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BSAVA Clin Path > 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
How to RBCs adapt to chronic anaemia?
2-3-DPG upregulated = lowered Hb affinity for O2
26
What are common blood film findings in splenic HSA? What other conditions can cause similar changes?
Schistocytes, acanthocytes, keratocytes Haemangioma, splenic torsion, DIC
27
When can haemorrhage be accompanied by elevated serum bilirubin?
Bleeding into tissue - macrophages reabsorb and break down RBCs
28
What is a leucoerythroblastic response and when is it seen?
Presence of immature RBCs and granulocytic precursors in the circulation. Acute blood loss, IMHA
29
Describe the appearance of spherocytes
Small, round, dense cell, no central pallor
30
What conditions are spherocytes associated with?
IMHA, snake bite, (zinc toxicity), (bee stings).
31
Describe the appearance of schistocytes
Fragmented RBCs with pointed, irregular projections
32
What conditions are schistocytes associated with?
DIC, HSA, splenic torsion, iron-deficiency anaemia, myelofibrosis, heart failure, doxorubicin toxicity, caval syndrome
33
Describe the appearance of keratocytes
Spiculated RBC with 2 horn-like projections
34
What conditions are keratocytes associated with?
DIC, HSA, vasculitis, caval syndrome
35
Describe the appearance of acanthocytes
Irregular symmetrical projections
36
What conditions are acanthocytes associated with?
Liver disease, HSA, DIC, lymphoma, glomerulonephritis, renal disease, internal haemorrhage
37
Describe the appearance of echinocytes
Small, regular surface projections
38
What conditions are echinocytes associated with
Artefact (thick smear), snake bite, glomerulonephritis, uraemia, neoplasia, pyruvate kinase deficiency
39
Describe the appearance of codocytes
Target cells - rim of Hb surrounding pale area and central 'button' of Hb
40
What conditions are codocytes associated with?
Regenerative anaemia, renal/hepatic/lipid disorders
41
Describe the appearance of ovalocytes/dacrocytes
Oval/tear shaped
42
What conditions are ovalocytes/dacrocytes associated with?
Myelofibrosis, neoplasia, (artefact)
43
Describe the appearance of eccentrocytes
Clear area on one side of red cell bordered by membrane
44
What conditions are associated with eccentrocytes?
Oxidative injury (eg zinc)
45
Describe the appearance of leptocytes
Large area of central pallor with thin rim of Hb
46
What conditions are associated with leptocytes?
Iron deficiency
47
Who is more prone to iron-deficiency anaemia and why?
Young animals - low iron stores, BM already actively producing RBCs to match growth rate
48
What CBC parameters change in iron-deficiency anaemia and in what order?
1 - v MCV 2 - v MCHC
49
What other CBC change is associated with chronic haemorrhage?
Persistent thrombocytosis
50
What abnormal RBCs are seen in iron deficiency anaemia?
Leptocytes +/- codocytes and schistocytes
51
What test can be used for early detection of iron deficiency anaemia?
Retic-hb
52
What is the most sensitive parameter for assessing response to iron supplementation in iron-deficiency anaemia?
Retic-hb
53
How can AID and IDA be distinguished
AID rarely PCV <20% AID IDA Serum iron v/n v TIBC v/n n/^/v Ferritin ^/n v BM iron ^ v
54
What does serum iron measure? When is it low?
Iron-bound transferrin and ferritin IDA, AID (sequestration of iron in macrophages), PSS
55
What is TIBC? When is it low? How is it affected by IDA?
Indirect measurement of transferrin AID, liver disease, PLN Normal or low/high
56
How is % transferrin saturation calculated? What does it indicate? How is it affected by IDA or AID?
Serum iron/TIBC % transferrin binding sites occupied by iron Low in IDA, variable in AID
57
How is BM iron assessed? What stain is used? When can it not be used?
Staining BM aspirate with Prussian blue Cats (no stainable iron in BM of healthy cats)
58
What is the most accurate marker of assessing iron stores in dogs?
BM haemosiderin stores
59
How does ferritin vary in disease states?
IDA - low AID - normal/high (APP) Increased in IMHA, histocytic sarcoma and liver disease
60
How does reticulocyte hb vary in AID and IDA?
Low in IDA Low in AID - tends to be more modest reduction
61
What are the important causes of haemolytic anaemia?
IMHA (1ry/2ndry) Infections (Mycoplasma haemofelis, babesiosis, FeLV) Oxidative damage Microangiopathic Inherited defects Severe hypophosphataemia Snake bite/bee sting Haemophagocytosis
62
What type of bilirubin accumulates in IMHA?
Unconjugated initially Progresses to mix of conjugated/unconjugated when maximum excretion of conjugated exceeded, backs up in hepatocytes and overspills
63
Is there a gender predisposition in IMHA?
Females over-represented
64
What % of IMHA is 1ry
60-75%
65
Which immunoglobulins are associated with different types of IMHA?
IgG - extravascular IgM - intravascular
66
What toxicosis is associated with marked spherocytosis?
Zinc (rare)
67
How can haemoglobinuria be confirmed?
Free Hb stains green with NMB
68
Why are serial dilutions performed in Coomb's testing?
Overcomes the prozone effect - caused by excess antiglobulin leading to failure to agglutinate
69
How does immunosuppressive treatment effect Coomb's tests?
Tends to remain +ve for days/weeks
70
What is the sensitivity/specificity of Coomb's test?
61-82% 95-100%
71
When is neonatal isoerythrolysis seen?
Type A kittens, type B mother Type B cats have naturally occurring anti-A antibodies - absorbed from colustrum
72
What are the infectious causes of haemolytic anaemia?
FeLV Haemotropic mycoplasmas Babesia spp
73
What species of haemotropic mycoplasma have been identified in cats?
M. haemofelis Candidatus M. turicensis Candidatus M. haemominutum Candidatus M. haematoparvum-like
74
How can M.haemofelis be diagnosed
During parasitaemia - pale purple small cocci/rods rt-PCR
75
What Babesia species are present in Europe, are they large or small?
B. vogeli, B. canis (large) B. microti-like, B. gibsoni (small)
76
What co-infection is common with babesiosis?
Ehrlichia
77
How can organism detection of Babesia app be maximised
Capillary blood (ie ear) or cells from capillary tube underneath Buffy coat
78
What is the test of choice for diagnosis babesiosis?
PCR
79
Where is feline babesiosis most commonly reported? Which species is involved?
Africa (South Africa) Babesia felis
80
What are the mechanisms by which oxidative damage causes haemolysis
Heinz body formation Direct membrane damage - eccentrocyte formation Oxidation of ferrous iron to ferric iron, resulting in methaemoglobin formation
81
What species is most prone to Heinz body formation and why?
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
What substances are associated with Heinz body formation in dogs and cats?
Paracetamol, onions, zinc
83
What disease is Heinz body anaemia associated with in cats?
Liver disease - especially hepatic lipidosis
84
How to Heinz bodies damage red cells?
Reduce deformability leading to entrapment in the spleen Altered membrane permeability
85
Is Heinz body formation associated with extra/intravascular haemolysis?
Both
86
What CBC findings are associated with Heinz body anaemia?
Low hct and RBC (true) High Hb and MCHC (interference)
87
In what species can Heinz bodies be normal and at what level?
Cats <10% RBCs
88
What conditions (and drug) in cats are low to moderate Heinz bodies not associated with anaemia?
Diabetes mellitus, hyperthyroidism, lymphoma Propofol
89
What toxins are associated with oxidative injury causing direct RBC damage? What RBC abnormality is associated with this type of damage?
Zinc Naphthalene (moth balls) Eccentrocytes
90
Which toxin is most associated with oxidative injury leading to methaemoglobin formation?
Paracetamol
91
What inherited RBC defects are reported and what breeds are they associated with?
Pyruvate kinase deficiency - Basenjis, Beagles, Dachsunds, WHWT, Cairn Terriers, Labrador retrievers, Pugs. Abyssinian, Somali, DSH Phosphofructokinase deficiency - ESS, American Cocker, Whippets, Wachtelhunds
92
What are the features and prognosis of pyruvate kinase deficiency in dogs and cats?
Dogs - highly regenerative moderate/severe anaemia, progressive myelofibrosis/osteosclerosis, liver failure, death 1-5y Cats - mild/moderate anaemia, may live to advanced age
93
What are the features and prognosis of PFK deficiency?
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
How does hypophosphataemia cause haemolysis? When is it seen?
ATP depletion => increased RBC rigidity Insulin tx and referring syndrome
95
What tumours are associated with haemolytic anaemia?
Histiocytic sarcoma Hepatosplenic T-cell lymphoma
96
What breeds are predisposed to haemophagocytic histiocytic sarcoma? What tissues are typically involved?
BMD, Golden Retrievers, Rottweilers, Labrador Retrievers Liver, lung, bone marrow
97
Which cell lines are involved in aplastic anaemia?
All
98
What order to cellular deficiencies develop in BM disease?
Leucopenia <5 days Thrombocytopenia 8-10 days Anaemia - later
99
What are the possible mechanisms of aplastic anaemia?
Drugs - oestrogen, TMPS, fenbendazole, griseofulvin (c), azathioprine Infections - Parvo, Ehrlichia, sepsis, FeLV Idiopathic
100
What are the recognised forms of immune mediated NRIMHA and how to the BM findings differ?
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
What causes of secondary PRCA have been reported?
EPO tx Parvo FeLV (C)
102
What are the causes of myelofibrosis
IMHA PRCA Neoplasia Toxic (phb/PK deficiency) [Idiopathic (primary)]
103
What drug is associated with folate depletion?
Phenobarbital
104
What are the mechanisms of AID?
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
What endocrine diseases are associated with anaemia?
Addisons/hypoT Cortisol/thyroxine enhance effects of EPO
106
What do BM aspirates/core sampling allow superior evaluation of?
Aspirates - cellular detail Core - cellularity, presence of fibrous tissue
107
What are the causes of 2ndry (physiologically appropriate) erythrocytosis?
Chronic pulmonary disease R => L shunting Altitude Persistent methaemoglobinaemia
108
What are the causes of 2ndry (physiologically inappropriate) erythrocytosis?
Renal neoplasia (carcinoma, adenocarcinoma, fibrosarcoma, lymphoma) - local hypoxia vs EPO production Renal cysts Hydronephrosis Extra-renal neoplasia - caecal leiomyosarcoma, schwannoma, nasal fibrosarcoma
109
Describe canine blood types
DEA 1 thought to be single group variably expressed in a continuum rather than comprising different blood types
110
Which cats have naturally occurring isoantibodies
Type B cats have anti-A isoABs
111
What does total hb > cellular hb on a CBC indicate?
Intravascular haemolysis

BSAVA Clin Path (25 decks)

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