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Meded Histopathology Revision Lecture 2013 Part 2 Copy HISTOPATHOLOGY ICSM MED ED 5TH YEAR REVISION SERIES 2013 Part 2 28 th March 2013 MR GUY MARTIN MBBS BS C MRCS CORE SURGICAL TRAINEE T HE R OYAL LONDON & S T B ARTHOLOMEW ’ S H OSPITAL OVERVIEW ° Revision sessions organised and run by The Medical Education Society ° We are not examiners / lecturers ° These lectures are not formal Imperial College lectures ° No promises about completeness ° General overview, key principles, example questions ° You will require more in depth specific knowledge ° Please fill in the feedback forms! OVERVIEW ° General principles ° System specific pathology ° Cardiovascular ° Bone and joint ° Connective tissue ° Breast ° Neurological and cerebrovascular ° Respiratory ° GI Tract ° Hepatobiliary and pancreas ° Genitourinary tract QUIZ TIME HOW MUCH DID YOU PAY ATTENTION ? NEUROPATHOLOGY, CEREBROVASCULAR DISEASE & TRAUMA “Alzheimer’s is the cleverest thief, because she not only steals from you, but she steals the very thing you need to remember what’s been stolen” - Jaord Kintz EMQ – DEMENTIA ° A 75yr man with a previous history of a CABG and fem-pop bypass. His memory has been deteriorating steadily over the last year or so, with a marked deterioration just after the Christmas period ° A 75yr man complains that he is losing his memory, and his wife says that he tends to be better in the evening. He also has mobility problems, and now finds it difficult to complete tasks like making a cup of tea before the water goes cold. Histology – alpha synuclein deposits in cortex ° A 75 year old retired vicar is brought to see his GP by his concerned wife. Her concern was his behaviour over the last few months, he was becoming quite verbally abusive, recently calling his son a “massive wanker” at Christmas Dinner. Histology – Neuronal Tau Bodies arranged spherically A. Alzheimar’s Disease D. Multi-infarct dementia B. Pick’s disease E. Normal pressure C. Lewy body dementia hydrocephalus EMQ – DEMENTIA ° A 75yr man with a previous history of a CABG and fem-pop bypass. His memory has been deteriorating steadily over the last year or so, with a marked deterioration just after the Christmas period -D ° A 75yr man complains that he is losing his memory, and his wife says that he tends to be better in the evening. He also has mobility problems, and now finds it difficult to complete tasks like making a cup of tea before the water goes cold. Histology – alpha synuclein deposits in cortex -C ° A 75 year old retired vicar is brought to see his GP by his concerned wife. Her concern was his behaviour over the last few months, he was becoming quite verbally abusive, recently calling his son a “massive wanker” at Christmas Dinner. Histology – Neuronal Tau Bodies arranged spherically -B A. Alzheimar’s Disease D. Multi-infarct dementia B. Pick’s disease E. Normal pressure C. Lewy body dementia hydrocephalus CEREBROVASCULAR DISEASE ° Cerebrovascular disease – 3 key pathologies ° Infarction ° Haemorrhage ° Aneurism BASIC NEUROANATOMY CEREBRAL PERFUSION -ANATOMY http://missinglink.ucsf.edu/lm/ids_104_cns_injury/response%20_to_injury/watershed.htm WATERSHED AREAS OF CEREBRAL PERFUSION http://missinglink.ucsf.edu/lm/ids_104_cns_injury/response%20_to_injury/watershed.htm INFARCTION ° The most common form of cerebrovascular disease ° CVA vs TIA ° Thrombotic vs embolic ° Embolic more common – ICA / LA / PICA ° Thrombosis commonly at carotid bifurcation ° Localisation / distribution ° Site of occlusion ° Time of development ° Presence / absence collateral flow ° Systemic perfusion pressure HAEMORRHAGE ° Traumatic vs non-traumatic INTRA-PARENCHYMAL HAEMORRHAGE ° Haemorrhage into the substance of the brain ° Middle age to late adulthood ° Typically non-traumatic ° Hypertension 50% clinically significant cases ° Atherogenic ° Charcot-Bouchard micro-aneurysms ° Sudden onset with signs/symptoms raised ICP ° Poorly localised INTRA-PARENCHYMAL HAEMORRHAGE SUB-ARACHNOID HAEMORRHAGE ° Sub-arachnoid haemorrhage ° Traumatic ° Non-traumatic – Berry aneurysm rupture / AVM ° Congenital defect of tunica media ° 1% population ° PCKD, coaractation of the aorta ° Poor prognosis – 70% mortality ° Sudden onset ° Thunderclap headache ° Severe headache, vomiting and LOC ° 20% with herald bleed SUB-ARACHNOID HAEMORRHAGE CNS TRAUMA ° CNS Trauma ° ¼ all accidental deaths ° Significant mortality/morbidity ° Principle injury patterns in CNS trauma ° Extra-dural haemorrhage ° Sub-dural haemorrhage ° Sub-arachnoid haemorrhage ° Parenchymal injury CNS TRAUMA -HAEMORRHAGE Imaging / Location Injury Clinical Features Management Lucid interval – Disruption of Lens shaped Outside deterioration – death Extra-dural arteries from middle haematoma dura mater Associated with skull meningeal artery Surgical drainage fracture Insidious onset Between (alcoholics/elderly) Concave Rupture of bridging Sub-dural arachnoid Headache, haematoma veins and dura sensory/motor Surgical drainage symptoms “star shaped Thunderclap Under the Traumatic / non- appearance” Sub-arachnoid headache arachnoid traumatic Conservative/em Meningism bolisation Within Damage to brain Compressive / Intra-cerebral Surgical drainage brain tissue substance localising signs CNS TRAUMA CNS TRAUMA –PARENCHYMAL INJURY ° Traumatic parenchymal injury ° Traumatic intra-cerebral haemorrhage ° Concussion ° DAI (diffuse axonal injury) ° Contusions ° Vasogenic / cytotoxic oedema CEREBRAL OEDEMA ° Swelling of brain substance ° Generalised – hypoxia, metabolic disturbance, trauma, HTN ° Local – haematoma, ischaemia, tumour ° Acute – cytotoxic ° Damaged cells leak Na/K osmotic shift ° Chronic – vasogenic ° Dilation of cerebral vessels hydrostatic shift ° Complications ° Vascular injury/damage ° Intracranial nerve damage ° Obstruction to CSF flow ° Herniation CNS TRAUMA –MONRO-KELLIE CNS TRAUMA –PRESSURE EFFECTS http://missinglink.ucsf.edu/lm/ids_104_cns_injury/herniation/herniation.htm CNS NEOPLASMS CNS NEOPLASMS ° Secondary (metastatic) ° Most common – breast/lung ° Multiple / well demarcated ° Primary ° Gliomas, meningiomas, neuromas, pituitary, lymphoma, neuroendocrine Generalised – raised ICP / seizures Specific – focal neurology/local mass effect/paraneoplastic effect PRIMARY CNS NEOPLASMS ° Primary brain tumours ° Brain parenchyma, spinal cord or meninges ° Clinical effect depends on location and tumour type ° Rarely metastasise outside CNS ° Gliomas ° Astrocystomas (60%) ° Most common, slow growing, aggressive with time ° Oligodendrogliomas ° Slow growing. Calcification. Epilepsy ° Ependymomas ° Lining of ventricles. Hydrocephalus PRIMARY CNS NEOPLASMS ° Meningiomas ° Derived from arachnoid cells ° Most common adjacent to sinuses and typically in adults ° Slow growing – principle mass effects / skull erosion ° Raised ICP +/- focal neurology ° Primary CNS Lymphoma ° Associated with HIV / AIDS and non-Hodgkins B-cell ° Primary Neuroepithelial neoplasms ° Primitive small cells, classically affecting the cerebellum ° Children / <20yrs with raised ICP and cerebellar signs NEURODEGENERATIVE DISORDERS ° Broad spectrum conditions characterised by: ° Accumulation of abnormal proteins ° Neuronal damage ° Multiple cognitive deficits ° Memory impairment ° Loss of executive function DEMENTIA ° Aphasia (laguage) ° Apraxia (motor planning) ° Agnosia (recognition) DEMENTIA ° “Development of multiple cognitive deficits that include memory impairment and at least one of the following cognitive disturbances: aphasia, apraxia, agnosia or a disturbance in executive functioning. The cognitive deficit must be sufficiently severe to cause impairment in the occupational or social functioning and must represent a decline from a previously higher level of functioning” ° 30% of those >80yrs ° 7% of population aged 65-80yrs NEURODEGENERATION –THE BASICS ° Axonal damage ° Direct insult, neuronal death, axonal transection ° Primary damage Wallerian degeneration ° Demyelination ° Myelin provided by oligodendrocytes ° Primary – genetic defects of myelin ° Secondary – inflammation, toxic/metabolic factors ° Neuronal inclusions ° Nuclear / cytoplasmic inclusions seen in physiological and pathological conditions NEURODEGENERATION –THE BASICS Small spherical nuclear inclusions in liver Marinesco Bodies insufficiency Hirano bodies Rod like lipofuscins in ageing brains Bunina bodies Pathological inclusions of MND PD + Lewy body dementia Lewy bodies α-synuclein /ubiquitin plaques Pick’s bodies Pick’s disease Ageing, AD and progressive supra-nuclear palsy Neurofibrillary tangles Major antigenic component is phosphrylated tau Bielschowsky’d staining (β-amyloid, ubiquitin, Senile plaques phosphorylated tau) Neuritic or diffuse NEURODEGENERATIVE DISORDERS ° Alzheimer’s dementia ° Vascular / multi-infarct dementia ° Lewy body dementia ° Pick’s disease ° Huntingdon’s disease ° Others ALZHEIMER’S DISEASE ° 1907 Alois Alzheimer ° 50-75% dementia (5/1000 people) - leading cause of disability ° 20% those >80yrs ° Most cases sporadic, <10% inherited (pre-senilin gene) ° Definitive diagnosis only as post mortem ° Key features ° Severe brain atrophy – hippocampus, amygdala, frontal lobe ° Formation of senile plaques/neurofibrillary tangles neuronal loss with reactive astrocytosis ° Amyloid plaques (β-amyloid) ° Neurofibrillary tangles (paired helical filaments) ° Dystrophic neuritis (phosphorylated tau) ALZHEIMER’S DISEASE VASCULAR/MULTI -INFARCT DEMENTIA ° Very common ° Arteriopaths ° 25% of dementia ° Cumulative affect of multiple small CVA’s ° Sudden onset and step-wise progression LEWY BODY DEMENTIA ° 3rd most common cause of dementia ° 15-25% of cases
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