Path - Sem 2

Question 1

name 4 functions of the mesangium

Answer 1

1. Structural support of glomerular capillary loops.
2. secretion of vasoactive factors and cytokines.
3. phagocytosis
4. Contraction to control glomerular cappillary blood flow

Question 2

What clinical features suggest pylonephritis rather than cystitis?

Answer 2

Cant always distinguish on clinical features. cystitis is less likely to be accompanied by loin pain (stretching of the renal capsule) and a systemic inflammatory response i.e. fever, chills, malaise etc.

Question 3

what does benign nephrosclerosis look like histologically? (4)

Answer 3

sclerosed glomeruli, patchy tubular atrophy, interstitial chronic inflammation and fibrosis, and hyalinised arterioles.

Question 4

name 3 causes of secondary glomerulonephritis

Answer 4

SLE, hep B and C, Drugs

Question 5

Current evidence suggests that the cause of cognitive decline in Alzheimer’s disease results from which one of the following?

Answer 5

Interference in synaptic transmission by monomers of Abeta protein

Question 6

What is hydrocephalus? Explain how it can develop in bacterial meningitis

Answer 6

Hydrocephalus is an increased volume of CSF. In meningitis it can be caused by the exudate itself, or, later, the scarred, organised exudate blocking arachnoid granulations, impairing CSF drainage.

Question 7

A 72-year-old man had a 6-month history of episodic loss of vision in his right eye. A bruit was heard on auscultation of his right carotid artery.
Explain how the patient’s visual symptoms are likely to be related to the disease process causing the carotid bruit

Answer 7

The cause of the carotid bruit is probably atherosclerosis. This has probably given rise to a thromboembolus or an atheroembolus that has travelled to the right retinal or opthalmic artery and temporarily occluded blood flow causing ischaemia of the retina and thus transient monocular blindness.

Question 8

Name 3 common pathologies in heart that cause emboli

Answer 8

MI (and subsequent LV aneurysm), infective endocarditis, atrial fibrillation

Question 9

how do haemosiderin-containing macrophages come about? in what pathology?

Answer 9

Macrophages phagocytose red blood cells following haemorrhage and the iron from haemoglobin is stored as haemosiderin. occurs in haemmorages

Question 10

A 62-year-old ophthalmologist presented to his general practitioner complaining of a 6 week history of increasingly severe headaches which were not relieved by over the counter analgesics. He had also noted some loss of sensation of the right upper limb, a right visual field defect and he had begun to limp. He had no prior history of migraine or other relevant past medical history.

On examination he was noted to have some impairment of language comprehension, reduced sensation on the right arm and face, a partial right homonymous hemianopia, increased tendon jerk reflexes and abnormal plantar reflex on the right.

which region is the lesion likely to be? explain each symptom? why is tumour most likely? likely diagnosis

Answer 10

Tumour in left parieto-temporal.

Loss of sensation right upper limb, reduced sensation right arm and face: left somatosensory cortex or adjacent thalamocortical fibres (parietal white matter).

Limp, increased tendon jerk reflexes and abnormal plantar reflex on the right: left corticospinal tract (internal capsule).

Impairment of language comprehension - Wernickes area (left posterior temporal cortex) and/or related white matter.

Partial right homonymous hemianopia: left optic radiation in parietal and/or temporal white matter.

Tumour most likely to be gliablastoma:
Intracerebral haemorrhages and infarctions will present with a short history of symptoms (minutes-hours), as will a subarachnoid haemorrhage (SAH). SAHs typically cause severe headache (from pressure or traction on the meninges) but they can also bleed into the brain causing focal cerebral symptoms and signs.Headache is not typically caused by stimulation or destruction (e.g. as in an intracerebral haemorrhage or infarct) of the brain tissue itself.

Question 11

In above case What is a likely cause of the headache and blurred optic disc margins?

Answer 11

The likely cause is raised intracranial pressure.

Blurred optic disc margins are suggestive of papilloedema, one cause of which is raised intracranial pressure (ICP), which may also cause headaches. The raised ICP here is caused by the space occupying nature of the tumour. Headaches are not typically caused by stimulation or destruction of cerebral tissue itself. Pain results from traction, pressure or inflammation of pain sensitive structures in the cranial cavity e.g. meningeal arteries, dura at base of brain, venous sinuses.

Question 12

what is papilloedema and its cause?

Answer 12

optic disc swelling that is caused by increased intracranial pressure.

Question 13

what would be expected histologically in the above case

Answer 13

The lesion is very cellular. The cells show marked pleomorphism, including nuclear pleomorphism, and coarse nuclear chromatin. Occasional cells show prominent nucleoli. Multinucleate tumour cells are present and there is necrosis.

Question 14

From what normal protein (full words please) in the brain does amyloid develop in Alzheimers?
Does amyloid deposit intracellularly or extracellularly?

Answer 14

In Alzheimer’s disease it is composed of A beta protein which is derived from the normal protein amyloid precursor protein (APP). extracellularly

Question 15

describe 4 histological abnormalities in Hashimoto’s

Answer 15

Germinal centres, Chronic inflammation infiltrate (lymphocytes and plasma cells), reduction in follicles, fibrosis

Question 16

describe moltinodular goitre histologically (4)

Answer 16

Follicles - large variation in size.
Fibrosis
Cholesterol Crystals
Haemosiderin Macrophages

Question 17

what causes foot ulcers in diabetics (4)?

Answer 17

recurrent trauma as the patient’s sensation is frequently poor due to peripheral neuropathy.
Healing is impaired due to poor blood flow as a result of atherosclerotic narrowing of supplying arteries and probably also diabetic microangiopathy

Question 18

what can be seen in a renal EM of a diabetic in regard to the Basement membrane? how does this related to proteinurea

Answer 18

thicker.
the thickened glomerular capillary basement membrane is believed to allow more protein to escape into the urine as a result of changes to the charge (less negative) and size of pores in the basement membrane. Remember that both plasma proteins such as albumin and the filtration membrane are negatively charged.

Question 19

describe the differences of a pancreas histologically in type 1 and 2 diabetes

Answer 19

Amyloid, a pathologic extracellular protein, is frequently seen in the pancreatic islets in type 2 diabetes mellitus. Type 1 diabetes results from immune destruction of beta islet cells in the pancreas - thus a lymphocytic infiltrate is typically seen.

Question 20

Histological features of a Grave’s thyroid (3)?

Answer 20

scalloping of colloid, lymphocytic infiltrate and tall, crowded epithelial cells

Question 21

From what is synovial fluid derived?

Answer 21

plasma fluid filtrate + lubrication (hyaluronic acid).

Question 22

What makes up the extracellular matrix of hyaline cartilage? (5)

Answer 22

Type II collagen 
hyaluronic acid produced by chondrocytes
proteoglycans such as aggrecan
glycosaminoglycans such as chondroitin sulfate
water

Question 23

What 2 main ‘tissues’ are contained within the medullary cavity?

Answer 23

Bone marrow contains variable proportions of haemopoietic tissue and adipose tissue depending on how active it is.

When adipose tissue predominates in the marrow cavity, the marrow macroscopically appears yellow (rather than red) and it is referred to as yellow marrow.

Question 24

In rheumatoid arthritis, cartilage of affected joints is destroyed and the joint surfaces can ultimately become joined by fibrous tissue and even bone. Explain how, incorporating the role of relevant cytokines and other molecules.

Answer 24

The specified terms were pannus, fibrous or fibrosis, bone or bony, and cytokine.

Cytokines produced by T cells, such as interferon gamma and IL-17, promote the production of further inflammatory cytokines, growth factors and other molecules such as IL-1, IL-6, TNF, TGF-beta and matrix metalloproteinases by synoviocytes and macrophages. Cartilage is degraded by metalloproteinases and immune mechanisms. Fibroblasts proliferate in response to TGF-beta and pannus (granulation tissue) grows into the joint, eroding the cartilage and resulting in the formation of fibrous tissue. This unites the bone ends, now devoid of cartilage, resulting in fibrous ankylosis, and the scar tissue may ultimately become ossified.

Question 25

Explain from first principles the likely pathogenesis of the fever, anaemia and elevated CRP and ESR

Answer 25

Cells involved in the inflammatory process, particularly macrophages, release cytokines such as IL-1, IL-6 and TNF.

These increase the local production of of prostaglandins in the hypothalamus which raise the body temperature set point. Mechanisms to increase heat production such as increased skeletal muscle tone and shivering and reduce heat loss via sympathetic activation causing vasoconstriction are activated, leading to an elevation in temperature.

The above cytokines also stimulate the liver to increase the production of acute phase reactants. These include fibrinogen, hepcidin, serum amyloid associated protein and C reactive protein.

Erythrocyte sedimentation rate (ESR) refers to the height of red blood cells (RBCs) in a tube at the end of an hour after they have settled as a result of gravity. In acute phase responses, fibrinogen produced in excess by the liver and immunoglobulins cause RBCs to clump together. The clumped RBCs fall faster thus the height in the tube is greater after an hour.

Question 26

Amyloid deposition may occur in patients with rheumatoid arthritis. The amyloid frequently deposits in multiple organs rather than just one. What is the name of the precursor protein of amyloid in rheumatoid arthritis and what is its origin? Name four (4) other diseases in which this type of amyloid can occur.

Answer 26

The amyloid in rheumatoid arthritis is derived from serum amyloid associated (SAA) protein, an acute phase protein produced in excess by the liver in inflammatory states. Prolonged excess occurs in chronic inflammatory disease states. Other diseases in which this type of amyloid can occur include tuberculosis, inflammatory bowel disease, bronchiectasis, chronic osteomyelitis (and in association with certain malignancies).

Question 27

Explain how and why squamous metaplasia occurs in the cervix during the reproductive years. What name is given to the region where this change occurs? Is this a physiological or pathological process? (6 marks)

Answer 27

During the reproductive years, the squamo-columnar junction is at the external os. Under the influence of oestrogens, expansion of the cervical stroma occurs, resulting in eversion of the columnar endocervical epithelium near the os out onto the ectocervix. Here it is exposed to the more hostile vaginal environment and it undergoes metaplasia to the more protective stratified squamous epithelium.

This is a normal physiological process.

The region at the external os that spans the squamo-columnar junction and area where metaplasia occurs is known as the transformation zone.

Question 28

Explain, with reasons, the pathological significance of the transformation zone (please don’t use abbreviations). What relevance does this have to taking a cervical smear?

Answer 28

The transformation zone is the region at the external os where squamous metaplasia occurs. HPV preferentially infects this metaplastic squamous epithelium. As a result of persistent HPV infection, this metaplastic squamous epithelium may become dysplastic and subsequently give rise to invasive squamous cell carcinoma.
It is thus also the region from where cervical smears should be taken such that HPV, premalignant and even malignant changes can be detected.

Question 29

Normal stratified squamous epithelium appears eosinophilic on low power. The severely dysplastic epithelium appears basophilic on low power. Why?

Answer 29

The dysplastic epithelium contains cells with much higher nuclear:cytoplasmic (N:C) ratios (i.e. relatively more nuclear material to stain with haematoxylin) than normal squamous cells. The nuclei may also be hyperchromatic.

Question 30

What is the natural history of carcinoma of the cervix?

Answer 30

The tumour invades locally into adjacent tissues such as uterus, vagina, bladder and rectum. It metastasises via lymphatics to local lymph nodes and via blood to distant sites such as liver and lung. Death may occur from extensive local invasion, from distant metastases, weight loss or pneumonia.

Question 31

describe histologcally normal cervical epithelium? compare with cancerous?

Answer 31

Normal superficial squamous cells have abundant cytoplasm with small uniform nuclei. Cells from deeper down will have a larger uniform nucleus that takes up a greater proportion of the cell (they thus have a higher N:C ratio). Dysplastic and malignant cells will typically have a larger than normal nucleus (thus a higher than normal N:C ratio) and the nucleus will generally be irregular, hyperchromatic

Question 32

The presence of endocervical cells (as well as squamous cells) in the smear indicates that it is a satisfactory smear. Why?

Answer 32

The presence of endocervical cells as well as squamous cells indicates that the smear is from the transformation zone (which is from where it should be taken), which includes the squamocolumnar junction.

A smear from further out on the ectocervix will only contain squamous cells and may not contain the metaplastic squamous cells where HPV and dysplasia typically occur

Question 33

what is a leiomyoma? where most common? describe histologically

Answer 33

benign smooth muscle lesions. common in uterus. Diagnostic features include that the lesion/s are well circumscribed, the cells show features of smooth muscle cells and the nuclei are small and uniform, with small or inconspicuous nucleoli, are not hyperchromatic, there are few/no mitoses and there is no necrosis

Question 34

What are the 3 main groups of primary neoplastic lesions of the ovary, and from which cells in the normal ovary are they believed to originate?

Answer 34

Primary ovarian neoplasms fall into one of 3 main groups: the germ cell tumours, derived from the germ cells or oocytes, tumours derived from stromal cells (sex cord -stromal tumours) and the epithelial tumours (most common) which are believed to originate from the surface mesothelium, which may undergo a metaplastic process to give rise to the epithelial tumours.

Question 35

Briefly explain the main function of the red pulp of spleen

Answer 35

remove (via macrophages) old and abnormal red blood cells and particulate matter from the blood. Store platelets

Question 36

Name and briefly explain the relevance of 5 important features of a tumour (and draining lymph nodes) to the prognosis and/or subsequent management of the patient that will be included in a pathology report.

Name 2 extra for carcinoma of breast

Answer 36

Specific tumour type: Different types have different behaviours and different risks of metastases.

Tumour grade: Reflects how quickly a tumour is likely to grow and metastasise. Higher grade = more aggressive.

Tumour size: Larger size = more likely for metastases to have already occurred

Lymphovascular invasion: If present indicates increased likelihood of metastases even if no metastases detected.

Nodal metastasis: Once metastasised cure is more difficult as can’t cure surgically - need alternative therapies to treat metastases.

Breast specific.
Oestrogen and progresterone receptors: If ER positive, tumour growth may be controlled with anti-oestrogen drugs.

Presence of HER2 amplification: If present, tumour growth may respond to herceptin.

Question 37

Mrs AS, a 56 year-old woman with rheumatoid arthritis of the small joints of the hands and also osteoarthritis of the left knee, had a 2.5cm ductal carcinoma completely excised. No metastatic tumour was found in the sentinal axillary lymph node, however, lymphovascular invasion had been identified histologically adjacent to the primary tumour. No distant metastases had been identified at the time of original diagnosis.
Ten years later she was found to have an obstructive picture on liver function tests and she died following an epileptic seizure.

If she was to have an autopsy, name and briefly describe, including the location, the macroscopic features of four (4) different pathological abnormalities that are present or are likely to be present in this patient.

Answer 37

Liver and brain metastases: Multiple pale, focally necrotic lesions with ill-defined (or well-defined) margins.

Rheumatoid arthritis: Nodules/villi of synovium +/- pale scar tissue in affected small joints of hands.

Osteoarthritis of L knee: eroded, fibrillated cartilage, bony outgrowths at edge of joint.

Rheumatoid nodules (common in rheumatoid arthritis): firm nodules over elbows

Question 38

What factors influence the timing of removal of sutures from skin?

Answer 38

Partly dependent on the vascularity of the area and mechanical stresses likely to occur in the area.

The key feature, however, is the time it takes for sufficient granulation tissue to form to hold the edges of the wound together.