5 Hematologic Diseases Flashcards
- responsible for recognition and processing of foreign antigens (viruses, fungi, bacteria)
- protective function
lymphoid tissue
During response to antigenic challenges, how do lymph cells respond?
lymph cells proliferate –> results in enlargement of the lymphoid tissue (hyperplasia)
Sites of lymphoid tissue:
- lymph nodes
- lymphoid tissue of Waldeyer’s ring
- aggregates of lymphoid tissue normally scattered throughout the oral cavity: oropharynx, soft palate, lateral tongue, floor of mouth
- head and neck region
Where can lymphoid hyperplasia occur?
any site of lymphoid tissue
Intraoral indications of lymphoid hyperplasia:
- description
- size
- color
- locations (3)
- discrete, nontender, submucosa swellings
- < 1 cm in diameter
- normal, dark pink, creamy yellow-orange hue
- posterior lateral tongue, floor of mouth, wall of pharynx
reasons for enlarged lymph nodes: acute vs chronic infection
Acute- enlarged, tender, relatively soft, freely moveable
Chronic- enlarged, rubbery firm, nontender, freely movable, history of a previous inflammatory illness, should be a lack of progressive enlargement
differentials (2) for multiple persistently enlarged nontender lymph nodes
lymphoma
HIV infection
peak of tonsillar size
peaks early during the second decade of life (usually more prominent in younger people)
symmetric vs asymmetric LARGE tonsils
As long as the large tonsils are symmetrical and asymptomatic, we do nothing!
Tonsillar asymmetry is a potentially serious sign that should be evaluated further to rule out the presence of a malignancy.
decrease in the volume of RBCs (hematocrit) or in the concentration of hemoglobin
anemia
often a sign of underlying disease
anemia
Symptoms related to decreased O2 carry capacity due to anemia:
- tired
- headache
- lightheaded
- pallor of mucosa
genetic disorder of hemoglobin synthesis–> hemoglobinopathy
sickle cell anemia
genetic cause of sickle cell anemia
thymine substituted for adenine in DNA –> altered codon results in valine instead of glutamic acid in the beta-globin chain of hemoglobin
- deoxygenated hemoglobin molecule is prone to molecular aggregation and polymerization
- RBCs undergo deformation and take on a rigid sickle shape
sickle cell anemia
sickle cell trait vs disease
Sickle cell trait = one allele is affected (45-50% of hemoglobin is normal, no significant clinical manifestations)
Sickle cell disease = both alleles affected (1:350-400 black people in the US)
1:350-400 black people in the US
sickle cell disease
tissue/organ affected by sickle cell anemia
any tissue or organ
Clinical findings of sickle cell anemia? How many patients have severe involvement?
- highly variable clinical findings
- 1/3 of patients have severe involvement
patients with sickle cell anemia are more prone to these infections
S. pneumoniae (thought that susceptibility develops following splenic destruction from repeated infarctions)
delayed growth and development from sickle cell anemia
impaired kidney function and ocular abnormalities due to repeated occlusive episodes in small vessels
when the sickling of erythrocytes becomes severe
sickle cell crisis
Causes (5) of sickle cell crisis:
- most have unknown cause
- hypoxia
- infection
- hypothermia
- dehydration
A sickle cell crisis causes extreme pain from ______ and ______ of affected tissue. What are the most common affected locations?
ischemia and infarction / long bones, lungs, and abdomen most affected
How long do episodes of sickle cell crisis last?
3-10 days
tx for sickle cell crisis
- supportive care, fluids, rest, analgesics
- avoid exposure to cold, dehydration, and strenuous exercise to avoid sickle cell crisis
oral manifestation: hair on end appearance of skull bones
sickle cell anemia
oral manifestation: reduced trabecular pattern of the mandible due to increased hematopoiesis in marrow
sickle cell anemia
oral manifestation: asymptomatic pulpal necrosis
sickle cell anemia
oral manifestation: increased prevalence of osteomyelitis
sickle cell anemia
tx for sickle cell anemia
- continuous prophylactic penicillin therapy until age 5 to prevent S. pneumoniae infection
- pneumococcal vaccination
- hydroxyurea –> increases fetal form of hemoglobin
- avoid exposure to cold, dehydration and strenuous exercise to avoid sickle cell crisis
- genetic counseling
tx: continuous prophylactic penicillin therapu until age 5 to prevent S. pneumoniae infection
sickle cell anemia
tx: pneumococcal vaccination
sickle cell anemia
tx: hydroxyurea –> increases fetal form of hemoglobin
sickle cell anemia
tx: genetic counseling
sickle cell anemia
disorders of hemoglobin synthesis due to reduced synthesis of either the alpha-globin or beta-globin chains of the hemoglobin molecule
thalassemias
among the most common inherited human conditions
thalassemias
Degree of clinical severity of thalassemia varies depending on? How many mutations have been documented for beta-thalassemia alone?
depends on genetic alteration and if it is heterozygous or homozygous / 200 different mutations
heterozygous vs homozygous state of thalassemia
Heterozygous- adequate amount of normal hemoglobin can be made, affected patient experiences few signs or symptoms
Homozygous- problems are often severe or even fatal
cause of thalassemias
when one of the Hb chains is not being made in adequate quantities, so a normal amount of Hb cannot be made –> excess globin chains accumulate within the erythrocyte and compromise cell structure and function –> abnormal erythrocytes recognized by spleen and selected for destruction (hemolysis)
Thalassemia minor or major? one defective gene for the beta-globin molecule is inherited
minor
Thalassemia minor or major? no significant clinical manifestations are usually present
minor
Thalassemia minor or major? 2 defective genes for the beta-globin molecule
major
another name for thalassemia major
Cooley’s or Mediterranean anemia
develops in the first year of life because a severe microcytic, hypochromic anemia develops when fetal hemoglobin synthesis ceases after 3-4 months
thalassemia major
Thalassemia minor or major? RBCs are extremely fragile and survive for only a few days
major
Thalassemia minor or major? rate of hematopoiesis is greatly increased (up to 30x normal), although ineffective this is an attempt to maintain adequate oxygenation
major
result of increased rate of hematopoiesis with thalassemia major
- massive bone marrow hyperplasia
- hepatosplenomegaly from extramedullary hematopoiesis
Thalassemia minor or major? reduced trabecular pattern of the mandible resulting from increased hematopoiesis
major
Thalassemia minor or major?painless enlargement of the mandible and maxilla due to marrow hyperplasia
major
tx of thalassemia major
blood transfusions administered every 2-3 weeks
Result of repeated blood transfusions from tx of thalassemia major? What is particularly affected? Can lead to?
- can lead to hemochromatosis- an abnormal deposition of iron throughout body tissues
- heart, liver, and endocrine glands are particularly affected by the toxic accumulation of iron
- can lead to death
an abnormal deposition of iron throughout body tissues due to frequent blood transfusions
hemochromatosis (from tx of thalassemia major)
failure of hematopoietic precursor cells in the marrow to produce enough of all types of blood cells
aplastic anemia
How is aplastic anemia an immune-mediated disease?
cytotoxic T lymphocytes target hematopoietic cells in the marrow
stem cells do not seem to undergo normal maturation despite normal or increased levels of cytokines
aplastic anemia
Potential triggers of immune-mediated destruction (aplastic anemia):
Exposure to toxins
- benzene exposures
- chlororamphenicol (antibiotic no longer available orally in US)
- certain viral infections (hepatitis nonA, nonB, nonC, nonG)
3 things deficient with aplastic anemia and their side effects:
1) erythrocyte deficiency- decreased oxygen-carrying capacity of the blood, fatigue, lightheaded, tachycardia, weakness
2) thrombocytopenia- bruising and bleeding problems, retinal and cerebral hemorrhages
3) neutropenia, leukopenia, granulocytopenia- loss of WBCs, higher susceptibility to bacterial and fungal infections
Oral manifestations:
- pale mucosa due to decreased RBCs
- gingival hemorrhage and hyperplasia
- petechiae, purpura, and ecchymosis
aplastic anemia
dx blood studies reveal pancytopenia (low granulocytes, platelets, and reticulocytes)
aplastic anemia
tx of aplastic anemia
- spontaneous recovery can occur in mild cases
- antibiotics to prevent infections
- transfusions of RBCs and platelets*
- replace defective marrow* (bone marrow transplantation, peripheral blood stem cell transplantation)
How do you replace defective marrow when treating aplastic anemia?
- bone marrow transplantation
- peripheral blood stem cell transplantation
- increased susceptibility to bacterial infections
- caused by decreased production or increased destruction of neutrophils
neutropenia
oral mucosal infections may be the first sign of this condition
neutropenia
can be congenital/genetic or acquired
neutropenia
acquired causes of neutropenia
- malignancy crowds out and destroys normal marrow elements
- medication induced
- B12 deficiency
- viral infections can increase destruction of neutrophils and decrease production of them (Hep A and B, rubella, measles, varicella, HIV)
- some bacterial infections
medications that cause neutropenia (4)
- chemotherapeutics
- antibiotics (penicillin, sulfonamides)
- tranquilizers
- diuretics
Clinical findings:
- pts tend to develop bacterial infections
- gingival ulcers
- premature periodontal bone loss with loss of primary teeth
neutropenia
Bacterial infections that patients with neutropenia tend to develop and where?
- Staph aureus and gram-neg organisms
- middle ear, oral cavity, and perirectal areas
tx: antibiotic therapy, for oral involvement very good OH and frequent cleanings
neutropenia
- certain ethnic groups that consistently have neutrophil counts that would qualify as neutropenia (as low as 1200/mm3)
- individuals are healthy
- appears to have no effect on health of the patient
- neutrophil counts respond to bacterial challenge
benign ethnic neutropenia (African and Middle Eastern)
decreased # of circulating blood platelets
thrombocytopenia
normal # of circulating blood platelets
200,000-400,000/mm3
Causes of thrombocytopenia (3):
1) Reduced production- due to drugs or malignancy affecting marrow
2) Increased destruction- immunologic reaction to drugs, heparin, reaction to infection
3) Sequestration in the spleen- normally 1/3 of platelets are sequestered in the spleen, but some diseases lead to splenic enlargement and a greater number of platelets are retained there
oral lesions are often initial finding, evident < 100,000 mm3, petechiae/ecchymosis/hematoma
thrombocytopenia
If you see evidence of this in your patient, refer to their physician for evaluation.
thrombocytopenia
Treatment:
- If drug related: discontinue drug immediately, platelet count returns to normal after several days
- Platelet transfusion
- Possible corticosteroids
thrombocytopenia
previous name for Langerhans cell histiocytosis
histiocytosis X
proliferation of Langerhans cell histiocytes
Langerhans cell histiocytosis
- dendritic mononuclear cells found in the epidermis, mucosa, lymph nodes, and bone marrow
- APCs, present antigens to T cells
Langerhans cell histiocytes
clonality studies suggest this is a neoplastic disorder
Langerhans cell histiocytosis
Why do studies suggest that Langerhans cell histiocytosis is a neoplastic disorder?
- cells develop clonally –> grow from one “parent” cell
- with varying numbers of eosinophils, ly,phocytes, plasma cells and multinucleated giant cells
> 50% of patients under age 15, 10-20% have jaw involvement
Langerhans cell histiocytosis
affects 5 children and 1-2 adults per million population
Langerhans cell histiocytosis
classifications of Langerhans cell histiocytosis
Unifocal disease (eosinophilic granuloma) –> single-system disease with single site of involvement
Multifocal disease (Hand-Schuller-Christian disease) –> multiple sites of involvement in single organ system
Multifocal multisystem disease (Leterer-Siwe disease) –> multiple involved sites in more than one organ system
Name the classification of Langerhans cell histiocytosis: localized form, bony lesions without visceral involvement
unifocal disease (eosinophilic granuloma)
Which form of Langerhans cell histiocytosis is this?
Clinical characteristics:
- seen in older children and adults
- asymptomatic or local pain
unifocal disease (eosinophilic granuloma)
radiograph: RL areas, vary from punched out RL areas to ill-defined, teeth “floating in space”
Langerhans cell histiocytosis
histo: mixed inflammatory cell infiltrate consisting of Langerhans histiocytes, variable numbers of eosinophils, lymphocytes, plasma cells, and neutrophils, has special stains to identify
Langerhans cell histiocytosis
birbeck bodies/granules on SEM
Langerhans cell histiocytosis
tx of Langerhans cell histiocytosis
- depends on lesion size and degree of tissue involvement
- surgery, radiation, chemotherapy
- individually or in combination
- surgery for accessible jaw lesions
- possible intralesional injections of corticosteroids
Neutropenia is a decrease in number of circulating neutrophils below _______.
1,500/mm^3
