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What are the immunological mechanisms behind type I, II, III and IV hypersensitivity reactions?

Give some examples of type I, II, III and IV hypersensitivity reactions.

Outline some treatment strategies for allergies.

Name some major causes of anaphylaxis.

Type I anaphylaxis, allergies, asthma Type II transfusion reaction, autoimmune haemolytic anaemia, goodpasture syndrome Type III SLE, glomerulonephritis Type IV contact dermatitis, multiple sclerosis, Diabetes mellitus type 1, rheumatoid arthritis, IBD, tuberculosis

Type 1 IgE ! mast cell activation ! release of mediators (histamine, leukotrienes, prostaglandins, PAF, cytokines) ! inflammatory cell recruitment Type 2 binding of allergen to antibody (IgG / IgM) ! phagocytosis / lysis of target cell by complement, leukocyte recruitment Type 3 Antigen:antibody complexes ! complement activation ! leukocyte recruitment Type 4 T cell activation ! cytokine release ! inflammation and macrophage activation, T-cell mediated toxicity

Foods peanuts, tree nuts, eggs, strawberries Drugs penicillin, sulphonamines, local anaesthetics, salicylates Stinging insects bees, wasps, ants Blood products Latex healthcare workers / occupational Radiocontrast media Idiopathic

Allergen avoidance house cleaning, food education, changing habits related to pets Long-acting antihistamines Corticosteroid sprays Cytokine / enzyme inhibitors IL-4, IL-5, IL-13, lipooxygenase

List some clinical features of anaphylaxis.

Outline the three (major) types of shock.

Describe the classes of shock and their clinical features.

Define the terms macule, papule, patch, plaque, nodule, pustule scale, vesicle and bulla.

Hypovolaemic blood loss, fluid loss (burns, diarrhoea, vomiting, sweating) Cardiogenic MI, heart rupture, arrhythmia, myocarditis, pulmonary embolism, tamponade Distributive septic (infection), anaphylactic, neurogenic

Circulatory low blood pressure & pulse pressure, tachycardia Skin pruritis, urticarial, erythemia CNS agitation, confusion, coma Respiratory tachypnea, bronchoconstriction, cyanosis Systemic shock, death Metabolic hyperkalaemia, increased lactate, metabolic acidosis

Macule flat lesion <5mm Papule raised lesion <5mm Patch flat lesion >5mm Plaque raised flat-topped lesion >5mm Nodule raised spherical lesion >5mm Pustule discrete, pus-filled, raised lesion Scale dry, horny, plate-like lesion Vesicle fluid-filled lesion <5mm Bulla fluid filled lesion >5mm

Class Class I Class II

Blood Loss <15% 15-30%

Class III


Class IV


Characteristics ~Asymptomatic completely compensated Compensated shock tachycardia, cool skin, confusion, thirst, weakness, lactic acidosis Failure of compensation hypotension, tachycardia, oliguria Irreversible and immediately life-threatening: cardiac arrest, organ failure, anuria

Give a brief explanation of pemphigus, bullous pemphigoid, dermatitis herpetiformis and porphyria.

Outline the stages of eczema development.

Outline the forms of psoriasis.

Outline the actions of glucocorticoids.

A. Initial dermal oedema & perivascular infiltration by inflammatory cells B. Spongiosis and microvesicle formation C. Parakeratosis D. Progressive acanthosis E. Hyperkeratosis

Pemphigus Ab-mediated breakdown of keratinocytic desmosomes ! lack of adhesion between keratinocytes (acantholysis) Bullous pemphigoid Ab-mediated breakdown of hemidesmosomes ! lack of adhesion to basement membrane ! bullae Dermatitis herpetiformis pruritic, urticarial plaques & vesicles associated with specific HLA types and coeliac disease Porphyria disturbances of porphyrin

Carbohydrates - ! glucose uptake and use; " gluconeogenesis Proteins - "breakdown, ! formation Lipids redistribution of fat (as observed in Cushings syndrome HPA axis negative feedback # ! glucocorticoids Cardiovascular - ! vasodilation, ! fluid exudation Musculoskeletal - !osteoblast and " osteoclast activity Inflammation - overall decreased 1. Psoriasis vulgaris - eruptive , chronic plaque & inverse forms o Peak incidence at 22 years; M = F o Stimulated by scratching/rubbing 2. Pustular psoriasis - pustules on normal or inflamed skin 3. Psoriatic arthritis - psoriasis of skin/nails with arthropathy 4. Erythrodermic psoriasis - serious condition


Outline how glucocorticoids decrease inflammation.

List some of the side effects of glucocorticoids.

List some of the effects of histamine on H1, H2 and H3 receptors.

Describe the difference between sedating and non-sedating antihistamines in terms of uses.

Suppression of the bodys response to infection or injury Adrenal insufficiency (with sudden withdrawal) Iatrogenic Cushings Syndrome Osteoporosis Avascular necrosis of the head of femur Tendency to hyperglycaemia ! Diabetes Muscle wasting Growth retardation in children o o o o o o o o o !leukocyte influx/activity !angiogenesis ! fibrosis (modified transcription of collagenase) ! clonal expansion of T and B cells ! IgG production ! cytokine production (inhibition of transcription) ! prostanoid production (inhibition of cyclooxygenase 2) ! other chemical mediators (histamine, nitric oxide) ! complement components in blood

Sedating anticholinergic effect; used to treat allergies, motion sickness, itching, nausea Non-sedating (poor CNS penetration) used to treat allergies

H1 lungs, skin, GIT ! o Smooth muscle activation o Vasodilation o Increased vascular permeability o Activation of sensory nerve endings (pruritis) H2 GIT ! gastric secretion H3 - CNS

Describe some of the causes of burns.

Describe the pathogenesis of burn damage.

Using the rule of nines, state what percentage each part of the body is worth.

Outline burn classification, including area of skin involved, clinical features and healing time.

Burns cause protein degeneration ! coagulative necrosis Rapid shift of body fluids into interstitial compartments # plasma protein loss # generalised oedema Excess heat loss through the burn # hypermetabolic state # "nutritional needs Ideal site for growth of microorganisms # Pseudomonas aeruginosa, MRSA, Candida infections # sepsis

Heat - open flame, hot liquid, steam, hot surfaces (smoke inhalation may occur) Caustic chemicals strong acids, strong alkalis, phenols, mustard gas, phosphorus, petroleum Electricity may cause extensive internal damage with minimal apparent cutaneous injury Radiation prolonged exposure to solar UV radiation (sunburn) or other radiation (e.g. X-ray)

New Classification Superficial Superficial partial thickness Deep partial thickness Full thickness

Area Involved Epidermis

Clinical Features Erythema, oedema, tenderness Erythema, moist, blistering, tenderness Painless, pale, dry, non-blanching Painless, dead appearance, thrombosed vessels Charred appearance, dry, brown, painless

Healing 3-6 days, no scarring 7-20 days, pigment change >21 days, scarring;

Arms = 9% each Chest = 9% Abdomen = 9% Head & neck = 9% Thighs = 9% each Legs = 9% each Back of trunk = 18% Perineum = 1%

Some dermis

Full dermis Subcutaneous tissue Underlying muscle


Never heals, severe risk of contracture; grafting needed

Give the parkland formula for fluid resuscitation.

List some of the ANZBA guidelines for referral to a burns unit.

Outline some of the early complications of burns.

List the phases of wound healing.

Burns > 10% TBSA Burns of the face, hands, feet, genitalia, perineum or major joints Full thickness burns >5% TBSA Electrical burns Chemical Burns Inhalation injury Circumferential burns of the limbs or chest Burns in children/elderly Burns in patients with pre-existing medical disorders that could complicate management, prolong recovery or affect mortality Any burn patient with associated trauma (e.g. fall-related injury)

mL crystalloid in 24h = 4 x weight (kg) x %TBSA burned

(half is given in first 8 hours post-burn; other half in following 16 hours)

1. Haemostasis vasospasm, platelets, fibrin 2. Inflammation vasodilation, permeability, chemotaxis, cells 3. Granulation tissue formation mesenchymal cells, angiogenesis 4. Wound contraction - myofibroblasts 5. ECM deposition & remodelling collagen synthesis (type 1)

Loss of fluid (water/electrolytes) from the plasma leads to Oedema, haemoconcentration, dehydration ! hypovolaemic shock Poor vascular perfusion " risk of hypothermia Lactic acid production (due to hypoxia) leads to !pH Increased protein catabolism can cause rhabdomyolysis rapid breakdown of skeletal muscle Loss of the skins barrier function increases the risk of infection and subsequent sepsis Pseudomonas aeruginosa Staphylococcus aureus Kelebsiella Escerichia coli Candida albican

Describe split thickness and full thickness skin grafts, and outline some of their benefits and drawbacks.

Give details on the clinical definition of SIRS.

List some common sites of origin of pathogens causing sepsis.

Outline the pathogenesis of septic shock.

Split Thickness Two or more of the following: Temperature > 38C or <36C Heart rate >90 bpm Respiratory rate >20 breaths / minute PACO2 <32 mmHg White cell count >12,000 cells/mm3 or <4,000 cells/mm3, or >10% band forms Drawbacks Benefits Description Epidermis with variable amounts of dermis Retains more skin-like properties Less prone to contractures Cosmetically more appealing Limited to smaller wounds

Full Thickness Epidermis with all of dermis Commonly taken from thigh or buttocks The same donor area can be harvested once it has healed after a couple of days Broader range of action More fragile and contracts more during healing

Genitourinary tract indwelling catheters Abdomen cholecystitis, peritonitis, intra-abdominal abscess, appendicitis, pancreatitis Lungs Pneumonia, empyema CNS meningitis Skin/soft tissue cellulitis, trauma, catheters

Outline the four strategies of antimicrobial therapy.

List some broad spectrum and narrow spectrum penecillins.

State the class and mechanism of: cephalexin, doxycycline, gentamycin, sulfadiazine, ciprofloxacin.

State a use for: acyclovir, gancyclovir, interferon alpha, atazanavir.

Narrow benzylpenecillin, flucloxacillin Moderate ampicillin, amoxicillin Broad piperacillin, ticarcillin

Prophylaxis perioperative, patients with ascites, travellers (malaria), immunocompromised patients Empiric antibiotic therapy (broad spectrum) CAP, VAP, fever Pathogen-direct therapy without knowing resistance profile Susceptibility-guided therapy

Acyclovir herpes simplex, shingle Gancyclovir cytomegalovirus Interferon alpha hepatitis B & C Atazanavir - HIV

Cephalexin 1st generation cephalosporin; -lactam ring inhibits cell wall synthesis by binding to bacterial transpeptidase and preventing peptidoglycan cross-linking Doxycycline tetracycline; bind and inhibits 30s ribosomal subunit Gentamycin aminoglycoside; bind & inhibits 30s ribosomal subunit Sulfadiazine sulphonamide; inhibits folate synthesis by competing with PABA Ciprofloxacin fluoroquinolone; inhibits DNA gyrase

Give to examples and outline the mechanism of polyene and azole antifungals.

Name the bones forming the orbit.

Outline the passage of lacrimal fluid from the lacrimal gland to the nasal cavity.

Describe the function, location and innervation of the intrinsic muscles of the eye.

Frontal bone (roof) Ethmoid bone (medial / posterior wall) Lacrimal bone (medial wall) Palatine bone (posterior wall) Maxilla (medial / inferior wall) Zygomatic bone (lateral / inferior wall) Sphenoid bone (lateral / posterior wall) Polyenes (amphotericin B, nystatin) bind to ergosterol in fungal cell walls ! channel formation / electrolyte leakage Azole (ketoconazole, fluconazole) block ergosterol synthesis by inhibition of a precursor

Muscle Ciliary

Function Accommodation for distance

Location Muscle fibers in the ciliary body Circularly arranged fibres in the iris Radially arranged fibres in the iris

Innervation Parasympathetic from oculomotor nerve (CNIII) Parasympathetic from oculomotor nerve (CNIII) Sympathetic from superior cervical ganglion (T1)

1. Lacrimal gland secretes lacrimal fluid o Anterior superolateral region of orbit o Orbital and palpebral parts 2. Lacrimal duct 3. Conjunctival sac area covering eyeball 4. Lacrimal papillae and canaliculi drain lacrimal fluid from the medial angle of the eye (lacrimal lake) to the lacrimal sac 5. Lacrimal sac 6. Nasolacrimal duct delivers lacrimal fluid to inferior nasal meatus

Sphincter pupillae


Dilator pupillae


Describe the function and innervation of the extrinsic eye muscles.

Describe the effects on vision of a lesion at the level of the (a) optic nerve, (b) optic chiasm, (c) optic tract and (d) geniculocalcarine tract.

Outline the types of melanocytic naevi.

Describe the macroscopic morphology of a malignant melanoma.

Muscle Levator palpabri superioris Superior rectus Inferior rectus Medial rectus Lateral rectus Superior oblique Inferior oblique


Function Elevation of upper eyelid

Oculomotor (CNIII)

Elevation, adduction, medial rotation of eyelid Depression, adduction, lateral rotation of eyeball Adduction of eyeball Abduction of eyeball Depression, abduction, medial rotation of eyeball Elevation, abduction, lateral rotation of eyeball

Abducens (CNVI) Trochlear (CNIV) Oculomotor (CNIII)

A. Asymmetry B. Border - irregular C. Colour varied (black, brown, red, dark blue, grey) D. Diameter - >6mm E. Elevation 1. Junctional naevus nests along dermoepidermal junction 2. Compound naevus nests grow into underlying dermis 3. Intradermal naevus mature lesions that lose their epidermal part

List the five growth phases of malignant melanoma.

Outline the types of melanoma and give a feature of each.

List four differential diagnoses of malignant melanoma.

Describe some important characteristics that aid in identifying basal cell carcinoma.

Superficial Spreading Melanoma (SSM) 75% Commonly arises from pre-existing melanocytic naevi Slow change over 1-5 years from a flat lesion to a glossy dark lesion Nodular Melanoma (NM) 14% Usually form de novo from normal skin Rapid growth to a small blue/black lesion greater vertical growth than horisontal Invades and metastasises earlier than SSM Lentigo Maligna Melanoma (LMM) - 8.5% Melanoma in situ - begins as an irregular macule, extends radially Usually on the face Acral Lentigenous Melanoma (ALM) 0.5% Occur mostly on palms, soles or under nail beds May be associated with sun exposure A. Lentigenous melanocytic hyperplasia B. Lentigenous junctional naevus C. Lentigenous compound naevus (dysplastic naevus) D. Early melanoma radial growth E. Advanced melanoma vertical growth + malignant spread to dermis and vessels

Rarely metastasise malignancy lies in the fact that they can grow extensive locally Presents as pearly papules, often containing prominent, dilated subepidermal blood vessels (telangiectasias) Palisading - cells at the periphery of the tumour cell islands tend to be arranged radially with long axes arranged in parallel

Naevi - dysplastic, blue or Spitz Solar lentigo (freckle) Basal cell carcinoma Seborrhoeic keratosis

Name some therapeutic antibodies and state their target as well as what they are used to treat.

Name some conditions that affect fitness to drive.

Outline the process of erythropoiesis.

Describe the changes in site of haematopoiesis over the course of embryogenesis and life.

Epilepsy Diabetes hypoglycaemia, end-organ damage Cardiovascular disease sudden arrythmia, syncope, stroke, MI Syncope Visual pathologies Psychiatric conditions behavioural disorders, drug abuse, schizophrenia Sleep disorders narcolepsy, chronic insomnia

Target Drug Used to Treat Antibody/Complement-dependent cytotoxicity CD20 CD33 CD52 HER2/neu VEGF EGF-R Rituximab Gemtuzumab Alemtuzumab Herceptin Avastin Cetuximab Non-Hodgkins Lymphoma Acute myelogenous leukaemia Chronic lymphocytic leukaemia Breast cancer Colorectal cancer Colorectal cancer

Disruption of cellular signalling

In Utero 1. The foetal yolk sac is the main haematopoietic organ until 6 weeks 2. The liver and spleen predominate until 6 months o Haematopoietic stem cells (HSCs) colonise liver at 5 weeks o Liver haematopoiesis is mainly erythroid o B-cell development first begins in the foetal liver at 7 weeks and shifts to bone marrow at 12-14 weeks 3. Foetal bone marrow is colonised by HSCs at 8 weeks o Bone marrow haematopoiesis is mainly myeloid After Birth Infants and children - all bones contain active marrow tissue Adults - all blood cells produced in red marrow of axial skeleton

Stimulated by erythropoietin (EPO) from the juxtaglomerular cells 1. Proerythroblast day 1 2. Basophilic erythroblast day 2 3. Polychromatic erythroblast day 3 4. Normoblast day 4 5. Reticulocyte day 5-7 6. Erythrocyte

Classify anaemia by aetiology.

Give some examples of microcytic, normocytic and macrocytic anaemia.

List some of the functions of iron.

Give five aetiologies of iron deficiency.

Microcytic (low MCV) - iron deficiency, thalassaemia, chronic disease, sideroblastic anaemia Normocytic (normal MCV) infections, inflammatory disease, aplastic anaemia, malignancy, haemorrhage Macrocytic (high MCV) o o Megaloblastic - B12/folate deficiency Non-megaloblastic ,- alcohol, liver disease, hypothyroidism, pregnancy

1. Blood Loss Anaemia Acute trauma Chronic - GIT lesions, gynaecologic disturbances 2. Anaemia from Impaired Erythropoesis Defective Hb production - iron deficiency, chronic disease, sideroblastic anaemia, thalaessamias Defective DNA synthesis B12/folate deficiency Disturbance in proliferation/differentiation of stem cells chronic renal failure, aplastic anaemia, bone marrow infiltration 3. Haemolytic Anaemia Intrinsic RBC abnormalities haemoglobinopathies, membrane defects, enzyme deficiency, paroxysmal nocturnal haemoglobinuria Extrinsic causes immune, infectious, chemical, physical trauma

1. Oxygen transport (haemoglobin) 1. Blood loss - occult GIT bleeding, menstruation, blood donation 2. Pregnancy 3. Rapid growth (especially 0-2 years) 4. Malabsorption 5. Dietary insufficiency rare in industrialised countries 2. Cellular respiration (TCA cycle, electron transfer chain etc.) 3. DNA synthesis 4. Neurotransmitter synthesis 5. Hormone synthesis 6. Embryogenesis (myelin synthesis) 7. Host defence (neutrophil killing)

Which of the following increases in iron deficiency anaemia: serum iron, TIBC, transferrin saturation, serum ferritin

Outline several different aetiologies of B12 deficiency anaemia.

Name some clinical features of B12 deficiency anaemia.

Outline several aetiologies of folate deficiency.

1. ! Intake - inadequate, vegetarian or vegan diet 2. ! Release from food loss of pepsin secretion 3. ! Release from cobalophilin ! pancreatic exocrine function 4. ! Binding to intrinsic factor o Pernicious anaemia - autoimmune atrophic gastritis o Gastrectomy e.g. due to gastric cancer 5. ! Absorption o Ileal pathology lymphoma, resection, ileitis o Malabsorption coeliac disease, Crohns disease o Competition with parasites 6. " Requirement pregnancy, hyperthyroidism

Total iron binding capacity. The rest decrease.

! Intake - alcoholics, elderly Malabsorption e.g. coeliac disease, Crohns disease " Requirement o Pregnancy o Infancy o Disseminated cancer o Malaria o Sickle cell anaemia/ Thalassaemia Folate antagonists e.g. methotrexate

Signs of anaemia weakness, pallor Glossitis sore tongue Paraesthesia peripheral sensory neuropathy (early) ! absent reflexes (late) Mild jaundice sequestration of large cells in spleen ! "haemolysis ! "bilirubin Splenomegaly/ hepatomegaly Delerium/dementia

Give several examples of autoimmune diseases.

Describe some of the physiological changes that occur with ageing.

List some of the major geriatric syndromes.

List several aetiologies of hypo- and hyper-calcaemia.

! homeostatic threshold (minor illness/injury ! major consequences) ! cardiovascular reserve ! muscle strength ! joint and skeletal stability ! PNS and CNS function ! renal function ! special senses vision, hearing, balance

Mediated by Antibodies/Immune Complexes Autoimmune haemolytic anaemia Autoimmune thrombocytopaenia Myasthenia gravis Graves Disease Goodpasture Syndrome Systemic Lupus Erythematosus (SLE) Polyarteritis nodosa Mediated by T Cells Type-1 diabetes mellitus Multiple sclerosis Rheumatoid arthritis Systemic sclerosis Sjogren syndrome Inflammatory bowel disease Inflammatory myopathies

Hypocalcaemia Chronic kidney disease Vitamin D deficiency Hypoparathyroidism Acute pancreatitis Sepsis Meds anticonvulsants, antimicrobials, hypercalcaemia drugs Hypercalcaemia Primary hyperparathyroidism (90% in ambulatory cases, 20-30% in hospitalised patients) Other endocrine causes thyrotoxicosis, phaeochromocytoma, excess vitamin D Malignancy myeloma, lymphoma, cholangiocarcinoma Medications - thiazide diuretics, lithium Immobilisation Chronic renal disease

1. Impaired cognition (confusion) o Delerium dehydration, infection o Dementia vascular dementia, Alzheimers o Depression e.g. grieving 2. Instability (falls) osteoporosis, lack of physical activity, impaired vision, medications, environment 3. Immobility 4. Incontinence 5. Iatrogenic disease

Outline the major clinical features of hypercalcaemia.

Outline some aetiologies of primary and secondary osteoporosis.

Describe the nature and importance of a monoclonal gammopathy of uncertain significance (MGUS).

Describe the pathogenesis of multiple myeloma.

Primary osteoporosis Post-menopausal - ! oestrogen following menopause Senile - !GF potency with age Disuse - localised to a certain region Stones - disseminated calcium phosphate deposition at [Ca2+] 17mg/100mL Bones bone pain, pathologic fractures Moans constipation, distended abdomen, vomiting Psychic groans - depressed neuronal activity, lack of appetite, irritability, poor cognition Renal features polyuria, polydipsia, nocturia, haematuria

Secondary osteoporosis Endocrine parathyroid, thyroid, gonad, pituitary pathologies Medications anticoagulants, chemotherapy, corticosteroids, anticonvulsants, alcohol Neoplasia multiple myeloma, carcinomatosis GIT malnutrition, malabsorption, hepatic insufficiency, vitamin C/D deficiencies Rheumatological disease

Myeloma cell proliferation leads to Osteoclast activation (MIP1) ! o Bone destruction hypercalcaemia, bone pain, fractures o Nephrocalcinosis ! renal failure Monoclonal antibodies ! o Hyperviscosity blurred vision, dizziness, " consciousness o Bence-Jones proteinuria o Renal failure dehydration, confusion, nausea / vomiting Bone marrow infiltration ! o Thombocytopaenia bruising, poor wound healing, epistaxis o Neutropaenia - infections o Anaemia fatigue, weakness, dyspnoa, pallor Elevated gamma globulin band (M spike) on serum electrophoresis but asymptomatic May have a slow, progressive, demyelinating sensorimotor neuropathy Usually only diagnosed during routine investigations or when investigating co-morbid conditions ~10% progress to symptomatic plasma cell neoplasm e.g. multiple myeloma after 20 years (1-1.5%/year) Monitoring of patients with MGUS is important for detecting progression to multiple myeloma etc.

Outline the diagnostic criteria of multiple myeloma.

Name some of the foramina of the inferior skull and what travels through them.

Name the muscles of mastication.

List the layers of the scalp.

Incisive foramen - nasopalatine nerve, sphenopalatine vessels Greater palatine foramen - greater palatine nerve & vessels Lesser palatine foramina - lesser palatine nerve & vessels Pterygoid canal - pterygoid nerve and vessels Foramen ovale - mandibular nerve (V3) Foramen spinosum - middle meningeal artery Foramen lacerum - filled with cartilage Carotid canal - internal carotid artery & plexus Foramen magnum - spinal cord, vertebral arteries and nerve plexuses, anterior and posterior spinal arteries, accessory nerve (XI), meninges Condylar canal - emissary veins Hypoglossal canal - hypoglossal nerve (XII) & vessels Jugular foramen - internal jugular vein, inferior petrosal sinus Stylomastoid foramen - facial nerve (VII)

1. Evidence of lytic bone lesions 2. Bence-Jones proteinuria 3. Bone marrow infiltration by plasma cells

SCALP Skin Connective tissue Aponeurosis (epicranial) Loose areolar tissue Pericranium Temporalis Masseter Medial pterygoid Lateral pterygoid

List some of the major muscles of facial expression and their actions.

List the muscles of the tongue and their function.

Outline a strategy for assessment of the chest X-ray.

Name some major aetiologies of hoarseness.

Intrinsic Superior longitudinal shortens tongue, curls apex & sides of tongue Inferior longitudinal shortens tongue, uncurls apex and turns in downwards Transverse narrows & elongates tongue Vertical flattens & widens tongue Extrinsic Genioglossus protrudes tongue; depresses centre Hyoglossus depresses tongue Styloglossus elevates & retracts tongue Palatoglossus depresses palate, elevates back of tongue

Orbicularis oculi closes eyes Levator palpabrae superioris opens eyes Nasalis opens and closes nostrils Orbicularis oris closes mouth Buccinator sucks in cheeks Platysma opens mouth

Laryngitis viruses, bacteria, irritants, excessive use of voice Benign laryngeal growths papillomas, cysts, polyps, chondromas, lipomas, nodules Laryngeal cancer Compression of larynx e.g. oesophageal cancer Thyroid disease thyroiditis, goitre Vocal cord pathology trauma, stenosis Nerve pathology left reccurent nerve palsy / compression, motor neurone disease Foreign body


Airway midline, patient Bone symmetrical, fractures, lytic lesions, defects Breast shadows Cardiac silhouette should take up <50% of chest width Costophrenic angles Diaphragm sharp edges, not raised or flat Edges apices, pneumothorax, pleural thickening Extrathoracic tissues Fields well inflated lung fields, no effusions, infiltrates, nodules Gastric bubble present / obscured / absent Hilum nodes, masses Instrumentation lines, tubes

Name some major causes of lymphadenopathy.

Outline some of the major things to assess in examination of lymphadenopathy.

Contrast Hodgkin and Non-Hodgkin lymphoma.

Give examples of indolent vs. aggressive Non-Hodgkin lymphoma and describe how these two types differ in prognosis and treatment.

Location localised or generalised Size (<1cm = benign; >2.25 cm = 80% malignant) Consistency hard, soft, rubbery Fixation chronic infection or malignancy Tenderness inflammation (infection, malignancy) Signs of inflammation Splenomegaly systemic illness (infectious mononucleosis, lymphoma, leukaemia, SLE, sarcoidosis

Infection bacterial, mycobacterial, fungal, chlamydial, parasitic, viral Benign immune disorder autoimmune (RA, SLE), serum sickness, drug reactions, Langerhans cell histiocytosis Malignant immune disorder leukaemia, lymphoma, monoclonal gammopathy, malignant histiocytosis Other malignancies breast, lung, melanoma, head & neck, GIT, germ cell Lipid storage diseases Gauchers disease, Niemann-Pick disease Endocrinopathies thyroid disease, adrenal insufficiency Miscellaneous sarcoidosis, amyloidosis, dermatopathic lymphadenitis

Type Indolent

Examples Follicular lymphoma CLL MALT lymphoma DLBCL ALL Mantle cell lymphoma

Prognosis Survival - years ~incurable Survival months w/o Tx 60% complete remission with aggressive chemotherapy

Treatment Defer if asymptomatic

Hodgkin Often localised to a single axial group of nodes (cervical, mediastinal, para-arotic) Orderly contiguous spread

Non-Hodgkin More frequent involvement of multiple peripheral nodes Non-contiguous spread Often Waldeyer ring and mesenteric nodes involvement Extra-nodal presentation common


Active chemotherapy

Rarely mesenteric node and Waldeyer ring involvement Extra-nodal presentation rare

Very Aggressive

Burkitt Lymphoma

Outline the Ann Arbor staging guidelines for lymphoma.

List the drugs that make up CHOP for Non-Hodgkin lymphoma and ABVD for Hodgkin lymphoma.

List the major cell features for follicular lymphoma,

Name and describe the major cell type of Hodgkin lymphoma, and its major variants.

I 1 lymph node region or single nodal tissue involved CHOP cyclophosphamide, doxorubicin, vincristine, prednisone ABVD doxorubicin, bleomycin, vinblastine, dacarbazine II 2+ lymph node regions on the same side of the diaphragm involved III lymph node regions on both sides of the diaphragm involved IV disseminated / multiple foci of 1 organ / extanodal tissue involved

Reed Sternberg cells (originate from germinal centre B cells) o Large cells with multiple / single-multilobated nuclei o Large inclusion-like nucleoli Mononuclear variant single nucleus with large nucleolus Lacunar variant delicate, folded or multilobate nucleus, abundant cytoplasm Lymphohistiocytic (popcorn) variant polypoid nucleus, inconspicuous nucleoli

Follicular lymphoma centrocytes (small), centroblasts (large) Diffuse large B cell lymphoma large cells, vesicular nucleus, 2-3 nucleoli, abundant cytoplasm Burkitt lymphoma high mitotic index, numerous apoptotic bodies Mantle cell lymphoma small cells, irregular nuclear contours, scant cytoplasm

Outline the morphology of the histological subtypes of Hodgkin lymphoma.

Explain some of the major terminology related to euthanasia including terms related to consent and who carried out the procedure.

Define the terms physician-assisted suicide, terminal sedation and the double effect.

Give some arguments for and against euthanasia.

Consent Voluntary euthanasia: conducted with the consent of the patient Non-voluntary euthanasia (mercy killing): euthanasia on a patient who cannot consent (incompetent) Involuntary euthanasia (murder): euthanasia against the expressed wish of a person Procedure Passive euthanasia (letting die): withholding of life-sustaining treatment (e.g. respirator, medications) Active euthanasia (killing): use of lethal substances or forces (usually by a doctor) to a person

Nodular sclerosis frequent lacunar cells with only a few Reed Sternberg cells; mixed leukocyte infiltrate Mixed cellularity mononuclear & Reed Sternberg cells, mixed leukocyte infiltrate Lymphocyte-rich mononuclear & Reed Sternberg cells, T-cell infiltrate Lymphocyte depletion Reed Sternberg cells, relative lack of infiltrate Lymphocyte predominance lymphohistocytic cells, infiltrate of follicular dentritic cells

Arguments For Ethically right - autonomy and rights No moral difference between killing and letting die the result is the same Beneficence - promoting well-being of patients It happens already A legitimate part of palliative care Death with dignity low subjective quality of life Suicide is not illegal (in many western countries) so why shouldnt assisted suicide be allowed?

Arguments Against Morally wrong life is sacred There is a moral difference between killing (caused by a person) and letting die (caused by a disease) Hippocratic oath integrity of medical profession The slippery slope will lead to spread of other killing practices e.g. non-voluntary euthanasia Palliative care eliminates the need for euthanasia The value of human suffering (~religious) Who can decide when someones life is not worth living?

Physician-assisted suicide: a person takes their own life with help from a doctor regarding: 1. Prescription of lethal drugs 2. Advice dosing, which drugs 3. Setting up equipment that patient activates to end their life Terminal sedation: use of sedative drugs to induce unconsciousness in terminally ill patients o Includes withholding / withdrawing of artificial nutrition and hydration Double effect: giving enough pain relief to control a persons pain but also hasten death o Pain relief is intended, death is (ostensibly) foreseen but unintended

Summarise Australias stance on ending a patients life.

Outline some major aetiologies for fever.

Outline some strategies for mosquito avoidance.

State the vector that transmits some of the major vector-borne diseases.

1. Infections viral bacterial, malaria, syphilis etc. 2. Malignancy lymphoma, carcinoma 3. Rheumatological disorder SLE, sarcoid, rheumatoid arthritis 4. Drug fever reaction with medicine (usually accompanied by rash) 5. Pulmonary embolism (mild fever) 6. Osteomyelitis Active voluntary euthanasia is illegal Physician-assisted suicide is illegal Terminal sedation is tolerated

Ross River virus Culex & Aedes mosquitoes Japanese encephalitis Culex mosquitoes Yellow fever Aedes aeqypti mosquitoes African trypanosomiasis glossina fly American trypanosomiasis reduviid bugs Leishmaniasis sand flies Filariasis - mosquitoes Malaria Anopheles mosquitoes Typhus fever - lice Scrub typhus - chiggers Spotted fever - ticks Trench fever - lice Plague - fleas

Elimination of areas mosquitoes breed standing water e.g. old tyres, empty containers Insecticide-impregnated bed nets repel, block or kill mosquito Insecticide spraying of house walls Destruction of adults bug spray Mass treatment of infected people

Outline the life cycle of the Plasmodium species.

Outline three major features of Plasmodium falciparum that makes it more pathogenic than the other species.

Name three important histologic features of Plasmodium species and how they are used to distinguish between species.

What is the length of the fever cycle for each of the species of Plasmodium?


Sporozoite in female mosquito salivary glands is transmitted into human blood when mosquito feeds Within minutes sporozoites attach to and invade parenchymal liver cells Within liver cells, plasmodium species multiply over 2 weeks into tissue schizonts Schizonts eventually rupture to release 10,000-40,000 merozoites o P. vivax and P. ovale some cells dormant within liver as hypnozoites Merozoites attach to and invade red blood cells Within red blood cells plasmodium species grow in a digestive vacuole and hydrolyse haemoglobin a. Ring form b. Trophozoite single chromatin mass c. Schizont multiple chromatin masses ! each develops into a merozoite The schizonts rupture to release merozoites back into the circulation ! invade RBC ! the cycle continues Some merozoites enter a sexual stage - microgametocyte (M), macrogametocyte (F)

1. Ability to infect red blood cells of any age ! higher parasite burdens and profound anaemia(other species affect only older cells) 2. Clumping together of infected red cells (rosettes) ! sticking to endothelial cells lining small blood vessels! blocking of blood flow ! manifestations of cerebral malaria 3. Stimulation of cytokine production (TFN, IFN-, IL-1) ! suppressed red blood cell production ! fever ! tissue damage (through NO production)

2. 3. 4. 5. 6.

7. 8.

P. falciparum 48 hours P. vivax 48 hours P. malariae 72 hours P. ovale 50 hours

1. Schffner dots o Found in the trophozoite stage of P. ovale and P. vivax o Used to distinguish P. vivax and P. falciparum 2. Ring forms o Single ring vivax, ovale, malaria o Double ring falciparum 3. Gametocytes o Rounded - vivax, ovale, malaria o Banana-shaped falciparum

What drugs are used to treat P. vivax and P. ovale, and why do they specifically need a different type of treatment?

In Australia, what anti-malarial is used against chloroquine-resistant Plasmodium falciparum?

List some clinical features of dengue fever.

List some clinical features of dengue haemorrhagc fever.

Malorone (atovaquone + proquanil)

Tissue schizonticides primaquine / tafenoquine This is because these two species can lie dormant in the liver as hynozoites, and blood schizonticides (e.g. chloroquine) only target erythrocyte forms while tissue schizonticides target hypnozoites and gametocytes Tissue schizonticides are almost always given in combination with another anti-malarial, because they dont target erythrocyte forms.

Bruising - petechiae, ecchymoses, purpura Bleeding from mucosa, GIT, injection sites Haematemesis or melaena Signs of plasma leakage pleural effusion, ascites, hypoproteinaemia

Can be asymptomatic (50-90%) Fever sudden onset, usually self-limiting (3-7 days) Severe back pain (break-bone fever) important feature for differential diagnosis Macular rash o Initial rash first day o Secondary rash as fever abates (beginning on trunk, spreading to the extremities & face) Headache / retro-orbital pain Depression

What are some guidelines for minimising risk while travelling?

Outline the pathogenesis of primary pulmonary tuberculosis.

Give some information on the pre- and post-ganglionic neurons, as well as the neurotransmitters used in the autonomic nervous system.

List some of the effects of the parasympathetic nervous system.

0-3 weeks entry into macrophages 1. Endocytosis entry of M. tuberculosis into macrophages 2. Replication within phagosome by blocking fusion of phagosome and lysosome > 3 weeks T cell response 3. Activation of TH1 cells by alveolar macrophages (IL-12, TLR2) 4. Activation of macrophages to become bacteriocidal (IFN-) o IFN- stimulates NO synthase ! destruction of mycobacterial constituents 5. Stimulation of granuloma formation and caseous necrosis (IFN-) o Macrophages differentiate into epithelioid histiocytes characteristic of granuloma

1. Food avoid fruit with damaged skin, uncooked food, fish, shellfish 2. Fluid - boil water / drink bottled water in contaminated areas 3. Flies avoid insects generally + avoidance strategies 4. Sun use sunscreen 5. Swimming avoid swimming with open cuts/wounds 6. Safety belts if possible 7. Stress minimise stress 8. Safe sex

SLUDGE BBB Salivation Lacrimation Urination Defacation GastroEmesis Bronchorrhoea Bronchospasm Bradycardia

Parasympathetic - ganglia lie close to the end organs Preganglionic neurons acetylcholine acts on nicotinic Ach receptors Postganglionic neurons acetylcholine acts on muscarinic Ach receptors Sympathetic - neurons synapse in paravertebral ganglia Preganglionic neurons acetylcholine acts on nicotinic Ach receptors or the adrenal medulla Postganglionic neurons noradrenaline acts on adrenergic receptors

Outline the generation of action potentials in cardiac pacemaker cells.

Outline the generation of action potentials in cardiomyocytes.

Outline which ECG leads focus on which parts of the heart.

Give normal lengths for the PR interval, the QRS complex and the QT interval.

Phase 0: rapid depolarisation influx of Na+ (!INa) Phase 2: rapid repolarisation closure of Na+ channels ("INa) Phase 3: plateau opening of slow L-type Ca2+ channels; decrease in K+ permeability (!ICa, !IK) Phase 4: return to RMP opening of K+ channels ("IK)

1. Gradual depolarisation activation of funny channels that allow passage of Na+ and K+ (!INa, "IK) 2. Depolarisation to threshold opening of voltage-gated T-type Ca2+ channels (!ICaT) 3. Impulse generation opening of voltage-gated L-type calcium channels # Ca2+ influx (!ICaL) 4. Return to resting membrane potential opening of voltagegated K+ channels # K+ efflux (!IK)

PR interval should be < 0.2 seconds QRS complex should be < 0.12 seconds QT interval should be <0.4 seconds

I - left lateral II inferior aspect III inferior aspect aVR right atrium aVL left lateral aVF inferior aspect V1 & V2 right atrium & ventricle V3 & V4 IV septum / anterior left ventricle V5 & V6 anterior & lateral left ventricle

Quickly describe the ECG pattern for each type of heart block.

Describe the ECG patterns on leads V1 and V6 for left and right bundle branch block.

What are the ECG manifestations of left and right atrial hypertrophy?

What is a pathological Q wave (on an ECG)?


1st degree heart block - ! PR interval 2nd degree heart block o o o Mobitz type 1 (Wenckebach) - ! PR gradually "failure of AV conduction " ! PR gradually etc. Mobitz type 2 random missing ventricular contractions, with normal PR interval and atrial contractions Advanced 2nd degree heart block 2:1 (2 P waves per QRS), 3:1 (3 p waves per QRS) etc.

3rd degree (complete) heart block) no beats conducted to ventricles, random abnormal QRS complexes due to a slow escape mechanism

Right atrial hypertrophy # peaked P wave, increased QRS height Q waves >1small square across and >2mm deep Left atrial hypertrophy # broad and bifid P wave, increased WRS height

What type of arrhythmia is this? What are the effects of high and low calcium / potassium on an ECG?

What type of arrhythmia is this? What type of arrhythmia is this?

Low potassium # T wave flattening and a hump on the end of the T wave called a U wave High potassium # peaked T waves and no ST segment Low Calcium # !QT interval High Calcium # "QT interval

Atrial flutter

Nodal / Junctional escape

Atrial fibrillation

Outline some general causes of arrhythmia.

Explain how each type of class I antiarrhythmics slow down the heart rate, and give a generic name for each.

Give a mechanism and generic name for type II, III and IV anti-arrhythmics.

Define somatisation, hypochondriasis, pain disorder and Munchhausen disorder.

1. Structural abnormalities ventricular septal defect, atrial septal Ia (quinidine, dispyramide) slows AV conduction " ! phase 0 length " ! QRS duration Ib (lidocaine) rapidly associates with Na+ and then dissociates before next beat " prevents premature beats but no effect on conduction Ic (flecainide, encainide) slow association / dissociation " act over entire cardiac cycle for general # in excitability defect, valvular disease 2. Thyroid disease hypo/hyperthyroidism 3. Rheumatic heart disease 4. Ischaemia acute or chronic 5. Drugs digoxin, Ca2+ channel blockers, -blockers, L-Dopa 6. Electrolytes K+, Ca2+, Mg2+ 7. Social drugs alcohol, smoking, caffeine

Somatisation: experiencing and reporting physical symptoms for which there is no / insufficient discoverable cause Hypochondriasis: preoccupation with the belief / fear of having severe illness based on misinterpretation of benign physical signs Pain disorder: constant or transient pain that cannot be explained Factitious (Munchausen) disorder: deliberate production of symptoms e.g. placing razorblade in urethra, injecting faecal matter / bacteria into a vein II (metaprolol, propranolol) -blockers " # influx of Na=/Ca2+ " ! refractory period III (amiodarone, sotalol) K+ channel blockers " prolongation of action potentials " ! refractory period IV (verapamil, diltiazem) Ca2+ entry blockers " # phase 2 length " # action potentials " slowing of conduction in SA and AV nodes

List some common psychogenic symptoms.

Outline the pathogenesis of atherosclerosis.

List some major aetiologies of myocardial ischaemia.

Outline the three types of angina pectoris.

!" Endothelial injury # !vascular permeability, leukocyte adhesion, thrombosis Accumulation of LDL in vessel wall #" Monocyte entry into intima & differentiation # macrophages # foam cells o Oxidation of LDL by free radicals from macrophages o Uptake of oxidised LDL by macrophages # foam cells $" Death of foam cells (necrotic core) %" Release of factors stimulating migration of smooth muscle cells and platelets &" Adhesion of platelets, accumulation of ECM molecules (fibrous cap) '" Atheroma (plaque) = lipid accumulation + necrotic core + fibrous cap

Chest pain inframammary, usually localised Breathlessness air hunger Fatigue may fluctuate throughout the day Dizziness / faintness Anxiety Palpitations sinus tachycardia / benign ventricular extrasystoles Globus hystericus constant lump in throat GIT symptoms nausea, bloating, diarrhoea, food intolerance Paraesthesia (pins & needles) Amnesia / related cognitive symptoms

1. Stable Angina Caused by imbalance in coronary perfusion and myocardial demand physical activity, excitement etc. Usually relieved by rest or nitroglycerin 2. Prinzmetal Variant Angina Caused by coronary artery spasm unrelated to physical activity, heart rate or blood pressure Generally responds to nitroglycerin or calcium channel blockers 3. Unstable / Crescendo Angina Increasingly frequent pain, often of prolonged duration Mostly caused by disruption of an atherosclerotic plaque Serves as a warning that an acute myocardial infarction may be imminent

Decreased Perfusion 1. Occlusion - atherosclerosis (90%), emboli 2. Vasospasm 3. Shock Increased Demand 1. Hyperthyroidism 2. Fever 3. Heavy exertion 4. Hypertrophy 5. Pregnancy Decreased Availability 1. Anaemia 2. CO poisoning 3. R to L shunt (congenital)

List the three ECG changes with myocardial infarction and their relative persistence.

Outline a strategy for acute treatment of myocardial infarction.

Outline a strategy for managing myocardial infarction after acute treatment.

List some complications of myocardial infarction.

MOAN 1. Morphine pain reduction 2. Oxygen may not actually help if pulmonary function is normal, but wont be harmful 3. Antiplatelet drugs (aspirin/clopidogrel) inhibit platelet aggregation 4. Nitrates (Glycerol Trinitrate) peripheral vasodilation ST elevation transient, reverts after a few days Pathological Q waves persist for life T wave inversion reverts after weeks

Contractile dysfunction cardiogenic shock, pulmonary oedema Arrhythmias due to myocardial irritability, conduction disorders Myocardial rupture Pericarditis Right ventricular infarction rare in itself but common following infarction of posterior left ventricle Infarct extension adjacent to existing infarct Infarct expansion stretching, thinning and dilation of infarct region Mural thrombosis Ventricular aneurysm Papillary muscle dysfunction

Medical Management 1. Antiplatelet (e.g. aspirin/clopidogrel) -, to reduce clotting 2. -blocker to reduce heart rate and blood pressure 3. ACE inhibitor - to decrease blood pressure 4. Statin - to reduce LDL cholesterol Surgical Treatment Percutaneous coronary intervention (PCI) dilation of coronary stenosis by balloon inflation Coronary stent insertion of mesh tube to maintain patency Coronary artery bypass surgery usually only in the case of complications e.g. ventricular septal defect or mitral regurgitation Lifestyle Changes Diet reduce fats, cholesterol and weight Stop smoking (minimal drinking is okay) Normal Exercise

Give some information about the causes and resulting ejection fraction of the three types of cardiomyopathy.

List the three major causes of cardiac hypertrophy.

List some causes of systolic (left and right) and diastolic heart failure.

Outline four compensatory mechanisms that actually worsen heart failure.

LV Ejection Fraction

Mechanisms of Heart Failure Impairment of contractility (systolic)

Causes Genetic, alcohol, peripartum, myocarditis, haemochromatosis, sarcoidosis, idiopathic Genetic, Friedrich ataxia, storage diseases, infants of diabetic mother Amyloidosis, radiationinduced fibrosis, idiopathic



1. Hypertension pressure overload 2. Valvular Disease pressure/volume overload 3. Myocardial infarction- regional dysfunction with volume overload
Hypertrophic 50-80%

Impairment of compliance (diastolic) Restrictive 45-90%

! Afterload due to ! resistance and ! volume ! Contractility due to SNS stimulation NaCl & H2 O retention due to SNS and RAAS Left ventricular remodelling hypertrophy, dilation, fibrosis

Left-Sided Heart Failure 1. Ischaemic heart disease 2. Hypertension 3. Aortic and mitral valvular diseases 4. Cardiomyopathies Right-Sided Heart Failure 1. Left heart failure (!pressure in pulmonary circulation " !work for right side of the heart) 2. Cor pulmonale parenchymal lung disorders, pulmonary hypertension, pulmonary thromboembolism Diastolic Heart Failure 1. Hypertension (elderly) 2. Primary cardiomyopathies

List some clinical features of left and right-sided heart failure.

Outline a strategy for managing heart failure based on presence symptoms.

For the two major anticoagulants, describe their mechanisms and adverse effects.

State the mechanism and some adverse effects for a few major antiplatelet drugs.

Left Heart Failure Breathlessness orthopnoea, paroxysmal nocturnal dyspnoea, tachypnoea Presence of S3 Pulmonary crackles (crepitations), pleural effusion ! heart size Secondary mitral regurgitation Skeletal muscle loss, fatigue, tiredness, weakness Right Heart Failure Elevated JVP Secondary tricuspid regurgitation Hepatomegaly Fluid retention ascites, pitting oedema in legs


Mechanism Inactivates cyclo-oxygenase, irreversibly inhibiting TXA2 (proaggregation) and prostacyclin (platelet activator) " ! platelet aggregation Inhibits ADP-dependent activation of GPIIb/ IIIa receptor that is necessary for adhesion Inhibits thromboxane synthase " #TXA2 " # platelet aggregation

Adverse Effects Some ! in risk of hemorrhagic stroke ! gastric acid Drug Heparin Mechanism Bind & activates Antithrombin III " !inhibition of thrombin (factor IIa) " !fibrin formation Inhibits Vitamin K reductase " Vit K not converted to active form " prevention of formation of factors II, VII, IX & X (TV stations) Adverse Effects Haemorrhage Osteoporosis Hypersensitivity Haemorrhage Birth Defects Interaction with foods

Aspirin (an NSAID)


Haemorrhage Warfarin Haemorrhage Nausea


For the two major fibrinolytics, state their mechanism and adverse effects.

Briefly outline the mechanism of action for each of the classes of antihypertensives.

Outline some major causes of chest pain.

List some causes of sudden, acute and chronic breathlessness.

1-Adrenoceptor antagonists - block action of noradrenaline, #peripheral resistance ACE Inhibitors - block ACE, #effects of angiotensin II, !effects of bradykinin AT1 Receptor Antagonists - block AT1 receptors, # effects of angiotensin II -Adrenoceptor Antagonists - block effects of noradrenaline on receptors ("#TNF) Ca2+ Channel Blockers - # Ca2+ entry into cardiovascular muscle cells, # constriction Diuretics - # reabsorption/ !secretion of water Loop diuretics Na/K/Cl symporter in thin ascending loop Thiazides Na/Cl symporter late ascending loop / early distal tubule Spironolactones aldosterone inhibition (Na/K pumps in distal tubule) Endothelin Antagonists - inhibit ETA/ETB receptors, # effects of endothelin (vasoconstrictor) Endopeptidase Inhibitors - !ANP (#breakdown by endopeptidase) " vascular relaxation


Mechanism Indirectly activates plasminogen - forms a complex with plasminogen that activates other plasminogen molecules " lysis of fibrin by plasmin

Adverse Effects Antigenic can activate immune responses Activated plasmin also breaks down clotting factors (II,V, VIII), " similar to haemophilia

Streptokinase (derived from streptococci)

tPA (Tissue Plasmin Activator)

Activates plasminogen directly, preferentially at the fibrin surface (less breakdown of other clotting factors)

Some breakdown of other clotting factors

Sudden (seconds to minutes) Pneumothorax Pulmonary embolism Pulmonary oedema Aspiration Anaphylaxis Anxiety Chest Trauma Acute (hours to days) Asthma Respiratory infection Lung tumour Pleural effusion Metabolic acidosis

Chronic (months to years) COPD Cardiac failure Anaemia Arrhythmia Valvular heart disease Chest wall deformities Cystic fibrosis Pulmonary hypertension

Cardiovascular Myocardial Infarction Angina Pectoris Pericarditis Aortic dissection Respiratory Pulmonary embolism Pneumothorax Pneumonia Lung cancer Functional Anxiety Hyperventilation

Chest Wall Trauma Fracture Costochondritis Gastrointestinal Oesophageal reflux Oesophageal spasm Peptic ulcer Aerophagy Gall bladder disease

Outline the elements necessary for establishing negligence due to inappropriate disclosure.

List some types of information that need to be disclosed in order for informed decision making.

Outline Virchows triad for thrombosis formation.

Define Lines of Zahn and describe their significance.

Nature of illness Proposed approach Expected benefits Common side effects Material risks Who will undertake the procedure Degree of certainty Consequences of not proceeding Long term effects Time & cost involved

1. A duty of care was established 2. There was a breach of the required standard of care o Reasonable person standard a reasonable person in the patients position would attach significance to the information regarding risk o Particular person standard the medical practitioner should be aware that the particular patient would attach significance to the information regarding risk 3. Causation can be established o The patient must prove that they would not have had the treatment if they had been adequately informed o Issues are judged individually and subjectively to decide whether this is true under the circumstances to limit effect of hindsight bias 4. Damage occurred

1. Endothelial Damage Particularly in the heart and arterial circulation high flow rates normally prevent clotting

Laminations due to pale platelet & fibrin deposits alternating with darker RBC-rich layers Signify that a thrombus has formed in rich-flowing blood Distinguish antemortem thrombosis and non-laminated postmortem clots

2. Alterations in Blood Flow Turbulence contributes to arterial and cardiac thrombosis by causing endothelial injury caused by ulcerated atherosclerotic plagues, hyperviscosity Stasis contributes to venous thrombosis caused by aneurysms, AMI, mitral valve stenosis, sickle cells 3. Hypercoagulability Primary (genetic) - factor V Leiden mutation, prothrombin mutation, methylene THF reductase mutation, increased factor VIII, IX, XI, fibrinogen Secondary (acquired) immobilisation, MI, AF, tissue injury, cancer, prosthetic valves, DIC, heparin-induced thrombocytopaenia, antiphospholipid antibody syndrome

Describe four different outcomes of thrombosis.

List some risk factors for deep venous thrombosis.

List some clinical features of deep venous thrombosis.

Outline a treatment strategy for deep venous thrombosis.

Strongest Hip /knee replacement Fracture Major surgery Major/multiple trauma Spinal cord injury Moderate CHF or respiratory failure Malignancy / chemo HRT / oral contraceptives Central venous lines Paralytic stroke Thrombophilia Previous VTE

Weakest Bed rest >3 days Obesity Immobility from sitting Increased age Varicose veins Pregnancy / post-partum Dehydration Smoking

1. Propagation accumulation of additional platelets and fibrin ! enlargement 2. Embolisation thrombi dislodge and travel to other sites 3. Dissolution fibrinolysis ! rapid shrinkage and total disappearance 4. Organisation and Recanalisation ingrowth of endothelial cells, smooth muscle cells and fibroblasts

Anticoagulation o Initially begin LMWH and begin warfarin while still on LMWH (warfarin inhibits protein C & S and can lead to an early hypercoagulable state) o Uncomplicated DVT 3-6 months of warfarin o Second episode of DVT prolonged or lifelong warfarin Surgery - indicated when coagulation is ineffective o IVC filter prevents the thrombus from ascending; o Surgical embolectomy only for acute iliofemoral DVT with good prognosis Thrombolysis - indicated in limb-threatening DVT o Urokinase

Leg pain Leg erythema Swelling below knee (distal DVT) or up to groin (proximal DVT) Pain relieved by rest Change in leg colour Leg warmth (calor) Leg tenderness Ipsilateral pitting oedema Palpable cord (thrombosed vein) Collateral superficial venous dilation Homans sign (pain on dorsiflexion of ipsilateral foot)

Outline some consequences of pulmonary embolism.

List the major PIOPED clinical features of pulmonary embolism.

List some causes of varicose veins.

Differentiate between true aneurysms, false aneurysms and arterial dissection.

Dyspnoea Pleuritic chest pain Cough Haemoptysis Tachypnoea Crackles Tachycardia S4 Accentuated pulmonic component of S2

Pulmonary infarction (10%) - classically haemorrhagic o Raised red-blue area in early stages o Within 48 hours red cell lysis, infarct becomes paler and then red-brown (haemosiderin) o Fibrous replacement occurs at the margins ! scar Haemorrhage Respiratory o Acute alveolar dead space, pneumoconstriction, hypoxaemia, hyperventilation o Later regional loss of surfactant, pulmonary infarction Cor Pulmonale -" pulmonary vascular resistance ! "right ventricular afterload ! RVF (severe) Death due to respiratory failure or acute right-sided heart failure (cor pulmonale)

True aneurysm involving an intact attenuated arterial wall or thinned ventricular heart wall o Saccular aneurysm spherical outpouchings (5-20cm in diameter) often containing thrombi o Fusiform aneurysm diffuse, circumferential dilation of a long vascular segment False aneurysm defect in the vascular wall ! extravascular haematoma Arterial dissection blood enters the arterial wall itself, dissecting between layers

Idiopathic (most common) Pregnancy / childbirth Congenital lack of valves Marfans syndrome Hereditary defects in the vein wall Compressive tumour masses (pelvis) Proximal thrombosis

List the most probable and most serious causes of leg pain.

Define stereotyping, transference and counter-transference.

List some common co-morbidities of obesity.

Outline major causes of valvular disease, specifically for regurgitation and stenosis of the mitral and aortic valves.

Stereotyping- assuming characteristics about someone based on one characteristic (e.g. obese person) Transference - unconscious redirection of feelings for a significant person to the doctor Counter-transference - unconscious direction of feelings for a significant person to a patient

Most Probable Cramps Sciatica Muscular injury Osteoarthritis Overuse injury

Most Serious Vascular Neoplasia Infection

Mitral Stenosis Post-inflammatory scarring (rheumatic heart disease) Aortic Stenosis Post-inflammatory scarring (rheumatic heart diease) Senile calcific aortic stenosis Calcification of congenitally deformed valve Mitral Regurgitation Leaflet abnormalities - post-RHD scarring, infective endocarditis, mitral valve prolapse, drugs Tensor abnormalities - papillary muscle rupture / fibrosis, rupture of chordae tendinae LV abnormalities - LV enlargement (myocarditis, DCM), mitral annular ring fibrosis Aortic Regurgitation Leaflet abnormalities - post-RHD scarring, infective endocarditis, marfan syndrome Aortic disease - degenerative aortic dilatation, syphilitis aortitis, ankylosing spondylitis, rheumatic arthritis, marfan syndrome LV abnormalities - LV enlargement (myocarditis, DCM), mitral annular ring fibrosis

GIT gallstones, pancreatitis, abdominal herniae, steatosis, cirrhosis Metabolic metabolic syndrome, DMII, dyslipidaemia Cardiovascular HTN, CAD, CCF, arrhythmias, ischaemic stroke Respiratory obstructive sleep apnoea Musculoskeletal osteoarthritis, gout, low back pain Gynaecologic abnormal menses, infertility, polycystic ovaries Genitourinary urinary stress incontinence Opthalmologic cataracts Neurologic idiopathic intracranial hypertension Cancer oesophagus, colon, gallbladder, prostate, breast, uterus, cervix, kidney Post-operative deep venous thrombosis, atelectasis Psychosocial social isolation, discrimination, low self-esteem, binge eating, depression

Very briefly explain the pathogenesis of rheumatic fever.

Describe the morphology and significance of Aschoff bodies.

Outline some of the major aetiological pathogens of infective endocarditis.

List the major aetiologies for each type of cardiac murmur.

Distinctive lesions encountered in acute rheumatic fever, consisting of: Lymphocyte foci (~T cells) Occasional plasma cells Anitschkow cells plump activated macrophages with abundant cytoplasm & central nuclei Antibody and T cell-mediated immune response to group A streptococci cross-reacts with self proteins of the heart.

Pansystolic tricuspid regurgitation, ventricular septal defect Midsystolic aortic / pulmonary stenosis, hypertrophic cardiomyopathy, aortic sclerosis, atrial septal defect Late systolic mitral prolapse Early diastolic aortic / pulmonary regurgitation Mid diastolic mitral / tricuspid stenosis Presystolic mitral / tricuspid stenosis Continuous patent ductus arteriosus

Streptococcus viridans (50-60%) normal flora of oral cavity; colonise normal valves S. aureus (10-20%) normal flora of skin; colonise normal or deformed valves Enterococci HACEK Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella S. epidermidis most prosthetic valve endocarditis Culture-negative (10-15%)

Outline some of the information that can be gathered and some of the procedures that can be performed using cardiac catheterisation.

Name the carpals in order, starting proximally.

Follow the airways from trachea to alveoli.

Outline the three types of acquired atelectasis.

Some Lovers Try Positions That They Cant Handle Proximal Row o o o o Scaphoid Lunate Triquetrum Pisiform Trapezium Trapezoid Capitate Hamate Diagnostic: o Measure pressures o Sample blood to assess oxygen saturation o Cardiac biopsies o Inject radioopaque contrast medium to image anatomy of the heart & vessel flow Therapeutic: o Angioplasty ( stenting) o Valvuloplasty o Intravascular ultrasound o Intravascular echocardiography

Distal row o o o o

1. Resorption atelectasis o Complete obstruction ! resorption of oxygen trapped in alveoli ! # lung volume o The mediastinum shifts towards the atelectic lung o Caused by excessive secretions (e.g. mucus) bronchial asthma, chronic bronchitis, bronchiectasis, postoperative states, aspiration of foreign bodies, bronchial neoplasms 2. Compression atelectasis o Filling of the pleural cavity (partially/fully) with fuild exudates, tumour, blood or air o The mediastinum shifts away from the affected lung 3. Contraction atelectasis o Local or generalised fibrotic changes in the lung / pleura prevent full expansion

Conducting Airways 1. Trachea 2. Primary bronchi 3. Lobar bronchi 4. Segmental bronchi 5. Intrasegmental bronchi 6. Bronchioles 7. Terminal bronchioles Respiratory Airways 8. Respiratory bronchioles 9. Alveolar ducts 10. Alveolar sacs 11. Alveoli

List some major causes of acute lung injury.

Outline some causes of primary and secondary respiratory failure.

List some of the clinical features of respiratory failure.

Describe the spirometry results for obstructive and restrictive lung disease.

Type I Respiratory Failure (acute hypoxaemia) V/Q mismatch asthma, COPD, pulmonary embolism R!L shunt - intrapulmonary AV malformations, consolidation (pneumonia) Impaired diffusion oedema, emphysema, interstitial lung disease Type II Respiratory Failure (hypercapnia) CNS impairment - drug OD, brainstem injury, hypothyroidism Neuromuscular impairment - myasthenia gravis, Guillain-Barre syndrome, phrenic nerve injury Respiratory muscle weakness fatigue, myopathy, electrolyte derangements Increased respiratory load -!resistance (bronchospasm), " pulmonary compliance (atelectasis, alveolar oedema), " chest wall compliance (pneumothorax, pleural effusion)

Infection sepsis, diffuse pulmonary infections, gastric aspiration Physical / injury - mechanical trauma, pulmonary contusions, neardrowning, fractures with fat embolism, burns, ionising radiation Inhaled irritants - oxygen toxicity, smoke, irritant gases, chemicals Chemical injury - heroine / methadone overdose, acetylsalicylic acid, barbiturate overdose, paraquat Haematological conditions - multiple transfusions, DIC Pancreatitis Uraemia Cardiopulmonary bypass Hypersensitivity reactions - organic solvents Drugs

Features of Hypoxaemia Dyspnoea Cyanosis Restlessness, confusion, anxiety, delirium Tachypnoea, tachy/bradycardia Hypertension Arrythmia Features of Hypercapnia Dyspnoea + headache Hyperaemia (peripheral + conjunctival) Hypertension Tachycardia, tachypnoea Impaired consciousness Papilloedema Asterixis

List some of the major causes of community-acquired pneumonia.

List some of the major causes of nosocomial pneumonia.

Describe the four stages of lobar pneumonia.

State some of the factors used to assess PSI score for pneumonia severity.

Gram negative bacteria Klebsiella (4%) Escherichia coli Pseudomonas(5%) MRSA Polymicrobial (13%) Unknown(33%)

Pneumococcus (30-60%) Haemophilus influenzae (10%) Moraxella catarrhalis Staphylococcus aureus Mycoplasma (10-30%) Legionella (2-10%) Chlamydophila (5-10%) Gram negative bacteria Viruses influenzae, HMPV, RSV, adenovirus Unknown (40-50%)

o o o o o o o o o o o

> 50 years Altered mental status Pulse > 125 bpm Respiratory rate >30 /min Systolic BP <90 mmHg Temperature <35 or 40 History of neoplastic disease History of CHF History of cerebrovascular disease Renal disease Liver disease 1. Congestion lung is heavy, boggy, and red with intraalveolar fluid containing few neutrophils 2. Red hepatisation massive confluent exudation with neutrophils, RBC, fibrin within alveoli 3. Grey hepatisation disintegration of RBC and persistence of fibrinosuppurative exudates 4. Resolution digestion of consolidated exudate # granular, semifluid debris

State several sources of pathogen for lung abscesses.

Outline the four requirements for consent and refusal of treatment.

Briefly explain the law in Australia regarding refusal of treatment for children in the cases of blood transfusion, immunisations, and newborn screening.

Outline the anatomical distribution of the different types of emphysema.

1. Aspiration acute alcoholism, coma, anaesthesia 1. A voluntary decision 2. An informed decision o Awareness of consequences / risks o Awareness of alternatives 3. A competent patient (some asymmetry) o Competent until proven incompetent must be rebutted by demonstrating impairment o Patients are not obliged to demonstrate competence doctor must demonstrate incompetence 4. Consent to / refusal of a specific procedure under specific circumstances 2. Preceding primary lung infection post- pneumonia / transplant 3. Septic embolism thrombophlebitis, vegetations of IE 4. Neoplasia secondary infection, especially when the bronchopulmonary segment is obstructed 5. Miscellaneous direct penetration, local spread, haematogenous spread o Direct traumatic penetration o Spread of infection from oesophagus, spine, subphrenic space, pleural caivyt o Haematogenous seeding by pyogenic organisms Primary crytogenic lung abscess unknown cause; when all other causes have been excluded

Centriacinar respiratory bronchioles (distal alveoli spared) of upper lobes Panacinar from respiratory bronchioles # terminal alveoli; inferior & anterior parts of lung Paraseptal distal acinus (proximal portion normal); usually upper lobes Irregular any / all parts of the acinus, anywhere in the lung

1. Refusing blood transfusions transfusion is mandatory where life is at risk; overrides parental refusal 2. Refusing immunisations - no legal coercion in Australia i.e. immunisations can be refused 3. Refusing newborn screening - screening is almost universal and routine, but no legal requirement

List the major airway changes that occur with asthma.

Outline the immediate and late pathogenesis of asthma.

List some major causes of bronchiectasis.

Describe the main features of restrictive lung disease.

Immediate Phase Mediated by mast cells Major effects: bronchospasm, vasodilation, !vessel permeability, recruitment of late phase cells 1. 2. Binding of allergen to IgE on mast cell surface # mast cell granulation Stimulation of B cell IgE production by mast cell mediators

1. Inflammation o Mediated by activated T2H lymphocytes secrete cytokines o IL-5 activation of eosinophils o IL-4/IL-13 expression of IgE on mast cells & eosinophils o IL-4 - expression of eosinophil-chemotaxins on endothelium 2. Bronchoconstriction - proteases from mast cell degranulation 3. Oedema - from inflammation 4. "Mucus secretion 5. Smooth muscle hypertrophy - GFs from inflammatory cells 6. Damage to epithelium & shedding - from inflammation

Late Phase Mediated by TH2 cells Major effects: smooth muscle hypertrophy 1. 2. 3. Influx of TH2 cells, eosinophils, inflammatory cells Secretion of cytokines by eosinophils (cysteine leukotrienes, cytokines, chemokines, toxic proteins) Release of growth factors by inflammatory cells smooth muscle hypertrophy and hyperplasia

Clinical Dyspnoea " lung volumes "compliance Radiological Diffuse infiltrates and ground-glass shadows Pathological Diffuse, chronic inflammation Fibrosis of alveolar interstitium

Obstruction cystic fibrosis, primary ciliary dyskinesia, tumour, foreign body, mucus impaction Infection (necrotising) bacteria, viruses, fungi Immune hypergammaglobulinaemia, immunodeficiency Other rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, post-transplantation

Describe the different types of coal workers pneumoconiosis.

Outline the morphology of pulmonary hypertension.

Outline the major medical conditions associated with smoking.

What is Goodpasture Syndrome?

Medial hypertrophy of muscular and elastic arteries Atheromas of pulmonary artery

Anthracosis small, harmless accumulations in the lungs (smokers and city dwellers) Simple CWP aggregates of coal dust-laden macrophages forming macules; no significant dysfunction Complicated CWP severe fibrosis and scarring in areas of dust accumulation; respiratory insufficiency

Right ventricular hypertrophy Plexiform lesions (advanced) a web of capillary formations that span the lumens of small vessels

Cancer lung, lip, mouth, pharynx, larynx, oesophagus, pancreas, bladder, kidney, cervix COPD both chronic bronchitis and emphysema Atherosclerosis Myocardial infarction by promoting atherosclerosis Peptic ulcers increased stomach acid secretion Neonatal effects (maternal smoking) - "birthweight, !mortality (perinatal), ! childhood asthma

Autoimmunity against 3 chain of collagen IV # inflammatory destruction of BM of renal glomeruli and pulmonary alveoli Mostly in males in teens or 20s; ~90% are active smokers

List some major organ systems affected by sarcoidosis.

Outline the major morphological features of usual interstitial pneumonia (UIP).

Discuss some of the outcomes of several major paraneoplastic syndromes occurring with pulmonary carcinoma.

Which types of pulmonary carcinoma tend to be peripheral and which tend to be central / hilar? Give a typical morphological feature of each.

Patchy interstitial fibrosis Fibroblastic foci in bronchiolar walls Honeycomb lung (chronic) fibrosis & lining of cystic spaces with type II pneumocytes

Lungs fibrosis & hyalinisation Lymph nodes especially hilar & mediastinal Spleen Liver Bone marrow Skin nodules, plaques, flattened lesions Eye iritis Lacrimal glands Salivary glands Muscle

Adenocarcinoma peripheral (glands, more likely to spread) Bronchioalveolar peripheral (butterflies on a fence, less likely to spread) Squamous cell carcinoma hilar (variable differentiation) Small cell carcinoma hilar (nests of oatlike cells, little cytoplasm, malignant)

Hormone-Secreting Tumours ADH ! Hyponatraemia ACTH ! Cushing syndrome PTH ! hypercalcaemia Prostaglandin E & some cytokines ! hypercalcaemia Calcitonin ! hypocalcaemia Gonadotropins ! Gynaecomastia Serotonin & Bradykinin ! carcinoid syndrome (intermittent diarrhoea, flushing and cyanosis) Other Syndromes Lambert-Eaton myasthaenic syndrome - muscle weakness ( autoantibodies to neuronal Ca2+ channel) Peripheral neuropathy usually only sensory Acanthosis nigricans Hypertrophic pulmonary osteoarthropathy ! digital clubbing

Outline some clinical features indicative of invasion of a pulmonary carcinoma.

What is the involvement and prognosis of the two stages of small cell pulmonary carcinoma?

Outline a treatment strategy for nonsmall cell pulmonary carcinoma.

Describe some general mechanisms that lead to pleural effusion, and give an example of a condition that can cause each.

Involvement Confined to one side of the chest and regional lymph nodes Extending beyond limited stage

Median Survival

Pleural effusion (pleura) Hoarseness (left recurrent laryngeal nerve) Dysphagia (oesophagus) Diaphgram paralysis (phrenic nerve) Rib destruction (chest wall) Horners syndrome (sympathetic ganglia) Pericarditis/tamponade (pericardial involvement)

Limited stage

18 months

Extensive stage

9 months

!Hydrostatic pressure congestive heart failure !Vascular permeability pneumonia "Osmotic pressure nephrotic syndrome !Intrapleural negative pressure atelectasis "Lymphatic drainage mediastinal carcinomatosis

Resectable stages I, II and IIIa o Surgery resection of tumour solitary metastasis (or pneumonectomy / lobectomy if localised) o Adjuvant chemotherapy (not stage I) cisplatin or carboplatin o Radiation therapy after chemotherapy for stage IIIa or in patients who cannot have surgery Non-resectable stages IIIb and IV o Confined to chest high dose chemotherapy (cisplatin / carboplatin) + radiation therapy o Extrathoracic disease radiation therapy focused on local sites + systemic chemotherapy

List some major causes of pleuritis.

List some causes of non-productive cough.

Outline some clinical features of hepatic failure (not portal hypertension).

Describe the three major pathological events occurring with liver cirrhosis.

Chronic bronchitis Bronchiectasis Pneumonia Asthma Foreign body (late response) Lung abscess Tuberculosis (when cavitating) Smoking morning coughs

Tuberculosis Pneumonia Lung infarcts Lung abscess Bronchiectasis Rheumatoid arthritis Disseminated lupus erythematosus Uraemia Diffuse systemic infections Metastasis Radiation treatment

1. Death of hepatocytes - surviving hepatocytes stimulated to regenerate & proliferate as spherical nodules 2. Extracellular matrix deposition - deposition of collagen I & III in space of disse ! fibrotic septal tracts o Proliferation of hepatic stellate cells due to chronic inflammatory cytokines, mediators from kupffer cells and endothelial cells, in response to disruption of ECM, and direct activation by toxins 3. Vascular reorganisation connection of vessels in the portal region to terminal hepatic veins

Jaundice Peripheral oedema (hypoalbuminaemia) Cerebral dysfunction (hyperammonaemia) Faetor hepaticus musty/sweet & sour body odour (GIT bacteria convert methionine to mercaptans which are then shunted from the portal into the systemic circulation) Palmar erythema Spider naevi Hypogonadism Gynaecomastia Impaired oestrogen metabolism (!oestrogen)

Describe the morphology of liver cirrhosis.

Outline the major clinical consequences of portal hypertension.

What is the mechanism of spread for each type of viral hepatitis, and which types are likely to become chronic?

What do IgM, surface antibody and core antibody mean clinical in the context of hepatitis serology?

1. Ascites serous fluid accumulation in the peritoneal cavity 2. Portosystemic shunting haemorrhoids, oesophageal varices, caput medusae 3. Congestive splenomegaly 4. Hepatic encephalopathy

1. Bridging fibrous septa bands / scars linking portal tracts with one another and portal tracts with terminal hepatic veins 4. Parenchymal nodules hepatocytes surrounded by fibrosis, resulting from hepatocyte regeneration 5. Disruption of liver architecture diffuse fibrosis and parenchymal injury

IgM = acute infection Surface Ab only = vaccinated/passive immunity Core Ab + surface Ab = active immunity - past infection Surface/Core Ag + IgM = active infection Surface/Core Ag only = chronic infection Surface Ag only = carrier

Faecal oral Hepatitis A & E Parenteral Hepatisis B & D ~Blood only - Hepatitis C

Chronic Hepatitis B (5%) and C (75%) ! cirrhosis, carcinoma

For which type of hepatitis is interferon -2b indicated? For which type is it indicated in chronic cases only?

What are the major aetiology organisms of liver abscess? What are the major methods of spread?

Outline some major patterns of druginduced hepatic injury and the drugs associated with them.

What is the basic pathogenesis of hepatic steatosis?

Bacterial - Escherichia coli, Klebsiella spp., Proteus, Enterococcus, Staphylocccus aureus, Streptococcus fecalis Amoebic Entamoeba histolytica Fungal Candida Albicans (only severe immunosuppression) Indicated for all cases of hepatitis B Indicated for chronic cases of hepatitis C (with ribavirin)

Modes of Spread Portal vein (24%) appendicitis, diverticulitis, colitis Arterial supply (15%) infective endocarditis, pyelonephritis Ascending biliary infection (30-60%) cholecystitis, cholangitis, pancreatitis Direct invasion Penetrating injury Unknown (20%)

1. Shunting of normal substrates away from catabolism and toward lipid biosynthesis 2. Impaired assembly and secretion of lipoproteins 3. Increased peripheral catabolism of fat

Hepatocellular cholestasis contraceptives, anabolic steroids Cholestasic hepatitis antibiotics, phenothiazines Hepatocellular necrosis methyldopa, phenytoin, acetaminophen Steatosis ethanol, methotrexate, corticosteroids Steatohepatitis amiodarone, ethanol Fibrosis methotrexate, enalapril Granulomas sulphonamides Neoplasms oral contraceptives, anabolic steroids

Outline the morphology of alcoholic hepatitis.

What are the major causes of death for people with alcoholic liver disease?

What is Wilsons disease and what are some of the manifestations of it?

Outline the aetiologies of hereditary and acquired haemochromatosis.

1. Hepatic coma 2. Massive GIT haemorrhage 3. Infection 4. Hepatorenal syndrome 5. Hepatocellular carcinoma

1. Hepatocyte swelling & necrosis single / scattered foci of cells undergo swelling and necrosis, due to accumulation of fat, water and proteins 2. Mallory bodies accumulation of cytokeratin filaments and proteins ! eosinophilic cytoplasmic clumps 3. Neutrophilic reaction entry of neutrophils into the hepatic lobule and accumulation around degenerating hepatocytes 4. Fibrosis activation of sinusoidal stellate cells and portal tract fibroblasts

Hereditary haemochromatosis mutations in HFE, transferrin receptor 2 (TfR2), hepcidin, haemojuvelin (HJV) Haemosiderosis (secondary haemochromatosis) o Parenteral iron overload transfusions, long-term dialysis, aplastic anaemia, sickle cell disease, myelodysplastic syndromes, leukaemias, iron-dextran injections Ineffective erythropoeisis -thalassaemia, sideroblastic anaemia, pyruvate kinase deficiency
Increased oral intake of iron Congenital antranferrinaemia Chronic liver disease Neonatal haemochromatosis

Accumulation of toxic levels of copper in tissues, especially the liver, brain and eye (! caeruloplasmin) Liver steatosis (fatty liver), acute chronic hepatitis (cirrhosis) Brain affects the basal ganglia ! atrophy and cavitation ! behavioural changes, psychosis, tremor Eye Kayser-Fleischer rings (green-brown deposits in the cornea)

o o o o

How does haemochromatosis cause damage to tissues?

What are the three growth patterns of hepatocellular carcinoma?

List some major causes of productive cough.

Outline some major causes of upper GI bleeding.

Unifocal, large mass Multifocal, widely distributed masses of various size Diffusely infiltrative

1. Lipid peroxidation (iron-catalysed free radical reactions) 2. "collagen formation by activation of hepatic stellate cells 3. Interaction of ROS / iron with DNA ! lethal cell injury

Gastritis Ulcer gastric, duodenal, stomal (NSAIDs, alcohol) GORD Oesophageal varices due to portal hypertension (~cirrhosis) Mallory-Weiss syndrome Carcinoma - gastric / oesophageal Anticoagulant therapy Vascular malformations Hereditary haemorrhagic telangiectasia

Infection URT, LRT, TB, whooping cough Inhaled irritants smoke, dust fumes Inhaled foreign body Bronchial neoplasm Interstitial lung disorders fibrosing alveolitis, extrinsic allergic alveolitis, pneumoconioses, sarcoidosis Left ventricular failure GORD; hiatus hernia Postnasal drip Pleural irritation

Outline the effects of alcohol on metabolic pathways.

State some pathologies associated with heavy alcohol consumption.

What are some options for acute management of oesophageal variceal bleeding?

List the three main aetiological agents of infectious oesophagitis.

Brain: o Impaired development o Wernicke-Korsakoff syndrome (vision changes, ataxia, impaired memory) o Psychological cravings, irritability, antisociality, depression, anxiety, panic, psychosis, hallucinations/delusions, sleep disorders Gastrointestinal: o Cancer of mouth, trachea, oesophagus o Liver cirrhosis, hepatitis o Chronic gastritis o Pancreatitis Blood: anaemia Heart: alcoholic cardiomyopathy Systemic: " risk of diabetes type 2


Hyperlactacaemia, hyperuricaemia, acidosis o !NADH/NAD+ ratio due to usage by ADH ! "pyruvate / lactate o "lactate ! acidosis ! #renal excretion of uric acid ! hyperuricaemia ! lipogenesis and " lipid oxidation o "NADH/NAD+ ratio ! " -glycerophosphate ! "triglyceride ! fatty accumulation o # citric acid cycle activity ! # fatty acid oxidation o # hepatic release of lipoproteins o " mobilisation of hepatic fat o " hepatic uptake of dietary lipid from blood " protein synthesis - unknown mechanism Glucose metabolism o Acute intoxication ! hypoglycaemia ! sudden death o "NADH/NAD+ ratio blocks gluconeogenesis ! #availability of TCA intermediates (e.g. OAA) o Depleted glycogen stores unable to buffer blood glucose level


3. 4.

Herpes virus Cytomegalovirus Candida albicans

Endoscopic band ligation Splanchnic vasoconstrictors (following stabilisation) splanchnic vasoconstrictors o Octreotide well-tolerated, no systemic effects (1st line) o Vasopressin may cause MI; not to be used with GTN Prophylactic antibiotics Balloon tamponade direct compression of varices, to prevent bleeding on failure of endoscopic / pharmacologic therapy, or in the unavailability of emergency endoscopy Liver transplantation patients with uncontrolled bleeding and end-stage liver disease

Outline the three morphological changes that occur with GORD.

List some major clinical features of GORD.

What is Barrett Oesophagus?

What are the histological features of Barrett oesophagus?

Heartburn (pyrosis) often after meals, may worsen with bending over / lying down, relieved by antacids Acid regurgitation of sour-tasting gastric contents Dysphagia & indigestion Epigastric pain Belching Globus (lump in throat) Halitosis (bad breath) Upper GI bleeding 1. Hyperaemia redness of the oesophagus on endoscopy 2. Eosinophilic infiltrate, followed by neutrophils 3. Basal hyperplasia exceeding 20% of total epithelial thickness

Goblet cells (not normally in the oesophagus) diagnostic; indicative of intestinal metaplasia Dysplasia may or may not be present; low grade or high grade; confers increased risk of neoplasia o " epithelial proliferation o Atypical mitoses o Nuclear hyperchromasia and stratification o Irregularly clumped chromatin o " nuclear:cytoplasmic ratio Metaplasia (! intestinal cells) within the oesophageal squamous mucosa A complication of GORD (10% of symptomatic cases) mostly in white males ages 40-60 Normal G-O junction Confers increased risk of oesophageal adenocarcinoma

Where in the oesophagus do adenocarcinoma and squamous cell carcinoma generally occur?

List some risk factors for peptic ulcer disease.

What are the histological features of inflammatory & hyperplastic polyps?

Describe the two growth patterns of gastric cancer.

H. pylori infection (50% of the worlds population) Chronic NSAID use (e.g aspirin - #prostaglandins) Hypercalcaemia (chronic renal failure / "PTH) Genetic Factors (more common in O blood group) Smoking (#blood flow) Age (>45 years old) Male Gender (3x more common) Alcohol Adenocarcinoma distal 1/3 of oesophagus & gastric cardia Squamous cell carcinoma middle 1/3 of oesophagus

Intestinal growth pattern Bulky tumours composed of glandular structures May penetrate the gastric wall, but typically grow along broad cohesive fronts Diffuse growth pattern Cells are discohesive - no glands Signet-ring cells cells with mucin vacuoles that expand the cytoplasm and push nucleus to the periphery Linitis plastica large areas of infiltration, diffuse rugal flattening and a rigid, thickened wall Irregular cystically dilated and elongated glands Oedematous lamina propria

Outline the pathogenesis of acute pancreatitis.

List the major aetiologies of acute pancreatitis.

Outline the major morphological changes that occur with acute necrosis.

List the major clinical features of acute pancreatitis.

Metabolic alcoholism, hyperlipoproteinaemia, hypercalcaemia, drugs (azathioprine) Genetic o Cationic trypsinogen (PRSS1) mutation o Trypsin inhibitor mutation (SPINK1) o CFTR mutation (cystic fibrosis) Mechanical gallstones, trauma, operative / endoscopic injury Vascular shock, atheroembolism, vasculitis Infectious mumps

1. Pancreatic duct obstruction gallstones, biliary sludge ! " intrapancreatic pressure ! accumulation of enzyme-rich fluid in the interstitium 2. Primary acinar cell injury in cases caused by viruses, drugs, ischaemia, shock or direct trauma 3. Defective intracellular transport of proenzymes ! activation by lysosomal hydrolases 4. Alcohol consumption ! secretion of protein-rich pancreatic fluid ! deposition of protein plugs, obstruction of pancreatic ducts

Abdominal pain constant, intense, often referred to upper back and occasionally left shoulder Anorexia, nausea, vomiting Signs of malabsorption, including steatorrhoea Pallor, excessive sweating, fever

Oedema Fatty necrosis Acute inflammation Proteolytic destruction of parenchyma Destruction of blood vessels

Where are most pancreatic cancers situated? What is an outcome of this kind of cancer?

List some general causes of abdominal pain.

Differentiate between Crohn disease and ulcerative colitis.

What is the major gene mutation associated with Crohn disease?

Inflammation IBD, appendicitis, cholcystitis, pancreatitis, salpingitis, diverticulitis Perforation duodenal ulcer, gastric ulcer, faecal peritonitis, biliary peritonitis Obstruction biliary colic, bowel obstruction, ureteric colic, acute urinary retention, intestinal infarction Haemorrhage ruptured ectopic pregnancy, ruptured spleen / liver, ruptured ovarian cyst, ruptured AAA Torsion sigmoid volvulus, torsion of ovarian cyst, torsion of testes

Head of pancreas cancer Usually obstructs the distal common bile duct causing post-hepatic jaundice.

Crohn Disease Bowel Region Distribution Wall NOD2 (nucleotide oligomerisation binding domain 2) Ulcers Fat / vitamin malabsorption Malignant potential Toxic Megacolon Ileum / colon Skip lesions Thick Deep Yes Yes No

Ulcerative colitis Rectum + colon Continuous / diffuse Thin Superficial No Yes Yes

Outline intestinal features of inflammatory bowel disease.

Outline extra-intestinal features of inflammatory bowel disease.

Outline the four phases of nutrient absorption that can be affected in malabsorption.

Outline the major aetiologies of ischaemic bowel disease.

A PIE SACK Aphthous ulcers Pyoderma gangrenosum Iritis (uveitis) Erythema nodosum Sclerosing cholangitis Ankylosing spondylitis Clubbing Kidney nephrotic syndrome

Crohn - usually begins with intermittent attacks of relatively mild diarrhoea, fever and RLQ pain o Upper GIT involvement nausea, vomiting, epigastric pain, obstruction o Iron-deficiency anaemia o Malabsorption iron deficiency anaemia, general malaise, weight loss, loss of energy o Perianal abscesses, anal fissures, rectovaginal fistulae Ulcerative colitis - presents with a triad of diarrhoea, bloody stools and tenesmus o Rectal bleeding, abdominal pain, tender abdominal mass o Systemic features (late) tachycardia, fever, anorexia

Mucosal infarction and mural infarction usually result from acute / chronic hypoperfusion Cardiac failure Shock Dehydration Vasoconstrictive drugs Transmural infarction usually results from acute vascular obstruction Atherosclerosis Aortic aneurysm Hypercoagulable states Oral contraceptive use Embolisation of cardiac vegetations or aortic atheromas

1. Intraluminal digestion proteins, fats, carbohydrates broken down before absorption 2. Terminal digestion hydrolysis of carbohydrates and peptides by brush border disaccheridases & peptidases 3. Transepithelial transport nutrients, fluids and electrolytes are transported across the SI wall 4. Lymphatic transport of absorbed lipids

What are the two watershed areas at highest risk of bowel infarction?

Outline the pathogenesis of diverticulum formation and diverticulitis.

What is the difference between internal and external haemorrhoids? What are the different degrees of haemorrhoids?

What are the four major endogenous regulators of vomiting whose receptors are targeted by antiemetics?

1. Focal weakness - due to o Discontinuities where nerves, arterial vasa recta and connective tissue penetrate the inner circular muscular layer ! less reinforced and more likely to form diverticula o Lack of external longitudinal muscular layer in the colon this layer becomes taeniae coli 2. " Intraluminal pressure due to o Exaggerated peristaltic contractions o Western dietary factors (!#GIT motility) low fiber, high fat, high refined carbohydrates 3. Faecalith impaction causes diverticulitis o Lodging of faecalith in diverticulum ! compression of colon wall ! inflammation, ischaemia

Splenic flexure superior and inferior mesenteric arterial circulations end Sigmoid colon / rectum mesenteric, pudendal, iliac circulations end

Histamine (H1 receptors) Acetylcholine (muscarinic receptors) Dopamine Serotonin (5-HT3 receptors)

Types Internal haemorrhoids dilation of superior haemorrhoidal plexus (above anorectal line) External haemorrhoids dilation of inferior haemorrhoidal plexus (below anorectal line)

Severity 1st degree remain in the rectum 2nd degree prolapse on defecation, spontaneously reduce 3rd degree prolapse on defecation, reduce manually 4th degree remain persistently prolapsed

What are the four classes of laxatives, their mechanism and an example of each?

What are the major antimotility agents?

List some different types of rectal bleeding and give a cause for each.

List the five types of diarrhoea and give an example of each.

Opiates Complex effects involving " tone & rhythmic contraction as well as # propulsive activity and sphincter contraction Codeine and loperamide are the main opiates used Loperamide is relatively selective for the GIT and undergoes enterohepatic cycling (# cramping)

Bulk laxatives (methylcellulose, bran, psyllium) carbohydrates that retain water ! expansion of the GIT ! promote peristalsis Osmotic laxatives (MgSO4, lactulose) osmotically draw water into the GIT Faecal softeners (docusate sodium) affect faecal composition Stimulant laxatives (castor oil, anthraquinones) - " electrolyte & water secretion by mucosa

Deranged Motility Osmotic

Hyperthyroidism, IBS, diabetic neuropathy Lactose intolerance, laxatives Physical blanketing (Giardia), reduced surface area (coeliac disease), maldigestion (pancreatic insufficiency) Inflammatory bowel disease, Infection (shigella/ entamoeba) Enterotoxin-mediated (cholera), hormonal, villous adenoma

Bright red blood in toilet separate from faeces internal haemorrhoids Bright red blood on toilet paper internal haemorrhoids, fissure, anal carcinoma, pruritis, anal warts Blood on underwear o With mucus - 3rd/4th degree haemorrhoids, prolapsed rectum, mucosal prolapse o No mucus ulcerated perianal haematoma Blood in faeces o Mucus colorectal carcinoma, proctitis, colitis, mucosal polyp, ischaemic colitits o No mucus small colorectal polyp, small colorectal carcinoma o Large amounts of mucus (little blood) villous papilloma of rectum / colon) o With mentstruation (rare) rectal endometriosis Melaena GIT bleeding (usually upper) with long transit time to anus Torrential haemorrhage (rare) diverticular disorder, angiodysplasia




Outline some indications for colonoscopy.

List the boundaries of the inguinal canal, as well as the type of hernia that occurs through it.

What is the significance of Hesselbachs triangle, and what are its boundaries?

Inguinal herniae where do they protrude through and are they congenital or acquired?

Site of indirect inguinal hernias Anterior external oblique aponeurosis Medial conjoint tendon (formed by the internal oblique and transversalis abdominis) Lateral Inguinal ligament (formed by the external oblique aponeurosis) Posterior transversalis fascia

Colorectal cancer screening Polyp evaluation and removal Bowel resection pre/post surgery Inflammatory bowel disease management Severe acute bleeding to identify a bleeding site and perform therapeutic intervention Decompression of the colon in the case of sigmoid volvulus

Indirect inguinal hernia (60%) Through the deep ( superficial) inguinal ring Due to a congenital defect patent processus vaginalis Direct inguinal hernia (30%) Through Hesselbachs triangle Due to acquired weakness in the abdominal wall

Site of direct inguinal hernia Medial rectus abdominis muscle Superolateral inf.epigastric vessels Inferior inguinal ligament

Outline the pathogenesis of abdominal herniae.

What are the major pathological events that lead to bacterial / chemical entry into the body cavity causing peritonitis?

What are some possible complications of surgery?

Leakage of bile / pancreatic enzymes ! sterile peritonitis Perforation or rupture of the biliary system ! highly irritating peritonitis bacterial superinfection Acute haemorrhagic pancreatitis leakage of pancreatic enzymes and fat necrosis Foreign material induces granulomas and fibrous scarring Endometriosis haemorrhage into the peritoneal cavity Ruptured dermatoid cysts release keratins that invoke an intense granulomatous reaction Perforation of abdominal viscera


" Intraabdominal pressure o Obesity o Ascites o Pregnancy o Chronic cough, especially COPD o Constipation ! straining to defecate o Urinary outflow obstruction o Heavy lifting Peritoneal dialysis Weakened/Defected membranes / muscles o Congenital patent processus vaginalis ! indirect o Progressive weakening of connective tissue age, smoking, systemic disease, chronic steroids o Congenital collagen abnormalities

2. 3.

Pulmonary bronchitis, atelectasis, bronchopneumonia, lung abscess, PE Cardiovascular shock (neurogenic / hypovolaemic), haemorrhage, DVT Gastrointestinal ileus (delayed return of intestinal movements), vomiting, abdominal distension Urinary urinary retention, uraemia Wounds haematoma, infection, stitch abscess, cellulitis, dehiscence