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596 Cards in this Set
- Front
- Back
Factors that affect rate of diffusion |
Concentration, surface area, solubility, membrane thickness, molecular weight
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Conditions that increase membrane thickness
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Lung fibrosis, pulmonary edema, pneumonia, membranous glomerulonephritis
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Conditions that affect surface area of the membrane
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Exercise (increases SA), emphysema (decreases SA)
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Osmoles Vs. mole Vs. mEq
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150 mM of NaCl = 300 mOsm. Moles yield osmoles. 10 mOsm Ca++ = 20 mEq
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Characteristics of protein-mediated transport
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More rapid than diffusion, transport can be saturated (Tm), is chemically specific, substances compete for transporter
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Types of protein transport
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Facilitated (down a concentration gradient), active (against gradient, requires ATP)
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Primary active transport
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ATP consumed directly by the transporter. E.g. Na/K countertransport
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Secondary active transport |
Depends indirectly on ATP. E.g. Na/glucose cotransporter in the renal tubule depends on Na/K countertransporter
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Constitutive endocytosis
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Vesicles are continuously fusing with the cell membrane
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Receptor-mediated endocytosis
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The ligand binds receptor near clathrin-coated pits. More rapid and specific than constitutive endocytosis.
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Simple diffusion curve in a graph
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Linear. Slope increases if diffusion area or concentration increases. Slope decreases if membrane thickness increases
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Facilitated diffusion curve in a graph
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Reaches a plateau which represents Tm. Adding more transporters raises Tm, shifts curve up and right.
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Amount of total body water
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60% of weight in kg. 70kg = 42 L
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Amount of intracellular fluid
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2/3 of total body water or 40%. 42 L --> 28 L ICF
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Amount of extracellular fluid
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1/3 of total body water or 20%. 42 L --> 14 L ECF
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Amount of interstitial fluid
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2/3 of ECF. 14 L --> 10 L ISF
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Amount of plasma volume
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1/3 of ECF. 14 L --> 4 L plasma
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Effective osmolarity
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Represented by non-penetrating solutes such as Na. If effective osmolarity increases, cells shrink and vice versa.
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Capillary membranes
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Are freely permeable to substances dissolved in plasma except proteins. Separate ISF and plasma.
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Isotonic fluid loss diagram
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Decreased ECF, no change in ICF. Causes: hemorrhage, isotonic urine, diarrhea, vomiting
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Loss of hypotonic fluid diagram (hypovolemia)
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Decreases ECF and ICF, increases osmolarity. Causes: dehydration, sweating, diabetes insipidus.
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Gain of hypertonic fluid diagram
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Increases osmolarity and ECF, decreases ICF. Causes: salt tablets, mannitol, hypertonic saline, aldosterone
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Gain of hypotonic fluid diagram
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Decreases osmolarity, increases ECF and ICF. Causes: SIADH, drinking tap water, primary polydipsia.
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Gain of isotonic fluid diagram
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Osmolarity stays the same, ECF increases. Causes: isotonic saline infusion.
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Loss of hypertonic fluid diagram
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Osmolarity decresaes, ECF decreases, ICF increases. Causes: mineralocorticoid deficiency
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↓ECF, no change in osmolarity or ICF, isotonic urine
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Loss of isotonic fluid. Causes: hemorrhage, diarrhea, vomiting
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↓ECF, ↓osmolarity, ↑ICF
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Loss of hypertonic fluid or hyponatremic hypovolemia. Aldosterone deficiency.
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↓ECF, ↑osmolarity, ↓ICF, little concentrated urine
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Loss of hypotonic fluid or hypernatremic hypovolemia. Cause: Dehydration
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↓ECF, ↑osmolarity, ↓ICF, lots of diluted urine
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Loss of hypotonic fluid or hypernatremic hypovolemia. Cause: diabetes insipidus
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↑ECF, no change in ICF or osmolarity
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Gain of isotonic fluid. Cause: isotonic saline infusion
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↑ECF, ↓osmolarity, ↑ICF
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Gain of hypotonic fluid or hyponatremic hypervolemia. Causes: hypotonic saline, SIADH, tap water.
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↑ECF, ↑osmolarity, ↓ICF
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Gain of hypertonic fluid. Causes: salt tablets, mannitol, aldosterone excess
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Volume of distribution formula
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Vd = Amount given or dose / Concentration
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Tracer to measure plasma volume
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Not permeable to capillaries - albumin
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Tracer to measure ECF
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Permeable to capillaries but not membranes - inulin, mannitol, sodium, sucrose
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Tracer to measure total body water
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Permeable to capillaries and membranes - tritiated water, urea
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Blood volume Vs. plasma volume
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Blood volume is plasma plus RBC --> plasma volume / 1-Hct
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Effect of urea solution on cell volume
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If urea is the only solute, effective osmolarity is 0 --> cell swells.
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Equilibrium potential
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Electrical force required to balance the chemical force of an unequeal concentration of ions
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Conductance
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Permeability to an ion
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Electrochemical gradient
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Exists when the electrical and/or chemical forces are not balanced. Its what determines difussion of the ion.
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Types of channels
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Ungated, voltage-gated, ligand-gated
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↑[K]o
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Depolarization
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↓[K]o
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Hyperpolarization
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↑gK
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Hyperpolarization
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↓gK
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Depolarization
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↑[Na]o
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Depolarization
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↓[Na]o
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Hyperpolarization
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↑gNa
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Depolarization
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↑[Cl]o
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Hyperpolarization
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↓[Cl]o
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Depolarization
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↑gCl
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Depolarization
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Characteristics of sub-treshold potentials
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Proportional to stimulus stregth, not propagated, decremental with distance, summation
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Characteristics of action potentials
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Independent of stimulus strength, propagated unchanged in magnitude, summation not possible
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Factors that affect conduction velocity of the action potential
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Cell diameter and amount of myelination are directly proportional to conduction velocity
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Absolute refractory period
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No stimulus can depolarize the cell
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Relative refractory period
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A large stimulus can depolarize the cell
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Neuromuscular transmission
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Action potential travels down axon and opens pre-synaptic Ca channels --> calcium influx --> release Ach vesicles --> Ach diffuses and attaches to nicotinic ion channels --> ↑gNa --> end-plate depolarization (local) spreads to areas with voltage-gated Na channels --> depolarization of muscle fiber
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Excitatory postsynaptic potentials
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Transient subtreshold depolarizations due to ↑gNa --> summation reaches axon hillock at the junction of cell body and axon --> voltage-gated Na channels depolarize the axon
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Inhibitory postsynaptic potentials
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↑gCl or ↑gK hyperpolarize the cell and lower treshold for depolarization
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Electrical synapse
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Action potential transmitted from one cell to the next via gap junctions, without synaptic delay and in both directions. Cardiac muscle, smooth muscle.
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Sarcomere A band
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Contains overlapping actin and myosin. Does not shorten during contraction.
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Sarcomere H zone
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Contains thick myosin filaments. Shortens during contraction.
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Sarcomere I band
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Contains thin actin filaments. Shortens during contraction.
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Sarcomere Z line
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Within the A band.
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Sarcomere M line
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Within the H zone.
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Actin
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Structural protein of the thin filaments, contains attachment sites for myosin cross-bridges.
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Myosin
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Structural protein of the thick filaments, contains cross-bridges that attach to actin. Has ATPase activity to terminate actin-myosin cross-bridges. ATP decreases actin-myosin affinity.
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Tropomyosin
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Part of thin filaments. Covers the actin attachment sites for the myosin cross-bridges
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Troponin
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Part of thin filaments, binds calcium, which moves tropomyosin out of the way exposing actin binding sites for cross-bridges.
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What happens if calcium is removed from sarcoplasmic reticulum?
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Muscle goes back to resting state. Removal of calcium requires ATP.
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Rigor mortis
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Depletion of ATP - cycling stops with myosin attached to actin - (muscle contracted).
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Muscle contraction steps
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Action potential travels down T-tubules --> activates dihydropiridine voltage sensors --> foot processes are pulled aways from ryanodine calcium release channels of sarcoplasmic reticulum --> calcium is released --> calcium attaches to troponin --> tropomyosin moves exposing actin binding sites for myosin cross-bridges --> myosin binds actin --> myosin ATPase breaks down cross bridges producing active tension and shortening --> contraction terminated by active pumping of Ca into the sarcoplasmic reticulum.
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Myosin ATPase
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Hydrolizes ATP to supply energy for active tension and shortening. ATP decreases myosin-actin affinity
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Sarcoplasmic calcium-dependent ATPase
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Supplies energy to terminate contraction and pump Ca back into sarcoplasmic reticulum.
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Source of calcium for skeletal muscle contraction
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Sarcoplasmic reticulum. No extracellular calcium is involved because it doesn’t have voltage-gated Ca channels.
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Source of calcium for heart and smooth muscle contraction
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Sarcoplasmic reticulum and extracellular. Cardiac and smooth muscle have voltage-gated calcium channels.
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Tetanus
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Multiple action potentials increase release of calcium thus increasing contraction. Muscle cells have a short refractory period.
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Preload
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Stretch prior to contraction. ↑ preload --> ↑ prestretch of the sarcomere --> ↑ passive tension
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Afterload
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The load the muscle is working against. ↑ afterload --> ↑ cross-bridge cycling --> ↑ active tension
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What is the best measure of preload?
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Sarcomere length
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Preload-length tension curve
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It’s a function of the length of the relaxed muscle. A positive parabola.
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Isometric contraction
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Active tension is produced but length stays the same. Afterload is greater than active tension, load not moved.
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How is active tension produced?
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Calcium binds troponin --> tropomysion exposes actin sites --> myosin cross-bridges bond to actin --> myosin ATPase generates energy to break cross-bridge link --> cycle repeats --> active tension. The more cross-bridges that cycle, the greater the active tension.
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Total tension
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Passive (preload) tension + active (afterload) tension
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Active tension curve
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It's a function of the number of cross-bridges capable of cross-linking with actin. Negative parabola.
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What is L0?
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The optimum length to produce maximum active tension. Beyond L0, muscle is overstretched; below L0, it's understretched.
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Isotonic contraction
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Muscle contracts and shortens to move the load. Occurs when total tension equals the load.
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Most energy demanding phase of cardiac cycle
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Isovolumetric contraction. Active tension is generated. Equivalent to isometric contraction of skeletal muscle.
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Relationship between load, muscle force and muscle velocity
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↑ ATPase activity --> ↑ velocity; ↑ muscle mass --> ↑ force generated; ↑ afterload --> ↓ velocity
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Regulation of skeletal muscle force and work
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↑ frequency of action potentials, ↑ recruitment, ↑ preload and ↑ afterload --> ↑ force and work
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Regulation of cardiac and smooth muscle force and work
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Factors that regulate force and work are preload, afterload and contractility (which is altered by hormones). No summation nor recruitment.
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Characteristics of white muscle
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Large mass, high ATPase activity (fast muscle), anaerobic glycolysis, low myoglobin
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Characteristics of red muscle
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Small mass, low ATPase activity (slower muscle), aerobic metabolism (mitochondria), high myoglobin.
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Characteristics of skeletal muscle
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Actin and myosin form sarcomeres, sarcolema lacks junctional complexes, each fiber innervated, troponin binds calcium, high ATPase activity, triadic contacts by T-tubules at A-I junctions, no calcium channels on membrane
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Characteristics of cardiac muscle
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Actin and myosin form sarcomeres, gap junctions, electrical syncytium, troponin binds calcium, intermediate ATPase activity, dyadic contacts by T-tubules near Z-lines, voltage-gated calcium channels.
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Characteristics of smooth muscle
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Actin and myosin not organized in sarcomeres, gap junctions, electrical syncytium, calmodulin binds calcium, low ATPase activity, lacks T-tubules, voltage-gated calcium channels.
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Pressure in the right ventricle
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25/0 mmHg
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Pressure in the pulmonary artery
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25/8 mmHg
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Mean pulmonary artery pressure
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15 mmHg
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Pulmonary capillary pressure
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7-9 mmHg
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Pulmonary venous pressure
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5 mmHg
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Left atrium pressure
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5-10 mmHg
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Left ventricle pressure
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120/0 mmHg
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Aortic pressure
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120/80 mmHg
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Mean arterial blood pressure
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(Systolic - diastolic / 3) + diastolic = 93 mmHg
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Skeletal muscle capillary pressure
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30 mmHg
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Renal glomerular capillary pressure
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45-50 mmHg
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Peripheral vein pressure
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15 mmHg
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Right atrium pressure (central venous)
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0 mmHg
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Systemic ciruit Vs. pulmonary system
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Cardiac output and heart rate is the same as they're connected in series. The systemic circuit has higher resistance and lower compliance therefore work of the right ventricle is lower.
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Highest resistance segment of the systemic circulation
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Arterioles. Also responsible for greatest pressure drop.
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Largest and smallest cross-sectional areas of the systemic circuit
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Largest: capillaries; smallest: aorta
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Fastest and slowest velocities in the systemic circuit
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Velocity is inversely proportional to cross-sectional area. Aorta has fastest velocity; capillaries have slowest velocity.
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Largest blood volumes in the cardiovascular system
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Systemic veins then pulmonary system have the largest blood volume. Both represent reservoirs due to high compliance.
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Poiseuille equation
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Q = P1 - P2 / R;
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Determinants of resistance
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R ∝ vL / r4; if radius doubles, resistance decreases to 1/16; if radius decreases by half, resistance increases 16-fold
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Reynolds number
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RN = diameter x velocity x density / viscosity. If > 2,000 --> turbulent flow; if < 2,000 --> laminar flow
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Vessel with the most turbulent flow
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Aorta - has large diameter, high velocity. In anemia (↓ viscosity) --> aortic murmur
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Features of a series circuit
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Flow is the same at all points; the total resistance is the sum of all resistances; adding a resistor decreases flow at all points and vice versa;
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↓ resistance, ↑ capillary flow, ↑ capillary pressure
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Arteriole dilation - beta agonists, alpha blockers, ↓ sympathetic, metabolic dilation, ACEIs
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↑ resistance, ↓ capillary flow, ↓ capillary pressure
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Arteriole constriction - alpha agonists, beta blockers, ↑ sympathetic, angiotensin II
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↓ resistance, ↑ capillary flow, ↓ capillary pressure
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Venous dilation - ↑ metabolism
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↑ resistance, ↓ capillary flow, ↑ capillary pressure
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Venous constriction - physical compression, ↑ sympathetic
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↑ capillary flow, ↑ capillary pressure, no change in resistance
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↑ arterial pressure - ↑ CO, volume expansion
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↓ capillary flow, ↓ capillary pressure, no change in resistance
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↓ arterial pressure - ↓ CO, hemorrhage, dehydration
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↓ capillary flow, ↑ capillary pressure, no change in resistance
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↑ venous pressure - CHF, physical compression
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↑ capillary flow, ↓ capillary pressure, no change in resistance
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↓ venous pressure - hemorrhage, dehydration
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Characteristics of parallel circuits
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The reciprocal of the total resistance is the sum of the reciprocal of the individual resistances. Connecting a resistance in parallel lowers resistance, total resistance is always less than individual resistances.
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Parallel circuits with greatest resistance
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Coronary > cerebral > renal > pulmonary
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What happens if a parallel circuit is added?
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TPR decreases, pressure would decrease but a compensatory increases in CO maintains same pressure. Obesity.
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What happens if a parallel cuircuit is removed?
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TPR increases, blood pressure increases, CO might decrease to compensate increased blood pressure.
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Wall tension
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T ∝ Pr. In aneurysm, tension is high due to greater radius.
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Factors that increase systolic pressure
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↑ stroke volume, ↓ HR, ↓ compliance
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Factors that decrease systolic pressure
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↓ stroke volume, ↑ HR, ↑ compliance
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Factors that decrease diastolic pressure
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↓ TPR, ↓ HR, ↓ stroke volume, ↓ compliance
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Factors that increase diastolic pressure
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↑ TPR, ↑ HR, ↑ stroke volume, ↑ compliance
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Factors that increase pulse pressure
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↑ stroke volume (systolic > diastolic); ↓ compliance (systolic increases and diastolic decreases)
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Determinants of mean arterial pressure
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MAP = CO x TPR
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What happens to cardiac output and mean arterial pressure if TPR increases?
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MAP increases and CO decreases
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What happens to cardiac output and TPR if mean arterial pressure decreases?
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TPR decreases, CO decreases but then increases to compensate and maintain blood pressure
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Hemodynamic changes in hemorrhage
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Loss of circulating volume and CO --> less firing of carotid sinus (↓ BP) --> reflex sympathetic ↑ in TPR and CO --> ↓ venous compliance --> ↑ circulating volume --> compensated CO and BP
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Hemodynamic changes during exercise
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Dilation of arterioles --> ↓ TPR --> ↓ BP --> less firing of carotid sinus --> reflex sympathetic ↑ in CO --> ↑ BP
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Hemodynamic changes due to gravity
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↑ venous pressure, ↑ pooling of blood in veins, ↓ circulating blood volume (CO), ↓ BP --> compensation via carotid sinus --> ↑ TPR, ↑ HR
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Effects of inspiration on blood flow
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↓ intrapleural pressure --> ↑ venous return --> ↑ right ventricle output --> splitting of S2 --> blood in pulmonary circuit increases --> ↓ venous return to left heart --> ↓ systemic pressure --> reflex increase in HR
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Effects of expiration on blood flow
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↑ intrapleural pressure --> ↓ venous return --> ↓ pulmonary blood volume --> ↑ output of left ventricle --> ↑ systemic pressure --> reflex bradycardia
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What factor controls blood flow to capillaries?
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↑ resistance of arterioles --> ↓ capillary flow and pressure; ↓ resistance of arterioles --> ↑ capillary flow and pressure
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What factors affect capillary exchange?
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Exchange is by simple diffusion only. Proteins do not cross the capillary membrane. Factors that affect diffusion rate are: surface area, membrane thickness, concentration gradient, solubility
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When does the rate of uptake become perfusion-limited?
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When concentration of the substance reaches equilibrium between capillary and tissue. ↑ blood flow converts perfusion-limited uptake to diffusion-limited again.
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When does the rate of uptake becom diffusion-limited?
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When concentration between capillary and tissue are not in equilibrium.
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What forces favor reabsorption?
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Capillary oncotic pressure and interstitial hydrostatic pressure
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What forces favor capillary filtration?
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Capillary hydrostatic pressure and interstitial oncotic pressure
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What happens to filtration in lung capillaries when intrathoracic pressure decreases?
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↓ intrathoracic pressure promotes filtration. In ARDS --> ↓ intrathoracic pressure --> pulmonary edema
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Conditions that affect capillary hydrostatic pressure
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Essential hypertension increases resistance and decreases capillary hydrostatic pressure. Hemorrhage decreases capillary hydrostatic pressure and promotes reabsorption.
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Conditions that affect capillary oncotic pressure
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Increased by dehydration. Decreased by liver and renal disease and saline infusion
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Conditions that affect interstitial oncotic pressure
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Increased by lymphatic blockage and increased capillary permeability to proteins (burns)
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Conditions that affect insterstitial hydrostatic pressure
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Increased by negative intrathoracic pressure in ARDS
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Fick principle
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Measures cardiac output. Flow = O2 consumption / O2 concentration difference across the organ
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Intrinsic autoregulation of blood flow
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Resistance of arterioles is changed in order to regulate flow. No nerves or hormones involved. Independent of BP.
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Metabolic hypothesis of autoregulation
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Tissue can produce a vasodilatory metabolite that regulates blood flow. Example adenosine in coronaries.
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Tissues that have autoregulation of blood flow
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Cerebral, coronary and exercising skeletal muscle circulations
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Extrinsic regulation of blood flow
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Controlled by nervous and hormonal influences. NE via β2 vasodilates, via α1 constricts (dose dependant). Angiotensin II constricts.
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Tissues that have extrinsic regulation of blood flow
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Resting skeletal muscle, skin
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Lowest venous PO2 in the body
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Coronary circulation due to maximal extraction of O2. To increase delivery of oxygen, flow must increase.
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Factors that control coronary circulation
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Coronary circulation occurs in diastole and its determined by stroke work of the heart. Exercise increases volume work and coronary flow. Hypertension increases pressure work and coronary flow. Vasodilation is mediated by adenosine.
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Factors that control cerebral blood flow
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Flow is proportional to arterial PCO2. Hypoventilation increases PCO2 and flow. Hyperventilation decreases PCO2 and flow. PO2 determines flow only if theres a large decrease in PO2.
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Factors that control cutaneous blood flow
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↑ sympathetic tone --> constriction of arterioles --> ↓ blood flow, ↓ blood volume in veins --> ↑ velocity (↓ cross-sectional area). Increased skin temperature --> vasodilation --> heat loss
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Highest venous PO2 in the body
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Renal circulation
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Factors that control renal circulation
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Small changes in blood pressure invoke autoregulatory responses. Sympathetic may influence blood flow in extreme conditions (hemorrhage, hypotension)
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Characteristics of pulmonary circuit
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Low pressure, high flow, low resistance, very compliant, hypoxic vasoconstriction.
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Pulmonary response to exercise
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↑ CO --> ↑ pulmonary pressure --> pulmonary vessel dilation (due to high compliance) --> large ↓ resistance --> ↓ pulmonary pressure
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Pulmonary response to hemorrhage
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↓ CO --> ↓ pulmonary pressure --> pulmonary vessel constriction --> large ↑ resistance --> less blood volume
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Fetal circulation: percent O2 saturation in umbilical vein
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80% O2 saturation
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Fetal circulation: percent O2 saturation in inferior vena cava
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26% O2 saturation. Mixes with hepatic vein blood --> step up to 67%
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Fetal circulation: percent O2 saturation from inferior vena cava into right atrium
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67% O2 saturation. Blood from inferior vena cava enters right atrium and passes through foramen ovale
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Fetal circulation: percent O2 saturation in superior vena cava
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40% O2 saturation. Mixes with blood from inferior vena cava (67%) and passes to right ventricle at 50% saturation
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Fetal circulation: percent O2 saturation in right ventricle
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Contains blood from superior vena cava mixed with IVC --> 50% saturation. Passes through pulmonary vein and 90% is shunted through the ductus arteriosus into aorta
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Fetal circulation: percent O2 saturation in ascending aorta
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Contains blood from inferior vena cava --> 67%
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Fetal circulation: percent O2 saturation in brachiocephalic trunk
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Blood from left ventricle (67%) mixes with blood from ductus arteriousus (50%) --> yields 65%
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Fetal circulation: percent O2 saturation in descending and abdominal aorta
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Blood from left ventricle (67%) mixes with blood from ductus arteriousus (50%) --> yields 60%
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Ion channels present in the heart
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Ungated K, voltage-gated fast Na, voltage-gated calcium, inward rectifying iK1, delayed rectifying iK
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Voltage-gated Na channels of the heart
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Open and close fast upon depolarization of the membrane
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Voltage-gated calcium channels of the heart
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Open upon depolarization, close more slowly than sodium channels. Partly responsible for the plateau (phase 2)
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Inward rectifying iK1 channels of the heart
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Open under resting conditions, depolarization closes them, they reopen during repolarization phase.
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Delayed rectifying iK channels of the heart
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Very slow to open with depolarization (late plateau), and close very slowly. Partly responsible for repolarization
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Phase 0 of the ventricular action potential
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Fast Na channels open, ↑ gNa causes depolarization. Inward rectifying iK1 channels close.
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Phase 1 of the ventricular action potential
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Slight repolarization due to transient potassium current and the closing of sodium channels
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Phase 2 of the ventricular action potential
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Slow Ca channels open, ↑ gCa, ↓ gK. Plateau phase is due to slow calcium current and decreased K current
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Phase 3 of the ventricular action potential
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Slow Ca channels close, the delayed rectifier iK reopen, ↑ gK. K efflux causes repolarization.
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Phase 4 of the ventricular action potential
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Voltage-gated and ungated potassium channels are open, ↑ gK. The delayed rectifiers close but are responsible for the relative refractory period.
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Why can't the heart be tetanized?
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A long absolute refractory period extends through most of the contraction. Short relative refractory period.
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How do premature ventricular depolarizations occur?
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Action potential develops during the relative refractory period, but the earlier the potential, the shorter in amplitude and duration it will be
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Funny current
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In specialized cells of the heart. It's a voltage-gated sodium channel the opens during repolarization and closes during depolarization. The sodium influx during phase 3 slowly depolarizes the cell towards treshold.
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Phase 0 of SA nodal cells
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Depolarization due to opening of voltage-gated slow Ca channels.
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Phase 3 of SA nodal cells
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Repolarization due to ↑ gK.
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Phase 4 of SA nodal cells
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Gradually depolarizes cell towards treshold due to funny current - ↑ gNa
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Effects of sympathetics on pacemaker cells
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Slope of phase 4 increases due to ↑ funny current and ↑ gCa. Action via β1 receptors.
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Effects of parasympathetics on pacemaker cells
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↑ gK causing hyperpolarization and ↓ sodium funny current decreasing slope of phase 4. Effect via M2 receptors.
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Fastest conducting cells of the heart
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Purkinje cells
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Slowest conducting cells of the heart
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SA nodal cells
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PR interval
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Due to conduction delay of AV node. 0.12 - 0.2 seconds or 120 to 200 miliseconds
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QRS complex
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Ventricular depolarization - should be less than 0.12 seocnds.
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QT interval
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Indicates ventricular refractorieness. Normal between 0.35 - 0.44 seconds.
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Effect of hypercalcemia in ECG
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Shortened QT interval (< 0.35 seconds).
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Effect of hypocalcemia in ECG
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Prolonged QT interval (> 0.44 seconds)
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Drugs that shorten QT interval
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Digitalis
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Drugs that prolong QT interval
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Quinidine, procainamide
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Effect of intracerebral hemorrhage in ECG
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Inverted T waves with prolonged QT interval
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ST segment
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Indicates conduction through ventricular muscle. Corresponds to plateau phase of action potential.
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First-degree block in ECG
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Slowed conduction through AV node. PR interval > 200 msec
|
|
Second-degree block in ECG
|
Some impulses not transmitted through AV node. Missing QRS complexes following P wave.
|
|
Third-degree block in ECG
|
No impulses conducted from atria to ventricles. No correlation between P waves and QRS complexes.
|
|
Sinus rhythms
|
Normal, bradycardia or tachychardia
|
|
Atrial flutter
|
Repeated succession of atrial depolarizations. Continuous P waves. Saw-tooth appearance.
|
|
Atrial fibrillation
|
No discernable P waves, irregular QRS
|
|
Ventricular fibrillation
|
No identifiable waves. Chaotic, erratic rhythm.
|
|
Causes of left axis deviations
|
Left ventricular hypertrophy or dilation, conduction defects of left ventricle, AMI on right side
|
|
Causes of right axis deviations
|
Right ventricular hypertrophy or dilation, conduction defect of right ventricle, AMI on left side
|
|
Initial AMI in ECG
|
ST segment depression, prominent Q waves, T wave inversion
|
|
AMI in ECG
|
ST segment elevation, T wave inversion, prominent Q waves
|
|
Resolving AMI in ECG
|
Baseline ST, inverted T waves, prominent Q waves
|
|
Stable infarct in ECG
|
Prominent Q waves
|
|
Indices of left ventricular preload
|
LVEDV, LVEDP, left atrial pressure, pulmonary venous pressure, pulmonary wedge pressure (swan-ganz)
|
|
Sarcomere length in skeletal muscle Vs. heart muscle
|
In skeletal muscle it's close to L0. In heart muscle, sarcomere legth is below optimal, therefore increased preload moves sarcomere legth towards optimal for maximal cross-bridge linking
|
|
Factors that increase slope of cardiac function curve
|
↑ inotropy, ↑ heart rate, ↓ afterload
|
|
Factors that decrease slope of cardiac function curve
|
↓ inotropy, ↓ heart rate, ↑ afterload
|
|
Factors that shift vascular function curve up and to the right
|
↑ blood volume, ↓ venous compliance
|
|
Factors that shift vascular function curve down and to the left
|
↓ blood volume, ↑ venous compliance
|
|
Factors that increase slope of vascular function curve
|
↓ SVR
|
|
Factors that decrease slope of cardiac function curve
|
↑ SVR
|
|
What is contractility and what influences it?
|
Contractility is the force of contraction at a given preload or sarcomere length. Due to changes in intracellular calcium
|
|
Indices of contractility
|
dp/dt (change in pressure/change in time); ejection fraction (stroke volume/EDV)
|
|
Changes to the action potential induced by increased contractility
|
↑ slope (↑ dp/dt), ↑ peak left ventricular pressure, ↑ rate of relaxation, ↓ systolic interval
|
|
Changes to the action potential induced by heart rate
|
↓ diastolic interval
|
|
Cardiac function curve in hemorrhage
|
↓ preload (down); ↑ contractility to partially compensate (left)
|
|
Cardiac function curve in excersice
|
↑ contractility (up, same preload)
|
|
Cardiac function curve in volume overload
|
↑ preload (right); ↓ contractility (slightly down)
|
|
Cardiac function curve in CHF
|
↓ contractility (down); ↑ preload (right)
|
|
Afterload
|
Force that must be generated to eject blood into aorta. ↑ afterload in hypertension, ↓ afterload in hypotension. Acute ↑ in afterload --> ↓ stroke volume, ↑ EDV, ↑ preload
|
|
Parasympathetic innervation of SA and AV nodes
|
Left vagus predominates in AV node, right vagus predominates in SA node
|
|
Effect of inspiration on heart rate
|
Inspiration makes intrathoracic pressure more negative --> increase venous return --> Brainbridge reflex (stretch receptors in the right atrium) --> tachychardia
|
|
Baroreceptor reflex
|
Baroreceptors in the aortic arch send afferents via vagus nerve; baroreceptors in the carotid sinus via glosopharyngeal; baroreceptor center is in the medulla. ↑ firing of baroreceptors is sensed as ↑ blood pressure --> ↑ parasympathetic, ↓ sympathetic
|
|
Acute reflex changes when blood pressure increases
|
↑ afferent baroreceptors --> ↑ parasympathetic, ↓ sympathetic
|
|
Acute reflex changes when blood pressure decreases
|
↓ afferent baroreceptors --> ↓ parasympathetic, ↑ sympathetic
|
|
Acute reflex changes with occlusion of the carotid
|
↓ afferent baroreceptors --> ↓ parasympathetic, ↑ sympathetic, ↑ blood pressure, ↑ heart rate
|
|
Acute reflex changes with a carotid massage
|
↑ afferent baroreceptors --> ↑ parasympathetic, ↓ sympathetic, ↓ blood pressure, ↓ heart rate
|
|
Acute reflex changes if baroreceptor afferents are cut
|
↓ afferent baroreceptors --> ↓ parasympathetic, ↑ sympathetic, ↑ blood pressure, ↑ heart rate
|
|
Acute reflex changes in orthostatic hypotension or fluid loss
|
↓ afferent baroreceptors --> ↓ parasympathetic, ↑ sympathetic, ↑ blood pressure, ↑ heart rate
|
|
Acute reflex changes in volume overload
|
↑ afferent baroreceptors --> ↑ parasympathetic, ↓ sympathetic, ↓ blood pressure, ↓ heart rate
|
|
S1 heart sound
|
Closure of mitral and tricuspid valves; terminates ventricular filling, starts isovolumetric contraction
|
|
S2 heart sound
|
Closure of aortic and pulmonary valves; terminates ejection phase, begins isovolumetric relaxation
|
|
Isovolumetric contraction
|
Beginning of systole, ventricular pressure is increasing but aortic and mitral valves are closed. Most energy consumption occurs here
|
|
Ejection phase
|
Aortic valve opens when isvolumetric contraction generates high enough pressure; ventricular volume decreases. Most work done here.
|
|
Isovolumetric relaxation
|
Ventricular pressure decreases; volume is end-systolic volume; aortic and mitral valves are closed
|
|
Filling phase
|
Opening of the mitral valve passes volume to ventricle followed by atrial contraction
|
|
Stroke volume
|
EDV - ESV
|
|
Ejection fraction
|
Stroke volume / EDV
|
|
a wave of the venous pulse
|
Produced by contraction of the right atrium
|
|
c wave of the venous pulse
|
Bulging of the tricuspid valve into the right atrium during ventricular contraction
|
|
v wave of the venous pulse
|
Wave rises as the atrium is filled; terminates when the tricuspid valve opens
|
|
y wave of the venous pulse
|
Opening of tricuspid valve and atrial emptying
|
|
Aortic stenosis
|
Increase in afterload. Systolic murmur, concentric hypertrophy.
|
|
Aortic insufficiency
|
↑ preload, ↑ ventricular and aortic systolic pressures, ↓ aortic diastolic pressure, diastolic murmur, eccentric hypertrophy
|
|
Mitral stenosis
|
↑ pressure and volume in left atrium, enlargement of left atrium, diastolic murmur
|
|
Mitral insufficiency
|
↑ atrial volume and pressure; systolic murmur
|
|
Tidal volume
|
Volume of air that enters and leaves the lung in a single cycle. 500ml
|
|
Functional residual capacity
|
Amount of air in the lungs after passive expiration. 2,700ml
|
|
Inspiratory capacity
|
Maximal volume of gas inspired from FRC. 4,000ml
|
|
Inspiratory reserve volume
|
Air that can be inhaled after normal inspiration. 3,500ml
|
|
Expiratory reserve volume
|
Air that can be expired after a normal expiration. 1,500ml
|
|
Residual volume
|
Air in the lungs after maximal expiration. 1,200ml
|
|
Vital capacity
|
Maximal air that can expired after maximal inspiration. 5,500ml
|
|
Total lung capacity
|
Air in the lungs after maximal inspiration. 6,700ml
|
|
Total ventilation
|
Total ventilation = Tidal volume X respiratory rate.
|
|
Dead space
|
Regions that contain air but do not exchange O2 and CO2
|
|
Anatomic dead space
|
Conducting zones. Approximately equal to person't weight in pounds.
|
|
Alveolar dead space
|
Alveoli with air but without blood flow
|
|
Physiologic dead space
|
Anatomic dead space plus alveolar dead space
|
|
Alveolar ventilation
|
Tidal volume - anatomic dead space X respiratory rate.
|
|
Lung recoil
|
Force that collapses the lung. As the lung enlarges, recoil increases and vice versa.
|
|
Intrapleural pressure
|
Normally -5 cmH2O. Force that expands the lung. The more negative, the more lung expansion.
|
|
Lung mechanics before inspiration
|
Glotis is open but no air is flowing - alveolar pressure = 0. Intrapleural pressure and lung recoil are equal but opposite. Gravity increases intrapleural pressure at the apex and decreases it at the bases. Apex alveoli are more distended.
|
|
Lung mechanics during inspiration
|
Diaphragm contracts, intrapleural pressure becomes more negative. Expansion of alveoli makes alveolar pressure negative causing air to flow into the lungs.
|
|
Lung mechanics at the end of inspiration
|
Intrapleural pressure and recoil are the same but opposite. Alveolar pressure returns to zero and air stops flowing in.
|
|
Lung mechanics during expiration
|
Diaphragm relaxes, intrapleural pressure increases, lung recoil collpases the lung. Alveoli compress the air and alveolar pressure becomes positive and air flows out of the lungs until alveolar pressure is back to zero. Lung recoil and intrapleural pressure become equal but opposite.
|
|
Assisted control mode ventilation
|
Inspiration is initiated by the patient or the machine if no signal is detected.
|
|
Positive end-expiratory pressure
|
Does not allow intraalveolar pressure to return to zero at the end of expiration. The larger lung volume prevents atelectasis.
|
|
What is lung compliance?
|
It's the change in volume with a change in pressure. Increased compliance means more air flows in with a given change in pressure. Decreased compliance means the opposite. The steeper the slope of the lung inflation curve, the greater the compliance. Emphysema = very compliant; fibrosis = not compliant.
|
|
Components of lung recoil
|
1) the tissue's collagen and elastin fibers and 2) the surface tension (greatest component)
|
|
Functions of surfactant
|
Lowers lung recoil and increases compliance (↓ surface tension) more in small alveoli than large alveoli; reduces capillary filtration forces reducing tendency to develop edema.
|
|
Pathophysiology of respiratory distress syndrome
|
Low surfactant --> ↑ recoil, ↓ compliance (a greater change in intrapleural pressure is necessary to inflate the lungs); alveoli collapse (atelectasis); more negative intrapleural pressures promote capillary filtration (pulmonary edema)
|
|
Airway resistance
|
R = 1/r4; first and second bronchi have less radius than alveoli, therefore more resistance. Ach increases resistance (bronchoconstriction), catecholamines decrease resistance (bronchodilation)
|
|
Effect of lung volume on airway resistance
|
↑ lung volume --> ↑ radius --> ↓ resistance. The more negative the intrapleural pressure, the less resistance
|
|
Lung volumes in obstructive disease
|
↑ TLC, ↑ RV, ↑ FRC, ↓ FEV1, ↓ FVC, ↓ FEV1/FVC
|
|
Lung volumes in restrictive disease
|
↓ TLC, ↓ RV, ↓ FRC, ↓ FEV1, ↓ FEV, ↑ FEV1/FVC
|
|
Pressure of alveolar O2 and CO2
|
PAO2 = 100mmHg; PACO2 = 40mmHg
|
|
Pressure of venous pulmonary capillary O2 and CO2
|
PvO2 = 40mmHg; PvCO2 = 47mmHg
|
|
Pressure of arterial pulmonary capillary O2 and CO2
|
PO2 = 100mmHg; PCO2 = 40mmHg
|
|
Which factors affect PCO2?
|
Metabolic CO2 production and alveolar ventilation
|
|
Relationship between alveolar ventilation and PACO2
|
Inversely proportional. Hyperventilation decreases PACO2; hypoventilation increases PACO2.
|
|
Relationship between PAO2 and PACO2
|
↓ PACO2 --> ↑ PAO2 (hyperventilation); ↑ PACO2 --> ↓ PAO2 (hypoventilation)
|
|
Which factors affect PAO2?
|
Atmospheric pressure, oxygen concentration of inspired air and PACO2
|
|
What determines oxygen content?
|
Hemoglobin concentration. 1.34ml O2 combines with each gram of hemoglobin.
|
|
Amount of dissolved oxygen in the blood
|
0.3 volumes %; 0.3ml per 100ml of blood. Determines PO2 which acts to keep oxygen bound to Hb
|
|
What determines oxygen attachment to hemoglobin?
|
PO2 and the affinity of the individual attachment sites. The higher the affinity, the less PO2 is needed to keep it attached
|
|
What determines PO2?
|
Amount of oxygen dissolved in plasma. Normally 0.3 volumes %.
|
|
Site 4 of hemoglobin
|
Oxygen is attached at 100mmHg. Least affinity, last site to be saturated.
|
|
Site 3 of hemoglobin
|
Oxygen is attached at 40mmHg. More affinity than site 4, less affinity than site 2.
|
|
Site 2 of hemoglobin
|
Oxygen is attached at 26mmHg which is p50. More affinity, second site to be saturated.
|
|
Site 1 of hemoglobin
|
Oxygen remains attached under physiologic conditions. Highest affinity, first site to be saturated.
|
|
Factors that shift oxygen dissociation curve to the right
|
↑ CO2, ↑ 2,3BPG, fever, acidosis
|
|
Factors that shift oxygen dissociation curve to the left
|
↓ CO2, ↓ 2,3BPG, hypothermia, alkalosis, HbF, methemoglobin, carbon monoxide, stored blood
|
|
How is CO2 carried in the blood?
|
5% dissolved; 5% attached to Hb (carbamino compounds); 90% as bicarbonate.
|
|
Main drive for ventilation
|
H+ ions from dissociated H2CO3 which stimulate central chemoreceptors. H2CO3 is proportional to PCO2 of CSF
|
|
Central chemoreceptors
|
Sense [H+] which is proportional to PCO2 and H2CO3 of the CSF (not systemic)
|
|
Peripheral chemoreceptors
|
Carotid bodies (afferents via IX), aortic bodies (afferents via X). Monitor PO2 and [H+/CO2]
|
|
Main drive for ventilation in severe hypoxemia
|
Peripheral chemoreceptors sense PaO2 (dissolved oxygen) once PaO2 falls to 50-60mmHg.
|
|
Ventilatory response to chronic hypoventilation
|
Peripheral chemoreceptors are the main drive for ventilation eventhough PaCO2 is increased.
|
|
Ventilatory response to anemia
|
PaO2 and PACO2 are normal, therefore neither peripheral nor central chemoreceptors respond.
|
|
Central control of ventilation
|
Apneustic center in the caudal pons promotes prolonged inspiration. Pneumotaxic center in the rostral pons inhibits apneustic center. Efferents are from the medulla to the phrenic nerve (C1-C3) to the diaphragm
|
|
Differences in ventilation between the base and the apex of the lung
|
Base intrapleural pressure is -2.5, alveoli are compliant and small with a small volume of air but receive a large amount of ventilation; Apex pressure is -10, alveoli are large and stiff and contain a large volume of air but receive small amount of ventilation.
|
|
Differences in blood flow between the base and the apex of the lung
|
Blood vessels of the apex are less distended, have more resistance and receive less blood flow. Blood vessels of the base are more distended, have less resistance and receive more blood flow
|
|
Ventilation/perfussion relationship at the base of the lungs
|
Blood flow is higher than ventilation, the relationship is less than 0.8; the bases are underventilated, ↑ shunts
|
|
Ventilation/perfusion relationship at the apex of the lungs
|
Blood flow is lower than ventilation, the relationship is more than 0.8; the apex are overventilated, ↑ dead space
|
|
What does a ventilation/perfussion relationship under and over 0.8 mean?
|
Under 0.8 (at the bases) lungs are underventilated and less gas exchange takes place, therefore PACO2 and end-capillary PCO2 will be higher and PAO2 and end-capillary PO2 will be lower.
|
|
What is hypoxic vasoconstriction?
|
A decrease in PAO2 causes vasoconstriction and shunting of blood through that segment.
|
|
What is the effect of a thrombus in a pulmonary artery?
|
Blood flow decreases, therefore ↑ Va/Q --> ↓ PACO2, ↑ PAO2
|
|
What is the effect of a foreign object occluding a terminal bronchi?
|
Ventilation decreases, therefore ↓ Va/Q --> ↑ PACO2, ↓ PAO2
|
|
What constitutes a pulmonary shunt?
|
Regions of the lung where blood is not ventilated. Low Va/Q relationship.
|
|
What constitutes alveolar dead space?
|
Regions of the lung where there's no blood flow in spite of ventilation. High Va/Q relantionship
|
|
Va/Q > 0.8
|
Represents alveolar dead space. Can be reversed with supplemental O2
|
|
Va/Q < 0.8
|
Represents a pulmonary shunt. Cannot be reversed with supplemental O2
|
|
What is the normal A-a gradient?
|
5-10 mmHg
|
|
Hypoventilation
|
↓ PAO2 but diffusion and A-a gradient are normal. Perfusion-limited defect.
|
|
What is a perfusion-limited defect?
|
There's a lung problem but A-a gradient is normal
|
|
What is a diffusion-limited defect?
|
There's a lung problem where A-a gradient is below normal, therefore diffusion isn't normal
|
|
Diffusion impairment lung defect
|
Due to structural problem (↑ thickness or ↓ surface area). A-a gradient is more than normal. Supplemental oxygen compensates structural deficit but increased A-a gradient remains. Fibrosis, emphysema.
|
|
Diffusion capacity of the lung
|
Its measured with CO because it's a diffusion-limited gas. Structural problems decrease CO uptake. It's an index of surface area and membrane thickness.
|
|
Pulmonary right-left shunt
|
↓ Va/Q. There is an increased A-a gradient that is unresponsive to supplemental O2. Atelectasis or ARDS.
|
|
PO2 in atrial septal defect
|
↑ Right atrial PO2, ↑ right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary blood flow and pressure
|
|
PO2 in ventricular septal defect
|
No change in right atrial PO2, ↑ right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary flow and pressure
|
|
PO2 in patent ductus arteriosus
|
No change in right atrial PO2 nor right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary flow and pressure
|
|
Effect of sympathetic stimulation in the GI tract
|
↓ motility, ↓ secretions, ↑ contraction of sphincters
|
|
Effect of parasympathetic stimulation in GI tract
|
↑ motility, ↑ secretions, ↑ relaxation of sphincters (except LES which contracts), ↑ gastrin release
|
|
Hormones of the GI system
|
Gastrin, CCK, secretin, GIP
|
|
Stimulus for gastrin secretion
|
Stomach distension. Stomach acid in the duodenum inhibits gastrin release
|
|
Sources of gastrin
|
G cells of the stomach, antrum, duodenum
|
|
Actions of gastrin
|
Stimulates acid secretion by parietal cells, increases motility and secretions.
|
|
Source of secretin
|
S cells of the duodenum
|
|
Stimulus for secretin release
|
Acid entering the duodenum
|
|
Actions of secretin
|
Stimulates HCO3 secretion by pancreas to neutralize acid entering duodenum
|
|
Source of CCK
|
Cells lining the duodenum
|
|
Stimulus for CCK secretion
|
Fat and amino acids entering duodenum
|
|
Actions of CCK
|
Inhibits gastric emptying, stimulates pancreatic enzyme secretion, stimulates contraction of the gallbladder and relaxation of sphincter of Oddi.
|
|
Source of GIP
|
Duodenum
|
|
Stimulus for GIP secretion
|
Fat, carbs and amino acids
|
|
Actions of GIP
|
Inhibits stomach motility and secretion
|
|
Properties of GI smooth muscle
|
Stretch stimulates contraction, electrical syncytium with gap junctions, pacemaker activity
|
|
Factors that inhibit gastric motility
|
Acid in the duodenum (secretin), fat in the duodenum (CCK), hypoerosmolarity in duodenum, distension of duodenum
|
|
Factors that stimulate gastric motility
|
Distension of the stomach and ACh
|
|
What are the different contractions of the intestines?
|
Segmentation contractions (mixing), peristaltic movements (propulsive).
|
|
What factors control the ileocecal sphincter?
|
Distension of the ileum relaxes, distension of the colon contracts
|
|
What are the different contractions of the colon
|
Segmentation contractions (haustrations), peristalsis and mass movements
|
|
Composition of salivary secretions
|
Low in NaCl because of reabsorption; High in K and HCO3 because of secretion; alpha-amylase begins digestion of carbs; fluid is hypotonic due to NaCl reabsorption and impermeability of ducts to water
|
|
Parietal cells
|
Located in the middle part of the gastric glands. Secrete HCl and intrinsic factor.
|
|
Chief cells
|
Located in the deep part of the gastric glands. Secrete pepsinogen which is converted to pepsin by acid medium. Pepsin begins digestion of proteins to peptides
|
|
Mucous cells of the stomach
|
Located in the superficial part if the gastric glands (gastric pits). Secrete mucus and HCO3. Secreteion is stimulated by PGE2
|
|
Ionic composition of gastric secretions
|
High in H+, K+ and Cl-, low in Na+. Vomiting produces metabolic alkalosis and hypokalemia.
|
|
Control of acid secretion
|
Acetylcholine, histamine and gastrin stimulate parietal cells to secrete acid.
|
|
Secretion of acid by parietal cells
|
CO2 is extracted from the blood and combined into H2CO3 by carbonic anhydrase. H+ ions are exchanged by the proton pump for K+ ions (active antitransport)
|
|
Pancreatic amylase
|
Hydrolyzes α-1,4-glucoside bonds forming α-limit dextrins, maltotriose and maltose
|
|
Pancreatic lipase
|
Needs colipase which displaces bile from surface of micelles. Lipase digests triglycerides to two free fatty acids and one 2-monoglyceride
|
|
Cholesterol esterase
|
Hydrolizes cholesterol esters to yield cholesterol and free fatty acids
|
|
Pancreatic proteases
|
Trypsinogen is converted to trypsin by enterokinase --> chymotrypsinogen is converted to chymotrypsin by trypsin --> procarboxypeptidase is converted to carboxypeptidase by trypsin
|
|
Ionic composition of pancreatic secretions
|
Isotonic due to permeability of ducts to water and high in HCO3. Stimulated by CCK and secretin.
|
|
What are the primary bile acids?
|
Cholic acid and chenodeoxycolic acid. Synthesized in the liver from cholesterol.
|
|
How are bile salts formed?
|
Bile acids (cholic and deoxycholic) are conjugated with glycine and taurine which mix with cations to form salts.
|
|
What are the secondary bile acids?
|
Formed by deconjugation of bile salts by enteric bacteria - deoxycholic acid (from cholic acid) and lithocolic acid (from chenodeoxycholic acid). Lithocholic acid is hepatotoxic and is excreted.
|
|
Enterohepatic circulation
|
Bile acids are reabsorbed only in the distal ileum. Resection or malabsoption syndromes lead to steatorrhea and cholesterol gallstones.
|
|
What are the components of bile?
|
Conjugated bile acids (cholic and chenodeoxycholic), billirubin, lecithin and cholesterol.
|
|
How are carbohydrates absorbed?
|
Glucose and galactose via active secondary Na cotransporter. Fructose is absorbed independently
|
|
How are amino acids absorbed?
|
Secondary active transport linked to Na and receptor-mediated endocytosis.
|
|
How are lipids absorbed?
|
Micelles diffuse to the brush border then digested lipids (2-monoglycerides, fatty acids, cholesterol and ADEK vitamins) diffuse into enterocytes. Triglycerides are resynthesized and packaged as chylomicrons with apoB48. Leave the intestine via lymphatics to thoracic duct.
|
|
↑ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF
|
Efferent arteriole constriction
|
|
↓ glomerular pressure, ↑ peritubular pressure, ↑ RPF
|
Efferent arteriole dilation
|
|
↓ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF
|
Afferent arteriole constriction
|
|
↑ glomerular pressure, ↑ peritulbuar pressure, ↑ RPF
|
Afferent arteriole dilation
|
|
Afferent arteriole dilation
|
↑ glomerular pressure, ↑ peritulbuar pressure, ↑ RPF, ↑ GFR
|
|
Afferent arteriole constriction
|
↓ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF, ↓ GFR
|
|
Efferent arteriole dilation
|
↓ glomerular pressure, ↑ peritubular pressure, ↑ RPF, ↓ GFR
|
|
Efferent arteriole constriction
|
↑ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF, ↑ GFR, ↑ FF
|
|
Plasma oncotic pressure changes as blood flows through the nephron
|
Oncotic pressure increases because filtered fluid increases protein concentration. Oncotic pressure is resposible for peritubular reabsorption
|
|
Normal capillary hydrostatic pressure of the glomerulus
|
45 mmHg
|
|
Normal capillary oncotic pressure of the glomerulus
|
27 mmHg
|
|
Normal hydrostatic pressure of bowman's capsule
|
10 mmHg
|
|
Normal GFR value
|
120 ml/min
|
|
Normal RPF value
|
600 ml/min
|
|
Normal filtration fraction value
|
FF = GFR/RPF = 120mi/min / 600ml/min = 0.20
|
|
Effect of sympathetic stimulation in the nephron
|
↓ GFR, ↑ FF, ↑ peritubular reabsoption
|
|
Effect of angiotensin II in the kidney
|
Vasoconstriction of the efferent arteriole more than afferent --> maintains GFR
|
|
Filtered load
|
Rate at which a substance filters into Bowman's capsule = FL = GFR x Free plasma concentration
|
|
Excretion of a substance in the urine
|
Excretion = filtered load + (amount secreted - amount reabsorbed) = filtered load + transport OR urine concentration X urine flow rate
|
|
Characteristics of a Tm system
|
Carriers become saturated, carriers have high affinity, low back leak. The filtered load is reabsorbed until carriers are saturated - the excess is excreted.
|
|
Renal treshold for glucose
|
180 mg/dl or 1.8 mg/ml. Represents the beginning of splay.
|
|
Tm rate of reabsorption of glucose
|
375 mg/min. Represents the maximum filtered load that can be reabsorbed when all carriers in the kidney are saturated (end of splay region).
|
|
Glucose reabsorption graph
|
At normal glucose levels, the amount filtered is the same as the amount reabsorbed. At treshold (beginning of splay), the excretion curve starts to ascend and the amount filtered exceeds the amount reabsorbed.
|
|
Substances that are reabsorbed using a Tm system
|
Glucose, amino acids, small peptides, myoglobin, ketones, calcium, phosphate.
|
|
Characteristics of a gradient-time system
|
Carriers are not saturated, carriers have low affinity, high back leak
|
|
Substances that are reabsorbed using a gradient-time system
|
Sodium, potassium, chloride and water
|
|
Substances secreted using a Tm system
|
PAH. 20% filtered, 80% secreted.
|
|
Graph for PAH secretion
|
At low plasma concentration secretion is 4 times the filtered load. When carriers become saturated, secretion reaches a plateau and the amount excreted is proportional to the amount filtered.
|
|
How is the net transport rate for a substance calculated?
|
Net transport rate = filtered load - excretion rate = (GFR X Px) - (Ux X V)
|
|
Effects of blood pressure changes in the kidney
|
GFR and RBF are maintained constant within the autoregulatory range. Urine flow is directly proportional to blood pressure due to pressure natriuresis and pressure diuresis.
|
|
What is clearance and how is it calculated?
|
It's the volume of plasma cleared of a substance over time. Clearance = excretion / Px = Ux X V / Px
|
|
Characteristics of glucose clearance
|
At normal glucose levels, clearance is zero. Above treshold levels, clearance increases as plasma concentration increases but never reaches GFR as there's always glucose reabsorption.
|
|
Characteristics of inulin clearance
|
A constant amount of inulin is cleared regardless of plasma concentration (parallel line to x axis). Inulin clearance is equal to GFR because it's not secreted nor reabsorbed. If GFR increases, clearance increases (line shifts upward), and vice versa.
|
|
Characteristics of creatinine clearance
|
A constant amount of creatinine is cleared regardless of plasma concentration, but creatinine clearance is more than GFR because some is always secreted.
|
|
Characterisics of PAH clearance
|
As plasma concentration increases, clearance decreases because carriers that mediate active secretion become saturated. At normal levels, PAH clearance = RPF because all is excreted.
|
|
How is GFR calculated using inulin?
|
GFR is equal to inulin clearance because it's only filtered and none is secreted nor reabsorbed. Cin = GFR = Uin X V / Pin
|
|
How is creatinine production calculated?
|
Creatinine production = creatinine excretion = filtered load of creatinine = [Cr]p X GFR. Creatinine is filtered and secreted, not reabsorbed.
|
|
How does inulin concentration change as it passes through the nephron?
|
Inulin becomes more concentrated as it passes through the tubules because water is being reabsorbed and not inulin.
|
|
Gold standard to measure GFR
|
Inulin clearance because it's filtered but not secreted nor reabsorbed.
|
|
Gold standard to measure RPF
|
PAH clearance because some is filtered and the remaining is all secreted.
|
|
How is effective RPF calculated?
|
PAH clearance = RPF = Upah X V / Ppah
|
|
How is renal blood flow calculated?
|
ERPF / 1-Hct; ERPF = Upah X V / Ppah
|
|
What does positive free water clearance mean?
|
Water is being eliminated. Hypotonic urine is being formed to increase plasma osmolarity.
|
|
What does negative free water clearance mean?
|
Water is being conserved. Hypertonic urine is being formed to lower plasma osmolarity.
|
|
How is free water clearance calculated?
|
V - (Uosm(V) / Posm)
|
|
Which substance is cleared the most: PAH, inulin, glucose, creatinine
|
PAH
|
|
Which substances are cleared more than glucose?
|
Sodium, inulin, creatinine, PAH
|
|
Which substance is cleared the least: PAH, inulin, glucose, creatinine
|
Glucose
|
|
Which substances are cleared more than inulin?
|
Creatinine, PAH
|
|
Which substances are cleared less than creatinine?
|
Inulin, glucose, sodium
|
|
Transporters in the luminal membrane of the proximal tubule
|
Secondary Na/glucose cotransporter, secondary Na/amino acid cotransporter, secondary Na/H countertransporter
|
|
What substances are reabsorbed in the proximal tubule and how much?
|
Na (2/3 of filtered load), glucose (100%), amino acids (100%), HCO3 (indirectly, 80%), H20 (2/3), K (2/3), Cl (2/3)
|
|
Tubular osmolarity at beginning and end of proximal tubule
|
At the beginning and end is isotonic with plasma but only 1/3 of the filtered load.
|
|
Transporters in the basal membrane of proximal tubule
|
Na/K ATPase - luminal membrane secondary Na transporters depend on this.
|
|
Transporters in the basolateral membrane of proximal tubule
|
Na/K ATPase - luminal membrane secondary Na transporters depend on this.
|
|
Most energy-dependant process in the nephron
|
Active reabsorption of Na by the basal and basolateral Na/K ATPase
|
|
Characteristics of the loop of henle
|
Descending limb is permeable to water so water difuses out and intraluminal osmolarity increases to 1,200mOsm Ascending limb is impermeable to water and Na is actively pumped out by Na/K/2Cl pump so fluid becomes hypotonic. Flow is slow, anything that increases flow, decreases capacity to concentrate urine.
|
|
Characteristics of the collecting duct
|
Impermeable to water unless ADH is present. ADH increases permeability to H20 and urea to concentrate urine. Tight junctions with little back-leak.
|
|
Specialized cells of the distal tubule and collecting duct
|
Principal cells (aldosterone) and intercalated cells (create HCO3)
|
|
Actions of principal cells of the distal tubule and collecting duct
|
Aldosterone increases Na receptors in the membrane and increases primary transport by Na/K ATPase. Secondary transport of Na and secretion of K.
|
|
Actions of intercalated cells of the distal tubule and collecting duct
|
. |
|
Actions of the distal tubule and collecting duct |
Reabsorption of Na and secretion of K (stimulated by aldosterone), acidification of the urine (secretion of H and creation of HCO3)
|
|
Urine buffer systems
|
H2PO4- (dihydrogen phosphate) (tritratable acid) buffers 33% of secreted H. NH4+ (amonium) (nontritratable acid) buffers the remaining secreted H.
|
|
How is potassium affected by acidosis?
|
High concentration of ECF H --> H diffuses to ICF --> K diffuses to ECF --> hyperkalemia
|
|
How is potassium affected by alkalosis?
|
Low concentration of ECF H --> H diffuses to ECF --> K diffuses to ICF --> hypokalemia
|
|
Potassium dynamics in acute alkalosis
|
Hypokalemia, ↑ intracellular K, ↑ renal K excretion, negative K balance
|
|
Potassium dynamics in chronic alkalosis
|
Hypokalemia, ↓ intracellular K, ↑ renal K excretion, negative K balance
|
|
Potassium dynamics in acute acidosis
|
Hyperkalemia, ↓ intracellular K, ↓ renal K excretion, positive K balance
|
|
Potassium dynamics in chronic acidosis
|
Hyperkalemia, ↓ intracellular K, ↑ renal K excretion, negative K balance
|
|
How is potassium balance in acute acidosis?
|
Positive (potassium is reabsorbed)
|
|
How is potassium balance in acute alkalosis?
|
Negative (potassium is excreted)
|
|
How is potassium balance in chronic alkalosis?
|
Negative (potassium is excreted)
|
|
How is potassium balance in chronic acidosis?
|
Negative (potassium is excreted)
|
|
How is plasma potassium concentration in alkalosis?
|
Hypokalemia
|
|
How is plasma potassium concentration in acidosis?
|
Hyperkalemia
|
|
What is the difference in potassium dynamics between acute and chronic alkalosis?
|
Acute alkalosis --> ↑ intracellular K; Chronic alkalosis --> ↓ intrecellular K
|
|
What is the difference in potassium dynamics between acute and chronic acidosis?
|
Acute acidosis --> ↓ renal K excretion, positive K balance; Chronic acidosis --> ↑ renal K excretion, negative K balance
|
|
Changes in respiratory acidosis
|
Hypoventilation --> ↑ PaCO2 --> ↑ H and slight ↑ in HCO3 --> ↓ pH
|
|
Changes in respiratory alkalosis
|
Hyperventilation --> ↓ PaCO2 --> ↓ H and HCO3 --> ↑ pH
|
|
Changes in metabolic acidosis
|
Gain of H or loss of HCO3 --> ↓ HCO3 --> ↑ pH. To see if gain of H or loss of HCO3 check anion gap.
|
|
Changes in metabolic alkalosis
|
Loss of H or gain in HCO3 --> ↑ HCO3 --> ↑ pH. To see if gain of H or loss of HCO3 check anion gap.
|
|
Normal values of PCO2, HCO3 and pH
|
pH = 7.4; PCO2 = 40mmHg; HCO3 = 24mmol/L
|
|
↑pH, ↑ HCO3, ↑PCO2, ↓PO2, alkaline urine
|
Partially compensated metabolic alkalosis
|
|
↓pH, ↑PCO2, ↑HCO3, ↓PO2, acid urine
|
Partially compensated respiratory acidosis
|
|
↑pH, ↓PCO2, ↓HCO3, normal PO2, alkaline urine
|
Partially compensated respiratory alkalosis
|
|
↓pH, ↓PCO2, ↓HCO3, normal PO2, acid urine
|
Partially compensated metabolic acidosis
|
|
Normal plasma anion gap value
|
PAG = 12
|
|
Conditions that increase plasma anion gap
|
Lactic acidosis, ketoacidosis, ingestion of salicylate
|
|
Hyperchloremic non-anion gap metabolic acidosis
|
Loss of HCO3 (as in diarrhea) causes increased absorption of solutes and water, increasing Cl. Therefore ↓HCO3 and ↑Cl with a plasma anion gap of 12.
|
|
Factors that affect hormone binding protein synthesis
|
Estrogen increases binding proteins; androgens decrease binding proteins. In pregnancy there's increased total hormones with normal levels of free hormone.
|
|
Site of synthesis of CRH
|
Paraventricular nucleus
|
|
Site of synthesis of TRH
|
Paraventricular nucleus
|
|
Site of synthesis of PIF
|
Arcuate nucleus
|
|
Site of synthesis of GHRH
|
Arcuate nucleus
|
|
Site of synthesis of GnRH
|
Preoptic region
|
|
Site of synthesis of ADH
|
Supraoptic and paraventricular nuclei
|
|
How do hypothalamic hormones reach the anterior pituitary?
|
Hormones are released in the hypophyseal-portal system
|
|
Hypothalamic hormones
|
GHRH, GnRH, PIF (dopamine), TRH, CRH, Somatostatin, ADH, prolactin
|
|
Anterior pituitary hormones
|
ACTH, TSH, LH, FSH, GH, prolactin
|
|
Sheehan syndrome
|
Ischemic necrosis of the pituitary due to severe blood loss during delivery. Causes hypopituitarism.
|
|
Obstruction of pituitary stalk
|
Adenoma compresses pituitary stalk and decreases secretion of anterior pituitary hormones except prolactin.
|
|
What prevents downregulation of pituitary receptors?
|
Pulsatile release of hypothalamic hormones.
|
|
Hyperprolactinemia
|
Results from dopamine antagonists or pituitary adenomas that compress the pituitary stalk. Amenorrhea, galactorrhea, decreased libido, impotence, hypogonadism
|
|
What hormone controls release of cortisol and adrenal androgens?
|
ACTH
|
|
What hormone regulates release of aldosterone?
|
Angiotensin II and also potassium in hyperkalemia
|
|
Layers of the adrenal cortex
|
From external to internal: glomerulosa (aldosterone), fasciculata (cortisol), reticularis (androgens). "Salt, Sugar and Sex; the deeper it goes the sweeter it gets"
|
|
Consequences of loss of zona glomerulosa
|
No aldosterone: loss of Na, ↓ECF, ↓blood pressure, circulatory shock, death
|
|
Consequences of loss of zona reticularis
|
No cortisol: circulatory failure (cortisol is permissive for cathecolamine vasoconstriction), can't mobilize energy stores during exercise of cold (hypoglycemia)
|
|
Consequences of loss of adrenal medulla
|
No epinephrine: decreased capacity to mobilize fat and glycogen during stress. Not necessary for survival.
|
|
What are the 17-OH steroids?
|
17OHpregnenolone, 17OHprogesterone, 11-deoxycortisol, cortisol. Urinary 17OH steroids are an index of cortisol secretion.
|
|
What is the rate-limiting enzyme for steroid hormone synthesis?
|
Desmolase - converts cholesterol into pregnenolone
|
|
What are the 17-ketosteroids?
|
DHEA and androstenidione
|
|
DHEA
|
Weak androgen 17-ketosteroid conjugated with sulfate to make it water-soluble
|
|
What is measured as an index of androgen production?
|
Urinary 17-ketosteroids. In females and prepubertal males is an index of adrenal 17-ketosteroids. In postpubertal males is an index of 2/3 adrenal androgens and 1/3 testicular androgens.
|
|
Stimulus for the zona glomerulosa
|
Angiotensin II and potassium in hypekalemia stimulate production of aldosterone
|
|
Hormone responsible for negative feedback for ACTH release
|
Cortisol
|
|
Enzyme deficiencies that produce congenital adrenal hyperplasia and low cortisol levels
|
21β-OH, 11β-OH and 17α-OH all result in low cortisol levels.
|
|
21β-OH deficiency
|
No aldosterone: loss of Na, ↓ECF, ↓blood pressure in spite of high renin and angiotensin II, circulatory shock, death. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, hypotension (persmissive for catecholamines), fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism
|
|
11β-OH deficiency
|
Excess 11-deoxycorticosterone: Na and water retention, low-renin hypertension. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism
|
|
17α-OH deficiency
|
Excess 11-deoxycorticosterone and low aldosterone (no AII): Na and water retention, low-renin hypertension. No cortisol: skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia; corticosterone partially compensates low cortisol levels. No 17-ketosteroids: male pseudohermaphrodite, no testosterone, no estrogen.
|
|
↓17OH-steroids ↑ACTH, ↓blood pressure, ↓mineralocorticoids, ↑17-ketosteroids
|
21β-OH deficiency
|
|
↓17OH-steroids ↑ACTH, ↑blood pressure, ↓aldosterone, ↑11-deoxycorticosterone, ↑17-ketosteroids
|
11β-OH deficiency
|
|
↓17OH-steroids ↑ACTH, ↑blood pressure, ↑ aldosterone, ↑11-deoxycorticosterone, ↓17-ketosteroids
|
17α-OH deficiency
|
|
Stress hormones
|
GH, Glucagon, cortisol, epinephrine
|
|
Actions of GH in stress situations
|
Mobilizes fatty acids by increasing lipolysis in adipose tissue
|
|
Actions of glucagon in stress situations
|
Mobilizes glucose by increasing liver glycogenolysis
|
|
Actions of cortisol in stress situations
|
Mobilizes fat, carbs and proteins
|
|
Actions of epinephrine in stress
|
Mobilizes glucose via glycogenolysis and fat via lipolysis.
|
|
Metabolic actions of cortisol
|
1) Protein catabolism and delivery of amino acids; 2) lipolysis and delivery ofr fatty acids and glycerol 3) gluconeogenesis raises glycemia; also inhibits glucose uptake.
|
|
Permissive actions of cortisol
|
Enhances glucagon (without cortisol --> fasting hypoglycemia); enhances epinephrine (without cortisol -->hypotension)
|
|
α-MSH
|
Stimulates melanocytes and causes darkening of skin. Synthesized along with ACTH from pro-opiomelanocortin.
|
|
↑cortisol, ↓CRH, ↓ACTH, no hyperpigmentation
|
Primary hypercortisolism
|
|
↓cortisol, ↑CRH, ↑ACTH, hyperpigmentation
|
Addison disease - primary hypocortisolism
|
|
↑cortisol, ↓CRH, ↑ACTH, hyperpigmentation
|
Secondary hypercortisolism
|
|
↓cortisol, ↑CRH, ↓ACTH, no hyperpigmentation
|
Secondary hypocortisolism
|
|
↓cortisol, ↓CRH, ↓ACTH, no hyperpigmentation, symptoms of excess cortisol
|
Steroid administration
|
|
Cushing syndrome
|
Protein depletion, weak inflammatory response, poor wound healing, hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, osteoporosis, purple striae, hirsutism, hypertension, hypokalemic alkalosis, buffalo hump
|
|
Actions of aldosterone
|
↑Na channels in lumen of principal cells, ↑activity of Na/K ATPase of principal cells --> increases Na reabsorption. Also ↑ secretion of K and H leading to hypokalemic metabolic alkalosis.
|
|
Addison disease
|
↑ ACTH, hyperpigmentation, hypotension (no aldosterone, no cortisol), hyperkalemic metabolic acidosis (no aldosterone), loss of body hair (no androgens), hypoglycemia, ↑ ADH secretion
|
|
Causes of secondary hyperaldosteronism
|
CHF, vena cava constriction, cirrhosis, renal artery stenosis
|
|
Primary hyperaldosteronism
|
Na and water retention, hypertension, hypokalemic metabolic alkalosis, ↓ renin and angiotensin, no edema due to pressure diuresis and natriuresis.
|
|
Primary hypoaldosteronism
|
Na and water loss, hypotension, hyperkalemic metabolic acidosis, ↑ renin and angiotensin II, no edema
|
|
Secondary hyperaldosteronism
|
↑ renin and angiotensin II, ↑ Na and water retention in venous circulation, edema
|
|
Factors that influence ADH secretion
|
↑ osmolarity --> ↑ ADH secretion; ↓ blood volume --> baroreceptors --> medulla --> ↑ ADH secretion
|
|
Actions of ADH
|
Inserts water channels in luminal membrane of collecting ducts, increases reabsorption of water.
|
|
Central diabetes insipidus
|
Not enough ADH secreted. Dilute urine is formed in spite of water deprivation. Responds to injected ADH.
|
|
Nephrogenic diabetes insipidus
|
ADH is secreted but ducts are unresponsive to it. Dilute urine is formed in spite of water deprivation or injected ADH.
|
|
SIADH
|
Excessive secretion of ADH in spite of low osmolarity. Concentrated urine is formed.
|
|
↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↓ ECF, ↑ osmolarity
|
Diabetes insipidus
|
|
↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↓ ECF, ↑ osmolarity
|
Dehydration
|
|
↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↑ ECF, ↓ osmolarity
|
SIADH
|
|
↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↑ ECF, ↓ osmolarity
|
Primary polydipsia
|
|
Actions of ANP
|
Atrial stretch or ↑ osmolarity --> ANP secretion --> dilation of afferent, constriction of efferent --> ↑ GFR --> natriuresis; also decreases permeability of collecting ducts to water.
|
|
Delta cells of the pancreas
|
Between alpha and beta cells, represent 5% of islets. Secrete somatostatin.
|
|
Alpha cells of the pancreas
|
Near the periphery of the islets, represent 20%. Secrete glucagon.
|
|
Beta cells of the pancreas
|
In the center of the islets, represent 60-75%. Secrete insulin and C peptide.
|
|
Insulin receptor
|
Has intrinsic tyrosine kinase activity. Insulin receptor substrate binds tyrosine kinase, activates SH2 domain proteins: PI-3 kinase (translocation of GLUT-4), p21RAS.
|
|
Tissues that require insulin for glucose uptake
|
Resting skeletal muscle and adipose tissue
|
|
Tissues independent of insulin for glucose uptake
|
Brain, kidneys, intestinal mucosa, red blood cells, beta cells of the pancreas.
|
|
Anabolic hormones
|
Insulin, GH/IGF-1, androgens, T3/T4, IGF-1 (somatomedin C)
|
|
Effects of insulin on potassium
|
Increases Na/K ATPase uptake of K. Insulin + glucose used to treat hyperkalemia.
|
|
Mechanism of insulin release
|
Glucose enters β cells and is metabolized --> ↑ ATP --> closes K channels --> ↑ depolarization --> ↑ Ca influx --> exocytosis of insulin.
|
|
Factors that stimulate secretion of insulin
|
Glucose, arginine, GIP, glucagon
|
|
Factors that inhibit insulin release
|
Somatostatin, norepinephrine via α1 receptors
|
|
↑ glucose, ↑ insulin, ↑ C peptide
|
Type 2 diabetes
|
|
↑ glucose, ↓ insulin, ↓ C peptide
|
Type 1 diabetes
|
|
↓ glucose, ↑ insulin, ↑ C peptide
|
Insulinoma
|
|
↓ glucose, ↑ insulin, ↓ C peptide
|
Factitious hypoglycemia (insulin injection)
|
|
Actions of somatomedin C
|
Increases cartilage synthesis at epiphyseal plates (↑ bone length). Also ↑ lean body mass. Protein-bound and long half-life correlates to GH secretion. Also called IGF-1.
|
|
Secretion of GH
|
Pulsatile during non-REM sleep; more frequent in puberty due to increased androgens; requires thyroid hormones; decreases in the elderly.
|
|
Factors that stimulate GH secretion
|
Deep sleep, hypoglycemia, exercise, arginine, GHRH, low somatostatin
|
|
Factors that inhibit GH secretion
|
Negative feedback by GH on GHRH; positive feedback on somatostatin by IGF-1
|
|
Dwarfism
|
Due to GH insensitivity during prepuberty
|
|
Acromegaly
|
Due to excess GH in postpuberty. Enlargement of hands, feet and lower jaw, increased proteins, decreased fat, visceromegaly, cardiac insuficiency.
|
|
Composition of bone
|
Phosphate and calcium precipitate forming hydroxyapatite in osteoid matrix.
|
|
Actions of PTH
|
Rapid actions: increases Ca reabsorption in distal tubules and decreases phosphate reabsorption in proximal tubules, thus lowering blood phosphate and lowering solubility product which leads to bone resorption and raises plasma Ca. Slow actions: increases number and activity of osteoclasts (via osteoclast activating factor released by osteoblasts), increases activity of alpha-1 hydroxylase in the proximal tubules which increases active vitamin D and absorption of Ca and phosphate in the instetines.
|
|
Clinical features of primary hyperparathyroidism
|
↑ plasma Ca and ↓ plasma phosphate, phosphaturia, polyuria, calciuria (filtered load of Ca exceeds Tm), ↑ serum alkaline phosphatase, ↑ urinary hydroxyproline, muscle weakness, easy fatigability.
|
|
Clinical features of primary hypoparathyroidism
|
↓ plasma Ca and ↑ plasma phosphate, hypocalcemic tetany due to increased excitability of motor neurons.
|
|
↑ PTH, ↑ Ca, ↓ phosphate
|
Primary hyperparathyroidism. Causes: parathyroid adenoma (MEN I and II), ectopic PTH tumor (lung squamous CA)
|
|
↓ PTH, ↓ Ca, ↑ phosphate
|
Primary hypoparathyroidism. Cause: surgical removal of parathyroid.
|
|
↑ PTH, ↓ Ca, ↑ phosphate
|
Secondary hypoparathyroidism due to renal failure (no active vitamin D, decreased GFR)
|
|
↑ PTH, ↓ Ca, ↓ phosphate
|
Secondary hyperparathyroidism. Causes: deficiency of vitamin D due to bad diet or fat malabsorption.
|
|
↓ PTH, ↑ Ca, ↑ phosphate
|
Secondary hypoparathyroidism due to excess vitamin D.
|
|
Vitamin D synthesis
|
Dietary and skin cholecalciferol is hydroxylated by 25-hydroxylase in the liver and activated to 1,25 di-OH cholecalciferol by 1-alpha hydroxylase in the proximal tubules.
|
|
Actions of 1,25 di-OH cholecalciferol
|
Increases Ca binding proteins by intestinal cells which increases intestinal reabsorption of Ca and phosphate. Also increases reabsorption of Ca in the distal tubules. Increased serum Ca promotes bone deposition.
|
|
Osteomalacia
|
Underminerilized bone in adults due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.
|
|
Rickets
|
Underminerilized bone in children due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.
|
|
Excess vitamin D
|
Leads to bone reosprtion and demineralization
|
|
Synthesis of thyroid hormones
|
1) Iodine is actively transported into follicle cell; 2) thyroglobulin is synthesized in the RER, glycosylated in the SER and packaged in the GA; 3) Peroxidase is found in the luminal membrane and catalizes oxidation of I-, iodination of thyroglobulin and coupling to form MITs and DITs; 4) iodinated thyroglobulin is stored in the follicle lumen.
|
|
Structure of thyroid hormones
|
T4 has iodine attached to carbons 3 and 5 of both fenol rings; T3 has iodide attached to carbons 3 and 5 of the amino terminal fenol ring and the 3 prime carbon of the hydroxyl end fenol ring; reverse T3 has iodide in carbon 3 of the amino terminal fenol ring but not carbon 5.
|
|
Secretion of thyroid hormones
|
Iodinated thyroglobulin is endocytosed from the lumen of the follicles into lysosomes. Thyroglobulin is degraded into amino acids, T3, T4, DITs and MITs. T4 and T3 are secreted in a 20:1 ratio. DITs and MITs are deiodinated and iodine is recycled.
|
|
Transport of thyroid hormones
|
99% is bound to TBG, 1% is free. T4 has greater affinity for TBG and a half-life of 6 days. T3 has greater affinity for nuclear receptor and is the active form with a 1 day half-life. 50:1 T4/T3 ratio in periphery.
|
|
Activation and degradation of thyroid hormones
|
5' monodeiodinase activates T4 into T3. 5-monodeiodinase inactivates T4 into reverse T3.
|
|
Actions of thyroid hormones
|
↑ metabolic rate by ↑ Na/K ATPase except in brain, uterus and testes; essential for brain maturation and menstrual cycle; permissive for bone growth; permissive for GH synthesis and secretion; ↑ clearance of cholesterol; required for activation of carotene; ↑ intestinal glucose absorption; ↑ affinity and number of β1 receptros in the heart.
|
|
Effects of hypothyroidism in newborns
|
↓ dendritic branching and myelination lead to mental retardation.
|
|
Effects of hypothyroidism in juveniles
|
Cretinism results in ↓ bone growth and ossification --> dwarfism. Due to lack of permissive action on GH.
|
|
Control of thyroid hormone secretion
|
Circulating T4 is responsible for negative feedback of TSH by decreasing sensitivity to TRH. T4 is converted to T3 in the thyrotroph to induce negative feedback.
|
|
Effects of TSH
|
Rapid actions: ↑ iodide trapping, ↑ synthesis of thyroglobulin, ↑ reuptake of iodinated thyroglobulin, ↑ secretion of T4; late effects: ↑ blood flow to thyroid gland, ↑ hypertrophy of follicles and goiter.
|
|
↓ T4, ↑ TSH, ↑ TRH
|
Primary hypothyroidism; ↑ TSH is the more sensible index
|
|
↓ T4, ↓ TSH, ↑ TRH
|
Pituitary (secondary) hypothyroidism
|
|
↓ T4, ↓ TSH, ↓ TRH
|
Hypothalamic (tertiary) hypothyroidism
|
|
↑ T4, ↑ TSH, ↓ TRH
|
Pituitary (secondary) hyperthyroidism
|
|
↑ T4, ↓ TSH, ↓ TRH
|
Graves disease
|
|
Pathophysiology of iodine deficiency
|
Thyroid makes less T4 and more T3 so actions of T3 may be normal but low levels of T4 stimulate TSH secretion with development of goiter. Thus euthyroid with goiter.
|
|
Clinical features of hypothyroidism
|
↓ basal metabolic rate with cold intolerance, ↓ cognition, hyperlipidemia, nonpitting myxedema (mucopolysacchride accumulation around eyes retains water), physiologic jaundice (↑ carotene), hoarse voice, constipation, anemia, lethargy
|
|
Clinical features of hyperthyroidism
|
↑ metabolic rate with heat intolerance and sweating, ↑ apetite with weight loss, muscle weakness, tremor, irritability, tachycardia, exophthalmos.
|
|
Leydig cells
|
Stimulated by LH; produce testosterone for peripheral tissues and Sertoli cells. Testosterone provides negative feedback for LH secretion by pituitary.
|
|
Sertoli cells
|
Stimulated by FSH; produce inhibins (inhibits secretion of FSH), estradiol (testosterone is converted by aromatase), androgen binding proteins and growth factors for sperm. Responsible for development of sperm in males. Also MIH in male fetus.
|
|
↓ sex steroids, ↑ LH, ↑ FSH
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Primary hypogonadism or postmenopause.
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↓ sex steroids, ↓ LH, ↓ FSH
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Pituitary hypogonadism or constant GnRH infusion (downregulates GnRH receptors of pituitary.
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↑ sex steroids, ↓ LH, ↓ FSH
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Anabolic steroid therapy. LH supression causes Leydig cell atrophy with decreased Leydig testosterone which suppresses spermatogenesis.
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↑ sex steroids, ↑ LH, ↑ FSH
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Pulsatile infusion of GnRH
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Fetal development of male structures
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LH --> Leydig cells --> testosterone --> Wolffian ducts (internal male structures: epididymis, vasa deferentia ans seminal vesicles). Testosterone + 5-alpha reductase --> dihydrotestosterone --> urogenital sinus and external organs. MIH by Sertoli cells --> regression of Mullerian ducts and female structures.
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