pathology of hematopoiteic system Flashcards
hematopoiesis
-process of how blood cells are made
-made in:
embryo: yolk sac
fetus: liver, spleen, bone marrow, lymph nodes
neonates: bone marrow of long/ flat bones, red marrow.
adults: bone marrow in all regions of flat/long bones. see yellow marrow.
-extra-medullary hematopoieses EMH due to need.
basic concepts of hematopoiesis
- Bone marrow is located in multiple sites but responds as a single tissue
- Samples can be taken from any bone with red marrow:
- Proximal femur, iliac crest, proximal humerus of dogs and cats
- Sternum of horses
- Proximal rib of cattle
- Aspirates and core biopsies
pathology of bone marrow and blood cell
-end result depends on which type of cell damaged.
* Multipotent stem cells = multiple cell lines affected
* Committed stem cells = one or more lines affected
* Differentiated cells = one cell type affected.
-alterations are reflected in peripheral blood. decreased cell lines=cytopenias, anemias
increases in cell lines= cytoses and philias.
-in the bone marrow, changes are reflected as increased or
decreased cellularity the changes in red hematopoetic tissue (red marrow) to adipose tissue (yellow marrow)
bone marrow and blood cells degeneration and necrosis
-hematopoietic tissues are highly active and susceptible to insults.
-radiation/ toxins and drugs. viral agents. immune mediated or idiopathic causes.
bone marrow inflammation
-osteomyelitis: * Inflammation of the bone (osteitis)
and the medullary cavity (myelitis).
bone marrow hypoplasia/ aplasia
-decreased proliferative activity
-more yellow, white marrow than red
causes: bone marrow suppression (estrogen, chronic renal disease)
-lack of nutrients (iron, B12, folate)
-endocrine disorders (hypothyroidism)
bone marrow hyperplasia
-proliferative response more red replaces yellow
-response to increased peripheral demand or hypodunction of blood cells.
–Erythroid hyperplasia ➝ response to anemia
–Megakaryocytic hyperplasia ➝ response to ↓ platelets
-myloid hyperplasia (neutrophilia, esoniphilia, monocytosis) from bacterial infections, parasites, chronic infections.
bone marrow atrophy
-serous atrophy of fat
* Gelatinous transformation of fat within the marrow. Due to cachexia. (severe stage of emaciation) due to cancer ect.
hematopoietic neoplasia
- Affect primarily:
- Bone marrow
- The circulating blood (leukemia)
- Lymphoid tissue (lymph nodes, spleen, thymus, etc)
-divided into lymphoproliferative and myeloproliferative diseases:
lymphoproliferative diseases
-neoplastic disorders of lymphocytes (t, b NK cells)
-lymphoma (in bone marrow/blood)
-lymphoid leukemia (neoplastic lymphocytes in tissues/organs)
-plasma cell tumors
Myeloproliferative
Disease
-histocytic neoplasia
-myloid leukemia
-mast cell tumors
canine lymphoma
-most common canine hematopoitic neoplasia
-older or middle ages animals
-85% habe multicentric lymphoma
-enlarged lymph nodes with firbosis
-organomegly
-thickening of tubular organs
-hypercalcemia of malignancy sometimes seen.
types of lymphomas
- Alimentary (tubed organs, intestines)
> multicentric
> thymic (lung)
-cutaneous (skin)
feline lymphomas
-most common malignant neoplasia of cats
-Alimentary > multicentric
> thymic > miscellaneous
forms
* Leukemia and bone
marrow involvement are
common
-path: feline leukemia virus FeLV. 10-20% cats.
* FeLV is associated with mediastinal and multicentric T cell lymphoma
* Young cats!
bovine lymphoma forms
-ezonitc bovine lymphoma
* Sporadic Bovine Lymphoma
* Calf form
* Juvenile form / Thymic form
* Cutaneous form
Enzootic bovine lymphoma
-adult cattle
* Bovine leukemia virus (retrovirus)
* 30% of infected cattle → persistent lymphocytosis
* < 5% of infected cattle → lymphoma
* Multicentric lymphoma of B cell origin.
-more common in dairy
-transmission by arthropods, breeding, tagging.
-lesions in heart, abomasum, uterus and spinal canal.
Sporadic bovine lymphoma
-Not associated with a viral infection!
-Affects young animals, 3 forms:
1 calf form: young, symmetrical lymphadenopathy. leukemia. kidney, liver, spleen. (multicenteric)
2: juveiline form= thymic form: mediastinal mass.
3 cutaneous form: 2-3 yr old. plagues or nodular raised skin lesions which leads to systemic. survive 12-18 months.
porcine lymphoma
-most common neoplasm of pigs
-multicenteric
-often less than 1 yr, more in females
-heriditory form (large white pigs)
reaction of bone to injury and disease
- Two processes usually occur together
* removal of damaged bone
* resorption or lysis
* production of new bone. - Injury to the periosteum (and
endosteum) will usually be
followed by new bone production.
-bone density will change is response to use wolffs law.
fractures and path (on exam)
- physical discontinuity in a bone
resulting in instability and pain - A normal bone fractures due to excessive
force → traumatic fracture - An abnormal bone fractures under normal
force → pathologic fracture
fracture repair 5 phases
1 - inflammation and injury. tearing of perio and endostium, rupture of BV. growth factors
2- organization of the hematoma
3- callus formation external and internal callus
4- callus remodeling
5- callus modeling
fracture repair phase 1
Phase 1 – Injury and inflammation
* tearing of the periosteum & endosteum
* rupture of blood vessels of the bone
* surrounding soft tissue injury
hematoma
ischemia
inflammation-> growth factors
fracture repair phase 2
Organization of the hematoma
* activation of undifferentiated
mesenchymal (stem) cells
* neovascularization
fracture repair phase 3
-Callus formation: external and internal callus
-distant to the fracture gap
* ‘favorable’ environment BS is still intact, lots of O2 so osteoblasts → woven bone
-near the fracture gap
* ‘poor’ environment
* fibroblasts & chondroblasts
* cartilage is later replaced via endochondral ossification
-begins 24 hr
-36 hours for bone production
-can see callus on xray at 2 weeks
-time varies with age, health, nutrition ect.
fracture phase 4
-callus remodeling
* woven bone replaced by lamellar bone
* compact bone formed in cortex
* cancellous bone in metaphysis / diaphysis
-during callus remodeling bone marrow may be filled with bone
fracture phase 5
Callus modeling
* Restoration of bone to its original form & function
* Months to years
nonunion/ delayed union/ malunion
-nonunion: failure a fractured bone to heal
-delayed: longer/slower than normal healing time of a bone. lack of progress after 3 months and healing after 6 months.
-malunion: healing which results in deformity
Complications of Fracture Repair
- inadequate blood supply
- instability
- infection
- fragments of necrotic bone or soft tissue
- other underlying disease
- pathologic fracture
Disorders Associated with the Physis
- Physeal / growth plate fractures
* Salter-Harris fractures - Growth retardation lattices
- Growth arrest lines
- Premature closure
- Osteochondrosis / osteochondritis
Physeal or growth plate fractures
- Physis is composed of cartilage
- Weak compared to bone
- More easily injured / fractured
- Physis is site of growth
- injury can affect growth
capital femoral physeal fracture in cats-common in young under 2 yr overweight neutered males.
Salter-Harris classification scheme for physeal fractures
S – straight across
(separated or slipped)
A – above (or away from joint)
L – lower (into joint)
T -through everything all together
E -through everything all together
R – rammed (ruined / crushed)
Growth retardation lattices
- Thin lines to wide bands of osteosclerosis
in the metaphysis, parallel to the physis - GRL are due to impaired osteoclastic
activity and retention of 1° spongiosa - Typically detected in aborted, stillborn, or
neonatal animals - Look for the underlying cause
Premature closure
- Partial (or focal)
- alters shape
- Complete (or diffuse)
- short bones
- Many causes
- trauma, vitamin A toxicity, Mn
deficiency, radiation, other
congenital spinal stenosis
Osteochondrosis
“The focal or multifocal failure (or delay)
of endochondral ossification resulting in
localized thickening of hyaline cartilage.”
Physis or articular surface
* articular-epiphyseal (AE) complex
* Not as stable a bone
* Subject to injury
plasma cell tumors
- Cutaneous Plasmacytoma
* Common skin masses in dogs
* Surgical excision is usually curative - Extramedullary Plasmacytoma
* Arising at sites other than BM / skin
* Often affect the GI tract
* More aggressive, may metastasize to
the lymph nodes
Multiple Myeloma
-plasma cell tumor
-dogs> cats
* Malignant tumour of plasma cell
origin arising in the bone marrow
* Neoplastic (clonal) plasma cells
secrete immunoglobulin leading to
hypergammaglobulinemia
Multiple myeloma clinical signs
Clinical diagnosis of multiple myeloma is based on finding 2 - 3 + of the
following features:
* Increased plasma cells in bone marrow
* Punched out lesions on radiographs
* Monoclonal gammopathy
* Hypercalcemia
* Light chain (Bence-Jones) proteinuria
Lymph node metastasis
- Common with carcinomas, melanomas, mast cell tumors…
- May see lymph node enlargement
- Variable effacement of normal architecture.
Thymus – Structure and function
- Structure
– Composed of epithelial tissue and lymphoid tissue
– Lobulated and split into cortical and medullary areas - Function
– Proliferation & maturation of T cells
thymus diseases
-thymic aplasia/hypoplasia from congenital immunodeficeincy
-lymphocytolysis, thymic atrophy: can lead to acquired immunodeficiency from malnutrition, drugs, infections.
-thymic hemmorage/ hematoma
thymic hemorrhage
- In dogs, sudden death is occasionally seen due to hypovolemic shock
resulting from massive
thymic/mediastinal hemorrhage - Several implicated causes: trauma, ruptured aorta, anticoagulant rodenticide
thymus primary neoplasm feautures
- Space occupying mass in
cranial mediastinum - Dyspnea
- 2 main differentials (thymic lymphona, or thymoma)
thymic lymphona
Neoplastic proliferation of
T-lymphocytes
-Often younger animals (cats,
calves, and dogs)
Malignant behavior
Thymoma
-Neoplastic proliferation of
Epithelial cells
-Dogs, sheep, goats
-Slow growing, encapsulated
spleen structure and function
-red pulp: sinusoids, spenic cords= filter blood. RBC storage and hematopoieses
-white pulp: T cells, B cells= immune response.
siderofibrosis = gamna-gandy bodies
-spleen is granular white, yellow deposites in splenic capsule.
-incidental finding maybe due to hemorrhage.
-fibrous tissue, mineral deposits, hematoidin.
splenic contraction
- Contraction of the smooth muscle in the capsule/trabeculae
- Occurs with catecholamine release, shock, acute splenic rupture
- Gross: Small dry spleen with wrinkling of the capsule
-can have areas of black looking like infarctions.
splenic rupture
- Fairly common
- Primary - trauma
- Secondary to splenomegaly,
splenic neoplasia. - Potential sequelae include
hemoabdomen and splenosis
Splenic rupture → splenosis
splenosis: seeding of splenic explants on peritoneal surfaces forming accessory spleens.
-small red nodules within the omentum.
spleen circulatory disturbances
-Active hyperemia (acute systemic infection)
-Passive congestion (vascular pooling shock, barbituate administration, hemolytic anemia
-splenic infarction
-splenic hematoma
-grossly: dark blue or black, oozes blood when cut.
Splenic Infarcts
-Ischemic necrosis of the spleen
-causes:
1. Vascular damage
2. Hypercoagulable states
3. Splenomegaly (of any cause)
4. Septic emboli
splenic hematoma
- Common in dogs
- Trauma
- Often associated with nodular hyperplasia or vascular tumours
-gross: red nodular mass, very large, soft and dark red.
-use histo to rule out neoplasia
acute spenitis ( Multifocal necrotic or suppurative splenitis)
-caused by tularemia, or yersenosis (Yersinia pseudotuberculosis).
-gross: miliary white foci in the spleen, may also be in lymph node and liver.
Acute splenitis – Septicemic splenitis
-causes: African swine fever
* Erysipelas
* Anthrax*
-gross: splenomegaly, dark discoloration, engorged viscous blood.
anthrax pathogenesis for septic splenitis events
-caused by bacillus anthracis
-ingested spoores or contact
-lymphagitis and lymphadentis
-massive bacteriemia (sepsis) and toxemia
-increased vascular permeability and impaired coagulation
-sudden death
-take blood smear from ear
chronic spenitis - granulomatous splenitis
- can be nodular or diffuse.
-causes: myobacterium avium in chickens.
-hispoplasmosis in dogs.
spleen growth disturbances
-Aplasia
-Atrophy
-Benign nodular hyperplasia
-Lymphoid hyperplasia
-Hyperplasia of the monocyte-
macrophage system
-Extramedullary hematopoiesis
Lymphoid hyperplasia of spleen
-hyperplasia of white pulp
-response to blood-borne chronic antigenic stimulation
-Malignant Catarrhal Fever, Bovine
primary splenic neoplasias
-Lymphoproliferative diseases:
Lymphoma/Leukemia*
-Myeloproliferative diseases:
-Histiocytic sarcoma*
-Mastocytosis*
-Hemangioma
-Hemangiosarcoma
Others: Fibrosarcoma,
Fibrohistiocytic nodules, etc
Splenic hemangioma
-benign tumor of endothelial origin
-gross: single, soft, dark red nodular mass
-histology is needed.
Splenic hemangiosarcoma
-primary neoplasm
-most common malignant tumor of canine spleen
-gross: single to multiple masses, dark red
-leads to splenic rupture, hemaabdomen, peritoneal seeding. common masses in liver.
histocytic proliferative disorders
-cutaneous histiocytoma: common begin skin mass
-reactive histocytosis
-histocytic sarcoma
Histiocytic Sarcoma
- Malignant neoplasia of macrophages
or dendritic cells - Breed predispositions
- Bernese Mountain dog, Rottweiler,
Flat-coated Retriever - Can be solitary of multiple:
- Solitary lesions
- Subsynovium (joints), subcutis
- Lymph nodes, spleen or liver
- Multiple lesions
- Disseminated histiocytic
sarcoma = Malignant
histiocytosis
mast cell neoplasia
-mast cells are in connective tissue but originate in bone marrow.
-common cutaneous mast cell tumors in dogs.
-systemic mastocytosis are visceral mast cell tumors to the hematopoietic system and other organs
secondary bone marrow neoplasia
- Results of
metastasis of
a tumour
from a
distant site to
the bone
marrow - Can be a
carcinoma or
a sarcoma
Myelophthisis
-Replacement of hematopoietic tissue within
the bone marrow by abnormal tissue.
-fibrosis-> myelofibrosis
-neoplastic cells-> leukemia
-can result in pancytopenia due to competition for space and nutrients.
lymph nodes structure and function
-filtration of lymph and immune response.
-outer cortex (B cells)
-inner cortex (T cells) and medulla
enlarged lymph node differentials
-lymphadentitis
-lymhoid hyperplasia
-hyperplasia of monocyte system
-primary or secondary neoplasia
Lymphadenopathy
-enlargement of the lymph nodes from unknown causes
Lymphadenitis
- An inflammatory response to an
infectious agent within the node
not reactive hyperplasia which is antigen driven response.
-acute: the result of a
regional lymph node
draining a site of
infection/inflammation and
becoming infected
Chronic lymphadenitis
- With chronicity the
lymph nodes
become large,
irregular, and firm
due to fibrosis
-can then be suppurative or granulatamous.
-path: could be rhodococcus equi.
Equine Strangles
- Streptococcus equi subsp
equi - Inflammation of the URT
→ abscesses in the
mandibular,
retropharyngeal and
parotid LN - May fistulate to the
surface
Caseous lymphadenitis
- Chronic suppurative lymphadenitis in sheep & goats
-caused by Corynebacterium pseudotuberculosis
-enters via shear wounds, drains in regional LN.
-* Chronic suppurative
inflammation, caseous necrosis & fibrosis - As lesion progresses →
characteristic concentric
laminations
Nodular granulomatous lymphadenitis bovine
-bovine tuburculosis caused by myobacterium bovis.
-enlargement of lymph nodes with yellow nodules.
Diffuse granulomatous lymphadenitis pigs
-Postweaning multisystemic wasting syndrome (PMWS):
Porcine Circovirus type 2
-gross enlargement of mesenteric lymph nodes
Benign Reactive Hyperplasia of lymph nodes
- Immunological reaction = response to antigen presentation or circulating
interleukin levels - Causes lymph node enlargement
- Can be localized or generalized
- Lymph nodes draining site of local infection or vaccination
Secondary lymph node neoplasia
- Lymph node metastasis:
- Common with carcinomas, melanomas, mast cell tumors…
- May see lymph node enlargement
One basis of staging tumor malignancy - Stage 0: regional node normal
- Stage 1: regional node enlarged but still freely moveable
- Stage 2: regional node enlarged and fixed
Lymph node: Neoplasia
Secondary lymph node neoplasia
