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Anaemia Flashcards

1
Q

What is anaemia?

A

* Decreased red blood cell density- haematocrit/ PCV, RBC, haemoglobin level

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2
Q

What are the clinical signs of anaemia?

A

Weak/ lethargic/ dull, pale mucous membranes, tachycardic, tachypneic, +/- cool extremities & weak peripheral pulses, +/- heart murmur, +/- icterus, possible shock

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3
Q

What causes Regenerative Anaemia?

A

Red cell loss from haemorrhage or haemolysis

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4
Q

What causes Non-regenerative anaemia?

A

Decreased red cell production

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5
Q

With regenerative anaemia, what do you see from the marrow response?

A

Reticulocytosis, polychromasia, hypochromic macrocytic anaemia

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6
Q

With non-regenerative anaemia, what do you see from the marrow response?

A

No response. Pre-regenerative or non-regenerative, no reticulocytosis, minimal polychromasia, normocytic normochromic or hypochromic microcytic

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7
Q

What does intravascular haemolysis mean?

A

Rupture of RBC within the circulation

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8
Q

What does extravascular haemolysis mean?

A

Phagocytosis of RBC by macrophages in spleen, bone marrow, and liver

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9
Q

What does haemoglobinemia mean?

A

Excessive haemoglobin in plasma

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10
Q

What does Bilirubinaemia mean?

A

Excess bilirubin in plasma

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11
Q

What is erythropoietin?

A

The principle growth factor promoting viability, proliferation and differentiation of erythroid progenitor cells into rubriblasts

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12
Q

Where is EPO produced?

A

In the kidney in adults and to a lesser extent in the liver in response to hypoxia. In the fetus EPO is produced in the liver

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13
Q

What other growth factors and hormones promote erythropoiesis with EPO?

A

Stem cell factor, GM-CSF IL-3, TPO and androgens, glucocorticoids, growth hormone, thyroid hormone, insulin, IGF-1

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14
Q

What are the stages of erythropoeisis?

A

Rubriblast, prorubricyte, rubricyte, metarubricyte, reticulocyte, erythrocyte

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15
Q

What happens in the per-acute stage of regenerative anaemia?

A

No change Hct or protein

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16
Q

What happens in the acute I phase of regenerative anaemia? How long is this phase?

A

Within hours. Decreased Hct and protein, fluid shift extravascular to intravascular space, activation of RAAS, no evidence regeneration (pre-regenerative)

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17
Q

What happens in Acute II phase of regenerative anaemia?

A

Within 5 days. EPO produced–> marrow stimulation, decreased Hct and protein, evidence of regeneration

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18
Q

What will you see with intravascular haemolysis?

A

Haemoglobinuria, haemoglobinaemia, +/- hyperbilirubinaemia, bilirubinuria, regenerative (unless peracute)

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19
Q

What are some causes of intravascular haemolysis?

A

Immune mediated disease (IMHA), Infections e.g. Clostridium sp. infection, severe hypophosphatemia, zinc toxicosis, copper toxicosis, oxidative injury (red maple toxicity in horses) genetic disease e.g. PFK deficiency in dogs

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20
Q

What do you see with extravascular haemolysis (within tissues)?

A

Phagocytosis by macrophages in the spleen, liver, and bone marrow venular sinuses, hyperbilirubinemia, bilirubinuria, regenerative (in most cases), spherocytosis (if immune mediated), schistocytes and keratocytes (if fragmentation)

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21
Q

What are some causes of extravascular haemolysis?

A

Immune mediated disease, infectious disease e.g. erythrocyte parasites, oxidative damage (intra and extravascular), neoplasia e.g. haemangiosarcoma, fragmentation e.g. DIC, heartworm, drugs e.g. penicillins, genetic disease e.g. hereditary stomacytosis

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22
Q

What will you see with IMHA?

A

Spherocytosis, auto-agglutination and in saline positive agglutination, Coombs test, exclusion of other primary diseases e.g. neoplasia, infection, or drug therapy

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23
Q

How do we assess for regeneration?

A

Blood smear (polychromasia) Reticulocytosis Macrocytosis & hypochromasia (large erythrocytes with less haemoglobin, normocytic anaemia does not been it has to be non-regenerative Bone marrow evaluation- erythroid hyperplasia Serial monitoring of PCV/CBC to assess improvement

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24
Q

What are some blood smear changes seen with regenerative anaemia?

A

Polychromasia, macrocytosis, anisocytosis, hypochromasia (last three only indication in horses), increased Howell-Jolly bodies, increased nucleated RBCs (nRBCs), basophilic stippling

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25
What are the two forms of reticulocytes in cats?
Aggregate reticulocytes= polychromatophils (released in low numbers in normal dogs (1%) and cats (0.4%) and Punctate reticulocytes (more mature form with only a few fine reticulin granules, have a long maturation time in cats (\> 2 weeks) so up to 10% punctate reticulocytes are seen in health
26
What is the best way to assess the degree of regeneration and if it is regenerative?
Absolute reticulocyte count Non regenerative (dog \< 80) (cat 500) (cat \>200)
27
What is MCV?
Mean corpuscular volume \* average volume of erythrocytes, measured value \* Increase- macrocytic, decrease = microcytic
28
What is MCHC?
Hb per avg. erythrocyte \* Increased= not possible. Occurs with haemolysis, lipaemia, heinz bodies \* decreased= hypochromic
29
What is RDW?
Red cell distribution width \* measures the variation in cell size \* Increased RDW indicates anisocytosis- could reflect macrocytosis and/or microcytosis
30
What is the equine response to anaemia?
Appears non-regenerative as do not release polychromatophils/ reticulocytes, do not release nucleated RBCs, may have macrocytosis as only indication of regeneration on haemogram/ blood smear
31
What are the mechanisms of non-regenerative anaemia?
\* Reduced erythropoeisis= not making enough erythrocytes \* Defective erythropoeisis= making abnormal reticulocytes
32
What are some causes of reduced erythropoiesis?
Anaemia of inflammatory or chronic disease Decreased EPO production (renal disease) Marrow disease Immune mediated (pure red cell aplasia) Infections Iron deficiency B12 or folate deficiency Lead poisoning Marrow disease Genetic disease e.g. macrocytosis of poodles
33
What are the mechanisms of anaemia of inflammatory disease?
Iron sequestration (hepcidin mediated), decreased erythrocyte survival, impaired production
34
What are laboratory findings of anaemia of inflammatory disease?
normocytic, normochromic, mild to moderate anaemia that is fairly stable, decreased serum iron
35
What are some causes of decreased EPO production?
Chronic renal disease- mild to moderate anaemia is due to decreased EPO production, reduced RBC lifespan, GIT bleeding and uraemia suppression of erythropoeisis and Endocrine disease- hypoadrenocorticism, hypoandrogenism, hypopituitarism (mechanisms not understood)
36
What is myelophthisis?
Infiltration of marrow by neoplastic cells e.g. lymphoma Causes non-regenerative anaemia (bone marrow is sick)
37
What is myelofibrosis?
Fibrosis of the marrow Causes non-regenerative anaemia (bone marrow is sick)
38
What is myeloproliferative disease?
e.g. chronic myeloid leukemia, myelodysplastic syndrome Causes non-regenerative anaemia (bone marrow is sick)
39
What can cause marrow toxicity?
Bracken fern, phenylbutazone, hyperestrogenism, chemotherapy Causes non-regenerative anaemia (bone marrow is sick)
40
What is aplastic anaemia?
Concurrent leukopenia (decrease in the number of WBCs) and thrombocytopenia Causes non-regenerative anaemia (bone marrow is sick)
41
What is non regenerative immune mediated haemolytic anaemia?
Pure red cell aplasia= selective loss of erythroid precursors from marrow Appears to be immune mediated based on response to corticosteroids and/or lymphocytotoxic drugs Immune targeting can occur at any stage e.g. reticulocytes, rubricytes, rubriblasts
42
What are some infectious causes of non regenerative anaemia?
FeLV (killing of erythroid stem cells and progenitor cells along with dyserythropoiesis (macrocytic anaemia)), Anaplasma infection (Ehrlichia canis infects monocytes, causes pancytopenia), Parvovirus (killing of rapidly dividing cells (haematopoietic cells, lymphoid cells, intestinal crypt cells), causing pancytopenia
43
What are some causes of defective erythropoiesis?
Iron deficiency, B12 or folate deficiency, Lead poisoning, Marrow disease, genetic disease
44
What are the classic lab finding in iron deficiency anaemia?
Microcytic hypochromic anaemia, MCV and MCHC can be normal (esp. with early iron deficiency when the anaemia is still regenerative)
45
What are some causes of iron deficiency?
Chronic external blood loss (heavy parasitism, GIT bleeding, chronic haematuria), Defective iron transport/ metabolism e.g. hepatic insufficiency, very rarely due to iron deficient diet
46
What is lead poisoning?
Results in defective haeme synthesis, commonly due to lead ingestion e.g. lead weights, lead paint
47
What are the clinical signs of lead poisoning?
GIT and nervous system signs e.g. anorexia, diarrhoea or constipation, seizures, weakness, anaemia only seen with chronic toxicity
48
What are the lab findings?
Inappropriate metarubricytosis (i.e. not accompanying a regenerative response) and basophilic stippling
49
What are some other causes of defective erythropoeisis?
vitamin B6 deficiency (defective haeme synthesis), copper deficiency (Cu is involved in iron absorption from intestine), congenital porphyria in cattle (regenerative anaemia)
50
What is Phosphofructokinase (PFK) deficiency?
Metabolic disorder, causes decreased 2,3 DPG resulting in alkaemia induced haemolysis. PFK is important in the embde-meyerhof pathway- anaerobic pathway for the generation of ATP and NADH from G
51
What is pyruvate kinase (PK) deficiency?
Metabolic disorder, causes decreased RBC lifespan, increased 2,3 DPG, macrocytic hypochromic anaemia with marked reticulocytosis progressing to myelofibrosis. PK is important in the embde-meyerhof pathway- anaerobic pathway for the generation of ATP and NADH from G
52
What is methaemoglobin reductase deficiency?
Metabolic disorder, causes cyanosis, exercise intolerance. Methaemoglobin reductase: Hgb must be in reduced state to carry oxygen (oxyhaemoglobin Fe2+) as Methaemoglobin (Fe3+) can't carry oxygen
53
what is G 6 P reductase deficiency?
Metabolic disorder, haemolytic anaemia due to oxidative damage, horses. G 6 P dehydrogenase is part of the pentose phosphate pathway- which produces NADPH which is a reducing agent for neutralization of oxidants.
54
What is erythrocytosis/ polycythaemia?
Increase in red cells (increase in Hct, PCV, RBCs, or Hgb, can be relative or absolute, absolute can be appropriate or inappropriate,
55
What are some clinical signs of erythrocytosis/ polycythaemia?
Seizures, behavioural changes, red mucous membranes, thromboembolic disease
56
What are some causes of RELATIVE erythrocytosis/ polycythaemia?
Dehydration (enteritis, diuresis, water deprivation), redistribution of erythrocytes- splenic contraction (adrenalin/ epinephrine mediated, most common in cats and horses, concomitant thrombocytosis)
57
What are some causes of ABSOLUTE erythrocytosis/ polycythaemia?
Primary- erythroid neoplasia, secondary- increased EPO production (hypoxia), secondary- endocrinopathy associated (EPO normal)- hyperadrenocorticism, hyperthryoidism, acromegaly (excess growth hormone)
58
What does Rouleaux mean?
Normal in cats and dogs In other species think increased protein
59
What does agglutination mean?
Grape like clusters, immune mediated disease concern
60
Anisocytosis
Variability in cell size
61
Poikilocytosis
Variability in cell shape
62
What are polychromatophils?
Seen in a regenerative response. Larger, basophilic erythrocytes. Immature cells. Are reticulocytes (identified with special stains e.g. new methylene blue)
63
Aggregate reticulocytes
Polychromatophils
64
Punctuate reticulocytes
More mature form with only a few fine reticulin granules
65
Basophilic Stippling
Seen in a regenerative response, aggregation of residual RNA, most common in ruminants. Can also indicate lead poisoning or dyserythropoiesis (lead disrupts maturation)
66
Howell Jolly Bodies
Seen with a regenerative response. Nuclear remnants. Seen in low numbers in normal horses and cats.Increased numbers are seen with accelerated erythropoiesis or post splenectomy, hypercortisolaemia, and chemotherapy. Can also indicate dyserythropoeisis
67
What will we see with immune mediated haemolysis?
Agglutination, spherocytes, ghost cells
68
When would you see Heinz bodies and what are they?
Oxidative damage. Round structure protrudes from membrane or lighter staining spot in cytoplasm. Denatured precipitated Hb.
69
When would you see eccentrocytes? What are they?
Oxidative damage. Oxidative injury to the RBC membrane. Hb becomes condensed on one side. More frequent in dogs.
70
What are some causes of oxidative damage?
Toxins (garlic, onions), Metabolic disease (hyperthyroidism, Diabetes mellitus)
71
What might cause poikilocytes- Echinocytes?
Spiculated erythrocytes, often artifact, pathological cause- electrolyte depletion, strenuous exercise (horses), uraemia, glomerulonephritis
72
Poikilocytes- codocytes?
Target cells- increased cell membrane Hgb Causes: regenerative response, liver disease (increased lipid in cell membrane), lipid metabolism disorders
73
Poikilocytes- acanthocytes
Irregular membrane projections Causes: splenic disease, liver disease, iron deficiency, intravascular damage (seen with schistocytes)
74
Poikilocytes- schistocytes
Cell fragments Causes: intravascular damage due to rigid or malformed blood vessels (DIC, haemangiosarcoma), altered turbulent blood flow (vasculitis, endocarditis, caval syndrome with heart worm infection), Iron deficiency
75
Poikilocytes- ovalocytes
Oval shaped erythrocytes, associated with bone marrow disease, hepatic disease, and glomerulonephritis. Normal in camelids.
76
Poikilocytes- Keratocytes and blister cells
Indicate microvascular angiopathy/ shear injury Associated with DIC, iron deficiency, haemangiosarcoma, liver disease, marrow disease
77
Brief talk about haemoglobin breakdown- where it occurs- main points
78
What are the stages of anaemia in terms of teh erythroid maturation pool?
79
Describe would you see with IMHA likely. Describe.
80
When would you see rouleaux? When is it normal? What does it look like?
81
Describe an aggregate reticulocyte and a punctuate reticulocyte.
82
What does Mycoplasma haemofelis look like and what species does it impact?
cat
83
What does babesia canis look like and what species does it impact?
Dog
84
What is Dirofilaria immitis microfilaria? What species does it impact most?
Dog and heartworm
85
What do blister cells look like? What do they indicate
Microvascular angiopathy/ shear injury. DIC, iron deficiency, haemangiosarcoma, liver disease, marrow disease
86
What do eccentrocytes look like? And what do they indicate?
Oxidative damage to the RBC membrane. Hb becomes condensed on one side. More frequent in dogs.
87
What does Trypanosome sp. look like? What species does it impact?
88
What does plasmodium sp. look like? What species does it impact?
89
What does anaplasma platys look like? What species does it impact?
Cattle
90
What does mycoplasma look like? What species does it impact?
Lots
91
What species does Theileria orientalis impact? What does it look like?
Cattle
92
What are some causes of decreased EPO production?
Chronic renal disease Endocrine disease i.e. hypoadrenocorticism
93
What cells are targeted with non-regenerative IMHA?
Immune targeting can occur at any level- Rubriblast, prorubricyte, rubricyte, metarubricyte, reticulocyte, erythrocyte

Respiratory (11 decks)

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