Patho revision

• Causes (aetiology) of disease


  • Cancer
  • Inflammation
  • Infection
  • Congenital disorders
  • Degenerative disorders
  • Iatrogenic disorders
  • Metabolic Disorders
  • Autoimmune Disorders
  • Trauma
  • Genetic disorders
• Tumors of the reproductive system

  • Malignant
  • Benign
• Benign tumors


  • Uterine Fibroids
  • Benign Prostatic hypertrophy
• Breast Cancer aetiology


  • Major cause of death in women
  • (10% of all cancers worldwide)
  • Incidence continues to increase after age of 20
  • Strong genetic predisposition
  • Identification of specific genes related to cancer
  • Hormones also a factor
  • Specifically exposure to high estrogen levels
  • Role of exogenous estrogen (birth control pills, supplements) still controversial
• Breast Cancer


  • Normal cells divide when needed and stop
  • Cancerous cells have mutations in their genes that destroy is ability to stop dividing
  • Signal transduction pathways primarily affected are P13K/AKT and RAS/MEK/ERK
  • Genes affected include p53, PTEN, BRCA1 and BRCA2
  • Cause for the mutations: ? Environmental factors, genetic predisposition, high oestrogen exposure
• Carcinoma of the Breast: Pathophysiology

  • Malignant cells spread at early state
  • First to close lymph nodes (Axillary nodes)
  • In most cases, several nodes infected at time of diagnosis
  • Metastasizes quickly to lungs, brain, bone, liver
  • Tumor cells graded on basis of degree of differentiation or anaplasia
  • Tumor then staged based on size of primary tumor, # lymph nodes, presence of metastases (TNM classification)
  • Presence of estrogen and progesterone receptors is a major factor in determining how to treat the pt's cancer
• Breast Cancer—Signs and Symptoms

  • Initial sign is single, hard, painless nodule
  • Mass is freely movable in early stage
  • Becomes fixed
  • Advanced signs: Fixed nodule, Dimpling of skin, Discharge from nipple, Change in breast contour
  • Biopsy confirms diagnosis of malignancy
• Receptor status


  • Oestrogen
  • Progesterone
  • HER2
• Receptor status


  Breast cancer cells can be characterised by the presence or absence of three cell surface receptors
• Breast Cancer: Treatment


  • Surgery
  • Chemo and radiation
  • Removal of hormone stimulation
• Breast Cancer: Treatment


  • Lumpectomy is preferred; removal of tumor
  • Mastectomy is sometimes necessary
  • Some lymph nodes removed as well, # removed depends on the spread of the tumor cells
  • Impairs draining of lymph; swelling and stiffness of arm common
  • For hormone responsive cancers, removal of hormone stimulation: Premenopausal women - ovaries removed, Postmenopausal women - hormone-blocking agent
  • ER(+) have good prognosis, HER(+) have poor prognosis but respond well to treatment with monoclonal antibodies trastuzumab in conjunction with chemotherapy
• Benign Prostatic Hypertrophy (BPH)—Pathophysiology


  • Common in older men, varies from mild to severe
  • Change is actually hyperplasia of prostate
  • Nodules form around urethra
  • Result of imbalance between estrogen and testosterone
  • No connection with prostate cancer
  • Incomplete emptying of bladder leads to infections
  • Continued obstruction leads to distended bladder, dilated ureters, renal damage
  • If significant, surgery required
• Prostate Cancer is common in men older than 50 and ranks high as cause of cancer death
• Prostate Cancer—Pathophysiology


  • Most are adenocarcinomas from tissue near surface of gland
  • BPH arises from center of gland
  • Many are androgen dependent
  • Tumors vary in degree of cellular differentiation, the more undifferentiated the more aggressive and the faster they grow and spread
  • Metastasis to bone occurs early (Spine, pelvis, ribs, femur)
  • Cancer has typically spread before diagnosis
• Prostate Cancer: Incidence and Etiology

  • Cause not determined, but genetic, environmental, hormonal factors play a role
  • Common in North American and northern Europe
  • Incidence higher in black population than white
  • Genetic factor?
  • Testosterone receptors found on cancer cells
• Prostate Cancer—Diagnostic Tests


  • 2 helpful serum biomarkers: Prostate-specific Antigen (PSA) is a useful screening tool for early detection, and Prostatic acid phosphatase is elevated when metastatic cancer present
  • Ultrasound and biopsy confirms diagnosis
• Prostate Cancer—Treatment


  • Surgery and radiation, but risk of impotence or incontinence
  • When tumor androgen sensitive: orchidectomy (removal of testes) or Antitestosterone drug therapy
  • 5 yr survival rate is 85-90%
• Cervical Cancer—Etiology


  • Strongly linked to STDs, specifically Human papillomavirus (HPV) and Herpes simplex virus type 2 (HSV-2)
  • Virus exerts direct effects on host cell or may cause antibody reaction
  • Increased antibodies have been associated with increasing dysplasia
  • High risk factors include multiple sex partners, promiscuous partners, sexual intercourse in early teen years, pt history of STDs
  • Environmental factors such as smoking can predispose women
• Prevention and screening


  1. HPV Vaccination for 12-13 yr olds

  2. Routine PAP smears for women age 26-64 yrs
• PAP smear


  Papanicolaou stain is a mutichromatic staining technique commonly used in cytopathology
• Cervical Cancer—Pathophysiology


  • Staging: Normal, Mild Dysplasia, Carcinoma in situ, Invasive carcinoma
  • Local direct spread, Distant metastasis
• Cervical Cancer—Signs and Symptoms

  • Asymptomatic in early stage, can be detected by Pap test
  • Invasive stage indicated by irregular vaginal bleeding or spotting
  • Anemia and wt loss can accompany
  • Lower abdominal pain, Fatigue, loss of appetite
• Cervical Cancer—Treatment


  • Biopsy to confirm diagnosis
  • Surgery and radiation to treat
  • 5 yr survival rate 100% if carcinoma still in situ
  • Prognosis for invasive depends on the extent of the spread of cancer cells
• PID—Etiology


  • Arise from sexually transmitted diseases like Gonorrhea and Chlamydiosis
  • Prior episodes of vaginitis or cervicitis precedes development
  • Can also result from IUD or other contaminated instrument that can perforate wall and lead to inflammation and infection
  • Long-term concerns: infertility, high risk of ectopic pregnancy
• PID—Signs and Symptoms


  • Lower abdominal pain (1st indication), Sudden and severe or gradually increasing in intensity
  • Tenderness during pelvic exams
  • Purulent discharge at cervix
  • Dysuria, Fever and leukocytosis can occur
  • Depends on causative organism
• PID—Treatment


  • Aggressive antibiotics like Cefoxitin and doxycycline
  • Recurrent infections common
  • Sex partners should be treated as well
  • Follow-up appt to ensure eradication
• Renal Pathophysiology by Niroshini Nirmalan, Senior Lecturer in Biomedical Sciences, University of Salford, UK.
• The Renal system


  • Kidneys (Urine formation)
  • Ureters
  • Bladder
  • Urethra (Urine collection, storage and excretion)
• Functional Unit of the Kidney is the NEPHRON

  • Glomerulus
  • Proximal Tubule
  • Loop of Henle
  • Distal Tubule
  • Collecting Duct
• Functions of the Kidney

  • Regulation of water and electrolyte balance and pH
  • Removal of waste from blood and excretion of urine
  • Secretion of hormones: Renin, Erythropoietin, Vitamin D3
• Polycystic Kidney Disease (PKD)


  • Multiple fluid filled cysts in the kidney
  • Most forms inherited (commonly autosomal dominant)
  • May lead to renal failure (5th, 6th decade of life)
• Signs and symptoms of PKD

  • Abdominal mass
  • Hypertension
  • Haematuria (blood in urine)
  • Urinary tract infections
  • Backache
  • Commonly detected in utero (ultrasound)
• Pathophysiology of PKD


  • Mutations in genes encoding proteins polycystin 1 and polcystin 2
  • Defects in cilia mediated signalling activity
  • Often bilateral involvement of the kidneys
  • Cysts may occur in other organs (liver, brain)
• Treatment of PKD


  • Mild forms managed with dietary changes
  • More severe forms will require dialysis or transplant
• Wilms' Tumour (Nephroblastoma)


  • Most common primary malignant renal tumour of childhood (peak age 3y)
  • Accounts for about 6% of all paediatric malignant disease
  • First described by German Surgeon Max Wilms
• Signs and symptoms of Wilms' Tumour

  • Abdominal mass (very common)
  • Blood in urine (haematuria)
  • Hypertension
  • Fever and abdominal pain
• Chronic Renal Failure


  • Progressive, irreversible nephron loss
  • Usually due to chronic kidney disease
  • Common causes are Diabetes and hypertension
  • 75% of the kidney function can be lost before its noticed
• Chronic renal failure (CRF)

  • GFR <60 mL/min/1.73 m2 for 3 months irrespective of the presence or absence of kidney damage
  • Normal GFR is ~100-130 mL/min/1.73m2, value is adjusted to body surface area
• Chronic Renal Failure: Causes

  • Diabetes
  • Hypertension
  • Glomerulonephritis
  • HIV
  • Polycystic kidney disease
  • Kidney infections & obstructions
  • Drugs
• Recognizing Clues of Chronic Renal Failure

  • Protein in urine
  • Elevated biochemistry results: Creatinine, Urea, Potassium, Mg
  • Anaemia from decreased RBC production, shortened RBC survival (lack of erythropoietin)
  • Serum Calcium decreases