Smith.Ch.37.Diseasesofhematopoeitic and Hemolymph sys Flashcards
acute massive blood loss induces hypovolemic shock characterized by:
tachycardia
tachypnea
cold extremities
pale mucous membranes
muscle weakness
eventual death (resulting from CV collapse)
When do you see changes in PCV or total protein with acute blood loss?
within 12 to 24 hours
Hypovolemic shock should be treated with administration of:
40 to 80 ml/kg of sodium containing crystalloid fluids
Hypertonic saline can be administered at what dose, to temporarily reverse the pathophysiologic sequelae of severe hemorrhagic shock?
2 to 4 ml/kg 7.2% sodium chloride
Why is the total volume of crystalloid solution required is much greater than the volume of blood lost because
crystalloid solutions distribute throughout the extracellular space
Why is blood transfusion viewed as a temporary therapeutic procuedure?
because crossmatch- compatible allogeneic RBCs are removed from circulation by mononuclear phagocyte system (MPS) w/in 2 to 4 days of transfusion
Describe routine blood typing crossmatch:
incubating wash RBCs from donor (major) and recipient (minor) with serum from the other
Why is the first blood transfusion of whole blood to a horse or ruminant, not previously transfused or senstized by immunization or pregnancy usually well tolerated
b/c natural alloantibodies are o flow concentration adn weak activity
Severe anaphylactic reactions to blood transfusion should be treated with
epinphreine (0.01 to 0.02 mg/kg
When does normal bone marrow start to replace cells, in cases of acute hemorrhage?
w/in 5 days
Define hemoperitoneum
accumulation of blood in the abdominal cavity
**can be life threatening
Causes of hemoperitoneum in the horse
trauma
postoperative abdomina lhemorrahge
neoplasia
complications from pregnancy an dfoaling (utero-ovarian, middl euterine, external ilaic artery rupture)
organ rupture
mesenteric injury
coagulopathies
ovarian hemoatoma
systemic mayloidosis
idiopathic hemoperitoneum
The underlying cause of hemoperitoneum is identified in what percentage of cases?
76%
What are the most common causes of hemoperitoneum in horses?
trauma (spleen and in mares, repro tract & assoc vessels)
neoplasia
Hemorrhagic abdominal effusion is characterized by high red cell count of:
RBC> 2, 400, 0000 RBC/microL
PCV >18%
total protein >3.2 g/dL
*normal t high luek count
What are early indicators of hypovolemia d/t acute blood loss?
central venous pressure
blood lactate concentration
Primary goals of therapy in hemoperitoneum
- tx hypovolemic shock
- restore perfusion & O2 delivery to tissues
- correcting fluid deficits
- stopping further blood loss
- preventing complications
Which carries the worse prognosis pre or post partum hemorrhage?
prepartum: 100% vs
postpartum: 20% mortality
Causes of hemothorax in neonatal foals
lacerated lung or vessels from fractured ribs
Is exercise induced pulmonary hemorrhage a recognized caused of major blood loss in horses?
no
Causes for chronic blood loss
bleeding GI lesions
certain renal diseases
hemostati cdysfunction
blood sucking external parasites
haemonchosis (esp goat sand sheep)
Causes of GI hemorrhage
- Neoplasia
Horses: gastric SCC
cattle: abomasal lymphoma - parasitism
- mucosal ulceration
NSAID tox in horses
abomasal ulcers: cattle
Renal sources of chronic blood loss
renal neoplasia (Rare)
congenital renal vascular anomalies (RARE)
idiopathic hematuria
idiopathic recurrent hematuria of Arabian horses
How does iron deficiency anemia develop?
With loss of erythrocyte iron secondary to chronic severe blood loss
** hypoferremia or reduce serum ferritin develops with INC total Fe binding capacity and reduction in marrow iron
What is a good source of iron for patients?
good quality forages
NSAID pathogenesis in right dorsal colitis
inhibit cycolooxygenase – (COX1 than inducible CO2 expressing during state of inflammation
–> causes inhibition of prostaglandin E production
–> hypoxic or ischemic GI mucosal damage and delayed mucosal healing
What 2 components are involved in hemostasis?
- coagulation
- fibrinolysis
function: arrest bleeding from damaged blood vessel and maintain nutrient blood flow
After a blood vessel is damaged, what occurs
vasoconstriction occurs
rapid adherence of plts to subednothelial collage
after rapid adherence of platelets to a damaged blood vessel, then
triggeres aggregation, contraction and granule secretion (basic plaetlet reaction)
What platelet phospholipoprotein provides the necessary surface to catalyze interactions among activate coagulation proteins that result in thrombin formation?
platelet factor 3
What are zymogens?
precursor forms of procoagulant proteins that circulate in the blood
**must be altered during coagulation to become active
When is the extrinsic coagulation system activated?
When lipoprotein tissue factor (TF) gains access tohte bloo stream
Where is tissue factor located?
widely dsitirbuted in most tissues
(endothelial cells * monocytes
When is intrinsic coagulation system activated?
When blood is exposed to a negatively charged surface (e.g. activated platelets)
When factor XII and prekallikrein in the intrinsic coagulation pathway have reciprocal activation, then
the intinstric pathway stimulats formation of numerous inflammatory mediators such as kinins and complement
What is thrombin generated from?
formation of activated factor X (Xa)
Function of thrombin
catalyzed the conversion of fibrinogen to fibrin
promotes plt aggregation
enhances cofactor activities of factor V and VIII
activates factor XIII & protein C
Examples of plasma anticoagulant proteins include:
- serpins: inhibit activate coagulation factors
- protein C system: directed against cofactors V and VIII
- Antithrombin III (AT III): main inhibitor of thrombin and Xa
heparin accelerates which anti-coagulant protien by 2000 fold?
AT III
Function of activated protein C
destroys factors V and VII
** limiting its own activation
** depn on thrombin and entohelial cofactor, thrombomodulin
What is plasmin?
primarily responible for degradation of fibrin
Plasmin exists in plasma as the zymogen
plasminogen
What zymogen has a high affinity for fibrin?
plasminogen
**as well as tissue plaminogen activator (tPA)
What ist he main physiologic inhibitor of plasmin
alpha 2 antiplasmin (alpha 2-AP)
**competes with the binding of plasminogen to fibrin and clot contains equal amounts of both glycoproteins
Why does a blodo clot not lyse spontaneously?
b/c of molar balance betwen alpha 2- antiplasmin and plaminogen
What is a potent stimulus for release of endothelial tpA
stasis of blood upstream fro teh occluded vessel
What is the most important factor that determines the rate of fibrinolysis?
the rate of fibrin formation
Breeds that have prekallikrein deficiency?
miniature hroses in US
belgian horses in Canada
Abnormal blood parameters from horses with prekallkrein deficiency?
prolonged aPTTs
normal PTs
What is the mode of inheritance of prekallikrein deficiency in horses?
likely autosomal recessive
**underlying genetic mutation has not been determined
Measurable deficiencies in factor XI activity have been reported in what breeds?
Holstein cattle (US, Canada & UK)
Japanese Black cattle
Activation of factor XI occurs in what step of coagulation pathway?
intrinsic pathway
** second step
Factor XI deficient Holsteins show what clotting time abnormalities?
normal PTs
prolonged aPTTs
How is Factor XI deficiency inherited?
autosomal recessive trate
What gene encodes factor XI?
F11
What spp & breeds have Factor VIII deficiency?
- horses: thoroughbreds, standardbreds, quarter horses, tennessee walking horses
- cattle: hereferods & japanese brown cattle
sheep: alpine white sheep
Coagulation panel results in a patient with Factor VIII deficiency:
normal PT
prolonged aPTT
Clinical signs of factor VIII deficiency (hemophilia A)
inappropriate bleeding incidents: epsitaxis
petechial hemorrhage
formation of IM hematomas
hemoarthorsis
hemopericardium
hemoperitoneium
prolonged, life-threaning bleeding at sites of invasiv procedures, umbilical cords and castration
Animals with true Factor VIII deficiency should also have normal levels of what other factor?
vWF
Factor VIII deficiency (Hemophilia A) inheritance
X linked and recessive
** clinical dz reportedin male horses and cattle
Treatment of factor VIII deficiency in humans
factor replacement therapy
Prognosis for animals with factor VIII deficiency (hemophilia A)
poor
**most owners choose euthanasia
Von willebrand factor function
stablizes factor VIII in circulation
promotes plt endothelial adhesion at site sof vascular injury
Von willebrand factor deficiency reported in
-a QH filly
-simental cattle- 10 mo Heifer
What are the vitamin K dependent coagulation factors?
factor II, VII, IX and X
Deficiency of vitamin K dependent factors have been reported in?
5 lambs from a flock of rambouillet sheep
coagulation profile of vit K deficient coagulation factors:
prolonged aPPT and pT
Suggested genetic mutation results in vit K
deficient coagulation factors in sheep?
autosomal recessive
**single nucleotide polymorphism exon 4 of the gene encoding y-glutamyl carboxylase (GGCX)
**mutation creates a STOP codon leading to premature termination of the protein
Fibrinogen deficiency has been reported in what spp?
Saanen kid (goat)
border leicester lamb
Clinical coagulation tests for vitamin K dependent coagulation factors cannot be differentiated from what other deficiency in the coagulation cascade?
fibrinogen deficiency
Describe the steps in the coagulation cascade:
Define Thrombasthenias
rare
inherited defectsin platelet function
result in spontaenous or excessive bleeding
Thrombastenias coagulation panel
normal aPTT, PT and plt count
**INC plt or buccal mucosal bleeding times
Glanzmann Thrombasthenia
quantitative or qualitative deficiencies of the plt membrane integrin alphaIIbBEta3 (glycoprotein IIb-IIIa)
-alpha11b and Beta3 proteins: expressed by separate genes & form heterodimers that bind fibrinogen and mediate plt aggregation
Glanzmann Thrombasthenia: platelet dysfunction
unable to aggregate in response to collagen or ADP
** blood forms loose clots with limited serum separation & decreased tensile strength
Glanzmann Thombasthenia has been reported in what breeds?
-thoroughbred cross gelding– homozygous mutation in exon2
-Quarter horse filly- heterozygous or exon 2 missense mutation & 10 base pair deletion in second ITGA2B allele
-Peruvian Paso horse
-Oldenburg filly: homozygous for distinct missense mutation in exon 2
Recommendations for owners of Glanzmann thrombasthenia horses?
-alert for signs of bleeding requiring supportive care
-regularly monitor for anemia
Atypical equine thrombasthenia is a case report in
1 thoroughbred filly
What is atypical equine thrombasthenia?
AET plts have significantly reduced fibrinogen binding & limited prothrombinase activity & reduced factor V released from AET plt alpha grnaules
Simmental Hereditary Thrombopathy: blood has what:
diminished clot retraction
reduced aggregation in response to ADP or collagen
**SHT platelets fail to aggregate in response to the calcium ionophore A23187
Bovine Chediak Higashi Syndrome is characterized by
abnormal secretory granules in plts, leuks, & melanocytes
Bovine Chediak Higashi syndrome has been identified in what breeds?
Holstein
Brangus
Japanese Black cattle
Pathogenesis of Bovine Chediak Higashi syndrome that leads to bleeding
Dense granules have markedly reduced the ADP content & release disproportionately less ADP– plts aggregate normally in reponse to ADP
**CHS plts have slow & transient aggregation in response to collagen
Bovine Chediak Higashi syndrome gene mutation
Missense mutation in gene encoding protein lysosomal trafficking regulator LYST
**autosomal recessive- 8.8% Japanese Black cattle were carriers
Clinical signs of Bovine Chediak Higashi Syndrome
-hypopigmentation of skin, hair & eyes
-photophobia
-increased susceptibility to infection
**present with infections or inapprorpiate bleeding
Define vasculitis
inflammation and necrosis of blood vessel walls, regardless of size, location or cause
Cause of vasculitis in large animals:
secondary to manifestation of a primary infectious, toxic or neoplastic disorder
**has characteristics of the hypersensitivity vasculitis in humans
Clinical manifestations of vasculitis
-demarcated areas of dermal or subcutaneous edema
- infarction, necrosis and exudation
-hyperemia, petechial and ecchymotic hemorrhages
-ulceration of mucous membranes
–>besides skin can occur in any organ system: lameness, colic, dyspnea, and/or ataxia
Name examples of vasculitis syndromes with predominant cutaneous involvement
equine purpura hemorrhagica (EPH)
equine viral arteritis (EVA)
equine infectious anemia (EIA)
equine granulocytic anaplasmosis (EGA)
Definitive diagnosis of vasculitis involves:
histopathology of involved vessels
**full thickness punch biopsies
Define purpura hemorrahgic
noncontagious disease of horses characterized by vasculitis leading to extensive edema and hemorrhage of the mucosa and subcutaneous tissues
What bacterial organisms have been known to cause/lead to purpura hemorrhagica?
Streptococcus equi (**Vaccination against S. equi)
Streptococcus zooepidemicus
Rhodococcus equi
Corynebacterium pseudotuberculosis
Clinical signs of equine purpura hemorrhagic usually occur within what time frame of development of respiratory infection?
2 to 4 weeks
What age range are commonly affected by equine purpura hemorrhagica?
young to middle aged horses (mean 8.4 years, range 6m to 19 yrs)
Predominant clinical signs of purpura hemorrhagica
subcutaneous edema of all four limbs
lethargy
anorexia
fever
hemorrhages on mucous membranes
tachycardia
(other C/S: tachypnea, reluctance to move, serum exudation from the skin, colic, epistaxis).
The predominant laboratory abnormalities seen with Equine purpura hemorrhagica?
anemia
neutrophilia
hyperproteinemia
hyperfibrinogenemia
hyperglobulinemia
elevated mm enzymes
thrombocytopenia–Rarely seen
Skin biopsy of equine purpura hemorrhagica
acute luekocytoclastic or nonluekocytoclastic vasculitis with necrosis of blood vessels
-marked dermal and subcu hemorrhage, protein rich edema, multifocal areas of dermal infarction
What immune complex deposition on blood vessel walls have been identified in Equine purpura hemorrhagica?
IgM or IgA ,strep M protein (type III hypersensitivity rxn)
what are the 4 types of hypersensitivity reaction
Horses with infarctive purpura hemorrhagica present with clinical signs of:
colic
lameness
muscle swelling
stiffness
Horses with infarctive purpura hemorrhagica may have what changes on bloodwork?
high CK values
What is the recommended treatment for purpura hemorrhagica?
Antibiotics (penicillin)
hydrotherapy/limb bandages/light exercise (handwalks)
IV fluids
Prolonged treatment with corticosteroids (2-4 weeks)
Corticosteroid treatment regimen recommended for treatment of Purpura hemorrhagica?
**minimum of 2 to 4 weeks
* dexamethasone: 0.04 to 0.2 mg/kg IV q24 (morning)
*prednisolone: 0.5 to 1 mg/kg PO q24 (morning)
Possible complications of purpura hemorrhagica
skin sloughing
laminitis
cellulitis
pneumonia
diarrhea
What is the prognosis for purpura hemorrhagica?
fair with early aggressive therapy & supportive care
-retrospective: 53 horses: mortality rate of 7.5%
Equine viral arteritis (EVA) is an infectious disease characterized by:
pan vasculitis
edema
hemorrhage
abortion in pregnant mares
Equine viral arteritis describe the infectious organism:
enveloped, spherical, postive stranded RNA virus (diamter 50 to 70 nm)
-nonarthropod borne virus
Equine viral arteritis virus epidemiology
order: nidovirales
family: ARterivridae
Equine viral arteritis clinical signs:
pyrexia
lethargy
anorexia
limb edema
stiffness
rhinorrhea
epiphora
conjunctivitis
rhinitis
abortion
edema (periorbital, supraorbital, ventrum, mammary gland, scrotum or limbs)
Other: urticarial rash, abortion, resp signs, ataxia, mucosal eruptions, submaxillary lymphadenopathy and intermandibular and shoulder edema
With natural exposure to Equine viral arteritis (EAV) , what is theepidemic abortions rate?
abortion rate: <10% to >60%
Abortion due to Equine viral arteritis occurs in what months of gestation?
3 to 10 months
Do mares infected with Equine viral arteritis become chronic shedders and have fertility problems?
No
What is the pathogenesis of EAV in blood vessels?
localized in endothelium, medial myocytes and pericytes
– virus causes vasculitis with necrosis of the tunica media, abundant vascular and perivascular lymphocyte & lesser granulocytic infiltration with karyorrhexis, loss of endothelium and formation of large fibrinocellular stratified thrombi
How is EAV transmitted?
aerosols from respiratory, urinary, or reproductive tract secretions of acutely affected animsl
**semen from persistent infected stallions
Does EAV remain viable in frozen semen?
Yes (fresh, chilled and frozen semen
Is transmission of EAV through fomites possible?
yes
With natural exposure to EAV does it cause short or long term immunity?
Long-term immunity
How long does it take for mares/geldings to eliminate the infection?
w/in 60 days
What percentage of acutely infected stallions become persistently infected?
30 to 60%
In stallions where is the virus maintained?
w.in the accessory organs: ampullae, vasa deferentia
Seroprevalence for EAV is common is what breeds?
standardbred
warmblood breeds
** has been recently estab. in Quarter horses
How can EAV be diagnosed?
virus isolation
viral nucleic acid (PCR)
serology
How can a diagnosis of EVA be made on serology?
fourfold or more increase din serum neutralizing antibodies between acute and convalescent samples (3 weeks apart)
Stallions that test with a positive titer of 1:4 should be tested for persistent infection by virus isolation from what sample?
sperm rich ejaculate
Prior to vaccination of stallions for EAV, what should be performed?
Should have serum submitted to a US department of Agriculture (USDA) approved laboratory to confirm seronegative status
After a stallion is vaccinated for EAV, what should then be performed?
Horses should be isolated for 28 days
**can potentially shed the virus (MLV vaccine)
Is there evidence that vaccinated stallions become carriers?
No
Anaplasma phagocytophila describe appears within neutrophils/eosinophils
vacuoles/ inclusion bodies (1.5 to 5 miccrom in diameter) in cytoplasm
-pleomorphic
-contain one or more coccobacillus or large granular aggregates (morulae)
Anaplasma phagoctyophila cases in horses most commonly occur during which season (s)
late fall
winter
spring
Is Anaplasma phagocytophila considered zoonotic?
Yes- human infection can occur via tick bite or transmission of infected blood
What are the vectors of Anaplasma phagocytophila ?
Ixodes pacificus- California
Ixodes scapularis- eastern and midwestern US
Ixodes ricinus- Europe
What are potential/proposed reservoirs for Anaplasma phagocytophila?
white footed mice
chipmunks
white tailed deer
dusky footed wood rats
cervids
lizards
birds
Anaplasma phagocytophila: observed pancytopenia is thought to be caused by:
cytolysis
induction inflammation
cell sequestration
consumption
desruction
Clinical signs of Anaplasma phagocytophila
early signs: FUO, partial anorexia
reluctance to move
fever (102.9-106.3F)
mild to mod tachycardia (50 to 60 bpm)
decreased appetite
limb edema
petechiation
icterus
weakness
ataxia
recumbency
What is the incubation period for Anaplasma phagocytophila?
Believed to be less than 14 days
What is the prepatent period for Anaplasma phagocytophila in experimental exposure to infected ticks or inoculation with infected blood?
experimental exposure to infected ticks: 8 to 12 days
inoculation with infected blood: 3 to 10 days
Anaplasma phagocytophila clin path abnormalities:
anemia
leukopenia characterized by granulocytopenia and lymphopenia
thrombocytopenia
What is the definitive diagnosis of Anaplasma phagocytophila?
morulae w/in the cytoplasm of neutrophils and eosinphils
OR
positive PCR assay in peripheral blood
False positive Anaplasma phagocytophila morulae can occur with
Dohle bodies in toxic neutrophils
What does a four fold increase in IFA titer for Anaplasma phagocytophila mean?
confirms recent exposure
Pathologic findings of Anaplasma phagocytophila
petechiae and ecchymosis of subcu tissue
edema of ventral abdomen, limbs and prepuce
proliferative and necrotizing vasculitis, thromboses and perivascular cuffing in sucu tissue, fascia, kidneys, heart, brain, lungs, ovaries and testes
What is the treatment of choice for Anaplasma phagocytophila?
oxytetracyline: 7 mg/kg
or doxycycline
Anaplasma phagocytophila if left untreated, resolves in what time frame?
in 2 to 3 weeks if left untreated
Prevention for Anaplasma phagocytophila?
tick control
Mechanisms of thrombocytopenia
- decreased production
- abnormal sequestration (spleen)
- inc consumption or destruction
At what level of thromboctyopenia can spontaneous hemorrhage start to occur?
<10,000/uL
When is prolonged bleeding from wounds, injections, or surgical procedures and propensity to form hematomas after minor trauma seen?
<40,000/uL
Persistent life-threatening hemorrhage due to thrombocytopenia can be treated with transfusion of what biologic products?
fresh whole blood
platelet rich plasma (preferable)
Causes of Immune mediated thrombocytopenia
- primary
- secondary
drug administration, neoplasia or other immunologic disorders (EIA lymphoma, autoimmune hemolytic anemia)
Thrombocytopenia in a horse, with obvious primary disease should the prompt a workup to rule out what disease process?
DIC
Alloimmune thrombocytopenia of neonates include clinical signs of
depression
loss of suckle
a bleeding tendency
blood loss
rapidly developing anemia d/t profound thrombocytopenia
Alloimmune thromboctyopenia in foals results from what?
*multiparous dams
* immunoglobulins form mare, found in her plasma, serum and milk bind to the foal’s platelets
Differentials for alloimmune thrombocytopenia in foals include
neonatal sepsis
neonatal maladjustment syndrome
neonatal isoerythrolysis
Laboratory abnormalities associated with alloimmune thrombocytopenia
severe thrombocytopenia (<40,000/L)
prolonged bleeding time
abnormal clot retraction
normal thrombin time, PT, APTT, plasma fibrinogen
+/- INC FDPs (fibrin degradation products)
In IMTP what is seen on bone marrow aspirate or biopsy?
megakaryocytic hyperplasia
Definitive diagnosis of IMTP
demonstration of INC quantities of plt assoc IgG or C3 or anti-plt activity in serum
**flow cytometry (detect plt surface assoc IgG (PSAIgG)
Without PSAIgG testing, the diagnosis of IMTP can be made based on:
small vessel hemorrhagic diathesis and severe thrombocytopenia in a horse with normal coagulation times & no other evidence of DIC
**response to therapy– supports diagnosis
pathogenesis of IMTP
plt destruction mediated by antibodies coating the plt surface that cause premature plt removal from circulation by MPS
In secondary IMTP pathogenesis is
Ig bound to plt surface is part of an immune complex composed of antibody that directed against a drug, microbe or neplastic ag
**nonspecifically attached to plt Fc receptor
Thromboctypenia caused by the chrysotherapy (gold therapy) may persist for how long after discontinuation of therapy?
weeks to years
Why is the spleen the major site of plt phagocytosis?
- much antiplt antibody is secreted locally
- more than 30% of circulating plts are normally stored there
- stagnant splenic blood flow allows sensitized plts to pass slowly through a dense network fo phagocytic cells
Effect of treatment with corticosteroids for IMTP?
improve capillary integrity
impair clearance by the MPS
decrease number and avidity of macro Fc receptors
impair antiplt ab production
impede plt ab interactions
inc thrombocytopoeisis
Blood coagulation proceeds with what 3 key reactions:
- formation of activated factor X
- formation of thrombin
- formation of fibrin
The pathologic process of DIC is described as
widespread fibrin deposition in the microcirculation and development ofhemorrhagic diathesis caused by the consumption of procoagulants and hyperactivity of fibrinolysis
DIC in large animals is described in association with what other disease processes:
localized or systemic septic processes
neoplasia
Gi disorders
renal disease
hemolytic anemia
what renal disease is caused by DIC
ischemic cortical necrosis followed by acute tubular necrosis
Negative effects of DIC can be seen in which organs?
GIT (microvascular thrombosis)
Renal (acute tubular necrosis)
Pulmonary (micorvascular thombrosis, uncommon in lg animals)
CNS (neurologic signs, uncommon in lg naimals)
Lamina (digital ischemia)
What diseases must be differentiated from DIC:
IMTP
wafarin toxicosis (horses)
moldy sweet clover toxicosis
inherited coagulation abnormalities
Diseases initiate DIC by what 2 major mechanisms?
- generation of excessive procoagulant activity within the blood
- contact of blood with abnormal surfaces
Gram negative endotoxins stimulate DIC through
direct factor XII activation
cytokine production by mononuclear phagocytes
What is the net result of any triggering mechanism for DIC is
exaggerated generation of systemic thrombin which causes widespread microcirculatory thrombosis
What are the effects of thrombin in DIC:
-activates factor XIII to render fibrin more resistant to fibrinolysis
-enhances cofactor actiity of factors V and VIII
-induces plt aggregation and exposure of plt phospholipid
In DIC plasmin contributes to factor consumption by destorying factors:
V, VIII, XIIa, IX, XI
**in addition to fibin and fibrinogen
Plasmin contributes to factor consumption in DIC by destroying factors
V, VIII, XIIa, IX and XI
The macrophage system in the liver and spleen play a vital role in pathogenesis of DIC, how?
Tissue fixed macro normally remove FDPs & activated clotting factors, until their rate of formation exceeds the ability of ht eMPS to clear them
IV fluid administration in the treatment of DIC
helps prevent organ dysfunction after microvascular thrombosis & correct existing acid-base or electrolyte imbalances
Flunixin meglumine treatment in DIC
mitigates the effects of endotoxin caused by eicosanoids an dused at dose of 0.25 mg/kg IV q8h
Corticosteroids int he tretmetn of DIC
reduce phagocytic action of the MPS and potetniate hte vasoconstrito effects of catechoalmines
What can be administered if DIC is causing life threatening hemorrhage (rare in lg animals)?
fresh plasma (15 to 30 ml/kg) to replace used coagulant and anticoagulant proteins
What can be administered to stall disseminated microvascular thrombosis that precipitates organ failure in DIC?
low molecualr weight heparin
For heparin to work in the treatment of DIC, what must be true?
appropriate ammounts of ATII, which is necessary for heparin to work and is often depleted by DIC
What are clinical signs of warfarin toxicosis in horses?
hematomas
ecchymosis of mucous membranes
epistaxis
hematuria
How are horses potentially exposed to warfarin?
rodenticides
** used to be a tx for horses with navicular dz
Coagulation panel abnormalities with warfarin toxicosis
prolongation of PT (earliest sign)
APTT becomes prolonged eventually
+/- blood loss anemia and hypoproteinemia
The diagnosis of warfarin toxicosis is made by:
history of exposure
clinical signs of large vessel hemorrhagic dithesis
prlonged PT w/ or w/o APTT
Mechanism of Warfarin toxicsosi
-competitive inhibition of vitamin K– necessary for liver production of clotting factors II, VII, IX and X
Which clotting factors require the presence of vitamin K?
II, VII, IX and X
What are drugs/factors that can enhance warfarin toxicosis/unbinding from protein?
- phenylbutazone– allowing greater proprotion of administered drug to be unabound and active
- hypoalbuminemia– “”
- corticosteroids and thyroxin– inc receptor affinity and clotting factor catabolism
- barbiturate, rifampin, chloramphenicol– induce hepatic microsomal enzyme activity that can accelerate warfarin metabolism & reduce
therapeutic response to a given dose - reduction of Vitamin K in diet
- liver disease
Treatment of warfarin toxicosis
Vitamin K1 (0.5 to 1 mg/kg Sc or IM) every 6 hours until PT is normal and stable
fresh plasma (provide clotting factors)
Which vitamin K drug should not be used in horses (in regards to treatment of warfarin toxicosis)?
Vitamin K3– b/c it has poor therapeutic action & highly nephrotoxic for hosres
warfarin is what kind of anticoagulant
coumarin derivative
What is a natural coumarin that horses can be exposed to that causes toxicosis?
moldy sweet clover (Meliltous spp) or silage containin dicoumarol
Natural coumarins in sweet clover can be converted to
dicoumarol when hay or silage isi mproperly cured adn old forms
Early signs of Sweet clover toxicosis
epistaxis
melena
subcu hematomas
periarticular swellings
***visible swelling at points of trauma
Sweet clover toxicosis is most commonly seen which geographic location?
Northern Plains states
Clinical pathology abnormalities associated with sweet clover toxicosis:
prolonged PT (earliest abnormalities)
plt count normal
Pathogenesis of moldy sweet clover toxicosis
Identical to warfarin toxicosis:
Dicoumarol interferes with hepatic synthesis of clotting factors II, VII, IX and X by inhibiting vitamin K
Moldy sweet clover toxicosis appears in cattle how many days after ingestion?
within 2 to 7 days
**lower levels of dicoumarol (<70 mg/kg) in feed may prolong the onset of signs for up to 3 months
What si the toxic level of dicoumarol in sweet clover ?
10 mg//kg of feed
Is grazing sweet clover dangerous?
No, b/c of its high forage yield, usually harvested as silage, which should carry less danger of molding when properly cured
List infectious causes of Hemolytic Anemia:
Parasitic:
- Anaplasmosis
-Babesiosis
-Hemobartonellosis
-Eperythrozoonosis
-Theileriasis
-Trypanosomiasis
Bacterial:
-Leptospirosis
-bacillary hemoglobinuria
Viral:
-Equine infectious anemia (EIA)
list causes of immune mediated hemolytic anemia
Autoimmune hemolytic anemia
neonatal isoertyrholysis (NI)
Drug induced: penicillin, trimethoprim-sulfamethoxazole
list causes of heinz body hemolytic anemia
phenothiazine toxicity
wild onion poisoning
red maple leaf poisoning
List less common causes of hemolytic anemia in large animals
severe cutaneous burns
L-tryptophan indole intoxication
water intoxication
post-parturient hemoglobinuria
copper poisoning hemolytic syndrome in horses with liver failure
erythropoietic porphyria in Holstein cattle
Several common clinical signs are seen in animls with severe hemolytic anemia, regardless of teh cause, what are those:
mucous membrane pallor
fatique
depression
anorexia
Icterus seen with hemolytic anemia is dependent on:
rate of red cell destruction
liver’s ability to exrete bilirubin
What are signs of enhanced erythropoietic response:
anisocytosis
polychromasia
reticulocytosis
presence of nucleated red blood cells in circulation
What is the life cycle of Anaplasma within a tick?
Enters the midgut epithelial cell, completes the first round of replication
– migrates to salivary epithelial cells & undergoes second round of replication
–enters saliva– where can be passed to another host
In regards to Anaplasma, what does it mean that organisms can be transmitted transtadially?
from larvae to nymps and nymphs to adults
**indicating that ticks can becom infective and transfer anaplasma spp toa new host after only a single molt
When are clinical signs of anaplasma seen (in regards to percentage of red cells infected)?
when >15% of rbcs are infected
Bovine anaplasmosis:
anemia occurs because of:
splenic and hepatic macrophage mediated phagocytosis fo infected erythrocytes
Anaplasma marginale expresses a variety of major surface proteins, which accounts for what immunologically?
allow sfor different bacterial surface strcutures leading to immune evasion and persistent infection in the animal
Bovine anaplasmosis: protective immunity requires what?
induction of both antibody against ht eouter membrane proteins and macrophage activation for enhance pahcytosis and bacterial killing
Bovine anaplasmosis: whlie the immune system controls the acute phase of infection– organisms are not complete cleared from blood due to
emergence of antigenic variants
Bovine anaplasmosis: infected animals demonstrate cyclic subclinical peaks of rickettsemia and immune response every:
6 to 8 week period
Bovine anaplasmosis, A. marginale: In the United State infection is endemic where:
West, Midwest and SE
Bovine anaplasmosis: endemic regions are maintained by
prevalence of competent tick vectors and persistently infected carrier cattle
What role do wild ruminants play in the transmission of anaplasma?
unkonwn role?
Bovine anaplasmosis: incubation period
10 to 30 days (as long as 60 days)
Bovine anaplasmosis: calf exposure clinical signs
lethargy
anorexia
24 to 48 hours
Bovine anaplasmosis: adult acute disease
**highly susceptible
high fever (103 to 106)
tachycardia
tachypnea
anorexia
lethargy
dec milk production )9dairy cows)
Bovine anaplasmosis: why do cattle stagger or become aggressive?
as a result of cerebral hypoxia associated with anemia
Does hemoglobinuria occur with Bovine anaplasmosis?
No because hemolysis occurs extracellularly
differential diagnosis for Bovine anaplasmosis:
**dzes produce anemia and or icterus
babesiosis, bacillary hemoglobinuria, leptospirosis
hepatotoxic plant poisonings (Senecio)
chemical
other causes of liver disease
copper poisoning in sheep
Bovine anaplasmosis: what occurs if animal survies the acute crisis?
recovered animals remain carriers for life & serve as a reservoir for ongoing transmission
Does Anaplasma ovis cause severe disease in sheep?
usually asymptomatic
** can cause anemia esp in immunosuppression
Bovine anaplasmosis: On necropsy what is a common pathology seen?
splenomegaly
Bovine anaplasmosis: what sample can be sumitted to confirm diagnosis?
detection of A marginal infected rbcs within capillaries of Giemsa stsianed histo sections
Definitive diagnosis of acute anaplasmosis requires
Identification of A. marginale or A ovis infected rbcs by microscopic exam
OR
PCR of aniamls with severe anemia
What is used for official testing of anaplasma by many regulatory agencies?
competitive enzyme linked immunosorbent assay
**high sensitivity and specificity
Bovine anaplasmosis: what are the antibiotics of choice?
tetracyclines
what are vaccine control measures for available Bovine anaplasmosis?
-endemic regions: beef cattle allowed to become infected at a young age
- live vaccine licenses in Australaia, AFrica, Asia and central and south america (not USA)
-killed vaccines are less efficacious and reqmultiple immunizations (licenses in 14 states)
Bovine anaplasmosis: control measures besides immunoprophylaxis
-quarantine and serologic screening using cELISA
-strategic use of pastures, insecticides and management of herd additions
-prevent iatrogenic transmission
Acute babesiosis is characterized by
fever
hemolytic anemia
icterus
hemoglobinuria
death
Babesia bigemina characteristics
appears in mature rbcs as nonpigmented, paired, pear shape bodies joined at an acute angle
irregularly shaped, round, or amoeboid forms also seen
babesia bovis characteristics
small, pleomorphic
signle round body or paired pear shaped bodies joined at an obtuse angel within mature RBCs
B. bovis vs B. bigemina
B. bovis is the most virulent
Natural transmission of B. bovis and B. bigemina
ticks from the genus Boophilus
Life cycle of Babesia within the tick
Ticks infected transovarially (vetrically)
-female infected by ingestion of parsaite during engorgement
-babesial orgnaisms reproduced /win tick- reproducign organsims incorporated withind eveloping tick embryos
-babesia transmittedt o new certebrate hosts by feedign of ensuing tick larvae nymphs or adults
Larval ticks can trasmit what species of babesia?
B. bovis
**not B. bigemina– not transmitted until the larvae have molted into the nymphal or adult stages
Can Babesia bovis and bigemina be transmitted iatrogenically?
yes
Incubation period Babesia bovis and bigemina
less than 5 days to 3 weeks
Babesia bovis and bigemina cause of anemia
IV dstruction of erythorcytes by escaping merozoites following intraerythorcytic reproduction of the babesia by binary fission
With Babesia bovis and bigemina, why can massive lysis occur even though the parasitemia may be less than 1%?
because osmotic fragility of the whole RBC population increases terminally
immune mediated condition may result in the spleen removing adamged and healthy RBCS from circulation
Babesia bovis and bigemina: what causes the clinical signs of emtabolic acidosis and anoxia?
parasite associated proteolytic enzymes are released into hte plasma– interact with bood components
Clinical signs of cerebral babesiosis
hyperexcitability
convulsions
opisthotonos
coma
death
what is the pathogenesis of cerebral babesiosis?
anoxia and or RBC blockage of cerebral capillaries
All cattle breeds are susceptible to babesiosis, but what breeds exhibit a degree of resistance to Babesia bovis and bigemina?
bos indicus breeds
Which spp have a natural immunity to babesiosis?
calves
Why are calves resistant to babesiosis
-suspect maternal immunity
RBCS contain factors indepednet of ab that provide an innat eresistance to severe babesiosis
What happens with calves infected with babesios under 9 months of age?
minimum reaction to dz and become asymptomatic carriers
How long do carriers remain resistant to babesiosi clinical disease?
at least 4 years
Babesia bovis and bigemina: carrier state can be over come by:
stress such as calving, malnutrition or concurrent disease
What are other conditions that may exhibit some of the same signs as babesios
anaplasmosis
trypanosomiasis
theileriosis
leptospirosis
chronic copper toxicity
bacillary hemoglobinuria
When can Babesia spp be detected in smears made from peirpheral blood?
in acute infection
A positive diagnosis of Babesia requires?
Giemsa stined thin blood smears
positive serology (IFA, ELISA< CF)
PCR
B bovis favors capillaries in what locations?
brain and kidney– b/c major energy producing pathway of Babesia is anaerobic glycolysis
Postmortem findings on cattle that die peracutely of babesios
characteristic of acute hemolytic crisis
Prognosis for babesios
Poor: hemoglobinuria or cerebral signs
PCV>12% respond well to treatment
What are beneficial control measures for prevention of babesiosi
eradication of boophilus tick vectors effect control in USA
– reduce tick ifnestations: controlled range burning, cultivation, prolonged pasture rest, use of repellents
Piroplasmosis of the horse is caused by what organism?
Babesia caballi and Theileria equi
What is a unique characteristic of T. equi
intraerythrocytic parasites divide into four cells to forma Maltese cross
Babesia caballi and Theileria equi are transmitted by
ticks of genera:
Dermacentor
Hyalomma
Rhipicephalus
Life cycle of B caballi in tick?
passed transovarially (vertically) from one tick generation to the next
Life cycle of T. equi in tick?
only transstadially (horizontally): one tick stage (larvae or numphs) becomes infected and dz agent is passed to the enxt certebrate host in the next tick stage (nymph or adult)
What species is naturally infected with Theileria equi?
zebras in africa
Babesia caballi and Theileria equi survivors become
chronic carriers
Babesia caballi and Theileria equi incubation period
5 to 28 days
Babesia caballi and Theileria equi clinical signs
hemolytic anemia
jaundice
hemoglobinuria
death
generalized signs: depression, anorexia, incoordination, lacrimation, mucous nasal discharge, welling of eyelids and freq lying down or are seen
Difference in clinical disease between Babesia caballi and Theileria equi
Theileria equi: most pathogenis and responsible for greater incidence of hemoglobinuria and death
Babesia caballi: more persistent fever and anemia
Differential diagnosis for Babesia caballi and Theileria equi
equine monocytic ehrlichiosis
EIA
liver fialure with hemolytic anemia
other hemolytic anemias of the horse
What is the official tesing method for Babesia caballi and Theileria equ?
cELISA test
PCR available
Babesia caballi and Theileria equi post mortem features:
similar to hemolytic crisis, jaundice is prominent
What is the drug of choice for eliminating the carrier state of animals infected with Babesia caballi and Theileria equi
imidocarb
higher doses– cause colic in horses
Control of Babesia caballi and Theileria equi?
control of tick infestation does much to reduce disease incidence
** no vaccines available
Diagnosis of Babesia caballi and Theileria equi in the US
veterinarian can enroll the horse in the USDA controlled treatment program
Haemobartonella bovis is located where on teh rbc?
epicellular organism that is closely associed with the surface of erythrocytes
**may appear as a rode shape, an ovoid or in chains wtih conventional stains
Does haemobartonella bovis cause anemia?
Rarely
Eperythrozoon wenyonii (mycoplasma weyonii) infection causes
in normal cattle– usually latent & not assoc with clinical signs
if C/s– causes mild depression ,fever and modest anemia
Mycoplasma ovis (epertythrozoon ovi) can produce what clinical sigsin sheep?
profound depression anemia
significant death loss in young lambs
Theileriasis is caused by?
a small hemoparasite of the genus Theileria tha tinfects lymphocyte and erythrocytes of ruminants
Theileria is most common seen in what locations?
tropical and subtropical climates
Theileria is spread by
blood sucking arthropods
**particularly Ixodidae family
What is the cause of East coast fever?
Theileria parva
**highly fatal disease in Africa
Describe trypanosomes
flagellated protozoal organism
Trypanosoma congolensi causes what disease in cattle in africa?
Nagana
Trypanosoma theileri (Trypanosoma americanum) is seen in north america, and is usually pathogen or nonpathogenic?
nonpathogenic
Leptospira infections that produce hemolytic syndrome are seen with what species?
most commonly calves and lambs
Bacillary hemoglobinuria is caused by
Clostridium haemolyticm (clostridium novyi type D)
Where is bacillary hemoglobinuria endemic?
in poorly drained areas of the western United States
Pathognesis of bacillary hemoglobinuria?
organism finds a favorable environment for development in areas of pre-existing liver damage most often have been produced by migrating liver flukes
–>bact produce a focal liver lesion
Clinical manifestation of bacillary hemoglobinuria?
severe depression
anorexia
fever
hemoglobinemia
hemoglobinuria
**develop C/S rapidly
**death loss are often seen
Equine infecitou sanemia virus (EIAV) epidemiology
family: Retroviridae
Genus: lentivirus
**RNA virus
Pathogenesis of EIAV
–uses virally coded reverse transcriptase to convert RNA genome to a DNA intermediate that is integrated into the shot’s genome by another virally encoded enzyme integrase
-integrated DNA (provirus) usurps the host cell to replicate its genome, manufacture viral proteins and assemble the virally encoded proteins into virionsthat bud from the cell
**results in lifelong infection
he test for identificaiton of EIAV equids that are seropositive?
the Coggins test AGID and ELISA
Most horses with EIAV have what clinicals signs?
most are inapparent arriers and are healthy
How can EIAV be transferred?
blood transfered from an inapparent to carrier: instruments, blood products or by insect vectors
The clinical form of Equine infectious anemia is characterized by three defined temporal stages:
- acute
- chronic
- Inapparent
Acute stage of Equine infectious anemia:
high fever
thrombocytopenia
nonspecific signs of malaise (lethargy and inappetence)
+/- ecchymoses or petechiae
Chronic stage of Equine infectious anemia
C/s during episodes of viremia and clinical quiescnece & low viremia
Inapparent stage of Equine infectious anemia
once levesl fo ciremia are immunologically contained and no c/s are detected
What can precipitate clinical disease of Equine infectious anemia?
Episodes of stress
Corticosteroids
Which horses pose the biggest risk of transmision to uninfected horses?
horses with high-titered viremia
EIA: What mechanism of viral replicaiton allows for generation of viral variants that differ genetically from preexisting ones?
DNA dependent RNA polymerase (reverse transcriptase) that imisincroporates nucleotides, resulting in changes in teh viral genoma
Pathogenesis of EIAV in DIC/thrombi formation
EIAV replication in endothelial cells may play role in DIC by viral damage to endothelial cells–> exposure of subendothelial–> plt aggregation and formation of thrombi
–> tissue edema by transudation of fluid from compromised small vessels
EIA: clinpath during clinical disease
profoudn thrombocytopenia
– progression to DIC
EIA in chronic infections: clin. path
anemia– d/t intravascular hemolysis, extravascular hemolysis and depression of bone marrow erythropoiesis
Clin path during the inapparent stage of infection of EIA
inc plasma total solids and globulin concentrations
mild anemia
dec albumin concentrations
What are high risk regions for EIA in teh US
Texas Oklahoma lousiana and Arkansas
States are considered as low risk for EIA in the US
mid-Atlantic area, New England, Alaska, Hawaii
Pathogenesis of autimmune hemolytic anemia
-antibodies combine with complement and antigens on red cell membrane–> lead to rapid removal of affected cells from circulation
Clinical signs of severe hemolytic anemia (IMHA)
marked anemia (PCV<15%)
depression, pale mucous membranes, variable icterus, elevated heart and respiratory rate and variable to intermittent fever
Secondary autoimmune hemolytic anemia in horses has been associated most often with what other primary problems:
purpura hemorrhagica
lymphoma
other neoplasms
protein losing enteropathy
chronic bacterial infections
What drugs have been associated with IMHA in hroses?
procaine penicillin
trimethoprim sulfamethoxazole
What does the direct Coombs test detect?
presence of antierythrocyte antibodies and/or complement on teh red cell memrbane
False negative results to the Coombs test are possible and occur due to
low concentrations of antibody
low binding ot he red cell membrane
prior to treatmetn with corticosteroids
Autoimmune hemolytic anemia has rarely been reported in alg animals but can is due to a secondary problem such as
- association with certain types of neoplasia
- with a variety of viral, bact, rickettsial and protozoal infections
- following exposure to certain drugs
- in assoc with other immune mediated disorders like systemic lupus erythematosus
Initiating factors for autoimmune disorders are not completely understood but may related to
alterations in red cell membrane through direct or indirect injury–> elcits abnormal resposne by the immune system
Most commonly affected red cells are removed form circulation at a rapid rate by what ?
reticuloendothelial system of the liver and spleen
Spherocytes on blood smears are characteristic diagnostic feature of what disase?
autoimmune hemolytic anemia
**most commonly seen in human and canine patients
What would ctreatment with corticosteroids contraindicated in horses with IMHA?
b/c therapy must be directed at the primary agent
**corticosteroids can cause recrudescnce of viremia in horses with EIA
what blood factors are associated with NI in horse foals?
Qa Qb Qc Aa Pa and Dg and donkey factor in mule foals
**most ommon antigens are Qa and Aa
Heinz body hemolytic anemia can develop following exposure to what oxidizing agents?
phenothiazine, methylene blue, acetylphelhydrazine or plants with wild or domestic onions, members of the Brassica family (rape or kale) and wilted or dried leaves of the red maple (acer rubrum)
-sheep- low in molybdenum diets= chronic copper tox
-cattle- grazing rye grass or selenium deficient pastures in Florida
Clinical signs of heinz body hemolytic anemia
weakness
lethargy
anorexia exercise intolerance
death loss
mucpale mucous mebranes
INC HR and RR
Temp WNL
Clinical signs of horses with red maple leaf tox
subclinical or
lethargy, muddy or cyanoti cmucous mebranes, tachycardia, inappetence, weakness, colic, icterus, brown discoloration fo the blood and pigmenturia
RARE: sudden death
Clinical signs of horses with red maple leaf tox
subclinical or
lethargy, muddy or cyanoti cmucous mebranes, tachycardia, inappetence, weakness, colic, icterus, brown discoloration fo the blood and pigmenturia
RARE: sudden deathWhen do hroses develop clinical red mpale leaf toxicosis?
Clinical signs of horses with red maple leaf tox
subclinical or
lethargy, muddy or cyanotic mucous membranes, tachycardia, inappetence, weakness, colic, icterus, brown discolorationof the blood and pigmenturia
RARE: sudden death
When do horses develop clinical red maple leaf toxicosis?
during summer and fall
**high morality rate in comb of rapidly progressive hemolytic anemia and formation of methemoglobin
What are heinz bodies?
round, oval to serrated, refractile granules located near the cell margin or protruding from the cell
***visualized best with vital stains like crystal violet or new methylene blue applied to unfixed blood smears
Maple leaf tox clin path abnormalities
total plasma protein remains within normal limits
Coombs test negative
depletion of red cell mass
reduced glutathione
methemoglobinemia
INC osmotic fragility
modest elevations of liver derived serum enzyme activities
What renal injury can occur d/t red maple leaf tox?
renal failrue secondary to hemoglobin nephrosis
How common is renal insuffieicny in horses with red maple leaf toxicosis
40% of cases
Inflammatory leukogram is present in what percentage of cases of red maple leaf toxicosis
75% of cases
How are Heinz bodies formed?
by precipitation of oxidatively denatured hemoglobin
Hemoglobin contains with rbc is constantly undergoing mild oxidative stress assoc with oxygen transport–> leads to generation of
superoxid radicals and hydrogen peroxide within teh cell
What mecnaism cowithin the red cell counteract oxidative processes?
by production of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and reduced glutathione
How does selenium deficiency contribute to Heinz body anemia?
impeding the ability of the cells to repond to oxidative stress
__ selenium deficiency results in a derase in glutahtione peroxidase, a selenium containing enzyme
What component of red maple leaves is ipmliatedin teh oxidation of hemoglobin, methhemoglobin formation and Heinz body anemia?
Gallic acid
Methemoglobin formation in red maple leaf toxicosis results from
oxidative change of hemoglobin iron to nonfunctional ferric state
Normally methemoglobin formation is usually prevented by
glutathione reductase
ascorbic acid
reduced glutathione
What are the consequence of methemoglobinformation
cannot laod or transport oxygen
**gives blood brown color and mucous mebranes
Why are IV fluids indciated in HEinz body anemia?
to prevent renal damage seondary to hemoglobinuria or azotemia
Are corticosteroids beneficial in the treatment of heinz body anemia?
No, have an increased risk of death
What is the mortality rate of experimental and naturally occurring red maple leaf toxicosis?
60 to 65%
Intravascular hemolysis has been reported in horses following severe cutaneous burns affected what percentage of their body surface?
more than 25%
What is the pathophysiology of hemolysis associated with intravascular hemolysis following cutaneous burns?
production of hydroxyl radicals by complement activated neutrophils
What has been shown to be beneficial for burn treatment in humans?
early fluid therapy
free radical scavencers
supportive and wound care
control pain and inflammation
sepsis prophylaxis
Water intoxication- what is it?
massive water intake may produce marked hypotonicity o fbody fluid with subseueetn IV hemolysis of RBCs
When is water intoxication a problem?
when milk reared calves when they first given access to unlimited quantites of water
Clinical signs of water intoxication
severe neuro signs: depression, convulsions, coma
respiraotry distress
hemoglobinuria
death
What are clinicopathologic features of water intoxication?
hemolytic anemia
hypoproteinemia
hyponatremia
hypochloremia
hyposmolality
hemoglobinuria
hypothenuria
Clinical signs of water intoxication
severe neuro signs: depression, convulsions, coma
respiratory distress
hemoglobinuria
death
Treatment of water intoxication?
**restrict water
hypertonic saline (return sodium to 120 to 125 mmol/L)
mannitol
corticosteroids
Postparturient hemoglobinuria: commonly affected animals
high-producing multiparous cows that develop C/S during the first month after calving
Postparturient hemoglobinuria syndrome characterized by
intravascular hemolysis
hemoglobinuria
anemia
C/S of Postparturient hemoglobinuria
depression
decreased feed consumption
decreased milk production
anemia (marked at 4 to 5 days)
hemoglobinuria
icterus
Suspected pathogenesis of Postparturient hemoglobinuria
Hypophosphatemia– low intracellular phosphate may interfere with energy metabolism–> affects cell viability & ability of red cells to deal with potential hemolysis
Treatment for Postparturient hemoglobinuria
1.blood transfusion & IV fluids– highly valuable animals
2.correct hypophosphatemia: sodium acid phosphate: 60 g/300 ml of water IV, followed by oral supplementation with 200 to 300 g sodium phosphate salts every 12 hours
Which spp is most susceptible to the toxic effects of copper?
lambs
**sheep, goats and cattle
Which breed of sheep is more resistant to copper toxicity?
meirno sheep> british breeds
Ingestion of copper pathway
ingested salts of cooper absorbed through enterocytes by carrier proteins
2. transported to blood by in loose complexes with albumin and aa
3.ionic copper internalized by hepatocytes
4. redistributed in bile, packed in lysosomes in protein complexes or used for formation of ceruloplasmin
Hemolysis caused by copper
Free inorganic copper is an oxidant– partticpiate in the FEnton rxn
–>cellular damage related to oxidative hydroxide and peroxides (not copper oxidation)–> leads to denaturation of proteins within RBCs
Hemolysis caused by copper
Free inorganic copper is an oxidant– participate in the Fenton rxn
–>cellular damage related to oxidative hydroxide and peroxides (not copper oxidation)–> leads to denaturation of proteins within RBCs
The hemolytic phase of copper poisoningis often initated by:
Noxious stimuli
-shipping, hierarchal change, admin of oxidative drugs, starvation or change of housing
What diets have increased resistance to hemolytic crisis in sheep caused by copper toxicosis?
High protein diets
What are sources of copper that have been responisble for copper accumulation in animals?
trace mineralized salt
inappropriately formulated cereal grain mixtures
forages from pastures that have been fertilized by swine or chicken manure
orchard pastures contam by copper containing fungicides
rations containing more than 20$5 chicken litter
diets that contain high concen of palm kernal oil
What is the toxic dose of copper dependent upon?
Variable
Dependents on duration of exposure
animals genetic
amount of molybdenum being fed
What two minerals inhibit the absorption of copper?
High dietary inc and Iron– these elements share a competitive affinity for metallothionein
What reduce decreases the absorption of molybdenum from plants, thus increasing the potential for pathologic accumulation of copper in herbivores?
soil sulfates
Which spp is resistent to high dietary conentrations of copper?
Horses
Clinical signs of Copper toxicosis occur when and then see clinical signs fo what organs?
**asymptomatic until onset of hepatic necrosis
–> rapid onset: anemia, myopathy, neurologic, renal and hepatic disease
Copper toxicosis clinical signs
inappetance
lethargy
weakeness
recumbency
cool extremities
pallor
grayish discoloration of the mucous membranes
+/- poor pulses qulaity, tachypnea, hypotension, hypothermia
In copper toxicosis feces can be what color?
dark or yellowish discoloration– do not contain hemoglobin unless secondary abomasal ulceration occurred
Necropsy findings of animals with copper tox
-pale/icteric in hemolyzing animals
-liver: pale, yellow
lungs: firm
-kidneys: black, metallic sheen d/t entrapped hemoglobin
-urinary bladder: serosanguineous urine filled
How long is hepatic necrosis detectable in cases of copper toxicity on microscopic exam?
412 days post poisoning
Can diagnosis of copper toxicosis be made on liver biopsy or plasma concentrations of copper?
Normal hepatic copper and plasma copper concentrations have been reported
**but may be diagnostic
With cllin path abnormalities, when are consistent hematologic changes seen?
Not until 24 hours after hemolytic crisis
What are clin path changes that occur during the acute hemolytic crisis caused by Copper tox?
Heinz body formation
intrascular hemolysis
methemoglobinemia (as much as 5%)
decrased PCV
increased concen of plasma bilirubin, AST, GGT, ALP, Tbili, CK crea, plasma urea nitrogen, plasma ceruloplasmin
Describe urine in copper tox
color: dk brown to black
- high concen of protein, blood and hemoglobin casts
Treatment of Copper tox with D-penicillamin causes
increases urinary copper excretion by 10 to 20 fold
**single dose therapy the effect is transient and insifignificant for reudcing total hepatic copper load. treat daily for 6 days
Copper tox: animals with acute hemolytic syndrome should be treated with:
-insufflated oxygen
-VItamin E
Treatment with ammonium tetrthiomolybdate has been recommended for treatmetn of acute hemolytic crises due to Copper tox, for what MOA?
reduces lyosomal and cytosolic opepr in hyepatocytes
Prevention of copper toxicosis for pastures that are heavily contaminated with copper
top dress the pasture with molybdenum phosphate
