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100 Cards in this Set
- Front
- Back
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What are 4 possible complications associated with hypertension?
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1. Pulmonary edema due to reduced systemic CO
2. Increased afterload, greater work for the heart. Weakened heart has reduced CO 3. Aneurysm and stroke 4. Blood pools in lower extremities, increased lymph formation, edema, thrombosis |
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What is the primary cause of hypertension?
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Excessive fluid volume in the vascular system
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What regulates plasma volume and composition as well as the ionic composition of the extracellular and intracellular fluid?
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The kidneys
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What is the plasma volume relative to the ECF?
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Relatively a small fraction of the ECF
3.0 L RBC volume is about 2 L = 40% |
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What are the primary ions in extracellular fluid?
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Na+ and Cl-
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What are the primary ions in the cytosol?
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K+, phosphate, organic ions and proteins
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Where are Ca2+ and HCO3- higher in the ECF or the Intracellular fluid?
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ECF
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What is the importance of the larger protein concentration of the plasma?
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Provides colloid osmotic pressure to retain fluid in capillaries.
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What does the presence of free solutes result in and what does it create?
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Reduces the amount of "free water" molecules (free energy of water) so the gradient for water movement is from pure water to the solution. This creates an osmotic pressure.
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How is osmotic pressure measured?
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As the hydrostatic pressure required to prevent net movement from water to solution
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When will osmotic pressure be greater (or more positive)?
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For a more concentrated solution
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What separates a solution from pure water?
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Semipermeable membrane (permeable to water and not solutes)
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What is the equation for osmotic pressure corrected for non-ideality?
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pi = CRT
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What is the osmolality of body fluids?
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250 mOsm/kg even though the total solute concentration is about 300 mOsm
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How can osmotic pressure be predicted?
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From the total solute concentration, corrected for non-ideality
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Approximately how much of cardiac output is delivered to the kidneys via the renal arteries and how much of that is plasma?
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1/4 of cardiac output (1,100-1,200 ml/min) is delivered to the kidneys via the renal arteries
Of that, about 660-720ml is plasma (assume hematocrit of 40). |
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In glomeruli, how much of the plasma is filtered into the nephrons?
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20% of the plasma (125ml/min or 180 l/day)
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How many nephrons are found in each kidney?
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1 million
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How are solutes and water returned to the circulation in the kidneys?
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Solutes and water a reabsorbed back into the blood and returned to the circulation via the renal vein
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How much of the filtered plasma is excreted as urine normally?
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1% (about 1ml/min or 1.5 L/day)
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Where does the capillary network of the glomerulus filter the blood plasma?
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Into Bowman's capsule and the filtrate flows into the tubular segments of the nephron
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What are the two types of nephrons found in the kidneys?
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Cortical
Juxtamedullary (~15%, ~40 mm in length) |
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What are the two components found in each nephron?
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Renal corpuscle
Complex tubular system |
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Where does the final urine pass from?
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Final urine passes from the collecting ducts in the ducts of Bellini
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What are the three elements of Renal Function?
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1. Glomerular Filtration
2. Tubular Reabsorption 3. Tubular Secretion |
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About how much plasma flow is filtered and what happens to the portion that is not filtered?
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20% of the plasma flow is filtered
The other 80% passes to the peritubular capillaries GFR = 125 ml/min = 180 L/day |
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What percentage of Na+, Cl- and water are reabsorbed and what happens to K+, organic ions and drugs?
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About 99%
K+ may be secreted as are organic ions (uric acid) and drugs. |
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What is the final urine production each day?
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1.5 L/day
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What are the two portions of the renal corpuscle?
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1. Glomerulus - capillary tuft
2. Bowman's capsule - visceral (podocytes) and parietal (simple squamous) layers |
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What is the vascular pole?
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Afferent and efferent arterioles
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What is the urinary pole?
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Connection w/ proximal tubule
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How do the glomerular capillaries filter large amounts of filtrate that is very low in protein content?
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Accomplished by a specialized structure that includes the endothelium, a thick basement membrane and foot processes of podocytes that wrap around the capillary. Passage of proteins larger than about 16,000 molecular weight are restricted.
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What is loss of protein in the filtrate termed as?
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Nephrotic syndrome
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How do glomerular filtration pressures compare to pressures for systemic capillaries?
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Glomerular filtration pressures are much greater than for systemic capillaries and almost no protein is filtered despite large volume flow!
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What is inulin?
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An inert polysaccharide with a molecular weight of about 5.5 Kd. It is freely filtered but neither reabsorbed or secreted so the amount of plasma filtered should equal the amount of plasma secreted
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What is the filtered load?
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Pin X GFR
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What is the urinary excretion?
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Uin X V
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What is the relationship between amount filtered and amount excreted?
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Pin X GFR = Uin X V
Amount filtered = Amount excreted |
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What is creatinine and how does it help estimate GFR?
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Creatinine is a naturally occuring metabolite that is present in the plasma, it is filtered and only marginally reabsorbed or secreted. Measuring urine volume and the urine and plasma creatinine concentrations allows an estimate of GFR.
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What is the GFR as a measure of creatinine?
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GFR = (Ucr x V)/Pcr
Termed creatinine clearance - clinically 24 hour urinary creatinine output is used to evaluate renal function |
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What is the normal glomerular filtration rate and what does a decline in glomerular filtration result in and indicate?
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A normal GFR is about 125 ml/min
Results in the accumulation of creatinine in the plasma This is a diagnostic for reduced GFR in renal disease A GFR less than 25 ml/min shows an exponential increase in the Plasma creatinine concentration. |
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How much of the fluid of the body is found in intracellular fluid?
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2/3
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What is the inulin clearance if inulin is neither reabsorbed or secreted?
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The plasma filtered is "cleared" of inulin.
Inulin clearance = GFR |
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What is the clearance of glucose which is completely reabsorbed so all is returned to the plasma?
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Glucose is completely reabsorbed so all is returned to the plasma. Clearance = 0
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What is clearance if most solutes are partially (but mostly) reabsorbed?
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Clearance > 0
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What is clearance if some solutes are secreted?
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Clearance > GFR
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How is para-aminohippuric acid (PAH) secreted and what kind of information does it provide as a result?
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Para-aminohippuric acid (PAH) is almost completely secreted from the blood in addition to that filtered.
So, PAH clearance provides an approximation of renal plasma flow |
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What is the ratio of inulin clearance/PAH clearance equal to?
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Inulin clearance/PAH clearance =
GFR/renal plasma flow = Filtration fraction |
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Why is the colloid osmotic pressure of the peritubular capillaries increased and how does it facilitate the return of reabsorbed solutes and water to the circulation?
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Because of the large percentage of plasma filtered
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Why does the protein leaving the efferent arteriole more concentrated and have a greater colloid osmotic pressure?
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Because protein is not filtered and water is filtered
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What does the greater colloid osmotic pressure of the efferent arteriole facilitate?
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The removal of solutes and water absorbed across the nephrons
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What is the filtration fraction?
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Filtration Fraction = GFR/RPF = 125/625 = 0.2 or 20%
20% of the plasma is filtered |
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What exerts a strong colloid osmotic pressure in the peritubular capillaries that draws fluid into the capillaries as it is reabsorbed across the tubular cells?
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The protein concentration of the blood which is elveated
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What is the % filtered load reabsorption of water, Na+, K+, Ca2+, HCO3-, Cl- Glucose, and Urea?
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Water 99.2%
Na+ 99.4% K+ 86.1% Ca2+ 98.2% HCO3- 99.9% Cl- 99.2% Glucose 100.0% Urea 50% |
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What is the functional role of the proximal tubule?
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67% of Na+, Cl- and Water reabsorbed - isoosmotic (they are removed in the same amounts as in the filtrate so the osmotic concentration doesn't change.
100% of glucose and amino acids reabsorbed - completely removed Secretion of organic wasted (uric acid etc) and toxins or medications |
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What is the functional role of the loop of Henle?
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25% of NaCl, 15% of Water reabsorbed
Sets up osmotic gradient in peritubular fluid |
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What is the functional role of the distal tubule?
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7% NaCl, 8-17% of water reabsorbed
Na+/K+ is balanced |
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What is the functional role of the collecting duct?
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Reabsorption of NaCl and Water
Regulated by anti-diuretic hormone Site of final urine concentration |
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What is the general mechanism for tubular reabsorption?
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The Na+/K+ pump is found in the basolateral membrane of most tubular cells. What varies is the apical entry mechanism. Other solutes may diffuse across the paracellular pathway where "tight junctions" are more leaky. Other molecules, such as water may diffuse across the apical and basolateral membranes, or between the cells.
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How do the NaCl and water concentrations remain the same even though the quantity of both has been reduced by 50-70%?
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Because Na+ and Cl- transport generates most of the osmotic gradient and NaCl and water are removed in about the same proportion.
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What does tubular fluid to plasma concentration ratio provide?
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An index of the relative reabsorption of a solute relative to water
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How is glucose transported across the proximal tubule?
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Glucose is absorbed by first entering the cells from the tubular fluid via a Na+/Glucose exchange protein (SGLT). Once in the cell it diffuses out of the basolateral membrane through a glucose transport protein in the glut family.
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How are Na+ and Cl- ions transported across the proximal tubule?
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Na+ is transported out of the cell via the Na+/K+ pump.
Cl- is thought to diffuse via the paracellular pathway, drawn by the positive charge of Na+ |
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What happens in the proximal tubule if there is an elevated filtered load?
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Because there are a limited number of SGLT molecules, elevated filtered load will exceed the transport maximum and glucose will appear in the urine (diabetes mellitis).
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How is H+ transported across the proximal tubule?
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H+ secretion with a Na+/H+ antiport protein in the apical membrane.
Note that H+ secretion is coupled to HCO3- reabsorption and that Na is transported out across the basolateral membrane via the Na+/K+ pump. |
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What is urinary pH typically?
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5.5-6.5
Acidic because of the need to eliminate acidic metabolites and retain bicarbonate |
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What is involved in organic ion secretion and what is secreted this way?
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Organic ion secretion actively pumps molecules into the tubular lumen and draws them from the plasma in the peritubular capillaries.
Many drugs are SECRETED in this manner. A similar mechanism exists for organic cations |
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What percentage of nephrons in the human kidney are juxtamedullary, i.e. their loops of Henle project into the inner medulla?
What do these loops do? |
20%
Create the osmotic gradient necessary for conserving water by concentrating the urine |
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What is the active transport component of the loop of Henle?
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The ascending THICK limb
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What is the ascending thick loop of Henle specialized for?
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Active transport that is driven by the Na/K pump
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What is present in the apical membrane of the cells in the thick ascending limb that makes it unique?
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Cell in the thick ascending limb have a Na-K-2Cl (NKCC) cotransport protein in the apical membrane. Transport is "driven" by the inward directed Na+ gradient and completed by basolateral channels (K+ and Cl-)
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What is the co-transport protein found in the thick ascending loop of henle inhibited by?
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"loop diuretics" (furosemide = lasix)
-Furosemide -Ethacrynic acid -Bumetanide |
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How does the thick ascending loop of Henle operate?
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Salt reabsorbed from the ascending thick loop accumulates in the peritubular space. This dilutes the fluid in the ascending loop and draws water out of the thin descending loop, concentrating the tubular fluid delivered to the ascending loop
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What is "counter current multiplication"
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Greater Na+ and Cl- concentration delivery to the ascending thick limb is transported out, further diluting the fluid entering the distal tubule and concentrating the peritubular fluid.
Transport out of the ascending thick loop dilutes fluid entering the distal tubule, concentrates salt in the peritubular space and draws water out of the descending loop. |
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What helps maintain the concentration gradient of the loop of Henle and what is it termed?
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Blood flow in the vasa recta takes up salt and water. Salt becomes concentrated in the descending vasa recta and water is absorbed. The ascending vasa recta passes close to the descending branch so water is transferred and returned to the circulation. This is termed counter current exchange.
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What happens as dilute fluid enters the early distal tubule?
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Fluid becomes further diluted by NaCl reabsorption.
The apical entry step is mediated by a Na+/Cl- exchange protein that is inhibited by thiazide diuretics |
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What does salt retention promote?
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Water retention and hypertension
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What occurs in the late distal tubule and the early collecting tubule?
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Na+ is reabsorbed and K+ is secreted via apical channels. Na+ uptake is limited by apical epithelial Na+ channels and transported across the basolateral membrane via the Na-K pump. The mineralcorticoid, aldosterone, stimulates both steps and blockers of aldosterone in addition to Na+ channel blockers are used to reduce salt retention which leads to fluid retention and hypertension. Water is also reabsorbed to variable degrees depending on the need for regulation of plasma volume and osmotic concentration.
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How is water absorption mediated?
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By water conducting membrane proteins (water channels) called aquaporins. The are present in the proximal tubule, descending loop of Henle as well as the medullary collecting duct. Water moves from a more dilute solution to a more concentrated solution.
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What happens in the medullary collecting duct?
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Salt and water are reabsorbed. The specific aquaporin in the apical membrane of the collecting duct is expressed in the apical membrane in response to stimulation by antidiuretic hormone (ADH)
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What occurs as water is reabsorbed?
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As water is reabsorbed, urea becomes more concentrated in the tubular fluid. By the time the fluid reaches the collecting duct its concentration may be over 500mM. ADH also increases urea permeability so urea leaks into the peritubular fluid and back into the loop of Henle.
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What is the maximal concentrating ability of the human kidney?
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1,200 mOsm/L
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What is antidiruesis?
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The production of a small volume of concentrated urine.
ADH is synthesized in the preoptic and paraventricular nucleii in the hypothalamus and stimulated when osmoreceptors detect an increase in osmotic concentration (dehydration) or a decrease in blood pressure. |
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What is diuretic condition?
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Low ADH levels result in diuretic condition in which the dilute tubular fluid entering the collecting duct passes through and a larger volume of dilute urine is formed.
The distal tubule continues to remove NaCL to produce a dilute tubular fluid. Low ADH level result in reduced water reabsorption so a large volume of dilute urine is formed. |
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What do loop diuretics (e.g. furosemide) do?
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Prevent the accumulation of NaCl gradients in the peritbular space and thus osmotic reabsorption in the collecting duct.
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What do thiazied in the early distal tubule and Na+ channel blockers (e.g. amiloride) do?
What does aldosterone do? |
Prevent salt retention and consequent water retention and hypertension.
Aldosterone stimulates salt retention |
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Where does K+ secretion occur if dietary intake is high?
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Secretion occurs in the late distal tubule and cortical collecting duct.
K+ secretion is enhanced by Na+ uptake even though they are transported by separate channels. Both Na+ reabsorption and K+ secretion are stimulated by aldosterone. |
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How do K+ sparing diuretics such as amiloride work?
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Inhibit Na+ reabsorption
This decreases the charge gradient for K+ secretion. K+ sparing diuretics are used in conjunction with other diuretics that cause K+ to be lost when urine production increases. |
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What is the juxtaglomerular apparatus?
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Cells of the distal tubule, the macula densa contacting the juxtaglomerular cells of the arterioles
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How are the changes in the composition of the distal tubular fluid detected?
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Detected by the macula densa that communicates with smooth muscle cells and juxta glomerular cells to regulate GFR and tubular function
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What is the macula densa?
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The region of the distal tubule that passes between the afferent and efferent arterioles - detects changes in GFR from the composition of the tubular fluid in the distal tubule
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How does normal GFR move tubular fluid through the nephron?
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Quickly
Tubular fluid passes through the distal tubule with less time for solute reabsorption |
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How does reduced GFR move tubular fluid through the nephron?
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Slowly
Tubular fluid passes through the distal tubule with more time for solute reabsorption |
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What is tubuloglomerular feed back?
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The signal is transmitted to the juxtaglomerular cells in the efferent arterioles. Smooth muscle relaxes in afferent and constricts in efferent arterioles so filtration pressure increases to maintain GFR
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What is the primary effect of tubuloglomerular feedback?
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"Autoregulation"
Limits GFR at elevated blood pressure while maintaining GFR and renal blood flow as blood pressure declines, thus protecting plasma volume |
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How does tubuloglomerular feedback work?
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The dilution of the fluid in the distal tubule is detected by the macula densa. The signal is transmitted to the juxtaglomerular cells that release renin.
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How does renin release control aldosterone levels?
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1. When the kidney senses a drop in blood flow (reduced GFR) it releases a peptide, renin into the circulation
2. Renin acts as an enzyme to cleave a 10 amino acid fragment, angiotensin I from a larger protein, angiotensinogen, that is made by the liver and released into the circulation. 3. Angiotensin I is carried to the lungs where an enzyme, angiotensin converting enzyme (ACE) cleave 2 amino acids to give the 8 amino acid peptide, angiotensin II (AII) 4. All is carried by the circulation to the adrenal cortex where it stimulates the release of aldosterone into the circulation. |
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After being produced by the lungs, Angiotensin II stimulates the adrenals and what other organ?
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Stimulates the posterior pituitary to release ADH to promote fluid retention when blood pressure drops. Angiotensin II also has a vasoconstriction effect on vascular smooth muscle, also causing hypertension.
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What can yield too much hypertension and what is used to placate it?
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Angiotensin II can yield hypertension. A commonly used medication for hypertension is the use of ACE inhibitors which promote vasodilation and control blood pressure.
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What is a potent vasoconstrictor?
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Angiotensin II
The signal for initiating cross-bridge formation in smooth muscle is the activation of myosin light chain kinase by increased Ca2+ concentration in the cytosol that allows cross bridge formation and ATP cycling. Notice that this can be stimulated by either release from interna (ER) or uptake from external (ECF) sources. Ca2+ channel blockers reduce uptake from the ECF and also promote vasodilation. |
