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795 Cards in this Set
- Front
- Back
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what type of nephrons account for most of the nephrons in the kidney?
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cortical nephrons
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how much glucose is absorbed in the proximal tubule of a normal, healthy adult?
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100%
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how much ion absorption takes place in the proximal tubule?
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70% by magnitude
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where does all secretion take place in the nephron?
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proximal tubule
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what are the contractile cells that are between loops in the Bowman's capsule that regulate glomerular filtration?
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mesangial cells
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what part of a Bowman's capsule is continuous with the remainder of the renal tubule?
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outer basement membrane
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what is the main function of the renal glomerulus?
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filtration
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what are the two portions of the proximal tubule?
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proximal convoluted tubule (winds randomly)
proximal straight tubule (enters medulla) |
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how does aldosterone affect the distal nephron (not the mechanism)?
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leads to Na and Cl reabsorption
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how does ADH affect the distal nephron (not the mechanism)?
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leads to water reabsorption
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describe the proximal tubular cells of the renal tubule
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cuboidal cells with deep basal membrane invaginations, apical tight junctions, and microvilli (brush border)
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describe the distal tubular cells of the renal tubule
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short epithelial cells with highly invaginated basal membranes
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what are the two types of cells in the collecting duct?
what type of epithelial cells are they? |
principal cells = light cells
intercalated cells = dark cells both are cuboidal epithelial cells |
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describe the branching of the renal arteries
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renal arteries -> segmental arteries -> interlobar arteries ->arcuate arteries -> afferent arterioles -> glomerular capillaries -> efferent arterioles -> peritubular capillaries
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into how many segmental arteries does each renal artery divide?
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8
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where do the segmental arteries become interlobar arteries?
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after they enter the renal sinus
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where are arcuate arteries formed?
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from interlobar arteries over the renal pyramids
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what percent of the plasma water in the afferent arterioles is filtered by the glomerulus?
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about 20%
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what are the two special characteristics of glomerular capillaries?
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BP is double that which is in other capillaries (about 55mmHg)
between two arterioles (not arteriole and venule) |
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what is the function of the peritubular capillary bed in superficial (cortical) nephrons?
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delivery of nutrients to epithelial cells and acceptance of reabsorbed and secreted substances
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what is the function the peritubular capillary bed in medullary nephrons?
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follow the loop of Henle and serve as osmotic exchanger for the production of urine
aka vasa recta |
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where is erythropoietin added to the blood?
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from interstitial cells in the kidney cortex
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what is the signal for release of EPO?
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hypoxia in kidneys
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what is the effect of EPO?
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travels to bone marrow
increases production, maturation, and release of RBCs increases oxygen carrying capacity of blood |
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why does chronic renal failure usually lead to anemia?
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deficient EPO production, so RBCs aren't produced and released as efficiently
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what enzyme converts vitamin D3 into its active form?
where is it found? |
1alpha-hydroxylase
kidneys |
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how does renal failure lead to bone disease?
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renal failure -> hyperphosphatemia -> inhibits 1alpha-hydroxylase -> malabsorption of calcium -> parathyroid gland hyperfunction -> bone disease
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what is thromboxane A2?
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potent vasoconstrictor
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what are prostaglandins (E2 and I2)?
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vasodilators
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what is the effect of prostaglandins on the kidneys?
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increase renal blood flow
increase of Na excretion increase of renin release inhibition of the action of ADH on collecting ducts |
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what drugs inhibit the action of phospholipase A2?
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cortisone
prednisone |
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what drugs inhibit the action of cyclo-oxygenase?
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NSAIDs
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what are the four triggers of renin release?
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decreased pressure in afferent arteriole (intrarenal baroreceptors)
increased renal sympathetic activity decreased delivery of NaCl to the macula densa PGE2 and PGI2 |
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by what cells is renin produced?
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juxtaglomerular cells
extraglomerular mesangial cells |
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what is the function of renin?
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converts angiotensinogen (from the liver) into angiotensin I
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what are granular cells?
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aka juxtaglomerular cells
cells in the afferent arteriole primarily, which produce and secrete renin |
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what group of cuboidal epithelial cells represents the start of the distal convoluted tubule?
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macula densa
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how is low NaCl detected by macula densa cells?
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decreased BP -> decreased GFR -> decreased capillary hydrostatic pressure in peritubular capillaries -> increased reabsorption of Na and Cl in proximal tubule -> macula densa in distal convoluted tublule sense low NaCl
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what is the effect of low NaCl detected by macula densa cells?
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facilitates PGE2 formation, which triggers juxtaglomerular cells to release renin
reduces adenosine formation, which would otherwise inhibit renin release and would cause vasoconstriction in afferent arteriole |
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what is the effect of adenosine on kidneys?
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inhibits renin release
causes vasoconstriction in afferent arteriole |
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what is the function of kallikrein?
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converts kininogen to kinins (mostly bradykinin)
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what is the function of a kininase?
what is an example of one? |
convert kinins to inactive peptides
angiotensin converting enzyme (ACE) |
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what are the functions of kinins?
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vasodilator (via NO and PGI2)
inhibits Na reabsorption by inner medulla collecting ducts |
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what effect does ACE inhibitor have on renal blood flow?
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increases the half-life of kinins, allowing them to stick around longer and vasodilate more
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what is the 60-40-20 rule?
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water is 60% of body mass
intracellular fluid is 40% of total body mass and extracellular fluid is 20% interstitial fluid is 15% of total body mass and intravascular is 5% (both are subdivisions of ECF) |
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what is the effect of fat on body water composition?
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increased fat causes water composition to be lower
decreased fat causes water composition to be lower |
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what is the effect of age on body water composition?
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increased age causes decreased water composition
(higher in infants than in elderly) |
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what substances can be injected to measure extracellular fluid volume?
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inulin
mannitol sulfate |
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what substances can be injected to measure plasma volume?
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labeled protein (125 I-albumin)
Evans Blue dye (binds tightly to plasma proteins) |
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what is the formula for total blood volume?
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plasma volume / (1 - hematocrit )
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how is ISF calculated?
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ECF - plasma = ISF
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how is ICF calculated?
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total body water - ECF = ICF
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in body fluid compartment boxes, what is given by the area of each box?
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amount of solute present in a compartment
Amount = concentration (y-axis) * volume (x-axis) |
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what happens to the body fluid compartment boxes when 2L of isotonic solution are added?
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all isotonic fluid is added to ECF
no change in osmolarity, so no water shifts ECF volume increases (as does total volume) by 2L, which decreases plasma protein concentration and hematocrit |
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what happens to body fluid compartments when 2L of hypotonic solution is added (e.g. pure water)?
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hypotonic fluid is added to ECF
osmolarity of ECF is lower than ICF, so water shifts into the cells intracellular and extracellular osmolality falls until new equilibrium is reached |
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what happens to body fluid compartments when 2L of hypertonic solution is added (e.g. 5% NaCl solution)?
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hypertonic fluid is added to ECF
osmolarity of ECF is higher than that of ICF, so water shifts out of the cells intracellular and extracellular osmolality increases until new equilibrium is reached |
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what is an isoosmotic volume contraction?
what are the effects on body fluid compartments? |
hemorrhage
plasma exudation through burned skin GI losses (vomiting, diarrhea) initially fluid is lost from plasma and then repleted from ISF ECF: volume decreased, osmolality unchanged ICF: volume and osmolality unchanged |
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what are examples of hyperosmotic volume contractions?
what are their effects on body fluid compartments? |
decreased water intake
diabetes insipidus diabetes mellitus excessive sweat evaporation initially fluid is lost from plasma, which becomes hyperosmotic, causing a fluid shift from ICF to plasma ECF: volume decreased, osmolality increased ICF: volume decreased and osmolality increased |
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what are examples of hypoosmotic volume contractions?
what are their effects on body fluid compartments? |
renal loss of NaCl because of adrenal insufficiency (Addison's Disease)
fluid and electrolytes are lost from plasma, which becomes hypoosmotic and causes water to shift from ECF to ICF ECF: volume decreased and osmolality decreased ICF: volume increased and osmolality decreased |
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what are examples of isoosmotic volume expansion?
what are their effects on body fluid compartments? |
oral or parenteral intake of large volumes of isotonic NaCl
fluid is added to plasma ECF: volume increased, osmolality unchanged ICF: volume unchanged, osmolality unchanged |
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what are examples of hyperosmotic volume expansion?
what are their effects on body fluid compartments? |
oral or parenteral intake of large volumes of hypertonic fluid
plasma osmolality increases, causing water to shift from interstitium into plasma, thereby initially increasing plasma volume, but increase in osmolality of ECF causes water to flow out of ICF ECF: volume increased, osmolality increased ICF: volume decreased and osmolality increased |
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what are examples of hypoosmotic volume expansion?
what are their effects on body fluid compartments? |
water intoxication or SIADH
initially water enters plasma, causing a decline in plasma osmolality and a shift of water into interstitial space and a decrease in interstitial fluid osmolality, which causes a water shift from ECF to ICF ECF: volume increased, osmolality decreased ICF: volume increased, osmolality decreased |
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what type of fluid is sweat (tonicity)?
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hypotonic
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how is plasma osmolarity calculated at the patient bedside?
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2Na + Glucose + Urea = (mmol/L)
mmol/L for all 2[Na] + [Glucose]/18 + [Urea]/2.8 mEq/L for Na mg/dL for glucose and urea |
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what device is used to determine blood osmolarity in clinical laboratories?
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osmometer
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define clearance
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volume of plasma that is completely cleared of a substance x by the kidneys per unit time
ratio of urinary excretion to plasma concentration |
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what is the formula for renal plasma clearance?
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Cx = UxV / Px
Cx - clearance of substance x Ux - urine concentration of substance x V - urine flow rate Px - plasma concentration for substance x |
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what is the formula for urinary excretion of substance x?
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Ux * V
Ux - urine concentration of substance x V - urine flow rate |
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to what is the glomerular filtration rate equal?
what is important about it? |
renal clearance of inulin
inulin is freely filtered, but neither secreted nor absorbed |
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what is the formula for GFR?
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GFR = [(UIN*V) / PIN] = CIN
GFR - glomerular filtration rate UIN - urine concentration of inulin V - urine flow rate PIN - plasma concentration of inulin CIN - clearance of inulin |
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what is the formula for filtered load?
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FL = Px * GFR
FL - filtered load Px - plasma concentration of x GFR - glomerular filtration rate |
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what is the formula for excreted load?
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EL = Ux * V
EL - excreted load Ux - urine concentration of x V - urine flow rate |
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what does the difference between filtered load and excreted load indicate?
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filtered load - excreted load
if positive: substance was reabsorbed if negative: substance was secreted |
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what does the ratio of filtered load to excreted load indicate?
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excreted load / filtered load
excreted fraction (percent) of filtered substance |
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why can creatinine clearance work as an estimate of GFR in nomal people?
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secreted only to a small extent by proximal tubule
plasma creatinine concentration is overestimated **two errors compensate for one another** |
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what are the advantages for using creatinine rather than inulin to determine GFR? what are the disadvantages?
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no infusion necessary (natural product of muscle creatine phosphate)
no bladder catheterization necessary (urine collected over long periods of time) may not work in severe chronic renal failure may not work with drugs that inhibit tubular secretion of creatinine |
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to what is PAH clearance nearly equivalent?
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renal plasma flow
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from where does PAH come?
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derivative of glycine and p-amino-benzoic acid
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why is PAH good for measuring renal plasma flow?
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it is both filtered and secreted, allowing it to be nearly completely removed from plasma in one passage
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how much of at-rest blood flow is directed to the kidneys?
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20-25%
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where is blood flow higher/lower in the kidneys?
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higher in cortex (allows high rate of plasma filtration)
lower in medulla (prevents osmotic gradient from washing out) |
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what is the formula for renal blood flow?
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Q = dP / R
Q - flow dP - change in pressure R - resistance |
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what is the most important determinant in GFR?
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hydrostatic pressure in glomerular capillaries
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what happens to GFR when afferent resistance is increased?
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GFR decreases
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what happens to GFR when efferent resistance is increased?
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GFR increases
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what is the function of prostaglandins in regulating arteriole resistance?
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inhibit excessive vasoconstriction of afferent and efferent arterioles
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what is the formula for effective RPF?
what assumption is made? |
effective RPF = [U] * V / ([RA] - [RV]) =CPAH
effective RPF - effective renal plasma flow U - urine concentration of PAH V - urine flow rate RA - renal artery concentration of PAH RV - renal vein concentration of PAH 1. RA is taken from a peripheral vein assuming it to be equivalent 2. RV is assumed to be zero, because we assume that all is cleared via filtration and secretion |
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what is the formula for renal blood flow?
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Renal Blood Flow = RPF / (1 - hematocrit)
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what is a filtration fraction?
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percentage of plasa volume that is filtered through the glomerular capillary membrane to become glomerular filtrate
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what is the normal filtration fraction?
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about 20% of plasma volume
about 180L per day |
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what is the formula for filtration fraction?
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FF = GFR / RPF
FF - filtration fraction GFR - glomerular filtration rate - equal to inulin clearance RPF - renal plasma flow - equal to PAH clearance |
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what is the most common measure of renal function on its own?
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filtration fraction
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what are the most common causes of poor renal blood perfusion?
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decreased blood volume (GI bleeding, burns, diarrhea, excessive diuretic therapy)
movement of fluid from intravascular space to tissue (pancreatitis, peritonitis, rhabdomyolysis) decreased blood circulation (heart failure, peripheral vasodilation from sepsis) decrease in Kf (diabetes mellitus, hypertension) |
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what accounts for many cases of acute renal failure?
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failure to perfuse the kidneys with blood
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what are the two mechanisms for autoregulation of renal blood flow between 80 and 180mmHg (MAP)?
what is the effect of this autoregulation? |
myogenic mechanism
tubuloglomerular mechanism causes a constant GFR over these blood pressures |
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what is the myogenic mechanism of autoregulation of renal blood flow?
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increased BP -> increased blood vessel diameter -> activation of stretch-activated Ca channels - > contraction of smooth muscle cells of vasculature
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what is the tubuloglomerular mechanism of autoregulation of renal blood flow?
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increased perfusion pressure -> increased [NaCl] in distal tubule -> ATP released from macula densa cells -> converted to ADP and then adenosine -> vasoconstriction of afferent arteriole
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what modulates vasoconstriction at the afferent arterioles?
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ADENOSINE
angiotensin II |
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what is the overall importance of the tubuloglomerular mechanism of autoregulation?
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prevents excessive urinary Na loss when GFR is increased
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what are the effects of moderate levels of angiotensin II on renal blood flow?
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vasoconstriction in afferent (less responsive) and efferent (more responsive) arterioles
decrease in renal blood flow increase in GFR |
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what are the effects of high levels of angiotensin II on renal blood flow?
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activates mesangial cells, resulting in a decrease in surface area of glomerular capillaries -> mild decrease in GFR
vasoconstriction of afferent and efferent arterioles -> decrease in GFR increased sympathetic -> decrease in RBF |
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what is the normal pH range of the body?
what is the normal [H] in the blood? |
7.37 - 7.42
45-35 nmol/L |
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at what pH does a patient have acidemia?
at what pH is acidemia considered lethal to the body? |
pH < 7.37
pH < 6.8 |
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at what pH does a patient have alkalemia?
at what pH is alkalemia considered lethal to the body? |
pH > 7.42
pH > 8.0 |
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what is the effect on ECF pH when a change is made in the ICF pH?
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ECF pH will change in the same direction, but with smaller magnitude
also, vice versa |
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what is the volatile acid source in the body?
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H2O + CO2 <-> H2CO3 <-> H + HCO3
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how are non-volatile acids formed in the body?
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protein metabolism
sulfur containing AA (met, cys) -> H2SO4 cationic AA (arg, lys, hist) -> HCl phosphorous-containing proteins and phosphoesters of nucleic acids -> phosphoric acid |
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how does production of non-volatile acid production affect an adult on a typical American diet?
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net production of nonvolatile acids is about 1mEq H / kg / day
as long as carbs and fats are completely oxidized to CO2 and H2O, there is no acid-base problem |
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what does a chemical buffer consist of?
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acid
conjugate base |
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what is the function of chemical buffers in the body?
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minimize pH changes
NOT designed to rid body of hydrogen ions |
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what are the ECF chemical buffers?
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HCO3 / CO2
plasma proteins inorganic phosphate (HPO4 / H2PO4) |
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what are the chemical buffers in the intracellular fluid?
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proteins (e.g. hemoglobin)
organic phosphate compounds (ATP, ADP, AMP, G1P, 2,3-DPG) some HCO3 / CO2 |
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what are the chemical buffers in the bone?
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phosphate salts
carbonate salts |
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what is the body's most important buffer system?
what two components can be added to or removed from the body? |
HCO3 / CO2 system
HCO3 can be removed/added CO2 can be removed/added |
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what organs control the bicarb/CO2 buffer system?
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lungs
kidneys |
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what is the Henderson-Hasselbach Equation?
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pH = pKa + log ([A-] / [HA])
A- = conjugate base HA = acid |
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what is the equation for pKa?
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pKa = -log Ka
Ka - equilibrium constant for an acid |
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how does the pKa relate to the strength of the acid?
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lower pKa values mean stronger acid
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how does the law of mass action relate to the bicarb/CO2 buffer system?
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Ka = ([H] [HCO3] / [CO2] [H2O])
concentration of carbonic acid is very low and thus neglected concentration of water is very large so small changes are neglected Ka = ([H] [HCO3] / [CO2]) |
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what is the equation for dissolved CO2 in the blood?
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CO2 (dissolved) = 0.03*PCO2
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what is the Henderson Equation?
why do many clinicians prefer using it? |
[H]*[HCO3] = PCO2*[H2O]
[H] = (24*PCO2 / [HCO3]) many clinicians prefer it because it doesn't include any logarithms |
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what is the isohydric principle?
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in any fluid compartment, all buffer pairs are in equilibrium with the same [H]
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what is the effect of metabolic acidosis on respiratory compensation mechanisms?
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metabolic acidosis -> decreased bicarb -> hyperventilation -> decreased PCO2
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what is the effect of metabolic alkalosis on respiratory compensation mechanisms?
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metabolic alkalosis -> increased bicarb -> hypoventilation -> increased PCO2
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what are the respiratory compensation mechanisms?
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mechanism to change plasma pH by varying the respiratory rate, which can begin within 1-3 minutes, but has only limited ability to restore normal values
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what are the renal compensation mechanisms?
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mechanism to change plasma pH by kidneys reabsorbing filtered bicarb, forming titratable acid, synthesizing and excreting H as NH3/NH4
it may take hours or days to correct imbalance has large ability to restore normal values |
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what is the bottom line for the reabsorption of filtered bicarbonate?
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Net reabsorption of filtered HCO3
no net secretion of H+ no new bicarb is synthesized |
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what is the effect of respiratory acidosis on the reabsorption of filtered bicarbonate?
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respiratory acidosis ->
increased PCO2 -> increased reabsorption of HCO3 |
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what is the effect of respiratory alkalosis on the reabsorption of filtered bicarbonate?
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respiratory alkalosis ->
decreased PCO2 -> decreased reabsorption of HCO3 |
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how is filtered bicarbonate reabsorbed?
|
H and HCO3 are produced in cells (carbonic anhydrase converts CO2 and H20 to carbonic acid, which then quickly dissociates)
H are secreted into tubule with Na-H exchanger HCO3 is reabsorbed with Na (on basolateral cell membrane) tubular H combines with filtered HCO3 (spontanteously and then is broken into H2O and CO2 by brush border carbonic acid) |
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what is the function of brush border carbonic anhydrase?
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after tubular H combines with filtered HCO3 to make carbonic acid, brush border carbonic anhydrase splits it into water and carbon dioxide
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where is filtered bicarbonate reabsorbed?
|
proximal convoluted tubule
most protons are secreted and cause the reabsorption of ~90% of filtered bicarbonate |
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how is the reabsorption of filtered bicarbonate regulated?
|
regulated by the filtered load
at low plasma bicarb levels, all of filtered bicarb is reabsorbed at high plasma bicarb levels, bicarb spills out into the urine because reabsorptive capacity is exceeded |
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what is the net effect of carbonic anhydrase inhibitors?
|
decreased bicarbonate reabsorption
weak diuretic |
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how do carbonic anhydrase inhibitors work?
|
inhibits conversion of CO2 and H2O to carbonic acid and subsequently H and HCO3
since Na is countertransported with H and there is less H, less sodium is reabsorbed greater sodium, bicarb, and water loss in the urine Carbonic anhydrase inhibitors are weak diuretics |
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what are the main uses for carbonic anhydrase inhibitors?
|
glaucoma treatment
anticipation of respiratory alkalosis during high altitude mountain climbing |
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what is the bottom line of titratable acid?
|
net secretion of H+
net reabsorption of newly synthesized HCO3 |
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when is titratable acid formed?
|
when buffers in the tubular urine are titrated by secreted H+
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what buffers contribute to titratable acid?
|
H2PO4-
creatinine buffers (other than ammonia) |
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how are titratable acids measured in the urine?
|
measured by titrating urine with NaOH until the urine is back to the blood pH
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how much new bicarbonate is added to the blood by titratable acids?
|
for each mEq of titratable acid excreted, one mEq of new bicarbonate is added to the blood
|
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what type of cells have the K/H-exchanger?
|
alpha-intercalated cells
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how are titratable acids created in urine?
|
carbonic anhydrase converts CO2 and water to carbonic acid which quickly dissociates to H and HCO3
bicarb is counter transported across the basolateral membrane with chloride protons are counter transported across the apical membrane (countertransport with K, and by proton-ATPase) H combines with filtered buffers and is excreted |
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where are titratable acids formed?
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throughout the nephron, primarily at alpha-intercalated cells
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how are titratable acids regulated?
|
availability of buffers - urine pH cannot drop below 4.5, so the only way then to get rid of more protons is to supply more buffer (done as ammonia)
aldosterone - stimulates H secretion (at proton ATPase) |
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what is included in the term "ammonia"?
|
ammonium ion (NH4+)
free base (NH3) |
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what is the bottom line of excretion of ammonia in the urine?
|
net secretion of H+
net reabsorption of newly synthesized HCO3- |
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how does ammonia excretion happen?
|
ammonia is synthesized in proximal tubule cells from AA precursors and diffuses into tubule (free base) or is countertransported with Na (ammonium ion)
H is counter-transported with Na into the tubule, where it combines with the free base ammonium ion cannot diffuse across the membrane, so it is stuck in the tubule and excreted |
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what is the counter ion for ammonium in the urine?
|
chloride
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what is the main amino acid precursor for ammonia?
|
glutamine
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where is ammonia synthesized in the nephron?
|
proximal tubule cells
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how much bicarb is added to the blood by the generation of ammonia in the blood?
|
for each mEq of ammonium ion excreted, one mEq of new bicarbonate is added to the blood
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what locations of the nephron are important in excretion of ammonia?
|
proximal convoluted tubule - produces most ammonium ion and free base ammonia
thick ascending limb - ammonium ion is reabsorbed and accumulates in the medulla collecting duct - free base ammonia diffuses into acidic urine, where it is trapped as ammonium ion |
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how is excretion of acid as ammonia regulated?
|
by pH - decreased intracellular pH stimulates ammonia synthesis; H combines with NH3 to make ammonium ion which is excreted and increases the gradient for ammonia diffusion
adaptive increase in ammonia synthesis - adaptive increase (which takes several days) supplies more buffer |
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what is the equation for renal net acid excretion?
|
EA = UTA + UA -UB
EA = renal net acid excretion UTA = urinary titratable acid UA = urinary ammonium ion UB = urinary bicarb all in mEq/day |
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in what form is most acid excreted?
|
ammonia > titratable acid
|
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what is the order that acid/base regulatory processes occur?
|
distribution and buffering in ECF
cellular buffering processes respiratory compensation renal base excretion (bicarb) renal acid excretion (titratable acid and ammonia) |
|
|
what are the four simple acid-base disturbances?
|
respiratory acidosis
respiratory alkalosis metabolic acidosis metabolic alkalosis |
|
|
what are the serum values for pH, bicarb, and PCO2 from respiratory acidosis?
what is the compensatory response? |
pH - low
bicarb - high PCO2 - very high kidneys increase H excretion (increase plasma bicarb) |
|
|
what are the serum values for pH, bicarb, and PCO2 from respiratory alkalosis?
what is the compensatory response? |
pH - high
bicarb - low PCO2 - very low kidneys increase bicarb excretion (decrease plasma bicarb) |
|
|
what are the serum values for pH, bicarb, and PCO2 from metabolic acidosis?
what is the compensatory response? |
pH - low
bicarb - very low PCO2 - low alveolar hyperventilation; kidneys increase H excretion |
|
|
what are the serum values for pH, bicarb, and PCO2 from metabolic alkalosis?
what is the compensatory response? |
pH - high
bicarb - very high PCO2 - high alveolar hypoventilation; kidneys increase bicarb excretion |
|
|
how can you differentiate between alkalosis and acidosis?
|
pH
body's defense mechanisms, by themselves, cannot correct the disorder |
|
|
how can you differentiate between a respiratory pH problem and a metabolic pH problem?
|
for respiratory, look at PCO2 (high PCO2 indicates respiratory acidosis, low PCO2 indicates respiratory alkalosis)
for metabolic, look at bicarb (high bicarb results in metabolic alkalosis; low bicarb results in metabolic acidosis) |
|
|
what is the compensatory response for metabolic acidosis?
|
compensation in respiration, decreasing PCO2 by hyperventilation
|
|
|
what is the compensatory response for metabolic alkalosis?
|
compensation in respiration, increasing PCO2 by hypoventilation
|
|
|
what is the compensatory response for respiratory acidosis?
|
compensation in renal acid secretion, increasing plasma bicarb
|
|
|
what is the compensatory response for respiratory alkalosis?
|
compensation in renal acid secretion, decreasing plasma bicarb
|
|
|
what is the definition of respiratory acidosis?
|
abnormal process characterized by CO2 accumulation
|
|
|
what are the causes for respiratory acidosis?
|
bottom line = hypoventilation
insufficient neural drive for ventilation inadequate movement of respiratory muscles or thoracic cage airway obstruction lung disease |
|
|
describe the chemistry for respiratory acidosis
|
as dissolved carbon dioxide increases, Le Chatelier's principle says that it will drive the reaction towards carbonic acid, which then spontaneously decomposes into protons and bicarb
|
|
|
how much does plasma bicarb increase in chronic respiratory acidosis?
acute? |
chronic - bicarb increases about 4mEq/L for each 10mmHg
acute - bicarb increases about 1mE/L for each 10mmHg |
|
|
what is the definition of respiratory alkalosis?
|
abnormal process causing the loss of too much CO2
|
|
|
what are the causes of respiratory alkalosis?
|
bottom line - hyperventilation
voluntary hyperventilation anxiety direct stimulation of respiratory center (fever, meningitis) hypoxia caused by severe anemia or high altitude |
|
|
what is the definition of metabolic acidosis?
|
decreased bicarb concentration, characterized by a gain of acid (other than carbonic acid) or loss of base
|
|
|
what are the common causes of metabolic acidosis?
|
failure of kidneys to excrete acid at an adequate rate (acute and chronic renal failure)
excessive intake or production of nonvolatile acids loss of bicarbonate |
|
|
in what ways can intake or production of nonvolatile acids be excessive?
|
ketoacidosis (e.g. diabetes)
lactic acidosis ingestion of acidifying agents (ammonium chloride) poisons (salicylate, methanol, ethylene glycol) |
|
|
how can loss of bicarbonate be excessive?
|
excessive urinary excretion (renal tubular acidosis
diarrhea |
|
|
for what is an anion gap useful?
|
evaluating the etiology of metabolic acidosis
|
|
|
how is anion gap calculated?
|
sum of cations = sum of anions
[Na] = [Cl] + [HCO3] + [UA] [UA] = [Na] - [Cl] - [HCO3] UA - unmeasured anions |
|
|
what is a normal anion gap?
|
8-12 mEq/L
|
|
|
from what does an increased anion gap metabolic acidosis develop?
|
unmeasured anion (ketone bodies, lactic acid, toxins) is increased to replace bicarb
Methanol Uremia Lactic acid Ethylene glycol pAldehyde Ketone bodies Salicylates |
|
|
from what does a normal anion gap metabolic acidosis develop?
|
when chloride ions are increased to replace bicarbonate
diarrhea renal tubular acidosis ammonium chloride ingestion |
|
|
what is the definition of metabolic alkalosis?
|
increased bicarb concentration characterized by the gain of strong base or bicarbonate or loss of acid (other than carbonic acid)
|
|
|
what are the common causes of metabolic alkalosis?
|
excessive alkali intake
vomiting of gastric acid juice abnormal renal loss of H+ (hyperaldosteronism or hypokalemia |
|
|
how much of the compensatory buffering for metabolic acidosis occurs in the cells and bones?
|
about 1/2
H+ enters cells in exchange for K; hyperkalemia can develop |
|
|
how much of the compensatory chemical buffering for metabolic alkalosis occurs in cells?
|
about 1/3
|
|
|
what is the main effect of PGE2 and PGI2 in the kidneys?
|
vasodilators, mainly at the afferent arterioles
cause a dampening effect on renal vasoconstriction |
|
|
what is the function of TXA2?
|
vasoconstrictor
|
|
|
what are the three effects of increased activity of renal sympathetic nerves?
|
constrict renal arterioles
increase renal prostaglandin synthesis and release, causing dilation of renal arterioles increase plasma angiotensin II, causing increased prostaglandin synthesis and release (vasoldilation) as well as renal arteriole constriction |
|
|
why are NSAIDs especially dangerous for patients with some degree of renal impairment?
|
NSAIDs inhibit the production of prostaglandins, which are the damper for the sympathetic system so that it doesn't completely constrict the afferent arterioles
|
|
|
what is the effect of low levels of dopamine on the kidneys?
|
vasodilator
|
|
|
what sympathetic receptor is found in the renal arteries and arterioles?
|
alpha1 receptors
beta1 receptors |
|
|
what is the effect of sympathetic stimulation on renal arteries and arterioles?
|
increases resistance in afferent and somewhat less in efferent arterioles
decreases renal blood flow |
|
|
what is the effect of sympathetic stimulation on angiotensin II?
|
stimulates secretion of angiotensin II
decrease in RBF and GFR overall increase in FF |
|
|
what is the effect of sympathetic stimulation of alpha1 receptors in the kidney?
|
increases resistance in afferent and somewhat less in efferent arterioles
decreases renal blood flow |
|
|
what is the effect of sympathetic stimulation of beta1 receptors in the kidney?
|
releases renin
|
|
|
what is the effect of sympathetic stimulation of prostaglandin production in the kidneys?
|
increase
|
|
|
what is the effect of parasympathetic stimulation in the kidney?
|
there is no parasympathetic influence on the kidney
|
|
|
what is the effect of sympathetic innervation on autoregulation?
|
sympathetic innervation has no part in autoregulation
raises MAP at the expense of renal blood flow |
|
|
what is the effect of very high ADH on kidneys?
|
cause contraction of afferent and efferent arterioles
cause contraction of mesangial cells to decrease GFR extreme response during hemorrhage and shock |
|
|
what is the effect of diabetes mellitus on the basement membrane?
|
increases the thickness of the glomerular basement membrane
|
|
|
what are the three components of the renal filtration apparatus?
|
endothelial cells with fenestrations of ~0.1um
basal lamina surrounds glomerular capillaries epithelial cells with podocytes, that create 25-60nm wide slits |
|
|
by what mechanisms are substances sieved in the kidneys?
|
by size - nothing over 4nm can pass
by charge - negative substances repelled; positive substances attracted |
|
|
by what is glomerular filtration determined?
|
Starling forces
GFR = Kf (PGC - PBS - piGC) Kf - filtration coefficient PGC - glomerular capillary hydrostatic pressure PBS - hydrostatic pressure in Bowman's space piGC - glomerular capillary colloid osmotic pressure |
|
|
what is the oncotic pressure in Bowman's space?
|
zero
|
|
|
how do hydrostatic and oncotic pressures change through non-renal capillary beds?
|
hydrostatic pressure is relatively low and falls with distance due to the resistance and blood flow
osmotic pressure hardly changes with distance |
|
|
how do hydrostatic and oncotic pressures change in the glomerulus?
|
hydrostatic pressure is high and hardly changes with distance due to efferent arteriolar constriction
osmotic pressure rises with distances, which increasingly opposes filtration |
|
|
on what does the filtration coefficient depend?
|
porosity of surface area
|
|
|
on what does the glomerular capillary hydrostatic pressure depend?
|
MAP
resistance of afferent and efferent arterioles |
|
|
on what does the hydrostatic pressure in Bowman's space depend?
|
downstream resistance
|
|
|
on what does the glomerular capillary colloid oncotic pressure depend?
|
plasma protein concentration
|
|
|
how can the glomerular capillary hydrostatic pressure decrease the glomerular filtration rate?
|
blood loss
sympathetic and high levels of angiotensin II |
|
|
how can the glomerular capillary hydrostatic pressure increase the glomerular filtration rate?
|
hypertension
low/moderate levels of angiotensin II |
|
|
how can the hydrostatic pressure in the Bowman's space decrease the glomerular filtration rate?
|
obstruction of collecting duct
obstruction of ureter or urethra |
|
|
how can the glomerular capillary colloid oncotic pressure decrease the glomerular filtration rate?
|
increase in plasma proteins
dehydration |
|
|
how can the glomerular capillary colloid oncotic pressure increase the glomerula filtration rate?
|
decrease in plasma proteins
isotonic fluid infusion nephrotic syndrome |
|
|
what is a typical glomerular filtration rate in a young, 70-kg, male adult?
|
125 mL plasma / minute
|
|
|
what is a typical glomerular filtration rate in a newborn?
|
20 mL plasma / minute
|
|
|
what is a typical glomerular filtration rate in a young adult female?
|
110 mL plasma / minute
|
|
|
what is BUN and what is a normal level?
|
blood urea nitrogen
9-18 mg/dL |
|
|
what is a greatly elevated BUN?
what does this indicate? |
>60 mg/dL
indicates moderate to severe renal failure |
|
|
why is creatinine a preferred method of indicating decreased GFR (over BUN)?
|
creatinine changes less frequently than BUN
|
|
|
what is indicated by a low BUN?
|
little significance for the kidney
liver problem malnutrition alcoholism overhydration pregnancy |
|
|
what is a normal level for creatinine?
|
0.6 - 1.2 mg/dL
|
|
|
when do creatinine levels rise?
|
not until about half of the kidney is destroyed
|
|
|
what is indicated by double serum creatinine levels?
|
indicate half GFR
|
|
|
what is indicated by threefold increase in serum creatinine levels?
|
indicates 75% loss of kidney function
|
|
|
what can cause increased BUN?
|
kidney problems
GI bleeding (causes urea formation in liver) |
|
|
what can cause increased creatinine?
|
kidney problem
eating a lot of cooked meat |
|
|
what is indicated by a high BUN:Creatinine ratio?
|
a problem before the kidney
|
|
|
what is a normal BUN:Creatinine ratio for an adult?
|
10:1 - 20:1
|
|
|
what is a BUN:Creatinine ratio for prerenal azotemia patient?
|
> 20:1
|
|
|
what can cause an elevated BUN:Creatinine ratio?
|
congestive heart failure
dehydration decreased renal blood flow |
|
|
why does BUN increase proportionally more than creatinine?
|
urea is reabsorbed but not creatinine
|
|
|
where is glucose reabsorbed?
|
98% in the early proximal tubule
2% beyond the distal convoluted tubule |
|
|
what is the apical membrane transport protein for glucose?
|
SGLT
|
|
|
what is the basolateral membrane transport protein for glucose?
|
GLUT1
GLUT2 |
|
|
how is glucose filtered?
|
freely filtered
|
|
|
how well is glucose reabsorbed?
|
0-200 mg/dL - 100% reabsorption
200-350 mg/dL - splay >350 mg/dL - constant reabsorption at Tm |
|
|
how is glucose excreted?
|
starts below Tm due to splay
linear increase above Tm |
|
|
where is urea synthesized?
by what reaction? |
in the liver
2NH3 + CO2 +4ATP -> CO(NH2)2 + H20 |
|
|
what is a normal range for urea?
for urea nitrogen? |
18-36 mg/dL (4.5mM)
9-18 mg/dL |
|
|
where is urea reabsorbed or secreted?
|
proximal tubule - passively follows water reabsorption, but doesn't keep up
descending limb of loop of Henle - diffuses into tubular fluuid distal nephron - impermeable to urea inner medullary collecting tubule - reabsorption by facilitated (stimulated by ADH) |
|
|
how does urea move in the inner medullary collecting tubule?
|
urea is reabsorbed by facilitated transport in the medullary collecting tubule
this is stimulated by ADH |
|
|
what is the effect of reabsorbing urea in the inner medullary collecting tubule?
|
urea is trapped and plays a role in the concentration of urine
|
|
|
where is PAH synthesized?
|
in liver
derivative of glycine and p-aminobenzoic acid |
|
|
how much urea is filtered in the kidneys?
|
urea is freely filtered
|
|
|
how much PAH is filtered in the kidneys?
|
10-20% of PAH is unbound and this is what is filtered at the glomerulus
|
|
|
how much PAH is bound to proteins?
|
80-90%
|
|
|
how much PAH is secreted?
|
80-90% (all that is left after the unbound 10-20% is filtered at the glomerulus, at least until the nephron reaches its transport maximum)
|
|
|
what allows PAH to be an indicator of RPF?
|
RPF = renal plasma flow
since PAH is fully (100%) cleared from the plasma, it can be used as an indicator for RPF |
|
|
how much PAH is reabsorbed in the nephron?
|
none
|
|
|
what is the equation for excreted PAH load?
|
E = F + S
E = excreted load F = filtered load S = secreted load |
|
|
where is myoglobin synthesized?
|
muscle
|
|
|
why is myoglobin found in the blood?
|
it is released at a constant rate from skeletal and cardiac muscle
|
|
|
what happens to myoglobin in the blood under normal conditions?
|
it is fully filtered and excreted in the urine
|
|
|
how is myoglobin reabsorbed?
|
by the proximal tubule cells by receptor-mediated endocytosis
|
|
|
what happens when myoglobin is reabsorbed?
|
inside the cells, it is degraded within lysosomes
|
|
|
what is rhabdomyolysis?
|
a condition in which skeletal muscle (rhabdomyo) tissue breaks down rapidly (lysis) as a result of damage to the muscle
causes excess myoglobin in the blood, and excess myoglobin reabsorption in the kidneys |
|
|
what is an important complication of rhabdomyolysis?
|
acute renal failure
|
|
|
what can cause rhabdomyolysis?
|
trauma (crush syndrome)
severe burns hyperthermia ischemia |
|
|
why is excess myoglobin dangerous for renal tubules?
|
reabsorbed myoglobin causes oxidative injury to tubular cells
obstructs renal tubules by forming protein precipitation complexes |
|
|
on what does the clearance of weak acids and bases depend?
|
urinary pH (acidity)
|
|
|
when is the clearance of a weak acid highest?
lowest? why? |
highest at alkaline urine
lowest at acidic urine only the uncharged form (HA) can pass over the tubular membrane (this form dominates at low pH, so more is reabsorbed and less is excreted) |
|
|
when is the clearance of a weak base the highest?
lowest? |
highest in acidic urine
lowest in alkaline urine |
|
|
what is the effect of estrogen and progesterone at the level of the hypothalamus and pituitary?
|
high levels inhibit secretion of LH/FSH
low levels stimulate secretion of LH/FSH |
|
|
what is the effect of androgens at the level of the hypothalamus and anterior pituitary?
|
inhibits secretion of LH/FSH
|
|
|
what is the function of inhibin?
|
acts at pituitary to inhibit secretion of FSH
|
|
|
what is the regulatory effect of prolactin?
|
inhibits ovulation
probably via inhibition of GnRH |
|
|
what is the length of the average human menstrual cycle?
|
approximately 28 days
|
|
|
how is day 1 of the menstrual cycle defined?
|
first day of menstrual bleeding
|
|
|
when is a woman in the follicular or proliferative phase of her menstrual cycle?
|
from day 1 (first day of bleeding) until ovulation
usually lasts 10-14 days |
|
|
when is a woman in the luteal or secretory phase of her menstrual cycle?
|
from ovulation until the onset of her next menses
begins 14 days before menses |
|
|
how many oocytes are present in a fetal ovary by the 20th week of gestation?
|
~6-7 million
|
|
|
when does continuous atresia begin in a woman's oocytes?
|
at mid-gestation, a baby girl's oocytes begin continuous atresia
|
|
|
what is ovarian follicle atresia?
|
the periodic process in which immature ovarian follicles degenerate and are subsequently re-absorbed during the follicular phase of the menstrual cycle
|
|
|
how many oocytes are present in a woman's ovary at birth?
|
1-2 million
|
|
|
how many oocytes are present in a woman's ovary at puberty?
|
about 300,000
|
|
|
how many oocytes are present at/after menopause?
|
0
|
|
|
how many oocytes are ovulated during a woman's life?
|
400-500
|
|
|
what is the preantral phase?
|
hormone-independent phase when primordial follicles grow and differentiate quickly
ovum + single layer of granulosa cells |
|
|
what receptors are upregulated in the preantral phase of the menstrual cycle?
|
FSH receptors are upregulated
|
|
|
what type of follicles develop into Graafian follicles?
on what is this transition dependent? |
class 5 (early antral) follicles
highly dependent on FSH partially dependent on LH |
|
|
what is a Graafian follicle?
|
mature preovulatory follicle
|
|
|
what happens in the first 5 days of follicular development?
|
a cohort of 3-10 follicles is "selected" (by elevated blood FSH) in the late luteal phase of the previous cycle
|
|
|
what selects the cohort of follicles which will develop in the menstrual cycle?
|
elevated blood FSH levels
increases the number of granulosa cells induces aromatase enzyme in granulosa cells |
|
|
what is the function of granulosa cells?
by what is this stimulated? |
aromatize androstenedione and other androgens secreted by thecal cells, and to secrete the estradiol created thus
aromatase is stimulated by FSH |
|
|
what is the function of thecal cells?
by what is this stimulated? |
produce androstenedione and other androgens
stimulated by LH |
|
|
how are LH receptors induced on the surface of thecal cells?
|
FSH binds to its receptor and induces LH receptors
|
|
|
what happens to the endometrium if a fertilized egg does not implant?
|
the functional zone is shed
|
|
|
what happens to progesterone and estradiol levels when the functional zone of the endometrium is shed?
|
levels of progesterone and estradiol decline
|
|
|
what is the function of endothelin-1?
|
contracts spiral arteries from functional zone of the endometrium, causing ischemia and tissue injury
|
|
|
how is the functional zone of the endometrium shed?
|
increase in endothelin-1 contracts spiral arteries causing ischemia and tissue damage
activation of matrix metalloproteinases that degrade collagen and other matrix components prostaglandins (PGF2alpha) stimulate myometrial contraction, increasing tissue detachment |
|
|
what is the function of matrix metalloproteinases?
|
degrade collagen and other matrix components
important in the shedding of endometrium |
|
|
when does the shedding of the functional zone of the endometrium take place?
|
first five days of woman's menstrual cycle
follicular/proliferative phase |
|
|
what happens to PAI-1 during the first five days of a woman's menstrual cycle?
|
PAI-1 = plasminogen activator inhibitor-1
it is inhibited, allowing the activation of the protease plasmin |
|
|
why is plasmin activated during the first five days of a woman's menstrual cycle?
|
catalyzes fibrinolysis and prevents blood clotting, so that tissue fragments from the functional zone of the endometrium can be expelled mixed with liquefied blood
|
|
|
what is the average volume of blood lost in a woman's menstrual cycle?
|
30-50mL
|
|
|
how is plasmin activated during the first five days of a woman's menstrual cycle?
|
plasminogen activator inhibitor-1 (PAI-1) is inhibited, which allows the activation of plasmin
|
|
|
what is the cause of PMS?
|
PMS = pre menstrual syndrome
cause has not been identified affects up to 75% of women during childbearing years |
|
|
what are the symptoms of PMS?
|
acne
bloating fatigue backaches sore breasts headaches constipation diarrhea food cravings depression irritability difficulty concentrating difficulty handling stress |
|
|
when does a single dominant follicle develop during?
|
days 6-10 (early)
|
|
|
what happens to estrogen levels during days 6-10 of a woman's menstrual cycle?
|
slowly increase
|
|
|
what happens to FSH levels during days 6-10 of a woman's menstrual cycle?
|
circulating FSH levels decline
feedback inhibition by estrogen, and perhaps inhibin B |
|
|
what happens to the endometrium during days 6-10 of a woman's menstrual cycle?
|
proliferates, primarily as a response to estrogen secreted by dominant follicle
glands are present but are straight and non-secretory |
|
|
describe the glands in the endometrium during days 6-10 of a woman's menstrual cycle
|
present, but straight and non-secretory
|
|
|
what is the primary signal to the endometrium to proliferate?
|
estrogen from the dominant follicle
|
|
|
when does a Graafian follicle form?
|
days 11-13
|
|
|
what induces the expression of LH receptors on granulosa cells?
|
FSH and estrogen
|
|
|
when do granulosa cells and theca interna cells begin to luteinize?
|
days 11-13 of menstrual cycle
follicular/proliferative phase |
|
|
when do granulosa cells become capable of secreting progesterone?
|
days 11-13
in response to LH |
|
|
how do estrogen levels change during days 11-13 of a woman's menstrual cycle?
|
increase rapidly
peak on day 13 |
|
|
how does the endometrium change during days 11-13 of a woman's menstrual cycle?
|
continues to proliferate in response to estrogen
glands are still non-secretory |
|
|
describe the cervical mucus that is produced in response to high estrogen levels (low progesterone)
|
copious amounts of a watery, elastic mucus
|
|
|
describe the cervical mucus produced in response to high progesterone levels (low estrogen)
|
decreased amounts
thick and viscous |
|
|
when does estrogen feedback change from negative to positive?
what is the critical factor? |
day 14
critical factor is the presence of high estrogen levels for about 48 hours |
|
|
what is the effect of positive feedback of estrogen?
|
stimulates a surge in LH secretion, which subsequently stimulates ovulation
|
|
|
when is ovulation stimulated?
|
38 hours after LH rise
|
|
|
what are the effects of LH during ovulation?
|
stimulates ovulation (about 38 hours after rise)
induces granulosa cells and thecal interna to form corpus luteum |
|
|
what is the function of the corpus luteum?
|
secretes progesterone and some estrogen
|
|
|
what are the indicators of ovulation?
|
1degC temperature increase (progesterone secretion by corpus luteum)
spinnbarkeit (stretchability of stringy mucus) mittelschmerz (abdominal pain) spotting (decrease of estrogen) |
|
|
what is mittelschmerz?
|
one-sided, lower abdominal pain that occurs in women at or around the time of an egg is released from the ovaries (ovulation)
|
|
|
describe changes in endometrium at day 15
|
growth/proliferation is nearly complete
glands are still non-secretory |
|
|
what is significant about whether endometrial glands are secretory or not?
|
indicates whether the endometrium is receptive to implantation
(when the glands are secretory, the endometrium is receptive to implantation) glands become secretory between days 16-21 |
|
|
what happens to progesterone levels during days 16-21 of a woman's menstrual cycle?
|
progesterone secretion increases
|
|
|
what are the effects of increased progesterone secretion during days 16-21 of a woman's menstrual cycle?
|
inhibits estrogen-induced endometrial growth
stimulates endometrial gland proliferation and secretion inhibits LH secretion |
|
|
what happens to estrogen levels during days 16-21 of a woman's menstrual cycle?
|
estrogen secretion increases
|
|
|
what is the effect of increased estrogen secretion during days 16-21 of a woman's menstrual cycle?
|
inhibits FSH secretion
|
|
|
under the influence of what hormone(s) do the uterine glands become secretory?
|
PROGESTERONE
estrogen (to some extent) |
|
|
when (in a woman's menstrual cycle) should implantation occur?
|
days 21-22
|
|
|
what are progesterone and estrogen levels during days 21-22 of a woman's menstrual cycle?
|
progesterone is high
estrogen is high |
|
|
when is the endometrium fully developed?
|
days 21-22 of a woman's menstrual cycle
|
|
|
what hormone suppresses uterine contractions that might endanger implantation?
|
progesterone
|
|
|
what happens to the corpus luteum during days 23-28 of a woman's menstrual cycle?
|
if implantation fails to occur, the corpus luteum starts to regress
|
|
|
what causes the corpus luteum to regress on failure of implantation?
|
decreased sensitivity to LH
decrease in circulating LH |
|
|
what is the effect on hormone levels of the regression of the corpus luteum?
|
rapid decline in progesterone and estrogen
increase in FSH secretion |
|
|
what is the primary cause of detachment of the endometrium?
|
decline in progesterone
|
|
|
what is the primary cause of increased FSH secretion during days 23-28 of a woman's menstrual cycle?
|
decline in estrogen
|
|
|
what is function of the increase in FSH during days 23-28 of a woman's menstrual cycle?
|
"select" a new cohort of follicles for maturation and development
|
|
|
what is the relative potency of 17-beta-Estradiol to estrone?
|
100:1
|
|
|
where is estradiol produced?
under influence by which hormones? |
granulosa cells
LH and FSH |
|
|
what is the significant source of testosterone for aromatization into estradiol?
|
theca interna cells supply testosterone and androstenedione which are then aromatized into estradiol
|
|
|
what are the regulatory effects of estrogen on LH?
|
low estrogen -> negative feedback -> inhibit LH production
high estrogen-> positive feedback -> LH surge |
|
|
from what is estrone created?
in what population is it found? |
androstenedione
menopausal women |
|
|
where is estrone produced?
|
granulosa cells
adipose cells liver skin |
|
|
what hormone drives the development of female secondary sex characteristics?
|
estrogen
|
|
|
what hormone drives the development of keratinization of vaginal lining?
|
estrogen
|
|
|
what hormone drives the development of spinnbarkeit (long cervical threads)?
what is their function? |
estrogen
indicated that ovulation is imminent allow sperm to more easily enter the uterus |
|
|
what hormone drives the development of a thicker endometrium?
|
estrogen
|
|
|
what hormone drives the development of increased actin and myosin of myometrium, as well as increasing its sensitivity to oxytocin?
|
estrogen
promotes spontaneous contractions for sperm transport |
|
|
what hormone drives the development of enhanced spontaneous contractions of uterine tubules?
|
estrogen
promotes sperm transport |
|
|
what hormone drives the development of increased LH receptors on ovarian follicles?
|
estrogen
promotes follicular growth |
|
|
what hormone drives the development of enhanced ductal number and size in breast?
|
estrogen
|
|
|
what are the metabolic effects of estrogen?
|
lower blood cholesterol (not true for high doses)
increase Ca retention increase steroid-binding protein synthesis (thyroglobulin) |
|
|
what hormone drives growth and closure of epiphyseal plates in women?
|
estrogen
|
|
|
what are the ratios of relative potency for progesterone to 17alpha-hydroxyprogesterone and for progesterone to 20alpha-hydroxyprogesterone?
|
progesterone to 17alpha-dihydroxyprogesterone:
100 : 40-70 progesterone to 20alpha-dihydroxyprogesterone: 100 : 5 |
|
|
what hormone prepares the uterus to receive an embryo and maintains it during pregnancy?
|
progesterone
|
|
|
what hormone increases leukocyte infiltration of vaginal epithelium?
|
progestagens
|
|
|
what hormones produce thick cervical mucus as a natural fertilization barrier?
|
progestagens
|
|
|
what hormones decrease spontaneous activity of uterus?
|
progestagens
|
|
|
what hormones increase endometrial gland secretion?
|
progestagens
|
|
|
what hormones stimulate the growth of the mammary glands, but suppress the secretion of milk?
|
progestagens
|
|
|
what are the metabolic functions of progestagens?
|
compete with aldosterone receptors -> cause mild Na loss
make lungs more sensitive to CO2 -> increase respiratory rate increase body temp by 1degC |
|
|
why does inulin provide a measure of water reabsorption?
|
it is neither secreted nor absorbed, so the degree of inulin concentration along the nephron provides a measure of water absorption
|
|
|
what is the equation for the fraction of filtered water reabsorbed?
|
1 - (1 / [TF / P])
TF - tubular fluid concentration of inulin P - plasma concentration of inulin |
|
|
what is indicated by the ratio of tubular fluid concentration to plasma concentration of a substance?
|
the degree to which it is reabsorbed or secreted
[TF / P]x < 1.0 indicates that the reabsorption of X is greater than the reabsorption of water [TF / P]x > 1.0 indicates that the reabsorption of X is smaller than the reabsorption of water or net secretion [TF / P]x = 1.0 indicates that X is either not reabsorbed or is reabsorbed in proportion with water |
|
|
for what is the double ratio useful?
|
in the case that [TF / P]x = 1, the double ratio can tell you whether X is not reabsorbed or is reabsorbed in proportion with water
|
|
|
what is the equation for a double ratio?
|
[TF / P]x / [TF / P]inulin
if double ratio equals 0.3, then X and water are reabsorbed proportionally and 30% of the filtered X remains in the urine |
|
|
is creatinine absorbed, secreted, or neither?
|
secreted in proximal tubule
|
|
|
is inulin absorbed, secreted, or neither?
|
neither
|
|
|
why is the transport efficiency in the proximal tubule high?
|
very high ratio of surface area to tubular volume
|
|
|
what is actively reabsorbed in the proximal tubule?
|
Na
K Cl glucose amino acids |
|
|
what makes the proximal tubule highly water permeable?
why is it arranged like this? |
many aquaporin I channels on the apical and basolateral membranes
highly permeable so that water can follow active reabsorption passively |
|
|
how much filtered water is reabsorbed in the proximal tubule?
|
2/3
|
|
|
what is the osmolarity of the renal tubular fluid in the proximal tubule (as compared to plasma)?
|
tubular fluid in the proximal tubule is isoosmotic to plasma
|
|
|
what is important about the tight junctions of the proximal tubule?
|
permeable to ions, but not organic solutes
only small electrolyte gradients across tubular epithelium large organic solute gradients across tubular epithelium |
|
|
comparatively, what is larger in the proximal tubule, the electrolyte gradient or the organic solute gradient?
|
organic solute gradient across the tubular epithelium of the proximal tubule is very large, whereas the electrolyte gradient in the same place is fairly small
|
|
|
what is secreted in the proximal tubule?
|
H+
organic acids bases certain drugs (e.g. penicillin) |
|
|
why does inulin concentration increase in the proximal tubule?
|
inulin is neither secreted nor reabsorbed
water is reabsorbed, so the urine is concentrated |
|
|
why does PAH concentration increase in the proximal tubule?
|
PAH is secreted into the proximal tubule
concentration increases more steeply than inulin, because in addition to water reabsorption causing concentration there's secretory increase in concentration |
|
|
why does urea concentration increase in the proximal tubule?
|
~50% of filtered urea is passively reabsorbed
concentration still increases because water is reabsorbed |
|
|
what is the pattern for chloride concentration in the proximal tubule?
|
initially is concentrated, lagging behind until it diffuses into the blood in the late proximal convoluted tubule
|
|
|
how does osmolality change in the proximal convoluted tubule?
|
doesn't change, because though the amounts of Na and K in the tubular fluid decrease, the concentrations do not change
(simultaneous water reabsorption) |
|
|
what is the trend of bicarb concentration in the proximal convoluted tubule?
|
bicarb is preferentially reabsorbed with Na
decreases below 1 |
|
|
what is the trend of amino acid concentration in the proximal convoluted tubule?
|
extensively reabsorbed by secondary active transport and is normally completely gone from tubular fluid
|
|
|
what is the trend of glucose concentration in the proximal convoluted tubule?
|
extensively reabsorbed by secondary active transport and is normally completely gone from tubular fluid
|
|
|
in the proximal convoluted tubule, what is the major driving force for the reabsorption of solutes and water?
|
sodium reabsorption
|
|
|
on what does the uptake of reabsorbed fluid by the peritubular capillaries depend?
|
starling forces
(high colloid pressure and low hydrostatic pressure favor absorption) |
|
|
what are the Na transporters on the apical cell membrane in the proximal convoluted tubule?
|
Na -Glucose cotransporter
Na-AA cotransporter Na-phosphate cotransporter |
|
|
where are organic ions secreted?
|
proximal tubule
anions and cations are secreted by separate carriers |
|
|
what are the effects of secretion of H+ in the proximal tubule?
|
makes urine more acidic
increases urine flow promotes excretion of ammonia |
|
|
what is phenol red?
|
pH indicator dye
organic anion |
|
|
what is p-aminohippurate?
|
measurement of RPF
organic anion |
|
|
what is probenecid (Benemid)?
|
inhibitor of penicillin secretion and uric acid reabsorption
organic anion |
|
|
what is penicillin?
|
antibiotic
organic anion |
|
|
what is furosemide?
|
aka Lasix
loop diuretic drug inhibits Na/K/2Cl transporter organic anion |
|
|
what is acetazolamide?
|
aka Diamox
carbonic anhydrase inhibitor organic anion |
|
|
what is histamine?
|
vasodilator
stimulator of gastric acid secretion organic cations |
|
|
what is Cimetidine?
|
aka H2 blocker
treatment for gastric and duodenal ulcers organic cation |
|
|
what is cisplatin?
|
cancer therapeutic agent
organic cation |
|
|
what is quinine?
|
antimalarial drug
organic cation |
|
|
what is norepinephrine?
|
neurotransmitter
organic cation |
|
|
what is tetraethylammonium?
|
aka TEA
ganglion blocking drug K-channel blocker organic cation |
|
|
what is creatinine?
|
end product of muscle metabolism
organic anion and organic cation (-)ive and (+)ive charged groups at physiological pH (zwitterion) |
|
|
what is special about creatinine secretion?
|
can be secreted by either anion or cation transport proteins
|
|
|
what is a special feature late in the proximal tubule?
|
Na is reabsorbed with chloride
Na is moved across apical membrane by Na/H exchanger and across basolateral membrane by Na/K countertransport Cl is moved across apical membrane by Cl/base exchanger and then passively diffuses through pores in the basolateral membrane |
|
|
what happens in the descending limb of the loop of Henle?
|
osmotic gradient increases from 300 -> 1400 as you go further into the medulla
H20 is reabsorbed (10% of filtered amount) no active transport some passive transport |
|
|
why does the molarity of the loop of Henle partially equilibrate?
|
passive reabsorption of Na and urea in this portion of the nephron
|
|
|
what happens in the thin segment of the ascending limb of the loop of Henle?
|
low water permeability
NaCl absorption (probably some active transport) |
|
|
what happens in the thick segment of the ascending limb of the loop of Henle?
|
very low water permeability
NaCl absorption by active transport reabsorption of NaCl causes osmotically dilute fluid |
|
|
how much Na and Cl are absorbed in the thick segment of the ascending limb of the loop of Henle?
|
20-25% of filtered Na and Cl
the largest amount absorbed after the proximal convoluted tubule |
|
|
what are the most powerful diuretics?
why? |
loop diuretics
inhibit Na/K/2Cl cotransporter, which is the driving factor for reabsorption of 20-25% of filtered water (the largest amount after the proximal convoluted tubule) |
|
|
what is the effect of active transport of salt coupled with low water permeability in the ascending limb of the loop of Henle?
|
tubular fluid is osmotically diluted
interstitial fluid is osmotically concentrated |
|
|
what promotes the reabsorption of cations through tight junctions in the thick ascending limb cell?
|
transepithelial voltage
(lumen is positive and ISF is negative) |
|
|
how much filtered Na is reabsorbed in the loop of Henle?
|
20%
|
|
|
how much filtered K is reabsorbed in the loop of Henle?
|
25%
|
|
|
how much filtered Ca is reabsorbed in the loop of Henle?
|
30%
|
|
|
how much filtered Mg is reabsorbed in the loop of Henle?
|
65%
|
|
|
how much filtered water is reabsorbed in the loop of Henle?
|
10%
|
|
|
what transporter is responsible for creating the transepithelial voltage in the thick ascending limb of the loop of Henle?
what is the implication of this? |
Na/K/2Cl cotransporter
since this transporter is inhibited by loop diuretics, they can cause a depletion of electrolytes other than Na, K, and Cl (i.e. Ca, Mg, NH4) |
|
|
how do loop diuretics work?
|
inhibit Na/K/2Cl cotransporter in the thick ascending limb of the loop of Henle
|
|
|
how is sodium transported across the basolateral membrane in the thick ascending limb of the loop of Henle?
|
Na/K ATPase
|
|
|
how do thiazide diuretics work?
|
inhibit the Na/Cl cotransporter in the early distal convoluted tubule
|
|
|
how much filtered Na is reabsorbed in the early distal convoluted tubule?
|
9%
|
|
|
what happens in the early distal convoluted tubule?
|
Na and Cl are reabsorbed by the Na/Cl cotransporter
Water permeability is low and is not influenced by ADH tubular fluid is diluted and osmolarity decreases |
|
|
what is the transepithelial voltage in the early distal convoluted tubule?
|
negative tubular fluid
positive in ISF |
|
|
how is sodium transported across the basolateral membrane of the early distal convoluted tubule?
|
Na/K ATPase
|
|
|
what is ENaC?
|
sodium selective channel in principal cells in the late distal tubule and collecting duct
presence on membrane is stimulated by aldosterone |
|
|
by what mechanism do K sparing diuretics (e.g. amiloride) work?
|
inhibit ENaC, the sodium selective channel in the late distal tubule and collecting duct principal cells
|
|
|
what increases the number of ENaC channels in the late distal tubule and collecting duct principal cells?
|
aldosterone
acts in all parts of the collecting duct system |
|
|
what changes water permeability in all parts of the collecting duct?
|
ADH
low water permeability without ADH high water permeability with ADH |
|
|
how does Na move across the basolateral membrane of late distal tubule and collecting duct principal cells?
|
Na/K ATPase
|
|
|
what factors increase ADH release?
|
cellular dehydration (increase in effective plasma osmolarity)
hypovolemia (decrease in total blood volume; decrease in effective arterial blood volume) pain, trauma, emotional stress, nausea, fainting, most anesthetics, nicotine, morphine, angiotensin II |
|
|
what factors decrease ADH release?
|
ethanol
atrial natriuretic peptide |
|
|
by what mechanism does ADH work?
|
binds a V2 receptor, which is a G-protein coupled receptor that activates adenylyl cyclase
adenylyl cyclase converts ATP to cAMP cAMP activates PKA which then induces the fusion of aquaporin-2 lined vesicles with the cell membrane cAMP increases gene transcription in the nucleus to increase aquaporin-2 synthesis |
|
|
where are V1 receptors found?
by what signalling cascade do they work? |
on blood vessels
via Ca-IP3 cascade |
|
|
what are the receptors for ADH?
where are they? |
V1 - blood vessels
V2 - collecting duct epithelial cells |
|
|
what are the two types of cells in the late distal tubule and collecting duct?
|
Type 1 - principal cells - histologically light
Type 2 - intercalated cells - histologically dark (consists of alpha- and beta-intercalated cells) |
|
|
for what are alpha-intercalated cells responsible?
|
secretion of protons and reabsorption of K by a H/K ATPase
|
|
|
for what are beta-intercalated cells responsible?
|
secretion of bicarbonate
|
|
|
compare and contrast the proximal convoluted tubule with the distal nephron
|
PCT - high transport capacity, high water permeability, low transepithelial gradients, leaky tight junctions, coarse control
distal nephron - low transport capacity, low water permeability, high transepithelial gradients, tight tight junctions, fine control |
|
|
why are intercalated cells histologically dark?
|
lots of mitochondria are present within them
|
|
|
what are the molecular defects and clinical features of renal glucosuria?
|
Na-dependent glucose cotransporter
glucosuria, polyuria, polydipsia, polyphagia |
|
|
what are the molecular defects and clinical features of cystinuria?
|
amino acid transporter
kidney stone disease **80% of stones are composed of Ca, and the remainder of other substances such as cysteine in this case** |
|
|
what are the molecular defects and clinical features of Bartter syndrome?
|
Na/K/2Cl cotransporter
K channel Cl channel salt wasting hypokalemic metabolic alkalosis |
|
|
what are the molecular defects and clinical features of Gitelman syndrome?
|
thiazide sensitive Na-Cl cotransporter in distal convoluted tubule
salt wasting hypokalemic metabolic alkalosis hypocalciuria |
|
|
what are the molecular defects and clinical features of Liddle syndrome?
|
increased open time and number of principal cell Na channels independent of aldosterone
hypertension hypokalemic metabolic alkalosis |
|
|
what are the molecular defects and clinical features of nephrogenic diabetes insipidus?
|
vasopressin-2 or aquaporin-2 deficient
polyuria polydipsia |
|
|
how does water act as a diuretic?
|
inhibits ADH secretion
|
|
|
how does ethanol act as a diuretic?
|
inhibits pituitary ADH secretion
|
|
|
how do ADH-R antagonists act as a diuretic?
|
inhibit action of ADH
|
|
|
how do caffeine and theophyline act as diuretics?
|
decrease Na reabsorption and increase GFR
|
|
|
by what mechanism do mannitol and glucose act as diuretics?
what is their clinical use? |
osmotic diuresis
frequen - metabolically harmless |
|
|
by what mechanism do thiazides act as diuretics?
what is their clinical use? |
inhibits Na/Cl cotransporter in early distal tubule
hypertension peripheral edema |
|
|
by what mechanism do loop diuretics work?
what is their clinical use? |
i.e. furosemide (Lasix)
inhibit Na/K/2Cl cotransporter in thick ascending limb of loop of Henle crises (e.g. acute pulmonary edema |
|
|
by what mechanism do K-retaining natriuretics work as diuretics?
what is their clinical use? |
inhibit aldosterone (e.g. spironolactone)
inhibit Na reabsorption by ENaC (e.g. amiloride) combined with loop or thizide diuretics to offset urinary K loss |
|
|
by what mechanism do carbonic anhydrase inhibitors work as diuretics?
what is their clinical use? |
decrease H secretion with resultant increase in Na and K excretion
treatment of glaucoma |
|
|
how do thiazide and loop diuretics lead to hypokalemia?
|
NaCl reabsorption is inhibited and a much larger Na load is delivered to the distal tubule and collecting duct
Na reabsorption is stimulated, coupled with K secretion this, in combination with the increased tubular flow leads to urinary K loss and hypokalemia |
|
|
what is caused by loss of hydrogen ions in urine?
|
metabolic alkalosis
|
|
|
what can be caused by K sparing diuretics by themselves?
|
hyperkalemia
|
|
|
what is the relative tonicity of sweat (to the blood)?
|
sweat is hypotonic to blood
|
|
|
what is important about the reabsorption for sodium?
|
the relatively low fraction of filtered Na that is excreted by the kidneys is of critical importance in Na balance
|
|
|
what are the causes of hyponatremia?
|
not consuming enough Na in diet
too much sweat or urine being overhydrated IV rehydration w/o enough Na diuretics cause higher Na excretion than H2O high ADH poorly controlled diabetes, heart failure, liver failure, kidney disorders |
|
|
what are the symptoms of hyponatremia?
|
confusion
drowsiness muscle weakness seizures rapid fall in Na causes more severe symptoms than slow fall |
|
|
what are the causes of hypernatremia?
|
dehydration
diuretics can cause to excrete more water than Na (not common) |
|
|
what are the symptoms of hypernatremia?
|
weakness
sluggishness at very high levels, confusion, paralysis, coma, seizures |
|
|
what is the effect of Na on the ECF?
|
if you lose salt you will also lose water, decreasing the ECF
if you increase salt intake, you will drink more water, increasing the ECF |
|
|
what is the major regulator for aldosterone?
|
angiotensin II
|
|
|
what are the sensors for ECF volume?
|
cardiovascular stretch receptors
kidneys |
|
|
how much Na is moved in the nephron?
|
100% is filtered
proximal convoluted tubule - 70% thick ascending loop of Henle - 20% late distal convoluted tubule - 6% collecting duct - 3% 1% is excreted in urine |
|
|
what is the glomerulotubular balance?
|
in response to an increase in GFR (and hence filtered Na), proximal convoluted tubules and loop of Henle reabsorb more Na
this blunts the effect of an increase in GFR on Na excretion and prevents excessive urinary loss |
|
|
where is aldosterone produced?
|
zona glomerulosa of adrenal cortex
|
|
|
what are the triggers for aldosterone release?
|
angiotensin II
serum K ACTH |
|
|
what is the main function of aldosterone?
|
salt retention by distal nephron
stimulates ENaC presentation on principal cell membranes |
|
|
what issues cause too much aldosterone?
|
Conn syndrome
17-alpha-hydroxylase deficiency |
|
|
what issues cause too little aldosterone?
|
Addison disease
21-beta-hydroxylase deficiency |
|
|
what is the effect of an adrenalectomy on Na balance?
|
no aldosterone is produced, so no Na retention in the collecting duct
decrease of 1.6% of Na over days this may result in circulatory collapse |
|
|
how do Starling forces increase the back leak of Na into the renal tubule?
|
decreased Na reabsorption
capillary fluid uptake decreases interstitial hydrostatic pressure increases widening of tubule tight junctions enhanced back-leak of Na |
|
|
what are the stimuli for the release of atrial natriuretic peptide?
|
atrial distension
sympathetic stimulation angiotensin II endothelin |
|
|
what are the effects of atrial natriuretic peptide?
|
decrease systemic vascular resistance -> decreased arterial pressure
decrease central venous pressure -> decreased cardiac output -> decreased arterial pressure increased GFR -> natriuresis/diuresis -> decreased blood volume -> decreased central venous pressure -> decreased cardiac output -> decreased arterial pressure |
|
|
how does ANP act?
|
inhibits Na reabsorption at inner medullary collecting ducts
|
|
|
what are the sodium and natriuretic (salt losing) hormones?
|
atrial natriuretic peptide (ANP) - from atria
brain natriuretic peptide (BNP) - from brain and ventricles urodilatin - from kidney guanylin, uroguanylin - from small intestine prostaglandins and bradykinin inhibit Na reabsorption |
|
|
what is NEP?
|
neutral endopeptidase
an enzyme which degrades atrial natriuretic peptide and opposes renin-angiotensin-aldosterone system |
|
|
what are the effects of renal sympathetic nerves on sodium balance?
|
decreased Na excretion
|
|
|
what are the effects of renal sympathetic nerves?
|
reduced GFR and RBF
direct effects on tubular cells via norepinephrine renin release decreased sodium excretion |
|
|
what are the effects of estrogen on sodium balance?
|
direct effects on tubular cells
overall, decreased sodium excretion |
|
|
what are osmotic diuretics?
|
a compound that is filtered but not reabsorbed (mannitol or glucose above Tm)
|
|
|
what are the effects of sulfate, phosphate, and ketone bodies on Na balance?
|
promote Na excretion to maintain electroneutrality
|
|
|
what is a normal concentration of potassium (normokalemia)?
|
3.5-5.0 mEq/L
|
|
|
what is hypokalemia?
|
<3.5 mEq/L
|
|
|
what is hyperkalemia?
|
>5 mEq/L
|
|
|
what are the causes of hypokalemia?
|
Addison disease
acute renal failure chronic renal failure (GFR<20mL/min) diuretics can cause excretion of more K than H2O GI fluid losses (diarrhea, vomiting) |
|
|
what are the symptoms of hypokalemia?
|
slight decrease - minor symptoms
low - eventually leads to increased insulin production very low - fatigue, confusion, muscle weakness, cramps, arrhythmias |
|
|
what are the causes for hyperkalemia?
|
hyperaldosteronism
kidney failure K retaining diuretics |
|
|
what are the symptoms of hyperkalemia?
|
first signs might be arrythmias
[K] > 7mEq/L is dangerous [K] = 10-12mEq/L is usually fatal |
|
|
to what does hypokalemia lead?
|
metabolic alkalosis
|
|
|
to what does hyperkalemia lead?
|
metabolic acidosis
|
|
|
what causes K to shift to the outside of cells?
|
decreased extracellular pH
digitalis lack of O2 hyperosmolality hemolysis infection ischemia trauma |
|
|
what causes K to shift into cells?
|
increased extracellular pH
insulin epinephrine |
|
|
how does K move in the nephrons?
|
filtered freely (100%)
proximal convoluted tubule - 30% distal convoluted tubule - 5-20% collecting duct - 1-15% excreted - 1-15% (usually 15%) |
|
|
what are the effects of increased potassium intake?
|
increases plasma potassium
increases aldosterone secretion increases plasma aldosterone increases luminal membrane permeability to Na and K and increase in basolateral membrane N/K-ATPase activity in collecting duct principal cells increases K secretion increases K excretion also, increase in plasma K causes increased uptake of K by collecting duct principal cells and increased K secretion/excretion |
|
|
what is the effect of sulfate, phosphate, and ketone bodies on K balance?
|
promote K exxcretion to maintain electroneutrality
|
|
|
what is the effect of increased Na excretion on K balance?
|
usually causes increased K excretion
sweeping away effect: less Na reabsorption causes less H2O reabsorption which increases tubular flow rate more Na means more Na reabsorption, which increases basolateral Na/K-ATPase activity |
|
|
what is the effect of decreased Na excretion on K balance?
|
usually no change in K excretion
Na deprivation -> inc. aldosterone secretion -> inc. plasma aldosterone -> inc. K secretion Na deprivation -> dec. GFR and inc. proximal Na reabsorption -> dec. fluid delivery to cortical collecting ducts -> dec. K secretion sum leads to unchanged K excretion |
|
|
what is the major site of phosphate reabsorption?
|
proximal tubule
secondary active transport (Na/phosphate) |
|
|
what is the effect of high PTH on phosphate?
|
causes phosphaturia and urinary cAMP by a cAMP signalling mechanism
|
|
|
what is the use of excreted phosphate?
|
acts as urinary pH buffer
|
|
|
how does phosphate move in the nephrons?
|
freely filtered (100%)
proximal convoluted tubule: 30-40% late distal convoluted tubule: 5-20% excreted: 5-20% |
|
|
what hormone increases calcium absorption from the GI tract?
|
1,25-dihydroxycholecalciferol
|
|
|
what hormone increases calcium absorption from bones?
|
1,25-dihydroxycholecalciferol
|
|
|
what hormone decreases calcium absorption from bones?
|
calcitonin
|
|
|
what are the effects of PTH on bones, the kidney and intestines?
|
bones - enhances release of calcium by osteoclasts
kidney - enhances active reabsorption of calcium and magnesium from distal tubules and the thick ascending limb intestines - enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D |
|
|
what is a normal plasma concentration of calcium?
|
2.5 mmol/L
5 mEq/L 10 mg/dL |
|
|
what causes hypocalcemia?
|
widespread infection (sepsis)
low PTH vitamin D deficiency |
|
|
what stimulates 1alpha-hydroxylase?
|
hypocalcemia
hypophosphatemia high PTH |
|
|
what are the symptoms of hypocalcemia?
|
weakness
paresthesias confusion seizures Chvostec's sign long QT |
|
|
what is Chvostec's sign?
|
one of the signs of tetany seen in hypocalcemia. It refers to an abnormal reaction to the stimulation of the facial nerve. When the facial nerve is tapped at the angle of the jaw (i.e. masseter muscle), the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcemia (ie from hypoparathyroidism, pseudohypoparathyroidism, hypovitaminosis D) with resultant hyperexcitability of nerves. Though classically described in hypocalcemia, this sign may also be encountered in respiratory alkalosis, such as that seen in hyperventilation, which actually causes decreased serum Ca2+ with a normal calcium level due to a shift of Ca2+ from the blood to albumin which has become more negative in the alkalotic state.
|
|
|
what are the causes of hypercalcemia?
|
bone cancer or Paget's disease
high PTH |
|
|
what are the symptoms of hypercalcemia?
|
slight increase: no symptoms
moans (GI): constipation, nausea stones (kidney): stones groans (neuronal): confusion, memory loss bones: fractures, aches |
|
|
what calcium is filtered at the glomerulus?
|
5-10% of plasma calcium that is complexed to phosphate, citrate, bicarbonat and other ions
45-50% of plasma calcium that is in free or ionized form |
|
|
what calcium is not filtered at the glomerulus?
|
40% of plasma that is bound to protein
|
|
|
how does calcium move in the nephron?
|
33-40% reabsorbed in proximal convoluted tubule
10% reabsorbed in distal convoluted tubule 5% reabsorbed in collecting duct 0.5-2% excreted in urine |
|
|
where is calcium reabsorption not coupled?
|
distal convoluted tubule
|
|
|
what is the effect of PTH on calcium reabsorption in the nephron?
|
increases calcium reabsorption and decreases urinary excretion
|
|
|
what is the effect of loop diuretics on calcium balance?
|
decrease calcium reabsorption and increase urinary excretion
|
|
|
what is the effect of thiazide diuretics on calcium balance?
|
increase Na excretion, but increase Ca reabsorption and decrease urinary excretion
|
|
|
what type of diuretics are used to treat hypercalcemia?
|
loop diuretics
|
|
|
what type of diuretics are used to treat hypercalciuria?
|
thiazide diuretics
|
|
|
what is the normal plasma concentration of Mg?
|
1.7-2.3 mEq/L
|
|
|
where is 99% of the body Mg located?
|
in bone and cells
|
|
|
how is magnesium found in plasma?
|
20% is bound to proteins
80% is filterable |
|
|
where is the main site of magnesium reabsorption?
why? |
thick ascending limb of Henle's loop
due to voltage difference |
|
|
how is Mg moved in the nephron?
|
70-75% reabsorption in the proximal convoluted tubule
12% reabsorption in the early distal convoluted tubule 5-10% reabsorption in the collecting duct 5-10% excretion in the urine |
|
|
what is the reason for producing an osmotically concentrated urine?
|
kidneys save water for the body
|
|
|
what is indicated by pale yellow urine?
|
normal urine with urobilinogen
|
|
|
when is urine clear?
|
after excess water or diuretics (coffee, beer)
|
|
|
when is urine deep yellow?
|
excess sweating
|
|
|
when is urine dark yellow?
|
liver problems or jaundice
|
|
|
when is urine orange?
|
eat too many carrots or too much vitamin C
|
|
|
when is urine brown?
|
liver disease
hepatitis melanoma cancer copper poisoning |
|
|
when is urine greenish?
|
urinary tract infection
bile problems certain drugs excess of vitamin B (light green) |
|
|
when is urine blue?
|
pseudomonas bacterial infection
high levels of calcium |
|
|
when is urine reddish?
|
bladder infection
kidney stones bladder stones food (beets, blackberries, rhubarb, candy) poison (mercury) |
|
|
what can cause characteristic smells of urine?
|
many food products such as asparagus
|
|
|
what can cause urine to smell foul?
|
bacteria
|
|
|
what can cause urine to smell sweet?
|
diabetes mellitus
|
|
|
what can cause urine to smell musty?
|
liver disease
|
|
|
what can cause urine to smell stingy?
|
acidity
|
|
|
what is the normal pH of urine?
|
4.6-8.0
|
|
|
what can cause more acidic urine?
|
ketoacidosis
starvation diarrhea |
|
|
what can cause more alkaline urine?
|
kidney failure
urinary tract infection vomiting |
|
|
describe the pH profile of the nephron
|
pH 7.4 at glomerulus
pH 6.7 at beginning of descending limb of loop of Henle pH 7.4 at bottom of loop of Henle pH 6.7 at top of ascending limb of loop of Henle pH 4.6-8.0 at end of collecting duct |
|
|
what is osmotic clearance?
|
volume of plasma cleared of osmotically active particles per unit time
|
|
|
how is osmotic clearance calculated?
|
cosm = (Uosm x V) / Posm
cosm - osmolar clearance V - urine flow rate Uosm - urine osmolarity Posm - plasma osmolarity |
|
|
how is free-water clearance calculated?
|
cH2O = V - cosm
cH2O = V (1 - (Uosm/Posm)) |
|
|
what is free-water clearance?
|
difference between the urine flow rate and the osmolar clearance
|
|
|
when is free-water clearance positive?
|
low ADH
volume of pure water subtracted from plasma, or free water excreted |
|
|
when is free-water clearance negative?
|
high ADH
volume of pure water added to plasma, or free water is reabsorbed |
|
|
what are the countercurrent exchangers in the nephron?
|
vasa recta
goal - water is kept out of the medulla, and solutes (NaCl, urea) are kept in the medulla |
|
|
what is the countercurrent multiplier of the nephrons?
|
loop of Henle
goal - establishment of an osmotic gradient in the medulla by depositing NaCl in the medulla |
|
|
what is the osmotic equilibrating device of the nephrons?
|
collecting ducts
goal - dependent on ADH, luminal fluid will be equilibrated more or less with the surrounding interstitium; urine recycling concentrates urea in medulla |
|
|
what is the tonicity of tubular fluid in the distal convoluted tubule?
|
tubular fluid is hypotonic to the interstitial fluid
|
|
|
what happens to urine in the presence of ADH?
|
water is reabsorbed into the concentrated medullary ISF
urine becomes hypertonic |
|
|
what happens to the urea concentration in the blood?
|
as blood flows up from the papilla, it loses urea to the medullary ISF
|
|
|
what is the process of urea recycling in the concentrating mechanism of the nephron?
|
tubular fluid urea increases as urea diffuses in from the ISF and water is reabsorbed
late distal tubule and outer medullary collecting duct - tubular urea concentration increases b/c ADH increases water reabsorption, but no transport of urea inner medullary collecting ducts - ADH increases water and urea reabsorption |
|
|
how is urea transported in the inner medullary collecting ducts?
|
facilitated transport UT1
increased by ADH |
|
|
what is the overall theme of urea recycling?
|
urea reabsorbed from the collecting tubule is recycled and trapped in the medulla
|
|
|
how do the volume and osmotic concentration of plasma change between when they enter the vasa recta and when they exit?
|
volume and osmotic concentration of the exiting plasma exceed that of entering plasma
|
|
|
why is the volume and osmotic concentration exiting the vasa recta higher than that entering the vasa recta?
|
solute trapping is not complete
rate at which solute is carried out of the medulla exceeds that carried in water, reabsorbed from the descending limb of the loop of Henle and from collecting tubule, is carried out by the vasa recta |
|
|
how does urine come out in the presence of ADH?
|
osmotically concentrated
|
|
|
how does urine come out in the absence of ADH?
|
osmotically dilute
|
|
|
what are the factors that affect urinary concentrating ability?
|
relative length of loop of Henle
relative width of the inner medulla (longer and wider is better) |
|
|
what are the effects of ADH on urine production?
|
increases water permeability of late distal tubule and collecting ducts
increases Na/K/2Cl cotransport, enhancing countercurrent multiplication stimulates urea reabsorption in inner medullary collecting duct, enhancing urea recycling |
|
|
what is responsible for imposing "maleness" on a default female pattern?
|
Y chromosome
|
|
|
what is SRY?
|
sex-determining region of Y
crucial gene on Y chromosome for maleness; works in combination with other genes for normal development |
|
|
what gene induces the expression of Muellerian Regression Hormone (anti-Muellerian factor) by sertoli cells?
|
SRY (sex-determining region of Y)
|
|
|
from where is anti-Muellerian hormone secreted?
what induces its secretion? |
sertoli cells
SRY (sex-determining region of Y) |
|
|
what are the two types of ducts present in early fetal development?
which is for each sex? |
Wolffian duct - male ducts
Muellerian duct - female ducts |
|
|
what causes the regression of the muellerian ducts in a female?
|
SRY induces muellerian inhibiting hormone secretion from sertoli cells
muellerian inhibiting factor actually causes the regression of the muellerian ducts (acting in a paracrine fashion) |
|
|
what is necessary for the adequate development of male parts?
|
MIF from sertoli cells causes regression of muellerian ducts
testosterone from Leydig cells drives the development of epididymis, vas deferens, seminal vesicles, and ejaculatory ducts |
|
|
in what hormonal fashion does MIF act on the muellerian ducts?
in what fashion does testosterone act on the Wolffian ducts? |
both hormones act in a paracrine manner on their respective ducts
|
|
|
what is necessary for the adequate development of female parts?
|
absence of a Y chromosome
|
|
|
how are female parts developed?
|
Muellerian ducts spontaneously degenerate as long as no MIF is produced and they then spontaneously develop into fallopian tubes, uterus, and upper portion of vagina
|
|
|
what develops from wolffian ducts?
|
epididymis
ductus (vas) deferens seminal vesicles ejaculatory ducts |
|
|
what develops from muellerian ducts?
|
uterine (fallopian) tubes
uterus upper portion of vagina |
|
|
what are the parts of the external genitalia at week 8 of fetal life?
|
urethral groove bounded by paired urethral folds
urethral folds bounded by labioscrotal swellings urethral groove is surmounted by the genital tubercle/glans |
|
|
into what do the urethral folds develop?
|
corpus spongiosum
labia minora |
|
|
into what do the labioscrotal swellings develop?
|
scrotum
labia majora |
|
|
into what do the genital tubercle/glans develop?
|
corpora cavernosa
glans penis or clitoris |
|
|
what is significant about the external genitalia of fetuses at the eighth week?
|
external genitalia of both sexes are identical
|
|
|
what hormone plays a major role in the development of male genitalia?
what hormone plays a minor role? |
5alpha-dihydrotestosterone (DHT) plays a major role
testosterone plays a minor role |
|
|
what is critical in the development of female genitalia?
what hormone plays a role? |
absence of testosterone and anti-muellerian hormone is critical
gonadal estrogen plays a role for normal female development |
|
|
what is the HPG axis?
|
hypothalamic-pituitary-gonadal axis
|
|
|
what causes the initiation of puberty?
|
pulsatile GnRH release
|
|
|
what are the proportion changes in gonadotrophs at puberty?
|
before puberty FSH > LH, and after puberty LH > FSH
at the onset of puberty, nocturnal, low-amplitude pulses of LH at night begin |
|
|
what is gonadarche?
|
onset of gonadal functioning
|
|
|
what is adrenarche?
|
onset of androgen dependent signs of puberty
|
|
|
what is caused by gonadarche?
|
rise in gonadal sex steroids as a result of HPG axis activation
|
|
|
what is caused by adrenarche?
|
pubic hair
axillary hair acne adult body odor |
|
|
why does adrenarche not prove that central puberty is underway?
|
it is independent of gonadal sex steroid production
|
|
|
what is caused by estrogens?
|
breast development in boys and girls
growth acceleration skeletal maturation genital changes |
|
|
what is caused by androgens?
|
body hair
body odor acne in boys and girls growth acceleration skeletal maturation genital changes |
|
|
what is stage 1 of female sexual development?
|
prepubertal
no sexual development |
|
|
what is stage 2 of female sexual development?
|
breast budding
first pubic hair body odor height spurt |
|
|
what is stage 3 of female sexual development?
|
breasts enlarge
pubic hair darkens pubic hair becomes curlier vaginal discharge |
|
|
what is stage 4 of female sexual development?
|
onset of menstruation
nipple is distinct from areola |
|
|
what is stage 5 of female sexual development?
|
fully mature female
pubic hair extends to inner thighs increases in height slow, then stop |
|
|
what is stage 1 of male sexual development?
|
prepubertal
no sexual development |
|
|
what is stage 2 of male sexual development?
|
testes enlarge
body odor |
|
|
what is stage 3 of male sexual development?
|
penis enlarges
pubic hair starts growing ejaculation (wet dreams) |
|
|
what is stage 4 of male sexual development?
|
continued enlargement of testes and penis
penis and scrotal sac deepen in color pubic hair curlier and coarser height spurt male breast development |
|
|
what is stage 5 of male sexual development?
|
fully mature male
pubic hair extends to inner thighs increases in height slow, then stop |
|
|
what is the average age of onset of puberty?
what is the range? |
average: 10-10.5 years
range: 7.5-13 years |
|
|
what is the first sign of puberty in females?
|
breast buds
|
|
|
what is the first sign of puberty in males?
|
growth and descension of testicles
|
|
|
how soon after the onset of puberty does pubic hair begin to grow?
|
within 6 months
|
|
|
when does the peak growth spurt occur in females?
|
on average 1.3 years before the first period (menarche)
|
|
|
when does menarche usually occur?
|
2-2.5 years after the onset of puberty
|
|
|
how much later (on average) does the peak growth spurt occur in boys than in girls?
|
about 2 years later in boys than in girls
|
|
|
what hormones are involved in the growth spurt and epiphyseal maturation and closure?
|
estrogen
testosterone |
|
|
what are the parts of the body that are earliest to reach adult size?
|
head
hands feet |
|
|
what is the order that parts of the body reach adult size?
|
legs
trunk body width shoulder width |
|
|
what is primary amenorrhea?
|
absence of menarche by age 16 in the presence of normal growth and secondary sexual characteristics
|
|
|
what are the most frequent causes of primary amenorrhea?
|
50% - chromosomal abnormalities
20% - hypogonadotropic hypogonadism 15% - absence of uterus, cervix, and/or vagina 5% - transverse vaginal septum 5% - pituitary disease |
|
|
what is secondary amenorrhea?
|
absence of menses for more than 3 cycles or six months in women who were previously menstruating
|
|
|
what are the most frequent causes of secondary amenorrhea?
|
40% - ovarian disease (PCOS)
35% - hypothalamic dysfunction (anorexia, exercise, stress) 19% - pituitary disease (hyperprolactinemia, thyroid problems) 5% - uterine disease |
|
|
how high is the prevalence of PCOS?
|
6-8% of women
|
|
|
what is PCOS?
|
polycystic ovarian syndrome
|
|
|
what are the signs and symptoms of PCOS?
|
polycystic ovaries -> ovulatory dysfunction
multiple follicles secrete excess androgens -> hirsuitism, acne elevation of LH:FSH ratio insulin resistance -> hyperinsulinemia, obesity possible congenital enzyme effect -> elevated DHEA-S |
|
|
what causes elevated LH:FSH ratio in PCOS?
|
primary, or secondary to high estrogen, androgen, and elevated levels of inhibin
|
|
|
what are the key words to indicate Kallman Syndrome?
|
hypogonadism
+ poor sense of smell |
|
|
what is Kallman Syndrome?
|
a hypogonadism (decreased functioning of the glands that produce sex hormones) caused by a deficiency of gonadotropin-releasing hormone (GnRH), which is created by the hypothalamus
aka hypogonadotropic hypogonadism, familial hypogonadism with anosmia, hypothalamic hypogonadism |
|
|
what levels of LH and FSH are found in Kallman Syndrome?
|
low LH
low FSH |
|
|
what are the symptoms of Kallman Syndrome in males?
|
anosmia
delayed puberty micropenis |
|
|
what are the symptoms of Kallman Syndrome in females?
|
anosmia
delayed puberty lack of secondary development |
|
|
what is Klinefelter syndrome?
|
XXY genotype present in a male
|
|
|
what are the symptoms of Klinefelter syndrome?
|
absence of frontal baldness
tendency to grow fewer chest hairs breast development female type pubic hair pattern small testicles reduced fertility and very low sperm count poor beard growth narrow shoulders wide hips long arms and legs difficulty in social interactions (lack of insight, poor judgment, inability to learn from experience) rudimentary internal male structures |
|
|
what is Turner Syndrome?
|
genetic condition in which a female does not have the usual pair of two X chromosomes
|
|
|
what are the symptoms of turner syndrome?
|
SHORT STATURE (always)
low hairline shield-shaped thorax widely spaced nipples shortened fourth metacarpal small fingernails brown spots (nevi) characteristic facial features fold of skin at base of neck constriction of aorta poor breast development elbow deformity rudimentary ovaries gonadal streak no menstruation |
|
|
what is the prevalence of abortions in fetuses with Turner syndrome?
|
98% of fetuses with Turner syndrome spontaneously abort
(10% of total US abortions) |
|
|
how good is the intelligence in patients with Turner syndrome?
|
normal intelligence
may have attention-deficit disorder may have problems with visual-spatial organization |
|
|
what disorder produces the "perfect woman"?
|
the perfect woman is a man
androgen insensitivity of XY individuals |
|
|
what are the LH and FSH levels in patients with Turner syndrome?
|
normal LH levels
normal FSH levels |
|
|
what are the LH and FSH levels in patients with androgen insensitivity of XY individuals?
|
mildly elevated testosterone and LH
normal FSH |
|
|
what are the symptoms of androgen insensitivity of XY individuals?
|
sparse pubic and body hair due to defective androgen receptor
breast development normal since secrete some estrogens and since androgens can be aromatized to estrogens in peripheral tissues |
|
|
what are the symptoms of 21beta hydroxylase deficiency in boys?
|
precocious development of secondary sex characteristics (early pubic hair and phallic enlargement)
accelerated linear growth advanced skeletal maturation salt-wasting crises |
|
|
what are the symptoms of 21-beta-hydroxylase deficiency in girls?
|
ambiguous genitalia (enlarged clitoris)
acne baldness hirsuitism no breast development no menstruation compromised fertility normal muellerian structures (b/c no MIH is present) no Wolffian structures since adrenal androgens not high enough |
|
|
what are the adrenal hormone levels in 21-beta-hydroxylase deficiency?
|
high adrenal androgens
low glucocorticoids low mineralocorticoids |
|
|
what are the adrenal hormone levels in 11-beta-hydroxylase deficiency?
|
high adrenal androgens
low glucocorticoids high deoxycorticosterone |
|
|
in what ways is 11-beta-hydroxylase deficiency similar to or different from 21-beta-hydroxylase deficiency?
|
similar androgenic manifestations
presents with hypertension |
|
|
what are the adrenal hormone levels in 17alpha-hydroxylase deficiency?
|
low adrenal androgens
low glucocorticoids high mineralocorticoids |
|
|
what are the symptoms of 17alpha-hydroxylase deficiency in boys?
|
genitals vary from phenotypic female to ambiguous
may go undetected until puberty |
|
|
what are the symptoms of 17-alpha hydroxylase deficiency in girls?
|
often undetected until puberty
delayed sexual maturation - adrenal glands cannot secrete androgens necessary for pubic and axillary hair growth - ovaries cannot secrete androgens or estrogens necessary for sexual maturation |
|
|
what is the function of 5-alpha-reductase?
|
convert plasma testosterone into DHT
happens in the prostate, scrotum, penis, bone, and skin |
|
|
what are the internal sexual characteristics of boys with 5alpha reductase deficiency?
|
wolffian ducts develop into male ductal structures due to testosterone
muellerian structures absent due to MIH reduced or absent spermatogenesis |
|
|
what are the signs and symptoms of 5alpha reductase deficiency?
|
inguinal or abdominal testes
male ductal structures before puberty, males follow a female pattern (no external genitalia); after puberty male characteristics become apparent increase in muscle mass and deepening of voice due to testosterone reduced or absent spermatogenesis no facial hair, no enlargement of prostate, no temporal hair recession |
|
|
in what population is 5-alpha reductase deficiency particularly prevalent?
|
Dominican Republic
|
|
|
where is sperm produced?
|
seminiferous tubules
|
|
|
what comprises the blood-testis barrier?
|
tight junctions between sertoli cells
|
|
|
what are the interstitial cells in the testis?
|
leydig cells
|
|
|
what is the function of Leydig cells?
|
synthesize androgens
|
|
|
what are the two compartments of the testes?
what is in each? |
adluminal compartment - contains special fluid produced by sertoli cells
basal compartment - composition is close to blood and lymph |
|
|
where do spermatogonia undergo mitosis?
|
along the basal lamina
outside of blood-testis barrier |
|
|
what are the stages of germinal epithelium of the testicle?
|
spermatogonia
1st order spermatocyte 2nd order spermatocyte spermatid mature spermatid spermatozoa |
|
|
how long does it take for sperm to mature?
|
64 days
|
|
|
how many spermatozoa mature each day?
|
128 million daily
|
|
|
for what is the pulsatile release of GnRH necessary?
|
upregulate/maintain pituitary receptors on anterior pituitary
stimulates FSH and LH production |
|
|
what feedback inhibitor is released from sertoli cells in response to FSH?
|
inhibin
|
|
|
where is inhibin produced?
in response to what? what is its effect? |
sertoli cells
FSH inhibits FSH at anterior pituitary and at hypothalamus |
|
|
where does LH act?
|
Leydig cells
stimulates testosterone production reinforces spermatogenic effect of FSH |
|
|
what are the inhibitory actions of testosterone?
|
inhibits LH of anterior pituitary directly
inhibit GnRH from hypothalamus |
|
|
what are the three factors necessary to determine male development?
what are these factors controlled by in fetal life? |
testosterone (from Leydig cells)
DHT (from prostate) MIF (from sertoli cells) controlled by hCG instead of LH |
|
|
when are hormone levels lowest in males?
|
child
FSH > LH |
|
|
what are the hormone levels in puberty?
|
pulsatile release of GnRH -> pulsatile release of FSH and LH
LH surge at night -> Leydig cells -> testosterone |
|
|
what is the mechanism for the testosterone surge at 2-3 months of age in infants?
|
unknown
|
|
|
from what is testosterone made?
where does this come from? |
cholesterol
50% from de novo synthesis 50% from recycling via LDL endocytosis |
|
|
what are the products of Leydig cells?
|
testosterone
DHEA androstenedione |
|
|
what are the products of Sertoli cells?
|
DHT
estradiol |
|
|
what are the main sources of DHT and estradiol?
|
mainly in target tissues such as prostate and adipose tissue
mainly from fat |
|
|
what type of cells are activated by FSH?
what type of cells are activated by LH? |
FSH - sertoli cells
LH - leydig cells |
|
|
what initiates spermatogenesis?
|
FSH binding to sertoli cells
|
|
|
by what mechanism do FSH receptor act?
|
cAMP signalling
|
|
|
what are the proteins synthesized by Sertoli cells?
|
ABP
androgen binding protein, which binds to testosterone to maintain high concentrations in the seminiferous tubules |
|
|
what hormone maintains adulthood spermatogenesis by binding to Leydig cells?
|
LH
|
|
|
by what mechanism do LH receptors signal?
|
cAMP
|
|
|
how is testosterone found in the blood?
|
54% bound to albumin
44% bound to testosterone binding globulin 2% unbound |
|
|
what type of testicular cells produce testosterone and release it into the circulation?
|
leydig cell
|
|
|
from where does testosterone in sertoli cells originate?
|
leydig cells produce testosterone and transfer some of it to Sertoli cells
|
|
|
what happens to testosterone in Sertoli cells?
|
can be converted to estradiol
can be bound to androgen binding protein (ABP) and then released into the lumen of the seminiferous tubules can be converted to DHT, which binds to ABP and maintains male accessory glands is converted |
|
|
what is the relative abundance of LH and FSH in men during reproductive years?
during senescence? |
reproductive years: LH > FSH
senescence: FSH > LH |
|
|
what causes senescence in men?
|
decrease of testosterone, but not abruptly
|
|
|
in men, what are the sites for the main production of DHT and estradiol?
|
target tissues such as prostate and adipose tissues
|
|
|
what enzyme is responsible for converting testosterone to estradiol?
|
aromatase
|
|
|
what enzyme is responsible for converting testosterone to DHT?
|
5alpha-reductase
|
|
|
what enzyme is responsible for converting testosterone to 17-ketosteroids?
where does this occur? |
17beta-dehydrogenase
liver, kidney |
|
|
what enzymes are responsible for converting testosterone to conjugates?
where does this occur? |
conjugating enzymes
liver, kidney |
|
|
what are the androgenic effects of androgens?
|
induce and maintain differentiation of male somatic tissue
induce secondary sex male characteristics induce and maintain accessory sex organs required for libido and potency support spermatogenesis regulate GnRH and LH |
|
|
what are the anabolic effects of androgens?
|
influence sexual and aggressive behavior
promote protein anabolism (muscle growth) promote somatic growth and ossification (closure of epiphyseal plate) stimulate erythropoietin secretion of kidney (increase RBC production) |
|
|
what are the relative potencies of androgens?
|
DHT - 100%
testosterone - 50% androstenedione - 8% |
|
|
what is DHT associated with?
|
differentiation of penis, scrotum, and prostate
prostate growth male hair pattern (baldness) sebaceous gland activity (acne) |
|
|
what is released from Sertoli cells?
|
immature sperm
seminal plasma |
|
|
how long does it take for sperm to travel through seminiferous tubules and rete testis?
|
12 days
|
|
|
what happens to sperm in the epididymis?
|
concentrated 100-fold
fructose, carnitine, glycerylphosphorylcholine and glycoproteins are added become ready for fertilization become motile |
|
|
where do spermatazoa mature?
|
epididymis
|
|
|
what type of energy is used by spermatozoa?
|
anaerobic respiration
|
|
|
how long are spermatazoa viable?
|
40-45 days in presence of androgens
androgens are supplied by ABP transport |
|
|
what is added to sperm in the epididymis?
|
fructose
carnitine glycerylphosphorylcholine glycoproteins |
|
|
what is the path of sperm through the male reproductive tract?
|
seminiferous tubules
rete testis epididymis vas deferens ampulla seminal vesicles add seminal fluid prostate bulbourethral glands make urethra slippery urethra |
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|
how do spermatozoa travel through the vas deferens?
|
active movement via muscular activity of vas deferens
|
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|
what is the function of the ampulla?
|
produces fructose as anaerobic substrate for sperm
|
|
|
what is the function of the seminal vesicles?
|
produce seminal fluid (50-60% of ejaculate)
|
|
|
what is in the seminal fluid produced by the seminal vesicles?
|
ascorbic acid
inositol amino acids phosphorylcholine prostaglandins bicarbonate (to neutralize vaginal acidity) |
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|
why is it important to have bicarbonate in male ejaculate?
|
to neutralize vaginal acidity
|
|
|
what is added to male ejaculate by the prostate?
|
citric acid
proteolytic enzymes slightly alkaline |
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what is the function of the bulbourethral gland?
|
produces clear, viscous pre-ejaculate to lubricate the urethra
|
|
|
what is the function of PSA?
|
PSA = prostate specific antigen
liquifies the semen in the seminal coagulum and allows sperm to swim freely believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm |
|
|
how many sperm cells are in ejaculate?
|
approximately 60 million per ejaculation
|
|
|
on what is the success of a sperm in reaching the uterus dependent?
|
how watery the cervical mucus is, which is dependent on estrogen concentration
|
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|
where does most fertilization happen?
|
the ampullae of the fallopian tubes
|
|
|
how are spermatozoa transported to the ampullae?
|
muscular contractions of vagina, uterus, and oviduct
|
|
|
what is capacitation?
|
maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte
occurs in the female reproductive tract after ejaculation surface of sperm cell is solubilized by uterine fluid allows increased energy metabolism, enhances motility |
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what is the acrosome reaction?
|
surface membrane of the sperm fuses with the underlying acrosomal membrane
exposes enzymes from acrosomal vesicles sperm can pass to the zona pellucida |
|
|
what allows sperm to move forward into an egg?
|
whiplashing beats of tail propel the sperm forward into the egg
|
|
|
what is the cortical block to polyspermy?
|
electrical change that holds entire membrane depolarized for minutes
enzymes from the ovum prevent further polyploidy |
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|
what part of the sperm fuses with an egg when it begins to penetrate?
|
middle and posterior sperm head fuses with ovum membrane
|
|
|
when does nuclear fusion occur between a sperm cell and an ovum?
|
20-24 hours after fertilization
18-21 hours after second polar body is expelled |
|
|
when is the second polar body expelled from an ovum?
|
2-3 hours after fertilization
|
|
|
what is syngamy?
|
the process of union of two gametes to form a zygote
|
|
|
what increases the implantation rate of oocytes?
|
when spermatozoa have undergone acrosome reaction
|
|
|
what induces the acrosome reaction in in vitro fertilization?
|
calcium ionophores
|
|
|
what nerve fibers mediate an erection?
|
parasympathetic fibers
non-adrenergic, noncholinergic fibers |
|
|
what substances mediate erections?
how? |
VIP
NO dilate blood vessels in erectile tissue of penis, which compresses veins and blocks blood outflow |
|
|
what nerve fibers mediate ejaculation?
|
sympathetic nerve fibers
|
|
|
what muscles contract during ejaculation?
|
contraction of urogenital diaphragm supports ejaculation
contraction of internal sphincter of bladder prevents retrograde ejaculation |
|
|
what factors should be taken into account when taking a history for male infertility?
|
diabetes, MS
chemotherapy high fevers lubricants may be spermicidal pesticides, alcohol, drugs, hot tub |
|
|
what factors should be taken into account when performing a physical for male infertility?
|
habitus, height, weight, span
BP, skin, hair breasts genitourinary exam neurological exam |
|
|
how long after ovulation does it take before oocytes die?
|
24 hours (day 14 or 15)
|
|
|
through what layers must a sperm cell pass to fertilize an egg?
what does it use to pass through these? |
corona radiata
zona pellucida (glycoprotein layer) enzymes from the sperm acrosome |
|
|
what triggers oocyte activation so that it completes the 2nd meiotic division?
what happens next? |
sperm fusion with ovum
extrusion of second polar body |
|
|
how does a male pronucleus form?
|
the sperm head enlarges after it's inside the egg, as its chromatin decondenses
|
|
|
from where do the mitochondria of a zygote come?
|
from the mother/the egg
|
|
|
when does a 16-32 cell morula form?
|
4-5 days after fertilization
|
|
|
when does a blastula or blastocyst form?
|
32-64 cell stage
|
|
|
when does a zygote reach the uterus?
|
3-5 days after fertilization
|
|
|
when is implantation?
in what form is the fertilized egg? |
6-7 days after ovulation
day 21 or 22 of the menstrual cycle blastocyst |
|
|
what two parts form the placenta?
|
chorion - extraembryonic membrane of the fetus
decidua - endometrial tissue of the mother |
|
|
when does the corpus luteum begin to fail?
|
day 24 of menstrual cycle
must be rescued shortly after implantation to be viable |
|
|
what rescues the corpus luteum?
|
syncytiotrophoblast, which releases hCG and makes the corpus luteum enlarge
|
|
|
what hormone is hCG similar to?
|
LH
|
|
|
when are levels of hCG maximal?
|
8-13 weeks
|
|
|
what is the basis of virtually all pregnancy tests?
|
hCG
|
|
|
what stimulates testosterone and male sex differentiation in fetal males?
|
hCG
|
|
|
what promotes DHEA synthesis by fetal adrenal gland?
|
hCG
|
|
|
what stimulates the maternal thyroid while she is pregnant?
|
hCG
|
|
|
what hormone is responsible for morning sickness?
|
hCG
|
|
|
what bridges the gap between ovarian and placental maintenance of a fetus?
|
hCG
|
|
|
what hormone maintains progesterone secretion and relaxin secretion from the corpus luteum?
|
hCG
|
|
|
where does fetal DHEAS come from?
|
60% from fetal adrenal gland
40% from maternal adrenal gland |
|
|
how does a fetus pick up maternal DHEAS?
|
extracts it from maternal blood, removes the sulfate, and aromatizes it to estrone and estradiol
|
|
|
what happens to a large portion of DHEA-S in the fetus?
where? |
converted to 16alpha-OH-DHEAS
in the fetal liver |
|
|
what happens to 16alpha-OH-DHEAS?
|
converted to estriol in the placenta
|
|
|
in the fetus, what estrogens are in higher proportion?
|
large increase in estriol in relationship to estrone and estradiol
|
|
|
what estrogen accounts for 90% of the estrogens in maternal urine?
|
estriol conjugates
|
|
|
if estradiol is the major circulating estrogen, why are so much more estriol conjugates found in maternal urine?
|
estriol has a short half-life
|
|
|
why can estriol be used to monitor fetal-placental health?
|
it requires transport of steroids from placenta to fetus and back
|
|
|
what are the functions of estrogens on the uterus during pregnancy?
|
increase blood flow to uterus
stimulate growth of decidua and myometrium stimulate myometrial contractility soften cervix |
|
|
what are the functions of estrogens on the breasts during pregnancy?
|
augment ductal growth in conjunction with other hormones
increase secretion of prolactin upregulate progesterone receptors |
|
|
what are the metabolic functions of estrogens during pregnancy?
|
inhibit some actions of insulin in conjunction with other hormones
|
|
|
what becomes a major progesterone secreting tissue in a pregnant woman?
|
placenta (syncytiotrophoblast)
production does not require fetal tissue at all |
|
|
what hormone maintains the endometrium?
|
progesterone
|
|
|
what hormone is immunosuppressive and helps to prevent rejection of the placenta and fetus?
|
progesterone
|
|
|
what causes miscarriages to occur?
|
placenta does not secrete progesterone before the corpus luteum regresses
|
|
|
what is hPL?
|
human placental lactogen
aka chorionic somatomammotropin (hCS) |
|
|
what is hPL similar to in structure and function?
|
human growth hormone
though hPL is 100x less active |
|
|
what is the function of hPL?
|
modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus
|
|
|
what are the drawbacks of hPL?
|
may cause insulin resistance
may cause carbohydrate intolerance contributes to gestational diabetes (though not the only cause of it) |
|
|
what hormones are produced by placenta?
|
GnRH
TRH CRH GHRH somatostatin ACTH TSH 1,25-dihydroxyvitamin D |
|
|
what are the sources of activin A?
what are the actions of activin A? |
placenta and fetus
stimulates hCG and progesterone |
|
|
what are the sources of follistatin?
what are the actions of follistatin? |
placenta and fetus
inhibits hCG and progesterone |
|
|
what are the sources of relaxin?
what stimulates it? |
corpus luteum, decidua and placenta
hCG stimulates its release |
|
|
what are the actions of relaxin?
|
relaxes mother's pelvic outlet
softens cervix decreases uterine muscle contraction early-prevents abortion late-facilitates birth |
|
|
what is the function of prostaglandins in pregnancy?
|
induce cervical softening
|
|
|
what hormone stimulates contraction of the myometrium during parturition?
|
oxytocin
|
|
|
what hormone provides positive feedback via a neuroendocrine reflex to stimulate oxytocin release?
|
oxytocin
|
|
|
what is the most likely to have a role in timing the onset of labor?
|
fetal CRH
resulting cortisol triggers a rise in the circulating estrogen/progesterone ratio |
|
|
in a normal labor at term, the initiating stimulus for uterine contraction is what?
|
a rise in the maternal plasma progesterone/estrogen ratio
|
|
|
what is an amniotomy?
|
artificial rupture of membranes
"breaking the patient's water" to accelerate parturition |
|
|
what is pitocin?
|
synthetic oxytocin
|
|
|
why can oxytocin not be used for early induction?
|
oxytocin receptors are upregulated relatively late in the pregnancy
|
|
|
why can sex be used to induce labor?
|
semen has prostaglandins, which "ripen the cervix" to make it softer
not scientifically proven |
|
|
what causes the main contraceptive effect of hormonal contraceptives?
|
synthetic progestagens
|
|
|
how do hormonal contraceptives work?
|
progestagens decrease pulse frequency of GnRH by negative feedback
this decreases FSH (inhibits follicular development and estrogen increase) and LH overall prevents ovulation by inhibiting LH surge also thicken cervical mucus and interfere with endometrial development |
|
|
what is in combination pills?
how are they administered? |
progestin & estrogen
taken daily for 3 weeks and discontinued for 1 week with menstruation occurring 1-2 days after |
|
|
what is the effect of estrogen in the combination contraceptive pills?
|
suppresses FSH and impairs early follicular development so that lower amount of progestin is required
|
