1. Blood:
    • Plasma and Cellular Elements of Blood
    • Hematopoiesis
    • RBC Physiology
    • Coagulation
  2. Plasma:
    • 92% water
    • 7% proteins
    • 1% organic mol (AA, glucose, lipids, N wastes), ions (Na+, K+, Cl-, H+, Ca2+), trace elements, vitamins, O2, and CO2
  3. Plasma Proteins:
    albumins *60% (prescence of proteins makes osmotic pressure higher; carriers)

    • globulins (clotting, enzymes, antibodies, carriers)
    • fibrinogen (essential to clotting) *30%
    • transferrin (transports iron)

    immunoglobulins (antibodies; secreted by specialized blood cells rather than by liver)

    • Functions:
    • clotting
    • defense against foreign invaders
    • carriers for steroid hormones, cholesterol, drugs, and iron
    • act as hormones or enzymes
  4. Cellular Elements:
    • RBCs (erythrocyes)
    • WBCs (leukocytes)
    • platelets (thrombocytes)
  5. RBCs:
    • have lost their nucleus by the time they enter the blood stream
    • play key role in transporting O2 from lungs -> tissues
    • CO2 from tissues -> lungs

    shape creates greater surface area for fast diffusion

    25% of blood cells being produced by marrow, have a longer life span
  6. WBCs:
    • only fully functional cells in circulation
    • play key role in body's immune response
    • defend against foregin invaders
    • work is usually carried out in tissues rather than in circulatory system
    • Five types of WBCs:
    • lymphocytes *immunocytes

    monocytes (in tissues: macrophages) *phagocytes

    • neutrophils
    • eosinophils *granulocytes
    • basophils (mast cells)

    Diapedesis: WBC leaves

    Are replaced more frequently because they have a shorter life span, 75% of blood cells being produced by marrow
  7. Platelets:
    • lack a nucelus
    • split off parent cell, megakaryocyte
    • short lived, 10 days
    • many nuclei
    • contain granules filled with clotting proteins and cytokines
    • activated when blood vessel wall damaged
    • play a role in coagulation
  8. Hematopoiesis:
    • the synthesis of blood cells
    • embryo forms clusters -> blood cells -> liver, spleen, and bone marrow produce -> liver and spleen dont produce after birth -> production continues in the marrow until age 5 -> continues to decrease as we age
  9. Cytokines:
    • control hematopoiesis
    • peptide proteins released from one cell that affect the growth or activity of another cell

    • erythropoietin - controls RBC synthesis, hormone; but made on demand rather than stored in vesicles; produced in kidney cells
    • CSF - made by endothelial and WBCs
    • IL -vreleased by one WBC to act on another, role in immune system; mobilizes hematopoietic stem cells
    • thrombopoietin - produced by liver, influences growth of megakaryocytes
  10. Erythropoiesis:
    • RBC production controlled by erythropoietin (EPO) and several cytokine
    • hypoxia: low O2 levels in the tissues (HIF-1) stimulates EPO synthesis and release
    • put more hemoglobin into circulation to carry O2
    • EPO gene cloned in 1985 -> now available
    • used in therapy, abuse in sport
  11. Hemoglobin:
    • 4 subunits
    • HbA- Adult
    • HbF - Fetal; increased affinity to O2; pulls O2 from HbA (mother)
    • Requires iron Fe from diet -> absorbed to small intestine by active transport -> transported in blood by transferrin -> RBC use Fe to make heme group of hemoglobin -> excess iron stored (liver) as ferritin -> bone marrow uses to make Hb -> liver metabolizes biliruben; execretes in bile -> metabolites execreted in urine or feces
    • Vit B12; intrinsic factor to absorb
    • HbS - sickle cell
    • elevated biliruben levels in blood = jaundice, causes skin and white of the eyes to take on a yellow cast. normally occurs in newborns whos fetal Hb is being broken down and replaced with adult Hb; also liver disease causes jaundice, liver is unable to process or excrete biliruben
  12. RBC Disorders:
    • Polycythemia vera- people in high altitudes, too many RBC, viscocity makes heart work harder, may be due to BM cancers
    • Anemias-
    • hemorrhagic: Fe deficiency; common in women
    • hemolytic: due to genetic diseases or infections, autoimmune or drug induced, malaria
    • pernicious: B12 deficiency or instrinsic factor lacking (stomach)
    • renal: kidneys dont produce (EPO)
  13. Sickle Cell Anemia:
    • abnormal hemoglobin
    • crystallizes when it gives up its oxygen
    • sickle cells become tangled with other sickle cells causing cells to jam and block blood flow in tissues
    • creates tissue damage and pain from hypoxia
    • NO being tested as treatment
  14. Hemostasis:
    • stopage of bleeding
    • too little: hemophiliac -> bleed too much
    • too much: thrombus/ emboli -> blood clots
    • Three major steps -
    • vasconstriction - vessels constrict; paracrines released by endothelium -> decreases blood flow and pressure in vessel
    • platelet plug - temporary blockage of hole; platelets stick to exposed collagen -> releases cytokines -> released more platelets that stick to each other
    • coagulation - clot formation seals hole until tissue is repaired; series of enzymatic reactions end in formation of fibrin protein fiber mesh that stabalize platelet plug
  15. Instrinsic Pathway:
    collagen exposure; all necessary factos present in blood; slower
  16. Extrinsic Pathway:
    Uses TF released by injured cells and a shortcut
  17. Common Coagulation Pathway:
    Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> clot
  18. Structure of Blood Clot:
    • as it forms it incorporates plasmin, the seeds of its own destruction
    • Plasmin: enzyme from plasminogen, activated by thrombin, breaks down fibrin polymers into fibrin fragments (fibrinolysis) -> removes clot
  19. Clot Busters:
    • dissolve inappropriate clots
    • enhance fibrinolysis
    • t-PA: tissue plasminogen activator; dissolves clot faster
    • *Vit K necessary for liver to make clotting proteins
  20. Anticoagulants:
    • "blood thinner" prevent blood from clotting
    • by blocking one or more steps in fibrin forming cascade
    • ihhibit platelet adhesion -> plug prevention
    • Ex. asprin -> inhibits plug, heparin -> inhibits thrombin, Protein C -> inhibits clotting factors V and VIII
  21. Hemophilia:
    • coagulation disorder
    • coagulation cascade lacking or defective
    • Hemophilia A, factor VIII deficiency, most common
    • sex linked, ususally affects only males
  22. Hematocrit:
    • ratio of RBCs to plasma
    • column of packed red cells is measured
    • normal range of hematocrit 40-54% male 37-47% female
  23. Mechanics of Breathing:
    • structure and function of respiratory pumps
    • gas exchange with blood
    • role of surfactant and pressure differences on rate of exchange
    • regulation of respiration
  24. Functions of Respiratory System:
    • O2 exchange: air -> blood, blood -> cells
    • CO2 exchange: cells -> blood, blood -> air
    • Regulation of body pH: retaining/ excreting CO2
    • Protection of alveoli -> blood
    • Vocalization
  25. On its way to the lungs, air passes through
    the pharynx, the larynx, then the trachea
  26. External Respiration:
    • the exchange of air between the atomosphere and the lungs
    • the exchange of O2 and CO2 between the lungs and blood
    • the transport of O2 and CO2 by the blood
    • the exchange of gases between blood and the cells
  27. The ciliated epithelium of the trachea and bronchi helps:
    move mucus to the pharynx
  28. The Airways:
    • 3 upper airway functions -
    • warming, humidifying, and filtering
    • mucocilary escalator depends on secretion of watery saline - cystic fibrosis
    • mucus
    • H2O
    • pseudostratified columnar epithelium
    • goblet cells: secrete mucus
    • alveoli: function is the exchange of gases between themselves and blood type II secrete surfactant: chemical mixes with thin fluid lining the alveoli to aid lungs as they expand during breathing
  29. Pulmonary Circulation:
    • pulmonary trunk; receives low-02 blood from R. ventricle -> divides into 2 pulmonary arteries -> 02 blood returns to L atrium via pulmonary veins
    • high flow rate, but pulmonary BP is low
    • distance shorter, resistance is low; R. ventricle doesnt have to pump as forcefully
  30. Gas Laws:
    • Dalton's: total P exerted by a misture of gases is the sum of P exerted by individual gases
    • air we breath: N2 78%, 02 21%, H20/ vapors
    • P @ sea level: 760 mmHg
    • Boyle's: P1V1=P2V2
    • gases move down pressure gradients
  31. Bends:
    • N2 is important for divers
    • come up too fast N2 bubbles in blood -> Nitrogen Narkosis
  32. Exchange of gases between lung and lung capillaries:
    external respiration!
  33. Ventillation:
    • air flows due to pressure gradients
    • inspiration: contraction of diaphragm 60-75% volume change
    • 25-40% due to external intercoastals and scalene muscles
    • expiration: relaxation of inspiratory muscles
    • elastic recoil of pleura and lung tissue reinforce muscle recoil
    • passive unless forced -> internal intercoastals and abdominal muscles
  34. Spirometry:
    • for pulmonary function tests
    • measures lung volumes during ventilation
  35. Aveolar and Intrapleural Pressures:
    • lungs unable to expand and contract on their own
    • during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated
  36. Surfactant:
    • from aveolar type II cells
    • detergent like complex of proteins and PL; disrupts cohesive forces between water molecules -> decreased surface tension -> decreased work of breathing
  37. Lung Compliance and Elastance:
    • compliance: ability of lungs to stretch
    • low compliance in fibrotic lungs (and other lung diseases) and when not enough surfactant
    • elasticity: ability to return to original shape
    • low elasticity in case of emphysema due to destruction of elastic fibers
    • normal lung is both compliant and elastic
  38. Airway Resistance:
    • influences work of breathing
    • determinant: airway diameter
    • CO2: bronchodilation
    • parasympathetic neurons: contricts
    • no sympathetic neurons but Beta2 receptors: bronchodilation
    • histamine: contriction
  39. Efficiency of Breathing: Rate and Depth
    • heart efficiency? CO= HR x SV
    • pulmonary ventilation: PV= RR x LV (tidal volume) 12x 500
    • 150 ml anatomic dead space
    • alveolar ventilation: RR x 350
  40. Matching Ventilation with Aveolar Blood Flow:
    • lung has collapsible capillaries -> reduced blood flow at rest in lung apex
    • increased CO2 in exhaled air -> bronchodilation
    • decreased 02 in ECF around pulmonary arterioles -> vasoconstriction of arteriole (blood diverted)
  41. Gas Exchange and Transport:
    • Dissolve CO2 and 02 for transport
    • Transport 02 - role of hemoglobin
    • Transport CO2
    • Regulate ventilation
  42. Diffusion and Solubility of Gases:
    • Ficks: diffusion rate surface rate x conc. gradient x mem. permeability\ membrane thickness
    • diffusion is most rapid over short distances
    • solubility of a gas depends on solubility of mol. in particular liquid and on pressure gradient and temperature
  43. Review Dalton's Law:
    Total atmospheric pressure as sea level = 760 mmHg

    • 21% 02 P02= 160 mmHg
    • 78% N2 PN2= 593 mmHg
  44. Gas Exchange in Lungs and Tissues:
    • gases flow from regions of higher partial pressure to regions of lower partial pressure.
    • 02 moves from aveolar (100 mmHg) to capillaries (40 mmHg)
    • P02 is lower in the cells 02 diffuses down its partial pressure gradient from plasma into cells
    • PC02 is higher in tissues than in capillaries
    • PC02 40 mmHg in aveoli 46 mmHg in tissues therefore the gradient causes C02 to diffuse out of the cells into the capillaries
  45. Lower Aveolar P02:
    • Diffusion rate decreases and you don't get enough 02
    • main factor that affects 02 content of air is altitude
    • low aveolar ventillation is know as hypoventillation
    • increased airway resistance
    • decreased lung compliance
    • CNS depression
  46. Pathological Conditions that Reduce Aveolar Ventilation:
    • emphysema: destruction of aveoli = less surface area for gas exchange
    • fibrotic lung disease: thickened aveolar membrane slows gas exchange, loss of lung compliance may decrease aveolar ventilation
    • pulmonary edema: fluid in interstitial space increases diffusion distance
    • asthma: increased airway resistance, decreased aveolar ventilation
  47. Aveolar Membrane Changes:
    • aveolar P02 may be normal but respiratory membrane changes affect gas exchange
    • increased membrane thickness = fibrotic lung disease
    • decreased surface area = emphysema
  48. Oxygen Transport in Blood:
    • 98% carried by Hemoglobin (oxihemoglobin) -> transported inside RBCs
    • rest is dissolved in plasma
    • at the cells where where 02 is used and plasma P02 falls Hb gives up its 02
    • we must have adequate amount of Hb in our blood to survive
  49. 02-Hb Dissociation Curve:
    • 20 mmHg exercising muscle 30%
    • 40 mmHg normal resting cell 75%
    • 100 mmHg normal of aveoli 98%

    • Factors effecting:
    • pH decreases
    • temperature increases (cold = left shift -> gives off less 02 -> stronger affinity to Hb)
    • PC02 increases
    • HbF increases (left shift)
  50. C02 Transport in Blood:
    • 7% directly dissolved in plasma
    • 70% transported as HC0- (bicarbonate) dissolved in plasma; acts as buffer; provides additional means of C02 transport from cells to lungs
    • 23% bound to Hb
    • excess C02 in blood = hypercapnia -> leads to acidosis, CNS depression and coma
  51. Regulation of Ventilation:
    stimuli- emotions and voluntary control -> higher brain centers -> limbic system -> medulla oblongata and pons -> somatic motor neurons for inspriation (effects scalenes, external intercoastals, diaphragm) or expiration (effects internal intercoastals, abdominals)

    stimuli- C02 -> medullary chemoreceptors -> medulla OR carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla

    stimuli- 02 and pH -> carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla oblongata or pons
  52. The Kidneys:
    • regulation of ECF volume and BP
    • regulation of osmolarity
    • maintenance of ion balance
    • homeostatic regulation of pH
    • excretion of wastes
    • production of hormones
  53. Processes of Urinary System:
    • Filtration
    • Reabsorption
    • Secretion
    • Excretion
  54. Filtration:
    • Movement of fluid from blood to lumen nephron
    • composition is like that of plasma - plasma proteins (water and dissolved solutes)
    • once in the lumen, considered outside the body
  55. Renal Corpuscule: Passage across 3 barriers
    • filtration takes place in the Renal Corpuscule
    • 3 barriers:
    • glomular capillary endothelium (fenestrated capillaries= large pores)
    • basement membrane
    • epithelium of bowmans capsule
  56. 3 Types of Pressures Influence Filtration:
    • hydrostatic pressure in capillaries: blood pressure; filtration takes place along nearly the entire length of the glomerular capillaries
    • colloid osmotic pressure: pressure gradient is due to the presence of proteins in the plasma
    • hydrostatic pressure in bowman's capsule: presence of fluid in the capsule creates fluid pressure that opposes fluid movement into the capsule
  57. Glomerular Filtration Rate (GFR):
    • filtration takes place in the glomerulus of a nephron
    • average GFR 180L/day, 60 times per day, 2.5 times per hour
    • amount of fluid filtered into Bowman's capsule per unit of time
    • influenced by: net filtration pressure (determined by renal blood flow and blood pressure) and the filtration coefficient (surface area of glomerular capillaries and permeablity of interface between the capillary and bowman's capsule)
    • surface area of kidneys depends on how many functional nephrons
  58. GFR Closely regulated:
    • GFR is constant over a wide range of blood pressures
    • MAP remains between 80 mmHg and 180 mmHg, GFR averages 180L/day
    • controlled by regulation of blood flow through the renal arterioles
    • resistance on GFR increases in the afferent arteriole hydrostatic pressure decreases -> decrease in GFR
    • resistance on GFR increases in the efferent arteriole hydrostatic pressure increases -> increase in GFR
  59. GFR Regulation:
    • autoregulation: kidneys maintains a constant GFR with normal fluctuations in blood pressure
    • protect the filtration barriers from high blood pressures that might damage them
    • myogenic response- instrinsic ability of smooth muscle to respond to pressure changes
    • tubuloglomerular- paracrine signaling mechanism through which changes in fluid flow through the loop of henle, influence GFR
  60. Myogenic Response:
    • increased blood pressure -> smooth muscle in arteriole wall stretches -> stretch sensitive ion channels open -> muscle cells depolarize-> opens voltage gated Ca2+ channel -> smooth muscle contracts -> increases resistance to flow -> blood flow through arteriole deminishes -> decreases filtration pressure on glomerlus
    • *a decrease in GFR helps the body conserve blood volume
  61. Tubuloglomerular Feedback:
    GFR increases -> flow through tubules increases -> flow past macula densa increases -> paracrine from macula densa to afferent arteriole -> afferent arteriole constricts -> resistance in afferent arteriole increases -> hydrostatic pressure in glomerulus decreases -> GFR decreases
  62. GFR Regulation:
    • reflex regulation: hormones and the ANS alter glomerular filtration by changing resistance in arterioles and altering filtration of coefficient
    • neural control is mediated by sympathetic neurons that innervated afferent and efferent arterioles
    • hormones also influence arteriolar resistance by acting as podocytes (change size of glomerular filtration slits- widen more surface area for filtration GFR increases) or mesangial cells (contraction changes the glomerular capillary surface area available for filtration
  63. Reabsorption:
    • more than 99% of the fluid entering the tubules must be reabsorbed into the blood as filtrate moves through the nephrons
    • most takes place in proximal tubule, other in distal segments of nephrons
    • allows kidneys to return ions and water to plasma to maintain homestasis
    • clears foreign materials from plasma quickly
    • filtering ions and water into the tubules simplifies their regulation
  64. Reabsorption may be active or passive:
    • Na+ reabsorbed by active transport
    • Anion reabsorbed by electrochemical gradient
    • water moves by osmosis following solute reabsorption
    • urea/permeable solutes are reabsorbed by diffusion
  65. Na+ reabsorption in the proximal tubule:
    • Na+ enters the cell through membrane proteins, moving down its electrochemical gradient
    • Na+ is pumped out the basolateral side of the cell by the Na+-K+-ATPase
  66. Na+-linked glucose reabsorption in the proximal tubule:
    • Na+ moving down its electrochemical gradient using SGLT protein pulls glucose into the cell against its concentration gradient
    • glucose diffuses out the basolateral side of the cell using GLUT protein
    • Na+ is pumped out by Na+-K+ATPase
  67. Characteristics of Renal Transport:
    • renal transport can reach saturation; the transport rate at saturation is the transport maximum
    • the plasma concentration at which glucose first appears in the urine
    • specificity
    • competition
  68. Secretion:
    • transfer of molecules from ECF into the lumen of the nephron
    • depends mostly on membrane transport systems
    • enables the nephron to enhance execretion of a substance active process, requires moving substrates against their concentration gradients
    • 2nd route of entry into tubules for selected molecules
    • mostly transepithelial transport; depends on secondary active transport mostly
    • rapid removal of substances
  69. Excretion:
    • rate depends on the filtration rate and whether the substance is reabsorbed, secreted, or both
    • excretion of H20, excess ions, nitrogenous waste, toxins, and other foreign molecules
    • excretion = filtration - reabsorption + secretion
    • kidneys clean or clear plasma of certain substances
    • clearance= plasma volume completely cleared of that substance per minute
  70. Clinical importance of GFR and Clearance:
    • GFR: is an indicator for overall kidney function
    • clearance: non-invasive way to measure GFR (insulin/ creatine)
    • substance is filtered and reabsorbed but not secreted the clearance rate is less than GFR
    • substance is filtered and secreted but not reabsorbed the clearance rate is greater than GFR
  71. Micturition:
    • urine -> renal pelvis -> ureter -> bladder -> smooth muscle contractions
    • urine is stored in bladder until released in micturition
    • bladder can hold about 500 ml
    • opening between bladder and urethra is closed by two rings of muscle called sphincters
    • tonic stimulation from CNS maintains contraction of the external sphinctor except during urination

    stretch receptors fire -> parasympathetic neurons fire; motor neuron stop firing -> smooth muscle contracts; internal sphinctor passively pulled open; external sphinctor relaxes
  72. Renal Failure:
    • symptoms when < 25% functional neurons
    • causes: diabetes, HBP, kidney infections, chemical poisoning
    • 75% of kidney destroyed for symptoms to occur
    • *why you can donate kidneys
    • CAPD- Continuous Ambulatory Peritoneal Dialysis
    • *urea will come out by diffusion
  73. Fluid and Electrolyte Balance:
    • explain homeostasis of:
    • water balance (ICF/ECF volumes)
    • electrolyte balance (osmolarity)
    • acid-base balance (pH)
  74. Body's Integrated Responses to Changes in Blood Volume and Pressure:
    decreased blood volume and pressure -> volume receptors in atria, carotid, and aortic baroreceptors -> increased ADH (vasopressin) cardiovascular system, behavior, or kidneys -> increase cardiac output/ vasocontriction, thirst causes increased water intake, increased ECF and ICF volume -> increased blood pressure OR conserve H20 to minimize further loss

    increased blood volume and pressure -> volume receptors in atria, endocrine cells in atria, and carotid and aortic baroreceptors -> cardiovascular system, kidneys -> decrease cardiac output, increase salts and H20 in urine, decrease ECF and ICF volume -> decreased blood pressure
  75. Water Balance:
    • kidneys maintain H20 balance by regulating urine concentration
    • kidneys cannot replenish lost water, all they can do is conserve it
  76. Renal Medulla Creates Concentrated Urine:
    • when maintenence of homeostasis requires eliminating excess water, the kidneys produce copius amounts of dilute urine with an osmolarity as low as 50 mOsM
    • removal of excess water in urine is know as diuresis
    • drugs that promote the excretion of urine are called diuretics
    • when kidneys conserve water the urine becomes concentrated
    • kidneys control concentration by varying the amounts of water and Na+ reabsorbed in the distal tubule and collecting duct
    • to produce dilute urine the kidney must reabsorb solute without allowing water to follow by osmosis
    • reabsorption of varying amounts of H20 and Na+ established by Loop of Henle and Collecting duct (where kidneys create hyposmotic fluid)
  77. ADH- Vasopressin:
    • released from posterior pituitary
    • controls water reabsorption by adding or removing water pores in the apical membrane
    • vasopressin acts on target cells -> water pores inserted into the apical membrane -> water move out of lumen by osmosis
    • collecting duct is impermeable to water without vasopressin
    • aquaporin: water pores; AQP2- water channel regulated by vasopressin
  78. Diabetes Mellitus:
    • primary sign of diabetes mellitus is an elevated blood glucose concentration
    • any additional nonreabsorbable solute that remains in the lumen forces additional water to be excreted causes osmotic diuresis
    • osmotic diuresis in untreated diabetics causes
    • polyuria: excessive urination and
    • polydipsia: excessive thirst as a result of dehydration and high plasma osmolarity
  79. Concentrated Vs. Dilute Urine:
    • concentrated: presence of ADH- insertion of H20 pores
    • maximal H20 permeability -> net H20 movement stops at equilibrium
    • maximal vasopressin, the collecting duct is freely permeable to water, water leaves by osmosis and is carried away by the vasa recta capillaries
    • dilute: no ADH, DCT and CD impermeable to H20
    • osmolarity can plunge to 50 mOsM
    • in the abscence of vasopressin, the collecting duct is impermeable to water and the urine is dilute
  80. Loop of Henle- Countercurrent Multiplier:
    • key to kidneys ability to produce concentrated urine is the high osmolarity of the medullary interstitium
    • leads to hyperosmotic IF in medulla
    • hyposmotic fluid leaving LOH
    • transfers water and solutes
  81. Na+ Balance and ECF Volume:
    • Na+ concentration affects plasma and ECF osmolarity
    • normal 140 mOsM
    • Na+ affects BP and ECF volume
    • higher ECF would draw water from the cells shrinking them and disrupting normal cell function
    • additon of NaCl raises osmolarity ->
    • vasopression secretion (causes kidneys to conserve waster and concentrate urine) and thirst (prompts us to drink water
    • increased salt and water intake increases ECF volume and BP -> triggers series of control pathways brings them back to normal
  82. Aldosterone:
    • regulates Na+ and K+ excretion in last 1/3 of DCT and CD
    • increased aldosterone secretion -> increased Na+ absorption
    • steroid hormone synthesized in the adrenal cortex
    • secreted into the blood and transported on a protein carrier to its target
    • primary target = P cells by simple diffusion
    • low blood pressure stimulates aldosterone secretion
    • aldosterone combines with cytoplasmic receptor -> hormone receptor complex initiates transcription in nucleus -> new protein channels and pumps are made -> aldosterone induced proteins modify existing proteins -> result is increased Na+ reabsorption and K+ secretion
  83. Acid-Base Balance:
    • pH of a solution is a measurment of its H+ concentration
    • the normal pH of the body is 7.4
    • enzymes and membrane channels are particularly sensitive to pH because the function of these proteins depends on their shape
    • pH too low- acidosis neurons become less excitable and CNS depression results - excrete H+ and reabsorb K+
    • pH too high- alkalosis neurons become hyperexcitable, firing action potentials at the slightest signal - reabsorb H+ and excrete K+
    • K+ imbalance associated with acid base imbalance
    • renal transporter that moves K+ and H+ ions in an antiport fashion
  84. Acidosis:
    • due to aveolar hypoventilation, C02 retention -> elevated plasma PC02
    • respiratory depression, increased airway resistance, impaired gas exchange
    • metabolic: due to gain of fixed acid or loss of bicarbonate
    • lactic acidosis, ketoacidosis, diarrhea
    • buffer capabilities exceeded once pH change appears in plasma
  85. 3 Mechanisms for Regulating pH Changes:
    • Buffers: 1st defense, immediate response
    • Ventilation: 2nd, can handle 75% of most pH disturbances
    • Renal Regulation: of H+ and HC03-, final, slow but very effective
  86. Alkalosis:
    • due to aveolar hyperventilation in the absence of increased metabolic C02 production
    • causes: anxiety, excessive artifical ventilation, aspirin toxicity, fever, high altitude
    • compensation = renal, filtered bicarbonate which if reabsorbed could act as a buffer and increase pH more
    • metabolic: due to loss of H+ into intracellular space
    • vomiting, NG suction, antacid overdose
    • compensation = rapid
  87. Digestion:
    • motility
    • secretion
    • digestion
    • absorption

    pepsin vs. trypsin pH optimum

    pancreas: 99% exocrine -> bicarbonate (HC03-), enzymes (amylase), lipase, protease (trypsin/ chymotrypsin) 1% endocrine -> insulin/ glucagon (antagonists)
  88. Motility:
    • 2 purposes: forward movement of food, and mechanical mixing (duodenum)
    • GI smooth muscles contract spontaneously
    • pacemaker cells depolarize -> generate slow wave potentials
    • APs spread throughout longitudinal muscles (gap junctions) -> wave of contraction
    • parasympathetic stimulates GI tract
    • most digestion occurs in small intestine
    • cycles of smooth muscle contraction and relaxation are associated with spontaneous cycles of depolarization and repolarization = slow wave potentials
    • slow wave potentials reach threshold -> voltage gated Ca2+ channels in the muscle fiber open -> Ca2+ enters -> cell fires action potential(s) -> depolarization result of Ca2+ entering cell -> initiates muscle contraction
  89. Different Patterns of Contraction:
    • tonic contractions: sustained for minutes or hours occur in smooth muscle sphinctors and in the anterior portion of the stomach
    • phasic contractions: contraction-relaxation cycles lasting only a few seconds occur in posterior region of the stomach and in small intestine
    • peristaltic contractions: push a bolus forward
    • occurs mainly in esophagus
    • influenced by hormones, paracrine signals, and ANS
    • segmental contractions: segments of intestine alternately contract and relax- lead to mixing
    • occur randomly along the intestine or at regular intervals
  90. Secretion:
    • 9 L of fluid a day
    • 7 L composed of water and ions -> secreted into lumen of tract
    • Acid: parietal cells secrete HCl into the lumen of the stomach; 1-3 L per day in stomach; pH as low as 1
    • bicarbonate is absorbed in blood -> buffering action makes blood leaving stomach less acidic -> "alkaline tide"
    • bicarbonate: some secreted by duodenal cells, most from pancreas
    • requires high levels of carbonic anhydrase
    • acinar cells secrete digestive enzymes
    • duct cells secrete NaHC03
    • digestive enzymes: secreted by salivary glands or pancreas or by epithelial cells in small intestine
    • synthesized on rough ER packaged by GC -> vesicles -> stored in the cell
    • secreted in an inactive proenzyme (zymogens); must be activated in GI lumen
    • mucus: made in special exocrine cells (mucous cells) in stomach and goblet cells in intestine (10-24%)
    • salivary glands also secrete mucus
    • saliva: secreted by salivary glands
    • controlled by ANS
    • parasympathetic innervation primary stimulus
    • bile: secreted from hepatocytes or liver cells
    • bile salts (emulsifiers- fat breakdown), bile pigments (bilirubin), cholesterol
    • secreted into hepatic ducts -> gall bladder where its stored -> during a meal sends bile to duodenum
  91. Digestion Overview:
    • mechanical breakdown aids enzymatic breakdown
    • enzymatic breakdown converts macromolecules into absorbable units
    • optimal pH of enzymes indicates location of activity
  92. Absorption:
    • small intestine absorbs most nutrients
    • fats absorbed into lacteals (lymph capillaries)
    • everything else absorbed into blood
    • alcohol and aspirin across gastric epithelium
    • additional H20, ions, some vitamins absorbed in large intestine
  93. COH Digestion and Absorption:
    • complex COH and disaccharides must be digested if they are to be absorbed
    • starch and glycogen broken down by enzyme amylase
    • glucose and galactose absorption uses transporters identical SGLT and GLUT2
    • fructose is not Na+ dependant; moves across apical membrane by facilitated diffusion on GLUT5 and across basolateral membrane by GLUT2
  94. Lactose Intolerance:
    • cannot absorb lactose
    • lactose left in GI tract
    • osmotic diarrhea, polydipsia, polyurea
  95. Colon Cancer:
    • genetic
    • 2nd most common cause of cancer deaths
    • cellulose (indigestible) = fiber, roughage
    • roughage in diet helps food move through; less exposure to carcinogens that sit in body and mutate
    • trypsin -> digests proteins
  96. Protein Digestion and Absorption:
    • plant proteins are least digestible
    • 30-60% of protein found in GI lumen is from dead sloughing cells
    • enzymes for protein digestion: endopeptidases (proteases) and exopeptidases
    • proteases: attack peptide bonds in the interior of the aa chain, break a long chain into fragments; secreted as inactive proenzymes; ex- pepsin (stomach), trypsin, and chymotrypsin (pancreas)
    • exopeptidases: chop off at ends; ex- carboxypeptidase (pancreas)
    • proteins absorbed as free AA, dipeptides, and tripeptides
    • absorption of proteins can lead to food allergies (gluten)
    • drug companies develop indigestible protein/ peptide drugs (modified vasopressin)
  97. Fat Digestion:
    • 90% of our fat calories come from triglycerides
    • carried out by lipases -> triglycerides -> monoglyceride + 2 free FA
    • fats form large clumps of chyme (hard to digest)
    • phospholipids are digested by pancreatic phospholipase
    • liver secretes bile salts into small intestine to increase the surface area available for digestion
    • requires colipase secreted by pancreas; displaces some bile salts -> form micelles
    • many fats absorbed by simple diffusion
  98. Vitamin and Mineral Absorption:
    • fat-soluble vitamins (A,D,E,K) are absorbed in small intestine along with fats
    • the water soluble vitamins (C,B) are absorbed by mediated transport
    • B12 transporter only found in ileum; only recognizes B12 with intrinsic factor secreted by stomach
    • B12 deficiency: pernicious anemia
    • mineral absorption occurs by active transport
    • iron ingested as heme iron- more readily absorbed by endocytosis
    • Fe2+ absorbed by apical cotransport with H+ on a protein
    • iron uptake is regulated by hepcidin secreted by liver
    • Ca2+ absorption in the gut - passive
  99. Absorption of H20 and Na+:
    • mostly in small intestine, some in colon
    • enterocytes (small intestine) and colonocytes absorb Na+ using 3 membrane proteins - Na+ channels, Na+Cl- symporter, and NHE Na+-H+ exchanger
    • in small intestine absorption takes place through SGLT and Na+-amino acid transporters
    • H20 follows
  100. Cephalic Phase:
    • Chemical and mechanical digestion begins in the mouth
    • salivary secretion under ANS control
    • mechanical digetion: chewing
    • chemical digestion: salivary amylase, and lysozyme
    • swallowing reflex: deglutition
  101. Gastric Phase:
    • 3 functions of stomach:
    • storage
    • digestion
    • protection
    • bicarbonate creates a chemical buffer barrier underlying the mucus
  102. Intestinal Phase:
    • bicarbonate neutralizes gastic acid
    • activation of pancreatic zymogens
    • digestive enzymes -> enteropeptidases
    • goblet cells secrete mucus for protection and lubrication
    • most fluid absorbed in small intestine
    • diarrhea can cause dehydration
  103. The Immune System:
    • protection from disease causing invaders
    • removal of dead/ damaged tissues and cells
    • recognition and removal of abnormal cells
  104. Vocabulary:
    • pathogen: bacteria, viruses, fungi, protozoans, parasites
    • antigen: substances that trigger the body's immune response and can react with products of that response
    • antibody: proteins secreted by certain immune cells, bind to antigens and make them more visible to the immune system
    • innate immunity: present from birth and is the body's nonspecific immune response to invasion
    • acquired immunity: is directed a specific invaders and for this reason is the body's specific immune response
  105. Leukocytes:
    • Basophils: (mast cells) rare -> release chemicals that mediate inflammation and allergic responses
    • Neutrophils: 50-70% ingest and destroy invaders
    • Eosinophils: (cytotoxic) 1-3% destroy invaders (antibody coated parasites)
    • Granulocytes^
    • Monocytes: (macrophages in tissue) 1-6% ingest and destroy invaders; antigen presentation
    • 3^Phagocytes
    • Lymphocytes: (plasma cells) B (plasma/memory cells) T (cytotoxic T/ helper T cells) NK cells; specific responses to invaders, including antibody production
    • Dendritic Cells: (langerhans) (cytotoxic) recognize pathogens and activate other immune cells by antigen presentation
    • 3^antigen presenting
  106. Immune Response:
    • Innate: nonspecific
    • hinders pathogen entry and dispersion through body
    • strengthens specific immune system
    • Acquired: specific
    • inactivation of specific pathogen
    • must be primed first
    • specific resistance = immunity
  107. Innate Immunity:
    • consists of patrolling and stationary leukocytes that attack and destroy invaders
    • clears the infection or contains it until acquired immune response is activated
    • physical barriers include skin, protective mucous lining, ciliated epithelium, acidity of stomach, lysozyme- enzyme with antibacterial activity
    • phagocytosis: macrophages, neutrophils, and NK cell attack and destroy pathogens/ foreign mol. nonspecifically
    • attracted to areas of invasion by chemical signals -- chemotaxis (bacterial toxins or cell wall components, activated leukocytes)
    • macrophages toll-like receptors activate the cell to secrete inflammatory cytokines
    • phagocytes recognize bacteria and produce antibodies against them "tagged"
    • opsonins: antibodies that tag bacteria with plasma proteins; convert unrecognizable particles into "food" for phagocytes
  108. Natural Killer Cells:
    • recognize virus infected cells and induce them to commit apoptosis before it can replicate
    • also attack tumor cells
    • secrete interferons
  109. Cytokines:
    • inflammatory response is created when activated tissue macrophages release cytokines
    • chemicals attract other immune cells, increase capillary permeability, cause fever
    • histamine: found in mast cells; active mol that helps initiate inflammatory response when mast cells degranulate
    • bring more leukocytes to the injury site
    • opens pores in capillaries causing swelling or edema
    • increases blood flow to the area, making it hot, red, and swollen
    • antihistamines: block the action of histamine at its receptor
    • histamine + mast cells, lipid mediators responsible to anaphylactic shock and bronchodilation
  110. Interleukins:
    • IL-1 is secreted by activated macrophages and other immune cells; role is to mediate the inflammatory response
    • alters blood vessel endothelium to ease passage of WBCs and proteins
    • stimulate production of acute-phase proteins by liver
    • induces fever
    • stimulates cytokine and endocrine secretion
  111. Bradykinin:
    • has same vasodilation effects as histamine
    • stimulates pain receptors
    • pain draws brains attention to injury
  112. Complement System:
    • act as opsonins
    • chemical attractants for leukocytes
    • agents that cause mast cell degranulation-
    • MAC: complement insert themselves into the membrane of pathogen -> creating pore -> water and ions enter the cell -> cell swells and lyses
  113. Acquired Immunity:
    • antigen specific responses
    • lymphocytes: B cell -> plasma cells (secrete antibodies), T cells -> attack and destroy or regulate cells, NK cells -> attack and destroy
    • lymphocytes release additional cytokines to enhance inflammatory response
    • active immunity: occurs when body is exposed to pathogen and produces own antibodies. can happen naturally or artificially (vaccinations) ; makes memory cells
    • passive immunity: occurs when we acquire antibodies made by another animal. ex. mother to infant, & injections containing antibodies ; no memory
  114. Lymphocytes:
    • B lymphocytes activated -> become plasma cells; antibodies that attack that antigen -> memory cells; 2nd immune response to same antigen = much faster
    • T lymphocytes -> direct attack -> effector cell or memory cell
  115. Antibodies:
    • IgG: make up 75% of plasma antibody in adults; activate complement
    • IgA: found in external secretions - saliva, tears, mucous, breast milk; disable pathogens before they reach the internal environment
    • IgE: allergic responses - binds with mast cell and antigen, mast cell degranulates -> release histamine
    • IgM: on surface of B cells; associated with primary immune responses and react to blood group antigens; activate complement
    • IgD: appear on surface of B cells; role is unclear
  116. Antibody Functions:
    • act as opsonins -> coat antigens, facilitate recognition and phaogocytosis
    • make antigens clump -> enhances phagocytosis
    • inactivate bacterial toxins
    • activate complement -> cell swell and lyse
    • activate mast cells -> mast cell degranulate -> release histamine -> inflammatory response
    • activates immune cells
  117. Importance of MHC molecules:
    • encoded with specific set of genes
    • every nucleated cell of the body has MHC on its membrane
    • "silverspoon" that feeds T Cells
    • T Cells cannot recognize free antigen without MHC present
    • MHC Class I- found on surface of all nucleated cells - used to present peptides from intracellular invaders
    • T cell recognizes cell with MHC I and kills it
    • CTL recognizes MHC I
    • MHC Class II- found on surface of antigen presenting cells and B cells
    • T helper cells recognize MHC II creates immune response
  118. CTLs:
    • CD8 or TK
    • attack and destroy cells displaying MHC I -ag complexes

    T cell recognizes virus infected cell with MHC I ->release perforin molecules create protein channels in target cell membrane -> granzymes enter through perforin channels -> activate an enzyme cascade that triggers apoptosis in target cell
  119. Defense Against Bacteria:
    • activates complement system -> chemical signals (chemotaxis) attract leukocytes -> opsonins; enhance phagocytosis -> degranulation of mast cells -> secrete histamine (increase permeability; inflammatory response) -> formation of MAC (cells swell and lyse)
    • phagocytosis -> if bacteria are not encapsulated macrophage can begin ingesting if they are antibodies must coat before ingested (opsonization)
  120. Defense Against Viral Infections:
    macrophage ingests virus -> macrophage presents antigen fragment (MHC II) -> secretes cytokines (inflammatory response/ interferon induce host cell to produce antiviral proteins) and activate helper T cells -> activates B cells and cytotoxic t cells -> b cells become plasma cells and secrete antibodies -> cytotoxic t cells attack MHC I viral infected host cell -> apoptosis
  121. Allergic Response:
    • 1st exposure: allergen ingested and processed by APC (MHC II) -> APC activates helper T cell -> activates B cell (memory b and t cells retain memory of exposure to allergen) -> becomes plasma cell -> secretes antibodies
    • 2nd exposure: memory activates T cells, antibodies secreted -> cytokines, complement proteins, degranulation of mast cell -> inflammation response
  122. Anaphylaxis:
    • most severe IgE mediated allergic reaction
    • mast cells -> histamine
    • speed up heart, hives, bronchocontriction, BP increased
    • widespread vasodilation crashes BP
  123. Blood Typing:
    • Type A: anti B antibodies in plasma
    • Type B: anti A antibodies in plasma
    • Type O: both anti A and anti B antibodies in plama
    • Type AB: have no antibodies to A or B antigens
  124. Recognition of Self:
    • when self tolerance fails the body makes antibodies against its own components through T cell- activated B lymphocytes
    • autoimmune disease
  125. Fast Moving Area:
    • stress alters immune system function
    • pathogen -> immune cells -> endocrine cells -> target cell
    • stress -> brain -> endocrine cell -> target cell
  126. Reproduction and Developement:
    • human chromosomes
    • gametogenesis
    • fertilization
    • early development
    • paturition
  127. Sex Determination:
    • 44 autosomes
    • 2 sex chromosomes (X&Y)
    • XX female XY male
  128. Gametogenesis:
    • starts in urtero- resumes at puberty
    • mitosis: germ cell proliferation
    • meiosis: DNA replicates but no cell division
    • 1st meiotic division: primary gamete divides into two secondary gametes
    • 2nd meiotic division: secondary gamete divides
    • fertilization (if not fertilized egg passes out of body) -> zygote
    • women are born with all the eggs, oocytes they will ever have
    • men manufacture sperm continuously from the time they reach reproductive maturity
  129. Abnormal Karyotypes:
    • XO: Turner Syndrome
    • XXX: Triple-X Syndrome
    • XXY: Kilinefelter Syndrome
    • XYY: Jacob Syndrome
    • Trisomy 21: Down Syndrome
  130. Turner Syndrome:
    • XO
    • broad, webbed neck, stature reduced, edema in ankles and wrists
    • relatively normal lives but no functional ovaries
    • 1 in 2,000 births
  131. Klinefelter Syndrome:
    • XXY
    • usually normal- may be tall and have small testes
    • infertile
    • 1 in 1,500 males
  132. Hormonal Control of Reproduction:
    • GnRH (hypothalamus) controls secretion of FSH and LH (anterior pituitary) -> act on gonads
    • FSH is required along with sex hormones to maintain gametogenesis
    • LH works primarily on endocrine cells, stimulating production of sex hormones
    • estrogen alternates between + and - feedback
    • lower estrogen have - feedback effect
    • estrogen rise rapidly to a threshold or above for at least 36 hrs feedback changes from - to + LH is stimulated
    • intersitial cells produce androgens
  133. Male Reproduction:
    • in males LH is called ICSH
    • seminiferous tubules: site of sperm production
    • has spermatogonia and sertoli cells
    • adjacent sertoli cells are linked together by tight junctions that form an additional barrier between the lumen of the tubule and the intersitial fluid outside
    • spermatogenesis: sperm production
    • sertoli cells: secrete proteins regulate sperm development; nourish spermatagonia
    • leydig cells: secrete testosterone; also convert it to estradiol LH target
  134. Female Reproduction:
    • female humans produce gametes in monthly cycles
    • 3 phases-
    • follicular phase: growth in ovary 10days - 3wks
    • ovulation: one or more follicles have ripened; ovary released oocyte(s) during ovulation
    • luteal phase: corpus luteum secretes hormones that continue the preparations for pregnancy; if pregnancy does not occur the corpus luteum ceases to function after about 2wks; ovarian cycle begins again
    • changes in endometrial lining-
    • menses: ovary corresponds to menstrual bleeding from the uterus
    • proliferative phase: endometrium adds a new layer of cells in anticipation of pregnancy
    • secretory phase: hormones from the corpus luteum convert the thickened endometrium into secretory structure; no pregnancy = loss in layers of secretory endometrium during menstruation
  135. Hormonal Control of Menstrual Cycle:
    • GnRH from hypothalamus
    • FSH and LH from anterior pituitary
    • estrogen, progesterone, inhibin, AMH from ovary
    • estrogen dominant in follicular phase
    • ovulation is triggered by surges of FSH and LH
    • progesterone is dominant in luteal phase (estrogen is also present)
  136. Procreation:
    • erection: parasympathetic activation, sympathetic inhibition; NO brings blood -> penis
    • ejaculation: sympathetic activation of duct system smooth muscle
    • erectile dysfuction: stress and age; physiological, hormonal, neural, vascular insufficiency
  137. Fertilization:
    • takes place in the distal part of the fallopian tube
    • of the millions of sperm only about 100 make it
    • to fertilize the egg the sperm must penetrate both an outer layer of granulosa cells and zona pellucida
    • to get past barriers sperm release powerful enzymes that dissolve cell junction and zona pellucida
    • the first sperm to reach the egg finds sperm binding receptors on egg membrane and fuses membranes
    • the sperm nucleus then sinks into eggs cytoplasm
    • once the egg is fertilized it becomes a zygote and undergoes mitotic division
  138. Developing Zygote Implants in Endometrium:
    • zygote moves from distal fallopian tube -> uterine cavity over 3-4 days
    • under influence of progesterone
    • implantation on uterine wall - 7days after fertilization
    • ovulation -> fertilization 1 -> cell division 2-4 -> blastocyte reaches uterus 4-5 -> blastocyte implants 5-9
  139. hCG:
    • peptide hormone secreted by chorionic villi and developing placenta
    • structurally related to LH and binds to LH receptors
    • under the influence of hCG the corpus luteum keeps producing progesterone to keep endometrium intact
    • 7th week placenta takes over progesterone production and corpus luteum degenerates
    • hCG production by placenta peaks at 3 months then diminishes
    • hCG also stimulates testosterone by developing testes in male fetuses
    • chemical detected by pregnancy tests
  140. Labor and Delivery:
    • paturition = birthing process:
    • fetus is normally head down -> rhythmic uterine contractions push head against softened cervix stretching and dialating it -> once the cervix is fully dialated and stretched the uterine contractions push fetus out through the vagina -> placenta detaches from the uterine wall and is expelled
    • 38-40 weeks of gestation
    • initiation of postive loop requires a uterus that is ready to respond to these stimuli
    • fetus drops lower in uterus -> cervical stretch -> uterine contractions -> cervical stretch -> oxytocin from posterior pituitary prostagladins from uterine wall -> uterine contractions
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