anatomic path final

Most important neuroectodermal cells?

• neurons

• astrocytes

• oligodendrocytes

• schwann cells

• ependymal cells

Most important mesenchymal cells of the CNS?

• microglia

• cells that make up the meninges

What is the functional unit of the nervous system?

neurons

Neurons are very hungry for ______ + ______, making them very ______ to physiological changes.They are ______-lived and have a _____ _____ of morphologies.

• Neurons are very hungry for glucose + oxygen, making them very sensitive to physiological changes.

• They are long-lived and have wide variety of morphologies

What is the most numerous glial cell type in the CNS? What are its fxns?

• astrocytes

• fxns

  • maintain extracellular environment

  • interconnect w/ other astrocytes to form a monitoring system

  • participate in the formation of the blood-brain barrier

  • remove excess NTs

  • participate in the CSF-brain barrier

What are the 2 different types of oligodendrocytes, where are they found, and what do they do?

• interfascicular oligodendrocytes

  • found b/t axons

  • fxn: make myelin

• satellite oligodendrocytes

  • found surrounding neuronal cell bodies

  • fxn: regulate perineural microenvironment

What is the fxn of microglia?

• resident macrophages of CNS

• fxn: reactive proliferation, immunosurveillance, immunoregulation, and phagocytosis

Where are ependymal cells found + what is their fxn?

• found as the epithelial cells lining the ventricular system

• fxn:

  • produce CSF

  • circulate CSF

  • regulate flow of materials b/t CSF + CNS

What are the meninges + what is their fxn? Where is the subarachnoid space located + what stuff is inside of it?

• meninges = layered membranes that surround the brain + spinal cord

• fxns:

  • provide support

  • contain CSF

• subarachnoid space is located b/t the arachnoid mater + pia mater (leptomeninges)

  • contains:

    • vasculature

    • nerves

    • CSF

List the cells of the CNS from most to least sensitive to injury

• neurons > oligodendrocytes > astrocytes > microglia > blood vessels

The nervous system has _____ lymphatic vessels. Necrotic areas have _____ granulation tissue. This, combined w/ the fact that the nervous system is very _____, makes _____ necrosis followed by _____ common and demonstrates the unique way the nervous system responds to damage.

• The nervous system has no lymphatic vessels.

  • makes it hard to drain fluid

• Necrotic areas have no granulation tissue

  • meaning no fibroblasts depositing collagen

• This, combined w/ the fact that the nervous system is very fatty, makes liquefactive necrosis followed by cavitation common and demonstrates the unique way the nervous system responds to damage.

Why is malacia a common sequelae of necrosis in the CNS?

• high fat + macrophages eat up dead tissue + no granulation tissue being laid down (fibrosis) → loss of tissue → softening = malacia

What are the main glial cells that respond to dmg in the CNS? What do they do?

• microgliosis + recruitment of blood monocytes

  • microglia + peripheral macrophages → become gitter cells and eat up dead tissue

• astrocytosis

  • activated astrocytes hypertrophy, recruit other cells, try to fill in gaps in tissue

    • proliferative astrocytes are the CNS’s way of trying to copy fibroblasts

• satellitosis

  • when activated astrocytes ± oligodendrocytes surround neurons

What is neuronal necrosis? What does it look like? What are the causes + outcomes?

• neuronal necrosis = necrosis of neurons

• appearance:

  • shrunken, hypereosinophilic, red = dead

  • astrocytosis + satellitosis

  • neuronophagia

• causes:

  • hypoxia/ischemia

  • toxins

  • excitotoxins (excessive NTs can stimulate neurons to death)

  • viruses

• outcomes:

  • lost neurons are not replaced bc they are terminally differentiated cells

What is central chromatolysis? What does it look like? Causes?

• reversible, sublethal change in neurons

• appearance:

  • swollen cell bodies

  • loss of Nissl substance

• causes:

  • axonal dmg

    • caused by: viruses, metabolic disturbances, toxins, nutritional deficiencies, infarctions, neuronal degen.

Where do bacterial hematogenous CNS diseases often occur?

Bacterial hematogenous CNS diseases often occur at the interface b/t gray + white matter in the brain bc of the abrupt change in vascular flow/luminal diameter

What happens in rapid vs slow ischemia in the CNS?

• infarction = necrosis d/t ischemia

• rapid ischemia → neurons die w/i minutes

• slow ischemia → blood supply can adapt by anastomosing + compensating

What sequence of events led to this lesion? This cat also had bronchoalveolar carcinoma, is this lesion linked to the cancer?

• vascular occlusion → ischemia → infarction → malacia

• bronchoalveolar carcinoma metastasized to brain → cut off blood supply by occluding vasculature

Name the lesion + observations that support that diagnosis

• lesion: cerebral edema

• observations:

  • widened gyri

  • less apparent sulci

  • diffusely swollen appearance

Which type is associated w/ hydropic degen? Which is associated w/ increased vascular permeability + inflammation?

• hydropic degen → cytotoxic edema

• increased vascular permeability + inflammation → vasogenic edema

Name the lesion

brain, cerebral edema

4 portals of entry/pathways of spread into CNS + which is most common

• direct extension

  • penetrating trauma, extensional infxns

  • ex) HBC, gunshot, etc

• hematogenous = bloodstream

  • most common

• leukocyte trafficking = agents hitch a ride on macrophages + lymphocytes

  • ex) bac, viruses, protozoa

• retrograde axonal transport = agents invade via peripheral nerves + axons

  • ex) rabies, Listeria

5 defense mechanisms/barrier systems of the CNS + what they’re composed of

• blood-brain barrier

  • endothelial cells + BM + astrocytic endfeet

• glia limitans

  • astrocytic endfeet + pia mater

• blood-CSF barrier

  • choroid plexus + arachnoid

• CSF-brain barrier (ependymal barrier)

  • ependymal epithelial cells + astrocytic endfeet

• innate + adaptive immune system

For patterns of inflammation in the CNS:

1. serous to suppurative/purulent responses can be the result of _____ _____.

2. eosinophil responses occur in _____ _____ of pigs and in _____ _____ _____.

3. lymphoplasmacytic + histiocytic responses can be caused by _____ + _____

4. granulomatous inflammation can be the result of infection by _____, ______. and some _____ species like ______.

1. serous to suppurative/purulent responses can be the result of bacterial infection.

2. eosinophil responses occur in salt poisoning of pigs and in parasitic larval migration.

3. lymphoplasmacytic + histiocytic responses can be caused by viruses + protozoa.

4. granulomatous inflammation can be the result of infection by fungi, protozoa, and some bacteria species like Mycobacterium.

Define hydrocephalus vs hydranencephaly. List causes for each

• hydrocephalus = dilation of the ventricular system d/t CSF accumulation in the ventricles or subarachnoid space

  • lined by ependymal cells

  • brain tissue compressed

  • causes: in utero viral infxn, developmental abnormality of the ependymal cells/ventricular system, breed disposition

• hydranencephaly = a CSF-filled cavity replacing the cerebral hemispheres

  • cavity not lined by ependymal cells

  • little/no cerebrum

  • causes: teratogenic viral infxns, toxin exposure, nutrient deficiencies

Name lesion + supporting observations

• lesion: hydrocephalus

• observations:

  • bilateral dilation of lateral ventricles

Name it

brain hydranencephaly

Name the lesion in this calf + provide a possible pathogenesis. What kind of developmental disturbance would it be?

• brain: meningocele

• pathogenesis: congenital defect in caudodorsal aspect of skulll allowed meninges to herniate into a large pouch only covered by skin

  • developmental disturbance: dysplasia

What is an abscess? What portals of entry usually cause cerebral abscesses to occur? What is the exudate called?

• abscess = localized collection of pus w/i a fibrous capsule

• common portals of entry:

  • direct extension

  • hematogenous

• exudate: purulent/suppurative

morph it

• brain: severe, acute, multifocal, necrosuppurative/purulent encephalitis

• lesion: cerebral abscess

What is meningitis? What is the most common pathogenesis in domestic animal species?

• meningitis = inflammation of the meninges

• most commonly caused by bacteria like E. coli + Streptococcus infiltrating leptomeninges + subarachnoid space hematogenously in domestic animal species

morph this tissue from a calf

• meninges: severe, acute, diffuse fibrinopurulent meningitis

morph this tissue from a horse

• meninges: severe, acute, diffuse fibrinopurulent meningitis

Lymphocytic inflammation in the CNS is often indicative of what kind of infection?

viral

What are the 3 classifications of mycoses?

• systemic/deep mycoses = systemic spread throughout body + internal organs

• angioinvasive fungi = invade blood vessel walls

• superficial mycoses = infxn limited to just surfaces of skin, hair, etc

What are the 4 major systemic mycoses?

• histoplasmosis

• cryptococcosis

• blastomycosis

• coccidioidomycosis

Granulomatous inflammation in the CNS is often caused by infection of what?

• fungi

• protozoa

• some bacteria like Mycobacterium

What are the 3 major viral neurological diseases in the horse?

• rabies

• arboviral encephalomyelitis

• equine herpesvirus 1

What is the pathogenesis of equine protozoal myelitis?

• sporocysts of Sarcocystis neurona passed in feces of opossum (definitive host) → horse ingests contaminated feed/water → virus enters CNS via leukocyte trafficking → parasite activates + replicates in CNS → lymphoplasmacytic inflammation + necrosis

What is this lesion?

• equine protozoal myelitis causing a focal area of hemorrhage

What is this lesion in this horse? What is it likely caused by?

• brain: verminous encephalitis

• likely caused by aberrant migration + hematogenous spread of nematode parasites

What is this lesion in a horse + what is it caused by?

What is the black arrow pointing at in this horse? Is it likely malignant or benign? What is a possible sequelae of this mass?

• lateral + 4th ventricles choroid plexus: cholesteatoma

• concurrent pituitary adenoma

• benign

• can possibly cause occlude drainage in ventricular system → cause hydrocephalus

What are the 7 major neurological diseases of the ox?

• polioencephalomalacia

• listeriosis

• TEME

• fibrinopurulent meningitis

• bovine viral diarrhea

• rabies

• bovine spongiform encephalopathy

What is this lesion in this cow? What supporting observations do you see? What is it caused by?

• polioencephalomalacia

  • cavitation/liquefactive necrosis in the gray matter

  • necrotic areas autofluoresce under blacklight

• caused by thiamine deficiency OR sulfur toxicosis OR lead toxicosis

This cow was demonstrating facial paralysis, ear droop, excessive salivation, eyelid droop, and lack of menace response. No gross lesions were observed but this slide from her brainstem did show something. What is disease + lesion? What is the pathogenesis

• listeriosis

• can see microabscesses on the microscope slide

• pathogenesis: Listeria bacteria invade thru wounds in oral mucosa → invade CN 5 → travel via retrograde axonal transport to the medulla oblongata + midbrain → invasion into adjacent cells → acute inflammation → necrosupparative meningoencephalitis w/ vasculitis

Tissue from a cow. What’s wrong? Pathogenesis?

• histophilosis

  • multifocal areas of necrohemorrhagic + purulent encephalitis

• pathogenesis: respiratory tract colonized by Histophilus somni → bacteria replicates locally → gets into bloodstream → septicemia → bacteria invades brain hematogenously and deposits at the gray + white matter interface → endothelial apoptosis/dmg → vasculitis + secondary thrombosis → ischemia → infarction

Name the lesion + 2 possible causes in this tissue from a calf.

• cerebellar hypoplasia

• caused by:

  • spontaneous congenital defect

  • teratogenic viral infection (often bovine viral diarrhea)

5 major neurological diseases in small ruminant

• fibrinopurulent meningitis

• listeriosis

• scrapie

• polioencephalomalacia

• enterotoxemia

Pathogenesis of prion diseases?

• animal picks up protease resistant prion protein from environment or ingestion → prion protein replicates in lymphoid tissue → prion invades CNS via leukocyte trafficking or retrograde axonal migration up cranial nerves

What are the 5 major neurological diseases in pigs?

• fibrinopurulent meningitis

• edema disease

• pseudorabies, rabies, PRRSV

• neurotropic enteroviruses (teschovirus, astrovirus, sapovirus)

• water deprivation/sodium toxicosis

What are the 5 major neurological diseases in the dog?

• hydrocephalus

• canine distemper (morbillivirus)

• rabies

• ischemic myelopathy

  • secondary to IVDD or IV disc cartilage embolism

• primary brain neoplasms

Name the lesion in this dog. Supporting observations?

• lesion: hydrocephalus

• observations:

  • severely dilated lateral ventricles

  • atrophy of the cerebrum

Morbilliviruses like CDV and measles can cause ______ ______, which is a condition in which the body forgets how to fight previously encountered pathogens. Morbilliviruses do that by preferentially infecting and depleting ______ _ and _ ______, which are responsible for long-term immune protection.

• Morbilliviruses like CDV and measles can cause immune amnesia, which is a condition in which the body forgets how to fight previously encountered pathogens.

• Morbilliviruses do that by preferentially infecting and depleting memory T and B lymphocytes which are responsible for long-term immune protection.

pathogenesis of rabies

• bite wound from infected animal → rabies virus enters + replicates in muscle → rabies enters spinal cord via peripheral nerves → rabies travels via retrograde axonal transport to brain → rabies spreads to salivary glands + eye

• results in rabies viral encephalitis

In rabies virus encephalitis, neurons can have intracytoplasmic viral inclusions called _____ _____

Negri Bodies

Spinal cord injuries in dogs:

• _____ = inflammation of the spinal cord

  • _____ = inflammation of spinal cord gray matter

  • _____ = inflammation of spinal cord white matter

• _____ = necrosis of the spinal cord

  • usually d/t _____ or _____

• _____ ______ = pathology caused by traumatic injury like HBC

• disc rupture vs protrusion

• myelitis = inflammation of the spinal cord

  • poliomyelitis = inflammation of spinal cord gray matter

  • leukomyelitis = inflammation of spinal cord white matter

• myelomalacia = necrosis of the spinal cord

  • usually d/t inflammation or ischemia

• traumatic myelopathy = pathology caused by traumatic injury like HBC

• type 1 IVDD herniation = disc rupture

  • associated w/ chondrodystrophic breeds

• type 2 IVDD herniation = disc protrusion/bulging disc

  • associated w/ older dogs of any breed

5 major neurological diseases in the cat

• FIP

• cryptococcosis

• cerebellar hypoplasia

  • secondary to feline panleukopenia virus infection in utero

• meningioma

• purulent otitis media/interna → meningitis

Lesion in this cat + cause

• serofibrinous ventriculitis + hydrocephalus d/t FIP

Lesion in this cat + cause

• meningoencephalitis w/ focal areas of gelatinous clumps d/t cryptoccosis

Lesion in this cat + pathogenesis

• cerebellar hypoplasia

• pathogenesis: intrauterine infection w/ feline panleukopenia virus → virus infects Purkinje cells → viral-infected cells destroyed → decreased growth + differentiation of Purkinje cells → cerebellar hypoplasia

Name the lesion in this cat. Benign or malignant?

• meningioma

• technically benign

• neoplasms of the brain:

  • astrocytes → ____

  • neurons/progenitor cells → ____/____

  • oligodendrocytes → ____

  • ependymal cells → ____

  • meninges → ____

  • metastatic lymphocytes → ____

  • metastatic endothelial cells → ____

• astrocytes → astrocytoma

• neurons/progenitor cells → neuroblastoma/medulloblastoma

• oligodendrocytes → oligodendroglioma

• ependymal cells → ependymoma

• meninges → meningioma

• metastatic lymphocytes → lymphosarcoma

• metastatic endothelial cells → hemangiosarcoma

What is the fxnal subunit of the liver? What is the portal triad?

• hepatic lobule = stacks of hepatocytes w/ portal triads at each corner arranged around central veins

• portal triad:

  • hepatic a

  • hepatic portal v

  • bile duct

As blood drains from the portal triad to the central vein via the ____ → oxygen concentration ____ + hepatocytes get ____ metabolically active. This makes the ____ area hepatocytes more sensitive to hypoxic stress.

• As blood drains from the portal triad to the central vein via the sinusoids → oxygen concentration decreases + hepatocytes get more metabolically active.

• This makes the centrilobular area hepatocytes more sensitive to hypoxic stress.

3 major portals of entry of insults to the liver

• direct extension

  • ex) physical trauma

• hematogenous

  • ex) portal v or systemic

• biliary

  • retrograde biliary transport = agents coming up via common bile duct

3 defense mechanisms the liver has against insults

• structural

  • like omentum

• immunologic

  • like Kupffer cells (resident macrophages)

• biochemical

  • think enzyme inhibitors that prevent premature activation of enzymes

What are some ways the liver responds to injury?

• hepatocyte vacuolar degeneration

• hepatocyte necrosis + apoptosis

• atrophy of hepatocytes or entire liver

• inflammation

• fibrosis + hepatocellular regeneration + bile ductular proliferation = cirrhosis

• neoplasia

3 types of vacuolar change in hepatocytes

• hydropic → water accumulates inside vacuoles

• glycogen → glycogen accumulates inside vacuoles

• lipidosis → lipid accumulates

Most common causes of hydropic degeneration in hepatocytes?

• hypoxia

• certain toxins

• infections

• physical injury

• nutritional deficiencies

• metabolic

Hepatocyte vacuolar glycogen accumulation likes to happen in which species? Hepatic lipidosis likes to happen in which species?

• glycogen accumulation → dogs

• hepatic lipidosis → cats

3 different pathogenesis of glycogen degeneration? What is the most common one

• hyperadrenocorticism (aka steroid hepatopathy) is most common

  • inc glucocorticoids → inc glycogen synthetase activity → inc hepatic storage of glycogen → severe hepatocellular swelling + degeneration

• diabetes mellitus

  • pancreatic islet cell destruction → dec insulin → hyperglycemia → cells uptake glucose → convert glucose to glycogen → glycogen accumulation → hepatocellular swelling + degernation

• glycogen storage disease

Prolonged exogenous prednisone administration → induction of ____ ____ → enhanced hepatic storage of ____ → severe hepatocellular ____ → steroid hepatopathy

Prolonged exogenous prednisone administration → induction of glycogen synthetase → enhanced hepatic storage of glycogen → severe hepatocellular vacuolation → steroid hepatopathy

What is hepatic lipidosis? Pathogenesis? 3 primary causes?

• intracytoplasmic accumulation of TGs

• pathogenesis: occurs when the rate of intrahepatic TG accumulation exceeds degradation/release as lipoproteins

• 3 primary causes

  • excessive delivery of FAs to liver

    • abnormal production

  • decreased oxidation of FAs

    • abnormal utilization

  • impaired lipoprotein synthesis/release

    • abnormal utilization/mobilization

3 causes of hepatocellular atrophy

• apoptosis

• inadequate caloric intake

  • d/t portosystemic shunts, starvation, etc

• hepatic amyloidosis

4 patterns of hepatocellular degeneration/necrosis, what they look like, and common causes

• random

  • multifocal, discrete, pale spots

  • hematogenous invasion of viruses, bac, protozoa

• zonal

  • centrilobular

    • enhanced lobular pattern

    • hypoxic injury + toxic agents activated by cytochrome p450

  • midzonal

  • periportal

• panlobular

  • entire hepatic nodules necrosed

  • massive necrosis = panlobular necrosis affecting most of the liver

    • commonly caused by blue green algae, torsion, vitamin e deficiency

• bridging

  • hemorrhagic necrosis expanding from 1 centrilobular area to another

5 morphological classifications of inflammatory hepatobiliary disease

• acute hepatitis

• chronic hepatitis

• cholangitis

• cholangiohepatitis

• interface hepatitis/piecemeal necrosis

The liver is ____ at regenerating lost hepatic mass. If there is loss of normal ECM scaffolding, then you’ll get ____ proliferation which produces _____ _____ w/ _____ bile flow. These act like ____.

The liver is good at regenerating lost hepatic mass. If there is loss of normal ECM scaffolding, then you’ll get nodular proliferation which produces regenerative nodules w/ abnormal bile flow. These act like shunts.

What is liver cirrhosis? What does it cause?

• cirrhosis = fibrosis + nodular regeneration + biliary hyperplasia

• causes end stage liver + compromised hepatic fxn

What is hepatic failure? What are the 2 types? What are some common consequences?

• hepatic failure = liver can’t adequately perform normal fxns d/t insufficient fxnal hepatic mass

• 2 types

  • acute = abrupt loss of hepatic fxn (days)

  • chronic = progressive loss of hepatic fxn (months to years)

• common consequences

  • hepatic encephalopathy

  • coagulopathy → hemorrhage

  • hypoalbuminemia which can cause decreased capillary oncotic pressure → causing edema + ascites

  • portosystemic shunts

  • icterus

  • photosensitization

What is cholestasis? What are the 2 types? What does it cause?

• cholestasis = obstructed bile flow

• 2 types

  • intrahepatic

    • d/t hepatic canaliculi swelling

  • extrahepatic

    • d/t mass or cholelith

• causes hyperbilirubinemia → icterus/jaundice

What are the 3 categories of causes for icterus?

• pre-hepatic

  • overproduction of bilirubin

• hepatic

  • impaired uptake, metabolism, or secretion of bilirubin

• post-hepatic

  • cholestasis

What is hepatic passive congestion? What is it caused by? What are the 2 types?

• fluid back-up in liver

• almost always d/t cardiac dysfxn (especially R-sided heart failure

• acute + chronic

What does acute passive congestion look like compared to chronic?

• acute

  • slight hepatomegaly

  • dark red in color

  • blood flows freely from cut surface

• chronic

  • significant hepatomegaly w/ very rounded edges

  • significantly enhanced lobular pattern especially on cut surface

What is a portosystemic shunt? What does it result in? What are the 3 types of congenital portosystemic shunts?

• abnormal communication b/t portal vein + systemic circulation where the liver is bypassed

• portosystemic shunt → reduced hepatic circulation →

  • decreased delivery of trophic factors to liver → microhepatica (abnormally small liver)

  • decreased removal of toxins, bacteria, and ammonia from systemic circulation → hepatic encephalopathy

• 3 types

  • intrahepatic

  • extrahepatic

  • hepatic microvascular dysplasia/portal vein hypoplasia

Difference b/t congenital extrahepatic shunts + hepatic microvascular dysplasia? What breed is associated w/ each?

• extrahepatic = single shunt from main trunk of portal vein to systemic circulation vein, bypassing liver

  • commonly affects small breed dogs + cats

  • avg age at presentation: 6-18 months

• hepatic microvascular dysplasia/portal vein hypoplasia = abnormal formation of liver microvasculature → altered lobular blood flow

  • commonly affects small breed dogs

  • avg age at presentation: 3 yrs

What is portal hypertension? 3 types + common causes?

• increased pressure w/i hepatic portal vein

• 3 types:

  • prehepatic

    • portal vein thrombosis, embolism, obstructing mass

  • hepatic

    • fibrosis, amyloidosis, granulomatous inflammation

  • posthepatic

    • R-sided heart failure

Pathogenesis of hepatic amyloidosis? How does it cause portal hypertension?

• chronic inflammatory state → persistently elevated serum-amyloid A → conversion of SAA to AA → too much AA being deposited into various organs → amyloidosis

• excessive amyloid deposition in the liver can cause resistance to blood flow into or w/i the sinusoids → portal hypertension

3 common causes of hepatic copper accumulation? Why is copper accumulation bad?

• primary defect in copper metabolism

• cholestasis → defective biliary excretion of copper

• excessive dietary intake of copper

• excess copper → increased reactive oxygen species → lipid peroxidation

Gross patterns of liver infection + pathogenesis

Dx + pathogenesis in this liver from a feedlot steer

• dx: multifocal hepatic necrosis

• pathogenesis: Fusobacterium necrophorum present in rumen → ruminal acidosis d/t diet → loss of ruminal mucosal integrity → F. necrophorum enters portal circulation → F. necrophorum infects liver → liver necrosis

What are the 2 major types of hepatotoxins + their expected pattern of injury?

• toxins that cause direct hepatocellular injury

  • expect periportal pattern

• toxins transformed by liver to toxic metabolites by cytochrome p450

  • expect centrilobular pattern