Lect 2 - Haematology Flashcards
Haematology is divided into the study of [2]
Formed (cellular) elements
Soluble fraction of blood (plasma)
The cellular components of haematology includes [3]
Erythrocytes, leukocytes and platelets
Haematopoietic growth factors include [3]
Proteins, colony stimulating factors (CSF) and interleukins (ILs)
At birth, almost all the bones of the body are involved in haematopoiesis, however, by adulthood, active haematopoiesis occurs mainly in the [5]
Marrow of the vertebrae, ribs, sternebrae, pelvis and metaphyses of long bones
When there is great demand for blood cells or when there is unregulated blood cell proliferation, active haematopoiesis may return to [2]
Extramedullary sites e.g. liver, spleen
To the diaphyses of long bones
Haemopoitic stem cells (HSC) are
Pluripotential stem cells that have the ability to differentiate into different cell types
What are the daughter cells of HSC [2]
Myeloid and lymphoid
How do HSC differ from daughter HSC
HSC are self renewing cell
HSC daughter cells commit to alt differentiation pathways and are not self renewing
The erythrocyte mass in the body consists of [3]
The stem cell compartment - bone marrow
The maturation and proliferation compartment - bone marrow
Circulating erythrocytes
A portion of the pluripotential stem cells becomes committed to erythropoiesis and differentiates into
Eryrthroid progenitor cells
Name the two sets of erythroid progenitor cells identified [2]
Burst forming unit erythroid (BFU-E)
Colony forming unit erythroid (CFU-E)
Erythropoiesis is regulated by [2]
Tissue hypoxia (main stimulus) and growth factors/hormones
What regulatory hormone is elaborated in response to hypoxia and where does it come from
Erythropoietin (EPO) from the peritubular interstitial cells of the kidney
What is the most important growth factor for maintenance of erythropoiesis
EPO
What growth factors stimulate BFU-E to differentiate into CFU-E and the differentiation of CFU-E into the erythroblast (rubriblast) [4]
EPO, IL-3, G-CSF and GM-CSF
EPO, IL-3, G-CSF and GM-CSF stimulate
Differentiation of BFU-E into CFU-E and CFU-E into erythroblast (rubriblast)
The first recognizable erythroid precursor in the bone marrow
Rubriblast
The maturation sequence of the erythroid cells is [6 steps]
Rubriblast > Prorubricytes > Rubricytes > Metarubricytes > Reticulocytes (Polychromatophil) > Mature erythrocyte
Newly released blood cells stain blue/bluish grey with this stain? and are called what?
Wright/Wright Giemsa stain and are referred to as polychromatophils
Newly released blood cells when stained with this basic dye? are referred to as what?
New Methylene Blue stain and referred to as reticulocytes
These are aggregates of denatured hemoglobin cause by oxidative damage which also stain well using New Methylene Blue
Heinz bodies
When are polychromatophilic cells usually seen
Regenerative anaemias
<1% reticulocytes are normal in what species [3]
Dogs and pigs and sometimes cats
Reticulocytes are absent in what species even with regenerative anaemia
Horse….they do not release reticulocytes into circulation
Early reticulocytes are called
Aggregate reticulocytes
Aggregate reticulocytes mature into
Punctate reticulocytes
What species has both aggregate and punctate reticulocytes…and which should be counted when doing reticulocyte count
Cats
Aggregate
Reticulocytes are generally released when there is increased demand for RBCs, so an increased number can be seen in the peripheral blood with
Regenerative anaemias
The process from rubriblast to mature red cell takes
4-7days
The process from rubriblast to mature red cell takes 4 – 7 days but can be accelerated under erythroid marrow stimulation to
2-3days
Nucleated red blood cells ( e.g rubricytes and metarubricytes) can occasionally appear in the peripheral blood and can be a sign of a regenerative response ( increased demand for RBC). This is termed
An appropriate response
With “an appropriate response” to anaemia there is also a concurrent increase in
Reticulocytes
Inappropriate rubricytosis is
Rubricytosis without an concurrent increase in the reticulocyte count
Nucleated RBC are cleared by the
Spleen
Inappropriate rubricytosis can be a result of
Splenic dysfunction or neoplasia or bone marrow disease
In animals, the erythrocyte is shaped like
A biconcave disc
RBC biconcave disc shape is most prominent is what species
The dog
The diameter of canine RBC are
7microns - other species RBC are smaller
Which species has a prominent central pallor
Canine
What is poikilocytosis
Variation in RBC shape
Which species RBC has a marked poikilocytosis
Goats
What is anisocytosis
Variation in RBC size
Which species exhibit anisocytosis [2]
Cows and goat
The RBC of mammals lack a what
Nucleus (Non-nucleated)
What species have ellipsoidal shaped non nucleated RBC
Camelidae - camels, llamas, alpacas
What species of animals have oval/ellipsoidal nucleated RBC [4]
Avian, Fish, Amphibian and Reptile
Rouleaux formation is commonly seen in what species [3]
Horse
Cats may also show tendency in health
Dogs show little rouleaux unless inflammatory disease is present
Rouleaux formation should be differentiated from
Agglutination seen in cases of IMHA
What is basophilic stippling
Aggregates of RNA in RBC
What type of stain is used to view basophilic stippling
Wright’s
When and in what species is basophilic stippling seen
Lead poisoning in dogs
Regenerative anemias in cats and ruminants
Heinz bodies are usual observed in what species and why
Cats
Their Hgb has more sulphdryl grps than other species and the spleen is less efficient at removing heinz bodies
Howell Jolly bodies are
Nuclear fragments seen in newly released RBC
What conditions are Howell Jolly bodies usually observed [2]
Regenerative anemias and splenectomized anemias
Howell Jolly bodies can be normally found in low numbers in which species [2]
Dogs and Cats
What is a hypochromic cell
Reduced volume of Hgb so that the area of pallor is exaggerated
Hypochromic cells are most noticeable in what condition
Dogs with iron deficiency
Hypochromasia is measured as a decrease in what
MCHC
What is a macrocyte
An erythrocyte with an increase volume
Macrocytosis detected as an
Increase in MCV
Macrocytosis/increase in MCV are usually seen in [3]
Regenerative anemia
Hereditary poodle marrow dyscrasia
FeLV infection
What is a microcyte
An erythrocyte with a decreased volume
Microcytosis is detected as a
Decrease in MCV
What condition is microcytosis observed concurrently with hypochromasia [2]
Iron deficiency anemia and hepatic failure in dogs
Some breed of dogs have natural lower MCV, give examples [4]
Akita, Shiba, Chow Chows, Shar Pei
What are spherocytes
Dense, spherical RBC
When can you find spherocytes [3]
IMHA
Coral Snake Bites
Zinc Toxicity
What are schistocytes
Irregular fragment of RBC
When can you find schistocytes [6]
DIC Microangiopathic hemolytic anemia CHF Hemangiosarcoma Glomerulonephritis Myelonephritis
What is an echinocyte (Crenated cell, Burr cell)
RBC with several evenly spaced projections
When can you find echinocytes [3]
Electrolyte abnormalities
Uremia
In vitro change (artifact)
What is an acantocyte (Spur cell)
RBC with two or more unevenly spaced blunt projections
When can you find acanthocytes
Hemangiosarcoma
Liver disease
What are keratocytes (2)
There are two types
Blister which preceds Helmet
When can you find keratocytes
DIC
Microangiopathic hemolytic anemia
What are codocytes (Target cell)
RBC containing a dense central area of Hgb
When can you find codocytes
Liver disease
Regenerative anemia
What are dacrocyte
Tear shaped RBC
When can you see dacrocytes
Myleofibrosis
Pure red cell aplasia
Myeloproliferative disease
Artifact
What are stomatocytes
RBC with a slit like clear opening near the center
When can you find stomatocytes
Hereditary stomatocytosis in Malamutes
Chronic anemia
In vitro change (artifact)
In the body iron exists as many forms…list them (6)
Hemoglobin Storage iron Myoglobin Labile iron Tissue iron Transport iron
Majority 55-65% of the body’s iron exist in the form of
Hemoglobin
Most iron exist as hemoglobin, what is the second highest (33%) form
Storage iron
There are two types of storage iron, name them
Ferritin - iron protein complex
Haemosiderin - more stable but less availble than ferritin
What form of iron is the best indicator of iron stores in the body
Ferritin
What is the ferritin lvl in true iron deficiency compared to anemia of inflammatory disease
True iron deficiency - low
Anemia of inflammatory disease - normal or high
What causes the increase in ferritin lvl during anemia of inflammatory disease
Scavenging of iron from tranferrin to ferritin where it becomes less available to invading organisms
Inflammatory cytokines stimulate the production of what from hepatocytes
Hepcidin
What is the role of hepcidin
Inhibits absorption of iron from intestines and release from macrophages
How does haemosiderin differ to ferritin
Higher iron to protein ratio and is not water soluble
Haemosiderin can be observed under what stain
Prussian blue
What form is the iron in haeme
Ferrous (Fe2+) that can bind to O2
Where is myglobin found
Muscles
Myoglobin has what percent of iron
3-7%
Which species of animals is the iron content of myoglobin higher (2)
Dogs and Horses
The plasma iron pool is in dynamic with this pool
The labile iron pool
The iron in the tissue pool is important because
It forms an integral part of enzyme systems
Iron is transported in plasma bound to a protein called
Transferrin
Bound iron is measured as
Serum iron
Iron is transported as what to the red cell compartment
Ferrotransferrin
What is total iron-binding capacity (TIBC)
The measure of plasma to carry iron
TIBC is increased in chronic iron deficiency most species EXCEPT
Dog
Disorders of anaemia associated with chronic iron deficiency and inflammatory/chronic disease can usually be differentiated by examination of bone marrow for stainable iron EXCEPT in what species
Cat
Stainable iron is not present in the bone marrow of normal cats
The main function of Hgb is
To carry O2, CO2 and buffer H+
95% of CO2 is transported as
HCO3-
CO2 + H2O ↔ H2C03 ↔ H+ + HCO3¯ is catalyzed by
Carbonic anhydrase
Which species have higher intracellular K+ concentrations [4]
Man, horse, pig and some ruminants (mainly among sheep)
Which species have low intracellular K+ conc [4]
Some sheep, goats, buffalo and cattle
Intracellular Na+ and K+ are similar to plasma in what species [2]
Dogs and Cats
Examples of defects in glycolytic enzymes? [2] and what may result
Pyruvate kinase deficiency and PFK deficiency
Hemolytic anemia
Pyruvate kinase deficiency are found in what breeds of animals [5]
Besenji, Beagle, West Highland white terrior and Abyssinian and Somali Cats
PFK deficiency are found in what breeds of animals [2]
English Springer Spaniels and American Cocker Spaniels
What factors cause a left shift in the O2 dissociation curve [4]
Decreased 2,3-DPG
Decreased CO2
Decreased Temp
Increased PH
What factors cause a right shift in the O2 dissociation curve
Increased 2,3-DPG
Increased CO2
Increased Temp
Decreased pH
A right shift in the O2 dissociation curve means
Lowering of O2 affinity of Hgb i.e fovouring release of O2 to tissues
Vice versa for left shift
The average RBC span for the following species are
Cow, Sheep, Horse, Cat, Bird
Cow - 160 Sheep - 150 Horse -145 Cat - 70 Bird - 35
RBC are removed by [2]
Extravascular routes - phagocytosis by the MPS of the spleen
Intravascular lysis - release of Hgb into the plasma
Iron from degraded RBC are stored as ferritin or haemosiderin in what
Macrophages
The protoporhyrin ring is catabolized by haema oxygenase to
Biliverdin
Biliverdin converted via biliverdin reductase to
Bilirubin
Bilirubin is transported to the liver by
Albumin
In the liver bilirubin is conjugated to
Bilirubin diglucuronide and excreted in bile into the intestines
The conjugated bilirubin by bacterial action in the intestines is degraded to
Urobilinogen which can be excreted in urine
Urobilinogen can be further degraded to
Stercobilinogen
What species final end product is biliverdin and why
Birds - they lack biliverdin reductase
Free oxidized form of haemoglobin is complexed to
Haemopexin which is cleared by the liver
What is hematocrit
The percent of RBC in blood
In what species, is the Hgb conc 3x the haematocrit
Dog
MCV is measured in
Femtoliters
MCHC is measured in
grams/L
As a general rule, regenerative anaemias are usually a result of? Describe it in terms of MCV and MCHC
Hemorrhage or hemolysis
Macrocytic, hypochromic
Reticulocytosis occurs in what type of anemia
Regenerative
How much time does it take for reticulocytes to appear in regenerative anemias
3-4days
The more severe the anemia the……reticulocyte response?
The greater the reticulocyte response
In anemias due to blood loss (hemorrhagic anemias) there is a decrease in what [2]
RBC and protein
In anemias due to accelerated RBC destruction (hemolysis), there is a decrease in what
RBC but normal plasma protein
Anemias due to reduced or defective erythropoiesis tend to be
Non regenerative
Hemorrhagic anemias may be [4]
Acute or Chronic,
External or Internal
In hemorrhagic anemias -
A low plasma protein lvl in a regenerative anemia is suggestive of what type of blood loss. Compare with alternative.
External
Internal blood loss - may be only mildly decreased as it is reabsorbed
In hemorrhagic anemias - What species may show an increase in Hct shortly after acute blood loss and why?
Horse - splenic contractions
In hemorrhagic anemia - Chronic blood loss is characterized by impaired what? why?
Erythropoiesis due to iron exhaustion
In hemorrhagic anemia - Anemia due to chronic blood loss gradually becomes (MCHC, MCV)
Hypochromic, Microcytic
*Iron deficiency anemia seen in dogs and ruminants
What evidence may you look for to determine is blood anemia is due to chronic blood loss
Bleeding into the gi tract (tarry stool/melena)
Hemolytic anemia which occurs as a result of increase red blood cell destruction within the body may be [4]
Congenital or Acquired
Intravascular or Extravascular
In hemolytic anemia - in may disease conditions when intravascular hemolysis is present what else is occuring
Extravascular haemolysis
In hemolytic anemia - PCV (also hemoglobin, RBC) and protein lvl are
PCV (also hemoglobin, RBC) decreased
Protein often normal
Hemolytic anemia - signs of extravascular hemolysis [2]
Icterus
Bilirubinuria
Hemolytic anemia - signs of intravascular hemolysis [4]
Hemoglobinemia and hemoglobinuria
Icterus and bilirubinuria
Hemolytic anemia - changes in RBC morphology…what so you look for [4]
Sperocytes
Acanthocytes
Parasites
Heinz bodies
Hemolytic anemia - Immune mediated: cause, diagnostic test, RBC morphology
Antibody reacts with target antigens on the RBC membrane or
reacts with drug/infectious agent which adheres to RBC
Coombs Test
Spherocytes or agglutination
Hemolytic anemia - Toxins/chemicals e.g. [7]
Acetaminophen, zinc, copper toxicity
Bacterial toxins from Leptospira/Clostridia
Snake/Spider bite venoms
Hemolytic anemia - RBC parasites e.g. [2]
Mycoplasma hemofelis
Babesia
Hemolytic anemia - Mechanical injury of RBC e.g.
Hemangiosarcoma
Hemolytic anemia - Inherited RBC deficiency [2]
PK and PFK deficiency
Hemolytic anemia - exposure to oxidizing agents e.g. [3] What clues can you look for?
Acetaminophen
Garlic
Onion
Heinz bodies
Hemolytic anemia - Hypophosphatemia e.g.
Diabetic ketoacidotic cats receiving insulin therapy
What are some congenital causes of hemolytic anemia and the species in which they affect
Porphyrias - cattle, cat, swine
PK deficiecy - dogs and cats
PFK deficiency - dogs
In congenital/inherited hemolytic anemia the type of hemolysis is generally
Extravascular
Bovine congenital erythropoietic porphyria occurs at birth. What precaution is taken in calves
Protection from sunlight due to photosensitization
Deficiency of PFK results in
Decreased ATP and 2,3-DPG formation
Acquired haemolytic anemias are more common than congenital haemolysis and occur mainly
Extravascularly (MPS) system
Acquired haemolytic anemia - Viral - Equine infectious anemia..What is the most prominent CBC result.
How do you diagnose
Thrombocytopenia
AGID (Coggin’s Test)
Acquired haemolytic anemia - Feline leukemia virus. Regenerative?MCHC? MCV?
Non regenerative, normochromic and sometimes macrocytic
Acquired haemolytic anemia - Leptospirosis common sign is
Icterus
Acquired haemolytic anemia - Icterus in Leptospirosis is a result of
Intravascular hemolysis due to the production of haemolysin
Acquired haemolytic anemia - Anemia from Leptospirosis is less pronounced in what species
Dogs
Acquired haemolytic anemia - Bacillary haemoglobinuria is caused by [2]
C. haemolyticum and C. novyii type D
Acquired haemolytic anemia - Bacillary haemoglobinuria affects what species [2]
Cows and Sheep
Acquired haemolytic anemia - Bacillary haemoglobinuria is result of what toxin?
Beta-toxin
Acquired haemolytic anemia - What species of Babesia is found in dogs [2]
B. canis and B. gibsoni
Acquired haemolytic anemia - What species of Babesia is found in cows [4]
B. bovis, B. bigemina, B. divergens and B. major
Acquired haemolytic anemia - What species of Babesia is found in horses [2]
Theileria equi and B. caballi
Acquired haemolytic anemia - What species of Babesia is found in cats [2]
B. felis and B. cati
Acquired haemolytic anemia - What species of Babesia is found in sheep [3]
B. ovis, B. foliata and B. motasi
Acquired haemolytic anemia - these piroplasms appear as signet ring bodies or bipolar safety pins
Cytauxzoon felis
Acquired haemolytic anemia - this is the only tick bourne vector
Dermacentor variablis
Acquired haemolytic anemia - Rickettsial disease - Anaplasmosis is the disease of what species [2]
Cattle and sheep
Acquired haemolytic anemia - Rickettsial disease - Anaplasma species in cattle are [2]
A. marginale and A. centrale (less pathogenic)
Acquired haemolytic anemia - Rickettsial disease - A. ovis infects [2]
Sheep and Goats
Acquired haemolytic anemia - What is the difference between Anaplasmosis and the other anemia causing Rickettsial disease
Anaplasmosis organism is found in the erythrocyte
Mycoplasmosis parasite is found on the surface of the erythrocyte
Acquired haemolytic anemia - Rickettsial disease - Haemoplasmosis appear in different forms, list them [3]
Coccoid, ring and rod-shaped
Acquired haemolytic anemia - Give examples of oxidizing agents and the species they affect
Acetaminophen - Dogs and Cats
Red maple leaves - Horse
Rape seed - Cows
Acquired haemolytic anemia - Copper toxicity occurs in which species [3]
Cattle, sheep and swine
Normocytic normochromic non regenerative anaemia with normal or increased neutrophils and platelets can be due to [6]
Lack of erythropoietin Inflammatory disease/chronic disease FeLV associated anemia Immune mediated anemia Liver Disease Hypothyroidism/adrenocorticism
Normocytic normochromic non regenerative anaemia with decreased neutrophils and platelets can be due to [2]
Aplastic anemia
Myelophthistic anemia
Causes of aplastic anemia
Damage to the multipotential stem cell or bone marrow
Ehrlichia, parvo virus, FeLV, FIV
Estrogen, chemotherapy, bracken fern
Causes of myelophthistic anemia
Bone marrow is replaced by neoplastic cells
Microcytic hypochromic non regenerative anaemias with variable neutrophils and platelets can be due to [3]
Iron deficiency
Anaemia of inflammatory disease
Portosystemic shunts/liver insufficiency
Macrocytic normochromic non regenerative anaemias with variable neutrophils and platelet
Vitamin B12 and folate deficiency
FeLV infection
Erythroid neoplasia
What is erythrocytosis
Is an increased [RBC] in peripheral blood. It is detected by finding an increased PCV/HCT, increased [RBC], or increased [Hgb]
What is polycythemia
Increase in red blood cells
What the types of erythrocytosis [2]
Relative and Absolute
What is the difference between relative and absolute erythrocytosis
Relative - no increase in total erythrocyte mass
Absolute - increase erythrocyte mass
Relative erythrocytosis can be caused by [2]
Dehydration
Splenic contraction and release of splenic blood into circulation
Explain how dehydration leads to erythrocytosis
Decreased plasma volume but no change in RBC numbers in body, causing a relative increase in the RBC count. The total protein will usually be increased as well
Explain how Splenic contraction and release of splenic blood into circulation leads to erythrocytosis
Contraction occurs due release of epinephrine in response to excitement, fright or exercise. Splenic blood contains a high concentration of RBCs and causes an erythrocytosis (common in dogs and horses)
What are the types of absolute erythrocytosis [2]
Primary and Secondary
Primary absolute erythrocytosis can be cause by
Myeloproliferative disease
What are the types of secondary absolute erythrocytosis [2]
Appropriate and Inappropriate
Appropriate secondary absolute erythrocytosis can be caused by
chronic hypoxia of cardiac and/or pulmonary disease leads to increased erythropoietin production
Inappropriate secondary absolute erythrocytosis can be caused by
Inappropiate EPO production by renal tissue because of renal cysts, renal neoplasms
Inappropriate EPO production by certain neoplasms e.g hepatoma, leiomyosarcoma
