Pathology Flashcards
Common complications of diabetes?
Angina, MI, Peripheral vascular disease
Kidney failure
Skin infections
Cataracts
Neuropathy
What is non-enzymatic glycosylation?
Glucose combining with AAs and proteins without the need for enzymes
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
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
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
Three main molecular pathways for pathology in diabetes?
Glycated proteins
Polyol pathway disruption
Activation of protein kinase C
Two types of angiopathy in diabetes?
Microangiopathy - Leaky, and thicker basement membranes, in capillaries, arterioles and venules
Macroangiopathy - Atheroma
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
What organ is particularly affected by diabetic microangiopathy?
The kidney, thickening of the glomerulus
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
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
What is dysplasia?
The stage where cells show neoplastic characteristics but are contained within the basement membrane and are not yet invasive
Histological features of dysplasia/neoplasia?
Hyperchromatic - darker nuclei than usual
Irregular and varying in size and shape
Nuclear/cytoplasmic ratio is increased
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
4 most common pathological gynaecological diagnoses?
Endometriosis
Fibroids
Endometrial cancer
Cervical cancer
What is endometriosis?
The presence of endometrial glands or stroma in abnormal locations outside the uterus
What does endometriosis cause?
Infertility
dysmenorrhoea
dyspareunia (pain after intercourse)
Pelvic pain
Treatment options for endometriosis?
Progestagens
GnRH analogues
Laser ablation
What is a fibroid?
Leiomyoma (benign smooth muscle tumour)
Most commonly found in myometrium
Symptoms in fibroids?
Abnormal bleeding
Compression of the bladder
Fibroid risks?
Increased risk of:
- Miscarriage
- Fetal malpresentation
- Uterine malcontractions
- Postpartum haemorrhage
Fibroid (leiomyomata) treatments?
Surgery
Hormonal manipulation
Arterial embolisation
The two pathogenetic groups leading to endometrial cancer?
1: Background prolonged oestrogen stimulation related to obesity and anovulatory cycles
2: Poorly differentiated, older age
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
