CIRCULATORY

DISORDERS IN
RUMINANTS
Overview

▶ Congenital heart disease

▶ Copper Poisoning

▶ Leptospirosis

▶ Cold Water Hemolysis/Hemoglobinuria

Congenital Heart Disease

▶ Simple
▶ VSD (most common congenital heart defect)
▶ ASD, PDA less frequent
▶ Complex anomalies infrequent
▶ Tetralogy of Fallot
▶ Persistent truncus arteriosus
▶ Pulmonic valve atresia
▶ Tricuspid valve atresia
▶ Hypoplastic left ventricle
▶ Hypoplastic right ventricle
Congenital Heart Disease

▶ Left-to-right shunt
▶ Workload both chambers is increased
▶ More left than right
▶ Animal has reduced cardiovascular functional capacity
▶ Failure to thrive/grow

▶ Right-to-left
▶ Added effect of hypoxemia (PaO 2 25-30mmHg)
▶ Animals do poorly
 Congenital Heart Disease

▶ Clinical signs
▶ Variable
▶ Simple defects
▶ Small and uncomplicated defects may be asymptomatic
▶ Inc idental murmurs
▶ Larger defects may be initially without signs and then gradually progress

▶ Complex defects
▶ Moderate to severe exercise intolerance
▶ May be associated with cyanosis due to right to left shunting
Congenital Heart Disease

▶ Cases may present as respiratory distress

▶ Must differentiate from pneumonia

▶ Previously stable case may present as sudden onset
“pneumonia” following unaccustomed exercise

▶ Poor growth rate (common)

▶ Animals may decompensate with first calving (e.g. cow
with large VSD)
Congenital Heart Disease
▶ Differentiating simple from complex
▶ Echocardiography
▶ Murmur ofsimple VSD usually loudest well forward on right side
(membranous VSD)
▶ Murmur of VSD associated with complex anomaly often loudest
on left (smooth septal)
▶ If hypoxia, then probably complex
Congenital Heart Disease
▶ Prognosis grave other than for simple VSD

▶ Small VSD may have reasonable prognosis

▶ May predispose to endocarditis
▶ May become significant late in gestation/early calving
▶ May have reduced milk production
 Subpulmonic

Perimembranous
Copper Poisoning

▶ Syndrome of acute hemolysis

▶ Usually seen in sheep

▶ Usually, chronic copper poisoning

▶ Susceptibility:
▶ Sheep > ca ttle > pig > horse
Copper Poisoning -
Etiology
▶ Primary copper poisoning
▶ Acute poisoning
▶ Acute ingestion of large quantities

▶ Chronic poisoning
▶ Ingestion of small quantities of excess copper over time
(most common form)

▶ > 10-15 ppm dry matter

▶ Concomitant low dietary molybdenum levels

Copper Poisoning

▶ Etiology
▶ Secondary copper poisoning
▶ Syndromes in which intake of non-toxic/ normal quantities of copper
in association with certain plants result in toxicity and an acute
hemolytic crisis
▶ Trifolium subterranium, Helitropium euranium, Senecio spp.
Copper Poisoning
▶ Pathogenesis
▶ Hemolysis caused by copper induced auto-Ab?
▶ Hemoglobin oxidation by copper promotes RBC fragility
▶ Oxidation à methemoglobin à Heinz bodies à mechanical
hemolysis

▶ Episodes precipitated by stress

▶ PCV can drop rapidly - from normal 40% to 10% in
<48 hrs
▶ All animals in a group are at risk
▶ Same animal at repeated risk
Copper Poisoning
▶ Clinical presentation
▶ Acute
▶ Chemical damage GI mucosa (protein coagulation), fluid loss,
circulatory collapse, shock - most die

▶ If survive
▶ Diarrhea

▶ Intravascular hemorrhage
Copper Poisoning
▶ Clinical presentation
▶ Chronic
▶ Poorly understood

▶ Initially no clinical signs as liver copper levels rise

▶ Liver stores copper, excreted in bile but
reabsorbed
▶ Acute hemolytic crisis preceded by hepatic
necrosis
▶ Release of copper into bloodstream
▶ Severe hemolytic crisis and further liver damage
 Copper Poisoning
▶ Clinical signs
▶ Acute poisoning
▶ Gastroenteritis
▶ Diarrhea, abdominal pain, shock
▶ Dysentery & jaundice if survive >12-24 hrs

▶ Chronic poisoning
▶ Anorexia, depression, tachycardia,
tachypnea
▶ Pallor, jaundice, hemoglobinuria, if survive
>24 hrs, may show neuro signs
▶ Anemia (+ methemoglobinemia) may show
hypoxemia, dyspnea (anemic hypoxia)
Copper Poisoning

▶ Clinical pathology
▶ Anemia
▶ Hemoglobinemia, hemoglobinuria
▶ Elevated liver enzymes (highest just before crisis)
▶ +/- methemoglobinemia

▶ Blood copper levels elevated during crisis

▶ Blood copper levels 5- 20 ppm (normal <1 ppm)
▶ Liver copper levels >1000 ppm (normal <350 ppm)
▶ Kidney copper levels >50 ppm
Copper Poisoning
▶ Treatment
▶ If clinica l signs are evident
▶ Grave prognosis, euthanasia should be considered
▶ Symptomatic management
▶ IV fluid therapy
▶ Oxygen insufflation
▶ Blood transfusions
▶ Chelator therapy (sheep)
▶ D-penicillamine (Cuprimine, 52 mg/kg x 6 days)
▶ 100 mg ammonium molybdenate and 1 g anhydrous sodium
sulfate daily PO
Copper Poisoning
▶ Treatment
▶ Of presumed exposed animals
▶ Minimize stress
▶ Dietary ammonium molybdenate
▶ May reduce blood copper levels
▶ Ammonium tetra-thiomolybdate 50-100 mg/sheep,
twice weekly, orally
▶ Cattle (used in outbreaks)
▶ Sodium molybdate 3g and sodium thiosulfate 5g daily
PO
Copper Poisoning

▶ Prevention

▶ Keep copper in feed as low as possible (less

than 15 ppm)

▶ Ensure adequate dietary intake of

molybdenum

▶ Fertilize molybdenum deficient pastures

Leptospirosis

▶ Organism

▶ Spirochete bacterium

▶ Genus: Leptospira

▶ Aerobic, motile, saprophytic

▶ Gram-stain poorly
Leptospirosis

▶ Serovars of Leptospira interogans

▶ A number ca n ca use disease in ruminants
▶ hardjo, pomona, icterohemorrhagia, gryppotyphosa,
canicola
▶ Most common
▶ hardjo- considered host adapted
▶ pomona- considered non-host adapted
▶ Widespread, zoonotic
Leptospirosis

▶ Host-adapted serovars

▶ Special growth requirements?

▶ Often ca use reproductive disorders

▶ Chronic persistent infections, endemic

▶ Acute infections in accidental hosts

Leptospirosis

▶ Maintenance host characteristics

▶ High susceptibility to infection

▶ Renal or reproductive infections

▶ Efficient transmission between hosts

Leptospirosis

▶ Non-adapted serovars

▶ C ause acute disease in individuals

▶ May ca use acute outbreaks

▶ Cases usually sporadic

Leptospirosis

▶ Accidental host characteristics

▶ Low susceptibility to infection

▶ Severe disease

▶ Renal infection short duration

▶ Transmission between hosts inefficient and sporadic

Leptospirosis

▶ Epidemiology
▶ Environmental survival appears dependent on
warm, wet climatic conditions

▶ Skin abrasions, mucous membranes

▶ Source: urine, fetus, uterine fluids, venereal

▶ Recovered ca ses still shed

▶ Intermittent. Cows shown up to 500 days
Leptospirosis

▶ Pathogenesis
▶ Multiplication in bloodstream
▶ Invasion spleen, liver, brain
▶ Direct damage to blood vessels and liver
▶ Invasion of kidney favoring proximal tubules
▶ Placental invasion- fetal infection
▶ If recovery: antibodies eliminate, except: renal, eye,
uterus
▶ Some serogroups: hemolysin -> hemoglobinuria
Leptospirosis

▶ Clinical manifestations
▶ Acute
▶ Hemolytic syndrome (calves and lambs)
▶ Subacute

▶ “Chronic” abortion/infertility

▶ Occult
Leptospirosis

▶ Calves (Usually <1 month)

▶ Acute disease
▶ High mortality, slow recovery
▶ First sign may be sudden death
▶ Severe pyrexia, anorexia, depression
▶ Petechiation

▶ Acute hemolytic anemia, hemoglobinuria, pallor

▶ Dyspnea, tachycardia, tachypnea (shock)
▶ Usually pomona
Leptospirosis

▶ Effects on microcirculation- direct damage to vessels

▶ Decrease blood volume, decrease peripheral vascular
resistance
▶ Tachycardia
▶ Hemolysis- severe
▶ Loss of oxygen carrying capacity
▶ Tachycardia, tachypnea.

Peripheral constriction to attempt to maintain blood volume- but

vessels are damaged.
Vascular damage results in edema.
Hypoxia also causes vasodilation and causes cell death which
potentiates edema.
In the lungs this worsens the tachypnea and causes dyspnea.
Leptospirosis
▶ Sheep
▶ Outbreaks in sheep are rare
▶ Acute/subacute
▶ Sudden death: septicemia (septic shock)
▶ Pyrexia, depression, stiffness
▶ Hemoglobinuria, pallor, jaundice
▶ Abortion
▶ All ages, lambs most susceptible
▶ Pomona, Hardjo
Leptospirosis
▶ Adult cattle
▶ Primarily serovar Hardjo
▶ Initial infection
▶ Can see pyrexia/anorexia, agala ctia, stiffness

▶ When recently introduced

▶ Mastitis, agalactia in high percentage herd
▶ Abortions few weeks later (<30%)
▶ Sequelae
▶ Persistence in reproductive tract
▶ Infertility
▶ Venereal transmission
Leptospirosis
▶ Adult cattle (hardjo)
▶ Abortions
▶ Systemic infections lead to fetal death
▶ Placentitis may not be present
▶ Abortion may occur at any stage (endemic)
▶ Last trimester fetus may mount immune response and
recover
▶ Mastitis
▶ No gland inflammation
▶ Mild yellow to orange with clots
Leptospirosis

▶ Adult cattle (pomona)

▶ Subacute disease
▶ Fever anorexia, stiffness, hemoglobinuria, jaundice
▶ Fall in milk yield +/- yellow/orange mastitis
▶ Abortion 3-4 weeks later
Leptospirosis
▶ Diagnosis
▶ Culture
▶ Requires special techniques, can take 5 weeks to months
▶ Only of value acute cases
▶ Dark field microscopy
▶ Specialized facilities
▶ Ac ute cases
▶ Antigen detection
▶ Not routine use
▶ PCR
▶ Urine only, does not differentiate species
Leptospirosis
▶ Diagnosis
▶ Serology
▶ Antibodies inconsistently detected and significance difficult to
interpret
▶ Rising titres (4-fold) suggests recent infection
▶ Have to take a cute and convalesc ent

▶ Problems with endemic herds

▶ How to interpret
▶ Once abortions, acute phase is gone
Leptospirosis – Antibiotic Treatment

▶ Acute Onset:
▶ Tetracycline, oxytetracycline, penicillin, ceftiofur,
tilmicosin, tulathromycin
▶ Erythromycin, tiamulin, tylosin – may not eliminate
the renal ca rrier state
▶ Long-acting oxytetracycline & sustained-release
ceftiofur will eliminate the renal carrier state
Leptospirosis
▶ Vaccination
▶ Serovar specific
▶ Animal infected with same serovar will show
anamnestic response to vaccine
▶ Vaccine reduces urinary shedding
▶ Can vaccinate as young as 4 weeks
▶ Vaccinating ca lves reduces their risk of becoming
urinary shedders later in life
Leptospirosis
▶ But
▶ Need to repeat vaccination (6 months- 1 year)
▶ Does not prevent abortion/renal carriage shedding of
hardjo in endemic herds
▶ Despite vaccination hardjo can become established in
clean herds
▶ By reducing natural immunity may make herd more
susceptible to outbreak
▶ Recent study: 238 surface protein antigens à 71%
induced immune response à no infection protection of a
hamster animal model (Murray et al., 2013).
Leptospirosis

▶ Control
▶ Difficulties with testing make it too difficult to identify
carriers
▶ Hygiene
▶ Avoid wet areas (temporary habitats)
▶ Reverse isolate unvaccinated animals
▶ Isolate known affected groups
Cold Water
Hemoglobinuria
▶ Ingestion of large amounts of cold water associated with
intravascular hemolysis and hemoglobinuria
Cold Water Hemoglobinuria
▶ Usually seen in ca lves
▶ Adults - rumen acts as buffer
▶ Usually after period of water deprivation
▶ Intravascular hemolysis in the intestinal wall
▶ Absorption of water lowers blood electrolytes
▶ Decreased osmotic pressure
▶ Osmotic fragility of red cells highest at 4-5 months
▶ Cold water (12-14°C) at an amount of 12% of their body weight
▶ Hemolysis - ~1 hour after ingestion
Cold Water
Hemoglobinuria
▶ Clinical signs
▶ Tachycardia due to anemic anoxia
▶ If carrying capacity sufficiently low then “perfusion” fails even
if volume sufficient- oxygen not supplied

▶ Cell death
▶ Vasodilation, vascular integrity fails
▶ Edema, cell death
▶ Convulsions, coma, pulmonary edema, brain edema, death
are all possible