Physiology Exam Study Guide PDF

Study Guide Tissue Types and Cell Injury / Adaptation / Death A. Tissue Types 1. Briefly describe the hierarchy of tissue organization i. Chemical level (a) Atoms combine to form molecules ii. Cellular level (a) Cells...

Study Guide Tissue Types and Cell Injury / Adaptation / Death A. Tissue Types 1. Briefly describe the hierarchy of tissue organization i. Chemical level (a) Atoms combine to form molecules ii. Cellular level (a) Cells (a) Composed of lots of different molecules iii. Tissue level (a) Composed of cells AND the extracellular matrix they produce iv. System level (a) Composed of lots of different tissue types (b) For example, our skin includes all of the following tissue types (a) Epithelial tissue (i) The “skin cells” (i.e., the epidermis) and their extracellular matrix (ii) Blood vessels (b) Connective tissue (i) Loose connective tissue which fills space (i.e., the dermis) and its extracellular matrix, such as areolar tissue 1. Extracellular matrix includes collagen, elastin, proteoglycans to “glue” all of the cells together (ii) Blood, which supplies nutrients to the skin cells (c) Nervous tissue (i) Receptors and nerves, which give us sensation 2. Briefly describe the concept of the extracellular matrix i. Fluids and molecules secreted by cells ii. Influences the structure and function of that tissue type (a) For example: (a) The extracellular matrix secreted by bone cells makes bone tissue is hard and rigid (b) The extracellular matrix secreted by tendon cells makes tendon tissue stretchy (like a rubber band) 3. Briefly describe the most common molecules in the extracellular matrix (a) Collagen (a) Provides structure and strength (b) Triple helix structure (b) Elastin (a) Provides elasticity (stretchiness) (c) Proteoglycans (a) Fill space (b) Attract water – this determines how “soft” a tissue will be (i) Example – Cartilage has lots of proteoglycans, so it can provide some “cushioning” to joints  (d) Integrins – The “glue” which connects cells to other cells, and also to the other various proteins mentioned above 4. Describe the four general categories of tissue, including function i. Epithelial Tissue (a) Serves the following functions, depending on location (a) Provides protection (e.g., skin, cornea) (b) Lines organs (e.g., inside of blood vessels, inside of intestines) (c) Produces glandular secretion (e.g., mucus, sweat) ii. Connective Tissue (a) Functions include: (a) Filling spaces (i) “Connective Tissue Proper” (ii) Blood (b) Structural support (i) Cartilage (ii) Bone (iii) Ligament (iv) Tendon (c) Energy storage (e.g., adipose tissue) (b) Fibroblasts are an important cell for connective tissue (a) Produce collagen, elastin, etc. (b) Involved in tissue healing / repair iii. Muscle (a) Able to contract to produce movement (b) Three types (a) Skeletal (under voluntary control) (b) Smooth (i) Lines organs (e.g., blood vessels, intestines) (ii) Not under voluntary control (c) Cardiac iv. Nervous (a) Transmits electrical impulses to carry information B. General Cellular Injury / Adaptation 1. Name factors which influence the reversal of injury / return to homeostasis i. Mechanism of injury ii. Duration of injury without intervention iii. Severity of injury 2. Discuss the free radial theory of cellular injury i. Reactive oxygen species (ROS) (a) Oxygen with unpaired electron (a) Reacts with various molecules (b) Can form toxic chemicals (i) Toxic to normal cells (ii) Toxic to pathogens  (b) Normal part of metabolism (c) Formed continuously ii. Excess ROS production is “oxidative stress” (a) Cause cell injury and potentially cellular death (b) Implicated in MOST lifestyle disease processes (c) Caused by MANY stimuli (a) Excessive exercise (b) Radiation (c) Tobacco smoke (d) Heat 3. Describe the role of antioxidants in relation to ROS i. Neutralize ROS (a) Prevent DNA and cell damage ii. Endogenous antioxidants [specific names not mentioned in book] (a) Glutathione (b) Peroxidase (c) Catalase iii. Exogenous antioxidants (a) Vitamin C, E, beta-carotene 4. Describe the relationship between exercise, free radicals, and antioxidants i. Exercise itself acutely causes increased ROS formation [beyond that described in book] (a) Impairs muscle force production (b) ROS cause cell to adapt to develop more endogenous anti-oxidants and repair mechanisms (a) “Exercise is the best antioxidant” ii. Excessive exercise causes significant oxidative stress (a) “Excessive” is relative (a) Depends on person’s baseline fitness 5. Briefly describe three ways by which genetic alterations cause cellular injury/death, and some examples of these diseases i. Alterations in structure/number of chromosomes that cause abnormalities (a) Down’s syndrome ii. Single mutations in genes which change protein expression (a) Sickle cell anemia iii. Interaction of multiple genetic mutations, which may interact with various environmental factors (a) Type II diabetes (b) Obesity 6. Name the possible responses to physical stress (or lack thereof) i. Decreased stress tolerance (atrophy) ii. Maintenance iii. Increased stress tolerance (a) Hypertrophy – Increase in the size of cells (b) Hyperplasia – Increase in the number of cells  iv. Injury v. Death 7. Name the types of mechanical stressors which can initiate a cellular response i. Overstretch ii. Compression iii. Friction iv. [Anoxia is listed with this, but it is not a mechanical stressor, rather it is metabolic] C. Cellular Injury 1. Describe the process of reversible cell injury i. Increased sodium and calcium into cell ii. Increased cellular swelling iii. Impaired organelle function (a) Impaired mitochondrial function decreases ATP production (a) This causes impairments in other cellular function (b) Cellular acidosis causes further impairments iv. Reversal happens as long as (a) Nucleus remains undamaged (b) Energy source is restored (c) Toxic injury is neutralized v. When reversal happens, the cell returns to its normal state of function 2. Describe the key responses to chronic cellular stress, and provide examples of each i. Atrophy (a) Reduction in size of cell / organ (b) Examples (a) Bone loss (b) Muscle wasting (c) Brain cell loss ii. Hypertrophy (a) Increase in size of cell (a) In response to increased (i) functional demands (ii) Hormonal input (b) True hypertrophy only occurs in cardiac and skeletal muscle (i) Cannot increase number of cells (c) Example (i) Left ventricular hypertrophy due to 1. Exercise training 2. Hypertension iii. Hyperplasia (a) Increase in number of cells (a) In response to increased functional demands (i) Increased hormonal stimulation (ii) Physical stimulation (iii) Often occurs simultaneously with hypertrophy  (b) Examples (a) Callus formation on skin (b) Thickened uterine wall lining due to estrogen exposure (c) Smooth muscle proliferation in various diseases (i) Tubular obstruction 1. Bronchi in obstructive airway diseases 2. Urethra in prostate enlargement 3. Blood vessels in hypertension iv. Metaplasia (a) Change in cell morphology an function, converting one cell type into another (b) Examples (a) Ciliated pseudostratified epithelium becomes squamous epithelium in smokers v. Dysplasia (a) Increase in cell numbers AND loss of morphology AND loss of tissue organization (a) Occurs in chronically injured areas undergoing hyperplasia/metaplasia 3. Describe the processes / consequences of irreversible cell injury i. Ultimately results in cell death (a) Apoptosis (a) Genetically mediated (b) Programmed (c) No inflammatory response (b) Necrosis (a) Active process of degrading dead cells (b) Nuclear and mitochondrial damage occurs (c) Lysosomes release digestive enzymes in cytoplasm (i) Self-digesting of dead tissue (ii) Facilitates phagocytes breaking down dead tissue (d) Contents from dead cells released into ECF and ultimately circulation (i) Example: CK elevations in myocardial infarction (e) Requires removal for repair/regeneration (f) Can cause gangrene formation (i) Bacterial infection  Study Guide Connective Tissue - Bone A. Describe the general structure of bone 1. Cortical bone (also known as Compact Bone) i. Tough outer layer ii. Majority of bone in the body iii. Covered by periosteum on superficial surface (a) This contains blood vessels 2. Cancellous Bone (also known as Trabecular Bone or Spongy Bone) i. Spongy, mesh plates ii. In contact with bone marrow B. Describe the cellular and non-cellular components of bone 1. Cellular Component i. Osteoblasts (a) Immature bone cells (b) Secrete extra-cellular matrix to give bone its material properties (c) Eventually can: (a) Become osteocytes (see below) (b) Become bone lining cells (c) Die via apoptosis ii. Osteocytes (a) Mature bone cells (b) Maintain extracellular matrix (a) Response to mechanical loading (b) Response to hormones iii. Osteoclasts (a) Break down extracellular matrix (a) Releases minerals into the blood stream (b) Provides space for osteoblasts to secrete new extracellular matrix iv. Bone Lining Cells 2. Non-cellular Component (extracellular matrix, secreted by osteoblasts) i. Non-mineralized (a) Osteoid is the main non-mineralized component (a) Collagen is main protein in osteoid ii. Mineralized (a) Hydroxyapatite is main mineralized component C. Differentiate between the two classifications of bone based on the tissue’s maturity level 1. Immature bone = woven bone i. Also known as “primary bone” ii. Found during fracture repair process (and also in fetal growth) iii. Weaker than mature bone (a) Irregular collagen structure  (b) Less mineral content in osteoid 2. Mature bone = lamellar bone i. Also known as “secondary bone” ii. Forms in remodeling process (i.e. woven bone has stressors placed upon it, and remodels) iii. Stronger than woven bone (a) Osteon structure of concentric rings (a) Adapted based on stressors placed upon it (b) Osteocytes houses in lacunae (c) Haversian canals contain blood vessels and lymphatic vessels (d) Volkmann’s canals connect osteons together (b) More mineral content in osteoid 3. Both, cortical bone and cancellous bone can exist in immature forms D. Describe the process of fracture repair 1. Occurs by regeneration and remodeling i. No scar ii. Return to optimal functioning possible 2. Duration is dependent upon multiple factors i. Fracture site ii. Type iii. Treatment iv. Soft tissue involvement v. Individual factors, including (a) Age (b) Immunocompetency (c) Nutritional status 3. Phases of healing i. Internal bleeding delivers cells to the site of injury, which secrete a number of growth factors, and eventually results in clotting (a) Fibroblasts (b) Platelets (c) Osteoprogenitor cells (a) Bone precursor cells (b) Can become osteoblasts, osteoclasts, etc. (d) Mesenchymal cells (a) Can become (i) Fibroblasts (ii) Chondroblasts (produce cartilage) (iii) Osteoprogenitor cells (e) Inflammatory cells ii. Hematoma forms (a) Lasts about a week iii. Inflammation occurs (a) Granulation tissue forms (a) Fibrosis  (b) Neovascularization (new blood vessel formation) iv. Soft callus forms after about 2 weeks (a) Osteoclasts clear necrotic bone (b) Periosteum and endosteum regenerate (a) Different into (i) Hyaline cartilage (soft callus) (ii) Bony spicules (hard callus) (c) Soft callus formation immobilizes fracture site v. Hard callus begins to develop (1+ week after soft callus) (a) Fibrocartilage (b) Endochondral ossification occurs (a) Transformation of cartilage to bone vi. Remodeling occurs (a) Months to years (b) Woven bone replaced with lamellar bone (c) Excessive callus is resorbed (d) Bone remodels in relation to mechanical stresses placed upon it (Wolff’s law!)  Study Guide Inflammation A. Name the four signs of inflammation and relate them to the precipitating events (Table 6-3) 1. Erythema (redness) – Vasodilation and increased blood flow 2. Heat - Vasodilation and increased blood flow 3. Edema – Increased vascular permeability and hydrostatic pressure, causing filtration into interstitial spaces 4. Pain – Multiple causes i. Direct trauma ii. Edema causing pressure iii. Nerve endings swelling iv. Chemical mediation B. Differentiate acute vs. chronic inflammation 1. Acute i. Chiefly edema (including fluid and plasma proteins) and neutrophilic migration 2. Chronic i. Includes lymphocytes, plasma cells, and macrophage infiltration (a) Attracted by chemotaxis from other cells (b) Promote growth of endothelial cells and fibroblasts (a) Granulation tissue forms ii. Angiogenesis / Neovascularization iii. Fibrosis iv. Tissue destruction C. Provide examples of conditions that would cause acute and chronic inflammation 1. Acute i. Infections ii. Tissue necrosis iii. Foreign bodies iv. Immune Reactions 2. Chronic i. Extensive necrosis ii. Sites where regeneration of tissue parenchyma is not possible (a) Heart (b) CNS (c) PNS iii. Underlying cause is not addressed (a) Persistent injurious agent iv. Repeated episodes of acute inflammation D. Briefly describe granulomatous inflammation 1. Aggregate of macrophages and lymphocytes E. Differentiate exudate, transudate, and effusion 1. Exudate is high protein fluid with high cellular content i. Dependent upon increased vascular permeability  2. Transudate is low protein fluid with minimal cellular content i. Dependent upon Starling’s forces causing filtration ii. No increase in vascular permeability 3. Effusion is the leakage of either of these into anatomic space (or potential space) i. Can be exudate or transudate F. Describe the role of vascular alterations in inflammation 1. Goal: increase movement of plasma proteins and circulating cells out of intravascular space to get to the site of injury i. Process of “exudation” (a) Increased capillary permeability (a) Increased inter-endothelial spaces (b) Fluid and protein leakage ii. Vasodilation (a) Increased blood flow to the area [initially] iii. Decreased blood flow to the area (a) After leakage of fluid out of the area (b) Increased viscosity of the blood iv. Clotting of fluid due to increased fibrinogen v. Migration and accumulation of leukocytes (a) Destroy pathogen G. Describe the role of leukocytes in inflammation and the process by which this occurs 1. Role i. Remove / eliminate injurious stimulus ii. Release toxic substances to kill, inactivate, and degrade pathogens iii. Clean up the area by phagocytosis iv. Release growth factors for healing/regeneration 2. Process i. Stasis = Engorgement of blood vessels causing a slowing of blood flow in the region ii. Margination = Accumulation of leukocytes to endothelial cells of blood vessel walls (a) Possible because of adhesion molecules (a) Bind leukocytes to other leukocytes (b) Bind leukocytes to capillaries / venules iii. Diapedesis = Leukocytes actively migrate out of blood vessel, by squeezing between endothelial cells, to reach the interstitial space iv. Chemotaxis = The use of chemotactic agents (chemokines) which attract other cells to move into the area H. Briefly describe the role of the lymphatic system in the inflammatory response 1. Lymphatic vessels drain exudate from the interstitium i. Reduce edema ii. Removal of inflammatory stimuli iii. Removal of leukocytes 2. Phagocytes present antigens to immunocompetent B and T cells in the lymph nodes i. Proliferation of lymphocytes ensues ii. Lymphadenopathy = enlargement of lymph nodes  iii. Further adaptive immune response as necessary I. Define lymphangitis 1. Inflammation of the lymphatic vessels i. Red streaks under the skin ii. Painful to palpation J. Describe the key inflammatory mediators 1. Histamine i. Synthesized and stored in granules within mast cells, basophils, and platelets ii. Effects (a) Endothelial contraction (a) Increased vascular permeability (b) Exudation (b) Vasodilation (c) Bronchoconstriction iii. Inactivated in ~2mmgHg fails to increase flow further (i) So, when the interstitium is packed with LOTS of fluid, there becomes a point at which the lymphatic vessels are running at full capacity and cannot keep up with removing the fluid (ii) This will result in edema 2. Name the factors which are responsible for lymphatic pumping i. Contraction of lymph vessel walls (a) Smooth muscle automatically contracts when lymphatic vessels stretched ii. Rhythmic compression of lymphatic vessels (a) Skeletal muscle contraction (b) Movement (c) Arterial pulsation (d) External compression F. Edema 1. State the two VERY broad causes of extracellular edema, and provide clinical examples of edema for each i. Increased fluid filtration (a) Examples – Anything which increases vascular permeability (more “leakage” from capillaries) (a) Example – histamine (i) Think of somebody having an allergic reaction and having a puffy face – THAT is in part from histamiine (b) Example – inflammatory response (c) Example – capillary damage (burns) ii. Decreased fluid reabsorption (a) Examples – Anything which increases venous resistance (and thus pressure) (a) Blood clots (b) Heart failure (blood can’t get out of heart, so it backs up in the veins, which backs up to the capillaries) (c) Localized external compression (e.g., applying a tourniquet) (b) Examples – Anything which slows / stops lymphatic flow (a) Tumors which block lymph flow (b) Surgery which removes lymph vessels (mastectomy is common example) (c) Parasitic worms in lymphatic vessels (elephantitis) iii. (Or a combination of both of these) 2. Differentiate between pitting edema and non-pitting edema, including the mechanism accounting for differences in tissue compliance i. Edema – accumulation of fluid in the interstitial space (a) NOTE: We are talking about EXTRAcellular edema here. It is also possible to have INTRAcellular edema, but we are not covering that here  ii. Pitting Edema – so much fluid has accumulated in the interstitium that the fluid is no longer in gel form, but rather as free fluid (a) Remember, normally the proteoglycans and water bind to form gel (b) Pitting edema is like having “puddles” of water in the interstitial space (c) It is called “pitting” because if you press your finger into the site of edema, hold it a few seconds, and then remove it, the area remains indented (the “pit”) (a) The reason for this is because the pressure from the finger pushed those “puddles” out into the surrounding area Section 5c (Vascular Function) G. Relate how distensibility of arteries and veins relates to their respective anatomy and how a change in volume influences a change in pressure 1. Arteries and arterioles have more (thicker) smooth muscle layer compared to veins and venules 2. Thinner walls in veins means that veins have greater distensibility than arteries and arterioles i. In other words, veins expand more for a given blood pressure than arteries do ii. Thus, veins serve as a reservoir for blood (a) More blood is found within veins in our body than in the arteries H. Compare the relationship between volume and pressure in the arterial and venous systems 1. Small changes in volume have a major effect in arterial pressure i. In other words, if we add more blood to the body, this will ultimately cause a significant increase in arterial blood pressure, since the arteries are not as distensible 2. Large changes in volume have a small effect on venous pressure i. In other words, if we add more blood to the body, this will ultimately have LITTLE effect on venous blood pressure, since the veins will just expand outwards I. Briefly describe how aortic distensibility influences systemic circulation 1. Aorta fills with blood during systole and distends 2. During diastole, the aorta recoils i. This recoil means that the aorta is applying inward pressure against the blood ii. This forces blood to move to sites of lower pressure iii. Because of the aortic value, blood can only move away from the heart iv. So, the elastic recoil of the aorta keeps blood moving throughout the systemic circulation even during cardiac diastole (i.e, blood continues to move in the arteries even when the heart is “relaxed”) J. Define pulse pressure 1. The difference between systolic arterial blood pressure and diastolic arterial blood pressure 2. For example, if systolic arterial blood pressure is 120mmHg and diastolic arterial blood pressure is 80mmHg, pulse pressure is 40mmHg (120-80=40) K. Briefly describe how pulse pressure is clinically interpreted 1. A high pulse pressure is called a “bounding” pulse i. It means there is a large difference between systolic and diastolic arterial pressure, but does not tell us why: (a) This could be a high systolic with normal diastolic (a) Example: A healthy exercise BP of 140/80 (pulse pressure 60)  (b) This could be elevated systolic and diastolic, but systolic is elevated way more than diastolic (a) Example: Hypertension with a BP of 150/90 (pulse pressure 60) (c) This could be a normal systolic with low diastolic (a) Example: Normotensive with a BP of 120/60 (pulse pressure of 60) 2. A low pulse pressure is called a “thready” pulse i. It also does not tell us why, similar to above ii. Clinically, it is MOST likely to be due to a LOW SYSTOLIC pressure, rather than a high diastolic pressure L. Name the two MAJOR factors which influence arterial pulse pressure, and relate how changes in these ultimately influence pulse pressure 1. Stroke volume i. Greater SV means greater rise and fall of pressure ii. Remember, stroke volume depends on a few factors (covered separately in greater detail): (a) Cardiac contractility (how hard the heart is contracting) (b) Afterload (how much resistance the ventricle has to overcome to get the blood out into the aorta) 2. Compliance of the arterial tree i. Noncompliance increases arterial pressure ii. This is related to sympathetic nervous system activation (covered in greater detail separately) (a) Sympathetic nervous system activation generally causes arterial/arteriolar vasoconstriction (b) This means the arteries/arterioles become LESS distensible (MORE rigid) (c) This generally increases systolic arterial pressure (more than diastolic arterial pressure) (a) That increases pulse pressure M. Explain why mean arterial pressure is not simply the average of systolic and diastolic pressure at rest, and how this changes with high heart rates (e.g. during exercise) 1. More time is spent in diastole than systole i. This means that diastole contributes more to the average pressure than systole does 2. During exercise, the relative time spent in diastole decreases N. State the normal value for right atrial pressure, and briefly describe why this matters 1. Approximately 100mg/dL), but below diabetes threshold (e.g.,