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GratefulHyperbolic

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University of Arizona

Zoe Cohen

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physiology homeostasis human body medical education

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This document is a part of a foundational course on physiology, covering learning objectives, definitions, and introduction to homeostasis. It contains details about homeostatic processes and the interactions of organs in the human body.

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Class of 2028 WEEK 1 - 3 FOUNDATIONS Approach to the Use of Labs Metabolism disciplines and...

Class of 2028 WEEK 1 - 3 FOUNDATIONS Approach to the Use of Labs Metabolism disciplines and Imaging FUNCTION Pharmacology Immunology Pathological Basis of Clinical Medicine Physiology Introduction to Blood Pharmacokinetics Introduction to Genetics Embryology BLOCK AY 2024-2025 INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS Block: Foundations Block Director: James Proffitt, PhD Session Date: Monday, July 29, 2024 Time: 9:00 – 10:00 am Instructor: Zoe Cohen, PhD Department: Physiology Email: [email protected] INSTRUCTIONAL METHODS Primary Method: IM13: Lecture ☐ Flipped Session ☐ Clinical Correlation Resource Types: RE18: Written or Visual Media (or Digital Equivalent) INSTRUCTIONS Please review learning objectives and the notes before attending this session. READINGS N/A LEARNING OBJECTIVES 1. Define homeostasis. 2. Describe a homeostatic process in the human body. Give specific examples of how all the organs work together. 3. Describe how dysfunction in a single organ can lead to dysfunction of another organ. 4. List the steps associated in the loss of homeostasis in heat stroke. CURRICULAR CONNECTIONS Below are the competencies, educational program objectives (EPOs), disciplines and threads that most accurately describe the connection of this session to the curriculum. Related Related Competency\EPO Disciplines Threads COs LOs CO-01 LO #1 MK-02: The normal structure and Physiology N/A function of the body as a whole and of each of the major organ systems CO-01 LO #2 MK-02: The normal structure and Physiology N/A function of the body as a whole and of each of the major organ systems CO-01 LO #3 MK-05: The altered structure and Physiology N/A function (pathology & pathophysiology) of the body/organs in disease Block: Foundations | COHEN [1 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS Related Related Competency\EPO Disciplines Threads COs LOs CO-01 LO #4 MK-05: The altered structure and Physiology N/A function (pathology & pathophysiology) of the body/organs in disease CONTEXT: This lecture on homeostasis aims to introduce the fundamental concept of functional interaction/interdependence among organ systems in the human body, as well as to illustrate how dysfunction of a single organ may lead to multiple organ dysfunction. In all blocks of the ArizonaMed curriculum, it will be critically important to have this concept in mind as you seek to understand the bases for inter-organ interaction and the consequences of dysfunction in a particular organ or organ system for other organ systems. WHAT IS PHYSIOLOGY?__________________________________ Physiology is the study of normal body function. It might not seem as “sexy” as a ischemic stroke, hypovolemic shock, or Goodpasteur’s disease (things you’ll learn about in your training here at UACOM), but without having a strong base of understanding HOW things should work, it’s much harder to diagnose what the issue is when things don’t work (as well as how to treat it). Because of this, Physiology will appear in every block during the pre-clerkship curriculum. Spend the time now learning how things should work, and disease and treatment become much easier! Block: Foundations | COHEN [2 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS IMPORTANT PHYSIOLOGICAL FUNCTIONS: Feedback Loops: Feedback is defined as the ability of a system to change in a way to maintain homeostasis. Biological systems (including us) operate based on a series of inputs and outputs, each caused by and causing a certain event. Biological systems contain many types of regulatory circuits, both positive and negative. As in other contexts, positive and negative do not imply that the feedback causes good or bad effects. A negative feedback loop is one that tends to slow down a process, whereas the positive feedback loop tends to accelerate it. In a positive feedback mechanism, the output of the system stimulates the system in such a way as to further increase the output. Common terms that could describe positive feedback loops or cycles include “snowballing” and “chain reaction”. Without a counter-balancing or “shut- down” reaction or process, a positive feedback mechanism has the potential to produce a runaway process. The majority of positive feedback loops in healthy individuals have to do with gestation and birth of an infant. Most biological feedback systems are negative feedback systems. Negative feedback occurs when a system’s output acts to reduce or dampen the processes that lead to the output of that system, resulting in less output. In general, negative feedback loops allow systems to self- stabilize. Negative feedback is a vital control mechanism for the body’s homeostasis. Examples are everywhere, including blood pressure regulation, heart rate, temperature control…and many many more. Flow Down Gradients: Flow is the movement of “stuff” from one point in a system to another point in the system. 1. Molecules and ions in solution move from one point to somewhere else. 2. Fluids (blood, lymph) and gases (air) move from one point to another. 3. Heat moves from one place to another. Block: Foundations | COHEN [3 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS Flow occurs because of the existence of a gradient between two points in a system. 1. Differences in concentration (concentration gradients) cause of molecules and ions in solution to move toward a region of lower concentration. 2. Differences in electrical potential (potential gradients) causes ions in solution to move. 3. Differences in pressure (pressure gradients) between two points in a system cause substances to move toward a region of lower pressure. 4. Differences in temperature (temperature gradients) between two points cause heat to flow. The magnitude of the flow is a direct function of the magnitude of the energy gradient that is present – the larger the gradient the greater the flow. More than one gradient may determine the magnitude and direction of the flow. 1. Osmotic (concentration gradient) and hydrostatic pressures together determine flow across capillary walls. 2. Concentration gradients and electrical gradients determine ion flow through channels in cell membranes of neurons and muscle cells. There is resistance or opposition to flow in all systems. 1. Resistance and flow are reciprocally related, the greater the resistance the smaller the flow 2. Resistance is determined by the physical properties of a system 3. Some resistances are variable and can be actively controlled 1. ion channels in a membrane can open and close (increasing resistance) 2. arterioles and bronchioles can constrict and dilate 3. piloerection can increase the resistance to heat flow in many mammals OVERVIEW OF HOMEOSTASIS: The foot bone is connected to the leg bone! ☺ Although this childhood song is anatomically and physiologically lacking, it does have one thing correct…Everything in the body is “connected” to everything else. This idea of connectedness is termed “homeostasis”. The Encyclopedia Britannica (online edition) defines homeostasis as “any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival”. If homeostasis works, life goes on…if it doesn’t, death occurs. Block: Foundations | COHEN [4 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS A good example of homeostasis in medicine is the control of body temperature. In humans, normal body temperatures hover around 37° C (98.6° F). However, various factors such as; exposure to hot or cold, hormonal changes, changes in metabolic rate, or disease states can cause body temperature to increase or decrease. Temperature regulation is controlled by the hypothalamus in the brain. When changes in temperature are sensed, compensatory mechanisms, which include shunting of blood to the skin or core, perspiration, or shivering happen. Control center: thermoregulatory center in brain Receptors: temp Effectors: sweat sensitive cells in glands activated skin and brain Stimulus: Body Temp Rises Stimulus: Body Temp Falls Receptors: temp Effectors: skeletal sensitive cells in muscles skin and brain Control center: thermoregulatory center in brain But what happens when this feedback loop is unsuccessful? In the body, the cardiovascular system supplies oxygen and nutrients to every cell in the body. Without this, the cells become non-functional. If we first look at how certain organs (specifically some of the organs introduced in this block) work together, we can understand the seriousness if homeostasis fails. The cardiovascular system consists of a pump (heart), a series of tubes (vessels) and the delivery substance (blood). The system works because of pressure differences between the left side of the heart and the right side of the heart. If the pump can’t generate pressure, the system is dysfunctional. Likewise, if there is low pressure within the vessels (due to increased diameter) or because there’s a decrease in blood volume, not enough nutrients or gases are making it to our organs. Heat related diseases are something we in Arizona should understand. Heat related issues fall along a continuum from Heat Rash (also known as “prickly heat”, which is caused by blockage of sweat glands) to Heat Cramps (loss of body salts), to Heat Exhaustion (increased body salt and fluid loss, which leads to headache, nausea, dizziness, weakness and irritability) and finally Block: Foundations | COHEN [5 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS ending in Heat Stroke (the most serious form of heat related illness, where the body is no longer able to rid itself of excess heat and core temperature begins to rise, leading to central nervous system dysfunction, coma and possibly death). Let’s look briefly at many of the organs that are introduced in Foundations and how they work together. Skin: The skin has three main functions: protection, regulation and sensation. The skin provides protection from: mechanical impacts and pressure, variations in temperature, micro-organisms, radiation and chemicals. In terms of regulation, skin helps us regulate body temperature and fluid balance. In terms of sensation, the skin contains an extensive network of nerve cells that detect and relay changes in the environment. CV System: Our pump system that allows blood with nutrients to get to all cells within the body. The heart and vessels allow transport of nutrients, oxygen, and hormones to cells throughout the body as well as removal of metabolic wastes (carbon dioxide, nitrogenous wastes). The blood also contains the cells of the Immune System, which defend the body against foreign microbes and toxins, and platelets, which play a role in coagulation. The combination of blood and the vessels it moves through allows the cardiovascular system to play a role in temperature regulation. Respiratory System: The respiratory system is involved in breathing, also called pulmonary ventilation. In pulmonary ventilation, air is inhaled through the nasal and oral cavities (the nose and mouth). It moves through the pharynx, larynx, and trachea into the lungs. Then air is exhaled, flowing back through the same pathway. Changes to the volume and air pressure in the lungs trigger pulmonary ventilation. Inside the lungs, oxygen is exchanged for carbon dioxide waste through the process called external respiration. This respiratory process takes place through hundreds of millions of microscopic sacs called alveoli. Renal System: The function of the kidneys is to remove liquid waste from the blood in the form of urine; keep a stable balance of salts and other substances in the blood; and produce erythropoietin, a hormone that aids the formation of red blood cells. It also senses and plays a role in regulation of blood pressure. Spleen: The spleen plays multiple supporting roles in the body. It acts as a filter for blood as part of the immune system. Old red blood cells are removed from circulation in the spleen, and platelets and white blood cells are stored there. GI Tract: The large, muscular tube that extends from the mouth to the anus, where the movement of muscles, along with the release of hormones and enzymes, allows for the digestion of food. Also called the alimentary canal or digestive tract. __________________________________________________ Case study: A 38 year old male went for a hike up to Finger Rock in the Santa Catalina Mountains on August 5th 2015 (temp 106 F, Humidity 55%). After finishing the hike, he complained of dizziness, finally falling into an “apathic” state. Emergency Medical personnel were called and while being treated, the patient suffered a seizure before falling into a coma. Block: Foundations | COHEN [6 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS What happened? Skin: Liquids help to cool us down by allowing the body to produce sweat. However, liquids are also necessary for bodily functions, such as keeping up blood pressure. You can lose large amounts of body fluid in the form of sweat without noticing any effects, but at a certain point the body will reserve the remaining fluid for vital functions and stop sweating. Sweat evaporates more rapidly in dry weather, cooling the body more efficiently than in humid weather. When working in humid conditions, the core temperature rises more rapidly. This is why weather forecasts add a humidity factor or heat index to represent how you will actually feel outdoors. CV System: In an effort to decrease heat, the vessels (specifically the arterioles) nearest the skin dilate…increasing heat dissipation. When this happens, there is less volume available to meet the needs of other organs. In addition, when sweating, there was a decrease in total blood volume due to fluid loss. The combination of vasodilation and decreased blood volume leads to decreased blood pressure (the driving force of blood though the CV system). The heart must then work harder to try and move blood through the body. However, the heart is also working with reduced delivery of oxygen and nutrients. When this happens, the contractile cells of the myocardium are unable to contract as forcefully, decreasing blood pressure and delivery of blood to all organs. There is also the chance of changes in heart rhythm (arrhythmias), further decreasing blood delivery. Respiratory System: Less blood enters the pulmonary system (both for supplying the structures of the lungs, and for gas transfer). Two things happen…first, the structures aren’t receiving oxygen and nutrients needed to maintain their integrity, which can allow pathogens to enter the blood stream. A person suffering from heat stroke will also increase respiratory rate, which can lead to respiratory alkalosis. Over time, the cells of the respiratory system start to die due to lack of oxygen and nutrients and there’s a switch to a metabolic acidosis Renal System: Renal dysfunction in heat stroke can be caused by direct thermal injury, volume depletion, or muscle cell breakdown (rhabodomyolysis). Dysfunctional kidneys lose the ability to filter substrates, which can lead to fluid retention, increased blood pressure, and changes in mental status. Spleen: If the cells of the spleen aren’t getting oxygen and nutrients, they will be unable to work in the role of a filter (especially a place to remove red cells), and a person can become Block: Foundations | COHEN [7 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS jaundiced (due to increased circulating bilirubin from death of red cells not cleared from the system). The spleen also acts as a secondary lymphoid structure and loss of function can be associated with increased risk of infection. GI tract: Excessive heat exposure reduces intestinal integrity. Heat-stress causes blood to move to the periphery in an attempt to maximize radiant heat dissipation, and this blood redistribution is supported by vasoconstriction of the gastrointestinal tract. As a result, reduced blood and nutrient flow leads to hypoxia at the intestinal epithelium, which ultimately compromises intestinal integrity and function. What didn’t happen that should have? Questions to think about and discuss. 1. What would you predict his blood pressure was when EMTs arrived? What did they do about it? Would they give him fluids? Would they give him O2? 2. What would you guess his vital signs were: respiratory rate? shallow or deep? BP? Heart rate? Cardiac output? Temp—skin? core?? 3. What would have caused this person to have a seizure? 4. How would you counsel this patient/future patients to avoid this situation in the future? Controlled Hypothermia As you can see, the body continuously engages in coordinated physiological processes to maintain a stable temperature. In some cases, however, overriding this system can be useful, or even life-saving. Hypothermia is the clinical term for an abnormally low body temperature (hypo- = “below” or “under”). Controlled hypothermia is clinically induced hypothermia performed in order to reduce the metabolic rate of an organ or of a person’s entire body. Controlled hypothermia often is used, for example, during open-heart surgery because it decreases the metabolic needs of the brain, heart, and other organs, reducing the risk of damage to them. When controlled hypothermia is used clinically, the patient is given medication to prevent shivering. The body is then cooled to 25–32°C (79–89°F). The heart is stopped and an external heart-lung pump maintains circulation to the patient’s body. The heart is cooled further and is maintained at a temperature below 15°C (60°F) for the duration of the surgery. This very cold temperature helps the heart muscle to tolerate its lack of blood supply during the surgery. Some emergency department physicians use controlled hypothermia to reduce damage to the heart in patients who have suffered a cardiac arrest. In the emergency department, the physician induces coma and lowers the patient’s body temperature to approximately 91 degrees. This condition, which is maintained for 24 hours, slows the patient’s metabolic rate. Because the patient’s organs require less blood to function, the heart’s workload is reduced. Block: Foundations | COHEN [8 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS This section is just FOR YOU!! I’ve been chatting with pre-med and medical students for years, and one area that has come up over and over is that there is a “new language” that needs to be learned. That’s true…luckily, much of that language is Latin! Here is a chart with some common Latin terms that will hopefully help! **This is NOT a definitive list…but a good place to start! Word Part Meaning Examples Meaning of example a-, an, non Without, Not Apnea, Anuria Not breathing, Without urine Ab-, ef- Away Abductor muscle, Muscle pulling away Efferent neuron from midline, carrying info away from brain Ad-, af- Toward Afferent neuron, Carrying info toward Adductor muscle brain, muscle pulling toward midline -alg Pain Neuralgia, fibromyalgia Nerve pain, muscle pain Ang(i)-, vaso Vessel Angiogenesis, Making new blood vasodilator vessel, increase radius of vessel Ante-, pre-, pro- Before Prenatal, antebrachial, Before birth, before the promonocyte upper arm, before the monocyte is mature Anti-, contra- Against, resisting Antibody, Resisting a foreign contraindicated body, against using Arthr(o), artic- Joint Arthritis, articulation Joint inflammation, joint -ase Enzyme Maltase, lipase Enzyme breaking down maltose, enzyme breaking down fats Aut(o)- Self Autoimmunity Self-immunity Bi-, di-, diplo- Two Bicuspid valve Heart valve with 2 leaflets Brady- Slow Bradycardia Slow heart rate Cephal-, -ceps Head Hydrocephalus, biceps Water in brain (in the fermoris head), 2-headed muscle by femur -cide Kill Spermicide Sperm killer Circ-, peri- Around Circumcision, Cut around (i.e. male periodontal foreskin), around the teeth -clast Break, destroy Osteoclast Cells that destroy bone cells -crine Secrete, release Endocrine gland Glands that secrete hormones Cyan- Blue Cyanosis Bluish tint to skin Dia-, per-, trans- Through, separate, Diarrhea, permeable, Flow though across transcutaneous (intestines), across a membrane, across skin Dys-, mal- Bad, painful, difficult Dyspnea, malnutrition Difficulty breathing, bad nutrition/diet Ectop- Displaced Ectopic pregnancy Displaces pregnancy -emia Blood Hyperglycemia High blood sugar En-, endo-, intra- Inside, within Endosteum, intraocular Space inside bone, inside the orbit of the eye Epi- Upon, over, above Epidermis Layer of skin over the dermis Block: Foundations | COHEN [9 of 10] INTRODUCTION TO PHYSIOLOGY: HOMEOSTASIS Equi- homo-, iso- Same, equal, balanced Homeostasis, isotonic Constant balance of body systems, equal solute Ex-, ecto- Outside Extracellular fluid Solute/fluid located outside cell -gram Something written Electrocardiogram Print out of electrical (ECG) activity of the heart -graph Writing apparatus Electrocardiograph Machine used to make an ECG Hem- Blood Hemothorax Blood that has leaked into chest cavity Hemi-, semi- Half Cerebral hemisphere One half of the brain Hist- Tissue Histology Study of tissues Hypo-, infra-, infer-, Under, below, less Hypotonic, Lesser solute sub- submandibular concentration, under the jaw -itis Inflammation Appendicitis Inflammation of the appendix Inter- Between Interstitial fluid Fluid between cells Lys, lyze Break apart, dissolve Hydrolysis, lysosome Breaking down, organelle that digests Med-, meso-, meta- Middle Mediastinum Middle space of chest cavity Micro-, -ole, -ule Small Microscope, arteriole, Apparatus to view small venule objects, small artery, small vein Mono-, Uni- One Monozygotic, unicellular Twins from same zygote (identical), 1- celled organism Morph, -plasty Shape Morphology, rhinoplasty Distinguishing by shape, nose shaping Mort, necro- Death Post mortem, necrotic After death, dead tissue tissue Neo- New Neonatal Newborn Olig- Little, few Oliguria Very little urine produced Ost- Bone Osteoblast, Maker of new bone osteomyelitis cells, bone infection -ostomy Make an opening Tracheostomy Make an opening in the trachea Para Beside Parathyroid glands Small glands embedded into the sides of the thyroid gland Path Disease Pathogenic bacteria Disease causing bacteria Phago Eat, feed Phagocyte Eating cell -phasia Speech Dysphagia Difficulty speaking Phobia, phobe Fear Hydrophobia Fear of water -plasia Growth, formation Hyperplasia Excessive growth Post After Post natal After birth Pseudo False Pseudounipolar neuron Neuron common in the eye Super, supra Above, over Superior vena cava, Veins bringing blood supraorbital from above the heart, over the eye Tachy Fast Tachycardia Faster than normal heart rate Block: Foundations | COHEN [10 of 10] INTRODUCTION TO ANATOMY Block: Foundations Block Director: James Proffitt, PhD Session Date: Monday, July 29, 2024 Time: 10:00 am - 11:00 am Instructor: James Proffitt, PhD Department: Cellular & Molecular Medicine Email: [email protected] INSTRUCTIONAL METHODS Primary Method: IM13: Lecture ☐ Flipped Session ☐ Clinical Correlation Resource Types: RE18: Written or Visual Media (or Digital Equivalent) INSTRUCTIONS Please read lecture objectives and notes prior to attending session. READINGS Read lecture notes prior to session. LEARNING OBJECTIVES 1. Describe and demonstrate standard anatomical position 2. Describe the planes of anatomical section 3. Apply the planes of anatomical section to medical imaging 4. Apply the following terms to describe the position of anatomical structures: anterior/posterior, rostral/caudal, superior/inferior, medial/lateral, proximal/distal, dorsum/palmar/plantar, deep/superficial/intermediate, external/internal, unilateral/bilateral, contralateral/ipsilateral. 5. Describe the contents of a nerve, including afferent and efferent components 6. Explain the clinical relevance of spinal cord segments, cranial nerves, dermatome, myotome, peripheral nerve territories, and referred pain. 7. Compare and contrast the function and distribution of the central nervous system, somatic peripheral nervous system, visceral peripheral nervous system 8. Describe the structural, functional, and organizational differences between arteries and veins, including route of bloodflow 9. Explain the clinical relevance of anastomosis, collateral circulation, venous drainage, and lymphatic drainage 10. Apply the concepts of deep and superficial to explain fascial layers and structural layers 11. Compare and contrast the structure of a cavity, a bursa, and a potential space 12. Describe how relationships between organ systems can be used to organize knowledge in a somatic example (muscular compartment) and a visceral example (small intestine). 13. Explain the clinical relevance of anatomical variation Block: Foundations | PROFFITT [1 of 27] INTRODUCTION TO ANATOMY CURRICULAR CONNECTIONS Below are the competencies, educational program objectives (EPOs), course objectives, session learning objectives, disciplines and threads that most accurately describe the connection of this session to the curriculum. Related Related Competency\EPO Disciplines Threads COs LOs CO-01 LO-01 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-02 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-03 MK-02: The normal Gross anatomy EBM: Diagnostic structure and function of Imaging/Radiology the body as a whole and of each of the major organ systems CO-02 LO-04 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-02 LO-05 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-06 MK-05: The altered Gross anatomy N/A structure and function (pathology & pathophysiology) of the body/organs in disease CO-02 LO-07 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-08 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-09 MK-05: The altered Gross anatomy N/A structure and function (pathology & pathophysiology) of the body/organs in disease CO-01 LO-10 MK-02: The normal Gross anatomy N/A structure and function of Block: Foundations | PROFFITT [2 of 27] INTRODUCTION TO ANATOMY Related Related Competency\EPO Disciplines Threads COs LOs the body as a whole and of each of the major organ systems CO-01 LO-11 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-12 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems CO-01 LO-13 MK-02: The normal Gross anatomy N/A structure and function of the body as a whole and of each of the major organ systems NOTES INTRO All of my lecture notes will contain: (1) a Key Terms list (bolded in the written lecture notes) that focuses on the most important basic vocabulary you will need to understand apply the concepts learned in this lesson (2) a curated list of helpful online resources (3) written lecture notes explaining the major concepts. Focus on applying your knowledge to clinical scenarios presented in lesson materials, AMBOSS, your USMLE practice books, or develop some on your own with friends with tools like UWorld, Sketchy, Boards and Beyond, or Anki. Additional citations are included at the end of the notes when needed. Key Terms: Directional Terms, Anatomical Planes, and Organizational Concepts Standard Anatomical Position Sagittal Median Parasagittal Transverse Frontal Anterior Posterior Rostral Caudal Superior Inferior Lateral Medial Proximal Distal Dorsum Palmar Plantar Block: Foundations | PROFFITT [3 of 27] INTRODUCTION TO ANATOMY Superficial Deep Intermediate External Internal Dermatome Myotome Referred Pain Anastamosis Collateral Circulation Venous Drainage Lymphatic Drainage Myofascial compartment Anatomical Structures Afferent (Sensory) Fiber Efferent (Motor) fiber Cranial Nerve Spinal Nerve Somatic peripheral nervous system Visceral peripheral nervous system Artery Vein Venous plexus Lymph Node Lymphatic Duct Fascial layer Structural layer Small intestine Offline & Online Resources Textbooks No textbook is required, but we recommend a copy of Moore’s Essential Clinical Anatomy. You may want to look into several decent books that you can get used for cheap (some of these, such as Netter's or Moore's textbooks, are easier to find cheap copies of through booksellers). You can also fine online textbooks through the UA Health Sciences Library (see below). It is up to you what resources you use for everyday class activities outside of the notes and slides, but we do provide a copy of Grant’s Dissector in Lab Netter Atlas of Human Anatomy Moore's Clinical Anatomy Thieme Atlas of Anatomy McMinn & Abraham's Clinical Atlas of Human Anatomy A great dissection book that could be a guide for your own dissections is Grants Dissector. Grant's Dissector copies are included with each table in the laboratory. Block: Foundations | PROFFITT [4 of 27] INTRODUCTION TO ANATOMY School-owned Resources You will have access to Acland's Video Atlas of Human Anatomy through UA Libraries. This atlas contains videos of real human tissue preparations that will compliment your dissections. To access the Acland's Atlas visit https://libguides.library.arizona.edu/acland and log in with your UA credentials. Health Science Library Databases and online textbooks: http://ahsl.arizona.edu/top- resources Free Online Resources: University of Michigan's BlueLink website has a wide variety of free resources based on real cadaver dissections, including Youtube videos, instructional dissection videos, self-quizzes, and a picture atlas. Access all BlueLink resources here: https://sites.google.com/a/umich.edu/bluelink/curricula For quick information and quizzes, Teach Me Anatomy is helpful and has a website and free phone app: https://teachmeanatomy.info/ If you are interested in Radiology and its relationship to anatomy, check out Radiopaedia: https://radiopaedia.org/?lang=us Cross sections of a real human body are available to view at the Visible Human Project: https://www.nlm.nih.gov/research/visible/visible_human.html UBC Medicine's Neuroanatomy playlists: https://www.youtube.com/channel/UCE4a1o3GMKCRSgHflXqZs8Q/playlists The Noted Anatomist: https://www.youtube.com/channel/UCe9lb3da4XAnN7v3ciTyquQ If you want to know about anatomical variations, visit this site: https://www.anatomyatlases.org/AnatomicVariants/AnatomyHP.shtml Paid Online Resources & Apps: A popular mobile app for learning anatomy is Visible Body. The apps are not free, but you can keep them forever: https://www.visiblebody.com/en-us/ An additional, very detailed app is Complete Anatomy. This is a subscription-based app but has a lot of information: https://3d4medical.com/ If you have access to VR equipment for gaming or other activities apps such as 3D Organon https://www.3dorganon.com/ can be installed for Oculus and other VR headsets. LO 1 Whenever we use directional terms in anatomy, we imagine our patient to be in standard anatomical position (Fig. 1). This is a pose where the patient is: standing up, looking forward, arms down to the side, palms facing forward, legs parallel, toes facing forward. No matter the position of your patient or donor body in lab, always use directional terms as if the patient is in standard anatomical position. This is to ensure consistent use of directional terminology, even though parts of our body are mobile. LO 2 The body can be divided into parts based on three imaginary planes that intersect the body (Fig. 1). These are the sagittal, transverse (aka axial), and frontal (aka coronal) planes. Block: Foundations | PROFFITT [5 of 27] INTRODUCTION TO ANATOMY Figure 1: Demonstration of the anatomical planes of section in standard anatomical position. Sagittal & Median Planes (A); Frontal Plane (B); Transverse Plane (C). Moore et al., 2015 The sagittal plane divides the body into right and left halves. One individual cut along the sagittal plane that divides the body directly down the middle is known as the median plane. All other sagittal plane cuts on either side of the median plane can be called parasagittal. The transverse plane divides the body into top and bottom halves. The frontal plane divides the body into front and back halves. LO 3 For most clinical disciplines, anatomy outside of surface anatomy will be visualized through the use of medical imaging techniques such as X-Ray radiography, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound. Each of these techniques will take 3D anatomy and visualize it in 2D, which means that many of you will spend a lot of time extrapolating what is happening to your patient in 3D from 2D images (Fig. 2). This is one reason why it is critical to take advantage of the opportunity to work with our donor bodies, as well as practice interpolating between imaging to 3D anatomy and back. Block: Foundations | PROFFITT [6 of 27] INTRODUCTION TO ANATOMY Figure 2: Visualization of CT image of the abdomen in transverse plane. Note that the image is in inferior view (i.e., looking up toward the head). This is the primary view in transverse sections in radiology, though in neurology brain scans are typically viewed from superior view (i.e. looking at the top of the head down toward the feet). Moore et al., 2015. Because CT and MRI collect information in 3D that is then displayed in 2D slices, anatomy can be viewed in any of the 3 anatomical sections (Fig. 3). These data can then be used by image processing software to render 3D models of anatomical structures and pathologies. Figure 3: CT image slices showing planes of section through a skull. Transverse (A); Frontal (B); Midsagittal/median (C). Angelopoulos, 2008. Dental Clinics of North America Block: Foundations | PROFFITT [7 of 27] INTRODUCTION TO ANATOMY Ultrasound also renders 3D anatomy as 2D slices, although the images are based on interface differences that reflect sound waves rather than material density. Ultrasound images are typically displayed in transverse or sagittal plane, but can image in any true plane or oblique plane based on the position of the transponder (Fig. 4). Figure 4: Schematic of ultrasound transponder placement (blue box) for a nerve block in the neck. The cross section shows a schematic of the transverse anatomical plane of the neck. LO 4 Comparative anatomical relationships are described using an array of paired terms, some of which reference planes of section (Fig. 5). Each of these terms are relative, and depend on the comparisons being offered (e.g., the heart is superior to the stomach, the stomach is inferior to the heart). Anterior (ventral), refers to structures nearer to the front of the body, posterior (dorsal) refers to structures nearer the back (e.g., the sternum is anterior to the esophagus, the vertebrae are posterior to the heart). Within the head (especially the brain), we use rostral to describe structures closer to the nose, caudal to refer to structures closer to the back of the head. Superior (cranial) refers to structures closer to the head, inferior (caudal) refers to structures closer to the foot. Medial refers to structures closer to the median plane, lateral refers to structures farther away from the median plane. Terms can be combined to increase specificity. For example, superomedial means closer to the head and nearer to the midline, whereas inferolateral means closer to the feet and father from the midline. Each of these terms can also be used to refer to parts of individual structures (e.g., Block: Foundations | PROFFITT [8 of 27] INTRODUCTION TO ANATOMY the posterior side of the heart, the medial side of the left lung, the distal end of the quadriceps, the proximal end of the triceps brachii). Within a limb we have terms that indicate proximity to the attachment of the limb to the trunk when comparing structures. Proximal means closer to the attachment to the trunk (e.g., the knee is proximal to the ankle), and distal means farther from the attachment to the trunk (e.g., the elbow is distal to the shoulder). These terms also apply to the position in a feature along a linear structure as a function of distance from its origin (e.g., distal in an artery is further along its length and proximal is closer to its origin). Dorsum refers to superior aspect of structures that protrude from the body, such as tongue or nose. The foot and hand also have a dorsum (superior surface of foot; posterior surface of hand). The hand also has a palmar surface (palm), and the foot has a plantar surface (sole). Figure 5: Demonstration of directional anatomical terms. Moore et al., 2015 Anatomical structures are also positioned in layers, such that some structures are closer to the exterior surface and others are further into the tissue. We use terms such as superficial, intermediate, and deep to refer to proximity to the surface of the body. Superficial means Block: Foundations | PROFFITT [9 of 27] INTRODUCTION TO ANATOMY closest to the surface (i.e., skin), deep means closest to the core of the body or limb, and intermediate means in between these layers. Within a single organ, external means farther from the core of the structure, whereas internal means closer to the core of the structure. Many anatomical structures are paired, possessing left and right members. Structures that are paired in this fashion are called bilateral. Structures from only one side are unilateral. Midline structures lack laterality. We also have terms for whether structures occur on the same side: ipsilateral; or opposite side: contralateral. LO 5 The body is composed of multiple anatomical systems that are organized by both structure and function. Each of these systems is composed of distinct combinations of cell and tissue types which determine their structural properties, and therefore their function. In turn, these systems have a gross structure that determines now they work at the macro-scale and therefore how they can become dysfunctional clinically. You will focus on the micro-scale of these systems in your histology, pathology, and physiology work; we will focus on the macro-scale. Note that many of these systems have some degree of overlap due to multiple functions (e.g., some organs have dual functions such as digestive and endocrine). In this session, rather than going over every system in detail, we are going to work on some foundational principles and organizational features that will help you arrange your knowledge going forward. One of the most important of these involves understanding nerves, because nerves are the control system of the body. Your patients will report pain, numbness, weakness, and other disfunctions that are either due to disfunction of the nerves themselves, or something the nerve is detecting. Therefore, it’s critical that we start with innervation. Nerves are bundles of axons, cells of the nervous system, wrapped in myelin and supportive glial cells (Fig. 6). These axons are arranged in sequential bundles all wrapped in connective tissue, forming a nerve. Axons are cells that can either deliver a signal from the brain or spinal cord to a target structure (motor) or receive sensory input from a target structure like pain, pressure, temperature and deliver it to the brain or spinal cord (sensory). Therefore, most nerves (excepting some from the brain) are both motor and sensory, though some terminal branches of nerves might have primarily sensory components. The details of nerve anatomy will be further explored in histology, but for now I want you to understand two things: (1) nerves contain both sensory and motor axons together; (2) nerves are often associated with blood vessels in wrappings of fascia/fat known as neurovascular bundles. In the lab, nerves appear light in color and are noncollapsible (unlike blood vessels that have a Block: Foundations | PROFFITT [10 of 27] INTRODUCTION TO ANATOMY Figure 6: Summary of the structure of a nerve. Note the myelin from the supporting cells and multiple layers of connective tissue surrounding the axons. Axons within these nerves will be motor and sensory! Moore et al., 2015 lumen). They often feel firm due to their wrappings of perineurium and epineurium; I often liken them to a partially cooked flat or football-shaped pasta noodle. LO 6 The nervous system (Fig. 7) is the control center of the body, controlling and regulating both conscious (such as motion and conscious sensations) and unconscious (such as homeostasis or organ function) processes. The nervous system consists of a central portion that includes the brain and spinal cord, which relays with the peripheral portion formed by nerves (cranial nerves from brain, spinal nerves from the spinal cord). Each of these systems is ultimately made up of neuron fibers that either send out information to the periphery to initiate or augment a function, or bring information back to the central nervous system that relays inputs about the environment or condition of the body. Block: Foundations | PROFFITT [11 of 27] INTRODUCTION TO ANATOMY Figure 7: Summary of the nervous system. Note the number of spinal nerves and cranial nerves Moore et al., 2015 Some of the most critical issues faced by patients are nervous system disorders. Helpfully for you clinicians-in-progress, nerves are not arranged randomly. They have a specific layout that allows you to localize where problems might occur based on the location and type of symptoms reported and signs observed. Furthermore, the arrangement of the nervous system forms an excellent structural framework for learning anatomy because nervous supply is segmental, lending itself to chunks of information for studying. Block: Foundations | PROFFITT [12 of 27] INTRODUCTION TO ANATOMY Figure 8: Summary of spinal nerves. Note that spinal nerves (containing motor and sensory fibers) can recombine to form a plexus, or interconnected network, of nerves. Do not learn the individual nerves now. This leads to functional redundancy; a single spinal nerve lesion usually cannot totally disrupt total motor function, though it can lead to symptoms such as pain, localized numbness and some weakness. Moore et al., 2015 Cranial nerves, of which there are 12 pairs, will be studied in-depth in the neuro block. For now, I want you to recognize that there are 12 pairs of cranial nerves with specific functions that can be motor, sensory, or both and that cranial nerves are the primary peripheral nerves of the head. Spinal nerves, on the other hand, are always both motor and sensory; there are 31 pairs of spinal nerves. Each spinal nerve contributes to a segment of sensory innervation to skin and a particular array of muscles. Furthermore, spinal nerves contribute to segmental innervation of the organs of the body; this arrangement is a helpful tool for localizing problems because of their segmental and location-specific nature. The specifics of spinal nerve anatomy will be studied in greater detail in MSS and Neuro blocks, but I want to establish some key principles now. The first is that spinal nerves exit at levels that we number according to association with vertebrae; in the cervical region spinal nerves exit above the vertebrae, in the thoracic, lumbar, and sacral/coccygeal levels they exit below. A mnemonic to remember the numbers is: eat breakfast at 8 (cervical); eat lunch at 12 (thoracic); go home at 5 (lumbar) eat dinner at 6 (sacral + coccygeal). Block: Foundations | PROFFITT [13 of 27] INTRODUCTION TO ANATOMY As spinal nerves exit (Fig. 8) they can recombine together to form interconnected nerve networks called plexuses. This means that many peripheral nerves are actually composed of neurons from multiple spinal nerves. This enables a degree of functional redundancy; if a single spinal nerve is damaged the structures innervated by that spinal nerve can have some function through the action of other spinal nerves, though your patients will have noticeable symptoms regardless. Figure 9: Schematic of the dermatome and myotome. Note that these are innervated by spinal nerves that are both sensory and motor. For nerves to muscles, motor fibers activate the muscle and sensory fibers detect pain+proprioception; for the skin sensory fibers detect stimuli and motor fibers for glands and smooth muscle. Moore et al., 2015 The reason your patient will still experience functional deficits is because each spinal nerve has what is called a myotome and a dermatome (Fig. 9), which is due to an association between nerves, skin, and muscles formed early in embryonic development. The myotome consists of all muscles innvervated by that spinal nerve level on that side. The dermatome consists of all skin innervated by that spinal nerve on that side. Both collections of axons contain motor and sensory fibers, but clinically we often focus on one or the other because damage to the neurons of the myotome can inflict muscle disfunction (typically weakness) and damage to the neurons of the dermatome can inflict paresthesia (numbness + tingling/shooting pain). It is often trickly to use myotomes clinically because a patient might be resistant to moving and because individual muscles are often part of multiple myotomes, though it is possible and we will expand on that in MSS (reflex arcs can also be used and you’ll explore that in neuro). Dermatomes and sensory innervation is particularly useful because you can check sensation more easily; you’ll hear this a lot in future lectures. It should be noted as in all things anatomical, there can be substantial variation in dermatomes and myotomes between individuals, depending on region. Dermatomes (Fig. 10) in particular are helpful because there are easy external landmarks for them such as the thumb for C6, nipple for T4, umbilicus for T10, and big toe/dorsomedial foot for L5. Therefore, any issue affecting the spinal nerve (or peripheral nerve from that level) can be localized using dermatomes. In reality dermatomes are not cleanly demarcated but fuzzy gradients due to fiber overlap. Block: Foundations | PROFFITT [14 of 27] INTRODUCTION TO ANATOMY Figure 10: Hypothesized dermatome map based on studies of spinal nerve lesions. Note that in reality these dermatomes have substantial overlap and have varying levels of reliability. Use anatomical landmarks to find territories dominated by particular dermatomes such as the thumb for C6, the nipple for T4, and the umbilicus for T10 Moore et al., 2015 When learning dermatomes and the nerves that supply these regions, it should be noted that dermatomes do not directly match peripheral nerve territories (Fig. 11). This is because a single dermatome can be found across multiple peripheral nerves (due to plexus and branching of spinal nerves into different terminal branches). Therefore, you will learn basic dermatomes as well as key landmarks for specific peripheral nerves. Specific injury patterns can damage certain peripheral nerves more than others due to position, such as vulnerability of the ulnar nerve to elbow fracture. In such a case, you would observe numbness in the sensory region of the ulnar nerve (medial hand), which corresponds to the C8 dermatome since the C8 spinal nerve contributes to the ulnar nerve. Block: Foundations | PROFFITT [15 of 27] INTRODUCTION TO ANATOMY Figure 11: Example of how peripheral nerve territories differ from dermatome maps. Note that the C6 dermatome contains sensory fibers from the median nerve, radial nerve, and lateral cutaneous nerve of the forearm. This is because the C6 spinal nerve branches to contribute to multiple peripheral nerves in the brachial plexus. Moore et al., 2015 Lastly, I will note that spinal nerve segmentation applies to supply to internal structures as well. This innervation pattern is complicated and will be explored in later blocks, though we will discuss some basic principles below. For now, I want you to understand that nerve supply to organs is also segmental, and this means that if organs are impacted by a problem your patient may experience pain that can be vaguely referred to a particular area of the body wall (Fig. 12). This phenomenon, referred pain, is due to cross-talk between sensory neurons from organs and sensory neurons from the external body. A general pattern you may observe is that structures that are lower in the body, such as the colon, refer pain more inferiorly than more superior structures such as the heart and the gallbladder. This is a handy tool in your diagnostic toolkit when working with your patient. We will discuss this division in innervation between the body wall and the organs below. Figure 12: Referred pain map. For now, just note general patterns in segmentation (more superior structures refer pain more superiorly). Moore et al., 2015 LO 7 The nervous system is complicated (Fig. 13), but a few key distinctions should be introduced now to help you understand its function (as well as some clinical features such as where we feel pain from organs). The first of these is that the central nervous system (brain and spinal cord-CNS) is housed within the skull and vertebral column, and sends out processes (nerves) to the periphery. The central Block: Foundations | PROFFITT [16 of 27] INTRODUCTION TO ANATOMY nervous system consists of multiple tracts of neurons that deliver and process information to (e.g. motor controls) and from (e.g. sensation) the periphery. Nerves in the periphery are collectively referred to as the peripheral nervous system (PNS). These nerves consist of afferent fibers (bringing information into the CNS) and efferent fibers (sending information out of the CNS). These nerves can either innervate muscles, bones, and the body wall (somatic PNS) or visceral structures such as organs (visceral PNS). Figure 13: Summary of the somatic and visceral peripheral nervous system, showing connection to the brain. Moore et al., 2015 The types of information carried, as well as whether we are conscious of it or not, is determined by this division between somatic and visceral divisions: Somatic o Motor innervation (efferent) = conscious and/or reflexive control of muscle o Sensory innervation (afferent) = sensation such as pain, touch, proprioception. This type of information is conscious and localized Visceral o Motor innervation (efferent) = the two autonomic systems that interact to govern homeostasis Block: Foundations | PROFFITT [17 of 27] INTRODUCTION TO ANATOMY ▪ Parasympathetic (rest + digest) = derived from cranial nerves and spinal nerves in lower back (sacrum), promotes response such as vasodilation in gut, lower heart rate, etc. ▪ Sympathetic (fight or flight) = derived from spinal nerves in the thorax and lumbar areas of the back, promotes response such as vasoconstriction in gut, sweating, etc. o Sensory innervation (afferent) = sensation that is unconscious for control of autonomic reflexes, OR noxious stimuli (e.g. ischemia) that can be experienced as pain (often diffuse-compare a stomach ache to stubbing your toe). Pain location can often tell you what organ is affected. In organs above the pelvis, pain fibers travel along the same pathway as sympathetics. LO 8 Figure 14: Summary of the circulatory system including systemic (A) and pulmonary (B) circulations. (C) displays a more complete summary, including odd arrangements that allow for filtration such as in the kidney and liver. In the liver we have a portal system, where veins subdivide into capillaries for a functional purpose prior to reforming into large veins once again. The main portal system in humans is within the abdomen and liver; smaller portal systems exist to facilitate hormone transport. Moore et al., 2015 Block: Foundations | PROFFITT [18 of 27] INTRODUCTION TO ANATOMY The circulatory system delivers blood to different regions of the body to facilitate gas and nutrient exchange, as well as provide a pathway for immune molecules (Fig. 14). The circulatory system is divided into two circulations: a pulmonary circulation between the heart and lungs, and a systemic circulation between the heart and the rest of the body. These two circulations enable efficient gas exchange and nutrient delivery, allowing us to maintain a high level of metabolic activity. The circulatory system contains three types of vessels; arteries, capillaries, and veins. In gross anatomy, we will primarily focus on arteries and veins (Fig. 15). Structurally, arteries are built to maintain high pressure and deliver blood away from the heart, including relatively thick smooth muscle and elastic fibers. This arrangement gives arteries a bulbous appearance and a “springy” feeling in lab; they typically appear more robust than veins. Veins are built to facilitate draining blood and delivery back to the heart under low pressure following the recombination of capillaries, typically including valves, superficial and deep collateral flow to allow muscles to assist in blood return, and rarely have thick smooth muscle except in larger vessels. In lab, this means that veins will often appear depressed or floppy, and will often be dark colored due to clotted blood following embalming. A helpful mnemonic to remember the function of each vessel: arteries away; veins drain. This Figure 15: Structural differences between veins and arteries. Note the thickness of the arteries in particular; this difference will be obvious in lab. Moore et al., 2015 is true irrespective of the oxygen content of the blood (in systemic arteries carry O2 rich, CO2 poor blood, in pulmonary O2 poor, CO2 rich blood). Block: Foundations | PROFFITT [19 of 27] INTRODUCTION TO ANATOMY Blood vessels usually exist in parallel (Fig. 16), with arteries paralleled by veins (the technical term for this is accompanying veins or venae comitantes). Veins and arteries typically share a fascial sheath that encloses them in wrapping; nerves can very commonly be associated with Figure 15: Schematic showing how veins accompany arteries in fascial sheaths. Note that in this case the accompanying vein forms a plexus around the artery, rather than a single trunk. Moore et al., 2015 these vascular bundles protected by fascia and fat, forming neurovascular bundles. As one moves from the largest veins (e.g., superior/inferior vena cava; iliac veins, femoral/popliteal veins, subclavian and axillary veins) to smaller veins, it is common for veins to form an interconnected network that surround the arteries called a venous plexus. LO 9 Blood supply and drainage follows several functional arrangements that are clinically useful. The first of these is that arteries and veins form interconnections known as anastomoses (singular, anastomosis). These are particularly prevalent in areas of high mobility or functional importance where blood vessels can become constricted or where prevention of blockage or enhancement of bloodflow is critical (e.g., brain, gut, nose, shoulder, elbow, knee, hand, foot). These anastomoses provide enhanced bloodflow or detours around blockages, ensuring critical bloodflow is maintained. Anastamosis is particularly critical in clinical settings because it can be used to ensure bloodflow when an artery must be subjected to a clinical intervention. For example, surgical procedures Figure 16: Schematic of anastomosis surrounding the shoulder blade. Note that the interconnections provide detours for bloodflow in case one vessel is compressed. Moore et al., 2015 Block: Foundations | PROFFITT [20 of 27] INTRODUCTION TO ANATOMY that require clamping of the axillary artery can still maintain bloodflow to the distal upper limb because of the anastamotic network of vessels surrounding the shoulder blade (Fig. 17). Sometimes, small anastomoses between vessels can become pathologically and dangerously enlarged due to diseases affecting bloodflow, especially in the venous drainage. Figure 17: Summary figure of lymphatic drainage in the body at a gross level (A), and micro level from capillary to afferent vessel, to node, to efferent vessel, to node/duct (B). Note that lymphatic drainage often roughly parallels venous drainage. Moore et al., 2015 Another key concept is understanding the patterns of venous drainage, both in terms of overall territories drained as well as superficial vs. deep drainage patterns (Fig. 18). Veins typically drain vascular territories through deep veins that are assisted by muscular contraction, and superficial veins that act as key drainage routes that are interconnected with deep vessels through smaller communicating veins. Venous access to the circulatory system can occur via superficial veins (e.g., great saphenous vein) or through deep veins that are more superficial or accessible, visualized with ultrasound. Furthermore, maintenance of healthy veins and flow between superficial and deep vessels is critical to bloodflow and avoiding clotting or venous disorders. Lastly, venous drainage patterns can affect the transport of infection, cancer, and drugs. Lymphatics will not often be visualizable in gross lab, but it is key to understand the lymphoid system (Fig. 18). For now, I want you to understand why we care about lymphatics: lymphatics reabsorb much of the extracellular fluid and material not reabsorbed by capillaries, preventing edema (swelling due to excess fluid). Furthermore, the lymphatic system is a key component of the immune system protecting us against pathogens in the drained fluid. and also absorbs dietary fat. Because of its critical function as fluid transport, infection and cancer can travel Block: Foundations | PROFFITT [21 of 27] INTRODUCTION TO ANATOMY along lymphatic drainage routes much as they can with veins. Therefore, in anatomy it is critical to have a general appreciation for general patterns of lymphatic drainage. A particularly relevant example is the spread of prostate or cervical cancer via venous systems to the vertebral column, or the spread of breast cancer to axillary lymph nodes and ultimately the venous system. LO 10 Fascia is connective tissue underneath the skin that protects and supports muscles and organs. Between the skin and the deeper structures (muscle, viscera, bone) there are two main layers of fascia: superficial fascia (including fat and loose connective tissue), and deep fascia, which is devoid of fat and is typically composed of tendinous dense regular connective tissue (Fig. 19). The deep fascia directly overlies muscles and can vary widely in thickness, from very thick and stout (over muscles of abdomen and limbs) to nearly obsolete (over the facial muscles). There are other fascial layers that you will observe in cases where extra strength is needed, such as the abdominal wall (these layers can derive muscle tendons). You will also observe fascial coverings of organs deep to the body wall and bones to protect and lubricate organs. These coverings typically have specific names depending on the organ they cover (e.g., pericardium, pleura, meninges, see Concept LO 8 below). Layers between fascial planes can be separated and used to access structures for clinical procedures. These layers are not easily appreciated on embalmed donor bodies. Figure 19: Example of fascial layers from the abdominal cavity. Note that in this case there are multiple layers of deep fascia (not always true, see the muscular compartment example below). Moore et al., 2015 LO 11 Deep to the body wall are true 3D spaces that contain organs and other visceral structures (Fig. 20). These spaces protect, lubricate, and assist in the function of viscera. For example, the thoracic cavity protects the lungs, but also changes shape with the action of muscles to drive respiration. Voluntarily increasing pressure within the abdominal cavity is essential to assisting the abdominal and pelvic organs in actions such as eliminating waste and giving birth. Block: Foundations | PROFFITT [22 of 27] INTRODUCTION TO ANATOMY Figure 20: Illustration of the three major compartments of the trunk. Cavities are separated via muscles (e.g., diaphragm at inferior ribcage) or fascia (e.g., inferior border of peritoneal sac near pelvic inlet). Moore et al., 2015 The primary cavities of the body are the thoracic cavity, abdominal cavity, and pelvic cavity. The cranial cavity within the skull is another. Each of these cavities has bony and (in most cases) muscular components forming a wall. Within that wall, there are additional fascial coverings (bursae, meninges) that shield the organs within. Clinical Correlations: Fluid Buildup in Anatomical Spaces Anatomical spaces can act as reservoirs for pathological fluid buildup. Fluid build up can interfere with normal organ function (such as air buildup in the thoracic cavity in the case of pneumothorax) or determine routes of infection (drainage of pus into the space between the rectum and uterus due to gravity). Spaces can also be used for clinical purposes, such as pumping fluid into the abdomen to remove waste products through diffusion with peritoneal dialysis. Synovial bursae are closed sacs of connective tissue that contain lubricating serous fluid (Fig. 21). They are found in areas subject to friction. Bursae are found covering tendons and within joints, facilitating joint and tendon movement. Bursae are also found covering organs such as the heart, lungs, and abdominal viscera. The layer of the bursae that touches the body wall is referred to as the parietal layer, whereas the layer that touches the organ itself is known as the visceral layer. Block: Foundations | PROFFITT [23 of 27] INTRODUCTION TO ANATOMY Figure 21: Illustration of bursae surrounding a tendon (A) and an analogy for the anatomy of bursae surrounding organs (bursa is the balloon, organ is the fist). Moore et al., 2015 The serous fluid-filled layer between parietal and visceral layers of bursae are typically collapsed or nearly so. Pathological fluid buildup between layers can separate these layers, creating a true 3D space. These are known as potential spaces-which typically exist due to pathology or clinical intervention. Potential spaces are not limited to bursae-they exist wherever there are layers of tissue that can be separated (for example, the subdural space between layers of meninges covering the brain). Realized potential spaces are usually a problem, as they interfere with the lubricating/protecting function of bursae, or put pressure on vulnerable organs, nerves, and vessels. Furthermore, like with venous and lymphatic drainage potential spaces can act as a route of infection spread and cancer metastasis. LO 12 Anatomical systems do not exist in isolation, they are integrated with other systems into multilayered and multifunctional regions. These multifunctional organizations can be used to chunk anatomical knowledge and improve learning through organization. To gain practice in examining how different systems interact, let’s focus on two examples: a myofascial compartment-somatic (Fig. 22) and the small intestine-visceral (Fig. 23). Block: Foundations | PROFFITT [24 of 27] INTRODUCTION TO ANATOMY Figure 22: Transverse section of the leg (section between knee and ankle) displaying three myofascial compartments (1 anterior, 1 posterior, 1 lateral). Note the location of muscles, vessels, and nerves, including superficial nerves and vessels just under the skin. Moore et al., 2015 In the somatic system, systems are typically in layers of muscle and fascia. Within the limbs, myofascial compartments are layers of muscle encircled by connective tissue, that often contain neurovasculature (arteries, veins, nerves). These compartments are typically multilayered from superficial to deep, for example in the posterior compartment of the leg (Fig. 22), you can observe several layers of muscle. Deep to several of these muscles close to the bone there are several deep vessels and nerves. Typically, nerves and vessels that supply muscles are deep to those muscles. Exceptions are often clinically relevant, because critical neurovasculature can become damaged more easily. Superficial to the compartments are layers of superficial fascia and adipose tissue, that often support superficial vessels (especially veins) and superficial nerves (detecting sensation from the skin). Critically, many muscles in compartments are innervated by a small number of nerves and often share common functional roles, so you can learn anatomy by compartment rather than memorize things separately. That way, you only have to learn the main role of the region, and the exceptions. Innervation and bloodflow are excellent ways to organize knowledge. Block: Foundations | PROFFITT [25 of 27] INTRODUCTION TO ANATOMY Figure 23: Schematic of the small intestine. Note the relationship between connective tissue suspending the organ, which transmits critical vasculature and nerve. Additional nerves and vasculature run along the surface of the organ, to integrate with internal layers of muscle, neurovasculature, and lymphatics. Moore et al., 2015. Visceral organs also have integration of multiple systems, as can be observed in the small intestine (Fig. 23). For example, the intestine is suspended from the body wall by a sheet of connective tissue containing fat and critical neurovasculature. These vessels supply (artery) or drain (vein) the organ, whereas the nerves either modulate the activity of the organ (autonomic or visceral motor) or detect conscious/unconscious stimuli from the organ (visceral sensation). Organs can be more difficult to organize than somatic structures, but their blood supply and nervous supply is typically segmental (e.g., many structures of the superior abdomen, or foregut, all receive bloodflow primarily form the celiac trunk of the aorta. Therefore, you can group structures into broad regions based on this supply, or organize them by their containing cavity (e.g. thoracic, abdominal, pelvic). The system of organization into compartments or segments/watersheds supplied by particular nerves and vessels is critical to first-level diagnostic thinking because your patient will present differently based on the anatomy affected. Patients will come in reporting pain, or a particular disfunction. Therefore, it is important to consider how these organizational schemes can help you differentially diagnose issues that may arise in the clinic. LO 13 Block: Foundations | PROFFITT [26 of 27] INTRODUCTION TO ANATOMY Figure 24: Schematic of anatomical variation of the artery that feeds the gallbladder. Critical to account for this variation during gall bladder surgery so as to not ligate the artery incorrectly. Moore et al., 2015. The anatomy that you will engage with in your donor bodies and in your patients will inevitably vary from the textbook diagrams. Variation is the currency of biological evolution and humans are no exception. Some variations are clinically relevant (e.g. Fig. 24), because they can alter your clinical algorithm or chosen course of action. We will present some of the most common variations, but learning anatomy by creating associations between structures (e.g., this arterial branch has X destination and goes with Y nerve) will help you adapt when you see a new variant. Block: Foundations | PROFFITT [27 of 27] EVIDENCE BASED DECISION MAKING 101 Block: Foundations Block Director: James Proffitt, PhD Course: Pathways in Health and Medicine Course Director: Barbara Eckstein, MD Session Date: Monday, July 29, 2024 Time: 11:00 - 12:00 pm Instructor: Keith Primeau MD, MPH Department: Emergency Medicine Email: [email protected] INSTRUCTIONAL METHODS Primary Method: IM07: Discussion, Large Group (>12) ☐ Flipped Session ☐ Clinical Correlation Resource Types: RE18: Written or Visual Media (or Digital Equivalent) INSTRUCTIONS Please read lecture objectives and notes prior to attending session. READINGS Study Examples (for pre-session practice problems/self-study and class discussion): The RECOVERY Collaborative Group. "Dexamethasone in Hospitalized Patients with Covid-19." The New England Journal of Medicine 384.8 (2021): 693-704. https://www.nejm.org/doi/10.1056/NEJMoa2021436. The RECOVERY Collaborative. "Azithromycin in patients admitted to the hospital with Covid-19 (RECOVERY): a randomized, controlled, open-label, platform trial." Lancet. 397.10274 (2021): 605-12. https://www.sciencedirect.com/science/article/pii/S0140673621001495. LEARNING OBJECTIVES 1. Identify the components of a good clinical question and construct a clinical question using these components. 2. Identify the four steps of the practice of EBM. 3. Given a series of clinical research abstracts, rank them in order of the level of evidence each provides in support of a specific clinical question assuming they are well done studies. 4. Be able to construct a clinical question using the PICO Model 5. Apply a “best practice model” to make a decision about a clinical question. 6. Reconstruct the Evidence Pyramid and explain the rationale behind each level’s rank. Block: Foundations | PRIMEAU [1 of 7] EVIDENCE BASED DECISION MAKING 101 CURRICULAR CONNECTIONS Below are the competencies, educational program objectives (EPOs), course objectives, session learning objectives, disciplines and threads that most accurately describe the connection of this session to the curriculum. Related COs Related LOs Competency\EPO Disciplines Threads CO-06 LO-01 MK-04: Cognitive, affective and Clinical skills EBM: Biostatistics social growth and development CO-06 LO-02 MK-06: The foundations of Clinical skills EBM: Evidence-Based therapeutic intervention, Medicine including concepts of outcomes, treatments, and prevention, and their relationships to specific disease processes CO-06 LO-03 MK-09: Critical thinking about Clinical skills EBM: Clinical/Translational medical science and about the Research diagnosis and treatment of disease CO-06 LO-04 MK-10:L The scientific method Clinical skills EBM: Evidence-Based in establishing the cause of Medicine disease and efficacy of treatment, including principles of epidemiology and statistics CO-06 LO-05 MK-06: The foundations of Clinical skills EBM: Evidence-Based therapeutic intervention, Medicine including concepts of outcomes, treatments, and prevention, and their relationships to specific disease processes CO-06 LO-06 PBLI-05: Locating, appraising, Clinical skills EBM: Evaluation of Health and assimilating evidence from Science Literature scientific studies related to clinical care PRACTICE PROBLEMS AND SELF-STUDY Try and complete the practice problems prior to class or sometime later in the week depending on your study style. See the pre-session practice problems at the end of these notes. These concepts are relatively straightforward but as we progress in the EBDM curriculum, many concepts, particularly the statistical calculations you need to know and understand, require repetition in order to be able to quickly answer board questions and understand how evidence applies to your patients. CONTEXT Our understanding of the human body in health and disease is constantly being refined by new discoveries from medical research including clinical case reports, retrospective and prospective studies, clinical trials, and systematic reviews. Evaluating new discoveries and knowing how and when to implement them to achieve better patient care is the domain of Evidence-Based Decision Making (EBDM). The ability to make clinical decisions based on best available evidence is among the most important skills you can develop in becoming Block: Foundations | PRIMEAU [2 of 7] EVIDENCE BASED DECISION MAKING 101 an effective, compassionate physician. Medicine is constantly and rapidly evolving. EBDM skills will enable you to counsel patients effectively on disease risk factors, provide the most informed diagnoses, as well as evaluate, prescribe, and monitor the best therapeutic strategies for your patients. This session will explore how to frame useful clinical questions and the kinds of evidence that are brought to bear in finding answers to clinical questions. Note that though some of these concept overlap with research, EBDM mastery is essential for all practicing clinicians. It is not the art of designing a study to answer a question, but applying the existing knowledge-base to answer a clinical question to treat the patient in front of you. KEY CONCEPTS a. Evidence Based Medicine as a Paradigm Shift i. EBM emerged in the 1970’s simultaneously with increasing recognition of the enormous value of clinical research findings. Milestone discoveries from epidemiological studies, such as the Framingham Study, suggested that clinical practice decisions should be based upon clinical research findings – NOT only a physician’s intuition and knowledge of pathophysiology. There are countless examples of medications or therapies that make sense from an understanding of physiology, but do not work in practice. ii. Physicians with training in Clinical Epidemiology, most notably in Canada and the United Kingdom launched ambitious programs to promote EBM. Some of these pioneers included Drs. Gordon Guyatt, David Sackett, Scott Richardson, Bryan Haynes, Deborah Cook and Drummond Rennie. The term “Evidence Based Medicine” was first published in 1991. ACP J Club 114A-16. 1. These Clinicians and scientists built off of previous pathophysiologic frameworks such as Koch’s Postulates and the Bradford Hill Criteria. Instead of following the previous paradigms of studying disease states and applying that knowledge to patient care, the modern EBM movements use a patient-centered framework in which clinicians ask what is the best course of action to accomplish a patient- centered goal and how does the best available evidence support that clinical action. iii. 2 key principles – 1. Clinical decisions are VALUE laden 2. A Hierarchy of evidence exists iv. The doctor is not always right 1. Decisions should be Evidence Based whenever possible 2. The “art” of Medicine has led to great variation in practice which is not typically in the patient’s best interests! b. Hierarchy of Evidence i. Evidence: any empirical observation about an apparent relationship between events constitutes potential evidence – including elements of the history and physical exam (these are often taken in an unsystematic manner and therefore prone to bias and error). Prior medical history, diagnostic tests, radiographs, etc. also constitute evidence. Medical Knowledge contained within scientific medical literature, textbooks, reputable web sites and online clinical resources/apps, and expert opinion from individual persons also constitute evidence that might be applicable to a specific patient. ii. Hierarchy: a grading scheme that ranks evidence based upon its inherent scientific merit – the better the science, the better the evidence. Intuition without evidence would be at the bottom of this hierarchy. This is because of the assumed potential for bias, unsystematic observation, conflicts of interest and physician over-confidence. The Block: Foundations | PRIMEAU [3 of 7] EVIDENCE BASED DECISION MAKING 101 Randomized Controlled/Clinical Trial (RCT) is considered the gold-standard for an individual study design about therapeutic interventions. Evidence Pyramid c. Critical Appraisal of Evidence and Literature i. Critical appraisal: The systematic process of assessing and interpreting evidence, considering its validity, results, and relevance. To practice evidence-based decision making, physicians must be able to judge strong from weak evidence – quickly and many times every day! ii. Basic steps of critical appraisal of a medical research article include evaluating the general focus of the evidence; the internal, construct, and external validity of the evidence; the results and conclusions. 1. Internal Validity: The extent to which a piece of evidence supports a claim about cause and effect. In other words, does a study reliably prove or disprove what it is intending to study. What is the quality of the actual study as it relates to what it is trying to prove? a. You can think of this as the most pure evaluation of whether a study is any good? Did it have acceptable methods, unbiased results, and did the authors come to a reasonable conclusion based upon the study and results? b. We will go into this in great detail further in the EBDM curriculum. Understanding statistical measures, clinical and statistical significance, risk of bias, study design, etc. are essential aspects of internal validity. 2. External Validity: The extent to which a piece of evidence can be applied outside the context of that study. Can the study’s findings be applied to the patient in front of you or a population you are looking at? 3. Construct Validity is the degree to which a test measures what it claims to be measuring. This is often a part of internal validity. For example, do IQ tests truly measure intelligence? iii. Systematic Reviews – published exhaustive critical appraisals of the scientific literature – ideally of RCTs – related to a practical clinical topic or questions. The Cochrane database contains gold-standard reviews covering thousands of topics. Block: Foundations | PRIMEAU [4 of 7] EVIDENCE BASED DECISION MAKING 101 d. The 4 Steps of EBDM i. Ask: a physician should form answerable questions relevant to a patient’s care – one construct is PICO (patient, intervention, control, outcome). ii. Acquire: Searching for answers used to require physical access to printed journals through subscription or institutional access, now we fortunately hold nearly all of human knowledge, copious cat videos, and dank memes within the palms of our hands. iii. Appraise: systematic critical appraisal is used to assess the quality of a piece of evidence. This can first be broadly done by stratifying pieces of evidence through the widely accepted hierarchy and then individually assessing a piece of evidence for quality, validity, and bias. iv. Apply: application of the newly acquired and appraised medical knowledge to the patient’s care AND to the physician’s knowledge base – this is a powerful way to maintain lifelong learning. v. Some EBM frameworks add a fifth A: reAssess, to describe reevaluating your patient to see their results from the clinical decision that you applied. e. PICO – Patients, Intervention, Control, Outcome. A fundamental concept in evidence-based medicine is the structured clinical question. The PICO model has become as standard for stating a searchable question. i. Patient – refers to the population group to which you want to apply the information; cannot be too specific or you will have trouble finding evidence in the literature. Good choices: elderly women, diabetic children, patients with stage IV colon cancer. Bad choices: 72 year-old women, diabetic children with a hemoglobin A1c between 7.8 and 9.4 ii. Intervention – therapy, harmful exposure, or diagnostic test you want to find evidence for. iii. Comparison/control – the alternative to the therapy, harmful exposure or diagnostic test that you are interested in finding evidence for. Commonly this would be placebo or the standard approach to therapy or diagnostic testing. iv. Outcome – the meaningful endpoint of interest to you or your patient. Beware of “surrogate markers” or potentially non-important pseudo-markers of disease. f. The Enlightened Patient i. Patient values: subjective beliefs and belief systems, vary across people and cultures. They are the underlying foundation for preferences or an individual’s choices about health care. ii. The World is flat…patients routinely search the internet for answers to their clinical questions and have access to many of the same resources as physicians. Now, social media algorithms enhance this through bombarding laypersons (and clinicians) with evidence of drastically variable quality. This is a mix of good and bad – why? iii. EBDM incorporates Patient Values…the pioneers of EBM emphasized the need to include the p

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