Blood • How much blood do you have? • What is in it? • What is serum?
Haematopoiesis • Where does it occur? • Flow chart • Erythropoesis
Structure of Haemoglobin • Structure • Types (and when you get them)
Thalassaemia • α-Thalassaemia • β-Thalassaemia • Major • Minor
Sickle Cell Anaemia • What is it • Who gets it • When can it be a good thing
Reading a FBC • Hb • PCV • RCC • MCV • MCH • MCHC • RDW • WBC • Platelets • ESR • Reticulocytes
Anaemia • Types • Classifications • Signs and symps
Iron Physiology • Mad pic from last year • Absorption (haem and non haem) • Storage in the body • Causes of deficiency • Iron Studies
More ? • Blood groups • Rhesus • Transfusion reactions
Definitions and Examples • Hyperplasia • Hypertrophy • Atrophy • Metaplasia • Dysplasia • Anaplasia • Aplasia • Hypoplasia • Hamartoma • Heterotopia • Neoplasia
Cancer • Excessive & unregulated cell proliferation • Non lethal genetic damage / multi-hit hypothesis • Loss of cell cycle regulatory function / checkpoints (MMR and tumour suppresor genes) • Gain of oncogenes which drive proliferation • Anaplasia / lack of differentiation: loss of the structural and functional differentiation of the normal cell type • Potential for invasion or metastasis
Robbins seven steps of malignancy • Self-sufficiency in growth signals: Tumors have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation. • Insensitivity to growth-inhibitory signals: Tumors may not respond to molecules that are inhibitory to the proliferation of normal cells such as transforming growth factor-β (TGF-β), and direct inhibitors of cyclin-dependent kinases. • Evasion of apoptosis: Tumors may be resistant to programmed cell death, as a consequence of inactivation of p53 or other changes. • Defects in DNA repair: Tumors may fail to repair DNA damage caused by carcinogens or unregulated cellular proliferation. • Limitless replicative potential: Tumor cells have unrestricted proliferative capacity, associated with maintenance of telomere length and function. • Sustained angiogenesis: Tumors are not able to grow without formation of a vascular supply, which is induced by various factors, the most important being vascular endothelial growth factor (VEGF). • Ability to invade and metastasize: Tumor metastases are the cause of the vast majority of cancer deaths and depend on processes that are intrinsic to the cell or are initiated by signals from the tissue environment.
Benign vs Malignant • Features from history • Clinical Features • Gross Features • Microscopic Features • What tissue is adenoma from? Benign or malignant? • What is carcinoma from? • What is sarcoma from?
Grading and Staging • Grading • Microscopic/pathological assessment. Degree of differentiation, mitoses etc and other features mentioned before. “How aggressive” • Staging • The extent of the disease. Path, radiological and clinical information. TNM system or named systems. • TNM: T 0-4, N 0-3, M 0 or 1 • Named: Dukes, Clark’s,
Clinical Effects of Tumours • General effects / consitutionalSx • Malaise, lethargy, WL, fevers, night sweat etc • Local effects • Compression/obstruction, ulceration/haemorrhage, rupture/perforation, infarction • Paraneoplastic • Endocrine, hypercalcaemia, clubbing and HPOA, neuropathy, skin rashes
Prostate • Prostate zones vs lobes • Which zone does most BPH originate in? • Which zone does most Ca originate in? • What is the middle (median) lobe between? • Top or bottom? • Where is the base of the prostate? • Where is the apex of the prostate?
Bladder outflow obstruction 1 • Name some other causes of bladder outflow obstruction, other than BPH and prostate Ca? • Bladder tumours or fibrosis, urethral strictures, obstruction by FB or stones, congenital narrowing of the urethra, congenital urethral valves, neuromuscular dysfunction, drugs (anticholinergics, sympathomimetics). • List some symptoms of BOO • Increased frequency, nocturia, hesitancy, poor stream, terminal dribbling, urgency & urge incontinence, UTI due to chronic retention • What is urge incontinence? • Involuntary leakage of urine accompanied by, or immediately preceded by, urgency (ie a sudden uncontrollable impulse to evacuate).
Bladder outflow obstruction 2 • What is the cut-off for nocturia? i.e. how many times per night? • Van Dijk et al (2002) at least twice per night, ICS definition (2002) is the complaint that the individual has to wake at night one or more times to void. • What is the incidence of BPH? • ↑ with age. Histological evidence in 20% by 40yo, 70% by 60yo and 90% by 70yo, but only 50% with histo evidence show clinically detectable prostatic enlargement (and only 50% of these report clinical symptoms). • What is innervation of the detrusor muscle? • S2-4 parasympathetic innervation via the pelvic plexus.
BPH • What is the pathological mechanism involved in BPH? • Stromal-epithelial interactions stromal cells produce 5α-reductase (which converts testosterone to DHT), which acts in an autocrine fashion on other stromal cells; or in a paracrine fashion on epithelial cellsproliferation • What treatment options are available for BPH? • Medical therapy (alpha1 receptor antagonists, 5alpha reductase inhibitors, GnRH agonists) and surgical therapy (TURP, TUIP, prostatectomy). • Why do patients with BPH experience hesistancy? • Greater resistance for the detrusor to overcome, and the detrusor may be weakened. Can also be an impairment of dilation of the bladder neck.
PSA • What is PSA? • A glycoprotein / serine protease produced by non-malignant and malignant epithelial cells of the prostate. Prostate specific but not disease specific. • In what conditions is it raised? • Prostate cancer, prostatitis, prostate infarction, perineal trauma and BPH. • What else can cause a rise in PSA? • Prostate biopsy can increase PSA levels up to tenfold for 8-10 weeks. UTI. Ejaculation (can increase for 6-48hrs). Prostatic massage can, but reportedly negligible (UpToDate states leads to transient elevations of only 0.26 to 0.4 ng/mL, and PSA can be measured immediately after DRE)
PSA screening • For a cut-off of 4.0 ng/mL • sensitivity was 21 % for detecting any prostate cancer and 51 percent for detecting high-grade cancers. • specificitywas 91 % • PPV is ~30 % increases to 42 to 64 percent for PSA levels >10 ng/mL ng/mL. • NPV of 85%