Disease Processes Notes PDF

Disease Processes- Learning objectives Week 0 Cell death and adaptation e List the main differences between apoptosis & necrosis. 33yAt42JnkxG5z Apoptosis...

Disease Processes- Learning objectives Week 0 Cell death and adaptation e List the main differences between apoptosis & necrosis. 33yAt42JnkxG5z Apoptosis Necrosis - Active form of cell death - Passive form ofcell death - Part of normal physiology and pathology Only occurs in pathology - Acell can die by apoptosis and notkill One cell dying can kill neighbouring cells neighbouring cells causing an infarct - Does NOTstimulate an inflammatory Stimulates acute inflammation response response @ What determines whether a stimulus causes atrophy or infarction? An infarction is an area of necrosis which is considered to be pathological, whereas atrophy (decrease in cell size/number) occursat tissue level and can be either be a part of physiology or pathology. In a 33yAt42JnkxG5z 33yAt42JnkxG5z young person atrophy could arise due from autophagy or apoptosis but in an older person it’s mainly caused by apoptosis. The speed at which a stressor is applied sudden or slow, as well as how severe the stressor is. If the stressor occurs at a slow rate, it might give the cells some time to recover and result in atrophy. If the stressor is sudden, the cells die by necrosis which stimulate an acute inflammatory responseand lead to an infarction @ What effect does ageing have on cells & organs? Atrophy in an older person is considered to be apoptosis, since old cells have lost the ability to regenerate and undergo autophagy. Atrophy in a young person can be either autophagyor apoptosis @ What is meant bylabile, stable & permanent cells, give some examples. 33yAt42JnkxG5z 33yAt42JnkxG5z Labile — cells are continuously dividing - Epithelial cells e.g. skin, GIT, reproductive, urinary tracts, lining of endocrine ducts - Haemopoietic stem cells Stable — can divide when stimulated - Epithelial cells e.g. liver, kidney, pancreas, lung - Smooth muscle cells, fibroblasts, endothelial Permanent — cells do not divide - Cardiac and skeletal myocytes - CNS neurons e@ Define ischaemia, hypoxia/hypoxemia, necrosis, infarction, autophagy, apoptosis, atrophy, hypertrophy, hyperplasia & metaplasia. Ischaemia — reduced/lack of blood supply 33yAt42JnkxG5z Hypoxia/hypoxemia — lack of oxygen/lack of oxygen in the blood Necrosis — catastrophic cell death Infarction — area of necrotic tissue Autophagy— cells shrink but still alive Apoptosis — programmedcell death Atrophy — decreasein tissue/cell size/number leads to shrinking through autophagy or apoptosis Hypertrophy — increasein cell size Hyperplasia — increase in cell number Metaplasia — The change from one normal, well-differentiated cell type to a different normal well- differentiated cell type typically in response to a change in the cellular environment or the application of stress. It’s reversible if the environment changes back or the stressor is removed > thinkswap 1689902761 Find more study resources at https://www.thinkswap.com  @ Give some examples of cell types that are considered epithelial, connective & ‘other’ Epithelial - Forms the covering and lining of body cavities, organs, vessels (surface) and makes up the secreting portions of glands (glandular) Connective - most abundant and widely distributed tissues in body. Supports and strengthens other tissues, protects and insulates organs, main source of immune functions. Includes macrophages, fibroblasts, adipocytes, leukocytes. Loose, dense, cartilage, bone, and blood 33yAt42JnkxG5z Muscular - produces movement. Skeletal - attaches tendon to bone,voluntary control. Cardiac - pumps blood, involuntary control. Smooth - Found in hollow organs and vessels, involuntary control Nervous - Neurons and neuroglia (protects and supports neurons) Others — peritoneum, pleura, mesothelial lining of organs - germ cells, haemopoietic cell 33yAt42JnkxG5z - neutrophils, lymphocytes, macrophages Week 1 Neoplasia 33yAt42JnkxG5z 33yAt42JnkxG5z @ Define neoplasia, tumour, malignancy, dysplasia, -in-situ & metastasis/metastasize. Neoplasia - new abnormal growth; also called a tumour could be benign or malignant Malignancy - malignant tumour = cancer. Can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death Dysplasia - not a cell adaptation but a pre-cancer exchange. A disordered abnormal growth, a loss in uniformity of individual cells (mutation). Encountered mainly in metaplastic epithelia. Dysplasia may be a precursor to a malignant transformation, but it does not always progress to cancer 33yAt42JnkxG5z 33yAt42JnkxG5z Carcinoma in-situ - pre-invasive neoplasm in the epithelium. Dysplasia within the epithelium but does not penetrate the basement membrane (better prognosis if caught at this point). Once the tumour cells breach the basement membrane, the tumour becomes invasive Metastasis/metastasize - the next step of invasion, the spread of a tumour cells to distant sites and set up for secondary growth 33yAt42JnkxG5z e@ Nomenclature of tumours (construct/deconstruct the name based upon the cell of origin & the nature of the growth). Cancers only form in dividing cells and if cells are forced to divide more frequently, they are most likely to make.a mistake or their daughter cells mutate which can become dysplastic. In addition, there is increased level of oxidants and other chemical mediators capable of damaging DNA at sites of chronic inflammation -oma = benign -carc- = malignant, epithelial origin - increase in incidence with age -sarc- = malignant, connective tissue origin 33yAt42JnkxG5z Adenoma - benign glandular epithelial tumours Cyst - growing a fluid-filled sack, secretary epithelium e.g. in the ovaries Leio - smooth Myo - muscle Chondro- cartilatge > thinkswap 1689902762 Find more study resources at https://www.thinkswap.com  Hemangio - blood vessel/endothelial cell - connective tissue Meningioma - meningeal cell/meninges (benign) Blastoma - a type of cancer caused by malignancies in precursor cells during fetal development, which are commonly referred to as blasts e List the basic risk factors for the development of mutation & tumourgenesis. The ability for cells to divide like labile or stable cells. Epithelial cells are most vulnerable as they are 33yAt42JnkxG5z labile (constantly dividing) or stable (able to divide) and are on the interface between the body and potential stressors. While metaplasia and hyperplasia are normal cellular adaptations, they can increase the risk of dysplasia which can then mutate into benign or malignant tumours. 33yAt42JnkxG5z Carcinomas are morelikely to occur at sites of chronic inflammation. When chronic inflammation occursat sites whereepithelial cells are present, the epithelial cells will also respond to growth factors and repeatedly divide in a futile attempt to repair. This increased proliferation (cell division) of 33yAt42JnkxG5z 33yAt42JnkxG5z epithelial cells puts them at risk of making mistakes when copying their DNA and passing on 33yAt42JnkxG5z mutations. @ Understand the 8 behavioural changesthat occur in cancer cells as a result of multiple mutations Essential alterations for malignant transformation: - Proliferation without external stimuli - Insensitivity to growth-inhibitory signals - Evasion of apoptosis; - Defects in DNA repair (malignant tumours have more unstable DNA) - Limitless replicative potential - Sustained angiogenesis - Ability to invade and metastasize (cancer cells produce enzyme that can breakdown connective 33yAt42JnkxG5z tissue and invade through the layers of an organ) - Predilection for aerobic glycolysis produces less ATP but more lactate which can contribute to making building blocks for more cancer cells (Warburg Effect) e List the main differences between benign & malignant tumours. Benign Malignant - localised and do not metastasize - Can metastasize (usually die from secondary - encapsulate cancer rather than primary) - homogenous - infiltrative growth pattern - well-differentiated - heterogenous, sub-populations with differing - generally slower growth, but many exceptions degrees of differentiation, proliferation and (e.g. in the brain whereit can be lethal) aggression - Some populations within the malignancy will grow quickly sometimes outstripping the growth of their blood supply and thus undergoing necrosis in areas. Both benign & malignant tumours can undergo necrosis if they outgrow their bloody supply or there is bleeding within the tumour, it is more common in malignancies that are fast growing. Some apoptotic pathways have been switchedoff in tumour cells. 33yAt42JnkxG5z Both benign and malignant tumours are composed of mutated cells, however in benign tumours, the cells have not got the mutations that allow cells to invade & metastasize e List the 3 main routes of metastasis & common sites affected. Blood - arterial spread travels throughout the system and can give rise to tumour emboli. Venous invasion follows the venous flow of blood and usually end up in the lungs 33yAt42JnkxG5z > thinkswap 33yAt42JnkxG5z Find more study resources at https://www.thinkswap.com 1689902764  Lymph - transport through lymphatics is the most common pathway for the initial dissemination of carcinomas. Sarcomas may also usethis route Direct seeding - seeding of body cavities and surfaces may occur whenever malignant tumours penetrate through membrane. Most often involved is the peritoneal cavity but also, pleural, pericarial, subarachnoid cavities, and joint spaces Most common sites: lungs and liver (only other organ with venous blood supply, comes from GIT) from the flow of venous blood, bone and brain 33yAt42JnkxG5z The lungs are the most commonly affected organ as all venous blood returns to them & cancers usually spread first in the lymphatic & venous systems. The liver is our largest visceral organ & thus gets a large amount ofarterial blood but it is also the metabolic organ of drugs, hormones & the macronutrients from food absorbed by the GIT, which are carried to the liver via the portal venous system for processing. Many cancersfirst enter the blood at capillary beds or through thin-walled venules and get carried in venous blood to the liver and lungs. Once we have more haematogenous mets (clumps or emboli of cancer cells travelling in the blood) they go to areas that get a lot of arterial blood like the brain & bones. @ What must take place before cancer develops? Mutations during hyperplasia and metaplasia may lead to dysplasia. Dysplasia can progress into carcinoma-in-situ, which is the epithelial malignancy that has yet to penetrate through the basement membrane that sits beneath the epithelial layer. Once the cancer cells start to secrete enzymes that breakthrough the connective tissue, it allows the cancer to invade and metastasize. @ Understand the importance of early detection/the significance of metastatic disease The state of metastasis is key to prognosis. If tumour is identified early before metastasis, the 33yAt42JnkxG5z localised tumour may be removed and person may be cured. However,if the malignant tumour has infiltrated and metastasised to other areas of the body, it becomes moredifficult to remove 33yAt42JnkxG5z Week 2 Inflammation and Repair e@ Define hyperaemia, oedema (exudate vs transudate), effusion, resolution, organisation, ulcer & abscess. Hyperaemia - increase in blood flow Oedema - excessfluid in the interstitial fluid - Exudate: formed in acute inflammation - increased hydrostatic pressure and inflammatory mediators make vascular walls more permeable = high protein oedema: fluid which has plasma 33yAt42JnkxG5z proteins (act as signalling molecules in repair process once leaked out), cellular debris/necrotic cells, white blood cells and sometimes microorganisms. - Transudate: formed when fluid leaks out due to increased hydrostatic pressure (venous outflow production e.g congestive heart failure) or decreased colloidal osmotic pressure (decreased protein synthesis e.g. liver failing/increased protein loss e.g kidneysfailing) Effusion - build up of excess fluid between the membrane layers of body cavities 33yAt42JnkxG5z Ulcer - occurs in necrotic tissue and resultant inflammation exists on or near a surface Abscess- are localised collections of purulent inflammatory tissue 33yAt42JnkxG5z 33yAt42JnkxG5z > thinkswap 1689902765 Find more study resources at https://www.thinkswap.com 33yAt42JnkxG5z  @ What form of cell death causes an inflammatory response? Necrosis causes an acute inflammatory response. Necrosis can occur from a complete blockage (occlusion) of a blood vessel; ruptured blood vessel & haemorrhaging; burns (chemical, electrical, thermal); some infections, severe trauma like a crush injury; direct cell injury through surgery or foreign object including a blade, bullet etc. @ What are the 3 features of acute inflammation? Hyperaemia - increased blood flow to the site of inflammation due to vasodilation (induced by chemical mediators on the smooth muscle) 33yAt42JnkxG5z Oedema -chemical mediators act on vessel wall and increase the interendothelial space causing high protein plasma and fluid to leak out leading to exudates Recruitment of neutrophils (blood leukocytes) - accumulate along the vascular endothelium and then migrate throught the vascular wall into the interstitial tissue After a transient reflexive period of vasoconstriction, vasodilation leads to hyperaemia. The increased 33yAt42JnkxG5z permeability of the vessels allows serum & proteins to enter the affected tissue forming oedema which because ofits high protein content can be referred to as exudate. Neutrophils are activated and are attracted to the acutely inflamed tissue, migrating through the vessel walls. Neutrophils are phagocytic and the primary cell to associate with acute inflammation, however they have a short lifespan and will be aided my macrophagesthat will finish the job of neutrophils as well as remove apoptotic neutrophils. Acute inflammation can result in resolution, organization or chronic inflammation. @ What are the 3 possible outcomes of acute inflammation? Healing by resolution - healing without scarring. Permanent tissueslike the brain and heart will never heal by resolution as neurons, skeletal and cardiac myocytes do notdivide. In labile/stable tissues resolution is not possible when a lot of tissue has been lost or when thereis overlying infection, poor immunity, poor nutrition or interruption of healing. Healing by organisation - with scarring = loss of functional tissue, if fibrosis develops in a tissue space 33yAt42JnkxG5z occupied by an inflammatory exudate. Both typesof healing involve proliferation of various cells, and close interactions between cells and the ECM Chronic inflammation - if the stressor is persistent and not removed @ What are the 3 main components of granulation tissue & their role/purpose in repair? Granulation tissue is the immaturescar, the tissue that forms the scar and so will occur in acute inflammation that heals through organization and it will always be present in chronic inflammation as part of the repeated attempts at repair. Granulation tissue is composed of: 1. Fibroblasts secreting collagen protein. Macrophages coordinating events & cleaning up debris Ss 3. Angiogenesis, the formation of new blood vessels to provide nutrients and blood gases during the repair process. The formation of granulation tissue involves macrophages moving into the necrotic tissue and continue to removeit along with the increasingly apoptotic population of neutrophils. Fibroblasts 33yAt42JnkxG5z > thinkswap 1689902765 Find more study resources at https://www.thinkswap.com 33yAt42JnkxG5z  would migrate into the area and secrete collagen fibres tofill in the space once occupied by dead myocytes and newcapillaries (angiogenesis) would sprout into the area to provide growth factors, oxygen and nutrients for the granulation tissue. Oncethe dead tissue is removed and the space filled with collagen, the fibroblasts and macrophages migrate away leaving the largely acellular protein (collagen) scar. Because of the avascular nature of the scar, the new vessels regress through apoptosis and the collagen fibers contract as it matures. @ What are the consequences of healing through organisation? While healing through organisation and scarring does allow repair and fills in tissue deficit so the body can survive, it lacks the functions of the tissue it replaces. Over time, scar tissue contracts and pulls surrounding tissue with it causing a distortion. If organisation were to happen in myocytes (that are permanent cells), the scar represents a weak point that can form an aneurysm and predisposes thrombus formation. Scar tissue lacks the strength of the normal cardiac muscle & will not relay electrical impulses in the same way as the normal heart muscle. 33yAt42JnkxG5z @ What are the 3 main causes of chronic inflammation? - Unresolved acute - for example when the stimulus causing the acute response remains. - Repeated acute - “Special” cases such as infections and auto-immune reactions, where thereis little/no acute 33yAt42JnkxG5z response preceding the chronic inflammation e@ Define the 3 general features of chronic inflammation? 1. Ongoing tissue injury and destruction 2. Infiltration of lymphocytes 3. Repeated attempts at repair through the formation of granulation tissue and, when occurring in stable/labile tissues, proliferation of parenchymal cells. Chronic inflammation occurs when a stimulus causing cellular injury remains or is repeatedly applied or when our immune system attacks something that it shouldn’t. In chronic inflammation we get ongoing cellular injury, either caused by the stimulus or our body’s immune cells (lymphocytes) and repeated attempts at repair. The attempts at repair include the formation of granulation tissue (immature scar tissue composed of macrophages,collagen secreting fibroblasts and angiogenesis which is the growth of newcapillaries that supply the area with oxygen, glucose and growth factors). e@ Describe the possible negative consequencesof chronic inflammation When chronic inflammation occursin stable or labile tissues that contain epithelial cells, surrounding epithelial cells will proliferate (undergo hyperplasia) in a futile attempt to repair. This increase in proliferation & the presence offree radicals increases the chance of mutation. However,it is not the granulation tissue that causes cancer & repair does not necessarily involve cell division. 33yAt42JnkxG5z 33yAt42JnkxG5z In addition, there is increased level of oxidants and other chemical mediators capable of damaging DNA at sites of chronic inflammation 33yAt42JnkxG5z @ What is meant by sterile & non-sterile sites in the human body? Sterile — free from bacteria and micro-organisms Non-sterile — may contain bacteria and micro-organisms @ Understand the main differences between the innate & adaptive system Innate system - non-specific (e.g. acute inflammation), non-specific reinforcement. E.g neutrophils, macrophages,cytokines 33yAt42JnkxG5z > thinkswap 1689902767 Find more study resources at https://www.thinkswap.com  Adaptive system - specific responses (slower), memory. E.g. lymphocytes @ ~=Have a basic understanding of what autoimmune & hypersensitivity responses are. Autoimmune disorders - immune system attacking something that is normally functioning Hypersensitivity disorders - immune system over reacts to stimulus @ Have a basic understanding of what is meant by the term immune-compromised & the patients at risk Immune-compromised patients are those whose acquired/innate immune systems are not working effectively; they have genetic predispositions to certain diseases; are receiving drugs/treatments; or 33yAt42JnkxG5z have comorbid conditions Week 3 Haemodynamics @ Define congestion, oedema, effusion, transudate, ischaemia, haemorrhage, thrombus, embolus, aneurysm, atheroma, atherosclerosis, hypertension, stasis & hypercoagulability. Congestion - Passive build-up/increase of blood within a vessel. (It generally occurs in low pressure 33yAt42JnkxG5z circuits like the hepatic portal system, pulmonary circuit & systemic venous circuit and leads to increased hydrostatic pressure & a tendency towards transudate formation). 33yAt42JnkxG5z 33yAt42JnkxG5z Transudate: forms when fluid leaks out of the vessel due to increased hydrostatic pressure (venous outflow obstruction or systemic increases in venous pressure e.g congestive heart failure) or decreased colloidal osmotic pressure (decreased protein synthesis e.g. liver failing/increased protein loss e.g kidneysfailing) Ischaemia — lack of blood supply Haemorrhage — damageto a vessel, all constituents leaking out Thrombus — attached blood clot. In the arteries it starts as an endothelial injury from turbulent blood (abnormal blood flow from systemic hypertension) and hypercoaguability may promote thrombosis. In the venous circuit, it is usually caused bystasis Embolus — anything undissolved travelling in the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction - Pulmonary emboli: derive primarily from lower extremity deep vein thrombi. May lead to 33yAt42JnkxG5z right-sided heart failure, pulmonary haemorrhage, pulmonary infarction or sudden death - Systemic emboli: derive primarily from heart valves, aortic aneurysms, atherosclerotic plaques. 33yAt42JnkxG5z Aneurysm — localized abnormal dilation of artery or ventricle of the heart. They form in areas of high pressure where there are weakened areas. In arteries, they can form in areas of artherosclerosis and in the heart ventricles in areas of scarring - altered tissue is weaker and bulges out in response to the high pressure Atheroma — a sclerotic plaque representing an area of chronic inflammation within the intima wall of an artery = infiltration of lymphocytes, ongoing tissue injury and destruction, and repeated attempts at repair through granulation tissue and proliferation of surrounding cells e.g. in the smooth muscle cells of the tunica media. Oxidised lipids (which are eaten by macrophages and smooth muscle cells turning them into foam cells) including cholesterol and calcium (calcium often gets deposited at sites of necrosis and chronic inflammation = calcifies artery wall) will also be found at the injury site > thinkswap 1689902770 Find more study resources at https://www.thinkswap.com  Atherosclerosis — the process of atheroma. An arterial disease, chronic inflammation within the intima lining of the artery. Reduced vascular elasticity = increased vascular resistance = swelling/bleeding in plaque Artherosclerosis encourages turbulent blood flow which causes platelets and cells to form thrombi in the arterial circuit due to endothelial injuries. When the endothelium is lost there is decreased nitric oxide and prostacyclin synthesised in the region and more pro-coagulative factors released which encourages morefibrin, platelets and RBCs to adhere to the growing clot/thrombus. Aneurysms frequently form in areas of atherosclerosis and so the same reasoning applies. In addition, the aneurysm being a blind-ended sack can entrap cells and proteins. Hypertension — high blood pressure. Systemic hypertension is a result of increased cardiac output (e.g. 33yAt42JnkxG5z hypervolemia) and increased systemic vascular resistance (e.g. atherosclerosis, renal disease) 33yAt42JnkxG5z Stasis — blood not flowing/flowing slowly. Generally seen in low pressurecircuits like venous circuit Hypercoaguability — increased tendency of blood to coagulate/clot abnormally and produce thrombi e Identify blood flow & pressure differences in the systemic, pulmonary & (systemic) venous circuits Systemic circuit: the movement of oxygenated blood from the heart through the body to provide oxygen and nutrients to the tissues while bringing deoxygenated blood back to the heart. Blood travels through arteries at high pressure to reach organs around the body. Arteries have a smaller lumen but thicker muscle walls to pump blood. Systemic veins and venules contain more blood than systemic arteries and arterioles. Pulmonarycircuit: is the movement of blood from the heart to the lungs for oxygenation, then back to the heart again. Oxygen-depleted blood from the body leaves the systemic circulation when it enters the right atrium through the superior and inferior venae cavae. Veins have a bigger lumen but thinner muscle wall blood flows through them at low pressure. Hypertension in the pulmonarycircuit = increased pulmonary blood flow = leads to congestion and an increase in hydrostatic pressure = oedema Portal hypertension in venous circuit = congestion in the portal system, which leads to increased hydrostatic pressure = oedema and ascites Anything that increases blood flow in the systemic circuit (hypertension) can lead to an increasein hydrostatic pressure e.g. overactivation of RAAS, increased vasoconstriction = blood volume increases, venous obstruction = blood passively builds up @ How do the normal functions of the kidneys impact upon blood pressure and composition? Kidneys directly regulate blood pressure - when blood volume/pressurerises, the kidneys respond by allowing more water to flush from the body in urine. When blood volume/pressureis low, the kidneys conserve water (and sodium chloride) and returned to the bloodstream. The kidneys produce erythropoietin which acts on the red bone marrowto stimulate the synthesis of 33yAt42JnkxG5z RBCs. Blood is mainly water and the levels of water are regulated by the kidney through the renin — angiotensin — aldosterone system (RAAS). Aldosterone acts at the distal convoluted tubules to retain 33yAt42JnkxG5z sodium and reabsorb water from the filtrate, so instead of being lost in urine it is retained in the blood thus increasing blood volume. The kidneys also regulate the levels of various ions and blood pH by reabsorption from the filtrate and secretion intoit. In addition to controlling blood volume, the kidneysare able to control vascular resistance through the release of renin and the activation of angiotensin 2, which as the name suggests causes vascular > thinkswap 1689902771 Find more study resources at https://www.thinkswap.com  constriction thus increasing blood pressure. Thereis cross stimulation between the sympathetic nervous system and RAASso that stimulation of RAASwill also result in an increase in SNS stimulation. @ Compare superficial with deep vein thrombi (DVT) Superficial venous thrombi do not usually embolise. Deep vein thrombi (DVT) frequently embolise. Superficial thrombi frequently give symptoms including DVTs may be asymptomatic or give mild symptoms pain and swelling/oedema, ulceration of overlying skin33yAt42JnkxG5z like swelling distal to the clot. DVTsare often very large and not strongly attached to the wall of the vein and so they can embolise as a very large mass causing catastrophic outcomes. 33yAt42JnkxG5z e@ List the risk factors for DVT & track their path if they embolise Risk factors for DVT: hypertension, atherosclerosis DVT that forms an embolus: Femoral or Iliac vein > Inferior vena cava > Right atria > right ventricle > Pulmonary arteries > LUNGS = pulmonary emboli Fragmented thrombi from DVTsare carried through progressively larger veins and the right side of the heart before slamming into the pulmonaryarterial vasculature. e@ List the main risk factors for the development of atherosclerosis? Being male, increasing age, being of Aboriginal or Torres Strait Islander descent. 33yAt42JnkxG5z Smoking, diabetes, systemic hypertension, hyperlipidaemia (increased LDL & reduced HDL), visceral adiposity, etc @ How do the kidneys contribute to systemic hypertension? 33yAt42JnkxG5z In responseto a real or perceived fall in blood pressure/cardiac output the kidneys activate the renin- angiotensin Il-aldosterone system (RAAS), which results in: Aldosterone induces the kidneys to increase sodium and water retention > increasing blood volume Angiotensin II leads to vasoconstriction > increased vascular resistance > increased blood pressure @ What vascular pathologies does atherosclerosis predispose towards? Atherosclerosis is a major cause of arterial thrombi becauseit is associated with loss of endothelial integrity and abnormal blood flow (turbulence) which leads to emboli and aneurysms @ What are 4 waysin which atherosclerosis can cause death? - Bleeding and swelling within the atherosclerotic lesion can block/occlude the vessel leading to ischemia of downstream tissue, which leads to an infarct - Thrombus formation can lead to occlusion of the vessel and infarction. - Emboli may break off a thrombus and travel until stopped when it occludes a smaller vessel, which 33yAt42JnkxG5z leads to an infarction 33yAt42JnkxG5z - Atherosclerosis is a risk factor for aneurysm formation which can burstor give rise to thrombi and emboli, which can lead to hypovolemic shock (if major artery in the body) or haemorrhagic stroke(if in the brain) and death pH ® thinkswap Find more study resources at https://www.thinkswap.com 1689902771 33yAt42JnkxG5z  In addition, atherosclerosis can lead to slow chronic reductions in blood supply causing tissue atrophy, which while notlife-threatening reduce the functional reserve of organs and in the brain predispose us towards further pathologies. 33yAt42JnkxG5z @ What are the possible consequences of having atherosclerosis in the abdominal aorta, coronary arteries, carotid & cerebral arteries? In abdominal aorta - embolous will travel down towards lower limbs and cause gangrene In aorta - if atherosclerosis causes aneurysm = bleed to death; aneurysm could cause hypovolemic shock In coronary arteries - myocardial infarction, ischaemic heart disease 33yAt42JnkxG5z In carotid & cerebral arteries - thrombus embolus = ischaemic stroke, aneurysm = haemorrhagic stroke, cerebral atrophy, cerebral vascular disease Week 4 Cardiac Pathology Congestive Heart Failure — a clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle(s) to fill with or eject blood thus resulting in congestion of blood trying to enter the failing ventricle and reducing the amount of blood being ejected with each contraction. E.g. from ischaemic heart disease 33yAt42JnkxG5z @ What is the difference between angina & a myocardial infarction (MI) Both are caused by ischaemia but in angina is transient myocardial ischaemia and blood is restored to the tissue before necrosis occurs. Necrosis is seen in a myocardial infarction because thereis a complete obstruction of blood flow in the coronary arteries, and this will trigger an acute 33yAt42JnkxG5z inflammatory response and repair process. e@ Describe the inflammation & repair that occurs following an MI The infarcted tissue would stimulate the acute inflammatory response so there would be hyperaemia, oedema and the infiltration of the tissue by neutrophils. Hyperaemia increases hydrostatic pressure 33yAt42JnkxG5z causing fluid to leak from the vessels into the damagedtissue. In addition, increased vascular permeability allows plasma proteins to also enter the damaged tissue hence the oedema is an exudate. Becausethe heart is a permanent tissue, the formation of granulation tissue would follow; macrophageswill move into the necrotic tissue and continue to removeit along with the increasingly apoptotic population of neutrophils. Fibroblasts would migrate into the area and secrete collagen 33yAt42JnkxG5z fibres tofill in the space once occupied by dead myocytes and newcapillaries (angiogenesis) would sprout into the area to provide growth factors, oxygen and nutrients for the granulation tissue. 33yAt42JnkxG5z Oncethe dead cells are removed and the tissue deficit filled with collagen, the macrophages and fibroblasts migrate away and the new capillaries regress (die of by apoptosis). As this is a case of organization as part of acute inflammation, the granulation tissue would mature into a collagen scar which contracts over time pulling the edges of parenchymal tissue together e@ Briefly describe what complications can occur following an MI 33yAt42JnkxG5z The adult human myocardial cells are permanent and so incapable ofproliferation thus healing is through organisation. It is good that this can occur so that it is possible to survive following a heart attack. However, the scar tissue is weaker than the original myocardium and this area of weakness may form an aneurysm and rupture. In addition, the scar tissue can encourage a thrombus or blood clot to form over it which can shed emboli into the circulation. The scar tissue will also not relay 33yAt42JnkxG5z electrical impulses in the same way as the original tissue and overall the remaining myocytes will have to take on a greater workload. > thinkswap 1689902771 Find more study resources at https://www.thinkswap.com  @ Describe the causesofleft- versus right-sided heart failure (HF). Left sided Heart Failure Right sided Heart Failure Most often caused by: ischaemic heart disease, Most often caused by: left-sided heart failure as systemic hypertension from atherosclerosis, any increase in the pulmonarycirculation from aortic/mitral valvular disease left-sided failure inevitably burdens the right; valve disease, pulmonary hypertension caused by Due to passive congestion of blood backing up in COPDs or pulmonary emboli 33yAt42JnkxG5z the pulmonarycirculation; stasis of blood in the left-sided chambers; and inadequateperfusion of Due to pulmonary hypertension — high blood downstream tissues leading to organ dysfunction pressurethat affects arteries in lungs and the right side of the heart @ What are the ‘backward’ effects of left- versus right sided HF & what symptoms do they cause. 33yAt42JnkxG5z Left sided Heart Failure Right sided Heart Failure - reduced venous return of oxygentated blood - congestion in the systemic venouscircuit = fluid from pulmonarycircuit buildup in lower limbs and veins (jugular) = - Fails to receive enough blood, blood builds up in increase venous pressure = oedema in venous lower pressure circuits = pulmonary congestion system = increased hydrostatic pressure = pulmonary - congestion and necrosis in organs (liverand oedema kidneys) with a large outflow into the vena cava Symptoms: Dyspnea- shortness of breath/cough Symptoms: peripheral oedema - swollen legs and 33yAt42JnkxG5z with blood-tinged phlegm from microscopic ascites haemorrhaging in lungs First organ to be affected: lungs First organ to be affected: liver 33yAt42JnkxG5z 33yAt42JnkxG5z @ What are the ‘forward’ effects of HF i.e. what compensatory mechanisms are triggered from a reduction in cardiac output? Left sided Heart Failure Right sided Heart Failure - blood builds up in lower pressurecircuits 33yAt42JnkxG5z - can’t pump blood into lungs (pulmonary - reduced cardiac output = renal compensation congestion) = reduced gas exchange = less via RAAS: reduced renal perfusion, increased oxygen, more carbon dioxide in body 33yAt42JnkxG5z vascular resistance, salt/water retention, - decreased cardiac output = renal compensation increased blood volume via RAAS Angiotensin II = increased vasoconstriction = increased vascular resistance Aldosterone = increase retention of sodium/water = increase in blood volume Blood pressure will appear normal due to the loss of cardiac output, even though kidneys are compensating e@ Describe some of the common causes & possible consequences of endocarditis. Endocarditis is inflammation of the inner lining of the heart, typically in the valves. Endocardial cells are stable, and will proliferate if stimulated to. However, valves are mainly connective tissue and are avascular so will take longer to heal following an acute inflammatory response. If valves are infected by micro-organisms and infective endocarditis occurs, bacteria could colonise the platelet thrombus and eventually embolise to spread the infection to distant sites 33yAt42JnkxG5z Stenosis = valve does not open properly = vascular resistance = heart has to work harder to pump = predisposing to congestive heartfailure 33yAt42JnkxG5z > thinkswap 1689902734 Find more study resources at https://www.thinkswap.com  Incompetence= valve does not close properly = backflow of blood = chamber of heart affected is moreprone to fluid overload = predisposing to congestive heart failure @ Describe some of the common causes & possible consequences of pericarditis. 33yAt42JnkxG5z Pericarditis is inflammation of the membranous sac surrounding the heart. Pericardial disease can be causedby infection, autoimmune disease, secondary cancer or spread of an inflammatory response caused by a myocardial infarction. An acute inflammatory response could lead to haemorrhage due to weakened areas. Some possible consequences are pain, constrictive pericarditis and cardiac tamponade, which reduces diastole, stroke volume and cardiac output potentially leading to failure. @ What impact does ageing have on the cardiovascular system? As we age, welose functional cells due to increased senescence. Cells become less efficient as there are less mitochondria to help power them. Since there are fewer cells, hypertrophy can be seen in myocytes as the heart has to work harder Aging also increasesthe stiffness of large arteries and atheroscelerosis 33yAt42JnkxG5z Week 5 Resipratory Pathology 33yAt42JnkxG5z Atelectasis - incomplete expansion of the lungs, collapsed lung, producing areas ofrelatively airless pulmonary parenchyma. 33yAt42JnkxG5z - Compression atelectasis results whenever significant volumes offluid (transudate, exudate or blood), tumour or air (pneumothorax) accumulate within the pleural cavity - Resorption atelectasis stems from complete obstruction of the airway e.g. from a tumour, mucosal plug - Contraction atelectasis occurs when focal or generalised pulmonary or pleural fibrosis (tissue becomes damaged/scarred - organisation) preventsfull lung expansion @ Define the 4 main COPDs(asthma, chronic bronchitis, bronchiectasis & emphysema), their causes & possible consequences, pay particular attention to atopic asthma. Chronic Obstructive Pulmonary Diseases (COPDs) - caused by impaired (increased resistance) airflow due to partial or complete obsrtuction at any level of the bronchial tree (trachea -> bronchi -> terminal and respiratory bronchioles). Decreased max airflow rates during forced expiration measure via FEV;, FEV,/FVC (less than 80%) 33yAt42JnkxG5z Chronic Bronchitis - persistent productive cough that lasts for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause. Common in habitual smokers and inhabitants of air polluted cities. Those with asthma or cystic fibrosis are also at risk as they have increased mucous secretion in the airways as well. chronically inflamed airways: accelerates decline of lung function, lead to cor pulmonale/heart failure, cause atypical metaplasia, hyperplasia, and dysplasia of respiratory epithelium which could transform into cancer : Cigarette smoke/pollutants damageciliary action of the respiratory epithelium and thickening of bronchial walls, preventing clearance of mucous (formation of mucous plug) and increasing risk of infection Bronchiectasis - Irrerversible and progressive dilation of bronchi and bronchioles due to destruction of smooth muscle and elastic tissue caused by chronic necrotizing infections (from bacterial infections 33yAt42JnkxG5z like pneumonia), bronchial obstruction (from tumour, foreign bodies, mucous), cystic fibrosis, COPDs. Emphysema - Irreversible and progressive (ongoing acculmulation of inflammatorycells) destruction of alveolar walls without obvious firbrosis. Airspaces become abnormally enlarged from the 33yAt42JnkxG5z destruction of alveolar wall, which leads to oxidative stress, apoptosis, and less surface area > thinkswap 1689902735 Find more study resources at https://www.thinkswap.com 33yAt42JnkxG5z  (capillaries) for gas exchange. Inflammation and loss of elasticity means lungs can expand but deflate poorly = difficultly exhaling carbon dioxide. Causes: chronic bronchitis. Asthma, coal dust exposure, smoking, genetics (congential a-1-anti-trypsin deficiency) Asthma - chronic inflammatory disorder of the conducting airways caused by hyper-reactive airways. Marked by episodic bronchospasm due to increased airway sensitivity to a variety of stimuli, inflammation of the bronchial walls, and increased mucous secretion. @ What is pneumoconiosis, which particles are commonly implicated in Australia & what can they cause. A restrictive pulmonary disease. Chronic interstitial lung disease caused by inhalation of mineral dust/particles encountered in the workplace e.g. coal - anthracosis, silica - silicosis, asbestos - asbestosis. (The disease is chronic as the stimulus remains, the repeated attempts at repair increase the risk of cancer in these patients) In pneumoconiosis the lung may heal through organisation, which distorts the normal structure of the lung making it hard to breath, which can result in weight loss, respiratory failure & Cor pulmonale, Prognosis depends on: amount inhaled, shape/size of particles, solubility of particles, toxicity of particles, additional irritants (smoking) 33yAt42JnkxG5z @ Describe the innate defenses present in the conductive & respiratory portions of the lungs. 33yAt42JnkxG5z 33yAt42JnkxG5z Ciliated epithelium & mucous, cough/sneeze reflex, macrophages, gobletcells, anything that is not a lymphocyte (adaptive immunity). Conditions that can reduce these innate defenses @ What is pneumonia & what are the major differences between lobar & bronchopneumonia. Pneumonia is a bacterial/viral/fungal pulmonary infection of the alveoli. Bronchopneumonia common, mainly affecting immune-compromised individuals and involving an opportunistic infection (less virulent). Whereas, lobar pneumonia involves bacteria of high virulence, which are either breathed in or travel to the lungs during septicaemia/sepsis. It may affect anyone who encounters the pathogen (previously healthy people) and results in a strong acute inflammatory response that affects the entire lung or lobe oflung. Possible complications: necrosis - abscess, fibrosis, supparative fluid in the pleural cavity, haematological dissemination of bacteria (endocaritis, meningitis, osteomyelitis, glomerulonephritis) e Using a diagram, describe the pathogenesis of the 2 most common primary cancers affecting the 33yAt42JnkxG5z lungs. 33yAt42JnkxG5z 33yAt42JnkxG5z Metaplasia: ‘Change from 1 well- differentiated/mature cell type into another well-differentiated cell type 33yAt42JnkxG5z qo |, Phenotype abnormal inechelerdnans Increase cell number @ Why are the lungs a common site for secondary cancers? 33yAt42JnkxG5z > thinkswap 1689902735 Find more study resources at https://www.thinkswap.com  Cancers that enter the blood usually do so from lymph, capillaries or venules and since all venous blood returns to the lungs for re-oxygenation, they are commonly affected by secondaries @ Howare the lungsaffected by left ventricular failure? Pulmonary congestion is the passive accumulation of blood within the vessels of the lung that may be caused by obstruction of blood flow through the lungs or through the left side of the heart, which may be caused byleft-ventricular heart failure or mitral and aortic valve disease. @ How do lung diseases contribute to right ventricular failure? Pulmonary congestion leads to pulmonary hypertension (there is increased resistance to blood 33yAt42JnkxG5z entering the lungs) & therefore the right ventricle will work harder & thus hypertrophy. Pulmonary congestion is a consequence ofleft ventricular failure. Week 6 Renal Pathology ¢ renalbody, pay particular 33yAt42JnkxG5z attention to the cardiovascular, haematological & skeletal systems. Causes: systemic hypertension, diabetes, heart diseases, obesity, smokers, over 60 33yAt42JnkxG5z Cardiovascular - leads to the over-activation of the renin-angiotensin Il-aldosterone system. Angiotensin II stimulates vasoconstriction which increases vascular resistance - aldosterone initiates the retention of sodium and which retains water and increases blood volume - increased blood volume = increased hydrostatic pressure = oedema which can be worsenedif the patient suffers from proteinuria = loss of proteins in urine = reduced plasma proteins and oncotic pressure - an overactivated RAASleads to systemic hypertension - systemic hypertension is a risk factor of atheroscelrosis which can cause left ventricular hypertrophy and ischaemic heart disease. Cross activation with sympathetic nervous system = increased heart rate and force of contraction Skeletal 33yAt42JnkxG5z - reduced activation of vitamin D, which decreases the absorption of calcium in the small intestine. - decreased levels of calcium stimulates the thyroid gland to secrete more parathyroid hormone, which the kidneys no longer respond to,but still signals to osteoclasts to release calcium and phosphate from bonesinto the blood - calcium is unable to be absorbed, so is mostly excreted in urine, however excess phosphate remains in the blood and causes soft-tissue calcification leading to renal osteodystrophy. Calcium building up in arteries can lead to stenosis and eventually atherosclerosis Haematological - reduced erythropoietin = reduced synthesis of erythropoiesis leading to anaemia and lethargy. Worsenedif patient suffers from haematuria - metabolic acidosis from kidneysinability to remove H+ from the blood and synthesis of bicarbonate ions. As a result, the tissues take up excess H+ in exchange for K+ which leads to hyperkalaemia - excess potassium in the blood. Hyperkalaemia can cause muscle stiffness or potentially life threatening cardiac arrhythmias - increased nitrogenous wastes due to kidney’s inability to remove urea contributes to chronic posining due to uraemia which leads to poor immunity (increased infections), anorexia, neuropathy, abnormal platelet functions 33yAt42JnkxG5z > thinkswap 1689902738 Find more study resources at https://www.thinkswap.com  @ What are the main malignancies that affect the male & female urinary systems? Renal Cell Carcinoma - kidney epithelial cell; invades through the renal capsule Causes: smoking, obesity, radiation, acquired cystic disease, genetics (rare) Early stages are asymptomatic but tumour is large at the time of diagnosis and patients present with haematurai, mild flank pain, abdominal mass Transitional Cell (Urothelial) Carcinomas Patients with urinary cancers often present with blood in the urine, mild flank pain, an abdominal 33yAt42JnkxG5z mass or obstruction late in the progression of the disease, the early stages are asymptomatic. Nephroblastoma - a malignant tumour originating in nephrons Males - Benign prostatic hyperplasia (adenoma) and Carcinoma of the prostrate (adenocarcinoma) @ What are common causes of glomerulonephritis & possible consequences? 33yAt42JnkxG5z Acute Glomerulonephritis - inflammation of the glomeruli (where blood is filtered in each of the nephrons). Often leads to chronic condition and renal failure Common causesare blood-born stimuli (frequently immune mediated) and affect all the glomeruli in both kidneys (inflammation) which leads to renal failure. Inflammation can lead to swelling of the endothelium, lowering blood flow, and necrosis. Inflammation alters the permeability. Results in: lowered urinary output (from lowered glomerular filtration rate as kidneys lose function), proteinuria, haematuria, hypertension, persistent headache Chronic glomerulonephritis leads to chronic kidney failure by progression of the disease process (usually an immunologically- stimulated inflammation) from its origin in the glomeruli to the tubulo- 33yAt42JnkxG5z interstitial area and to the blood vessels. The arterial vessels in the glomerulus also provide blood supply to other areas of the kidney. All areas of the kidney can become involved leading to reduction in function. Both kidneys are commonlyinvolved and as the function of both kidneys reduces, the clinical state of end-stage renal failure follows. @ Why is the renal papilla susceptible to toxic injury & ascending infections? 33yAt42JnkxG5z The renal papilla is the apex of the renal pyramid which projects into the minor calyx. At this point, urine is at it’s most concentrated so anytoxins will highly affect the area. 33yAt42JnkxG5z Papillary necrosis occurs in analgesic nephropathy (chronic renal disease caused by excessive intake of analgesic mixtures) and in acute pyelonephritis mainly in diabetics and in those with urinary tract obstruction & ascending infections, as the renal papilla is more delicate. 33yAt42JnkxG5z Pylonephritis is an ascending infection that effects the pelvis tubules and medulla (including renal papillae) and is unilateral. Acute inflammation is caused by a bacterial infection (like UTI) that reaches by blood or by spreading to the kidney from the lower urinary tract. Chronic is formed by repeated infections or obstruction in the lower urinary tract e.g. urinary stones @ What are the major differences between ascending & descending infections & why are the 33yAt42JnkxG5z former more common in females versus males? Routes of entry for microbes infecting the kidney include haematogenous (descending) and urinary (ascending) spread. Descending infections are likely to be blood-borne and affect both kidneys diffusely (both males and females), which leads to renal failure. > thinkswap 1689902739 Find more study resources at https://www.thinkswap.com 33yAt42JnkxG5z  Ascending infections are morelikely to affect 1 kidney and usually only a segment of that kidney (females at higher risk). Ascending infections start as inflammation in the bladder (cystitis) and ascend through the urinary tract (ureters) to the kidneys where they develop into pyelonephritis. Ascending infections are more common in females due to their shorter urethras, which shortens the33yAt42JnkxG5z distance that bacteria must travel to reach the urinary bladder, as well as the close proximity of the urethra to the gastrointestinal tract/anus which is non-sterile. Menopausecan lead to more UTIs in 33yAt42JnkxG5z women as the decreased secretion of mucous makesit more prone to bacterial infections. Lack 33yAt42JnkxG5z antibacterial function of prostrate fluid @ What are the possible causes & consequences of urinary stones? Causes: Stasis of urine which may be caused by obstruction of urine flow Infection which can contribute to obstruction and act as a nidus 33yAt42JnkxG5z Pre-existing or previous incidence of stones Dehydration due to excessive water loss (diarrhea, vomiting, excessive sweating, lack of food/fluid intake) Calcium metabolism disorders (rare) and gout which wewill cover in bone and joint week 33yAt42JnkxG5z Consequences: 1. Pain - urinary/renal colic if stone is in muscular tube (ureter) and peristaltic wave compresses the wall on the stone causing ischaemia and pain (colic pain comes and goes with each peristaltic wave) 2. Bleeding from damage tolining epithelium of renal pelvis or urinary tract (clinical summary: painful haematuria - stoneslikely; painless haematuria - urinary tract cancer is possible); 3. Obstruction of urine flow - depends on the site (ureteric stone at high risk, bladder stone less risk of obstruction) - obstruction leads to infection, stones and renal atrophy (hydronephrosis - where one or both kidneys become stretched and swollen as a result of urine build-up); 33yAt42JnkxG5z 4. Predispose to infection - stone may damage lining epithelium reducing the defence against microorganism invasion; obstruction also predisposes to infection; 5. May encourage morestone formation (nidus). 6. May causechronic irritation (metaplasia from transitional to stratified squamous epithelium) and cancer. 7. Severe cases can result in loss of water (dehydration) and hyponatraemia (unlikely in Australia as treatment administered). Week 8 Boneand Joint Pathology 33yAt42JnkxG5z Osteoarthritis Rheumatoid arthritis Gout Wear & tear resulting in Chronic autoimmune destruction Common systemic metabolic loss of cartilage. of joints that may affect any disorder - from the breakdown of synovial joint (joints that have purines (found in meat and Degenerative joint disease space between the adjoining alcohol) which creates uric acid bones) in the body & causes systemic inflammation. Causes: Causes: Causes: Aging, predisposing joint Genetic predisposition and Hyperuricaemia in vulnerable deformity, underlying environmental influences. Affects people (not everyone with systemic disease e.g. women more than men hyperuricaemia gets gout diabete, affects both though), heavy alcohol genders Can be diagnosed at any age but consumption, obesity, fructose- Becauseit’s caused by typically it is first diagnosed in sweetened drinks. Affects more wear & tear it is mostlikely middle age men than women (rare before to occur in the elderly, menopause) overweight or people who thinkswap Find more study resources at https://www.thinkswap.com 1689902743  have engaged in sports Increased incidence in age but such as netball, AFL & can be diagnosed at any stage of running life Progression: Progression: Progression: Thereis little inflammation Pannus formation around the joint Monosodium urate crystals form compared to other forms space (extra growth/deformities = in joints & soft tissues causing of arthritis but reactive pain, swelling, damage) 33yAt42JnkxG5z severe pain & inflammation bone growth & swelling to Persistent synovitis surrounding soft tissues The joints are affected by chronic inflammation (type IV cell mediated response) Consequence: Consequence: Consequence: Tends to affect weight Affects multiple and smaller joints Often affects the big toe (tophi) bearing joints (1 or 2) in hands and feet in men Causes pain and impaired Bone erosion, cartilage & tendon In women, tends to affect joints movement degradation > irreversible joint in the hands deformation Uric acid urinary stones can also form in kidneys and increaserisk 33yAt42JnkxG5z of kidney disease @ List the main types of fractures & how healing may be impaired Simple - closed, broken bone has not pierced skin Greenstick - closed, small, slender crack in bone, can occur in children (bone notfully mineralised) Impacted - 2 bones forced (compressed) against each other 33yAt42JnkxG5z Compounded - open fractures lead to greater risk of bacterial infection (osteomyelitis in bone and bone marrow) and mostdevastating Comminuted - bone is shattered into small pieces, most devastating Healing can be impaired if we move the bone while it’s repairing; if it becomes infected; poor nutrition; or if it’s a pathological fracture (occurs in bones already weakened by disease) Spiral haematoma > soft callous > hard callous > remodelling Pathologic fractures - pre-existing bone diseases: osteoporosis, osteomalacia/rickets (under- mineralised organic matrix and osteoid = softening of bones) , osteomyelitis, primary & secondary malignancies, paget’s disease, renal osteodystrophy e List the factors that contribute to attaining peak bone mass Physical activity Genetic factors Good nutrition Hormonal influences as we are growing and developing 33yAt42JnkxG5z 33yAt42JnkxG5z Important to attain peak bone mass as bone atrophies with age @ List the risk factors for the development of osteoporosis; the possible consequences of 33yAt42JnkxG5z osteoporosis & how bone loss may be retarded/accelerated Risk factors include: low starting bone mass (determined by genetics, diet & exercise), ageing, 33yAt42JnkxG5z reduced physical activity, amenorrhea, loss of oestrogenic activity after the menopause, sarcopenia Consequences: pathological fractures, reduced activity/independence, impacts on drug prescription and other diseases 33yAt42JnkxG5z thinkswap Find more study resources at https://www.thinkswap.com 1689902744  Bone loss may be accelerated by: glucocorticoids, corticosteroids, chronic use of non-steroidal anti- inflammatory drugs (e.g. ibuprofen, asprin), amenorrhea (loss of menstrual cycle - can be seen in women with eating disorders), reduced muscle mass/sarcopenia Bone loss may be retarded by: testosterone, oestrogen, resistance/weight training 33yAt42JnkxG5z 33yAt42JnkxG5z 33yAt42JnkxG5z @ What are 2 complications of Paget's disease of bone and why might they occur? Deformed bone (weight bearing in weak bones) and pathologic fractures (weak bone less resistant to external forces). Also, pain and compression of cranial nerves which may cause deafnessor visual disturbances as a result of bony foramina - acoustic and optic nerves becoming narrower due to abnormal bone increasing in thickness, osteosarcoma, hydrocephalus resulting from narrowing of foramina which obstructs cerebrospinal fluid flow. Treatment: calcitonin and biophosphates @ List the tumours that occur in the skeletal system (reviewing what was covered in neoplasia week). Benign tumours: Chondroma, osteoma, fibroma, giant cell tumour Malignant: Osteosarcoma - will most likely be seen in children as their bones arestill continuously developing, Chondroscarcoma, Ewing’s sarcoma (develops during embryogenesis) Bone is actively growing in young people and most osteosarcomas occur in the actively growing 33yAt42JnkxG5z 33yAt42JnkxG5z epiphyseal plates. Increased proliferation is a major risk factor in the development of cancer. Once the active growth of bones has been completed the risk of developing osteosarcoma plummets. @ Why are the bones frequently affected by metastatic/secondary cancer? The boneshavea rich blood supply and contain many growth factors. Bone is very vascular, so arterial metastases are easily distributed to this site plus it’s a good site for tumour cells to become trapped. Bone metastases are found in more than 25% of people who die from cancer over all but 75% of people who die from breast cancer. @ What impact doesrenal failure have on the musculoskeletal system? The healthy kidneys activate vitamin D which is required by the gut to absorb calcium and the kidneys regulate the levels of calcium and phosphatein the blood. Under the influence of parathyroid hormone (PTH), the healthy kidneys activate more vitamin D, secrete phosphate and reabsorb calcium from the filtrate thus keeping it in the blood. 33yAt42JnkxG5z Chronic renal failure can cause renal osteodystrophy (under mineralization of bone & soft tissue calcification). In failure, the kidney may not be able to convert vitamin D into its active metabolite (activated by chemical changes in the kidney) and without active vitamin D the gut cannot absorb calcium from food, which results in low levels of serum/blood calcium. 33yAt42JnkxG5z The control of the plasma concentration of calcium is finely controlled, PTH is released in response to low serum calcium and promotesresorption of calcium from bonesby osteoclasts and induces the kidney to retain calcium in blood, excrete phosphateand activate more vitamin D. In renal failure, less vitamin D is activated and calcium is lost in urine so serum levels decline resulting in increased PTH secretion. The result is liberation of calcium from bones which forms complexes with the high levels > thinkswap 33yAt42JnkxG5z Find more study resources at https://www.thinkswap.com 1689902745  of phosphatein the blood which can be depos