA
• See drive mutations of AML on page 951, AML alter genes that encode transcriptions factors needed for
normal myeloid differentiation, consequently differentiation becomes arrested. These mutations affect
the epigenome, suggesting that epigenetic alterations are key in AML. Mutations may lead to
proliferation by activating growth factor signaling, as well as decreased rate of apoptosis. Thus, bone
marrow and peripheral blood are characterized by leukocytosis and a predominance of blast cells.
Increase in immature blasts. Displacement causes bleeding, anemia, infection.
4 4
Below is a list of the specific topics that you should know for exam 4.
1. Know Infectious mononucleosis: patho, clinical manifestations, diagnostics,
treatment & complications. (p 945)
• Benign, acute, self limiting, lymphoproliferative clinical syndrome characterized by acute viral
infection of B lymphocytes (B cells)
• Assoc. with human tumors, such as B- cell and T- cell lymphoma, Hodgkin lymphoma, and
nasopharyngeal carcinoma,
• Linked to posttransplant lymphoproliferative diseases and gastric carcinoma
• Most common cause: EBV; HSV
SYMPTOMS
• Pharyngitis, lymphadenopathy, fever
• Individuals with immunodeficiency the proliferation of infected B Cells may be uncontrolled and can
lead to B Cell lymphomas/those with malaria/HIV increased risk of EBV ass lymphomas, include.
Burkitt lymphoma.
• EBV not documented from environmental sources, HUMANS are major reservoir
• More than 90% of individuals have antibodies to EBV
• 50-85% of children are infected by age 4, usually asymptomatic and provide immunity
• Symptomatic IM usually affects young adults btwn 15-24 yrs old ,males have a later peak 18-24.
• Overall incidence 6-8 cases/1000 persons/yr
• IM uncommon in >40, if does occur, commonly from CMV
TRANSMISSION
• Person to person (virus is shed in salivary secretions at high levels for a prolonged time) viral oral
shedding persists for about 6 months, once infected, virus may be intermittingly shed in oropharynx for
decades
• Breastfeeding
• Sexual transmission
• Virus initially infects the oropharynx, nasopharynx, and salivary epithelial cells with later spread into
lymphoid tissue inro and B cells. Once the virus enters the blood stream, the infection spreads
systemically.
PATHOPHYSIOLOGY
1 1
, • Immunocompetent- unaffected B cells produces antibodies (IgG,IgA,IgM) against the virus. At the
same time, massive activation and proliferation of cytotoxic T cells (CD8) directed against EBV
infected cells. Immune response against EBV infected cells is largely responsible for cellular
proliferation in the lymphoid tissue (lymph nodes, spleen, tonsils, and occasionally liver) Sore throat
and fever are caused by inflammation at the site of initial viral entry and initial infection (mouth and
throat )
CLINICAL MANIFESTATIONS:
• Incubation period for IM 30-50 days
• Early flu like symptoms-h/a, malaise, joint pain, fatigue, may appear during first 3-5 days although
some people are without symptoms
• At the time of diagnosis, commonly present with class group of symptoms:
Fever, sore throat, cervical lymph node enlargement, and fatigue
• Pharyngitis is diffuse with whitish/grayish green thick exudate, can be painful
• Progression: generalized lymphadenopathy, enlarged spleen, atypical activated T lymphocytes
(mononucleosis cells) in the blood
• Self-limiting, recovery occurs in a few weeks; fatigue 1-2 months after resolution
• Splenomegaly clinically evident 50% of the time, rare, but most common cause of death
Complications:
• liver or spleen enlargement, hepatic failure, meningitis, encephalitis, Guillain-Barre syndrome, Bell
palsy, pleural effusion. Eye manifestations, eyelid and periorbital edema, dry eyes, keratitis,
conjunctivitis. Reyes syndrome in children with ebv infection. Pulm and resp failure have been
documented but in immunocompromised.
Diagnostics & treatment:
• based on Hoagland's criteria of at least 50% lymphocytes and at least 10% atypical lymphocytes in the
blood in the presence of fever, pharyngitis, and adenopathy confirmed by a positive serologic test.
Serologic tests are used to determine a heterophile antibody response.
2. Know the leukemias: patho, clinical manifestations, diagnostics, treatment &
complications p. 947
• Clonal malignant disorder of the bone marrow and usually but not always of the blood
2 2
, • Common pathological feature of all forms is uncontrolled proliferation of malignant leukocytes,
causing overcrowding bone marrow and decreased production of and function of normal hematopoietic
cells
• Chromosomal abnormalities and translocations common
• When genes become mutated, they create genomic aberrations that block cell maturation and activate
pro-growth signaling pathways that prevent apoptic cell death
• World Health Organization (WHO) groups lymphoid neoplasms into 5 broad categories, defined by
cell of orgin:
1. Precursor B-cell neoplasms (immature B cells)
2. Peripheral B-cell neoplasms (mature B cells)
3. Precursor T-cell neoplasms (immature T cells)
4. Peripheral T-cell and NK (natural killer)-cell neoplasms(mature T cells and NK Cells)
5. Hodgkin Lymphoma (Reed Sternberg [RS] cell and variants)
• Acute Leukemia characterized by undifferentiated or immature cells, usually a blast cell. Onset
ABRUPT and RAPID. Without tx, short survival time.
• Chronic Leukemia, predominant cell is more differentiated but does not function normally, with
SLOW progression
• Four General Types of Leukemia:
-Acute Lymphocytic (ALL)
-Acute Myelogenous (AML)
-Chronic Lymphocytic (CLL)
-Chronic Myelogenous (CML)
• Leukemia is more common in adults/higher incidence in males
• Rates of induced remission and survival in most types has increased
PATHOPHYSIOLOGY
• Most lymphoid neoplasms arise from B-cell and T-cell differentiation pathways
• Hypothesis of origin for leukemias is “clonal disorders driven by genetically abnormal progenitor cells
or stem like cancer cells (SLCCs) 85-90% of lymphoid neoplasm are of B-cell origin, followed by T-
cell tumors, and rarely NK cell tumors.
• Abnormal immature white blood cells, called leukemic blasts, fill bone marrow and spill into the
blood. They “crowd out” the bone marrow, compete for growth factors and cause cellular proliferation
of the other cell lines to decrease or cease.
3 3
, • Genetic translocations (mitotic errors) are observed in leukemic cells
• most common genetic abnormality is reciprocal translocation between chromosomes 9 and 22 -t (9;22,
the Philadelphia chromosome. First observed in people with CML, present in 95%. A single most
leukemia and lymphoma does not lead to an aggressive malignancy. (p 950)
• In most cases leukemic cells are ejected into the blood where they accumulate, these cells also infiltrate
and accumulate in the liver, spleen, lymph nodes, and other organs, throughout the body. The
presentation of large numbers of leukemic cells in the blood may be one of the indicators of leukemia,
however, leukemia is still a primary disruption of bone marrow
• Environmental factors such as cigarette smoke, benzene, and ionizing radiation may increase risk of
developing leukemia, as well as infections with HIV, hepatitis C virus, or the human T-cell
leukemia/lymphoma virus type 1 (HTLV-1). Also, drugs that cause bone marrow depression may
predispose individuals to leukemia.
ACUTE LEUKEMIAS (p 951)
• 2 types: Acute Lymphocytic leukemia (ALL) /Acute Myelogenous Leukemia (AML)
• ALL disease of the bone marrow, aggressive and fast growing, too many lymphoblasts (immature
lymphocyte with altered morphology) or lymphocytes in the bone marrow and peripheral blood. It is
also called acute lymphoblastic leukemia. Increased rink to ALL link to exposure to x rays before birth,
ionizing radiation, post tx with chemo, certain chemo exposures, paint strippers, and certain genetic
conditions.
• AML is a disease of the bone marrow, an aggressive fast -growing leukemia, highly heterogenous
disease. Malignancy of stem cell precursors of the myeloid lineage re blood cells, platelets, wbcs,
(except b and t cells) characterized by overproductions neoplastic clonal myeloid stem cells or
myeloblasts (there are 6 groups of AML (P. 951) more common in adults.
• People from developed countries and higher socioeconomic classes have increased incidence of ALL
PATHOPHYSIOLOGY
• ALL progress from malignant transformation of immature B or T cell progenitor cells (like a stem cell)
Most cases of ALL occur in children and In first decade. Adult mortality rate HIGHER
• Chromosomal aberations in all disrupt normal B and T cell development by causing dysregulation of
expression and function of transcription factors. Most T ALLS have mutations in NOTCH1 a gene ,
necessary for normal T cell development.
• Many B- ALLs have mutations affecting genes required for differentiation of early precursor cells, such
as PAX5, TCF3, ETV6, RUNX1. By altering these “prime” regulatory factors, the mutations promote
maturation arrest and increased self- renewal creating a stem cell phenotype. the identification of
mutations found in ALL is ongoing and includes mutations that drive cell growth and mutations that
increase tyrosine kinase activity and RAS signaling.
• AML IS MOST COMMON ADULT LEUKEMIA
• See drive mutations of AML on page 951, AML alter genes that encode transcriptions factors needed for
normal myeloid differentiation, consequently differentiation becomes arrested. These mutations affect
the epigenome, suggesting that epigenetic alterations are key in AML. Mutations may lead to
proliferation by activating growth factor signaling, as well as decreased rate of apoptosis. Thus, bone
marrow and peripheral blood are characterized by leukocytosis and a predominance of blast cells.
Increase in immature blasts. Displacement causes bleeding, anemia, infection.
4 4
