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What are the four main functions of the kidneys?
- Secretes Hormones: Renin, EPO, 1,25 Vit. D
- Excretes Waste: Urea, uric acid, creatinine
- Acid-Base balance
- Water and electrolyte balance.
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What are the two types of nephrons?
- Cortical nephrons: 7/8, short loops of henle
- Juxtamedullary nephrons: 1/8, long loops of henle.
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What is the autoregulatory (pressure) range of the kidneys, what are the two mechanisms?
- 90-180 mm Hg
- Myogenic: smooth muscle contracts when distended
- Tubuloglomerular feedback: juxtaglomerular apparatus responds to concentration of NaCl or Chloride ions delivered--
- Decreased NaCl: afferent arteriole vasodilation -> increased GFR
- Increased NaCl: afferent arteriol vasoconstriction -> decreased GFR.
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What are the three structures comprising the glomerulus?
- Fenestrated capillary endothelium: covered with negatively charged compounds
- Basement Membrane: extracellular negatively charged proteins
- Epithelial cell layer of Podocytes.
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The decrease in GFR in most diseased states is due to?
- Reduction in membrane surface area,
- Including decrease in number of nephrons.
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What materials are not freely filtered across kidney membranes?
- Albumin and other large plasma proteins
- Lipid soluble/protein bound substances.
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What is the osmolarity of the fluid in Bowman's space (ultrafiltrate)?
300 mOsm: same concentration of substrates as plasma, except for proteins.
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What is the formula for the filtration fraction?
- FF = GFR/RPF
- Usually 20% for a freely filtered substance (120/600).
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What is the main determinant of GFR?
Glomerular capillary pressure.
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What is the effect of sympathetic stimulation to kidneys?
- Arteriolar vasoconstriction leading to:
- Decreased GFR
- Incresed FF
- Increased reabsorption (increased oncotic pressure of peritubular capillaries).
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What is the effect of parasympathetic stimulation of kidneys?
There is no parasympathetic innervation of kidneys.
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What is the effect of Angiotensin II on the kidneys?
- Efferent arteriolar vasoconstriction
- Maintains GFR with decreased RPF and increased renal resistance.
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What is the formula for clearance of a substance?
- Clearance of x = (Ux x V)/Px
- Ux: Urine conc
- V: Urine flow rate
- Px: Plasma conc.
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What is the gold standard to measure renal clearance, what is really used?
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What is nephrotic syndrome?
- Non-inflammatory injury to glomerular epithelium or basement membrane
- Marked increase in proteinuria
- Little to no change in GFR.
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What is nephritic syndrome?
- Inlammation mediated injury to glomerular endothelium or basement membrane
- Marked decrease in GFR
- Red cell casts in urine.
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What are the three transport mechanisms?
- Simple diffusion: no help
- Facilitated diffusion: channel, no energy
- Active transport: ATP energy against gratient.
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What is the significance of PAH at low plasma conc?
- No PAH is reabsorbed, and PAH is actively excreted from peritubular cavities
- Low plasma conc: All plasma PAH excreted, clearance equals renal plasma flow.
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What is the equation for renal blood flow?
Renal blood flow = RPF/(1-HCT).
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What substances (drugs) compete for the organic anion transporter (excretion into tubule)?
- PAH
- Penicillin
- Furosemide
- Acetazolamide
- Salicylates.
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What substances (drugs) compete for the organic cation transporter (excretion into tubule)?
- Morphine
- Atropine
- Amiloride
- Cimetidine
- Procaineamide.
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What is the formula for net transport rate?
- Net transport rate = filtered load - excretion rate
- = (GFR x Px) - (Ux x V).
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How much of filtered Na is reabsorbed in the proximal tubules, what follows Na?
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What are other changes in the proximal tubule?
- Metabolites: 100% reabsorption of carbohydrates, proteins, amino acids, peptides, ketone bodies
- Bicarbonate: 80-90% reabsorbed
- Secretion: secretion of organic anions and cations (PAH, penicillin, morphine, etc.).
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What acts as a countercurrent multiplier to create the osmolar gradient in the medullary interstitium?
The loop of henle.
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Is the descending limb permeable to water, solutes?
- Yes, permeable to water
- Much less (little to no) permeable to solutes.
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Is the ascending limb permeable to water, what is it also referred as?
- Not permeable to water
- Diluting segment of nephron.
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What channel is located on the ascending loop of Henle?
Na-K-2Cl channel.
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What is reabsorbed in the early distal tubule, through what channels?
- Na, Cl: Through NaCl symporter - Na pumped out with Na-K ATPase
- Ca: Passively through Ca channels - extruded via Ca ATPase or Ca-3Na antiporter -- also bound by calbindin within cell.
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What two cells make up the late distal tubule, functions of each?
- Principal cell: reabsorbs some Na and H2O, secretes K
- Intercalated cell: Secretes H+ to lumen, bicarb to circulation, or vice versa -- acid-base balance.
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Active and passive reabsorption of Na is stimulated by?'
Aldosterone.
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H+ in urine is found in what two forms?
- H2PO4-: dihydrogen phosphate - phosphate buffer system (33%) - titratable acid
- NH4+: ammonium - ammonium buffer system (66%) - nontitratable acid.
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The total net loss of acid equals the net gain of?
Bicarbonate - HCO3-.
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What is Renal Tubular Acidosis Type II?
- Diminished capacity of proximal tubule to reabsorb bicarbonate
- Low plasma bicarb and acid urine
- Ex: Fanconi syndrome.
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What is Renal Tubular Acidosis Type I?
- Inability of distal nephron to secrete and excrete fixed acid
- Alkaline urine: pH> 5.5-6
- Metabolic acidosis with high urine pH.
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What is the effect of aldosterone on potassium?
Stimulates secretion in distal tubules and collecting ducts.
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What is the effect of acidosis/alkalosis on potassium?
- Acidosis: K shifted extracellularly (exchanged for H+)
- Alkalosis: K shifted intracellularly.
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What are the two main factors affecting potassium secretion?
- Filtrate flow
- Negative potential of lumen in distal tuble and collecting duct.
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What are the neuromuscular, cardiac, metabolic consequences of hyperkalemia?
- Neuromuscular: Fatigue, weakness
- Cardiac: High T waves, low ST, ventricular fibrillation
- Metabolic: Metabolic acidosis.
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