Pathology (PDF)

1. Aetiology, or causes, includes genetic factors (inherited or associated mutations) and acquired factors such as infections, nutrition issues, and exposure to chemicals or physical agents. 2. Pathogenesis, or progression of a disease. 3. Cell or tissue changes, which may be eithe...

1. Aetiology, or causes, includes genetic factors (inherited or associated mutations) and acquired factors such as infections, nutrition issues, and exposure to chemicals or physical agents. 2. Pathogenesis, or progression of a disease. 3. Cell or tissue changes, which may be either morphological (affecting structure) or biochemical (affecting function). 4. Clinical manifestations, which include the symptbaoms noted by the person with the disease, the signs noted by another, and the prognosis or probable outcome. 5. Atrophy 6. Atrophy refers to the decrease in organ or tissue size due to reduced cell size and number. It can be physiologic (common during foetal development) or pathologic. Physiologic atrophy occurs when the body eliminates unnecessary structures to redirect nutrients, such as a thymus decrease in adolescence. Pathologic atrophy has various causes, such as disuse (from immobilisation), denervation (loss of nervous signals), loss of endocrine stimulation, ischemia (reduced blood supply), inadequate nutrition, and pressure (e.g. from tumour growth). CAN BE PHYSIOLOGICAL OR PATHOLOGICAL Hypertrophy Hypertrophy is the enlargement of cells, leading to an increase in the size of the affected organ. Physiologic hypertrophy occurs due to increased workload or hormone stimulation, such as muscle enlargement in bodybuilders. Pathologic hypertrophy can occur in the heart when faulty valves or hypertension increase end- diastolic volume. PHYSIOLOGICAL (EXCERICE) Hyperplasia Hyperplasia is an increase in the number of cells due to a stimulus, and may accompany hypertrophy. Physiologic hyperplasia occurs with hormones, like breast and uterine growth during puberty and pregnancy, or as a compensatory response after organ damage. Pathologic hyperplasia might result from excessive hormone or growth factor action, leading to conditions like benign prostatic hyperplasia or endometrial hyperplasia. If growth control mechanisms fail, uncontrolled proliferation may cause cancer Metaplasia Metaplasia is a reversible change where one cell type is replaced by another better suited to handle stress. For instance, cells in the respiratory tract change to a different type of cell due to chronic irritation from smoking. While the new cell type may cope with stress, it loses the original protective function, increasing infection risk. Metaplasia should be reversed when possible, as prolonged irritation can lead to malignant metaplasia and potentially cancer. Dysplasia Dysplasia involves disorganised changes in cellular shape, size and organisation, leading to abnormal hyperplasia with immature cells. Unlike metaplasia, dysplasia produces irreversible, random and immature cell types, indicating the first stage of cancer. If left untreated, dysplasia can progress to a tumour on the basement membrane, which it can penetrate to become malignant cancer. Apoptosis Apoptosis, a programmed cell death, involves a well-organised breakdown of cell contents, which are packaged inside membranes for immune cell clearance. It regulates cell balance during development, eliminates pre-cancerous and virus- infected cells, and maintains immune system integrity. In contrast, necrosis is pathologic cell death caused by injury, where cell contents spill out, triggering inflammation. Apoptosis involves cell shrinkage, bubble-like protrusions, DNA fragmentation and organelle breakdown, resulting in the formation of membrane- enclosed packages. These packages release signals to attract phagocytic immune cells for clearance, displaying a lipid molecule, phosphatidylserine, on their surfaces to aid in phagocytosis. Necrosis Necrosis is an unregulated form of cell death caused by external damage to cell membranes, leading to loss of ion balance. Lysosomal enzymes escape and destroy the cell from within, causing morphological changes. Organelles may also escape, leading to inflammation. Different types of necrosis have varied appearances, depending on the the cause. Common types are: Coagulative necrosis: The cell's external skeleton remains intact while internal components are damaged. Eventually, inflammation occurs, and white blood cells remove the damaged cells. In some areas of the body, like the heart, coagulative necrosis appears as pale segments of tissue without proper blood flow. Liquefactive necrosis: This is different as it involves cells being completely broken down and liquified by enzymes. This type of necrosis is commonly associated with bacterial infections, which trigger a large number of white blood cells to accumulate. The enzymes from these cells destroy infected cells, and eventually, a yellow pus-filled abscess is formed as the debris is drained away. Caseous necrosis: This type of cell death is commonly seen in tuberculosis. It forms granulomas, clusters of immune cells that attempt to kill bacteria but end up dying in the process. The cells do not maintain their structure but are only partially broken down, resulting in granular debris with a cheese-like appearance. Gangrenous necrosis: This is not a specific type of necrosis but is a term used clinically when necrosis affects a limb, often the lower limb, in different planes. It is usually caused by severe blood deficiency or ischemia, and in some cases, infection may lead to 'wet gangrene' with coagulative and liquefactive necrosis combined. INFLAMMATION: Acute inflammation is a fundamental process that occurs when the body is trying to defend itself against harmful stimuli, such as injuries, infections, or tissue damage. Trigger and purpose: Acute inflammation is triggered by various factors, like pathogens (bacteria, viruses), physical injuries (cuts, burns), chemicals or foreign substances. Its primary purpose is to eliminate the harmful agent and initiate the healing process. Immediate response: Once the body detects the harmful stimuli, it quickly responds by releasing chemical signals, such as histamines and cytokines, into the bloodstream. These chemicals cause the blood vessels in the affected area to dilate and become more permeable, which allows immune cells and fluid to move from the blood vessels to the site of injury or infection. Acute inflammation is characterised by the four classic signs: redness, heat, swelling and pain (often also accompanied by loss of function). Phases: Acute inflammation has two main phases – the vascular phase and the cellular phase. The vascular phase involves changes in blood flow and increased vascular permeability. The cellular phase involves the migration of immune cells to the site of inflammation to fight off the harmful agent. Vascular stage: In the vascular stage, arterioles and venules at the site of injury constrict briefly, then dilate. Dilation promotes congestion while an accompanying increase in capillary permeability leads to movement of fluid into the damaged tissue. The build up of fluid in the damaged tissue results in the five classic stages of inflammation, including redness, heat, swelling, pain and loss of function. As fluid leaves the capillaries, the blood remaining in circulation becomes more viscous, flows slower and clotting occurs. Emigration-leukocytes begin to adhere to the vessel wall after injury, here neutrophils cling to the walls od the capillaries in the inflamed area. They then squeezer through the wall in a process called diapedesis and move into the inflamed tisues. The leukocytes move through the tissue guided by chemical signals in a process called chemotaxis which neutrophils then follow. Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. The cellular stage culminates in phagocytes engulfing and degrading bacteria and cellular debris in a process called phagocytosis. Products of phagocytosis, along with plasma and blood cells, form exudate which accumulates causing swelling and pain. Chronic inflammation-associated with lymphocytes and marcrophages, proliferation of blood vessels while actuse is charactersied by fluid and plasna exudate and neutrophils -contraction of endothelial cells=increases gaps -trandate-fluid leakage -execudate-fluid and protein leakage -fluid accumulates in extravascular spaces=oedema Chemotaxis-leukocytes migrate towards the site of infection/injury along a chemical gradient, the move by extending pseudopods. Phagocyotis-accumulate at the site, then engulf and break down foreign invaders and damaged cells. Plasma-derived mediators These are produced by the liver, and include coagulation factors and complement proteins, which need to be activated. The plasma contains four interrelated systems of proteins: complement, kinins, coagulation factors, and the fibrinolytic system, which produce various mediators of inflammation. Activated complement proteins attract neutrophils and macrophages, increase vascular permeability, and stimulate histamine release from mast cells. They also adhere to bacteria, making them easier targets for phagocytes. The kinin system, activated by coagulation factor XII, increases vascular permeability, with bradykinin causing pain and itching during inflammation. The coagulation system converts fibrinogen into fibrin, forming a protective mesh over injury sites, activating complement and bradykinin. Fibrin proteases during coagulation promote endothelial activation and leukocyte recruitment. The fibrinolytic system generates plasmin, counterbalancing clotting and producing other inflammatory mediators. Cell-derived mediators These are released by immune cells. When foreign antigens are detected, certain cells like mast cells, platelets, neutrophils and macrophages release vasoactive substances like histamine and serotonin, initiating inflammation. Histamine from mast cells causes blood vessel dilation and increased vascular permeability. Platelets release serotonin, leading to rapid vasoconstriction. Macrophages and neutrophils release nitric oxide, which relaxes smooth muscles, reduces platelet aggregation and aids in immune cell recruitment, and has antimicrobial effects. Prostaglandins, produced from plasma membranes of cells, cause inflammation, pain and fever during tissue damage or infection. Aspirin, an anti-inflammatory drug, works by inhibiting the enzyme involved in prostaglandin synthesis. Chronic Inf;a,,ayion” infilitration of marcophages and lymphocytes and involves repair, involving nre vessel proliferation (antiogensis) and fibrous (fibroplasts) -Mediates by cytokines and growth factors produces by macrophafges and lymphotosys. Scarring -Can be caused from acute inflammation (aetiological agent persists,weak immune-low blood cell count as from elderly system, neutrophiles unable to ereadicate the foreign substance.) 2.Repeated bouts of acute inflammation (acute epiosdes remit and relapse until ultimately the tissue is chronically inflamed (binge alcohol and food consumption may it worse.) 3.Chronic inflammation developing from onset (some bacterial and viral proteins, non—microbial- metal, glass and wood splinters) Granuloma-layers of macrophages=epithoiloid cells=multinucleated giant cells The wound healing process Wound healing is a complex process involving four phases: haemostasis, inflammation, proliferation and maturation. In haemostasis, platelets form a clot to stop bleeding. Inflammation involves immune cells removing damaged tissue and attracting factors necessary for healing. During proliferation, new granulation tissue forms, and the wound contracts. In maturation, collagen is realigned along tension lines, and the wound gains strength. Fibroblasts play a crucial role in producing collagen and fibronectin, essential for wound healing. Angiogenesis, the formation of new blood vessels, ensures sufficient oxygen and nutrients for new tissue. Finally, during remodelling, collagen transitions from type III to type I, leading to scar maturation and reduced scar thickness. The process may continue indefinitely. Healing, regeneration and repair Regeneration replaces injured cells with the same type, sometimes leaving no trace of the injury, while repair results in permanent scar formation with connective tissue. The capacity for regeneration varies with tissue and cell type. Labile cells constantly divide, replacing cells that are destroyed (for example, blood cells and skin cells). Stable cells start dividing after injury and can regenerate in some organs (for example, the liver and kidney). Connective tissues and some cells lining blood vessels are stable cells. Permanent cells like nerve, skeletal and cardiac muscle cells do not regenerate and are replaced by fibrous scar tissue. Week 3 Hypersensitivity disorders refer to excessive or inappropriate activation of the immune system Type 1: Also known as immediate hypersensitivity or allergic reaction, type 1 hypersensitivity is a pathological reaction caused by the release of certain substances from mast cells. It is commonly triggered when IgE antibodies respond to environmental substances, binding with mast cells in different tissues. This can lead to inflammation when the body encounters those substances again. Immediate hypersensitivity can affect various tissues and varies in severity among individuals. Examples of such reactions include hay fever, food allergies, bronchial asthma and anaphylaxis. (Histamine release from mast cells Type 2: Also called antibody-mediated disorders, type 2 hypersensitivity is a condition where our antibodies interact with certain cells, leading to the complement-assisted destruction of those cells. This reaction can happen shortly after exposure to a harmful substance, such as mismatched blood during a transfusion. -minutes to hours, interaction of antibodies and surface antigen, complement Haemolytic anaemia Type 3: Also known as immune complex disorders, type 3 hypersensitivity occurs when insoluble antigen-antibody complexes form in the body. These complexes trigger complement fixation and localised inflammation. They tend to deposit in blood vessels at specific sites like branches or high- pressure areas, such as the kidney glomeruli and joint synovial membranes. The immune complexes formed in the bloodstream can lead to damage when they interact with the vessel lining or settle in tissues like the kidney glomeruli, blood vessels and joint synovium. This process involves the interplay of immune complexes, inflammatory responses, and the release of inflammatory mediators, all contributing to tissue damage. The reaction may manifest 3 to 10 hours after exposure to the antigen. -Hours, insoluble antigen-antibody complexes, deposit in tissue, complement system and inflammation. Type 4: also known as cell-mediated immunity, type 4 delayed hypersensitivity is where mechanisms of cell-mediated immunity produce harmful effects. Unlike other hypersensitivity reactions that involve antibodies, this type is mediated by sensitised helper T cells. It leads to conditions like contact dermatitis triggered by environmental antigens. When activated, these T cells release cytokines, attracting more macrophages and neutrophils, causing inflammation and skin lesions. The actual tissue injury is caused by these immune cells. Delayed hypersensitivity can also damage tissues during graft rejection and various infections. Compared to other hypersensitivities, reactions are delayed, taking 24 to 72 hours to show signs or symptoms -24 to 27 hours, mediated by helper t cells, recruiting macrohpages, neutorphols and inflammation. Infections Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems in the body. It causes redness of the skin and is triggered by environmental factors like UV exposure, smoking and hormones. SLE develops when the body's immune cells misrecognise and attack its own cells, forming antibodies that circulate in the blood and deposit in tissues like the kidneys, heart and joints, causing inflammation. Common symptoms include fever, joint pain and rash in women of childbearing age. Diagnosis is challenging and requires meeting specific criteria, such as skin rashes, ulcers, arthritis, renal disorders, and neurological or hematologic issues. SLE patients may also have abnormal antibodies, like antinuclear antibodies and lupus anticoagulant, which increase the risk of blood clots. Treatment involves managing symptoms and preventing flare-ups with measures like avoiding sunlight, and using corticosteroids and immune suppressants -Antibodies against blood cells are often produced (anaemia, leukopenia\-antiphosoplolipid sundrome (body produces antibodies that target proteins bound to phospholipids. lupus,) -Increases reisk of blod clots e.g stroke) Treatment: preventing and limtiting severity of flares. Avoiding environmental triggers, antimalaria drugs for joint pain and skin raches, non steroidal anti-inflammatory drugs to relive fever and muscle aches. Limiting immue response with corticosteroids and or immune suppressants, heparin or warfarin for pateinsts with APS WEEK 4: Neoplasia Cancer is a disorder of altered cell differentiation and growth. Adaptive changes including hyperplasia, metaplasia and dysplasia are all reversible, but if the stressor remains, the cell will eventually undergo more permanent changes, resulting in unregulated cell growth and division. This is known as neoplasia, which literally means ‘new growth’. Normal versus cancerous cells Cancer cells have defects in the control mechanisms for cell division and apoptosis. Normally, cell renewal and repair involve proliferation, differentiation and apoptosis. Normal cells have strict controls on growth and division, only dividing when necessary and undergoing apoptosis if damaged. In cancer, critical proteins malfunction due to genetic mutations, leading to excessive and uncontrolled cell proliferation and changes in cell differentiation. Tumours form when cells lose control of proliferation, and may be classified as benign or malignant. Malignant or cancerous tumours consist of cells that have also lost control over differentiation. Cancer cells also develop mechanisms to evade apoptosis, even when dysfunctional and given signals to undergo cell death. Cancer development: Normal cells- cell proliferation/cell division, differentiation/or specialisationacquire the functional characteristics and apoptosis,) In cancer cells- excessice or uncontrolled proliferation that is unregulates, can be well differentiated cells or less differentiated/abornmal looking cells andevasion of apopotis Common characteristics: -Self sufficiency in growth factors-oncogenes, insensitvitty to anti-rowth signals, evades apoptosis, angiogenesis, limtless replicative potential and tissue invasion and metastasis (to other organs) Carcinogen-substances capable of causing cancer. Increases the rick of cancer (e.g environment, genetic, diet, infection, metabolic and hormonal factors) Cancerouscells at primary site (growth signals increase/stops grow signals) Angiogenesis-cancer cells acquire the capacity to draw out their iwn blood supply and vessels and new blood vessels are formed ensuring cancer cells receive a continual supply of oxygen and other nutrients Benign tumours Benign tumours tend to grow slowly and do not spread. Benign cancers of surface epithelial tissues exhibit finger-like projections called papillomas, while those of solid and surface glandular epithelial tissues are termed adenomas. The names of these tumours indicate their cell of origin (such as squamous cell papilloma) or the tissue they originate from (such as thyroid adenoma). Adenomas that grow into the organ's lumen (e.g. in the colon) are referred to as polyps. Malignant tumours Malignant tumours can grow rapidly and will always invade and destroy nearby normal tissue. Parts of these cancers may also break off and spread throughout the body (a process called metastasis). Malignant tumours of epithelial origin are termed carcinomas, and those of glandular epithelium are termed adenocarcinomas. Further classification involves adding the tissue of origin, such as adenocarcinoma of the prostate or squamous cell carcinoma of the larynx. In connective tissues, benign tumours have the suffix -oma, and malignant tumours have the suffix -sarcoma, like lipoma and liposarcoma for adipose tissue and osteoma and osteosarcoma for bone. Benign-surface epithealis=papillomas and glandular epithelia=adenomas Differences between benign and malignant- characteristic of the tumour cells, rate of growth, local invasion and the ability to metastaze Bening-slow growing. Well-differentiated cells/resemble normal cell, remains localised and surrounded by rime of connective tissue called a fibrous capsule Malignant-rapid growth, lack a well defined capsule so infiltrate surrounding tissue, readily metastasize and loss of cell differentiation-anaplastic or de differentiate. Anaplasia (forms backward to an earlier dedifferentiated state- loss of normal tissue architecture, loss of specialised functions, pleomorphism-cells vary in size and shape, hyperchromatic or dark stained nuclei, higher nuclear cytoplasmic ratio, abnormal mitotic figures and giant cells Grade-pathological diagnosis (dysplasia) Stage-degree of spread (provides common language, guides treatment, estimated prognosis , allow comparison of results over time, standardizes clinical tirals.) Tests-physical, imaging-mri, lab tests and pathological or surgical reports. Tumour stage (local and primary tumour growth (e.g T0=no tumor, TIS: carcinoma in SITU and T1,2,3=size and extent of tumour Nodal status () also same system in the lymph nodes=N0. M0=no metastasis Metatasis- M1.1 inclused type or location Stage 1-4-can be clinically or pathologically SKIN CANCER: Most skin cancers are non-melanomas, either basal cell or squamous cell carcinomas. Melanomas are the least common, but have a much greater chance of metastasising, and have the highest mortality rate. Squamous cell carcinoma is the most common type of mouth cancer, accounting for 9 out of 10 cases. Basal cell carcinoma begins in basal cells. Most common and rarely matsastis, Prolonged sun exposure, parely papules often containing prominent dilated sub-epidermal blood vessels, ulcerate, Local Invasion of bone or facial sinuses after year, -squamous cell carcinoma beings in the squamous cells. malignant tumours of the outer epidermis caused from sun explosure. Tars and poil, chronic ulcers, old burn scares and ingestion of arsenic and ionizing radio also cause it especially if immunosuppressed. Prevents antigen presentation Appear as sharply deinfed, red scaling plaques, more advanced invasive lesions are nodular scale and ulcerate. Less than 5% metastates. Mucosal aquamous cell carcinomas are generally a much more agreeisvie Melanoma beings in the melanocytes (pigment cells). Uv light exposure, presence of pre existing nevi and hereditary predisposition. The progression starts abnormal melanocytes grow in the skin. Sydplasia,radial growth/proliferate, hyperplasia or dysplasia, vertical growth into depper dermal layers, metastatic -lympth nodes, soft tissue and lungs. Symptons- Asymmetry, boarder ireegularity, colour, diameter and evolution Nevi or moles are common congenital or acquired tumours of the skin that are benign -Dystplastic nevi have the capacity to transform into malignant melanoma (large, irregular size and shape, borders and colour WEEK 5: DISORDERS OF BLOOD FLOW Odema All cells in our body are bathed in fluid, which delivers oxygen and nutrients for their survival. This fluid moves from the blood into the interstitial space through capillary walls. This process is the balance between an outward force driving fluid out of the capillary (called filtration) and an inward force driving fluid in (called reabsorption). Hydrostatic pressure=Fluid moves from capillary to the tissue-fluis leaves the capillary, protein stays- as the blood pressure weakens the outward force of hydrostatic pressure is countered by thr inward force of osmotic pressure-fluid enters the capillary, attracted to protein Oedema can result from increased blood pressure (or hydrostatic pressure), decreased protein levels in the blood (or colloid osmotic (also called oncotic) pressure) or from a blockage in the lymphatic vessels. Another distinction is transudate fluid, which is non-inflammatory and has low protein and cellular content, and exudate fluid, which has higher levels and usually results from inflammation. The impact of oedema depends on where it is occurring; oedema of the brain can be life threatening, while oedema of the ankles can be uncomfortable but also a sign of disease. Such conditions bear various names, including pleural effusion in the lungs, pericardial effusion around the heart, and ascites in the abdomen. Oedema can be associated with conditions like heart failure, liver cirrhosis, kidney failure and nephrotic syndrome. Widespread oedema throughout all of the subcutaneous tissues=Anasarca Oedema surrounding the lungs=Pleural effusion Oedema around the heart= Pericardial effusion Build-up of fluid in the peritoneum=Ascites Occurs in the lower extremities, feet and legs=Peripheral oedema Normal circulation=arteries, capillaries, veins, lyumphatics (components of blood include plasma=water and proteins and cells=ethrocytes, immune cells and platelets Oedema- Build up of fluid. Can happen through: Increased hydrostatic pressure, decreasesoncotic pressure, obstruction of lymphocytes, excessive permeability (inflammation), mis regulation of sodium and water (water retention). Transudate vs exudate -Transudate is a fluid low in protein and low cellular content , can be caused by increases hydrostatic pressure or decreased osmotic pressure (just the fluid part is being moved). Movement of fluid -Exudate is high protein and high cellular content, happens though inflammatory process of lymphatic obstruction. vessel become more leaky, fluid is leaving the vessels. Mild cases= caused from sitting in one position for too long, eating too much salt, premenstrual ,pregnancy, medications and underlying medical conditions Heart failure, congestive heart failure, decreases cardiac output-fluid leakage out of capillaries, increase in hydrostatic pressure, left-sided heart failure=pleural effusion-fluid backs up and leaks into the lungs/right sided heart failure=Anasarca-right ventricle-fluid leaks into tissues and organs) Liver-Cirrhosis -alcohol abuse(reduction in the formation of plasma proteins. Fluid may accumulate- abdominal cavity-ascites or legs,m Jaundice and enlarged liver Kidney-Increase sodium and water, increases in hydrostatic pressure, disease-oedema in legs and face. Delcine of proteins in the blood. Nephrotic syndrome-damage the kidney filtering system (glomeruli)-proteinuria, hypoalbuminemia-low levels of albumin/protein in the blood amd decreases oncotic pressure (legs, feet, ascited, hands and face, anascarca) Single limb oedema- lymphodema-caused by blockage of a lymph vessel or blood clot THROMBOSIS: When you cut yourself, what happens? A clot will form to prevent blood loss. Sometimes, blood can clot in unwanted situations, called hypercoagulability, which can lead to pathological consequences. Various factors contribute to clot formation, such as vessel injury, changes in blood flow and alterations in blood coagulation. Endothelial cell damage and certain conditions such as high cholesterol, smoking and high blood pressure increase thrombosis risk. When a thrombus forms, it breaks off forming an embolus and forms an embolism elsewhere in the body. This may disrupt blood flow and contribute to many diseases. A thrombus or thromboembolus will usually, however, simply break up, in a process called lysis. Thrombosis can lead to ischemia, infarction and embolism. Pulmonary embolisms, caused by venous thrombi, are common and can be life-threatening. Multiple clots may cause pulmonary haemorrhage, infarction or pulmonary hypertension. Thromboembolism can also lead to stroke or affect other organs, causing irreversible damage. Embolus-blockage of vessels elsewhere Injury to blood vessels- normal trigger for coagulation cascade, damage to endothelial cells which can be causes by high levels of cholesterol in plasma, cigs, bacteria, high blood pressure, turbulent flow and high blood gluclose levels. Increased coagulation-following major trauma or burn, some cancers, pregnancy, elderelty, obesity, nephrotic syndrome and smoking and oral contraceptives. Alterations from normal blood flow-stasis or reduced blood flow or turbulence or increased blood flow (plaque formation within blood vessels which decreased oxygenation of tissues and damage. Eddy currents. What happens to a thrombus- lysis by enzymes sych as plasmin, reoriganisation into a stact (permanently block blood flow, Ischaemia/infracrtion (impair or occulate blood flow to tissue. Embolization (thrombus detaches and enters circulation, infraction and necrosis, venous thromboisis can lead to pulmonary embolism. Systemic embolisms lodge in lower exteemeinties (70%)followed by viscare, bran and upper limb (all 10%) pulmonary embolism- circulates to the lungs which results in clinically silent/resolve by fibrinolysis, sudden death pulmonary haemorrhage/infarction/hypertension Atherosclerosis Atherosclerosis is a leading cause of death, but do you know what is actually happening inside your blood vessels in this disease? Put simply, atherosclerosis is a disease in which plaques that are made up of fat, cholesterol and other substances build up in artery walls. The development of plaques involves endothelial damage, foam cell formation, smooth muscle proliferation and fibrous plaque formation. Stable plaques obstruct blood flow, while unstable plaques can rupture and cause thrombosis. It affects coronary and cerebral arteries, leading to strokes, heart attacks or peripheral artery diseases. Risk factors include age, gender, family history, hypercholesterolemia, smoking, obesity, hypertension and diabetes. Can lead to: coronary arteris disease/heart attack, stroke, peripheral artery disease. Progresssion: takes years 1. Endothelial cell injury (chemicals from smoking, immune mechanisms, high blood pressire, elevated LDLS) Adhesion of monocytes 2. Migration of inflammatory cells (LDLS accumulate in subendothelium, immune response initiated, monocytes transfom into macrophages which start phagocytosis of LDLD) 3. Smooth muscle cell proliferations and lipid deposition (release toxic oxygen species that oxidise LDLS which ingested by macrophafes to form foam cells. Smooth muscle proliferation release growth factors and stimulates smooth muscle cell migration and proliferation and stimulates the extracellular matrix.) Foam cells=Fatty streaks (thin,flat,ywllow discoloration) 4. Gradual development of the plaque with a lipid core Hypertension is probably the most common of all health problems in adults and is the leading risk factor for cardiovascular disorders. Hypertension occurs when the force of blood against artery walls is consistently high, more than 140/90 mm Hg. Both diastolic and systolic components are important, and it is influenced by blood volume, viscosity, heart pumping and artery resistance. There are stages of hypertension based on blood pressure readings, ranging from pre-hypertension to severe hypertension. It can develop over years without symptoms, but it causes damage to blood vessels and organs. Uncontrolled high blood pressure can lead to serious health issues, including myocardial infarction, stroke, kidney damage and organ failure. Risk factors include age, family history, obesity, lack of physical activity, smoking, excessive salt intake and certain chronic conditions. Detection and control through lifestyle changes and medication are essential to prevent complications Symptons- headaches, shortness of breath, nose bleeds, dizziness, fatigue and ringing in ears  Complications-arterioscleroisis-thickening and hardening/loss of elesticity, atherosclerosis, aneurysm-bulging, ischaemia. Heart failure. Kidney-glomerular injury/glloscleoris, albuminure, renal injurt WEEK 6: CONGENITAL DISORDERS Congenital disorders are defects of structure or function that are present at or before birth. These conditions affect about 4–8% of all births, with higher rates in developing countries. Causes The causes are often multifactorial, involving genetic and environmental factors. Genetic disorders stem from changes in DNA, including deletions, mutations and chromosomal abnormalities. Environmental factors such as alcohol, smoking, infections and nutrient deficiencies can exacerbate genetic susceptibilities, leading to birth defects. Development The timing of susceptibility varies during embryonic development; early organs such as the nervous system are most sensitive. Common congenital disorders include trisomies such as Down syndrome, craniofacial defects, heart and skeletal abnormalities, metabolic disorders, gastrointestinal defects and neural tube defects. Poor maternal health, bacterial and viral infections, lack of education around toxin intake (particularly drugs, alcohol and smoking) and low access to surgical and early postnatal care contribute to higher rates in developing countries. Prevention and management Prevention and management strategies include education about avoiding toxins and infections during pregnancy, improving maternal health, surgical interventions and identifying genetic contributors. Maternal supplementation with beneficial nutrients can reduce risks, exemplified by folate to prevent neural tube defects. Enhancing genetic knowledge and promoting healthier pregnancies can help mitigate congenital disorders. Disorders of sexual developmen Disorders of sexual development (DSDs) are conditions where sex development is atypical, affecting chromosomes, genitals, or other body parts. DSDs don't affect a person's identity. Some gender diverse people use the term intersex but might not have a DSD. Genetic changes in DSD individuals can alter sex chromosomes, hormone receptors or enzymes. This leads to a wide range of physical differences, sometimes making it hard to distinguish biological male from biological female. Normally there are three stages of sex development: Chromosomes Gonads Genitals DSDs can cause mismatched or unclear genitalia and internal organs, causing uncertainty about male or female appearance. Underlying: effect the number of sex chromosomes, mutate the function or expression of the sex determining gene SRY, affect the sensitivity of sex hormone receptors, alter the function of the enzymes responsible for sex hormone synthesis. Turner's syndrome A condition where individuals lack a full set of sex chromosomes (45 X,O), making them neither fully male nor female genetically. It's more common than realised, with 1/10 spontaneously aborted foetuses having this genetic makeup. It results from chromosomal errors during meiosis. Turner's syndrome causes various symptoms like short stature, physical features like webbed neck and broad chest, heart anomalies and infertility. Treatment involves growth hormone to increase height and hormone therapy to develop secondary sex characteristics and prevent issues like osteoporosis. Klinefelter's syndrome A disorder where individuals inherit an extra X chromosome (47, XXY), making them genetically male but often displaying female secondary sex characteristics. It's a common cause of male hypogonadism, with symptoms including small testes, breast growth, reduced body hair, tall stature and fertility issues. This condition is caused by non-disjunction of sex chromosomes during meiosis, particularly in females, and is linked to advanced maternal age. Testicular dysgenesis leads to decreased testosterone production and increased estrogen, causing feminisation. Diagnosis involves clinical assessment, hormone measurements and karyotyping. Treatment typically involves lifelong testosterone supplementation. Androgen insensitivity syndrome (AIS) A genetic disorder where genetically male individuals (46, XY) don't respond to male hormones due to mutations in the androgen receptor gene. It causes feminisation of secondary sex characteristics and variable virilisation. Complete AIS (CAIS) leads to externally female genitalia despite a Y chromosome, while partial AIS (PAIS) presents ambiguous genitalia. Diagnosis involves hormone measurements and genetic testing. Treatment depends on severity and includes estrogen replacement for CAIS and high-dose androgen therapy for PAIS. Gonadectomy may be necessary to prevent malignancy in undescended testes. AIS patients often require psychological support for gender identity challenges. Neural tube defects Neural tube defects (NTDs) are relatively rare yet serious congenital malformations affecting the brain, spinal cord or spine. The section delves into neural tube formation (neurulation), touching on defects in brain and spinal cord development. NTDs impact 0.1% to 0.5% of global births, often tied to genetic mutations and predispositions, although improved understanding of environmental factors has reduced incidence. Folic acid fortification, maternal health awareness and advanced prenatal screening contribute to this reduction. Normal brain development involves neural plate fusion, with neural crest cells forming various tissues such as peripheral nerves and craniofacial bone and cartilage. NTDs arise when neural tube closure goes awry, leading to severe conditions like anencephaly, iniencephaly, craniorachischisis, encephalocele and spina bifida. Spina bifida Some characteristics of spina bifida are as follows. Risk factors These include lack of folate, genetics, maternal health, medications and increased body temperature during early pregnancy. Females more then males and more common among Aboriginals. Family history, some medications, poorly controlled diabetes. Obesity, body temp. Types The three main types are: spina bifida occulta, meningocele, and myelomeningocele. Occulta is common and mild, often unnoticed. Meningocele involves a sac of spinal fluid, less severe  but can impact mobility and bladder control. Myelomeningocele is severe, with spinal cord and nerves protruding through the spine; prone to infection, it can cause lifelong mobility issues. Complications These include mobility problems, orthopaedic issues, surgical scar-related nerve binding, skin problems, pressure ulcers, latex allergy, urinary tract infections, gastrointestinal disorders and depression in adolescents. Scoliosis and hip. Skin problems due to impaired pain sensation in lower body. Craniofacial defects Craniofacial defects result from disruptions in the formation of the face, skull and jaws during development. The intricate process of facial formation involves the convergence of different components, akin to puzzle pieces. Neural crest cells play a pivotal role in craniofacial development, forming facial bones and structures. If neural crest cells are deficient, conditions such as Treacher Collins syndrome can occur, leading to severe craniofacial abnormalities. Environmental factors such as excessive maternal alcohol intake can cause foetal alcohol syndrome, with characteristic facial features and brain defects. Premature fusion of skull sutures, known as craniosynostosis, affects skull shape and brain growth. Animal models, such as mice with TCOF1 gene mutations, aid in understanding disease pathogenesis and potential treatments. Tissue failure=cleft lip/palate Failed neural crest cell survival=Treacher Collins syndrome Environmental toxins-Foetal alcohol syndrome-small jaw and forehead, brain damage Failure of correct bone growth-craniosynostosis-gaps between flat bones of skull, produce more bone. Congenital heart defects Common congenital heart defects (CHD) include various issues with the heart's structure that disrupt its normal functioning. Septal defects in the atria or ventricles are common, involving holes in the walls between chambers. Significant CHDs include the following: Patent ductus arteriosus is when a foetal vessel connecting the pulmonary artery to the aorta remains open after birth, mixing oxygenated and deoxygenated blood. Pulmonic stenosis refers to the narrowing of the pulmonary artery, impairing blood flow to the lungs. Tetralogy of Fallot is characterised by four defects, including a ventricular septal defect, pulmonary valve narrowing, aorta displacement and right ventricular hypertrophy. Coarctation of the aorta involves a constriction in the aorta, reducing blood flow to the body. Transposition of the great arteries is a life-threatening condition where the aorta and pulmonary artery are connected to the wrong chambers, leading to insufficient oxygenation. These defects can cause blue discolouration in lips, fingers and toes due to inadequate oxygenation. Detection and surgical correction are crucial for managing these conditions. Ventricular septal defect Atrial septal defects-hole in heart, oxygenated and deoxygenated blood mix Week 7: The term ischaemic heart disease describes heart disease caused by impaired coronary blood flow and the imbalance between blood supply and oxygen demand. The primary cause is atherosclerosis or plaque buildup, which is worsened by age and risk factors such as hypertension and smoking. It is a leading cause of death. Diseases of the coronary arteries can cause a spectrum of disorders, which include angina and myocardial infarction Angina Also known as angina pectoris, angina is chest pain caused by insufficient blood flow to the heart muscle due to artery blockages or spasms. There are three types: stable angina (caused by exertion), variant angina (due to artery spasms) and unstable angina (linked to plaque disruption). Stable angina arises during physical activity and can be relieved by rest. Variant angina occurs at rest due to artery spasms, often responding to vasodilators. Unstable angina is serious, possibly leading to heart attack, with worsening symptoms such as sudden onset angina, lasting more than 15 minutes. Angina can feel like pressure, heaviness, tightness, burning or choking, sometimes radiating to the arms, neck or jaw. It can also cause breathlessness, sweating and nausea, increasing heart rate and blood pressure. A myocardial infarction, commonly known as a heart attack, is the death of heart muscle tissue due to inadequate blood flow. The main cause is atherosclerotic plaque rupture in a heart artery, causing clot formation and rapid blockage. This leads to tissue death, which doesn't regenerate. The heart's response to lack of blood triggers an ischaemic cascade. Infarction affects cells near the artery first, expanding over time. Chest pain is a common symptom, often radiating to the arm, jaw, neck or abdomen. Complications include arrhythmias, -bradycardia-heart rate is slower than normal, tchycardia-fast or irregular heart rhytgm of fibrillations-heart quivers instteadt of pumping due to disorganised elecrrical activity. heart failure, aneurysms and sudden cardiac death, often linked to coronary artery disease. Sudden cardiac death is preceded by erratic heart rhythms and requires immediate intervention. Myocarcinal rupture-most common 3 to 7 daysa after infarction Pericarditis -inflamation and swelling of the covering of the heart, can occur in the days or weeks following a heart attack. Infaract expansion-thinning and dilation of the infaracted region. Events of early phase of healing Thrombus formation-results from local loss of contractibility, causing stasis with endocardinal damage Ventricular aneurysm-late complication and is a bulge of the wall Lactic acid build up Atheroma-build up of fatty tissue, over time  Chronic ischaemic heart disease-history of myocardinal Infaraction, progressive heart failure as a consequence (accumulated ischaemic myocardinal damage or inadequate compensatory responses.) Sudden cardiac death (24 of symptons. Not myocardinal infarction (block to blood supply_. Usually results from an electrical disturbance and is life threatening ventiruclar fibrillation. Stroke A stroke occurs when blood supply to the brain is disrupted, either due to a blocked artery (ischaemic stroke) or a ruptured artery (haemorrhagic stroke). The brain receives oxygen through carotid and vertebral arteries, connected at the Circle of Willis, supplying over 80% of the cerebrum. Brain cells die without oxygen and nutrients, and a stroke will affect up to 1.9 million brain cells per minute. Symptoms vary depending on the affected brain area and the extent of oxygen deprivation, but commonly include sudden headaches, confusion, difficulty speaking, weakness/paralysis, vision problems and unsteadiness. The FAST test checks for the following signs: Face drooping Arm weakness Speech difficulty Time to call emergency Almost 30,000 Australians experienced a stroke last year, which equates to one stroke every 19 minutes, making it a leading cause of mortality and disability. Risk factors include age, gender, family history, high blood pressure, smoking, diabetes, high cholesterol, obesity and inactivity. Following a stroke, the patient will endure months and months of rehabilitation, learning to talk, walk and do basic activities Ischaemic strokes About 80% of strokes are ischaemic, and they occur when blood flow in cerebral vessels is interrupted due to narrowed or blocked arteries. A transient ischaemic attack (TIA) or mini stroke is a brief disruption of brain blood supply, sharing stroke symptoms but lasting less than 24 hours. Brain cells in the affected area die when deprived of oxygen and nutrients, typically within minutes to hours. A TIA warns of the risk of a major stroke, indicating potential clotting or plaque issues. Plaques of cholesterol can accumulate on artery walls, narrowing or blocking arteries, leading to thrombotic strokes. Embolic strokes occur when a clot from elsewhere obstructs a brain vessel. Haemorrhagic strokes While less common, haemorrhagic strokes have a higher fatality rate than ischaemic strokes. They result from bleeding within the brain, often due to an artery rupturing as a result of an aneurysm, arteriovenous malformation, head injury, or from high blood pressure. Subarachnoid haemorrhage is bleeding between brain membrane layers. Stroke effects depend on the brain section affected. Brain healing involves gliosis forming around damaged areas, and lost brain tissue being replaced by cerebrospinal fluid. Neuroplasticity enables brain rewiring, with damaged functions transferring to healthy regions, aiding recovery. Repetitive practice enhances recovery by reinforcing new neural connections. Combining neuroplasticity and repetition boosts brain recovery during rehabilitation therapy. WEEK 9: Neurological disease Multiple sclerosis (MS) is a neurodegenerative disease caused by damage to the myelin sheaths enveloping neurons within the central nervous system (CNS), leading to neuronal and axonal destruction. Mainly affecting the central nervous system, MS results in a variety of symptoms such as fatigue, mood changes, vision problems, difficulty speaking, muscle control issues and pain. Causes: The disease's aetiology and incidence are complex. Theories implicate genetic factors impacting the blood-brain barrier (BBB); compromised BBB may facilitate immune cell entry into the brain, promoting MS development. Another theory points to the importance of sunlight and vitamin D in maintaining a healthy BBB, with lower latitude regions having higher MS incidence. Additionally, viral infections might trigger an autoimmune response, targeting myelin. The prevalence is higher in females, possibly due to genetic links and increased susceptibility to infections. While these theories provide insights, the precise cause remains uncertain, prompting ongoing research to better understand and manage MS. Development and treatment Sclerosis refers to tissue hardening and scarring, comparable to atherosclerosis in arteries. In multiple sclerosis, there is a formation of plaques, which have defined borders, appear depressed or glassy, and are variable in size. They are visible on brain MRIs as white areas. As the disease progresses, the plaques enlarge, and this leads to more severe symptoms. The acute phase of active plaque evolution involves immune cells attacking myelin and axons, while the chronic phase of inactive plaque sees scarring and astrocyte proliferation. A regenerative phase, the shadow plaque, is thought to be an attempt at remyelination. Remyelination is hindered in active plaques by ongoing inflammation, and in inactive plaques by scar tissue preventing contact with axons. Remyelination is ineffective in an active plaque because the inflammatory response continues. And in a inactive plaque its ineffective because the gliosis/scar presents a barrier to oligodendrocytes reaching axons. A stem cell therapy, autologous hemopoietic stem cell transplant, aims to replace the immune system to halt myelin attack. This therapy, akin to cancer treatments, shows promise but remains the only approved stem cell therapy for MS. Remove the immune system and replace it with a nonprime immune system, patiens own stem cells are replaced into the blood stream and expanded and grown in the lab while the patient undergoes chemotherapy to partyl remove the immune system and is then returned through infusion in the vein which would no longer attack the myelin cell antigen. -Affects 1:1000 people and onset between 20-40 years of age. Signs: Optic neuritis: inflammation of the optic nerve (50% of people), causes blurred vision, loss of colour and blindness. Usually resolves over a few weeks. -depression, changes of behaviour/mood, mouth and throat, speaking and swallowing, walking/controlling muscle, pain, bladder and urinary.  A specific BBB “permeability” gene, S1PR2, is more highly expressed in woman. -MS: futhur away from the equator the more likely it is. (Vitamin D=higher BBB and viral infection is more common in places further away from the equator.) Bacterial infection creates antigen which similar of antigen on found on myelin, so then T helper cells kill the cells and myelin, T helper cells make B cells and create macrophages and antibodies which disintegrate the BBB. ALL A THEORY. Motor neuron diseases (MND) are a group of idiopathic neurodegenerative disorders that lead to progressive loss of motor control and muscle weakness. They affect between 1 in 12,000 to 1 in 100,000 individuals, generally afflicting men in their mid-fifties. MNDs cause a devastating decline, with survival averaging two to five years post-onset. While the exact cause remains unknown and the disease often arises sporadically, genetic and environmental factors are implicated. -UMN: generally in the cortex or brainstem and connect the brain to the appropriate level of the spinal cord and synapse with and control LMN -LMN can be spinal or cranial nerve, and directly regulate all muscle function. LMN are mostly affected. Cranial nerve LMN control of eyes, face, toungue and Spinal LMN control all other muscles in the body. Progression of MND MND affects two types of neurons: upper motor neurons (UMN) and lower motor neurons (LMN), which collaborate to regulate muscle function. It primarily targets LMNs, leading to muscle atrophy, paralysis or spasms. Symptoms vary widely, encompassing muscle weakness, coordination issues, spasticity and voice problems; cognitive impairment typically emerges later. Common MNDs, amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy (PBP) involve both UMN and LMN damage. ALS, also known as Lou Gehrig's disease, affects both spinal and respiratory muscles, leading to eventual respiratory failure. PBP usually follows ALS, and specifically affects the brain stem, causing issues with swallowing, speaking and emotional control. Death usually results from breathing difficulties or complications related to swallowing problems and lung infections-aspiration pneumonia. Cerebral palsy is a common congenital disorder, impacting movement and motion. Contrary to misconceptions, it is not a single disorder but a group of conditions resulting in difficulties with movement, balance and coordination. The name 'cerebral palsy' derives from 'cerebral' (brain) and 'palsy' (muscle disorder), denoting a muscle disorder stemming from brain neuron defects or death. Primarily caused by hypoxia, where foetal brain oxygen supply is compromised, cerebral palsy can arise during gestation or shortly after birth. Risk factors include preeclampsia, maternal smoking, cardiovascular issues, trauma and respiratory disorders, contributing to brain injury and neuron demise. Effects Cerebral palsy presents through movement and coordination challenges, accompanied by possible slurred speech, developmental delays, intellectual disabilities, feeding difficulties and seizures. Its most prevalent form involves damage to the cerebral cortex (70-80). Subtypes are distinguished by brain regions affected: Spastic – characterised by stiff movements due to cortex damage. (hemiplegia, diplegia, quadriplegia and asymmetric displegia-both areas but one side more, triplegia-three limbs)  Dyskinetic – involving involuntary, variable and jerky motions due to basal ganglia damage. (10-20%) hypertonia (high contractiblity) and hypotonias-swicthes between. -Dysonia-twisting/repetitive movements -Athetosis- Slow/big movements -Chorea-Dance like, Irregular movements Ataxic – causing balance and coordination deficits due to cerebellum neuron loss. (5-10%) Can affect any part of the body and can impede walking, picking up an object, use cutlery and speak. Interventions Cerebral palsy's complex origins and varying types necessitate a comprehensive approach to prevention and management. Protective measures include promoting maternal health by avoiding smoking, alcohol, obesity and attending to cardiovascular fitness. Also helpful are interventions such as magnesium sulphate and antibiotics during maternal infections, antibiotics, and corticosteroids to manage inflammation. -Usually caused in defect in normal brain development in utero or shortly after birth (0.2% of all births) leading to death of fetal brain tissue. Can be in adults from stroke or spinal cord injury. Commonly due to hypoxia (caused by preeclampsia which is high BP or poor placental perfusion) Smoking causes carbon monoxide poisoning. Could also be infection (rubella and chickenpox), meningitis, premature birth, heavy metal poising and head trauma. Parkinson's disease Parkinson's disease affects about 70,000 Australians, typically diagnosed around age 65, but it can appear earlier in young onset cases. While its cause is mostly unknown, there's a suspected genetic link, with the primary characteristic being a loss of dopamine production in the brain. This occurs mainly in the substantia nigra of the brain, characterised by a loss of pigment-producing cells. Lewy bodies, abnormal protein aggregates, and cell death also mark the condition. Symptoms include motor dysfunction, tremors, shuffling gait, and as it progresses, dementia and depression. Though not lethal itself, Parkinson's significantly degrades patients' quality of life as they age. Although there's no cure, treatments like Levodopa can increase brain dopamine levels. Dopamine is a neurotransmitter (hormone) and involved in reward, addictions, motor control and hormone release.  Cell death within the substantia nigra leads to subsequent defects due to the loss of dopamine in the basal ganglia, thalamus, striatum and cortex. Symptoms appear when 70- 80% of dopamine is lost. Alzheimer's disease Alzheimer's affects about 48 million people globally, contributing to 70% of dementia cases. It's categorised into sporadic and familial forms. Sporadic Alzheimer's, common in people over 65, lacks clear causes. Familial Alzheimer's, linked to specific gene mutations, is rarer and has earlier onset. The disease's pathology involves amyloid plaques and tau tangles. Amyloid plaques result from misfolded amyloid precursor proteins, inhibiting glucose utilisation and leading to cell death, they are also found between neuronal cells. Tau tangles disrupt cell function by destabilising microtubules, causing neurons to die, and contributing to brain atrophy. They are found within neuronal cells. (basically, the destabilisy the cytoskeleton? And the neuron can no longer transport nutrients between cell body and dendrites so they die which causes atrophy. ) Symptoms include memory loss, emotional instability and depression. Alzheimer's is characterised by severe brain atrophy, with the cortex and hippocampus shrinking, causing cognitive and memory deficits. -Areas affected include the cortex (movement, thinking and planning and memory), hippocampus (learning and memory) and shrinks severly, Ventricles grow larger from cerebrospinal fluid which puts more pressure on the brain. Clumps of protein (Amyloids plaques and tau tangles) grow in the brain, then protein strands twist damaging brain cells (neurons.) Because of this brain cells die and certain oarts of the brain shrink. WEEK 10: Respiratory disorders Chronic obstructive lung disease is caused by a group of lung diseases that lead to damage of lung tissue with persistent and progressive limitations of air flow. Chronic bronchitis and emphysema are the two most common causes and often coexist, with both conditions coming under the umbrella-term 'chronic obstructive pulmonary disease' (CPD). Smoking is implicated in 95 percent of cases of both chronic bronchitis and emphysema, however the pathophysiological mechanisms, and clinical complications that underpin either disorder may be quite different Symptons include shortness of breath, pain, blood pressure changes, oedema and death. Normal lung function: trachea split into bronchi then secondary bronchi then bronchioles and in that alveoli tree. Surrounded by smooth muscle that allows contraction and expansion to regulate the flow of air into the bronchioles. Lung disease: restrictive is the reduced ability to fill lungs uo with air can be due to alveolar damage or reduced compliance Restrictive examples: pneumoconiosis/silicosis/asbestosis-hypersensitivity and inflammation following inhalation of particles in dust. Pneumonia and Acute respiratory distress syndrome (ARDS) and non-lung disorders which impact the lungs-mesothelioma, neuromuscular disorders, chest wall trauma. Pneumonia-infection of lungs leading to inflammation in the bronchi or bronchioles and exudate accumulation in alveoli. Bacterial is worse because of fluid accumulation. Two main types: bronchopneumonia and lobar pneumonia (all bronchi and bronchioles are excutading and more fluid in the lung.) if left untreated it can lead to oedema and ARDS, caused by damage to the capillary-alveolar barrier. Alveoli leaks. Releases fibrin and neutrophils which causes scar formation. and obstructive is reduced ability to fully exhale air, no gas exchange. Obstructive diseases: cystic fibrosis, bronchitis, emphysema and late stage Chronic obstructive pulmonary disease (COPD) Cystic fibrosis: Also affects all organs that sectrete mucous (intestines), production of salty sweat, it’s a genetic defter in one gene causes the disease. It affects secretion of fluids those which are usually thin become thick. This is because of a mutant channels does not move chloride ions through the channel causing sticky muscus to build on the outside of the cell. (WATER DOES NOT MOVE INTO THE MUCUS AS MUCH BECAUSE OF SALT.) The treatment is oral sprays to help thin it out and antibiotics minimise infection. Gene transfer approaches have also bee attempted to place a functional copy of the gene. Lung transplant is often also necessary later in life due to long term inflammation. Bronchitis: Acute (chest cold): Usually a viral infection but can be caused by pollution or bacteria (usually 3 weeks) and is the thickening of bronchial tubes, and increased mucus production. vs Chronic: hypersecretion, productive cough that last for longer than 3 months per year for more that 2 consecutive years. Primary caused by smoking. Often a precurser to both emphysema and COPD. Changes that occur cause of chronic bronchitis: Constant irritation in the large airways lead to increase in the size and number of submucosal glands and mucus and inflammation and increased risk of infection. Hyperplasia of smooth muscle occurs and goblet cells as well. Cant get air out with force. Most of the obstruction to airflow is in the bronchioles. Complications are increased CO2 and decreased in O2 in the blood(hypoxemia) as the body responds to airway obstruction through decreased ventilation (lazy respiratory centre in the brain) and increased cardiac output. Other complications are dyspnoea (airway obstruction), pneumonia, right-sided heart failure and cardiac hypertrophy and late stage COPD and respiratory failure and cancer. Blue appearance=elevated hemoglobin. Overweight Emphysema: Destruction of alveolar walls. Permanent dilation of airway distal to terminal bronchioles, happens cause of chronic exposure to irritants causes repeated inflammation and neutrophil activity which secretes proteases which kills the type 1 and 2 alveoli and destroy its wall. Reduced surface area to participate in gas exchange and a lot of foreign particles in the lungs. Loss of ability to restrict and inflate/loss of elastic recoil. Symptoms include: increased volume of lung which can create a barrel chest (less oxygen in the lungs and body and muscle waste away). Pink appearance. Inflammation and high white blood cell activity (neutrophils) lead to tissue damage, these dissolve alveolar septum. Antiprotease=antitrypsin, which protects tissue by inhibiting protease (neutrophil), synthesised in liver, genetic mutations exist and people that have a mutation in this gene in people and makes it a pre-disposing factor. Treatment includes lung transplantation and emphysemic lung volume reduction surgery where a large portion if the diseased lung is removed. Hyperventilation increasing obstruction. Obstruction cause of loss or radial traction and air is trapped and airway is collapsed. Old and thin. Chronic obstructive pulmonary disease (COPD) : can cause significant heart problems, through pulmonary hypertension=hypoxic pulmonary vasoconstriction. Increased RBC lead to hypercoagulability of blood and risk of thrombi and lead to pulmonary embolism, increased risk of atheroscleroisis and contribute to heart failure and isechameic heart failure. -Hypoxic pulmonary vasoconstriction=Blood flow is directed away from alveoli which are not participating in gas exchange (low partial pressure of O2). Blood doesn’t go to all alveoli but blood flow doesn’t decrease so theres a back flow of pressure on pulmonary artery. So there is an increased pressure on the artery and it gets thicker (e.g smooth muscle) to adapt, which causes problems in the right side of the heart (cor pulmonale), entrance gets smaller and right side will undergo hyperphory and not pump as efficiently and eventual failure. COPD also causes lung cancer as they share risk factors and inflammation increases the risk of cancer. Osterporosis is also a problem with advanced COPD. It affects bone, bone loss is also caused by smoking as well as vitamin D deficient, low body mass index. (36-60% of COPD). Because of systematic inflammation and release of inflammatory cytokines stimulates breakdown of bone. Forced vital capacity: Maximum toal volume of air which can be exhaled from the lungs following the deepest breath possible. Forced expiratory volume: Volume at 1 seconds of amount of air which can be exhaled. These are both used to determine lung function. In restrictive lung disease- the ratio of these stays the same but both are reduced (FEV:FVC_ In obstructive: Fvc is similar, retain dead air exhale is decreased COVID-19: COVID-19, the disease caused by the coronavirus SARS-CoV-2, has caused a worldwide pandemic for over two years. COVID-19 is a relatively new disease, so there is limited natural immunity in the community, although with high vaccination rates, the threat posed by this virus has substantially reduced. However, COVID-19 can spread quickly, causing respiratory signs and symptoms ranging from mild to severe and long-term conditions. There is still ongoing work to better understand the pathogenesis linked directly to COVID-19. Comprises of a crown of spikes on their surface. Zoonotic virus. Risk factors include: pre-excisting conditions (hypertension, coronary artery disease and diabetes), immunocompromised, elderly, obese, male- is hypothesised. Three major molecules: ACE2-acts as a receptor for SARS binding. TMPRSS2-trasmembrane protease, cleaves and activated SARS-2. And Cathepsin L-also cleaves and activated. Can cause pneumonia in severe conditions and critical includes acute respiratory distress syndrome, may have shock and heart failure. Acute respiratory distress syndrome: covid affects epithelial cells in alveoli, lot of cell injury membrane which secretes chemokines that start inflammation and recruits neutrophils and cytokines that damage and release into the bloodstream to other organs, scarring of alveoli. Cytokine storm=overtly aggressive inflammatory response and can cause multi organ failure and lung injury (degrade tissue in organs.) cytokines also strong expression of interferon and can induce ACE2 expression increasing potential for virus entry into other cells. Asthma is an increasingly common reversible obstructive airway condition, currently affecting almost three million Australians. It is a type I hypersensitivity reaction. Triggerable. Airways are inflamed acutely. Genetic predisposition-Trigger= airway inflammation= Hypersecretion of mucus, airway muscle constriction and swelling bronchial membranes= narrow breathing passages=wheezing, cough, shortness and tightness in chest (clinically variable). Atopic and non-atopic (late onset), Atrophy. Genetic defects in genes which regulate and mediate the immune response. Environmental triggers also confer susceptibility and cause an attack. Neither factor alone can trigger an attack. Treatment= medication to reduce inflammation, relieve muscle spasm and constriction and mucus secretion as well as reduce histamine production. Also preventing or limiting exposure to trigger. Preventors=inhaled corticosteroids. Reduce airway sensitisation to trigger, reduce swelling and mucous, reduce histamine production. Reliver=Bronchodilators. Act on receptors to relax smooth muscle and reduce bronchoconstriction and bronchial spasm. May have side effects of vasodilation in heart. Long-term=corticosteroids taken in tablet or liquid form. WEEK 11: Diabetes, renal, liver and gastrointestinal system disorders Diabetes Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of energy and comes from the food you eat. Insulin, a hormone made by the pancreas, helps glucose from food get into your cells to be used for energy. When someone has diabetes, their body doesn’t make enough – or any – insulin or doesn’t use insulin effectively. Glucose then stays in your blood and doesn’t reach your cells. Over time, having too much glucose in your blood, called hyperglycaemia, can cause health problems. Complications include acute issues such as diabetic ketoacidosis, hyperosmolarity, hyperglycaemia and chronic complications due to blood vessel damage, termed microvascular disease. Microvascular complications include diabetic retinopathy (eye damage), diabetic nephropathy (kidney damage), neuropathy (nerve damage), diabetic foot ulcers due to poor wound healing, infections and reduced immunity. Type 1 Type 1 diabetes typically emerges in childhood. It is characterised by insulin deficiency due to the destruction of pancreatic beta cells, often triggered by autoimmune mechanisms. Diabetic ketoacidosis is a severe complication, where insulin deficiency prompts the body to use fatty acids for energy, leading to ketone formation and acidosis. Without treatment, it can result in unconsciousness. Absolute insulin deficiency T lymphocytes (helper and cytotoxic T cells, macrophages) Genetic: Mutations in the class II MHC molecules on chromosome HLA-D, mutations in the T cell inhibitory receptor CTLA-4 Environmental: Infections, Molecular mimiary Type 2 Type 2 diabetes commonly develops in adulthood and is associated with obesity and genetic factors. It arises from insulin resistance in peripheral tissues followed by beta cell dysfunction, coupled with inadequate pancreatic insulin secretion. Obesity plays a significant role, as fat cells release cytokines affecting insulin sensitivity. Additionally, adipose tissue releases hormones, which influences insulin resistance. Genetic: family history Environmental factors: obesity and inactivity Genetic-abnormalities in insulin signalling. Role of free fatty acids- potent inhibitors of insulin signalling. Adipocytokines-adiponective: insensitivity Beta cell dysfunction: unable to adapt tp peripheral insulin resistance and increased insulin section (b cell degeneration and hyperplasia.) Hyperglycaemia-abnormally high blood glucose levels, Gluconegiensis-liver releases glucose, non carbohydrates (lipids and proteins -> gluclose SYMPTONS: Hyperosmolarity- polyuria or increased frequency of urination. Polydipsia- increased thirst due to high blood glucose that raises the osmolarity of blood and makes it more concentrated. Polyphagia-increased hunger is due to the loss of excess glucose in urine. Fatigue, muscle weakness and poor blood flow are additional symptons Complications Microvascular disease( diabetic retiopathy=eye damage due to damage of the fine blood vessels of the retine due to longterm high blood glucose. Diabeteic nephropathy=end stage renal disease. Diabetic neuropathy=nerve damage (numbness or tingling, also affects sutonmoic functions sich as erectile dysfunction and difficulty in digestion and foot ulcers), Hyperglycemia (poor wound healing). Macrovascular disease=heart disease (coronary, cerebral and peripheral artery diseases leads to stroke and myocadrinal disease. -Ketoacidosis= reliance on fatty acids for energy and raises keytones which can cause dehydration and unconscious Chronic kidney disease: The kidneys receive approximately 25 percent of the cardiac output per minute, normally producing one to two litres of urine per day. Most drugs along with other wastes products are excreted by the kidneys and they have an important role in homeostasis and hormone synthesis. So, when things go wrong with the kidney, it impacts on almost every area of the body. Systemic effects and progressive, long-term damage to the kidneys include excessive inflammation, persistent infections, pH imbalances and altered blood flow. Prevalence Chronic kidney disease (CKD) encompasses conditions involving a gradual, sustained loss of kidney function lasting over three months, with evidence of kidney damage and/or reduced function. CKD is widespread, affecting 1 in 10 Australian adults and contributing to 1 in 9 deaths. Elderly, indigenous populations, and those in remote, disadvantaged areas are at higher risk. CKD closely associates with cardiovascular disease and type 2 diabetes. Risk factors include obesity, inactivity, poor diet, smoking, hypertension, diabetes, family history, and being of Aboriginal or Torres Strait Islander origin. Progression Diagnosis requires decreased kidney function for three months and evidence of damage, such as urinary protein or albumin, blood in urine, or scarring on imaging. CKD's early symptoms are often subtle, so it is often undetected until advanced stages, with symptoms appearing when kidney function is at about 25% of normal. CKD has five stages, determined by a measure of the kidneys' waste-clearing ability called the glomerular filtration rate (GFR). As CKD progresses through the stages it can lead to harmful waste accumulation and disrupt hormone production, electrolyte balance and blood pressure regulation. Hypertension damages blood vessels, affecting glomeruli and causing nephrosclerosis. Glomerulonephritis, or inflammation of the glomeruli, can result in permanent kidney damage. More advanced stages of CKD also manifest with oedema, anaemia, respiratory issues, hyperkalaemia, calcium imbalance, uraemia and weight loss. Causes: Glomerular disease, chronic infections, vascular disease, congenital anomalies, unrinary tract obstructions, collagen diseases, nephrotic agents and endocrine diseases-diabetes. Vascular disease: hypertension -damage blood vessels reduce bloody supply to the kidnsey. Damage glomerulus which causes focal segmental sclerosis-hardening of sections of glomerulus and nephroscleosis-hardening of entire nephron. Glomerrular disease-inflmaation of the glomeruli, post-streptococcal glomerulonphitis, immune complex forms-antibodies to stretpcoccis. Immune response-immune complex settles in glomeruli=inflammation, complement proteins and recruit immune cells=damage glomeruli Complications-reduce renal function, unrine frequently of diffucilty urinatinf, water retention, generalised oedema. Anaemia/fatigue, respiratory symptons-shortness of breath/reduced oxygen, high potassium, hyperphosphatemia, calcium in the bones reduces. And Vitamin D deficiency. Uraemia-retein waste products and toxins. Bad breath-nausea and vomiting. Neuropathy-cent think clearly and fatigue. Liver failure: liver damage initially leads to inflammation and the liver can regenerate at this stage. However persistent inflammation can result in fibtosis, the accumulation of sac tissue. As fibrosis progresses it can develop into cirrhosis, where extensive scarring distors liver architecture compromising its functions.Cirrhosis can lead to complications like jaundice, pale stools, dark urine, bleeding tendencies, fluid accumulation (ascites), portal hypertension, mental confusion (hepatic encephalopathy) and more. Severe cases culminate in end-stage liver failure, necessitating a liver transplant for cure. Liver disease can be classified as acute or chronic. Acute liver failure is rare, triggered by toxins or viral infections, but rapid, with a high mortality rate. Chronic liver failure occurs gradually and is often linked to long-term alcohol use, viral infections (hepatitis B, C, D), non-alcoholic fatty liver disease, medication toxicity, inherited metabolic disorders, autoimmune diseases and structural abnormalities. Diagnosis and treatment Recognising liver failure's early symptoms – nausea, fatigue, jaundice, dark urine – is crucial, but diagnosis can be complex due to overlapping symptoms. It's important to address the underlying causes of liver disease to prevent or manage liver failure and its complications.