Pathology Flashcards

Question

Describe examples of each type of hypertrophy

Answer 1

* Physiological: skeletal muscles with exercise, uterus in pregnancy, breasts in lactation * Pathological: prostate in BPH, heart in chronic hypertension One of each to pass

Answer 2

* Hyperplasia is an increase in number of cells in organ usually resulting in increase in volume, occurs in cellular population capable of synthesising DNA thus permitting mitotic division * Hypertrophy is an increase in size of cells, causes an increase in size of organs * Hypertrophy and hyperplasia often co-exist 2/3 to pass

Answer 3

* Decreased oxidate phosphorylation and **decreased ATP production** * **Failure of Na pump** causing K efflux and Na influx * Cell swelling triggers **calcium influx** * Further decreased ATP production, enzymes activated, causing decreased glycogen and protein synthesis * **Cytoskeleton changes**: loss of microvilli, "bleb"formation, "myelin figures" from degenerating cell membranes, causing mitochondrial swelling 3 of 4 bold to pass

Answer 4

1. Severe mitochondrial swelling 2. Extensive damage to plasma membrane (including "myelin figures") 3. Lysosomal swelling 4. Necrosis or apoptosis Any 2 to pass

Answer 5

**Increased injury to ischaemic cells with restoration of perfusion**. Due to generation of **reactive oxygen** and nitrogen species Calcium re-enters the cell **activating inflammation and complement cascades** At least one concept to pass

Answer 6

Initial reversible Irreversible (prolonged ischaemic injury and necrosis) 2/2 to pass

Answer 7

* Replacement of one normal cell type with another normal cell type; can be adaptive or pathological * Columnar to squamous (respiratory - chronic irritation eg. smoking; excretory ducts due to stones eg. salivary, bile) * Squamous to columnar (Barrett's oesophagus) * Connective tissue (myositis ossificans) Correct definition and 2 examples to pass

Answer 8

Malignant transformation Reversibility/resolution Ongoing 2 to pass

Answer 9

A reprogramming of epithelial stem cells of undifferentiated mesenchymal cells Involving signals from cytokines, growth factors, ECM components, genes, DNA methylation

Answer 10

* Usually irreversible injury * Often adjacent inflammation * **Swollen cells** * Increased eosinophilia * Myelin figures (whorls of cell membrane bits) * Nucleus faces (karyolysis), may shrink (pyknosis) and then fragments (karyorrhexis) * Organelle disruption -> amorphous mass * **Cell membrane disrupted**, contents released Bold to pass

Answer 11

* **Coagulative** (architecture preserved) * **Liquefactive** (digestion -> liquid viscous mass) * Caseous (friable white) * Gangrenous (typically coagulative, superimposed liquefaction from infection) * Fat necrosis (focal areas of fat destruction) * Fibrinoid necrosis Bold to pass

Answer 12

* The first is the inability to reverse **mitochondrial dysfunction** (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury * The second is the development of profound **disturbances in membrane** function Bold to pass

Answer 13

1. Cardiac muscle - CK and troponin 2. Liver - Alkaline phosphatase 3. Hepatocytes - transaminases 1 example to pass

Answer 14

Abnormal accumulation of **triglycerides** within parenchymal cells

Answer 15

Liver Heart, muscle, kidneys Need 2 to pass

Answer 16

* Alcohol abuse * Toxins * Protein malnutrition * Diabetes mellitus * Obesity * Anoxia * Starvation * In the liver it results from defects in any one of the events in the sequence from fatty acid entry to lipoprotein exit Need 2 to pass

Answer 17

90% near major arterial **branch points** * **Anterior** cerebral artery/anterior communicating artery (40%) * Middle cerebral artery/Anterior choroidal artery (34%) * Internal carotid artery / posterior communicating artery (20%) * Basilar artery / posterior communicating artery Multiple in 20-30% cases at autopsy Bold to pass

Answer 18

* Increased likelihood with **size** (>10mm) - 50% risk of rupture per year * May occur at anytime but in amount 1/3 associated with **acute increases in ICP** (e.g straining at stool; orgasm) Bold to pass

Answer 19

* Acute events (hours to days) - **ischaemic injury (stroke)** from **vasospasm** (especially basal SAH) * Late events (healing process) - meningeal fibrosis and **scarring**; may lead to obstruction to **CSF flow** and/or to CSF absorption * Death Two of bold to pass

Answer 20

Medial muscular layer thins as approaches neck and has thickened hyalinised intima, covered with normal adventitia

Answer 21

1. Acute onset of **severe headache**, often with loss of consciousness 2. **25-50% die at the time** 3. **Re-bleeding is common** 4. Vasospasm in vessels other than the bleeding site can cause secondary ischaemic injury 5. In the healing phase, meningeal fibrosis and scarring can cause secondary hydrocephalus 3 or 4

Answer 22

* **Arterial thrombosis** - **atherosclerosis** most common * Cerebral emboli * Lacunar infarcts from small vessels * Cerebral arteritis * Arterial dissection * Venous infarction Thrombus + one to pass

Answer 23

* Left atrium/ventricle thrombus * Valvular vegetations * Patent foramen ovale causing paradoxical emboli * Carotid plaque At least 2 to pass

Answer 24

* **Thrombotic occlusion** - **atherosclerosis** most common * **Embolism** - AMI, mural thrombus, valvular heart disease, AF, vascular surgery and shower embolism, fat embolism, endocarditis * Inflammatory process leading to luminal narrowing - infectious vasculitis, autoimmune vasculitis, primary angiitis of the CNS

Answer 25

* Haemorrhagic **red** - multiple, sometimes confluent, petechial haemorrhages typically associated with **embolic** events. Thought to be secondary to **reperfusion** either via collateral of dissolution of materials. Greater risk if anticoagulated * Non-haemorrhagic (**pale/bland anaemic** - usually associated with **thrombosis** Bold causes and concepts

Answer 26

* Complications higher with embolic/haemorrhagic CVAs * Trying to reverse injury in ischaemic penumbra * In non-haemorrhagic CVA little macroscopic change can be seen within the first 6 hours * Earlier treatment leads to better outcome and less haemorrhagic risk

Answer 27

* **Global cerebral ischaemia** (ischaemic/hypoxic encephalopathy) when there is a **generalised reduction** of cerebral perfusion * **Focal cerebral ischaemia** follows reduction of blood flow to a **localised area** of the brain Both types and description to pass

Answer 28

* **Embolic** - from cardiac mural thrombi, thromboembolism from arteries, tumour, fat or air * **Thrombotic arterial occlusion** - in situ thrombosis (large vessel disease * **Vasculitis** (small vessel disease) - infections (immunosuppression and aspergillus, CMV encephalitis, syphilis, TB); non-infectious e.g polyarteritis nodosum, primary angiitis * **Others** - amphetamine, cocaine, heroin, dissecting aneurysm extra cranial arteries, hypercoagulable states 3 causes plus 1 example of each

Answer 29

* **Lacunar infarcts** (in lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, pons) * **Slit haemorrhage** * **Hypertensive encephalopathy** * **Massive intracerebral haemorrhage** 4 out of 4 to pass

Answer 30

* **Arterial thrombosis, cerebral embolism** * *Lacunar* - arteriosclerosis of the vessels in the lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus and pons * *Arteritis* - giant cell, polyarteritis nodosum, SLE, infectious * *Arterial dissection* * *Venous infarction* - hanging, venous sinus thrombosis Need bold and one italic to pass

Answer 31

* Source - usually from the heart (**mural thrombus, valvular vegetations**) - **plaques from carotid bifurcation**; - **paradoxical emboli** in patent foramen ovale * Precipitant - AF / cardioversion * Consequence - most commonly **lodges in MCA**, often at branch points, **causes ischaemia** due to poor collateral flow Need at least 1 cardiac and 2 sources in total to pass

Answer 32

* **Vasogenic**: BBB disruption, increased vascular permeability. Fluid shift intravascular to intercellular spaces of brain. May be generalised or localised (inflammation or neoplasm) * **Cytotoxic**: increased intracellular fluid due to neuronal, glial, or endothelial injury eg. generalised hypoxic/ischaemic insult or metabolic damage. Interstitial or ependymal oedema around (lateral) ventricles due to the high pressure of hydrocephalus Bold to pass or basic understanding of two mechanisms

Answer 33

* Flattened gyri * Narrowing of sulci * Compression of ventricles and/or basal cisterns * Herniation 3 of 4 to pass

Answer 34

* **Subfalcine** herniation - asymmetric expansion of cerebrum displaces the cingulate gyrus under the falx cerebri * **Transtentorial** or uncal herniation - medial aspect of the temporal lobe is compressed against the free margin of the tentorium * **Tonsillar herniation** - displacement of the cerebellar tonsils through the foramen magnum 2 of the 3 bold plus correct description

Answer 35

* **Alzheimer's disease** * Frontotemporal dementia * Multi-infarct dementia (vascular) * Parkinson's disease (Lewy bodies) * Creutzfeld-Jakob disease * Neurosyphilis Bold + 2 others to pass

Answer 36

* **Lysis of transmembrane protein amyloid precursor protein by beta and gamma secretes produces A, B and C terminal portion of APP** * AB peptides aggregate into amyloid fibrils and can be directly neurotoxic * C-terminal portion of APP involved in cell signalling and transcription regulation * Severity of Alzheimer's disease is related to loss of synapses

Answer 37

**Hypertension and cerebral amyloid** are the main causes. Other causes include systemic coagulation disorders, neoplasms, vasculitis, aneurysms and vascular malformations 1 of two bold an two others to pass

Answer 38

* Hypertensive intracerebral haemorrhage may originate in the putamen (50-60% of cases), thalamus, pons, cerebellar hemispheres (rarely). * Accept basal ganglia, brainstem At least 2 to pass

Answer 39

There is a deposition of amyloidogenic peptides in the walls of medium- and small- calibre meningeal and cortical vessels. This deposition can result in weakening of the vessel wall and risk of haemorrhage Bonus question

Answer 40

* Extradural * Subdural * Subarachnoid (including intraventricular) * Intraparenchymal 3 of 4 to pass

Answer 41

* Dural **artery tear** (eg. middle meningeal), **usually associated with a skull fracture** * Strips off the dura from the skull * May be a lucid period before acute LOC Must get bold to pass

Answer 42

* **Altered consciousness secondary to a head injury** * **Transient** neurological dysfunction * Transient respiratory arrest * Transient loss of reflexes Features include headache, amnesia, N&V, concentration and memory issues, perseveration, irritability, behaviour/personality changes, dexterity loss, neuropsychiatric syndromes Must get bold + 3 features

Answer 43

* Turbid * Low sugar * High protein * Pleocytosis with neutrophil predominance * Raised neutrophils * +ve bacteria on gram stain or culture 2 to pass

Answer 44

**Viral** Chronic TB Fungal Chemical/drug induced Carcinomatous 3 out of 5 including bold

Answer 45

* Neonates: E.coli and Group B Strep * Children: **Streptococcus pneumoniae**, H.influenza * Adolescent/young adults: **Neisseria Meningiditis, Strep. pneumoniae** * Older adults: Strep pneumoniae, Listeria 1 per age group, must mention bold

Answer 46

* Acute pyogenic: bacterial * Aseptic: viral, chemical * Chronic inflammation: TB infiltration, carcinomatous Must have bacterial, viral and one other

Answer 47

* Raised lymphocytes * Moderately raised protein * Normal glucose * Clear * No bacteria seen

Answer 48

* E. coli * Coxsackie * Non-paralytic polio

Answer 49

* Distinct episodes of **neurological deficits separated in time** * Myriad of presentations as lesions separated by space * Unilateral visual impairment (optic neuritis) is common, brainstem, cord lesions Bold to pass

Answer 50

* Exact etiology not determined * **Autoimmune, demyelinating** disorder, to white matter lesions separated in space * Genetic linkage * ?Microbial/viral triggers * CD4+ Th1 T cells react against myelin antigens, release cytokines, activate macrophages. Inflammatory cells create **plaques** Need bold to pass

Answer 51

* Mildly **elevated protein** * Moderate pleocytosis * Increased proportion of gamma globulin * Oligocloncal bands - reflects B cells Bold to pass

Answer 52

* Diminished facial expression * Stooped posture * Slowness of voluntary movement * Festinating gait (progressively shortened, accelerated steps) * Rigidity * "Pill-rolling" tremor 3 of 6 to pass

Answer 53

* Conditions that cause damage to the **nigrostriatal dopaminergic system** * Parkinsons disease * Post-encephalitis * Familial forms * Trauma/injuries * Drugs - dopamine antagonists/toxins/pesticides * Multiple system atrophy, progressive supranuclear palsy Bold +2 to pass

Answer 54

* No unifying mechanism identified * Misfolded protein/stress response triggered by alpha-synuclein aggregation * Defective proteosomal function due to the loss of the E3 ubiquitin ligase parkin * Altered mitochondrial function caused by the loss of DJ1 and PINK1 * Genetic variants with gene defects * Possible damage to dopaminergic cells from toxins drugs/autoimmune conditions Bonus question

Answer 55

* Death of distal part * Axonal cone of growth 1-2mm per day * Growth through Schwann cell structure * Regenerating clusters

Answer 56

* **Acute phase** - haemorrhage, necrosis, axonal swelling in the surrounding white matter at level of injury * **Late phase** - area of neuronal destruction becomes cystic and gliotic, secondary wallerian degeneration involving long white matter tracts, liquefactive necrosis often seen in CNS 1 acute and 1 late to pass

Answer 57

* Complete or incomplete * Spinal shock - **quadriplegia**/flaccid paralysis, total anaesthesia, areflexia * If above C4, **respiratory compromise** (diaphragmatic paralysis) * Neurogenic shock: hypotension, bradycardia, warm dry skin etc. * Incomplete syndromes, anterior and central cord Bold to pass

Answer 58

* **Rupture of aneurysm** * Loss common causes include extension of traumatic haemorrhage, hypertension intracerebral bleed into ventricular system, AVM, bleeding disorders, tumours Bold to pass

Answer 59

* Generally unknown, not 'congenital' * Polycystic kidney * Ehlers Danlos type 4 * Neurofibromatosis type 1 * Marfan's * Fibromuscular dysplasia * Aortic coarctation 2 out of 6 to pass

Answer 60

**Early** * vasospasm and additional ischaemic injury * raised ICP **Late** * meningeal fibrosis and scarring * CSF obstruction Need 2 to pass

Answer 61

Subdural blood comes from damage to **bridging veins between the brain and the venous sinuses** (displacement of the brain with trauma can tear the veins at the point where they penetrate the dura to enter the sinuses) -> **blood between the dura and the arachnoid** Bridging veins to pass

Answer 62

* **Elderly** - veins stretched and more movement due to brain atrophy * Infants - thin walled bridging veins Bold to pass

Answer 63

Extradural haemorrhage occurs with a **rupture of a meningeal artery**, usually associated with a skull fracture, leads to accumulation of arterial blood **between the dura and the skull** Bold to pass

Answer 64

**Axonal microscopic injury** * Micro findings include **axonal swelling and focal haemorrhagic lesions**. * Believed to **damage the integrity of the axon at the node of Ranvier** -> **alterations in axoplasmic flow** * **Commonly found with 'coma' but no cerebral contusions**

Answer 65

* Male * Smoking * **Age >60** * Family history * Connective tissue disease * Vasculitis * Hypertension * Diabetes * Atherosclerosis 5 to pass

Answer 66

* **Atherosclerotic plaque** in intima compresses media with **degeneration and weakness of wall** and cystic medial degradation * Local inflammation * **Proteolytic enzymes** with collagen degradation - role of matrix metalloproteinases * Loss of vascular smooth muscle cells * Inappropriate synthesis of non-elastic ECM 2 of 3 bold to pass

Answer 67

* **Rupture** - increase with diameter (higher if >5cm) and can be retro- or intra-peritoneal with rapid fatal haemorrhage * *Obstruction* - ischaemia from branch vessels obstruction eg. mesenteric, vertebral, renal * *Embolism* - plaque or thrombus * *Impingement or compression* of adjacent structure eg. ureter * *Painless mass* Bold and 2 others

Answer 68

* Related to size * 4-5cm is 1% per year * 5-6cm is 11% per year * >6cm is 25% per year

Answer 69

* An aneurysm is a localised dilatation of the abdominal aorta * It is usually between the renal arterial and the bifurcation of the aorta into iliac vessels * The aneurysm often contains atheromatous ulcers covered with mural thrombi, with thinning and destruction of the media

Answer 70

* Atherosclerosis * Congenital (cystic medial degeneration) * Mycotic * Syphilis * Trauma * Immunological

Answer 71

* **Hypertension**, aorta of hypertensive patients have medial hypertrophy of vasa vasorum and degenerative changes in the media * Connective tissue disease (inherited or acquired) * Both of the above cause **weakness in the media** * An aortic dissection starts with an **intimal tear** and the blood dissect in the media either vitally or proximally leading to a tear in the media Bold to pass

Answer 72

By site of involvement: * Stanford Type A proximal; Type B distal * Debakey: 1 - ascending and descending; 2 - ascending only; 3 - descending only Either classification to pass

Answer 73

* Rupture back into intima or through adventitia * Rupture out or into pericardial, pleural or peritoneal cavity * Cardiac tamponade, aortic insufficiency, MI, distal ischaemia, spinal cord ischaemia * Death 3 examples to pass

Answer 74

* **Intimal tear** into media of aorta * **Strips along laminar planes** * **Blood flow dissects the media resulting in medial haematoma** * Cystic medial degeneration Bold to pass

Answer 75

* Men aged 40-60 with **hypertension** * Connective tissue disorders eg. Marfans * Complication of arterial cannulation * Trauma Bold + 1 other

Answer 76

Both: rupture Type A : * dissects to aortic root involving coronary ostia (MI) * pericardial tamponade * dissects into great vessels leading to cerebrovascular accident Type B: * dissects into renal, mesenteric, spinal and distal arterial tree causing inschaemic/infarction At least four complications to pass

Answer 77

* **Concentric left ventricular hypertrophy** * Left ventricular outflow obstruction * MI (without coronary artery disease) * Syncope * Aortic dissection * Heart failure * Endocarditis Bold +3 others to pass

Answer 78

* Calcific/degenerative * Bicuspid valve * Rheumatic heart disease 2 to pass

Answer 79

* Rheumatic disease involves more than one valve (aortic and mitral) * Absence of features of MS/MR * Absence of features of aortic regurgitation Bonus question

Answer 80

* **Age** - normal valve 70-90 years; bicuspid 50-70 years * Bicuspid valve or other congenital abnormality * Wear and tear, chronic injury * Hyperlipidaemia, hypertension, inflammation Bold and one other to pass

Answer 81

* **Calcification** * **Stenosis** * Regurgitation * Infective endocarditis * Aortic dilatation * Dissection Bold +2 others

Answer 82

* Most common valvular abnormality * **Wear and tear** - calcification on normal or bicuspid valves * Clinical attention in 6-7th decade in bicuspid valves, 89th decade in previously normal valves * Heaped up **calcified masses within cusps** - protrude through to outflow tracts * Functional valve area decreased Bold to pass

Answer 83

* **Hypertension** * **Hyperlipidaemia** * Toxins from **cigarette smoke** * Homocysteine * Infectious agents * Inflammatory cytokines (TNF) can also stimulate pro-atherogenic patterns of endothelial cell gene expression * The two most important causes of endothelial dysfunction are **haemodynamic disturbances and hypercholesterolaemia**. **Local flow disturbances** leads to increased susceptibility of certain portions of a vessel wall to plaque formation Bold to pass

Answer 84

* Lower abdominal aorta * Coronary arteries * Popliteal arteries * Internal carotid arteries * Vessels of the circle of Willis 3 of 5 to pass

Answer 85

* **Rupture, ulceration or erosion** of the intimal surface of atheromatous plaques exposes the blood to highly thrombogenic substances and induces **thrombosis**. Such thrombosis can partially or completely occlude the lumen and lead to downstream ischaemia * **Haemorrhage into a plaque** - rupture of the overlying fibrous cap, or of the thin-walled vessels in the areas of neovascularisation, can cause intra-plaque haemorrhage * **Atheroembolism** - plaque rupture can discharge atherosclerotic debris into the bloodstream, producing microemboli. * **Aneurysm formation** - atherosclerosis induced pressure or ischaemic atrophy of the underlying media, with loss of elastic tissue, causes weakness resulting in aneurysmal dilation and potential vessel rupture 2 of 4 bold to pass

Answer 86

* Stable: dense collagenous and **thickened fibrous caps** with **minimal inflammation** and **small underlying atheromatous** core * Vulnerable: **thin fibrous cap, large lipid core and increased inflammation** - prone to rupture 2 Bold parts from each

Answer 87

* **Endothelial injury and dysfunction** * Lipoprotein (mainly LDL) accumulation and oxidation in vessel wall * **Monocyte adhesion and migration into intima and transformation into foam cells and macrophages** * Platelet adhesion * **Smooth muscle cell migration from media into intima** * Subsequent smooth muscle cell proliferation in intima * **Enhanced lipid accumulation within intimal cells (macrophages and smooth muscle cells)** Bold to pass

Answer 88

* Endothelium * Fibrous cap * Necrotic centre * Foam cells * Cholesterol crystals * Calcium

Answer 89

* Heterogenous group of diseases of the myocardium associated with **mechanical and/or electrical dysfunction** that usually exhibit inappropriate **ventricular hypertrophy or dilation** * Primary cardiomyopathy can be congenital or acquired * Secondary cardiomyopathy have myocardial involvement as a component of a systemic or multi system disorder Bold to pass

Answer 90

**Hypertrophic** - 75% genetic cause, autosomal dominant **Dilated** - alcohol, myocarditis, idiopathic, peripartum, genetic **Restrictive** - infiltrative, amyloidosis, sarcoidosis Bold with one example for each

Answer 91

**Valve dysfunction** (incompetent mitral/tricuspid) **Mural thrombi and embolisation** Lethal **arrhythmia** **AF** **Death** from progressive failure Any 2 bold to pass

Answer 92

**Infections** - viral, bacterial, fungal, protozoal **Metabolic** - hyperthyroidism, nutritional **Infiltrative** - sarcoid, carcinoma **Immunological** - autoimmune myocarditis **Drugs/toxins** - alcohol, chemotherapy Ischaemic Hypertensive Valvular 3/5 bold and examples

Answer 93

* Dilated: cardiac dilatation, **poor LVEF (<40%), impaired contractility** - systolic dysfunction * Hypertrophic: myocardial hypertrophy, **normal or high LVEF, impaired compliance** - diastolic dysfunction Bold for each

Answer 94

* **Myocardial hypertrophy without ventricular dilatation** * **Asymmetrical septal thickening (septum>>free wall)** * Impaired diastolic filling and left ventricular outflow obstruction in 25% of cases Bold to pass

Answer 95

* Heart failure * Sudden death, ventricular arrhythmia * AF, mural thrombus/embolisation * Stroke * Infective endocarditis mitral valve Need 3 of 5 to pass

Answer 96

Right sided heart failure that is **not secondary to left sided heart failure (pure RHF)**. It can be acute (eg. massive PE) of chronic (chronic lung disease) Bold to pass

Answer 97

Diseases that cause **pulmonary hypertension** * Diseases of pulmonary parenchyma (COPD; fibrosis; bronchiectasis) * Diseases of pulmonary vessels (primary pulmonary HTN, recurrent PE, extensive pulmonary arteritis) * Disorders affecting chest movement (marked obesity; kyphoscoliosis, neuromuscular) * Disorders causing pulmonary arterial constriction (hypoxaemia, metabolic acidosis, chronic OSA, altitude sickness) Bold plus 3 others to pass

Answer 98

* Pulmonary congestion is minimal whereas engorgement of the systemic & portal venous systems may be pronounced * Heart: right ventricular hypertrophy and dilatation; leftward bulging or septum * Liver/portal system: congestive hepatomegaly; centrilobular necrosis; congestive splenomegaly * Pleura, pericardial and peritoneal spaces: effusion; ascites * Subcutaneous tissues: oedema (dependent and peripheral portions of body) At least 3 to pass

Answer 99

**Cardiac factors** * Degenerative mitral valve prolapse (myxomatous) * Calcific aortic stenosis * Bicuspid aortic valve * Prosthetic valves * Congenital valve defects * Rheumatic heart disease **Host factors** * Bacteraemia (dental or surgical procedure, loss of skin integrity) * IVDU * Immunodeficiency * Drug induced immunosuppression * Malignancy * Neutropaenia * Diabetes * Alcohol 4 to pass - 2 from each group

Answer 100

* **Streptococcus viridans** * **Staph aureus** * Staph epidermidis * Enterococci * Gram negative bacilli * HACEK - haemophilus, actinobacillus/aggregatibacter, cardiobacterium, eiwenella, Kinsella) * Fungal Bold and one other to pass

Answer 101

**Local** * Erosion/destruction of tissue (valve or myocardium) * Abscess formation (ring abscess) **Systemic** * Septic infarcts - brain, lung, kidneys, mycotic aneurysms * Embolic phenomena - subcutaneous tissues (splinter haemorrhages, laneway lesions, oslers nodes * Retina (roth spots) * Glomerulonephritis (immune mediated) 1 local and 1 systemic to pass

Answer 102

When **cardiac function is impaired** and/or the **heart is unable to maintain a cardiac output** sufficient for the body's metabolic needs Bold to pass

Answer 103

**Pump failure** **Systolic dysfunction (contractile dysfunction)** e.g. myocardial contractile dysfunction secondary to ischaemia, AMI, pressure or volume overload, dilated cardiomyopathy **Diastolic dysfunction (inadequate filling)** eg. LV hypertrophy, myocardial fibrosis, amyloidosis, pericarditis **Others**: arrhythmia, regurgitant flow **Left heart failure** - IHD, HTN, valvular diseases **Right heart failure** - secondary to left heart failure, PE, pulmonary HTN

Answer 104

* Lung: breathlessness, orthopnoea, paroxysmal nocturnal dyspnoea, APO, pleural effusions * Cardiac: 3rd HS, gallop, displaced apex beat, AF, murmur, elevated JVP * Renal: RAA activation, fluid retention, pedal oedema, AKI * Brain: confusion secondary to hypoxia * Hepatic: engorgement, ascites, cirrhosis 3/5 organ system symptoms to pass

Answer 105

**IHD, valvular heart disease, HTN**, cardiomyopathy, fluid overload 2 bold and one other to pass

Answer 106

* Infarction * Ischaemia of myocardium * Calcification * Hypertrophy of cardiac myocytes * Interstitial fibrosis 2 to pass

Answer 107

* Nutmeg liver * Centrilobular necrosis (results from central hypoxia) * Centrilobular fibrosis * **Congestion/oedema leading to fibrosis and necrosis**

Answer 108

Primary (essential) and secondary Need both to pass

Answer 109

**Renal** * Acute glomerulonephritis * CKD * PCKD * Renal artery stenosis * Renal vasculitis * Renin-producting tumours **Endocrine** * Adrenocortical hyperfunction - Cushings, aldosteronism, congenital adrenal hyperplasia * Exogenous hormones - steroids, oestrogen, sympathomimetics * Pheochromocytoma Acromegaly Hyperthyroidism **Cardiovascular** * Coarctation of aorta * Polyarteritis nodosa * Increased intravascular volume * Increased cardiac output **Neurologic** * Increased ICP * Sleep apnoea **Psychogenic** * Acute stress * Surgery * Pain 6 examples from at least 3 different systems

Answer 110

Multiple genetic polymorphisms and interacting environmental factors. **Genetic factors** * Familial, multi-gene foci interactions * Single gene disorders altering Na reabsorption **Vasoconstrictive influences** * Vasoconstriction/structural change in vessel wall -> increased peripheral resistance -> primary hypertension **Environmental factors** * Stress * Obesity * Smoking * Physical inactivity * High salt intake 2 of 3 bold, with detail

Answer 111

Major risk factors for atherosclerosis * Coronary artery disease * Cerebrovascular disease * Aortic dissection * Renal failure * Cardiac hypertrophy * Cardiac failure * Multi-infarct dementia * Retinal changes 4 of 7 to pass

Answer 112

Clinical syndrome characterised by * SBP > 200, DBP >120 * Renal failure * Encephalopathy * CVS abnormalities * Retinal haemorrhages * +/- papilloedema * Often superimposed on previous benign hypertension * <5% of hypertensive patients * Rapidly rising BP * Untreated -> death in 1-2 years Must mention 3 organ systems to pass

Answer 113

* Left ventricular hypertrophy * Absence of another cause * Systemic hypertension

Answer 114

* Thick left ventricular wall * No dilation * Left atrial enlargement * Increased weight of heart 3 of 4 to pass

Answer 115

* Stiffness * Impaired diastolic filling * AF * HF * Sudden cardiac death

Answer 116

**Acute plaque change** - Rupture, fissuring, erosion, ulceration or haemorrhage into atheroma **Thrombosis** - Platelet adhesion, aggregation & micro-thrombi formation - Platelet release of mediators causing vasospasm - Activation of coagulation pathway leading to thrombus **Vasoconstriction** stimulated by: - Circulating adrenergic agonists - Locally released platelet contents - Endothelial cell dysfunction causing decrease NO - Perivascular inflammatory cell mediators **Vessel occlusion leading to** - Decreased myocardial blood flow - Myocyte necrosis 3 of 4 bold and understanding of each process

Answer 117

* Contractile dysfunction (LVF, RVF, cardiogenic shock) * Arrhythmias * Myocardial rupture (free wall, ventricular septum, papillary muscle) * Ventricular aneurysm * Pericarditis / effusion / tamponade * Mural thrombus * Papillary muscle dysfunction 3 to pass

Answer 118

* Free wall -> tamponade (1-10 days) * Septum -> VSD and left to right shunt * Papillary muscle dysfunction - severe mitral regurgitation

Answer 119

* **Hypertrophy and dilatation**, increased oxygen demand * **Ischaemia and depressed cardiac function** * **Scar formation** leads to **stiffening** and hypertrophy

Answer 120

* Nutritional - **protein, Vitamin C** * Metabolic - **acidosis** * Circulatory - **arterial or venous** * Hormonal - **glucocorticoids** Need 3 of 4

Answer 121

**Reversible** * **Within seconds** there is cessation of aerobic metabolism, decreased ATP production and lactic acid production * **Within one minute** there is loss of contractility * **Within a few minutes** there are ultrastructural changes such as myofibrillar relaxation, cell and mitochondrial swelling and depleted glycogen **Irreversible** * **Within 20-40 minutes** there is irreversible myocyte injury - defects in sarcolemmal membrane and cell leakage * There is initially subendocardial then transmural myocyte death * **Within one hour** there is microvascular injury * **From 2 hours** there is coagulative necrosis Reversible and irreversible to pass with minutes to hours concept

Answer 122

Early: no damage Later: * reperfusion haemorrhage * acceleration of disintegration of **damaged** myocytes * exaggerated contraction of myofibrils * some **new injury** from oxygen free radicals

Answer 123

* **Chest pain** - dull or sharp, pleuritic, positional * Fever * Congestive failure * Pericardial **frictional rub** * Constrictive pericarditis would give distant of muffled heart sounds, elevated JVP and peripheral oedema 2 features to pass

Answer 124

* **Infectious: viral**, pyogenic bacteria, TB, fungal * **Immune mediated**: rheumatic fever, SLE, scleroderma, post cardiotomy, * Post MI (Dressler's) * Drug hypersensitivity reaction * AMI * Uraemia * Neoplastic * Trauma * Radiation Bold + 1 other

Answer 125

* **Serous**: usually non-infectious inflammation (RF, SLE) but also viral, uraemia, tumours * **Fibrinous/serofibrinous** (most common) post MI, trauma, Dressler's * **Purulent/suppurative**: almost always bacterial invasion from local infection, lymphatic of blood seeding or at operation * **Haemorrhagic** * **Caseous (TB)** 2/5 to pass

Answer 126

**Vascular** **Macro atherosclerosis** * coronary artery disease * peripheral vascular disease * hypertension * cerebrovascular accident **Microangiopathic** * thickened basement membrane * increased permeability of capillaries to plasma proteins * nephropathy - sclerosis, basement membrane thickening, glomerulosclerosis * retinopathy - haemorrhages, exudates, neovascularisation, detachment * neuropathy Bold + 3 clinical complications

Answer 127

**Type one** * Early onset * Normal or underweight * Decreased insulin production * Circulating islet autoantibodies * Polyuria, polydipsia, polyphasia +/- ketoacidosis * Genetic linkage * Dysfunction in T cell resulting in islet antibodies **Type 2** * Usually adult onset * Often overweight * Increased blood insulin * No islet autoantibodies * Insulin resistance Age + 2 clinical + 1 pathology to pass

Answer 128

* **Insulin deficiency** and glucagon excess -> decreases peripheral utilisation of glucose whilst increasing gluconeogenesis -> severe **hyperglycaemia** * Hyperglycaemia causes **osmotic diuresis** and dehydration * Insulin deficiency increases **lipolysis and free fatty acid production**. Free fatty acids are converted to **ketone bodies** by the liver. If rate of ketone bodies production exceeds rate of utilisation by peripheral tissues -> ketonaemia and ketonuria * Decreased urinary excretion of ketones leads to systemic metabolic ketoacidosis Bold to pass

Answer 129

1. Genetic predisposition 2. Precipitating event 3. Autoimmune destruction of islet cells 4. Subclinical leading to overt DM Bonus question

Answer 130

Infections (Coxsackie, mumps, measles, CMV, rubella, EBV) may induce tissue damage and inflammation, leading to the release of B cell antigens. OR the viruses produce antigens which mimic self-antigens with the immune response cross-reacting with self-tissue

Answer 131

**Insulin resistance** * Decreased ability of the peripheral tissues to respond to the secreted insulin * Secondary to either genetic predisposition or obesity/lifestyle factors * Quantitive and qualitative **beta cell dysfunction** manifests as inadequate insulin secretion in the face of insulin resistance and hyperglycaemia * Initial beta cell hyperplasia maintains normoglycemia with increased levels of insulin secretion * Early and subsequent late failure manifests as impaired glucose tolerance and diabetes * Genetic predisposition to B-cell failure Bold to pass

Answer 132

* Osmotic diuresis - hypovolaemia, risk of thrombosis * Electrolyte losses - Na, K, PO₄ * Hyperosmolality - changes in conscious state 2 to pass

Answer 133

* Clinical hyperfunction * Thyroid enlargement * Infiltrative opthalmopathy * Infiltrative dermopathy First two to pass

Answer 134

* Autoimmune: variety of antibodies * Auto-antibodies to TSH receptors * LATS - IgG mimics TSH, thyroid stimulating immunoglobulin At least 2 to pass

Answer 135

Classification based on **hormone cell type** * Prolactin cell * Growth hormone cell * Thyroid stimulating cell * ACTH cell * Gonadotroph cells * Mixed GH-prolactin cell Bold and two cell types

Answer 136

* **Prolactinoma**: amenorrhoea, galactorrhea, loss of libido, infertility * **Somatotroph**: gigantism or acromegaly * **ACTH** - Cushing's syndrome * **Gonadotroph**: local effects (headaches, visual impairment, diplopia, pituitary apoplexy); hypogonadism (lethargy, loss of libido, amenorrhoea)

Answer 137

Hypermetabolic state caused by elevated circulating levels of T3 and T4 Need to know

Answer 138

* **Cardiac** - tachycardia, arrhythmias, CCF * Neuromuscular - tremor, proximal myopathy * **Ocular** - wide staring gaze, lid lag, proptosis * CNS - anxiety, emotional lability, insomnia * Skin - warm, flushed, increased sweating * **Heat intolerance** * **Thyroid storm** - fever, tachycardia, arrhythmia Bold to pass

Answer 139

* **Diffuse toxic hyperplasia (Grave's disease**) * Toxic multi nodular goitre * Toxic adenoma/carcinoma * Neonatal from material Graves disease * Thyroiditis Bold + 1 more to pass

Answer 140

* **Thrombophlebitis** * **Sepsis** to injection side, lungs, heart valves or bones * **Viral inoculation** - HIV, hepatitis

Answer 141

* 10% of hospitalised IVDUs * Distinctive form **involving right sided valves, especially tricuspid** * Most are **staph aureus**

Answer 142

* CNS: encephalopathy including headache, dizziness, memory disturbance even coma * PNS: peripheral neuropathy * Haematological: microcytic hypochromic anaemia, haemolysis, characteristic basophil stippling of red cells * Renal: renal tubular injury * CVS: hypertension * Genitourinary: male infertility, failed ovum implantation

Answer 143

* High affinity for sulfhydryl groups: binds to aminilevuline acid dehydrates and ferroketolase, involved in heme synthesis * Competition with calcium ions; interferes with nerve transmission and brain development * Inhibition of membrane associated enzymes including Na/K ion pumps

Answer 144

The sudden death of an infant under 1 year of age which remains unexplained after thorough investigation and autopsy

Answer 145

* **Parental risks**: young mum <20 years, maternal smoking or drug use, low socioeconomic class * **Infant risk**: premature, low birth weight, male, SIDS in sibling, brainstem abnormalities * **Environment** - prone sleeping, soft bedding and co-sleeping, hyperthermia At least 3 to pass

Answer 146

* Emphysema is a consequence of **high protease (elastase) activity with low anti-protease activity** * Smoking increases neutrophils and macrophages in alveoli, neutrophils release elastase and macrophages enhance elastolytic activity - inhibition of **alpha 1 antitrypsin** * Oxidants in smoke, oxygen free radicals from neutrophils

Answer 147

Oropharynx Larynx Lung Oesophagus Stomach Pancreas Bladder 3 to pass

Answer 148

* Sublethal doses -> delayed effects; **mutations**, chromosome aberrations, genetic instability * Larger doses **kill proliferating cells** -> haematopoietics, gut most prone. Vessel endothelial cell injury causes delayed organ dysfunction * Larger still - **overt tissue necrosis** * Delayed consequences include fibrosis - scarring when parenchymal cells can't regenerate, when vessels are damaged * **Carcinogenesis** - skin, leukaemia, osteogenic sarcomas, lung cancer, thyroid cancer in children

Answer 149

* Features are dose-dependent * <200rem: subclinical, mild N&V, minor neutropenia * 200-600rem: haematopoietic, N&V, neutropenia * 600-1000rem: GI, N&V, diarrhoea, severe neutropenia, death from shock and infection within 2 weeks * >1000rem: CNS: severe N&V, coma within 3 hours, no lymphocytes, death within 36 hours

Answer 150

* **Carcinogenesis**: esp. leukaemias and thyroid cancer in children * Blood vessels: fibrosis, narrowing * Skin: radiation dermatitis, impaired healing * Heart: pericardial fibrosis leading to constrictive pericarditis * Lungs: radiation pneumonitis with intraalveolar and interstitial fibrosis * Kidneys and urinary tract: peritubular fibrosis, loss of glomeruli, bladder fibrosis * GIT: oesophagitis, gastritis, enteritis, colitis, proctitis, fibrosis leading to strictures and obstruction * Breast: fibrosis * Ovary & testes: fibrosis and infertility * Eyes: cataracts * CNS: transverse myelitis Bold +3 other systems

Answer 151

According to depth of injury * **Superficial** - confined to epidermis * **Partial thickness** - extends to dermis * **Full thickness** - involves subcutaneous tissue Bold to pass

Answer 152

**Early** * Hypovolaemic shock (especially >20% BSA) * Compartment syndrome (circumferential LL burn) * Associated injuries (inhalation burn, CO poisoning) * Airway compromise * Hypermetabolic state **Late** * Infection/sepsis (pseudomonas) * ARDS * Multi organ failure * Skin grafting, scarring, cosmetic * Psychological 2 early and 2 late to pass

Answer 153

Wallace "rule of nines" Lund and Browder diagram

Answer 154

* **Polyneuropathy**: symmetrical peripheral polyneuropathy; myelin degeneration leading to axonal disruption in motor and sensory fibres and reflex arcs * **Cardiovascular consequences (Wet beriberi)**: peripheral vasodilation, AV shunting, high output failure, dilated cardiac chambers * **Wernicke-Korsakoff syndrome** Wernicke's: opthalmoplegia, nystagmus, ataxia, higher centre dysfunction Korsakoff's: permanent impairment of remote recall, confabulation 2 with some details to pass

Answer 155

* Mammillary bodies * Periventricular region of thalamus * Floor of 4th ventricle * Anterior cerebellum At least one to pass

Answer 156

* Required co-factor for a liver microsomal carboxylase which carboxylates a glutamate residue in factors 2, 7, 9, 10 and Protein C and S * Necessary for binding calcium and thus functional activity of the proteins Need all factors to pass

Answer 157

* Fat malabsorption syndrome * Destruction of endogenous Vitamin K-synthesising flora in the gut by broad spectrum antibiotics * Neonates (small liver reserves, no bacterial flora and low vitamin K in breast milk) * Diffuse liver disease (hepatocyte dysfunction interferes with synthesis of vitamin K dependent factors 3/4 to pass

Answer 158

A **series of conversions of inactive pro-enzymes to activated enzymes**, culminating in the formation of thrombin which then converts the soluble plasma protein fibrinogen into the **insoluble fibrillar protein fibrin**

Answer 159

**Restriction of factor activation** to sites of exposed phospholipids Natural anticoagulants generated: * **Antithrombins** - inhibit the activity of thrombin and other serine proteases (IXa, Xa, XIa, XIIa); AT3 activated by binding to heparin like molecules on endothelium ->utility heparin in thrombosis * **Protein C&S** - vitamin K dependent proteins characterised by ability to inactivate factors Va and VIIIa * **Plasmin** - plasminogen to plasmin by factor XII dependent pathway or 2 groups of plasminogen activators - breaks down fibrin and interferes with polymerisation - resulting split products also act as weak anticoagulants * **Tissue factor pathway inhibitor**

Answer 160

* Component of haemostasis resulting in thrombosis (with endothelium and platelets) * Series of enzymatic conversions * Proenzymes converted to activated enzymes resulting in formation of thrombin * Comprises extrinsic and intrinsic pathways * **Extrinsic pathway** - activated by tissue factor (lipoprotein), exposed at its of tissue injury * **Intrinsic pathway** - activated by Factor XII * **Pathways converge where activation of Factor X occurs** * **Common pathway** - factor X, prothrombin, thrombin, factor V, calcium, then fibrinogen converted to fibrin and ultimately cross linked fibrin Bold to pass

Answer 161

* **Sepsis** (bacterial endotoxins and AgAb complexes) * **Major trauma / burns / surgery** * **Certain cancers** (AML (promyelocitic), adenocarcinoma of lung, colon, stomach, pancreas) * **Obstetric complications** - placenta, amniotic fluid, dead fetal tissue 3 of 4 categories

Answer 162

* Exposure of subendothelial matrix activates platelets and the coagulation cascade * TNF causes tissue factor to be expressed from endothelial cells * TNF up-regulates the expression of adhesion molecules on endothelial cells to allow leucocytes to bind and damage endothelial cells * Direct trauma to endothelial cells from AgAb complexes, temperature extremes or micro-organisms 3 points required to pass

Answer 163

* Decreased Hb (microangiopathic haemolytic anaemia) * Increased WCC * **Decreased platelets** * Decreased fibrinogen * Increased PT/INR * Increased APTT * **Increased fibrin degradation products**

Answer 164

* Major trauma releases tissue thromboplastins * Both sides of clotting cascade are activated * 2 major consequences - deposition of fibrin within microcirculation leading to **ischaemia/microthrombosis** of vulnerable organs; and a **consumptive coagulopathy** - platelets and clotting factors leading to a **bleeding diathesis** Bold to pass

Answer 165

* **Release of tissue factor or thromboplastin substances** into the circulation, shift towards pro-coagulation, extrinsic pathway * **Widespread injury to epithelial cells** causing release of tissue factor, platelet aggregation, intrinsic coagulation pathway * Resultant formation of **micro-thrombi** throughout the circulation due to **consumption of platelets, fibrin & coagulation factors**, activation of **fibrinolysis** and **bleeding**

Answer 166

A **detached intravascular** solid, liquid or gaseous mass that is **carried by the blood** to a **site distant** from its point of origin

Answer 167

* Thromboembolism : pulmonary (venous) or systemic (arterial) * Fat embolus * Gas embolus * Amniotic fluid embolus * Air embolus

Answer 168

Systemic thromboembolism refers to emboli **in the arterial circulation**

Answer 169

* Venous thrombi tend to lodge primarily in one vascular bed (the lung) * Arterial thrombi can travel to a wide variety of sites the point of arrest depends on the source and the relative amount of blood flow that downstream tissues receive. Major sites include lower exterminates and the brain Bonus question

Answer 170

* Areas of ischaemic necrosis: dominant histologic characteristic is ischaemic necrosis * White infarcts occur in solid organs with end-arterial circulation * Acute inflammation happens within hours; reparative response follows * Factors influencing infarct development: nature of vascular supply (end artery vs presence of collateral blood supply), rate of occlusion, vulnerability to hypoxia, oxygen content of blood, calibre of occluded vessel Bonus question

Answer 171

95% **arise in the deep veins of the leg** - pass up to right side of heart and into pulmonary vasculature. Size determines where they lodge

Answer 172

* **Primary** - factor 5 Leiden, protein C&S deficiency, antiphospholipid syndrome * **Secondary** - stasis/immobilisation, long haul flights, active malignancy, trauma/burns/surgery, pregnancy, OCP, indwelling catheters At least 1 primary and 2 secondary

Answer 173

* Most clinically silent 60-80% * Cough * SOB * Fever * Chest pain * Haemoptysis * Tachycardia/pnoea * Sudden death * Cor Pulmonale * CVS collapse * Pulmonary haemorrhage/infarction, over time multiple emboli may cause pulmonary hypertension and cor pulmonale 5 to pass

Answer 174

* **Associated with long bone fractures**, rarely soft tissue injury/burns * Only 10% symptomatic * **Pulmonary insufficiency** - SOB, tachypnoea, tachycardia * **Neurologic symptoms** - irritability, restlessness, delirium, coma * **Anaemia** - due to RBC aggregation/haemolysis * **Thrombocytopaenia** - platelet adhesion/aggregation, leads to petechial rash 3 to pass

Answer 175

Primary haemostasis = formation of platelet plug * Endothelial damage exposes extracellular matrix (collagen, vWF) * Platelet activation * Adherence (via Gp1b to vWF) * Shape change (flat to round) * Secretion (ADP, thromboxane A2, calcium) and negative charge phospholipid * Platelet aggregation (platelet Gp2b-3a receptors via fibrinogen) Platelets +3

Answer 176

* Vascular damage and exposure of **tissue factor** converts factor VII to VIIa * This in turn causes a series of amplifying enzymatic reactions that leads to the deposition of a **fibrin clot (secondary haemostasis)** * Factor X is converted to factor Xa, which in turn covers prothrombin (factor II) to thrombin, which converts fibrinogen to fibrin (fibrin network) Bold plus concept

Answer 177

Extrinsic and common coagulation pathways At least 1 to pass

Answer 178

* **Vasoconstriction**: arteriolar, reflex neurogenic, enhanced by endothelin * **Primary haemostasis**: extracellular matrix exposed, platelet adherence/activation - platelets aggregate and forms a plug * **Secondary haemostasis**: tissue factors exposed, factor III, thromboplastin, factor VII, platelet plug consolidated - thrombin/fibrin generated * **Thrombus & anti-thrombotic effect** - fibrin polymerises to form permanent plug, tPA regulates 3/4 steps and understanding of concept to pass

Answer 179

* **Prothrombin time - extrinsic pathway** - factors VII, X, II, V, fibrinogen (including vitamin K dependent factors) * **Partial thromboplastin time - intrinsic pathway** - factors XII, XI, IX, VIII, X, V, II, fibrinogen Bold and which one is Vit K dependent

Answer 180

* **Conversion of prothrombin to thrombin** requiring calcium and activated factor V as co-factors. Occurs on surface of damaged endothelium or activated platelets * **Thrombin catalyses fibrinogen to fibrin** in presence of calcium * **Thrombin catalyses factor XIII to XIIIa** in presence of calcium leading to **cross linking of fibrin** Bold to pass

Answer 181

* **Plasmin is produced from circulating plasma protein plasminogen**, either by factor XIIa - dependent pathway, or by plasminogen activators * **Plasmin breaks down fibrin** to fibrin degradation products (d-dimer) and disrupts polymerisation * **t-PA from endothelial cells** most important plasminogen activator and most active when attached to fibrin. Urokinase is like TPA and is a circulating protein * Free plasmin is inactivated by alpha 2 plasmin inhibitor Bold is essential

Answer 182

Area of **ischaemic necrosis** caused by **arterial** or venous occlusion

Answer 183

* **Arterial thrombosis** * **Embolism** * Vasospasm * Haemorrhage into plaque * Extrinsic vascular compression (by tumour or oedema) * Torsion of vessel * Traumatic rupture * Entrapment in hernial sac * Venous thrombosis Bold +2

Answer 184

* Nature of vascular supply eg. dual vs end arterial * Rate of occlusion development - time for collaterals to develop * Vulnerability to hypoxia of the tissue type * Oxygen content of blood 2 to pass

Answer 185

* Ischaemia prevents delivery of energy substrates, while hypoxic tissue can still produce energy by anaerobic glycolysis * Ischaemia tends to injure tissues faster than hypoxia

Answer 186

Increased interstitial fluid

Answer 187

* **Inflammatory** - (acute/chronic) - infection, tissue necrosis, foreign body, immune, traumatic * **Non-inflammatory** - increased hydrostatic pressure (eg. cardiac failure, DVT), hypoproteinaemia (chronic liver disease, nephrotic syndrome), lymphatic obstruction, sodium retention 2 examples from each to pass

Answer 188

* **Inflammatory** - exudate, **high protein concentration** * **Non-inflammatory** - transudate, **low protein concentration** (effectively an ultrafiltrate of plasma)

Answer 189

* Hydrostatic pressure * Colloid osmotic pressure * Normal capillary walls - most protein remains intravascular, fluid leaks out. Fluid out of vessel at arteriolar end. Most fluid returned to vessels at venular end. small amount of fluid returns via lymphatics 2 points plus concept

Answer 190

* **Increased hydrostatic pressure** - 1) local venous, venous obstruction, compression, thrombosis; 2) local arteriolar, dilation, heat, neurohumeral dysregulation; 3) systemic, CCF, constrictive pericarditis, impaired venous return * **Reduced plasma oncotic pressure** - mainly protein loss eg. nephrotic syndrome or poor production eg. cirrhosis, malnutrition, gut loss * **Inflammation** - acute or chronic inflammation, angiogenesis * **Lymphatic obstruction** - inflammatory, neoplastic, post-surgical, post-irradiation * **Sodium retention with water** - renal insufficiency, activation of RAAS, renal hypoperfusion 3 out of 5 bold, must include first 2. 5 conditions covering three groups

Answer 191

* Lung - dyspnoea, orthopnoea, PND, APO, pleural effusions * Cardiac - 3rd heart sound, displaced apex beat, AF, murmurs, JVP elevation * Renal - fluid retention, pedal oedema, AKI * Brain - confusion secondary to hypoxia * Hepatic - congestion, ascites, cirrhosis late 3 out of 5 organs

Answer 192

* Decreased cardiac output * Decreased renal perfusion * Secondary aldosteronism * Increased blood volume * Increased venous pressure At least 3 to pass

Answer 193

* Local: impaired venous outflow - thrombosis, external pressure, prolonged dependency with inactivity * Generalised impaired venous return - CCF, constrictive pericarditis, ascites * Arteriolar dilatation - heat, neurohumeral dysregulation 2 categories

Answer 194

* **Primary haemostatic plug** * Provides surface to **recruit and concentrate activated coagulation factors** Bold to pass

Answer 195

* Von Willebrand's factor on endothelium most important * Bridging platelet surface receptors (Gp1b) and collagen * Also collagen direct to platelet collagen receptors and interaction with extracellular fibronectin

Answer 196

* Vascular injury - extracellular matrix constituents, especially **collagen** * **Adhesion**: vWF bridges, stabilises initial platelet adhesion * Secretion from two types of granules - **Calcium, ADP** key to aggregation; phospholipid complex ket to intrinsic pathway * **Aggregation** - primary haemostatic plug - coagulation cascade - thrombin - then platelet contraction - fibrin stabilises the aggregate 3 to pass

Answer 197

Reduction in cardiac output or the effective circulating blood volume the result is hypotension followed by **impaired tissue perfusion** and **cellular hypoxia**

Answer 198

* Cardiogenic e.g AMI, cahdioteoxins, arrhythmia * Hypovolaemic eg. haemorrhage, burns, GI losses * Septic/systemic inflammation eg. sepsis, pancreatitis, trauma (independent of haemorrhage) * Distributive eg. anaphylactic, adrenal crisis * Neurogenic eg. spinal injury, spinal anaesthetic * Obstructive eg. tension pneumothorax, cardiac tamponade, PE 3 categories with 1 example of each

Answer 199

* Non-progressive - reflex compensatory mechanisms maintain vital organ perfusion * Progressive - tissue hypo-perfusion and onset metabolic disturbances (lactic acidosis) * Irreversible - non-reversible tissue and cellular injury

Answer 200

* Narrowed pulse pressure * Increase cap refil time * Tachycardia * Hypotension * Tachypnoea * Cool clammy skin * Cyanotic skin * Oliguria * Altered mental state

Answer 201

**Systemic hypoperfusion due to reduced effective circulating blood volume** resulting in **impaired tissue perfusion** and cellular hypoxia Bold to pass

Answer 202

**Non-progressive phase** * Reflex compensation * Vital organ perfusion * Baroreceptors * Catecholamines * Renin/angiotensin * ADH * Sympathetic stimulation (tachycardia, peripheral vasoconstriction, decreased urine output) **Progressive phase** * Anaerobic glycolysis * Lactic acidosis * Decreased vasomotor response * Increased peripheral pooling * Hypoxic injury * DIC * Vital organ failure **Irreversible phase** * Lysosomal enzyme release * Nitric oxide release * Decreased myocardial contractility * AKI * Bacteraemic shock from ischaemic gut 3 phases with 4/3/2 point from each phase respectively

Answer 203

Combination of **direct microbial injury** and activation of host inflammatory responses e.g. by **endotoxins** (lipid A, O, Ag) * Inflammatory mediator release: TNF, IL-1,-6,-8,-10, prostaglandins, NO, platelet activating factor, reactive O2 species * Activation innate cells of immune system - neutrophils, macrophages and monocytes * Humoral interaction to activate complement and coagulation pathways * Direct endothelial injury and activation * Metabolic abnormalities (insulin resistance and hyperglycaemia, glucocorticoid excess/deficiency) * Immune suppression (activation counter-regulatory mechanisms with anti-inflammatory mediators, lymphocyte apoptosis, hyperglycaemia inhibits neutrophils) Bold + 2 to pass

Answer 204

End organ and system dysfunction including: * Cardiomyopathy * Hypotension * ARDS * DIC * Renal failure * Death 3 to pass

Answer 205

* Interaction with innate cells of immune system - examples neutrophils, macrophages, monocytes * Interaction with humeral cells of immune system to activate complement and coagulation pathways * Direct action on endothelium (complex, not fully understood). Toll-like receptors recognise microbial elements. End result is **mediator release** examples TNF, IL-6,-8,-10 2 to pass

Answer 206

Induction of procoagulant state by: * **Increased tissue factor production** * Decreased production of **protein C** * Tissue factor pathway inhibitor **thrombomodulin** * **Decreased fibrinolysis** by increasing plasminogen activator inhibitor Combined with stasis (decreased washout of activated coagulation factors) resulting in activation of thrombin and fibrin rich thrombi 2 & 4 and understanding of process

Answer 207

* Extent and virulence of infection * Immune status of host * Presence of other co-morbid conditions * Pattern and level of mediator production Bonus question

Answer 208

* Thrombosis * Increased vascular permeability * Vasodilation 2 to pass

Answer 209

* **Bacterial cell wall lipopolysaccharides** usually from gram -ve bacilli * Consists of a generic fatty acid core and a complex polysaccharide coat unique for each species Bold to pass

Answer 210

* **Dose dependent activation of neutrophils, macrophages and monocytes** -> increased mediator release -> local/systemic inflammatory response * Activation via: LPS binding protein, CD14 receptor via IC toll I receptor * Mediators: TNF, IL-1, -6, -8 chemokines -> cytokine release * High dose: syndrome of septic shock - systemic vasodilation, decreased myocardial contractility, widespread endothelial injury -> alveolar capillary damage (ARDS), activating coagulation system -> DIC 3 to pass

Answer 211

* **Bacterial toxin (endotoxin or exotoxin) binds to lipopolysaccharides binding protein in serum** * Complex binds to receptors on leucocytes and endothelial cells * Induce release and synthesis of inflammatory mediators * Induce direct cell damage Bold + 2

Answer 212

* **Endothelial injury (damage to vessel)** * **Alteration in blood flow** (stasis, turbulence) * **Hypercoagulability** of blood

Answer 213

* **Propagation** (eg. resulting occlusion) * **Embolisation** * **Dissolution** * **Organisation** * **Recanalisation** 3 to pass

Answer 214

* Adhesions * Hernia * Malignancy * Volvulus * Intussusception * Mesenteric infarct * Strictures (due to Crohn's, radiation, mesenteric ischaemia) 4 to pass

Answer 215

* **Weakness/defect in abdominal wall**, protrusion of serous lined such of peritoneum (hernia sac) * **Visceral protrusion** - small bowel, large bowel, omentum most often involved * **Entrapment of hernia sac in a narrow neck** causes pain * Ongoing obstruction -> venous stasis, oedema -> incarceration and strangulation. * Common locations (inguinal, femoral, scars, umbilical) Bold + 2 others

Answer 216

* **Intestinal perforation** * **Intestinal ischaemia** * Peritonitis * Sepsis * Abscess * Electrolyte disturbance * Vomiting and aspiration * Death Bold to pass

Answer 217

**Vibrio cholera = gram negative bacteria** (comma shaped/flagella)

Answer 218

* **Non-invasive** * **Flagella proteins** for attachment and colonisation * **Preformed enterotoxin** - 5 B subunits and one A subunit. B subunit **binds** to intestinal (mainly duodenum/jejunum) epithelial cells and has retrograde transport in ER. A subunit activates G protein and cAMP, opening CFTR and **releases chloride into lumen, leading to secretion of bicarbonate, Na and water, causing diarrhoea which overwhelms colonic resorption** 4 bold to pass

Answer 219

* Non-invasive in gut lumen * **Release of enterotoxin** * **Secretory diarrhoea** * Acts on G proteins

Answer 220

* **H pylori** * Chronic bile reflux * NSAIDs * Autoimmune * Allergic response * Infections * Radiation * Mechanical * Psychological stress * Chronic irritants (coffee, alcohol, caffeine) * Crohn's, amyloid Bold + 2 to pass

Answer 221

* Most common cause * Predominantly antral * High acid production * Hypogastrinaemia * Generates ammonia * Disruption normal mucosal defence mechanisms 2 to pass

Answer 222

* Bleeding (15-20%) - accounts for 25% of ulcer deaths * Perforation * Obstruction * Gastric adenocarcinoma (complication of chronic H.pylori pangastritis) 2 to pass

Answer 223

* Transmural inflammation of bowel with skip lesions * Non-caseating granulomata * Fissures and fistulae * Mouth - anus * Chronic, relapsing * Mucosal ulceration 2 to pass

Answer 224

* Migrating polyarthritis * Sacroilitis * Ankylosing spondylitis * Erythema nodosa * Finger clubbing * Sclerosing cholangitis * Uveitis * Mild hepatic pericholangitis * Renal disorders due to trapping of the ureters * Systemic amyloidosis * GI tract cancer * May occur prior to intestinal symptoms 3 to pass

Answer 225

* Strictures * Fistulae * Malabsorption syndromes * Extra-intestinal manifestations * Neoplasia, less common than UC

Answer 226

A **gram negative rod** which is a facultative **anaerobe**. It is a normal GI pathogen Bold to pass

Answer 227

* Endotoxins are lipopolysaccharides in the other membrane of the **cell wall of Gram-negative bacteria which cause injury via the host immune response** * Exotoxins are proteins that are **secreted by the bacterium and cause direct injury** Bold concepts to pass

Answer 228

* UTIs * Prostatitis * Epididymo-orchitis * Infectious enterocolitis * Cholecystitis * Bacterial peritonitis 3 to pass

Answer 229

* **Enterotoxic E.coli** - food and water, travellers diarrhoea; heat labile toxin -> increased cAMP -> increased chloride secretion and decreased absorption (like cholera); heat stable toxin -> increased cGMP * **Enterohaemorrhagic E.coli** - beef, especially ground, milk and vegetables; shigella-like toxin; large outbreaks with bloody diarrhoea and haemolytic uraemic syndrome; small risk of TTP * **Enteroinvasive E.coli** - food, water and person to person; no toxins, invades mucosa and colitis * **Enteroaggregative E.coli** - adheres via **adherence timbre**; dispersin removes negative charge; has shigella like toxin and ETEC heat stable toxin; causes non-bloody diarrhoea and is prolonged in AIDS 2 of any 4 groups to pass and 1 feature of any 2 to pass

Answer 230

* **Viral**: rotavirus, norovirus, enteric adenovirus * **Bacterial**: ingestion of preformed toxin: staph aureus, vibrios and clostridium perfringens. Enteroinvasive organism: invade and destroy mucosal epithelial cells (E.coli, Shigella, Salmonella) * **Parasites**: giardia limblia, amoeba

Answer 231

* Colitis caused by **overgrowth of C.difficile** (also Salmonella, S.aureus) * Associated with antibiotic use * Forms a **pseudomembrane** made up of adherent layer of inflammatory cells and debris Bold to pass

Answer 232

* **Advanced age** * **Hospitalisation** * **Antibiotic treatment** 2 bold to pass

Answer 233

* 30% hospitalised patients colonised, but most asymptomatic * **Fever**, leukocytosis, **abdominal pain**, cramps, hypoalbuminaemia, watery **diarrhoea**, dehydration, rarely gross bloody diarrhoea * Diagnosis - usually detection of toxin * Treat with metronidazole and vancomycin Bold to pass

Answer 234

* **Acute arterial obstruction** - atherosclerosis, aortic aneurysm, hypercoagulable state, OCP use, embolism * **Intestinal hypoperfusion** - cardiac failure, shock, dehydration, vasoactive drugs * *Systemic vasculitis* - HSP, Wegeners granulomatosis * *Mesenteric venous thrombosis* - hypercoagulable state, invasive neoplasm, cirrhosis, trauma, abdominal masses * *Miscellaneous* - radiation, volvulus, stricture, amyloid, diabetes Bold to pass. Minimum 2 from each bolded group. 2 from non-bolded

Answer 235

* Severe **pain**, may be transient * Tenderness * Peritonism * Nausea and vomiting * Bloody diarrhoea * Melaena * Shock * Hyper/hypothermia * Sepsis Bold +3 features

Answer 236

* **Watershed zones** - splenic flexure, sigmoid colon and rectum - located at end of arterial supply * Surface epithelium: villi more at risk than crypts * Intestinal capillaries run from crypts up to villi to surface

Answer 237

* Initial hypoxic injury * **Secondary reperfusion injury** - major injury in this phase - free radical production, neutrophil infiltration, inflammatory mediator release * Magnitude of response determined by: vessels affected, time frame over which ischaemia develops Bold to pass

Answer 238

* Congestion * Oedema and haemorrhage in wall * Lumen contains bloody fluid * Mucosal necrosis * Gangrene * **Metabolic** and cardiovascular derangement eg. acidosis/fluid balance * **Perforation**, often leading to death Bold +2 more

Answer 239

* Strictures - submucosal involvement * Segmental, patchy mucosal degeneration 1 to pass

Answer 240

* H.pylori secretes **urease**, which generates free ammonia; and a **protease** which breaks down glycoproteins in the gastric mucosa * H.pylori makes **phospholipases** -> damage surface epithelial cells glycoprotein complexes * H.pylori enhances gastric secretion and impairs duodenal bicarbonate secretion. This enhances metaplasia. * Several H.pylori proteins are immunogenic -> evokes **strong immune response** in the mucosa. Activated T and B cells are both seen in chronic gastritis caused by H.pylori * Thrombotic occlusion of surface capillaries is promoted by a **bacterial platelet activating factor** * Other antigens (including **lipopolysaccharide**) recruit inflammatory cells to the mucosa * Damage to the mucosa is thought to permit **leakage of tissue nutrients** into the surface microenvironment, thereby sustaining the bacillus.

Answer 241

* Disruption of normal bowel flora (antibiotics) allowing overgrowth of C.difficile * C.difficile elaborates toxins that cause: - ribosylation of small GTPases - disruption of epithelial cytoskeleton - tight junction barrier loss - cytokine release - apoptosis * Denuded surface epithelium * Superficial lamina propria contains dense infiltrate of neutrophils and occasional fibrin thrombi in capillaries * Damaged crypts are distended by mucopurulent exudates that erupt "volcanically" * Coalesce to form the pseudomembrane Toxin +1 other to pass

Answer 242

Pseudomembrane is an adherent layer of inflammatory cells and debris at sites of colonic mucosal injury

Answer 243

**Gram -ve bacillus** - enterbacteriacae family - flagellated

Answer 244

* Caused by **salmonella typhi** (endemic) and **paratyphi** (travellers) * Endemic in India, Mexico, Phillipines, Pakistan, El Salvador, Haiti * Taken up mononuclear cells in the underlying lymphoid tissue in **gut invades** M cells * Reactive hyperplasia in lymph tissue * **Disseminates by blood**

Answer 245

* Causes fever, anorexia, vomiting and bloody diarrhoea * Blood cultures +ve in 90% with fevers * Subsequent bacteraemia with fever and flu-like symptoms

Answer 246

* **Invades epithelium (low oxygen environment)** * Taken up by macrophages * Gut wall **inflammation** * Neural reflex pathway

Answer 247

* **Inflammatory bowel disease** * Severe ulcerating inflammatory disease * Limited to colon and rectum - continuous distribution (no skip lesions) - extends only into mucosa and submucosa (not transmural) - pancolitis is entire colon affected * Superficial broad based ulcers * Pseudopolyps * Malignant potential * Toxic megacolon Bold +2

Answer 248

* Polyarteritis * Sacroillitis, ankylosing spondylitis * Uveitis * Skin lesions * Pericholangitis * Primary sclerosing cholangitis 4 to pass

Answer 249

* Primary sclerosing cholangitis * Toxic megacolon * Neoplasia 2 to pass

Answer 250

* Often multi-focal * Carcinomas are often infiltrative without obvious exophytic masses 1 to pass

Answer 251

* **Blood loss**: acute, chronic * **Increased RBC destruction**: Inherited genetic: Spherocytosis, G6PD, Thalassaemia, Sickle cells. Ab mediated: transfusion, drugs, rhesus disease. Mechanical trauma: HUS, DIC, TTP, cardiac valves, runners. Infectious: malaria. Toxic: envenom, clostridia * **Decreased RBC production**. Inherited genetic: Fanconi's, thalassaemia. Nutritional: B12/folate, iron. Erythropoietin deficit: renal failure, chronic disease. Immune: aplastic anaemia Bold main headings +1 example of each

Answer 252

* Causes: chronic blood loss, poor diet, impaired absorption, increased requirements * Iron stores used up first - **ferritin** and haemosiderin * Once reserves depleted **serum iron and transferrin** decreased * Erythroid activity increases, no iron in marrow macrophages. Red cells become **hypochromic and microcytic** Bold to pass

Answer 253

* Hereditary spherocytosis: Northern Europe * G6PD: 10% African American, Africa, Middle East, Mediterranean * Sickle cell: African descent, up to 30% * Thalassaemia triat: Africa, Asia, Mediterranean, India * Pernicious: Scandinavian, caucasian 1 correct with example

Answer 254

* Intravascular/extravascular * Extrinsic/intrinsic to the RBC * Hereditary/acquired One classification to pass

Answer 255

* Decreased RBC left span due to **premature destruction** * Increased erythropoietin and erythropoiesis * Accumulation of products of Hb catabolism * Reticulocytosis Bold +1 other to pass

Answer 256

* Mechanical injury: cardiac valves, microangiopathic, repetitive physical trauma * Complement fixation: ABO incompatible blood transfusion * Intracellular parasites: malaria * Exogenous toxins: clostridia 2 to pass

Answer 257

* **Haemoglobinaemia** * Haemoglobinuria * Unconjugated **hyperbilirubinaemia** (jaundice) from catabolism of haem groups in mononuclear phagocyte system * Hemosiderin and renal hemosiderosis * Decreased serum haptoglobin due to binding with free Hb and then cleared by monophagocyte system * Free Hb oxidised to metHb * Reticulocytosis Bold +1 other to pass

Answer 258

* **Chronic blood loss - GI tract**, menorrhagia * Increased requirements - pregnancy, children * Dietary lack - developing world, infants (prolonged breastfeeding), elderly, extreme diet * Impaired absorption - coeliac gastrectomy Bold +3 others

Answer 259

* General - fatigue, weakness, dyspnoea, angina * Features of cause - melaena, menorrhagia 4 for pass

Answer 260

* Koilonychia * Alopecia * Glossitis * Pica * Pharyngeal swab 1 for pass

Answer 261

* **Microcytic hypochromic anaemia** (low Hb) * Low iron levels * Low ferritin levels * High transferrin levels * Low transferrin saturation levels .

Answer 262

* **Immunologically mediated** (possibly autoimmune) destruction of gastric mucosa -> chronic atrophic gastritis * **Likely an autoreactive T-cell response -> gastric mucosal injury and production of autoantibodies** which may exacerbate epithelial injury * Loss of parietal cells leads to reduced intrinsic factor production which in turn leads to reduced vitamin B12 absorption from the gut, resulting in macrocytic anaemia Bold to pass

Answer 263

* Insidious onset and progressive unless treated * **Moderate to severe megaloblastic anaemia. Weakness, tiredness, pallor** * Leukopenia and thrombocytopaenia * Mild jaundice (ineffective erythropoiesis and enhanced peripheral haemolysis) * Atrophic glossitis (shiny glazed appearance) * Neurologic manifestations may include spastic paraparesis, sensory ataxia and severe paraesthesias

Answer 264

* A reduction in amount of activity of factor VIII * Factor VIII is a co-factor for factor IX in the activation of factor X * X-linked recessive trait. Therefore males and homozygous females. * 30% have no family history so probably due to a new mutation

Answer 265

* Lack of factor VIII affects the intrinsic pathway, inappropriate fibrinolysis, inadequate coagulation * Normally, the extrinsic pathway produces initial burst of thrombin activation, that activates the intrinsic pathway. Unable to do so in Haemophilia * Thrombin activates the intrinsic pathway via factors XI and XII * Thrombin activate Thrombin activatable fibrinolysis inhibitor, which inhibits fibrinolysis First 2 points to pass

Answer 266

* <1% severe * 2-5% moderate * >6-50% mild

Answer 267

* **Hereditary** blood disorder * **Haemoglobinopathy** Bold to pass

Answer 268

* Haemolysis/Haemolytic anaemia * Microvascular occlusions (crises/tissue ischaemia = severe pain in affected organs eg. bones, lungs, liver, spleen) * Splenic enlargement, infarct and dysfunction (increased susceptibility to infection - encapsulated organisms (eg. strep pneumonia, haemophilus influenza) 2 to pass

Answer 269

* Hypoxia * Dehydration * Drop in pH 2 to pass

Answer 270

**Decreased production of platelets** * Generalised diseases of bone marrow - aplastic anaemia, leukaemia, cancer * Selective impairment of platelet production - drug induced (alcohol, thiazides, cytotoxic) - infections (measles, HIV) * Ineffective megakaryopoiesis - megaloblastic anaemia, myelodysplastic syndromes **Decreased platelet survival** * Immunological destruction - autoimmune (ITP, SLE) - drugs (quinidine, heparin, sulfamethoxazole) - infections (mononucleosis, HIV, CMV) * Non-immunological destruction - DIC, TTP, giant haemangioma, sequestration * Hypersplenism * Dilutional 2 bold and 2 examples in each

Answer 271

* Triggers: primary (idiopathic ITP) or secondary (drugs, HIV) * Chronic - more common - young adult women * **Formation of antibodies against platelet** membrane glycoproteins (2b/3a) - antibodies evident 80% * Opsonised platelets susceptible to phagocytosis (mononuclear) * Spleen probably major site of removal - 80% improve after splenectomy (site destruction + autoantibody synthesis) * Acute - disease of childhood * Viral illness - abrupt onset; antiplatelet autoantibodies; self-limiting; resolved usually within 6 months Bold to pass

Answer 272

Haem: * Increased bleeding time with normal platelets * Increased PT time (types 1 & 3) Clinical: * Spontaneous bleeding from mucous membranes * Increased bleeding from wounds * Menorrhagia * Bleeding into joints rare except in type 3 3 out of 4 to pass

Answer 273

* **Type 1** and **Type 3** associated with decreased circulating vWF. Type 1 most common (70%), autosomal dominant and usually mild. Type 3 autosomal recessive and severe * **Type 2** has defective vWF, autosomal dominant, mild severity and 25% of cases 2 to pass

Answer 274

* Prolonged bleeding time and normal platelet count, possibly increased partial thromboplastin time * Either quantitive or qualitative deficiency in vWF leading to factor VIII dysfunction * Main function is facilitation of adhesion of platelets to subendothelial collagen in haemostasis * Increases the half life of factor VIII from 2.5 to 12 hours

Answer 275

* Bone marrow * Circulating * Lymph nodes * Spleen * Peripheral lymphoid tissue 4 to pass

Answer 276

* Specific receptor complex (IgM) * Transformation to plasma cell * Production of specific immunoglobulin

Answer 277

* CD4+ T helper cells * Cytokines (IL-4 and -5) * B cell stimulated by antigen in presence of cytokines

Answer 278

* Acid gastric secretions * Viscous mucosal layer * Lytic pancreatic enzymes * Bile detergents * Secreted IgA antibodies * Competition for nutrients with commensal bacteria * Clearance by defaecation 3 to pass

Answer 279

* **Mucociliary blanket** within upper airways for trapping large microbes * **Coughing** (clears microbes from trachea) * **Ciliary action** within trachea and large airways (moves them up to be swallowed) * **Alveolar macrophages** or neutrophils attack and destroy microbes 2 to pass

Answer 280

* Smoking * Cystic fibrosis (viscous secretions) * Aspiration of stomach contents * Trauma of intubation * Viral infection * Bacterial infection 3 to pass

Answer 281

* B lymphocytes * CD4+ helper T lymphocytes * CD8+ cytotoxic T lymphocytes * Natural killer cells B and T to pass

Answer 282

* Adaptive immunity - circulate widely and re-circulate (especially T cells - respond to foreign substances/antigens). Can become effector or memory cells * B cells: recognises Ag via membrane IgM/IgD - plasma cell - secretes Ig/Ab = humoral immunity. Also have complement * T cells: Ag specific T cell receptor - binds to Ag on cells (on MHC molecules on APCs) - activates cell depending on type cell mediated immunity * CD4/T helper recognise class II MHC bound Ag: cytokine release - leads to macrophage activation, inflammation and B cell stimulation * CD8/T cytotoxic recognise class I MHC bound Ag: infected cell destruction * NK cells - kill infected and tumour cells. No prior exposure needed. Healthy cell class I MHC - inhibits NK cells. Can secrete cytokines and trigger inflammation

Answer 283

* Exposure to **antigen** * Presentation of antigen to **T helper cells** by dendritic cells * T helper cells differentiate into Th2 cells * These release cytokines that act on **B cells to produce IgE** * **IgE** binds to **mast cells** * **Repeat exposure to the antigen** - binds to and cross-links IgE antibodies on surface of mast cells - release of **vasoactive amines** and **lipid mediators** (immediate reaction) and cytokines (late phase reaction) from mast cells * **Action of mediators on end organs** results in clinical manifestations of anaphylaxis: vasodilation, vascular leakage, smooth muscle spasm. Antigen, IgE, mast cells and 3 other bolds to pass

Answer 284

* Skin * Respiratory (upper and lower) * GI tract * Cardiovascular * Neurological 2 to pass

Answer 285

* Vasodilation * Increased vascular permeability * Smooth muscle spasm/bronchospasm * Cellular infiltration * Epithelial damage 3 to pass

Answer 286

A **rapid** immunologic reaction due to **antigen and antibody (IgE)** combining Bold to pass

Answer 287

* **Previous Ag exposure** results in activation of Th2 cells results in **IgE antibody production** by B cells * IgE binds to mast cells * **Repeat Ag exposure**, Ag-Ab bind and results in **mast cell degranulation** * **Vasoactive amines** (histamine) and lipid mediators (leukotrienes, prostaglandins) released. * May have **late phase reaction** (cytokines) 3 bold to pass

Answer 288

* Vascular dilation/oedema - histamine, leukotrienes * Smooth muscle contraction - leukotrienes, histamine, prostaglandins * Mucous production 2 to pass

Answer 289

Ongoing inflammatory reaction without additional exposure to triggering antigen

Answer 290

* Phase 1 - initial rapid with vasodilation, vascular leakage - smooth muscle spasm and glandular secretion 5-30 minutes subsides after 60 minutes. Mediators include biogenic amines, enzymes, eg. proteases, proteoglycans eg. heparin, cytokines * Phase 2 - 2-24 hours - infiltration of basophils, eosinophils, neutrophils, CD4+ with tissue destruction especially mucosal 2 with time frame and at least 2 mediators to pass

Answer 291

**Hypersensitivity caused by antibodies that react with antigens present on cell surfaces or in the extracellular matrix** Antigens can be intrinsic to the membrane or extrinsic eg. drug metabolites Bold to pass

Answer 292

* **Opsonisation and phagocytosis: IgG antibodies opsonise cells plus complement activation** generates C3b & C4b recognised by phagocyte Fc and protein receptors resulting in **phagocytosis & destruction of opsonised cells**. Examples: transfusion reaction, autoimmune haemolytic anaemia, thrombocytopenia * **Complement and Fc receptor mediated inflammation: antibodies bind to fixed tissue** such as basement membranes, extracellular matrix **activates complement**, which generates by-products particularly chemotactic agent C5a. **Increase vascular permeability**. Examples: glomerulonephritis, vascular rejection in organ grafts * **Antibody mediated cellular dysfunction:** antibodies directed against cell surface **receptors impair or dysregulate function without causing cell injury or inflammation**. Examples: myasthenia graves, Graves's disease, insulin resistant diabetes Bold 2/3 with 1 example for each to pass

Answer 293

**Caused by antibodies that react with antigens present on cell surface or in the extracellular matrix**. Antigens can be intrinsic to the membrane or matrix or extrinsic eg. drug metabolite

Answer 294

* Transfusion reaction * Autoimmune haemolytic anaemia * Myasthenia gravis * Grave's disease * Vascular rejection in organ grafts

Answer 295

* Antibodies directed against cell surface receptors may bind to the receptors and either * Up-regulate their function - ie. Graves disease * Down-regulate their function ie myasthenia gravis

Answer 296

**Antibodies bind antigens and then induce inflammation** directly or by activating complement. The recruited leukocytes produce tissue damage by release of lysosomal enzymes and generation of toxic free radicals. 3 phases: * Formation of **antigen antibody complexes (immune complexes)** in circulation * Disposition of **immune complexes** in various tissues * **Inflammatory reaction** at the site of deposition, causing tissue injury Bold to pass

Answer 297

* Serum sickness * SLE * Polyarteritis nodosa * Post-strep glomerulonephritis * Acute glomerulonephritis * Reactive arthritis * Arthus reaction 2 to pass

Answer 298

* Arthritis * Skin lesions * Vasculitis * Nephritis * Fever 2 to pass

Answer 299

* **Type 3 hypersensitivity** * Phase 1: **Formation of immune complexes**: Protein Ag, 1/52 -> Ab -> blood -> Ag-Ab complexes * Phase 2: **Deposition** of immune complexes. Medium size, antigen excess most pathogenic. High pressure filtration in glomeruli and joints * Phase 3: **Tissue injury** caused by immune complexes leading to **acute immune reaction** on day 10 3 phases

Answer 300

* IgG and IgM bind to leukocyte Fc receptors * Leukocyte recruitment and activation * Release of proteases/lysosymal enzymes leading to damage * Deposition, activation and consumption of complement and decreased C3 levels leading to inflammatory reaction and tissue damage

Answer 301

* Fever * Urticaria * Arthralgia * Lymph node enlargement * Proteinuria 3 to pass

Answer 302

* Renal glomeruli * Joints * Skin * Heart * Serosal surfaces * Small blood vessels 3 to pass

Answer 303

* **Complement cascade** - classical pathway; Opsonins C3b - resulting in phagocytosis; Chemotactic factors C5 fragments C5b67; Anaphylotoxins C5a, C3a; Membrane attack complex C5-9 * **Inflammatory mediators** liberated from neutrophils and macrophages, histamine, PAF, prostaglandins * Hageman factor, kinins * Oxygen free radicals Bold to pass

Answer 304

* Perivascular cellular infiltrates * Tissue oedema * Granuloma formation * Cell destruction 2 to pass

Answer 305

* Type 1 diabetes * Multiple sclerosis * Rheumatoid arthritis * Inflammatory bowel disease * Guillain Barre * Contact sensitivity dermatitis * Tuberculin reaction * Granulomatous diseases * Viral hepatitis 2 to pass

Answer 306

* Responses of differentiated effector T cells * T helper 1 cells -> cytokines, interferon gamma, stimulates and **activates macrophages** -> inflammation * T helper 17 cells -> chemokines, cytokines, IL-17,-22, **recruit neutrophils and monocytes, CD4 cells** * **Tuberculin reaction** starts **8-12 hours**, peaks **21-72 hours** * **Perivascular cuffing**, endothelial hypertrophy, **epithelioid** cells, **granuloma** 3 bold to pass

Answer 307

* Th1 cells are activated and secrete cytokines that are responsible for the delayed type reaction - IL-12, IFN-gamma, TNF, lymphotoxin, chemokines. * Accumulation of mononuclear cells around small veins and venules, **perivascular cuffing**, increased **microvascular permeability, escape of plasma proteins** and **deposition of fibrin** in interstitium * T cell mediated cytotoxicity - sensitised CD8+ T cells (cytotoxic T lymphocytes) kill Ag bearing target cells

Answer 308

* In a naive individual, **CD4+ T cells** differentiate into Th1 cells after recognising antigen presented on APCs in association with class II MHC molecules. * **Th1 cells** can enter the circulation and remain in the **memory** pool of T cells for long periods (years) 2 bold to pass

Answer 309

* It is a cell mediated type of hypersensitivity initiated by specifically sensitised T lymphocytes * It includes the classes delayed type of hypersensitivity reactions initiated by CD4+ (Th1) cells and direct cell mediated cytotoxicity mediated by CD8+ (CTL) cells

Answer 310

* **Superficial mucosal infection** - mouth, vagina, oesophagus * **Superficial cutaneous infection** - intertrigo, nappy rash, balanitis, folliculitis, paronychia * Chronic mucocutaneous (T-cell defects, endocrinopathy) * **Invasive (disseminated)** - myocardial/abscess/endocarditis, cerebral abscess/meningitis, renal/hepatic abscess, endopthalmitis, pneumonia Bold + 1 examples from each category

Answer 311

* **Phenotypic switching** to adapt rapidly to changes in host environment * **Adhesion to host cells** - implies determinant of virulence - via adhesins (several types) * **Production of enzymes** (proteases and catalases) degrade extracellular matrix proteins and may aid intracellular survival * Secretion of adenosine - blocks neutrophil degranulation 1 bold to pass

Answer 312

* Gram +ve bacilli * Anaerobic * Spore-forming

Answer 313

* Gas gangrene (perfringens) * Tetanus (tetani) * Botulism (botulinum) * Diarrhoea (difficile) 3 to pass

Answer 314

* Normally ingested * In the cytoplasm, the "A" fragment cleaves the protein "synactobrevin". * Synactobrevin is needed for fusion of neurotransmitter vesicles * Results in **flaccid paralysis** Must have some idea of this plus bold

Answer 315

* Release enzymes - hyaluronidase; collagenase * Virulence factors - TOXINS * **Alpha toxin** - multiple actions - phospholipase C: degrades membranes; muscle; RBC - release phospholipid derivatives - ITP - prostaglandins - these cause derangement in cell metabolism and cell death At least 2 and alpha toxin

Answer 316

* **Acute laryngotracheobronchitis** in children * Inflammatory/spasmodic **narrowing of the airway** produces barking cough, inspiratory stridor * Causes are predominantly viral, especially **parainfluenza virus**, RSV, adenovirus and influenza are others Bold to pass

Answer 317

* Relatively rapid onset * Alterations in vascular calibre that **increase blood flow** * **Leaky microvasculature**: structural changes in microvasculature that permit plasma proteins and leucocytes to leave circulation. This leads to oedema * **Emigration of leucocytes (especially neutrophils)**, their accumulation at site of infection, and activation to eliminate offending agent * Duration of hours to days Bold to pass

Answer 318

* Cold sores * Gingivostomatitis * Encephalitis * Genital herpes * Keratitis * Disseminated visceral herpes (oesophagitis, bronchopneumonia, hepatitis, eczema herpeticum) At least 3 to pass

Answer 319

* Viral nucleocapsids travel from the skin / oropharynx / genitalia to the **nucleus in the sensory neurone** * During **latent period**, only viral mRNA is produced, no viral proteins are made to escape immune recognition * Reactivation from latency occurs by **avoiding immune recognition**, inhibiting the MHC class I recognition pathway and elude humeral immune defences by producing receptors for the Fc domain of immunoglobulin and inhibitors of complement. * Vesicular eruption along **dermatome of one or more sensory nerves**.

Answer 320

* **EBV** transmitted by close contact (saliva) * Envelope g/protein binds to B cells * Viral infection begins naso/oropharyngeal **lymphoid tissues** (esp. tonsils) * EBV accesses submucosal lymphoid tissues * B cell infection 1) **lysis** infected cells and virion release (minority) or 2) **latent** infection (EBV genes expressed) * Symptoms appear on initiation host immune response (cellular CD8+ cytotoxic T and NK cells) * Atypical lymphocytes (characteristic) * Reactive T cell proliferation lymphoid tissues - lymphadenopathy and splenomegaly * IgM Ab (viral capsid Ag) and later IgG * Healthy - cease viral shedding with few resting B cells but acquired defects may cause B lymphomas Bold to pass

Answer 321

* Classically - fever, sore throat, lymphadenitis, splenomegaly * Atypical presentation common - fatigue, lymphadenopathy, hepatitis, rubella-like rash 4 clinical features to pass

Answer 322

* 4-6 weeks most **resolve** - some fatigue longer * **Hepatic dysfunction** - jaundice, abnormal LFTs * **Splenic rupture** * Other systems - nervous, renal, lungs, heart * Transformation - **lymphomas** 3 to pass

Answer 323

* **Attacks CD4+ T cells** * **Profound immunosupression** * **Opportunistic infections** * **Neoplasma** * Neurologic manifestations .

Answer 324

* 75% sexual, **heterosexual** globally more common, female partners of IVDUs * Abetted by STDs * **Parenteral**: IVDUs major, blood products almost eliminated * **Mother-to-infant** in utero, at delivery, in breastmilk * Needle-stick 0.3%

Answer 325

* **Single stranded RNA** - 8 helices * Spherical capsule * Bound by nucleoprotein that determines type (A, B or C) and a lipid bilayer that contains both haemagglutinin and neuraminidase Bold to pass

Answer 326

* **ABC** (determined by a nucleoprotein) * **Haemagglutinin and neuraminidase** (determined by proteins on the bilipid envelope)

Answer 327

* **Antigenic shift** for pandemics * **Antigenic drift** for epidemics * Both H and N are changed by recombination of RNA from animal viruses Bold to pass

Answer 328

Only in influenza type A * Drift - mutation of the haemagglutinin and neuraminidase antigens allowing escape from most host antibodies (epidemic) * Shift - antigens replaced via recombination of RNA segments with those of animal viruses (pandemic) * Type B and C do not show drift or shift, mostly infect children, who develop antibodies preventing re-infection

Answer 329

* **2 mechanisms - cytotoxic T cells and macrophages** * Cytotoxic T cell kill virus infected cells, an intracellular anti-influenza protein is induced in macrophages by cytokines IFN- alpha and IFN - beta * Future infection is prevented (haemagluttinin Ab) and ameliorated (neuroaminidase Ab) Bold to pass

Answer 330

* **Attachment of virus to upper respiratory tract epithelium** * Necrosis of cells followed by inflammatory response * Interstitial inflammation with outpouring of fluid into alveoli * **Secondary infection by staph/strep** Bold to pass

Answer 331

* Malaria is a **protozoal** infection, intracellular **parasite** * **Plasmodium falciparum**, P.ovale, P.vivax, P.malariae Bold +1 more subtype

Answer 332

* Infectious stage (sporozoite) is found in saliva of female anopheles **mosquito** * Sporozoites released into blood and attach and **invade hepatocytes** * **Multiply** rapidly * **Hepatocyte ruptures**, released up to 30,000 merozoites * P. viva and ovale have dormant hepatic stage therefore can relapse * Released merozoites from liver **bind to** surface of **RBC**, grow in vacuole. * In RBC, become trophozoite (single chromatin), then schizont (multiple chromatin masses) then each chromatin becomes merozoite again * **RBC lyses** and new merozoites infect additional RBCs. Only erythrocytic parasites cause illness

Answer 333

* **Fever**, severe **anaemia**, acute renal failure, **cerebral symptoms**, pulmonary oedema, DIC * Congestion and enlargement of spleen * Infected RBCs clump -> ischaemia due to poor perfusion -> manifestations of cerebral malaria (vessels plugged with parasitised RBCs, local venous stasis, local hypoxia and inflammatory infiltrate) * Acute renal failure (Hb casts in tubules, pigment etc in glomerulus) * Stimulates cytokines, TNF, IFN, IL-1 -> pulmonary oedema, fever, shock Fever +1 to pass

Answer 334

* All do: sporozoite -> liver -> merozoites formed -> release and bind to RBC -> Hb hydrolysed -> trophozoite -> schizont -> merozoite/gametocyte * P.falciparum: **infects RBCs of any age**, causing **clumping/rosetting** so ischaemia, high cytokine production, **high level parasiteaemia**, severe anaemia, cerebral symptoms, renal failure, pulmonary oedema, death * Others: infect only new or old RBCs, P.vivax and ovale form latent hypnozoites (relapses), low parasitaemia, mild anaemia, rarely splenic rupture, nephrotic syndrome

Answer 335

* **Inherited alterations in RBCs; HbS** trait, HbC, Duffy Ag negative * Repeated exposure stimulates immune response: antibody and T lymphocytes (P. falciparum avoids this) Bold to pass

Answer 336

* Single stranded **RNA virus**, a membrane of the **paramyxovirus** family. * There is only one strain of virus - so preventable be vaccine 1 bold to pass

Answer 337

Respiratory droplet spread

Answer 338

* Viral pneumonia (60% of deaths) * Conjunctivitis and keratitis - scarring and blindness * **Acute measles encephalitis** (1:1000) Adults > Kids * Subacute sclerosing panencephalitis (1:100,000) * Diarrhoea (enteropathy) * Immunosuppression * Croup Bold +1 other

Answer 339

* T-cell mediated immunity controls the infection and produces the rash - a hypersensitivity reaction to viral antigens in the skin (no rash if deficient cell mediated immunity) * Antibody mediated immunity to Measles virus protects against reinfection

Answer 340

* CD46 (complement regulatory protein): inactivates C3 covertases; present on all nucleated cells; binds viral haemoagglutinin protein * SLAM (Signalling lymphocytic activation molecule): involved in T cell activation; only present on cells of the immune system; binds viral haemagglutinin protein Bonus questions

Answer 341

* Common coloniser of oropharynx - 10% of population at any one time, carry it for months * Spread by respiratory droplets * most people develop immune response and clear it - protected against later infection from this serotype * Invasive diagnosis when encounter new serotype * Invades respiratory epithelium, then blood stream * Capsule allows evade immune response by prevention of opsonisation and complement destruction * Mortality still approximately 10% despite antibiotic treatment 3 to pass

Answer 342

* Death * Sepsis * Necrotising vasculitis * Seizures * SIADH * CVA * Hydrocephalus * Meningitis * Sensorineural hearing loss * Cognitive impairment 4 to pass

Answer 343

* Other bacteria: E.coli & Group B strep, strep pneumoniae, Listeria, Haemophilus, * Viral: enterovirus, measles * Other: TB, rickettsial, carcinoma, autoimmune, chemical 2 bacteria plus viral to pass .

Answer 344

* Aerobic * Gram negative diplococci * Coffee bean shaped * Require chocolate blood agar * 13 serotypes of N.meningitidis .

Answer 345

* Meningitidis * Gonorrhoea

Answer 346

* **Surface proteins**: involved in adherence - express receptors for fibrinogen to bind to host endothelial cells, and artificial materials and evade immune response * **Secreted enzymes**: degrade proteins (promoting invasion and destruction) eg. lipase degrades skin lipid associated with ability to produce abscess * **Secreted toxins** that damage host cells: - alpha toxin (membrane depolarisation); beta toxin (sphingomyelinase); exfoliative A and B toxin; gamma toxin; super antigens (toxic shock and food poisoning) Toxins with example plus 1 other bold to pass

Answer 347

* Use of tampons * Post op wound infection * Post partum * nasal packs * Staph or strep skin infection

Answer 348

* Hypotension (shock) * Acute renal failure * Coagulopathy * Respiratory failure * Soft tissue necrosis at site of infection * Generalised erythematous rash 3 to pass

Answer 349

* **Staph aureus** * **Strep pyogenes** * Clostridium perfringens * Aerobic gram negative bacilli * Pseudomonas aeruginosa * Clostridium tetani Bold +1 to pass

Answer 350

* Skin/soft tissue: cellulitis, impetigo, abscess, folliculitis, paronychia, necrotising soft tissue infection * Pneumonia * Endocarditis * Osteomyelitis/septic arthritis * Food poisoning * Toxic shock syndrome

Answer 351

* Hypotension (shock) * Renal failure * Coagulopathy * Liver disease * Respiratory failure * Generalised erythematous rash * Soft tissue necrosis at site of infection 4 to pass

Answer 352

* **S.aureus** - skin, pneumonia, osteomyelitis * **S.epidermidis** - opportunistic eg. prosthetic valves * **S.saprophyticus** - UTI in women 2 to pass

Answer 353

**Gram positive cocci in pairs** or chains

Answer 354

* **Rheumatic fever** * **Glomerulonephritis** * Erythema nodosum, rash, myoclonus, myalgia, arthritis, neuropsychiatric sequelae 1 bold +1

Answer 355

* Mouth - dental caries - S.mutans * Skin - erysipelas - S.pyogenes * Skin - scarlet fever - S.pyogenes * ENT - pharyngitis - S.pyogenes * Lungs - pneumonia - S.pnuemoniae/pneumococcus * CNS - meningitis - S.agalactiae * Neonatal sepsis * CVS - endocarditis - S.viridans 4 to pass

Answer 356

* Acute **suppurative: skin, throat, lungs and heart valves** * Examples of different species as previous card

Answer 357

* Capsules - pyogenes, pneumoniae * M protein - prevents phagocytosis * Complement C5a peptidase * Pneumolysin - lyses target cells (s.pneumoniae) and activates complemet * Pyrogenic exotoxin - rash and fever * Sucrose -> lactic acid - S.mutans 3 to pass

Answer 358

Chicken pox and shingles

Answer 359

* Starts with aerosol or direct contact spread * Haematogenous dissemination * Vesicular skin lesions occur about 2 weeks post-exposure. Rash begins centrally and spreads centrifugally in multiple waves. Rash initially macular with rapid progression to a vesicle * After a few days, the vesicles rupture, crust over then heal * Some virus lies dormant in dorsal root ganglia and reactivated later with immunosuppression

Answer 360

* Lung - interstitial pneumonia * Nervous system - encephalitis, transverse myelitis * Skin and mucous membranes - shingles, bacteria superinfection * Gut - necrotising visceral lesions 3 to pass

Answer 361

* Mucous membranes * Skin * Neurones

Answer 362

* Reactivation of a latent virus * Erodes immune response * Dormant in sensory ganglion * Interstitial pneumonia * Visceral lesions * Encephalitis

Answer 363

* **Vasodilation**: opening of arterioles and capillary beds mediated by histamine and nitric oxide (NO) leading to increased blood flow * **Increased vascular permeability** * **Stasis**: due to plasma protein permeability and increased viscosity Bold to pass

Answer 364

* Endothelial contraction / retraction: gaps in venules due to histamine, bradykinin and leukotrienes, causing immediate transient response (lasting 15-30 minutes). Other stimuli (eg. UV radiation, burns, some bacterial toxins) result in delayed prolonged leakage (delay 2-12 hours and may last hours to days) * Direct vascular endothelial injury (eg. in severe burns, microbial toxin injury), rapid onset but may last days * Leukocyte mediated leakage: in venules and pulmonary capillary, long lasting (hours) * Trancytosis: increased transport of fluid and protein through endothelial cells, VEGF increases number +/- size transport channels

Answer 365

* >20 proteins (including C1-9) - once activated, trigger cascade * Recruitment and activation of lymphocytes (C3a, C5a) - inflammation trigger * Formation Membrane Attack Complex (MAC) - causing cell lysis * Phagocytosis (C3b) - phagocyte recognises C3b bound to microbe 2 to pass

Answer 366

* Substances release from necrotic cells * Microbial products * Cell injury * Mechanical irritation 2 to pass

Answer 367

* **Histamine**: vasodilation, increased vascular permeability, endothelial activation * **Prostaglandins**: vasodilation, increased vascular permeability * **Leukotrienes**: increased vascular permeability, chemotaxis, WC adhesion & activation * **Platelet activating factor**: vasodilators, increased vascular permeability, chemotaxis, WC adhesion, degranulation * **Complement**: WC chemo and activation, vasodilation * **Cytokines** (TNF, IL-1): endothelial activation (adhesion), fever, pain, hypotension, decreased vascular resistance * **Chemokines**: chemotaxis, WC activation * **Kinins**: increased vascular permeability, vasodilation, pain, smooth muscle contraction 4 to pass

Answer 368

* **Dilation of small vessels** leading to increase blood flow * **Increased permeability of the microvasculature** enabling plasma protein and leukocytes to leave the circulation * **Emigration of leukocytes from the microcirculation to the site of injury** Bold to pass

Answer 369

This is a multistep process mediated and controlled by adhesion molecules and chemokines. * **Margination**: occurs when leukocytes adopt a peripheral position along the epithelium. Rolling (transient adherence mediated by selecting), activation and firm **adherence** (mediated by integrins) to the endothelium * **Transmigration** (diapedesis) across the endothelium. Migration through inter endothelial spaces typically in post-capillary venules * **Chemotaxis**: leukocytes move toward the site of injury along a chemical gradient of chemoattractants, which can be exogenous or endogenous Bold to pass

Answer 370

* Most common exogenous agent **bacterial products** * Endogenous: IL-8, **C5a**, and leukotrienes B4. * All bind to specific receptors and promote polymerisation of actin Bold +1 .

Answer 371

* **IL-1** * TNF * Prostaglandins * Bradykinin * Neutrophils and macrophages * Lysosomal enzymes * Oxygen metabolites * NO Bold +1

Answer 372

* **Serous inflammation**: thin fluid from plasma or mesothelial lining cells eg. burns, effusions (pericardial, pleural) * **Fibrinous inflammation**: more severe injuries and greater vascular permeability allows larger molecules such as fibrin eg. characteristic of inflammation in body cavities (pericardial sac, meninges, pleura) * **Suppurative/purulent inflammation**: large amounts of pus/purulent exudates - neutrophils, necrotic cells, oedema fluid e.g. organism type * **Ulcers**: local defect in surface of an organ tissue 2 with examples

Answer 373

* **Complete resolution +/- scarring** * **Abscess formation** (suppurative inflammation) * **Fibrosis** (fibrinous inflammation) * **Chronic inflammation** 2 to pass

Answer 374

* **Neutrophils first 6-24 hours** * Monocytes 24-48 hours * Neutrophils may last longer (4 days) in pseudomonas * Lymphocytes in viral * Eosinophils in hypersensitivity Bold + 1 other

Answer 375

* More numerous in the blood * Respond more rapidly to chemokines * May attach more firmly to adhesion molecules * Neutrophils are short lived - disappear after 24-48 hours (monocytes live longer) 1 to pass

Answer 376

* **Recognition and attachment** to materials (opsonins) mediated by receptors * Killing of microbes: **phagocytosis / engulfment / killing and degradation** * **Release of products** - amplify the inflammatory reaction (lysosomal enzymes, reactive oxygen/nitrogen) 3 to pass

Answer 377

* Changes in blood flow: transient construction, **vasodilation** (NO mediated) lead to **increased flow** * **Increased permeability**, loss of protein-rich fluid * Fluid loss & dilation lead to **stasis/congestion** * Leukocytes accumulate at vascular endothelium, endothelium expresses adhesion molecules, leukocytes adhere and migrate out

Answer 378

* Chemically mediated **endothelial cell contraction** (caused by eg. histamine, leukotrienes, substance P) * Endothelial injury direct / microbes / leukocytes eg. burns * Increased transcytosis of fluids/proteins via channels of connected vesicles / vacuoles stimulated by factors eg. VEGF 2 to pass

Answer 379

* **Macrophages** * Lymphocytes * Eosinophils * Neutrophils (scarce) * Multinucleate giant cells * Plasma cells * Mast cells Bold +2 to pass

Answer 380

* **Continued recruitment** of monocytes (continued expression of adhesion molecules and chemotactic factors - macrophage activation factor) * Local proliferation of macrophages * Immobilisation of macrophages (migration inhibition factor)

Answer 381

* **Persistent infection**: TB, syphilis, abscess, empyema, osteomyelitis * **Prolonged exposure to an agent**: exogenous - foreign body, persistent trauma, silica -> silicosis; endogenous - lipid -> atherosclerosis * **Autoimmune**: rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, SLE At least 3 examples from at least 2 categories

Answer 382

* Inflammation for a **prolonged period** (week or more) * Characterised by **macrophages**, lymphocytes and plasma cells * With simultaneous active inflammation / **tissue destruction** and **attempts at repair** by connective tissue, fibrosis

Answer 383

* **Products associated with tissue injury**: toxic oxygen metabolites, proteases, neutrophil chemotactic factors, coagulation factors, arachidonic acid metabolites, nitric oxide * **Products associated with fibrosis**: growth factors (PDGF, FGF, TGF); fibrogenic cytokines; angiogenesis factors (FGF); "remodelling" collagenases 5 to pass

Answer 384

* **Plasma protein system involved in immunity** against microbes * Complement proteins numbered C1-9 are present in plasma in inactive forms

Answer 385

* **Classical pathway**: involving antigen-antibody complex * **Alternate pathway**: triggered by microbial surface molecules (eg. endotoxin), no antibody involvement * Lectin pathway: plasma mannose-binding lectin binds to carbohydrate on microbe * All pathways result in cleavage and activation of C3 (most important and abundant complement component) Highlighted & way activated to pass

Answer 386

* **Vascular effects**: increased permeability; vasodilation (via C3a, C5a mediated histamine release from mast cells) * Leucocyte adhesion, chemotaxis and activation: via C5a * Phagocytosis: C3b acts as opsonin on microbe and leads to phagocytosis * Cell lysis by the membrane attack complex (MAC) - composed of multiple C9 molecules Bold +1 other

Answer 387

* Vascular phenomena * Leukocyte adhesion, chemotaxis and activation * Phagocytosis 3 to pass

Answer 388

* Opsonisation (C3b) * Chemotaxis (C5) * Anaphylotoxins (C3a & C5a) * Membrane attack complexes (C5-9) 3 to pass

Answer 389

* Localised * Excess of antibody * Large immune complexes - precipitates - vasculitis

Answer 390

Widely distributed in tissues, richest sources: * Mast cells * Basophils * Platelets 2 to pass

Answer 391

* **Dilation of the arterioles** * **Increased vascular permeability of the venules** * Can cause constriction of large arteries

Answer 392

* **Hepatic steatosis** - fatty change, perivenular fibrosis * **Hepatitis**: liver cell necrosis, inflammation, Mallory bodies, fatty change, fibrosis * **Cirrhosis**: extensive fibrosis, hyperplasticity nodules * **Hepatocellular carcinoma**

Answer 393

* **Steatosis and hepatitis are reversible** * Cirrhosis is irreversible Bold to pass

Answer 394

* **Portal hypertension** * GI bleeding * Hepatic failure * Coagulopathy * HCC * Hepatorenal syndrome * Hepatopulmonary syndrome * Encephalopathy * Infection Bold +3 to pass

Answer 395

* Hepatocyte swelling and necrosis: single or scattered foci, swelling due to accumulation of fat, water and protein * Mallory bodies: eosinophilic cytoplasmic inclusions in degenerating hepatocytes, characteristic but not specific features * Neutrophilic reaction: accumulate around degenerating hepatocytes * Fibrosis: prominent activation of sinusoidal stellate cells and portal tract fibroblasts At least 3 to pass

Answer 396

* **Chemical irritation of obstructed gallbladder** * Mucosal phospholipase hydrolyse luminal lecithin to toxic lysolecithins * Protective glycoprotein mucus layer disrupted * Allows bile salts to have detergent action on exposed mucosal epithelium * Prostaglandins contribute to inflammation * Gallbladder dysmotility develops * Distension and increased intraluminal pressure decreases mucosal blood flow Bold +2 to pass

Answer 397

* **Bacterial infection - cholangitis/sepsis** * Perforation and localised abscess * Rupture and peritonitis * Biliary fistula * Porcelain gallbladder Bold +2 to pass

Answer 398

* Acalculous (10%) - rarer, in predisposed individuals, slower often masked * Ischaemia, end arteries * Other promoting features - sludging micro-crystals, stasis, local inflammation, distention * Sepsis with hypotension, immunosuppression, major trauma and burns, diabetes, infection, severe atherosclerosis (drugs/Abs) 3 to pass

Answer 399

* Right upper quadrant or epigastric pain * Mild fever, anorexia, tachycardia, sweating, nausea and vomiting, tender RUQ (Murphy's) 4 to pass

Answer 400

* Acute RUQ or epigastric pain and tenderness, mild fever, anorexia, tachycardia, sweating, nausea, vomiting * Calculous often more sudden, but can be mild & self-limiting * **Acalculous more insidious - may have no gallbladder symptoms** - usually in patient with other illness - risk of complications higher eg. perforation/gangrene Bold to pass

Answer 401

* **Bacterial infection: cholangitis, sepsis** * Gallbladder perforation and abscess formation * Gallbladder rupture and peritonitis * Biliary enteric fistula * Aggravation pre-existing conditions Bold +2 others

Answer 402

* **Age** - - 25% in the >80 years * **Gender** - women >men * **Environmental factors** - OC, pregnancy - increase expression of hepatic lipoprotein receptors and stimulates hepatic HMG-CoA reductase - enhancing cholesterol uptake and synthesis * Obesity, rapid weight loss * **Acquired disorders** - gallbladder stasis - neurogenic or hormonal * **Hereditary factors** - eg. genetic factors encoding for hepatocyte proteins that transport biliary lipids - ATP-binding cassette transporters 3 to pass

Answer 403

Requires the following simultaneous conditions: * **Bile supersaturated with cholesterol** * Hypomotility of gallbladder * **Cholesterol crystal nucleation** - accelerated * Hypersecretion of mucous in the gallbladder traps crystals - **aggregation into stones**

Answer 404

* Hepatocellular steatosis (fatty change) - reversible * Alcoholic hepatitis - reversible * Cirrhosis - non-reversible * Hepatocellular carcinoma - non-reversible 1 reversible and 1 non-reversible

Answer 405

* Occurs **diffusely** throughout the liver * **Parenchymal nodules (regenerating hepatocytes)** surrounded by dense **bands of fibrous scar** * **Disorganised architecture** * Variable degrees of **vascular / portosystemic shunting** * Elements of progression and regression 3 to pass

Answer 406

* **Alcoholic liver disease 60-70%** * Viral hepatitis 10% * Biliary diseases - 5-10% * Primary haemochromatosis - 5% * Wilson disease * Alpha 1 anti-trypsin deficiency * Idiopathic - 10-15% * Cardiac disease

Answer 407

**Hepatitis A virus** - small unenveloped single stranded RNA picornavirus, icosahedral capsid Bold to pass

Answer 408

Faecal oral spread

Answer 409

* Self-limiting illness * No carrier state * No chronic state * No association with hepatocellular carcinoma * Rarely leads to fulminant disease * Low fatality rate of 0.1% 3 to pass

Answer 410

* **Acutely IgM-anti HAV** * Faecal shedding of the virus ends as IgM titre rises (2-12 weeks) * IgM Ab (months) * Replace by IgG anti-HAV (years) Bold to pass

Answer 411

* Oral faecal transmission * Incubation period: 2-6 weeks * No carrier state or chronic hepatitis or cause hepatocellular cancer * Rarely causes fulminant hepatitis so the fatality rate is about 0.1% 3 to pass

Answer 412

* In developed nations - 50% at age 50 years have serological evidence of exposure * In developing countries - approaching 100% serological evidence by late teens 1 to pass

Answer 413

* Cirrhosis and **portal hypertension** with development of **oesophageal varices** * **Coagulopathy** due to loss of synthetic function (unable to produce coagulation proteins) 2 to pass

Answer 414

* Jaundice * Upper GI bleeding * Hepatorenal syndrome * Hepatic encephalopathy * Ascites / pleural effusions * Splenomegaly * Hypogonadism (testicular atrophy, amenorrhoea) * HCC 3 to pass

Answer 415

* Congenital (ie. vertical, most common worldwide) * Contaminated blood products - IVDU, transfusions, needle stick injury * Bodily fluids - eg. sexual 2 to pass

Answer 416

* Asymptomatic * Acute hepatitis * Non-progressive chronic hepatitis * Carrier state 2 to pass

Answer 417

* **Recovery** - >90% * Fulminant hepatic necrosis <0.5% * **Chronic hepatitis** * Healthy **carrier state** Bold to pass

Answer 418

* **HBeAg, HBsAg** * HBV-DNA, **Anti-HBc IgM** * Anti-HBe 2 bold to pass

Answer 419

**Flaviviridae** family **RNA** virus 1 bold to pass

Answer 420

* **IVDU** 54% * Multiple sex partners 36% * Recent surgery 16% * Needle stick 10% * Multiple contacts with HCV infected person 10% * Health care workers 1.5% * Unknown 32% * Children (perinatal) 6%

Answer 421

* Incubation 2-26 weeks (mean 6-12 weeks) - **Accumulation in 85%** * HCV RNA detectable in 1-3 weeks * Anti HCV Ab 50-70% while symptomatic * Usually a mild disease * **Persistent infection -> chronic hepatitis 80-85%** * Cirrhosis 20-30% (5-20 years) * Fulminant hepatitis rare Bold to pass

Answer 422

* Highly stable core, **extremely variable envelope (E protein)** * RNA polymerase inherently unstable, frequent mutations, multiple *quasispecies* found in any one patient * Genomic and antigenic variability * Actively inhibits interferon mediated cellular response at many levels 2 to pass

Answer 423

* Incubation period (2-26 weeks) * HCV-RNA (detectable for 1-3 weeks co-incident with transaminitis) * Anti-HCV antibodies emerge. Only about 50% detectable during symptomatic acute infection. Remainder after 3-6 weeks. IgG/IgM. IgG persists

Answer 424

* RNA virus * Must **always be in conjunction with hepatitis B** * **Acute infection** - indistinguishable from classic acute hepatitis B. Exposure to serum containing both hepatitis B and D. HBV must establish first to provide HBsAg necessary for development of complete HDV viridons * **Superinfection** - chronic HBV carrier exposed to new inoculum to HDV. Disease develops 30-40 days later * Helper-independent latent infection - in liver transplantation patients Bold to pass

Answer 425

* Severe acute hepatitis in previously unrecognised HBV carrier * Exacerbation of pre-existing mild chronic hepatitis B * 80-90% chronic progressive disease and cirrhosis 1 to pass .

Answer 426

* **IgM anti-HDV** - most reliable marker of recent HDV exposure but late and short lived * HBV and HDV co-infection - best with IgM against both HDAg and HBcAg At least 1 to pass

Answer 427

* Acute enlarged red (green) liver, ballooning degeneration, cholestasis and plugs, isolated cells of clusters necroses, cytolysis/apoptosis, bridging necrosis, architecture disarray * Regeneration hepatocyte proliferation, sinusoidal cell reactive changes (debris in Kupfer cells, influx of monocytes), portal tract inflammation

Answer 428

**Predominantly unconjugated** * Increased production of bile: haemolysis, resorption of haemorrhage, thalassaemia * Increased hepatic intake: drug interference with membrane carrier systems eg. Gilbert syndrome * Impaired conjugation: physiological jaundice of newborn, breathing milk, Gilbert syndrome, hepatitis **Predominantly conjugated** * Impaired bile flow (cholangiopathy, biliary stricture, malignancy, choledocholithiasis) * Deficiency canalicular membrane transporters (Rotor syndrome) Bold +1 cause each

Answer 429

* Icterus * Pruritis * Fetor hepaticus * Palmar erythema * Spider angiomata * Hypogonadism * Gynaecomastia * Encephalopathy (asterixis) * Coagulopathy * Hepatorenal syndrome * Hepatopulmonary syndrome * Portal hypertension 5 to pass

Answer 430

* Renal failure in patient with severe chronic liver disease with no obvious cause for the renal failure * Features include: sodium retention; impaired free water excretion and decreased renal perfusion and GFR

Answer 431

* **Gallstones** * **Alcohol** * Iatrogenic * Viral * Hyperlipoproteinaemia * Hypercalcaemia * Drugs * Trauma * Shock * Vasculitis * Genetic mutations * Scorpion bite * Atheroembolism * Duct obstruction (tumour, parasites, etc) Bold +1 to pass

Answer 432

* **Autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes** eg. trypsinogen * Causes interstitial inflammation and oedema, proteolysis, fat necrosis and haemorrhage * Three potential pathways for initiation of pancreatic pathways: 1) pancreatic duct obstruction; 2) primary acinar cell injury; 3) defective intracellular transport of proenzymes within acinar cells Bold to pass

Answer 433

* Haemolysis * DIC * Fluid sequestration * ARDS * Diffuse fat necrosis * Peripheral vascular collapse * Shock * Acute renal tubular necrosis 3 to pass

Answer 434

* **Marked elevation of serum amylase** in first 24 hours * **Rising serum lipase** within 72-96 hours * Glycosuria - 10% cases * Hypocalcaemia - poor prognostic sign if persistent * Leukocytosis * Acute renal failure Bold + 2 to pass

Answer 435

* Range from trivial **inflammation** and oedema to extensive necrosis and haemorrhage * Microvascular leakage with oedema, **lipolysis** by enzyme, acute inflammatory reaction, proteolysis of parenchyma, destruction of blood vessels * Fatty acids released combine with calcium to precipitate as salts, acini, ducts and islets can all be involved * Red black haemorrhage mixed with yellow white fat necrosis * Extra pancreatic fat necrosis eg. in omentum * Peritoneal fluid with fat globules Bold to pass

Answer 436

* Parenchymal fibrosis, reduced number and size of acini with relative sparing of islets of Langerhans * Variable dilation +/- blockage of pancreatic ducts * Destruction of exocrine parenchyma and in later stages destruction of endocrine parenchyma * Calcification 3 to pass

Answer 437

* Irreversible impairment of pancreatic function including: diabetes, steatorrhoea, malabsorption * Chronic attack not immediately life threatening but long term outlook poor (50% 20-25 mortality) * Disease may be silent * Amylase, lipase may not raise in chronic attack * Pseudocyst 3 to pass

Answer 438

* Increased resistance to total blood flow * Pre-hepatic - portal vein thrombosis or narrowing * Hepatic - **cirrhosis**, massive fatty change, schistosomiasis, granulomatous disease eg. sarcoid/TB * Post-hepatic - severe right heart failure, constrictive pericarditis, hepatic vein occlusion Bold +1 from each other group

Answer 439

* **Ascites** - with potential for infection * **Porto-systemic shunts**: varices, haemorrhoids, spider naevi * Congestive **splenomegaly** - thrombocytopaenia/pancytopaenia * **Hepatic encephalopathy** 2 to pass

Answer 440

* Sinusoidal hypertension - starling forces : increased pressure and decreased albumin * Increased formation of hepatic lymph - exceeds capacity of thoracic duct - percolates into peritoneum * Splanchnic vasodilation with decreased BP -> renal retention of sodium and water due to secondary hyperaldosteronism 2 to pass

Answer 441

* Complete/incomplete * Open/closed * Comminuted * Displaced * Pathologic * Stress 3 to pass

Answer 442

* **Haematoma** fills fracture gap - provides fibrin mesh framework (hours) * **Influx** of inflammatory cells, fibroblasts, new vessels (days) * Haematoma organising -> **procallus** * **Ossification -> bony callus** (2-3/52) * Callus matures, **remodelling** (6 weeks) 4 to pass

Answer 443

* **Inadequate immobilisation** * Marked displacement / soft tissues * Vascular compromise * **Infection** (open fractures, foreign bodies) * Systemic factors - nutrition, osteoporosis, smoking, diabetes Bold +1 to pass

Answer 444

Initial large volume of callus - portions not **physically stressed** are **resorbed**, reducing callus size/altering contour

Answer 445

* **Hyperuricaemia** * Primary gout (90%; often idiopathic); overproduction (diet, unknown enzyme defects); reduced filtration / excretion with normal production * Secondary gout (10%; known cause, secondary effect is gout): leukaemias/tumour lysis psoriasis; inborn errors of metabolism (overproduction with increased excretion); chronic renal disease (reduced excretion) Bold +1 primary and secondary cause

Answer 446

* Hyperuricaemia * **Precipitation of urate crystals into joints** in synovium/cartilage * **Release of crystals into synovial fluid** (?trauma) * **Inflammatory response initiated** - crystals phagocytose by macrophages and neutrophils; release of inflammatory mediators by macrophages (interleukins, cytokines); resulting in further neutrophil chemotaxis; neutrophils also release inflammatory mediators (free radicals, leukotrienes, lysosomal enzymes) - acute arthritis Bold to pass

Answer 447

* Age and duration of hyperuricaemia * Genetic predisposition/ ETOH/ obesity/ drugs eg. thiazides/lead toxicity Bonus questions

Answer 448

* **Acute arthritis - crystallisation of urates within or around joint** * An event possibly trauma initiates the release of crystals into the synovial fluid * **Chronic arthritis** with repeated attacks - formation **tophi** in the inflamed synovial membrane and periarticular tissue * **Nephropathy** - deposit urate crystals in kidney and formation **uric acid stones** 3 bold to pass including arthritis

Answer 449

* Genetic and environmental (mechanical) * Age - virtually ubiquitous (80-90%) after 65 * Other exacerbating diseases eg. obesity, diabetes, injury, abnormal joints 2 to pass

Answer 450

* **Chondrocyte injury** * Early OA: **chondrocytes proliferate (cloning) and secrete inflammatory mediators**, collagens, proteoglycans, and proteases which initiates secondary inflammatory changes * Later OA: repetitive injury and chronic inflammation lead to chondrocyte drop out, marked loss of **cartilage** and extensive subchondral bone changes 2 bold to pass

Answer 451

* Mostly **asymptomatic** <50 years * Deep, achy **pain** worse with use, **morning stiffness, crepitus and limited range of movement** * **Oligoarthritis 95%** (occasionally generalised or early) * Impingement on spinal foramen by osteophytes results in cervical and lumbar nerve root compression and **radicular pain**, muscle spasms, **muscle atrophy** and neurological deficits * Common: hips, knees, lower lumbar and cervical vertebrae, PIP, DIP of the fingers, 1st MCP. Not wrist, elbow or shoulders 2 to pass

Answer 452

* Haematogenous spread of organism to bone * Extension from a contiguous site * Local bone injury and direct organism entry 2 to pass

Answer 453

* **Staphylococcus aureus** >80% of pyogenic ones * Others: E.coli, Klebsiella pneumoniae * Pseudomonas aeruginosa from IVDU and GU * Haemophilus influenzae and Group B strep in neonates Bold +1 to pass

Answer 454

* **Acute inflammation** - neutrophilic * **Abscess** - sub-periosteal/surrounding soft tissue * **Necrosis** - dead bone - sequestrum * Involucrum (fibrous tissue and reactive bone deposition) forms around devitalised infected bone Bold to pass

Answer 455

**Resolution** **Chronic - up to 25%** * Acute flare-ups * Pathological fracture * Endocarditis * Severe sepsis * SCC in draining sinus tracts * Sarcoma in infected bone Bold +1 to pass

Answer 456

* Triggered by exposure of genetically susceptible host to an arthritogenic antigen resulting in chronic inflammatory change * Continuing autoimmune reaction with activation CD4 helper T cells and inflammatory mediators and cytokines that destroy the joint * **Genetic susceptibility** - associated with HLA-DRB1 alleles * **Autoimmunity** - once inflammatory synovitis initiated autoimmune reaction T cells result in chronic destruction Autoimmune plus one other

Answer 457

* **Rheumatoid nodules** - elbow forearms, lumbar * **Fibrinoid necrosis** of lymphocytes * **Vasculitis** - purpuric, nail bed, neuropathy, ulcers At least 3

Answer 458

* Joint destruction * Renal failure

Answer 459

* **Joints** - perivascular inflammatory infiltration CD4+ helper T cells, plasma cells, macrophages * Increased vascularity * Organising fibrin, rice bodies * Neutrophil accumulation * Osteoclastic - juxta-articular erosion, subchondral cysts, osteoporosis * Pannus * Fibrous ankylosis - bony ankylosis 3 to pass

Answer 460

* **Staph** * **Strep** * Gonococcus * H influenza * Gram negative - E coli, Salmonella, Pseudomonas Bold to pass

Answer 461

* Immunosuppression - diabetes, steroids, other * Joint / trauma / surgery / prosthesis * Chronic arthritis, IVDU 2 to pass

Answer 462

* **Loosening of intercellular junctions** - down regulation of E-cadherin expression - mutations in gene for catenins * **Attachment of basement membrane / interstitial connective tissue components** - increased density of laminin and integrins * **Degradation of extracellular matrix** - proteases by tumour cells or induced stroma cells - matrix metalloproteases - type 4 collagenases and plasminogen activators * **Migration of tumour cells** - within circulation, aggregate in clumps, arrest and extravasate to distant sites, adhesion to endothelium and egress through basement membrane

Answer 463

* Collagenases produced by tumour cells or surrounding stromal tissue * Cleave type 4 collagen of epithelial and vascular basement membranes * Generate, from ECM, factors that promote angiogenesis, tumour growth and tumour cell motility

Answer 464

**Invasion of extracellular matrix** * Clonal expansion, growth, diversification, angiogenesis * Invasion of ECM * Metastatic subclone * Adhesion and invasion of basement membrane * Passage through ECM * Intravasation **Vascular dissemination and homing** * Interaction with host lymphoid cells * Tumour cell embolus - platelet tumour aggregates * Adhesion to basement membrane * Extravasation * Metastatic deposit * Angiogenesis * Growth

Answer 465

* Adhesion molecules whose ligands expressed preferentially on target organs * Chemokine receptors for target chemokines highly expressed in some organs * Target tissue may be unpermissive environment

Answer 466

Symptom complex in cancer-bearing patient not readily explained by tumour spread local or distant, or by hormones produced by the tumour tissue itself

Answer 467

* Ectopic hormone production and give example - SIADH (small cell lung/brain) - hypercalcaemia (PTH peptide) * Immunologic/autoimmune Eaton-Lambert, dermatomyositis * Tumour antigens

Answer 468

**Endocrinopathies** * Cushing - small cell lung cancer (ACTH) * SIADH - small cell lung cancer, intracranial (ADH) * Hypercalcaemia - squamous cell lung cancer, breast * Carcinoid - bronchial adenoma, pancreatic cancer and stomach * Polycythaemia - renal **Nerve and muscle syndromes** * Myasthenia - bronchogenic cancer * CNS/neuro (breast) **Dermatological** * Acanthosis nigricans (gastric, lung, uterine) * Dermatomyositis (bronchogenic, breast) Endocrinopathies with at least 2 examples and at least one other to pass

Answer 469

* Not generally understood * Anorexia * Elevated BMR

Answer 470

* **Tumour cell adhesion molecules** ligands preferentially expressed on target organ cells * **Chemokines** for target tissues * **Chemoattractants** from target organs

Answer 471

* Abnormal growth of a tissue * Growth exceeds and is uncoordinated with that of the original tissue * Growth continues in the absence of the stimuli which evoked the change * Preys on host and serves no purpose Must get the gist of all 3 points

Answer 472

* Local and metastatic direct effects - pressure, bleeding, ulceration, rupture and infarction * Cachexia * Hormonal * Paraneoplastic: endocrinopathies with 3 examples (bushings, SIADH, hypercalcaemia, hypoglycaemia, carcinoid syndrome); nerve and muscle (myasthenia); skin (acanthosis nigricans); bone (clubbing)

Answer 473

Clinico-pathology entity, **acute reduction of renal function** with morphological **tubular injury (usually)**. Reversible Bold to pass

Answer 474

* **Ischaemia**/abnormal blood flow. Systemic (thrombosis and hypovolaemia) and intra-renal (antipathies, malignant hypertension) * **Toxic injury to glomeruli / tubules** - myoglobin, drugs, contrast * Acute tubular interstitial nephritis - hypersensitivity reaction to drugs, IgA nephropathy * Obstruction (post-renal) - tumour, clots, stones Bold and 1 other category - 1 example for each

Answer 475

Highly variable * Initiation phase: decreased urine output with elevation of urea (<36 hours) * Maintenance phase: sustained decreased output (40-400ml/day), **oliguria** salt and water overload, uraemia, hyperkalaemia, metabolic acidosis * Recovery phase: **increased output** and hypokalaemia. Increased vulnerability to infection. May last for months Know initial decrease followed by diuresis

Answer 476

* Massive proteinuria, with the daily loss of 3.5g or more of protein (less in children) * Hypoalbuminaemia, with plasma albumin levels less than 30g/L * Generalised oedema * Hyperlipidaemia and lipiduria 3 to pass

Answer 477

* Loss of colloid osmotic pressure * Loss of serum albumin * Accumulation of water and sodium in tissues * Due to compensatory secretion of aldosterone: mediated by hypovolaemia, increased ADH, increased sympathetic system 3 to pass

Answer 478

* Derangement of glomerular capillary walls resulting in increased permeability to plasma proteins. Either structural damage or physicochemical alterations * Hypoalbuminaemia 1) secondary to above and 2) inability of liver to synthesis enough replacement albumin and 3) additionally increased renal catabolism of filtered albumin * Generalised oedema secondary to 1) loss of colloid osmotic pressure of blood. Compounded by 2) sodium and water retention due to activation of RAAS, enhanced ADH secretion, stimulation of sympathetic system and reduction in natriuretic factors * Hyperlipidaemia causes increased liver synthesis, abnormal lipid transport and decreased catabolism * Lipiduria is a combination of increased production and increased glomerular permeability

Answer 479

* Primary glomerular disease (95% kids and 60% adults) eg. focal segmental, membranous, minimal change, membranoproliferative * Systemic disease: diabetes, amyloidosis, SLE, drugs (NSAIDs), infections (malaria, hepatitis B and C, HIV), malignancies

Answer 480

* **Group A beta-haemolytic streptococci** * Typically post pharyngeal/skin infections (impetigo) * An **immunologically mediated disease** - usually type 3 * Granular **immune deposits in the glomeruli** - particularly GBM - leading to leaking glomeruli * Streptococcal antigen found in the glomeruli * Complement activation - low serum complement * Elevated titres of anti-streptococcal antibodies * Nephritis associated streptococcal plasmin receptor 2 bold and +1 other

Answer 481

* 1-4 weeks after a streptococcal infection of the pharynx or skin (impetigo) * Malaise, fever, nausea, oliguria **and haematuria** * Red cell casts, mild **proteinuria**, periorbital and other **oedema**, mild to moderate **hypertension** * 95% will recover quickly in 1-3 weeks, 4% chronic, 1% severe acute renal failure. Adult onset has worst prognosis * Depleted C3 and almost always strep antigens 2 bold and 2 other

Answer 482

* **Less benign in adults** * Sporadic cases and 60% fully recover (better recovery rates in epidemic outbreaks) * In the remainder glomerular lesions resolve less quickly or not at all. Prolonged proteinuria, haematuria and hypertension. Outcomes slow resolution, chronic glomerulonephritis or rapidly progressive glomerulonephritis Bold to pass

Answer 483

* Strains of group A beta haemolytic strep with M protein in wall * Rarely others

Answer 484

**Placental ischaemia** is the key feature leading to: * Reduction in PGI2 and PGE2 * Increased renin/angiotensin II * Increased thromboxane and endothelial dysfunction * Resulting in systemic hypertension and DIC Bold +1

Answer 485

Usually started after 32 weeks gestation, characterised by: * Hypertension, oedema and proteinuria * Headache and visual disturbances are common * Eclampsia is characterised by convulsion and coma 3 to pass

Answer 486

* Placental infarcts * Retroplacental haematomas * Villous ischaemia * Prominent syncytial knots * Thickened trophoblastic basement membrane * Villous hypovascularity * Fibrinoid necrosis * Intramural lipid deposition 3 to pass

Answer 487

* **Gram -ve bacilli** (>85%), endogenous organisms * E.coli, proteus, klebsiella, enterobacter * Staph, funghi, viruses in immunocompromised and renal transplant patients Bold +3 organisms to pass

Answer 488

* Colonisation to distal urethra * Entry into bladder * Urinary tract obstruction / stasis of urine * Vesicoureteric reflux * Intrarenal reflux .

Answer 489

* Urinary tract obstruction * Instrumentation * Vesico-ureteric reflux * Pregnancy * Females up to 50 years * Males >50 years * Abnormalities - congenital/acquired * Diabetes * Immunosuppression 4 to pass

Answer 490

* Congenital - urethral valves and strictures; bladder neck obstruction, ureteropelvic narrowing; reflux * **Calculi; prostatic hypertrophy** * **Tumours** - prostate, bladder, cervix/uterus * Inflammation - prostatitis; urethritis; retroperitoneal fibrosis * Sloughed papillae, clots * Pregnancy * Uterine prolapse * Cystocele * Functional - neurogenic (spinal cord/diabetic) Bold +1 to pass

Answer 491

* **Pain** due to distention or symptoms of underlying process eg. renal colic * Asymptomatic (in unilateral complete or partial) * Polyuria and nocturia * Calculi, hypertension, distal tubular acidosis * Oligo-anuria * Hyperkalaemia, increased urea and creatinine Bold to pass

Answer 492

* Infection * Stone formation * Atrophy / hydronephrosis / obstructive uropathy (if chronic) -> renal failure * Complications of renal failure 3 to pass

Answer 493

* Reduced GFR * Progressive **dilation** of the proximal ureter, renal pelvis and calyces (hydronephrosis) * Renal **parenchymal atrophy** * Blunting apices of the pyraminds * Interstitial inflammation leading to interstitial fibrosis * Enlargement of kidney * Eventual result is a large (150-20cm) thin walled **non-functional cystic** structure Bold to pass

Answer 494

* **Calcium** oxalate and phosphate - 70% * Struvite or triple (magnesium, ammonium, phosphate) - 15-20% * Uric acid - 5-10% * Cystine - 1-2% Bold +1 to pass

Answer 495

* Increased concentration of stone constituents * Changes in urinary pH * Decreased urine volume * Bacteria

Answer 496

* Pain * Haematuria * **Infection** * **Obstructive renal impairment** 1 bold + 1 other

Answer 497

* Initial **injury to alveolar capillary membranes** (endothelium) * **Acute inflammatory response** - neutrophil mediated * Results in **increased vascular permeability** and alveolar flooding * **Fibrin disposition** * Formation of **hyaline membranes** * Widespread **surfactant abnormalities** (damage to type 2 pneumocytes * Eventually - organisation with scarring 3 bold to pass

Answer 498

* **Infection** - sepsis, diffuse pulmonary infection, gastric aspiration * **Physical/injury** - trauma - head, pulmonary, fractures, near drowning, burns, radiation * **Inhaled irritants** - O₂ toxicity, smoke, irritant gases and chemicals * **Chemical injury** - heroin, barbiturate, acetylsalicylic acid, paraquat * **Haematological conditions** - multiple transfusions, DIC * **Other** - pancreatitis, uraemia, cardiopulmonary bypass, hypersensitivity 1 example from 3 groups

Answer 499

* Death * Survival with organisation and **scarring**

Answer 500

Disorder of the conducting airways usually caused by an immunological reaction, marked by episodic **bronchoconstriction** due to airway sensitivity to a variety of stimuli, **inflammation** of the bronchial walls, and increased **mucous** secretion Bold to pass

Answer 501

A wide range of inflammatory cells are involved - lymphocytes, eosinophils, mast cells, macrophages, neutrophils 2 to pass

Answer 502

* **Atopic** - most common. IgE (type 1) hypersensitivity reaction - Th2 mediated. It is characterised by an immediate (bronchoconstriction) and late-phase (inflammation) reactions. Th2 cytokines, IL-4, -5 and -13 are important mediators (IL-17 and -9) * **Non-atopic** - no evidence of allergen sensitisation (& negative skin test). Family history is rare. * **Drug induced (eg. aspirin)** * **Occupational (ep. epoxy fumes)** Must list at least 2 types including atopic and trigger mechanism

Answer 503

**Atopic** - triggered by environmental factors (dust, pollens, food, etc.) in synergy with other pro-inflammatory co-factors such as respiratory viral infections. Positive family history and skin test for allergens **Non-atopic** * Viral respiratory infections (rinovirus, parainfluenza, RSV) * Inhaled air pollutants - smoking, sulfur dioxide, ozone, nitrogen dioxide * Exercise induced * Exposure to cold 2 triggers

Answer 504

* Increased airway responsiveness * Episodic bronchoconstriction * Bronchial wall inflammation * Increased mucous 3 to pass

Answer 505

* **IgE mediated type 1 hypersensitivity** * **Environmental allergens/triggers** (eg. dust, pollens, foods, drugs) Bold +1 trigger

Answer 506

**Allergen exposure** produces IgE * Re-exposure triggers mast cell degranulation / cytokines * Bronchoconstriction * Mucous production * Vasodilation / increased vascular permeability Bold + concept

Answer 507

* Initial sensitisation to inhaled allergen (antigen) - favours IgE production and eosinophil recruitment * Immediate phase - minutes. Re-exposure to antigen triggers antigen induced cross linking of IgE bound to IgE receptors on mast cells in airways and release of chemical mediators. This results in opening of tight junctions between epithelial cells * Antigens then enter mucosa to release further mediators (via mast cell and eosinophil activation) and cause bronchoconstriction / oedema / mucous secretion +/- hypotension * Mediators act directly or via neural reflexes to induce bronchospasm / increased vascular permeability / mucous production / recruit mediator releasing cells from blood * Late phase asthma - hours. Recruited leukocytes arrive initiates fresh round of mediator release and epithelial damage and airway constriction

Answer 508

* Antigen + IgE = mast cell degranulation * Release of preformed mediators - open epithelial tight junctions - allow antigen to cross mucosa * Activates mucosal mast cells and eosinophils - more mediator release * Directly of through neuronal reflexes - bronchospasm, increased vascular permeability, mucous production, additional cell recruitment 3 to pass

Answer 509

Bronchiectasis is a disease characterised by **permanent dilation of bronchi** and bronchioles caused by **destruction of the muscle and elastic tissue**, resulting from or associated with chronic necrotising **infections**. Also scarring and persistent infections Bold to pass

Answer 510

* **Congenital / hereditary** - CF, immunodeficiency, ciliary dyskinesia * **Post-infectious (necrotising pneumonia)** - staph aureus, Haemophilus, TB, pseudomonas, adenovirus, HIV, influenza, fungi, aspergillosis * **Bronchial obstruction** - tumour, foreign body, mucous impaction * **Other** - RA, SLE, inflammatory bowel disease, post-transplantation 4 causes to pass

Answer 511

* Microscopic fat globules travelling in the circulation * Long bone fracture * Soft tissue trauma / burns - rare * Very common with severe skeletal injury but rarely (<10%) of clinical significance 2 to pass

Answer 512

* Mechanical obstruction of microvasculature (lungs & brain): fat globules / aggregated platelet and RBCs * Biochemical injury: FFAs from fat globules > endothelial injury, platelet activation & mediator release

Answer 513

* Asymptomatic (majority) * Neurological: altered LOC * Pulmonary: increased resp rate, SOB, hypoxia * Haematological: thrombocytopaenia & anaemia 2 to pass

Answer 514

* PEs originate from **DVT** (95% from lower limb) * Fragmented thrombi from DVTs are carried through the venous system and into the right side of the heart before lodging in the **pulmonary artery vasculature**: main pulmonary artery, pulmonary artery bifurcation or smaller branching arteries Bold to pass

Answer 515

Clinical manifestations depend on size and location of the thrombus in the pulmonary vasculature * Most PEs (60-80%) are small and produce no symptoms nor signs * Positive symptoms: chest pain, dyspnoea, collapse / syncope * Positive signs: hypoxaemia / tachypnoea, tachycardia, hypotension, shock / sudden death, acute right heart failure 5 to pass

Answer 516

* Fat (bone marrow) * Air / other gas * Amniotic fluid * Foreign body (eg. fragment of catheter) 2 to pass

Answer 517

* Primary - factor V Leiden, antiphospholipid syndrome, prothrombin mutations * Secondary - obesity, OCP, cancer, immobilisation, long haul flights, pregnancy, hip fractures 1 primary and 3 secondary factors

Answer 518

* **Extent of pulmonary artery blood flow obstructed** * Size of the vessel occluded * Number of emboli * Overall cardiovascular status * Release of vasoactive factors ie. thromboxane A2 Bold +2 to pass

Answer 519

Relates to size and number of emboli and overall status of cardiovascular system * Asymptomatic * Sudden death * Large PE - chest pain, dyspnoea, shock * Small PE - transient chest pain, cough and in predisposed individuals pulmonary infarct causing tachycardia, tachypnoea, haemoptysis, fever, pleural rub * Pulmonary hypertension 3 to pass

Answer 520

Chronic lung condition characterised by **irreversible** enlargement of the airspaces **distal to the terminal bronchiole**, accompanied by destruction of alveolar walls **without fibrosis** 2 bold to pass

Answer 521

* **Mild chronic inflammation (neutrophils + macrophages) - mediator release** (eg. leukotriene B4, IL-8, TNF) - causes damage and sustains inflammation * **Protease-antiprotease imbalance - destructive effect of high protease activity** in patients with **low anti-protease activity** - 1% of patients with emphysema have alpha - 1- antitrypsin deficiency (inhibits proteases, including elastase, secreted by neutrophils) * **Oxidant-antioxidant imbalance - abundant reactive oxygen species** (superoxide dismutase, glutathione) **In smoke depletes antioxidant mechanisms**, incite tissue damage 2 bold to pass

Answer 522

* "Pink puffer" = emphysema. Barrel chested, dyspnoeic, prolonged expiration, hyperventilation. Relatively normal gas exchange until late in disease * "Blue bloater" = chronic bronchitis. Hx of recurrent chest infections with purulent sputum, less dyspnoea, decreased respiratory drive. Patient is hypoxic and cyanotic. Peripheral oedema results from *cor pulmonale* and RV failure 2 distinguishing clinical features to pass

Answer 523

* Bullous lung disease * Expiratory airflow limitation * Infection * Respiratory failure * Pneumothorax * Cor pulmonale, congestive heart failure 3 to pass

Answer 524

* Smokers have **increased neutrophils & macrophages in alveoli** - smoking stimulates neutrophil chemotactic factor (eg. IL-8), nicotine chemotactic, smoke activates alternative complement pathway * **Smoking stimulates release of neutrophil elastase**, proteinase 3, Catepsin G * Smoking increases elastase activity in macrophages (not inhibits by alpha-1-antitrypsin) * Reactive oxygen species in cigarette smoke deplete glutathione and superoxide dismutase

Answer 525

* **Centri-acinar** - involves central or proximal parts of acinar - sparing distal alveolar, involvement of upper lobes and apices, primarily in male smokers associated with chronic bronchitis * **Panacinar** - uniform destruction and enlargement of acinus, predominantly in lower basal zones, associated with alpha 1 antitrypsin deficiency * **Distal acinar** - paraseptal * **Irregular emphysema** - air space enlargement with fibrosis First two to pass

Answer 526

* **Tobacco smoking** * **Environmental exposures**: radiation, asbestos, air pollution (particulates), occupational inhaled substances (nickel, chromates, arsenic) * **Genetic mechanisms**: dominant oncogenes (c-MYC, k-RAS) & loss of tumour suppressor genes (eg. p53, RB) * **Precursor lesions**: squamous dysplasia, carcinoma in situ, atypical adenomatous, hyperplasia Tobacco smoke + 2 concept areas to pass

Answer 527

* Cough - 75% * Weight loss - 40% * Chest pain - 40% * Dyspnoea - 20% 3 to pass

Answer 528

* SIADH - hyponatraemia * ACTH - Cushing's syndrome * Hypercalcaemia - parathormone, parathyroid hormone-related peptide or prostaglandin E * Hypocalcaemia - calcitonin * Gynaecomastia - gonadotropins * Carcinoid syndrome - serotonin, bradykinin 3 to pass

Answer 529

* **Adenocarcinoma** - more common in women * **Squamous cell carcinoma** - more common in males * **Small cell carcinoma** - very malignant * Large cell carcinoma - undifferentiated Bold to pass

Answer 530

* **Local invasion** * **Direct seeding** of cavities / surfaces * **Lymphatics** * **Haematogenous** * Surgical instruments/nerves 3 to pass

Answer 531

* Airway obstruction -> pneumonia, abscess, local collapse * Obstruction of SVC leading to SVC syndrome * Pleural effusion * Pericarditis or tamponade * Hoarseness * Dysphagia * Diaphragmatic paralysis (phrenic nerve) * Horner syndrome (sympathetic ganglia) 5 to pass

Answer 532

* Increased incidence among people with heavy exposure to asbestos * Asbestos bodies found in increased numbers in lungs of patients with mesothelioma * Long latent period for mesothelioma * No increased risk of asbestos workers who smoke. Asbestos workers more at risk of dying from lung carcinoma 2 to pass

Answer 533

* **Pleura** * **Peritoneum** * Pericardium * Tunica vaginalis * Genital tract Bold to pass

Answer 534

* **Strep pneumoniae** * Mycoplasma pneumoniae * Haemophilus influenzae * Moraxella catarrhalis * Staph aureus * Klebsiella pneumoniae * Pseudomonas aeruginosa * Legionalla pneumoniae Bold +2 others

Answer 535

* Extremes of age * Underlying chronic disease such as COPD, diabetes, CCF * Immunodeficiency: congenital or acquired, abnormal splenic function, decreased splenic function or asplenia 3 examples from 2 groups to pass

Answer 536

* Aspiration of **gastric** contents * Type of **patient** - decreased consciousness, debilitated, abnormal gag, repeated vomiting * **Chemical and bacterial** * **>1 organism** (aerobes > anaerobes) * **Necrotising** * Death / **abscess** 4 bold to pass

Answer 537

* **Bacterial or viral** * **Variable** pneumonia dependent on - etiology or host response * **Pre-dispose** - extremes age, chronic disease etc * **Agents** - strep pneumonia, haemophilus influenza * Clinical course modified by **antibiotics** * **Complications** - empyema, endo/pericarditis, meningitis 5 bold to pass

Answer 538

* Interstitial pneumonitis * Lack of exudate * Different clinical picture

Answer 539

* Mycoplasma, Q fever, Legionella * Viruses

Answer 540

* Aerosols/artificial aquatic environments - cooling towers, water supplies etc. Also in other moist conditions * Aspiration of aerosolised organisms or aspiration of contaminated water

Answer 541

Underlying co-morbidities - cardiac, renal, immune, haematological, transplant patients especially

Answer 542

Urinary antigen or fluorescent antibody test on sputum. Culture is gold standard

Answer 543

* Primary infection * **Primary complex** (localised caseation) (Ghon complex is primary Tb with mediastinal nodes) * Primary complex may heal or lead to latent lesions * **Latent period** or progressive primary TB (latter of which may lead to military TB) * Latent lesion reactivated leading to **secondary TB**. (Re-infection may also lead to secondary TB) * Secondary TB occurs as localised (pulmonary or extra-pulmonary) caveating destructive lesions OR progressive secondary TB * Progressive secondary TB may lead to **miliary TB**

Answer 544

* **Clinical features** in at risk patients (history and examination) and apical lung consolidation / cavitation on **CXR** * **Microbiological confirmation** - acid fast smears and cultures (3-6 weeks solid agar media, 2 weeks liquid media) - PCR * Other eg. Mantoux test Bold to pass

Answer 545

* Infection by M. tuberculosis airborne - usually person to person airborne droplet spread * M tuberculosis enters alveolar macrophages and replicates by blocking phagosome / lysosome fusion leading to bacteraemia * Immunity through T cell mediated delayed type hypersensitivity reaction that also causes hypersensitivity and tissue destruction - in particular granuloma formation and caseation * Re-exposure or reactivation causes heightened immune reaction as well as tissue destruction

Answer 546

Pattern of disease that arises in a previously sensitised host

Answer 547

* May follow shortly after primary infection (<5%) * **Reactivation of latent organisms** - typically in areas of low disease prevalence * **Reinfection** - typical in regions of high prevalence 2 to pass .

Answer 548

* Locale - **apical upper lobe in secondary** * **Area - inflammation / granuloma** / multinucleate giant cells * Central **caseous necrosis** * **Cavitation** * **Healing with fibrosis and calcification** * Complications include tissue destruction, **erosion of blood vessels, military spread, pleural effusion, empyema, fibrous pleuritis** 3 to pass

Answer 549

**The process of blood vessel formation in the adult** via two methods: * Branching and extension of existing vessels * Recruitment of endothelial progenitor cells Bold + 1 other

Answer 550

* Wound healing * Chronic inflammation * Proliferating endometrium * Tumours 2 to pass

Answer 551

* Vasodilation * Proteolytic degradation of basement membrane * Endothelial cells migrate to angiogenic stimuli * Maturation * Stabilisation: endothelial cells from pre-existing vessels become motile & proliferate to form capillary sprouts * Recruitment of peri-endothelial cells for support structure formation 3 to pass

Answer 552

* Fibrosis - excess deposition of collagen & ECM in chronic disease * **Frustrated healing / chronic inflammation** * **Persistent stimulus** (infections, autoimmune, trauma) * Macrophage / leukocyte stimulation * **Growth factors**: PDGF, FGF, TGF - leading to **proliferation of fibroblasts**, endothelial cells 4 to pass

Answer 553

* Cirrhosis * Chronic pancreatitis * Pulmonary fibrosis * Pneumoconiosis * Constrictive pericarditis * Glomerulonephritis 3 to pass

Answer 554

* Inflammatory process * Fibroblast migration and proliferation * Angiogenesis and formation of granulation tissue * Extracellular matrix deposition * Tissue remodelling * Wound contraction * Acquisition of wound strength

Answer 555

* Growth factors: TGF-beta, PDGF, EGF, FGF * Cytokines: IL-1, TNF 2 to pass

Answer 556

* Tissue environment and extent of tissue damage * Intensity and duration of stimulus * Conditions that inhibit repair: foreign bodies or inadequate blood supply, infection * Disease states that inhibit repair: diabetes / steroids * Nutrition * Genetic - keloid

Answer 557

**Increase in collagen synthesis** (type 1) and **reduction in collagen degradation** (first 2 months) then **structural modification** of collagen with cross linking and increased fibre size Bold to pass

Answer 558

Skin wound has **10% tensile strength at 1 week** and continues to improve over next 3 weeks and **plateaus at 3 months when tensile strength is 70-80%**. May never recover to 100%

Answer 559

* **Inflammation, proliferation, and maturation** * Phases overlap, and separation arbitrary. * The initial injury triggers platelet adhesion and aggregation and formation of clot on wound surface causing **inflammation** * **Proliferative phase**: formation of granulation tissue, proliferation and migration of connective tissue cells and re-epithelialisation of the wound surface * **Maturation** involved ECM deposition, tissue remodelling + wound contraction 2 phases in bold with correct descriptions

Answer 560

**Systemic factors** * Nutrition - protein and vitamin c deficiency * Metabolic status - diabetes mellitus - delayed healing * Circulatory status - inadequate blood supply or drainage (arteriosclerosis or varicose veins) * Hormones - glucocorticoids influence various components of inflammation, also inhibit collagen synthesis **Local factors** * Infection * Mechanical factors - early motion of wounds * Foreign bodies impede healing * Size, location and type of wound - mechanism of injury 2 of each to pass

Answer 561

* **Wound contraction generally occurs in large surface wounds** * The contraction **helps to close the wound by** decreasing the gap between its dermal edges + **reducing the wound surface area** * Important feature in healing by secondary union * Initial steps of wound contraction involve formation, at the edge of the wound, of a **network of myofibroblasts** Bold to pass

Answer 562

* **Formation of a blood clot - immediate** * **Neutrophil migration at wound margin - within 24 hours** * **Formation of granulation tissue (fibroblasts and vascular endothelial tissue). Blood vessels are leaky and proteins and fluid pass into the extravascular space leading to oedema - 24-72 hours** * Cell proliferation and collagen deposition - neutrophils are replaced by macrophages between 48-96 hours * Scar formation - leukocytic infiltrate, oedema and increased accumulation of collagen - second week * Wound contraction - formation of myofibroblasts at the wound edges that contract * Connective tissue remodelling * Recovery of tensile strength - 10% at 1 week to a peak of 70-80% at 3 months Bold 3 and 2 others

Answer 563

* Monocyte chemotaxis * Fibroblast migration and proliferation * Collagen synthesis * Collagenase secretion 2 to pass

Pathology Flashcards

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