Exam 3

Question 1

The nervous System

Answer 1

Brain

-Cerebrum, cerebellum, brainstem (pons, medulla)
-White matter: centrally = myelinated axons
-Grey matter: peripherally = neural bodies

Spinal cord

-Cervical
-Thoracic
-Lumbar
-Sacral sections with associated spinal nerves
-White matter: peripherally, funiculi, axons location
-Grey matter: centrally, “butterfly”, neurons located here

PNS

-Schawnn cells: myelinated (equivalent to oligodendrocytes in brain)
-Myelin = fat white

Question 2

Players in the Game

1. What are the intermingled myelinated axons, dendrites, glial cells?
2. Which are the neurons parts? and substance?
3. What cells contribute to homeostasis, healing and immune response? most significant contributor?
4. Which glial cells participate in metabolism of toxins (ammonia, heavy metals) and neurotransmitters? which do you find in GM and WM?

Answer 2

1. Neuropil = mixture of things
2. Dendrites, cell body, axon
   -Nissl substance: ER and polysomes (protein sysnthesis)
3. Glial cells: derived from neuroectoderm

-Astrocytes: support ionic/water balance, antioxidant concentrations, uptake, metabolism of neurotrasmitters, metabolism or sequestration of neurotoxins (ammonia, heavy metals).
PROTOPLASMIC astrocytes in GM
FIBROUS astrocytes in WM

-Ependymal cells (CSF)
-Oligodendrocytes

**Part of monocyte-macrophage system (phagocytic) MACROGLIAL cells in brains **

Question 3

Cerebro Spinal Fluid

1. Which cells line the ventricular system, aid in movement of CSF?
2. Which are the epithelial cells (modified EC) that produce CSF?
3. Explain the flow of CSF

Answer 3

1. Ependymal cells (EC)
2. Choroid plexus
3. LV - 3rd - CA - 4th -CC spinal cord.

-Left ventricle - 3rd ventricle - Cerebral Aqueduct - 4th ventricle - Central cannal spinal cord

Question 4

Meninges

1. What are the layers from superficial to deep?

Answer 4

DM - A - PM - Lepto

1. Dure matter, Arachnoid, Pia Matter, Leptomaninges: pia matter + arachnoid. Blood brain barrier

Question 5

Understanding Injury in the CNS

1. What are neurons most vulnerable cells, especially to? sensitive to what? hint: neurotransmitters
2. do neurons regenerate?
3. Which cells are most susceptible to ischemia in order of most to least?

Answer 5

1. Free radicals. Completely dependent on glucose in blood (no stores in brain)
   -Sensitive to excitatory neurotransmitters GLUTAMATE, ASPARTATE which are released in many injuries
2. No regeneration, death by apoptosis, necrosis
3. Susceptibility of structures CNS to ischemia
   Neurons - oligodendroglia - astrocytes - microglia - blood vessels

**Red neurons = dead neurons **

Question 6

Astrocytes

1. How do deep and superficial wounds heal in the CNS?
2. Compare fibroblast to astrocytes processes

Answer 6

1. Heal by proliferation of astrocytes (astrocytosis)
   -superficial wounds by fibroblasts (fibrosis) and proliferation of astrocytic processes
2. Fibroblasts produce a thick capsule unlike astrocytes, the thin capsule breaks down easily

Space occupying lesions are problematic! tumors, edema, hemorrhages, abscesses

Question 7

CNS Portals on Entry, Injury

Which port of entry does Cryptococcus in cats, FeLV, Blastomyces, and Listeria prefer?

Answer 7

1. Direct extension

-Trauma
-Extension of middle ear infection. Pyogranulomatous eats away bone, ex: cryptococcus in cats
-Nasal cavity, sinus infection, neoplasia though cribiform plate
-Bacterial osteomyelitis, neoplasia of vertebral bodies with extension into vetebrae and vertebral canal

2. Hematogenous

-Umbilical/ vascular infections
-Metastatic tumors

3. Leukocytic trafficking

-Lymphocytes, macrophages, FeLV, BLastomyces

4. Retrograde axonal transport

-Listeria

Question 8

Malformations of the CNS

1. Absence of brain, most common in what species? Characteristics
   Procencephalic hypoplasia a.k.a?
2. Dorsal midline cranial defect where meningeal and brain tissue protrude? Characteristics

Which one is hereditary in pigs and cats and associated with griseofulvin toxin?

Answer 8

1. Anencephaly (without a brain)

-Many times only rostral part absent, or very rudimentary (cerebral hemispheres). Varying degrees of the brainstem is preserved. Abnormality best designated PROSENCEPHALIC HYPOPLASIA
-Most common in calves and accompanied by other defects

Meningioceophalocele and Cranium Bifidum

2. Cranium bifidum

-Protruded material form sac (cele), covered by skin, lined by meninges (meningocele) or meninges + part of brain.
-Apperent grossly but diagnosis of presence or absence of brain tissue requires histo examination
-Hereditary, pigs, cats
-Toxins: GRISEOFULVIN in pregnant cats during first week of gestation

Question 9

1. Abnormal dilation of central canal of spinal cord? Characteristics and causes
2. Neuronal migration disorder? Characteristics, causes, species exceptions

Which one causes compression of spinal cord and WM, GM?

Which one affects Lhasa apso, kittens and lambs?

Answer 9

1. Congenital Hydromyelia

-Serous to clearish fluid in channel that carries CSF
-Damage to EPENDYMAL cells = disruption of CSF flow
-CSF accumulation - pressure on spinal cord, compression of white and grey matter
-Causes: infectious/genetic injury. Acquired hydromyelia: obstruction of central canal, infection, inflammation, neoplasia.

2. Lissencephaly

-Neuronal migration disorder
-Lack of normal cerebral gyri and sulci.
-Affects Lhasa apso, kittens, lambs.
-Exception: birds, rabbits, rats, mice which normally lack both and has no functional significance.

Question 10

1. Small fluid filled cavities in brains - communicates with subarachnoid space or lateral ventricle
2. Large cavities with lots of fluid. Usually occurs in utero during gestation

Answer 10

1. Porencephaly
2. Hydranencephaly
   -Severe form of porencephaly
   -Cavitation in WM of cerebrum (improper development of cerebrum)

Question 11

1. Gross lesions not usually seen but atrophy of cerebral gyri results in widening of sulci
   -Fast or slow progression?
   -Which are the valleys of the brain?
2. Parvovirus and Pestivirus can be causes. Mitotic cells are destroyed during late gestation, early neonatal periods. Clinical signs?

a. Kittens and puppies are affected by what virus?

b. Calves, piglets, and lambs are affected by what viruses?

Answer 11

1. Brain atrophy

-Slow progressive disease
-Cerebral cortical atrophy of aging
-Ceroid lipofuscinosis
-Various manifestations of selective multisytemic neural degeneration
-Sulci = valleys of brain

2. Cerebellar hypoplasia

-Viruses infect and destroy mitotic cells (external granule cell layer of cerebellum; still dividing during late gestational, early neonatal periods).
-Small cerebellum
-C/S: wide based stance, unable to stand. Vision problems, blindness, head tremors

a. Parvovirus: panleukopenia virus and canine parvovirus

b. Pestivirus: BVDV, classical swine fever virus (hog cholera), border disease.

Question 12

Hydrocephalus and Cerebral Edema

1. Causes
2. Breeds primarily affected
3. gross lesions.

Answer 12

Hydrocephalus

1. In utero viral infection, developmental abnormalities in ependyma or ventricular system. Infection, blockage of ventricular system.
2. Genetic predisposition: Toy dogs and brachycephalic
   Chihuaha, Lhaso apso, toy poodle.
3. Doming cranium, open fontanelles, thinned cranium bones, dilated ventricles, white matter atrophy, CSF remains where it is supposed to be

Cerebral Edema

1. Congenital brain swelling, enlargement of brain, increased diameter of vasculature, elevated intracranial pressure
2. Congenital edema: increased pressure following accumulation of fluid in interstitium, intracellularly, extravascularly
   **White matter: swollen, soft, damp, light yellow, loss of defined gyri and sulci. **

Question 13

What are some types of cerebral edema? which is the most common? What are the causes for each?

Answer 13

1. Cytotoxic edema: cell swelling
   -Hydropic degeneration of brain cells, increased intracellular fluid, normal vascular permeability.
   **Alter cellular metabolism (often due to injury and ischemia) **
2. Vasogenic edema (tissue swelling) increased vascular permeability, increased extracellular fluid. Most common type in animals, WM affected most’
   Vascular injury with breakdown of BBB
3. Hydrostatic interstitial edema: obstructive internal hydrocephalus, increased hydrostatic pressure of CSF.
   **Elevated ventricular hydrostatic pressure (hydrocephalus) **
4. Hypo-osmotic edema: abnormal osmotic gradient between blood and nervous tissue
   Osmotic imbalance (blood plasma vs. extracellular and intracellular microenvironment of the CNS

multiple mechanisms contribute to CNS edema

Question 14

What is the sequelae to brain swelling?

What is the sequelae of subdural hematomas?

Answer 14

Acute

-Localized or generalized compression against cranium
-Flattened gyri
-Shallow sulci
-Shift in position

Diffuse

-Herniation of brain
-Cerebellum herniation through foramen magnum = “coning” of vermis - protruding of cerebellum

Subdural hematomas

-Blood accumulates between dura matter and maninges, poorly circumscribed
-Pressure atrophy

Question 15

Brain Abscesses

What bacteria are associated with them?
Which lead to yellow watery to cream color? White to grey? Green to bluish-green?
What procedures can lead to brain abscesses?
What surround the abscess?

Answer 15

Bacteria

-Streptococcus spp., Staphylococcus spp., Corynebacterium spp., YELLOW, WATERY, CREAMY.
-E. coli and Klebsiella spp., WHITE/GREY, WATERY to CREAMY
-Pseudomonas spp., GREEN to BLUISH-GREEN

Procedures

-Dehorning: infection extends from nasal sinuses
-Docking: vetebral osteomyelitis
-Otitis interna
-Bacteremia
-Septicemia

Question 16

Meningitis

What do they all look like?

Leptomeningitis involves what layers of the meninges?

Answer 16

They all look like a fatty brain

1. Dura matter
2. Pie matter
3. Arachnoid

Leptomeningitis: Arachnoid and pie matter
Pic: suppurative bacterial meningitis: pale yellow-white exudate

Bacteria often isolated: Trueperella pyogenes, Pasteurella multicocida.

Question 17

Organism: facultative intracellular gram +

Species: Ruminants

Associated with: Spoiled silage and abrasions in the mouth of herbivores

What are the three forms?

What is the associated path of entry?

What are the gross lesions/signs?

Microabscesses or big pockets of purulent material?

_____ ganglioneuritis
_____ Vasculitis
_____ paralysis

C/S:

Answer 17

Listeria monocytogenes

1. Encephalic (meningoencephalitis)
2. Reproductive (abortions, still birth)
3. Septic form (young animals +/- in utero infections)

Retrograde axonal transport

Gross: malacia, hemorrhage, necrosis (brainstem), cloudy CSF

**Oral trauma, retrogade axonal transport (trigeminal nerve) migration to brainstem “star gazing” **

Microabscesses

Histological characteristics

-Necrosis, inflammation,
-Brainstem, grey and white matter microabscesses
-Neutrophils primarily
-Trigeminal ganglioneuritis
-/+ vasculitis

C/S: dullness, circling, unilateral facial paralysis, drooling (pharingeal paralysis)
Recumbency, paddling of limbs, death

Question 18

C/S: ataxic, circling, head press, appear blind, progression to convulsions, comatose, death

Gross: random variably sized red foci (hemorrhage), necrosis

What is the disease?

What is the pathogen involved?

What is the suspected pathogenesis?

What type of necrosis is involved?

What is the primary path of entry and vascular injury?

What species are primarily affected?

FYI: Does Maenheimia cause systemic vasculitis?

Answer 18

FYI: No

-Thrombotic meningoencephalitis

-Histophilus Somni, gram (-) causes
-Fibronecrotising vasculitis
-Septicemia, pneumonia, polyarthritis, myocarditis, abortion, thrombosis induced meningoencephalitis.
-Pathogenesis: respiratory tract initial replication, hematogenous spread to CNS. endothelial cell injury, thrombosis, infarction, necrosis (all organs).

-Frequency: cerebrum (GM/WM interface - spinal cord)

Question 19

No immunologic response or notable inflammation within CNS

No gross lesions of nervous system

What is the etiology?

What are the Ovine and bovine forms?

What is the path of entry?

Where does the PrpSc accumulate and how long does it take?

What is the ultimate sequelae?

What are the histological characteristics?

What do you see in cytoplasmic vacuolation?

In What cells does the prion amyloid first accumulates?

What animals are primarily affected and C/S?

What are diagnostic tests?

What portion of CNS is necessary for diagnosis in Scrapie?

Answer 19

Transmissible Spongioform Encephalopathies

Ovine spongioform encephalopathy (scrapie)

Bovine spongioform encephalopathy (BSE)

Etiology: proteninaceous infectious (prions)

PrPC: expressed throughout body - conformational change - alpha-helical portion PrCP diminises, Beta-sheet increases - formation of PrPSc (“sc” derived from scrapie prototype prion disease)
-Resist inactivation (heat, ultraviolet irradiation, enzymes)

Chronic Wasting Disease: saliva - blood, urine, prions ingested - replicate (Peyer’s patches, macrophages), WBC trafficking (LN - blood), CNS, neurons, neurons accumulate PrPsc (takes years) - neuro signs, death.

Histo

-Neuronal degeneration
-Increased basophilia
-Cytoplasmic vacuolation (white spots within the cell)
Astrocytes: abnormal protein first accumulates in astroglia cells in scrapie
-Spongioform change tends to affect gray matter **

Adult cattle (3-11 years old)
C/S: between 3-5 years
-Behavioral changes, abnormal posture, gait, incoordination, decreased milk production weight loss, despite appetite.

Sheep, goats
-C/S: limited to CNS. Scrapie Occurs naturally in domestic goats. Change in behavior, scratching, rubbing (puritus), loss of wool. Incoordination, weight loss despite appetite, trembling, recumbancy, death (1-6 months)
Medula oblangata for diagnosis

Tests
-IHC
-Western blot analysis
-ELISA to identify PrPSc in brain tissue

Question 20

Equine Viral Neuropathies

EEE: equine Eastern encephalomyelitis

WEE: Western equine encephalomyelitis

VEE: Venezuelan Equine encephalomyelitis

What genus and family of virus are associated?

What is the Target cell and pathogenesis?

Do all three viruses affect the grey matter?

What are the gross lesions?

Where are lesions best appreciated?

Histologic characteristics

What does it have it common with Thrombotic meningoencephalitis?

What are the C/S?

Which equine viral neuropathy has veen reported in cattle, sheep, and camelids, and pigs?

FYI: what is white matter disease?

Answer 20

Arboviruses: family Togaviridae

Target cell: neurons, also vasculitis, thrombosis. Red lesion, multifocal

Pathogenesis: mosquito bite - hematogenous spread, endothelial replication - monocyte-macrophage system, muscle, connective tissue **Lymphoid tissue, bone marrow: dellular depletion, necrosis, second viremia, hematogenous - CNS ** (neurons lesser extent ganglia)

In CNS all three viruses induce polioencephalomyelitis = grey matter disease

Gross lesions: +/- present, best appreciated in spinal cord.

FYI: Leukoencephalities = white matter disease

Histological characteristics

-GM of brain, spinal cord, perivascular cuffing, neuronal degeneration, cerebrocortical necrosis, perivascular edema, hemorrhage, necrotizing vasculitis; thrombosis, choroiditis; lepto meningitis.

What do they all have it common with Thrombotic meningoencephalitis? thrombosis, necrosis, hemorrhage.

C/S:

-Fever
-Rapid heart rate
-Anorexia
-Muscle weakness
-Aggression
-Head pressing
-Blindness
-Paralysis of facial muscles

EEE

-Also been reported in cattle, sheep, camelids, and pigs.

Question 21

West Nile Viral Encephalomyelitis or encephalomyelopathy?

What family of virus?

What animals are the primarily participants of the cycle?

Is the pathogenesis similar to equine encephamyelopathies viruses?

Target cells ____
Horses are ____ end species
____ matter specially

Gross lesions: gray matter
WNV hemorrhage more or less than EEE, WEE, VEE.

Histologic

____ cuffing
Lesions outside of nervous system ____

C/S: fever, ataxia, weakness-paralysis of hind limbs, tetraplegia, convulsions, coma, death.

Answer 21

West Nile Virus family Flavivirus

-Bird-mosquito cycle: wild songbirds, crows, American robins (propagation, dissemination)
-Birds: fulminate viremia - systemic spread.
-Neuron, microglial cells targets
-Similar pathogenesis to equine encephalomyelitis
-Horses: dead-end species, only infections of CNS
-Grey matter specially
-Gross: grey matter, hyperemia, hemorrhage especially lower brainstem, ventral horns of thoracolumbar spinal cord.
Gross: WNV hemorrhage
-Gross: WVN hemorrhage greater than encephalomyelopathies, also PERIVACULAR CUFFING

Histologic

-Birds, horses, acute polioencephalomyelitis, hemorrhage
-Mononuclear +/- neutrophils
-Lesions outside of nervous system in affected horses do not occur

Question 22

Herpesvirus

What type of virus is encephalitic herpesvirus?

____ infections

Which cells with inflammation/ necrosis?

Is hemorrhage and necrosis present?
____ vasculatis principal lesion = red, multifocal to coalescing variable sized lesions.

Answer 22

-Alpha herpesvirus
-LATENT infections
-Neurons, glial cells, endothelial cells
Yes, Hemorrhage, thombosis, -NECROTIC vasculitis.

Question 23

Alphaherpisvirus

Abortion, death, rhinopneumonitis

What does it cause primarily in adults?

Is it neurotropic or endotheliotropic of CNS?

INIB in neurons, but not observed in ____ lesions

Pathogenesis?

Latency: trigeminal ganglion

Gross and histo lesions related to ____ of ____

Answer 23

Equine Herpesvirus 1 (EHV-1)

-Adults: myeloencephalitis
-Unlike IBR, and pseudorabies in pigs, EHV-1 is NOT neurotropic

-Pathogenesis: viral inhalation, epithelial cells (nasopharynx) Lymphatic tissue, WBC trafficking, endotheliotropic of CNS, vasculitis, thrombosis, infarction.
-VASCULITIS of SMALL VESSELS
-INIB not observed in CNS lesions
-Hemorrhage, thrombosis, axonal, myelin swelling, neuron egeneration, mononuclear cell cuffing.
-Neuro disease may accompany or follow outbreaks of respiratory disease or abortion

Question 24

Suis herpesvirus 1

Zoonotic?

“Mad itch”

Young pigs: death

Mature pigs: persistently infected

Route of transmission: direct contact, aerosolizations.

Where does it replicate? and Pathogenesis?

Fetal maceration, mummification in ____

How do dogs become infected?

Common sequela ____

Suppurative or nonsuppurative meningeoncephalomyetis?

Neutrophils nor macrophages predominate

Respiratory, lymphoid system necrosis, GI, repro tract

Is it fatal in domestic/ wild animals?

What other species are affected?

Are INIB detected in pigs?

What are the typical lesions?

Intraneuronal inclusion bodies present?

Answer 24

Alphaherpesvirus

AKA: Aujesky’s disease

Not zoonotic

-Replication in upper respiratory epithelium, tonsil, local lymph nodes, sensory nerve endings TRIGEMINAL GANGLION - olfatory bulb - brain (also hematogenous route).

-PREGNANT SOWS

-Dogs/Cats infection via ingestion of infected meant

-FACIAL PRURITUS

-Suppurative meningoencephalomyelitis, trigeminal ganglioneuritis, neuronal degeneration and necrosis. Macrophages not predominant, NO neutrophils.

-Fatal in a variety of animals

-Cattle, sheep, dogs, cats

-INIB not commonly detected in pigs but can be present in neurons and astrocytes

-Nonsuppurative encephalomyelitis, ganglioneuritis, Yes, INTRANEURONAL INCLUSION BODIES

Question 25

Bovine Malignant Catarrhal Fever

Not an Alpha virus

Mucous and vasculitis (catarrhal)

Is it present worldwide?

Highly fatal, sporadic

What is the primary target tissue?

What are the two associated types?

Which is the most transmitted vector?

Gross lesions

WM most often involved

Histologic characteristics

C/S

Answer 25

-Gammaherpesvirus

-Cattle, other ruminants, present worldwide.

-Vasculature, lymphoid organs, epithelium (respiratory and GI), others

1. Sheep-associated form Ovine herpesvirus-2
2. Wildebeest-derived form Ovine herpesvirus-2. Africa herpesvirus-1 from wildebeest

-Sheep: most transmitted vector

-T-lymphocytes trafficking endothelial cells

-Gross lesions: nonsuppurative meningoencephalomyelitis, necrotizing vasculitis.

-Histo: brain, spinal cord, WM most often involved

-C/S: trembling, shivering, ataxia, nystagmus (involuntary rapid movement of the eye)

Corneal Edema

Question 26

Morbillivirus (family Paramyxoviridae)

What type of pneumonia?

Dog, wolf, hyena, ferret, bear, raccoon, lions, tigers, leopards affected

Is it pantropic?

Affinity for lymphoid, epithelium

CNS demyelination with or without much inflammation?

Does it affect the optic nerve?

Dogs: aerosol, nasal mucosa, macrophages (WBC trafficking), regional LN replication, primary, secondary viremia, CNS = encephalomyelitis, repiratory, bladder, GI, WBC trafficking, grey matter, white matter of CNS, epithelial cells, macrophages, disseminated through ventricular system, ependymal cells, astrocytes, microglia, periventricular WM lesions, especially 4th ventricle (myelin degeneration, swollen astrocytes)

Characteristic intracellular injury?

What is different about the effect on Oligodendrocytes?

INIB present?

Answer 26

-Canine Distemper

-Bronchointerstitial pneumonia

-Pantropic (affecting several tissues): Lung, GI, Urinary tract, skin, CNS (including optic nerve).

-CNS demyelination without much inflammation

-Affects the optic nerve

-White matter vacuolation (intramyelinin edema)

-All CNS susceptible but OLIGODENDROCYTES infection is usually defective (incomplete)

-INIB are present in astrocytes, distinct acidophilic also seen in the cytoplasm of epithelial cells throughout the body. Eosinophilic inclusions

Question 27

Canine Distemper

C/S

Histo

What are the target cells where INIB and ICIB can be found?

Answer 27

-Immunosuppression: secondary bacterial infections (conjunctivitis, rhinitis, bronchopneumonia)

-Neurologic signs: myoclonus, tremor, circling, hyperesthesia, paralysis, blindness

-Histo: demyelination, nonsuppurative encephalitis, leptomeningitis, preivascular cuffing, microgliosis, astrogliosis, neuronal degeneration, INIB, ICIB (neurons, astrocytes = target cells), cerebral cortex, thalamus, brainstem

Question 28

Old-dog Encephalitis

Long or short term?

Results in proliferation of nonsuppurative inflammatory cells

Lesions?

C/S

Answer 28

-Long-term persistent infection of CNS with a defective form of CDV (in experimental infections)

-Lesions: primarily cerebral hemispheres, brainstem

-Old-dog encephalitis mature dogs affected

-C/S: depression, circling, head pressing, visual deficits, seizures, muscle fasciculations

Question 29

FIP

What two virus?

Where do they replicate?

What other animal has a similar virus and CNS lesions?

Pathogenesis

C/S

Does it replicate in macrophages?

What type of lesion distorts and obscures the blood vessels? Where and what type of fluid?

Answer 29

-Two coronaviruses: antigenically/morphologically indistinguishable
-Avirulent (FECV): enteric, ingestion, infects replicates in enterocytes
-Virulent (FIPV): mutated coronavirus

-Ferrets, domestic cats, wild felids.

-Saliva, feces, direct contact (bites, wounds), in utero, replicates in macrophages, liver, serosal surfaces, uvea, meninges, ependyma, spinal cord.

-FIP all ages, between 3 months and 3 years most critical, death.

-Clinical signs by involvement of blood vessels. Seizures, behavioral changes, ataxia, paralysis.

-Pyogranulomatous inflammation distorts and obscures blood vessels in cerebral vasculature of circle of Willis.

-Exudate accumulation of serous fluid and fibrin mixed with neutrophils and histiocytes to pyogranulomatous, commonly

Question 30

FIP

What does the disease development depend on?

How can the virus be resisted/contained?

What type of effusion form is the no cell mediated immunity? and what are the two proposed mechanisms?

What form causes serositis, fluid in abdomen/thoracic cavities, inflammation?

Which for is a type III hypersensitivity and which is a type IV?

Both forms lesions: preferential small + medium sized veins, pyogranulomatous vasculitis, vascular necrosis, infarction.

Dry form lesions?

Answer 30

-Depends on the type/degree of immunity.

-Strong cell-mediated immunity: virus containment, resistance

-Wet effusion form (humoral not protective) Th1 response

1. Ag/Ab complement complexes: type III hypersensitivity - effusion, inflammation of small blood vessels
2. Antibody dependent enhancement: Ag/Ab complement complex infected macrophages - cytokines - increased vascular permeability, edema.

-Effusive form (wet)

-Dry (non-effusive form) partial cell-mediated immunity Type IV hypersensitivity.

-Dry form lesions: leptomeningitis, chorioependymitis, encephalomeyelitis, opththalmitis. CNS non-suppurative pyogranumolatous vasculitis. Perivascular WM: especially 4th ventricle, uvea, retina, optic nerve sheath.

Question 31

What virus causes Rabies?

Where does it replicate?

What type of path of entry?

Spreads to salivary glands

Histo: L/P/ macrophages, microgliosis (macs of brain)

What is the type and name of inclusion bodies?

Pathogenesis: preripheral nerves in skeletal muscles entered, ascends to dorsal root ganglion, enters spinal cord, ascends to the brain via ascending and descending nerve fiber tracts, infects brain cells, spreads to salivary glands, eye, and excreted saliva.

Necropsy Protocols

What parts of the CNS need to be collected? hint: HCMS

Answer 31

-Rhabdoviruses

-Replication at inoculation site (skeletal muscles)

-Retrogade movement along axons to spinal cord and brain. 12-100 mm per day, gives some time before reaching brain

-Intracytoplasmic inclusion bodies called Negri bodies

Necropsy

-Additional protection
-Collection of CNS tissues: hippocampus, cerebellum, medulla and optional spinal cord.
-Remainder of brain fixed in 10% neutral buffered formalin for histopath (10:1 ratio)

Question 32

Nervous system Fungal and parasitic infections

What systemic fungi Does it include?

Which fungi is not typically included unless it is a German shepherd affected?

Which fungi has particular affinity for CNS?

What are the lesions?

Does it include multinucleated giant cells in lesions?

Which fungi produces microabscesses seen under microscope?

Answer 32

-Coccidiodes immitis
-Blastomyces dermatiditis
-Histoplasma capsulatum
-Cryptococcus neoformans (has particular affinity for CNS)

-Does not include Aspergillus unless German shepherd

-Lesions: Granulomatous to pyogranulomatous inflammation. Neutrophils, macrophages (epithelioid type), Multinucleated giant cells also. Nodular granulomas

-Cryptococcus neoformans

Question 33

What fungi is

-Extraecllular/intracellular
-200-300 um in diameter spherules
-Endospores (<5um in diameter)
-Replicates via endosporulation

Answer 33

Coccidiodes immitis

Largest of the systemic fungi

10 times size of neutrophils, can use that as reference for size

Question 34

-Replicates via narrow-based budding
-Often intrahistiocitic
-Spherical
-Approximately 2-4 um in diameter and contain a 1-2 um basophilic nuclei surrounded by a clear zone (on histo)

Answer 34

Histoplasma capsulatum

-Can be confused with Sporothrix, but that one has cigar shape.

Question 35

Cryptococcus neoformans

What species are most commonly affected?

What is the approximate size and shape?

What makes the capsule distinguishable?

Answer 35

-Cats, dogs, horses
-Replicare via narrow based budding
-15-25 um and spherical to crescent shaped.
-15-20 um thick mucicarmine staining capsule

Question 36

-Approximately 15-25 um in size
-Replicate via broad based budding
-Have double contoured wall

Answer 36

Blastomyces dermatiditis

Question 37

Opportunistic fungi examples

Are they systemic?

What does the zygomycetes group target and what is an example of disease caused by it?

Answer 37

Not systemic

Zygomycetes group

Targets blood vessels, Hyphae form, ex: guttural pouch mycoses*

-Absidia corymbifera
-Mucor spp.
-Rhizomucor pusillus
-Rhizopus arrhizus

Aspergillus spp.

-Hyphae that are septae with parallel walls at an angle of less than 90 degrees

Angioinvasive: vascular thrombosis and infarcts in CNS

Question 38

CNS Parasites

Where do they cause the lesion?

1. Neospora Caninum: affinity for what? random or orgonized pattern?
2. N. hughesi: What species is affected? What does it resemble? what is the lesion?
3. Toxoplasma gondii: is the only one with parasitophorus vacuole (extracellular, intracytoplasmic). Affects, felids, old world monkeys, rats, cattle, horses seem highly resistant. Where does the parasite replicate?

Answer 38

1. Tissue cysts phases. Affinity for brain (cerebellum in dogs). Multifocal necrotizing lesions with glial nodules, mixed inflammatory infiltrate, also abortions
   White and grey matter of spinal cord but also pons and medulla
2. Horses, resembles Sarcocystis neurona causing EPM. Lesion is meningoencephalomyelitis
3. Intraintestinal life cycle and extraintestinal. Encephalomyelitis

Question 39

What organism causes Equine Protozoal Encephalomyelitis?

What is the definitive and intermediate host?

Pathogenesis: ingestion sporocysts multiply in visceral tissue, CNS inflammation, edema, tissue destruction, affecting both WM and GM

Gross lesions

Is the distribution random or not? What does it affect?

Animal age most vulnerable

C/S

Answer 39

-Etioloic agent: Sarcocystis neurona

-DH: opossum
-IH: avian

-Gross: brainstem, spinal cord (cervical, lumbar intumesces). Necrosis, random hemorrhages of white/grey matter.

-S. neurona: crescent-round, well-defined nucleus, schizonts with merozoites in aggregates or rosettes

-Young adult horses

-C/S: depression, behavioral changes, seizures, gait abnormalities, ataxia, unilateral facial nerve paralysis, head tilt, tongue paralysis, urinary incontinence, dysphagia, atrophy of masseter and or temporal muscles, atrophy of quadriceps and or gluteals.

Question 40

What protozoal organism causes atrophy of messeter muscle, temporal muscle, quadriceps and or gluteals?

Answer 40

Sarcocystis neurona

Equine Protozoal Encephalomyelitis

Question 41

What disease is associated with aberrant migration of Cuterebra fly larvae?

What species is affected?

What cerebral artery if affected?

What age?

Unilateral or bilateral

Necrosis and hemorrhages in what part of CNS?

Histo:

C/S:

Answer 41

-Feline Ischemic Encephalopathy

-Cuterebra fly larvae migrates from nasal cavity to brain.

-Middle cerebral artery preferred and affected

-Any age

-Unilateral, WM and GM of cerebrum

-Necrosis, hemorrhages: CNS leptomeninges

-Histo: vasculitis, thrombosis, ischemia, infarction, cerebral cortical atrophy.

-C/S: summer months, unilateral, depression, mild ataxia, seizures, behavioral changes, blindness.

Cerebral hemisphere undergoes necrosis, followed by cyst formation and collapse after phagocytic removal of the necrotic debris

Hydrocephalus ex vacuo

Question 42

Nervous system: Nutritional, Toxicologic diseases

Hepatic encephalopathy

What is the cause?

What is the neurotoxin? how does it form?

What is typically found in the urine?

Ammonia and other toxic metabolites also cause increased permeability of BBB, leading to vasogenic edema.

C/S: Alter osmoregulation, ataxia, depressed mentation, walking aimlessly, head pressing.

Answer 42

-Hyperammonemmia: acute/chronic liver failure, hepatic atrophy (vascular shunts)

-Ammonia formed in the GI by bacterial degradation of amines, amino acids, purines, urea from proteins in diet.
-Liver detoxifies it to less toxic urea normally, then excreted in urine.

-Amonia butyrate in urine

Question 43

What are the primary CNS cells affected in Hepatic Encephalopathy?

What other condition where inadequate clearance of ammonia can be similar?

What species are affected?

Lesions

1. Reversible bilateral, symmetrical spongy (vacuolation) change (intramyelinin edema) in areas of intermingling of gray and white matter
2. Formation of Alsheimer’s type II astrocytes: gray matter, large vesicular nuclei, peripheral chromatin, glycogen deposits, nucleoli or nuclear-type bodies. Occurs in diads, triplets or clusters.

In clumps not much chromatin in nucleus

Answer 43

-Astrocytes primary lesion (Alzeimer’s type II astrocytes)

-Similar renal encephalopathy, renal injury leads to inadequate clearance.

-Dogs, ruminants, horses

Question 44

What can vitamin B1 (Thiamine) deficiency lead to? RUMINANTS

Encephalopathy, encephalomyelitis, encephalomyelopathy, or polioencephalomalacia?

-Not a disease entity in itself

What species is most affected?

What plants can cause ulceration and hemorrhage due to being high in Thiaminase-containing enzyme?

Salt, lead, sulfur toxicosis: sulfite cleaves thiamine = polioencephalomalacia

What does polio means here?

Pathogenesis

Causes

Why are young ruminants more susceptible?

Lesions

Cattle 6-18 months and sheep younger age (2-7 months) affected

C/S

Histo: Acute vs, chronic stage

What cerebral portion is preferentially affected?

Histo lesion ____

Answer 44

-Polioencephalomalacia

-Cattle > sheep > goats

-Bracken fern

-Polio = gray matter necrosis

-Pathogenesis: decreased in ruminal thiamine, inactive thiamine analogues OR overgrowth of thiaminase producing microbes

-Causes: carb rich diet in cattle, little roughage > acidosis > rumen microflora changes.

• Young ruminants have not fully populated thimaine-producing microbes in rumen yet. Microbes synthesize thiamine.

-Gross lesions: if present are limited to cerebral cortex
-Swollen (cerebral edema) +/- brain displacement, herniation.
-Autofluorescence under UV light 365 -nm, autofluorescent bands of necrotic cerebral cortex.
**Difficult to pick up lesions, look for interface between gray matter and white matter. **
Bilateral symmetric laminar pattern of apple-green autofluorescence (from mitochondrial derivatives) involving full thickness of cortex indicates GM necrosis

-C/S: small ruminants depression, stupor, ataxia, head presssing, cortical blindness, opisthotonos, convulsions, recumbency, paddling, death.

-Histo: acute stage = zone of edema and acute neuronal necrosis affecting lamina of cerebral cortex. Chronic stage = areas of microcavitation in deep cortical laminae next to subcortical white matter are poorly stained compared to those in normal cortex.

Laminar cortical necrosis, edema, astrocyte swelling, bilateral symmetric focal lesions in carnivores: thalamus, midbrain or colliculi

Question 45

Vitamin B1 deficiency (thiamine) in CARNIVORES

Which monogastric carnivores have an absolute requirement for B1?

Fish diets (especially during heating) containing thiaminase = B1 deficient diets (enzyme cleaves B1)

Gross lesions

Histo

C/S

Answer 45

-Dogs, cats, mink, fox.

-Gross: necrosis, bilateral symmetric focal lesions, thalamus, midbrain or colliculi

-Histo: neuronal vacuolation, degenerations, necrosis, hemorrhage, astrogliosis, gitter cells.

-C/S: vomiting, wide-based stance, ataxia, spastic paresis, circling, seizures, recumbency, opisthotonus, coma, or death.

Question 46

Copper Deficiency

Cu deficiency involved, pathogenesis complex, interplay with other metals (Zn, Fe, Molybdenum)

What are the two forms?

What are the lesions?

Both forms affect GM and WM, wool, hair growth, pigmentation, musculoskeletal development, integrity of connective tissue.

Gross

Histo

Answer 46

1. Swayback congenital form: affects lambs newborn (ewes with inadequate dietary Cu). Lambs born dead, weak or unable to stand
   -Lesions: cerebrum, brainstem
2. Enzootic ataxia: onset is delayed for up to 6 months after birth.
   -Lesions: postnatal onset, brainstem, spinal cord.

-Gross: 50% of affected lambs have bilateral cerebrocortical rarefration in white matter

-Histo: asatrogliosis associated degeneration of white matter, neuronal necrosis.

Question 47

PNS nutritional deficiencies

What disease in horses is a sequale of very low vitamin E concentrations?

What is the primary factor involved?

What parts of the cell are affected?

Gross lesions

Histo

C/S

Answer 47

-Equine motor neuron disease

-Dietary factors, long-term (>1 year) of Vit E deficient feeds, other andtioxidant deficiencies

-Cell bodies, axons of lower motor neurons (ventral horn cells, cranial nerves)

-Histo: cell bodies are lost, replaced by astrogliosis, LMN axons, WALLERIAN DEGENERATION. Abundant lipofuscin in neurons, endothelial cells.

-Lesion: atrophy of type 1 myofibers secondary to loss of type 1 lower motor neurons

-C/S: progressive degeneration, loss of lower motor neurons, muscle atrophy, weight loss, difficulty standing, muscle fasciculation.

Progressive disease, chronic damage may be too far

Question 48

What toxicity leads to bilateral symmetrical poliomyelomalacia and Acute paralytic syndrome in feeder pigs?

Is the pathogenesis known?

Gross lesion

Histo

C/S

Answer 48

• Selenium Toxicity

-Unknown, possible niacin deficiency

-Bilateral (symmetric) softening, ventral spinal gray matter

-Histo: neural, glial necrosis and loss, microcavitation, astrogliosis, gitter cells
WALLERIAN DEGENERATION (injury to axonal body)

-C/S: alert, sternal recumbency, quadraplegia with flaccid paralysis of rear limbs. Cutaneous rough hair coats, partial alopecia, separation/sloughing hoofs.

Question 49

Quadripplegia with flaccid paralysis of rear limbs is a C/S of what disease?

It also includes sloughing of hoofs

Answer 49

Selenium toxicosis

Question 50

Progressive degeneration, loss of lower motor neurons, muscle atrophy, weight loss, difficulty standing, muscle fasciculation are c/s of what disease?

Answer 50

Equine lower montor neuron disease

Question 51

What commonly leads to Sodium Chlorida Toxicity?

What species are primarily affected?

Pathogenesis

Gross lesions

Histo

C/S

Answer 51

-Water deprivation syndrome, or salt poisoning

-Pigs, poultry, occasionally ruminants

-Overconsumption of sodium chloride complicated by limited drinking water = severe dehydration or water restriction of sufficient duration

-Hyperosmolarity (hypernatremia from excessive Na+ or severe dehydration) followed by rehydration and a “rapid” hypernatremic to normonatremic or hyponatremic shift

-When given free access to fresh water, acute hypernatremic to hyponatremic shift occurs within minutes the brain offsets osmotis imbalance by eliminating Na+, K+, Cl- ions by actively transporting ions into vasculature, early response cannot offset osmotic stress caused by increased organic osmolytes in brain - water enters the brain - brain swelling
Drink slowly!!

Gross: cerebral, leptomeningeal congestion, edema

Histo: cerebrocortical laminar neuronal necrosis (PEM)

Pigs perivascular eosinophils with laminar cortical necrosis is indicative of salt toxicosis

Question 52

What is perivascular eosinophils with laminar cortical necrosis indicative of?

Accompanied by c/s: inappetence, dehydration, head pressing, incoordination, blindness, circling, paddling, convulsions, often found dead?

Eosinophils, polioencephalomyelomalacia (PEM)

Answer 52

Salt toxicosis primarily in pigs

Question 53

What are the Group 1 Organophospahtes?

What does SLUD stand for?

How do they affect Ach receptors uptake?

Which is affected Parasympathetic nervous system or Sympathetic?

are the clinical signs common in cattle?

Answer 53

-OP esters, pesticides, fungicides, herbicides, or rodenticides, inhibiting cholinesterase

-Ach accumulates at synaptic or myoneuronal junctions = persistent depolarization

-Acute OP toxicosis = SLUD excessive Salivation, Lacrimation, Urination, Defecation.

-Parasympathetic: bradycardia, pupillary constriction. Skeletal muscle fsciculations, weakness, paralysis (death by respiratory failure)

-C/S: restlessness, generalized seizures (dogs, cats, uncommon in cattle)

-Gross: nervous system absent, nonspecific in other tissues

Question 54

Group 2 Organophosphates usually found in what?

What types of toxicosis can occur?

When does axonal injury occur?

C/S

Age most affected, less affected

Are proprioceptive deficits usually present?

Answer 54

-Cresyl (triorthocresyl phosphate) in hydraulic fluids, lubricants, flame retardants

-Chronic toxicosis: most common cause of chemical induced distal axonopathy in Vet Med

-Chronic/delayed toxicosis: unrelated to cholinesterase inhibition as seen in acute OP toxicosis

-Axonal injury occurs approximately 10-14 days post exposure

-OPs delayed neurotoxicity inhibit activity of enzyme neuropathy target esterase (function of enzyme not fully understood)

C/S: delayed 1-2 wks post exposure, sensory/motor neuropathy and spinal cord (proprioceptive deficits)

-Young animals: less seriously affected

-Adults recover slow and incomplete

Question 55

What is the most common cause of chemically induced distal axonopathy in vet med?

Answer 55

Group 2 organophosphates toxicosis due to chronicity

Question 56

Heavy Metals

Arsenic Toxicity

Primary entry pathway

Multisystemic?

Give examples of inorganic and organic toxic compounds & C/S

Which arsenicals have greater potential for neurotoxicity?

What type of lesions are present?

Histo

What cells are preferentially injured?

What is the mechanism behind inorganic arsenicals toxicity?

What C/S are present in pigs?

Answer 56

-Ingestion or cutaneous inorganic or organic arsenicals

-Yes, multisystemic nervous system

-Inorganic compounds: Herbicides and pesticides.
C/S: enteric disease with hepatic, renal manifestations, neurologic signs

-Organic arsenicals: feed additives in pig, poultry industries as growth promoters and control enteric diseases.&raquo_space;> potential for neurotoxicity

-No gross lesions

-Histo: cranial, peripheral nerves, spinal cord, axonal degeneration, fragmentation of myelin sheaths

-Distal segments of long ascending fibers can be preferentially injured

-Inhibit sulfhydryl enzyme systems, disrupt cellular metabolism (exact mechanism of organic unknown)

-Pigs: blindness, tracts, incoordination, paresis, paralysis related to spinal cord and peripheral nerve lesions.

Question 57

Lead Toxicosis

Does it show gross and histology lesions?

What species is primarily affected?

What objects are a common cause?

Horses: cranial neuropathy > laryngeal and facial paralysis

C/S and organ/systems affected

Preferential cells for injury

Gross lesions

What does it resemble in cattle?

Small animals, especially dogs ataxia, tremors, clonic-tonic seizures, blindness, deafness

Birds lead picked up while scavenging animals that were shot, fishing sinkers, gunshot wounds.

Do lesions in dogs include vascular damage (necrosis, thrombosis)?

C/S in cows

Answer 57

-No gross/histo lesions, if parachute
-Acute, subacute, chronic

-Cattle

-Barn paint (lead), farm buildings, car batteries.

-CNS, PNS< liver, kidney, GI, bone marrow, blood vessels, cerebral endothelial cells.

-Direct toxin to neurons, astrocytes, cerebral endothelial cells

-Gross: contents of rumen. CNS lesions usually absent, can resemble PEM of cattle.

-Lesions of lead encephalopathy in ruminants must be differentiated from other causes of PEM

-Lesions in dogs with MORE Vascular damage

-Cows: down, dead, diarrhea, teeth grinding (bruxism), circling, head pressing, incoordination, blindness.

Question 58

Microbial Toxins

What are the types of neurotoxins in Botulism?

What domestic species is primarily affected in N. America?

Which is the most prevalent type in N. America?

____ ____ gram (+) anaerobe, soil, spores germinate in ____ ____

C/S in horses

What is the mechanism?

What type of toxin is produced by the bacteria?

What is inhibited at the myoneuronal junction?

Do the toxins produce macroscopic or microscopic lesions?

Answer 58

-Type A, B, or C in N. America

-Horses, different forms of botulism affect foals (Toxicoinfectious, ingestion of spores from contaminated soil) and adult horses (contaminated forage, wounds, hoof abscesses, skin wounds, ulcers).

-Most prevalent is Type B Mid Atlantic states to Ky
-Type A Western US

-Clostridium botulinum, necrotic tissue

-Horses: progressive paralysis of muscles (limbs, pharynx, eyelid, tongue, tail)

-Replicate, produce EXOTOXIN, blood stream, myoneural junctions, binds receptors (presynaptic terminals of peripheral cholinergic synapses), INHIBIT Ach release, flaccid paralysis, diaphragm paralysis = death.

-NO

Question 59

What is the neurotoxin produced by Clostridium tetani (Tetanus)?

What is the mechanism?

How is C. tetani similar to C. botulinum?

Are microscopic or macroscopic lesions present?

C/S in horses

What inhibitory neurotrasmitter release is inhibited?

What myoneural junction is target for binding of neurotoxin?

Answer 59

-Tetanospasmin in anaerobic wounds.

-Toxin binds myoneural jucntions and or sensory receptors, retrograde axoplasmic flow, accross synaptic junctions to CNS, toxin transferred across synapses, toxin blocks release of inhibitory neurotransmitters (glycine, GABBA) generalized muscular spasms.

-Gram (+) spore forming anaerobe; soil.

-Except for anaerobic wound, NO

-Horses C/S: colic, muscle stiffness (lips, nostrils, ears, jaw (lockjaw), tail, hyperesthetic, rapidly spastic, tetanic paralytic symdrome.

Question 60

Clostridium perfringes Type D Encelopathy

It is a.k.a ____

What is the toxin produced?

What species only exhibits neurologic manifestations?

Gross lesions

Histo

Which CNS matter is affected?

Pericapillary hemorrhage, acute necrosis of ____ and ____

How are lambs found?

**Focal symmetric encephalomalacia, brain, basal nuclei, and rostral thalamus, sheep. Kidney enlarge, pale, fragile **

Answer 60

-Pulpy kidney disease, overeating disease

-Type D enterotoxemia: EPSILON TOXIN

-Sheep: all ages, except newborns, are susceptible.

-Peaks between 3-10 wks of age, and in feeder lambs shortly after arrival at a feedlot.

-Gross: absent-bilaterally symmetric foci of malacia, hemorrhagic foci with cavitation

-Other tissues: soft pulpy kidneys

-Histo: acute cases = edema, endothelial cell swollen, vesicular

-Both grey and white matter are affected
-Neurons and macroglia

Lambs are typically in good condition and found dead

Question 61

A BAbE DrivEs a CAB Every DaEi

Answer 61

Type A: alpha toxin
Type B: alpha, Beta, and Epsilon
Type C: alpha, Beta,
Type D: alpha, Epsilon,
Type E: alpha, Eiota

**Clostridium likes to cause hemorrhage, +/- gaseous necrosis (black leg) ***

Question 62

Microbial Toxins

Edema Disease (Enterotoxemic Colibacillosis)

What bacteria and strain produces Shiga-like toxin?

What species is primarily affected?

What age?

Main injury is angiopathy, edematous, hypoxic-ischemic injury.

Gross

What are the characteristic gross lesions?

Histo

Is inflammation the primary process?

C/S: initial ataxia, laterally recumbent, paddling limbs, comatose, dies within 24 hours. Pigs that survive for several days typically develop CNS lesions

Answer 62

-Some strains of E-coli

-Feeder pigs rapidly growing, fed high energy ratio.

-4-8 wks of age, younger and older pigs can be affected

-Gross: facial edema (gastric submucosa, colonic mesentery, lungs, thoracic effusion, pericardial sac, +/- Congestion, hemorrhage, Pallor, spongiosis of CNS parenchyma.

-Characteristic brain: bilateral symmetric foci of necrosis in caudal medulla.

-Histo: Endothelial cells become swollen and vesicular, but layer remains intact so thrombosis not a feature.

-No, inflammation is not the primary process

Question 63

Leukoencephalomalacia

How do horses become infected?

What is the culprit fungus?

What is the sequelae?

Primary toxin is ____

____ ____ primary injury

Gross lesion & characteristic

Primary species affected

C/S

Answer 63

-Horses: ingestion of moldy corn contaminated with fungus FUSARIUM MONILIFORM

-Acute fatal neuroligic disease

-Fumonisin B1

-Vascular damage (necrotic, thrombosis)

-Gross lesions: WM of cerebral hemispheres most common. Bilateral but now symmetric (unequal in severity)

-Characteristic malacia, liquefaction of affected WM due to breakdown of lipids accompanied by hemorrhage

-Hepatotoxicity can be the sole manifestation

-C/S: depression, head pressing, aimless wandering, blindness, seizures, rapid progression and death.

-Other species: pigs, generally with pulmonary, hepatic and renal manifestations.

Question 64

What disease presents with

-Characteristic malacia, liquefaction of affected WM due to breakdown of lipids accompanied by hemorrhage in horses due to fumonisin B1 toxin, derived from Fusarium moniliforme fungus, from moldy corn ?

Answer 64

Leukoencephalomalacia is also associated with hepatotoxicity, or hepatotoxicity can be sole manifestation

Question 65

What toxic plant is Yellow star thistle, Russian knapweed?

What is the morphologic diagnosis for gross lesions of bilateral or unilateral sharply demarcated foci of yellow discoloration and malacia in globus pallidus (pallidal), substantia nigra (nigro) ?

Histo

C/S

Lip/Tongue ____

Phagocytosis by ____ cells

Answer 65

-Centaurea spp.

-Morph Dx: Nigropallidal encephalomalacia

-Histo: necrosis, loss of neurons is primary lesion. Necrotic axons, glia, blood vessels.

-Horses: persistent chewing, difficulty in prehension of feed, drinking water.

-Lip/tongue paralysis, reduced jaw tone early in disorder
-Death due to emaciation, starvation.

-Gitter cells

Question 66

Black-faced sheep, black skinned pigs are congenitally predispose to what abnormal, but no-pathologic condition?

Answer 66

-Meningeal Melanosis

Question 67

What disease is age related in horses, incidental, but can occlude flow of CSF?

Where does it form?

Describe the lesion

What does the lesion elicit?

What does it result from?

Answer 67

-Cholesteatomas a.k.a cholesterol granulomas

-Form in choroid plexuses of ventricles in horses

-Tan to yellow-brown firm masses with smooth often glistening surface +/- mineral

-Elicit foreign body granuloma, fatty components to it.

-Result from edema and minor, but repeated hemorrhages within choroid plexuses - cholesterol deposits

Question 68

What breeds are primarily affected by Idiopathic Encephalitides of Dogs?

are males or females more affected?

CS: variable behavior changes, circling, spinal cord lesions, paresis, ataxia

Gross lesions

Two forms: Disseminated and Focal form (thalamus and brainstem)

Histo

White matter is the target

Underlying mechanism

Answer 68

-Young middle-aged small breeds (poodles, terriers)

-Female > male

-Gross: gray-white to red, expansive areas within WM of brain, brain stem, irregular, well-defined margins, gelatinous, rubbery or granular consistency

-Histo: perivascular cuffing (CD3+ lymphs, perivascular CD163+ macs), PCs neuts, restircted to WM
-Chronic: abundant perivascular deposition of reticulin collagen

-Underlying mechanism: T-lymphocytes mediated Type IV hypersensitivity but not proven

Question 69

Idiopathic Encephalitides of Dogs

What are the two variants of NECROTIZING Encephalitides?

Gross & Histo lesions for each

Is spinal cord involvement common?

Etiopathogenesis unknown, variable clinical signs, nonspecific, behavior changes, processing of sensory initiation of voluntary movement.

Answer 69

1. Necrotizing meningoencephalitis (NME) a.k.a Pug dog encephalitis. Almost always in small breed dogs

-Gross: bilateral foci of malacia, discolored cerebral hemispheres.
-Histo: meningoencephalitis, robust inflammation, nonsuppurative, marked gliosis
-Unlike GME (granulomatous meningo-encephalomyelitis) spinal cord involvement is not common

2. Necrotizing leukoencephalitis (NLE): predominantes in white matter

-Gross: Prominent bilateral cavitation, necrosis of cerebral white matter
-Histo: robust nonsuppurative inflammation, cavitation, edema, gitter cell infiltration

Question 70

Lysosomal Storage Diseases

Mechanism of injury, macrophages involvement

Causes

General Principle

Is Gangliosidoses inherited? recessive or dominant?

What happens if the genetic defect is mutant or instead residual synthesis of deficient enzyme?

Answer 70

-LSDs: substrates can’t be degraded by lysosomes, they accumulate and death of affected cells occurs. Macrophages have the same genetic defect, they die and release substrate in phagocytosed by other macs recruited from blood.

-Pressure atrophy on other organelles of the cell

-Causes: Reduction of lysosomal enzemy synthesis, synthesis of catalytically inactive proteins, defects in posttranslational processing of enzyme - misdirected to sites (extracellular) other than to lysosomes.
-Lack of enzyme activator, substrate activator protein required to assist with the hydrolysis of substrate. Lack of transport protein required for elimination of digested material from lysosomes.

-General principle: cell swelling, cytoplasmic vacuolation, many lipids and glycolipids are unique to nervous system, when there is lysosomal defect, neural cells often accumulate substrate

Gangliosidoses: is inherited autosomal recessive.
-Age of onset varies (different lysosomal enzymes)
-If mutant, enzyme is not synthesized at all = early onset
-If residual synthesis of deficient enzyme = later onset form

Gross lesion

-CNS vary among different types of LSDs
-Brain atrophy occurs with: **Globoid cell leukodystrophy: because of the loss of myelin. Ceroid-lipofuscinosis.

Histo Lesions

-Neurons: foamy, finely vacillated or granular cytoplasms.
-Specific features of stored material best appreciated by EM (electromicroscope)

Question 71

What is Ceroid-lipofiscinosis associated with?

Characteristics

Slow or fast progressive disease?

Gross lesions: what part is affected?

Histo: what part of the neuron is affected?

Answer 71

-VitE deficiency association
-Slowly progressive neurologic diseases

Characterized by abnormal sphingolipid (lipopigments) metabolism. Cats, dogs, sheep, cattle.
Lysosomal dysfunction not clearly identified

Gross lesions

-Atrophy of cerebral gyro, widening of sulci.
-Brain atrophy with carotid-lipofuscinosis (later stages of disease) in cerebral cortex, sometimes cerebellum.

Histo

-Neuron cytoplasm
-Eosihophilic granular material (H&E), decreased # of neurons, prominent reactive astrogliosis microgliosis.
-Pic: horse with carotid-lipofuscionosis

Question 72

What disease is characterized by primary demyelination of oligodendrocytes of CNS, Schwann cells of PNS as principal lesion?

What is the deficient enzyme activity? What does it result in?

Breeds: Cairn, West highland terrier = autosomal recessive. Others: Beagles, Mini poodles, Bassets, Pots, Bluetick hounds, DSH, DLH cats.

Affects mostly: animals < 1yr old.

Sequence of event: Early “normal” myelination progresses, then disruption.

Gross and Histo lesions

C/S: ataxia, limb weakness, tremos - paralysis, muscular atrophy, blindness.

What are globoid cells? activated blood monocytes

Answer 72

LSD: Lysosomal storage disease, Globoid Cell Leukodystrophy White matter target

-Disruption of normal myelin turnover due to deficient galactosylceramidase activity = accumulation of psychosis - primary demyelination, recruitment of phagocytes (resident microglia, trafficking blood monocytes)
= Infiltration of macs, become globoid cell after phagocytosis myelin byproducts.

Gross: discoloration of WM, especially cerebral hemispheres, spinal cord.

Histo: Loss of myelin, globoid cells containing galactocerebroside, PAS (+)

Peripheral Nerves also affected

**Primary demyelination - axonal degeneration and globoid cells.

Dx: biopsy sensory branches of peripheral nerves

Question 73

What is the term for the disease caused by viruses leading to underdevelopment of myelin?

What are some viral examples in specific species?

Answer 73

HYPOMYELINOGENESIS

-Hypomyelination

Classical swine fever (hog cholera) PESTIVIRUS

-Teratogenic in fetus
-Hypomyelinogenesis
-Cerebellar hypoplasia
-Microencephaly
-PI that results in inhibition of cell devision, function of selected tissues proposed

Border disease virus (also PESTIVIRUS)

-Lambs and goats
-Hypomyelinogenesis, primarily affecting WM of cerebrum, cerebellum.

Gross
-Difficult to distinguish between WM and GM of cerebrum, cerebellum.
PNS is unaffected
-In lambs: early inflammation, porencephaly-hydraencephaly, cerebellar hypoplasia, microencephaly, smaller diameter of spinal cord.

Question 74

What is the pattern of a traumatic brain injury such as dogs HBC?

Sequence of lesions?

What part of the neurons is severely affected?

Excessive release of glutamate, excitotoxicity, cell death, free radical formation, apoptosis, delayed inflammatory responses, end result = WALLERIAN DEGENERATION

Answer 74

-Diffuse brain injury (often present in concussion)
-acceleration/deceleration forces to many areas of CNS
-Diffuse axonal injury: variant of diffuse brain injury. Axons of large myelinated nerve fibers injured by shearing forces.

-Concussion, contusion, hemorrhage
-Compression, stretching, laceration of neurons/axons.

Question 75

What are some functional factors that play an important role in brain injury?

C/S: vary, give examples

How are concussion and concussion different?

Which type of contusion is
-Located at the impact site, lesion develops on same spot (rat and bat hit)
-Location on the opposite side of brain (rat and bat hit but injury on the back of brain)
-When two lesions occur together (coup-contrecoup, or countercoup-coup), first term indicates the site of severe injury

What are the condition involved in coup-countercoup concussion?

Answer 75

-Brain of a freely movable head is much more susceptible to injury than one that is fixed in place. Cranium and contents impact each other after non penetrating trauma - space between brain and cranium

C/S:
-transient unconsciousness and return to normal function to depression, abnormal behaviors
-Disorientation, irritability, semiconsciousness with responsiveness only to noxious stimuli.
-Unconsciousness with no response to stimulus

Spinal cord trauma

-Signs vary: paralysis (severance of cord or ruptured disc) paresis, ataxia (less severe injury)

Concussion

-Difficult to produce severe concussion in animals (margin between force os a stunning blow and one causing fatal injury is very small)
-Diffuse
-Transient (usually reversible)
-Temporary loss of consciousness
-No gross lesion
-Minimal microscopic lesion
-Uncommon in animals
-The smaller the brain, the less vulnerable it is to rotational forces and the larger are the forces necessary to cause concussion

Spinal concussions

-Immediate and temporary loss of function that sometimes follows severe direct blows

Contusion

-Brain bruising
-Associated with rupture of blood vessel and hemorrhage as resulting injury
Focal
-Does not always result in unconsciousness

Gross
-Superficial area of hemorrhage associated with skull fracture
-Large blunt object

Types of contusion

-Coup contusion
-Contrecoup
-Coup-contrecoup: conditions include head freely moveable, head accelerated rapidly, because the brain does not fill the cranial vault it may lag behind the movement. As a result the inside of the cranial vault may strike the stationary brain at the point of impact (coup injury) or on the opposite side (countercoup)

Question 76

What are some common causes of CNS hemorrhage in animals?

What is the most common cause?
Would it be a diffuse or focal hematoma?

Where is the lesion in an epidural, subdural, and subarachnoid hemorrhage?

Answer 76

Vasculatis (ex: fungal infections), trauma, contusion, penetrating wounds

-Trauma: most common cause = epidural, subdural, and subarachnoid under the pic matter (subpial). Brain (parenchymal)
-Diffuse or focal hematoma

-Epidural: between the calvaria and dura matter
-Subdural: between dura matter and arachnoid
-Leptomeningeal or Subarachnoid: in the subarachnoid space and pit matter
-Parenchymal: in the brain tissue

Question 77

What are the three patterns of lesions in PNS?

-Lower motor or sensory peripheral nerve injury: common in animals, lacerations, stretching, tearing, compression or contusion. Peripheral nerves have a greater capacity for repair.

Which way may or may not result in total recovery of function?
Degree of injury to the axon

Wallerian degeneration occurs in which types of axonal injury? what other tissue is damaged?

Match the images with the injury type

What is a neuroma?

Answer 77

1. Neurapraxia: mild injury; axon is intact; temporary conduction block, total recovery of function is possible
2. Axonotmesis: more severe damage, destroys axon but leaves connective tissue framework intact (results in Wallerian degeneration)
3. Mild neurotmesis: severance of nerve + destruction of supporting framework. Wallerian degeneration distal to injury, potential for regeneration but little chance or normal rein nervation.
4. Severe neurotmesis

-Destruction of framework - fibrosis between proximal and distal ends of nerve; gap may be large
-Fibrous tissue can obstruct regenerating proximal axon from reaching distal supporting framework of axon
-If regenerative response is exuberant but unproductive, a “potentially” palpable bulbous-like growth can form at severed stump of the proximal axon called “neuroma”

Question 78

Intervertebral disc disease

What are the types? in what anatomical plane orientation do they occur in dogs?

Which type is more painful?

What are the common affecting ages and breeds for each?

Which one presents with changes similar to pulposus fibrosus?

Answer 78

Occur dorsally in dogs

Type I Hansen herniation in IVDD

-Chondrodystrophic breeds: Dachschund, Pekingese
-Acute: progressive degeneration of discs, TRAUMATIC INJURY
-Genetic (chondroid) metaplastic change of nucleus pulposus
-Very painful
-6 mts of age, progresses rapidly - loss of elasticity of nucleus pulposus disk compresses blood vessels and spinal cord segment = ischemia, neuronal excitotoxicity, necrosis - stress on annulus fibrosis (degeneration changes similar to nucleus pulposus; annulus fibrosis is thinnest, weakest at point of contact with spinal cord) **most severe spinal cord damage (no time for collateral circulation to develop)
-Multiple disks can be affected

Type II Hansen

-Older dogs: 8-10 yr old
-Non-chondrodystrophic breeds German Shepherds, Labs, Doberman, Obese dogs
-Slower degeneration - gradual loss of elasticity places mechanical stress forces on annulus fibrosus = protrusion/compression of spinal canal
Less painful than type I

Question 79

Ichemic Myelopathy
(Fibrocartilaginous Embolic Myelopathy)

What species does it affect?

Which type/breed of dogs are mostly affected?

What injury is present?

In what way is it identical to IVDs?

What type of infarct?

Gross, Histo, and C/S

Answer 79

-All species, most common in dogs
-Larger breed, chondrodystriphic breeds
-Young or old

Lesion: herniation of fibrocartilage from intervertebral disk (nucleus pulposus) - fragmentation into vasculature - occlusive emboli

-Ventral spinal artery/vein and tributaries commonly affected (due to proximity to extruded disk material)

Gross

-Acute focal infarct involving cervical or lumbar spinal cord most commonly

Histo

-Emboli histochemically identical to fibrocartilage of nucleus pulposus of IVDs occlude meningeal or CNS arteries or veins, or both, in affected areas.

C/S

-Sudden onset of spinal cord deficits, sometimes cerebral involvement

Question 80

What disease is also called “Roaring” ?

What never is affected?

What muscle is affected? Which muscle is the main abductor of the larynx?

What are some causes?

Gross, Histo, C/S

Answer 80

PNS Injury

-Recurrent laryngeal nerve paralysis
-Atrophy of left dorsal cricoarytenoid muscles, dysfunction of larynx
Cricoarytenoid dorsalis: main abductor of larynx muscle

Gross

-Recognizable to being inapparent degeneration

Histo

-Wallerian degeneration
-Primarily a disease of large horse breed 2-7 yrs

Question 81

What disease is also known as Wobbler syndrome?

Characterized by stenosis, rapid compression of spina cord - hypoxia-ischemia, necrosis, compressed axons

Does Wallerian degeneration occurs?

White or gray matter affected?

What species and age group is primarily affected?

How many syndromes can occur?

What spinal vertebrae number are affected?

Answer 81

Equine Cervical Stenoic Myelopathy (CSM)

-Yes, Wallerian degeneration present
-Both white and grey matter, or either one affected by necrosis
-Young rapidly growing large breed horses and dogs
-Multifactorial disease: Oversupplemetation (protein, vitamins, minerals)

Gross

-Visible on saggital section of spinal cord

1. Cervical static stenosis syndrome C5-C7 compression, horses 1-4 yrs and compression regardless of head position
2. Cervical vertebral instability (dynamic stenosis) syndrome
   C3-C5 Narrowing of spinal canal during flexion of neck.

Canine Cervical Stenotic Myelopathy

-AKA Wobbler syndrome, vertebral instability, vertebral subluxation
-Great Dane, Doberman, Saint bernard, Irish setter, Fox terrier, Basset, Rhodesian, Old English sheep dog.
-Signs develop between 8 mt - 1 year
-Most often C5-C7 is affected
-Basset hound: C3

Question 82

What are the anatomical locations for diagnosis sample collection of different neurological diseases?

Answer 82

1. Rabies: CN V (trigeminal ganglion)
2. Pseudorabies CN V
3. Listeriosis CNV
4. Yellow start thistle/Russian knwpweed poisoning (horses): Globus pallidus and substantial nigra nuclei
5. Equine degenerative encephalomyelopahty: Medulla Oblongata
6. Transmissible spongiform encephalopathies: Medulla oblongata

Question 83

Primary tumors of the nervous system

Answer 83

Question 84

Are Astrocytomas benign or malignant?

Three types based on what?

Which type recapitulates features of astrocytes?

Which type displays high cellular pleomorphism and mitoses, necrosis?

Which type is characterized by hemorrhage and most poorly differentiated astrocytes?

What species and breeds are affected?

What is the common lesion site?

Answer 84

-All are malignant

Three types based on degree of differentiation

1. Diffuse astrocytomas
   -Most well differentiated astrocytes, loosely organized
   -Slow growing, less malignant, looks similar to normal tissue; solid or firm; gray-white, poorly demarcated
   Pilocytic gemistocytic variants: both recapitulate features of astrocytes
2. Anaplastic astrocytomas: high cellular pleomorphism and mitoses, necrosis
3. Glioblastoma multiforme
   -Hemorrhage
   -Increased pleomorphism, high mitotic rate, necrosis
   -Characterized by glomeruloid-llike vascular proliferation, serpiginous tracts of necrosis lined by neoplastic cells (pseudopalisading )
   -Most poorly differentiated astrocytes
   -Rapidly growing, more malignant, easier to discern because of necrosis, hemorrhage, cavitation, edema
4. Oligodendrogliomas

Brachycephalics: Bostons, Boxers, dogs 5-11 yrs, cats»horses, cattle, pigs

Common lesion site: cerebrum (temporal, pyriform lobes, that-hypothalamus, midbrain)

Less frequent: cerebellum, spinal cord.

Question 85

What neoplasia affects the cells that make myelin and have fatty appearance?

Breeds affected: Brachycephalic, 5-11 yrs old.

Sites: Cerebrum, brainstem, especially close to lateral ventricles.

Where do they tend to extend to?

Is the mass well-demarcated or not?

Answer 85

Oligodendrogliomas

-Tend to extend to meningeal, ventricular surfaces, dissemination via CFS, ventricular system to distant brains sites common

-Well demarcated mass, variable size, gray to pink-red and soft to gelatinous with areas of hemorrhage +/- cystic

Question 86

What type of tumors and location is most common in dogs than horses and cattle?

What age of dogs are affected?

Which ventricle is more affected than others?

Gross lesion

Answer 86

Choroid Plexus Tumors

-Papillomas (benign), carcinomas, epithelial cuboidal cells.
-4th ventricle > 3rd, lateral ventricles
-Hydrocephalus possible sequelae

Gross

-Well-defined, expansive, granular to papillary growth within ventricular system, gray-white-red, compresses adjacent tissue.

Question 87

What are the most common CNS neoplasm of dogs and cats, but rare in horses? hint: benign, uniquely occurs in 3rd ventricle of cats.

Age group affected

Lesion site

Gross

Histo

What are psammoma bodies?

Answer 87

Meningiomas

-Dogs 7-14 yrs, cats >10 yrs
-Dog lesion: brain, spinal cord, retrobulbar (optic nerve sheath)
-Cat lesion: uniquely occurs in 3rd ventricle, cerebral hemispheres, along cerebra, cerebellum and tentorium, rarely at base of brain
Compress (pressure atrophy) or invade underlying CNS parenchyma

Gross

-Dog:solitary, vary insize, well defined, spherical, lobulated, firm, encapsulated, gray-white +/- soft, areas of hemorrhage, necrosis

-Cat: mm to 2 cm in diameter multiple, can be incidental, old-age findings

Histo

-Microscopic findings, patterns subtypes as Type 1-4 most common in dog.
-Transitional
-Meningothelial
-Psammomatous
-Fibrous
-Atypical
-Malignant
-Almost all meningiomas: features typical of maningothelial or transitional type with psammoma bodies (are concentric lamellated calcified structures) being a common feature.

Question 88

Hemangiosarcoma

Where does it come from usually?

What species is mostly affected?

What color and pattern is the lesion?

What is the morphological diagnosis?

Answer 88

-Most are metastases from other organs
-Dogs > other
-solitary expansile red to dark red mass within the cerebral cortex
-Dx: primary or metastatic melanoma

Question 89

PNS Structure and Function

What are myelinated and non-myelinated axons made of?

What is the function of neurons neurofilaments and microtubules in PNS?

What are the PNS supporting cells?

Answer 89

-Neurofilaments: structural support
-Microtubules: (bidirectional axoplasmic flow of nutrients, trophic factors, maintenance of axon, neuronal integrity)

Supporting cells

Schwann Cells:

-Surround myelinated/nonmyelinated axons; produce myelin sheaths
-Guides axon during formation, maintenance of PNS, regeneration role

Fibroblast: of endomeurium

Satellite cells (schwann-like cells): dorsal root ganglia, supportive, non-myelinating role

Enteric division of PNS

-Digestive motility, secretion, absorption, blood flow.
-Myenteric plexuses (Auerbach’s plexuses): between longitudinal and circular muscles
-Submucosal plexuses (Meissner’s plexuses): innervate esophageal, intestinal smooth muscle.
-Injury to theses plexuses can lead to dysautonomias (discussed later).

Question 90

PNS Tumors

Bening and malignant nerve sheath tumors

What are the three types?

Answer 90

1. Schwannomas

-Derived from Schwann cells
-Dogs>cats, horses, cow

Gross: nodular thickening along nerve trunks/roots; firm/soft (gelatinous), white/gray

Histo: neoplastic Schwann cells with two patterns, known as Antoni type A and type B

2. Perineuriomas
   -Derived from perineurial cells
   -Behaves as a benign neoplasm
   -Vary rare variant
3. Neurofibromas
   -Consist of Schwann cells, perineurial cells, fibroblasts
   -Not common in domestic animals.

Tumors can occur most commonly in cows and dogs. The term nerve sheath tumor groups all morphologic diagnoses under a common umbrella

Question 91

What is the name for the degeneration of neurons in ganglia of enteric division of PNS?

What is it called in dogs and cats, llama sheep, cattle horses?

Is there a known cause?

What is the history characteristic?

Is it overly inflammatory?

C/S

Answer 91

Dysautonomias

-Key-Gaskell Syndrome
-Unknown cause; hereditary? toxins in cats?

Histo: neuronal chromatolysis, pyknosis to loss of neurons, proliferation of satellite cells

-Minimal to mild WBC infiltrates
-NOT overtly inflammatory

C/S

-Cats, dogs, varied; GI disturbances, urinary incontinence, mydriasis, unresponsive pupils, bradycardia.

Question 92

What is Peripheral Neuropathies Colonic Agangliosis (Morph) a.k.a?

What happens to the stasis of the gut?

What breed and markings of horses is primarily affected?

Answer 92

Lethal White Foal Syndrome

-Functional blockage of ileum and or colon because of lack of innervation
-Disorder involving development of the enteric division of the PNS.

-Foals of American paint horses with overo markings
-Homozygous dominant mutations in the endothelia-B receptor gene

Histo: myenteric and submucosal enteric ganglia are absent, areas affected vary; can extend anywhere between ileum and distal large colon

Affected foals die within days birth: functional blockage… born with white or nearly white skin

Question 93

Autoimmune Diseases

PNS neuromuscular junction diseases

What type of hypersensitivity is it?

What receptor is affected by antibodies? what is the result?

What does it occur often concurrently with?

What are some findings?

What are some causes?

Are there any gross lesions?

Answer 93

Myasthenia Gravis

Causes

-Aquired: autoimmune mechanism
-Antibodies to acetylcholine receptors (type II hypersensitivity) on postsynaptic muscle membranes - blocks Act binding
-Congenital: genetic abnormalities. Genetically determined deficiency in number of acetylcholine receptors.
-Concurrently with Thymic abnormalities Tymoma, thyme hyperplasia.

Results in flaccid paralysis of skeletal muscle

No gross or microscopic lesions in PNS or CNS

Findings: skeletal muscle atrophy, megaesophagus

Question 94

Lymphoid/Lymphatic System

How is lymphoid tissue/organs categorized?

Answer 94

1. Primary lymphoid organs
   -Where B, T lymphocytes proliferate, differentiate, mature.
   Thymus, Bone marrow, Bursa of Fibricius (birds)
2. Secondary lymphoid organs/tissue
   **Spleen, Lymph nodes (except reptiles, birds, amphibians,) Lymph nodules

Question 95

What primary lymph node organ is essential for development and function of the immune system?

Referred to as lymph-epithelial organ, composed of epithelial and lymphoid tissue (epithelial and lymphoid tumors) generated in bone marrow

Where is it formed in the fetus?

What type of lymphocyte population does it carry?

Where do most animals have it anatomically?

Anatomy of thymus: what are the components of each lobule? How is the lobule subdivided? What are Hassall’s corpuscles?

How does the thymus respond to injury?

What are some caused of lymphoid atrophy in lymphoid organs?

What is MALT?

What are some defense mechanisms, ports of entry?

Answer 95

Thymus

Formed from third pharyngeal pouch in fetus

Bone marrow derived progenitor cells lymphocyte population

Domestic animals: **Paired cervical lobes (left and right), intermediate lobe at thoracic inlet, and thoracic lobe (may be bilobed)

Thymus Anatomy

Connective tissue capsule: septa subdivided into lobules, each lobule has central medulla and surrounding cortex

1. Cortex: epithelial reticulum and lymphocytes
   -Stellate cells of epithelia reticulum form a supportive network
   -Lymphoid component: differentiation lymphocytes derived from precursor T lymphocytes in BM
2. Medulla: similar epithelial reticular cells
   -Hassall’s corpuscles: distinctive keratinized epithelial structures
   -Interdigitating dendritic cells (DCs) in medulla
   -Far fewer lymphocytes than in cortex
3. Thymic vasculature

Response to Injury

-Lymphoid atrophy
-Neoplasia: lymphoma, thymoma
-Hemorrhage
-Inflammation: rare, infectious agents (porcine circovirus)

General causes of Lymphoid Atrophy in Lymphoid Organs

-Lack of antigenic stimulus
-Toxins: lead, mercury, mycotoxins, halogenated aromatic hydrocarbons
-Chemotherapeutic agents: cyclosporin A, corticosteroids
-Ionizing radiation
-Viruses: CDV, canine and feline parvovirus, FIV, BVDV, classic swine fever virus, EHV-1 More common cause of thymus atrophy
-Malnutrition and Cachexia
-Aging

Portals of entry

-Main: hematogenous

Defense mechanisms

-Innate, adaptive immune responses
-Viruses, bacteria arriving in lymph and blood interact with cells of monocyte-macrophage system through phagocytosis and antigen presentation

MALT: mucosa associated lymphoid tissue

-Hematogenous
-Migrating macrophages
-Dendritic cells
-M cells (Peyer’s patches)

Question 96

What are some infectious agents that cause Thymitis?

Is thymitis common?

If thymitis is present how are other lymphatic organs?

What mycotoxins cause lymphocytolysis in thymic cortex?

How does malnutrition, aging and neoplastic have effects on the thymus?

Answer 96

-EHV-1 in aborted foals
-Classic swine fever
-BVDV
-Canine distemper
-Parvovirus feline and canine
-FIV

-Not common lesion
-Other organs also affected

PCV2, enzootic bovine abortion, salmon poisoning in dogs

-Mycotoxins: fumonisins B1, B2 and aflatoxin

There are not many specific toxins that target the thymus, is rather via immunosuppressive, immunostimulatory, DNA damage

Malnutrition and cachexia (may occur with neoplasia)
-Lead to secondary immunosuppression
-Thymic function is impaired in young malnourished animals: LYMPHOID ATROPHY (physiological/emotional stress): release of catecholamines, glucocorticoids

Aging
-All lymphoid organs atrophy with advancing age = immunosuppressed
-Thymic reduction in size occurs after sexual maturity (thyme involution)

Question 97

What are the effects of Myasthenia graves on the thymus?

What is Asymptomatic thymic hyperplasia associated with in juvenile animals? is the thymus symmetrical or asymmetrical?

Answer 97

-Autoimmune lynphoid hyperplasia of thymus from Myasthenia graves
-Juvinile animals in association with immunizations: symmetrical thymus size

Question 98

What species and age group is primarily affected by thymic hematomas and hemorrhage?

What is the main site of injury?

What are some common causes?

Answer 98

-Dogs: young animals

Causes

-Anticougulant rodenticides (warfarin, dicoumarol, brodicoum).
Medulla: main site of hemorrhage
-Dissecting aortic aneurysms
-Trauma (HBC)
-Idiopathic/spontaneous
Pic: acute thymic mediastinal, and pericardial sac hemorrhage

Question 99

What disease can lead to megaesophagus, aspiration pneumonia, resulting from autoantibodies directed toward acetylcholine receptors?

Pic: thymic lymphoma in cat

What type of components are present in the thymus?

Where does thymic lymphoma arise from?

Which is usually benign and is common in goats, often cystic?

Answer 99

Myasthenia gravis

1. Lymphoid component
2. Epithelial component

Neoplasms arise from either component

Thymic lymphoma: arises from T lymphocytes in thymus (very rarely B lymphocytes)
-Young cats, cattle > dogs

Thymomas
-Arise from epithelial component
-Usually benign
-Common in goats
-IM diseases: myasthenia graves and IM polymyositis occur with thymomas in dogs > cats.

Question 100

Describe the structure of lymph nodes?

How do they respond to injury/dysfunction?

Where are B-lymphocytes and T lymphocytes present in the lymph node? where is the monocyte-macrophage system?

What are the patterns of enlarged lymph nodes?

Answer 100

-Soft, pale tan, round, oval, or reniform organs
-Stroma capsule, trabeculae, reticulum
-Cortex “superficial (outer) cortex: lymphoid follicles, B lymphocytes
-Paracortex “Deep” T lymphocytes
-Medulla : medullary sinuses and cords
-Blood vessels: arteries, arterioles, High endothelial venueles, efferent veins
-Lymphatic vessels: afferent/efferent vessels; sinuses (sub scapular, trabecular, medullary)
-Monocyte-macrophage system - Sinus histiocytes

Response to injury

-Based in the systems:
1. Sinus histiocytes of monocyte-macrophage system (antigen presenting cells): first line of defense against infectious and noninfectious agents in incoming lymph
-Hyperplasia of macrophages (“sinus histiocytes”) notable in medullary sinuses
-Leukocytes (monocytes), harbor intracellular pathogens, arrive in blood or lymph - LN - disseminated throughout the body.

2. cortex (lymphoid follicles) antigenic ally stimulated lymph node (follicular hyperplasia): enlarged
3. paracortex: Paracortical atrophy: deficiency in lymphocyte production in BM, reduced differential selection of lymphocyte in thymus, or destruction of lymphocytes in lymph
   -Paracotical hyperplasia: nodular or diffuse appearance
4. medulla (medullary sinuses and medullary cords): dilation of sinuses, proliferation of histiocytes (“sinus histiocytes”) dilation of sinuses due to edema, inflammation, occasional fibrin, in addition to hyperplastic resident sinus histiocytes

Patterns

-Generalized enlarged LN: lymphadenopathy or lymphadenomegaly (more than one, multiple). systemic infection, inflammatory or neoplastic processes

-Single lymph node (or regional chain), area drained by that LN should be checked for lesions.

-Large mesenteric LNs: follicular hyperplasia, enlarged

Question 101

What are the portals of entry/spread LNs injury?

Who stimulate LNs to have Th1 or Th2 responses?

Answer 101

-Afferent lymphatic vessels: lymphatic spread
-Blood vessels: hematogenous spread
-Organisms to regional LNs through lymphatic vessels - transported to next LNs in chain - lymphatic vessels to cervical or thoracic ducts - disseminated

Defense mechanisms

-Innate, adaptive immune responses
-Structural: thick fibrous capsules

Responses to injury
1. Hyperplasia
2. Atrophy
3. Inflammation
4. Neoplasia: primary (lymphoma), metastatic

Macrophages

Question 102

Resembles LN with lymph follicles and sinuses, except they are filled with blood. What am I?

What is the function?

What species is commonly found?

What is the gross appearance?

Answer 102

Hemal Lymph nodes

-Filter blood, remove senescent RBCs (blood supply is small and functional important is not clear)
-Mostly found in ruminants, horses, primates, some canids.

-Small, dark red to brown nodes

Question 103

What are the different pigmentation of LNs and what is their importance?

What pigmentation results from Fascicola hepatica/magna infection?

Answer 103

Red

-Draining from hemorrhagic or acutely inflamed area
-Acute lymphadenitis
-Acute septicemias with endotoxin-induced vasculitis or DIC
-Postmortem hypostatic congestion

Black

-Tracheobronchial LN (draining of carbon pigment (pulmonary anthracosis))
-Skin tattoos

Brown (black/brown/rust)

-Melanin: animals with melanosis, chronic dermatitis, distinguish from metastatic melanomas
-Parasitic hematin: Fascicola magna (cattle) and Fascicola hepatica (sheep) in liver - hepatic lymph nodes
-Hemosiderin: hemorrhagic node or hemosiderin from congested, inflamed, hemorrhagic areas. Iron dextran intramuscular injections in piglets (supplement)

Green

-Tattoo ink
-Ingestion of blue-green algae (mesenteric LN)
-Massive eosinophilic inflammation
-Mutant Corriedale sheep (genetic defect: deficiency in excretion of bilirubin and phylloerythrin by liver)

Miscellaneous

-IV injected dyes (methylene blue or trypan blue)
-SQ drug injections
-Icteric LN

Question 104

What are some of the disorders that cause small lymph nodes in animals?

Large Lympho nodes causes and disorders

Answer 104

-Congenital disorders: SCID severe combined immunodeficiency
-Lack of antigenic stimulation: smaller organs as a result. SPF animals (specific pathogen free animals)

Viral infections

-EVH-1
-CSF
-BVDV
-CDV
-Fe/K9 parvovirus

Cachexia and malnutrition: glucocorticoids
-Aging
-Radiation

Enlarged LNs

-Lynphoid hyperplasia (follicular, paracortical)
-Hyperplasia of sinuses histiocytes, macrophage-monocyte system FIV, MCF
-Acute or chronic lymphadenitis
-Lymphoma: FeLV, BLV, Marek’s
-Metastatic neoplasia

Question 105

What is the causative agent of Equine Stangles a.k.a Acute suppurative Lymphadenitis?

What are the lymph nodes affected? Pic: dorsal view of larynx

What are the types of Chronic lymphadenitis? causative agents?

What species present with Caseous lymphadenitis due to mycobacterium pseudoparatuberculosis?

Answer 105

-Streptoccocus equi asp. equi

-Left and right retropharyngeal lymph nodes

Types

-Chronic suppurative lymphadenitis: C. pseudo tuberculosis (recurrent infection)

-Discrete granulomas: Mycobacterium tuberculosis complex, Foreign bodies, fungal infections ( can be disseminated, but individual fungi still invoke MF to coalescing granulomas)

-Diffuse granulomatous inflammation: Johne’s (mycobacterium paratuberculosis), PCV2

Pic: Caseous lymphadenitis Corynebacterium seudoparatuberculosis, LNs Sheep

Question 106

Where does lymphoma (a.k.a lymphosarcoma) arise from?

Gross lesion

C/S variations: arise at any stage in development/maturation of a lymphocyte - from precursor B or T lymphoblasts to mature Lymphoid B and T lymphocytes and NK cells.

Answer 106

-Malignancies arise in lymphoid tissue OUTSIDE the BM

-Diffuse to nodular enlargement of 1+ LNs.
-Cut surface is sift, white, bulging
Effaces corticomedullary architecture
-Lots of necrosis
-Lots of loss of architecture
Pic: lymphoma cranial mediastinal LNs cat

Question 107

What is the most common location for Lymphsarcomas in cats? Dogs?

Age?

Other sites/ organs?

Answer 107

-Mediastinal or alimentary tract
-10 yrs +
-Brain, spinal cord, kidney, nasopharynx.

Question 108

Bone marrow

Is the bone marrow highly or poorly vascularized?

Are lymphatics present in the BM?

What are the blood supplies?

What nerve types are present?

What is the role of BM macrophages?

What are the mechanisms of injury and disease?

Answer 108

-Highly vacularized
-No lymphatics
-Nutrient foramen artery, periosteal arteries, anastomose, from sinusoids within medullary cavity of bone

-Myelinated and non-myelinated nerve, low numbers of resident macrophages, lymphocytes, and plasma cells.
-Macrophages: role in iron storage and erythrocyte maturation

Injury and disease

-Hematopoietic tissue stem cells system: highly proliferative, undergoes sequential division as they develop and mature after they have stopped dividing
-Mature cells have different normal life spans, hours (neutrophils) to days (platelets) to months (erythrocytes) years (some lymphocytes)
-Respond rapidly and predictably to various stimuli
-Production and turnover of blood cells are balanced (numbers are maintain within normal ranges)

Composition of BM changes with age
RED MARROW: regresses in young animals, replaced with fat (YELLOW MARROW) in older animals.

-Bone marrow releases mostly mature cell types: but can release immature cells in response to certain physiological/pathological stimuli

Question 109

How is plasma cell Neoplasia classified?

How are they characterized?

What anatomical location is the most common site for extra medullary plasmacytomas?

What species is more affected?

Which type and site is mostly benign? How is it curatively treated?

Is Amyloid observed in a proportion of cases?

Answer 109

1. Myeloma or multiple myeloma
   -Arise in bone marrow
2. Extramedullary plasmacytoma (sites other than bone)
   -Skin of dogs > cats, horses
   -Pinnae, lips, digits, chin (most common). Also found in oral cavity, intestine > liver, spleen, kidney, lung, brain
   -Solitary most frequent

Most cutaneous extra medullary plasmacytomas are benign
-complete excision is curative
-Oral cavity, colorectal likely to have similarly
-May produce monoclonal immunoglobulins MONOCLONAL GAMMOPATHY
-Amyloid deposition observed in a proportion of cases YES

3. Both tumors

-Characterized perinuclear golgi or “halo” (plasma B cell)
-Karyomegaly (large nucleus), binucleation
-IHC (MUM1/IRF4 is particularly sensitive and specific for plasma cell neoplasms)

Question 110

What cells are characteristically associated with Histiocytic Disorders?

What anatomic locations are they present and affected?

What species are affected? which one is more affected?

What histocytic disorder affects dogs only?

Answer 110

Histiocytic Disorders

Categorized as

1. Macrophages
2. Dendritic cells

-Largerhans cells (LCs): skin, GI, respiratory, reproductive epithelia mucosa.
-Interstitial dendritic cells: perivascular spaces most organs

Histiocytic sarcoma and hemophagocytic histolytic sarcoma dog> cats

Histiocytic disorders: LN involvement in many conditions

-Canine cutaneous histiocytoma
-Canine LC histiocytosis
-Canine cutaneous and systemic histiocytosis
-Feline pulmonary LC histiocytosis
-Feline progresive histiocytosis
-Dendritic cell leukemia (dog)
-Canine reactive histiocytoses: not clonal neoplastic proliferations. Immune dysregulation consisting of activated dermal iDCs (and T lymphocytes)
a. Cutaneous histiocytoma (CH): skin draining LN
b. Systemic histiocytosis (SH): more generalized; skin and other sites (lungs, liver, bone marrow, spleen, LNs, kidneys, and orbital nasal tissues).

Question 111

What histiocytic disorder are Bernese mountain dogs, Rotts, Goldens, flat-coated retrievers predisposed to? Part of Histiocytic Sarcoma Complex

In what organs does it arise, and which are secondary affected?

What lesion patterns can occur?

How is it similar to multiple myeloma, plasmacytoma?

What is cellular atypia?

Answer 111

Histiocytic sarcomas - Disseminated

-Involves distant sites (replaced term malignant histiocytosis)

-Arises in almost any tissue (spleen, lung, skin, meninges, LN, BM, synovium)
-Secondary liver involvement

-Localized histiocytic sarcoma: focal solitary lesion or multiple nodules within a single organ
-Dessiminated histiocytoma: involve distant sites

Rapidly aggressive

Gross
-uniformely enlarged organs and or multiple coalescing

Histo
-marked cellular atypical (karyomegalic, multinucleate cells)

Question 112

Histiocytic sarcoma complex

Is hemolytic anemia regenerative or non-regen?

Coombs negative or positive?

Good or bad prognosis?

Where is the metastasis most frequently?

Why is splenomegaly present?

Answer 112

Hemophagocytic Histiocytic Sarcoma

-Dogs, cats
-Neoplasm of macrophages of spleen and BM
-Clinically, hemolytic regenerative anemia
-Coombs negative
-Worst prognosis
-Metastasis frequent to liver, +/- emboli in lung
-Non-mass forming infiltrate within BM and splenic red pulp, causing diffuse splenomegaly?

Question 113

Where do carcinomas and Sarcoma typically metastasize to?

Answer 113

-Carcinomas: regional LNs
-Other common metastatic neoplasm: mast cell tumor, melanoma

-Sarcomas most often metastasize hematogenously. More aggressive sarcomas (osteosarcoma) may spread to regional LN

Question 114

Where do we find the spleen?

How is it divided?

Answer 114

LEFT cranial region of the abdomen
Pancreas on the right

-Thick smooth muscle and elastic fiber capsule

1. Red pulp
   -Monocyte-macrophage system, vascular spaces, hematopoiesis in red pulp.
   -Filters blood
   -Removes foreign particles, bacteria, senescent or damaged RBCs, or infected with parasites
2. White pulp
   -Consists of PALS (peiarteriolar T lymphocytes) each with splenic lymphoid follicle surrounded by a marginal zone
   -Immunological functions: Activation of macrophages (APCs), proliferation of B lymphocytes, production of antibody, interaction of T lymphocytes and antigens, macrophages in white pulp follicles remove apoptotic B lymphocytes

-Marginal zone: interface of white and red pulp. Consists of macs, DCs, T and B gyms. Macrophages of marginal zone bridge the innate and adaptive immune responses.
-Germinal zone (B lymphocytes)
-Primary follicle
-Periarteriolar T lymphocytes (PALSs)

Pink/red: RBC, Purple/blue: Lymphocytes

Question 115

What is the primary site of hematopoietic tissue in the fetus?

Where does extra medullary hematopoiesis occur and under what condition is it stimulated?

What are the common conditions that lead to EMH in cats and dogs?

Answer 115

-Liver is primary in fetus, spleen makes minor contribution
-Shortly before or after birth the bone marrow becomes the primary hematopoietic organ

-Under certain condition (severe demand in prolonged anemia): splenic hematopoiesis can be reactivated = EMH extra medullary hematopoiesis

-EMH also found in nodular hyperplasia: severe bone marrow failure, myelostimulation, tissue inflammation, injury, repair, abnormal chemokine production.
-Dogs, cats: splenic EMH most commonly occurs with degenerative or inflammatory condition (hematomas, thrombosis); may occur without concomitant hematologic disease

Question 116

Splenic Congenital and Developmental Anomalies

1. failure of spleen to develop in utero, rare, effect on immune status is uncertain
2. Primary immunodeficiency diseases: small thymuses and LNs too. Young animals, involve defects in T and or B lymphs. Spleen are exceptionally small, firm, pale red and lack lymphoid follicles and PALS.
3. Congenital accessory spleen a.k.a (?) nodules of normal splenic parenchyma in abnormal locations. Usually small and may be located in gastrosplenic ligament, liver, or pancreas. Acquired
4. Fissure in splenic capsule. Horses&raquo_space; than other animals; no pathologic significance. Surface of fissure is smooth, covered by normal splenic capsule (picture)

Answer 116

1. Asplenia
2. Splenic hypoplasia
3. Congenital and Acquired Accessory Spleens a.k.a splenic choristomas
4. Splenic fissure

Question 117

Uniform Splenomegaly with a bloody Consistency (bloody spleen)

Causes?

Sequela?

Answer 117

1. Congestion due to gastric volvulus and splenic entrapment, splenic volvulus, all compress splenic vein
2. Acute hyperemia (septicemia) ex: anthrax = marked congestion, lymphocytolysis of follicles and PALS. Intravascular free bacilli (impression smears of peripheral blood) not normally necropsy due to aero sporulation spread.
3. Acute hemolytic anemia (autoimmune disorder or chemotropic parasite). Acute babesiosis, hemolytic crises in equine infectious anemia IMHA.
4. Barbiturate euthanasia, anesthesia, sedation

Ooze blood on cut surface

Question 118

Splenic nodules with a bloody consistency

Most common disorders?

Which one is associated with Cushing’s in dogs and it is due to what?

How does it affect cattle and pigs? associated with what disease in pigs?

Answer 118

1. Hematomas
   -Induced by nodular hyperplasia or hemangiosarcoma, trauma.
   -Capsule (splenic capsule, visceral peritoneum) over the hematoma can rapture - hemoperitoneum, hypovolemic shock, death.
2. Incomplete contracted areas of spleen
   -Smooth muscle fails to contract in response to circulatory shock (hypovolemic shock, cariogenic or septic) or sympathetic response, resulting in a lack of splenic evacuation of stored blood.
3. Acute splenic infarcts
   -Wedge-shaped or triangular lesions at margins of spleen
   -Dogs: hyper coagulable states (liver, renal disease, cushing’s), neoplasia, cardiovascular disease
   -Cattle: splenic vein thrombi with traumatic reticulates, splenic abscesses, portal vein thrombosis, arterial thrombosis in bovine theileriosis. Vascular endocarditis > multi organ infarcts.
   -Splenic infarcts are common in pigs with Classical swine fever
   -Acute splenic infarcts > subacute > chronic infarcts gross appearance similar to that of kidney
4. Hemangiosarcomas

Question 119

Uniform Splenomegaly with a Firm consistency - Meaty Spleen

Does it ooze on cut surface? associated with what disease and conditions?

Answer 119

-Do not ooze on cut surface
-Marked phagocytosis of cells, debris, or foreign material
-Proliferation or infiltration of cells: diffuse lymphoid and histiocytic hyperplasia, large disseminated, visible, white, bulging nodules.

-Diffuse granulomatous disease
-EMH
-Neoplasia
-Storage diseases or amyloidosis

Splenic Nodules with a Firm consistency

-Lymphoid nodular hyperplasia
-Complex nodular hyperplasia
-Primary neoplasms
-Secondary metastatic neoplasms
-Granulomas: mycobacterium, fungal organisms
-Abscesses
Pic: meaty spleen and hyperplasia

Question 120

Diffuse Granulomatous disease

Causative agents? Conditions?

Answer 120

-Mycobacterium, Brucella, Francisella tularensis
-Systemic mycoses: nodular but disseminated: Blastomyces, Dermatitidis, Histoplasma capsulatum.
-Protozoal infections that infect macrophages, Leishmania spp.

Gross lesion

-Multiple sub capsular splenic abscesses ex Rhodococcus equi, spleen horse pic

Question 121

Primary Neoplasm of the Spleen

All these types of neoplasm can produce nodular lesions instead or along with a diffusely enlarged spleen

Where do primary neoplasm arise from, type of cells?

Which primary neoplastic spleen diseases result in firm nodules?

How does the cut surface appearance vary? which ones are white and firm, gelatinous, soft and bulging?

Answer 121

Arise from

-Round cell tumors (LSA, leukemia, visceral mast cell tumor, histiocytic sarcoma).
-Stroma cells (fibroblasts, smooth muscle, endothelium)

Primary neoplastic disease of the spleen that result in firm nodules

-LSA (multiple subtypes)
-Histiocytic sarcoma
-Leiomyoma, leimyosarcoma
-Fibrosarcoma
-Myelolipomas, liposarcomas
-Myxosarcomas
-Unedintified pleomorphic sarcomas
-Solid hemangiosarcomas

Consistency and cut surface appearance varies

-Spindle cell tumor (leiomyosarcoma and fibrosarcomas) will be white and firm
-Liposarcomas, myelolipomas are soft and bulging
-Myxomatous neoplasms are gelatinous

Question 122

Hemangiosarcoma

What type of cell and neoplasm is it?

What species is especially affected?

Can it be easily differentiated from a hematoma?

Gross

Histo

Metastasizes in what disease process of dogs?

What other species are affected?

Is it useful to diagnose primary site?

Answer 122

-Malignant neoplasm of endothelial cells
-Common primary tumor of spleen especially is dogs

Gross
-Single multifocal, coalescing, dark red-purple masses and can not be easily differentiated from a hematoma
-Cut surface: bloody with varying amounts of soft red neoplastic tissue; in more solid areas neoplasm can be slightly more firm and white tan.

Metastatic spread occurs early in disease process: in dogs also right atrium of heart, retroperitoneal fat, and skin (dermal and or subcutaneous).

-MUltiorgan hemangiosarcomas: described in horses, cats, and cattle

Often metastasized at time of initial diagnosis, so may be difficult (and futile) to determine the primary site

Question 123

Secondary (metastatic) Neoplasm of Spleen

Does it form nodules in spleen or is it uniform splenomegaly?

Give examples of sarcomas associated with this condition

Answer 123

-Due to metastasis, often form nodules in spleen, not a uniform splenomegaly

-Include: sarcomas, carcinomas, or malignant round cell tumors
-Metastatic sarcomas: fibrosarcomas, leiomyosarcomas, chondrosarcomas, osteosarcomas
-Mammary, prostatic, pulmonary, anal sac gland, neuroendocrine carcinomas metastasize.

Question 124

Storage of material

What is the texture of the spleen?

What type of disease does Swainsonine toxicity in Astragalus Oxytropisplants cause?

What age group?

What are the major categories of materials stored?

What cells are commonly affected by the disease?

Answer 124

Amyloid

-May occur with primary (AL) or secondary (AA) amyloidosis.
-Spleen is firm, rubbery to waxy and light brown to orange
-Plasma cells tumors within the spleen may be associated with amyloid (AL) deposits

Lysosomal storage disease

-Group of inherited defects in metabolism characterized by accumulation of storage material within the cell (lysosomes)
-Genetic: lack of enzyme, produce inactive enzyme, last of activator proteins, or defect in posttranslational processing
-Acquired: exogenous toxins, plants that inhibit a particular lysosomal enzyme Swainsonine toxicity in Astragalus Oxytropisplants

-Animals < 1yr old

Major materials

-Mucopolysaccharides
-Sphingolipids
-Glycolipids
-Glycoproteins, glycogen
-Oligosaccharides

Macrophages are commonly affected by storage disease

Question 125

Miscellaneous disorders of the Spleen

What are gamma-handy bodies? What species and age group is most commonly affected? what part of the spleen has them more extensively?

1. Storage iron breakdown of RBCs, excessive amounts of splenic hemosiderin are seen when erythropoiesis is reduced (less demand for iron). From rapid destruction of RBCs in hemolytic anemias (increased stores of iron). Chronic heart failure. Injections of iron dextran or focal accumulations at sites of old hematomas. Infarcts, trauma-induced hemorrhages, present in siderofibrotic plaques.
2. a.k.a siderocalcific plaques, Gamma-Gandy bodies
   Gross: gray-white to yellowish, firm, dry encrustations on splenic capsule.

Answer 125

Gamma-Gandy bodies: siderocalcific plaques

1. Hemosiderosis = plaques
2. Siderofibrotic Plaques: Most extensive along the splenic margins. Extremely common in aged dogs and may represent sequelae to previous hemorrhages from trauma to spleen

Question 126

1. Caused by trauma
   -Thin capsule from splenomegaly > more susceptible to rupture. Sites of infarcts, hematomas, hemangiosarcomas and lymphoma
2. Contracted and often depressed below surface adjacent capsule
3. Echinococcus granulosus and Cysticercus tenuicollis. Commonly in wild animals

Answer 126

1. Rupture
2. Chronic splenic infarcts
3. Parasitic Cysts

Question 127

MALT pathways of entry and spread

Give examples of viruses and or pathogens that affect/invade MALT?

Answer 127

Mucosal Associated Lymphoid Tissue

-Site of mucosal immunity
-Diffused lymphoid tissues and aggregated lymphoid nodules, subcategorized

1. BALT bronchus associated lymphoid tissue
2. NALT Nasal-larynx and auditory tube ..
3. LALT Larynx …
4. ATALT auditory tube …
5. GALT Gut associated lymphoid tissue. Peyer’s patches and diffuse lymphoid tissue in the gut wall
6. CALT Conjuctiva …
7. Other lymphoid nodules (genitourinary tract)

Portal of entry for pathogens

Hematogenous: most common migrating macrophages, DCs, M cells.

-BVDV
-Bovine Coronavirus
-Rinderpest virus
-MCF
-FPV
-Canine parvo virus
=Lymphocyte depletion within MALT

-Escherichia coli
-Yersinia pestis
-Mycobacterium avian sap. paratuberculosis (MAP)
-L. monocytogenes
-Salmonella spp.
-Shingella flexneriulate

Site of replication for viruses (BVDV)

Question 128

Species Specific Lymphoid Diseases

Do all species get affected despite not all having LNs?

What are some exaple of Lymphoid disorders in horses? Ruminants? Which disease is characterized by large abscesses in horses? Which disease is associated with type III hypersensitivity and purpura hemorrhagica? Which disease is associated with retropharyngeal abscesses and compresses the pharynx?

Answer 128

-Even though some species don’t have lymph node they still have lymphoid follicles - nodules

Horses

SCID

-Arabian foals, autosomal recessive primary immunodeficiency disorder. Lack of T & B cells. Genetic mutation in gene encoding DNA-PKcs. Hypoplasia
-Normal at birth > diarrhea, pneumonia by 10 days
-Common secondary infections: Adenovirus, Cryptosporidium, Pneumocystis cabrini
-Die before 5 months of age
-Gross: hypoplastic LN and thymus (often grossly undetectable), spleen

Strangles

-Streptococcus equi ssp. equi
-Inhaled/ingested > invade tonsils, enter regional LN > Larged abscesses
-Retropharyngeal abscesses lead to compression of pharynx - respiratory stridor, dysphagia
-Abscesses rupture to skin surface or spread medially into guttural pouches, from chondroids
-Ruptured abscesses spread via blood/lymph to other organs Bastard strangles

Pupura Hemorrhagica

-Type III hypersensitivity reaction
-Necrotizing vasculitis in some horses with repeated natural exposure to S. equi ssp. equi or after vaccination in horses that have had strangles.

Rhodococcus Equi

-Chronic pyogranulomatous bronchopneumonia, lymphadenitis
-50% of foals also develop: pyogranulomatous ulcerative enterotyphlocolitis

Question 129

Disorders of Ruminants
Cattle Sheep and Goats

What is the pathogen associated with Johne’s disease? what species are primarily affected? Which are rarely affected by it? What are the characteristic lesions? What organ system?

What pathogen is associated with Anthrax? What species are particulary affected? What organ is markeldy enlarged and congested?

What pathogen is associated with BVD? What cells are preferentially infected? Species affected? What is a characteristic Hint: mesenteric lymph nodes and pryer patches.

What disease is caused by a gram + intracellular bacterium and enters through the skin wounds, drains to regional LN - disseminated to external and internal LNs, and other internal organs, including lungs? Give examples of some predisposing wounds. What species are affected? In What LNs are abscesses often detected?

Answer 129

Johne’s Disease

-Domestic, wild ruminants (rarely pigs, horses)
-Mycobacterium paratuberculosis

Characteristic lesions: Granulomatous enteritis to ieum, cecum, proximal colon; lymphangitis/Lymphadenitis or regional LN

Pathogenesis: bacteria are ingested, engulfed by monocyte cells overlying Peyer’s patches - transported to macrophages in lamina propria and submucosa

Anthrax

-Bacillus anthracis (Gram + bacillus) present in the soil in spores
-Cattle, sheep, goats: Fulminant septicemia
-Spleen markedly enlarged and congested

Bovine Viral Diarrhea

-BVDV: pestivirus
-Preferentially infected macrophages, dendritic cells, lymphocytes
-Cattle, sheep, goats
-Lymphoid depletion in mesenteric lymph nodes and Peyer’s patches (lymphocytois and depletion)
-Histo: marked lymphocytosis, necrosis of germinal centers in Peyers’s patches, thymic atrophy.

Splenic Abscesses

-Result of bacteremia or direct penetration by a foreign body from reticulum

Caseous Lymphadenitis

• C. psudotuberculosis (Gram + intracellular bacterium)
  -Shearing, tagging, tail docking, castration
  -Sheep, goats
  -External abscesses most often detected in mandibular and paranoid LN

Question 130

What disease is characterized by two overlapping syndromes, affects pigs, interstitial pneumonia is the major lesion, can affect more than one system, and has a predilection for lymphoid tissue?

What is the associated pathogen (s) when confection is present?

In what cells does replications occur, resulting in what?

Answer 130

Porcine Reproductive and Respiratory Syndrome (PRRS)

-Arterivirus
-Most connected: Streptococcus suis, Salmonella choleraesuis, Bordetella bronchiseptica, Mycoplasma hyopneumoniae.

Two overlapping clinical syndromes

1. Reproductive failure
2. Respiratory disease

-Bodily fluids - colonizes tonsils or upper respiratory tract (predilection for lymphoid tissue), spleen, thymus, LNs, Peyer’s patches - Replication in macrophages of lymphoid tissues, lungs - resulting in reduction in phagocytic and functional capacity of macs - secondary infections

Major lesions: interstitial pneumonia, generalized lymphadenopathy (tracheobronchial, mediastinal most commonly affected). Pale tan, occasionally cystic, and firm; some strains of virus also cause nodal hemorrhage.

Coinfections complicate the gross and histopathologic changes

Question 131

What opportunistic pathogen (resident of normal flora) can get into mandibular LNs and cause disease?

What is the name of the disease, and most affected age group of animals, and the species?

Answer 131

Porcine Jowl Abscess

-Streptococcus porcinus
-Colonizes oral cavity - tonsils - regional LN
-Mandibular LN most affected.
-Now rare because of improvements in husbandry, feeder design, and hygiene. “Teeth clipping in baby pigs”

Question 132

What disorder in dogs is similar to a disorder in Arabian horse, is autosomal recessive, affects Jack Russell terriers, and is a mutation in DNA-PKcs?

What is the most significant lesion/sequelae?
How long do affected dogs usually live? What breeds are associated with it? Where are the lesions?

Answer 132

Disorder of dogs
Severe Combine Immunodeficiency Disease

-An x-linked form of SCID in Basset hounds
Reduced numbers of T lymphocytes (which are nonfunctional

-Normal numbers of circulating B lymphocytes that are unable to class switch to IgG or IgA and reduced numbers of T lymphocytes (which are non-functional).
-Susceptible to bacterial/viral infections
-Rarely survive past 3 to 4 months of age
-Lesions: small thymus, tonsils, LN, Peyer’s patches (often grossly unidentifiable).
-Similar disease in Cardigan Welsh corgi puppies (but autosomal mode of inheritance)

Question 133

Leishmaniasis

What type of organisms is associated with it, what is the vector? What species are affected? What are the two forms?
What does it look similar to (other vector-borne disease). What cells are targeted? What does it look like in blood?

Answer 133

-Protozoa of genus Leishmania
-Dogs, other animals
-Sand fly

1. cutaneous
2. Visceral: emaciated, general enlargement of abdominal lymph nodes and hepatosplenomegaly

-Looks similar to trypanosome
-Macrophages target.
Flagellated in blood

Question 134

What disease/pathogen is associated with bronchointerstitial pneumonia, lymphopenia, affects dogs, has a predilection for lymphoid, epithelial, and nervous cells? Hint: oronasal secretions

Pathogenesis

What pathogens are commonly present in secondary infections?

What other disease is highly contagious in dogs, marked lymphoid atrophy of thymus and follicles of spleen is present, and disseminates to SI crypt epithelium? What is the route of transmission?

Is lymphocytolysis and bone marrow depletion of lymphocyte precursors a characteristic?

Answer 134

Canine Distemper Virus

• Macrophages in tonsil, respiratory tract, disseminates to spleen, LN, BM, MALT, Kuffner cells - necrosis of lymphocytes (especially CD4T) and depression of lymphopoiesis in BM - severe immunosuppression

-Secondary infections: Bordetella bronchiseptica, Toxoplasma gondii, Nocardia, Salmonella spp., and generalized demodicosis

Canine Parvovirus type 2 (CPV-2)

-Highly contagious dogs
-Feco-oral or oronasal - tropism for rapidly dividing cells - replication begins in lymphoid tissues of oropharynx, thymus, mesenteric LN - disseminated to SI crypt epithelium
-Lymphocytolysis and bone marrow depletion of lymphocyte precursors - immunosuppression
-Lymphocytolysis and bone marrow depletions of lymphocyte precursors - immunosuppression
-Marked lymphoid atrophy of thymus and follicles of spleen, LN, MALT - (especially Peyer’s patches)

Question 135

Disorder of Cats Name and causative agent?

-Highly contagious
-Often lethal
-Species: cats, raccoons, ring-tailed cats, foxes, minks.
-Causes immunosuppression
-Marked lymphoid atrophy of thymus, spleen, lymph node, MALT (particularly Peyer’s patches)

Answer 135

Feline Panleukopenia

-Parvovirus
-Target: rapidly dividing cells in S phase of division: lymphoid tissue, BM, intestinal mucosa.
-Feco-oral (nasal) route
-Replicates in macrophages in oropharynx