Increased risk of: - Miscarriage - Fetal malpresentation - Uterine malcontractions - Postpartum haemorrhage

Pathology Flashcards by leo Olney

Common complications of diabetes?

Angina, MI, Peripheral vascular disease

Kidney failure

Skin infections

Cataracts

Neuropathy

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What is non-enzymatic glycosylation?

Glucose combining with AAs and proteins without the need for enzymes

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Examples of how glycated proteins can cause pathology?

Glycated collagen and ECM traps LDL

Glycated cell-surface receptors affects their function e.g. activation of inflammatory cells

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What does polyol pathway disruption cause, and what is it?

It is when hyperglycaemia causes influx of glucose to the inside of the cell, metabolised to sorbitol and fructose

These increase osmotic pressure cause cellular swelling and accumulation of pro-inflammatory cytokines

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What does activation of protein kinase C in diabetes lead to?

Production of VEGF

Production of pro-inflammatory cytokines

Increase in endothelin-1 and decrease in NO

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Three main molecular pathways for pathology in diabetes?

Glycated proteins

Polyol pathway disruption

Activation of protein kinase C

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Two types of angiopathy in diabetes?

Microangiopathy - Leaky, and thicker basement membranes, in capillaries, arterioles and venules

Macroangiopathy - Atheroma

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Three reasons atheroma production is accelerated in diabetic patients?

Glycation of ECM in arterial walls traps LDL

Infalmmation causes damage to endothelium due to increased cytokines and vasoconstriction

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What organ is particularly affected by diabetic microangiopathy?

The kidney, thickening of the glomerulus

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Three eye conditions that are more likely to occur in diabetics?

Cataract - due to sorbitol production

Glaucoma - growth of abnormal vessels

Diabetic retinopathy - microangiopathy causes haemorrhages in retinal vessels

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What is the multistep hypothesis of carcinogenesis?

That carcinoma cells are clones of one single cell that accumulates a series of genetic alterations causing it to become cancerous

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What is dysplasia?

The stage where cells show neoplastic characteristics but are contained within the basement membrane and are not yet invasive

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Histological features of dysplasia/neoplasia?

Hyperchromatic - darker nuclei than usual

Irregular and varying in size and shape

Nuclear/cytoplasmic ratio is increased

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Stages of the adenoma-carcinoma sequence in the colon?

1: The aberrant crypt focus - loss of tumour suppressant APC
2: Low-grade dysplasia - Mutated KRAS (proto-oncogene) causes increased proliferation

Adenomas: benign polyps form

3: High-garde dysplasia - the polyp generates more gene abnormalities and undergoes more abnormal growth, still benign
4: Cancer

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4 most common pathological gynaecological diagnoses?

Endometriosis

Fibroids

Endometrial cancer

Cervical cancer

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What is endometriosis?

The presence of endometrial glands or stroma in abnormal locations outside the uterus

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What does endometriosis cause?

Infertility

dysmenorrhoea

dyspareunia (pain after intercourse)

Pelvic pain

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Treatment options for endometriosis?

Progestagens

GnRH analogues

Laser ablation

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What is a fibroid?

Leiomyoma (benign smooth muscle tumour)

Most commonly found in myometrium

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Symptoms in fibroids?

Abnormal bleeding

Compression of the bladder

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Fibroid risks?

Increased risk of:

Miscarriage
Fetal malpresentation
Uterine malcontractions
Postpartum haemorrhage

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Fibroid (leiomyomata) treatments?

Surgery

Hormonal manipulation

Arterial embolisation

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The two pathogenetic groups leading to endometrial cancer?

1: Background prolonged oestrogen stimulation related to obesity and anovulatory cycles
2: Poorly differentiated, older age

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Most common histological type of endometrial cancer?

60% - endometrial adenocarcinoma

Good prognosis

Where are samples taken from in cervical screening?

Transformation zone

How is HPV associated with cervical cancer?

Infection present in 99.7% of invasive cancers

What is a medullary carcinoma?

A carcinoma of calcitonin secreting cells

Process of amyloid formation/deposition?

Abnormal proteolysis of a protein causes it to take on a beta-pleated sheet structure, it is insoluble in this form and is deposited.

What are carcinoids?

Endocrine tumour with neurosecretory granules in their cytoplasm

Main defining features of small-cell carcinoma?

Very aggressive, normally in lung

Three main ways a pituitary tumour can present?

Compress and destroy surrounding tissue causing pituitary insufficiency Secrete active hormone Compression effects of adjacent structures e.g. compression of optic chiasm causing bitemporal hemianopsia

What effect does dopamine have on prolactin secretion?

Suppresses it

Symptoms of excess prolactin?

Amenorrhoea breast lactation

What are islet cell neoplasms?

Benign or malignant neoplasms of the pancreas secrete active hormones

Two types of germ cell tumours?

Seminoma (>30) and non-seminomatous

Markers of germ cell tumours?

Non-seminomatous: - alpha-fetoprotein - βHCG Seminomatous: - PLAP

Germ cell tumour prognosis?

Chemoradiosensitive, cure is likely

What are leydig cell tumours' features?

Often secrete androgens Can occur at any age Can secrete oestrogen (causing gynaecomastia)

Key marker for prostate tumour?

PSA - prostate specific antigen

Management of prostate cancer

Surgery Radiotherapy Hormonal manipulation: - Orchidectomy - gonadorelin analogues (to suppress LH) - anti-androgens

Three main criteria for prognostic factors for neoplasia, and examples within them?

Tumour itself: size/histological type Host: Age of host/presence of other conditions/Compliance with therapy Environment: Availability of treatment, expertise of caregiver

Meanings of T and N and M in TNM tumour classification?

T - local spread of tumour N - Involvement of regional lymph nodes M - Distant metastases

What are co-morbidities?

Other diseases that a patient may have

4 classifications of diabetic retinopathy?

Pre-proliferative Proliferative - New vessels growing Maculopathy - Macular oedema Advanced diabetic eye disease - Neovascular glaucoma - Traction detachments of new blood vessels become fibrosed and pull on the retina

3 Main causes of retinopathy?

Leakage Occlusion New blood vessel growth

Key features of diabetic retinopathy seen down an opthalmoscope?

Haemorrhages Hard exudate Cotton wool spots - cloudy swelling of retina, sign of vascular insufficiency to nerve fibre resulting in hold up of axoplasmic flow Vessel changes: - Venous beading - dilated veins with beaded, uneven edges, venous loops

Steps in treating a diabetic foot infection?

Resuscitation Antibiotics Surgery Optimise arterial flow Control swelling Off-load

Initial causes of a diabetic foot infection?

Skin defect e.g. minor trauma, tinea pedis Sensory neuropathy

What to check in a diabetic foot examination?

Look for: swelling/colour/hair growth Feel for: Dorsalis pedis pulse/posterior tibial pulse/temperature gradient Capillary refill Check for: areas of redness/wasting/fixed deformities

Theories explaining the pathology of ageing?

Loss of homeostasis causing cell injury/death Genetic theories: Gene regulation dysfunction and somatic mutations Cellular theories: Free-radicals/oxidative stress

What is the epitope of the antigen?

the specific region of the antigen that reacts with variable region of the antibody

What are hybridoma cells?

B-lymphocytes that are secreting a specific antibody that have been fused with malignant tumour cells so that enough antibody can be produced indefinitely

What does monoclonal mean?

Derived from a single cell

How does the test strip of a pregnancy test produce it's colour change in a positive reaction? What lab technique is this an example of?

At the bottom there is an antibody against hCG, bound to the bottom hCG binds to this antigen There is another antibody against hCG with an enzyme attached which then reacts with a dye molecule that then turns pink ELISA

Difference in immunohistochemistry and ELISA?

In immunohistochemistry the molecule we are testing for is on the slide and the followed by a primar and secondary antibody and dye, there is no 'sandwich' effect

What part of the cell is the oestrogen receptor located in?

The nucleus

What is carcinoma in situ (CIN)?

Carcinoma that is not malignant but has neoplastic changes, can reverse itself or go on to become malignant

Two most common types of cervical carcinoma?

Squamous cell carcinoma and adenocarcinoma