Cardio/Renal - Disorders of White and Red Blood Cells

What are the 3 relevant bleeding disroders?

- thrombocytopenia

- von willebrand disease

- hemophilia

What are the relevant red cell disorders?

Anemia:

- iron deficiency anemia

- pernicious anemia

- aplastic anemia

- hemolytic anemia:

- sickle cell anemia

- thalassemia

What are the relevant white cell disorders?

- agranulocytosis

- lymphoma

- leukemia

- multiple myeloma

Amenia can be either: (2)

• Decrease in hemoglobin concentration (oxygen carrying component of red blood cells)

or

• Decrease in hematocrit (volume of red blood cells)

T or F: Rather than being a disease itself, anemia is often a sign of an underlying disease

TRUE

Rather than being a disease itself, anemia is often a sign of an underlying diseases such as: `

• Renal failure

• Liver disease

• Chronic inflammatory conditions

• Malignancies

• Vitamin or mineral deficiencies

clinical manifestations of anemia are typically related to...?

the reduced oxygen carrying capacity of the blood

What are some clinical manifestations of anemia?

• Fatigue

• Shortness of breath

• Headache

• Dizziness

• Pale mucous membranes (usually palpebral conjunctiva is easiest to see)

pale mucous membranes, a clinical manifestation of anemia is easiest to see in what area of the body?

palpebral conjunctiva

What are some oral clinical manifestations of anemia?

• Glossitis

• Angular cheilitis

What is the most common cause of anemia?

iron deficiency

What is the most common nutritional deficiency in the world?

iron

What happens in iron deficiency anemia?

Amount of iron available to the body can't keep pace with need for iron in red blood cells

What are common causes of iron deficiency anemia? (4)

• Excessive blood loss

• Decreased intake of iron

• Decreased absorption of iron (celiac sprue)

• Increased demand for red blood cells (pregnancy)

What are treatments for iron deficiency anemia? (3)

• Eat diet high in iron

• Dietary supplement

• Treat underlying disease

Plummer-Vinson Syndrome is AKA?

Paterson-Kelly syndrome

What is Plummer-Vinson Syndrome (AKA Paterson-Kelly syndrome)

Rare condition in which patients have iron deficiency anemia in conjunction with glossitis and dysphagia

the pre-malignant condition of Plummer-Vinson Syndrome (AKA Paterson-Kelly syndrome) is associated with...

with oral and esophageal squamous cell carcinoma

clinical and oral symptoms of Plummer-Vinson Syndrome (AKA Paterson-Kelly syndrome)

• Burning sensation of oral mucosa (mucositis) and tongue (glossitis)

• Dysphagia

• Angular cheilitis

• Bald tongue (atrophy of papilla)

• Esophageal webbing• Spoon-shaped (koilonychia) and brittle nails

treatment of Plummer-Vinson Syndrome (AKA Paterson-Kelly syndrome)

• Dietary iron

• Evaluate for cancer

5-50% chance formalignancy

Pernicious anemia results from...

poor absorption of Vitamin B12 (Cobalamin, extrinsic factor)

Describe how one might develop pernicious anemia

Autoimmune attack on gastric mucosa prevents proper absorption

• Vitamin B12 needs intrinsic factor to be absorbed

• Intrinsic factor is produced by the parietal cells of the stomach

Vitamin B-12 is required for...

normal nucleic acid synthesis

Which anemia discussed puts patients at increased risk for gastric carcinoma?

pernicious anemia

T or F: vitamin B-12 deficiency is usually diet related

False.

Abundant in many foods so usually not a dietary deficiency

• Can be seen in elderly and strict vegetarians

the following are clinical features of?

• Generalized weakness and shortness of breath

• Numbness or tingling of the extremities

due to Vit B-12 being necessary for myelin maintenance

• Atrophy and erythema of oral mucosa

• Burning sensation of the tongue, lips, buccal mucosa, and other sites

pernicious anemia

treatment of pernicious anemia

• Intramuscular injections of Vitamin B12

• High dose of oral Vitamin B12

Which anemia discussed is a life-threatening hematologic disorder?

aplastic anemia

What happens in aplastic anemia?

Hematopoietic precursor cells do not produce adequate numbers of blood cells

Does aplastic anemia cause splenomegally?

NO

What causes aplastic anemia?

- Idiopathic

- drugs (chemotherapy)

- benzene

- viral infections

Clincal features of aplastic anemia?

3 different presentations depending on the cause

• Red blood cells = fatigue, tachycardia, lightheadedness

• Platelets = easy bruising/bleeding

• White blood cells = fungal and bacterial infections

Which anemia discussed has 3 different presentations depending on the cause?

aplastic anemia

• Red blood cells = fatigue, tachycardia, lightheadedness

• Platelets = easy bruising/bleeding

• White blood cells = fungal and bacterial infections

Oral findings in aplastic anemia:

- Hemorrhage

- petechiae

- pale oral mucosa

- gingival hyperplasia

What is hemolytic anemia?

premature destruction of RBCs

T or F: hemolytic anemia can be either acquired or inherited

true

hemolytic anemia can be associated with...

hyperbilirubinemia and jaundice

what are the two types of hemolytic anemia?

sickle cell anemia and thalassemia

Which hemolytic is an autosomal recessive disease?

sickle cell anemia

What is responsible for the crescent or sickle shape of RBCs

Defective hemoglobin

What is the most common type of hemolytic anemia

sickle cell anemia

sickle cell anemia is found most commonly in which groups?

people whose ancestors lived in areas affected by malaria

• The sickle cell gene results in protective effect against Plasmodium falciparum (the predominant parasite species that is most likely to cause severe malaria and death)

T or F: sickle cell anemia has specific oral manifestations

FALSE

how does sickle cell disease present?

• Malaise and weakness

• Muscle rigidity

• Widespread ischemia leads to death

radiographic findings of sickle cell disease

• "hair-on-end" appearance on skull

• "stepladder" trabeculae in posterior region of mandible/maxilla

thalassemia is a disorder of....

hemoglobin synthesis

• Reduced synthesis of alpha/beta globin chains

describe blood cell presentation thalassemia

Red blood cells are microcytic (small) and hypochromic (poorly hemoglobinized)

what are the two variants of thalassemia?

• α-Thalassemia

• β-Thalassemia

Mutations that cause thalassemia are common in

Mediterranean, African, and Asian regions in which malaria is endemic

• Just as in sickle cell anemia, these mutations protect against Plasmodium falciparum

Describe the difference between presentation in one abnormal allele vs. 2 abnormal alleles in B thalassemia.

1 abnormal allele- Thalassemia minor or β-Thalassemia minor trait

• No clinical manifestations

2 abnormal alleles- Thalassemia major (Cooley or Mediterranean Anemia)

• Severe microcytic, hypochromic anemia after 3-4 months

• Bone marrow hyperplasia

• Lymphadenopathy

thalassemia minor indicates abnormality in how many alleles? will there be any clinical manifesatations?

1 allele with no clinical manifestations

How does Beta thalassemia present clinically and radiographically?

• "chipmunk face" appearance = enlarged mandible and maxilla

• Radiographic presentation = "hair-on-end" appearance

What is the severe form of leukopenia (neutropenia)?

agranulocytosis

What results from decreased production or increased destruction of cells

agranulocytosis

what causes agranulocytosis?

• Exposure to drugs

• Marrow hypoplasia

• Overwhelming infection

clinical feature of agranulocytosis?

• Bacterial and fungal infections

• Oral lesions involve palate, buccal mucosa, tongue

---- Necrotizing, punched out ulcerations

---- Gingiva resembles necrotizing gingivitis

dental treatment of agranulocytosis includes:

Oral hygiene instructions with chlorhexidine rinse

what lymphomas fall under the under of Non-Hodgkin Lymphoma?

• B-cell lymphoma

• T-cell/ NK Lymphoma

A Malignant lymphoproliferative disorder describes what?

Hodgkin's lymphoma

Epstein-Barr virus has been linked to which lymphoma?

Hodgkin's lymphoma

which lymphoma has Male predilection?

Hodgkin's lymphoma

Reed-Sternberg cells are characteristic of?

Hodgkin's lymphoma

- "Owl-eye" nuclei seen microscopically

The following are characteristics of...

• Bimodal age and incidence

---- Occurs between 15-35 years old

---- Can occur after age 50

• Affects lymph nodes

- Cervical and supraclavicular nodes involved initially

Hodgkin's lymphoma

Majority of non-Hodgkin's lymphomas involve what?

B-cell lymphocytes

T or F: T- cell lymphomas are rare

TRUE

the following describes clinical presentation of?

• Slowly enlarging, non-tender mass of lymph nodes

---- As it progresses nodes become fixed

• Oral cavity (extranodal) - involve soft tissue or bone

• Bony involvement- vague pain with ill-defined radiolucency on radiograph

non-hodgkin's lymphoma

what is Burkitt lymphoma?

Malignancy of B-cell lymphocytes (Type of non-Hodgkin lymphoma)

---- Translocation t(8;14)(q24,q32) overexpressed MYC oncogene

Burkitt lymphoma mainly affects what groups?

children and young adults

What are the 2 types of Burkitt lymphoma?

- endemic

- sporadic

the following describes what?

Increased prevalence in areas where malaria is also seen

• Patients with the highest antibody titer to Plasmodium falciparum are most likely to develop Burkitt Lymphoma

• >90% of tumor cells express Epstein Barr Virus (EBV)

• 50-70% of cases involve the jaws

---- Posterior segments most common

---- Ratio of 2:1 maxillary involvement

endemic Burkitt lymphoma

the following describes what?

Involves abdominal region

• Occur in countries where malaria is not seen

• Less commonly express EBV (20%)

• Usually are abdominal tumors, but jaw lesions have been reported

sporadic Burkitt lymphoma

the following describe clinical findings of?

Facial swelling

• Proptosis

• Enlargement of gingiva

----Destruction of alveolar bone

----Deciduous tooth loss

Burkitt's lymphoma

radiographic findings of Burkitt's lymphoma

• Radiolucent

• Ill-defined margins

• Early sign- patchy loss of lamina dura

histopathology of Burkitt's lymphoma?

"starry sky" pattern

what is leukemia?

A cancer of white blood cells/leukocytes.

---Occurs in bone marrow and proliferates into peripheralblood

leukemia is classified by?

clinical behavior and histogenesis

• Chronic vs. acute (clinical behavior)

• Myeloid vs. Lymphoid (histogenesis)

The following describes clinical presentation of?

• Myelophthisic anemia- crowding out normal hematopoietic stem cells (white and red blood cells) by malignant cells

• Fatigue

• Thrombocytopenia (spontaneous gingival hemorrhage)

• Fever

leukemia

Intraoral findings for leukemia:

• Diffuse, boggy gingival enlargement (seen most frequently in AML or CML)

• Candidiasis

• Deep, punched-out neutropenic ulcers

• Herpetic infection (affect any area of oral mucosa)

What are the forms of leukemia?

• Chronic Myeloid Leukemia – peak prevalence 3rd-4th decade

---------[Philadelphia Chromosome – (9,22)]

• Chronic Lymphocytic Leukemia – most common type; primarily affects older adults

• Acute Lymphoblastic Leukemia– predominantly in children

• Acute Myeloid Leukemia – broad age range

what is the most common type of leukemia?

chronic lymphocytic

which type of leukemia is predominantly seen in children?

acute lymphoblastic leukemia

multiple myeloma is....

malignant tumor of plasma cells

Excluding metastatic disease, what makes up 50% of all malignancies involving bone?

multiple myeloma

what disease has a median age at diagnosis between 60 and 70 years old and is rarely diagnosed before 40?

multiple myeloma

Below are presenting symptoms of what?

• Bone pain - particularly lumbar spine

• Fatigue

• Renal failure – due to excess of Bence Jones proteins (light chains)

multiple myeloma

Radiographic features of multiple myeloma?

Multiple "Punched out" well-defined radiolucencies

thrombocytopenia is a...

decrease in platelets

what are 3 causes of thrombocytopenia?

- Reduced production from malignant cells or chemo

• Ex: aplastic anemia, leukemia

- Increased destruction from immune reactions

• Ex: medications, HIV, lupus, hemolytic anemia

- Sequestration in spleen

• Ex: splenomegaly from tumors, liver disease etc.

• Under normal conditions 1/3 of the platelet population is sequestered in the spleen

The following are clinical features of what?

• Can manifest starting around 100,000/mm3

• Spontaneous hemorrhage

----Petechiae - pinpoint hemorrhage

----Purpura - larger than a pinpoint but ≤ 2cm

----Ecchymosis - > 2cm

----Hematoma - accumulation of blood the produces a mass

thrombocytopenia

what is von willebrand disease?

Deficiency in a plasma glycoprotein von Willebrand factor (vWF)

-----helps with adhesion of platelets to damaged vessel walls – important in forming a blood clot

-----also binds to Factor VIII acting as a transport molecule

what is the most common inherited bleeding disorder?

von willebrand disease

von willebrand disease presents as...

Spontaneous bleeding from mucous membranes and excessive bleeding from wounds

What disorders mentioned is an X-linked recessive disorder?

Hemophilia A and B

Which disorders mentioned primarily effect males?

Hemophilia A and B

What happens in hemophilia A?

Reduced factor VIII activity

-----Factor VIII is needed to help activate Factor X in intrinsic pathway

this clinical presentation describes what disorder?

• Prolonged (partial thrombin time (PTT) - how long it takes blood to clot

-----In symptomatic cases easy bruising and massive hemorrhage after trauma or operations

-----Spontaneous hemorrhages are frequently seen in tissues subjected to mechanical stress, particularly the joints. Recurrent bleeds in this area lead to progressive deformities

Hemophilia A

What happens in Hemophilia B?

• Deficiency of factor IX

-----Factor IX works with Factor VIII to activate Factor X in the intrinsic pathway

clinical presentation of Hemophilia B?

Patients have prolonged partial thrombin time, PTT, how long it takes blood to clot