VM 605 Clin Path

What is clinical pathology?

study of disease; focusing on antemortem tests (ex: urinalysis, endocrine testing, CBC, chemistry)

What is Hematology?

study of the physiology of blood

What makes up blood?

plasma (fluid) and cells

What are the cellular components of blood?

erythrocytes, leukocytes, and platelets

What makes up the buffy coat?

WBC (AKA leukocytes) and platelets

Erythron includes

circulating RBCs and precursor (erythropoietin) cells in bone marrow

PCV (packed cell volume) tells us what?

PCV gives us an estimation of the RBC mass in the body

What is the purpose of erythron?

Carry OXYGEN to the tissues

What are the different types of hemoglobin (eventually may be clinically relevant)?

embryonic, fetal and adult-- and they have different oxygen affinities.

Clinical relevance: Sick sheep and goats may switch over to fetal type of hemoglobin as higher oxygen affinity which can alter RBC shape...

What are the roles of hemoglobin?

Carries iron which allows transport of Oxygen, carries some CO2 back to the lungs, acts as a pH buffer

What influences oxygen's affinity for hemoglobin?

body temp, pH, CO2 and RBC concentration of 2,3-DPG

True/False the oxygen carrying capacity is VERY REDUCED when hemoglobin takes the form of Methemoglobin?

TRUE

What is the classical clinical case associated with methemoglobin?

Acetaminophen (tylenol) toxicity in CATS

What are 2 clinical signs related to an increase in methemoglobin?

1. Cyanosis -- blue discoloration of the mucous membranes

2. Methehemoglobinemia (brown discoloration of mucous membranes, blood and urine)

What process do erythrocytes depend on for their energy?

Anaerobic glycolysis

What is the major energy source then for RBCs?

Glucose because that is the precursor molecule broken down during glycolysis

What is the normal mammal RBC shape?

biconcave disc (discocyte)

What species is the central pallor of the RBC most consistenly seen in?

dogs

What species has flat to oval RBC shape?

Camelids

What shape do exotic species like avian, reptile, amphibian, and fish RBCs have?

NUCLEATED, and oval

Where does the production of RBCs primarily occur in mammals?

Bone marrow

Hematopoiesis means

production of WBCs, platelets and RBCs

What is a common site for extramedullary hematopoiesis (EMH) (blood cell production outside of the bone marrow)

Spleen

What does the terms granulopoiesis/myelopoiesis mean?

production of WBCs

What is the term meaning the production of platelets?

thrombopoiesis

term for production of RBCs

erythropoiesis

What is the first erythrocyte precursor cell that we can see under the microscope?

Rubriblast

What is the lineage from least to most mature of erythroid precursor cells?

Rubriblast- prorubricyte- rubricyte- metarubricyte- reticulocyte- mature erythrocyte

In what species do we expect NOT to see reticulocytes?

horses

Where is erythropoietin (EPO) produced?

kidneys specifically peritubular interstitial cells

What does erythropoietin do?

regulates erythropoiesis; blocks apoptosis of certain precursors and increases hemoglobin synthesis

What is the MOST important stimulation of RBC production?

EPO (erythropoeitin)

approximately how many days does it take EPO progenitor cell to become a RBC?

5 days

What morphologic changes do erythroid precursor cells undergo during maturation?

- decrease in size

- lose nucleus

- (color shift from Blue to red) this is due to an increase in hemoglobin and decrease in RNA levels

What metal can inhibit heme synthesis?

Lead-- therefore lead toxicosis results in decreased Hgb production and increased Heme intermediates in RBCs

In mammals when does cell division stop for erythrocytes?

Rubricyte stage while still in bone marrow. (It occurs when a certain Hgb level is reached)

What nutrient /component is critical for hemoglobin syntehsis and erythropoiesis?

IRON

At which erythropoesis stage do mammalian nuclei become pyknotic/extruded (absent)

metarubricyte stage (duh last stage before cell is a reticulocyte/teenager and you know what that looks like)

What does nRBC stand for?

nucleated red blood cell

Occaisionally what may be present in circulation and observed on blood smears of mammals? And in this case which type of precursor cell is it normally?

nRBCs

metarubricytes

What can DECREASE EPO release?

Hormones and corticosteroids

What is regenerative response?

increased EPO to correct a decrease in erythrocyte mass (anemia)

In times of a regenerative response does RBC production time increase or decrease? (get faster/slower)

It gets faster (about 3ish days instead of 5)

What RBC precursor cell type is likely seen in a state of regenerative anemia in most species? (not really horses or cattle)

Reticulocytes

What does a low PCV indicate?

A low PCV indicates anemia

What can contribute to the development of anemia in disease?

the lifespan of RBCs if a condition like inflammation is chronic

What are the 2 routes of removal of old RBCs from circulation?

1. extravascular hemolysis **

2. intravascular hemolysis

** MAJOR process

What occurs in extravascular hemolysis?

phagocytosis by macrophages within the spleen (MPS-mononuclear phagocyte system)

What occurs in intravascular hemolysis?

spontaneous rupture of RBCs while in circulation

Erythropoietin is a key factor that controls RBC differentiation in erythropoiesis and is mainly produced by the ____.

A. Liver

B. Brain

C. Lung

D. Kidney

D. kidney

When is RBC morphology mainly evaluated?

Peripheral blood smear review

True/False: NO shape is pathognomonic for any specific disease

TRUE

What are polychromatophils?

reticulocytes that doe not have much RNA to visually stain that blue-purple color -- this is a subset population of reticulocytes

Do you want to be able to differentiate between polychromatopohils and reticulocytes or can you group them together when counting?

No want to be able to differentiate between those two poopulations

Polychromasia=

roughly how many of the purpley (polychromatophil) cells we are seeing in the blood smear

Explain the saying "All polychromatophils are reticulocytes but not all reticulocytes will be visible as polychromatophils"

So polychromatophils are reticulocytes that do not appear as red due to a less RNA therefore they will appear a more purple blue color. We call these cells polychromatophils to help us differentiate but ultimately they are still reticulocytes. However we cannot see "reticulocytes in the blue-purple stain that term is not interchangeable

Which stain do you use to visualize reticulocytes

Methylene BLUE

Which stain do you use to visualize polychromatophils?

Diff Quick/Wright Giemsa

True/False: In health reticulocyte numbers vary between species

TRUE

what does anisocytosis mean?

Variation in apparent size across a population of erythrocytes

Macrocytes mean...

Cells larger than normal RBC

Are polychromatophils and reticulocytes considered macrocytes?

True/yes

True/False:

Macrocytes can induce anisocytosis?

True (duh)

What type of RBC might you see in an FELV+ cat?

microcytes

In what breed of dog is it normal to see macrocytes?

poodles

Certain dog breeds of what region is it likely and normal to see microcytes?

East Asian Origin: Shiba Inu, Akita, Chow-Chow, Shar Pei

What systemic disease can cause microcytes?

Severe Liver disease & Portal systemic shunt (PSS)

What other factors should be conisdered when looking at macrocytes specifically if those noted are red-orange in color?

- sample age: this is because RBCs swell with longer storage (ex: transport)

- FeLV+ Cats

- anemic horses

- hereditary macrocytosis of POODLES

What are microcytes?

Erthrocytes that are smaller than normal

What can cause microcytes to be present in a blood smear?

- IRON DEFICIENCY ANEMIA

- vascular anomalies (ex: PSS) or severe liver disease

- Heinz body remnants

- Fragmentation of RBCs

May be seen in some healthy dog breeds of Asian origin (akita, chow chow, shar pei)

With what cell morphology might you see heinz body remnants?

microcytes

What is hypochromasia

DECREASED cytoplasmic staining of RBCs due to increased/exaggeration of central pallor

What can cause hypochromasia?

- Regenerative anemias--polychromatophils (don't have as much hemoglobin as mature RBCs)

- Iron deficiency

- BIRDS; lead toxicity and inflammation

Poikilocytosis

RBCs that deviate from normal morphology

What species is poikilocytosis common in?

healthy pigs (any age), young cattle, goats

What are acanthocytes?

Spiculated RBCs with unevenly spaced, irregular membrane projections (look like a little like long legged spikey ball)

What can cause acanthocytes

- cancer

- liver disease

- iron deficiency anemia

- Trauma within vascular system (heart failure)

-altered lipid metabolism

Why might you see acanthocytes?

Liver disease, TRAUMA to vasc., Iron def. anemia,

Cancer

In what species can it be normal to see acanthocytes?

young cattle and goats

Why can it be considered normal to see acanthocytes in young cattle and goats?

due to their ability to utilize fetal Hgb... there may be residual fetal Hgb

True/False: Acanthocytes are normal in young cattle and young goats

True

What are codocytes (TARGET CELLS)

Central area of hemoglobin separated from peripheral Hgb by a clear area

What can cause codocytes?

- regenerative response (when polychromatophils)

- Liver disease

- Iron deficiency anemia

What are echinocytes?

Spiculated (symmetrically) RBCs with evenly spaced, uniform membrane projections

What nicknames are there for echinocytes?

crenated cells, burr cells

Echinocytes are also called

burr cells or crenated cells

True/False: Echinocytes are common in healthy pigs and cats?

true

True/False: Most commonly echinocytes are an ex vivo ARTIFACT from changes in temp., pH, or drying

True

What are the pathologic causes of echinocytes?

- snake envenomation

- uremia

- electrolyte depletion

- lymphoma

- doxorubicin toxicity

- glomerulonephritis

What is a keratocyte?

1-2 cell membrane projections created from a ruptured vesicle

Blister cells: RBCs where the vesicle is still intact

What causes keratocytes?

- trauma in vascular system (fragmentation injury)

- oxidative damage

- iron deficiency anemia -- but this is due to the fragmentation

Blister cells are what?

keratocytes but with the vascular membrane still entact

What is a nickname for keratocytes?

helmet cells

How are helmet cells different from blister cells?

They differ by the vesicle--> in a blister cell the vesicle is still intact where in a helmet cell it is ruptured

What are ovalocytes?

Oval RBCs

In what species are ovalocytes normal in?

camelids and non-mammals (avian/reptiles/amphibians)

What is a nickname for ovalocytes?

elliptocytes

What are schistocytes?

Irregular RBC fragments due to trauma, including tortuous vasculature, intravascular fibrin strands (DIC), turbulent blood flow

What are causes of shistocytes?

trauma of some sort:

- tortuous vasculature

- intravascular fibrin strands (DIC)

- turbulent blood flow

True/False: Shistocytes are fairly uncommon to see. If you have a patient with a large quantity of these cells you should be worried?

True