midterm Flashcards

Question

Regulation of blood pressure (not flow) - brain centers - controlling MAP

Answer 1

• The body homeostatically regulates blood pressure by regulating mean arterial pressure (MAP) • Blood pressure is regulated by higher brain centers as well o Hypothalamus – mediates vascular responses for body and fight or flight responses o Cerebral cortex – learned and emotional responses (ex. blushing, fainting in response to blood or needles) • Respiratory and CV system work in tandem – increased CV activity usually results in increased respiration MAP = CO x TPR (where CO = HR x SV). MAP can be regulated by controlling (all will affect accumulation of blood in blood vessels): 1. Cardiac output a. By increasing or decreasing heart rate b. By increasing or decreasing the force of contraction – alter stroke volume. c. By increasing or decreasing venous return. 2. TPR (Total Peripheral Resistance) a. By increasing or decreasing vasoconstriction/vasodilation (arteriolar radius) – this is what is believed to cause hypertension most of the time 3. Blood Volume a. Can influence MAP indirectly – Increasing/decreasing blood volume  increases/decreases venous return  increases/decreases stroke volume. i. Kidney – can decrease or conserve water volume; cannot increase ii. Drinking or IV – required to increase volume iii. CV compensation – constriction/dilation through SNS; has limitations b. Also increases MAP directly – increases the hydrostatic pressure of the blood (pressing harder against the walls of the vessels) 4. MAP will also depend on distribution of blood in arteries and veins a. Arteries – low volume; only contain ~11% b. Veins – high volume; contain ~60%; can act as a reservoir where venous constriction causes increase in venous return & redistribution of blood to the arterial side (SNS can cause)

Answer 2

1. Baroreceptor reflex control – autonomic reflex; single most important mechanism for short term regulation of MAP (causes changes in TPR and CO); extremely fast response; always functioning a. Process i. Stimulus: changes in blood pressure (MAP) and pulse pressure ii. Receptors: Mechanical stretch receptors (baroreceptors) in aortic arch (monitors BP flowing to body) and carotid sinuses (measures BP flowing to brain) 1. Tonically active – frequency of firing AP in baroreceptor cells is directly proportional MAP within physiological limits 2. Exhibit adaptation – firing will initially increase/decrease; prolonged exposure to higher/lower MAP causes them to adapt firing to normal levels (hence short term) iii. Sensory nerves (input signal) project from the baroreceptors to the cardiovascular control center in the medulla (CVCC, integration center). 1. Medullary CVCC – controls output by sending signals through vagus nerve (PSNS) and sympathetic nerves (SNS) to heart and blood vessels (effectors); antagonistic control 2. Effector response that is opposite to initial stimulus – neg feedback b. At any given MAP, if pulse pressure increases, firing rate also increases c. Decreased MAP i. Ex. hemorrhage – causes a decrease in MAP and blood volume ii. Baroreceptor – only works to bring back towards normal MAP 1. Decreased MAP  decreased arterial wall stretch  decreased baroreceptor firing  CV control increases SNS (NE, E) and decreases PSNS a. SNS (NE, E) – increases vascular tone, increases ventricular contraction, increases SA node firing b. PSNS (Ach) – decreases effect on SA node 2. Results in – increased vascular constriction & increased TPR, increased EDV, increased SV, increased HR  increased MAP iii. to restore MAP – lost fluid must be replaced by shift in fluid balance or blood transfusion 1. decreased capillary hydrostatic pressure  decreased capillary filtration 2. increased AVP and angiotensin II  increased blood volume d. Increased MAP i. increased MAP  increased firing of baroreceptors in carotid artery and aorta  activation of sensory neurons  CV control 1. increased PSNS (Ach) – slowing of SA node 2. decreased SNS (NE, E) – arteriolar smooth muscle, ventricular myocardium, SA node ii. result in – decreased heart rate, decreased force of contraction, vasodilation & decreased TPR  decreased MAP e. Changes in BP can change – CO, TPR, or both (only one may be effective at a specific time) i. Can be activated as a result of local regulation ii. ex. increased BP causes vasoconstriction (local regulation) – constriction causes increase in MAP – activates baroreceptor 1. vasoconstriction has already been activated – CV center will likely decrease CO in order to decrease MAP f. Orthostatic hypotension triggers baroreceptor reflex – standing causes pooling of blood at feed & decreases venous return i. Venous return falls from 5L/min to 3L/min – causes decrease in MAP ii. Baroreceptor response – causes increased CO and TPR & increase MAP iii. Skeletal muscle pump – increased venous return when abdominals and leg muscles contract to maintain upright position 2. Blood volume control – long term regulation of MAP a. Indirect effect of blood volume on MAP i. Changes in blood volume increase/decrease MAP  influences venous pressure, venous return, EDV and SV  all affect cardiac output ii. MAP = CO x TPR  change in CO due to a change in volume will change MAP b. Direct effect of blood volume on MAP i. Increased blood volume increases the hydrostatic pressure on the walls of the arteries. c. Blood volume is regulated by hormones secreted by the brain, kidneys and heart – hormones influence fluid intake and urine output. i. Vasopressin (ADH) – from posterior pituitary; increases blood volume 1. Increases H2O reabsorption by the kidneys (diuretics increase the volume of urine produced and decrease blood volume; ADH does the opposite) 2. Also causes vasoconstriction ii. Renin – from kidney; increases blood volume 1. Triggers the conversion of plasma angiotensinogen into angiotensin II 2. Stimulates ADH release – increases H2O reabsorption by the kidneys iii. Atrial Natriuretic Peptide (ANP) – from heart; decreases blood volume 1. Increases Na+ and H2O excretion by the kidneys 2. Inhibits vasopressin secretion 3. Inhibits renin secretion (and production of angiotensin II). 4. Result: all together these responses increase urine output and reduce thirst

Answer 3

1. Failures of pressure homeostasis – slow changes in MAP result in “resetting” of baroreceptors (adaptation) and CV responses a. Opposes minute to minute changes but are only activated at the adjusted higher or lower pressure level – response to deviations from new set point 2. Hypotension – low MAP; flow out exceeds flow in & volume decreases a. Perfusion is not fast enough to clear wastes and bring in nutrients and oxygen b. May not be able to overcome gravity and o2 supply to brain is impaired (causes dizziness) 3. Hypertension – high MAP; typically due to chronic increase in TPR a. Flow in exceeds flow out & blood volume increases i. Perfusion is too fast to allow for adequate exchange between the blood and tissues ii. Walls of BV may cause weakened areas to rupture and bleed into tissues 1. cerebral hemorrhage – rupture occurs in brain; can cause stroke 2. can be fatal if it occurs in a major artery b. Primary hypertension i. Causes – obesity, stress, cholesterol, smoking, genetics, Na+ retention, and immune system responses 1. Initially – leads to ventricular hypertrophy (increase in cell size) 2. Eventually – myocardial contractile function diminishes over time & leads to congestive heart failure and edema 3. Increases risk of atherosclerosis, heart attack, kidney damage, and stroke ii. Treatments 1. Exercise, ↓ Na+ intake, and weight loss – lower resting MAP 2. Ca2+ channel blockers – promote vasodilation of vascular smooth muscle; decreases heart contractility and the rate of SA node depolarization 3. Diuretics (opposite function of ADH) – increase urinary excretion of Na+ and H2O; decreases CO with little effect on TPR 4. b-adrenergic receptor blockers – target b1 receptors; decreases NE and E stimulation of CO 5. Angiotensin-converting enzyme (ACE) inhibitors – blocks production of angiotensin II; decreases TPR c. Secondary Hypertension i. increase in MAP arising from other conditions (e.g. pregnancy)

Answer 4

1. 2 modes of transport – depends on lipid solubility a. Protein channels (intracellular channels) in endothelial cell membranes – transcellular b. Intercellular pores between adjacent cells – paracellular 2. Capillary density is directly proportional to metabolic activity of tissue’s cells a. Subcutaneous and cartilage – lowest concentration of capillaries b. Muscles and glands – highest 3. Structure – thinnest walls; only simple squamous endothelial layer & basal lamina a. Diameter is barely size of RBC; RBC must go singe file – allows maximum transfer of o2 4. 2 functions a. Rapid movement between capillaries and tissues – down partial pressure, electrochemical, concentration gradients i. Allows exchange sites for H2O, Na+, K+, glucose, amino acids, gases 1. Diffusion rate – determined by concentration between plasma and ISF 2. CO2 and O2 diffuse freely – will establish equilibrium by venous end ii. Mostly impermeable to macromolecules 1. Plasma proteins (e.g. albumin) are too large – they remain in capillary 2. Certain proteins can use transcytosis – selective; endocytosis into endothelial cell from plasma/ISF, exocytosis from cell on the other side iii. Velocity of flow through capillaries is very slow – due to total cross sectional & summed diameters (usually smaller = faster); there are a lot of them 1. Allows for max exchange of gases between tissues & RBC b. Maintain fluid balance between plasma and interstitial fluid. i. Distribution of ECF between plasma (25%) and ISF (75%) – state of dynamic equilibrium due to filtration and absorption of protein free fluid by capillaries ii. Due to bulk flow – driven through channels & fenestrations by hydrostatic and colloid osmotic pressure gradients (Starling forces) that augment diffusion process 1. Absorption – into capillary a. ISF hydrostatic pressure b. Plasma colloid osmotic pressure 2. Secretion – out of capillary a. Capillary hydrostatic pressure b. Colloid osmotic pressure

Answer 5

1. PC = capillary hydrostatic pressure (HP) Note in text, PC is given as PH a. HP within capillary – favours filtration b. declines as blood moves from arteriole (~37 mm Hg) to venule side (~17 mm Hg) of capillary – due to friction i. there are exceptions to this – in kidneys (only filter) and intestines (only absorb) 2. PI = interstitial fluid hydrostatic pressure a. HP outside capillary – favours absorption b. ~1 mm Hg 3. πC = plasma colloid-osmotic pressure (colloid refers specifically to osmotic pressure created by proteins) a. osmotic pressure within capillary due to nonpenetrating solutes (osmotically active) – favours absorption b. ~25 mm Hg 4. πI = colloid-osmotic pressure of interstitial fluid a. osmotic pressure due to nonpenetrating solutes within the ISF – favours plasma filtration (should be none; proteins are functionally non penetrating) b. ~0 mm Hg Net fluid movement 1. Net filtration pressure (hydrostatic pressure) a. Net P = PC – PI b. Movement due to HP – favours filtration along the entire length of capillary i. 37 – 1 = 36 mmHg ii. 17 – 1 = 16 mmHg 2. Net colloid osmotic pressure a. Net π = πC – πI b. Movement due to osmotic pressures – favours absorption along the entire capillary i. 25 – 0 = 25 mmHg 3. Net fluid movement a. Net fluid = Net P – Net π i. Arteriole end: 36 – 25 = +11 mmHg (filtration) ii. Venule end: 16 – 25 mmHg = -9 mmHg (absorption) b. Overall filtration is greater than absorption – creates excess

Answer 6

~3L/day of excess filtrate is taken up by blind ended lymphatic capillaries - Lymph passes through lymphatic vessels and lymph nodes – returns to the blood stream via lymphatic ducts & empty into veins near the jugular veins Edema – failure of this lymphatic system or disease states affecting one or more of the Starling forces produce o Causes an accumulation of ISF fluid in tissues due to: 1. Obstruction of lymph vessels • Elephantiasis – mosquito-borne filaria worms block lymphatic flow • Removal of lymph nodes – creates scarring and blockage of lymph vessels 2. Increased Net Filtration Pressure (Net P) • Lymphatic system cannot keep up • Heart failure promotes venous pooling – backing up blood into the capillaries; increases PC 3. Decreased Net colloid osmotic pressure (Net π) • Decrease in πc causes o liver disease – decreased plasma protein production o kidney disease – increased protein excretion = proteinuria o severe malnutrition – decreased protein intake • increase in πI o Histamine dilates arterioles (↑’s PC) and ↑’s intercellular pore size  increases capillary permeability for proteins

Answer 7

Blood – connective tissue specialized for transport and exchange of solute and fluids - Volume o Men - ~5-5.5L (70kg man) o Women - ~4L (58kg)

Answer 8

~3L 1/4 ECF a. Water (~90% weight) b. Dissolved solutes i. Proteins – determines plasma colloid osmotic pressure (πC ) and can act as a buffer to help maintain blood pH. 1. ~7% of weight 2. Without proteins, plasma is otherwise identical in composition to ISF a. Osmotic pressure created offsets the filtration favoured by hydrostatic pressure 3. Including: (90% is albumin, globulins, fibrinogen, transferrin) a. Albumins – 60% of all proteins i. Primarily responsible for πC (colloid osmotic pressure) ii. General carrier b. Globulins – clotting factors, enzymes, antibodies, carriers i. α, β globulins – transport lipids (cholesterol), some metal ions and hormones ii. γ (gamma) globulins are immunoglobulins/antibodies – defensive c. Fibrinogen – clotting protein (form fibrin threads) d. Transferrin – transports iron that is not part of hemoglobin e. Peptide/Protein Hormones 4. Liver makes most of the proteins and secretes them into the blood a. Some immunoglobins and antibodies are synthesized and secreted by specialized blood cells ii. Electrolytes (e.g. Na+, Cl-, H+, K+, Ca2+, HCO3-) 1. Functions: membrane excitability; buffers (HCO iii. Nutrients (e.g. glucose, amino acids, lipids, vitamins) iv. Gasses (e.g. O2, CO2, N2) v. Metabolic waste products (e.g. urea, nitrogenous waste, creatinine) vi. Trace elements and vitamins

Answer 9

~2L 1. Erythrocytes (Red Blood Cells or RBCs) a. Most numerous blood cell. Makes up >99% of blood cells. i. ~ 5 billion RBC’s per mL of blood. b. Results in flattened, biconcave disk-shaped cells – lack nucleus and organelles i. specialized for gas transport – o2 to tissues; co2 to lungs 1. do not metabolize – no mitochondria a. glycolysis is the primary source of ATP 2. unable to make new enzymes and proteins without nucleus – unable to renew membrane components; older cells are more likely to rupture ii. Shape is due to cytoskeleton components linked to transmembrane proteins 1. Flexible – able to squeeze through capillaries 2. Can modify shape due to osmotic changes in the blood (hypertonic = shrivel; hypotonic = swell without bursting due to shape) iii. Shape can change due to disease 1. Sickle cell anemia – crescent shaped 2. Spherocytosis – cells round spheres instead of flattened disk 3. Changes in size (mean corpuscular volume (MCV)) – can increase in decrease with different diseases 4. Hypochromic – pale c. Short-lived (~120 days) – rapidly produced in bone marrow i. May rupture as they try to squeeze through capillaries; may be phagocytized by macrophages d. Contain Hemoglobin (Hb) – oxygen transport i. Adult Hb (HbA) structure – most commonly (there is some variation) 1. Two a-globin 2. Two B-globin protein chains 3. Each globin are bound to an iron containing heme group. ii. Globin = protein chains; binds and transports CO2 iii. Heme = Red pigment molecule  porphyrin ring surrounding an iron (Fe2+) atom that reversibly binds to O2. 1. 70% of iron in body is found here 2. There are 4 hemes per Hb molecule – each Hb transports 4 O2; 4 Heme groups are identical 3. Gives blood its red colour which can be seen through skin as a pink colour especially in areas of thin skin (ex. the lips) iv. Iron metabolism for Hb synthesis 1. Iron from diet actively transported into blood - process a. transferrin binds Fe2+ after absorption in sm. Intestine and transports it to the blood b. taken up by bone marrow and used for heme  Hb  RBC 2. Excess iron is stored in liver – ferritin proteins store until required a. Excess iron is toxic e. RBCs live 120 days and are then broken down in spleen – many components are recycled i. Heme: 1. iron removed – stored in liver (as ferritin), muscle, & spleen to be recycled for future use. 2. Porphyrin ring  converted to bilirubin – coloured pigment; excreted in bile & feces; also filtered from blood into urine (metabolites of bilirubin give feces and urine their colour). a. Jaundice = excess bilirubin in blood DOES NOT CAUSE REDUCED HEMATOCRIT i. Causes 1. excess RBC breakdown 2. liver dysfunction a. Common in neonatal infants because their livers are not yet fully functional – phototherapy oxidizes bilirubin and allows for excretion 3. blockage of bile excretion ii. Symptoms – yellowing of skin and sclera of eye. ii. Globin: converted to amino acids and recycled. 2. Leukocytes (White Blood Cells or WBCs) – mobile cells that play a key role in the body’s immune system response (protection) a. Primarily act outside bloodstream b. The only fully functional cells in circulation i. Function in body immune response – defend against parasites, bacteria, viruses ii. Circulate through the body in the blood – work is usually carried out in tissues 3 subgroups c. Immunocytes – responsible for specific immune responses against invaders i. Lymphocytes – produced directly from Pluripotent stem cell. 1. T lymphocytes and B lymphocytes that produce specific immune responses involving antibodies directed against invaders d. Phagocytes – develop from the same committed progenitor cell; can engulf and ingest foreign particles via phagocytosis i. Monocytes – will leave circulation and develop into macrophages in the tissues ii. Neutrophils – also a granulocyte; first cells to exit capillaries and enter tissues in response to infection e. Granulocytes – contain cytoplasmic inclusions that give them a granular appearance i. Eosinophils – produce toxic compounds directed against pathogens (especially parasites) ii. Basophils (in tissues = mast cells) – secrete histamines (increases inflammation) and heparin (inhibits local clotting) iii. Also neutrophils 3. Platelets (formed from megakaryocytes). a. Cellular elements produced from fragmentation of large bone-marrow cells – parent megakaryocytes i. Grow so large due to repeated DNA replication without undergoing division (polyploid cells) ii. Outer edges of megakaryocytes extend through endothelium into lumen of blood sinuses in bone matrix – fragment into platelets b. Smaller than RBC – colourless and anucleate i. Still have organelles – mitochondria, SER, granules (cytokines and growth factors) c. Always present – lifespan is ~10 days d. Primary function is hemostasis – prevention of blood loss via coagulation in damaged blood vessels i. Also function in immunity – mediators of inflammatory response

Answer 10

1. % of blood that is erythrocytes - On average ~42% (women) and 47% (men) 2. Determined by Complete Blood Count (CBC). a. Blood is centrifuged – blood column separated into 3 layers: i. RBCs packed at the bottom of the tube – heavy ii. Middle layer of WBCs (also known as the buffy coat) iii. Upper layer of plasma – lightest b. Percentage of the blood column that is packed RBCs = hematocrit. 3. High hematocrit - can indicate a. Dehydration b. Polycythemia vera – condition causes the body to produce too many blood cells (both RBCs and WBCs), in which case hematocrit may be elevated to 60—70% c. Blood becomes viscous and more resistant to flow 4. Low hematocrit – anemias  low hemoglobin content of blood; decreases its ability to carry oxygen a. Occur due to i. Blood loss (hemorrhage) ii. Accelerated rate RBC loss iii. Decreased RBC production. b. Symptoms – tired and weak c. Examples: i. Hemolytic anemias – cells rupture at abnormally high rate; can be hereditary or acquired. 1. Hereditary spherocytosis – defective cytoskeletal elements change cell shape to a sphere that ruptures easily in response to osmotic changes. 2. Parasitic infections (acquired) such as malaria – parasite infects RBCs, proliferates and ruptures cells. ii. Sickle cell anemia – genetic disorder affecting amino sequence hemoglobin beta chain 1. Hb crystalizes when it gives up o2 – pulls RBC into crescent moon shape a. Become tangled – causes blockages in blood flow to tissues; creates tissue damage and pain 2. Can be treated with hydroxyurea – inhibits DNA synthesis; immature RBC produce fetal instead of adult Hb which interferes with crystallization iii. Aplastic Anemia – bone marrow has few stem cells, so all blood cell production is reduced (including RBCs). iv. Iron Deficiency Anemia – low iron levels due to dietary deficiencies, blood loss (e.g. menstruation), inability to absorb iron (e.g. Celiac’s disease which damages absorptive surface of intestine) 1. less iron  less heme  less hemoglobin 2. can have low RBC or low Hb – RBC are usually smaller and paler than normal v. Vitamin Deficiency Anemia - 1. Dietary deficiency or trouble absorbing Folic acid, Vitamin C, or Vitamin B12 leads to abnormal RBC production (fewer cells, & larger cells).

Answer 11

production of formed elements from pluripotent hematopoitic cells in the bond marrow 1. Pluripotent stem cells can develop into many types of cell types a. Become uncommitted stem cells  then progenitor cells  differentiate into RBC, WBC, and megakaryocytes b. Only 1 in 100,000 cells in bone marrow is an uncommitted cell – difficult to study and isolate i. Presents an therapeutic agent for cancer patients – can use blood from umbilical cord at birth 2. Bone marrow – soft tissue that fills hollow centers of bone; contains blood cells in different stages of development and supporting tissue a. Red marrow = active hematopoiesis i. Hematopoiesis – synthesis of blood cells; begins early in embryonic development and continues throughout lifetime 1. 3rd week fetal development – specialized cells in the yolk sac form clusters a. Some become endothelial lining of blood vessels & some become blood cells b. Relationship could explain why cytokines controlling hematopoiesis are released by vascular endothelium 2. Continued development – blood cell production spreads to liver, spleen, bone marrow 3. At birth – liver and spleen no longer produce blood cells 4. Continues in all bone marrow until age 5 – continued aging of child into adult will see a decrease in the active regions of bone marrow in blood cell production 5. Adults – pelvis, spine, ribs, cranium, proximal ends of long bones are active regions ii. Active bone marrow – red due to hemoglobin (o2 binding protein of RBC) 1. 25% of cells are RBC a. Lifespan is about 4 months 2. 75% are WBC a. Lifespan is much shorter – must be replaced more frequently i. ex. neutrophils – 6 hour half life; more than 100 million are produced every day b. Yellow marrow = inactive hematopoiesis i. Yellow due to high concentration of adipocytes ii. Inactive regions can resume cell production in times of need

Answer 12

Peptides or proteins released from one cell that affects the growth or activity of another cell; regulates specialization of stem cells into specific blood cells - Newly discovered cytokines are often called factors Types a. Interleukins (e.g. IL-3) i. variety of functions including stimulation of uncommitted stem cells to form committed progenitor cells. 1. Important role in immune system ii. Produced and released by WBCs to act on other WBCs iii. Numbered once their AA sequence has been identified b. Erythropoietin (EPO) i. Stimulates and controls erythropoiesis (red blood cell production) – assisted by other cytokines 1. Usually called a hormone – still a cytokine because it’s made on demand instead of being stored in vesicles like other peptide hormones are 2. Homeostatic – increased EPO production  more RBC  more hemoglobin  can bind more o2 ii. produced and released by the kidneys in response to low oxygen levels (hypoxia) 1. hypoxia stimulates production of transcription factor hypoxia-inducible factor 1 – turns on EPO gene to increase EPO synthesis 2. People who are adapted to live at high altitude have a higher hematocrit as a result. iii. Erythroblasts (nucleated)  Reticulocyte  Erythrocyte (anucleate) 1. Committed progenitor will differentiate into nucleated erythroblasts – maturation causes shrinking and loss of nucleus and other organelles 2. Leaves bone marrow as immature reticulocyte (anucleated) – enters circulation and matures into erythrocyte 3. Results in flattened, biconcave disk-shaped erythrocytes – lack nucleus and organelles. iv. Took a very long time to identify AA sequence but was used clinically very quickly 1. Erythropoiesis stimulating agents – can be beneficial to cancer patients; risk of blood clotting 2. There is possible risk of hematopoietic drugs causing hemtological disease c. Colony Stimulating Factors (CSFs) i. stimulate leukopoiesis (white blood cell production) – induces cell division and cell maturation in stem cells 1. once a leukocyte matures – it loses its ability to undergo mitosis ii. Secreted by endothelial cells, fibroblasts in bone marrow, and other leukocytes. 1. WBC are able to produce – allows leukocyte development to be tailored to bodies’ needs iii. Responds to need. (e.g. during bacterial infection, CSFs stimulate production of neutrophils and monocytes.; viral infections cause increase in proportion of lymphocytes). 1. When WBC are required – absolute number of leukocytes and relative proportions of different types of leukocytes in circulation change a. Clinically – differential white cell count assists in identification of type of infection (ex. bacterial vs viral) i. Controlling leukopoiesis – can assist in developing treatments for diseases that lack or have excessive amounts of leukocytes 1. Leukemias – diseases with abnormal growth and development of leukocytes 2. Neutropenia – too few leukocytes; unable to fight bacterial and viral infections d. Thrombopoietin (TPO) – glycoprotein (thrombocyte = platelet) i. regulates growth and development of megakaryocytes (and therefore platelet production). ii. Produced and secreted by the liver. iii. Not everything about them is understood

Answer 13

pluripotent hematopoietic stem cell lymphatic stem cell -> lymphocyte ``` uncommitted stem cell -> committed progenitor 1. - eosinophils 2. - basophils 3. neutrophil - monocyte 4. megakaryocyte -> platelets 5. erthythroblast -> reticulocyte -> erythrocyte ```

Answer 14

Preventing blood loss 1. Vasoconstriction (vascular spasm) a. Damage to blood vessel wall activates local pain receptors – triggers an increase in sympathetic activity & vasoconstriction that reduces blood flow to the site of damage. b. Platelets stick to exposed collagen fibers (not normally accessible since they’re in the ECF) and release platelet factors – ions/molecules/cytokines i. Some reinforce vasoconstriction including: 1. Serotonin (from secretory vesicles of platelets) 2. Thromboxane A2 (from platelet membrane) 2. Platelet Plug Formation a. Platelet adhesion – platelets stick to exposed collagen and release factors that attract other platelets to the site (positive feedback); fill in damaged area & form platelet plug. i. Integrins – membrane receptor proteins linked to cytoskeleton; allows binding & activates platelets and release platelet factors b. Platelet factors involved in aggregation: i. Platelet Activating Factor (PAF) – sets up positive feedback loop by activating more platelets 1. Initiates pathway that convert platelet phospholipids to thromboxane A2 ii. Serotonin (from secretory vesicles of platelets) 1. Also causes vasoconstriction iii. Adenosine diphosphate (ADP) (from platelet mitochondria) iv. Thromboxane A2 (from platelet phospholipids) 1. Also causes vasoconstriction c. Platelet plug formation cannot spread beyond the site of injury due to secretion of prostacyclin and nitric oxide (NO) from surrounding endothelial cells – blocks adhesion and aggregation i. Prevents thrombus – blood clots that adheres to undamaged blood vessel and blocks flow ii. Mutations affecting platelet function – can lead to clotting (heart attacks, strokes) or excessive bleeding 3. Coagulation (Clot Formation) – blood forms gelatinous clot a. Cascade/Network of factor interactions activated through two pathways almost simultaneously – will merge into one i. Intrinsic Pathway (Contact Activation Pathway) 1. Initiated by factors in blood exposed to collagen a. Collagen  activates tissue factor XII) ii. Extrinsic Pathway (Cell Injury/Tissue Factor Pathway) 1. Initiated when damaged tissues expose tissue factor a. Tissue Factor III/tissue thromboplastin  activates factor VII b. Each pathway results in activation of Factor X – formation is the start of the common pathway i. Factor X: 1. Combines with Ca2+, Factor V, and phospholipids – forms prothrombin activator. a. Prothrombin activator – converts prothrombin (inactive plasma protein) to thrombin (active) 2. Positive feedback onto extrinsic pathway – actives more Factor VII and tissue factor III c. Thrombin – enzyme i. Acts on Fibrinogen (soluble clotting protein in plasma) – produce insoluble Fibrin polymers. 1. Fibrin – forms a web of thread-like protein that covers the platelet plug and traps formed elements (RBCs). ii. Exerts positive feedback on intrinsic pathway - activates more Factor XI = plasma thromboplastin d. 2 dozen factors are involved – obtained from the diet, liver (plasma proteins), damaged tissue, and platelets i. Active Factor XIII (Fibrin Stabilizing Factor) – converts fibrin into a cross-linked polymer, and stabilizes the clot. ii. Vitamin K – required for synthesis of 4 factors (II, VII, IX, X) e. Clots – only temporary fix 4. Fibrinolysis (Clot Dissolution) – after blood vessel wall has been repaired a. Plasmin – fibrin digesting enzyme; breaks down clot (fibrinolysis) i. Thrombin and tissue plasminogen activator (tPA) – convert plasminogen (inactive) in clot to plasmin (active) b. Phagocytes remove the clot in clumps. SEE FLOW CHARTS

Answer 15

2 mechanisms limit the spread of clot 1. Inhibition of platelet adhesion 2. Inhibition of the coagulation cascade and fibrin production a. Anticoagulants – produced by the body & block parts of coagulation cascade  Body produces: • Heparin – inhibit active Factors IX-XII • Antithrombin III – inhibit active Factors IX-XII • Protein C – inhibit active factors V and VIII Errors in hemostasis 1. Thrombus = stationary clot in an undamaged vessel (increases resistance to blood flow) 2. Embolus = free floating clot a. can cause blockage of small vessels of the lungs (pulmonary embolism) or brain (cerebral embolism = stroke) or heart (coronary embolism – leads to myocardial infarction/heart attacks) b. can treat with fibrinolytic drugs, tissue plasminogen activator, antiplatelet agents, acetylsalicylic acid (aspirin) 3. Hemophilia a. Clotting is abnormal or absent b. Majority of people with hemophilia are lacking clotting factor VIII (also known as Antihemophilic Factor) c. Recessive sex linked – usually affects only males

Answer 16

1. Immunogens – substances that trigger the bodies immune response a. Antigens – immunogens that react with products of immune response 2. Leukocytes – carry out internal immune response a. Dependant on cell to cell communication i. Chemical communication – substances released by damaged or dying cells; cytokines (protein signal molecules released by one cell that affect the group of another) ii. Contact dependant signaling – surface receptors on one cell recognize and bind ot surface receptors on another cell 3. Main function of immune system – maintain homeostasis via a. Self cells i. Recognize and remove abnormal self cells – created when normal growth and development go wrong; cancerous, defective ii. Removing dead or damaged cells (ex. old RBC) b. Non self cells i. Prevent or limit infection due to viruses, bacteria, fungi, parasites (protozoans and worms), pathogens, allergens 1. Not all pathogens can be destroyed – sometimes body can only localize infection and prevent spread (ex. tuberculosis, malaria, herpes) 4. Early pathogen exposure – strengthens immunity a. Eradication of disease has seen an increase in autoimmune and allergic diseases (asthma, food allergies, IBS) b. Hygiene hypothesis – challenging the immune system strengthens it; too clean of an environment causes a weakened immune system (limited support) c. Suggested that it is not lack of exposure but lack of diversity in human microbiome

Answer 17

Leukocytes – communicate using cytokines o Cytokines – autocrine, paracrine, hormonal signals ``` Cell types o Macrophages (monocytes) o Dendritic Cells o Microglia (in the central nervous system) o Neutrophils o Mast Cells (from basophils) o Eosinophils o Natural Killer Cells o Lymphocytes (T and B Lymphocytes) ```

Answer 18

Least anatomically identifiable; integrated into the tissues of other organs - Positioned wherever pathogens are most likely to enter the body – ex. mucosal membranes of oral cavity - 2 anatomical components o Lymphoid tissue o Cells responsible for immune response Lymphoid tissues 1. Primary lymphoid tissues – location of leukocyte production a. Thymus gland – site of production of T lymphocytes b. Bone marrow – produces all other leukocytes i. Pluripotent stem cells ii. Plasma cells???????** 2. Secondary lymphoid tissues – location of leukocyte maturation, proliferation, interaction with pathogens a. Encapsulated tissues – have fibrous collagenous capsule walls; immune cells are positioned so they monitor ECF for foreigners i. Spleen – monitors blood; pathogens in blood will be exposed to active immune cells 1. 3 areas a. Red pulp – closely associated with blood vessels/sinuses; contains many macrophages that help to filter blood and phagocytize old RBCs b. White Pulp – similar in structure to lymph nodes; composed mainly of lymphocytes c. Capsule – outer protective casing ii. Lymph Nodes – monitor interstitial fluids via lymphatic system; also monitor blood (like the spleen) 1. Similar structure to spleen – has a capsule 2. Closely associated with capillaries of CV system a. Excess fluid from net filtration is picked up – pathogens that enter are passed through encapsulated lymph nodes on their way to the heart b. Once in lymphatic circulation – clusters of immune cells in lymph nodes try to capture to prevent spread b. Unencapsulated tissues – diffuse lymphoid tissues; aggregation of immune cells in other organs and tissues in the body i. Mucosal Associated Lymphoid Tissue (MALT) – diffuse lymphoid tissue lining digestive, respiratory, reproductive, urinary tracts. 1. Immune cells are positioned to intercept invading pathogens before they can enter general circulation 2. Includes a. Tonsils b. GALT (gut associated lymphoid tissue) – lies just under epithelium of the esophagus and intestines 3. Can be considered body’s largest immune organ

Answer 19

1. First line of defense a. Acts within minutes – lasts for hours b. Occurs independently of antibodies i. Some antibodies can help mediate the process if present 2. Characteristics a. Immediate and rapid response b. Non specific response – acts on anything identified as non self c. No memory cells – must be retriggered each time i. Response is not remembered by immune system d. Present from birth 3. Components a. First line of defense – physical, chemical, mechanical barriers i. Skin, mucous, tears, stomach acid b. Cellular barriers – circulating and stationary leukocytes programmed to respond to foreign materials i. Antigen presenting cells – dendrites and macrophages; required for both innate and adaptive responses ii. Ex. component of bacterial cell wall is recognized and ingested by phagocytes 1. Phagocytes – antigen presenting cells; present pieces of digested cell on their cell surface to attract cells involved in adaptive immune response

Answer 20

Physical barriers 1. Skin – tough protective outer layer a. Cells are keratinized b. Sweat from sweat glands – contains bactericidal chemicals (lysozyme) c. Sebum (oil) from sebaceous glands – blocks pores and reduces cracking in skin 2. Nose hairs and eyelashes – filter larger airborne particles 3. Mucous membrane – lines all body cavities/tracts that open to the outside of the body a. Respiratory, gastrointestinal, urinary, reproductive tracts b. Mucous produced by Goblet cells – traps pathogens and other particles Mechanical barriers – flushing mechanisms (cilia that move and create flow) 1. Mucociliary escalator a. Mucous membrane of respiratory tract – composed of ciliated pseudostratified epithelium i. Mucous produced by goblet cells traps microbes/debris b. Cilia in bronchi and trachea – beating (movement)pushes the mucus along with its trapped microbes/debris from the lungs towards the pharynx (throat). 2. Flow of tears – produced by the lachrymal gland; flow over the surface of the eye diagonally, removing microbes and debris. 3. Flow of urine – removes microbes and debris from the urinary tract. 4. Coughing and Sneezing – blows out irritants (at speeds ≥ 160 km per hour) Chemical barriers 1. Chemical molecules that activate leukocytes a. Chemotaxis – attract leukocytes b. Opsonin’s – molecules that coat foreign particles; mark for consumption by phagocytes c. Pyrogens – cytokines that raise temp of body by altering hypothalamic set point 2. pH – acidity creates inhospitable environment for microbes a. skin – pH = 4.5-6 (called the “acid mantle”) b. stomach – HCl; pH = 1-2 c. mucous membrane i. ex. nasal cavity – pH = 5.5-6.5 3. Enzymes – damage microbes (especially bacteria) a. Lysosomes – damage bacterial cell walls of unencapsulated bacteria i. Found in many body fluids – tears, sweat, saliva, intestinal and bronchial mucous, breast milk b. Proteases – antibacterial activity i. Ex. pepsin – digestive enzymes associated with gastrointestinal tract 4. Antibodies a. IgA (immunoglobin A) antibodies – binds to pathogens; clumps together and marks for phagocytosis in case they cross into the internal environment i. Found in many body fluids – tears, sweat, saliva, intestinal and bronchial mucous, breast milk 5. Acute phase proteins – plasma proteins produced in the liver; increase immediately following invasion a. Include – opsonins, C reactive proteins (CRP) b. Levels of acute phase proteins usually decline as immune response proceeds i. Chronic inflammatory disease – elevated levels persist (ex. rheumatoid arthritis) ii. Increased CRP – implicated in atherosclerosis coronary heart disease ** 6. Histamines – primarily found in granules of mast cells and basophils a. Actions – bring more leukocytes to injury to kill bacteria and remove debris by dilating blood vessels (increase flow) and opening pores in capillaries i. Capillaries – become leaky; plasma proteins are able to cross into ISF ii. Can lead to tissue edema (swelling) – pulls water with them due to osmotic flow b. Causes hot, red, swollen area 7. Complement system – part of initial response to bacterial invasion a. Cascade of over 30 proteins (found in ECF) that result in phagocytosis or lysis of foreign cells i. Proteins – secreted in inactive form and activated via cascade (similar to coagulation) 1. Act as chemotaxins – direct leukocytes to invading pathogens ii. C3 – most important protein in cascade 1. Specifically C3b portion – functions in opsonization (flagging/marking of bad cells) b. 2 pathways i. Classical pathway – requires that adaptive immune response has occurred 1. C1 proteins are activated by binding to antibodies (IgG, IgM) that are bound to pathogen/bacteria 2. Produces C3 and C3b ii. Alternative pathway – completely innate response 1. Carbohydrates on pathogen surface directly activate formation of C3 and C3b c. Function of both pathways i. C3 production – acts as opsonin that flags/marks pathogens for phagocytosis 1. Phagocytes – have C3 receptors 2. Opsonization – flagging/marking of bacteria for consumption by phagocytes a. Opsonins – chemical attractant; cause mast cell degranulation as well ii. C3b – helps to form membrane attack complexes (MAC) 1. MAC – group of lipids soluble proteins that insert themselves into cell membrane of pathogens and virus infected cells to form pores 2. C3b is converted to C5b – punctures holes in microbe cell membranes; allow Na+ and water to enter and cause lysis iii. C3a and C5a – by products of pathway; activate basophils and mast cells (inflammatory response) a. 8. Interferons a. Function of interferons i. Play an important role in short term innate immune defense against viruses ii. Reinforces other immune activities 1. Enhances macrophage phagocytic activity 2. Stimulates antibody production 3. Enhances action of NK cells b. Mechanisms i. Viral RNA enters cells (Covid-19, Influenza, west nile virus) 1. Viruses use host cell for replication ii. Host cells produce interferons a and B (alpha and beta) 1. Interferons act as paracrines – released from infected host cell and bind to cell membrane receptors on healthy neighbouring cells 2. Triggers production of antiviral proteins (AVPs) in healthy cells iii. Virus replication is blocked in neighbouring cells with AVPs 1. AVPs – are inactive if host cell is not infected c. Deficiency in interferon a and B is associated with more severe covid symptoms

Answer 21

Normal flora 1. Skin microbiome – commensal (friendly) bacteria on skin surface a. Breaks down sebum oil – releases fatty acids that contribute to low pH of skin surface i. Sebum oil – oil and proteins mixture released from sebaceous/oil glands in skin b. Outcompete harmful microbes 2. Gut microbiome – commensal bacterial in gastrointestinal tract a. Outcompetes harmful microbes b. Promotes production of antimicrobial peptides by intestinal epithelial cells i. Signal innate lymphoid cells in gut if pathogen is present – lymphoid cells release interleukin 22 ii. IL-22 – cytokine; stimulates production and secretion of antimicrobial proteins by the epithelial cells c. Reinforce tight junctions between epithelial cells in the gut – help maintain the physical barrier Immune cells of the body – includes all except T and B lymphocytes (adaptive only) - Many cells have functions in adaptive – they connect the 2 processes o Phagocytes – macrophages and dendritic cells that act as antigen presenting cells  Not all are antigen presenting

Answer 22

Inflammation – hallmark of innate immune response a. Functions o Attract immune cells and chemical mediators to site o Produces physical barrier to slow to spread of infections o Promote tissue repair once the infection is under control b. 4 signs of inflammation o Redness (rubor) o Heat (calor) o Swelling (tumor) o Pain (dolor) c. Requires recognition of bacteria by – local macrophages, neutrophils, mast cells o All have toll like receptors – able to detect bacterial cell wall components, lipopolysaccharide, flagella, etc. Inflammatory response: 1. Pathogen crosses physical barrier and enters body tissue 2. Complement system is activated a. Activation of phagocytosis – C3b as opsonin, flags microbe for phagocytosis b. Activation of mast cells c. Production of membrane attack complex d. Some complement proteins are chemotaxins 3. Phagocytosis of microbe by Resident Macrophages a. Resident macrophages may respond to toxins released by bacteria that have invaded via wound b. Macrophages release cytokines i. Interleukin 1 (IL-1) and Tumor necrosis factor-α (TNF- α) 1. Cause blood vessel endothelial cells to express adhesion molecules – help leukocytes to emigrate from blood vessels a. Ex. selectins 2. Stimulate liver to produce acute phase proteins – some are opsonins 3. Both also act as endogenous pyrogens and cause fever – higher temp increases macrophage activity ii. Interleukin 8 (IL-8) – acts as a chemotaxin for neutrophils 1. Neutrophil chemotactic factor – neutrophils have IL-8 receptor; helps attracts them to the infected area 4. Mast cells – release Histamine & other proinflammatory cytokines (bradykinin, IL-1, etc.) a. Potent vasodilator – causes localized vasodilation & increases blood present i. Causes redness and (rubor and calor) ii. Bradykinin can cause vasodilation b. Increases capillary permeability – plasma proteins can leave blood and enter ISF i. Increases the colloid osmotic pressure of the ISF (πI.) – fluid moves into the ISF causing swelling & localized edema. c. Pain – caused by local distension within the swollen tissue i. Swelling can cause loss of function. ii. Locally produced cytokines (e.g. bradykinin) stimulate pain receptors. d. Release chemotaxins that recruit neutrophils??** 5. Other leukocytes – emigrate from blood vessels into tissue (chemotaxis) a. Other leukocytes join i. Neutrophils come within 1 hour – attracted by chemotaxins ii. Blood monocytes follow – mature into macrophages over 8-12 hours. b. Steps of emigration: i. Margination – Neutrophils and Monocytes stick to endothelium of blood vessel ii. Rolling – selectins indicate to neutrophils and monocytes to slow down and “roll” along the interior of the vessel. iii. Diapedesis – neutrophils and monocytes leave the blood vessel using amoeba-like movement (squeeze themselves out through spaces between endothelial cells). iv. Migration – newly recruited phagocytes move through the tissue toward the injury site c. Phagocytosis by neutrophils & recruited macrophages (not only resident phagocytosis) 6. Neutrophil elimination – phagocytosis of used neutrophils by macrophages a. After they’ve ingested 5-20 microbes – they no longer work 7. Macrophages a. Recruited and resident macrophages – activated via Toll-like receptors, or opsonization by antibodies or complement proteins , continue eating b. Antigen presentation to Helper T cell occurs – link to Adaptive Immunity 8. Local inflammatory response – acts to separate infected tissue from healthy tissue so that infection cannot spread. a. Only occurs at the area of the injury. 9. Tissue heals a. Lymphatic system picks up extra tissues

Answer 23

- Circulate in the blood – function extravascularly o Some may live outside of tissues for hours, days, months - 6 basic types o Basophils & mast cells – not often in blood; granulocytes o Eosinophils – granulocytes o Neutrophils – granulocytes o Monocytes – create macrophages o Dendritic cells – not often in blood o Lymphocytes & derived plasma cells - 2 functional groups o Phagocytes – neutrophils, macrophages, dendritic cells o Antigen presenting cells – macrophages & dendritic cells; B lymphocytes in adaptive

Answer 24

Not all are antigen presenting Function of phagocytes 1. Identify microbes and other foreign particles by pathogen associated molecular patterns (PAMPs) with bind pattern recognition receptors (PRRs) on the phagocyte a. Ex. PRR – toll like receptors 2. Extensions of phagocyte cell membrane wrap around pathogen (with PAMP binding PRR) – results in engulfing pathogen a. Phagosome – ingested pathogen in cytoplasmic vesicle b. Phagosome fuses with lysosomes – contains digestive and oxidizing agents c. Phagolysosome – fusion of phagosome with lysosome • Within – microbes are killed by 1. O2 dependant phagocytosis - Uses oxidizing agents – ex. hydrogen peroxide, superoxide anion, nitric oxide) produced in the phagolysosome • Harmful to most cells/pathogens 2. O2 independent phagocytosis - Enzymatic breakdown of microbe by lysozyme (damages bacterial cell membrane), proteases, hydrolytic enzymes - Lysis by antimicrobial peptides • Ex. defensins – bind to cell membrane and form pores (similar to MACs); effective against bacteria, fungi, viruses 3. Can also ingest inorganic particles (asbestos and carbon) – cannot be digested/broken down enzymatically; they stay in cell 1. Macrophages – formed from monocytes a. Monocytes – not very common in the blood (1-6% of WBC) i. In tissues – enlarge and differentiate into phagocytic macrophages b. Many names i. Histiocytes – skin ii. Kupffer cells – liver iii. Osteoclasts – bone iv. Microglia – brain v. Reticuloendothelial – spleen c. Phagocytes in tissues – are larger and more effective than neutrophils; ingest up to 100 bacteria during their lifespan i. Migratory macrophages – move around and patrol tissues; can be recruited to a particular area as part of the innate immune response 1. Particularly in mucous membrane ii. Resident macrophages – single tissue; typically sessile (little movement or confined to one area) 1. Ex. alveolar macrophages in the lungs d. Innate immunity i. Remove dead/dying cells, cellular debris, old RBCs, dead neutrophils ii. Ingest and digest pathogens e. Adaptive immunity i. Antigen presenting cells – present antigens (pieces of digested pathogens) to T cells 2. Dendritic cells – long thin processes a. Phagocytes in tissues i. Found in skin (Langerhans cells) and other tissues ii. When activated – they migrate to lymphoid tissues (lymph nodes and spleen) b. Innate immunity i. Non specific pathogen recognition – ingest and digest pathogens c. Adaptive immunity i. Antigen presenting cells – present antigens to T cells in lymph nodes and spleen 3. Microglia a. Phagocytes in CNS – function as resident macrophages i. BBB blocks entry of other leukocytes and antibodies from the blood b. Innate immunity i. Remove dead/dying cells, cellular debris ii. Ingest and digest pathogens c. Adaptive immunity i. In healthy/homeostatic CNS – none 4. Neutrophils a. Phagocytes of blood – can leave circulation to enter tissues only in response to infection i. Most abundant WBC (50-70%) ii. Short lived – 1-2 days 1. Only consume 5-20 bacteria b. Structure i. Segmented nucleus – polymorphonuclear cells; 3-5 lobes 1. Can be used to identify 2. Immature – has horse shaped nucleus c. Innate immunity i. First cell recruited to site of infection – attracted by chemotaxins produced via complement activation ii. Non-selectively removes invading microorganisms iii. Releases 1. Pyrogens – fever causing cytokines 2. Chemical mediators of inflammatory response d. Adaptive immunity – none i. Not antigen presenting

Answer 25

Mast cells & Basophils 1. Non phagocytic granulocyte a. Mast cells – present in tissues i. Precursor are basophils – present in circulation (rare) b. Concentrated in CT of skin, lungs, gastrointestinal tract – where they are most likely to encounter pathogens 2. Covered with receptors for IgE – often bound to IgE a. Binding of IgE – triggers degranulation and release of chemical mediators of the innate immune response (indirectly assist in innate response) 3. Innate immunity – signalling of cytokine release and inflammatory response; releases a. Histamine – mediates inflammation; sensitized in allergy b. Heparin – anticoagulant c. Chemotaxins – recruitment of other immune cells (ex. neutrophils) 4. Adaptive immunity – release of histamine, heparin, chemotaxins in response to IgG and IgE ** Eosinophils 1. Cytotoxic cells – normally in peripheral circulation a. Related to neutrophils b. 1-3% of WBC c. Short lived – 6-12 hours d. Concentrated in GI tract, lungs, urinary and genital epithelia, & CT of skin i. Reflect role in parasitic invaders 2. Innate immunity a. Attack large, antibody coated parasites b. Exocytosis granzymes (hydrolytic enzymes) and Perforin on parasite cell surface – creates pore in cell membrane & kills parasite c. Allergic reaction – contributes to inflammation and tissue damage by releasing toxic enzymes and oxidative substances 3. Adaptive immunity – some roles in coordinating response of T cells Natural Killer cells 1. Innate (non specific) lymphocytes – cytotoxic a. Thought to develop in bone marrow and other tissues 2. Activated by interferons or macrophages a. Interferons – interfere with viral replication b. Macrophages – release cytokines that activate NKC to kill altered self cells (ex. viral or cancerous cells) 3. MHC I (major histocompatibility complex I) receptors – inhibitory effects on NKC actions a. Healthy cells – have MHC I b. Pathogenic cells – lack MHC I; will attack i. Altered self cells/tumors – lack MHC I ii. Viral infection – will down regulate MHC I expression 4. Innate immunity a. MHC I missing – activates NKC i. NK releases perforin in proximity to target cell – forms hydrophilic pore (similar to actions of MACs on bacterial cells) ii. Release granzyme B – cytotoxic enzyme that initiates apoptosis (cell death) 5. Adaptive immunity – none a. T and B lymphocytes function

Answer 26

1. Acquired immunity 2. Second line of defense after innate a. Detection and identification of pathogen b. Communication with other immune cells – organized response c. Recruitment of assistance and coordination of response d. Destruction or suppression of pathogen 3. Characteristics a. Slower – days to weeks b. Long lasting immunity – allows more rapid response to exposure next time i. Memory cells – remember (have receptors for) the epitopes and antigens of pathogens previously encountered c. Highly specific immune response i. Recognizes specific pathogen and initiates a unique response to it 1. Pathogen – infectious agent 2. Antigen – molecule body does not recognize as self 3. Epitope – part of antigen the interacts with receptors on T cells, B cells, and antibodies ii. Depends on ability of T cells, B cells, and antibodies to bind and recognize the epitopes on antigens 4. 2 divisions a. Cell mediated immunity – requires contact dependant signalling between immune cells (cytotoxic t-cells) and receptor on target b. Antibody mediated (humoral) immunity – production of antibodies by B lymphocytes and plasma cells i. Antibodies – proteins secreted by immune cells to carry out immune responses; bind to foreign substances to disable them & make them more visible to the cells of the immune system

Answer 27

Adaptive immunity cells – lymphocytes & derived plasma cells 1. Plentiful – adult body contains a trillion (20-35% of WBC) a. Only 5% in circulation 2. Each T and B cell can only bind to one antigen a. Clone – all the cells that bind that particular antigen; B cells with the same BCRs i. Millions of types ii. Body only keeps a few of each – if pathogen appear, the clone will reproduce in order to fight infection b. Specificity – in the proteins that become surface receptors or antibodies Production of lymphocytes - T lymphocytes – produced in thymus gland o During development – one set of immature lymphocyte precursor cells migrate from bone marrow - B cells – precursors remain in bone marrow 3 major types 1. T lymphocytes a. Helper T cells (Th or CD4+ cells) – direct/mediate adaptive immunity i. Type 1 (Th-1 cells) 1. Secrete a. INF-y (interferon-gamma) – activates macrophages b. IL-2 – activates cytotoxic T-cells 2. Mediate cell mediated immunity ii. Type 2 (Th-2 cells) 1. Secrete IL-4, IL-5, IL-6 – all help activate B cell growth, differentiation, and antibody production 2. Mediate humoral immunity (antibody mediated) immunity a. Activate B cells b. Cytotoxic T cells (Tc or CD8+ cells) i. Once activated – attack and destroy virus infected cells that have specific antigen ii. Cause apoptosis of infected cells 1. Release cytotoxic molecules – perforins and granzymes 2. Activate Fas – death receptor protein on host cell c. Regulatory T cells – prevent excess immune response by supressing other lymphocytes 2. B lymphocytes a. Responsible for humoral immunity – production of antibodies i. Most antibodies – in the blood (~20% of plasma proteins) ii. Antibodies are not toxic – cannot destroy antigens; only help immune system recognize iii. Most effective against extracellular pathogens – bacteria, parasites, antigenic macromolecules, viruses that have not yet invaded cells b. Naïve cells – exposed to antigen i. Create a primary immune response ii. Future exposures – secondary immune response c. Activated by Th-2 cells – clonal expansion occurs & cells develop into i. Plasma cells – effector cells 1. Produce antibodies/immunoglobins (globular proteins) – from their B cell receptors (BCRs) ii. Memory B cells – long lived cells that enter circulation 1. Allow for a more rapid response to a secondary infection – memory cells have B cell receptors that can bind to antigen & stimulate production of antibodies directly

Answer 28

1. Major histocompatibility complex (MHC-1 & MHC-2) – membrane protein complexes that display antigens a. Contact dependant signalling – when MHC antigen interacts with T cell immune receptor b. MHC-1 – found on nearly all nucleated cells; displays antigen that has epitome that binds to TCR of cytotoxic T cells i. Bind to CD8 protein receptors on cytotoxic T cells ii. Important for immune responses involving infected host/body cells c. MHC-2 – found on antigen presenting cells (macrophages, dendritic cells, B cells); display antigens that has epitome that binds to TCR of helper T cells i. Binds CD4 protein receptor on helper T cells 2. T cell receptors (TCRs) – protein receptors on T lymphocytes that recognize and bind to antigen presented by MHCs on surface of antigen presenting cell a. Unique for every antigen b. NOT antibodies 3. B cell receptors (BCRs) – protein receptors on B cells that recognize and bind to specific antigen (ex. on MHC-II of antigen presenting cell) a. Essentially antibodies on the surface of B cells i. Proteins that comprise variable region of receptor have high mutation rate – millions of possibilities for receptor phenotype ii. Clone – B cells with same BCRs b. Immune response requires appropriate clone for antigen to be selected i. Clonal selection – binding of antigen to BCR 1. Very specific – lock and key ii. Activation of B cells after recognition – via helper T cells iii. Clonal expansion – proliferation via mitosis 1. Produces plasma cells and memory cells 4. Antibodies – antigen recognition molecules; gamma globulin proteins a. Structure – 4 polypeptide chains in Y shape i. Fab – arms of Y 1. Variable region – each arm can bind to one antigen (2 total) 2. Each arm – one light chain (exterior), one heavy chain (continuous with Fc region) a. Chains are variable – gives them their specificity ii. Fc region – stem of Y; constant region that determines antibody class 1. Binds to immune cells b. 5 classes i. IgM – early immune response 1. Strongly activate complement system of innate immunity 2. React to antigens on RBC (AB blood groupings) 3. More specific immune response against bacteria and some viral infections ii. IgG - ~75% of all plasma antibodies 1. Released during secondary immune response – activates complement system of innate immunity 2. Passed from mother to fetus across placenta – imparts immunity newborn for first 6 months 3. More specific immune responses against bacteria and some viral infections iii. IgE 1. Protects against parasites 2. Fc region binds to mast cells – antibody mediator of allergic responses iv. IgA – found in secretion of mucous membranes 1. Digestive, respiratory, urinary, reproductive systems, tears, sweat, saliva, breast milk 2. Often associated with chemical barrier of innate immune response v. IgD – found of the surface of B cells 1. Function unknown – may play a role in B cell activation c. Function – bind to antigens to inactivate and remove them i. Facilitates phagocytosis 1. Antigen clumping 2. Inactivation of bacterial toxins 3. Opsonization of bacteria 4. Via complement system of innate response (classical pathway) ii. Cell lysis 1. Via complement activation (classical pathway) – formation of MACs iii. B cell activation – production of more antibodies

Answer 29

Primary response 1. Naïve T and B lymphocytes – exposed to pathogen 2. Clonal expansion occurs – mitosis of B cells and T cells that have the BCRs and TCRs for specifc antigen 3. Differentiate into effector cells and memory cells a. Effector B cells – plasma cells i. Plasma cells – produce antibodies b. Effector T cells – helper T cells, cytotoxic T cells 4. Memory B cells – remain in circulation; humoral immunity Secondary response – immune memory 1. Memory T and B lymphocytes in circulation are exposed to the same antigen that initiated their formation a. Clonal expansion – occurs more quickly; larger population of memory T and B cells than there was during primary response b. Increased number of i. Effector T and B cells 1. More plasma cells = more antibodies compared to primary response 2. More cytotoxic T cells = faster and more effective destruction of infected host cells ii. Memory T and B cells

Answer 30

Cell mediated immunity – effective against virus infected cells and cancerous cells Steps in secondary response: 1. Pathogen invades tissue 2. Phagocytosis by resident macrophages and dendritic cells – antigen presentation on MHC-II a. Type 1 helper T cells (CD4) – TCR binds to MHC-II; activates Th-1 cell i. Th-1 cell secretes IL-2 (cytokine) – activates cytotoxic T lymphocytes (CD8) b. Cytotoxic T cells – TCR binds to MHC-I complexes on infected host cells i. Release perforin onto infected cell – creates pore ii. Release granzymes into infected host cell – digests cell c. Infected cell undergoes apoptosis Primary response – would be similar - Would require antigen presentation to Naïve T cells – then clonal expansion between 2. And 2a. o Response would not be as quick or effective

Answer 31

Humoral Immunity – antibody mediated immunity Steps in secondary response 1. Pathogen invades tissue a. Recognized by toll like receptors or opsonized by complement of antibodies 2. Phagocytosis of pathogen by resident macrophage or dendritic cell – antigen presentation on MHC-II a. Type 2 helper T cells (CD4) – TCR binds to MHC-II; activates Th-2 cell i. Th-2 cell secretes IL-4, IL-5, IL-6 (cytokines) – activates: 1. B cells to proliferate (clonal expansion) 2. Plasma cells to produce antibodies 3. Antibodies facilitate a. Phagocytosis – act as opsonins b. Cell lysis (apoptosis) i. Via activation of classical complement pathway (MACs) ii. Activating degranulation of NKCs or eosinophils c. Facilitate production of more antibodies through actions on B cells Primary response – would be similar - Would require antigen presentation to Naïve B cell & clonal expansion between 2. And 2a. o Response would not be as quick or effective

Answer 32

1. Active immunity – body is exposed to the pathogen and produces its own antibodies via humoral response a. Natural – pathogen infects body through natural means i. Triggers a normal humoral response that leads to the production of antibodies ii. Person becomes ill and then recovers b. Artificial – vaccination i. Vaccines – mimic the pathogen 1. Can be a. Attenuated/killed pathogen b. Purified macromolecules c. DNA 2. Will cause slow primary response – harmless or mild symptoms ii. Fake pathogen triggers creates of antibodies and memory cells – long term immunity iii. Subsequent exposure to real pathogens produce fast and more effective secondary response 2. Passive immunity – the body acquires antibodies that were made my another individual or organism (horses, sheep) a. Natural – the antibodies crossing form mother to fetus across placenta or breast milk b. Artificial – injections that contain antibodies (antiserums) as opposed to attenuated pathogen i. Antivenin for snake bites ii. Convalescent serum for severe Covid-19 or Ebola – produced by taking antibodies from a recovered person and injecting them into someone who is ill to boost their immune response iii. Post exposure to rabies, tetanus, Hep B – if person was exposed and not vaccinated

Answer 33

Self tolerance – lack immune response to cells of body; begins in embryonic development - TCRs and BCRs – make randomly by DNA cutting and recombination processes o There is a small chance of producing TCRs and BCRs that are self reactive - Antigen recognition – leads to immune response o If self antigen is recognized – causes autoimmunity (ex. type I diabetes where body cells destroy islet cells that produce insulin) To prevent autoimmunity – during maturation, T cell clones and B cell clones have their TCR and BCR tested against self antigen & cells with TCR and BCR that recognize self antigen are destroyed or inactivated via 1. Clonal deletion a. Occurs - In thymus (T cells) and bone marrow (B cells) during fetal period up toa short time after birth - Can also occur in the peripheral tissues and circulation b. As T cells and B cells are produced – they are presented with self antigens - No recognition – cells escape into circulation - Recognition – clone undergoes apoptosis 2. Clonal inactivation (anergy) – occurs only in the tissues and circulation o Causes self reacting cells to become non responsive

Answer 34

immediate hypersensitivity - Overactivation in response to an antigen First exposure – allergen activates pathways that create memory B cells and plasma B cells a. Plasma B cells – produce IgE antibodies • IgE – become bound to mast cells Subsequent exposures – allergen interacts with IgE on mast cell a. Cause release of histamine and proinflammatory cytokines b. Creates a local inflammatory response in area of contact with allergen – red, swelling, heat, itch, etc

Answer 35

External respiration – exchange and transport of o2 and co2 o Pulmonary ventilation – between lungs and atmosphere; inspiration and expiration o Exchange between alveoli and blood & between blood and tissue cells o Transport from capillaries in the lungs to capillaries in the systemic tissues and back Internal respiration = cellular respiration o Use of o2 by mitochondria in cells to produce ATP o Co2 is formed as a waste product

Answer 36

1. Homeostatic pH regulation of body – via the concentration of co2 by increasing or decreasing respiratory rate a. CO2 + h2o = h2co3 = H+ + hco3- (carbonic anhydrase reaction) i. Increased breathing = less co2 = less acidic ii. Decreased breathing = more co2 = more acidic 2. Defending against microbes a. Mucociliary escalator – mucus traps pathogens and beating cilia move the mucus towards the pharynx b. Resident alveolar macrophages – phagocytize pathogens and debris in the alveoli 3. Metabolic function – modifies arterial concentration of chemical messengers a. Removes and inactivates some messengers and enzymes i. Ex. 30% of NE in venous blood is removed in the lungs b. Produces and actives other messengers and enzymes i. Ex. angiotensin converting enzyme (ACE) – converts angiotensin I to angiotensin II (regulator of MAP and water balance) 4. Vocalization – produced by moving air across the vocal cords in the larynx 5. Sense of smell – requires inspiration to move molecules in nasal cavity to stimulate olfactory receptors (free nerve endings) in the roof of the nasal cavity

Answer 37

Upper respiratory tract Components 1. Nasal cavity – warms, humidifies, and filters air with nasal hairs 2. Mouth – alternative route for air entry from the atmosphere; not as effective at warming/humidifying/ filtering as nose 3. Pharynx – common passageway of food and air 4. Larynx – contains the vocal cords ``` Lower respiratory tracts Components - Trachea - Bronchi - Bronchioles - Alveoli (lungs) ```

Answer 38

1. Thoracic cavity – formed by vertebral column, rub cage, associated muscles a. Muscles involved in breathing i. Diaphragm ii. External intercostals iii. Internal intercostals iv. Sternocleidomastoid v. Scalenes 2. Anatomy a. 2 lobes i. Right – 3 lobes ii. Left – 2 lobes b. Surrounded by pleura sac – double membrane i. Visceral pleura – inner membrane attached to the surface of the lung ii. Parietal pleura – outer membrane attached to the thoracic wall and diaphragm iii. Pleura cavity – space between; fluid holds membranes close together (due to adhesive forces of water molecules) and lubricates them during breathing c. ~23 divisions of branching – starting at trachea and ending at the alveoli i. Each division is shorter, narrower, thinner than previous

Answer 39

1. Conducting zone/anatomical dead space – trachea to primary bronchi, secondary bronchi, bronchioles a. Walls – cartilage (less as you move down), smooth muscle, elastic tissue i. Mucous secreting epithelium – conditions the air by warming, humidifying, filtering the air b. Gases are transported in and out via bulk flow – pressure gradients (high to low) c. Total air volume = ~150mL i. Anatomical dead space – filled with air but no gas exchange can take place 1. Ex. if you inspire 500mL, 150mL will be lost to dead space and only 350mL will reach the alveoli 2. Respiratory zone – respiratory bronchioles to alveolar ducts, alveoli a. Walls – thin; no cartilage i. Bronchioles – very little smooth muscle (if any) ii. Alveoli – no smooth muscle 1. Diameter of 1 alveoli = ~0.25m 2. Elastin fibres between alveoli – tensile strength; stretch/recoil properties b. Very large surface area – lots of capillaries for gas exchange c. Gases move via bulk flow & diffusion i. Pores of Kohn – gaps between alveoli; allow gas exchange between adjacent alveoli d. Post inspiration air volume (at rest) = ~3000mL i. Increase when taking deep breaths (ex. during exercise) 3. Respiratory membrane – 0.2-0.5 microns thick; site of gas exchange between lungs & blood a. Respiratory membrane is 3 layers i. Alveolar epithelium (wall) – 2 cell types 1. Type 1 alveolar cells – squamous polyhedral cells; make up most of alveolus; allow diffusion of gases a. Resident macrophages – patrol surface of type 1 2. Types 2 – spherical cells; secrete surfactant & reabsorb Na+ and h2o (prevent buildup of water in alveoli) ii. Basement membrane iii. Capillary wall – endothelium (flat simple squamous)

Answer 40

gases will move down pressure gradients (mmHg) - contraction & relaxation changes pressures in cavity Boyles Law  P1V1 = P2V2; relationship between volume and pressure 1. Pressure is inversely related to volume a. Ex. i. P1 = 100mmHg ii. V1 = 1L iii. V2 = 0.5 iv. P2 = (100)(1)/(0.5) = 200mmHg/L Daltons law  total pressure of mixed gases = the sum of the partial pressure (P) that each gas exerts independently 1. If humidity is high – this includes partial pressure of water vapour in air 2. Atmospheric pressure at sea level = 760mmHg a. Changes in altitude and humidity cause changes from 760mmHg i. Increased altitude = decrease Po2 (lower atmospheric pressure) ii. Increased humidity = decrease Po2 (lower % of gas in atmosphere) 3. Partial pressure of a gas = (atmospheric pressure)(% of gas in atmosphere) a. Ex. at sea level: Po2 = (760mmHg)(20.95%) = 159.22mmHg Equilibrium – when liquid is exposed to air; gas molecules can enter the liquid and dissolve until equilibrium is reached 1. At equilibrium  Pgas in air = Pgas in liquid a. Alveolar gas pressure affects pressure of gases dissolved in the blood plasma – gas will diffuse down their partial pressure gradients until equilibrium is reached i. O2 – alveoli to capillaries 1. Pulmonary arterial blood Po2 = 40mmHg 2. Pulmonary venous blood Po2 = 100mmHg 3. Alveolar Po2 = 105mmHg ii. Co2 – capillaries to alveoli 1. Pulmonary arterial blood Pco2 = 46mmHg 2. Pulmonary venous blood Pco2 = 40mmHg 3. Alveolar Pco2 = 40mmHg

Answer 41

can be used to determine normal/abnormal function during a pulmonary function test with spirometer 1. Tidal volume (TV) – volume air that moves into or out of lungs in one breath a. ~500mL at rest i. Inspiration = 500mL ii. Expiration = 500mL 2. Inspiratory reserve volume (IRV) – max volume of air that can be inspired following a normal breath in (beyond tidal volume) 3. Expiratory reserve volume (ERV) – max air volume that can be expired following a normal expiration 4. Residual volume (RV) – volume of air remaining in lungs following max expiration; helps to keep lungs inflated 5. Vital capacity (VC) – max volume of air that can be exchanged per breath a. VC = TV + IRV + ERV 6. Total lung capacity (TLC) – max amount of air that the lungs can hold a. TLC = TV + IRV + ERV + RV 7. Functional residual capacity (FRC) – amount of air held in the lungs after tidal expiration a. FRC = ERV + RV 8. Forced expiratory volume in 1 second (FEV1) – volume of air expired in one second during a forced maximal expiration after taking max inspiration a. Can be compared to vital capacity to determine lung function  FEV1/VC ratio i. Normal FEV1/VC = 0.80 (80%) ii. Obstructive lung disease – impaired expiration (shortness of breath) 1. Low FEV1/VC ratio (small FEV1) 2. Asthma, bronchitis (inflammation of bronchi), emphysema (walls of alveoli are damaged creating fewer larger alveoli), chronic obstructive pulmonary disease (COPD) iii. Restrictive lung disease – impaired inspiration; lungs can’t fully expand 1. Normal ratio but both FEV1 and VC values are low 2. Scoliosis (lateral curve of spine in thoracic region), pneumothorax (lung collapse), pulmonary fibrosis (thickening and scarring of lung), obesity

Answer 42

1. Atmospheric pressure (Patm) = 760mmHg (at sea level) a. All other pressures are calculated relative to this 2. Intra-alveolar pressure (Palv) = pressure within alveolar a. +1 to -1mmHg relative to Patm b. Between breathes  Palv = Patm c. Changes to Palv – contraction/relaxation of respiratory muscles 3. Intra-pleura pressure (Pip) = fluid pressure in pleura cavity; 756-753mmHg a. -4 to -7 mmHg relative to Patm – always negative during normal breathing and always less than Pip i. If Pip >/= Patm  pneumothorax (lung collapse) 1. Ex. stab wound – would cause puncture thoracic wall and Pip = Patm ii. Becomes more negative during inspiration ** b. Lungs and chest wall are elastic i. Opposing forces creates a negative pressure space so that Pip slightly decreases 1. Thoracic wall – recoils outward 2. Lungs – recoil inward ii. Cohesive forces of pleural cavity – holds lungs & wall together 4. Transpulmonary (transmural) pressure (Tp) = pressure gradient between alveoli and intrapleural cavity; recoil pressure of lungs a. Tp = Palv – Pip 5. Pressure gradient from Palv and Patm – drives ventilation a. F = P/R i. F = volume of inspiration/expiration ii. P = Patm – Palv 1. Greater the difference = more air will flow 2. Changes to Palv are made by contraction/relaxation of respiratory muscles iii. R = resistance of airway 1. Determined by diameter of bronchi/bronchioles a. SNS – bronchodilation (smooth muscle relaxes; beta receptors) b. PSNS – bronchoconstriction

Answer 43

Inspiration – tidal breathing (quiet) 1. Palv = Patm (between breaths) 2. Contraction of diaphragm (flatten) and external intercostal muscles (up and out) – chest wall expands a. Pip decreases – volume increases via expansion of thoracic cavity b. Tp increases (difference between Palv and Pip) – causes lungs (alveoli) to push out & lung volume to increase i. Increase in lung volume = decreases Palv c. Palv < Patm – causes air to move into alveoli 3. Air flow continues until Palv = Patm Deep inspiration – additional muscles are recruited to further increase expansion of thoracic cavity - Sternocleidomastoid & scalenes – pull ribcage superiorly Expiration – tidal breathing (quiet) - Passive during quiet breathing – no contraction of muscles 1. Palv = Patm (between breaths) 2. Relaxation of diaphragm and external intercostals – compress thoracic cavity a. Pip increases – compression of intrapleural sac b. Tp decreases (Palv – Pip) – causes lungs (alveoli) to recoil i. Decrease in lung volume = increase Palv c. Palv > Patm – causes air to move out 3. Airflow continues until Palv = Patm (then inspiration occurs) Deep expiration – active; utilizes abdominal and internal intercostal muscles

Answer 44

Ability of lung to stretch and expand/distend Measured by the change in lung volume as a result in the change in transpulmonary pressure CL = change in lung volume / change in Tp CL = change V/change P Compliance a. High = lungs stretch easily (easy inhalation) o Large changes in lung volume due to small changes in Tp o Obstructive lung diseases – difficulty expiring - High compliance; low recoil (not able to “snap back”) b. Low = stretches less easily; greater pressure is required to inflate (difficult inhalation) o Small change in volume due to large changes in Tp o Restrictive lung disease – difficulty inspiring - Low compliance; high recoil (able to “snap back”) Factors in compliance 1. Stretchability and elasticity of the lung tissue a. Lung tissue – surrounded by connective tissue that contains elastin and collagen fibres i. Elastin – allows stretch and recoil ii. Collagen – not elastic; provides strength b. Loss or buildup of tissue changes compliance i. Loss – increases compliance; decreases recoil 1. Age a. Loss of elastin and collagen – decreases recoil & increase compliance b. Impaired expiration 2. Obstructive lungs disease – impaired expiration ii. Buildup (especially collagen) – decreases compliance 1. Pulmonary fibrosis – stiffening of lungs due to chronic inhalation of fine particulate matter deep into lungs (asbestos, cigarette smoke) a. Triggers inflammatory response – leads to build up of collagen (scar tissue) i. Decreases compliance and impairs inspiration ii. Scar tissue also thickens membranes between alveoli – slows diffusion of gases b. Restrictive lung disease – impairs inspiration 2. Alveolar surface tension – attractive forces (hyd bonds) between water molecules on surface of alveoli resist alveolar expansion and decreases compliance a. Stretching type II alveolar cells – causes secretion of surfactant i. Surfactant – mix of phospholipids and proteins; disrupts the hydrogen bonds between water and decreases forces which restrict alveolar expansion 1. Increase compliance – prevents alveolar collapse b. Fetal development i. Synthesis begins ~24th week of fetal development – reaches adequate levels by 34th week ii. Newborn respiratory distress syndrome (NRDS) – deficiency in newborns that causes low compliance 1. Treatment – spraying artificial surfactant into lungs; artificial ventilation

Answer 45

Airway resistance – determined primarily by diameter of bronchi - F = P/R 1. Increased R = reduced airflow and ventilation a. Bronchodilation 2. Decreased R = increased airflow and ventilation b. Bronchoconstriction Resistance is influenced by 1. Breathing mechanisms a. Airways (bronchi and bronchioles) are connected to alveolar walls via connective tissue i. Radial traction – airways are pulled in the direction of alveoli 1. Inspiration – expansion of thoracic cavity and alveoli  increased radial traction pulls airways open & increases diameter a. Decreased resistance = increased airflow b. 2. Expiration – compression of thoracic cavity and alveoli  less radial traction & smaller diameter a. Increased resistance = decreased airflow 2. Smooth muscle tone a. Decreased = bronchodilation b. Increased = bronchoconstriction c. Controlled by i. Nervous system 1. PSNS – increases muscles tone & causes constriction 2. SNS – very little innervation; beta-2 receptors via epinephrine causes relaxation of smooth muscle & dilation ii. Paracrine agents 1. Histamine – mast cells; both effects will decrease diameter and increase resistance to flow a. Contraction of smooth muscle b. Stimulates mucous secretion iii. Co2 1. Increased co2 – dilation 2. Decreased co2 – constriction 3. Pathogenic states – obstructive respiratory diseases a. Asthma – episodes of inflammation and strong bronchoconstriction i. Due to hyperresponsiveness of smooth muscle to irritants – dust, cold, emotions ii. Chronically increases mast cells – increased histamine (constriction and mucous secretion) b. Chronic obstructive pulmonary disease (COPD) i. Emphysema – destruction and collapse of alveoli and smaller airways 1. Loss of elastic fibres and elastic recoil – increases compliance but impairs expiration 2. Trapped air in lungs – high residual air volume ii. Chronic bronchitis – often co-occurs with emphysema; inflammation of airways and accumulation of mucous increases resistance 1. Mast cells – secreting proinflammatory cytokines

Answer 46

Alveolar ventilation < pulmonary ventilation – not all air that enters respiratory tract during tidal expiration will go to alveoli due to anatomical dead space o End of inspiration – fresh atmospheric air fills dead space (150mL); lung volume is at max intake for a tidal breath a. During expiration – 150mL low o2 dead space air + 350mL high o2 alveolar air exits - Dead space – filled with 150mL of low o2 air b. During inspiration – 150mL low o2 dead space air + 350mL of high o2 air fills alveolus - Dead space – filled with 150mL high o2 air Total pulmonary ventilation per minute (minute ventilation) = (tidal volume)(respiratory rate) = (500mL/breath)(12 breaths/min) = 6000mL/min Total alveolar ventilation = (tidal volume – dead space volume)(respiratory rate) = (500 mL/breath – 150mL/breath)(12 breaths/min) = (350mL/breath)(12 breaths/min) = 4200 mL/min Changing alveolar ventilation: a. Increasing alveolar ventilation – increasing breath rate and depth (hyperventilation) o Increases alveolar Po2 and decreases Pco2 withing physiological limits o Because dead space volume does not change – depth of breath is more important than respiratory rate b. Decreasing alveolar ventilation – decreasing breathing rate and depth (hypoventilation) o Decreases alveolar Po2 and increases Pco2 within physiological limits

Answer 47

1. Eupnea – breathing is normal quiet (tidal) breathing a. 12-20 breaths/min 2. Bradypnea – decreased respiratory rate a. <12 breaths/min 3. Tachypnea – increased respiratory rate and decreased depth (panting) a. >20 breaths/min 4. Hypoventilation – decreased alveolar ventilation due to decreased resp rate and depth a. <12 breaths/min 5. Hyperventilation – increased alveolar ventilation due to increased resp rate and depth a. >20 breaths/min 6. Dyspnea – shortness of breath and difficulty breathing a. Severe symptom of Covid, pneumonia, others 7. Apnea – period of cessation of breathing; may occur in association with some breath disorders (ex. sleep apnea)

Answer 48

Ventilation perfusion coupling – matching the rate of airflow (ventilation) into alveoli with the rate of blood flow (perfusion) past the alveoli - Very important – blood from poorly ventilated alveoli will otherwise mix with blood from well ventilated alveoli and cause a decrease in Po2 in systemic arterial blood Local control of arterioles and bronchioles by o2 and co2 1. Matching requires local regulation of smooth muscle tone in bronchioles and pulmonary arterioles in response to changes in Po2, Pco2 in the air, blood, surrounding ISF 2. Response will be opposite in pulmonary vs systemic arteries a. In tissues • High co2/low o2 – needs more o2 o Dilating – decreases resistance and increases flow (brings more o2 and clears out co2) b. In alveoli • High co2/low o2 – that section will not oxygenate blood well o Constriction – increase resistance and slows flow to direct to better ventilated arterioles Pco2 1. Increases a. Bronchioles – dilate b. Pulmonary arteries – constrict (weak response) c. Systemic arteries – dilate 2. Decreases a. Bronchioles – constrict b. Pulmonary arteries – dilate (weak response) c. Systemic arteries – constrict Po2 1. Increases a. Bronchioles – constrict (weak response) b. Pulmonary arteries – dilate (weak response) c. Systemic arteries – constrict 2. Decreases a. Bronchioles – dilate (weak response) b. Pulmonary arteries – constrict c. Systemic arteries – dilate Matching perfusion to ventilation 1. Decreased ventilation to area of lung o Lower Po2, higher Pco2 in pulmonary blood  vasoconstriction in pulm art  decreased perfusion (blood flow)  perfusion matched to ventilation  diversion away to better ventilated areas 2. Decreased perfusion to area of lung o Lower Pco2, higher Po2 in alveoli  bronchoconstriction  decreased ventilation  ventilation matched to perfusion  diversion of airflow away from area of poor perfusion to areas with better perfusion ``` Pathologies 1. Decreasing ventilation o Pneumonia o Asthma o COPD – chronic obstructive pulmonary disorder o Kristi** - would restrictive diseases not also decrease ventilation 2. Decreased perfusion o Pulmonary embolism ```

midterm Flashcards

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