Chapter 1: Erythrocytes Flashcards
(204 cards)
1
Q
Describe the structure of hemoglobin.
A
Tetramer of 4 hemes and 4 globins (2 a and B dimers)
Each heme has an iron atom in the 2+ state
Globin is attached to each heme
2
Q
Heme synthesis is controlled at the first step by _____.
A
delta-aminolevulinic acid synthase
3
Q
What are 2 compounds that inhibit heme synthesis?
A
Lead and chloramphenicol
4
Q
What are porphyrins?
A
intermediates of heme biosynthesis
5
Q
How do the porphyrias occur?
A
enzyme deficiencies in the heme synthesis pathway–> accumulation of porphyrias and their precursors
6
Q
Iron is inserted into protoprophyrin to form heme by what enzyme?
A
ferrochelatase
7
Q
How does hepcidin control plasma iron concentrations?
A
it inhibits iron export by ferroportin from RBCs and macs by degrading ferrorotin
8
Q
Increased hepcidin–> increased or decreased iron availability?
Decreased hepcidin–> increased or decreased iron availability?
A
Increased hepcidin–> decreased iron availability
Decreased hepcidin–> increased iron availability
9
Q
How is iron transported in the blood?
A
by the gamma-globulin transferrin
10
Q
Is a serum iron measurement a reliable measure of total body iron stores?
A
no
11
Q
What are 5 conditions with decreased serum iron?
A
- iron deficiency
- acute and chronic inflammation/disease
- hypoproteinemia
- hypothyroidism
- renal disease
12
Q
What are 5 conditions with increased serum iron?
A
- hemolytic anemia
- hemolysis during sampling
- glucocorticoid excess in the dog (decreased in cattle with glucocorticoid excess)
- iron overload (acquired or hereditary)
- nonregenerative anemia
13
Q
What is total iron-binding capacity (TIBC)?
A
an indirect measurement of the amount of iron that transferrin will bind
14
Q
What is the unit of TIBC?
A
% saturation
15
Q
What is the unbound iron-binding capacity represent?
A
the numeric difference between TIBC and SI
16
Q
Hepcidin is made in the ___ and transported in the blood by ____.
A
Hepcidin is made in the liver and transported in the blood by a2-macroglobulin.
17
Q
What 2 proteins are necessary for transfer of iron from intestinal epithelium and macs to serum transferrin?
A
ferroportin 1 and DMT1 (divalent metal transporter 1)
18
Q
Iron is stored in macrophages as ____ and ____.
A
Iron is stored in macrophages as ferritin and hemosiderin.
19
Q
When is serum ferritin concentration decreased?
A
iron deficiency
20
Q
What conditions cause an increase in serum ferritin? (6)
A
- hemolytic anemia
- iron overload
- acute and chronic inflammation
- liver disease
- some neoplastic disorders (LSA, malignant histiocytosis)
- malnutrition (cattle)
21
Q
Which is a more stable storage form of iron, ferritin or hemosiderin? Which is more available?
A
Hemosiderin is more stable but less available
22
Q
What is the Embden-Meyerhof pathway?
A
- important in RBC metabolism
- anaerobic pathway where glycolysis makes ATP and NADH
- ATP is essential for membrane function and integrity
- NADH is used to reduce methemoglobin
23
Q
Which enzyme deficiencies in the Embden-Meyerhof pathway can lead to hemolytic anemia?
A
PK and PFK
24
Q
PK deficiency impairs ___ production–> what kind of anemia?
A
PK deficiency impairs ATP production–> macrocytic hypochromic anemia with 15-50% reticulocytes, myselofibrosis, hemochromatosis, decreased RBC lifespan, and accumulation of PEP and DPG
25
PFK deficiency results in decreased ____ concentration and what other lab abnormalities?
decreased erythrocytic 2,3 DPG concentration, normal or decreased Hct, persistent reticulocytosis, alkalemia which leads to hemolysis
26
What enzyme is the rate limiting enzyme in the pentose phosphate pathway?
G-6-P dehydrogenase
27
The pentose phosphate pathway produces what, which is important to RBCs how?
NADPH which is a major reducing agent in the RBC
It's a cofactor for reduction of oxidized glutahione (neutralizes oxidants that can denature Hg)
28
What happens in G6P dehydrogenase deficiencies?
hemolytic anemia under mild oxidative stress (Heinz bodies, eccentrocytes)
29
Hemoglobin is maintained in the ____ state which is necessary for transport of oxygen.
Hemoglobin is maintained in the reduced (Fe2+, oxyhemoglobin) state which is necessary for transport of oxygen.
30
Enzyme deficiencies in what enzyme lead to methemoglobin accumulation? Why?
Methemoglobin reductase-- because hemoglobin needs to stay in the reduced state to transport oxygen
31
What is the Rapoport-Luebering pathway?
allows formation of 2,3 DPG which is a regulatory protein in O2 transport
32
How is 2,3 DPG a regulatory protein in O2 transport?
increased 2,3 DPG favors O2 release to tissues by lowering the O2 affinity of Hg
33
What is the difference in mammal and bird erythropoiesis and where is occurs?
mammals- extravascularly in the bone marrow parenchyma
birds- in the vascular sinuses of the bone marrow
34
What are 3 characteristic morphologic changes that take place during maturation from the rubriblast to mature erythrocyte?
1. cells get smaller
2. nuclei get smaller and chromatin gets more aggregated
3. cytoplasmic color changes from blue to orange as Hg is formed and RNA is lost
35
In what stage does cell division stop in erythroid maturation?
late rubricyte stage
36
In what stage is the nucleus extruded in erythroid maturation?
metarubricyte (forms a reticulocyte)
37
Reticulocytes in most species remain in the BM for \_\_-\_\_ before release and ultimately mature in the blood or spleen. What species have their reticulocytes mature in the BM completely and release mature RBCs?
Reticulocytes in most species remain in the BM for 2-3 days before release and ultimately mature in the blood or spleen.
Horses and cattle
38
The time from stimulation of erythropoietic progenitor cell until reticulocytes are released is \_\_\_.
The time from stimulation of erythropoietic progenitor cell until reticulocytes are released is 5 days.
39
How can an increase of erythrocytes delivered to the blood occur?
1. mainly by increased SC input
2. shortened maturation time
3. earlier reticulocyte release
4. skipped cell divisions
40
Most Epo is made by what cells? What other organ can make it?
mainly made by peritubular interstitial cells of the kidney in response to hypoxia
10-15% made by liver (specific hepatocytes and Ito cells)
41
What are 3 major actions of Epo?
1. inhibition of apoptosis of newly formed progenitor cells and prorubricytes (allows them to mature)
2. stimulation of Hg synthesis in already dividing erythroid cells
3. switching of Hg synthesis in sheep from one adult type to another
42
Identify the normal hematopoietic cells and leukemic cells in BM.
A- myeloblast
B- promyelocyte
C- neutrophil myelocyte
D- neutrophil metamyelocyte and segmenters
E- neutrophil metamyelocyte, band, and segmenter
F- rubriblast, rubricyte, metarubricyte, 2 neut metamyelocytes, and a neut segmenter
G- 2 prorubricytes, 4 rubricytes, and an eos
H- 5 rubricytes
I- 5 rubricytes, a metarubricyte, and a polychromatophilic erythrocyte with an HJ body
J- immature megakayocyte with blue, granular cytoplasm
K- mature megakaryocyte with granular, pink cytoplasm
L- promyelocytes in canine myeloblastic leukemia
M- poorly differentiated mast cells in feline mast cell leukemia
N- plasma cells in canine plasma cell myeloma
O- lymphoblasts in canine ALL
43
What 3 things work with Epo to stimulate multiplication of BFU-E and its differentiation into CFU-E?
IL-3, GM-CSF, G-CSF
44
Model of hematopoiesis.
45
What are the average erythroid lifespans in circulation of these species:
Cow-
Sheep-
Horse-
Dog-
Pig-
Cat-
Bird-
Cow- 160 days
Sheep- 150 days
Horse- 145 days
Dog- 110 days
Pig- 86 days
Cat- 70 days
Bird- 35 days
46
What are the 2 routes that senescent erythrocytes are removed from the circulation in health?
1. Phagocytosis by macs (major route)
2. Intravascular lysis with release of Hg into plasma (minor route)
47
What happens to the RBC components once they are phagocytized by macs to be destroyed?
Erythrocytes release their Hg in the phagosome and it is split into heme and globin
Globin breaks down into its aas which are utilized
Heme in the iron is cleaved by heme oxygenase which forms CO and biliverdin
48
Describe iron breakdown in macs.
Iron released from Hg--\> Heme cleaved off by heme oxygenase--\> CO and biliverdin--\> biliverdin reduced by biliverdin reductase to bilirubin--\> bilirubin excreted in blood and goes to liver with albumin
49
Why are avian bruises green?
They lack biliverdin reductase so they can't form bilirubin from biliverdin (which is green and is the end product)
50
When Hg is free in the plasma, it binds ____ (which is a \_\_\_). This is then cleared by the \_\_\_.
When Hg is free in the plasma, it binds haptoglobin (which is an a2-globulin). This is then cleared by the liver.
51
Enough haptoglobin is available in the plasm to bind ___ of hemoglobin. Plasma appears pink/red when ___ to ___ of hemoglobin is present.
Enough haptoglobin is available in the plasma to bind 150 mg/dL of hemoglobin. Plasma appears pink/red when 50 to 100 mg/dL of hemoglobin is present.
52
When will you be able to detect Hg dimers in the urine?
When the plasma haptoglobin is saturated beyond the 150 mg/dL limit
53
With time, free Hg in the plasma is oxidized to \_\_\_\_, which dissociates to free \_\_\_, which complexes with the B-globulin, \_\_\_\_.
With time, free Hg in the plasma is oxidized to methemoglobin, which dissociates to free ferriheme, which complexes with the B-globulin, hemopexin.
54
What 2 complexes keep Hg from being lost in the urine?
heme-hemopexin complex
Hg-haptoglobin complex
55
What happens to Hg that passes into the glomerular filtrate?
It is either absorbed by the proximal tubules and catabolized to iron, bilirubin, and globin or if goes through unabsorbed, causes hemoglobinuria.
56
What is Hct?
percent of blood comprised of RBCs
57
What cells are in the buffy zone?
leukocytes and platelets
58
What is the Hct% formula?
Hct %= (RBC/uL) x MCV (fL)
59
Between PCV and Hct, which has the greater potential for error and why?
Hct because only dogs have RBC volume comparable to human RBCs
60
What methodology is used to determine Hg concentration?
colorimetric determination by the cyanmethemoglobin technique or the newer cyanide-free hemoglobinhydroxylamine complex method
61
What may falsely increase Hg concentration measurements? (4)
Heinz bodies, hemolysis, lipemia, Oxyglobin
62
Which measurement is the most direct indication of oxygen transport capacity of the blood?
Hb conccentration
63
Hb should be __ the Hct if RBCs are of normal size.
1/3
64
What is the value in the RBC count?
allows you to determine the MCV and MCH
65
Which types of dogs and breeds in this group have higher Hct/PCV normally?
Sighthounds- greyhound, saluki, whippet, afghan
66
What is the formula for MCV?
MCV (fL)= (PCV x 10)/RBC count (millions)
67
Why does iron deficiency cause microcytosis?
An extra cell division occurs before the critical cytoplasmic concentration of Hg is reached that is needed to stop DNA synthesis and cell division
68
Greyhounds normally have a higher/lower MCV?
higher
69
Why does cobalamin (vit B12) deficiency cause a macrocytic anemia?
There is an interference with nucleic acid synthesis that causes an inhibition of cell division--\> larger cells
70
Congenital macrocytosis occurs in which breed?
Poodles
71
What are some causes of macrocytosis?
**reticulocytosis**
being a greyhound
cobalamin deficiency
congenital in poodles
hereditary in alaskan malamutes, drentse-partrijshond, and min schnauzers
FeLV cats
RBC agglutination
72
What does MCH represent and what are the units?
how much Hb is in an average RBC in picograms
73
What is the formula for MCH?
MCH (picograms)= (Hb concentration x 10)/RBC (millions)
74
How is MCH related to MCV?
smaller RBCs have less Hb--\> lower MCH
bigger RBCs have more Hb--\> higher MCH
75
Why is MCHC a better determinant for cell Hb than MCH?
it corrects for cell volume
76
What does MCHC represent?
the average Hb concentration per average RBC in grams of Hb/100 mL of erythrocytes
77
What is the formula for MCHC?
MCHC (g/dL)= [Hb concentration (pg) x 100]/Hct (%)
78
Why would you have an increased MCHC?
in vitro or vivo hemolysis or treatment with oxyglobin
79
What is the formula for RDW?
RDW= (SDmcv/MCV) x 100
80
What does RDW tell you?
it's an index of the degree of anisocytosis or variation in the size of RBCs
81
What might cause an increased RDW?
reticulocytosis or anemias with significant microcytosis or macrocytosis
82
How big are normal canine erythrocytes?
7 um diameter
83
How big are normal cat erythrocytes?
5.8 um
84
How big are normal bovine erythrocytes?
5.5 um
85
How big are normal equine erythrocytes?
5.7 um
86
How big are normal porcine erythrocytes?
6 um
87
How big are normal ovine erythrocytes?
4.5 um
88
How big are caprine erythrocytes?
\<4 um
89
What is the average size of bird erythrocytes?
12 x 6 um
90
Why does hyperfibrinogeniemia or hyperglobulinemia cause rouleaux?
normal negative surface charge is masked and decreases the repelling nature of the RBCs
91
The degree of rouleaux correlates positively with \_\_\_.
erythrocyte sedimentation rate
92
What are causes of microcytosis?
iron and pyridoxine deficiency, remnants of Heinz body and fragmentation anemias, PSS, hyponatremia, healthy Asian breeds of dogs
93
Hyponatremia can affect red blood cell size how?
Makes RBCs microcytic (when put back into a normocytic solution like saline, they will swell and can get macrocytosis on the CBC)
94
What causes hypochromasia?
iron deficiency and lead toxicosis (from inhibition of Hg synthesis)
95
Describe echinocytes and what causes them?
evenly spaced spicules
Type 1- on periphery only; in vitro artifact (drying, temp, pH)
Type 2- all over cell; altered electrolytes with expansion of the outer layer; uremia, electrolyte depletion, lymphoma, doxorubicin, glomerulonephritis
96
Describe keratocytes (helmet cells) and what causes them?
1 or 2 projections that form a ruptured vesicle
oxidative damage to the membrane (same reasons as Heinz bodies)
97
Describe acanthocytes and what causes them?
spiculated RBCs with irregular, blunted projections
altered lipid:cholesterol ratios; HSA, gloemrulonephritis, lymphoma, liver disease
98
Describe schistocytes and what causes them?
irregular fragments from shearing by IV fibrin or turbulent blood flow
DIC, HSA, glomerulonephritis, CHF, myelofibrosis, chronic doxorubicin toxicosis, vasculitis, etc
99
Describe fusocytes and what animals have them normally?
elongated erythrocytes
healthy Angora goats
100
Describe elliptocytes and in what cases are they seen?
oval cells seen in healthy camelids
4.1 band deficiency in the RBC membrane in dogs causes them
occasionally seen in iron deficiency
101
What hereditary condition in dogs may cause elliptocytes?
4.1 band deficiency
102
Describe dacrocytes and when are they seen?
tear-drop shaped
if tails in the same direction, may be artifact
may be in llamas with iron deficiency anemia
103
Describe leptocytes and when are they seen?
thin cells with increased membrane:volume ratio; may look folded
have been seen in PSS
104
Describe target cells and when are they seen?
are actually leptocytes that are bell-shaped but look like targets on the smear; from increasing the amount of membrane via lipid and cholesterol insertion or by decreasing cytoplasmic volume like in hypochromia
may be from liver disease, iron deficiency, and reticulocytosis
105
Describe stomatocytes and when are they seen?
type of leptocyte that is bowl-shaped with oval areas of central pallor from expansion of the inner layer of the cell membrane
hereditary stomatocytosis in alaskan malamutes, drentse partrijshond, and min schnauzers
can be artifacts in thick areas
106
What represents basophilic stippling and when is it seen?
punctate aggregation of residual RNA
seen as a part of a regenerative response
anemia sheep and cattle and sometimes in feline anemia
can be seen in lead toxicosis (with metarubricytosis and minimal polychromasia)
107
What are Heinz bodies?
precipitated Hg
108
Up to \_\_% of feline erythrocytes can have Heinz bodies in health.
10%
109
Describe eccentrocytes and when are they seen?
Hg is condensed in one portion of the cell and leads a clear blister-like area in the remaining portion of the cell
from oxidative injury with lipid per oxidation and cross-linking of the membrane
110
In what situation may you see elevated numbers of nRBCs without anemia as an appropriate response?
hypoxia (Epo induced)
111
What conditions might have an inappropriate release of metarubricytes?
lead toxicosis, iron deficiency, copper deficiency, HSA, EMH, myelopthisis, IVD, hereditary macrocytosis of poodles, endotoxemia, bone marrow trauma, metastatic neoplasia of the marrow, myelofibrois, FeLV, MDS, leukemia (especially of erythremic myelosis in cats)
112
Nucleated RBCs have been reported in what breed of dog?
Miniature Schnauzers
113
What are erythroplastids?
anucleated fragments of erythrocyte cytoplasm occasionally found in bird smears
114
What are hematogones?
free erythrocyte nuclei in bird smears
115
The dog has up to \_\_\_% of aggregate type reticulocytes in health.
1%
116
What 2 types of reticulocytes occur in the cat?
Aggregate reticulocytes
Punctate reticulocytes
117
Which type of reticulocyte in the cat is used in the retic count and why?
Aggregate retics because punctate retics stay in circulation for 2-3 weeks.
118
Birds can have \_\_-\_\_% of reticulocytes in health.
4-5%
119
Why is the reticulocyte percentage a potential overestimate of bone marrow response to anemia?
retics released from the bone marrow into the blood of anemic animals are mixed with fewer mature erythrocytes--\> higher relative % of reticulocytes
larger, more immature retics are released earlier (shift retics) in response to anemia--\> they last longer in blood because they take longer to mature--\> higher % of retics
120
What's the formula for correcting retics?
Corrected retics= Observed retic % x (patient's Hct percentage/"normal" Hct percentage)
121
Corrected retic % greater than \_\_% in the dog and greater than \_\_% in the cat indicate bone marrow response to anemia.
Corrected retic % greater than 1% in the dog and greater than 0.4% in the cat indicate bone marrow response to anemia.
122
What is the formula for absolute retic count?
Absolute retic count/uL= Reticulocyte % (converted to a decimal) x (total RBC count/uL)
123
An absolute retic count greater than \_\_\_\_/uL in the dog and \_\_\_\_/uL in the cat indicates a regenerative response.
An absolute retic count greater than 80,000/uL in the dog and 60,000/uL in the cat indicates a regenerative response.
124
What is the formula for reticulocyte production index?
RPI= observed retics (%) x [observed Hct (normal Hct)] x [1 + blood maturation time]
125
Between hemolytic and external hemorrhage anemias, which has a more intense reticulocytosis? Why?
Hemolytic-- because iron from disrupted RBCs is more available for erythropoiesis than iron stored as hemosiderin
126
Reticulocytosis doesn't become evident until __ to ___ after the occurrence of anemia.
48-72 hours
127
Do dogs or cats have a greater reticulocyte response?
Dogs
128
What is unique about healthy suckling pigs and the number of retics they have?
they normally have high retic counts
129
The M:E ratio is usually determined to assess \_\_\_\_\_. What count is needed for proper identification of the ratio?
The M:E ratio is usually determined to assess the erythropoietic response to anemia. The WBC (specifically the neutrophil count) is needed for interpretation.
130
If the WBC count is within the reference interval, any change in the M:E ratio is due to \_\_\_\_\_.
If the WBC count is within the reference interval, any change in the M:E ratio is due to changes in the erythroid series.
131
A high M:E ratio in an anemic animal with a EBC count within the reference interval suggests what?
erythroid hypoplasia
132
A high M:E ratio in an anemic animal with an increased WBC count could be from ___ or \_\_\_.
this is more difficult to interpret because could be from myeloid (granulocytic) hyperplasia and/or erythroid hypoplasia
133
A low M:E ratio in an anemic animal with a WBC count within or above the reference interval suggests what?
early erythroid regeneration of ineffective erythropoiesis
134
Describe the relative percentages of the various stages in the myeloid and erythroid series in health.
80% of myeloid are metamyelocytes, bands, and segs
90% of erythroid are rubricytes and metarubricytes
135
What stains can be used to distinguish iron-deficiency anemia (decreased iron stores) from anemia of chronic disease (increased iron stores) by staining hemosiderin but not ferritin?
Perl's or Prussian blue
136
\_\_\_ mares bred to ___ stallions are at greater risk of having a second foal with neonatal isoerythrolysis.
Aa-negative mares bred to Aa-positive stallions are at greater risk of having a second foal with neonatal isoerythrolysis.
137
Which DEA groups in the dog are highly immunogenic and will sensitize recipients?
DEA-1.1 (Aa1)
DEA-1.2 (Aa2)
DEA-1.3 (Aa3)
138
What are 3 naturally occurring DEA antibodies in dogs?
anti-DEA-3 (Ba)
anti-DEA 5 (Da)
anti-DEA 7 (Tr)
139
Antibodies in mare colostrum to __ and __ blood types are most frequently involved in neonatal isoerythrolysis.
Antibodies in mare colostrum to Aa and Qa blood types are most frequently involved in neonatal isoerythrolysis.
140
What happens in type B cats transfused with A blood and type A cats transfused with type B blood?
Type B cats with natural anti-A abs can have severe hemolytic reactions when transfused with A blood
Type A cats with natural anti-B abs have early erythrocyte removal when transfused with B blood
141
Describe the major cross match.
Donor RBCs
Recipient serum
--detects abs in the recipient that will react with donor cells
142
Describe the minor cross match.
Donor serum
Recipient RBCs
--detects abs in the donor blood
143
What signifies an incompatible cross match in the dog and cat? What about the horse and cow?
in the dog and cat- agglutination
in the horse and cow- hemolysis
144
What does the direct antiglobulin test (DAT/direct Coombs') detect?
antibody and/or complement attached to the membrane of the patient's washed RBCs
145
What is the difference in monovalent and polyvalent reagents for the Coombs'?
monovalent tests for one antibody or complement
polyvalent tests for multiple
146
What does the indirect antiglobulin test (indirect Coombs') detect? Describe the test.
detects anti-RBC antibody in the serum of the patient
patient serum is tested against washed RBCs of the sire, offspring, or prospective donor (can use supernatant from colostral milk instead of serum to detect reactions against the offspring's cells)
147
What test can be used to detect antibodies in DAT-negative canine AIHA but is primarily a research tool?
DELAT (ELISA based)
148
What 3 things may cause hyperchromia?
hemolysis, Oxyglobin administration, and rare cases spherocytosis
149
What would the M:E ratio look like in a patient with regenerative anemia?
it would be decreased because of erythroid hyperplasia
150
Put these species in decreasing order of ability to mount a regenerative response
cat, cow, bird, horse, dog
Bird, dog, cat, cow, horse
151
What 2 lab findings on the CBC may suggest regenerative response to anemia in the horse?
increased MCV and RDW
152
How many days roughly does it take to start seeing signs of regeneration in the peripheral blood?
2-3 days
153
Name 6 examples of conditions where you would expect a nonregenerative anemia.
AID, renal failure, iron deficiency anemia, aplastic anemia, pure red cell aplasia, and endocrine disorders
154
Describe some major categories of causes of acute hemorrhage.
GI ulcers
Hemostasis defects (including hemophilia, DIC, toxicoses)
Neoplasia
Thrombocytopenia
Trauma
Surgery
155
Describe some major categories of causes of chronic hemorrhage.
GI ulcers
Neoplasia
Hemophilia
Parasitism
Vit K deficiency
156
In acute blood loss, describe the laboratory findings directly after the blood loss, within a few hours, and within a few days.
Within a few hours, the Hct is normal because all blood components are lost together. The spleen contracts to get high Hct blood into circulation so the Hct may be temprarily high.
Within 2-3 hours the blood volume is restored by addition of interstitial fluid, and you'll start to see lab signs of anemia and +/- hypoproteinemia.Platelet numbers usually increase. Neutrophilia usually w/i 3 hours.
48-72 hrs polychromasia and reticulocytosis are evident, plasma protein levels increase (return to normalize before Hct, RBC, and Hb conc)
Hemogram back to normal in 1-2 weeks if single hemorrhage
157
What are some lab findings in cases of chronic blood loss?
regeneration but less intensely than acute blood loss
hypoproteinemia
peristent thrombocytosis
iron deficiency anemia may develop as iron stores are depleted
158
Are reticulocyte counts typically higher in hemolytic anemias or external hemorrhages? Why?
Hemolytic anemias because iron from hemolyzed erythrocytes is more readily available for erythropoeisis than is storage iron or hemosiderin.
159
What are some lab findings that may be found in cases of hemolytic anemia?
Reticulocytosis
Normo or hyperproteinemia
Hemoglobinemia if intravascular
Neutrophilic leukocytosis
Hyperbilirubinemia
Hemoglobinuria
Abnormal RBC morphology based on the cause of the hemolysis
160
What are the 3 main RBC membrane antigens that are recognized in antibody/C3b mediated hemolysis?
Glycophorins, band 3, and spectrin
161
What are 5 major mechanisms leading to immune-mediated hemolytic anemia?
1. idiopathic (AIHA)
2. Infectious agents--\> alter RBC membrane to expose hidden antigens or from adsorption of immune complexes to the membrane in response to the pathogen
3. Drugs that adsorb to the RBC membrane and act as a hapten
4. Alteration in the immune system from lymphoid cell function disturbances or anything that triggers the immune system like infections or cancer
5. Paraneoplastic response to lymphoma or multiple myeloma
162
What does the direct antiglobulin or Coombs' test detect?
warm-active IgG alone, IgG plus C3, C3 alone, and rarely cold-active IgM on the RBC membrane
163
What is cold agglutinin disease?
When cold-reactive IgM on the surface of RBCs fixes complement in the absence of IgG
Associated with autoagglutination, IV hemolysis, acute onset, and severe signs
164
What is the significance of cold agglutinins that bind to RBC membranes below 10 to 15 degrees C?
They are usually insignificant and observed in blood specimens from many healthy animals.
165
What are 4 examples of RBC changes resulting in decreased RBC deformability which could lead to extravascular hemolysis?
1. Schistocytes
2. Spherocytes
3. Parasitized RBCs
4. Eccentrocytes or Heinz body-containing RBCs
166
What are 4 situations that may make an RBC susceptible to removal from the circulation?
1. antibody and/or C3b mediated
2. decreased deformability
3. reduced glycolysis and ATP content of the RBC (aging)
4. increased macrophage phagocytic activity
167
What are some lab abnormalities that may be seen with extravascular hemolysis?
1. regenerative response
2. normal or increased plasma protein
3. NO hemoglobinemia/uria
4. hyperbilirubinemia is hemolysis is of great enough magnitude
5. Hct may be normal if compensated by the bone marrow
6. neutrophilia, monocytosis, thrombocytosis are common
7. splenomegaly from EMH and incr mac activity
168
What are 2 examples of hereditary causes of hemolysis? Which breeds are represented in each of these diseases?
Phosphofructokinase deficiency- American Cocker Spaniel, English Springer Spaniel, mixed breeds with Spaniel heritage
Pyruvate kinase deficiency- Basenji, Beagle, Chihuahua, Dachshund, Pug, Miniature Poodle, West Highland White, Eskimo, Cairn Terrier, Abyssinian, Somali, DSH
169
What additional tests can be done in a case of suspected extravascular hemolysis to confirm?
Coombs' (+)
DELAT (+)
170
Which antibody is very affective at fixing complement, making it responsible for many of the cases of complement-mediated hemolysis?
IgM
171
If complement is fixed to C3, this promotes ____ and results in extra/intravascular hemolysis.
If complement is fixed to C9, this promotes ____ and results in extra/intravascular hemolysis.
If complement is fixed to C3, this promotes phagocytosis and results in extravascular hemolysis.
If complement is fixed to C9, this promotes formation of the MAC and a membrane pore and results in intravascular hemolysis.
172
What are the major mechanisms of intravascular hemolysis?
1. Complement-mediated lysis
2. Physical injury
3. Oxidative injury
4. Osmotic lysis
5. Other- castor bean, snake venom, bacterial toxins, Babesia infections
173
Oxidants affect the erythrocyte in which 3 ways?
1. denaturation of Hb with heinz body formation
2. oxidation and cross-linking of membrane proteins with eccentrocyte formation
3. oxidation of Hg iron (Fe2+) with the formation of metHg (Fe3+)-- interferes with O2 transport but doesn't cause anemia
174
What are the 2 major pathways that protect the RBC from daily exposure to oxidants?
1. reduced glutathione (kept in reduced state by pentose phosphate pathway)
2. iron is maintained in the reduced state by methemoglobin reductase
175
What would happen in a patient with methemoglobin reductase or glucose-6-phosphate dehydrogenase deficiency?
These are enzymes necessary to protect the RBC membrane from oxidant injury so you would get changes indicative of oxidant injury (heinz bodies, metHg, eccentrocytes)
176
What are some ways a cell can become susceptible to IV hemolysis secondary to osmotic lysis?
hypophosphatemia (esp in patients with diabetes)
membrane alterations that allow water to leak into the cell
hypotonic IV fluids
cold hemoglobinuria in cattle
177
What are some lab abnormalities that can be seen in cases of IV hemolysis?
1. Hx of drug, plant ingestion, recent transfusion or colostrum ingestion
2. regenerative response (may not be evident for 2-3 days)
3. hemoglobinuria\*\*
178
Hemoglobinemia is usually detected by:
1. ___ discoloration of plasma
2. Increased/decreased MCHC & MCH
3. Increased/decreased serum haptoglobin and hemopexin concentrations.
1. Red discoloration of plasma
2. Increased MCHC & MCH
3. Decreased serum haptoglobin and hemopexin concentrations
179
When does hyperbilirubinemia first occur in cases of a hemolytic episode?
bilirubin isn't formed until 8-10 hours after the onset of the hemolytic crisis
180
What are the CBC findings in aplastic anemia?
Pancytopenia (nonregenerative anemia, granulocytopenia, and thrombocytopenia)
181
Normocytic, normochromic anemia with normal to increased neutrophil and platelet counts and an increased M:E ratio caused by hypocellular erythroid marrow
These general types of anemia include which types of diseases (5)?
1. Anemia of erythropoietin lack (chronic renal disease, endocrinopathies)
2. AID
3. FeLV-associated nonregenerative anemias
4. Pure red cell aplasia
5. Trichostronglye infection, liver disease, Vit E deficiency (unknown mechanisms)
182
What cells in the kidney make Epo?
peritubular interstitial cells
183
What are 4 mechanisms for the development of nonregenerative anemia in cases of chronic renal failure?
1. Epo deficiency from destruction of peritubular interstitial cells
2. hemolysis from factors in uremic plasma
3. GI hemorrhage from abnormal platelet function and vascular lesions
4. inhibitors of Epo in uremic plasma
184
AID is mediated by which peptide?
hepcidin
185
What are the mechanisms of nonregenerative anemia in AID?
decreased hepcidin, decreased marrow responsiveness to Epo, blunted Epo release, impaired availability of iron to the RBC, shortened RBC lifespan
186
What are 7 lab findings in AID?
1. decreased normal serum iron concentrations
2. decreased to normal total iron-binding capacity
3. normal to increased serum ferritin concentration
4. normal to increased bone marrow macrophage iron stores
5. mild to moderate anemia that is usually nonprogressive
6. normocytic, normochromic RBCs
7. rarely microcytosis and hypochromia (must be very chronic)
187
Normocytic, normochromic anemia with neutropenia (except in myeloproliferative disorders) and/or thrombocytopenia, variable M:E ratio, generalized bone marrow hypocellularity and/or proliferation of abnormal cells
These types of anemia include the following:
1. aplastic anemia or pancytopenia
2. myelophthisic anemia
3. nonregenerative anemias from infectious agents
188
Aplastic anemia/pancytopenia is a disease of what type of cell?
multipotential stem cell in the bone marrow (or it can result from a disrupted bone marrow microenvironment)
189
Does anemia, thrombocytopenia, or leukopenia develop first in cases of aplastic anemia?
Leukopenia and thrombocytopenia happen before anemia because of their shorter lifespans
190
What are 5 casues of aplastic anemia?
1. Idiosyncratic drug reactions-- late estrogen toxicosis in dogs, chloramphenicol toxicosis in cats, phenylbutazone, TMS, albendazole
2. Chemicals and plants (bracken fern)
3. Irradiation
4. Cytotoxic T cell or antiobdy mediated
5. Infectious agents (FeLV, ehrlichia)
191
What are 5 examples of myelophthisic anemia?
1. myeloproliferative disorders
2. myelofibrosis
3. osteosclerosis
4. diffuse granulomatous osteomyelitis
5. metastatic cancer
192
Microcytic, hypochromic anemia with variable neutrophil and platelet counts, and usually a hypercellular marrow with a variable M:E ratio
Causes of this type of anemia include:
1. Iron deficiency
2. Pyridoxine deficiency
3. Copper deficiency
4. Dyserythropoiesis in English Springer Spaniels
5. Microcytosis without anemia in Asian breeds
6. Microcytosis with mild anemia in shunts
7. Drugs or chemical (chlormaphenicol, lead)
193
What does iron deficiency look like in the bone marrow early on? What about when it's more chronic?
Early on iron deficiency is associated with ineffective erythropoeisis and a hyperplastic marrow. With chronicity, the marrow becomes hypoplastic and microcytosis and hypochromia are more evident.
194
What are lab findings in iron deficiency anemia?
1. decreased serum iron concentrations
2. low percent saturation of transferrin
3. TIBC is often within the reference interval or increased
4. decrease/absence of marrow macrophage iron stores
5. decreased serum ferritin concentration
6. increased free erythrocyte protoporphyrin
7. microcytosis
8. hypochromasia
9. poikilocytosis
10. hypercellular BM early on with disporportionate number of late rubricytes and metarubricytes from extra cell divisions
11. low serum hepcidin concentrations
195
T/F: Hypochromia often precedes microcytosis in cases of iron deficiency.
False-- Microcytosis often precedes hypochromasia in cases of iron deficiency.
196
What is pyridoxine and how does it lead to an iron-lack anemia?
it is a vitamin and is a cofactor in heme synthesis; without it, there is a failure to utilize iron
197
How does copper deficiency lead to iron deficiency?
Copper-containing ceruloplasmin and hephaestin are important in iron absorption and transfer between intestine, macrophages, and transferrin.
198
How do the elliptical erythrocytes of members of Camelidae family appear in cases of iron deficiency?
they are microcytic and have irregular or eccentric areas of hypochromasia representing irregular Hg distribution
199
Macrocytic, normochromic anemia with variable neutrophil and platelet counts, M:E ratio is usually low because of hypercellular erythroid marrow
Cases of this type of anemia include:
1. ruminants grazing on cobalt-deficienct or molydbenum-rich pastures
2. Vit B12 and folic acid deficiencies
3. erythremic myelosis or erythroleukemia
4. congenital dyserythropoiesis and progressive alopecia of polled Hereford calves
5. FeLV infection
6. macrocytosis of Poodles
200
What are some blood smear/bone marrow findings in cases of Vitamin B12/folic acid deficiencies?
1. megaloblastoid erythroid precursors in the BM
2. enlarged, hypersegmented neutrophils in the blood smear
3. hypercellular BM indicating ineffective erythropoiesis
201
Common clinical pathology findings in animals with polycythemia vera include:
1. Epo- increased, normal or decreased?
2. PO2- increased, normal or decreased?
3. Platelets and leukocytes- increased, normal, or decreased?
1. Epo- usually in the reference interval or decreased
2. PO2- within the reference interval
3. Platelets and leukocytes- sometimes low
202
What is secondary absolute polycythemia?
Caused by increased Epo secretion
203
What are causes of appropriate compensatory secondary absolute polycythemia?
occurs during chronic hypoxia (low PO2) like in-
1. high altitude
2. chronic pulmonary disease
3. cardiovascular anomalies with right to left shunting of blood
204
When does inappropriate secondary absolute polycythemia occur?
in some cases of hydronephrosis or renal cysts, Epo-secreting neoplasms, and endocrinopathies
normal PO2 and no hypoxia
