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187 Cards in this Set
- Front
- Back
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Describe the mechanics of inspiration |
-contraction of diaphragm + external intercostal muscles -Increase in thoracic volume causes intraplueral space to expand, pressure to become more negative -Alveoli expand due to negative pressure overcoming force of elastin. Expnasion causes a decrease in alveolar pressure, air flows into lungs -Active process |
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Describe the mechanics of expiration |
-passive elastic recoil of lung and chest wall -w/ increased effort abdominal muscles contract, pushing up diaphragm and internal intercostal muscles contract forcing ribs down |
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What is meant by static condition? |
-no movement of air into, or out of the lungs -occurs at the end of expiration or end of maintained inspiration -Due to La Place's law, two forces equal in magnitude oppose each other -Force 1: distending pressure gradient (P) -Force 2: Tension of elastic lung tissue, elastin and collagen (T) P = 2T/r |
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List the four functions of surfactant |
*produced by type II cells 1. reduces surface tension at air-liquid interface - increases compliance. W/o surfactant Intrapleural pressure would need to be more negative to expand lungs 2. Allows surface tension to be proportional to volume - promotes uniform alveolar expansion (prevent smaller alveoli from emptying into larger alveoli 3. Allows hysteresis 4. Increases interstitial pressure, preventing edema |
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Define pneumothorax |
-Violation of the chest wall allows air entry into the intrapleural space -distending pressure gradient is disrupted and the lung collapses |
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Describe the effect of gravity on intrapleural pressure |
-Because of gravity, intrapleural pressure is less (more negative) at top of lungs than at bottom -During inspiration intrapleural pressure is decreased the same amount throughout, so alveoli under high pressure will expand more |
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Differentiate the two types of lung diseases |
1. Obstructive = increased airway resistance, obstructs airflow and narrow airways. Examples = asthma, emphysema, bronchitis 2. Restrictive = decreased compliance, restricts expansion and stiffens lungs + chest wall. Examples = pulmonary fibrosis, IRDS, pneumothorax, obesity |
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Describe the compliance of a child's lungs to that of an adult |
-C = ΔV/ΔP -Child's lung has is smaller, and thus ΔV will be smaller -Same pressures involved in both child and adult inspiration/expiration (ΔP is the same), but because ΔV is smaller for children, their lung compliance is less |
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Describe the pressure-volume curve and how lung disease changes the curve |
-Slope of the curve is equal to compliance; compliances decreases at higher volumes -In normal lung at transorgan pressure (alveolar pressure - IP pressure) of 5cm H2O, and chest wall pressure of -5cm H2O the lung volume is at FRC -In restrictive lung disease, lung compliance is reduced so slope is reduced; requires increased alveolar pressure and chest wall pressure to achieve change in lung volume |
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Highlight general transport along the nephron and the advantages/disadvantages of vascular filtration |
Filtration (passive) -> reabsorption (active) -> secretion (active) -> excretion Advantages of high filtration rate = foreign and harmful substances rapidly eliminated, and rapid adjustment to solute concentrations Disadvantages = Requires large and rapid reabsorption |
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Describe the main function of the proximal tubule, loop of henle, distal tubule and collecting duct |
Proximal tubule - reabsorption of majority of filtrate Loop of Henle - concentration of urine Distal tubule - dilution of urine Collecting duct - Control of excretion *Loop, DCT and collecting duct influence osmolarity and ICF volume. PCT reabsorption is large and does not changes osmolarity, influences ECF volume |
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List the different fluid compartments and their water percentages by volume |
Intracellular fluid (ICF) = 40% of body weight in water; 28L Extracellular fluid = 20% of body weight in water, consists of plasma (1/4 of ECF) and interstitial fluid (3/4 of ECF); 14L |
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Describe how body fluid compartments are measured |
-Basis: Inject solute and measure plasma concentration over time. Once steady state has been reached, you can extrapolate the curve to determine the initial concentration *Volume = (amount injected)/(conc. at time zero in plasma) -Total body water measured using a substance that distributes throughtout whole body (radioactive water, antipyrine) -ECF volume measured using substance that cannot penetrate cells (inulin, mannitol, etc.) -ICF = Total body water - ECF -Plasma volume measured using substance that does not penetrate endothelium (albumin) |
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Describe the difference in forces facilitating fluid movement b/w the plasma and interstitial and, the interstitial and intracellular compartments |
-Water movement b/w plasma and interstitium dependent on starling forces: balance of hydrostatic and oncotic pressure (impermeable proteins influence oncotic pressure) -Water movement b/w the ECF and ICF due to osmotic pressure, differences in osmolality |
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Describe the difference b/w plasma osmolality and protein oncotic pressure |
-Protein oncotic pressure does not take into account small solutes (i.e. Na+) as these move easily across endothelial cell barriers, and thus do not encourage water movement b/w plasma and interstitium. Small solutes DO NOT move easily across epithelial (ECF-ICF) barriers and thus water must move to equilibrate osmolality. -Alternatively changing protein concentration does little to affect osmolality as is represents <1% mOsm/kg water |
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What is the most cited osmolality and what solutes are responsible for ECF osmolality vs ICF osmolality |
Most cited osmolality = 287mOsm/kg, can be estimated: [Na+] x 2 Na+ (140mEq/L), Cl- (100mEq/L), HCO3- (24mEq/L) are responsible for extracellular osmolality ICF osmolality due to K+, organic sulfates, proteins and other solutes |
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Describe the ways in which water is lost/gained throughout one day |
Loss/gain = 2.5L/day Gain: Fluid intake (1.2L), food (1.0L), oxidative phosphorylation (0.3L) Loss: Urine (1.4L), Insensible (0.9L), feces (0.1L), sweat (0.1L at rest) |
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Describe the types of fluid imbalances |
Cellular dehydration = solute free water loss (i.e. insensible water loss) results in increased plasma osmolarity, hypernatremia; lethargy, confusion, disorientation Cellular edema = solute free water gain (i.e. ADH control problems), decreases plasma osmolatiry, hyponatremia, impairs blood flow to brain -> fainting Extracellular dehydration (hypovolemia) = loss of isoosmotic fluid (i.e. diarrhea), results in hypotension (decreased preload, decreased CO) Extracellular edema (hypervolemia) = excess Na+ intake (i.e. renal problems), increased plasma [Na+] and Osm, results in increased central venous pressure -> edema |
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Describe the role BUN and plasma [glucose] play in plasma osmolarity |
-Plasma osmolarity mostly dependent on plasma [Na+], but larger (10x) increases in BUN and glucose can also influence plasma OSM -Posm = (2[Na+])(BUN/2.8)([Glucose]/18) |
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Describe how the following values change in acute hyperglycemia: Posm, plasma [glucose], plasma [Na+] How does hyperglycemia contribute to water diuresis |
-increased plasma [glucose] raises Posm, yet dilutes plasma [Na+] -The glucose in the plasma will increase ECF osmolarity, to compensate solute free water will flow from the ICF to the ECF, driving [Na+] down -Glucose causes water movement from the ICF to the ECF, which will eventually be incorporated into urine -> Osmotic diuresis that raises [Na+] and Posm *Decrease of 1.6mEq/L of Na+ for every 100 mg/dL increase in glucose over 100mg/dL |
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Describe how the following values change in renal failure: Posm, BUN, plasma [Na+] How does renal failure contribute to hyponatremia |
-Increased Posm and BUN, but [Na+] remains constant -Because urea moves across cell membranes, changes in BUN will NOT cause a fluid shift from the ECF to ICF -HOWEVER, thirst and poor water excretion as a result will lead to water retention which will help reduce Posm and also [Na+] -> hyponatremia |
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Describe the difference between laminar and turbulent flow |
-Turbulent flow is proportional to the square root of the pressure gradient - takes more pressure to generate same flow, and is more likely to occur in larger airways where the velocity is high -Re = (2 x radius x velocity x density)/n -If Re > 2000, then flow is turbulent -Turbulent flow especially useful in mobilizing secretions |
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Describe the effect of lung volume on airway resistance and how this is related to obstructive lung disease |
-Lung volume is inversely proportional to airway resistance -As lung volume increases airway radius increases -> increases cross sectional area. *Remember cross sectional area is inversely proportional to resistance -In obstructive disease resistance is elevated at ALL lung volumes (i.e. upward shift of resistance vs volume plot) |
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Highlight neural/humoral control of airway resistance |
-Parasympathetic = constriction and increased mucosal secretion (ACh signaling via CN x, anticholinergics will block) -Sympathetic = dilation (via B2 receptors of smooth muscle, asthma inhalants = B agonists) -Inflammatory mediators (histamine), constrict -NO dilates -Hypocapnic constriction: low local CO2 causes local constriction |
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Describe dynamic compression (Equal pressure point theory) |
-During forced expiration pressure exerted by muscle on airways -Equal pressure point: where thoracic pressure = airway pressure. At every point above EPP, airway will be compressed, limiting the amount of flow during forced expiration -In normal lung, intact elastin + collagen provides enough tension to counteract thoracic compression, so that compression occurs in large airway supported by cartilage -In COPD lung, breakdown of elasticity or edema means compression in smaller airways. Breathing through pursed lips compensates by moving EPP to larger airway |
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Describe the role Antitrypsin plays in preventing obstructive disease |
-Inhibits elastase release by neutrophils -With Antitrypsin deficiency, individuals are at risk of emphysema late in life, and especially if they are exposed to cigarette smoke |
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Explain the importance of pH regulation |
-Fluctuations in pH change the structure and function of proteins -chemical buffers, lungs and kidneys act to regulate blood pH |
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Define buffers and describe how they regulate blood pH |
Buffers = mixture of weak acid/base and their conjugate base/acid -Mitigate changes in [H+] upon the addition of other acids/bases, but are only effective when the pH of the soln is with 1 unit of the buffer pKa -Lower pKa = stronger acid (0-2 strong, 3-7 weak, >8 very weak) -In blood HCO3- serves as conjugate base, CO2 is conjugate acid CO2 + H2O <-> H+ + HCO3-, catalyzed by carbonic anhydrase |
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Define normal blood pH, [H+] and how [H+] compares to other ions in the blood |
pH = -log [H+], normal blood pH = 7.4 -pH must be between 6.8 - 7.8 -normal [H+] is equal to 40nm, which is VERY low compared to Na+, K, HCO3-, Cl- which are all measured in mEq/L |
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Define buffer capacity and which factors affect buffer capacity |
-Buffer capacity = how resistant a soln is a changes in pH -Depends on the concentration of the buffer pair and the pKa/b of the buffer -Stronger buffer capacity = more acid/base required to change the pH by one unit -Most effective buffer is CO2/HCO3- because of large concentration of both, metabolism provides endless amount of CO2 |
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Define the Henderson-Hasselbach eqn |
pH = pKa + log ([base]/[acid]) -Describes changes to pH upon addition of an acid/base -Simplified version for bicarbonate buffer system: [H+] = 24(PCO2/[HCO3-]) |
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Aside from CO2/HCO3- buffer system, what other buffers exist in blood? |
1. Hemoglobin (histine residues), pKa ~ 6.5 2. Plasma proteins (histine residues) 3. Phospate, pKa ~ 6.8 *Multiple buffers allow for greater buffer capacity (resistance to pH changes) - For example blood resists pH change better than CSF which lack hemoglobin |
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Define 'open' system buffer and how it is different from a 'closed' system |
-Phosphate and hemoglobin/proteins serve as closed system buffers because their concentrations are limited -CO2/HCO3- serves as open system buffer as their concentrations can be adjusted relatively quickly via lungs and kidneys |
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How are FEV1, FVC, and FEV1/FVC changed in restrictive/obstructive disease? |
Restrictive disease = reduced compliance, decreases in both FEV1 and FVC, but same FEV1/FVC ratio Obstructive disease = increased resistance, decreases in FEV1, slight (if any) decrease in FVC, decreased FEV1/FVC (less than 75%) *Both will have decreased maximal flow rate |
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Describe the difference in mechanics of obstructive vs restrictive disease |
Obstructive = work to overcome airway resistance is high. Compensation via increased tidal volume, decreased frequency of breaths. Restrictive = Work to overcome elastic recoil is higher, decreased tidal volume, increased frequency of breaths |
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Describe the difference between variable intrathoracic and extrathoracic obstruction. How would the flow volume loop for each look? |
Intrathoracic obstruction = during expiration Intrapleural pressure (Ppl) becomes greater than than tracheal pressure (Ptr) - airways are compressed and maximal flow reduced. During inspiration Ptr > Ppl, so flow is not limited Extrathoracic = during expiration Ptr > Patm, so flow is not limited. During inspiration Patm > Ptr and the airway is compressed, reducing maximal flow |
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Define the time constant and list factors that affect it |
-Time constant = alveolar emptying time -Dependent on resistance and compliance of lung. Increases in resistance AND complianc will (i.e. emphysema) cause alveolar emptying to be delayed |
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Describe some of the issues that may occur during gas exchange leading to a high Paco2 or low Pao2 |
High Paco2 = hypoventilation (via low total or high dead space ventilation) Low Pao2 = low inspired oxygen (altitude), hypoventilation, diffusion impairment, intrapulmonary shunt, VA/Q mismatch |
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Define ventilation and the factors that affect it |
Ve = Vt x f OR Ve = (Va + Vd)f Not all gas participates in gas exchange, some is ventilated to dead space, only alveolar ventilation is perfused Va = Ve(1-(Vd/Vt)) |
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Compare alveolar and arterial Pco2. How are they calculated, and what factors cause a change in value? |
Paco2 and PAco2 are equal to each other, abnormalities affecting gas exchange have little effect -calculated: Paco2 = 0.863(Vco2/Va) -Normal Paco2 is 40torr -At constant CO2 production, Paco2 can be increased by 1) reducing total ventilation or 2) increasing dead space -Changes in Vco2 in the case of increased metabolic rate (i.e. exercise |
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Compare alveolar and arterial Po2. How are they calculated and why are they different? |
PAo2 = PIo2 - (PAco2/R) -Unlike CO2, abnormalities affecting gas exchange cause arterial O2 to be less than alveolar O2 -P(A-a)o2 is zero in the ideal lung, but always greater than zero in reality. Increased A-a difference in indicative of disease |
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List the three types of dead space and how dead space can be approximated using Bohr's eqn and Fowler's technique |
-Anatomical dead space = Gas that enters and stays in airways, does not participate in gas exchange (normal = 2.2mls/kg) -Alveolar = gas that enters alveoli, but is not perfused, so no gas exchange occurs -Physiological dead space = anatomical + alveolar -Bohr's eqn: Vd/Vt = (Paco2 - PETco2)/Paco2 -Fowler's technique: Anatomical dead space = 1/2 PETCo2 -Anatomical dead space increases w/ size, age, bronchodilators. Alveolar dead space increases w/ Zone I conditions, vascular occlusion |
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Low inspired oxygen and hypoventilation are two factors that contribute to low Pao2. Describe how |
PAo2 = PIo2 - (Paco2/R) OR PAo2 = FIo2 (Patm - 47) - (Paco2/R). -With low inspired oxygen, FIo2 will decrease bringing Pao2 down. With hypoventilation, Paco2 will increase, Pao2 will increase, also bringing Pao2 down |
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Differentiate metabolic vs respiratory acid-base imbalances |
Respiratory imbalances are due to the inability to maintain a Pco2 of 40mmHg. Increased Pco2 (hypercapnia) causes respiratory acidosis. Decreased (hypocapnia) causes respiratory alkalosis Metabolic imbalances are caused by alterations in plasma [HCO3-] from 24mEq/L. Increases (hypobicarbonatemic) cause acidosis. Decreases (hyperbicarbonatimic) cause alkalosis *Acute condition time span less than 12 hours in duration* |
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Describe the immediate response to acid/base imbalance |
-Buffering serves as the immediate response -Respiratory disturbances = more than 90% of buffering occurs within cells. Example: in the case of acidosis, increased Pco2 will shift eqn to produce H+, H+ buffering through formation of HbH+ -Metabolic disturbances = bicarbonate and non-bicarbonate buffers contribute to maintain pH. Example: in acidosis, increased [H+] shift eqn to production of CO2 and HbH+ |
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Describe the davenport diagram |
-graphical representation reflecting changes in pH, Pco2, and [HCO3-] during acid-base imbalances in the blood -Iso bars reflect changes in pH, with chages in [HCO3-] at a constant pCO2 and are connected via a buffer line -Primary disturbance will cause movement on the buffer line (to a new isobar and pH), and compensation will cause movement on the new isobar to normalize pH |
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List some of the key features of compensation |
-Not all compensations are equally effective -Metabolic compensation of primary respiratory disturbances is usually more efficient -Best compensated disturbance is respiratory alkalosis -In any case pH never returns back to its initial value |
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What information about acid-base imbalance can be made from [HCO3-] |
-Venous [HCO3-] nearly equivalent to venous CO2 -Low bicarbonate indicates metabolic acidosis OR compensated respiratory alkalosis -High bicarbonate indicates metabolic alkalosis OR compensated respiratory acidosis |
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Define the anion gap and describe it's relevance in acid-base disorders |
-Difference of measured cation and anions in plasma = [Na+] - [HCO3-] - [Cl-] -Na+ is greater than extra HCO3- and Cl-, normal difference is 12 ± 4 mEq/L -Hypercholremia (i.e. HCl addition) does not change the gap but is indicative of metabolic acidosis -Normochloremia (addition of lactic acid) increases the gap and is also indicative of metabolic acidosis |
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Describe the difference between pulmonary vasculature and systemic vasculature |
-Pulmonary vessels are are less resistant (10x) and more compliant (due to recruitment and distension) than systemic vessels, because of this there is less work by the right heart -Increased sympathetic activity decreases compliance, and only slightly increases resistance forcing blood back into systemic circulation |
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What factors regulate pulmonary vasculature? |
-Primarily regulated by hypoxia and passive mechanical factors -Autonomic innervation is sparse compared to systemic circulation and causes only minor changes in resistance -> reduces compliance to return blood flow back to circulation |
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Describe the mechanism for hypoxic pulmonary vasoconstriction |
-Hypoxia (low PAo2) is the most important regulator of pulmonary resistance, serves to preserve Pao2 -Low local PAo2 causes LOCAL vasoconstriction. This reduces blood flow to that section and sends it to areas of the lung with higher PAo2 *Pulmonary vascular response to low O2 opposite of systemic response - body vessels dilate in low O2. Also in lung wide hypoxia, vasoconstriction leads to pulmonary hypertension and edema |
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Describe the mechanism for passive control of pulmonary vasculature resistance |
-Forces that act to change resistance are tethering and transmural pressure -Ptm = Pi - Po. Pi changes based on volume/cardiac output. In cases on increased CO there is recruitment of new vessels (alveolar) and distension of already open vessels (extra-alveolar) -Po depends on where the vessels are located. For alveolar vessels low pleural pressure (i.e. inspiration) and/or alveolar edema will cause lung and alveolar expansion, this will compress these vessels. For extra-alveolar vessels, high pleural pressure (i.e. expiration) along with perivascular edema will cause compression of these vessels -Vessels are in series so resistance adds together and is lowest at FRC |
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Describe the effect of gravity on pulmonary circulation |
-Gravity increases vascular pressures with increasing lung depth, while alveolar pressure stays constant -At Zone 1: PA > Ppa > Ppv. Alveolar vessels are collapsed, and no perfusion (all dead space). Does not usually occur (unless tall, hemorrhage, PEEP, PPB) -Zone 2: Ppa > PA > Ppv. Flow depends on ΔP b/w artery and alveoli. Blood flow increases w/ depth since gravity facilities ΔP increase (waterfall zone). -Zone 3: Ppa > Ppv > PA. Flow increases with depth but at rate less than that of zone 2 |
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Describe how Va/Q distribution changes with lung height |
-Both ventilation and blood flow decrease as you move from bottom of the lung to the top -Blood flow rate of change is higher though, and Va/Q increases as you move form the bottom of the lung to the top -This is due to the affects of gravity on blood flow and ventilation in the lung, along with hypoxic pulmonary vasoconstriction compensation |
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Highlight the features of bronchial circulation |
-Broncial arteries originate from the aorta, make up 1% of cardiac output -Bronchial veins may drain into systemic circulation causing venous admixture, or into systemic veins via the azygous vein |
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Describe the conditions under which pulmonary edema occurs |
Most common: 1. LH failure (cardiogenic: leads to increased Pc) 2. Increased permeability (Kf) due to vascular damage (ARDS, non cardiogenic) Less common: 3. poor lymphatic clearance, 4. hemodilution *Decreased surfactant |
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Describe the conditions which cause O2 uptake to be limited by diffusion |
1. surface area for diffusion reduced by disease 2. Blood-gas barrier thickened by disease 3. Decreased time allowed for equilibration 4. Low O2 partial pressure gradient *In absence of these conditions, O2 is perfusion dependent |
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Define Fick's law and factors affecting diffusion |
V = A·d/T(P1-P2) A = area, decreased by embolism, bronchial obstruction, emphysema T = thickness = increased by edema, fibrosis Pressure gradient reduced for O2 at altitude and with hypoventilation |
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Describe the difference between perfusion dependent vs diffusion dependent gases |
Perfusion dependent: Reach equilibrium in blood very quickly. Therefore the amount taken up per unit time depends on the amount of blood delivered to the alveoli (i.e. N2) Diffusion dependent: Does not reach equilibrium in time that blood is presented to the alveoli (0.75s, i.e. carbon monoxide) |
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Describe why diffusion impairment effects O2 equilibration and not CO2 equilibration |
-In order to enter blood O2 must diffuse, so PO2 of blood dependent on diffusion AND reaction rate (Hb + O2 -> HBO2) -CO2 release is not dependent on diffusion, since CO2 is carried in the blood as bicarbonate, instead limited by reaction rate. *Diffusion impairment more likely to have larger effect on systemic circulation as gases must dissolve much farther |
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Describe diffusion capacity, how it is measured, and the implications of reduced diffusion capacity |
-Diffusion capacity measures the transfer of gas from the lungs to the capillaries -DLco is measured by having a patient inhale and exhale CO. CO uptake (Vco) divided by end tidal CO (PETco) yields DLco -This value is then used to calculate O2 diffusion capacity: DLo2 = 1.23·DLco -diffusion capacity for CO and O2 are nearly equal, but CO2 release is dependent on rxn rate, while O2 diffusion is dependent on both -A Low DLco implicates hypoxia, but NOT necessarily hypoxemia due to diffusion impairment (hypoxemia usually due to Va/Q mismatch in these cases) |
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Define GFR and RPF and the normal value for each |
RPF = renal plasma flow, measured at 625ml/min and renal blood flow calculated at RPF/(1-hematocrit) GFR = glomerular filtration rate, rate of fluid that moves from RPF (1/5 RPF) into Bowman's space *Filtration fraction = GRF/RPF. Solutes not filtered become concentrated in plasm leaving via the efferent arteriole |
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What criteria must a solute fulfill to be used to measured GFR |
-must be freely filtered -not reabsorbed by the tubules -not secreted by the tubules -not metabolized in kidney *Two substances that satisfy the criteria are inulin (exogenous) and creatinine (endogenous) *Differs from substance used to measure RPF in that RPF measuring substance are NOT freely filtered |
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What three forces drives glomerular filtration? |
GFR = kf(Pgc - (Pt + πgc)) -Pc (capillary hydrostatic pressure) drives fluid out of the capillaries into the PCT, while tubular hydrostatic pressure and capillary oncotic pressure drive fluid out of the PCT into the capillaries) |
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Why is it that protein osmotic pressure increases along the length of the glomerular capillary while plasma osmolality does not? |
-Because small solutes and water are filtered though capillaries and diffuse rapidly, equilibrium between the filtrate and plasma is reached so plasma osmolality remains the same -Plasma protein are too large and are negatively charged to pass through the capillary, so as water leaves these proteins become more concentrated, increasing the protein osmotic pressure along the length of the capillary *Changes in GFR DO NOT cause changes in plasma osmolality since isoosmotic fluid being secreted |
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Define filtration equilibrium |
-Point when net driving force for filtration is zero -Changes in resistance of efferent arteriole cause changes in Pgc, and thus GFR. Filtration equilibrium limits the influence of altered efferent resistance and compensates by changing protein osmotic pressure -As fluid is filtered out πgc increases to oppose filtration of fluid out of the capillary. Equilibrium is reached at a point on the capillary where Pt + πgc is equal to Pgc |
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What features are unique to glomerular capillaries (as opposed to other capillaries) |
-Glomerular capillaries are in b/w two capillaries, have low vascular resistance and high filtration rate. This causes: 1. Pgc to be high (high resistance of efferent) 2. Pgc to remain almost constant across the capillary due to low resistance 3. πgc to increase along the length of the capillary due to filtration |
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Describe the role the afferent arteriole plays in modulating GFR and RPF |
-Afferent arteriole may constrict/dilate in response to sympathetic activity and vasoactive substances (adenosine - causes constriction) -Constriction lowers RPF AND Pgc -> this causes decreased GFR -Dilation increases RPF and Pgc -> this increases GFR -There is little/no influence on the peritubular capillaries because no change in filtration fraction |
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Describe the roe the efferent arteriole plays in modulating GFR and RPF |
-Constriction lowers RPF and Ppc BUT increases Pgc -Dilation increases RPF and Ppc BUT decreases Pgc *Changes in Ppc and πpc will influence PCT reabsorption as filtration fration will change, this is the main role of the efferent arteriole resistance |
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Why is it that changes to efferent arteriole resistance produce small variable changes in GFR |
-GFR vs resistance curve: GFR will increase, then decrease -Increasing efferent resistance decreases RPF -> the result is increases filtration fraction -Increased filtration fraction will increase πgc, this will offset rises in Pgc -Lastly filtration equilibrium will be reached at shorter distance into the glomerular capillary, so Kf will decrease |
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What direct effects, if any, do changes to RPF have on GFR |
1. If there is no filtration equilibrium, changes to RPF will NOT change GFR - only changes to Pgc will change GFR 2. If there is filtration equilibrium, changes to RPF will increase GFR |
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Describe the difference between clearance and excretion |
-Clearance is the amount of solute excrete by the kidneys relative to plasma concentration: C = UV/P -Excretion is the amount of solute coming out of the body in urine per unit time = UV |
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Describe the difference between carrying capacity, O2 saturation and O2 content |
Carrying capacity = the volume of O2 that may be carried in blood: (1.34mLO2/gmHgb)x(15gmHgb/100mLBlood)x(0.97) + (0.003mLO2/dL-torr)x(100torr) Saturation = Actual O2 content as a percent of the carrying capacity, normally 97% O2 content = amount of O2 bound to hemoglobin + O2 that is physically dissolved |
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Define the Bohr effect |
-Oxygen dissociation curve influenced by temp, pH, Pco2 and 2-3 DPG -Right shift: increased temp, Pco2, 2-3DPG, or decreased pH -With right shift, O2 unloading becomes more efficient. This happens often in peripheral tissues where there is higher Pco2 and lower pH -Alternatively in lungs, Pco2 drops and pH raises to allow greater O2 to be bound at lesser Po2 |
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Explain why increasing FIo2 does not help in the case of a pulmonary shunt |
-Because non shunted hemoglobin is already nearly fully saturated with oxygen and shunted blood never comes into contact with oxygen, increasing FIo2 will have no effect on a pulmonary shunt |
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Describe the mechanism for pulmonary shunt |
-In some cases, bronchial occlusion, or pulmonary edema will prevent gas exchange at perfused alveoli -This blood (still venous: Po2 = 40, Co2 = 15) will mix with blood that is oxygenated (Po2 = 100, Co2 = 20). The mixing will cause Po2 and Co2 to drop in arterial blood (Po2 = 54, Co2 =17.5) -This blood will perfuse system and come back with Po2 and Co2 LESS than that of normal venous blood. Eventually a steady state will be reached (Po2 = 44, Co2 = 16.25) |
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Define intrapulmonary shunt fraction |
-Fraction of cardiac output reaching arteries without coming into contact with alveolar gas Qs/Qt = (Ccapo2 - Cao2)/(Ccapo2-Cvo2) |
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Describe the difference between true/absolute intrapulmonary shunt and venous admixture |
True/Absolute pulomnary shunt fraction MUST be measured on 100% O2 (FIo2 = 1.0) and includes anatomical shunt (normal) and alveolar shunt (pathological) Venous admixture is the percent of CO that bypasses gas exchange and is measured when FIo2 < 1.0. It will always be greater than the true shunt because it includes the true shunt (anatomoical and alveolar) and areas with shunt-like states: areas of Va/Q mismatch and diffusion impairment |
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Describe how CO poisoning and anemia effect oxygen transport? |
Anemia = Hgb concentration is low. Max O2 bound to Hgb is low, but p50 normal (better than CO poisoning assuming same PO2) CO poisoning = useful [Hgb] decreases with increasing CO, and curve shift left - prevents unloading of O2 Both cause decreased Cao2, Pvo2, Cvo2, but DO NOT effect PA/a O2 |
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Describe the function of the PCT and what two transport steps are needed to accomplish this goal |
-PCT reabsorbs the majority of the filtrate -First solutes move through the tubular epithelium - creating a osmolality gradient, water then follows via AQP1 (rate limiting step) -Second, water moves through the capillary endothelium due to differences in protein osmotic pressure (high πpc, low Ppc) - solutes follow by diffusion *reabsorption facilitated by "leaky" epithelia |
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How is reabsorption calculated? |
-Micropuncture of tubule allows assessment of tubular [inulin]. As water is reabsorbed, inulin remains. Tubular/Plasma inulin can be calculated -Fraction of GFR reabsorbed = 1 - (1/TFPinulin) -TP/Pinulin proportional to amount reabsorbed |
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Describe Glucose reabsorption in the early PCT |
-Normally glucose is 100% reabsorbed -Glucose enters the epithelial cell via 1 of 2 proteins: SGLT1 (high affinity), SGLT2 (high capacity: lowers to 0.8mg/dL) -Protein use secondary active transport: coupled with Na+ movement into the cell -Glucose then moves into the interstitium via facilitated diffusion *Because glucose transport coupled with Na+, build up of Na+ (i.e. faulty Na+/K+ ATPase) will prevent glucose reabsorption *Fasting glucose (80mg/dL) lower than plasma threshold (200mg/dL) |
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Describe phosphate reabsorption in the early PCT |
-Phosphate absorbed into epithelial cell via secondary active transport: coupled with Na+ movement into the cell -Transported into the epithelium via facilitated diffusion -PTH decreases the number of carrier proteins and increases phosphate excretion (*increases Ca2+ reabsorption in DCT) -Different from glucose reabsorption in that with glucose normal plasma conc. is below Tm conc. With phosphate, normal plasma conc is at Tm conc |
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Describe Na+ reabsorption in the early PCT |
-Sodium reabsorption via primary active and secondary active transport -Secondary transport: Na reabsorption into epithelial cell coupled with phosphate, glucose reabsorption and H+ secretion. Transport into interstitium via coupled transport w/ HCO3- -active transport into interstitium via Na+/K+ ATPase *Remember that Na+ absorption is coupled with HCO3- formation |
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Describe K+, Ca2+, and urea reabsorption in the early PCT |
-Reabsorption is passive and paracellular dependent on water reabsorption -Water diffuses into interstium via transcellular (aquaporin) and paracelluar routes -This creates conc. gradient in the PCT for solutes -Solutes diffuse into interstitium via epithelial junctions -Water reabsorption directly affects urea excretion/BUN |
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Describe the role that the late PCT plays in reabsorption |
-Reabsorption of NaCl (secondary active for Na and Cl AND passive for Cl-) and water -While water continues to diffuse via paracellular route, NaCl absorbed via antiporters: Na+/H+ antiporter (same as early PCT) and Cl-/anion antiporter (only in late PCT, prevents net HCO3- reabsorption) -H+ and anion combine and move back into the cell -Additionally Cl- diffuses into interstitium via paracellular route and causes water to follow *Absorption of water, Na+, Bicarb in early PCT increased tubular Cl- which acts as driving force |
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How do changes to tubular reabsorption or tubular fluid in the early PCT influence absorption of NaCl in late PCT? |
-Reabsorption of fluid in early PCT raise [Cl-] in the late PCT -This drives passive (paracellular transport) in the late PCT of Cl- (Na+ moves to maintain electric neutrality) -Osmotic diuretics will inhibit water reabsorption, and thus passive NaCl reabsorption in the late PCT -> ultimate result = hypovolemia and dehydration |
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Explain why proximal tubular reabsorption is characterized as isoosmotic |
-Proximal tubule is "leaky," water is reabsorbed as soon as solutes are reabsorbed - osmotic equilibrium is maintained -While the conc of certain solutes may changes, the TOTAL solute conc. remains the same -This means that changes in reabsorption DO not change plasma osmolality -Reabsorption can change ECF volume however |
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Define Glomerulotubular balance |
-GFR changes frequently (i.e. posture, level of activity) -GT balance allows adjustments to fractional reabsorption in response to changes in GFR (ensure constant NaCl reaches distal nephron) -Increased GFR = increased filtered load for solute -> increased PCT reabsorption rate for solute -MOREOVER- increase in GFR that is disproportional to change in RPF will increase πpc and drive water reabsorption -> increased NaCl reabsorption |
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Explain why changes in the resistance of the efferent arteriole cause changes in proximal tubular reabsorption |
-Efferent constriction increases proximal tubular reabsorption -Constriction raises Pgc causing increased GFR -> and thus decreased Ppc and increased πpc...this favors fluid (increased net Na+) reabsorption -Dilation has the opposite effect |
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Provide an overview of organic cation/anion secretion |
-Often referred to as tertiary active transport: 1) Na pumped out via Na+/K+ ATPase, 2) Na+ coupled import w/ a-KG, 3. a-KG export couples with PAH import...PAH facilitated diffusion into lumen -Secretion of anion/cation causes equilibrium shift in favor of protein-bound ion releae -At low conc. secretion rate determines excretion, at higher conc. excretion rate determined by filtration |
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Explain the role gravity and age has on Va/Q |
-Greater ventilation as base of lung and greater perfusion at the base of the lung (greater compliance), and greater perfusion at base of lung (greater intravascular pressure) -Excess perfusion > excess ventilaiton so Va/Q at base is LOWER than Va/Q at apex -Age increases Va/Q distribution: less areas of the lung with a Va/Q of 1 |
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what compensatory mechanism exist to keep Va/Q constant? |
-Hypoxic pulmonary vasoconstriction: diverts blood away form hypoxic regions of the lung in the case of excess blood flow) -Hypocapnic bronchoconstriction: diverts ventilation away from areas of the lung with low Pco2 (in the case of excess ventilation) |
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Describe the differences in Va/Q mismatch as a result of alveolar dead space vs as a result of intrapulmonary shunt |
In the case of alveolar dead space: Va/Q > 1. In the case of intrapulmonary shunt or venous admixture: Va/Q < 1 |
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Describe the difference between an ideal lung model vs a realistic lung model |
Ideal: PETco2 < PAco2 = Pcapco2 = Paco2 PETo2 = PAo2 = Pcapo2 = Pao2 Realistic: PETo2 > PAo2 due to alveolar dead space PAo2 > Pcapo2 due to diffusion impairment Pcapo2 > Pao2 due to intrapulmonary shunt |
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What is the effect of increased FIo2 on a Va/Q mismatch of < 1? |
-Because of low ventilation, arterial o2 content is less than normal (0.2mlO2/dl). When Va/Q < 1 O2 dissociation will be on steep part of the curve. In this case increasing FIo2 will increase PAo2 and thus Pao2. This response is different than the one in an intrapulmonary shunt - where increased FIo2 has no effect |
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Explain why Va/Q mismatch results in hypoxemia but seldom hypercapnia |
1. Chemoreceptors: sense increased Paco and stimulate increased ventilation. These sensors are less sensitive to hypoxia 2. High Va/Q areas compensate for low Va/Q areas: because CO2 dissociation curve is linear, areas with high CO2 will offload proportionately more CO2 to compensate for areas that offload low CO2 |
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Describe the difference in solubility of CO2 in plasma vs O2 |
O2 solubility = 0.003mLO2/dL-torr CO2 = 0.06mLCO2/dL-torr CO2 is about 20x more soluble in plasma CO2 content of arterial blood = 49mL, venous blood = 52.5mL Most CO2 in the form of HCO3-, very little actually bound to Hgb (as carbamino) |
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Describe the main difference between CO2 transport mechanics vs O2 transport |
1. CO2 dissociation curve is linear so any % change in ventilation will yield same % change in Pco2. Moreover, hyperventilation of some alveoli can compensate for hypoventilation of other alveoli (i.e. in the case of a shunt) 2. CO2 curve is higher and steeper, the ability of the blood to store CO2 is much greater. Also for any change in partial pressure, change in CO2 greater than change in O2 *For example, with a shunt or Low Va/Q the effect on CO2 exchange will be much less than that of O2 exchange |
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Define the Haldane effect |
-CO2 dissociation curve shifts to the right with increased [HgbO2] and to the left with [Hgb], as -This allows the blood to take up more CO2 where deoxyhemoglobin (i.e. working tissues) is higer - deoxyhemoglin a better buffer of H+ |
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Describe the Cl- shift |
Chloride shift, or hambruger shift is the shuttling of Cl- into the cell and HCO-3 out of the cell. This occurs mostly in venous blood and allows CO2 conversion in HCO3- which may be transported in the blood |
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What role does the kidney play in maintaining bicarbonate homeostasis |
1. Prevents loss of plasma [HCO3-] by reasborbing (~99.5%) 2. Regenerates HCO3- that is consumed in the buffering of acids produced by metabolic processes |
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Explain how bicarbonate is indirect |
-HCO3- is filtered into the tubule but cannot pass through the epithelium because it is a charged molecule -Must be combined with H+ to form CO2 (via CA), which may enter cells -Once CO2 enters cells, it combines with H2O to form H+ and HCO3- (via carbonic anhydrase), HCO3- transport to interstitium coupled with Na+ export in PCT, and Cl- import in the Collecting duct -In order to keep H+ available in the tubule, H+ export into tubule coupled with Na+ transport (via NHE3) in the PCT, and H+ (proton pump) in the collecting duct |
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Describe factors limiting HCO3- reabsorption and the consequences of limited reabsorption in the PCT |
Reabsorption limited by: 1. Leaky epithelium which allows H+ to move down gradient (slight +1mv in tubule) into interstitium - deplets H+ so that not all HCO3- is converted 2. Luminal carbonic anhydrase Consequence of this reabsorption parallels filtered load as HCO3- + H+ concentration serves as limiting reagent. Increased load = increased reabsoprtion. But % absorbed will never be 100% |
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What differences exist between the PCT and Collecting duct HCO3- reabsorption |
1. No luminal carbonic anhydrase in the collecting duct 2. junctions NOT permeable to H+ in collecting duct -ATP proton pump in collecting duct cells allow further acidification of urine (pH ~ 4.5) -H+ buffered via NH3 to form NH4+ -Cl- that was coupled with HCO3- transport moved into tubule and neutralizes NH4+ *While intercalated cells absorb bicarb, they are assisted by principal cells which absorb Na+ and create charge difference in the lumen |
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Define EAP and how the body adjusts to compensate for EAP |
EAP = endogenous acid production of strong or organic acids that drive a fall in the plasma bicarbonate Kidneys are able to secrete non-volatile acids into the urine. Protons liberated from acids will combine with HCO3- to form CO2. CO2 is 1) removed by the lungs, or 2) broken down into H+ and HCO3- for bicarb regeneration. H+ will be secreted to form T.A. or NH4+ |
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Describe the two types of chemoreceptors that stimulate changes in respiraiton |
Peripheral receptors (carotid/aortic bodies): Sense changes to Pco2, [H+], Po2 n the BLOOD Central chemoreceptors (medulla): sense changes to Pco2, [H+] in the CSF *Central receptors have greater impact to changes in respiration, but ONLY peripheral receptors will respond to hypoxia |
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Describe the difference between the relationship of Blood vs CSF Pco2 and Blood vs CSF [H+] |
-CO2 diffused across the BBB easily, changes in Paco2 reflected in Pcsfco2 in minutes -> Pco2 changes primarily drive chemoreceptor stimulation -H+/HCO3- ions diffuse with difficulty so changes in [H]a will not be reflected by changes in [H+]csf |
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Highlight factors that effect integrated responses to Pco2? |
1. Hypoxia/hypoxemia cause curve to shift left AND increases slope 2. Acidosis shifts curve left, alkalosis shifts right 3. Sleep decreases slope AND shifts the curve right 4. Narcotics/Anesthetics decrease slope AND shift curve right 5. COPD shifts decrease slope AND shift curve right |
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What is the difference b/w integrated response to hypoxia vs hypercapnia. Explain why there is a difference |
-Ventilation vs Pco2 curve is linear while ventilation vs Po2 curve is not -Increased Paco2: 1) directly stimulates increases ventilation, 2) causes higher [H+]a which stimulates increased ventilation, 3) causes higher Pcsfco2 (and thus higher [H+]csf). These all stimulate increase ventilation via peripheral and central chemoreceptor cooperation -decreased Pao2: 1) directly stimulates increased ventilation, 2) which decreases Paco2 leading to reduces Pcsfco2 and [H+]csf, opposing ventilation. In this case there is peripheral and central chemoreceptor opposition -In the case of hypoxia, increasing FIco2 will prevent chemoreceptor opposition |
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Describe what happens in chronic metabolic acidosis |
-Primary metabolic acidosis results in increased [H+]a. Increased ventilation reduces Paco2, Pcsfco2 and [H+]csf. This depresses the central ventilation stimulation -Over time [HCO3-]csf will drop to equilibrate decreases [H+]csf. When H+/HCO3- equilibrium in the csf is reached central respiratory stimulation will no longer be suppressed leading to further ventilation |
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Describe what happens in chronic CO2 inhalation |
Primary respiratory acidosis results in increased Paco2 which directly stimulates increased ventilation. It indirectly stimulates increased ventilation by increasing [H+]a along with Pcsfco2 and [H+]csf -Over time [HCO3-] levels in the blood AND csf rise to compensate for increased [H+]a and [H+]csf -> this resets central receptors at an increased CO2 level and blood [H]+ at an increased CO2 level |
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Describe CO2 retention |
When Paco2 levels remain elevated in the blood and CSF despite normal pH (i.e. chronic respiratory acidosis), CO2 retention is observed. In the case of CO2 retnetion, administering O2 will increase Pao2 but may also increase Paco2! |
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What three portions of the nephron are responsible for controlling osmolality? |
-Loop of Henle, distal tubule, and collecting duct -In these regions, junctions b/w epithelial cells are NOT permeable to water (no paracellular transport) and small molecules/water move separately |
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Together the loop of henle, distal tubule and collecting duct work together to serve a function. They also have specific functions that allow the common goal to be reached, define the common and specific functions |
Common: to control ICF/ECF through water/Na+ secretion Specific: Loop of henle -> Provides the osmotic driving force for water reabsorption in the collecting duct Distal tubule -> dilution of urine via NaCl reabsorption Collecting duct -> hormonal control of water/Na+/K+ secretion AND acidification of urine |
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Describe how Na+ and water transport differ in the loop of henle, distal tubule and collecting duct |
Descending limb: Na+ = none, Water = present Thin ascending limb: Na+ = passive, water = none Thick descending limb: Na+ = active, water = none Early distal tubule: Na+ = active, water = none Connecting tubule and collecting duct: = Na+ active (aldosterone), water = present (ADH) |
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Describe ion transport in the thick ascending limb |
Transcellular: NKCC2 protein imports K+ and Na+ with 2Cl-. Paracellular transport driven by the Na+/K+ pump which keeps the Na+ gradient Paracellular: ion diffusion into the interstitium is driven by K+ efflux out of the cell on the apical side. K+ effuses out of the cell on both the apical and basolateral side, but is greater on the apical side - this creates an electrochemical gradient which drives other positive ions (Na+, Ca2+, Mg2+ to the interstitium) *Loop diuretics inhibit NKCC2, this is especially important in the macula densa which is important RPF and GFR autoregulation |
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Describe ion transport in the distal tubule |
Transcellular: NCC protein couples Na+ transport with Cl- transport. Alternatively Ca2+ is imported into the cell (facilitated diffusion) and into the interstitium via Ca2+ ATPase and Na+/Ca2+ exchangers *Thiazide diuretics inhibit NCC protein, but increase Ca2+ reabsorption (less intracellular Na+ = more driving force for Ca2+) *PTH increases Ca2+ reabsorption in the distal tubule by increasing luminal pores, Na/Ca exhanger and Ca ATPase |
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Define load-dependent NaCl absorption and how it differs from glomerulotubular balance |
Load dependent NaCl reabsorption means that as more NaCl is delivered to the loop of henle and the distal tubule, more will be reabsorbed This is different from GT balance in that GT balance is dependent on the movement of solute and fluid together - and compensates for large changes in GFR and reabsorption. Load dependent reabsorption is dependent on the ability of solute to move WITHOUT fluid movement and compensates for very small changes. |
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Describe reabsorption in the collecting duct |
Na+ reabsoprtion dominant Principal cells: regulate water and Na+/K+ excretion and respond to ADH and aldosterone. Na+ reabsorption and K+ excretion are driven by the Na/K pump. Because Na+ reabsorption is so dominant, fluid in lumen becomes negative - prompting a net K+ secretion. *Na+ reabsorption and K+ secretion are coupled in the collecting duct |
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Explain how changes to tubular fluid in the collecting duct influence K+ secretion |
-As you progress down the collecting duct, [K+] increases (due to secretion by principal cells) -Increase in tubular [K+] serves as the limit for K+ secretion -Increasing tubular fluid by increasing GFR, decreasing PCT reabsorption, or the use of diuretics will increase the delivery of fluid to the collecting duct, and promote more K+ secretion. This can lead to hypokalemia |
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Describe the series of adjustments made when Na+ balance is increased |
1. Increase Na+ intake 2. Increased thirst + ADH 3. Increased water reabsorption until normal plasma osmolality reached 4. Increased ECF volume and arterial pressure 5. Increased Na+ excretion |
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Describe the role that increased ADH plays in regulating urine flow and osmolality |
-ADH increases with insensible water loss (increase in plasma osmolality) -Increased ADH -> decreases water excretion but does NOT change solute excretion -Overall result is an increase in urine osmolality, a decrease in urine flow, and a constant solute excretion rate w/ increased ADH |
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Describe how ADH decreases water excretion |
-ADH acts on distal nephron: Connecting tubule, cortical collecting tubule, Outermedullary collecting duct and inner medullary collecting duct -Activates expression of Aquaporin 2 |
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Highlight the Loop of Henle Countercurrent Exchange model |
Step 1: Single effect - Na+ moves into the interstitium from the ascending limb (active transport in the thick, passive in the thin) this raises the osmolality of the interstitium - creates an axial NaCl gradient. The fluid in the descending limb will lose water to reach equilibrium Step 2: Increased osmolality fluid shifts into ascending limb. Second cycle starts *After many cycles a gradient is created; limited by the length of the loop and the amount of fluid moving through the loop |
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Explain why water reabsorption along the medullary collecting duct increases, while at the same time NaCl reabsorption decreases. How is this beneficial? |
This is due to the the ascending limb permeability to NaCl. NaCl transport into the interstitium at the ascending limb causes an increase in interstitial osmolality. This increased osmolality serves as the driving force for water absorption in the medullary collecting duct even though NaCl permeability in the potion of the nephron decreases *This means that changes to aldosterone conc. will not affect the driving force of water reabsorption in the collecting duct |
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Describe the mechanism of vasa recta blood flow in the kidneys |
-countercurrent arrangement like the loop of Henle -> this allows axial NaCl gradient -Low blood flow allows vasa recta to reach equilibrium with osmolality w/ the interstitium -Blood that exits does have slightly higher [NaCl] than blood that enters -High blood flow would decrease time allowed to reach equilibrium and would result in washout -Vasa recta NaCl exchange with the interstitium is a consequence of water movement due to the high protein osmotic pressure in the capillaries |
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List some of the differences b/w COPD and Asthma |
Onset: Asmtha is early, vs COPD which is late Etiology: Asthma is immunologic, COPD due to exposure to risk factors Course: Asthma is intermittent, COPD is chronic Airflow limitation: largely reversibly in Asthma, not in COPD Clinical features: Asthma = episodic wheeze, chest tightening, COPD = chronic cough w/ sputum |
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List some of the risk factors for COPD |
-Cig smoke -Occupational dust/chemicals -Environmental tobacco smoke -Pollution *In addition to genetics, socio-economic status, and age |
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Highlight the mechanism of cigarette induced lung damage |
Smoke derived free radicals and oxidants leads to inactivation of antiproteases, lipid peroxidation, depletion of antioxidant defenses, neutrophil sequestration and transcription of proinflammatory cytokines -> Althogether this provokes epithelial permeability, inflammation and injury |
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List the changes to epithelial structure that cause airflow limitation/obstruction in COPD |
1. Increased mucous secretion (luminal obstruction) 2. Increased mucosal + peribronchial inflammation (obliterative inflammation) 3. Disrupted alveolar attachments (emphysema) |
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How is COPD diagnosed |
-Spirometry must be used to diagnose COPD -Diagnosed when FEV1/FVC < 70% predicted -Four levels of severity: mil, moderate, sever, very severe |
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Describe the function and mechanism for urea recycling |
-Urea produced in the liver via protein metabolism, toxic in high concentrations -In cases of water conservation body must be able to reabsorb water but not urea - this is when urea recycling is important -Urea moves out of the IMCD duct into the distal loop of henle (via UT-A2) -> this concentrates the tubular fluid urea -Does NOT effect water reabsorption since epithelium is permeable to urea - concentrated tubular fluid urea becomes even more concentrated as ONLY water is absorbed in the connecting, cortical and outer-medullary collecting ducts |
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Describe the role of ADH on urea recycling during water conservation |
-ADH increases collecting duct permeability to ONLY water in the connecting tubule, cortical and outer-medullary collecting duct, by upregulating AQP2. So [urea] will increase here -ADH increases collecting duct permeability to BOTH water and urea in the IMCD by upregulating AQP2 and UT-A1 |
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In what two ways is urea recycled? |
1. Urea diffuses out of IMCD and moves into distal descending limb of juxtamedullary nephron 2. Urea diffuses out of IMCD and moves into the vasa recta where it its transported up to short loops in the outer-medulla |
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Describe the changes in Na+/K+ secretion, urine osmolality, and urine flow when plasma ADH decreases from high level to zero |
1. solute (excretion/absorption) will REMAIN THE SAME 2. low ADH will increase water excretion so urine osmolality will decrease and urine flow will increase |
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Describe changes to tubular permeability/reabsorption in the case of water diuresis |
-Low plasma osmolality as a result of increase solute free water intake will decrease ADH to levels close to zero -Low ADH prevents water reabsorption in connecting tubule, and collecting duct -AND- decreased urea movement into the inner-medullary interstitium -Decreased passive NaCl transport from thin ascending limb prevents the establishment of high osmolality gradient used to reabsorb water in the collecting duct -BUT no overall change in NaCl since it is absorbed actively in the thick ascending limb ant DCT |
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Explain why water diuresis will NOT lead to hypokalemia while osmotic diuresis will |
-In water diuresis, increased water movement through collecting duct acts a driving force for increased K+ secretion -HOWEVER- low ADH acts as a counterforce. Since ADH increased apical K+ permeability, low ADH will help retain K+ -On the other hand, osmotic diuresis due to high conc. of solute that will not be reabsorbed, this high osmotic pressure will drive water into the tubular lumen, which will decrease tubular [K+] and drive K+ secretion/excretion *Osmotic diuresis will produce low K+, low Na, loss of free water |
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Explain the difference between loop vs distal tubular diuretics |
Loop diuretics inhibit NaCl absorption in the thick ascending loop. NaCl absorption here sets up the driving force for water reabsorption in the collecting duct. Loop diuretics inhibit the ability to concentrate of urine by interfering with the countercurrent exchange. More,ever, high NaCl entering the DCT which cannot compensate since it reabsorbs so little DCT diuretics: Impair the diluting ability by stopping NaCl transport in the DCT (DCT is major diluting segment). |
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Define the following: hypercapnea, eupnea, hypopnea, and hyperpnea, Cheyne-Stokes respiration. |
Hypercapnea: excessive Paco2 Eupnea: normal appearing depth and frequency Hyperpnea: increased breathing (tidal volume) Hypopnea: decreased breathing (tidal volume) Cheyne-Stokes: Instability in respiration control, period of hyperpnea alternate with perods of apnea |
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Identify the location of respiratory centers in the CNS and how severing the spinal cord effects ventilation |
-Centers located in the reticular formation of the medulla -Section above this point = breathing w/ rhythmic respiration but disorganized pattern -Section below this point = no breathing -Rhythmic respiration continues even in the absence of afferent input |
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Describe the 'off-switch' model of respiration |
-Inspiration is active while expiration is passive, because of this inspiratory neurons are primarily responsible for breathing pattern -Inspiratory neurons fire during inspiration and turn off to induce expiration |
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Highlight the pathways responsible for output to neural output to respiratory muscles |
-Two separate group exist: DRG and VRG DRG: located in nucleus tractus solitarius, almost exclusively inspiratory cells. Axons synapse primarily w/ phrenic motor neurons, some synapse w/ ext. intercostal motor neurons. Also send collateral axons to the VRG VRG: located in the nucleus ambiguus, both inspiratory and expiratory neurons. Axons synapse mostly w/ motor neurons of larynx/pharynx and ext./int intercostal and abdominals; some synapse w/ phrenic motor neurons |
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Define Odine's curse |
-Lesion of DRG axons to phrenic nerve result in failure of autonomic control of breathing |
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Describe the role of lung stretch receptors on respiratory patterns |
-Lung stretch receptors provide afferent signaling to DRG via CN X (vagus nerve) -Lung stretch receptors fire to Ib neurons which stimulate OFF neurons, which inhibit Ia neurons. -Normally, Ia neurons signal to inspiratory motor neurons so when lung stretch signaling reaches a certain threshold, they indirectly inhibit inspiratory activity |
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Describe the effect of a vagotomy on respiratory rhythm |
-Lung stretch receptors allow inspiration dependence on lung volume (Hering-Breuer reflex). After a vagotomy, inspiratory stimulation will be unresponsive to lung stretch -In order to compensate, the PRG will override to stop inspiration at a certain time regardless of lung volume -In the case of PRG and CN X lesion the result is apneustic respiration |
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Highlight the types of receptors in the lower airways and lungs |
Myelinated: Slowly adapting lung stretch receptors (assoc. w/ Hering-Breuer reflex), rapidly adapting irritant receptors Unmyelinated: J-receptors and C-receptors stimulated by edema/embolism and signal for laryngeal closure/apena followed by rapid shallow breathing |
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What is the effect of sleep on respiration |
-Sleep inhibits signaling (during inspiration) from the VRG to the larynx/pharynx - the result is heightened resistance in these airways -Decreases response to Paco2 with increasing depth of sleep means increased Paco2 at each level of sleep -However at stage 1 slepe there is a minimum ventilation independent on Paco2 -> wakefulness drive |
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Highlight the changes in physiology during increased activity (exercise) |
-Increased CO, tidal volume, frequency of breathing -Increased CO -> increased pulmonary arterial pressure causes distension and recruitment of new vessels resulting in overall decreases in pulmonary resistance and increased diffusion capacity of gases |
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Describe how ventilation is controlled during exercise |
-Increase in work rate -> increased O2 consumption -> increased CO (all linear relationships -When work rate is below anaerobic threshold ventilation is controlled via isocapnic hyperpnea -Above anaerobic threshold, control switches to hyperventilation -pH of blood increases with falling Paco2 because of latate buildup, which neutralizes HCO3- (bicarbonate conc. drops after AT, increased anion gap) -Pao2 remains constant |
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Highlight autoregulation of renal blood flow |
-Changes in pressure met with changes in resistance at the afferent arteriole to keep RPF and GFR constant in between 80 and 180mmHg. There are two mechanisms that control this 1. Myogenic: increased pressure -> increased wall stress -> activation of stress receptors -> smooth msucle contraction 2. Tubuloglomerular feedback : macula densa sense changes to perfusion rate and NaCl and will stimulate decreased GFR as perfusion rate and/or [NaCl] increases. Adenosine release by macula densa stimulates afferent afferent constriction |
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Describe why PAH is used to measure PRF as opposed to inulin |
-PAH binds to plasma albumin is not freely filtered -Unlike inulin, concentration in the renal vein is close to zero |
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Highlight some of the features of ADH |
-ADH (AKA vasopessin) secreted by the pituitary gland in response to changes in Posm (primarily) and chages in blood volume (less affect) -half life of 10-15 minutes -In decreased Posm, cells swell/stretch inhibiting release of ADH -In increased Posm, cells shrivel prompting release of ADH -Even at normal Posm, there is some basal plasma ADH |
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Explain why significant decreases in ECF (isoosmotic fuid loss greater than 15%) will lead to hyponatremia, and the consequences of hyponatremia |
-Loss of isoosmotic fluid will cause Posm to remain while pressure drops -> so ADH will be released -ADH will promote retention of water, driving down [Na]+ -Gain of solute free water (thirst) will cause cellular edema (especially problematic for the brain where expansion -> decreased blood floow and death |
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What is the function/mechanism for the RAAS? |
-Functions to maintain adequate blood volume (i.e. venous return) -Responds to decreases in blood volume, stretch OR increases in sympathetic activity -Stimuli induce renin release from kidney -> activation of angiotensin I (produced in liver) -> ACE (produced in lung) activate angiotensin II -> act to increase aldosterone and PCT Na+ reabsorption and SVR |
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What factors participate in renin regulaiton |
Increase Renin: increased sympathetic tone, afferent relaxation (in response to decreased perfusion pressure), low NaCl absorption by the macula densa Decreases renin: Angiotensin II |
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Describe the mechanism for macula densa regulation of renin |
-In response to low NaCl macula densa will drop to minimal levels adenosine, this will cause afferent dilation: increased RPF and GFR -If this still does not restore NaCl deilvery (adenosine minimal), macula densa will produce prostagladins which will promote secretion of renin from the juxtaglomerular cells of the kidney |
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Describe the dual function of the renal sympathetic innervation |
-At low firing rates renal sympathetics control renin release -At high firing rates renal sympathetics control both renin release and renal afferent arteriole resistance |
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Describe the relationship between thirst and ADH release |
-Both caused by the same stimulus: increase Posm -ADH serves to decrease water excretion -Thirst serves to increase water input -Both work together to restore plasma osmolality and prevent cellular dehydration |
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Contrast ADH and Aldosterone |
-ADH primarily released in response to increased Posm to control ICF. acts to increased AQP2 expression in the connecting tubule and Collecting duct. May be released as a result of LARGE deficits in blood volume, causing water retention and hyponatremia -Aldosterone primarily released in response to small changes in ECF. acts to increase Na+ reabsorption/K+ secretion and thus water absorption. Also induced by high plasma K+ to increased K+ excretion |
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Contrast the difference between tubuloglomerular feedback and renin control by the macula densa |
Tubuloglomerlar feedback: This allows autoregulation of GFR when pressure is between 80-180mmHG. In the case of reduced perfusion pressure/rate or NaCl delivery, REDUCED adenosine will cause afferent dilation Renin control: if the GT feed back is NOT enough to restore NaCl delivery even with minimal adenosine, then macula densa will release prostaglandins which will stimulate granula cell release of renin to activate RAAS and increase Na+ reabsorption in the collecting duct |
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Define ECV and explain the consequences of changes to ECV |
-While ECF refers to actual physical volume, ECV (effective circulating volume) is a conceptual volume based on vascular pressure -In the case of low vascular pressures and cardiac output (i.e. heart failure) the RAAS is activated to increased Na+ retention and thus water retention -In the case of increased ECV due to RAA activation the results are CHF, peripheral and/or pulmonary edema |
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Describe relative amount of Na+ absorption influenced by Aldosterone |
-Aldosterone controls very small quantity (2%) of Na+ reabsorption as most is done in the PCT and ascending limb -3 mechanisms allow for this: 1) load dependent Na+ reabsorption in the PCT and ascending limb, 2) GT Balance, 3) Autoregulation of GFR -These three mechanisms allow for low levels of angiotensin II, which at low levels main function is to regulate aldosterone |
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Explain the changes in renal regulation that occur when ECV loss become greater than 5% |
-Initially GT balance and autoregulation of GFR is enough to keep GFR and perfusion constant -In extreme loss, Renal sympathetics abolish autoregulation by constricting afferent arteriole and angiotensin II concentration raise to high levels to abolish GT feedback and raise aldosterone |
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List the 5 vascular receptors associated with ECV |
Cardiopulmonary: Atria, pulmonary vessels Arterial: carotid sinus, aortic arch, afferent arteriole |
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Explain the interaction b/w diuretics and the RAAS |
-Diuretics work to decrease ECF volume (increase Na+ excretion) -Decreases in ECF volume (>5%) activate the RAAS: -Renal sympathetics induce afferent constriction: decreasing RPF and GFR -High Angiotensin II constrict both arterioles, but because efferent constrictions results in smaller changes to GFR, the result of sympathetic and ANG II cooperation is decreased GFR and RPF, BUT INCREASED filtration fraction means greater PCT reabsorption (also aldosterone will up Na+ retention) -Na+ excretion that was initially increased by diuretics now returned to a normal state |
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Explain the consequences of very high aldosterone levels in the case of diarrhea and blood volume loss |
-Small decrease in ECV will limit aldosterone to moderate levels to increase Na+ reabsorption in the collecting duct. This will increase H+ and K+ secretion. If sustained this will lead to hypokalemia. To correct for hypokalemia, tubular K+ will be exchanged with H+ increasing HCO3- production -> metabolic alkalosis -SIGNIFICANT decrease in ECV have opposite effect: as high sympathetic activity and high angiotensin will cause large changes to GFR - increasing PCT reabsorption. Fluid will be very concentrated when it reaches the collecting duct. K+/H+ secretion will be attenuated prompting hyperkalemia and metabolic acidosis |
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Describe the physiological response to increased ECF |
-Decreased RAAS activity, sympathetic activity, ADH release (if Posm normal) -Increased ANP release, stimulated by atrial stretch |
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What role does ANP play in bringing ECF back to normal |
-Systemic vasodilation (incl. renal resistance) -Increase RPF, GFR but decreases PCT reabsoprtion -Increased Na+ excretion at the collecting duct |
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Define pressure naturesis |
-A phenomenon in which people with sustained high blood pressure have a higher Na+ excretion rate than normal in an attempt to return blood pressure to normal |
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Describe the effect of altitude on inspired an alveolar O2 |
PAo2 = FIo2 (Pb - 47) - (Paco2/R) -With increasing altitude the fraction of O2 remains the same but the barometric pressure (Pb) decreases -The result is a decrease in alveolar oxygen at increasing altitude |
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Describe the changes to ventilation that occur immediately upon ascent to high altitude vs changes after staying ata high altitude for two weeks |
Acute: Hypoxemia drives peripheral chemoreceptor induce hyperventilation. Hyperventilation lowers Paco2 and thus [H+]a along with Pcsfco2 and thus [H+]csf. Decreases arterial and CSF [H+] will oppose hyperventilation Chronic: Over time [HCO3-] in the arteries and CSF will drop to match that of [H+]. When equilibrium is reached, the brake on increased ventilation will be lifted - leading to a further increase in ventilation after. This adjustment takes 6-12 hours |
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Describe the changes in O2 diffusion upon ascent to high altitude |
-Hypoxia leads to increase sympathetic activity, increased HR and CO (and MAP), which leads to decreased time for capillary gas exchange. After a month these changes normalize (mixed venous Po2 and Co2 then increase) -Hypoxic pulmonary vasoconstriction -> high pulmonary pressures -> recruitment anddistention of vessels (more surface area fro gas exchange) -> abolish dead space but may lead to HAPE -Despite reduced PAo2 (diffusion gradient) and decreased transit time, there is not diffusion limitation |
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Describe how hemoglobin is affected by changes in altitude |
-Within 3-5 days hematocrit begins to rise -Hemoglobin curve shifted to the left by alkalosis and hypocapnia, but increased 2,3-DPG partially offsets this shift -> slightly greater O2 loading, but slightly lesser O2 unloading -Elevation in hematocrit leads to increased Cao2 -> this will also increase Cvo2 |
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Describe absorption atelectasis |
-Large volume of O2 absorption from alveoli with low Va/Q may cause the alveoli to collapse. This will result in a shunt. -Potential harmful affect of increased FIO2 |
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What factors lead to increase H+ secreiton |
-Increased aldosterone (Na+ reabsorption) -Decreased extracellular K+ -Increased Pco2, decreased intracellular pH -Inhibition of carbonic anhydrase |
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What are the primary causes and symptoms associated with metabolic alkalosis |
-Alkalosis causes overexcitability of CNS neurons muscle spasm, tetany, loss of consciousness, convulsions -Primary causes: 1) Vomiting (HCl/KCl loss) 2) loop/thiazide diuretics 3) post hypercpanic alkalosis 4) hyperaldosteronism |
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Describe the renal and respiratory responses to metabolic alkalosis |
Respiratory: hypoventilation (compensatory respiratory alkalosis) Renal: Increase in plasma [HCO3-] -> decrease in plasma [H+] -> decrease in intracellular [H+] -> decreased ability (gradient) of Na+/H+ exchanger -> decreased H+ secretion -> decreased [HCO3-] reabsorption |
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What factors are essential to the maintenance of respiratory alkalosis |
1. Hypokalmeia 2. Aldosterone excess 3. Volume depletion |
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Describe how the loss of gastric fluid drives metabolic alkalosis |
[HCO3-] = HCO3-/ECF volume -Loss of HCl/KCl due to vomiting cause an increase in the relative amount of HCO3- -Moreover Loss of NaCl results in the loss of ECF -All 3 increase [HCO3-] |
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Explain how diuretic use can exacerbate metabolic alkalosis |
-Loop/thiazide diuretics increase Na+ excretion and thus water excretion -Use eventually causes a decreases in the ECF volume -Decreased ECF volume w/ constant HCO3- means increased [HCO3-] |
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What are the primary causes of metabolic acidosis |
Hyperchloremic: Diarrhea or renal dysfunction (renal tubular acidosis) Normochloremic: Ketoacidosis, Lactic acidosis |
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Describe the renal and respiratory responses to metabolic acidosis |
1. Respirator: hyperventilation (compensatory respiratory alkalosis) 2. Decreased [HCO3-] -> increased intracellular [H+] -> net H+ secretion and increased Gln uptake -> increased NH4+ + increased T.A. -> HCO3- generation *Also reduced plasma [HCO3-] will result in a decreased HCO3- load, all of which will be reabsorbed |
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Explain how Diarrhea contributes to metabolic acidosis |
-Cells lining gut BELOW the pylorus secrete HCO3- and regnerate [H+], the opposite of most other cells -Drainage of fluids will cause loss of HCO3- along with Na+/Cl-/K+ *Secondary consequences is RAAS activation in response to fluid loss. May lead to hypokalemia |
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Explain how toxicants like methanol, ethylene glycol and aspirin lead to metabolic acidosis |
-Toxicants are metabolized to form pure H+ (i.e. aspirin) or organic acids that react with HCO3- and reduce the plasma [HCO3-] |
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Describe the mechanism for renal tubular acidosis |
RTA1 = defect in ability of distal tubule ability to acidify urine(faulty Na+/K+ ATPase) RTA2 = Defect in proximal tubules ability to reabsorb HCO3- RTA4 = Hypoaldosterone means little/no Na+ reabsorption, H+/K+ secretion -> hyperkalemia |
