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BSAVA Clinical Pathology > Chapter 4 > Flashcards

Chapter 4 Flashcards

1
Q

What factors control erythropoiesis?

A

EPO - most produced by kidney in response to renal tissue hypoxia
- smaller amounts produced in bone marrow macrophages and erythroid progenitors

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2
Q

What affects the effect of EPO?

A

Enhanced by thyroxine, GH and corticosteroids
Inhibited by inflammatory cytokines (IL-1, TNF)

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3
Q

Describe the stages of erythropoiesis

A

Pluripotent stem cells develop into erythroid precursors - burst forming units (BFU-E) (under influence of IL-3)
BFU-E - form colony-forming units (CFU-E)
CFU-E => rubriblasts (under influence of EPO, stem cell factor, IGF-I, glucocorticoids, IL-3, IL-6)
Rubriblasts => prorubricytes => basophilic/polychromatic rubricytes => metarubricytes - nucleus condensed, extruded and phagocytosed by nurse macrophage

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4
Q

What is the maturation time from BFU-E to reticulocyte?

A

7-9 days

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5
Q

How soon after formation are reticulocytes released into the circulation? How long do they take to mature?

A

24-48h
24-48h

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6
Q

Where do reticulocytes mature?

A

Mostly in the circulation, some in the spleen

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7
Q

How are reticulocytes different to RBCs?

A

Larger
Less Hb
Contain clumps of ribosomal RNA

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8
Q

How is a manual reticulocyte count performed?

A

Stain with new methylene blue or cresyl green

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9
Q

What are the possible causes of an increased MCV?

A

Regenerative anaemia
FeLV
Myeloproliferative disease
Familial macrocytosis (Toy/Miniature Poodles)
Hereditary stomatocytosis (Malamutes and Mini Schnauzers)
Aged blood samples
Autoagglutination
Hyperosmolality (ie hyperna++)

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10
Q

What are stomatocytes?
What breeds are affected by stomatocytosis - how does it affect them?

A

Cup-shaped RBCs formed when RBC take up excess sodium and water
Miniature Schnauzers - asymptomatic
Alaskan Malamutes - concurrent chondrodysplasia

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11
Q

What causes decreased MCV?

A

Iron deficiency
Liver disease
PSS
Anaemia of chronic disease
Familial microcytosis (Akitas)
Hyponatraemia

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12
Q

What causes increased MCHC?

A

Haemolysis - in vitro and in vivo
Lipaemia
Heinz bodies
Marked eccentrocytosis
Hyponatraemia

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13
Q

What breed is affected by microcytosis?

A

Akitas

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14
Q

What causes decreased MCHC?

A

Regenerative anaemia
Iron deficiency
Aged blood samples

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15
Q

How do dog and cat reticulocytes differ?

A

Dogs - aggregate
Cats - aggregate and punctate (smaller, contain less RNA).

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16
Q

When do reticulocytes appear and peak after haemorrhage?

A

Appear - 48 hours
Peak - 4-7 days

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17
Q

What are the timings of reticulocyte development in cats?

A

Aggregate => punctate - 12 hours
Punctate => mature - 10 days

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18
Q

What is a normal level of punctate reticulocyte counts in a cat?

A

10%

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19
Q

How should punctate/aggregate reticulocytes be counted?

A

Aggregate - reticulocytes
Punctate - RBCs (mature)

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20
Q

What do increased punctate reticulocytes indicate?

A

Regenerative response 2-4 weeks earlier

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21
Q

How is the absolute reticulocyte count calculated?

A

ARC = % reticulocytes x RBC x 10

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22
Q

What features of regeneration can be seen on blood films?

A

Polychromasia, anisocytosis
Howell-Jolly bodies (mostly cats)
Target cells
Nucleated RBCs
Basophilic stippling (rare)

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23
Q

What can circulating nucleated RBCs indicate?

A

Regeneration (ONLY if polychromasia)
Bone marrow disease
Splenic disease
Lead poisoning

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24
Q

When can polychromasia and increased reticulocyte counts be seen in the absence of anaemia?
In what breed is this most evident?

A

Stress, excitement - adrenaline leads to splenic contraction.
Greyhounds

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25
Q

How to RBCs adapt to chronic anaemia?

A

2-3-DPG upregulated = lowered Hb affinity for O2

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26
Q

What are common blood film findings in splenic HSA? What other conditions can cause similar changes?

A

Schistocytes, acanthocytes, keratocytes
Haemangioma, splenic torsion, DIC

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27
Q

When can haemorrhage be accompanied by elevated serum bilirubin?

A

Bleeding into tissue - macrophages reabsorb and break down RBCs

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28
Q

What is a leucoerythroblastic response and when is it seen?

A

Presence of immature RBCs and granulocytic precursors in the circulation.
Acute blood loss, IMHA

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29
Q

Describe the appearance of spherocytes

A

Small, round, dense cell, no central pallor

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30
Q

What conditions are spherocytes associated with?

A

IMHA, snake bite, (zinc toxicity), (bee stings).

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31
Q

Describe the appearance of schistocytes

A

Fragmented RBCs with pointed, irregular projections

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32
Q

What conditions are schistocytes associated with?

A

DIC, HSA, splenic torsion, iron-deficiency anaemia, myelofibrosis, heart failure, doxorubicin toxicity, caval syndrome

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33
Q

Describe the appearance of keratocytes

A

Spiculated RBC with 2 horn-like projections

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34
Q

What conditions are keratocytes associated with?

A

DIC, HSA, vasculitis, caval syndrome

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35
Q

Describe the appearance of acanthocytes

A

Irregular symmetrical projections

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36
Q

What conditions are acanthocytes associated with?

A

Liver disease, HSA, DIC, lymphoma, glomerulonephritis, renal disease, internal haemorrhage

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37
Q

Describe the appearance of echinocytes

A

Small, regular surface projections

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38
Q

What conditions are echinocytes associated with

A

Artefact (thick smear), snake bite, glomerulonephritis, uraemia, neoplasia, pyruvate kinase deficiency

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39
Q

Describe the appearance of codocytes

A

Target cells - rim of Hb surrounding pale area and central ‘button’ of Hb

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40
Q

What conditions are codocytes associated with?

A

Regenerative anaemia, renal/hepatic/lipid disorders

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41
Q

Describe the appearance of ovalocytes/dacrocytes

A

Oval/tear shaped

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42
Q

What conditions are ovalocytes/dacrocytes associated with?

A

Myelofibrosis, neoplasia, (artefact)

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43
Q

Describe the appearance of eccentrocytes

A

Clear area on one side of red cell bordered by membrane

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44
Q

What conditions are associated with eccentrocytes?

A

Oxidative injury (eg zinc)

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45
Q

Describe the appearance of leptocytes

A

Large area of central pallor with thin rim of Hb

46
Q

What conditions are associated with leptocytes?

A

Iron deficiency

47
Q

Who is more prone to iron-deficiency anaemia and why?

A

Young animals - low iron stores, BM already actively producing RBCs to match growth rate

48
Q

What CBC parameters change in iron-deficiency anaemia and in what order?

A

1 - v MCV
2 - v MCHC

49
Q

What other CBC change is associated with chronic haemorrhage?

A

Persistent thrombocytosis

50
Q

What abnormal RBCs are seen in iron deficiency anaemia?

A

Leptocytes +/- codocytes and schistocytes

51
Q

What test can be used for early detection of iron deficiency anaemia?

52
Q

What is the most sensitive parameter for assessing response to iron supplementation in iron-deficiency anaemia?

53
Q

How can AID and IDA be distinguished

A

AID rarely PCV <20%

                   AID            IDA Serum iron     v/n                v TIBC               v/n              n/^/v Ferritin            ^/n                 v BM iron             ^                  v
54
Q

What does serum iron measure?
When is it low?

A

Iron-bound transferrin and ferritin
IDA, AID (sequestration of iron in macrophages), PSS

55
Q

What is TIBC?
When is it low? How is it affected by IDA?

A

Indirect measurement of transferrin
AID, liver disease, PLN
Normal or low/high

56
Q

How is % transferrin saturation calculated?
What does it indicate?
How is it affected by IDA or AID?

A

Serum iron/TIBC
% transferrin binding sites occupied by iron
Low in IDA, variable in AID

57
Q

How is BM iron assessed? What stain is used?
When can it not be used?

A

Staining BM aspirate with Prussian blue
Cats (no stainable iron in BM of healthy cats)

58
Q

What is the most accurate marker of assessing iron stores in dogs?

A

BM haemosiderin stores

59
Q

How does ferritin vary in disease states?

A

IDA - low
AID - normal/high (APP)
Increased in IMHA, histocytic sarcoma and liver disease

60
Q

How does reticulocyte hb vary in AID and IDA?

A

Low in IDA
Low in AID - tends to be more modest reduction

61
Q

What are the important causes of haemolytic anaemia?

A

IMHA (1ry/2ndry)
Infections (Mycoplasma haemofelis, babesiosis, FeLV)
Oxidative damage
Microangiopathic
Inherited defects
Severe hypophosphataemia
Snake bite/bee sting
Haemophagocytosis

62
Q

What type of bilirubin accumulates in IMHA?

A

Unconjugated initially
Progresses to mix of conjugated/unconjugated when maximum excretion of conjugated exceeded, backs up in hepatocytes and overspills

63
Q

Is there a gender predisposition in IMHA?

A

Females over-represented

64
Q

What % of IMHA is 1ry

65
Q

Which immunoglobulins are associated with different types of IMHA?

A

IgG - extravascular
IgM - intravascular

66
Q

What toxicosis is associated with marked spherocytosis?

A

Zinc (rare)

67
Q

How can haemoglobinuria be confirmed?

A

Free Hb stains green with NMB

68
Q

Why are serial dilutions performed in Coomb’s testing?

A

Overcomes the prozone effect - caused by excess antiglobulin leading to failure to agglutinate

69
Q

How does immunosuppressive treatment effect Coomb’s tests?

A

Tends to remain +ve for days/weeks

70
Q

What is the sensitivity/specificity of Coomb’s test?

A

61-82%
95-100%

71
Q

When is neonatal isoerythrolysis seen?

A

Type A kittens, type B mother
Type B cats have naturally occurring anti-A antibodies - absorbed from colustrum

72
Q

What are the infectious causes of haemolytic anaemia?

A

FeLV
Haemotropic mycoplasmas
Babesia spp

73
Q

What species of haemotropic mycoplasma have been identified in cats?

A

M. haemofelis
Candidatus M. turicensis
Candidatus M. haemominutum
Candidatus M. haematoparvum-like

74
Q

How can M.haemofelis be diagnosed

A

During parasitaemia - pale purple small cocci/rods
rt-PCR

75
Q

What Babesia species are present in Europe, are they large or small?

A

B. vogeli, B. canis (large)
B. microti-like, B. gibsoni (small)

76
Q

What co-infection is common with babesiosis?

77
Q

How can organism detection of Babesia app be maximised

A

Capillary blood (ie ear) or cells from capillary tube underneath Buffy coat

78
Q

What is the test of choice for diagnosis babesiosis?

79
Q

Where is feline babesiosis most commonly reported? Which species is involved?

A

Africa (South Africa)
Babesia felis

80
Q

What are the mechanisms by which oxidative damage causes haemolysis

A

Heinz body formation
Direct membrane damage - eccentrocyte formation
Oxidation of ferrous iron to ferric iron, resulting in methaemoglobin formation

81
Q

What species is most prone to Heinz body formation and why?

A

Cats
HB formed by oxidation of the sulphydryl (-SH) groups on global chains
Cats have 8 -SH groups compared to 2 in other species

82
Q

What substances are associated with Heinz body formation in dogs and cats?

A

Paracetamol, onions, zinc

83
Q

What disease is Heinz body anaemia associated with in cats?

A

Liver disease - especially hepatic lipidosis

84
Q

How to Heinz bodies damage red cells?

A

Reduce deformability leading to entrapment in the spleen
Altered membrane permeability

85
Q

Is Heinz body formation associated with extra/intravascular haemolysis?

86
Q

What CBC findings are associated with Heinz body anaemia?

A

Low hct and RBC (true)
High Hb and MCHC (interference)

87
Q

In what species can Heinz bodies be normal and at what level?

A

Cats
<10% RBCs

88
Q

What conditions (and drug) in cats are low to moderate Heinz bodies not associated with anaemia?

A

Diabetes mellitus, hyperthyroidism, lymphoma
Propofol

89
Q

What toxins are associated with oxidative injury causing direct RBC damage?
What RBC abnormality is associated with this type of damage?

A

Zinc
Naphthalene (moth balls)

Eccentrocytes

90
Q

Which toxin is most associated with oxidative injury leading to methaemoglobin formation?

A

Paracetamol

91
Q

What inherited RBC defects are reported and what breeds are they associated with?

A

Pyruvate kinase deficiency - Basenjis, Beagles, Dachsunds, WHWT, Cairn Terriers, Labrador retrievers, Pugs. Abyssinian, Somali, DSH
Phosphofructokinase deficiency - ESS, American Cocker, Whippets, Wachtelhunds

92
Q

What are the features and prognosis of pyruvate kinase deficiency in dogs and cats?

A

Dogs - highly regenerative moderate/severe anaemia, progressive myelofibrosis/osteosclerosis, liver failure, death 1-5y
Cats - mild/moderate anaemia, may live to advanced age

93
Q

What are the features and prognosis of PFK deficiency?

A

Low grade RBC loss, marked regenerative response - may maintain normal PCV
Marked alkaline fragility
Hyperventilation/excessive barking => haemolysis
May have normal lifespan if alkalosis avoided

94
Q

How does hypophosphataemia cause haemolysis? When is it seen?

A

ATP depletion => increased RBC rigidity
Insulin tx and referring syndrome

95
Q

What tumours are associated with haemolytic anaemia?

A

Histiocytic sarcoma
Hepatosplenic T-cell lymphoma

96
Q

What breeds are predisposed to haemophagocytic histiocytic sarcoma?
What tissues are typically involved?

A

BMD, Golden Retrievers, Rottweilers, Labrador Retrievers

Liver, lung, bone marrow

97
Q

Which cell lines are involved in aplastic anaemia?

98
Q

What order to cellular deficiencies develop in BM disease?

A

Leucopenia <5 days
Thrombocytopenia 8-10 days
Anaemia - later

99
Q

What are the possible mechanisms of aplastic anaemia?

A

Drugs - oestrogen, TMPS, fenbendazole, griseofulvin (c), azathioprine
Infections - Parvo, Ehrlichia, sepsis, FeLV
Idiopathic

100
Q

What are the recognised forms of immune mediated NRIMHA and how to the BM findings differ?

A

Pure red cell aplasia - depletion of entire RBC series due to destruction of early precursors
PIMA
1 - maturation arrest at level of erythroid precursor targeted
2 - erythroid hyperplasia and complete maturation - reticulocytes targeted

101
Q

What causes of secondary PRCA have been reported?

A

EPO tx
Parvo
FeLV (C)

102
Q

What are the causes of myelofibrosis

A

IMHA
PRCA
Neoplasia
Toxic (phb/PK deficiency)
[Idiopathic (primary)]

103
Q

What drug is associated with folate depletion?

A

Phenobarbital

104
Q

What are the mechanisms of AID?

A

Increased production of hepcidin (APP) - limits dietary absorption of iron and mobilisation from stores
Shortened RBC survival - increased oxidative damage
Blunted EPO response (likely due to IL-1 and TNF)

105
Q

What endocrine diseases are associated with anaemia?

A

Addisons/hypoT
Cortisol/thyroxine enhance effects of EPO

106
Q

What do BM aspirates/core sampling allow superior evaluation of?

A

Aspirates - cellular detail
Core - cellularity, presence of fibrous tissue

107
Q

What are the causes of 2ndry (physiologically appropriate) erythrocytosis?

A

Chronic pulmonary disease
R => L shunting
Altitude
Persistent methaemoglobinaemia

108
Q

What are the causes of 2ndry (physiologically inappropriate) erythrocytosis?

A

Renal neoplasia (carcinoma, adenocarcinoma, fibrosarcoma, lymphoma) - local hypoxia vs EPO production
Renal cysts
Hydronephrosis
Extra-renal neoplasia - caecal leiomyosarcoma, schwannoma, nasal fibrosarcoma

109
Q

Describe canine blood types

A

DEA 1 thought to be single group variably expressed in a continuum rather than comprising different blood types

110
Q

Which cats have naturally occurring isoantibodies

A

Type B cats have anti-A isoABs

111
Q

What does total hb > cellular hb on a CBC indicate?

A

Intravascular haemolysis

BSAVA Clinical Pathology (25 decks)

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