Flashcards in Histopathology Deck (302):
Definition of closed fracture
Clean break with intact soft tissue
Definition of comminuted fracture
Splintered bone with intact soft tissue
Definition of compound fracture
Fracture site communicates with skin surface
Stages of fracture repair
1. Organisation of haematoma at # site (pro-callus)
2. Formation of fibrocartilaginous callus
3. Mineralisation of fibrocartilaginous callus
4. Remodelling of bone along weightbearing lines
Common sites for osteomyelitis in adults
Features of osteomyeltis
General: Fever, Malaise, Leucocytosis, Chills
Local: Pain, Swelling, Redness
60% positive blood cultures
X-ray: mixed picture eventually lytic.
Stages of Lyme Disease
Stage 1 - Early localised characterised by rash (90%) usually within 7-10 days and between 1 & 50cm diameter.
Often thigh, groin, axilla (earlobe in children)
Stage 2 - Early Disseminated affects many organs, musculoskeletal, heart, nervous system.
Stage 3- Late, persistent dominated by arthritis.
Clinical features of rheumatoid arthritis
+/- rheumaoid nodules
Skin manifestations of rheumatoid arthritis
Components of Felty's syndrome
Eye manifestations of rheumatoid arthritis
Lung manifestations of rheumatoid arthritis
Extra-articualr manifestations of RA
Skin manifestations: ulcers, pyoderma gangrenosum, nodules
Lung manifestations e.g. fibrosis
Eye inflammation and scleromalacia
Carpal tunnel and peripheral neuropathy
Systemic symptoms/signs: fever, malaise, fatigue, weight loss
Rheumatoid arthritis affects small joints of the hands sparing the...
Deformities seen in rheumatoid arthritis
Radial deviation of wrist
Ulnar deviation of fingers
Swan neck deformity of fingers
Boutonniere deformity of fingers
Z shaped thumb
Swollen MP and PIP joints
Dorsal subluxation of MP joints
Atrophy of small hand muscles (Valleys)
Stages (histological) in development of rheumatoid arthritis
1. Unknown antigen reaches synovial membrane
2. T cell proliferation associated with increased B cells and angiogenesis
3. Chronic inflammation and inflammatory cytokines
4. Pannus formation
5. Cartilage and bone destruction
Predominant inflammatory cell in the synovial space (in rheumatoid arthritis)
Joint most commonly affected by gout
When gout affects the big toe it is called
Causes (conditions) of pseudogout
Crystals found in pseudogout
Birefringence: Gout is... Pseudogout is...
Gout: Negatively birefringent crystals
Pseudogout: Positively birefringent crystals
First line treatment for acute gout
Potent NSAID e.g. 500mg BD naproxen
Prophylaxis of pseudogout
Low dose colchicine (BD)
Treatment of pseudogout
1 or 2 joints: Joint aspiration and intra-articular glucocorticoid (triamcinolone) injection
More than 2 joints: NSAIDs (first line) or colchicine
Prevention of gout
Acute attack: Potent NSAIDS e.g. naproxen (first line) or colchicine
Long term: allopurinol
Conservative: Reduced ETOH, and purine intake e.g. sardines, liver
Pseudogout crystal shape
Medication used for pseudogout prophylaxis
A Brodie abscess is...
A subacute osteomyelitis that has been contained to a localised area and walled off by fibrous and granulation tissue.This is termed as Brodie's abscess.
Most common causative organism in osteomyelitis
Epithelium: stratified squamous epithelium except the bottom part
Epithelial cell type in (most) of the oesophagus
What is the Z-line (oesophagus)
Columnar epithelium in the stomach, stratified squamous in the oesophagus. The transition between the 2 types is visible as a zig-zag line known as the Z-line. It is at the bottom of the oesophagus
Definition of ulceration in the GI tract
Erosion of the surface going beyond the muscularis mucosae.
What is Barrett's Oesophagus
AKA columnar lined oesophagus
Transformation of epithelial cells in the oesophagus from from stratified squamous epithelium to columnar epithelium
The columnar epithelium can be gastric type or intestinal type. Gastric type does not contain goblet cells. Intestinal type does.
Lose the sharp Z-line dividing white stratified squamous epithelium and red columnar epithelium.
In America for Barrett’s to be diagnosed the columnar epithelium must be intestinal type. In the UK this distinction is not made.
Barrett’s increased risk of cancer.
Squamous cell carcinomas produce...
How does H.pylori cause lymphoma
H. pylori induces production of MALT (Mucosal Associated Lymphoid Tissue) in the stomach. A location where MALT is not normally found. If the drive on the proliferation of this lymphoid tissue continues for too long it can cause lymphoma in the stomach.
H pylori causes adenoma of the stomach due to
Inflammation which leads to metaplasia, which becomes dysplasia, which becomes adenocarcinoma
Which type of H.pylori is associated with more chronic infection?
cag-A-positive H. pylori
It has a needle like appendage that injects toxin into intracellular junctions separating the cells. It allows the bacteria to attach and colonise more easily and potentiates damage to the epithelium. It causes more inflammation.
Helicobacter infection increases the risk of gastric cancer ...fold
H. pylori is gram...
Causes of gastritis
Drugs e.g. NSAIDs
IBD: Crohn's disease
Gastric cancer incidence high in which regions?
High incidence in Japan, Chile, Italy, China, Portugal, Russia
More common in men or women?
Most gastric cancers are which type?
Describe the 2 types of gastric adenocarcinoma
Intestinal type: well differentiated. More closely linked wit intestinal metaplasia. Large glands containing goblet cells producing mucus.
Diffuse types: poorly differentiated, single cells (signet ring cells) containing mucus, not forming glands. Linitis plastica refers to the appearance of the stomach, resembling an old leather water bottle.
Types of gastric cancer
Squamous cell carcinoma
Gastrointestinal stromal tumours (GIST): sarcoma. Mostly benign. Common enough that a significant number are malignant.
Gastric MALToma/ lymphoma usually originates from which cells?
B cells in the marginal zone of the MALT
Pathogens causing duodenal ulceration
Whipples disease: caused by tropheryma whippelii
Giardia common in which country
Antibodies found in coeliac disease
MALToma associated with coeliac disease originates from which cells?
(enteropathy associated T cell lymphoma
Coeliac disease produces which histological changes?
Flattening/atrophy of duodenal villi
Hyperplasia of duodenal crypts
Absences of ganglionic cells in myenteric plexus
Distal colon fails to dilate
Causes constipation, abdominal distension, vomiting, ‘overflow’ diarrhoea
Loss of function in RET proto-oncogene Cr10 and others...
...% of people with Hirschprung's are male
Gene associated with Hirschprung's
Treatment of Hirschprung's disease
Resection of affected part of colon (Distal)
Complete twisting of a loop of bowel at mesenteric base, around vascular pedicle
Leads to intestinal obstruction/infarction
In infants occurs in small bowel
Occurs in sigmoid colon in adults (common in elderly)
...% of diverticulae occur in the left colon
Pathogenesis of pseudomembranous colitis
Proliferation of C.diff bacteria e.g. due to antibiotic use
Production of A and B toxins by the c.diff bacteria
Inflammatory response and formation of pseudomembrane composed of inflammatory debris and white cells
Distinctive clinical features of C.diff colitis
Recent antibiotic exposure
Foul smelling stool (distinctive smell)
Treatment of C.diff colitis
Metronidazole or vancomycin
VANCOMYCIN MUST BE ORAL
Common sites for ischaemic bowel
Splenuc flexure (SMA transition to IMA)
Rectosigmoid (IMA transition to internal iliac)
Clinical features of IBD
Diarrhoea +/- blood
Peak age of Crohn's onset
Peak onset on teens/twenties
Histological features of Crohn's disease
Whole of GI tract can be affected (mouth to anus) – commonly found in the terminal ileum and the large bowel
Transmural inflammation – entire thickness of wall inflammed
Non-caseating granulomas (collections of macrophages)
Thick ‘rubber-hose’ like wall
Extra-intestinal manifestations of Crohn's disease
Peak age of onset of ulcerative colitis
Key histological features of ulcerative colitis
Involves rectum and colon in contiguous fashion.
May see mild ‘backwash ileitis’ and appendiceal involvement but small bowel and proximal GI tract not affected.
Inflammation confined to mucosa
Bowel wall normal thickness
Complications of ulcerative colitis
Adenocarcinoma (20-30 x risk)
Extra-intestinal manifestations of ulcerative colitis
Erythema nodosum, pyoderma gangrenosum
Primary Sclerosing Cholangitis (5.5% in pancolitis)
1st line drug for Crohn's maintenance treatment
Mesalazine (or other 5-ASA)
1st line drug for ulcerative colitis maintenance treatment
Mesalazine (or other 5-ASA)
Two types of lower GI adenomas
(can be a mixture of the two)
Histological features of (GI) tubular adenomas
Irregular, pseudo stratified, high nuclear to cytoplasmic ratio because they are dysplastic
Hamartomatous are seen in...
Juvenile polyps are...
Focal malformations of the mucosa and lamina propria
Usually seen in children under 5 years
Can cause bleeding
Features of Peutz Jeghers
Multiple polyps (hamartomatous)
Freckles around mouth
Increased risk of intussusception
Increased risk of malignancy: GI (including pancreas), gonad, breast
Gene affected in familial adenomatous polyposis (FAP)
Chromosome 5q21, APC tumour suppressor gene
Familial adenomatous polyposis (FAP) average:
Age of onset
Number of polyps
Familial adenomatous polyposis (FAP):
Minimum number of polyps
Mode of inheritance
Gardner syndrome is...
A variant of FAP with extra intestinal features such as:
multiple osteomas of skull & mandible
dental caries, unerrupted supernumery teeth
post-surgical mesenteric fibromatoses
Hereditary non-polyposis colorectal cancer features
Autosomal dominant mutation in DNA mismatch repair genes
Causes cancers in right colon (High frequency of carcinomas proximal to splenic flexure)
Causes few polyps
Fast progression to malignancy
Onset of colorectal cancer at an early age (under 50)
Poorly differentiated and mucinous carcinoma more frequent
Multiple synchronous cancers
Also associated with cancers of endometrium, ovary, small bowel, urinary system (including kidney)
Turcot syndrome is
Variant of Hereditary non-polyposis colorectal cancer (or FAP) also associated with brain cancers
Dukes staging of colon cancers
A = confined to wall of bowel
B = through wall of bowel (through muscularis propryia)
C = lymph node metastases
D = distant metastases
Causes of acute pancreatitis
Drugs (e.g. azathioprine, tetracycline, valproic acid, thiazide, co-trimoxazole)
Can be divided into 6 categories:
Obstruction of ducts
Poor blood supply (Shock and hypothermia)
Effect of chronic pancreatitis on calcium
First pancreatic pro-enzyme activated in pancreatitis pathophysiology
Trypsinogen to trypsin
Pancreatic enzymes released from which cells
How does gallstones cause pancreatitis
Stone lodged distal to merging of pancreatic and common bile ducts
Reflux of bile up pancreatic duct
Activation of trypsinogen to trypsin and then activation of ther pancreatic enzymes
How does alcohol (ethanol) cause pancreatitis
Alcohol leads to spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which can produce plugs which obstruct the smaller pancreatic ducts
Damage caused by release of lipases in pancreatitis
Fat necrosis: Fatty acids and glycerides bind with calcium and magnesium forming soaps seen as yellow/white foci.
Damage caused by release of elastases in pancreatitis
Damage to blood vessels and possible haemorrhagic pancreatitis
Damage caused by release of proteases in pancreatitis
Complications of acute pancreatitis
Pancreatic : pseudocyst, abscess
Gastrointestinal: UGI erosions, ileus, peritonitis
Systemic: shock, hypoglycaemia, hypocalcaemia
Pattern of injury in pancreatitis
Chronic inflammation with parenchymal fibrosis and loss of parenchyma
Duct strictures with intrapancreatic, calcified stones with secondary dilatations
Complications of chronic pancreatitis
Diabetes mellitus (it is the acini cells that are damaged not the islets of langerhans. Therefore a lot of pancreatitis is required to result in diabetes)
Carcinoma of the pancreas (?)
Pacreatic pseudocysts are lined by...
Fibrous tissue, granulation tissue, inflammatory cells
Most pancreatic carcinomas are...
Types of cystic neoplasms
Intraductal Papillary Mucinous Neoplasm (IPMN)
Risk factors for pancreatic carcinoma
Smoking - doubles the risk (25% of cases)
BMI and dietary factors e.g. meat and fat
Diabetes – doubles the risk (80% of cases)
Genetic e.g. Peutz-Jeghers syndrome (polyp with pigmentation around the buccal cavity and other areas)
Age (increases with age)
Components of the metabolic syndrome
Clinical features of acute pancreatitis
Severe epigastric pain radiating to back relieved by sitting forward.
Pancreatic intraductal neoplasia can lead to...
Mutation in which gene is commonly found in these lesions?
K-ras (95% of cases)
Macroscopic appearance of ductal carcinoma (pancreas)
Gritty and grey
Invades adjacent structures
Tumours in the head present earlier and, therefore, tend to be smaller
Microscopic appearance of ductal carcinoma
Set in fibrous stroma
Most pancreatic ductal carcinomas are in the...
Head of the pancreas
(followed by, diffuse, then body, then tail)
How and where does ductal pancreatic carcinoma spread
Direct: Bile ducts, duodenum
Lymphatic: Regional lymph nodes
2 main complications of ductal pancreatic cancer
Venous thrombosis: (they secrete mucin and once in the blood stream it activates the clotting cascade and forms thrombi in various parts of the body)
Features of cystic pancreatic tumours
Contain serous or mucin secreting epithelium (cf. ovarian tumours)
Usually benign, mucinous tumours may be malignant
Appearance of neuroendocrine tumours (islet cell)
Cells arranged in nests/trabeculae with granular cytoplas,
Clinical features of ductal carcinoma of the pancreas
Weight loss (cachexia and anorexia)
Upper abdominal and back pain (chronic, persistent and severe)
Bloods: low Hb, raised Bili, raised Ca, positive CA19.9
What is courvoiser's sign
Courvoisier's law (or Courvoisier syndrome, or Courvoisier's sign or Courvoisier-Terrier's sign) states that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones.
Usually, the term is used to describe the physical examination finding of the right-upper quadrant of the abdomen. This sign implicates possible malignancy of the gall bladder or pancreas and the swelling is unlikely due to gallstones
Pancreatic cancer tumour marker
Chemotherapy pancreatic cancer
Pancreatic neuroendocrine are usually secretory or non-secretory?
Types of secretory pancreatic endocrine tumour
Gastrinoma: Zollinger-Ellison syndrome
VIPoma: secrete vasoactive intestinal peptide and cause diarrhoea (chronic watery with expected effects) RARE
Glucagonoma: causes necrolytic migrating erythema
Tumours in MEN 2A
Tumours in MEN 2B
(also marfanoid phenotype)
Commonest type of pancreatic endocrine secretory tumour
Not likely to metastasise
What are Rokitansky-Aschoff sinuses?
Pseudodiverticulae in the gallbladder wall.
Not abnormal but associated with cholecystitis
Types pancreatic malformations
Ectopic pancreas: more common in stomach and small intestine
Pancreas divisum: failure of fusion of dorsal and ventral buds leading to increased risk of pancreatitis
Annular pancreas: second part of the duodenum is surrounded by a ring of pancreatic tissue continuous with the head of the pancreas. This portion of the pancreas can constrict the duodenum and block or impair the flow of food to the rest of the intestines. It can present with duodenal obstruction at approximately 1 year. However many cases will be asymptomatic.
Causes of increased epithelial lymphocytes in gut
Cows milk protein sensitivity
Post infective malabsorption
Causes of villous atrophy
Giardiasis (very rarely)
Nutritional deficiencies (b12 and folate, secondary to ability to synthesis new DNA)
Graft versus host disease
Microvillous inclusion disease (in children)
Common variable immunodeficiency
Complications of coeliac disease
Osteomalacia and osteoporosis
Autoimmune and other conditions associated with coeliacs disease
Dermatitis herpetiformis (prevalence = 100%)
Type 1 diabetes mellitus (prevalence = 7%)
Autoimmune thyroid disease
What is a Stereotactic biopsy?
I biopsy of an inoperable tumour.
Stereotactic neurosurgery involves mapping the brain in a three dimensional coordinate system. With the help of MRI and CT scans and 3D computer workstations, neurosurgeons are able to accurately target any area of the brain in stereotactic space (3D coordinate system). Stereotactic brain biopsy is a minimally invasive procedure that uses this technology to obtain samples of brain tissue for diagnostic purposes.
What is an open biopsy?
A biopsy of an inoperable but approachable tumour.
How to name a CNS tumour
Names derive from putative cell of origin
Grading of CNS tumours is based on...
Outcome: survival time
Grades of CNS tumour (and brief description of each)
Long-term survival / cured – Grade I
Cause death in more than 5 yrs – Grade II
Cause death within 5 yrs – Grade III
Cause death within 6 mo-1yr – Grade IV
WHO grading system for CNS tumours is only reliable for...
Diffuse astrocytomas and meningiomas
Most common type of primary CNS tumour in adults
Types of gliomas
Fibrillary, gemistocytic astrocytoma (all grades)
Oligodendroglioma (all grades)
Infiltrative gliomas: possible grades
Most aggressive form of glioma
Types of glial cells
Glial cells are non neuronal cells. They include:
In the peripheral nervous system glial cells include: Schwann cells and satellite cells.
80% of gliomas are which specific type?
Mutation of... is present in 80% of cases of diffuse astrocytomas
Features of diffuse astrocytomas
Most commonly in cerebral hemispheres but can be found elsewhere e.g. cewrebellum (10%) and brainstem (more common in children/young adults)
WHO grade 2, progressing in 5-7 years to grade 4 GBM
Most common in ages 30-40
Low vascularity but endothelial and capillary proliferation
No necrosis at core
IDH1 mutation in 80%
About ...% of glioblastomas develop from a lower grade astrocytoma
Features of an oligodendroglioma
5% of all primary brain tumours
Almost exclusively in cerebral hemispheres – frontal lobe in 50-60% of cases
WHO grade II – Anaplastic WHO grade III – difficult grading
Presents with long history of neurological signs – seizure is more frequent
Extends to grey matter
Better prognosis than astrocytomas – resection is important
80% mutation of IDH1; 75% codeletion 1p19q; usually normal p53
Features of pilocytic astrocytoma
WHO grade I
Usually 1st and 2nd decade - 20% of CNS tumours below 14 years and 15% between 14-18 years
Often cerebellar, optic-hypothalamic, brain stem
Often cystic. Always contrast enhancement
They can disseminate in the subarachnoid space (es: follow nerve roots)
Compressive margins (never diffuse infiltration)
Always show marked nuclear atypia and vascular/endothelial proliferation
Very often Rosenthal fibres (eosinophilic/pink staining) and granular bodies
Hallmark: Piloid “hairy” cell
WHO definition of a medulloblastoma
A malignant, invasive embryonal tumour of the cerebellum with preferential manifestation in children, predominantly neuronal differentiation, and an inherent tendency to metastasize via CSF pathway
Features of a medulloblastoma
Rare (0.5 per 100,000 year, in children)
75% arise in the vermis in children and hemispheric in adults
Present with cerebellar signs, cranial hypertension
WHO grade IV
Medulloblastomas present with...
Cerebellar signs, cranial hypertension
Features of meningiomas
24-30% primary intracranial tumours
Incidental in up to 10% of post-mortem
Usually adults – rare in patients younger than 40 (more aggressive)
Focal symptoms (seizure, compression)
Any site of craniospinal axis
Grading of meningiomas based on histology (and projected outcome)
Grade I – benign
Grade II (atypical) – 20% of meningiomas; 40% recurrence
Grade III (anaplastic) – 1% of meningiomas; often lethal in 1 year
What is the virchow robin space?
Why is important in CNS tumours?
It is the immunological space between an artery and vein and the pia mater. It can be expanded by leucocytes.
Psueudoinvasion of meningiomas can occur along the space.
Commonest type of CNS tumour
Tumours that most commonly metastasise to the CNS
Lung ca, melanoma, breast ca, renal ca and colon ca.
ICP is measured in mmHg and at rest, is normally...
mmHg for a supine adult
CSF is produced by...
Choroid plexus: 70-80%
Ependyma and subarachnoid vessels
Normal CSF volume is...
Types of hydrocephalus
Non-obstructive/communicating: reduced reabsorption
Obstructive/non-communicating: Actual obstruction to flow of CSF
70-80% of strokes are which type?
Embolic occlusion leading to stroke usually occurs in which vessels
Middle cerebral artery branches
Non-traumatic intraparenchymal haemorrhage most commonly occurs in...
Most common in basal ganglia
Risk factors for non-traumatic intraparenchymal haemorrhage
HTN (over 50% of bleeds)
clotting disorders, neoplasms, amyloid, vasculitis, vascular malformations
Signs/symptoms of intraparenchymal haemorrhage
Raised intracranial pressure; severe headache, vomiting, rapid loss of consciousness; focal neurology
Cerebral AVMs present with... they become symtomatic between ages of...
Haemorrhage, seizures, headache, focal neurological deficits
(the risk if bleeding is around 1% annually but rises if bleed occurs. The risk of re-bleed is around 6% annually)
What is a cavernous angioma?
Well-defined malformative lesion composed of closely packed vessels with no parenchyma interposed between vascular spaces
(so basically a cavernous space filled with vessels)
Features of a cavernous angioma
Presents after 50
Has a few feeding vessels
Bleeds at low pressure
Present with headache, seizures, focal deficits, haemorrhage (similar to an AVM)
Angiography is usually NEGATIVE unlike AVM
Treatment is surgical
Types of brain herniation
Transtentorial (uncal gyral, mesial temporal) – medial temporal lobe compressed against the free margin of the tentorium cerebelli
Subfalcine (cingulate gyrus) – cingulate gyrus displaced under the falx cerebri
Tonsillar – cerebellar tonsils through the foramen magnum, this causes brain stem compression
Cause of most sub-arachnoid haemorrhages
(In most of the 1% of people who have them they cause no problems.
Berry aneurisms tend to occur in the circle of willis at the junctions of the large vessels: most of them occur (80%) at the internal carotid artery bifurcation. The other 20% occur in the posterior circulation (vertibrobasilar circulation))
Common locations of berry aneurisms
Berry aneurisms tend to occur in the circle of willis at the junctions of the large vessels: most of them occur (80%) at the internal carotid artery bifurcation. The other 20% occur in the posterior circulation (vertibrobasilar circulation)
...% of people with berry aneurisms have multiple ones.
Risk factors for berry aneurisms
Autosomal dominant polycystic kidney disease
(ADPKD)Ehlers-Danlos syndrome (type IV)
Marfan syndrome (controversial 3)
coarctation of aorta
bicuspid aortic valve
neurofibromatosis type 1 (NF1)
hereditary haemorrhagic telangiectasia
alpha 1 antitrypsin deficiency
cerebral arteriovenous malformation: a flow related aneurysm
% of people who die within days of a berry aneurism bleed
50% die within a few days, “Warning Bleed”
Prognisis worse if rupture after a warning bleed
Components of GCS (just the responses tested)
eye response (max 4)
verbal response (max 5)
motor response (max 6)
Subdural bleeds are due to bleeding from which type of vessel?
Most extradural bleeds originate from which vessels
Unique feature of prion diseases
Proteinaceous infection only. No DNA or RNA involved.
List prion diseases found in humans
Fatal familial insomnia
Features of new varian CJD
Sporadic neuropsychiatric disorder
What is Gerstmann-Straüssler-Sheinker syndrome?
A familial version of CJD
Neuropathology of Alzheimer's disease
Extracellular plaques (protein deposition)
Neurofibrillary tangles (within neurons)
Cerebral amyloid angiopathy (CAA)
Neuronal loss (cerebral atrophy)
Key proteins in Alzheimer's disease
A-Beta peptide is part of which protein
Amyloid precursor protein
Notes: Role of APP unclear but is is physiological. The processing of the precursor protein can be amyloidogenic, in which case inact ABeta protein is released and can begin forming plaques.
Which form of tau is pathological
Hyperphosphororylated tau is the pathological form.
How is amyloid plaque formed in Alzheimer's disease
Amyloid precursor protein is processed. The processing of the precursor protein can be amyloidogenic, in which case inact ABeta protein is released. If a cell produces too much A beta it releases it, the A beta can then begin forming plaques.
Alzheimer's disease usually starts in which lobe?
Then progresses to parietal (difficulty dressing)
Then frontal (personality changes)
The occipital (difficulty recognising people)
What is Braack staging used for?
Staging of alzheimer's disease according to progression of tau pathology.
Stages 1 to 6. Disease starts in anterior hippocampus, spreads to posterior hippocampus, then temporal cortex, then occipital cortex.
Staging of Parkinson's using alpha synuclein. Stages 1-6.
Key protein in Parkinson's disease
Lewy bodies are immunopositive for this
Causes of parkinsonism
Idiopathic Parkinson’s disease
Multiple system atrophy
Progressive supranuclear palsy
Fronto-temporal neurodegenerative disorders
20 other disorders
Features of Pick's disease
Fronto-temporal atrophy (problems with decision making)
Marked gliosis and neuronal loss
Tau positive Pick bodies
Neurodegenerative diseases where Tau is a major protein
Progressive supranuclear palsy
Neurodegenerative diseases where alpha synuclein is a major protein
Multiple system atrophy (affects glial cells)
The anterior pituitary secretes
Pituitary adenomas are microadenomas if less than...
Peak age of pituitary adenoma incidence
Clinical features of growth hormone adenomas
Prepubertal children - gigantism
Adults - acromegaly
Diabetes mellitus, muscle weakness, hypertension, congestive cardiac failure
What is Sheehan’s syndrome
Hypopituitarism caused by ischaemic necrosis following PPH (pituitary enlarges during pregnancy).
Most cases of hypopituitarism caused by...
Nonsecretory pituitary adenomas – compress the other cells that do produce hormones
Clinical manifestations of anterior pituitary hypofunction
Children - growth failure (pituitary dwarfism)
Gonadotrophin deficiency - amenorrhea and infertility in women. Decreased libido and impotence in men
TSH and ACTH deficiency - hypothyroidism and hypoadrenalism
Prolactin deficiency - failure of post-partum lactation
The posterior pituitary releases...
antidiuretic hormone (ADH) and oxytocin
Role of calcitonin
promotes absorption of calcium by the skeletal system
Calcitonin is synthesised by...
Thyroid contains a population of parafollicular or ‘C’ cells that synthesize calcitonin
Non-thyroid disease associated causes of thyrotoxicosis
Struma ovarii (ovarian teratoma with ectopic thyroid)
Factitious thyrotoxicosis (exogenous thyroid intake)
Most common cause of endogenous hyperthyroidism is...
Grave's disease triad
Infiltrative ophthalmopathy with exophthalmos in up to 40%
Infiltrative dermopathy (pretibibial myxoedema) in a minority of cases
Most cases of thyroid carcinoma are...
Ionising radiation increases the risk of.... thyroid carcinomas
Histological features of papillary carcinoma
May have papillary architecture (but not all)
BUT diagnosis is based on nuclear features
Optically clear nuclei
May be psammoma bodies (calcification)
Clinical features of papillary thyroid carcinomas
Present as painless mass in neck
May present with metastasis in cervical lymph node
May present with swollen lymph nodes
10 year survival up to 90%
Peak age of thyroid carcinoma incidence:
Histological features of follicular thyroid carcinoma
May be well demarcated with minimal invasion or clearly infiltrative
Follicular thyroid carcinoma usually metastasises via bloodstream to..
Bone, liver, lungs
Histological features of medullary thyroid carcinoma
Neuroendocrine neoplasm derived from parafollicular C cells
Calcitonin produced is broken down and deposited as amyloid. Congo red dye can be used to show amyloid
Medullary thyroid cancer is associated with MEN....
Which type of thyroid carcinoma usually causes death within a year?
Parathyroid hyperplasia is associated with MEN...
Normal parathyroid gland is ...% fat
Clinical manifestations of hypoparathyroidism
Neuromuscular irritability - tingling, muscle spasms, tetany
Adrenal cortex contains.... cells
Adrenal medulla contains... cells
Cortex – epithelial cells
Medulla – neural cells
Zones of adrenal gland from outside to in
The adrenal medulla secretes
Adrenaline and noradrenaline
Zona glomerulosa (of adrenal gland) secretes
Zona fasciculata (of adrenal gland) secretes
Zona reticularis (of adrenal gland) secretes
Androgens and glucocorticoids
Most cases of Cushing's syndrome caused by
Most cases caused by administration of exogenous glucocorticoids
Effect of iatrogenic (administration of exogenous glucocorticoids) Cushing's syndrome on adrenals. Contrast with Cushing's disease
PCS – adrenals become hyper plastic (also with paraneoplastic cushings)
ICS – adrenal atropy
Most cases of primary hyperaldosteronism due to...
Bilateral adrenal hyperplasia
What is Waterhouse-Friderichson syndrome?
Adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection: Typically the pathogen is the meningococcus Neisseria meningitidis
3 Causes of acute adrenal insufficiency
Sudden withdrawal of corticosteroid therapy
Sepsis with DIC (Waterhouse-Friderichson syndrome)
Features of adrenocortical carcinomas
More commonly associated with virilizing syndrome than adenoma
Phaeochromocytoma rule of 10s
10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome
10% are bilateral
10% are malignant
In addition 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)
What is Von Hippel-Lindau (VHL) disease?
Von Hippel-Lindau (VHL) disease is an inherited disorder causing multiple tumours, both benign and malignant, in the central nervous system (CNS) and viscera. The most common tumours are retinal and CNS haemangioblastomas, renal cell carcinoma (RCC), renal cysts and phaeochromocytoma.
Tumours associated with the MEN sydromes are more or less aggressive than sporadic tumours?
Dose of ACTH in short synacthen test
Measure cortisol + ACTH at start of test
Administer 250 micrograms synthetic ACTH by IM injection.
Check cortisol at 30 and 60 minutes.
Genes associated with polycystic kidney disease
Renal failure due to PKD develops at what age?
Renal failure develops from 40-70 years
How is acute renal failure classified (what are the categories, and examples)?
Failure of perfusion
Acute tubular injury
Obstruction to urine flow
Why does acute renal tubular injury cause failure of glomerular filtration?
Blockage of tubules by casts
Leakage of fluid from tubules to interstitium reducing flow
Secondary haemodynamic changes
Glomerulonephritis sufficiently severe to cause renal failure is almost always associated with...
Glomerulonephritis presents with...
Presents with oliguria with urine casts containing red and white blood cells
Acute inflammation of glomeruli leading to reduction in glomerular filtration
Crescentic glomerulonephritis is....
Rapidly progressing glomerulonephritis. It is characterised by a progressive rapidly deteriorating in kidney function
Causes of crescentic glomerulonephritis
Immune complex: SLE, IgA nephropathy, post-infectious GN
Pauci-immune – associated with anti-neutrophil cytoplasm antibodies (ANCA)
What is pauci-immune glomerulonephritis
A type of crescentic glomerulonephritis associated with ANCAs in which only scanty deposits of immunoglobulin and complement are present in glomeruli.
The ANCA anatibodies cause neutrophil activation which leads to glomerular necrosis. The condition also involves vasculitis in other organs e.g. lungs (haemorrhage).
It is associated with causes of vascular inflammation including Wegener granulomatosis and microscopic polyangitis
Brief pathogenesis of renal thrombotic microangiopathy
Red blood cells may become damaged by fibrin leading to haemolysis – microangiopathic haemolytic anaemia
Caused by bacterial gut infection – usually E. coli
Releases toxin that targets the renal endothelium
Often associated with abnormalities of proteins that control activation of the complement pathway on endothelium
May be familial
Nephrotic syndrome involves proteinuria above...
Features of nephrotic syndrome
Breakdown of selectivity of the glomerular filtration barrier leading to massive protein leak
Proteinuria > 3.5g/day
Systemic causes of nephrotic syndrome
Local (primary glomerular disease) causes of nephrotic syndrome
Minimal change disease
Focal and segmental glomerulosclerosis
How to test for amyloid deposits (histology)
Stains with Congo red stain and looks green under polarised light (apple green birefringence)
Commonest amyloid proteins in kidney
AL (amyloid light chains) derived from Ig light chains
SAA: serum amyloid associated protein. Acute phase protein raised in certain chronic inflammatory conditions e.g. RA
80% of patients with AL (amyloid light chains) will have...
Nephrotic syndrome: Histological changes of minimal change disease:
Glomeruli look normal apart from loss of podocyte foot processes on electron microscopy
No changes on light microscopy
No immune deposits visible
Commonest cause of nephrotic syndrome in children is....
Minimal change disease
Which PRIMARY cause of nephrotic syndrome responds best to steroids...
Minimal change disease
Which PRIMARY cause of nephrotic syndrome responds least to steroids...
Membranous glomerular disease
Nephrotic syndrome: Histological changes of membranous glomerular disease
Light microscopy: Diffuse glomerular basement membrane thickening
Electron microscopy: Loss of podocyte foot processes and subepithelial deposits (spikey)
Immunofluorescence: Ig and complement in granular deposits along entire glomerular basement membrane
Nephrotic syndrome: Histological changes of focal segmental glomerularsclerosis
Electron microscopy: Loss of podocyte foot processes
Light microscopy: Focal and segmental glomerular consolidation and scarring. Hyalinosis.
Immunofluorescence: Ig and complement in scarred areas
Primary causes of membranous glomerulonephritis
Many associated with antibodies to phospholipase A2 receptor
Secondary causes of membranous glomerulonephritis
Manifestations of thin basement membranes
Hereditary defect in type IV collagen
In most cases microscopic haematuria is the only consequence
Commonest form of glomerulonephritis worldwide is...
Normal GFR is above...
Stages of chronic kidney disease. GFR in:
Stage 1: >90 (normal)
Stage 2: 60-89 (mild)
Stage 3: 30-59 (moderate)
Stage 4: 15-29 (severe)
Top 5 causes of chronic renal failure
Hypertension & Vascular disease (15%)
Reflux nephropathy (chronic pyelonephritis) (9.5%)
Polycystic kidney disease (9.4%)
List 4 malignant bone tumours
Giant cell (borderline malignancy)
Features of osteosarcoma:
Bone(s) commonly affected
X ray appearance
Malignant, mesenchymal cells, ALP positive
Elevated periosteum (Codman's triangle), Sunburst appearance
Features of chondrosarcoma
Bone(s) commonly affected
X ray appearance
Femur/ tibia/ pelvis
Lytic lesion with fluffy calcification, axial skeleton
Features of Ewing's sarcoma
Bone(s) commonly affected
X ray appearance
Genetic mutation found in most cases of Ewing's sarcoma
Translocation 11:22 (which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11)
Presentation of Ewing's sarcoma
Localized pain, swelling, and sporadic bone pain with variable intensity
Signs and symptoms of systemic inflammatory illness such as fever, anaemia and leucocytosis.
Presentation of osteosarcoma
Pain that may be worse at night
Pain in femur or immediately below the knee
Signs/symptoms of chondrosarcoma
Back or thigh pain
Malignant bone tumours more common in middle age/older people
Features of Giant cell tumour of bone
Bone(s) commonly affected
X ray appearance
20-40 years (F>M)
Osteoclast tyoe multinucleate giant cells on background of spindle/ovoid cells. Usually NOT malignant.
Lytic/lucent lesions right upto articular surface
What is osteosarcoma?
An osteosarcoma is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid
What is chondrosarcoma?
Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Resistant to chemotherapy and radiotherapy.
What is Ewing's sarcoma?
A malignant small, round, blue cell tumor. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle (collar bone)
Features of osteoid osteoma (adolescent)
Small benign bone forming lesion, night pain releived by aspirin.
Radiolucent nidus with sclerotic rim
Features of osteoma (middle age)
Head and neck
Bony outgrowths attached to normal bone
Gardners syndrome (a subtype of FAP): multiple osteomas, GI polyps, and epidermoid cysts
Radiolucent nidus with sclerotic rim
Features of osteochondroma
Adolescent (develop during skeletal growth and cease when the growth plates fuse at puberty)
Cartilage capped bony outgrowth
Hereditary multiple exostoses: multiple exostoses (bony spurs), short stature, and bone deformities.
Cartilage capped bony outgrowth
Well defined bony protuberance from bone.
What is diaphyseal aclasis?
Hereditary multiple exostoses (HME or MHE), also known as diaphyseal aclasis, is a rare medical condition in which multiple bony spurs or lumps (also known as exostoses, or osteochondromas) develop on the bones of a child. HME is synonymous with multiple hereditary exostoses and multiple osteochondromatosis
Features of enchondroma
Benign tumours of cartilage.
Ollier's syndrome: multiple enchondromas
Maffuci's syndrome: multiple enchondromas and haemangiomas
Lytic lesion, cottom wool calcification, expansile, O ring sign.
What is Ollier's syndrome?
What is Maffuci's syndrome?
Multiple enchondromas and haemangiomas
Features of fibrous dysplasia
Middle age (F>M)
A bit of bone is replaced by fibrous tissue.
Albright syndrome: polyostotic dysplasia, cafe au lait spots, precocious puberty.
Chines letters (misshapen bone trabeculae)
Soap bubble osteolysis
Shepherd's crook deformity
Features of sarcoidosis (by organ system)
Skin: Lupus pernio, erythema nodosum
CNS: Meningitis, cranial nerve lesions
Eyes: Uveitis, keratoconjunctivitis
Parotids: Bilateral enlargement
Lungs: BHL (bilateral hilar lymphadenopathy), fibrosis, lymphocytosis (CD4+ in BAL)
Liver: Hepatitis, cholestasis & cirrhosis
3 key lab features of sarcoidosis
Hypercalcaemia (due to Vit D hydroxylation by activated macrophages)
Clinical features of Kawasaki's disease
Erythema of palms & soles, desquamation
Coronary arteries may be affected (MI)
otherwise disease is self limiting
Features of polyarteritis nodosa
Polymorphs, lymphocytes, eosinophils
Arteritis is focal and sharply demarcated
Heals by fibrosis
More often renal and mesenteric arteries
Nodular appearance on angiography (small aneurysms
Polyarteritis nodosa usually happens in which arteries?
renal and mesenteric arteries
Cause of histological ‘Onion skin’appearance in scleroderma skin histology
Intimal thickening of small arteries
What is dyskaryosis
Abnormal cytologic changes of squamous epithelial cells characterized by hyperchromatic nuclei and/or irregular nuclear chromatin. May be followed by the development of a malignant neoplasm.
Cell type in the ectocervix
The ectocervix is covered with nonkeratinized stratified squamous epithelium
Precancerous changes in the ectocervix squamous cells is known as
Cervical intraepithelial neoplasia, CIN
Grades of cervical intraepithelial neoplasia
The risk of developing cancer is related to the grade of CIN. Most cases of CIN1 will go back to normal without any treatment.
CIN2 and CIN3 may develop into cancer in some cases, if left untreated
Cervical Glandular Intraepithelial Neoplasia is
Pre-cancerous change involving the inner glandular cells of the cervix.
Women of what ages are invited for cervical screening
Cervical screening is repeated every ... years
NHS cervical screening programme triage system
Low grade and borderline abnormalities have a HR-HPV test.
If HR-HPV positive – refer to colposcopy
If HR-HPV negative – routine recall
High grade abnormalities refer to colposcopy – no HR-HPV test
90% of genital warts caused by which HPV subtypes?
6 and 11
HPV subtype that cause most cervical cancers
16 and 18
Approx 70% of cervical cancers
Effect of smoking on HPV
Smoking can make clearing HPV from the body less effective and can make clearance of minor smear abnormalities slower and less efficient
General uses of fine needle aspirations (cytology)
Immediate on site evaluation
Rules out other diagnoses
Post adjuvant therapy staging
Differentiate a new primary from recurrence