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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.
What are the two types of nephrons?
- Cortical nephrons: 7/8, short loops of henle
- Juxtamedullary nephrons: 1/8, long loops of henle.
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.
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.
The decrease in GFR in most diseased states is due to?
- Reduction in membrane surface area,
- Including decrease in number of nephrons.
What materials are not freely filtered across kidney membranes?
- Albumin and other large plasma proteins
- Lipid soluble/protein bound substances.
What is the osmolarity of the fluid in Bowman's space (ultrafiltrate)?
300 mOsm: same concentration of substrates as plasma, except for proteins.
What is the formula for the filtration fraction?
- FF = GFR/RPF
- Usually 20% for a freely filtered substance (120/600).
What is the main determinant of GFR?
Glomerular capillary pressure.
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).
What is the effect of parasympathetic stimulation of kidneys?
There is no parasympathetic innervation of kidneys.
What is the effect of Angiotensin II on the kidneys?
- Efferent arteriolar vasoconstriction
- Maintains GFR with decreased RPF and increased renal resistance.
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.
What is the gold standard to measure renal clearance, what is really used?
What is nephrotic syndrome?
- Non-inflammatory injury to glomerular epithelium or basement membrane
- Marked increase in proteinuria
- Little to no change in GFR.
What is nephritic syndrome?
- Inlammation mediated injury to glomerular endothelium or basement membrane
- Marked decrease in GFR
- Red cell casts in urine.
What are the three transport mechanisms?
- Simple diffusion: no help
- Facilitated diffusion: channel, no energy
- Active transport: ATP energy against gratient.
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.
What is the equation for renal blood flow?
Renal blood flow = RPF/(1-HCT).
What substances (drugs) compete for the organic anion transporter (excretion into tubule)?
What substances (drugs) compete for the organic cation transporter (excretion into tubule)?
What is the formula for net transport rate?
- Net transport rate = filtered load - excretion rate
- = (GFR x Px) - (Ux x V).
How much of filtered Na is reabsorbed in the proximal tubules, what follows Na?
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.).
What acts as a countercurrent multiplier to create the osmolar gradient in the medullary interstitium?
The loop of henle.
Is the descending limb permeable to water, solutes?
- Yes, permeable to water
- Much less (little to no) permeable to solutes.
Is the ascending limb permeable to water, what is it also referred as?
- Not permeable to water
- Diluting segment of nephron.
What channel is located on the ascending loop of Henle?
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.
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.
Active and passive reabsorption of Na is stimulated by?'
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.
The total net loss of acid equals the net gain of?
Bicarbonate - HCO3-.
What is Renal Tubular Acidosis Type II?
- Diminished capacity of proximal tubule to reabsorb bicarbonate
- Low plasma bicarb and acid urine
- Ex: Fanconi syndrome.
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.
What is the effect of aldosterone on potassium?
Stimulates secretion in distal tubules and collecting ducts.
What is the effect of acidosis/alkalosis on potassium?
- Acidosis: K shifted extracellularly (exchanged for H+)
- Alkalosis: K shifted intracellularly.
What are the two main factors affecting potassium secretion?
- Filtrate flow
- Negative potential of lumen in distal tuble and collecting duct.
What are the neuromuscular, cardiac, metabolic consequences of hyperkalemia?
- Neuromuscular: Fatigue, weakness
- Cardiac: High T waves, low ST, ventricular fibrillation
- Metabolic: Metabolic acidosis.