Labmed - Histopathology 6

Front 1

Draw the layers of the meninges

Back 1

Front 2

What is the epidural space and where is it located.

Back 2

Space between the dura mater and the bone.

In the brain: potential space (dura touches skull)

In the spinal cord: anatomical space

Front 3

What intracranial haemorrhage can cause this morphology?

Back 3

Chronic subdural haemorrhage since there is no midline shift

Front 4

Describe the pathology

Back 4

Subfalcine herniation

Front 5

A patient suffers significant trauma to the right side of the head and is found to be paralysed on the right side (ipsilateral hemiplegia). What is the likely course of action?

Back 5

Acute trauma ⇒ Acutely increased ICP ⇒ Kernohan's notch (compression of the contralateral midbrain cerebral peduncle containing CoST)

Front 6

What is the pathology:

A. Subdural haemorrhage

B. Extradural haemorrhage

C. Infarction

Back 6

Infarction because the underlying structure is still visible

Front 7

Glasgow Coma Scale

Back 7

Eye opening: 1-4

Verbal: 1-5

Motor response: 1-6

Min: 3/15

Max: 15/15

Front 8

What part of the brain needs to be lesioned to cause structural coma?

Back 8

A. Reticular activating system (floor of 4th ventricle, peri-acqueductal grey and posterior thalamus)

B. Severe damage to both hemispheres

Front 9

What is the pathology?

Back 9

Burst lobe: contusion extending to subdural space

Front 10

What distinguishes contusion from laceration?

Back 10

Pia-arachnoid membranes are torn over the site of injury in laceration

Front 11

Histology of diffuse axonal injury

Back 11

Swollen axons and axonal retraction bulbs due to shearing forces

Front 12

Diagnosis of diffuse axonal injury

Back 12

Histology ⇒ Swollen axons and axonal retraction bulbs due to shearing forces

Front 13

Two complications of diffuse axonal injury

Back 13

Loss of consciousness

Risk of diffuse brain swelling

Front 14

Patient presents with progressive decline in GCS. He had undergone head injury while playing cricket and lost consciousness at that time but then awoke and felt relatively normal for a couple of hours. Likely diagnosis? How should the pt be managed? Possible complication?

Back 14

Extradural haematoma

= Epidural haemorrhage

Emergency evacuation of the haematoma

Complication: Herniation

Front 15

Pathophysiology of extradural haematoma

Back 15

Arterial rupture (typically: middle meningeal artery)

Front 16

What blood vessels cause haemorrhage in:

Extradural haemorrhage (EDH)

Subdural haemorrhage (SDH)

Back 16

EDH: Arterial rupture (typically: middle meningeal artery)

Acute SDH: Venous sinus rupture or small bridging veins rupture

Chronic SDH: Small bridging veins rupture

Front 17

Presentation of acute SDH

Back 17

Rapid onset of raised ICP

Front 18

Presentation of chronic SDH

Back 18

Personality change, memory loss ➙ No midline shift

Front 19

Management of subdural haemorrhage (SDH)

Back 19

Acute (blood is clotted): Invasive emergency evacuation

Chronic (blood is liquid): Burr hole evacuation

Front 20

Name the three types of cerebral oedema and their pathophysiology

Back 20

Vasogenic

Damage to the BBB

Cytotoxic

Influx of cations and water into cells due to membrane damage or energy depletion (ion pumps fail)

Interstitial

Damage to ependymal lining in hydrocephalus or osmotic imbalance

Front 21

Back 21

1 - Transtentorial herniation (= uncal herniation)

2 - Central herniation

3 - Subfalcine herniation

4 - Transcalvarial herniation

5 - Upward herniation

6 - Tonsillar herniation (= transforaminal herniation)

Front 22

One specific complication pertaining to bone injuries

Back 22

Fat embolism

Front 23

Diagnosis of brain death (and differential)

Back 23

Positive diagnosis of structural lesion

Coma

Loss of brainstem reflexes

No spontaneous respiration

Differential: Hypothermia, drug intoxication, metabolic/endocrine dysfunction

Front 24

What is the most likely cause of stroke among the following? Justify your answer.

A. Atherosclerosis in the circle of Willis

B. Atheroembolism from the origin of the internal carotid artery

C. Atherosclerosis of the external carotid artery

D. Haemorrhage of a major artery due to hypertension

E. DVT-derived embolism

F. Paradoxical cardiac embolus

G. Mural thrombus in the heart secondary to MI

Back 24

A, B, D, F and G all can all cause a stroke theoretically.

B, D, F, G are most common and B is the most common.

A. Can cause stroke but typically there is some functional reserve due to redundancy

B. Most likely

C. External carotid only supplies blood to the face and neck. Furthermore these are large arteries are unlikely to be obstructed by atherosclerosis.

D. Haemorrhagic stroke is 9x less likely than ischaemic stroke

E. Embolus from DVT could not travel to the brain except in paradoxical embolus

F. Can cause stroke but is less likely

G. Can cause stroke but is less likely

Front 25

Commonest site for infarction

Back 25

Territory of middle cerebral artery (or some of its branches)

Front 26

Likely cause

Back 26

Ischaemic stroke of MCA

Front 27

Likely cause

Back 27

Haemorrhagic stroke of the basal ganglia that has ruptured into the ventricles

Front 28

Three risk factors for stroke

Back 28

Diabetes, smoking, hypertension

(Hypertension is #1 for haemorrhagic stroke)

Front 29

Post mortem brain histology reveals eosinophilic (red) neurons. Name a possible diagnosis. Is it possible to be the cause of death?

Back 29

Ischaemic stroke 1-4/7 ago ⇒ Possible

Front 30

Post mortem brain histology reveals a cyst formed surrounded by gliosis and small number of persistent foamy Mϕ. Name a possible diagnosis. Is it possible to be the cause of death?

Back 30

Old ischaemic stroke 1/12-12/12 ago ⇒ Probably not the cause of death

Front 31

What do people die of in ischaemic stroke?

Back 31

Acute: Brain swelling (mostly oedema) ➙ Downward pressure ➙ Brain stem compression

Later: Complications (pneumonia, pulmonary emboli)

Front 32

Histological presentation of ischaemic stroke

Back 32

0-24h – Oedema (early)

1d-4d – Eosinophilic (red) neurons

5-12d – Endothelial proliferation and neovascularisation

5-30d – Nϕ infiltration and microglial activation

8-14d – Foamy Mϕ infiltration, gliosis

>50d – Cyst formed surrounded by gliosis and small number of persistent foamy Mϕ

Front 33

What are lacunar infarcts

Back 33

Atheroma at the base of small penetrating vessels ⇒ Small infarcts in deep GM/WM very common in elderly

Front 34

What are watershed infarcts

Back 34

Global hypoperfusion or hypoxia ⇒ Bilateral infarcts at junctions between arterial territories

Front 35

What is the pathophysiology of venous infarction? What is the two principal aetiologies and how do they present macroscopically?

Back 35

Front 36

Most common site of haemorrhagic stroke

Back 36

Basal ganglia/Internal capsule (b.c. large high flow vessels directly give rise to small ones)

Front 37

Pathogenesis of haemorrhagic stroke (most commonly)

Back 37

A. Hypertension ⇒ Charcot-Bouchard microaneurysms in small blood vessels ⇒ Rupture

B. Rupture of berry aneurysm

Front 38

Likely diagnosis?

Back 38

Subdural haemorrhage

Compression of the brain but no infiltration in sucli and fissures and banana-shaped

Front 39

Likely diagnosis?

Back 39

Subdural haemorrhage

Compression of the brain but no infiltration in sucli and fissures and banana shaped

Front 40

Likely diagnosis?

Back 40

Subdural and extradural haemorrhage

Compression of the brain but no infiltration in sucli and fissures and banana shaped (right) and lemon shaped (left)

Front 41

Likely diagnosis?

Back 41

Extradural haemorrhage

Compression of the brain but no infiltration in sulci and fissures and lemon shaped

Front 42

Likely diagnosis?

Back 42

Subarachnoid haemorrhage

No compression of the brain but infiltration of blood in sulci, fissures and brainstem

Front 43

Likely diagnosis?

Back 43

Subarachnoid haemorrhage

No compression of the brain but infiltration of blood in sulci, fissures and brainstem

Front 44

Two congenital causes of hydrocephalus

Back 44

Cerebral aqueduct stenosis

Cerebral aqueduct atresia

Front 45

Three mechanisms of acquired hydrocephalus

Back 45

CSF obstruction: SOL

CSF reabsorption ➘: Infection or haemorrhage

CSF production ➚: choroid plexus papilloma

Front 46

Paient suffers from headache, blurred vision and drop-attacks. What is the likely diagnosis? What other sign would you look for to support the diagnosis? What is a possible complication? How will you treat it?

Back 46

Hydrocephalus

Supported by papilloedema and increased head circumference

Complication: herniation

Treatment:

Ventriculo-peritoneal shunt

Endoscopic ventriculostomy (hole for drainage)

Front 47

Most common brain tumour in adults and infants

Back 47

Infants: Medullobastoma

Adults: Glioblastoma

Front 48

Treatment for gliobastoma, medulloblastoma and meningioma. Are they curable?

Back 48

Glioblastoma - Radio + Chemo (no surgery) ➙ Not curable

Medulloblastoma - Surgery + Radio + Chemo ➙ Long term remission

Meningioma - Surgery ➙ Curable

Front 49

Cells of origin of gliobastoma, medulloblastoma and meningioma.

Back 49

Glioblastoma - Astrocytes

Medulloblastoma - Immature or embryonal cells

Meningioma - Arachnoid “cap” cells of meninges (i.e. cells of the arachnoid granulations)

Front 50

Most likely site of gliobastoma, medulloblastoma and meningioma.

Back 50

Glioblastoma - Hemispheres

Medulliobastoma - Vermis (cerebellum)

Meningioma - Anywhere

Front 51

How do the following tumours propagate: gliobastoma, medulloblastoma and meningioma?

Back 51

Glioblastoma - Follows WM pathways

Medulloblastoma - Spreads via CSF

Meningioma - Usually don't propagate

Front 52

Histological presentation of gliobastoma, medulloblastoma and meningioma.

Back 52

Glioblastoma

Atypical, mitotically active, infiltrating astrocytes

Aggregation of Aϕ around a necrotic centre (palisading necrosis)

Medulloblastoma

Resembles neuroblasts with hyperchromatic nuclei and little cytoplasm

Cells are densely packed and may form rosettes

Meningioma

Lobules of meningothelial cells with concentric whorls that are called psammoma bodies when calcified

Front 53

What brain tumour typically presents as rosettes on histology

Back 53

Medulloblastoma

Front 54

What brain tumour typically presents as palisading necrosis on histology

Back 54

Glioblastoma

Front 55

What brain tumour typically shows whorls on histology

Back 55

Meningioma

Front 56

Name two tumours of the peripheral nerve sheath

Back 56

Neurofibroma

Schwannoma

Front 57

How do neurofibroma and schwannoma differ (3)?

Back 57

Neurofibroma

Contains Schwann cells and fibroblasts

Infiltrate parent nerve/Non-encapsulated

Part of Neurofibromatosis Type 1

Schwannoma

Contains Schwann cells only

Compresses parent nerve without infiltrating/Encapsulated

Part of Neurofibromatosis Type 2

Front 58

Pattern of inheritance of neurofibromatosis

Back 58

Autosomal dominance

Front 59

Name 3 tumours that are part of neurofibromatosis type 1 and 3 for type 2

Back 59

Type 1

Neurofibroma

Glioma (esp. optic nerve astrocytoma)

Phaeochromocytoma

Café au lait spots

Type 2

Bilateral vestibular schwannoma

Peripheral Schwannoma

Meningioma

Front 60

How can brain swelling be diagnosed in vivo and postmortem?

Back 60

Flattened gyri (on MRI or brain slices)

Front 61

What type of tumour mostly metastasise to the brain and how do they metastasise?

Back 61

Carcinomas are the most common tumour type to metastasise to the brain, but lymphoma can also do so. Metastatic deposits are blood-borne

Front 62

Confirmation of malignant meningitis

Back 62

CSF cytology

Front 63

What is butterfly glioma

Back 63

Spread of a glioblastoma through the corpus callosum

Front 64

Relation between glioma and astrocytoma and glioblastoma

Back 64

Glioma: Tumour of glial cells

Astrocytoma: Tumour of the astrocytes

Glioblastoma: Grade 4 astrocytoma

⇒ Gliobastoma is an astrocytoma that is a glioma

Front 65

Why can there be haemorrhage in the presence of glioblastoma of the temporal lobes? What is the outcome?

Back 65

Tumour in temporal lobe ⇒ Transtentorial herniation ⇒ Haemorrhage in the brainstem (Duret’s haemorrhage) ⇒ Death

Front 66

True or false: the grade of a brain tumour is the best factor to predict prognosis

Back 66

False, its location and size are more important

Front 67

Tumours in the cerebellopontine angle causing hearing loss. On imaging, tumour appears benign. What is it likely to be? Significance of the presence of this tumour bilaterally?

Back 67

Vestibular schwannoma

Bilateral ⇒ Likely from neurofibromatosis type 2

Front 68

Name one cause of stroke that is not due to the occlusion of an artery nor an haemorrhage. What are its aetiologies (4)?

Back 68

Venous infarction (esp. sagittal sinus thrombosis)

Aetiologies: Infection, pregnancy, hypercoagulable state, trauma

Front 69

Name one artery that, if rupture, may cause extradural haemorrhage

Back 69

Middle meningeal artery (it runs between the dura and the skull)

Front 70

What type of haemorrhage does a berry aneurysm cause?

Back 70

Subarachnoid haemmorhge

Front 71

Diagnosis?

Back 71

Ruptured berry aneurysms ⇒ SAH

Front 72

Back 72

Hydrocephalus

Front 73

What is gliosis?

Back 73

The process of scar tissue formation by astrocytes (the scar is not made of fibrous tissue as elsewhere in the body but by glial tissue)

Front 74

What is the disease?

Back 74

MS (plaques of grey areas in the white matter, esp. around ventricles)

Front 75

LP reveals oligoclonal bands of immunoglobulin in CSF. Name a likely diagnosis?

Back 75

MS

Front 76

3 clinical hallmarks of Parkinson's disease

Back 76

Resting tremor

Bradykinesia

Rigidity

Front 77

Pathogenesis of Parkinson's disease

Back 77

Degeneration of dopaminergic pigmented cells of substantia nigra

Front 78

Macroscopic appearance of PD

Back 78

Pallor of substantia nigra

Front 79

Microscopic appearance of PD

Back 79

Lewy bodies: Accumulation of α-synuclein inside nerve cells

Front 80

Post-mortem histology of base of brain shows accumulation of α-synuclein inside nerve cells. Likely diagnosis?

Back 80

PD

Front 81

Two treatment of PD

Back 81

L-Dopa

DBS

Front 82

Three clinical hallmarks of Huntington's disease

Back 82

Chorea

Psychiatric symptoms

Dementia

Front 83

Pattern of inheritance of Huntington's disease

Back 83

Autosomal dominant with anticipation

Front 84

Pathogenesis of Huntington's disease

Back 84

Toxic gain of function of mutated huntingtin gene ➙ Degeneration of cortico-striatal loops

Front 85

Macroscopic appearance of Huntington's disease

Back 85

Atrophy of head of caudate nucleus and cerebral cortex

Front 86

Microscopic appearance of Huntington's disease

Back 86

Aggregation of polyglutamine-containing fragments of huntingtin in nuclei and neurites of neurons

Front 87

Histology reveals aggregation of polyglutamine-containing fragments of huntingtin in nuclei and neurites of neurons. Diagnosis?

Back 87

Huntington's

Front 88

Clinical presentation if Alzheimer's disease

Back 88

Dementia (early: short term memory impairment, late: dysphasia and apraxia)

Front 89

Mutation of amyloid precursor protein is a risk factor to what neurological disease

Back 89

Alzheimer's

Front 90

Mutation of ApoE with presence of ε4 is a risk factor of what neurological disease

Back 90

Alzheimer's (positive risk factor)

Front 91

Mutation of ApoE with presence of ε2 is a risk factor of what neurological disease

Back 91

Alzheimer's (negative risk factor)

Front 92

Down’s syndrome is a risk factor for what neurological disease

Back 92

Alzheimer's

Front 93

What lobes are particularly affected in Alzheimer’s disease

Back 93

Medial temporal atrophy followed by neocortical atrophy

Front 94

What striking feature of Alzheimer's disease is visible on MRI?

Back 94

Hydrocephalus (compensatory for medial temporal atrophy and neocortical atrophy)

Front 95

Histology reveals extracellular deposition of β-A4 peptide in cortical plaques. Likely diagnosis?

Back 95

Alzheimer's

Front 96

Histology reveals extracellular deposition of β-A4 peptide in vessels. Likely diagnosis?

Back 96

Alzheimer's

Front 97

Histology reveals intracellular deposition of protein tau as neurofibrillary tangles. Likely diagnosis?

Back 97

Alzheimer's

Front 98

Treatment for Alzheimer's disease

Back 98

Cholinesterase inhibitors to soothe symptoms

Front 99

Macroscopic appearance of Alzheimer's disease

Back 99

Medial temporal atrophy followed by neocortical atrophy and compensatory hydrocephalus

Front 100

Clinical presentation of CJD

Back 100

Very variable but classically, rapidly progressive dementia

Front 101

What neurological disease can be acquired with mad cow disease

Back 101

Bovine spongiform encephalopathy (BSE) ➙ CJD

Front 102

Genetic test in patient is positive for Polymorphism of PRNP codon 129. What is the patient at risk of?

Back 102

CJD

(PRNP stands for PRioN Protein)

Front 103

Pathogenesis of CJD

Back 103

Prion protein (normal) becomes a prion (abnormal) and that prion causes other prion proteins in the body to because prion themselvesIn CJD, the prion protein is PrPC, whereas the prion is PrPSc.

Front 104

3 aetiologies of CJD

Back 104

Sporadic

Inherited

Acquired (e.g. mad cow)

Front 105

Microscopic appearance of CJD

Back 105

Triad: Spongiosis, neuronal loss, gliosis

Front 106

What test would you do to definitely diagnose CJD

Back 106

Check for deposition of PrPSc is diagnosis

Front 107

Deposition of PrPSc detected on histology of synapses. Diagnosis?

Back 107

CJD

Front 108

A patient has a genetic test for a research study and is found to have two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). What should you tell him and his family?

Back 108

Nothing, this is normal. Everyone has two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). Patients with HD have a mutated version of that gene.

Front 109

Significance of left pronator drift

Back 109

Focal pathology on the right

Front 110

Sudden onset of severe thunderclap headache is the presentation of what haemorrhage?

Back 110

Spontaneous subarachnoid haemorrhage

Front 111

Clinical presentation of intracerebral haemorrhage

Back 111

Sudden onset focal neurological deficit (stroke) ± collapse

Front 112

Three contraindications (officially, i.e. for the exam) to LP without prior CT

Back 112

New focal neurological signs

Reduced level of consciousness

Papilloedema (a relatively late sign of raised intracranial pressure)

Front 113

3 complications of SAH secondary to aneurysm

Back 113

Re-bleeding of the aneurysm

Hydrocephalus

Vasospasm

Front 114

Patient with SAH secondary to aneurysm rupture has deteriorating GCS score. Why can it be and what is the first investigation to confirm the diagnosis?

Back 114

Any complication of SAH (re-bleeding, hydrocephalus, vasospasm) can be the cause. Rebleeding and hydrocephalus would both be detected on CT.

Front 115

"Worst headache ever" is typically a sign of which haemorrhage?

Back 115

SAH

Front 116

Why would you monitor U&E in patients with any acute intracranial pathology?

Back 116

Risk of SIADH

Front 117

What collagen forms the bone matrix

Back 117

Type 1

Front 118

Effect of oestrogen on bone metabolism. Consequence for menopause and hypogonadism

Back 118

Oestrogen reduce bone resorption, increase bone formation

⇒ Menopause and hypogonadism are RF for osteoporosis

Front 119

4 endocrine diseases that may cause osteoporosis

Back 119

Hyperparathyroidism

Hyperthyroidism (increase metabolic rate of bone replacement)

Hypogonadism (⇒ oestrogen ➘ ⇒ bone reabsorption ➚ and bone formation ➘)

Cushing's (⇒ Cortisol ➚ ⇒ Calcium release from bone ➚)

Front 120

Two non-modifiable risk factors and two lifetime risk factors of osteoporosis

Back 120

Female >50

Smoking, alcohol

Front 121

Definition of osteoporosis

Back 121

Bone mineral density < µ - 2.5σ

Front 122

Define rickets and osteomalacia

Back 122

Rickets Failure to mineralise new bone at growth plates (children)

Osteomalacia Failure to mineralise new bone (adults)

Front 123

Most likely aetiology of rickets and osteomalacia. What other broad aetiology exists? How are they distinguished?

Back 123

Vitamin D deficiency

Phosphate deficiency (e.g. Fanconi's syndrome, X-linked hypophosphataemic rickets)

In phosphate deficiency, Vit D ➚

Front 124

3 S&S of rickets and osteomalacia

Back 124

Bone pain

Muscle weakness

Multiple bone deformities

Fractures

Short stature

Front 125

How are CaPO4ALPPTHVitamin D in:

Osteoporosis

Piget's

Ricket's

Osteomalacia

Hypophophataemic rckets

Renal osteodystrophy

Primary hyperparathyroidism

Familial hypocalciuric hypercalcaemia

Malignant hypercalcaemia

Back 125

Front 126

What is Fanconi’s syndrome?

Back 126

Disease of the PCT in which glucose, AA, uric acid, PO4 and HCO3 are passed into the urine, instead of being reabsorbed.

Front 127

How are Paget's disease and osteoporosis differentiated?

Back 127

Paget's: Bone deformity

Osteoporosis: Bone hypodensity

Front 128

Common sites of Paget's

Back 128

Pelvis

Vertebrae

Skull

Tibia

Front 129

Deafness with raised ALP is a flag for what disease?

Back 129

Paget's

Front 130

You suspect Paget's in one of your pt based on symptoms and raised ALP. What is the first line of investigation?

Back 130

Plain XR

Front 131

Pathogenesis of renal osteodystophy

Back 131

Chronic renal disease ⇒ Excretion of PO4 ➘ and Vitamin D is not activated ⇒ Hyperphosphataemia and Hypocalcaemia ⇒ Hyperparathyroidism ⇒ Bone reabsorption by osteoclasts ⇒ Osteodystrophy

Front 132

One complication of treatment of renal osteodystophy

Back 132

Adynamic bone disease: Vit D ➚ ⇒ PTH suppression ⇒ Chronic suppression of bone turnover