Analyse causes, iatrogenic factors, pathogenesis, morphology and complications of important O&G diseases.

Predisposition, Cause, Pathogenesis, Morphology and Complication

Before any disease, start with one fact: cells have only a small number of ways to respond to injury, and tissues have only a small number of ways to react. Pathology is not an endless list of conditions. It is a short repertoire of cellular and tissue responses, recombined in different organs by different causes. Once you hold that repertoire in your head, every O&G disease becomes a variation on the same handful of mechanisms. That is the whole point of this chapter, and it is why a strong pathology answer moves in a chain:

predisposing factor -> cause -> pathogenesis -> morphology -> clinical feature -> complication.

This chain prevents list-learning. Obesity is not merely "associated with" endometrial cancer. Obesity increases peripheral aromatisation and insulin resistance, which increases unopposed oestrogenic and growth-factor stimulation of endometrium, causing glandular hyperplasia and sometimes atypia; the morphology produces abnormal uterine bleeding and carries malignant potential. That is an exam-ready answer because each link explains the next.

The Cell's Limited Repertoire of Responses

Everything downstream rests on this foundation, so build it first. A cell exposed to an insult — hypoxia (too little oxygen), ischaemia (too little blood supply), mechanical trauma, toxins, infection, an immune reaction or a metabolic derangement — has only three possible fates:

1. Adapt and recover fully if the insult is mild and brief (reversible injury).
2. Survive but stay damaged, with ongoing impaired function.
3. Die, if the insult is severe or sustained.

That short list is the entire vocabulary of cell injury. The same insult can produce any of the three outcomes depending on its dose, its duration and the reserve of the host — which is exactly why the same organism causes self-limiting cervicitis in one woman and necrotising sepsis in another.

When cells do die, they die in one of two patterns, and the distinction matters because they look different, mean different things and behave differently clinically.

This single contrast explains a great deal of O&G. Apoptosis sculpts normal development (it regresses the paramesonephric or mesonephric ducts during sexual differentiation and prunes the trophoblast as the placenta matures), so it is not a disease. Necrosis — placental infarction, a degenerating fibroid, devitalised decidua after birth — always announces real tissue death and always recruits inflammation. When you see necrosis on a report, ask what cut off the blood or oxygen supply.

How Tissues Respond: Inflammation and Repair

Cells die one at a time or in sheets; tissues answer injury with one of three stereotyped programmes. Master these three and you can reconstruct most O&G pathology from first principles.

Acute inflammation is the immediate, stereotyped response to injury. Its five classical signs — redness, heat, swelling, pain and loss of function — all flow from two vascular changes: local vasodilatation (more blood, hence redness and heat) and increased vascular permeability (fluid leaks into tissue, hence swelling and pressure). Chemical mediators — histamine, prostaglandins, leukotrienes, bradykinin, complement and a large family of cytokines — recruit cells. The first responder is the neutrophil; the macrophage follows and supervises resolution. Acute inflammation of the fetal membranes is chorioamnionitis; of the endometrium, endometritis; of the tube, acute salpingitis. Same programme, different address.

Tissue repair and wound healing begins as acute inflammation settles. There are two routes. Regeneration restores the original tissue by proliferating cells of the same type. Repair by scarring lays down new connective tissue when the original cannot regenerate. A surgical wound with closely apposed edges heals by first intention: a clot forms, epidermis migrates across it, and fibroblasts and new vessels build granulation tissue that remodels with minimal scar. A gaping wound heals by secondary intention: far more granulation tissue forms, and myofibroblasts contract the defect while scar replaces the loss. The quality of healing depends on blood supply, infection, foreign material, movement and host metabolic state — which is why a diabetic, anaemic or HIV-affected caesarean wound heals badly. Defective healing gives dehiscence (too little union) at one extreme and keloid/hypertrophic scar (too much) at the other. Key mediators include transforming growth factor beta and epidermal growth factor.

Chronic inflammation is healing and inflammation happening at the same time rather than one after the other — either because a low-grade stimulus persists, or because the process is chronic from the outset. Histologically it is dominated by mononuclear cells (lymphocytes, plasma cells, macrophages) with fibroblast proliferation and fibrosis. A specific variant, granulomatous inflammation, is organised collections of epithelioid macrophages walling off something the body cannot digest — tuberculous infection, a foreign body, retained suture. (Granulomatous inflammation and granulation tissue are completely different things despite the similar name; do not confuse them.) Chronic pelvic inflammation is why PID leaves adhesions and tubal scarring long after the acute infection clears, and granulomatous inflammation is the reason genital TB matters in the South African setting.

Disorders of Growth: Adaptation Versus Neoplasia

The same logic of a small repertoire applies to growth. When a tissue is asked to do more, do less, or change, it has a defined set of adaptive moves — and a few of those moves are the first step on the road to cancer. Each can be physiological (normal, reversible, stimulus-driven) or pathological; the word tells you the structural change, not whether it is benign.

Read down the table and the cancer pathway falls out: a chronic stimulus drives hyperplasia, the epithelium may undergo metaplasia, atypia accumulates as dysplasia (still confined above an intact basement membrane), and unchecked clonal growth becomes neoplasia. Cervical disease is the cleanest worked example — squamous metaplasia in the transformation zone, then CIN/dysplasia, then invasive carcinoma once the basement membrane is breached.

A neoplasm is autonomous new growth; a tumour is simply a mass (so not every tumour is a neoplasm — a haematoma or an abscess is a mass but not a neoplasm). Neoplasms are benign (localised, non-invasive, non-metastasising, well differentiated) or malignant (locally invasive through the basement membrane, able to metastasise), and primary (arising at that site) or secondary (metastatic). The naming convention encodes the behaviour: the suffix -oma usually marks a benign tumour (leiomyoma), -sarcoma a malignant mesenchymal tumour (leiomyosarcoma), carcinoma a malignant epithelial tumour. Malignancy is diagnosed histologically on architectural loss (disordered tissue, basement-membrane destruction, invasion) and cytological atypia (abnormal nuclear size and shape, abnormal mitoses, a high nuclear-to-cytoplasmic ratio). At the molecular root, almost all malignancy comes down to two events: activation of oncogenes or loss of function of tumour-suppressor genes. Hold onto that — it is exactly what high-risk HPV exploits in the cervix.