Physiology Final Study Guide PDF

PHYSIOLOGY FINAL STUDY GUIDE WEEKS 1-4 Hypersensitivity is an increased immune response to antigens and produces undesirable clinical effects. ○ Type 1: Immediate Hypersensitivity, ATOPY IgE is produced and histamine is released causing allergic responses...

PHYSIOLOGY FINAL STUDY GUIDE WEEKS 1-4 Hypersensitivity is an increased immune response to antigens and produces undesirable clinical effects. ○ Type 1: Immediate Hypersensitivity, ATOPY IgE is produced and histamine is released causing allergic responses to occur ○ Type 2: Cytotoxic reactions to SELF-ANTIGENS Immune response to one’s OWN tissues GBS, Myasthenia Gravis ○ Type 3: Immune Complex Diseases Antigen-Antibody Complexes depositing around small blood vessels RA, SLE ○ Type 4: Cell-Mediated Immunity DELAYED reactions to allergens (48-72 hours) Transplant rejections, poison ivy Connective Tissue-Bone ○ Cortical bone (Compact bone) has a tough outer layer and is the majority of bone in the body, covered by periosteum ○ Cancellous bone (Spongy or Trabecular bone) has contact with bone marrow Cellular vs Non-Cellular ○ Cellular Osteoblasts: Immature bone cells that give bone its material properties Osteocytes: Mature bone responds to mechanical loading and hormones Osteoclasts: Break down ECM releasing minerals into bloodstream ○ Non-cellular Non-mineralized: Osteoid is the main component with collagen as main protein Mineralized: Hydroxyapatite is main component Fracture Repair ○ Internal bleeding calls cells to the injury site, they clot the blood with fibroblasts, platelets, osteoprogenitor, mesenchymal, and inflammatory cells. Then a hematoma forms and lasts about a week, while then inflammation occurs and new blood vessels form. Then soft callus forms immobilizing fracture site and turns into hard callus then remodeling begins which can take months to years replacing the woven bone with lamellar bone. Cytokines Effects on Satellite Cells ○ Enhanced resistance to oxidative stress (cell survival) ○ Block myofibrillogenesis (improve muscle healing) ○ Proliferation (cell division) ○ Differentiation (fusion to myofibers) ○ Angiogenesis (vascular supply to new muscle cells) Satellite job on muscle repair PHYSIOLOGY FINAL STUDY GUIDE ○ Satellite cells move into injured area and become muscle cells Satellite cells change themselves into contractile tissue (muscle cell) Innate vs Adaptive ○ Innate: Non-specific to a given pathogen, eliminates pathogens rapidly Exterior defense: epithelial, mucosa, and secretions Phagocytes: natural killers, neutrophils, macrophages Soluble mediators: proteins that induce the inflammatory response ○ Adaptive: Specific to different pathogens, creating a MEMORY to fight off in the future Humoral immunity Cell-mediated immunity Definitions ○ Antigen: any molecule binding to antibody or T-cell receptor ○ Immunogen: an antigen that provokes an immune response ○ Active immunity: protection following exposure to a given antigen Natural: exposure to flu from someone coughing Artificial: flu vaccine ○ Passive immunity: antibodies transferred from immune to non-immune person ○ Antibody: produced by B-lymphocytes ○ Granulomatous inflammation: aggregate of macrophages and lymphocytes ○ Exudate: high protein fluid with high cellular content, dependent with increased vascular permeability ○ Transudate: low protein fluid with minimal cellular content dependent on Starling's forces causing filtration and no increase in vascular permeability ○ Effusion: leakage of either into anatomic space ○ Diapedesis: leukocytes actively migrate out of blood vessels to reach interstitial ○ Chemotaxis: use of chemokines, which attract other cells to move into the area ○ Absolute refractory period: heart can’t be stimulated to contract at all ○ Relative refractory period: heart cannot be excited by normal signal, but can be by an especially strong signal ○ Preload: end diastolic pressure when ventricle is filled ○ Afterload: pressure in aorta (resistance in circulation), ventricles needing to work harder to get blood out ○ Escape beats: occur when ventricle hasn’t received stimulus from elsewhere Immunoglobulins ○ IgM: FIRST antibody ○ IgG: Long lasting immunity ○ IgA: Mucosa ○ IgE: Allergy ○ IgD: on mature naive B cells Cell-mediated immunity process ○ Macrophages and dendritic cells travel to lymph nodes and present antigens to T-cells. If they match it can be activated. If activated the T-cells replicate and a destruction of pathogens in lymph nodes happen, they travel through the body to PHYSIOLOGY FINAL STUDY GUIDE attack the pathogen and activate B-cells. Memory cells are also formed for a rapid response for a second exposure. Iatrogenic immunodeficiency ○ Cytotoxic drugs ○ Corticosteroids ○ Immunosuppressive drugs ○ Radiation therapy ○ Splenectomy Signs of Inflammation ○ Erythema (redness) ○ Heat ○ Edema ○ Pain Process of Blood Coagulation ○ Platelets circulate and seal the damaged site with platelet plugs and then a series of enzymatic reactions produce thrombin- fibrinogen converted to fibrin stops the bleeding and then the fibrinolytic system converts plasminogen to plasmin and clots the blood Diabetes Mellitus ○ Excess blood glucose causing blood to accumulate in urine causing sweet urine due to the glucose being filtered out and not be reabsorbed into the kidney creating an excess in urine and an increase in thirst ○ Type I: UNABLE to produce enough insulin ○ Type 2: insulin RESISTANT ○ Leads to atherosclerosis because of excess glucose causing endothelial damage, leading to plaques and vessels aren’t able to function properly, impairing flow to the target organs ○ GH, testosterone, thyroxine, fever all increase BMR ○ Set-point and body temperature High set point=SWEATING begins=High skin temperature Low sweat point=SHIVERING begins=Low skin temperature WEEKS 4-6 Cardiovascular Blood through heart: Deoxygenated blood→SVC/IVC→R atrium→Tricuspid valve→Right ventricle→Semilunar valve (pulmonary)-->Pulmonary artery→Lungs→Oxygenated blood→Pulmonary vein→Left atrium→Mitral valve→Left ventricle→Aortic valve→Aorta Blood flow at rest ○ 25% to kidneys, GI tract and skeletal muscles each Frank Starling method ○ Greater amount of blood in the heart gives greater contractile force, therefore SV ○ Greater stretch means greater elastic energy, thus greater contractile strength PHYSIOLOGY FINAL STUDY GUIDE ○ Greater atrial stretch means greater ANS stimulation of heart rate Electrical conduction ○ SA node (fastest)→Internodal pathways→AV node→AV Bundle→Bundle branches→ventricular muscle Neurotransmitters to Heart ○ Sympathetic: releases NE ○ Parasympathetic: releases ACh Fluid Compartments ○ Intracellular fluid (most fluid in body) ○ Extracellular fluid Vascular compartment (third largest fluid compartment) Containing albumin transporting hormones and drugs, globulins, and fibrinogen used for blood clotting. ○ Interstitial fluid (second largest compartment) Fluid in interstitium where water and dissolved electrolytes live Fluid movement between compartments ○ The water with electrolytes gets FILTERED out into the vascular and interstitial compartments and then gets REABSORBED from the interstitial fluid back to the capillaries which then 90% of fluid that was FILTEREDfrom capillaries, gets REABSORBED Starling's forces ○ Capillary hydrostatic pressure Promotes filtration (trying to escape from capillaries) ○ Interstitial fluid pressure Promotes absorption (trying to go back into the capillaries) ○ Plasma colloid osmotic pressure Promotes absorption by pulling fluid out of interstitium and back into the capillaries ○ Interstitial fluid colloid osmotic pressure Usually not present, but will promote filtration of proteins Pitting edema vs Non-pitting edema ○ Depends on the fluid buildup in the interstitial space and if it is free fluid to make it pitting edema Vascular Function - Arteries and arterioles are thicker smooth muscle layer Veins and Venules have thinner walls Therefore, veins can expand more than arteries creating a reservoir for blood ○ Arterial Pressure changes Adding more blood into the body will cause an increase in arterial blood pressure (arteries are not as distensible) Adding more blood to the body will have little effect on venous blood pressure because the thinner walls can expand outward. ○ Aortic Distensibility Influencing Systemic Circulation PHYSIOLOGY FINAL STUDY GUIDE Allowing the aorta to store energy during systole by distending as it fills with blood Diastole, the aorta recoils generating inward pressure that propels blood toward lower-pressure areas Aortic value only allows blood to move AWAY from the heart to prevent backflow Elastic recoil ensures continuous blood flow through the systemic circulation ○ Pulse Pressure Systolic arterial blood pressure MINUS Diastolic arterial blood pressure (the difference) ○ Interpretation of pulse pressure “Bounding” Pulse: large difference between systolic and diastolic arterial pressure (could be high or elevated systolic pressure with normal diastolic or normal systolic with low diastolic) “Thready” Pulse: low pulse pressure (clinically, most likely to be due to LOW systolic) ○ Stroke Volume Cardiac contractility Afterload (resistance ventricle overcomes to get blood out) Greater SV means greater rise and fall of pressure ○ Sympathetic Nervous System Activation Causes arterial vasoconstriction (arteries become less distensible or more rigid) Systolic arterial pressure increases (thus increases pulse pressure) ○ Right atrial pressure More time is spent in diastole (during exercise time spent in diastole decreases) Right Atrium (dependent on Venous blood pressure and Right Atrial Pressure) The heart needs to be able to pump out a lot of blood into the lungs via the Right Ventricle in order for the Right atrium to fully empty all the blood into the Right Ventricle. (if NOT blood will begin to build up into the Right Atrium causing an increase in Right Atrial pressure) ○ Gravity Influences arterial and Venous Pressure Minor Point or “Below the heart”: Gravity increasing blood pooling PHYSIOLOGY FINAL STUDY GUIDE Improper valve function will cause varicose veins (Enlarged, twisted veins) If the venous valves work properly, the Muscle pump will assist to push blood back towards the heart As a result, Venous return directly impacts end-diastolic volume (EDV), leading to a higher EDV during activity (increased EDV helps pump more blood out with each beat) ○ Vasoconstrictors Epinephrine and Norepinephrine (fight or flight response, directing blood to more essential organs) Angiotensin 2 (RAAS and regulating blood pressure along with fluid balance) Endothelin (released with blood vessel injury) Thromboxane (platelet aggregation, important role played with blood clot formation) Vasoconstrictors regulate blood pressure, vascular tone, and blood flow, particularly in response to stress, injury, or changes in blood volume. ○ Vasodilators Nitric Oxide (important for normal vascular function, deficiency in NO can lead to hypertension) Histamine (Type 1 hypersensitivity, released by mast cells and basophils) Decreased oxygen (Hypoxia, other vasodilatory factors are used to improve blood flow and oxygen delivery) H+ (anaerobic metabolism, causing smooth muscle to relax and dilation of blood vessels) ADP, AMP, Adenosine (increased metabolic activity or hypoxia) Lactic Acid (Anaerobic metabolism when oxygen supply is insufficient for the energy demands of the tissue) CO2 (byproduct of cellular mechanism, key for regulating blood flow to deliver oxygen) Vasodilators help regulate blood flow in response to various physiological demands, particularly during exercise, inflammation, and metabolic changes. ○ Blood Vessel Diameter Narrow Vessel -> higher resistance to flow Vasoconstriction increases resistance PROXIMALLY (more difficult for volume of blood to pass through, “traffic jam” of blood proximal ○ Total Peripheral Resistance (TPR) TPR -> Net resistance of all arteries and arterioles in the systemic circulation Diameter of all arteries and arterioles in the systemic circulation, meaning kidneys and GI tract any vasoconstriction at these sites will impact TPR If blood vessels diameter decreases due to pathologic changes (plaques or hypertrophy) will increase TPR PHYSIOLOGY FINAL STUDY GUIDE Viscosity of the Blood: “Thicker” blood (Greater) means more resistance occurs in dehydration, polycythemia, systemic clotting Reflexes ○ Reflex arc AFFERENT: input signal from specialized receptor CNS: Interpretation of afferent information EFFERENT: An output signal, from CNS to target site to produce physiologic response This process is automatic BUT higher brain centers can override Baroreceptor ○ Specialized receptors which detect changes in blood pressure Critical for maintaining short-term homeostasis of blood pressure (rapid response) ○ Abundant sites: Internal carotid arteries and Aortic arch ○ Low-pressure receptors: “Fine tuned” are found in areas of low pressure (Atria and Pulmonary Arteries), to respond to smaller fluctuations in pressure ○ Baroreceptor Reflex: Afferent signal: information of increased signals and increasing blood pressure (Baroreceptors increase action potential) CNS: Inhibition of vasoconstriction, activation of parasympathetic center Efferent: Blood pressure decreases due to vasodilation (decreased TPR, FR, and SV) Baroreceptors are able to sense decrease pressure then stimulates reflex with a strong sympathetic discharge (In a sense, saying the heart needs to pump faster) Central Nervous System ○ Vasomotor center (Reticular of Medullar and Lower Third of Pons) Vasoconstrictor area Vasodilator area Sensory area ○ Vasomotor tone: continuous activation of sympathetic nervous system causing slight vasoconstriction Adrenergic Receptors ○ Epinephrine and Norepinephrine: bind to alpha adrenergic receptors to cause vasoconstriction ○ Alpha adrenergic -> Vasoconstriction (found throughout the blood vessels) ○ Beta adrenergic-> Vasodilation (found in coronary arteries) ○ Exercise, Anxiety, Etc Alpha Receptors cause vasoconstriction of arteries thus increases TPR Vasoconstriction of veins -> increases venous return (plus EDV, SV, and CO) Beta receptors will cause an increase of cardiac contractility (increases SV and CO) PHYSIOLOGY FINAL STUDY GUIDE Vasodilation of coronary arteries will create more blood flow to the myocardium ○ Sympathetic Activation and Parasympathetic Inhibition Activation-> Arteriolar and Venous vasoconstriction with increased HR and SV Inhibition -> Increased HR Failure to pump blood out of Right Ventricle ○ If an increase resistance in the pulmonary arteries occur, the increase can create a cascade of events in the heart Increased resistance-> Right Ventricle cannot pump out blood Right Ventricle Failure-> Diastolic pressure increases Increased Right Ventricular Pressure-> Reduced pressure gradient between Right Atrium and Right Ventricle (harder for blood to exit the atrium thus more blood stays in the Right atrium) Right Atrial Pressure increase-> Reduced pressure Gradient between veins and Right atrium (decreased venous return, more blood stays in the veins) Venous Pressure Rises-> Interstitial fluid pressure and venous-end capillary hydrostatic pressure is reduced (reabsorbing fluid is harder which can lead to EDEMA) Cardiac Response to Exercise ○ Systolic blood pressure ALWAYS will increase during AEROBIC exercise (dependent on volume of active muscle) Diastolic pressure remains unchanged or can decrease ○ Metabolic Control of Blood Flow to Active Muscles During EXERCISE, vasodilators release in the ACTIVE muscle this causes an increase of blood flow, nitric oxide released as well Vasoconstriction, will cause blood to move away from non-working muscles in order to increase blood pressure All INACTIVE muscles experience vasoCONstriction (increase in TPR and BP) ACTIVE muscles vasodilate to allow more blood flow MORE muscle mass active-> Less increase of BP ○ Relationship between Muscle Mass and Blood Pressure If applying clinically, understanding exercise will involve MORE muscle mass resulting in a slight increase of BP therefore, performing WHOLE body activities could be more beneficial for patients with hypertension Week 7 Kidneys Urine Pathway: Nephrons -> papilla -> minor calyx -> major calyx -> renal pelvis -> ureter -> bladder -> urethra -> excreted to toilet Afferent = Incoming Efferent = outgoing PHYSIOLOGY FINAL STUDY GUIDE Blood Flow in kidney: Blood enters into the renal artery -> interlobar arteries -> arcuate arteries -> interlobular arteries -> Afferent arterioles -> glomerulus -> Efferent arteriole -> Peritubular capillaries -> interlobular vein -> arcuate vein -> interlobar vein -> renal vein Filtration in Nephron: Fluid filtered in Bowman's capsule -> fluid travels to proximal convoluted tubule -> fluid (glomerular filtrate) goes to Loop of Henle -> down thin descending limb -> thin ascending limb -> thick ascending limb -> goes through distal convoluted tubule -> different nephrons connect and pull fluid together Peritubular capillaries: have thin walls that allow filtration and reabsorption - Interfaces with proximal and distal tubule - Here we determine if we have reabsorption of filtrate or need more filtration out - What doesn’t get absorbed becomes urine Renal regulation of Water Balance Hydrated: If there is more water in Lumen, there is less need for reabsorption in peritubular capillary because of decreased plasma colloid pressure. More urine excreted. Dehydrated: If volume of fluid in peritubular capillary is more concentrated, more water is reabsorbed from lumen. Increased plasma colloid pressure. Less urine excreted. Hydration State Plasma Osmolarity ADH Secretion Urine Volume Urine Osmolarity Hyperhydration Decreased Suppressed Increased Low (dilute) Dehydration Increased Stimulated Decreased High (concentrated) Blood Pressure An increase in systemic BP allows the pressure of blood going to kidneys to be much higher. This increases pressure in afferent arterioles in glomerulus - which increases pressure in glomerular capillaries. A higher BP = greater hydrostatic capillary pressure around glomeruli = pushing more fluid into bowman's capsule (sodium, H20), = more filtrate LOW systemic blood pressure Juxtaglomerular cells -> signals juxtaglomerular apparatus -> the juxtaglomerular apparatus secretes renin - Renin finds angiotensinogen and activates it into Angiotensin 1 - Angiotensin 1 circulates blood stream and goes into lung and meets Angiotensin Converting Enzyme (ACE) from the lungs - ACE modifies Angiotensin 1 to Angiotensin 2 PHYSIOLOGY FINAL STUDY GUIDE - Angiotensin 2 releases aldosterone (from adrenal gland) - Aldosterone helps retain sodium Angiotensin 2 in blood - Vasoconstricts arteries - Increases cardiac output, increases TPR, Increases BP - Vasoconstricts Veins - greater venous return, stretches out ventricle - Increased EDV, increased contractility, increased stroke volume, increased cardiac output, increased BP Increased sodium intake - Increased sodium levels - Increased osmolarity in blood - Osmoreceptors recognize this and send signals of thirst in anterior hypothalamus - This leads to increase in sodium and overall fluid - Greater extracellular volume - Vasoconstriction - Greater venous return - stretches out ventricle, Increased EDV, increased contractility, increased stroke volume, increased cardiac output, increased BP Chronic increased sodium intake - Vasculature and tubule physiological changes - Less effective in voiding sodium through urine - High sodium retention - Hypertension Diuretics - Prevent reabsorption of sodium - Is an ACE inhibitor - Shuts down conversion of angiotensin 2 - Less aldosterone produced - Less sodium retention - More sodium voided - Contributes to lower BP Hormonal Regulation Hormone Source Effect on Kidney ADH (Vasopressin) Posterior Increases water reabsorption in collecting ducts by Pituitary increasing cell permeability. PHYSIOLOGY FINAL STUDY GUIDE Aldosterone Adrenal Increases sodium reabsorption in distal tubules and Cortex collecting ducts. ANP (Atrial Natriuretic Heart Inhibits sodium reabsorption, increasing sodium and Peptide) water excretion. Acid Base Balance and the Role of the Kidneys Key Processes Details Reaction CO2 + H2O ↔ H2CO3 ↔ H⁺ + HCO3⁻ (catalyzed by carbonic anhydrase). Hydrogen Ions (H⁺) Increase acidity; excreted by the kidneys. Bicarbonate Ions Act as a buffer; reabsorbed by the kidneys to maintain (HCO3⁻) blood pH (~7.4). Kidney's Role in pH Details Regulation Acidosis (low pH) Increases H⁺ excretion and HCO3⁻ reabsorption. Alkalosis (high pH) Reduces H⁺ excretion and HCO3⁻ reabsorption. Outcome Maintains systemic acid-base balance through dynamic adjustments. Micturition Reflex (Urination) PHYSIOLOGY FINAL STUDY GUIDE Bladder Anatomy Details Detrusor Muscle Smooth muscle responsible for bladder contraction; under involuntary control. Internal Urethral Involuntary muscle that controls urine retention. Sphincter External Urethral Voluntary skeletal muscle that allows conscious Sphincter control over urination. Nervous System Role in Micturition Regulation Sympathetic (L1- Relaxes detrusor (allows filling) and contracts internal L2) sphincter (retains urine). Parasympathetic Contracts detrusor (initiates voiding) and relaxes internal (S2-S4) sphincter (releases urine). Somatic (Pudendal Controls external sphincter for voluntary urination. Nerve) Urination Details Process Filling Phase - Sympathetic activation relaxes bladder and contracts internal sphincter. - External sphincter remains closed. Voiding Phase - Parasympathetic activation contracts bladder and relaxes internal sphincter. - External sphincter relaxes voluntarily. Bladder Details Compliance PHYSIOLOGY FINAL STUDY GUIDE Low Pressure Bladder stretches (high compliance) to store increasing urine Storage volume with minimal pressure rise. High Pressure At ~400-500 mL, pressure increases, triggering the micturition Trigger reflex (urge to urinate). Kidney Function and Glomerular Filtration Rate (GFR) Concept Details Definition of GFR Volume of plasma filtered by kidneys per minute (~90-120 mL/min in healthy individuals). Sympathetic Role Vasoconstricts afferent arterioles, reducing GFR during stress or low blood pressure to conserve fluids. Parasympathetic Minimal direct role but supports kidney function during rest. Role Clinical Decreased GFR indicates kidney dysfunction (e.g., acute injury or Significance chronic kidney disease). Chronic Conditions Affecting Kidney and Bladder Condition Effect on Kidney Function Hypertension - Sympathetic overactivation causes glomerular hypertension. - Leads to proteinuria, scarring, and chronic kidney disease. Diabetes - Excess glucose increases sodium reabsorption and hyperfiltration. - Sustained damage causes scarring and protein loss. Kidney Details Dysfunction and Exercise Fatigue and Impaired acid-base and electrolyte balance reduce muscle Weakness efficiency. PHYSIOLOGY FINAL STUDY GUIDE Fall and Fracture Muscle weakness, neuropathy, and reduced Risk calcium/vitamin D levels increase risks. Edema Impaired fluid regulation may cause swelling, limiting mobility and exercise tolerance. Anemia Reduced erythropoietin production lowers red blood cell count, decreasing oxygen delivery during exercise. Week 8 Blood PHYSIOLOGY FINAL STUDY GUIDE Hematopoiesis and Erythropoiesis Overview Topic Details Hematopoiesis Production of all blood cells, starting from hematopoietic stem cells (HSCs) in the bone marrow. Erythropoiesis Specific production of red blood cells (RBCs) from hematopoietic stem cells, regulated by erythropoietin (EPO). (from Kidney) Main Components Hematopoiesis produces RBCs, white blood cells (WBCs), and platelets. Erythropoiesis specifically focuses on RBCs. Erythropoiesis EPO from kidneys stimulates RBC production in response to low oxygen Regulation levels (hypoxia). Blood Cell Lineage Type of Progenitor Cell Types Derived Lymphoid B lymphocytes, T lymphocytes, Plasma cells, Natural killer cells Progenitors Myeloid Progenitors Erythrocytes (RBCs), Platelets, Granulocytes (neutrophils, eosinophils, basophils), Monocytes (macrophages) Hematopoietic Stem Origin for both lymphoid and myeloid progenitors, located primarily in the Cells bone marrow. Cytokines Influence Cytokines like EPO, G-CSF, ILs influence differentiation into specific blood cells. Cytokines and Signaling Molecules PHYSIOLOGY FINAL STUDY GUIDE Cytokine/Signaling Function Molecule Erythropoietin (EPO) Stimulates RBC production in response to low oxygen (hypoxia). Granulocyte-CSF (G-CSF) Stimulates differentiation of myeloid progenitors into granulocytes (neutrophils, eosinophils, basophils). Macrophage-CSF (M-CSF) Stimulates differentiation of myeloid progenitors into monocytes (which mature into macrophages). Interleukins (ILs) Influence differentiation of lymphocytes (B cells, T cells) and immune response activation. Colony Stimulating Factors Stimulate the proliferation and differentiation of blood cell (CSFs) progenitors in response to injury or infection. Blood Cell Production and Bone Marrow Topic Details Primary Site Bone marrow (vertebrae, pelvis, sternum, ribs) produces most blood cells in adults. Fetal Hematopoiesis Occurs in the liver and spleen during fetal development, later shifting to the bone marrow after birth. Bone Marrow Contains niches for hematopoietic stem cells and supports the Function differentiation of blood cell progenitors. Long Bone In childhood, long bones (e.g., femur) are important for blood production Contribution but decrease as the person ages. Red Blood Cell (RBC) Production (Erythropoiesis) PHYSIOLOGY FINAL STUDY GUIDE Stage of Details Development Hematopoietic Stem Differentiate into erythroid progenitors in response to EPO. Cells Proerythroblasts Immature RBCs formed from erythroid progenitors. Reticulocytes Immature RBCs released into the bloodstream, mature in 1-2 days to become erythrocytes. Mature Erythrocytes Fully mature RBCs, capable of oxygen transport, and lack a nucleus to prevent self-repair. Erythropoietin (EPO) Regulates RBC production by stimulating the maturation of proerythroblasts into reticulocytes, especially under low oxygen levels (hypoxia). Platelet Production Stage of Details Development Megakaryoblasts Precursor cells that differentiate into megakaryocytes. Megakaryocytes Large cells that fragment to form platelets, important for blood clotting. Platelets Fragments of megakaryocytes that circulate in the bloodstream, crucial for clotting and wound repair. Blood Cell Composition PHYSIOLOGY FINAL STUDY GUIDE Component Percentage of Total Description Blood Plasma 55-65% Mostly water (90%), with plasma proteins (albumin, globulins, fibrinogen), electrolytes, and other dissolved substances. Cellular 35-45% Includes RBCs, WBCs, and platelets. Components Hematocrit Measured as RBC The percentage of blood volume made up of RBCs, percentage in blood assessed using a centrifuged blood sample. Hematocrit and Blood Analysis Factor Details Normal Hematocrit 35-45% for adults; males typically 40-50%, females 35-45%. Levels Factors Affecting Dehydration increases hematocrit due to lower plasma volume. Physical Hematocrit fitness and exposure to high altitudes can also affect it. Critical Hematocrit Levels below 20% (acute blood loss) or low 20s (chronic anemia) are Levels indicative of severe conditions requiring urgent intervention. Spleen’s Role in Blood Cell Removal Topic Details Spleen Function Filters old or dysfunctional RBCs, removing them from circulation, and plays a key role in immune responses. Splenomegaly Enlargement of the spleen due to excessive accumulation of dysfunctional RBCs, common in sickle cell disease. PHYSIOLOGY FINAL STUDY GUIDE Spleen Rupture Splenomegaly increases the risk of spontaneous spleen rupture, often Risk requiring emergency medical attention. Exercise and Blood Volume Adaptation Details Increased RBC Exercise training stimulates the release of EPO, which increases RBC Production production, enhancing oxygen-carrying capacity. Increased Plasma Exercise also increases plasma volume, which helps maintain normal blood Volume viscosity and allows for better blood flow. Lower Blood The combination of increased blood volume and improved vascular health Pressure leads to reduced total peripheral resistance, lowering blood pressure. Blood Cell Production Outside Bone Marrow Topic Details Extramedullary Blood cell production outside the bone marrow, occurring in the liver or Hematopoiesis spleen under pathological or compensatory conditions. Conditions Severe anemia or certain blood disorders may trigger this process. Clinical Implications PHYSIOLOGY FINAL STUDY GUIDE Clinical Factor Details Reticulocytes Increased reticulocyte numbers may indicate acute blood loss or increased RBC demand due to hypoxia. Nucleated RBCs Presence of nucleated RBCs in the blood suggests accelerated hematopoiesis due to severe anemia or blood loss. Red Cell Distribution RDW measures variability in RBC size; increased RDW can indicate Width (RDW) immature or dysfunctional RBCs. 1. Hemoglobin and Iron Metabolism Structure and Function of Hemoglobin Hemoglobin's Role: Transports oxygen from the lungs to tissues and facilitates carbon dioxide removal. Structure: ○ Composed of 4 polypeptide chains (2 alpha, 2 beta) with a heme group in each chain. ○ Heme Group: Contains a porphyrin ring with an iron ion (Fe²⁺) at its center. Fe²⁺ binds oxygen molecules. ○ Oxygen Binding: Each hemoglobin molecule can carry 4 oxygen molecules (O₂). RBCs have about 270 million hemoglobin molecules, significantly enhancing oxygen transport efficiency. Breakdown of Hemoglobin 1. Senescent RBCs: ○ RBCs have a lifespan of ~120 days. ○ Removed from circulation by macrophages in the spleen and liver. 2. Components of Hemoglobin Breakdown: ○ Heme: Heme is separated from globin and converted to biliverdin (green pigment). Biliverdin is further reduced to bilirubin (yellow pigment). ○ Globins: Broken down into amino acids for recycling in protein synthesis. ○ Iron: Extracted from heme and: Recycled to produce new hemoglobin molecules. Stored as ferritin or hemosiderin in the liver for future use. Bilirubin Metabolism PHYSIOLOGY FINAL STUDY GUIDE Transport: ○ Unconjugated (indirect) bilirubin is bound to albumin and transported to the liver. Conjugation in the Liver: ○ Bilirubin is conjugated with glucuronic acid to become water-soluble. ○ Conjugated (direct) bilirubin is excreted into bile, which flows into the intestines. Intestinal Metabolism: ○ Bacteria in the intestines convert bilirubin into urobilinogen. ○ Urobilinogen is: Partially absorbed into the bloodstream and filtered by the kidneys, forming urobilin (yellow pigment in urine). Converted into stercobilin and excreted in feces (gives feces its brown color). Iron Metabolism Iron Forms: 1. Heme Iron (Fe²⁺): Found in animal products (e.g., red meat). Readily absorbed by enterocytes (intestinal cells). 2. Non-Heme Iron (Fe³⁺): Found in plant-based foods. Requires conversion to Fe²⁺ for intestinal absorption. Absorption: ○ Iron is absorbed in the duodenum: Fe²⁺ is absorbed directly. Fe³⁺ is reduced to Fe²⁺ by enzymes before absorption. ○ Once absorbed: Stored in enterocytes as ferritin (a short-term storage form). Exported into the bloodstream via ferroportin channels. In the blood, Fe²⁺ is oxidized back to Fe³⁺ and binds to transferrin for systemic transport. Storage: ○ Iron not immediately needed is stored in the liver as ferritin or hemosiderin. ○ Hepcidin, a hormone produced by the liver, regulates iron release from storage and absorption. 2. Anemia Definition: A condition characterized by insufficient oxygen transport due to: ○ Reduced RBC count. ○ Low hemoglobin concentration. ○ Dysfunctional RBCs. Types of Anemia 1. Hypoproliferative Anemia: ○ Causes: Reduced RBC production due to bone marrow failure (e.g., aplastic anemia). Nutritional Deficiencies: PHYSIOLOGY FINAL STUDY GUIDE Iron Deficiency: Results in small, pale RBCs (microcytic, hypochromic anemia). Vitamin B12/Folate Deficiency: Causes large, fragile RBCs (megaloblastic anemia). Chronic inflammation (anemia of chronic disease) alters iron metabolism, reducing hemoglobin synthesis. 2. Hemolytic Anemia: ○ Causes: Immune-mediated RBC destruction. Infections (e.g., malaria). Mechanical trauma (e.g., prolonged running leading to foot-strike hemolysis). 3. Blood Loss Anemia: ○ Causes: Acute trauma or surgery. Chronic blood loss (e.g., ulcers, menstruation). 4. Dilutional Anemia: ○ Causes: Increased plasma volume relative to RBCs, commonly observed during pregnancy. Symptoms and Complications: Symptoms: ○ Fatigue, pallor, shortness of breath. ○ Increased resting heart rate and cardiac output to compensate for low oxygen delivery. Complications: ○ Chronic anemia strains the heart, potentially leading to long-term damage. ○ Exercise capacity is reduced due to insufficient oxygen supply during activity. 3. Jaundice Overview: Yellow discoloration of skin and eyes due to elevated bilirubin levels in the blood. Types: 1. Pre-hepatic Jaundice: Excessive RBC destruction leads to elevated unconjugated bilirubin. Causes: Hemolytic anemia, sickle cell disease. 2. Hepatic Jaundice: Impaired liver function prevents bilirubin conjugation. Causes: Hepatitis, cirrhosis. 3. Post-hepatic Jaundice: Obstruction of bile ducts prevents bilirubin excretion. Causes: Gallstones, tumors. 4. Coagulation and Clotting Stages of Hemostasis: 1. Primary Hemostasis: PHYSIOLOGY FINAL STUDY GUIDE ○Vasoconstriction reduces blood flow to the injury site. ○Platelets adhere to exposed collagen and release thromboxane A2 to recruit more platelets, forming a platelet plug. 2. Secondary Hemostasis: ○ The coagulation cascade activates thrombin, which converts fibrinogen (inactive plasma protein) to fibrin. ○ Fibrin reinforces the platelet plug, creating a stable clot. Clot Dissolution: Fibrinolysis: ○ Plasmin, derived from plasminogen, breaks down fibrin to dissolve the clot. ○ Tissue plasminogen activator (tPA) facilitates plasmin formation. Disorders of Coagulation: Hemophilia: Genetic deficiency in clotting factors impairs hemostasis. Vitamin K Deficiency: Reduces synthesis of clotting factors (II, VII, IX, X). Thrombosis: Excessive clotting leads to conditions like pulmonary embolism or stroke. 5. Exercise and Blood Disorders Exercise-Induced Hemolysis: Endurance activities (e.g., long-distance running) cause RBC destruction through repetitive mechanical trauma. Iron Requirements in Athletes: Increased RBC turnover and iron losses through sweat necessitate higher dietary iron intake. Anemia and Exercise: Reduced oxygen-carrying capacity impairs performance. Anemic individuals experience earlier fatigue and reduced tolerance for physical activity. 6. Clinical Applications Erythropoietin (EPO): Stimulates RBC production, used therapeutically in cancer and chronic disease patients. Abuse in Sports: ○ Used to enhance performance by increasing hematocrit. ○ Risks: High hematocrit increases blood viscosity, leading to potential stroke or heart attack. Clinical Signs of DVT Visual Clues: ○ Asymmetry in leg size, color, or swelling between the affected and unaffected limb. ○ Redness (erythema) and swelling, particularly in the calf or thigh. ○ Difficulty visualizing anatomical landmarks, such as: Medial malleolus (ankle bone) obscured by swelling. PHYSIOLOGY FINAL STUDY GUIDE Loss of muscular definition in the affected limb. Key Symptoms: ○ Pain or tenderness, often described as aching or cramping. ○ Localized warmth over the affected vein. ○ Possible petechiae (small red spots) or other discoloration. Comparison: ○ A normal limb will show clear muscular definition and landmarks (e.g., tibia, malleoli). ○ The DVT-affected limb may appear larger, redder, and warmer, with reduced definition. Examples of DVT Observations 1. Lower Extremity DVT: ○ Classic Presentation: A visibly swollen calf or thigh with redness and asymmetry. The skin may appear taut due to edema. Associated symptoms like pain upon palpation or movement. ○ Case Note: A significant difference in leg size, particularly in the calf and ankle regions, is a hallmark sign. 2. Upper Extremity DVT: ○ Example Scenario: A patient developed arm swelling and redness following arthroscopic shoulder surgery. Swelling extended from the armpit (axillary region) to the forearm. ○ Considerations: Post-surgical swelling is common, but redness extending beyond the surgical site or involving significant axillary fluid accumulation warrants suspicion for DVT. 3. Darker Skin Tones: ○ Challenge: Redness may not be as visually prominent in darker skin tones. ○ Focus: Asymmetry in leg size, warmth, and swelling becomes more critical in identifying DVT in such cases. Diagnostic and Visual Clues Red Flags: ○ Acute changes in leg or arm size. ○ Skin discoloration, ranging from redness to cyanosis (bluish hue in severe cases). ○ Swelling that extends into the foot, ankle, or thigh, with differences in skin tone or texture. Additional Observations: ○ Presence of varicose veins in a limb may suggest venous insufficiency but does not exclude DVT. ○ Signs of cellulitis (dermal infection) may coexist with DVT, complicating the diagnosis. Cellulitis-associated redness often spreads along a distinct pattern. Clinical Urgency PHYSIOLOGY FINAL STUDY GUIDE Immediate Referral: ○ Any suspicion of DVT should prompt immediate referral to the Emergency Room. ○ Delaying referral increases the risk of embolization, leading to potentially fatal complications such as pulmonary embolism. ○ Clinical Decision: Referral should not be delayed even if the presentation seems mild. Early imaging (e.g., ultrasound) is crucial. Risk Factors and Considerations General Risk Factors: ○ Immobility (e.g., prolonged flights, post-surgery recovery). ○ Pregnancy and postpartum period. ○ Use of hormonal therapies or oral contraceptives. ○ Inflammatory conditions (e.g., cancer, autoimmune diseases). Specific Case Example: ○ A patient with a recent COVID-19 vaccination developed upper extremity DVT within two days. ○ Although rare, such cases highlight the need for vigilance after procedures or vaccinations. Athletes: ○ Endurance athletes may be prone to DVT due to: Muscle damage and inflammation. Dehydration and blood thickening during prolonged activity. Lungs Week 9-10 Definitions first ○ Ventilation - Movement of air through airways ○ Gas Exchange - Diffusion of Oxygen and carbon dioxide between the alveoli and blood stream ○ Gas Transport - Transportation of Oxygen or Carbon dioxide in blood and body fluid to and from the body’s tissue cells ○ Hemoglobin - Oxygen binding molecule in RBCs ○ Tidal Volume - Air moved with each breath ○ Respiratory Frequency - Breaths per minute ○ Minute Ventilation - Tidal volume X Respiratory Frequency - AKA Ventilatory Equivalent (VE) ○ Eupnea - Normal ventilatory rate and depth ○ Hyperpnea - Normal elevated ventilatory rate AND depth which MEET metabolic demand like during exercise ○ Hyperventilation -Elevated ventilatory rate and depth which exceeds metabolic demand ○ Tachypnea - Increased respiratory RATE, but NOT an increase in tidal volume “Shallow” breaths ○ Apnea - Stoppage of Ventilation ○ Dyspnea as symptom - Patient states that it is difficult to breath PHYSIOLOGY FINAL STUDY GUIDE ○ Dyspnea as sign - A clinician can observe signs of distress, gasping for air, accessory muscle breathing, pursed-lip breathing, etc ○ Phonation- Vocal cords are under control of somatic nervous system and control voice and our breathing ○ Abnormal vocal cord control - Ex. Exercise-induced laryngeal obstruction - Stridor - High pitched inspiratory sound ○ ○ Partial Pressure - ○ Perfusion - Mechanism of Pulmonary Ventilation ○ Big picture ○ Inspiration Resting - Contraction of diaphragm lengthens thoracic cavity to decrease intrapleural pressure and bring air into lungs Active - Additional muscle control for greater expansion of cavity External intercostals SCM Serratus Anterior Scalenes ○ Expiration Resting - Passive - Air is driven out of lungs by recoil of lungs, chest wall Active - Muscle control for greater force of exhale Rectus Abdominis Internal Intercostals Respiratory centers within the brain ○ Medulla Dorsal Respiratory Group - DRG Chiefly controls inspiration with respiratory ramp Diaphragm External intercostals Ventral Respiratory Group - VRG (inactive at rest) Chiefly controls expiration during heavy ventilation Actives accessory muscles - Internal Intercostals and rectus abdominis ○ Pons Apneustic Center Respiratory ramp - Gradually increases the signals sent to the DRG Causes a slow increase of signals to begin inspiration Pneumotaxic Center - Controls rate and depth Overrides the Apneustic center to stop signaling DRG Stopping inspiration Gets input from mechanoreceptors in lungs to detect stretch PHYSIOLOGY FINAL STUDY GUIDE Valsalva Maneuver Phases ○ Phase 1 Increase thoracic pressure - Vena Cava empty into R atrium Increase pressure in Right Atrium - Bainbridge Reflex Increase Stroke Volume - Increased Afterload ○ Phase 2 - Maintained increase in intrathoracic pressure Decreased venous return Decreased cardiac output Main Problem: Drastic reduction in cardiac output can cause fainting (syncope) or further cardiac ischemia ○ Phase 3 Intrathoracic pressure on the vena cava decreases Systolic blood pressure remains low during Baroreceptors are still firing at a high rate during Phase 3 Main Problem The coronary arteries can fill with more blood This sudden surge of blood (following a limited flow) could potentially destabilize a plaque or clot to cause a myocardial infarction ○ Phase 4 Cardiac output QUICKLY increases Systolic blood pressure QUICKLY increase Main Problem These quick increases in cardiac output abruptly raise blood pressure (albeit temporarily) This can potentially dislodge clots or rupture aneurysm Cough and sneeze consequences ○ In patients with recent thoracic or abdominal surgery, this could disrupt surgical repairs ○ In patients with thoracic or abdominal trauma, can disrupt healing or exacerbate trauma ○ This causes a sudden increase in blood pressure In patients with recent thoracic or abdominal surgery, this could disrupt surgical repairs In patients with recent brain surgery or brain vascular disease, this could increase intracranial pressure and cause damage (e.g. rupture aneurysm Cough Reflex ○ Larynx, Carina, or trachea mechanical or chemical stimulation ○ Afferent nerve impulses travel from vagus nerve to medulla ○ Rapid Inspiration ○ Epiglottis closes ○ Forceful Abdominal and intercostal contraction ○ Increase in pressure in lungs PHYSIOLOGY FINAL STUDY GUIDE ○ Sudden opening of epiglottis ○ Air explodes out Sneeze Reflex ○ Same as above but Initiated by irritation in nasal pathways (not trachea/Carina) Afferent impulses pass through fifth cranial nerve Uvula depressed to allow airflow through nose WEEK 10 Lungs Airway Anatomy Airway Anatomy ○ Cartilage decreases distally in airway ○ Smooth Muscle where there is no cartilage in bronchioles Airway resistance ○ Larger diameter will be lower resistance ○ Inspiration - airway resistance decreases As the lungs inflate, all tissues get pulled apart and opened ○ Expiration - Airway resistance increases As lungs deflate, tissues are compressed and size decreases ○ Bronchoconstriction - narrowing of bronchioles Parasympathetic (Acetylcholine) ○ Bronchodilation - expansion of bronchioles Sympathetic (Norepinephrine and epinephrine) ○ Pathologies of airway resistance Smooth muscle contraction (asthma attack) Inflammation (edema) Blockages in airway lumen (Mucus, foreign objects) ○ Medical interventions to reduce airway resistance Bronchodilators (activate B-adrenergic receptors - dilation) Inhaled steroids (reduce inflammation) Effects of decreased lung compliance (ie increased lung stiffness) ○ Takes more effort to inflate lungs ○ Lungs will not fill as well or as fully ○ Lung recoil is reduced and more effort for expiration Summary - Impaired gas exchange and increase ATP demands Partial pressure ○ Partial pressure is the atmospheric pressure multiplied by the percentage of the gas in the air 760mmHg X 21% O₂ = 160 mmHg O₂ Fraction inspiratory oxygen ○ FᵢO₂ - is the percentage of the air we breathe that is oxygen Normal atmosphere is 21% You can adjust this with supplemental oxygen PAO₂ = Alveolar partial pressure of oxygen ○ About 100-105mmHg at sea level PHYSIOLOGY FINAL STUDY GUIDE ○ Note, this is an UPPERCASE “A” \ PaO₂ = Systemic arterial partial pressure of oxygen ○ About 100mmHg at sea level (about the same as in the alveoli) ○ Note, this is a lowercase “a” PvO₂ = Systemic venous partial pressure of oxygen ○ About 40mmHg at sea level while at rest ○ DECREASES during exercise (as we extra more oxygen out of the blood at the level of the capillaries) Gas exchange ○ Gasses flow down concentration gradients High PAO₂ - low PvO₂ so O₂ gas flows into bloodstream ○ Oxygen travels through cells of lungs and interstitial space to get into capillary If there is pathology with any of the layers it will slow O₂ diffusion Ventilation-Perfusion Matching ○ Big picture - for gas to be exchanged between the alveoli and the bloodstream, there must be blood flow to the alveoli and proper airflow into alveoli If air or blood are restricted then there will not be adequate diffusion of Oxygen ○ Pulmonary embolism Blocking blood flow in one large or multiple small blood clots Causes a lack of perfusion to alveoli - no gas exchange Exercise changes ○ Increased open capillaries ○ Less resistance blood flow ○ Increase rate of blood flow Blood gas transport ○ Oxygen Bound to hemoglobin (97%) Dissolved (3%) ○ Carbon Dioxide Bicarbonate (~70%) Bound to hemoglobin (