Week 2 - Anemia Part 2

Question 1

What are your lab findings in a case of non-regenerative anemia?

Answer 1

Lab findings
* No polychromasia
* No reticulocytes or inadequate
* <80,000/uL (canine)
* <60,000/uL (feline)

Can rule out anemia of certain conditions with underlying disease, such as renal disease, and sometimes we need a bone aspirate to determine cause (to count neutrophils and platelets).

Question 2

Non-regenerative anemia results from?

Answer 2

• Impaired or decrease RBC production by the bone marrow due to what?

1. Defective erythrocyte production
2. Too Early for regeneration to happen when there is blood loss or destruction

Question 3

What are the causes of non-regenerative anemia?

Answer 3

1. Reduced erythropoiesis
2. Defective erythropoiesis

Bone marrow can not maintain erythropoiesis due to either reduced or defective.

Question 4

Examples of reduced erythropoiesis?

Answer 4

Reduced erythropoiesis
* Chronic dz (inflam. Neoplasia)
* Toxins: Bracken fern, estrogen, radiation
* Lack of EPO: chronic Renal dz, Hypoadrenocortisism, hypothyroidism
* Immune-mediated: pure cell aplasia
* Infections: FeLV, Anaplasma spp.
Parvovirus, Feline Panleukopenia
* Myelophthisis: Myelofibrosis, myeloproliferative disorders, osteopetrosis, osteosclerosis

Question 5

Examples of defective erythropoiesis?

Answer 5

1. Abnormal maturation:
   (A) Congenital dyserythropoiesis -Herefords
   (B) Erythremic myelosis - English Springer Spaniels
   (C) Macrocytosis of Poodles
   (D) Myelodysplastic syndrome
2. Disorders of Heme synthesis:
   (A) Chloramphenicol toxicity
   (B) Copper Def
   (C) Iron Deficiency
   (D) Lead poisoning
   (E) Molybdenum poisoning
   (F) Vit 6 def
3. Disorders of Nucleic acid synthesis
   (A) Vit B12 def
   (B) Malabsorption
   (C) Folic acid def

Question 6

What is the most common cause of non-regenerative anemia in domestic animals?

Answer 6

Anemia of inflammatory disease/anemia of chronic disease/anemia of inflammation is the most common cause of non-reg anemia in domestic animals.

AKA: anemia of chronic disease/anemia of
inflammation

Question 7

What would your lab results indicate in a patient suffering from anemia of chronic disease/anemia of inflammation?
What specific lab tests would you run?

Answer 7

1. Usually Mild to moderate anemia.
   - Could be clinically insignificant in some patients.
2. Normocytic (normal MCV) Normochromic (normal MCHC)
3. Low serum Iron
   - key features b/c iron is being seq. in MQs.

Other: low iron binding capacity, but this is not given by the CBC, and also elevated ferritin, not given by the CBC, which is why it is so important to evaluate leukogram in addition to CBC, etc to give diagnosis.

Question 8

List the infectious and non-infectious causes of anemia of inflammatory disease?

Answer 8

1. Infectious causes: Chronic infections with Babesia, Fungi, viruses, Protozoa
2. Non-infectious causes:
   § Autoimmune diseases
   § Toxins
   § Neoplasia

Question 9

Explain how anemia of inf. disease is a multifactorial process?

Answer 9

Multifactorial process
* Key mediators driven by Cytokines release
1. Impaired iron mobilization = iron availability
§ IL-6: induces Hepcidin (produced in liver and is considered an acute phase protein aka it increases in pplasma in response to inflamamtion) and is considered synthesis.
Hepcidin inhibits Iron transport from duodenal enterocytes and macrophages (M0) –> DECREASED Iron absorption and sequestered iron in M0 (Ferritin stores iron)

Low iron levels is a protective mechanism to deprive infectious agent of iron, but we know that iron is also imp for erythropoiesis. When we have low iron, we have low erythropoesis. MQ internalize lactoferrin to transfer iron into ferritin. Ferritin is a protein that stores iron in the cells. This whole thing is mediated by IL-6. IL-6 also has some effects in mobilixation and seq of iron and IL1 and TNFa have some degree in this roll too. If we upreg. ferritin expression, cdonsequ will be that we will promote storage and retention of iron so it ownt be available.

Question 10

How does decreased erythropoiesis lead to anemia of inflammatory disease?

Answer 10

2. Decreased erythropoiesis
   - Inappropriately low secretion of EPO
   - Decreases response of Bone Marrow to EPO
   o TNF-alpha (suppresses Erythropoiesis directly in BM). Could also be limitations of iron to have erythropoiesis (low iron = low RBC production).
   - Iron-limited erythropoiesis; Less Iron = => RBC production

Question 11

How does chronic renal disease cause non-regen anemia?

Answer 11

• Mechanisms
• 1-DECREASED EPO production = most common
• 2-suppressive effects of uremic toxins on bone marrow
• 3-blood loss, chronically from GI, Skin, other sites due to
  qualitative platelet dysfunction due to uremic toxins
• 4-shortened RBC survival due to mild hemolysis

Erythropoetin production is caused by destruction of the EPO secre3ting peritubular interstial cells. Could be hemorrhages due to uremic toxin inducing stimulus to kidney to induce eryothrpoesis. Main stimulus to kidney for this? Hypoxia. When there is hypoxia in kidney, the kidney then produces EPO.

Chronic renal disease –> uremic toxin –> conseq. bleeding and desrruction of cells.

Question 12

What are the lab findings for this chronic renal disease –> non-regen anemia?

Answer 12

Lab Findings:
* Normocytic
* Normochromic
* Moderate to severe non-regenerative anemia

Question 13

List the causes of Bone marrow erythroid hypoplasia –> Non-Regenerative anemia

Answer 13

• FeLV-induced erythroid hypoplasia (directly)
• Pure red cell aplasia
• Endocrine disorders
• Immune-mediated

Question 14

How does FeLV-induced erythroid hypoplasia cause Non-Regenerative anemia? What are the lab findings?

Answer 14

1. Damage or Killed to erythroid precursors selectively by virus itself.
2. Erythroid cells transform or no to become neoplastic
   * The erythrocytes are produced but with defects
   (maturation, metabolism, function)
   * Circulation of abnormal nRBCs

–> Lab Findings:
* Macrocytic normochromic anemia due to insyncronous maturation of nucleus relative to the cytoplasm of erythrocytes. Abnormal nucleated? RBC in circulation

Question 15

How does Pure red cell aplasia cause Non-Regenerative anemia? What are the lab findings?

Answer 15

• Marked hypoplasia or aplasia in Bone marrow b/c of the Erythroid cell lines.
• Unknown mechanisms—maybe Ab against EPO—
• Lab findings:
• Normocytic normochromic anemia
• blood film +/- spherocytes to help us discern non-regen anemia

Question 16

How can Endocrine disorders cause Non-Regenerative anemia?

Hypothyroidism

Answer 16

a. Hypothyroidism
* Dogs –> mild
* Lab findings: Normocytic normochromic anemia
- HCT = ~30%
- respond to therapy and then anemia is corrected so it is probably caused by lower metabolic rate caused by hypothyroid.
- absence of glucocorticoid? –> decreased synthesis of RBC but unknown how this happens.

Question 17

How can Endocrine disorders cause Non-Regenerative anemia?

Hypoadrenocortism

Answer 17

Hypoadrenocortism: Masked anemia By Dehydration

Question 18

How can Endocrine disorders cause Non-Regenerative anemia?

Hyperestrogenism

Answer 18

c. Hyperestrogenism
* Sources: Sertolli cell or ovarian granulosa cell tumors
* Lab findings: Moderate normocytic normochromic
anemia + thrombocytopenia and leukopenia
- Low platelets, low WBC
* Myelotoxicity effects in dogs. Mech is probably due to effects of estrogen at DNA level. We would have increased estrogens in animals due to: exogenous sources (rare in vet med) but the most common is iatrogenic source aka sertoli cell or (see source)

Question 19

How does Immune-mediated mechanisms cause non-regen anemia?

Answer 19

• AKA Precursor-directed immune-mediated anemia –
  PIMA-
• There are more immature RBCs than mature RBCs

Lab findings: severe normocytic normochromic
anemia (HCT <15-20%) - chronic normal WBC & platelets-
Spherocytes
No polychromasia

Req. bone marrow aspiration to RO other causes such as neoplasia.

BM aspirate: see eryhtroid hyperplasia, increase in BM iron, mild reactive lymphocytosis and plasmocytosis whichb is compatible with infective erythropoiesis.

Question 20

How do Nutritional deficiencies cause Non-Regenerative anemia?

Answer 20

• Iron Def. the MOST common anemia associated
  with nutritional deficiencies
• IT tends to be REGENERATIVE in early stages, unless it is
  complicated by Anemia of Inflam. Disease
  Lab Findings:
  Microcytic normochromic to hypochromic anemia –> cytoplasmic maturation arrest

Anemia of inf disease is mediate by ctokines (IL-6 –> hepsisdin –>mimpairs iron b./c heosiden induces pore absorption of GI and promotes seq. of iron in the ells. low available iron and low erythopoiesis.

iron defiiecney is most associated with chronic blood loss, more offten in GI where iron is absorbed. iron defieicy associa with ulcers, parasites, cutaneous blood loss that are heavily infested with fleas or ticks. inadquate dietary intakes we see in neonates is if they have a milk exclusive diet. not as common to see that so it is important to know the age of the animal;.

Question 21

What would the lab findings be for copper def. ?
What species are affected?
What role does copper play in anemia?

Answer 21

Copper Def.
* Pigs, dogs
Lab findings: Microcytic hypochromic

Copper is needed in oxidase iron to its ferritin state –> iron absorption –> iron transfer from intestinal cells into plasma.

Question 22

Non-Regenerative anemia of
Nutritional deficiencies are common in which dog breeds?

Which vitamins are important? What happens as a result of these vitamin deficiencies?

Answer 22

We see them in breeds specificlaly as a hereditary disease in border collies, beagles, and giatn schnouzers and cats.

in huamns, this is more common.

Question 23

Define Erythrocytosis.
How does this differ from Polycytemia?

Answer 23

Increased red blood cell mass

Must look at leukocytes and platelet counts to have a better idea of what your differential diagnosis would be.

Polycytemia (increase in number in ANY of cells in the blood) and erythrocytosis are NOT synonymous.

Question 24

What would your lab findings be in a patient with erythrocytosis?

Answer 24

Elevated HCT, RBC count + Hgb in peripheral blood

There are two types:

1. Relative elevated of RBC mass.
   - So you would see Relative Elevated HCT or RBC count with respect to the plasma AKA not a true increase in RBC mass.
   * Hemoconcentration which occurs with fluid depression, increased vascular permeability (e.g. in cases of dehydration, fluid shifts).
   - 30% of blood cells stored in spleen and can be released in splenic contraction when animals are excited or fearful, which si mediated by epinephrine. In horses who have a msucular spleen, we see thi phenomenon to increase the HCT or RBC.
   * Physiologic Redistribution: excitement, exercise
2. It is Absolute
   - pathological/abnormal most of the time.
   * Primary (Polycythemia vera) –bone marrow disorder-
   * Secondary -Due to Increased erythropoiesis

Prinmary or secondary due to:
- Appropriate (chronic hypoxia)
- Inappropriate EPO secretion

Question 25

Define primary erythrocytosis.

Answer 25

• Polycythemia Vera Independent of EPO to produce erythrocytes

proliferation of erytrocytes and increased HCT.

It is a neoplasm. RBC look normal and have a normal maturation sequence so the abnoral porlifation of other blood cell lines is rarely observed in domestic anials and therefore it should be called primary erythrocytosis and not plycthemia. It is thought that proliferation of erythoryter in this disease is due to erythrocytes having an abnormal clone of erythro-precursors that is either capable of proliertain independent of EPO andit is a discussion if poly exists?

Question 26

Define secondary erythrocytosis.

Answer 26

Stimulus will increase EPO. Hypoxia –> increase EPO (seen in animals with chronic heart or lung diseases.

E.g. congenital heart diseases: shunting of blood away from lungs and this is assocaited with seondary eryth than those with acquired heart disease.

lung disease –> hyypoxia –> chronic –> ?

high altitude: induced hypoxia –> long term it could lead to erythrocytosis.

if EPO is secreted without hypoxia as a stimiulus, then this is physiological inapropriate eyrhtorcytosis,. Seen most likely due to an increase in EPO in renal tumors b/c there is an induced renal hpoxia. In cases like this, we need to use imaging to see if there s an ccupying lesion in the kidney such as a cyst or a tumor.

1. Increased erythropoietin
   * Appropriate in chronic hypoxia
   * Cardiac arrest, respiratory disease
   * Inappropriate EPO secretion
   * Renal tumors
   Clinically will have Deep red mucous membranes due to more RBC mass in circulation and the blood has a higher
   Viscosity

Question 27

Answer 27

• Low Hct and Low RBC = likely has a case of anemia
• Hgb = measuring what is inside RBC and also what is inside the plasma (free Hgb). High Hgb makes no sense with low Hct and Low RBC.
• In internal control, the Hgb should be 1/3 of the Hct. So 18/3 = ~ 6. Hct should be 3 x Hgb. 17 x 3 = 51. These two # do not makes sense here. SO the Hct, MCHC, and the MCH, are calculated based on the Hct and depend on the Hgb measurement and the RBC count.

B/c Hgb is altered, the MCHC will also be altered and same with MCH. SO When there is hemolysis, aka leak of Hgb outside of RBC, we may see an increase in Hgb associated with a decrease # or RBCs aks low RBC but high Hgb that makes no sense you must think this is a case of hemolysis.

If animal is pigmented, have not been fasted enough, too much fat in plasma, increase bilirubin due to icterus –> alters Hgb reading which is why we don;t use Hgb to evaluate anemia in vet med.