Erythrocytes & Leukocytes Chs 1, 2 D&P Flashcards
1
Q
What does hemoglobin consist of?
A
Heme and globin, a tetramer, each heme has a iron and there is four hemes connected to four globin chains as dimers with alpha and beta chains.
2
Q
What is the action of lead on erythropoesis?
A
Lead inhibits most steps in heme synthesis.
3
Q
What are porphyrins?
A
Intermediates in heme synthesis and certain enzyme defeciencies lead to excessive accumulation of porpphyrins > porphyria; these compounds may escape the RBC and accumulate in tissues (like skin etc) and lost in urine etc. (I think also in photosensitization type II)
4
Q
What is hepcidin?
A
produced in liver and plays a role in iron metabolism, increased hepcidin means decrease in iron availability and its a component of acute phase response with IL-6 to control plasma iron conc by inhibiting iron export by ferroportin (it induces internalization and degradation of ferroportin) from enterocytes and macrophages. Main regulator of iron homeostasis
5
Q
How is iron transported in the blood?
A
Bound to transferrin, a gamma globulin I think
6
Q
Five conditions where you might have decreased serum Iron
A
Iron defeciency Acute and chronic inflammation Hypoproteinemia Hypothyroidism Renal dz
7
Q
Conditions with increased serum iron
A
Hemolytic anemia
accidental lysis or RBCs
Glucocorticoid excess
Iron overload - acquired or hereditary like in some birds like Mynahs and Toucans, and Salers cattle where you will see hemochromatosis which is a good gross image.
8
Q
How is iron stored in macrophages?
A
As ferritin and hemosiderin.
9
Q
What is ferritin? When is it increased and decreased?
A
Iron protein storage complex thats water soluble and a more labile form (hemosiderin is more stable and less available and comprised of denatured ferritin and protein), and small amounts can circulate in serum; serum amounts are decreased in iron deficiency and
increased with hemolytic anemia, iron overload, acute and chronic inflammation, liver dz and some neoplastic disorders, and malnutrition in cattle.
10
Q
Abnormalities in serum iron are related to what?
A
Absorbtive failures, nutritional defs, loss via hemorrahge, aberrant metabolism with diversion to macs at the expense of hematopoesis (ie chronic dz or inflammation).
11
Q
How does erythrocyte metabolism take place and why?
A
Embden-Meyerhof pathway (RBCs don’t have mitochondria); its an anaerobic pathway and glycolysis generates ATP and NADH (used to reduce methemoglobin).
12
Q
Important enzymes in the Embden-Meyerhof pathway? What happens with their deficiencies?
A
Pyruvate kinase (PK) and phosphofructosokinase (PFK) > defeciences >> hemolytic anemia (PK def = macrocytic hypochromic anemia; reported in several dog breeds and abyssian and somali cats. (PFK def = hematocrit is WNL or decreased and there is persistent reticulocytosis and alkalemia leading to hemolysis, also reported in dogs)
13
Q
Three other 3 pathways involved in RBC metabolism besides Emden Meyerhof?
A
Pentose phosphate pathway (ie Hexose monophosphate pathway) > produces NADPH via Glc -6-phosphate dehydrogenase and defeciency = hemolytic anemia when there is oxidative stress.
Methemoglobin reductase pathway (enzyme def = methemoglobin accumulation = cyanosis and brown mm and blood).
Rapoport-Leubering pathway. > formation of 2,3 diphosphoglycerate that plays a role in oxygen transport and release. Amount varies with spp. p7
14
Q
What is the name of the earliest RBC precursor cell?
A
Rubliblast, and the last stage before erythrocyte is reticulocytes (rubricyte and metarubricyte are in between)
15
Q
When is the nucleus extruded from the RBC during development?
A
At the metarubricyte stage (forming a reticulocyte). IN birds avian retics retain their nuclei.
16
Q
Where do retics mature?
A
IN cattle and horses its in the bone marrow and mature RBCs are released, in most other animals retics are released into blood and mature in the periph blood or spleen.
17
Q
Once stimulatino occurs how long before retics are released?
A
5 days. p9
18
Q
Where is EPO produced? Two factors that work with Epo to stim RBC production.
A
Peritubular interstital cells in the kidney and a little in the liver. (Ito cells and specific hepatocytes).
IL-3 from T lymphocytes and GM-CSF from T lymphocytes.
19
Q
Whats the average RBC lifespan in dogs and who has the longest and shortest of the different species?
A
Dogs is 110 days; cow is longest at 160 days and birds are only 35 days; cats are 70 days.
20
Q
What happens to heme when RBCs and hemoglobin are broken down in Macs?
A
The heme is cleaved by heme oxygenase forming Carbon monoxide and biliverdin . Biliverdin > Bilirubin (unconjugated) > excreted from Mac into blood > binds albumin and txported to liver where it would be conjugated in hepatocytes and secreted in the bile (I think). The Iron is released and probably goes into Ferritin or Hemosiderin
21
Q
What happens to hemoglobin in intravascular hemolysis? Whats the relationship between plasma hemoglobin and hemoglobinuria?
A
Its released into plasma and binds haptoglobin which prevents it from being lost in the urine, and then it is cleared from the blood by liver. Enough haptoglobin is present to bind 150mg/dl of hemoglobin and the plasma appears pink at 50-100mg/dl of hemoglobin so the plasma is pink before hemoglobinuria occurs.
If haptoglobin is saturated, hemoglobin saturated its lost in the urine freely. Over time its oxidized to methemoglobin > dissociates to free ferriheme > complexes with hemopexin.
22
Q
What happens to hemoglobin that passes into the glomerular filtrate?
A
Absorbed by the proximal tubules, catabolized to iron, bilirubin and globin. Hemoglobin not absorbed will end up in the urine. Tubular cells with hemosiderin may slough into urine and cause hemosiderinuria, so you can see renal cells with hemosiderin in them if there was intravascular hemolysis.
23
Q
Whats the difference between HCT and PCV
A
HCT is calculated using MCV and RBC level (RBC/ul), by multiplying them, and PCV is determined by centrifuge so there is less potential for error with PCV.
24
Q
What does a measure of hemoglobin concentration tell you?
A
Its the most direct indication of oxygen transport capacity of the blood and should be approximately one-third the HCT if erythrocytes are of normal size.
25
What factors will affect Hct, Hgb conc and RBC count all three togather?
Low values for all occur in anemia and overhydration. All will be increased in dehydration.
26
How is MCV (mean corpuscular volume determined and what factors will affect it?
(PCVX10) / RBC count = MCV
Reticulocytosis causes macrocytosis (increased MCV)
Iron deficiency causes microcytosis, dec. MCV, and it also occurs in portosystemic shunts.
Interference with nucleic acid synthesis prevents cell division so there is macrocytosis.
FeLV cats have macrocytosis.
RBC agglutination can cause a false increase in MCV.
27
What is MCH?
| What is MCHC?
MCH is mean corpuscular hemoglobin, how much Hb is present within an average RBC in picograms (PG)
MCHC is the average Hb concentration per average erythrocyte (g/dl), ie its a concentration. Note an increased MCHC will never occur, it cannot be produced inside the cells. But MCHC may be reduced in reticulocytes; hypochromia is low MCHC and may occur in Fe defeciency.
28
Best stain for Reticulocytes?
New methylene blue (RNA, DNA stain blue). Romanowsky stains like Diff-Quik are polychromic.
29
Comparison of canine and feline RBCs. Bovine, Equine, Porcine?
Felines lack the central pallor of canine RBCs and are a little smaller.
Bovine anisocytosis is common,
Equine lack central pallor also (like cats) and rouleaux formation is common.
Porcine show poikilocytosis (remember P for P).
30
Agglutination versus Rouleaux?
Agglutination is present if the erythrocytes remain clumped when blood is diluted 50:50 to 10:90 with physiologic saline. (ie as occurs in immune med dz.)
31
Two conditions where you see microcytosis?
Iron deficiency and Portosystemic shunts and some asian dog breeds.
32
When are spherocytes seen?
Immune med anemia and decreased MCV due to decreased membrane surface area, they are globoid cause the smaller cell must enclose a normal amount of Hemoblobin (I think these are basically smaller RBCs without central pallor, see pg 17)
33
What does polychromasia refer to
Blue gray RBCs with residual RNA, usually macrocytic. Polychromatophilic RBCs seen wtih Romanowsky stains are synonymous with reticulocytes seen with NMB stain. These indicate a regenerative response to anemia.
34
What is hypochromia? Name two causes.
Decreased ctyoplasmic staining and increased central pallor of the RBC caused by insufficient Hb, Iron def is the most common cause but it also occurs with lead toxicosis via inhibition of Hb synthesis (esp in birds).
35
What does poikilocyte refer to?
Generic term for abnormally shaped RBC. Specific types include Echinocytes, Keratocytes, Schistocytes, Acanthocytes, Fusocytes, Ellipotcytes, Dacrocytes, Leptocytes, Target cells / Codocytes, Stomatocytes and Spheroctyes.
36
Whats an echinocyte?
Spiculate RBC with uniform projections. Crenated RBCs that are in in vitro artifact of drying. May also be observed in uremia, electrolyte depletion, lymphoma, doxorubicin tox and glomerulonephritis.
37
What are keratocytes?
Helmet cells. RBCs with one or two projections that form a ruptured vesicle, these abnormalities often result from oxidative damage to the RBC membrane as seen with Heinz body formation.
38
What are schistocytes?
Irregular RBC fragments from shearing by fibrin or turbulent blood flow. DIC, HSA, glomerulonephritis, congestive heart failure, myelofibrosis, vasculitis.
39
What are acanthocytes?
Spiculated RBCs with two or more irregular, often blunted projections (in contrast with echinocytes that have regular uniform projections all over), thought to form as a result of altered lipid:cholesterol ratios in the RBC membrane. Seen in HSA (esp in the liver), glomerulonephritis, lymphoma, LIVER DZ.
40
What are dacryocytes?
Teardrop-shaped RBCs that may result from the inability of the RBC to return to its pre-existing shape after deforming in the vessels, not sure why this happens - cytoskeletal protein alterations. May be an artifact if all tails are in the same direction. Seen in llamas with Fe deficiency anemia.
41
Leptocytes.
Thin cells with an increased membrane:volume ration. Appear folded due to excess membrane. Have been associated with portosystemic shunts;
They are also called target cells or Mexican Hat cells, they are clear in the middle the a thick outer rim of membrane and may also have a spot in the middle like a hat.
42
What are target cells / codocytes?
A type of leptocytes that is bell shaped and resembles a target cause the Hb is at the periphery and in the middle of the cell. Associated with liver dz, Fe def anemia and reticulocytosis.
43
What are stomatocytes?
A type of leptocyte that is bowl shaped with oval areas of central pallor; due to expansion of the inner cell membrane and observed in hereditary stomatocytosis of Alaskan malamutes etc and may also be artifact of thick area of blood smear.
44
What are spherocytes?
Small dark microcytes that lack central pallor with reduced amount of membrane per unit volume. Readily detected only in the dog because of the normal abundance of central pallor. Seen with IMHA; result from partial phagocytic removal or Ab coated membrane or pitting of Heinz bodies. They get removed by splenic Macs d/t their reduced ability to deform/loss of flexibility.
45
Basophilic stippling.
Punctate aggregation fo residular RNA with Diff Quick stain. Anemic sheepa nd cattle. Same significance as polychromasia (ie reticulocytes) (regen anemia) and may be appropriate response in anemia. May also be seen in lead toxicosis where there would be metarubricytes (nucleated reds) with minimal polychromasia (ie inappropriate response - dyserythropoeisis) in an animal with normal RBC values.
46
What are Howell Jolly bodies?
Basophilic nuclear remnants in the cytolasm of RBCs, seen most often in accelerated erythropoiesis or post splenectomy.
47
Whats a Heinz body and when is it seen?
Round structure that protrudes from the membrane of a RBC, like a blister of membrane. Its denatured precipitated Hb due to oxidation and they appear as dark basophilic bodies with NMB stain. Cats are most susceptible due to a larger number of sulfhydral groups that increase susceptibility to oxidation, and the feline spleen is inefficient at removing these structures. Up to 10% of feline RBCs may have these in health.
48
Eccentrocytes.
RBCs with Hb condensed to one side of hte cell leaving a clear or bilster line area in the remaining portion of the cells. The result of oxidative injury with lipid peroxidation and cross linking of the cell membrane. p20
49
What is the meaning of nucleated reds in the bood smear and what is it called?
Metarubricytosis (can occur with rubricytes or earlier stages as well). It can be appropriate (with strongly regen anemias where you would also see reticulocytes) or inappropriate (ie with lead toxicosis, iron deficiency, copper deficiency, HSA, EMH, myelophthisis, endotoxemia, bone marrow dz, FeLV infection, myelodysplastic syndrome, leukemia, erythremic myelosis in cats.)
50
What are the three possible locations of RBC parasites and what are some specific parasites that occur in these locations?
Intracellular: (Hemoproteus, Leukocytozoon and Plasmodium of birds); (Cytauxzoon felis and Babesia felis of cats); (Anaplasm marginale, Babesia bovis, & bigemia of cattle); Babesia canis & gibsoni of dogs), (Babesia equi and caballi of horses).
Epicellular: (Mycoplasma haemofelis of cats and M. haemocanis of dogs and M. haemosuis of pigs); (Eperythrozoon wenyoni of cattle).
Extracellular: Filarids and Trypanosomes.
Microfilaria > (Dipetalonema reconditum and D. immitis of dogs); Setaria of horses).
Trypanosomes > (T. theileri, congolense and vivax of cattle); (T. cruzi of dogs); and (T. evansi of horses)
51
You see irregular to round to ring shaped magenta bodies in the RBCs and also may see them in the leukocytes in a blood smear, what are they?
Distemper inclusions. Stain pink with diff quick or other Romanowsky stain.
52
In what species will you not see reticulocytes?
HORSES; you will not see retics in the blood of horses in either health or regen anemia. IN ruminants you will only see retics in the blood with anemia cause of their long RBC lifespan but you may see a few normally in dogs and cats.
53
How do you calculate absolute reticulocyte count and what are the values indicating a regenerative response in dogs and cats?
Multipley the reticuolcyte percentage by the Total RBC count in uL so youhave absolute retic count in uL.
Dog: > 80,000 retics/uL = Regenerative response
Cat: > 60,000 retics/uL = Regenerative response
p22
54
In what type of anemia does the most severe reticulocytosis occur? When does it become evident in the blood and when is it at its max?
What about reticulocytosis in cattle and horses?
Most intense reticulocytosis occur in hemolytic anemia > external hemorrhagic anemias. (the iron is more readily available)
Not evident until 48-72 hrs and max at 7 days.
Doesn't occur in cattle until HCT is very low and DOES NOT ever occur in horses.
55
What does the lack of reticulocytes following anemia tell you?
The bone marrow is no responding. NONregen anemia.
56
Parts to assess on a bone marrow smear?
Proportion of adipocytes (approx 50%);
proportion of hematopoietic progenitor cells (approx 50%);
Megakaryocytes;
M:E ratio;
Maturation stages of myeloid & erythroid stages - percents of the different stages simply as mature or immature;
Iron in macrophages.
57
In health in a marrow smear what should the percentages of mature versus immature cells be for the myeloid and erythroid lines?
Myeloid: 80% should be mature (metamyelocytes, bands and segs.)
Erythroid: 90% should be mature (rubricytes and metarubricytes)
A high percent of immature (ie blasts) suggests hyperplasia, neoplasia, maturation abnormality; in the myeloid series you can have depletion of the mature series with shift toward immaturity.
58
How do you interpret the M:E in the bone marrow smear? (ie if its high or low)
First you need to have the CBC for the WBC counta nd RBC count.
If the WBC count is normal, any change in M:E is due to the erythroid series.
High M:E, normal WBC count = erythroid hypoplasia.
High M:E, anemic animal, increased WBC count = may be myeloid hyperplasia OR erythroid hypoplasia.
Low M:E in an anemic animal with a WBC count within or above the ref interval = RBC regen (or possibly ineffective erythropoesis).
59
What type of iron does Perls or Prussian stain detect? What about in cats? What will you see in Anemia of chronic dz when staining the marrow for iron?
Perl's or Prussian blue detects hemosiderin (insoluble iron) but NOT ferritin (soluble iron because its removed during staining). In anemia of chronic dz you see increased iron staining in the marrow. Hemosiderin is NOT seen in the feline marrow.
60
Which blood types in the dog have the greatest potential for txfusion reactions?
DEA 1.1, 1.2, 1.3 (DEA 1.1 and 1.2 form due to previous txfusion, ie not naturally occuring).
Anti DEA 3, 5 and 7 also occur naturally > RBC removal.
61
In the horse, Abs to what blood types are most frequently involved in neonatal isoerythrolysis?
Aa and Qa
62
What type of Abs occur in the cat to blood groups?
Type A and B blood types (Abs to the opposite type occur naturally in the cat without prior txfusion).
Type B cat with anti A abs > life threateninig hemolytic reaction with txfused with type A blood.
Type A cat with anti B abs > erythrocyte removal when txfused with type B blood. p25
63
For blood cross matching, whats a major versus minor cross match.
```
Major = RBCs of the donor against serum of the recipient. Detects Abs in the recipient that will react and destroy donor cells; a txfusion reaction will cause massive lysis of donated cells.
Minor = tests serum of donor against RBCs of recipient, ie trying to detect Ab in donor blood that would damage host RBC, less significant due to dilution in the recipient and probably only an issue for whole blood txfusions, not an issue if only packed RBCs txfused. p25
```
64
What does an incompatible blood cross match indicate?
Prior sensitization. Naturally occurring Abs are not usually present in enough numbers to cause transfusion reactions EXCEPT in A negative Type B cats that have naturally occurring anti-A Abs.
65
What are the indicators of an incompatible cross match?
Agglutination in most spp;
| hemodilution predominates in horse and cow.
66
What is the Antiglobulin / Coomb's tests? Direct versus indirect.
Coombs > used to confirm immune mediated hemolysis of RBCs.
The Direct Antiglobulin test (DAT) > detects Ab or complement attached to the membrane of patients washed RBCs
Indirect test > detects Anti RBC Abs in the serum of the patient (ie Abs to a potential donors, sires, offsprings RBCs). You can also test colostrum this way in cows and mares to see if it has Abs against other's RBCs.
67
What is the easiest and most accurate way to detect anemia?
Hct. (interpret in light of patients hydration status) (remember though this is a calculated value > multiple the volume of one RBC ie. MCV, by the number of RBCs in one ul of blood, aka the RBC level, and this tells you the volume or space in the ul of blood that is being taken up by the RBCs, and the remainder of the space in the ul of blood is serum proteins and fluid, so this calculated HCT will be affected by variations in MCV).
68
What are the three ways to classify an anemia?
1. According to MCV and MCHC. ie. normocytic, macrocytic or microcytic AND normochromic, hypochromic or hyperchromic; remember RBCs never overproduce Hb so hyperchromasia is due to hemolysis.
2. According to Marrow response. (ie. regen via polychromasia, retics with anisocytosis and increased RDW, macrocytosis and hypochromasia, decreased M:E in the marrow, regen suggests an extramarrow etiology like lysis or loss); (non regen suggests inadequate time so its acute still or chronic inflammation, renal dz, endocrine disorders, marrow dz, iron def, and all horses appear nonregen due to no reticulocytes).
3. According to Major pathophysiologic mechanism like hemorrhage anemia, destruction anemia like with hemolysis, or reduced / defective erythropoiesis.
69
Common lab findings in cases of acute Blood loss and when does it normalize?
HCT is initially WNL cause all blood components are lost.
As fluid from the interstitium restores blood volume within 48 to 72 hours HCT, RBC count and Hb concentration are reduced and hyoporoteinemia is observed.
Platelet numbers increase.
Neutrophilic leukocytosis.
Signs of regen like polychromasia, reticulocytosis by 48 to 72 hours, max out at 7 days.
Plasma protein levels normalize before HCT (within 2-3 days).
The entire hemogram should normalized within 1-2 weeks.
If marrow is broke you will see Thrombocytopenia and subsequent hemorrhage and the anemia looks non regen.
70
Lab findings in chronic hemorrhage?
Regen response that is weaker than with acute loss.
Hypoproteinemia. (UNLESS the hemorrhage is internal)
Persistent thrombocytosis
Iron def anemia may develop as iron stores are depleted (microcytosis, hypochromasia) (AGAIN UNLESS the hemorrhage is INTERNAL, the Fe is then recycled like the protein).
71
Common findings in hemolytic anemia.
Icterus if severe and acute.
Hemoglobinuria and hemoglobinemia if intravascular.
(note extravascular more common that intra)
HIgher retic counts than with hemorrhage due to iron recycling.
Normal or increased plasma protein concentration.
INtravascular hemolysis cause hyperproteinemia, hemoglombinemia and hyperchromasia (inc MCH and MCHC).
Neutrophilic leukocytosis and monocytosis
Hyperbilirubinemia, hemoglobinuria (hemoglobin degradation)
Abnormal RBC morphology like (Heinz bodies, RBC parasites, spherocytes, poikilocytes)
72
IN cases of extravascular hemolysis that are Antibody or complement mediated, what the the three most common membrane antigens recognized by Abs?
Glycophorins, band 3, and Spectrin.
73
What are the mechs by which extravascular hemolysis occurs?
1. Immune mediates stuff: Antibody or completement C3b binds the RBC and targets it for descruction by macrophages.
Macrophage phagocytosis may result in spherocytes formation as bites of RBC membrane are taken resulting in smaller RBC cell membrane with the same amount of cell contents.
Type II HS: IMHA/autoimmune dz; infectious agents like FeLV, EIA, Ehrlichia, M. haemofelis (alter rbc membrane or form immune complexes that fixes complement); haptens like penicillin; immune system dysregulation (ie in T cell function); paraneoplastic
IgM or IgG on the surface with complement fixation, even C9 and the MAC in some cases.
2. Defects or changes in RBC membrane reducing deformability. (ie forming schistocytes, or spherocytes in IMHA or parasitized RBCs or eccentrocytes and RBCs with Heinz bodies.)
3. Reduced glycolysis and ATP content of the RBC (dec glycolysis as in pyruvate kinase def and PFK def in animals).
4. INcreased macrophage phagocytic activity.
74
What are the clinical and lab findings with extravascular hemolysis? (4)
Chronic with insidious onset.
Hyperbilirubinemia (if the liver is overwhelmed - unconjugated early and the conjugated later on).
Neutrophilic, monocytosis and thrombocytosis.
Splenomegaly
75
What things may aid in determining the cause of extravascular hemolysis? (3)
- Dog breed like Cockers and springer spaniels get PFK def and Basengis and Beagles and others like Westies get PK deficiency and some just have a predist to hemolytic anemia like the Cocker etc.
- Positive Coombs test / direct antiglobulin test (test for Ig or C3 on patients RBCs)
- Abnormal RBC morphology like RBC parasites, spherocytes, schistocytes, keratocytes suggest the potential for phagocytosis.
76
What are the different mechanisms of intravascular hemolysis?
Note with this the hgb is released into plasma and then removed by the liver or excreted by the kidneys.
Also note that in most of these cases the RBC itself and its membrane are initially normal.
77
What are the five mechanisms of intravascular hemolysis?
1. Complement mediated lysis via C9 and Mac (not via C3, that would cause phago and extravasc hemolysis).(comlement fixation / mediated lysis usually mediated by IgM usually like in neonatal isoerythrolysis in foals and in transfusion reactions).
2. Physical injury (shearing via fibrin, ie microangiopathic anemia > schistocytes)
3. Oxidative injury (> denature Hb and heinz body formation, methemoglobin formation from Hb iron, and cross linking of membrane proteins with eccentrocyte formation)
4. Osmotic lysis
5. Alterations via other mechanisms (ie snake venom, castor beans, bacterial toxins like from C. novyi, Babesia sp.)
78
How is the RBC protected from oxidation?
Reduced glutathione neutralizes oxidants, its produced via the pentose phosphate pathway (deficiency of enzymes in the pathway leads to problems (ie glc 6 phosphate dehydrogenase def.).
Iron is maintained in the reduced state via methemoglobin reductase so accum of methemoglobin is minimized.
79
The main two RBC changes that suggest oxidative damage?
Heinz bodies or eccentrocytes.
80
What things can result in osmotic lysis of RBCs?
HYPOPHOSPHATEMIA (esp in diabetic patients)
Hypotonic IV fluids
Cold hemoglobinuria of cattle
81
What are some of the clinical and lab characteristics of intravascular hemolysis?
Acute or peracute onset
Regen response that may take 2 or 3 days to show up
*Hemoglobinemia (red plasma, inc MCHC or MCH)
*Hemoglobinuria (occurs when hemopexin and haptoglobin are saturated and renal tubule cells can't absorb and metab all the hemoglobinuria)
Hemosiderinuria (formed in renal tubule epi cells)
Hyperbilirubinemia (unconj early and conj later on)
Schistocytes, keratocytes, Heinz bodies, eccentrocytes, RBC parasites, Pos coombs test.
82
What is conjugated hyperbilirubinemia accompanied by?
Bilirubinuria
83
If bilirubin is elevated what must have happened - concise but comprehensive answer.
The amount of bilirubin present in the blood has exceeded the livers ability to absorb/uptake it, conjugate it and secrete it into the bile.
84
Categories of causes of reduced erythropoiesis?
```
Anemia of chronic disorders like neoplasia and inflammation
Cytotoxic bone marrow damage
EPO lack
Immune med dz
Infections
Myelophthisis
Abnormal maturation
Disorders of heme synthesis
Disorders of nucleic acid synthesis
pg36
```
85
Three compounds toxic to bone marrrow.
Estrogen, Bracken Fern, Phenylbutazone.
86
Three things that can decrease EPO production.
Chronic renal dz
Cushings
Hypothyroidism (also hypoituitarism)
87
Infections that can zap the bone marrow and dec erythropoesis (4)
Parvo/Pan leuk
FeLV
Anaplasma spp
Trichostrongyles (non blood sucking)
88
What are some causes of myelopthysis?
Leukemia/neoplasia
Myelofibrosis
Osteopetrosis/sclerosis
Myeloprolif disorders
89
What can cause defects in hemoglobin synthesis (4)?
Copper and Iron def.
Lead tox.
Molybdenum poisoning
90
What causes disorders of nucleic acid synthesis?
B12 def. / malabsorbtion
| Folic Acid deficiency
91
Primary versus secondary bone marrow failure.
Primary is due to intramarrow dz, lack of stem or progenitor cells.
Secondary is due to inadequate nutrients or growth factors like EPO, CSF, CKs, Iron, Cu etc.
92
How does the bone marrow appear when you have maturation abnormalities; when are these common?
Hypercellular.
| Common when you have nutritional defs, myelodysplastic syndrome, leukemia, hereditary dyserythropiesis.
93
What are the four causes of non-regen anemia (then there are 3 miscellaneous causes at the end)?
```
1Lack of EPO
2Anemia of inflammatory dz
3FeLV associated nonregenerative anemia
4Pure Red Cell aplasia
The three misc. conditions with unknown mechs include Trichostrongyle infections in cattle/sheep, Liver dz and Vitamin E def. in swine (the marrow is hyperplastic, and this also causes mulberry heart and hepatosis diatetica).
```
94
How does renal dz cause anemia?
Lack of EPO via peritubular interstitial cells.
Hemolysis caused by uremic plasma
GI hemorrhage from abnormal plt functio
Inhibitors of EPO in uremic plasma
95
What is the MOA for anemia of chronic dz?
Hepcidin. Made in response to inflammation and induced by IL-6.
There is lack of absorbtion of Fe and sequestration of Fe in cells;
also decreased marrow response to EPO and shortened RBC lifespan.
96
Name some common lab findings in Anemia of inflammatory dz?
Dec to normal serum Fe AND TIBC
Normal to inc. serum ferritin (for iron storage)
Normal to inc marrow macrophage Fe stores
Mild to moderate anemia thats non progressive
Normocytic normochromic rbc indices (you usually do not get signs of Fe def. with this like microcytosis/hypochromia).
Increased Cu and Zn concentrations
Inc serum Hepcidin conc.
97
What causes pure red cell aplasia?
Anemia with selective loss of RBC precursors in the marrow, appears to be autoimmune, some may be Coombs pos so would be non regen autoimmune hemolytic anemia.
98
What are the three categories or types of Normocytic, normochromic anemia with neutropenia, and/or with thrombocytopenia and variable M:E? What would the marrow look like?
The marrow would be hypocellular and /or there may be abnormal cells present.
1 Aplastic anemia or pancytopenia
2 Myelophthisic anemia
3. Non regen anemia due to infectious agents
99
What can cause aplastic anemia or pancytopenia?
Drug reactions like with estrogen, chloramphenicol, TMS etc,
Plants like Bracken Fern in ruminants and horses and Irradiation
and infectious agents like FeLV in cats and Ehrlichiosis in dogs.
100
What is an Leukoerythroblastic reaction?
Metarubricytosis without reticulocytosis and a neutrophilic left shift without inflammation; ie there is disruption of the normal marrow architecture and disorderly release of myeloid and erythroid precursor cells.
101
What are 7 causes of Microcytic, hypochromic anemia with variable neutrophil and plt counts and a hypercellular marrow? (3 are important)
1. *Iron def.
2. Pyridoxine def (vitamin that is cofactor in heme synthesis)
3 *Copper def (Cu containing ceruloplasmin are important in Fe absorption and transfer between intestine, macrophages and transferrin)
4 Dyserythropoesis in English Springer Spaniels (assoc with myopathy and cardiac dz)
5. Microcytosis without anemia in Asian dog breeds like Akita, Chow, Shar Pei and Shiba Inu.
6. *dogs with Portosystemic shunts. Has to do with alterations in Iron metabolism. There is normal to dec serum iron and TIBC, and serum ferritin is normal to increased.
7. Drugs or chemicals like chloramphenicol and lead can block synthesis of heme.
102
What are the causes of a Macrocytic, normochromic anemia? M:E is low due to hypercellular erythroid marrow. (3 are important)
ie we are talking Large cells with this.
1 *Ruminants grazing Cobalt-deficient or Molybdenum rich pastures.
2 *Vitamin B12 and folic acid defs. (usually with hypercellular marrow due to ineffective erythyropoiesis)
3 Erythremic myelosis or erythroleukemia
4 Congenital dyserythropoiesis (and progressive alopecia) of polled Hereford calves
5 *FeLV infection (erythroid marrow is hypo cellular)
6 Macrocytosis of Poodles
103
Causes of spurious or relative polycythemia? (ie the total RBC mass is normal)
Dehydration (plasma protein also increased)
| Redistribution of RBCs (excitement causes epinephrine release and splenic contraction; common in cat and horse)
104
Types and causes of Absolute polycythemia?
Primary > Myeloproliferative disorder of stem cells (EPO is normal or dec and PO2 is WNL)
Secondary > Increased EPO, ie Chronic hypoxia, high altitude, pulmonary dz, cardiovascular anomalies with R to L shunt; or inappropriate EPO secretion as in hydronephrosis or renal cysts or EPO secreting neoplasms like embryonal nephroma, renal carcinoma, uterine leiomyoma etc. and in certain endocrinopathies.
May cause seizures due to blood sludging and CNS ischemia.
105
What are the two types of WBC granules?
- Primary / azurophilic (lysosomes with stuff like myeloperoxidase, lysozyme etc and enzymes like acid hydrolases, elastase etc, larger and more electron dense on EM than secondary granules)
- Secondary / specific (Microbiacidal elements too like lysozyme same as primary, cathelcidins and enzymes like collagenase); more electron lucent on EM than primary granules).
106
In order of least to most mature, what are the stages of granulocytes?
Myeloblast (large round to oval nucleus and these are pink in contrast to rubriblasts which are blue) > Promyelocyte (may see granules) > Myelocyte (oval nucleus) > Metamyelocyte (indented nucleus with bulbous ends) > Band (U shaped nucleus) > Segmenter (nucleus separated into lobes (bovine neuts have pink or orange cytoplasm)
107
How is granulopoesis regulated during microbial invasion?
Stromal cells release GFs including CSFs like stem cell factor, granulocyte-CSF and granulocyte / macrophage-CSF.
CKs released from endothelial cells and fibroblasts produce CSFs.
108
What are CSFs and what do they do?
Glycoproteins.
Act on hematopoietic subpopulations in the marrow >>
increased cellular proliferation
cellular differentiation
inducement of / enhancement of cell function
and other mediators cause neut release from the marrow etc.
109
What are the two theoretic compartments of neutrophils in the bone marrow? what are the stages in each how much of the total cell pop do they occupy?
- Proliferation or mitotic compartment (myeloblast, promyelocyte and myelocyte; 4-5 cell divisions 3 of which are in myelocytes); in health approx 20% of neuts are in this compartment.
- Maturation compartment (metamyelocytes, bands and segs; cannot replicate, functionally mature. 80% of neuts are in this stage in health. 5 day supply of neuts in health.
110
What is a left shift?
IN times of neutrophil demand, when bands and younger forms are released from the bone marrow prematurely.
111
What are three mechanisms for increased neutrophil production?
```
increased stem cell recruitment
increased granulopoesis (ie increased cell divisions)
shortened marrow txit time (released into blood at faster rate)
```
112
What stimulates neutrophil release from the bone marrow?
G-CSF, GM-CSF, C5a, TNF-a
You get increased release from the marrow storage compartment and neutrophilia,
followed by a shift toward immaturity as the mature ones are all released. Eventually you get a left shift denoting a depletion of granulocyte reserve and a tissue demand for neutrophils.
113
Where is neutrophil concentration greatest in the blood?
Post capillary venules.
114
Which neutrophils are not counted on the WBC count?
The marginated neutrophil pool (MNP) that is adherent to the vascular endothlium. Only the CNP / circulating neutrophil pool is counted.
115
Compare the Marginated neutrophil pool versus circulating neutrophil pool in different species of domestic animal.
The MNP is equal to the CNP in the dog, horse and calf. The feline MNP is approx three times larger than the CNP.
116
What is the life of neutrophil in blood and how often are they replaced?
10 hours
| They are replaced approximately 2.5 times each day.
117
Where does neutrophil microbiacidal action occur?
In tissue BUT NOT in blood.
118
Characteristic neutrophil response to bacteria.
Respiratory burst. Digestion of complement components and fibrinogen and stim of inflammatory mediators.
119
What is the maturation sequence of the monocyte?
Monoblast (low frequency in the marrow and indistinguishable from the myeloblast)
Promonocyte
Monocyte (pink cytoplasmic granules are lysosomes with peroxidase, lysozyme, etc., and they have pseudopodia that may project from cell margins; lysosomes and vacuoles are seen in EM.)
120
What are the two populations of macrophages?
Macrophages derived from monocytes recruited from teh blood that are short lived, and then resident tissue macrophages that survive longer, weeks to months, are capable of division in tissue.
121
Whats the monocyte precursor cell?
Its a bipotential progenitor cell (CFU-GM) thats the same as the neutrophil progenitor cell.
122
What regulates monocyte production and maturation?
GFs and CKs like M-CSF, SCF, GM-CSF, IL-1, 3, 6
123
What is the case with the monocyte storage pool?
There is no monocyte storage pool like there is with neutrophils. But they do have a longer blood transit time than neuts (18-23 hours).
124
How do macrophages eliminate virus infected cells and tumor cells?
Antibody dependent cellular cytotoxicity.
125
What kind of granules to eosinophils have and whats in them?
Secondary / specific granules. These granules are lysosomes that contain major basic protein, acid hydrolases and an eosinophil specific peroxidase.
126
What is the major CK that controls eosinophil production?
IL-5
127
What is the blood transit time of eosinophils?
Very short, 30 minutes. ALso a marginal pool of eosinophils exists (and a storage pool also exists in the marrow)
128
What is the job or eosinophils and what do they release?
Attach to and kill helminths, mediated via antibody, complement and T lymphocyte perforins. They release major basic protein to generate toxic oxygen radicals via peroxidase activity.
129
What is the role of eosinophils in hypersensitivity reactions and allergic dz?
In HS reactions they may actually suppress them cause they are attracted by and inhibit chemical mediators liberated by mast cells during allergic reactions.
They can also promote inflammation in allergic c dz by binding to and cross linking igE and are activated to release their contents.
130
What mediates eosinophil recruitment?
IL5, IL-2, IL-16
131
In which tumors may you see tumor associated eosinophilia?
T cell lymphoma, fibrosarcoma, carcinoma and of course mast cell tumor.
132
Basophils are closely related to which other cell type?
They are ocean going mast cells and their granules cannot be diff'd. Their granules contain histamine, heparin, sulfated mycopolysaccharides but LACK acid hydrolases (unlike EOs).
133
What is the major CK that governs basophil growth and differentiation?
IL-3
134
What is the function of basophils?
```
Pretty similar to mast cells.
Immediate and delayed HS
Promotion of lipid metabolism via activation of lipoprotein lipase.
Prevention and promotion of hemostasis.
Rejection of parasites.
```
135
Are mast cells in blood?
NO, not in normal healthy mammals, the are in tissue only THe move from marrow to blood to tissue as non granulated mononuclear cells, establish residence in tissue and undergo further diff. Pretty similar to basophils but constitute a distinct cell line.
136
Besides HS, mast cells are also involved in what?
Fibrosis
137
What are lymphocytes with reddish cytoplasmic granules?
Mainly cytotoxic lymphocytes.
138
What is lymphocyte transformation or reactive lymphocytes? What do they look like?
Mature lymphocytes are not necessarily end cells, on appropriate stimulation they may transform into immunoblasts and plasmacytoid cells. and these immunocytes or transformed lymphocytes may be termed reactive lymphocytes.
They are large cells with intensely basophilic cytoplasm, a pale golgi zone and fine cytoplasmic vacuoles.
139
Where are B cells derived in birds?
Bursa of Fabricius (Thymus for T cells - in birds it separated lobes of T cells). Bone marrow is where B cells are derived in mammals.
140
What are bird secondary lymphoid organs?
Spleen, conjunctival or head associated lymphoid tissue (CALT / HALT), GALT and lymphoid aggregates in various tissue (BIRDS don't have lymph nodes).
141
About how long to lymphocytes live?
Two weeks.
142
How do lymphocytes circulate?
Recirculation through efferent ducts of LNs > Thoracic duct or right lymphatic duct > blood > post capp venules of the cortex of LNs (where receptors help move lymphocytes into tissue from circulation) > lymphoid tissue / parenchyma > efferent lymph again and out of the node to blood.
143
How is lymphocyte circulation determined? What are the majority of recirculating lymphocytes?
Its non-random and exhibit homing to their tissue of origin in health. Recirculation time is one to several hours and the majority of recirculating lymphocytes are long lived memory T cells. Most B lymphocytes in the blood are transient, most B cells stay in lymphoid tissue.
144
Which cells are cytotoxic?
CD8 T cells and NK cells (but NK cells do not require previous sensitization.)
145
Which spp has the largest platelets?
Feline platelets have the largest mean platelet volume of domesticated animals and are not lysed during leukocyte counting and may falsely elevate WBC count.
146
A couple of things that may cause abnormal WBC counting errors.
Clumping of leukocytes or fragile leukocytes
Abnormally large or clumped platelets
Excessive Heinz bodies which don't disintegrate when RBCs are lysed.
147
Leukopenia is usually caused by a decrease in which cell type?
Neutrophils, except in ruminants and some avian spp where lymphocytes predominate in the blood in health.
148
Degenerative left shift refers to what?
The number of bands and less mature neutrophils exceeds the number of segmented neutrophils.
149
What causes toxic change in neutrophils?
| What are the four manifestations or appearances of toxic change?
Any inflammatory disease severe enough to cause accelerated neutrophil production and shortened maturation time in the marrow.
1. Cytoplasmic basophilia (retained ribosomes)
2. Cytoplasmic vacuolation (foamy appearance and a severe change)
3. Dohle bodies (grey angular cytoplasmic inclusions, aggregates or RER, usually in feline blood smears)
4. Toxic granulation (prominent pink purple granulation of the cytoplasm, don't confuse with granules, represents severe toxemia).
150
What are some causes of nuclear hypersegmentation?
Steroids or cushings
Idiopathic
Cobalt def in cattle
Hereditary macrocytosis in Poodles
Abnormal vitamin B12 uptake in Giant Schnauzers
Myelodysplastic syndrome and some forms of leukemia
151
Causes of nuclear hyposegmentation?
Can look like bands, metamyelocytes or myelocytes; chromatin pattern suggests possible causes for this change.
Less aggregated chromatin > typical for left shift.
Coarse aggregated chromatin > Pelger Huet anamoly (cellular function not impaired, its an inherited dog thing, cats and rabbits too), also Pseudo Pelger Huet that is acquired and transient with chronic infection esp in cattle and admin of certain drugs.
152
What is the appearance of degranulated eosinophils?
Activated during disease and appear "moth eaten" because of cytoplasmic degranulation and vacuolation (Greyhounds have vacuolated eosinophils in health.
153
Organisms that may be seen within leukocytes (5)
```
Ehrlichia canis >
Ehrlichia ewingii >
Anaplasma phagocytophilum >
Hepatozoon
Distemper inclusions
Rarely Histoplasma or Toxoplasma orgs may be seen
```
154
Ehrlichia canis infects what cell
mononuclear cells (monocytes, lymphocytes of dogs, ie canine monocytic ehrlichiosis).
155
Ehrlichia ewingii infects what cell
infects neutrophils, eosinophls (canine granulocytic ehrlichiosis)
156
Anaplasma phagocytophilum infects what cell
neutrophils of dogs, horses, cattle, sheep goats
157
Anaplasma platys infects what cell
platelets of dogs
158
Hepatozoon infects what?
| What are the different spp and what do they look like?
Monocytes and neutrophils of mammals and RBCs of birds, reptiles and amphibians.
Hepatozoon canis (SA, Europe Africa, Asia) no or mild dz and can find large numbers of gametocytes in peripheral leukocytes.
Hepatozoon americanum (southern NA) severe illness with only rare peripheral gametocytes (I think this is the one seen in heart muscle).
Gametocytes are lightly basophilic, oval organisms measuring 4X9um with a round, eccentric nucleus.
159
Where are canine distempervirus inclusions observed?
in RBCs or Leukocytes, even before clinical signs. Range from 1-6um and appear magenta to red with Diff quick.
160
What is seen in neutrophils in lysosomal storage dz?
Enzyme deficiency > Accumulation of undigestable substances in lysosomes (ie fucosidosis, GM1 and 2 gangliosidoses, mucopolysaccharidosis.)
161
How does Chediak Higashi syndrome affect WBCs?
Abnormal fusion of lysosomes with eosinophilic granules in the cytoplasm of neutrophils. (cattle, Persian cats, mink, rats)
162
Birman cat neutrophil abnormality is characterized by what?
prominent fine eosinophilic granulation in neutrophils
163
In neutrophilia, how high can cell counts go in the absence of a left shift (for physiologic neutrophilia)?
Up to a two fold increase.
164
What is the mechanisms for physiologic neutrophilia? What accompanies it in terms of lymphocytes and why?
Epinephrine release in response to fear, excitement, sudden exercise; its a pseudoneutrophilia, mobilization of marginated neuts into the circulating pool, total blood numbers unchanged.
Concomitant lymphocytosis explained by two theories: Epinephrine blockage of receptors in endo cells prevents recirculation OR an unidentifed source of lymphs is released into circulation due to the Epi.
165
In which species is physiologic neutrophilia common / uncommon?
Uncommon in dogs.
Common in healthy cats where counts may exceed 39,000 and absolute lymphocytes count may exceed 36,000. Neutrophilia pronounced in the cat due to its larger MNP.
Common in young healthy horses
166
Three basic causes of neutrophilia?
Epinephrine response (no left shift
Corticosteroid response (no left shift)
Acute purulent inflammation (more segs released)
Chronic suppurative dz (more segs released)
167
With steroid administration what leukogram changes are seen?
```
Neutrophilia with out left shift
Lymphopenia
Eosinophenia
Monocytosis
(remember SMILED, segs and monos increased, lymphos and Eos decreased).
```
168
What is the mechanism of neutrophilia with steroid administration?
Decreased emigration into tissues, increased blood txit time.
Increased marrow release from storage pool (NOT bands)
Decreased stickiness of neuts, ie shift of cells from MNP to CNP.
169
Causes of lymphopenia with steroid administration.
Redist of recirculating lymphs, stay in lymphoid tissue or marrow longer.
Lysis of lymphos in the thymus or LN if long term admin (cortical or uncommited cells, not medullary cells). Effector B and T cells don't lyse.
170
Other causes of neutrophilia in cattle besides corticosteroid release?
```
Abomasal displacement
Mild fever
Ketosis
Dystocia
Feed overload
Indigestion
```
171
Other causes of neutrophilia in horses besides corticosteroid release?
Sustained muscular exercise. Lymphopenia is usually mild to minimal.
172
In what cases will you not have a left shift in a neutrophilia due to inflammation?
Mild inflammation that isn't severe enough.
| Long standing inflammation where production is balanced with usage.
173
What do lymphs and eosinophils commonly do in inflammation or infection?
Lymphopenia and eosinopenia. p68
174
What do monocytes do in inflammation?
Inconsistent finding to have monocytosis.
Stress can cause in dog / steroid induced monocytosis
Certian types of inflammation, ie granulomatous endocarditis.
175
What are the effects of endotoxin on neutrophils early in infection?
Increased adhesiveness of neutrophils, retention of neutrophils in the MNP, subsequent emigration into tissues, its a short term neutropenia and neutrophilia quickly follows.
176
What affects neutrophil count in blood during purulent inflammation?
Rate of release from bone marrow compared with emigration into tissues from the vasculature.
177
What constitutes a left shift in dogs, cats and large animals. (based on neutrophil numbers)
Bands greater than 1000/uL in dogs, cats and birds.
| Greater than 300/uL in LA.
178
Neutropenia with greater than 10% bands means what?
Clinically significant left shift and if bands outnumber segs then its called "degenerative"; if segs outnumber bands then its "regenerative."
179
In what non inflammatory condition may you see a left shift?
IMHA
180
What it called with severe purulent dz where you have marked neutrophilia with left shift that includes myelocytes, progranulocytes or myeloblasts in blood?
```
Leukemoid response (cause it has a similar blood profile to acute granulocytic leukemia.)
WBC counts may exceed 50,000 or even 100,000/uL such as in localized infection like pyometra or pancreatitis and certain forms of parasitism, IMHA, canine leukocytes adhesion deficiency. or even as a paraneopasltic syndrome.
```
181
Common range of WBC counts in dogs and cats?
10,000-30,000/uL
182
Common cause of neutropenia in dogs and cats?
Overwhelming Gram negative sepsis (parvo salmonella etc.) uterus, lung etc.
183
What are inflammatory leukograms in cattle like?
Like dogs and cats up to 4months of age, except less left shift.
Neutropenia is common on cattle but doesn't have as grave a prognosis as in other species.
Fibrinous, non purulent inflammation may show only minimal increase in neutrophil counts instead fibrinogen will be high.
Even when the inflammation is purulent it usually causes leukopenia, and neutropenia with severe left shift and lymphopenia, eventually returning to normal with continued left shift.
Usually WBC counts are lower than in dogs and cats but may get up to 60,000 with some infections like empyema or up to 100,000 with stuff like bovine leukocyte adhesion deficiency.
184
What are inflammatory leukograms like in horses?
Around 7000-20,000/uL, left shifts with neutrophilia are moderrate and with GI dz and endotoxemia like Salmonella may have a severe left shift with leukopenia or a normal leukogram.
Neutrophils responses usually mild so look at the Fibrinogen like in cattle in general.
185
Four other causes of neutrophilia not related to infection.
Immune mediated dz
Hemorrhage
Hemolysis
Neoplasia
186
What is the cause of pseudoneutropenia?
Margination of neutrophils, shift from CNP to MNP, endotoxin can stimulate this and then you get increased emigration of neutrophils from blood eventually causing transition to a true neutropenia.
187
What is the duration of inflammation when you see a neutropenia?
Acute or peracute before the marrow is ramped up, after a couple days granulocytic hyperplasia in the marrow occurs and then you see a response.
188
What are some causes of neutropenia?
EXCESS TISSUE DEMAND; REDUCED GRANULOPOIESIS; INCREASED INEFFECTIVE GRANULOPOIESIS
Radiation, cytotoxic drugs, (may also see thrombocytopenia and anemia)
Dz affecting hematopoietic stem cells (like pancytopenia or aplastic anemia).
Certain viral and rickettsial infections (Panleuk/parvo, FeLV, FIV, ehrlichiosis, endotoxemia.)
Estrogen, Bracken fern, myelopthisis, genetic disorders, drug reactions.
There is also a table on pg 72
189
What is cyclic hematopoiesis?
Autosomal recessive dz in Gray collies. Neutropenia at 11-14 day intervals, also affects RBcs and platelets.
190
What is excessive ineffective granulopoiesis?
Uncommon except in cats with FeLV and myelodysplastic syndrome; there is granulocytic hyperplasia and concomitant neutropenia; the marrow proliferating pool is expanded with a decrease in the maturation and storage pool of neuts (giving appearance of shift toward immaturity).
191
When does monocytosis occur?
May occur with neutrophilia cause both cell lines are derived from a common bipotential stem cell.
May be the most prominent change in leukogram during bacterial endocarditis and bacteremia.
Dz's with suppuration, necrosis, malignancy, hemolysis, hemorrhage, immune mediated, pyogranulomatous dz.
May occur in both acute and chronic stages of dz.
There is no marrow storage pool for monocytes.
192
Tissues commonly affected with eosinophilia?
Mast cell rich tissues like skin, lung, GI tract and uterus.
193
What is hypereosinophilic syndrome?
Think cats and Rottweiler dogs. This may be impossible to distinguish from eosinophilic leukemia. Both have eosinophilia with infiltration in mulitple organs. NOTE most localized inflammatory lesions with eosinophlis are NOT accompanied by eosinophilia in the blood.
194
Two things that cause eosinopenia?
Steroids and Epinephrine/catecholamine.
195
What is the relationship between the number of circulating basophilsa nd tissue mast cells?
Its an inverse relationship.
196
What kind of stuff causes baophilia?
parasitism, Allergic dz, drug reactions, stress in birds, neoplasia. p76 (ie some of the same dzs that cause eosinophilia.) Basophilia without eosinophilia would be rare.
197
Causes of lymphocytosis?
Physiologic response; chronic antigenic stimulation (viral, bacterial, rickettsial, fungal, protozoal etc).
*Hypoadrenocorticism, lymphoid neoplasia.
198
Does antigenic stimulation always cause lymphocytosis?
No, you can have big LNs without lymphocytosis and youc an also have reactive lymphocytes in the blood without having lymphocytosis.
199
If what specific infections in dogs may you see lymphocytosis?
Rickettsial infections like RMSF and canine ehrlhchiosis. Rule out lymphocytic leukemia.
200
What may cause persistent lymphocytosis in cattle?
Non neoplastic manifestation of bovine leukemia virus infection. Viral infection promotes B lymphocyte hyperplasia.
201
When is lymphopenia common?
The leukogram of sick animals.
202
What are some of the mechanisms of lymphopenia?
Corticosteroid induced redistribution.
Acute systemic infection
Viral infection > bacterial infection
Acquired T lymphocyte deficiency (most recirc lymphocytes are T cells and certain infections in neonates)
Immunosuppressive therapy or irradiation.
Loss of lymphocyte rich efferent lymph or afferent lymph
Disruption of LN architecture
Hereditary immunodeficiency (ie SCID or certain T lymphocyte defs., note B lymphocyte defs don't cause lymphopenia but would cause dec. serum Ig concentrations and in SCID you have both B and T decreases.
203
What does it mean if you have a leukogram where immature neuts are outnumbering segmenters?
Its a degenerative left shift and there is overwhelming infection or inflammation and if the degen left shift worsens, it suggests a poor prognosis. Always use absolute cell counts, not percents.
204
What suggests a better prognosis with sequential leukograms?
Disappearance of left shift.
Disappearance of toxic changes.
Resolution of lymphopenia or eosinopenia.
205
What suggests a gaurded or poor prognosis on the leukogram?
Neutropenia is always bad d/t risk of infection
Degen left shift (high tissue demand, outpacing marrow)
Extreme neutrophilic leukocytosis without left shift (leukemoid response) always bad until you rule out granulocytic leukemia.
Persistant lymphopenia.
Marked lymphocytosis until lymphocytic leukemia or lymphoma is excluded.
206
What are the different stages of lymphoma (ie I - V, what do they mean)?
1 - only a single lymphoid organ or tissue involved, excluding bone marrow.
2 - several LNs in a regional area involved
3 - Generalized LN involvement evident
4 - Liver and spleen involved (w/or w/out stage 3)
5 - In addition to primary solid tumor, its in the blood, marrow and/or other organs.
207
Mediastinal lymphoma is usually of what type?
T cell origin
208
What are the laboratory features of lymphoma?
Lymphopenia more common that lymphocytosis.
Leukemic blood profile in 20% of dogs.
Mild anemia
Hypercalcemia due to PTHrP
If they are thrombocytopenic and have marked anemia then likely its in the marrow.
209
With cutaneous epitheliotropic lymphoma what may be a finding in lab data?
Large morphologically abnormal lymphocytes in circulation, its called Sezary syndrome.
210
What is the most common typ eof lymphoid neoplasia in the cat?
Alimentary, followed by multicentric, mediastinal, renal, then other extranodal.
211
In the cat what type of lymphoma is gastric, and small intestinal? (ie B or T?)
Gastric is usually B cell, and small intestinal is T or B cell.
212
Where does large granular lymphoma occur in older cats? Whats the type?
In the Small intestine and its T cell and associated with a leukemic blood picture.
213
What are the characteristics of lymphoma that is mediastinal in cats?
Younger cats, T cell origin and usually FeLV positive.
214
Which pop of cats does spinal lymphoma occur, and nasal lymphoma in cats?
Spinal > Young FeLV positive cats
| Nasal > B cell, older FeLV negative cats
215
What type of lymphoma is FIV associated and where does it occur?
B cell origin, extranodal sites.
216
What may be seen in the hemogram in cats with lymphoma?
Hemogram changes uncommon but may include:
Macrocytic non-regen anemia
Giant platelets
Variable dyspoeisis of neuts and red cells, and /or leukemia
217
What are the characteristics of lymphoma in ferrets?
Its relatively common
Alimentary most common (think older ferrets)
Mediastinal form also occurs (T cell and in younger ferrets as in other species)
Most ferret lymphoma is T cell
May have mild to moderate anemia
218
What are the characteristics of Equine lymphoma?
Multicentric is most common, abdominal LNs affected.
SQ, splenic and mediastinal lymphoma may occur in the horse.
T cell most common; variable morphology and plasma cell and histiocyte infiltrates occur in both T and B cell lymphomas.
Cutaneous may be B or T cell.
Mediastinal is T cell as in other species.
May be indolent and wax and wane with hormone - estrogen and progesterone influences.
