Pathology of Haemic & Lymphoid System

What are the 3 reactions of circulating blood cells to injury?

1. Decreased survival

2. Altered distribution

3. Changes in structure or function

Term for Decreased Erythrocyte (RBC)

Anemia

Term for Decreased Reticulocyte (Immature RBC)

Reticulopenia

Term for Decreased Leukocyte (WBC)

Leukopenia

Term for Decreased Neutrophil

Neutropenia

Term for Decreased Lymphocyte

Lymphopenia

Term for Decreased Monocyte

Monocytopenia

Term for Decreased Eosinophil

Eosinopenia

Term for Decreased Basophil

Basopenia

Term for Decreased Platelets

Thrombocytopenia

Term for increased Erythrocyte

Erythrocytosis

Term for increased Reticulocytes

Reticulocytosis

Term for increased Leukocytes

Leukocytosis

Term for increased Neutrophils

Neutrophilia

Term for increased Lymphocytes

Lymphocytosis

Term for increased Monocytes

Monocytosis

Term for increased Eosinophils

Eosinophilia

Term for increased Basophils

Basophilia

Term for increased Platelets

Thrombocytosis

A broad term for Erythrocytes with ABNORMAL SHAPES, w/c can be subclassified based on specific shape changes.

Poikilocytes

T or F: Some specific shapes of RBC have unique diagnostic significance, while others are more non-specific.

True

The diagnostic significance of poikilocytes depends on these 3 factors:

1. Number

2. Shape

3. Context

True or False: Few misshapen RBC in blood from normal or ill animals may not hold a diagnostic value.

True

What are the 8 Types of Pokilocytes

D E C A D E S S

1. Dacryocyte

2. Echinocyte

3. Codocyte

4. Acanthocyte

5. Drepanocyte

6. Elliptocytocyte

7. Schizocyte

8. Spherocyte

This type of Poikilocyte is spherical w/ about 3-12 blunt tip of club-shaped spicules of varying lengths on their surface. These spicules are asymmetric or irregular.

Acanthocyte

This type of Poikilocyte is spiculated, & is a.k.a. crenated or “BURR“ cells. This has uniformed sharp spicules w/c are evenly spaced.

Echinocyte

This type of poikilocyte is linked to liver disease and lipid metabolism disorders.

Acanthocyte

This type of poikilocyte can be an artifactual change seen in stored or “old“ blood

Echinocyte

This type of Poikilocyte is a.k.a. the “Teardrop cell” & is associated with fibrotic states of marrow, hemolytic anemia, & drug reactions such as phenothiazine & chloramphenicol.

Dacryocyte

What are the 3 things Dacryocyte can be associated with?

1. Fibrotic marrow

2. Hemolytic Anemia

3. Drug reactions with PhenoThiazine & ChoramPhenicol

This type of Poikilocyte is a.k.a. “Target Cells” or Leptocytes. It has a normal central pallor, resembling a Bull’s eye

Codocyte

This type of Poikilocyte develops from excess membrane & decreased HgB (hemoglobin). It is also associated w/ Iron deficiency Anemia, Obstructive liver disease & Cirrhosis

Codocyte

What are the 3 diseases codocytes can be associated with?

1. Iron deficiency anemia

2. Obstructive liver disease

3. Cirrhosis

This type of Poikilocyte is a fragmented RBC that may be due to mechanical injury or through the trapping of RBC in the circulation by fibrin. (Ex. Thrombosis)

Schizocyte

This type of Poikilocyte is common in DIC (Disseminated Intravascular Coagulation), & iron deficiency anemia

Schizocyte

This type of Poikilocyte is normal in young ruminants

Schizocyte

This type of Poikilocyte is a.k.a. “Sickle cell” & is normal in deers.

Drepanocyte

Drepanocytes are poikilocytes associated with 2 things w/c are:

1. Blood parasites (Malaria & Trypanosomiasis)

2. Recessive gene defect in humans

This poikilocyte is elongated & has 3 types which distinctions are not clinically relevant, though some forms may occur more frequently in certain diseases.

Elliptocytes

What are the 3 types of Elliptocytes?

Type 1: Slightly oval-shaped & is formerly known as ovalocyte

Type 2: Rounded- oval shape

Type 3: Elongate elliptical

This type of poikilocyte indicates the presence of red cells with increased central thickness.

Spherocyte

What are the 2 causes of spherocytosis?

1. Membrane depletion

2. Accelerated RBC aging (As a result of a pathological process such as Immunohemolytic Anemia)

What are the 2 terms that refer to an increase in Red Cell Mass

1. Polycythemia

2. Erythrocytosis

What are the 2 things that can happen if there is polycythemia / erythrocytosis?

1. Hypervolemia

2. Hyperviscocity

What are the 4 subsequent disease manifestations of hypervolemia and hyperviscosity resulting from erythrocytosis / polycythemia?

1. Polyuria

2. Polydipsia

3. Neurologic abnormalities

4. Signs of Thrombosis or Mucosal hemorrhage

This is defined by an excess of peripheral RBC, HgB, & Hematocrit or PCV, beyond reference intervals.

Polycythemia / Erythrocytosis

What are the 5 histories relevant to erythrocytosis?

C R E M D

1. Cardiac ds. signs

2. Respiratory ds. history

3. Endocrine ds. signs

4. Medication history

5. Dehydration risk factors

A history of vomiting, diarrhea, polyuria, hypodipsia, and inappetence points to which specific risk factor when evaluating a patient for erythrocytosis?

Dehydration risk factor

A history of chronic cough, increased respiratory effort, brachycephalic obstructive airway syndrome (BOAS) points to which specific risk factor when evaluating a patient for erythrocytosis?

Respiratory disease history

A history of exercise intolerance, exertional pelvic limb weakness, syncope, or cyanosis (suggesting R-L shunting) points to which specific risk factor when evaluating a patient for erythrocytosis?

Cardiac disease signs

A history of polyuria, polydipsia, haircoat changes, & weight changes points to which specific risk factor when evaluating a patient for erythrocytosis?

Endocrine disease signs

A history of taking EPO (Erythropoietin)-stimulating drugs, diuretics, & SGLT2 (Sodium-Glucose Cotransporter 2) inhibitors points to which specific risk factor when evaluating a patient for erythrocytosis?

Medication history

What are examples of Erythropoietin-stimulating drugs?

1. Darbepoetin

2. Molidustat

What are examples of SGLT 2 inhibitor drugs?

1. Bexagliflozin

2. Velagliflozin

What are the 2 Types of Erythrocytosis / Polycythemia?

1. Relative erythrocytosis

2. Absolute erythrocytosis

This type of erythrocytosis is caused by decreased plasma volume (e.g. dehydration) & is most common in veterinary patients where RBC mass is normal.

Relative erythrocytosis

This type of erythrocytosis is where there is true increase in RBC mass due to disease.

Absolute erythrocytosis

What are the 2 Types of Absolute erythrocytosis?

1. Primary erythrocytosis

2. Secondary erythrocytosis

This type of Absolute erythrocytosis is a.k.a. Polycythemia Vera

Primary erythrocytosis

This type of absolute erythrocytosis is an autonomous, uncontrolled overproduction of RBC within the bone marrow that occurs independently of erythropoietin (EPO) stimulation.

Primary erythrocytosis or Polycythemia vera

What are the 2 causes of secondary erythrocytosis?

1. Appropriate - increased EPO release in response to hypoxia

2. Inappropriate - increased EPO, hormones, or cytokine release despite normal oxygen levels

This type of absolute erythrocytosis is an absolute overproduction of RBC that is driven by excessive stimulation from EPO.

Secondary erythrocytosis

What are the 3 endocrine-related diseases resulting to secondary erythrocytosis?

1. Hyperthyroidism in cats

2. Acromegaly in cats

3. Hyperadrenocorticism in dogs

What are the 3 diseases that cause inappropriate type of secondary erythrocytosis?

1. Renal neoplasia

2. Non-neoplastic renal lesions

3. Other neoplasms

What are the 4 diseases/situations that cause appropriate type of secondary erythrocytosis?

1. Lung disease

2. Heart disease

3. High altitude

4. Hemoglobin disorder

What are the underlying biological processes or pathways (mechanisms) that cause Anemia?

1. RBC loss (hemorrhage)

2. RBC destruction (hemolysis)

3. Insufficient RBC production (bone marrow suppression)

T or F: The origin of anemia can often be identified through examination & diagnostic methods.

True

Many of the clinical signs related to anemia are attributable to ________.

Hypoxia

What system is primarily impacted by anemia?

Circulatory system

What organs are primarily affected by anemia?

1. Heart

2. Kidneys

In asymptomatic patients or those presenting with unrelated illness, during what routine diagnostic procedure is anemia most frequently identified as an incidental finding?"

Complete Blood Count (CBC)

What are the 4 criteria used to classify anemia?

1. Cell size

2. HgB content

3. Etiology

4. Bone marrow response

What three terms are used to describe red blood cell sizes when classifying anemia?

1. Normocyte - normal

2. Macrocyte - abnormally large size

3. Microcyte - abnormally small size

What 2 terms are used to describe red blood cells based on HgB content when classifying anemia?

1. Normochromic - normal color

2. Hypochromic - below normal

What are the 4 primary causes used to classify anemia?

1. Blood loss

2. Hemolysis

3. Bone marrow diseases

4. Deficiencies in:

• iron

• copper

• cobalt

• folic acid

• B12

What hallmark cells are looked for on a blood smear to determine a patient's bone marrow response to anemia?

Immature RBC (Reticulocytes)

When classifying anemia based on how the bone marrow is reacting to the shortage of red blood cells, what are the 2 types of bone marrow response?

1. Regenerative

2. Non-regenerative

8 Clinical consequences of anemia

1. Pallor

2. Weakness

3. Tachycardia

4. Tachypnea

5. Heart murmur

6. Hypotension

7. Cardiomegaly

8. Left ventricular hypertrophy

7 Clinical signs of blood loss

1. External bleeding

2. Hematuria

3. Melena (Stool that contains digested blood)

4. Hematochezia

5. Petechiae

6. Ecchymoses

5 Clinical signs of hemolysis

1. Icterus

2. Hepatomegaly

3. Splenomegaly

4. Lymphadenomegaly

5. Pigmenturia

2 Clinical signs of decreased RBC production

1. Usually nonspecific & related to the underlying disease

2. Chronic kidney disease signs: vomiting, anorexia, weight loss

Regenerative anemia occurs when the bone marrow responds appropriately to a loss or destruction of RBCs by increasing the production of immature cells (reticulocytes) to compensate. What are the 2 primary situations that account for this response?

1. Hemorrhage (Blood loss)

2. Hemolysis (RBC destruction)

Based on onset & duration, what are the 2 types of hemorrhage?

1. Acute

2. Chronic

What are the 4 possible causes that result to acute loss?

1. Trauma

2. Perforation

3. Rupture

4. Coagulopathies (e.g. rodenticide toxicity)

A type of hemorrhage that may eventually become nonregenerative (e.g. GI bleeding)

Chronic loss

What are the 3 main causes of RBC destruction (hemolysis)

1. Non-immune membrane damage

2. Phagocytosis by neoplastic macrophages

3. Immune-Mediated Hemolytic Anemia (IMHA)

2 examples of non-immune membrane damage that cause hemolysis

1. Disseminated intravascular coagulation (DIC)

2. Caval syndrome

A serious, life-threatening blood disorder where the body’s clotting proteins become abnormally active.

Disseminated intravascular coagulation (DIC)

A severe, life-threatening stage of canine heartworm disease. It occurs when a large mass of adult heartworms migrates into the right side of the heart and the vena cava. This mass physically blocks blood flow and interferes with the heart's valves.

Caval syndrome

An example of phagocytosis by neoplastic macrophages that causes hemolysis

Hemophagocytic histiocytic sarcoma

A condition in which the body’s immune system attacks & removes its own RBC, leading to severe anemia.

Immune-Mediated Hemolytic Anemia

This type of anemia occurs when the bone marrow factory fails to produce enough new red blood cells to replace the old ones that are naturally dying out.

Nonregenerative anemia

2 scenarios where we see a non-regenerative anemia on a blood panel.

1. Preregenrative phase

2. Lack of RBC production

2 Causes of lack of RBC production leading to nonregenerative anemia

1. Medullary causes (Bone marrow disease)

2. Extramedullary causes (Systemic disease)

What are the 2 types of medullary causes for a lack of RBC production?

1. Primary - originates within the bone marrow

2. Secondary - external factors suppresses marrow function

Extramedullary causes for a lack of RBC production refer to systemic diseases or conditions where the bone marrow itself is physically healthy, but it stops producing RBCs. What is a condition that results to this?

Chronic Kidney Disease (CKD): This is the most common extramedullary cause. If the kidneys are damaged, EPO production drops, and the bone marrow never receives the "start" signal to manufacture RBCs.

What are the 3 compartments where leukocytes concentrate?

1. Bone marrow pool

2. Circulating pool

3. Marginal pool

One of the compartments where leukocytes await differentiation. (This also includes the lymph nodes and spleen)

Bone marrow

One of the compartments where leukocytes are carried at the circulation

Circulating pool

One of the compartments where leukocytes are present at the margins of blood vessels, binded at the endothelium

Marginal pool