Mind Map by , created almost 6 years ago

Doctorate Pathology (Systems Pathology) Mind Map on Neuropathology, created by melian.yates on 11/23/2013.

Created by melian.yates almost 6 years ago
General Pathoanatomy Final MCQs (201-300)- 3rd Year- PMU
Med Student
patho. practical slides
Neuropathology III - Raised ICP, SOL & Trauma
Matthew Coulson
Spanish Verbs
Niat Habtemariam
An Inspector Calls - Quotes
Pathology of Alimentary Tract 2 (Ruminant Forestomachs/ Glandular stomach)
Musculoskeletal Pathology
Liver Pathology
General Pathoanatomy Final MCQs (301-400)- 3rd Year- PMU
Med Student
General Pathoanatomy Final MCQs (401-519)- 3rd Year- PMU
Med Student
1 Anatomy
1.1 Brain
1.1.1 Grey Matter (Outside) Cerebral & Cerebellar cortex Contains neuronal cell bodies
1.1.2 White Matter (Inside) Contains axons, myelin sheaths, astrocyte fibers
1.1.3 Nuclei Foci of grey matter also occur w/in the white matter Ex. Olivary, red, cuneate, etc.
1.1.4 Meninges Protect CNS Encase CSF Support blood vesels Dura (Outside -thick (Packy)) -> Arachnoid -> Pia Matter (Inside - thin (Lepto)) Sunbarachnoid space (Blood vessels)
1.2 CNS Cell Types
1.2.1 1) Neurons Response to Injury Extremely vulnerable to injury High metabolic rate Little NRG storage An Axon to care for Axon has no Nissl (ribosomes) Can't make protein Can't dispose of own waste Neurons CANNOT regenerate Acute Necrosis Most common response Ischaemia O2 required for oxidative phosphorylation Cell's ATP drops & ion channels leak Ca 2+ enters cells => membrane damage Increased intracytoplasmic Ca2+ => ATPase => Decreased ATP Phospholipase => Decreased phospholipids Protease => Disruption of membrane & cytoskeletal proteins Endonuclease => Nucleus chromatin damage Red dead cells (Red cytoplasm) Pyknosis Hypoxia Hypoglycaemia (toy breed puppies -> seizures) Nutritional Deficiency (e.g. thiamine deficiency) Toxins (e.g. Pb & Hg) Laminar cortical necrosis Polioencephalomalacia Outer cortex "Melting" => Gelatinous material Ruminants Acute neuronal necrosis in a distinct pattern Causes: Salt poisoning (Pigs) Water deprivation Pb & Hg toxicity Polioencephalomalacia Polioencephalomalacia Cerebrocortical necrosis (CCN) Pathogenesis unclear Thiamine deficiency vs. sulfide toxicity Thiamine required for glucose metabolism => Hypoglycaemia Chromatolysis Swelling of the Neuron Powdery appearence => Nissel substances dispersed ( unraveling ER) NOT necrosis => Adaptive change Dissolution of Nissel bodies Ex. Equine dysautonomia (grass sickness) Wallerian degeneration Response of Axon to injury (Normally seen in white matter) Healing => Axoplasm (Myelinated - built up at point of injury => swollen axon) Neuroma => conglomeration of axons, axoplasm ("abortive attempt" at repair) Ex. tail dock neuroma No renegeration of basal lamina, inefficent clearance of debris & re-myelination (oligodendrocyte), inhibits axonal sprouting => Chances of repair low Breakdown of the nerve fiber DISTAL to the point of initiating injury Myelin sheath breaks up Vacuolation Transmissable spongioform encephalopathies (BSE, scrapie) Common artefact (Not fixed properly) Normal finding Lysosomal storage disease Early cell injury Some toxins
1.2.2 2) Glial cells (Neural glue) Astrocytes " Star-shaped", multiple dendritic extensions CNS equivalent of fibroblast Functions: Support Insulating synapses Detoxification BBB Produces cytokines Response to Injury Necrosis Astrocytosis (astrocyte hyperplasia) Astrogliosis (astrocyte hypertrophy & hyperplasia) Starting to produce glial fibers ("Fibrosis") Oligodendrocytes Look like circular nuclei (Circular cells), Myelinate axons Inefficient at re-myelinating in response to injury Myelinate axons Oligodendrocyte injury => De-myelination Microglial cells " Macrophage" Ependymal cells Line the ventricles Choroid plexus epithelial cells Produce CSF
1.2.3 Order of vulnerability to injury: Neurons > Oligodendrocytes > Astrocytes > Microglia > Blood vessels
2 General Responses to Injury (CNS & PNS)
2.1 Oedema
2.1.1 Vasogenic Most common form in animals Follows vascular injury Breaches BBB -> Increased permeability Fluid is extracellular Ex. Oedema disease in Pigs E.coli (bacterial infection of GI tract) Bacteria produce toxins in the intestine (endotoxaemia) Toxin enters bloodstream => Brain => Vasculitis, Leaky vessels
2.1.2 Interstitial Usually follows hydrocephalus Ventricles dilate & increased hydrostatic pressure => Fluid forced into parenchyma Fluid is Extracellular
2.1.3 Cytotoxic ATP deficit & Failure of Na+/K+ pump => Na+ & H2O build up in cell Fluid in Intracellular Hypoxia, Ischaemia, toxins (anything that inhibits ATP production) => Hydrophobic degeneration in other cells
2.1.4 Consequences Brain swells, becomes compressed => Herniation 1) Through the Foramen Magnum Most common 2) At Cingulate gyrus under the falx 3) Transtentorial herniation Ex. Cerebellar herniation Compresses Medulla (Resp. centers) => Sudden death
2.2 De-myelination
2.2.1 Primary: Myelin forms normally & then is selectively destroyed Impaired maintenance (i.e. infectious destruction of oligodendrocytes) Nutritional (Cu, Vit. B12) Toxins (Cyanide) Cytotoxic oedema Immune mediated (i.e. multiple sclerosis, canine distemper (Most common)) Proposed Pathogenesis: Oligodendrocytes die as a result of immune response against viral Ag on their surface Molecular mimicry Incorporation of neural elements into the virus during assembly resulting in anti-self response
2.2.2 Secondary: Loss of Myelin following axonal damage (i.e. Wallerian degeneration)
2.2.3 Vs. Dysmyelination => Myelin doesn't form properly in first place
2.3 Vascular Disturbances
2.3.1 Reduced blood flow (or complete blockage) leads to ischaemia
2.3.2 Consequences of ischaemia depend on: It's degree & duration Size & type of vessel involved Relative susceptibility of tissue to hypoxia
2.3.3 Consequences of ischaemia: Neuronal necrosis Vasogenic oedema The ischaemia is not a direct cause of the oedema, but the two could occur together if the ischaemia was the result of vascular damage Infarct(s) Necrosis of a tissue following obstruction of a supplying blood vessel Often well demarcated Causes: Thrombosis/thromboembolism (Uncommon in the CNS of animals, can see with DIC or sepsis) Emboli: FCEM (fibrocartilaginous embolic myelopathy), bone marrow embolism following fracture Vasculitis: Classical swine fever (hog cholera - pestivirus), MCF (malignant catarrhal fever -herpesvirus), Oedema disease (vasculitis caused by E.coli toxin) Malacia Grossly: appreciable softening of brain/spinal cord (usually resulting from necrosis) Histologically: Necrosis Occurs in infarcts, but there are other causes (toxicosis, hypoxia, nutritional, infectious or metabolic disease) The pattern & location of Malacia are often more Dx helpful than the lesion itself Symmetrical Malacia: Nutritional, Toxic, Metabolic, Genetic Asymmetrical Malacia: Vascular, Infectious, Traumatic
3 Inflammation of the Nervous System
3.1 Defence (against infection)
3.1.1 Skin Skull/vertebrae Meninges & CSF Barriers (CSF/ECF, CSF/blood, BBB) Microglia (monocyte/ macrophage system) Immunologic responses (innate & adaptive) BBB Endothelial cell Not fenestrated Tight junctions Fewer transporting vesicles P glycoprotein Astrocytes Pericytes
3.2 Inflammation is usually the result of infection
3.2.1 Bacteria, Fungi, Parasites (protozoa)
3.2.2 Main Routes of Entry Haemotogenous (most common) Direct Spread from adjacent structure (inner ear, skull sinuses) Injection Penetrating trauma Via peripheral nerves Leukocyte trafficking ("Trojan horse")
3.3 Sites of Inflammation
3.3.1 Epidural or subdural space Tends to result in abscess (Uncommon)
3.3.2 Meninges Leptomeninges - Pia & Arachnoid Matter (Leptomeningitis) Suppurative: Most common Bacterial (E.coli, Streptococcus, Haemophilus) Swollen brain, meninges opaque, OFTEN NO GROSS LESIONS Neutrophils predominate initially Usually fatal Usually of haemotogenous origin Eosinophilic meningoencephalitis: Porcine salt poisoning/ H2O deprivation Perivascular eosinophilic cuffing in the cerebrum & meninges Lymphocytic: Usually viral Granulomatous: Fungal disease & mycobacteriosis Idiopathic forms (Mainly Dogs) Pachymeninges - Dura matter (Pachymeningitis)
3.3.3 Parenchyma Encephalitis Inflammation of the cerebral parenchyma) Classified based on nature of Exudate: Suppurative Fibrinous Granulomatous Lymphoplasmacytic Eosinophilic Haemorrhagic Bacterial: Typically result in Abscesses (Suppurative inflammation - i.e. localized collections of neutrophils) Single or multiple depending on route Vary in size with a central, liquefied cavity Ex. E.coli, Streptococcus, Stapyhlcoccus, Pasteurella & Fusobacterium necrophorum Listeria monocytogenes (Listeriosis) Sheep, cattle goats 3 forms (CNS, abortion, sepsis) Compared to other bacteria, pathogenesis in CNS disease is a little different Oral mucosa -> Trigeminal nerve -> Trigeminal ganglion in brain Source: Silage (pH > 5.4 allows bacterial growth) Sxs: Circling, Facial nerve paralysis (unilateral), Drooling, Pharyngeal paralysis, Recumbancy, paddling, death Usually NO GROSS lesions White/grey matter junction predisposed Viral: Lymphoplastic inflammation Haematogenous & neural routes mainly Hallmark lesions (regardless of virus type): 1) Neuronal necrosis 2) Gliosis (glial nodules) 3) Vascular changes -lymphoplasmacytic cuffing Types of Virus: Neurtropic Viruses which can overcome innate immunity of brain Rabies (rhabdovirus) Encephalomyelitis & ganglionitis Lesions are macroscopic Intracytoplasmic, oval, pink inclusion bodies (Negri bodies) Aujesky's disease (Herpesvirus) Visna (Ovine lentivirus) Endotheliotropic EHV1 (Equine herpesvirus type 1) Classical swine fever (pestivirus) Infectious canine hepatitis (canine adenovirus) Endothelial cell damage leads to vascular injury & secondary parenchymal necrosis & haemorrhage Pantropic Canine distemper (morbillivirus) Infectious bovine rhinotracheitis (Bovine herpesvirus type 1) Respiratory, urogenital & CNS Virus can be latent in nerve ganglia Prion Diseases: Transmissable spongiform encephalopathies (TSEs) BSE, scrapie, chronic wasting disease A group of fatal neurodegenerative diseases which occur in a number of species Proteinaceous infectious particle Abnormal isoform of prion protein (PrP) in the brain -> PrPsc (common to all cases) PrPsc accumulates in nervous tissue as amyloid fibrils Long incubation period, difficult to Dx (no immune response) Agent is highly resistant Alpha helix -> beta pleated sheet No gross lesions; Characteristic microscopic lesions Spongioform change, Amyloid plaques, Astrogliosis Fungal/ Protozoa: Cryptococcus Opportunistic -Aspergillus Neospora Toxoplasma gondii Myelitis
4 Trauma
4.1 Less common in animals than man
4.1.1 Less risk, Better protection
4.2 Main forms of injury
4.2.1 Concussion
4.2.2 Contusion Pathogenesis: Head is moving, but suddenly stopped by solid object 1st point of impact = where object hits the head Head stops, brain doesn't Brain strikes inside of skull at first point of impact (Coup) Brain moves in cranium, stretching & tearing vessels & nerves on the opposite side to the original impact (Contrecoup)
4.2.3 Laceration
4.2.4 Haemorrhage Locations: a) Epidural b) Subdural c) Leptomeningeal d) Subpial e) Intramedullary
5 Response of Spinal Cord to Injury
5.1 Like the brain, can be affected by infectious, inflammatory, toxic, nutritional & neoplastic disease, & lesions can occur in its parenchyma
5.2 Traumatic injuries:
5.2.1 Concussion, contusion, haemorrhage & Compression Compression May arise within (Intra-medullary) or outside (Extra-medullary) the spinal cord Causes: Neoplasia Abscess Extradural Vertebral Intervertebral Fracture: Traumatic or pathological Vertebral bodies (e.g. due to abscess, metabolic disease, neoplasia) Invertebral disk disease (IVDD) Prolapsed disk can cause acute or chronic compression Chrondrodystrophic Nucleus pulposus replaced by chondroid tissue Degeneration of annulus fibrosus is 2ndary Young Dogs Non-chrondrodystrophic Degeneration begins in annulus fibrosis Nucleus undergoes fibrosis Middle aged dogs (TL) Age-related & not breed dependent Malformations (esp. vertebral) Wobbler horses (stenotic myelopathy): Vertebral canal narrows due to malformation & malarticulation of the cervical vertebrae (usually C3-C4) Cervical vertebral malformation-malarticulation (Dogs) - similar pathogenesis to wobbler horses Alantoaxial subluxation of toy Dogs (Hypoplastic dens leads to subluxation) Lesions are similar regardless of the cause Gross: Spinal cord may be indented or flattened Histologically: Myelin sheath ballooning in all funiculi w/ axonal swelling/loss, Myelin digestion chambers, Neuronal loss, gliosis, malacia (due to vascular damage), oedema
6 Congenital Malformations
6.1 Abnormal development of neural tube
6.2 May involve Spinal cord, Brain, Calvaria, Meninges &/or Vertebral column
6.3 Morphological
6.3.1 Hydrocephalus Increased accumulation of fluid within the cranial cavity Types: Internal (fluid w/in ventricles) Congenital form: Obstruction NOT found Common in brachycephalic dogs (mesenphalic aqueduct may be stenotic) Sporadic in cattle Acquired form: Causes: Obstruction due to inflammation (of meninges &/or ependymal cells) or space occupying lesions compression (neoplasms, abscesses & cholesteatomas) Common External (w/in arachnoid space) Communicating (w/in both locations) Hydrocephalus ex vacuo (ventricles dilate 2ndary to replace lost tissue)
6.3.2 Others Anencephaly (absence of brain) Lissencephaly (normal in mice, rats, rabbits & birds) Meningoencephalocoele Spinal: spina bifida, hydromyelia & syringomyelia
6.3.3 Cerebellar Defects Cerebellar hypoplasia Common Inherited: (Arab foals, Jersey cows, Chows, Corriedale sheep) Acquired: Environmental teratogens attack germinal cells in external granular layer of cerebellum (source of neurons) Ex. Bovine virus diarrhea (BVD), feline parvovirus, CSF (hog cholera), canine parvovirus, schmallenberg virus Cerebellar Abiotrophy Premature degeneration of nervous tissue elements after they have formed (form of atrophy) - probably inherited
6.4 Functional (biochemical abnormalites - ex. lysosomal diseases or leukodystrophies)
6.5 Causes:
6.5.1 Inherited
6.5.2 Environmental (most common) Toxic Infectious Nutritional Radiation
7 CNS Neoplasia
7.1 Primary
7.1.1 Meninges Meningioma Most frequent in Dogs & Cats Compressive, space-occupying lesion (seldom invades)
7.1.2 Glial cells Astrocytoma Most common glial tumor Brachycephalic breeds Solid, firm, grey-white (sometimes mottled red w/ areas of necrosis/haemorrhage) Oligodendroglioma Most common in Dogs (brachycephalic breeds) Soft, grey to pink/red & often gelatinous Ependymoma Mainly in ventricles (primarily lateral) May spread in the ventricular system via CSF Expansile, but can be invasive & destructive Choroid plexus tumors Rare, mainly Dogs, 4th ventricle
7.1.3 Neurons (very rare)
7.2 Secondary (Metastatic)
7.2.1 Haemangiosarcoma Mammary or Pulmonary Carcinoma Lymphoma Pituitary tumors Vertebral osteosarcoma
8 Idiopathic Diseases
8.1 Idiopathic Epilepsy
8.1.1 Small group of neurons periodically & spontaneously depolarize Structural : Neoplasma, inflammation, trauma Biochemical: Hypocalcemia, Hypoglycemia, Hepatic encephalopathy Idiopathic: No cause identified (indiviuduals have a low seizure threshold)
9 Diseases of Peripheral Nerves
9.1 Dorsal & Ventral roots, spinal ganglia, spinal & peripheral nerves, cranial nerves & peripheral components of the ANS
9.2 Trauma
9.2.1 Nerves are predisposed to injury because of: Superficial position Proximity to bone Proximity to injection sites
9.2.2 Laceration Avulsion ("pull out" - usually at roots) Transection Compression & stretching (following fracture or dislocation) => Wallerian degeneration
9.3 Infectious
9.3.1 Some infectious agents involve peripheral nerves as well as CNS
9.3.2 Ex. Rabies, Aujesky's disease, Neospora caninum, Toxoplasma gondii
9.3.3 Neospora caninum Dorsal roots (Dog) Equine Guttural Pouch mycosis Inflammation in the recurrent laryngeal nerve -> vocal cord hemiplegia Macaw Wasting Disease (Proventricular dilation syndrome) Non suppurative inflammation around myenteric ganglia => gastric dysfunction (wasting, anorexia, depression) => neurological signs (ataxia, seizures) Borna disease virus ?
9.4 Idiopathic/ Immune mediated
9.4.1 Coonhound paralysis Polyradiculoneuritis (racoon bites) => Quadriplegia Lesions in ventral roots of spinal nerves & in peripheral nerves
9.5 Neuropathies
9.5.1 Often breed related -> Inherited pathogenesis
9.6 Degenerative
9.6.1 Equine laryngeal hemiplegia ("roarers") Common Pathogenesis: Degeneration of left recurrent pharangeal nerve -> Atrophy of the left dorsal cricoarytenoid muscle -> Inability to abduct arytenoid cartilage & vocal fold => Airways partially obstructed on inspiration Cause: Idiopathic/ inherited, 2ndary to guttural pouch mycosis, Trauma 95% cases on Left
9.7 Toxic
9.7.1 Uncommon
9.7.2 Heavy metals (Pb, Hg, Thallium) Pb -> damages Schwann cells -> peripheral degeneration Hg -> Targets neuronal cell bodies -> 2ndary axonal degeneration in peripheral nerves
9.8 Neoplastic
9.8.1 Uncommon
9.8.2 Dogs
9.8.3 Peripheral nerve sheath tumors (Benign/ Malignant)
9.9 Nutritional/metabolic
9.9.1 Vitamin A & B, Pantothenic acid & Cu deficiency => Neuropathy Cu deficiency: Swayback (New born lambs) & enzootic ataxia (older lambs)
9.9.2 Metabolic: Diabetes mellitus, Hypothyroidism