Effects of radiation on bone marrow
Which cells affected first?
Leukopenia-->especially neutrophils- why? shortest lifespan
Bone marrow gets damaged-->DNA damage, ROS--> unable to replace n'phils--> susceptible to infection
platelets affected next, can't clot--> bleeding
Eventual anemia, intestinal tract, and skin epithelia destroyed.
a reduction in erythrocyte number and or the hemoglobin concentration i.e. decreased RBC, HCT/PCV and or Hb
Not a final diagnosis- must look for underlying cause
Anemia isn't a disease, it's a clinical finding.
Clinical features of acute anemia
Clinical features of chronic anemia
cardiac (haemic) murmur- develop murmur d/t change in blood viscosity (decrease in rbcs, decrease in viscosity, more turbulence)
Causes of anemia
1) decreased number of erythrocytes entering the blood i.e. decreased production/bone marrow issue
2) increased number of erythrocytes exiting the blood
decreased O2-->kidneys detect hypoxia-->increased EPO-->bone marrow increases RBC production.
If BM is functioning normally, increased numbers of reticulocytes appear in blood=regeneration (replacing damaged or lost rbcs)
NB: it takes 3-5 days for this to occur
Types of anemia
Non-regenerative: decreased production
can be due to primary BM disorder, or secondary BM disorder (i.e. renal failure, not enough EPO, not stimulating BM)
Regenerative: increased exit or turnover of RBCs
can be due to: 1) hemolysis (increased destruction of RBCS) a) intravascular or b) extravascular
or 2) hemorrhage a) internal or b) external
How do we tell if anemia is regenerative?
** increased number of reticulocytes in blood (nb not in horses)
Macrocytic hypochromic: increased MCV (because reticulocytes are larger), decreased MCHC because reticulcytes are bigger, Hb concentration is decreased, but not the AMOUNT of Hb.
increased polychromasia (abnormally high number of RBCs in blood) /increased anisocytosis (RBCs are of unequal size)
Sometimes see normoblasts
Basophilic stippling (cattle): tend to see blue/black dots on RBCs.
Acute: after accidents or sx
Chronic: bleeding from ulcers, neoplasms or parasites
Coagulopathies: e.g. rodenticide
Internal: animal isn't losing all red cells to outside world, macrophages can mop up and save iron.
external: less iron, less red-cells--> may have impact on BMs ability to make new RBCs.
Blood findings in hemorrhagic anemia
Normal in first few days--> pre-regenerative
Regenerative: polychromasia (increased number of RBCs in blood due to presence of reticulocytes)
Anisocytosis: difference in red blood cell size (reticulocytes bigger than rbcs)
Howell Jolly body: nuclear remnants in circulating erythrocytes (nb: presence usually signifies damaged spleen)
Thrombocytosis: increase in number of platelets in circulation--> reactive response
Neutrophilia: due to stimulation, stress and inflammation
All of these result in macrocytic hypochromic--> i.e. increased mean cell volume.
Degree of regeneration in hemorrhagic anemia factors
Degree of regeneration depends on:
severity of blood loss
location of bleeding: internal vs. external-- in internal bleeding, iron is available for Hb synthesis= greater regeneration
Proteins: not just red cells being lost--> hypoproteinemia (classicaly a panhypoproteinemia).
two important features:
1)reduced red blood cell survival time
2) iron from destroyed erythrocytes is retained in the body
Blood picture: markedly regenerative and additional finidings depend on pathogenesis.
Methods of red cell destruction in hemolytic anemia
1) extravascular lysis (phagocytosis)- mostly in spleen
2)intravascular lysis- RBCs being destroyed in the bloodstream.
Extravascular lysis of RBCs
Phagocytosis of red cells--> spleenic englargement
Iron and globin is reused
Haem--> biliverdin-->bilirubin (not h2o soluble)
Bilirubin transported by albumin (jaundice)
In liver, bilirubin and glucuronide are conjugated (h2o soluble)--> bile
nb: herbivores may have yellowish plasma anyway (don't confuse with jaundice).
Look for icterus in mucosal membranes, sclera. where there's more elastic fibers, that's where you see jaundice.
Lysis of RBCs in the circulation-->free Hb in the blood--> hemoglobinemia
Free Hb-->+haptoglobins-->phagocytosis-->jaundice (if amount exceeds phagocytic capability)
Saturation of haptoglobins-->Hb appears in kidneys-->Hemoglobinuria-->toxic nephrosis
Hematuria: post centrifugation- red cells sediment at bottom
Hemoglobinuria: post centrifugation, whole sample stays red.
Causes of hemolytic anemia
Inherited: phosphofructokinase deficiency of springer spaniels; pyruvate kinase deficiency of basenjis; NB inherited hemolytic anemia is REALLY rare.
Acquired: much more common- Infectious agents, oxidative compounds and toxins, fragmentation (increased mechanical trauma), immune-mediated.
Infectious hemolytic anemia
mycoplasma spp, babesiosis
blood picture of mycoplasma hemofelis infxn: small reddish magenta dots in blood cells. macs try to remove these cells. can trigger immune-mediated destruction as well.
blood picture of babesia divergens in cattle: pear-shaped bilobed organism in red cells; causes intravascular lysis--> hemoglobinuria.
Toxic and oxidative hemolytic anemia
Oxidative agents in drugs can reduce glutathione levels on RBCs
Haem iron can be oxidized to methaemoglobin (chocolately brown color to blood)
Oxidative damage to hemoglobin causes Heinz body formation--> destoryed by intra- or extravascular lysis.
heinz body: inclusions within rbcs composed of denatured hemoglobin.
inclusions on RBCs of denatured hb
nb: completely healthy and normal cats have heinz bodies
see heinz bodies in GI disease, diabetes, hyperthyroidism in cats
rarely seen in dogs except in onion/garlic poisoning.
easier to see on new methylene blue stain.
Causes of toxic/oxidative hemolytic anemia
cooper poisoning (ruminants)
paracetamol (cats especially)
brassicas (rape and kale)
red maple (horses)
Fragmentation hemolytic anemia
RBCs subjected to excessive trauma
features of intravascular lysis may be present
Schistocytes ( shredded red cells) and acanthocytes (intact red cells, but irregularly shaped (spiculated)
small vessel disorders: microangiopathic
large vessel disorders
valve lesion: stops heart valve from closing--> increased turbulence-->red cells bash against each other--> mechanical trauma
metastatic cancer (lungs): tumours disrupt capillary network--> increased mech. trauma to red cells.
thrombus in blood vessel: impeded blood flow in that blood vessel--> mechanical trauma of red cells trying to squeeze past thrombus.
Immune-mediated hemolytic disorders
Blood group incompatabilities: blood transfusion reaction (naturally occuring ABs to other blood groups); neonatal isoerthyrolysis
Immune-mediated hemolytic anemia generated against self-antigen/own red cells
hemolytic disease of the newborn
Maternal blood group ABs are absorbed from colostrum, destroying neonate's RBCs.
This occurs when mother's blood group is different to the new born's AND the mother has been previously sensitised to that blood grup (i.e. she's developed ABs to foal's red cell type, either from previous pregnancy, or vax, or blood products).
Dam with sensitization to foreign antigens-->formation of alloantibodies-->neonate ingests colstrum and absorbs antibodies which are dictate against own blood type--> destruction of RBCs-->occur via phagocytosis or intravascular lysis.
How to avoid isoerythrolysis
indirect coomb's test if mare has ABs against stallions RBCs. if sensitized, attach another AB to cause agglutination. if she does have ABs, can stop foal getting colostrum from mom.
signs develop 12-48 hours after birth.
IMHA in adults
secondary: under-lying trigger; i.e. drugs/toxins, infectious agents, neoplasia, vaccines?
Dogs often primary/idiopathic
other species uncommon and usually secondary.
Canine IMHA (auto-immune)
production of autoantibodies against own rbc
IgM or IgG
autoantibodies may be agglutinins (clumping) or lysins or incomplete (incomplete triggering of complement cascade)
Warm or cold reacting.
Warm antibody AIHA
reacting at body temp
incomplete IgG coats RBC
completely/partially phagocytosed in spleen (incomplete activation of complement cascade)
-spherocytosis (lose a little bit of RBC membrane- not biconcave, no area of central pallor)
-splenomegaly (due to increased spleen activity)
May partially activate complement- CB3 (opsonin) coated cells removed by macrophages
If ab is a strong activator of complement--> trigger membrane attack complex--> hemolysis-->more acute/severe disease.
high concentration of IgG or warm reactive IgM antibodies--> autoagglutination
clumping of RBCs-- IgM can hold many red cells
Slide agglutination test
demonstrates presence of antibody on red cells
differentiates rouleaux formation and autoagglutination. if it's IgM, will stay clumped in saline
Direct coombs test
blood sample with IMHA: antibodies shown attached to antigens on surface
AB that's been raised to CB3 and IgG on red cells
positive test result: rbcs agglutinate
Anemias of decreased red cell production
Secondary anemias: nutritional deficiency; inflammatory disease; chronic renal failure
Primary hypoplastic/aplastic anemias: bone marrow problem
Nutritional deficiency anemia
protein deficiency (starvation)
mineral deficiencies (iron, copper, cobalt)
vitamin deficiency (B12, folate)
seldom cause anemia in domestic species except for iron deficiency.
Iron deficiency anemia
can be regenerative or non-regenerative
Iron is an essential component of haem
iron deficiency interferes with hemoglobin production.
results in production of hypochromic microcytes (red cells with decreased amounts of Hb-->much larger area of central pallor)
Microcytes=small cells, likely seen because RBCs and Hb production is normally together and if we have decreased Hb d/t decreased iron, RBCs stay longer in BM and undergo another replication-->smaller.
Causes of irona deficiency anemia
Decreased iron intake: fast growing, large breed dogs, suckling piglets (intensive indoor pigs who can't root around in soil. also, sow milk low in iron)
Chronic blood loss: GI ulceration or neoplasia, inflammatory GI disease, parasites, clotting disorders.
Anemia of inflammation
v. common; multifactorial process
Mild to moderate non-regenerative anemia (normocytic, normochromic)
May be due to longstanding process- infectious, malignant, or other
Functional iron deficiency- not a lack of iron, just not able to use it
Some cytokines may inhibits EPO production or BM progenitor cells directly
nb: TNF can cause macrophages to sequester iron.
Anemia secondary to renal disease
functional marrow failure due to reduced EPO levels
Other potential factors: anemia of inflammation; uremic toxins- kidneys filter blood, lots of metabolite toxins can have suppressive effect
Primary hypoplastic/aplastic anemias
Celluarity of bone marrow is reduced
may involve multiple cell lines (erythrocytes, granulocytes, platelets)= aplastic anemia
or may only affect red blood cell line=pure red cell aplasia.
Pure red cell aplasia
immune-mediated: ABs against red cells or progenitor cells in BM
EPO replacement failure: in renal failure, can use recombinant human EPO- body develops ABs against own and human EPO
Classic aplastic anemia
drugs, chemical (some chemo agents have a myelo-suppressive effect)
infectious agents- FeLV
reduction or absence of all blood cell lines
development usually gradual starting with cells with shorter lifespan
selective depression of one or two lineages may occur
examples: bracken poisnoning in cattle
ehrlichia, parvo, felv
bleeding calf syndrome (association with mucosal dz vax)
increase in all cells of circulation/increased red cells in circulation
abnormally increased red cell mass (Increased RBC, HCT/PCV,Hb)
absolute or relative
absolute polycythaemias can be: primary (not controlled by EPO) or secondary (due to increased EPO production)
most commonly encountered form
increased RBC, PCV and Hb concentration due to decreased plasma volume--> dehydration
splenic contraction in exciteable animals
=transient form (esp. in horses and dogs)
Absolute primary polycythaemia
increased red cells being produced
aka: polycythaemia vera
uncontrolled expansion of red cell mass (not directed by EPO)
chronic myeloproliferative disorder
VERY RARE in animals
Secondary absolute polycythaemia
excess epo production: appropriate and non-appropriate
Appropriate: hypoxia is fundamental stimulus to EPO. causes of chronic hypoxia include: CV disease and chronic respiratory disase
Inappropriate: no hypoxia and EPO is produced uncontrollably: kidney neoplasms or non-neoplastic disorders e.g. cysts; other non-renal neoplasms.
Example of presentation of polycythemia
Polycythaemic conjunctiva; mucous membranes hyperemic due to massive increase in number of red cells.
Some cyanosis to mucous membrane edges-->blood viscosity has increased hugely, therefore perfusion to some places has decreased.
Clinical signs of polycythaemia
Relative: look for signs of dehydration
-tacky mucous membranes, sunken eyes, increased skin tent
neurologic (hyperviscosity- not perfusing properly)
weakness- muscles not perfused
signs attributable to underlying process (if secondary, e.g. chronic lung disease etc).