CRAMMED NOTES Atrophy = reduction in the size of cells Hypertrophy = increase in the size of cells Involution = reduction in the

number of cells Hyperplasia = increase in the number of cells Metaplasia = stable change to another cell type Cigarette smoke = metaplasia of columnar to squamous in the bronchial tree Bladder calculus = metaplasia of transitional to squamous in the bladder Salivary duct stone = metaplasia of columnar to squamous Gastric acid = metaplasia of squamous to columnar in the lower oesophagus Changing PH = change from columnar to squamous in the uterine cervix Chronic trauma = change from fibrocollagenous to osseous tissue Types of necrosis Coagulative Liquefactive Caseous Fat Gangrenous Fibrinoid

Enzymes Cardiac muscle damage = CK_MB, aspartate transaminase (AST), lactate dehydrogenase (LDH) Hepatocyte damage = alanine transaminase (ALT) Biliary epithelium = alkaline phosphatase Skeletal muscle = creatine kinase (CK-MM) Exocrine pancreas = amylase

Cardinal signs of inflammation Rubor Calor Tumor Dolor

Cellular mediators in acute inflammation Histamine Prostaglandins Leukotrienes Platelet activating factor Cytokines Nitric oxide Chemokines

Plasma derived mediators Bradykinin Activated Hageman factor (clotting) Plasmin (thrombolysis) Complement components

Causes of granulomatous inflammation Tuberculosis Sarcoidosis Histoplasmosis Crohns disease Primary biliary cirrhosis Rheumatoid nodule Granuloma annulare in skin Foreign bodies

Autosomal recessive diseases Cystic fibrosis Sickle cell anaemia Thalassaemia Haemochromatosis Wilsons disease Inborn errors of metabolism (glycogenoses etc.) Trisomy 21 = Downs syndrome Trisomy 13 = Pataus syndrome Trisomy 18 = Edwards syndrome

Autosomal dominant diseases Adult polycystic kidney disease Neurofibromatosis Familial hypercholesterolaemia Polyposis coli Huntingtons disease Myotonic dystrophy

X-linked disorders Haemophilia Muscular dystrophy The ultimate attributes of a malignant tumour are the ability to invade and metastasise Staging = indicates how far a tumour has spread within the body Grading = looks at the degree of differentiation, pleomorphism and mitotic rate

Staging systems TNM (tumour, nodes, metastasis) FIGO = gynaecological malignancy Dukes = colorectal carcinoma Breslow = melanoma skin cancer

Paraneoplastic syndromes Myopathy Neuropathy Cerebellar syndrome Dermatomyositis Hypertrophic pulmonary osteoarthropathy (HPOA) Hypercalacemia = PTH-like hormone Hypertension = renin secretion Cushings syndrome = ACTH secretion SIADH = ADH secretion Polycythaemia = erythropoetin secretion Fever = pyrogen secretion

Oncogenes ras myc n-myc erb-B2

Tumour suppressor genes P53 Retinoblastoma APC

Translocations and tumours

Chronic myeloid leukaemia (CML) = t(9;22) = fusion of bcr-abl and increased tyrosine kinase activity Follicular lymphoma = t(14;18) = upregulation of bcl-2 and inhibition of apoptosis Ewings sarcoma = t(11;22) Burkitts lymphoma = t(8;14) = c-myc expression

Viruses and cancer Epstein Barr virus (EBV) = Burkitts lymphoma, nasopharyngeal carcinoma Hepatitis B virus = Hepatocellular carcinoma Human papilloma virus (HPV) = cervical and skin carcinoma Human herpes virus 8 = Kaposis sarcoma HTLV-1 = Tcell leukaemia/ lymphoma

Tumour markers Alpha fetoprotein (AFP) = germ cell tumours and hepatocellular carcinoma Human chorionic gonadotrophion (HCG) = choriocarcinoma PSA = prostatic carcinoma Placental alkaline phosphatase = germ cell tumours of the testis Carcinomembryonic antigen (CEA) = gastrointestinal tract tumours CA125 = ovarian epithelial malignancy

Hypersensitivity reactions
Type 1 = allergic IgE mediated (asthma, hay fever, anaphylaxis etc) Type 2 = antibody-mediated (Goodpastures syndrome) Type 3 = immune complex mediated (serum sickness) Type 4 = T-cell mediated/ delayed hypersensitivity (granulomas, transplant rejection, contact dermatitis)

Organ specific autoimmune disease Skin = vitiligo Thyroid = Graves and Hashimotos thyroiditis Adrenal = Addisons disease Stomach = autoimmune gastritis (pernicious anaemia) Pancreas = type 1 diabetes mellitus Neuromuscular junction = myasthenia gravis Liver = primary biliary cirrhosis

Non-organ specific autoimmune disease Systemic lupus erythematosus Systemic sclerosis Rheumatoid disease Mixed connective tissue diseases

Auto-antibodies and disease Hashimotos disease = anti-microsomal, anti-thyroglobulin Graves disease = anti-TSH receptor DM, type 1 = anti-islet cell Pernicious anaemia = anti-parietal cell, anti-intrinsic factor Autoimmune hepatitis = anti-smooth muscle Primary biliary cirrhosis = anti-mitochondrial SLE = anti-double stranded DNA Sjogrens syndrome = anti-ribonucleoprotein Rheumatoid disease = rheumatoid factor (anti-IgG) Scleroderma = anti-centromeric

Opportunistic infections? Pneumocystis carinii Cryptococcus neoformans Histoplasma capsulatum Toxoplasma gondi Atypical mycobacteria Isospora belli Cryptosporidium Fungi such as Aspergillus Cytomegaloviris Herpes simplex virus

Vitamin deficiencies A = night blindness, keratomalacia B1 (thiamine) = beriberi, Wernickes encephalopathy B2 (riboflavin) = dermatitis, keratitis, neuropathy B6 (pyridoxine) = neuropathy B12 = megaloblastic anaemia, subacute degeneration of the spinal cord Niacin = pellagra Folate = megaloblastic anaemia C = scurvy D = rickets in childhood, osteomalacia in adulthood E = spinocerebellar degeneration K= bleeding tendency

Types of emboli Thrombo-embolism Fat embolism Amniotic fluid embolism Air embolism Septic embolism Tumour embolism Risk factors for atheroma Age Sex Smoking Hypertension Hypercholesterolaemia Diabetes mellitus Family history Others- stress, personality type, exercise history

Virchows triad Abnormality of blood constituent Abnormality of blood flow Abnormality of blood vessel Aneurysms and principal sites Atherosclerotic = abdominal aorta Syphilitis = ascending aorta and arch Berry = cerebral arteries Infective (mycotic) = anywhere

Types of vasculitis Polyarteritis nodosa = multiorgan Wegeners granulomatosus = nasal, lung and kidney Churg-Strauss = lung, kidney, skin Kawasaki = skin, heart Takayasu = aortic arch and brances Giant cell = temporal arteries Buergers disease = lower limb arteries Hypersensitivity = skin, kidney Connective tissue disease = widespread Complications of myocardial infarction Early: Sudden death Cardiogenic shock Arrythmias Later: Arrythmias Rupture of ventricular wall with tamponade Rupture of papillary muscle with valve failure Rupture of septum with ventricular septal defect Mural thrombosis Deep venous thrombosis Ventricular aneurysm Recurrent infarction or angina Cardiac failure Acute pericarditis Dresslers syndrome Predisposition to infective endocarditis Abnormal valves (prosthetic, congenital, rheumatic) with bacteramia Immunosuppresion Intravenous drug-abuse

Jones criteria for rheumatic fever Major: Carditis Polyarthritis Skin rashes Sydenhams chorea Fever Minor Flitting arthropathy Arthralgia Raised ESR or CRP Prolonged PR-interval on ECG

Diagnosis of rheumatic fever 2 major or 1 major + 2 minor + raised ASO titre or positive throat culture

Clinical classification of pneumonia Community-acquired Hospital-acquired (nosocomial) In the immunocompromised host Aspiration pneumonia

Types of interstitial lung disease Idiopathic or cryptogenic alveolitis Connective tissue disease Iatrogenic - drug-induced or radiation Pneumoconiosis Extrinsic-allergic alveolitis Sarcoidosis

Causes of ARDS Major trauma Septicaemia Acute pancreatitis Major burns Inhalation of noxious substances or aspiration of gastric contents Disseminated intravascular coagulation Obstetric complications (amniotic fluid embolism)

Extrinsic allergic alveolitis = hypersensitivity pneumonitis Farmers lung = actinomyces in mouldy hay Bird fanciers lung = pigeon faeces Bagassosis = actinomyces in mouldy sugar cane

Types of bronchogenic carcinoma Small cell carcinoma Squamous cell carcinoma Adenocarcinoma (inc. bronchioloalveolar carcinoma) Large cell carcinoma

Types of pneumothorax Spontaneous Traumatic Iatrogenic

Pleural effusions Cardiac failure = transudate Hypoalbuminaemia = transudate Infection = exudate Malignancy = exudate Infarction = exudates Autoimmune disease = exudates

Types of salivary gland tumours Benign: Pleomorphic adenoma Adenolymphoma (Warthins tumour) Malignant: Adenoid cystic carcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Polymorphous low-grade carcinoma Carcinoma ex-pleomorphic adenoma

Causes of lumps in the neck Thyroid = goitre, adenoma, carcinoma Submandibular gland = tumour, sialadenitis Lymph node = reactive, infective or neoplastic Bone = mandibular or dental cyts Carotid = paraganlioma of carotid bifurcation Types of chronic gastritis Helicobacter (HLO)-associated gastritis Autoimmune chronic gastritis Reflux gastritis

Complications of peptic ulcer disease Haemorrhage Penetration Perforation Stricture formation ? Malignant change

Commoner causes of malabsorption Pancreatic insufficiency (cystic fibrosis, chronic pancreatitis) Coeliac disease Resection of ileum Parasitic infestation Crohns disease Liver disease

Less common causes of malabsorption Bacterial overgrowth in blind loops of bowel or diverticulae Tropical sprue Whipples disease Lymphangiectasia Dissacharidase deficiency a-betalipoproteinaemia

Systemic complications of inflammatory bowel disease Erythema nodosum (skin) Pyoderma gangrenosum (skin) Iritis (eye) Arthropathy of large joints Sacro-ileitis Liver disease (sclerosing cholangiits, fatty liver, fibrosis)

Inherited polyposis syndromes Familial adenomatous polyposis = adenomatous polyps of the GIT (predominantly large bowel) Gardners syndrome = inc. soft tissue tumours, fibromatosis and osteomas Turcots syndrome = inc. brain tumours Peutz-Jeughers syndrome = hamartomatous polyps of small intestine, stomach and colon and pigmented lesions around mouth

Dukes staging for colorectal carcinoma A = not through muscularis propria B = through muscularis propria but nodes uninvolved C = lymph nodes involved D = distant metastasis (e.g. liver)

Causes of a right iliac fossa mass Acute appendicitis Yersinia infection Ileocaecal actinomyces Ileocaecal TB Caecal carcinoma Carcinoid tumour Lymphoma (e.g. Burkitts)

Functions of the liver Storage of glycogen Production of lipoproteins from dietary fat Protein synthesis (albumen, globulins, acute phase reactants, clotting factors, binding proteins) Bile synthesis Storage of many substances (iron, copper, glycogen, fat-soluble vitamins) Detoxification (nitrogenous compounds, hormones, drugs)

Hepatitis viruses A = RNA virus = faeco-oral spread B = DNA virus = parenteral spread = 10% chronic infection with risk of cirrhosis and liver cancer C = RNA virus = parenteral spread = high risk of chronic disease D = RNA virus = pathogenic only if co-infected with B virus E = RNA virus = similar to A

Causes of cirrhosis Alcohol Viral hepatitis Cryptogenic (idiopathic) Autoimmune disease Primary biliary cirrhosis Chronic biliary obstruction Haemochromatosis Wilsons disease Inborn errors of metabolism (e.g. A1-antityrpsin deficiency, tyrosinaemia)

Clinical signs of cirrhosis Ascites Splenomegaly Haemorrhoids Caput medusa Oesophageal varices Jaundice Bruising Gonadal atrophy Gynaecomastia Spider naevi

Complications of gallstones Chronic cholecystitis Acute cholecystitis Biliary colic Mucoceoele Empyema Gallbladder perforation Obstructive jaundice with cholangitis Secondary biliary cirrhosis Acute pancreatitis Gallstone ileus from cholecysto-enteric fistula

Risk factors for acute pancreatitis Gallstones Alcohol Trauma Ischaemia Drugs (e.g. thiazide diuretics) Hypercalcaemia Hyperlipoproteinaemia Viral infections (e.g. mumps)

Classification of Hodgkins lymphoma -Nodular lymphocyte predominant Hodgkins (NLPH) - Classic Hodgkins Nodular sclerosis Mixed cellularity Lymphocyte rich Lymphocyte depleted

The REAL/ WHO classification system is the currently favoured system for non-Hodgkins lymphoma

Splenomegaly Portal hypertension Infection (infectious mononucleosis = EBV, malaria, leishmaniasis, tuberculosis) Malignancy (lymphoma, leukaemia, secondary carcinomas) Extramedullary haemopoiesis Storage disorders (e.g. Gauchers disease) Haemolytic anaemia Sarcoidosis Amyloidosis Feltys syndrome

Myelodysplastic syndromes (FAB system) Refractory anaemia Refractory anaemia with ring sideroblasts Refractory anaemia with excess blasts Refractory anaemia with excess blast in transformation Chronic myelomonocytic leukaemia Myeloproliferative disorders Polycythaemia rubra vera Primary thrombocythaemia Agnogenic myeloid meaplasia (myelofibrosis) Chronic myeloid leukaemia

Functional effects of pituitary adenomata Prolactinoma = menstrual disturbance, galactorrhoea and infertility in women; silent in men ACTH = Cushings disease Growth hormone = gigantism before puberty; acromegaly after puberty

Features of hyperthyroidism Heat intolerance Sweating Weight loss Palpitation and atrial fibrillation Diarrhoea Anxiety

Malignant thyroid tumours Papillary carcinoma Follicular carcinoma Medullary carcinoma Anaplastic carcinoma Lymphoma

Causes of hypercalcaemia Bone metastasis Multiple myeloma Hyperparathyroidism Ectopic PTH production Sarcoidosis Vitamin D intoxication Milk-alkali syndrome

Cushings syndrome = excess glucocorticoids Conns syndrome = excess mineralocorticoids

Nephrotic syndrome Proteinuria (heavy) Hypoalbuminaemia Oedema Hyperlipidaemia Susceptibility to infections Susceptibility to thrombosis Nephritic syndrome Oliguria Haematuria Hypertension Mild oedema Very mild proteniuria Causes of nephrotic syndrome Minimal change nephropathy Membranous nephropathy Focal segmental glomerulosclerosis Diabetes Amyloid SLE

Crescents (overgrowth of epithelial cells lining Bowmans space) in glomerulonephritis: Goodpastures syndrome Wegeners granulomatosus Microscopic polyarteritis nodosa SLE

Diabetic renal disease Diabetic glomerulosclerosis (Kimmelstiel-Wilson) Hyaline arterioloclerosis with ischaemia Atheroma of renal artery and aorta with ischaemia Increased risk of acute pyelonephritis Renal papillary necrosis

Causes of papillary necrosis Pyelonephritis Hydronephrosis Diabetes mellitus Sickle cell anaemia Analgesic abuse (e.g. phenacetin)

Predisposing factors for UTIs Diabetes mellitus Pregnancy Structural abnormalities with stasis of urine Functional abnormalities with reflux of urine Immunosupression

Bilateral hydronephrosis Prostatic outflow obstruction Bladder tumour Urethral stricture Retorperitoneal fibrosis

Unilateral hydronephrosis Tumour in renal pelvis or ureter Ureteric calculus Bladder tumour near ureteric orifice

Testicular tumours Germ cell tumours Seminomatous: -Classic seminoma -Spermatocytic seminoma Non-seminomatous: -Emryonal carcinoma -Teratoma -Chroiocarcinoma -Yolk sac tumour Mixed tumour Non-germ cell Sertoli cell Leydig cell Lymphoma Sarcoma

Prosatitism Frequency Nocturia Dysuria Poor stream Urgency Hesitancy Stangury Post-micturition dribble

HPV 16 and 18 are the best known oncogenic viruses in cervical carcinoma

CIN -Cervical intraepithelial neoplasia, grade 1 (CIN 1) = abnormal cells in lower 1/3 of squamous epithelium = equivalent to mild dyskaryosis on smear -Cervical intraepithelial neoplasia, grade 2 (CIN 2) = abnormal cells in lower 2/3 of squamous epithelium = equivalent to moderate dyskaryosis on smear -Cervical intraepithelial neoplasia, grade 3 (CIN 3) = abnormal cells in all layers of squamous epithelium = equivalent to severe dyskaryosis on smear

Pathogenesis of endometriosis Retrograde menstruation Metaplasia of peritoneal epithelium Metastatic spread of endometrium Polycystic ovarian syndrome = Stain-Levanthal syndrome

Ovarian tumours Surface epithelial Germ cell Sex-cord/ stromal Metastatic Tumours of surface epithelium Benign = simple lining Borderline (uncertain malignant potential) = proliferative lining but no invasion Malignant = invasion

Meigs syndrome = association of ovarian fibroma (benign) with ascites and pleural effusion

Breast lump Fibrocystic disease Fibroadenoma Carcinoma Inflammatory (fat necrosis, abscess, mastitis) Histology of breast carcinoma Ductal Lobular Tubular Mucinous Medullary Metaplastic

Risk factors for breast cancer Family history of breast or other tumours (e.g. ovarian) Personal history of breast cancer Inheritance of BRCA1 and BRCA2 genes Atypical hyperplasia in fibrocystic breast disease Early menarche Late menopause Nulliparity Late birth of first child (>35 yrs) ? hormone replacement therapy Dietary and geographic factors

Prognostic factors in breast cancer Tumour size and local extent Nodal spread Tumour histology Tumour grade Lymphovascular invasion Hormone receptor status Expression of genetic abnormalities (e.g. p53 or c-erb-B2/ Her-2) Raised intracranial pressure (depending on severity and speed of onset) Vomiting Headache Papilloedema Papillary abnormalities Change in the level of consciousness Bradycardia Hypertension Neurogenic pulmonary oedema

Stroke Infarction: Atheroma Thrombosis Embolism Vasospasm Haemorrhage: Intracerebral = hypertension Subarachnoid = Berry aneurysm

Extradural haematoma = arterial bleeding = skull fracture = middle meningeal artery Subdural haematoma = venous bleeding = cortical bridging veins = elderly patients

Bacterial meningitis Neonates = E.coli, Listeria, Steptococci Children/ adolescents = meningococcus, Haemophilus influenzae Adults = Pneumococcus Neurodegenerative diseases
Motor neurone disease = most commonly amyotrophic lateral sclerosis = loss of anterior horn cells Parkinsons disease = loss of neurones from substantia nigra and locus ceruleus Huntingtons disease = atrophy of the putamen and caudate nucleus Alzheimers disease = generalised atrophy with severe temporal lobe changes Picks disease = frontal lobe dementia Lewy body dementia = overlap of Alzheimers and Parkinsons features with neuronal inclusions (Lewy bodies) Friedrichs ataxia = spinocerebellar and corticospinal tract degeneration

Phacamatoses
Neurofibromatosis, type 1 = neurofibromas, caf-au-lait spots, risk of malignant nerve tumours Neurofibromatosis, type 2 = bilateral schwannomas of eight cranial nerve (acoustic neuromas) Tuberous sclerosus = epilepsy, mental retardation, angiofibromas of skin and retinal hamartomas, angiomyolipomas of kidney and liver VonHippel-Lindau syndrome = haemangioblastomas of brian and spinal cord, renal cell carcinoma, phaeochromocytoma

Blisters in the skin Sunburn Urticaria Infections (e.g. herpes simplex or staphylococcal) Friction Bulllous pemphigoid Dermatitis herpetifomis Pemphigus

Malignant skin tumours Basal cell carcinoma Squamous cell carcinoma Malignant melanoma Osteoporosis = decrease in bone mass Osteomalacia = decrease in mineralisation of bone

Pathological fracture Osteoporosis Osteomalacia Malignant disease, primary or metastatic Pagets disease Inherited conditions e.g. osteogenesis imperfecta Seronegative arthritides Ankylosing spondylitis Reactive arthritis Reiters syndrome Psoriatic arthropathy Enteropathic arthropathy Type 1 diabetes Childhood/ adolescence onset Thin Keto-acidosis common Severe insulin deficiency Islet-cell antibodies Autoimmune mechanism HLA-linkage

Type 2 diabetes Middle-age/ elderly onset Obese Keto-acidosis rare Insulin end-organ resistance No auto-antibodies No autoimmune mechanism Polygenic inheritance

Amyloidosis Plasma cell dyscrasias = AL amyloid Chronic inflammation = AA amyloid Dialysis = beta-2 microglobulin Medullary carcinoma = calcitonin Alzheimers disease = AB4 protein Senile cardiac amyloid = transthyretin (prealbumin) Islet-cell amyloid = amylin