Histopathology Notes
Cardiovascular Disease
BP = CO x SVR
CO = HR x SV
Infarction
 Necrosis due to ischaemia
 Arterial
o MI
o Stroke
o Bowel infarction
o Acute limb ischaemia

Venous
o PE
o Torsion of vascular pedicle
o Sigmoid volvulus
o Testicular torsion

Modifiable
o Hypertension
o Diabetes Mellitus
o Smoking
o Hypercholesterolaemia
o Others - physical inactivity,
lipoprotein Lp(a)
Atherosclerosis
 Arterial wall thickening and loss of elasticity
Stages
 Endothelial cell injury
 Inflammatory response in vessel wall
o Oxidised LDL
 Formation of stable atherosclerotic plaque
o Vascular smooth muscle phenotype shift
 Complication of stenosis or plaque rupture
Risk Factors
 Non-Modifiable
o Age
o Sex
o Family history
o Others - Type A personality,
oestrogen deficiency
Complications
 Plaque-related Stenosis (angina, intermittent claudication)
 Plaque rupture
o Thrombosis (MI, stroke, acute limb ischaemia)
o Embolism (MI, stroke, acute limb ichaemia)
 Weakening of vessel wall (AAA)
Acute Coronary Syndrome
 Unstable angina
o No cardiac damage (normal
tropnin)

NSTEMI/STEMI
o Cardiac damage (raised tropnin)
Acute Limb Ischaemia

Thrombosis (60%)
o Hx of claudication/rest pain
o Onset over hours
o Signs of chronic
vascularinsufficiency
o Hard arteries
o No bruits

Embolism (30%)
o Recent MI, atrial fibrillation,
aneurysm
o Onset over seconds
o No evidence of previous disease
o Soft artery
o Bruits

Secondary
o Renal disease
o Endocrine disease
o Pregnancy
o Drugs



MI
HTN Cardiomyopathy
HTN Nephropathy
Hypertension
 140/90 (based upon additional risk factors)
 160/100 (absolute)

Primary (essential) - 95%
o Idiopathic
Sequalae
 HTN retinopathy
 CVA
 ↑ Glucose levels
 HTN encephalopathy
Cardiac Failure
A syndrome caused by any abnormality of the heart that may be characterised by a set of haemodynamic,
neural, and endocrine abnormalities
LVF


Causes:
o IHD
o Hypertension
o Valve disease
o Myocardial disease
Consequences:
o Impaired pulmonary outflow
 Congestion and oedema
o Reduced renal perfusion
 Salt and water retention +
ATN
o Reduced CNS perfusion
(encephalopathy)
RVF


Causes:
o Left-sided heart failure
(Congestive)
o Chronic Lung Pathology - Cor
Pulmonale
Consequences:
o Portal, systemic and peripheral
congestion
o Tricuspid regurgitation
o Renal congestion (R > L)
Cardiomyopathy
Hypertrophic
Dilated
Causes
Inherited (50% AD)
Sporadic cases
Idiopathic
Genetic
Infections e.g. viral
myocarditis
Toxins - alcohol,
chemotherapy
Restrictive
ARVD
Inflammation and thinning
of the right ventricular wall
Usually due to mutation in
cell adhesion genes
Valve Disease
Congenital
 Abnormalities e.g. Bicuspid valves
Features
Pathology - heavy muscular hypertrophy with poor
compliance
Often asymmetrical septal hypertrophy
Sequelae:
- Arrhythmias - AF
- LV outflow obstruction
- CHF
- Sudden deathYoung man
Syncope, FH of sudden death, Jerky pulse and double
apical impulse, Ejection systolic murmur (+/- mild mitral
murmur)
Four-chambered hypertrophy and dilatation
Poor prognosis
Progressive CCF
Progressive loss of mycoytes causing dilation + heart
failure + arrhythmias
Pathology - restriction of ventricular filling with
myocardial fibrosis
Key consequences:
- Arrhythmia
- CCF



Rheumatic fever/Endocarditis
Functional (e.g. Mitral/tricuspid valve
disease)
Degeneration (e.g calcific aortic stenosis)
Acquired
Stenosis
 Pressure overload + hypertrophy
 Develops slowly
Complications
 Hypertrophy
o LVF
o Worsening of IHD, heart failure
o Pro-arrhthymia
Regurgitation
 Volume overload
 Develops quickly or slowly


Dilation
o Mitral and atria
Risk of Endocarditis
Types
Rheumatic Fever
Infective
Endocarditis
Acute
Subacute
Pathogenesis
Acute inflammatory
disorder of children (5-15)
Post-streptococcal (5
weeks)
Usually stap. aureus
Very virilant, IV drug users,
Very severe
Usually strep. viridans
Less virulent, Prosthetic
valves, Long course
Features
Foci of fibrinoid necrosis → Aschoff
Bodies, Fibrinous pericarditis, Valvulitis
Fribrous thickening + commissural
fusion, MacCallum plaques
Bulky vegitations with lots of erosion
May produce an abscess
Small vegetations with little erosion
Pathology of the Lung
Respiratory Failure
 End-stage of all pulmonary disease
 PaO2 < 8 kpa
Type I respiratory failure
 Severe pneumonia, PE, asthma, fibrosis,
LVF
 V/Q Imbalance
o CO2 - Compensation (pCO2 normal/low)
o O2 – No compensation
Type II respiratory failure
 COPD, neuromuscular disease, severe
acute asthma
 Hypoventilation
o Impaired transfer of Co2 and O2
(pCO2 elevated)
Pulmonary Embolus
 95% of PE from deep vein thrombi in legs/pelvis
 Large - Instant death (acute cor pulmonale)
 Medium - Chest pain + pulmonary heamorrhage
 Small - Clinically silent (multiple → Pulm. HTN)
 Ix: ECG + D-Dimer
Primary Pulmonary Hypertension
 Unknown cause
 > 25mmHg pressure at rest
 Young women
RVF

Causes:
o Left-sided heart failure
(congestive)
o Chronic lung pathology → cor
Pulmonale


Complication → Right ventricular failure
Tx: vasodilators/lung transplantation

Consequences:
o Portal, systemic and peripheral
congestion
o Tricuspid regurgitation
o Renal congestion (R > L)
Obstructive pulmonary disease
These are characterized by an increased resistance to airflow (low FEV1 and FEV1/FVC < 0.7)
Asthma
 Kids > adults
 Chronic airways inflammation that is usually reversible




Part of an atopic trait
Can be severe and life-threatening
Macroscopic
o Overinflated, patchy atelectasis, mucus plugs
Microscopic
o Oedema, pulmonary infiltrates (eosinophils), smooth muscle and mucoal gland hypertrophy
Chronic bronchitis
 Chronic cough with production of sputum most days, for a least 3 months in 2 consecutive years
 Usually smoking/old patients
Emphysema
 Destruction/dilatation of the lung parenchyma distal to the terminal bronchioles
 Can be young (congenital conditions) or old
 Panacinar
o Uniform destruction of acinus (lower basal zones)
o A1AT deficiency
 Centriacinar
o Central/proximal respiratory tree (upper lobes/apices)
o Smokers
Bronchiectasis
 Permanent and abnormal dilatation of bronchi
 Associated with inflammation
 Congenital - Cystic fibrosis, severe immune deficiency
 Post-infectious (severe viral, bacteria, fungal pneumonia)
 Bronchial obstruction (tumour, foreign body)
 Complications
o Chronic infection with H.
influenzae
o Secondary infection with:
 Staph. aureus
 Moraxella catarrhalis
 Pseudomonas
o Right ventricular failure
o Amyloidosis
Cystic Fibrosis
 Autosomal recessive.
 Mutation in CFTR gene → hyperviscous secretions
 Complications:
o Bronchiectasis (recurrent infections - staph, H. influenzae, P. Aeruginosa, B. Cepacia)
o Pancreatic failure
o Sperm maturation defects
Restrictive pulmonary disease
Pulmonary oedema
 Causes:
o IHD
o Hypertension
o Valve disease
o Myocardial disease
 Consequences:
o Impaired pulmonary outflow
 Congestion and oedema
o Reduced renal perfusion
 Salt and water retention +
ATN
o Reduced CNS perfusion
(encephalopathy)
Pulmonary Fibrosis
 Laying down of fibrotic tissue in the lung
parenchyma
 Most important restrictive pathology
o FEV1/FVC > 0.7
Extrinsic allergic alveolitis
Pneumoconoses
Autoimmune
Drugs
Radiation
Lung cancer
 Benign (rare)
o Hamartomas,
o Clear cell tumours
o Papillomas
o Fribromas
o Asymptomatic
 Malignant

Local effects
o Bronchial obstruction → collapse

Characteristic features:
o Progressive shortness of breath
o Cyanosis (+ clubbing)
o Fine end inspiratory crackles
Hypersensitivity Pneumonitis - Immune reaction
from inhalation of antigens (fungal, bacterial, animal
protein, chemical)
Occupation-related
• Farmer’s lung (thermophilic actinomycetes)
• Bird fancier’s lung (avian proteins)
Pathology - interstitial pneumonitis + non-caseating
granulomas
Inflammatory lung conditions caused by inhalation
of mineral dusts.
Lag Period of up to 30 years
Over-reaction to deeply seated dust particles with
peristent inflammation
Types
• Coal dust (coal miners)
Lung nodules (coal macules) + massive fibrosis
• Silicosis (mining, quarrying, glass making)
Nodular fibrosis
• Asbestosis (ship building, construction)
•Diffuse fibrosis
Sarcoidosis
Non-caseating granulomas + multisystem disease
Rheumatoid arthritis
Lupus
Systemic sclerosis
Ankylosing spondylitis
Causes pneumonitis (may → fibrosis)
Reversible with early recognition
• Bleomycin
• Amiodarone
Well-recognised complication of therapy for:
• Primary Lung Tumours
• Breast Carcinoma
1-6/12 after therapy
o Non-small cell - 80%
 Squamous cell
 Adenocarcinoma
 Large cell
undifferentiated/alveolar
cell
o Small cell (neuroendocrine) - 20%
o
o
o
o
o
o

Impaired mucus clearance →infections
Invasion
SVC, brachial plexus, oesophagus
Extension through pleura/pericardium
Pleuritis and pericarditis
Lymphatic invasion → lymphangitis carcinomatosis
Distant effects
o Peptide production
o ACTH
o ADH
o PTH-like (particular to squamous)
o Para-neoplastic syndromes
o Lambert-Eaton myaesthenic syndrome, acanthosis nigrians, dermatomyositis
o Metastases (common in bone, brain and liver)
Pneumothorax
 Spontaneous
o Primary - apical blebs
o Secondary - COPD, asthma, pulmonary fibrosis, lung cancer
 Acquired
o Traumatic
o Iatrogenic - central line insertion, pleural aspiration, barotraumas
Asbestos related lung-disease
 Pleural plaques (marker of exposure)
 Asbestosis (pulmonary fibrosis)
 Adenocarcinoma (lung cancer - particularly in smokers)
 Mesothelioma
o Tumor of mesothelial lining (pleural, pericardial, peritoneal)
o Epitheliod, sacromatoid, biphasic, desmoplastic
o Estimated peak of disease around 2020
Hepato-biliary pathology
Hepatic Failure
Clinical syndrome occurring when > 90% functional capacity of liver is lost
Acute Liver Failure
 Common causes
o Acute Viral Hepatitis (AST > 1000)
 Hep. A/B/C, CMV/EBV
o Alcholic Hepatitis (AST < 300)
 Clinical Features
o Hepatic encephalopathy
o Irritability →sleep disturbance
→disorientation → coma
o Coagulopathy
o Jaundice (conjugated)
Chronic Liver Disease
 Persistent liver damage > 6 months without resolution
 Raised GGT + MCV
o Drug-related Hepatitis
 Paracetamol, NSAIDS,
antibiotics
o Infection (sepsis + multi-organ
failure)
o Hepato-renal syndrome/hepatopulmonary syndrome
o Progressive Fibrosis
o Cirrhosis
Cirrhosis
Whole liver involved with triad of:
 Fibrosis
 Nodules of regenerating hepatocytes


Distortion of liver architecture
Complications
o Hepatic failure (decompensation)
o Hepatocellular carcinoma
o Portal hypertension
o Ascites
 Causes
Cause
Alcohol
Viral hepatitis
Steatohepatitis
Wilsonʼs disease
Haemochromatosis
Alpha-1 anti-trypsin
o Porto-systemic shunts
o Oesophageal varices,
haemorrhoids, caput medusa
o Splenomegaly (hypersplenism)
Deficit
Features
Alcohol byproducts activate Hepatic Stellate
Cells → Fibrosis
3 distinct pathologies
- Alcoholic Hepatitis
- Alcoholic Fatty Liver
- Alcoholic Cirrhosis
Non-alcoholic liver disease
Similar appearance but associated with
metabolic syndrome
? Insulin resistance (reduced peripheral
lipolysis)
Continuum
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis (may lead to
cirrhosis)
Disorder of ATPase Copper transport
protein
Accumulation of copper in liver →
hepatolenticular degeneration
AD transmission
HFE gene C282Y mutation → excessive GI
absorption of iron
AR + manifests > 40 years old
Accumulation in multiple organs
Neurology + Kayser-Fleisher rings
Low caeruloplasmin + low copper
Liver
– cirrhosis
– hepatocellular carcinoma
Heart
– Congestive cardiac failure
– Conducting defects and arrhythmia
– Constrictive pericarditis
Endocrine
– Diabetes
– Panhypopituitarism
– Hypogonadotropism
Joints
– Chondrocalcinosis
Loss of Libido
deficiency
Autoimmune
Middle aged women with co-existant
autoimmune disease
High transaminases + raised IgG
ANA + anti-SM antibodies
Responds well to steroids
Primary biliary cirrhosis
 Intrahepatic bile ducts (cholangiocytes)
 Pruritus


Raised ALP + GGT
Anti-mitochondrial/IgM
Primary sclerosing cholangitis
 Sclerosis of Intra- and extrahepatic ducts
 Association with UC (75%)


Isolated raised ALP
Risk of cholangiocarcinoma

Liver cell adenoma
o Young women on COC
Hepatic Neoplasia
Benign Tumours
 Haemangioma
o Most common - 3% population
o Asymptomatic (incidental finding)
Malignant Tumours
 Hepatocellular Carcinoma
o Develop on background of cirrhosis/chronic inflammation
o 1/3rd→ DNA mismatch repaid

Cholangiocarcinoma
o Malignancy of intrahepatic bile ducts
o Non-specific presentation
o Jaundice, weight loss, pruritus, pain
o Present late with poor prognosis
Gallstones
 Types:
o Cholesterol (most common)

Risk factors
o Female
o Forty
o Pigment (haemolytic states)
o Fat
o Fertile
Annular Pancreas
 Failure of migration of the ventral bud
 Obstructs duodenum
 Presents in infancy with a similar picture to pyloric stenosis
Pancreas Divisium
 Incomplete fusion of the ventral and dorsal ducts
 Predisposes to
o Chronic Pancreatitis
o Pancreas Ca
o Fair
Acute Pancreatitis
 Inflammatory condition of the pancreas
 Causes
o Gallstones (45%)
o Ethanol (25%
o Trauma
o Steroids
o Mumps/Infections
 Symptoms:
o Epigastric pain radiating to back
o Relieved by sitting forward
 Signs:
o Unwell
o Fever
o Tachycardia/pnoeia
o Jaundice
 Complications
o Respiratory: ARDS, atelectasis,
pleural effusion
o Organ failure: myocardial
depression
o DIC
o
o
o
o
o
Autoimmune
Scorpion venom
Hyperlipidaemia, hypercalcaemia
ERCP
Drugs
o Associated with vomiting
o Local/general peritonitis +/- shock
and ileus
o Cullen’s Sign
o Grey-Turner’s signS
o Metabolic: hypocalcaemia,
hyperglycaemia, met acidosis
o Necrosis, pseudocyst , abscess,
infection
Chronic Pancreatitis
 Repeated episodes of pancreatic inflammation leading to structural damage and fibrosis
 Results in exocrine and endocrine dysfunction
 Symptoms
o Wt loss
o Exocrine dysfunction
o Poor appetite
o Endocrine dysfunction
o Pain
 Signs
o Epigastric tenderness
o Erythema ab igne
Pancreatic Tumours
 M>F
 Elderly
 Western Countries
 Risk Factors
o Lifestyle: smoking, alcohol
o Toxin exposure: naphthylamine (dye industry), benzidine
o Disease states: chronic pancreatitis, diabetes
o Congenital: pancreas divisum
 Symptoms
o Anorexia
o Chronic epigastric pain radiating to
o Malaise
back
o Weight loss
o Steatorrhoea
o Diabetes symptoms
 Signs
o Cachexia
o Painless obstructive jaundice
o Lymphadenopathy
o Palpable gallbladder
o Signs of EtOH use
o Hepatosplenomaegaly and ascites
o Thrombophlebitis migrans
o Marantic endocarditis
Pathology of the Gut
Achalasia
 Dysmotility disorder of the oesophagus
 Degeneration of Auerbach plexi
 Sequelae:
o Dysphagia (liquids and solids)
o Hypertrophy
o Squamous cell carcinoma
Hiatus Hernia
 Impaired lower
 oesophageal sphincter
 Reflux of gastric contents + oesophagitis
Reflux Oesphagitis/GORD
 Acidic gastric contents → lower oesophagus
 Risk factors:
o Increased IAP (obesity, posture, large meals, alcohol)
o Hiatus hernia
 Complications
o Peptic Stricture
 Scarring and deformation → narrowing
o Barretts Oesophagitis (10%)
 Columnar metaplasia
o Adenocarcinoma
Barrett’s Oesophagus
 Oesophageal columnar metaplasia
 Adaptive response to acidic damage


Dx at endoscopy and confirmed by
histology
Pre-malignant potential
Oesophageal Carcinoma
 Presents late
 Malaise, weight loss
 Progressive dysphagia

Squamous Cell (squamous differentiation)
o Smoking, alcohol, achalasia
o Middle-third
Gastritis
 Causes
o Infection (H. Pylori)
o Autoimmunity (→ Pernicious
Anaemia)
H. pylori
 Micro-aerophilic Gram-ve bacterium
 Infects gastric-type mucosa
 Predilection for antral colonisation

Adenocarcinoma (glandular
differentiation)
o Barrett’s oesophagus
o Lower third
o Drugs (NSAID’s)
o Alcohol


Increase in Gastrin production increases acid production
Faeco-oral and oro-oral transmission
Peptic Ulcer Disease
 Full thickness breaches in mucosa
 Solitary
 Common sites:
o Gastric antrum
o 1st part of duodenum
 Complications
o Haemorrhage (posterior)
Gastric Tumours
Adenocarcinomas
 Intestinal
o Inflammation → metaplasia →
dysplasia sequence
o H. Pylori-related
Gastric lymphoma
 No lymphoid tissue normally
 H. Pylori → migration hyper-stimulation of
B lymphocytes
 Haematemesis
o Perforation (anterior)
 Abdominal pain +
peritonitis
o Stricture (post-healing)
 Gastric outflow obstruction

Diffuse
o Normal mucosa
o SIignet ring cells
o Highly infiltrative + aggressive
(linitis plastica)


Can lead to Marginal cell lymphoma
Responds to antibiotics
Leiomyomas/leimyosarcomas
 Benign/malignant tumour of muscle
 Also affects:
o Uterus (fibroid)
o Oesophagus (rare <1% oesophageal tumours)
o Skin (solitary cutenous, multiple, angioleiomyomas)
Stromal Tumours
 Connective tissue origin
 Features:
o Over-expression of tyrosine kinase
KIT
o Exophytic
o May be treated with Imatinib
Coeliac disease
 Gluten-sensitive enteropathy
 Inappropriate T cell driven inflammation → lymphocytic enteritis
 Malabsorption (iron + folate)
 Clinical Features
o Adulthood
o Anaemia
o GI sx - discomfort, altered bowel habit (IBS-like)
o Failure to thrive in kids/adolescents
 Diagnosis
o Antibody serology
 IgA tissue transglutaminase
 IgA endomysial
o Small bowel biopsy (distal
 IgG antigliadin
duodenum)
 Complications
o Osteopaenia/osteoporosis
o Enteropathy-associated T cell
lymphoma (EALT)
o Deterioration despite good diet
control
o Extremely destructive
(obstruction/perforation)
Inflammatory Bowel Disease
 Excess wall-based inflammatory activity leading to relapsing and remitting disease






Ulcerative Colitis
Large intestine only (back-wash ileitis)
Extends proximally from the rectum
Mucosal layer only
Pathology:
o Diffuse mucosal inflammation
o Crypt abscess
Complications
o Dilatation + perforation
 Due to involvement of muscle
coat (transverse)
o Adenocarcinoma
 Flat, ill-defined tumours (not
usually polyps)
 Endoscopic surveillance





Extra-intestinal manifestations of IBD
o Arthritis (ankylosing spondylitis)
o Erythema nodosum
Crohns Disease
Any part of bowel (small bowel/colon)
Lesions “skip”
Full thickness involvement
Pathology:
o Patchy full thickness inflammation
with small lymphoic aggregates
o Non-caseating granulomas
o Deep fissuring ulcers
Complications
o Obstruction
o Fistulae formation
o Peri-anal disease
o Uveitis
Colo-rectal carcinoma
 Aetiology
o Western lifestyle: low-fibre diet, smoking
o Other disease states:
 Familial adenomatous polyposis (APC)
 Hereditary non-polyposis coli (MLH1)
 Peutz-Jeghers syndrome
 IBD
 Gastrectomy
 Multiple mutations required for Adenoma → carcinoma
 Mutation →spatial reorganisation of crypts
 Proliferative element accumulated superficially
 Exposure of element to luminal carcinogens→ further mutations
 Complications
o Chronic blood loss (IDA)
o Obstruction
o Perforation
Pathology of the Nervous System
Cerebrovascular Accident/Stroke
 Sudden onset neurological deficit lasting > 24 hours
 Attributable to a vascular cause
o Infarction (80%)
o Haemorrhage (20%)
Infarction
 Aetiology
o In-Situ Thrombus
 Rare
o Thrombo-embolism
 Internal carotid artery
Haemorrhage
 Hypertension
o Charcot-Bouchard aneurysms
o Basal ganglia + thalamus
 Cerebral amyloid angiopathy (10%)




Proximal Intracerebral
artery
Left atrium (AF)
Left ventricle/valves (postMI, endocarditis)
o Age-related (not to other amyloid
disease)
o Border of white matter
AV malformation (young patients)
Head Trauma
Subarachnoid
Under arachnoid
Trauma or
ruptured Berry
aneurysm
Clinical Features
LOC → lucid period
→
deterioration
(coning) → death
Insidious onset
(alcoholics/elderly)
Headache, sensory
and/or motor Sx
Sudden onset
Headache
Meningism
Intra-cerebral
Within brain tissue
Damage to brain
substance
Compressive and
localising signs
Extra-dural
Sub-dural
Location
Outside the dura
mater
Injury
Disruption of
arteries from the
middle
meningeal artery
Between arachnoid Rupture of
and dura
bridging vein
Management
CT (lens shaped
haematoma)
Neurosurgical drainage
Inv: CT
Rx: Surgical evacuation of
haematoma
Inv: CT, cerebral
angiography
Rx: Conservate/
Surgery (clipping/
embolisation)
Surgical drainage
Traumatic Parenchymal Injury
 Concussion
o Transient LOC with recovery over days (RAS damage)
 Diffuse axonal injury
o Stretching and tearing of white matter
o Post-traumatic dementia and veg. states
 Contusion
o Haemorrhages on superficial brain surface
o Coup and contracoup
 Traumatic intracerebral haemorrhage
o Deep contusions
o Associated with diffuse axonal injury + oedema + subarachnoid haemorrhage
Cerebral Oedema
 Causes
o Idiopathic
o Generalised
 Hypoxia



Metabolic disturbance
Trauma
Hypertension



o Localised
 Haematomas
 Ischaemia
 Tumours
Mechanisms
o Acute - cytotoxicity
o Chronic - vasogenic activity
 Damaged cells swell and
 Cerebral vessel become
leak Na/K.
leaky and fluid leaves
Clinical features
o Headache (stretch of receptors around intracranial blood vessels)
o Worse in morning + on movn
o Vomiting (stimulation of centres in pons/medulla)
o Papilloedema (swelling of optic disc)
Complications
o Vascular damage
 Central retinal vein compression → papilloedema
 Haemorrhage/infarct
o Intracranial Nerve damage (III/VI)
o Obstruction to CSF flow
o Herniation
Benign Intracranial Hypertension
 Pseudotumour cerebri
 Unknown cause:
o Obese females
Brain Tumours
Gliomas
 Astrocytomas (60%)
Oligodendrogliomas
 Slow growing with calcification. --> Epilepsy
Ependymomas
 Lining of ventricles → CSF blockage.
Meningiomas
 From arachnoid cells
 Most common adjacent to sinuses
 Slow growing but incessant
Acoustic Neuroma
 Arise from Schwann cells of CN VIII
 Unilateral
 Bilateral if NF II
 Lead to
Pituitary Adenoma
 Micro vs. macro
 Lead to:
Lymphoma
 Associated with HIV/AIDS
Neuroepithelial neoplasms
 Common in kids
 Medullablastoma
 Retinoblastoma
o Headache + papilloedema
o No focal neurology

Most common. Slow initially, aggressive
with time

Lead to:
o Compression
o Skull erosion
o VIII involvement - deafness
o V/VII involvement - facial
numbness/weakness
o Hormonal abnormalities (hypo- or
hyper-)
o Bitemporal hemianopia

Non-Hodgkin B cell lymphoma


Neuroblastoma
Ganglioblastoma
Dementia
 Multiple cognitive deficits including memory impairment and
o Loss of executive function
o Aphasia (language)
o Apraxia (motor planning)
o Agnosia (recognition)
Causes
Disease
Symptoms
Other Features
Alzheimer’s Disease
Memory loss (short term)
Relentless progression
Dysphasia and Dyspraxia
5-10 year survival
Persecutory beliefs
Vascular Dementia
Personality change
Stepwise progression
Labile mood
CVA risk factors
Preserved insight
Neuro sx
Lewy Body Dementia
Fluctuating Cognition
Worsened by anti-psychotics
Visual Hallucinations
Parkinsonism
Pick’s Disease
Frontal lobe/executive function
FH
impairment
Slow progression
Preserved memory
Personality change
Huntington’s Disease
SZ-like psychosis
20-40 yrs
Depression
Strong FH
Abnormal movements
Dementia occurs later
CJD
Seizures
Often presenile
Cerebellar ataxia
Rapid onset and progression
Myoclonic jerks
Parkinsonism
Degeneration of extrapyramidal nuclei +
Lewy Bodies
Loss of dopaminergic interplay in
substantia nigra
Multiple Sclerosis
Primary progressive (rare)
Inflammatory demyelinating disease of the
Relapsing and remitting
CNS associated with dissemination in time
and place.
Pathology:
• Scattered plaques of demyelination
• Focal myelin breakdown + astrocytic
scars
MND
Progressive within 5 years
Group of degenerative disorders of motor
Bulbar
neurones
Peripheral features (UMN + LMN) Most common – Amyotrophic Lateral
Sclerosis (motor cortex +
spinal cord)
Unknown cause (glutamate receptor likely
involved + apoptosis)
Renal Pathology
Glomerulonephritis
 Inflammation of the Glomeruli

Primary
o Idiopathic

Commonly associated conditions
o Lupus
o Diabetes mellitus
o Amyloidosis
o Infections (malaria, hepatitis B,
streptococcal)

Secondary
o Other disease process
o Vasculitis (Wegner’s)
o Malignancy
o Drugs
Nephritic Syndrome
 Triad of
o Proteinuria
o Haematuria
o Fluid overload
 Urine brown/coca-cola coloured
 Causes
o IgA nephropathy (adults)
o Post-strep Glomerulonephritis (kids)
Nephrotic Syndrome
 Triad of
o Proteinuria
o Oedema
 Associated with
o Hyperlipidaemia
o Reduced immunity
 Causes
o Minimal chane disease (kids)
o Diabetic nephropathy
Pyelonephritis
 Acute
o Ascending infection
o Unwell
o Loin pain +/- urinary symptoms
Renal Stones
Types of Stones
 Calcium oxalate (75%)
o Spikey and radio-opaque
o Metabolic/idiopathic
 Magnesium ammonium phosphate (17%)
o Large, radioopaque
o May form staghorn calculus
o Proteus UTIs
o Hypoalbuminaemia
o Hypercoagulation
o Membranous GMN
o Focal segmental GMN

Chronic
o Causes renal failure (important
cause in young adults)
o Reflux nephropathy

Uric acid (5%)
o Smooth, brown, radio-lucent
o Hyperuricaemia
Cysteine (1%)
o Yellow, crystalline, semi-opaqe
o Renal tubular defects, cystinuria

Increased solute concentration
Increased urine concentration
Stasis
Hypercalciuria (gut/renal)
Hypercalcaemia + hypercalciuria
Hyperoxaluria (tea, spinach, rhubarb)
Hyperuricaemia
Cystinuria
Thiazides decreasing calcium excretion
Dehydration
Increased dietary protein
Diuretics
UTIs
Congenital tract abnormalities e.g. pelvic-ureteric junction
obstruction/horse-shoe kidney
Complications
 Ureteric coli (PU junction, pelvic brim, VU
junction)
 Hydronephrosis


Hydronephrosis + infection
Recurrence
Endocrine Pathology
The Pituitary
Structure
Anterior
Posterior
Hormones
TSH
ACTH
FSH/LH
Function
Stimulate thryoid
Stimulate adrenal cortex
Stimulates Oestrogen and
testosterone production
Stimulate anabolism
Stimulate mammary glands
Stimulates Uterine muscles and
mammary glands
Causes water retention in kidney
tubules
GH
Prolcatin
Oxytocin
ADH
Prolactinoma
 Most common
 Men and post-menopausal women
 Non-specific presentations (headache/visual disturbance)
 Galactorrhoea + menstrual disturbance
 Rx - dopamine agonists (cabergoline/bromocriptine)
GH-secreting adenoma
 2nd commonest
 Kids - Gigantism
 Adults - Acromegaly
 Systemic disease - (cardiac + diabetes)
 Facial changes
o Thick skin + lips,
o Frontal bossing
o Mandibular protrusion
ACTH-secreting adenomas




Enlargement of hands and feet
Sweating +++
Carpal Tunnel syndrome
Diagnosis - Oral GTT
o Measure GH post-ingestion
o Normal - GH suppress
o Acromegaly - no response





Rarest
Cushing’s disease
Hypokalaemia + hypernatraemia
↑ ACTH + cortisol
High dose DEXA will suppress
Hypopituitarism
 Usually partial (non-specific clinical features)
 Causes
o Adenoma
o Metastases
o Iatrogenic(surgery/irradiation)
o Head injury
o Child birth
Thyroid
Hyperthyroid
Hypothyroid
Symptoms
Anxiety, Menstrual
Abnormalities,
Exopthalmos, Goitre,
Palpitations, Atrial
Fibrillation, Pre-tibial
Myxoedema
Depression, Lethargy,
Hoarse Voice,
Bradycardia,
Constipation, Slow
reflexes, wt gain, cold
intolerance, hair loss
Causes
Graves Multinodular
Goitre, Adenoma, Postpartum Thyroiditis
Tests
↑T4
↓TSH
Management
Carbimazole
Propylthiouracil
Radioiodine Tx
Hashimoto’s, Atrophic,
Synthetic failure,
Iatrogenic
↓T4
↑TSH (primary) or
↓TSH (secondary)
Levothyroxine
Symptoms
Moon face, thin skin,
easy bruising,
centripetal obesity,
striae, buffalo hump,
proximal myopathy
Causes
Iatrogenic, Pituitary
Tumour, Ectopic
production, Adrenal
Glandular tumour
Management
↓ steroids,
Ketoconazole,
metyrapone,
Trilostane
Systemically unwell,
hyperpigmentation,
postural hypotension,
hypoglycaemia
Autoimmune, TB,
Metastatic
Tests
↓K+, ↑ACTH, Low
dose
dexamethasone
suppression test (Dx)
High dose
dexamethasone test
(cause)
Short synacthen
test,
↓ Cortisol
Adrenal Cortex
Cushing’s
Syndrome
Addison’s
Disease
Multiple Endocrine Neoplasia
MEN I
Pituitary adenoma, Parathyroid hyperplasia, Pancreatic islet tumours
MEN IIa
Shipple’s disease
Pheochromocytoma, Medullary thyroid cancer, Hyperparathyroidism
MEN IIb
Phaechromocytoma, Medullary thyroid carcinoma, Neuromas