Cells, Fluids and Electrolytes PDF

Tony Santin Cells, Fluids and Electrolytes In the first week of Applied Pathology, we'll delve into the fascinating world of cells, the building blocks of life. We'll explore how cells adapt to stress and look at what happens when they're injured or die. We'll also explore the critical role of bod...

Tony Santin Cells, Fluids and Electrolytes In the first week of Applied Pathology, we'll delve into the fascinating world of cells, the building blocks of life. We'll explore how cells adapt to stress and look at what happens when they're injured or die. We'll also explore the critical role of body fluids like water and electrolytes, which play a vital role in cellular function and overall health. This week will also introduce you to “Paramedics in Practice”. These are real world cases which have direct connections to the weekly content. We'll actively connect this new knowledge to your existing anatomy and physiology background. The learning outcomes for this module are: 1. Identify the processes of cellular adaptation 2. Describe reversible and irreversible cellular injury 3. Identify common causes of cellular injury 4. Compare and contrast the types of cellular death 5. Describe the cellular processes which occur in response to hypoxia 6. Briefly describe reperfusion injury and how it applies to paramedic practice 7. Discuss the mechanisms of water movement in the body 8. Describe oedema and the processes by which it occurs  9. Discuss the normal role of sodium and pathological changes to sodium levels 10. Discuss the normal role of potassium and pathological changes to potassium levels SECTION 1: CELLULAR PATH OLOGY The Cell Cellular Adaptation Paramedics in Practice 1 Cellular Injury and Cell Death Hypoxia, Ischaemia and Infarction Paramedics in Practice 2 Reperfusion and Reperfusion Injury SECTION 2: FLUIDS AN D ELECTR OLY TES Body Water Oedema Paramedics in Practice 3 Sodium, Chloride and Water Potassium Paramedics in Practice 4 Lesson 1 of 13 The Cell Tony Santin A cell is described as: A collection of different types of tissues The smallest structural and functional unit of an organism The atoms and molecules which make up molecules SUBMIT C O NT I NU E The structure and function of cells should be revision for you. This was covered in BIO1203: Human Anatomy and Physiology 1. You will need a strong understanding of what cells are, and how they work, in order to understand pathology. You may wish to watch the following two short videos from Dr Matt and Dr Mike to refresh your knowledge of cells. YOUTUBE The Cell and Organelles The Cell and Organelles In this video, Dr. Mike outlines all the important structures and organelles within the human cell. VIEW ON YOUTUBE   C O NT I NU E YOUTUBE Cell Structure and Function Cell Structure and Function A brief overview of the characteristics and organisation of the cell. VIEW ON YOUTUBE  Recall that the normal, healthy state of equilibrium in the body is called homeostasis. Cells want to remain in a state of homeostasis.  However, cells exist in a dynamic state. They are constantly changing to meet the needs of the body. As such, they are subject to excessive demands and external stress, and can be damaged and even destroyed. C O NT I NU E The process of cellular injury is the basis for disease processes, so it is vitally important that we understand how cells adapt, are injured, or die, before we progress to discussing specific pathologies. Cells are surrounded by: The rough endoplasmic reticulum Epithelial tissues A phospholipid bilayer membrane SUBMIT Which of the following ions are predominantly intracellular? Potassium (K+) and Bicarbonate (HCO3-) Sodium (Na+) and Calcium (Ca2+) Magnesium (Mg+) and Chloride (Cl-) SUBMIT What's Next? Knowing the state of a normal healthy cell, we will now look at abnormal cell functioning: the basis of pathology. We will begin with Cellular Adaptation. C O NT I NU E Lesson 2 of 13 Cellular Adaptation Tony Santin Cells may adapt to stress placed upon them in an effort to maintain homeostasis. This is known as Cellular Adaptation. Cells are able to change to adapt to their environment. A cell which has adapted is not injured. But it is also not in its normal state. Cellular adaptation attempts to maintain homeostasis. Once the stress on the cell is removed the cell may return to its normal state. If the adaptation is overwhelmed, then injury will occur. The main ways in which a cell may adapt are: 1 Atrophy Hypertrophy 2 Hyperplasia 3  Metaplasia 4 5 Dysplasia C O NT I NU E A TR O P H Y H Y P ER TR O P H Y H Y P ER P L A S I A M ETA P L A S I A DY Atrophy is a decrease in cellular size. When occurring widely across an organ atrophy can be seen in a physical reduction in size of the organ. Atrophy is most common in skeletal muscle, cardiac tissue and the brain. Normal, or physiological, atrophy can occur during development, such as the natural reduction in size of the Thymus gland during childhood. Abnormal, or pathological, atrophy can occur due to a number of factors including decrease in workload or use (e.g., reduction in skeletal muscle size) and decreased blood supply or nutrition. In the image below we see an example of cerebral atrophy. In A there is a healthy brain. B shows an atrophied brain. Notice the reduction in volume and increase in size of the sulci Image adapted from Kumar et al. (2018).  A TR O P H Y H Y P ER TR O P H Y H Y P ER P L A S I A M ETA P L A S I A DY Hypertrophy is an increase in cellular size. When occurring widely across an organ hypertrophy can be seen in a physical increase in size of the organ. The heart, skeletal muscle and uterus are common sites for hypertrophy. Normal, or physiological, hypertrophy may occur in response to increased demand (e.g., skeletal muscle increasing), or hormones (e.g., uterine increase during pregnancy). Typically, physiological hypertrophy will resolve with time once the stimulus is removed. Abnormal, or pathological, hypertrophy may be due to chronic overload, such as in the heart from hypertension. Pathological hypertrophy is detrimental. In the illustration below we see an example of left ventricular hypertrophy. Notice how thick the walls of the left ventricle are. Image adapted from Lynch (2006). Retrieved from https://commons.wikimedia.org/w/index.php? curid=1490527)  A TR O P H Y H Y P ER TR O P H Y H Y P ER P L A S I A M ETA P L A S I A DY Hyperplasia is an increase in the number of cells. The cells undergo mitosis (cells splitting into two identical cells). As with hypertrophy this can result in a physical increase in size of the organ. Compensatory hyperplasia is a normal response to allow organs to regenerate. The liver uses hyperplasia to regenerate itself (it can regenerate 70% of its own mass within 2 weeks!). A callus on your hand from regular contact is another example of hyperplasia, as is wound healing. Pathological hyperplasia is an abnormal increase in cell numbers, due to either hormonal stimulation or growth factors. Prostatic hyperplasia is an example of pathological hyperplasia. Image adapted from Blaus (2015). Retrieved from https://commons.wikimedia.org/wiki/File:Benign_Prostatic_Hyperplasia_(BPH).png  A TR O P H Y H Y P ER TR O P H Y H Y P ER P L A S I A M ETA P L A S I A DY Metaplasia is a reversible replacement of one cell type with another. In some cases, the change is a protective mechanism – such as the changes in the oesophagus in response to chronic reflux. However, most metaplasia is not beneficial. Chronic irritation from smoking results in the loss of airway protection as normal epithelium is replaced with squamous cells. These do not have cilia or produce mucous. A subsequent consequence is the increased incidence of chest infections among smokers. Reversal of metaplasia can occur with time if the stimulus is removed. If it is not, a malignant (cancerous) process can occur as the cells become metaplastic. In the illustration below squamous cells can be seen replacing the normal columnar epithelium in response to smoking Image adapted from Kumar et al. (2018).  A TR O P H Y H Y P ER TR O P H Y H Y P ER P L A S I A M ETA P L A S I A DY Dysplasia is a change in the normal structure of cells; including size, shape and organisation. Dysplasia is not a 'true' form of cellular adaptation, and is related to hyperplasia. It is common in epithelial tissue in the uterus, cervix and endometrium, as well as the gastrointestinal tract and respiratory tract. Dysplasia is not a form of cancer but can progress to cancer if the affected cells progress through the basement membrane. In the illustration below we can see how normal cells may change in appearance with dysplasia Adapted from Yaja’ Mulcare (2022). Retrieved from https://www.healthline.com/health/cervical- dysplasia  C O NT I NU E Which forms of cellular adaptation may lead to malignancy (cancer)? Metaplasia and Dysplasia Atrophy and Hyperplasia  Hypertrophy and Hyperplasia Hyperplasia and Dysplasia SUBMIT A reduction in size of an organ is due to: Metaplasia Hypertrophy Atrophy Hyperplasia SUBMIT  C O NT I NU E Clinical Connection Many patient presentations are based on these cellular changes. Smokers have altered respiratory epithelium and are at an increased risk of chest infections. Patients with hypertension may develop hypertrophy of the myocardium, which can mimic a heart attack on an electrocardiogram. Age results in cerebral atrophy, increasing the risk of torn blood vessels and intracranial haemorrhage in trauma. While we do not assess patients at a cellular level, understanding these changes in the body will form the basis for your clinical decision making. What's Next? We will now look at our first case study for this course. These cases are known as "Paramedics in Practice" and will help you begin to apply pathology to patient presentations. C O NT I NU E Lesson 3 of 13 Paramedics in Practice 1 Tony Santin Paramedics in Practice presents you with real world cases which provide you with a means of applying pathology to paramedicine. You will discuss these cases in your tutorials. Ray: The Cattle Farmer Ray is a 68 year old male living on a cattle farm in the Laidley area. He called paramedics after he developed some central chest pain. Paramedics arrive on the property 28 minutes later, at which time Ray no longer has any symptoms. A typical, self reliant farmer, Ray does not wish to go to hospital. but allows paramedics to assess him. Paramedics find a blood pressure of 186/107. Ray has not seen a doctor in 10 years, so he does not know if this is normal for him. Paramedics conduct a 12 Lead ECG which shows a sinus rhythm with left ventricular hypertrophy. After a discussion with Ray about his presentation, Ray agrees to go with paramedics to be assessed at hospital. Paramedics hand Ray over, discussing their concerns with the registrar. Ray was admitted to hospital for 3 days, and was discharged with two new medications: Perindopril and Diltiazem. Prepare for your tutorial: Identify the key features of these cases, and apply the preceding content to determine what has happened to the patient. Be prepared to discuss this case with your group. What's Next? Cells which cannot adapt may become injured or die. We will now look at how cells are injured and what happens when they die. C O NT I NU E Lesson 4 of 13 Cellular Injury and Cell Death Tony Santin If the demands or stress on the cell exceed the ability of the cell to adapt, then Cellular Injury will occur. These injuries may be reversible or irreversible. An injury is reversible if the cell can return to its normal state when the stress is removed. Injured cells have reduced ability to perform their normal functions. There are a number of ways in which cells may be injured. These include the following: Hypoxia and Ischaemia Cells need Oxygen. But in some circumstances the Oxygen supply is reduced or absent. Hypoxia is an oxygen deficiency. Ischaemia is a deficit in blood supply. These terms are not interchangeable. They can occur independently, or together. Both hypoxia and ischaemia result in lack of oxygen getting to the cells. Hypoxia and ischaemia are the most common causes of cellular injury. Toxins Toxins exist everywhere in the environment. Some are almost unavoidable (such as air pollution) while others are deliberately introduced into the body (cigarette smoke, vaping, alcohol, or drugs). Substances which you think of as “normal” can also become toxic in excessive doses. Salt is an example. Oxygen is another. So is water. Infectious Agents You can probably think of many infectious agents. The SARS-CoV-2 Virus, more commonly known as COVID-19 is probably the first one you think of these days. Viruses and bacteria are the most commonly thought of. But there are also fungi, protozoa, prions and helminths that can cause infection. We will look at infectious agents in more detail in week 3. Immunological Responses The body’s immune system is designed to defend us against infection. However, the same processes which protect us, can also cause pathological injury. Allergic reactions (including anaphylaxis) and autoimmune diseases can result in pathological changes just as well as any other cause of pathology. We will look at the immune system in detail in week 3. Genetic Abnormalities Genetics are a non-modifiable risk factor for many conditions. Changes occur at a DNA level, with potentially significant downstream manifestations. Abnormalities in the genes can result in congenital conditions such as Down syndrome. Nutritional Imbalances On one end of the spectrum is nutritional deficiency resulting in starvation and significant impacts to health. At the other end we have excessive intake which can result in obesity and a completely different set of detrimental impacts on health. This may also be a causative factor (aetiology) for conditions such as type 2 diabetes mellitus. Physical Agents External damage can also result in cellular injury or cell death. Trauma, such as injuries sustained from a road traffic crash or an assault, as well as radiation, electrocution, burns and hypothermia can all cause pathological changes in the body. Age The most natural process of all. Age. Aging is not a pathological process. However, it does result in cellular changes. Over time cells will lose their ability to adapt to stress, leading to eventual cell death. When enough cells die, organs begin to fail. C O NT I NU E Ageing is a pathological process. True False SUBMIT Hypoxia is:  The excess of oxygen in a cell A deficit of blood supply Interchangeable with ischaemia An oxygen deficiency SUBMIT C O NT I NU E Irreversible injury leads to Cell Death. Cell death can occur through one of two processes. Apoptosis (pronounced a·pop·tow·suhs) or Necrosis (pronounced neh·krow·suhs).  When a cell is subject to an irreversible injury, cell death is inevitable. Apoptosis Apoptosis is the 'programmed' death of the cell. The cell will destroy its own DNA and nuclear proteins, breaking itself down into 'bite sized' pieces contained within cell membrane. The result is that the body will then clear these fragments through phagocytosis (where other cells 'eat' the fragments). The process is very 'clean' and does not result in any inflammation. Necrosis This is where the cell membrane falls apart, with enzymes spilled from inside the cell. These enzymes will break down the cell, but they can also damage surrounding tissue. The body reacts with an inflammatory response to clean up after the dead cell. Necrosis of different organs results in the leakage of intracellular proteins into the blood. These can be detected on blood tests at hospital and allow clinicians to identify if tissue death has occurred. Necrosis can occur in varying types depending on the mechanism behind the injury and the organs involved. You do not need to know the different types of necrosis, however recognition of the death of cells is vital, as this can lead to serious complications. Externally visible necrosis is often referred to as "Gangrene". This is actually a form of necrosis known as coagulative necrosis and appears as visibly dying tissue.  Graphic Image Warning Limb necrosis C O NT I NU E An injured cell subject to necrosis will: Destroy it's own components Break down and spill it's contents Contain the dead components inside the membrane  Result in inflammation SUBMIT Clinical Connection There are many situations where cell death is assessed by paramedics. The stereotypical necrotic limb (gangrene) is uncommon. More often paramedics are assessing for signs of cell injury and death. An electrocardiogram shows the injury and death of cardiac cells occurring during a heart attack. Blood tests at hospital will show markers which represent the necrosis and spilling of cell contents, confirming the death of a portion of the heart. What's Next? We will now look in detail at what happens when a cell does not receive Oxygen, and the subsequent process of cellular injury and cell death due to hypoxia. This is the first detailed pathological process we will investigate. C O NT I NU E Lesson 5 of 13 Hypoxia, Ischaemia and Infarction Tony Santin Cells which have insufficient Oxygen supply are said to be hypoxic. Some cells, such as those in the brain and heart, are particularly sensitive to hypoxia. Death of these cells can have catastrophic consequences. Hypoxia Hypoxia may be due to several causes: Reduced atmospheric oxygen 1 Loss of haemoglobin, or reduced haemoglobin function 2  Decreased production of red blood cells 3 4 As a result of respiratory or cardiovascular disease One of the changes which occurs when cells are hypoxic is cellular swelling. This is where the injured cells become swollen with water. Cellular swelling is due to ion-pumps in the cell membrane failing, which results in failures of the normal fluid movement between the extra- and intracellular space. The organelles within a cell may also become swollen during this process. The most common cause of hypoxia is ischaemia. Reduced blood flow, regardless of whether the blood is well oxygenated, will result in tissue hypoxia. C O NT I NU E Ischaemia Ischaemia is a reduction in blood flow to tissue or an organ. This restricted flow, regardless of the oxygen content in the blood, can still lead to cellular hypoxia and ultimately cell death. There are several factors which contribute to ischaemia:  Thrombosis: the formation of a blood clot within a blood vessel, 1 obstructing the flow. 2 Embolism: a foreign object, such as a blood clot or air bubble, lodging in a blood vessel and blocking the flow. Vascular stenosis: the narrowing of a blood vessel due to plaque buildup 3 or other factors including external pressure, reducing flow. 4 Hypovolemia: a severe decrease in blood volume due to dehydration, blood loss, or other causes, leading to inadequate blood supply to tissues. Vasospasm: the sudden constriction of blood vessels, which can be 5 caused by trauma, nerve impulses, or certain medications. The consequences of ischemia depend on the severity and duration of the blood flow restriction. When tissues are deprived of oxygen and nutrients due to ischemia, a cascade of events occurs including the loss of energy production by the cell, followed by cellular injury and eventually cell death. Cellular death which occurs as a result of ischaemia is known as infarction. The concept of "time is tissue" is crucial in managing ischemic events.  The longer a tissue is deprived of oxygenated blood, the greater the risk of cell death and permanent damage. Early recognition and intervention are essential for minimising tissue loss and improving patient outcomes. C O NT I NU E Reduced Oxygen in the atmosphere results in ischaemia. True False SUBMIT C O NT I NU E  The following video from Osmosis provides an excellent review of hypoxia. YOUTUBE Hypoxia & cellular injury - causes, symptoms, diagnosis, tr… Hypoxia & cellular injury - causes, symptoms, diagnosis, treatment & pathology VIEW ON YOUTUBE  C O NT I NU E Ischaemia may be due to:  Obstructed blood flow Reduced blood volume Low oxygen levels External pressure on blood vessels SUBMIT C O NT I NU E Clinical Connection Hypoxia and ischaemia are the most common cause of cell death. While some cells regenerate, others are permanently lost when they die.  Assessing a patient correctly and providing appropriate airway management and oxygenation can reduce or avoid hypoxic cell injury and cell death. Ischaemia is a time critical presentation in some cases, such as strokes and heart attacks. Recognition of ischaemic tissue may lead paramedics to provide reperfusion therapy on a scene or activate a care pathway which results in urgent surgical intervention at hospital. What's Next? We will now look at our second Paramedics in Practice case study for this course. This case will also be discussed in the tutorials. C O NT I NU E Lesson 6 of 13 Paramedics in Practice 2 Tony Santin Paramedics in Practice presents you with real world cases which provide you with a means of applying pathology to paramedicine. You will discuss these cases in your tutorials. Margaret: The Retiree Margaret is a 73 year old female living in Sumner Park. She called the ambulance today with some breathlessness and an episode of fainting after lunch. Paramedics are on scene in 11 minutes, and find Margaret pale, diaphoretic, and vomiting into a bucket. A rapid assessment reveals Margaret is having an acute myocardial infarction. Her 12 Lead ECG shows an anteroseptal ST Segment Myocardial Infarction. Paramedics phone the interventional cardiologist at the Princess Alexandra Hospital who accepts Margaret for primary percutaneous coronary intervention (stenting). Margaret goes into a VF arrest twice enroute to the hospital but is successfully defibrillated both times. Paramedics offload Margaret onto the operating table and hand over the cardiologist. The stenting procedure is completed successfully, and Margaret was discharged home one week later. Prepare for your tutorial: Identify the key features of these cases, and apply the preceding content to determine what has happened to the patient. Be prepared to discuss this case with your group. What's Next? Cells which are ischaemic can recover if adequate perfusion is restored in time. We will now look at the process of reperfusion, and how this can also lead to cellular injury. C O NT I NU E Lesson 7 of 13 Reperfusion and Reperfusion Injury Tony Santin Reperfusion is the restoration of adequate blood flow, and therefore oxygen, to the cells. Ischaemia-reperfusion injury occurs when the sudden return of oxygen results in further damage to the cell. Reperfusion injury is commonly seen in the heart, brain and kidneys. Reperfusion injury is believed to be due to the following mechanisms: 1 Oxidative stress Nitric oxide 2  Increased intracellular calcium 3 4 Inflammation 5 Complement activation We will only briefly discuss oxidative stress. The process is much more complicated than presented here. You only require a superficial understanding of reperfusion injury at this stage. O X I DA TI V E S TR ES S A group of molecules known as Free Radicals can result in cell damage. A specific subgroup of free radicals, the Reactive Oxygen Species (ROS) are often generated during the process of cellular injury. ROS include: Superoxide Hydrogen Peroxide Hydroxyl Radical These ROS exist in the body at all times and can be thought of as the byproduct of normal homeostatic processes. ROS are very good at causing damage. Luckily the ROS exist in numbers normally able to be kept in check by the body's own mechanisms. Extra ROS are produced by the mitochondria during ischaemia. When oxygen is then reintroduced through reperfusion, the oxygen molecules interact with the ROS, causing the ROS to rapidly multiply and cause further damage to the cells. This is reperfusion injury.  C O NT I NU E Restoring blood flow to a cell can in some cases lead to further injury known as: Reactive Oxygen Species Ischaemia-Reperfusion Injury Free Radicals Inflammation SUBMIT Clinical Connection  Some treatments provided by paramedics result in the resolution of ischaemia. This can in some cases lead to an ischaemia-reperfusion injury. In cases such as myocardial ischaemia, reperfusion can result in temporary cardiac dysrhythmias, such as ventricular fibrillation and ventricular tachycardia. Paramedics must be aware of this risk when managing such patients in order to adequately prepare for, and manage, such dysrhythmias. What's Next? Now that we have a basic understanding of cellular pathology, we can begin to look at how fluids and electrolytes move in the body, and how this affects the cells. Continue on to the next section of this module. C O NT I NU E Lesson 8 of 13 Body Water Tony Santin Total Body Water is the sum of water in all compartments of the body. Two thirds of total body water is intracellular fluid (ICF). Extracellular fluid (ECF) makes up the other third of total body water. ECF is divided into interstitial fluid (fluid between the cells) and intravascular fluid (fluid within the blood vessels). The following video from Osmosis is an excellent revision resource on body water. YOUTUBE  Hydration Hydration Why do we need hydration? Water is the main substance in our bodies, making up more than 50% of a person's body weight, and it's directly involved in every biochemical reaction in each cell in our body. Find more videos at http://osms.it/more. Hundreds of thousands of current & future clinicians learn by Osmosis. VIEW ON YOUTUBE  C O NT I NU E Under normal conditions, most water loss occurs through: Sweat  Urine Breathing Faeces SUBMIT C O NT I NU E Ensure you are familiar with the following terms before continuing. OS M OS IS H Y DR O S TA TI C P R ES S U R E O N C O TI C P R ES S U R E Osmosis is movement of water through a semi-permeable membrane from an area of low solute concentration to an area of high solute concentration. In cells, water moves across the lipid bilayer through aquaporins. Aquaporins are simply proteins in the cell wall which act as water channels to allow water to move in and out of the cell. Remember that lipid is hydrophobic. Without aquaporins, water would not be able to cross the cell membrane. Image By OpenStax - https://cnx.org/contents/[email protected]:fEI3C8Ot@10/Preface, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=30131189 OS M OS IS H Y DR O S TA TI C P R ES S U R E O N C O TI C P R ES S U R E Hydrostatic pressure is simply the pressure inside of the vessels. Fluid under pressure will tend to be pushed out of the vessels. For the most part, only water is pushed out by hydrostatic pressure. Proteins inside the vessel are typically too large to be pushed out. Hydrostatic pressure is highest in arteries due to the higher pressure in the arterial system. Image adapted from Kumar et al. (2018)  OS M OS IS H Y DR O S TA TI C P R ES S U R E O N C O TI C P R ES S U R E Also known as osmotic pressure. Oncotic pressure is the pull of fluid back into the vessel due to osmosis. There is a higher concentration of proteins like albumin inside the vessel, so water is osmotically drawn back into the vessel. Under homeostasis conditions, any fluid not drawn back in by oncotic pressure is collected by the lymphatic system. Oncotic pressure is highest in the veins. The low pressure in the venous system means that there is much less hydrostatic pressure. Image adapted from Kumar et al. (2018)  C O NT I NU E The following video from Physio Flip provides an animated understanding of how hydrostatic pressure and oncotic pressure affect fluid movement. YOUTUBE  Hydrostatic and osmotic pressure | Introduction to #edema Hydrostatic and osmotic pressure | Introduction to #edema https://www.patreon.com/physioflip 00:00 : Introduction to video 00:20 : Basic overview of fluid exchange at the capillaries 1:05 : Example and definition of edema (tissue swelling) 1:24 : Overview of fluid reabsorption in the capillaries. 1:38 : Definition of hydrostatic pressure (with an example! VIEW ON YOUTUBE  C O NT I NU E Fluid pressure is highest in: Veins  Arteries Lymphatics SUBMIT The osmotic movement of fluid back into a blood vessel occurs due to: Hydrostatic pressure Oncotic pressure SUBMIT C O NT I NU E  Clinical Connection The normal movement of water in the body can result in many pathological presentations such as swelling, which is known as oedema. Different patterns of oedema present with certain medical conditions and may be a sign of deteriorating health, such as in heart failure. Intravenous fluid therapy is a common treatment administered to many patients. The movement of this fluid in the body must be understood before commencing fluid therapy. Complications of fluid therapy can include pulmonary oedema (fluid inside the lungs). What's Next? With an understanding of how water moves in the body we can now look at what happens when the normal movement of water is interrupted, and how oedema develops. C O NT I NU E Lesson 9 of 13 Oedema Tony Santin Oedema (pronounced uh·dee·muh) is the accumulation of fluid in the interstitial space. Oedema is written as "edema" in American sources. If you are searching a database for information on oedema it is often helpful to search both spellings. There are four main causes of oedema. Increased Hydrostatic Pressure Increased hydrostatic pressure is due to either of: 1. Venous obstruction (e.g., blood clots, right heart failure, tight clothing)  2. Sodium and water retention (e.g., renal failure) Increased hydrostatic pressure pushes more fluid out of vessels than can be reabsorbed by oncotic pressure and the lymphatic system. Decreased Oncotic Pressure Decreased plasma oncotic pressure is the result of less albumin proteins in the vessels due to: 1. Less albumin produced (e.g., liver disease, malnutrition) 2. Loss of albumin (e.g., kidney disease, haemorrhage, discharge from burns) Without albumin, water is more likely to move to the interstitial space, and less likely to be pulled back into the blood vessels. Increased Capillary Permeability Increased capillary permeability is most commonly the result of inflammation and immune responses, which may be due to: Burns Crush injuries Inflammation (e.g., allergic reactions) Infection Lymphatic Obstruction Lymphatic obstruction may be due to infection or tumours  Water in the interstitial space is unable to be picked up by the lymphatic system, and oedema results. This is specifically known as lymphoedema. Oedema in the limbs is known as dependent oedema, which typically begins in the feet and ankles due to gravity and progresses up the lower limbs with increasing severity. Dependent oedema can also be seen in the buttocks and sacrum, particularly if the patient is bed bound. Dependent oedema is also known as pitting oedema due to the prominent feature of the ability to leave a pit, or dent, on the site when pressure is applied. Oedema can also occur organ in organs, such as the brain (cerebral oedema), lungs (pulmonary oedema) and abdomen (ascites). When oedema occurs in an organ is can become rapidly life threatening. Lower limb pitting oedema Image from James Heilman, MD, CC BY-SA 3.0 , via Wikimedia Commons Graphic Image Warning Cerebral Oedema (Notice there is almost no sulci seen. The gyri are all swollen.) Image adapted from Kumar et al. (2018) Oedema can be localised (contained to a region or organ), or generalised (systemic). C O NT I NU E Dr Mike presents a 2-minute summary of how oedema occurs in this video. YOUTUBE  Edema (Oedema) | In 2 minutes! Edema (Oedema) | In 2 minutes! In this super mini-lecture, Dr Mike explains the pathophysiology (cause) of oedema! VIEW ON YOUTUBE  C O NT I NU E Which of the following would be an example of a cause of increased fluid movement out of a vessel? Obstruction of lymph vessels due to cancer A blood clot in a vein  Decreased number of the protein albumin SUBMIT Increased capillary permeability results in: Increased fluid leaving the vessels Decreased fluid leaving the vessels Decreased number of the protein albumin SUBMIT C O NT I NU E Complications of Dependent Oedema The patient will experience swelling of the site, with reduced mobility and possible discomfort. Shoes and clothing will be tight fitting, potentially worsening the problem. Increased interstitial fluid results in a greater distance between blood vessels and cells. Nutrients, oxygen and waste must therefore travel further. Oedema may apply pressure to capillaries, reducing blood flow and resulting in ischaemia. This can lead to ulcers, and wounds will heal more slowly which increases the risk of infection. Clinical Connection Oedema is a sign of underlying disease processes. Limb oedema may be a sign of underlying cardiovascular or renal disease, requiring assessment at hospital. In some cases, the oedema itself may present a life threat, such as in the case of pulmonary oedema. Patients with fluid in their lungs require urgent recognition and potentially aggressive treatment to prevent respiratory arrest. What's Next? We will now look at our third Paramedics in Practice case study for this course. This case will also be discussed in the tutorials. C O NT I NU E Lesson 10 of 13 Paramedics in Practice 3 Tony Santin Paramedics in Practice presents you with real world cases which provide you with a means of applying pathology to paramedicine. You will discuss these cases in your tutorials. Phyllis: Of Forget-Me-Knot Paramedics are called to a local nursing home and led to the dementia wing, affectionately named Forget-Me-Knot. The assistant in nursing (AIN) leads paramedics to a room with a pleasant photo of a lady on the door with a name sign underneath: Phyllis. Phyllis is lying in bed with the covers pulled up snugly and is watching Wheel of Fortune on TV. She smiles at paramedics but otherwise goes back to her show. The AIN reports Phyllis would not come out to breakfast today because her leg hurts. Normally Phyllis would walk around with her walker and is very social in the dining room. But today she won’t budge. The AIN leaves to get the paperwork for the patient. After some coaxing Phyllis allows paramedics to examine her. As the sheets are pulled back paramedics find significant pitting oedema to Phyllis’ right foot and leg. It is swollen up to the thigh. Phyllis is carefully slid onto the stretcher and taken to hospital. Prepare for your tutorial: Identify the key features of these cases, and apply the preceding content to determine what has happened to the patient. Be prepared to discuss this case with your group. What's Next? We now turn our attention to electrolytes to round out our understanding of cellular function and cellular pathology. C O NT I NU E Lesson 11 of 13 Sodium, Chloride and Water Tony Santin Electrolyte is an umbrella term for a molecule which has either a positive or negative charge. The main positive electrolytes in the body are sodium, potassium, calcium and magnesium. The main negative electrolytes in the body are chloride, bicarbonate, phosphate and sulphate. Sodium Water and sodium have a very close relationship. Water moves based on osmotic gradients, and sodium creates a concentration gradient which allows this to occur. Sodium (Na+) makes up around 90% of extracellular cations (positively charged ions) and is responsible for regulating water balance and extracellular volume. The concentration of sodium is maintained by the kidneys, neural and hormonal processes. The anions (negatively charged ions) which are involved in water movement are chloride (Cl-) and bicarbonate (HCO3-). Chloride is the main anion in the extracellular fluid. It balances the charge of Sodium to maintain a neutral state. Chloride transport is passive and is proportionately related to sodium movement. The normal sodium concentration is 135 - 145mEq/L C O NT I NU E Review your understanding of tonicity before continuing. Dr Mike explains this in the following video. YOUTUBE  Tonicity VIEW ON YOUTUBE  The states of tonicity here show red blood cells shrinking (hypertonicity), normal red blood cells (isotonic), and swollen or bursting red blood cells (hypotonicity).  C O NT I NU E The normal range for sodium is: 125 - 135mEq/L 135 - 145mEq/L 145 - 155mEq/L SUBMIT The charge of sodium is balanced by: Chloride Potassium  Bicarbonate Magnesium SUBMIT C O NT I NU E Sodium levels above 145mEq/L are referred to as hypernatraemia. Sodium levels below 135mEq/L are referred to as hyponatraemia. Hypernatraemia Hypernatraemia results in a state of hypertonicity. Cellular shrinkage occurs as water moves out of the cell and into the extracellular space. Dehydration can result as the increased extracellular water is excreted from the body.  All cells are affected by hypernatraemia, but the neurons of the central nervous system are particularly affected. As a result, hypernatraemia can present with neurological symptoms such as weakness, lethargy and muscle twitching. Severe cases can progress to confusion, seizures and unconsciousness. Hyponatraemia Hyponatraemia results in a state of hypotonicity. Cellular swelling occurs as water moves from the extracellular space into the intracellular space. As with hypernatraemia, all cells are affected by hyponatraemia, and neurons of the central nervous system are particularly affected. Patients may present with nausea and vomiting, lethargy, headaches, and a feeling of apprehension. Severe cases may also present with confusion, seizures, and unconsciousness. Hyponatraemia is the most common electrolyte disorder in patients in hospital. It is associated with increased morbidity and mortality; i.e., a patient being managed for another condition is more likley to suffer long term ill effect, or die, if they have concurrent hyponatraemia. C O NT I NU E A patient with a sodium level of 120mEq/L is presenting with:  Hypernatraemia Hyponatraemia Normal sodium levels SUBMIT Clinical Connection Electrolyte imbalances can present in various ways. Patients with vague presentations, such as lethargy, weakness and dehydration may be presenting with a potentially serious condition. Careful history taking and assessment is required to provide appropriate care for these patients as many may refuse to go to hospital due to their mild and  vague symptoms. A worsening in their condition, however, could become life threatening. Recall that both high and low levels of sodium can result in seizures and unconsciousness, and hyponatraemia in particular increases the risk of morbidity and mortality in patients suffering any other condition. What's Next? We will conclude this module by looking at another major electrolyte and the related disorders: potassium. C O NT I NU E Lesson 12 of 13 Potassium Tony Santin Potassium is the primary intracellular cation. In conjunction with sodium, potassium levels determine the resting membrane potential. Although potassium is primarily intracellular, it is the extracellular levels of potassium which are measured. Potassium Like sodium, potassium is highly regulated by the body. The balance between intracellular and extracellular potassium is mediated by the sodium- potassium active transport system. The difference between the two is the primary cause of the resting membrane potential. The resting membrane potential is what allows for conduction of action potentials. Potassium has many other roles throughout the body which we will encounter in context throughout the course. In the same way sodium controls the extracellular osmolality, potassium contributes to the osmolality of the intracellular fluid. If cells rupture, then the high levels of potassium within are suddenly ejected into the extracellular space. This can cause a sudden increase in extracellular potassium levels. The normal (extracellular) potassium concentration is 3.5 - 5.0mEq/L C O NT I NU E Review your understanding of the resting membrane potential. Dr Mike explains this in the following video. YOUTUBE Resting Membrane Potential | Nervous System  Resting Membrane Potential | Nervous System VIEW ON YOUTUBE  C O NT I NU E The normal range for potassium is: 2.0 - 3.5mEq/L 3.5 - 5.0 mEq/L 4.0 - 6.5mEq/L SUBMIT Potassium and which other electrolyte are responsible for the resting membrane potential? Bicarbonate Chloride Sodium Magnesium SUBMIT C O NT I NU E Potassium levels above 5mEq/L are referred to as hyperkalaemia. Potassium levels below 3.5mEq/L are referred to as hypokalaemia. Hyperkalaemia It is relatively rare to have high potassium, as the healthy body manages extra potassium very effectively. An increase in extracellular potassium results in both a cellular uptake of potassium, and renal excretion of potassium. As the kidneys continue to clear excess potassium, cellular potassium levels return to normal. Causes of hyperkalaemia include: Excessive intake Decreased renal excretion Potassium shift from intracellular to extracellular fluid due to: Hypoxia Acidosis Burns Crush injury Major surgery Symptoms vary widely and are linked to the severity of hyperkalaemia. Mild cases may experience tingling, restlessness, diarrhoea. Severe cases can experience muscle weakness or paralysis. An increase in extracellular potassium without an increase in intracellular potassium will make the resting charge of the cell less negative. This is known as increased excitability. Cells are more likely to depolarise. This leads to cardiac dysrhythmias and eventually cardiac arrest. ECG changes will therefore be seen at varying levels of hyperkalaemia. Hypokalaemia It is important to note that the extracellular potassium level does not necessary reflect what is happening with the intracellular potassium level. As extracellular potassium is excreted, intracellular potassium will shift to the extracellular fluid. This can result in a normal potassium reading, while there may actually be intracellular hypokalaemia. Causes of hypokalaemia may include: Reduced intake Increased renal excretion Gastrointestinal losses through vomiting or diarrhoea Potassium shift from extracellular fluid to intracellular fluid Respiratory alkalosis Insulin therpay Gastrointestinal and renal losses are the most common causes of loss of potassium stores from the body. Mild hypokalaemia is usually asymptomatic. Severe hypokalaemia (