PART 3- THIRD LEARNING Flashcards
The bone marrow produces
platelets, erythrocytes, granulocytes (neutrophils, eosinophils, and basophils), monocytes and probably the bursa equivalent of B lymphocytes.
The status of the bone marrow cellular activity is reflected in
peripheral blood cell counts
The requirement for direct marrow examination the living animal is not a common practice but needs to be considered when there are:
- Inexplicable peripheral blood changes
- In cases of suspected myeloproliferative disorders
- Inexplicable peripheral blood changes such as:
a. The presence of cells with abnormal or atypical morphology
b. Inappropriate response to an anemia or infection;
c. The development of unexplained anemia and or leukopenia.
Growing animals show active red marrow which is replaced by
replaced by fat tissue as the animal mature
In old animals, active (red) marrow is restricted to the
flat bones and the endosteal area of long bones
Although the marrow respond to heavy demands following infectious insults, in some chronic infectious cases, the spleen, liver, adrenal and other areas where there are foci of primitive mesenchymal cells, production of hematopoietic cells occur at these sites and the process
extramedullary hematopoiesis
hematopoietic cells
Erythroid and myeloid precursors
undergo differentiation and maturation in marrow spaces before their release into vascular sinusoids.
erythroid and myeloid precursors
are entered b hematopoietic cells via diapedesis or proplatelet shearing
vascular sinusoids
structurally support the marrow
trabecular bone
produces trabecular bone
ostoeblasts
sit on a basal lamina and separate the vascular sinusoids lumens from marrow hematopoietic and stroma cells.
endothelial cells
line vascular sinusoids and release cytoplasmic fragments (platelets) into sinusoidal lumens.
megakaryocytes
provide structural and metabolic support to hematopoietic cells
stromal cells
constitute 25% to 75% of the total marrow space. the proportion of adipocytes increases with age.
adipocytes
mechanism of disease in bone marrow and blood cells
BONE MARROW
hypoplasia
hyperplasia
dysplasia
aplasia
neoplasia
myelophthisis (fibrosis, metastatic neoplasia)
necrosis
inflammation
BLOOD CELLS:
increased destruction
hemorrhage (erythrocytes)
consumption
neoplasia
altered distribution
abnormal function
- increased production of various cell lines which occurs frequently in response to demands by, or changes in the other parts of the body.
1) Hyperplasia
is used where the increased production is at the expense of the other cell lines.
MYELOID METAPLASIA
refers to the general reduction in the amount of cells produced in the bone marrow that are in circulation.
2) Pancytopenia
The response is generally that of marrow aplasia and may be caused by such factors
as irradiation, chemical and bacterial toxin and some drugs.
Causes of marrow depression include viral diseases such as
parvovirus, enteric infection of dogs and cats and feline leukemia virus infection, and Erhlichiosis.
is a term used to describe the metastasis of neoplastic cells to the bone marrow
5) MYELOPTHISIS
Commonly accepted hypotheses include:
a. Direct damage to mitotically active cells by various agents, and
b. failure of the microcirculation of bone marrow.
Drugs such as
phenylbutazone, and estrogenic drugs can also cause marrow aplasia
Necrosis of bone marrow result
pancytopenia
is the abnormal proliferation of fibroblast in the marrow cavity
4) MYELOFIBROSIS
that causes bone marrow depression include Bracken fern poisoning.
Phytotoxicities
Two hypotheses for this condition include:
a. As part of repair process following injury to bone marrow;
b. Fibroblastic proliferation as a consequence of a chronic hemolytic anemia
Myelofibrosis often produces characteristic morphological alterations in peripheral blood and include poikilocytosis, with the presence of
poikilocytosis, with the presence of elliptocytes, schizocytes and dacryocytes.
refers to a peripheral disorder associated with faulty maturation, development, and cell division involving one or all of the marrow cell lines
- Myelodysplasia, dysmyelopoiesis
The defect is basically the presence of abnormal stem cells in the marrow which may or may not progress into neoplasia.
- Myelodysplasia, dysmyelopoiesis
- refers to the abnormal proliferation of marrow cell lines and may include myelodysplasia and neoplasia
- Myeloproliferative disorder
Infiltration of neoplastic cells into other tissues can occur with enlargement of the liver and spleen ()
often being the most prominent feature
(hepatomegaly and splenomegaly)
are usually characterized by the presence of leukemia
Myeproliferative neoplasms
(presence in blood of large number of neoplastic cells of myeloid origin)
leukemia
The designation of such neoplasm referable to the cell type or the major cell stage involve (e.g.
(e.g. granulocytic leukemia, myeloblastic leukemia, myelocytic leukemia).
is the major site of blood formation (when marrow becomes fully developed).
Bone marrow
is a valuable diagnostic tool in the differential diagnosis of diseases characterized by alterations in the peripheral blood
Bone marrow examination
I. INDICATIONS AND LIMITATIONS
A. Indications
1) For confirmatory diagnosis of leukemia 2) Differential diagnosis of anemia e.g. megaloblastic anemia, nutritional anemia, normoblastic anemia
3) To confirm blood count findings, especially leukopenia, nonregenerative anemia, thrombocytopenia
the needle is advanced into the marrow cavity with stylet locked in place.
klima needle
B. Limitations
1) Difficulty in obtaining samples - usually contaminated with peripheral blood.
2) Adequate experience in bone marrow examination is required.
Stylet is then removed and syringe used to aspirate the marrow.
the stylet is in place for advancement through soft tissue and cortex.
Jamshidi neeele
on reaching the bone marrow , the needle is advanced without the stylet to create a core sample.
jamshini needle
is used to expel the sample into formalin.
probe (hooked)
C. Sites for collection
anterolateral part; this is the best source of bone marrow samples for dogs and cats.
1) humerus
sites for dogs and cats
2) iliac crest
11th or 12th;site for cattle, horses
4) rib
1st or 2nd sternebra; sites for cattle, horses, sheep
3) sternum
trochanteric fossa; the most preferred site for cats.
5) femur
III. PREPARATION OF ASPIRATED MATERIAL FOR EXAMINATION;
A. Bone marrow smear
- slide film method
- coverslip method
METHOD:
Bone marrow aspirate is mixed with EDTA and sieved in order to get only the marrow granules. The granules are washed with saline, embedded in 2% agar and fixed with 10% formalin.
- Agar-gel method
Methods
1. Bone marrow aspirate is allowed to clot and placed in
10% formalin for sectioning.
C. Stains
Wright’s, Wright-Giemsa, May-Grunwald-Giemsa
A. Degree of Cellularity
1. Hypoplasia may be
a) generalized
b) erythroid
- Hyperplasia
a) erythroid
b) granulocytic
c) megakaryocytic
B. Presence of all cell series include the ff.
- granulocytic
- erythrocytic
- megakaryocytic
C. Sequence of development
Mature cell types should outnumber
the immature forms
Developmental stages:
- Granulocytic series:
Myeloblast
progranulocyte
myelocyte
metamyelocyte
band cell
segmented granulocyte
- neutrophils
- eosinophils
- basophils
- Lymphocytic Series
lymphoblast
prolymphocyte
lymphocyte
- Monocytic Series
monoblast
promonocyte
monocyte
- Erythrocytic Series
rubriblast
prorubricyte
rubricyte
metarubricyte
reticulocyte
erythrocyte (RBCs)
- Thrombocytic series
megakaryoblast
promegakaryocyte
megakaryocyte
calculated by dividing the total number of granulocytes by the total number of granulocytes by the number of nucleated erythrocytes
M:E Ratio (myeloid: erythroid)
M:E Ratio
(myeloid: erythroid)
-in normal animals, the M:E ratio is
1:1
VI. Specific Findings in Anemia, Inflammation and Neoplasia:
Anemia
1. decreased M:E ratio, predominance of metarubricytes, punctate basophilia
- regenerative
larger than normal rubricytes with chromatin deficient nucleus; macrocytes and hypersegmented neutrophils are increased in number.
- megaloblastic
relative lymphocytosis;decreased erythroid production hence,high M:E ratio.
- aplastic
A. Inflammation
- slightly decreased M:E ratio
ACUTE
increased granulopoiesis,high M:E ratio, increased number of active macrophages
chronic
hours
increased M:E ratio and increased number of immature neutrophils
- after 24-48 hours
Neoplasia
- hyperplasia of myeloid cells with decrease in immature erythrocytes in dogs;increase of bone marrow lymphocytes to more than 30% in bovine.
- lymphosarcoma
- toxic
cytoplasmic basophilia and vacuolization, macrophages with phagocytosed cellular debris
characterized by proliferation and only
partial differentiation of a primitive mesenchymal cells
- Myeloproliferative Disorders
Enlargement of lymph nodes
The most frequent disorder of the lymph node encountered in domestic animals is
swelling of the lymph nodes
- Myeloproliferative Disorders
ex:
granulocytic,
megakaryocytic,- and
erythroleukemia
There are 3 conditions that cause the gross enlargement of the lymph nodes:
- Lymphadenitis
- Lymphoid hyperplasia (reactive lymph nodes)
- Neoplasia
Denotes the inflammation of the lymph node (a misnomer because a lymph node is not a gland).
Lymphadenitis
The lesion that accounts for the swelling is a combination of serous exudation with proliferation of lymphoid and reticular tissues
Lymphadenitis
This is common in most septicemic disease condition
Lymphadenitis
Necrosis of the lymphatic nodules maybe observed in generalized infection caused
viruses
In nodes draining areas of inflammation
- Lymphoid hyperplasia (reactive lymph nodes) -
- In nodes draining areas of inflammation. This include
follicular hyperplasia,
paracortical, and the
medullary cord are often packed with plasma cell
The most common being lymphosarcoma
- Neoplasia
There is increased number of macrophages. In some cases there may be difficulty in differentiating from neoplasia because of high cellularity and large number of immature cells
- Lymphoid hyperplasia (reactive lymph nodes)
There are 3 conditions that cause a reduction in the size of lymph nodes and are as follows:
1) Senile atrophy
2) Immunodeficiency disease
3) Lymphoid exhaustion
part of aging process
1) Senile atrophy
following chronic infection with destruction of lymphoid tissues.
It is characterized by hypocellularity of the cortex and medulla.
Lymphoid exhaustion
- Common findings includes lack of germinal centers and paracortical T-cells, or even absence of lymph nodes (e.g. in combined immunodeficiency syndromes of Arab foals).
2) Immunodeficiency disease
constitute the single largest component of the reticuloendothelial system
spleen
It performs numerous function including
hematopoiesis,
iron metabolism,
filtration and phagocytosis,
remodeling of red blood cells, and
removal of intracytoplasmic inclusions.
. It also serve as a very large reservoir of blood and carries on various immunologic functions.
spleen
In domestic animal species, the commonly encountered notable changes in the spleen during necropsy is related to its
size
both refer to a localized enlargement of the spleen.
localized splenomegaly and splenic mass
Splenic masses are either:
- Neoplastic
2.Non-neoplastic
commonly encountered splenic masses which are neoplastic include hemangioma and hemangiosarcoma, and lymphosarcoma. Others include leiomyosarcoma, leiomyoma, myelolipoma and occasional lymphoma.
Neoplastic
include hematoma, localized congestion and nodular hyperplasia.
.Non-neoplastic
There are four major categories of diffuse splenomegaly and are as follows:
1) Inflammatory and infectious splenomegaly
2) Hyperplastic splenomegally -
3) Congestive splenomegally
4) Infiltrative splenomegaly
due to splenitis and the enlargement is due to an increase in the number of lymphocytes, reticuloendothelial cells, neutrophilic granulocytes and erythrocytes in varying proportions.
1) Inflammatory and infectious splenomegaly
Most causes are:
infectious or granulomatous diseases
Changes that accompany splenitis include
lymphoreticular hyperplasia and hematogenous infiltration with inflammatory cells.
Splenitis can be classified as either acute, subacute, or chronic based on the course of the disease. It can also be classified based on the predominant cell types or exudate as:
a) Suppurative splenitis
b) Necrotizing splenitis
c) Eosinophilic splenitis
d) Lymphoplasmacytic splenitis
e) Granulomatous splenitis
when the predominating cell type is the neutrophil; the common cause include septicemic infections with pyogenic bacteria, bacterial infection secondary to torsion, protozoal infection like Toxoplasmosis and some mycobacterial infections like tuberculosis.
a) Suppurative splenitis
when necrosis predominate; most commonly caused by gas-forming anaerobes, Salmonellosis and viral disease like canine hepatitis, and splenic infarction.
b) Necrotizing splenitis
when lymphocytes and plasma cells predominate; occur in association with subacute and chronic disorders such as infectious canine hepatitis, erhlichiosis, pyometra, brucellosis, and hemobartonellosis.
d) Lymphoplasmacytic spleniti
when eosinophils predominate; observed in hypereosinophilic syndromes in dogs and cats.
c) Eosinophilic splenitis
when the predominant cell types are macrophages, epithelioid cells, lymphocytes and giant cell; occur in systemic mycosis and in some mycobacterial infections.
e) Granulomatous splenitis -
. This condition is associated with hemolytic disorders including hemolytic anemia, and drug induced hemolysis.
2) Hyperplastic splenomegally
The enlargement is due to hyperplasia of the reticuloendothelial and lymphoid components
2) Hyperplastic splenomegally
The spleen have a great capacity to store blood, and under normal circumstances may store between 10-20% of the total blood volume
3) Congestive splenomegally
Conditions that cause congestive splenomegally include:
Tranquilizers and anesthetics
Portal hypertension
resulting from right-sided congestive heart failure, obstruction of caudal vena cava by neoplasia, or of worms (as in caval syndrome of dirofilariasis).
Portal hypertension
the enlargement is due to infiltration of the spleen with neoplastic cells, splenic extramedullary hematopoiesis, and amyloid
4) Infiltrative splenomegaly
barbiturates and increase blood pooling by relaxing the smooth muscle of the splenic capsule resulting to pooling of blood;
Tranquilizers and anesthetics
amyloid
(“sago spleen”).
Other changes in the spleen
1) Dystopia
2) Accessory spleen
3) Rupture of the Spleen
4) Atrophy
5) Pigments
common in small animals and result from trauma. This may result to death due to massive hemorrhage. If eventually the rupture heals, extra-splenic tissues may be found scattered in the mesenteries and omentum.
3) Rupture of the Spleen
congenital and acquired defect of the diaphragm result to displacement of the spleen. However, no vascular engorgement occur that differentiate this condition to splenic torsion.
1) Dystopia
these are nodules or masses of splenic tissue seeded in the omentum which may be due to congenital defects or following trauma. They are of no pathologic significance except as an indicator of previous soft tissue injury.
2) Accessory spleen
as part of senile change; also may be observed in animals which dies of hemorrhage (shrunken spleen). The spleen is dry and may have a fibrous texture.
4) Atrophy
Hemosiderin and calcium may accumulate as subcapsular yellow pigmented calcareous bodies (Subcapsular siderotic nodules or plaques; Gamma-Gandy bodies) which are of no pathologic significance except an indication of previous hemorrhage.
5) Pigments
is a lobular composite organ of epithelial and lymphoid tissues, and reaches maximum development depending on the species, at the time of birth or up to puberty.
thymus
Disorders of the thymus include the following:
1) Agenesis or Hypoplasia as part of congenital immunodeficiency disease;
2) Hemorrhages following agonal death, strychnine poisoning or from septicemia;
3) Inflammation associated with viral diseases such as canine distemper, feline panleukopenia, and equine viral rhinopneumonitis;
4) Atrophy due to iatrogenic cortisone or as part of hyperadrenocortisolism; and
5) Neoplasms including epithelial thymoma and thymic lymphosarcoma
neoplasms are derived from lymphocytes or plasma cells; they usually form sarcomatous masses
A. Lymphoproliferative Neoplasia–
of the hematopoietic tissue is usually fatal, so a positive diagnosis would not be outrightly disclosed unless it is confirmed.
Neoplasia
Epithelial cells form the medullary cores and lymphocytes form the
cortices
I. Classification of hematopoietic neoplasia
A. Lymphoproliferative Neoplasia
B. Myeloproliferative Neoplasia-
form sarcomatous masses
- Lymphosarcoma
- Plasma cell myeloma
- Reticulum cell sarcoma
neoplasms are derived from cells normally produced in the bone marrow; (usually w/ anemia & thrombocytopenia)..
B. Myeloproliferative Neoplasia
ex:
- Granulocytic leukemia (may be neutrophilic, eosinophils, or basophilic)
- Erythremic myelosis
- Erythroleukemia
- Reticuloendotheliosis
- Monocytic leukemia
- Myelomonocytic leukemia
- Megakaryocytic leukemia
- Mast cell leukemia– usually originates from other tissues
- means a neoplastic proliferation of hematopoietic cells, characterized by appearance of immature cells in the peripheral blood; usually involves the bone marrow
Leukemia
may also be classed as:
a. aleukemic
b. subleukemic
c. leukemic
no increase in TLC, w/ few or no abnormal immature cells; should be confirmed by bone marrow examination.
a. aleukemic
normal or slightly high TLC, w/ few abnormal cell types
b. subleukemic
marked increase in TLC, w/ many abnormal and immature cells.
c. leukemic
II. Characterization of the Specific Types
A. Lymphoproliferative Neoplasia
2:
- Lymphosarcoma
- Plasma Cell Myeloma
a neoplasm of lymphocytes or their precursors; also called lymphocytic leukemia, leukosis, lymphocytoma, malignant lymphoma
- Lymphosarcoma
Classification:
a. According to anatomical origin (varies w/ each species)
1) Multicentric form
2. Alimentary form
3. Thymic form
involves the peripheral lymph nodes; liver, spleen & other viscera may be involved
1) Multicentric form
b. According to cell type
1) Lymphocytic lymphosarcoma
2) Prolymphocytic lymphosarcoma
3) Lymphoblastic
4) Histiocytic
5) Hodgkin’s type
neoplasm originates in the gut & mesenteric lymph nodes
Alimentary form
characterized by development of a large mass in the thymus and anterior mediastinal lymph nodes
Thymic form
rare
1) Lymphocytic lymphosarcoma
large cells,basophilic cytoplasm, mildly aggregated nuclear remnants
2) Prolymphocytic lymphosarcoma
reticulum cell sarcoma; larger & more pleomorphic cells than 3); prominent nucleoli, indented nuclei
4) Histiocytic
larger cell than 2),
prominent nucleoli, more basophilic cytoplasm, less chromatin condensation
3) Lymphoblastic
neoplasia of plasma cells or their precursors, may occur in bones or viscera (osteolysis, fractures); may be accompanied by hyperglobulinemia and nonregenerative anemia
- Plasma Cell Myeloma
rare; mixture of lymphocytes, plasma cells & eosinophils; multiple nuclei
5) Hodgkin’s type
B. Myeloproliferative Neoplasms:
- Granulocytic leukemia
- Myelogenous leukemia
- Reticuloendotheliosis
- Erythremic myelosis
- Erythroleukemia
- Monocytic leukemia
- Myelomonocytic leukemia -
- Megakaryocytic leukemia
- Mast cell leukemia
in dogs, cats
- precursor and immature forms outnumber the nature segmented forms
- Granulocytic leukemia
- Characteristics of leukemic cells:
a. extremely large
b. highly basophilic cytoplasm
c. Presence of nucleoli
d. vacuolation of the cytoplasm
rare in dogs, cattle; w/ marked neutrophilia, nonregenerative anemia
- Myelogenous leukemia
predominance of primitive, unclassified cells in the blood and bone marrow - seen in cats
- Reticuloendotheliosis
should be suspected when there is severe anemia, anisocytosis w/o polychromasia of erythrocytes; increased no. of large nucleated erythrocytes
- Erythremic myelosis
represents a progression from erythremic myelosis to granulocytic leukemia; occurs in dogs and cats.
- Erythroleukemia
neoplastic proliferation of monocytes w/ leukocytosis; predominance of immature monocytes in the bone marrow
- Monocytic leukemia
characterized by non- regenerative anemia w/ monocytoid leukocytosis; thrombocytopenia in terminal stages; reported in dogs
- Myelomonocytic leukemia
neoplastic proliferation of megakaryocytes w/c causes thrombocythemia w/ giant and bizarre platelets
- Megakaryocytic leukemia
determined by demonstration of mast cells in smears made from bone marrow or buffy coat; occurs in dogs w/ malignant cutaneous mast cell tumors; in cats, the disease originates in the RES tissue.
Mast cell leukemia
III. Clinicopathological findings in cases of lymphosarcoma
- Demonstration of neoplastic lymphocytes in the blood, bone marrow, needle aspirates from lymph nodes
- Most cases originate in lymph nodes or spleen, forming sarcomatous masses
- Lymph node biopsy and histologic exam show obliteration of architecture by lymphoid cells
- Immunologic tests - to demo. viral antigens or antibodies in cats and cows.
B. Myeloproliferative Disorders
- Severe, refractive, nonregenerative anemia
- Hepatomegaly and splenomegaly
- Lack of sarcomatous masses
- Lymph node enlargement
- Positive feline leukopenia virus (FeLV) test in 90% of cases in cats.
diseasaes of LEUKOCYTES ( non-neoplastic)
- Pelger-Heut Anomaly
- Granulocytopathy Syndrome
- Chedial_Higashi Syndrome
- Cyclic Hematopoiesis of the Canine (Gray Colie Syndrone)
- AbnormaL Neutrophil Granulation in BIRMAN CATS
- INCLUSIONS ASSOCIATED WITH INFECTION
is characterized by hyposegmentation of the granulocytes.
- Pelger-Heut Anomaly
this condition is reported in the dpg an is characterized by a reduced functional capacity of the neutrophils.
Granulocytopathy Syndrome
nuclear maturation appears to be complete because the chromatin is
condensed
cell size is normal
cytoplasm doesn’t contain immature granules
Neutrophils and eosinophils have a nonlobednnucleus that is frequently
round or oval.
neutrophils from such animals have reduced bactericidal activity
Deficiency in normal leukocyte function.
this syndrome was first described on milk but since then has detected in cattle, cats and the white tiger.
Chediak-Higashi Syndrome
affected animals exhibit varying amounts of
albinism and
increased susceptibility to infection
the disease was resported in persian CAts bred developed a
Blue-smoke coat
these cats had
-bleeding tendencies following
-surgery and
-hematomas at venipuncture sites were common.
-platelets are abnormal
this condition occurs only in thec ollie
Gray Collies syndrome
