16 Glomerular Filtration Rate (GFR) = amount of filtrate formed by BOTH kidneys per minuteNormal is 12.5 ml for each 1 mm Hg NFP for men & 10.5 ml for womenFor NFP = 10 mm HgGFR = 125 ml/minor 180 L/day
17 What would happen if glomerular hydrostatic pressure dropped to 50 mm Hg ?What would be the effect on GFR?
18 GFR Control1) Autoregulation = self regulation, no neural or endocrineMyogenic Mechanism = smooth muscle contracts when stretchedHow will smooth muscle of afferent arteriole react if BP decreases? If it increases?What effect will dilation of afferent arteriole have on GFR? Effect of constriction?
19 Juxtaglomerular Apparatus Juxtaglomerular cells =Smooth muscle in afferent arteriole, that secretes reninMacula densa = receptor cells in wall of DCTMesangial cells = specialized contractile cells that may also ??p 908
20 GFR Control1) Autoregulation: Tubuloglomerular Feedback = Juxtaglomerular apparatus monitors fluid entering DCT and adjustsGFR to maintainhomeostasisp 908
21 Juxtaglomerular Apparatus If GFR is too high macula densa detects the change & sends chemical signal to Juxtaglomerular cells, which constrict the afferent arteriole, and thereby reduce GFRp 908
22 What effect will this have on GFR? GFR Control2) Sympathetic Nervous SystemIn response to strenuous exercise the sympathetic N.S. redirects blood to heart, brain and skeletal muscle, and away from organs like kidneys by constricting the afferent arteriolesWhat effect will this have on GFR?
23 GFR Control 3) Renin-Angiotensin Mechanism When BP drops, sympathetic N.S. triggers release of renin by juxtaglomerular cellsRenin converts a plasma protein, angiotensinogen into angiotensin IAngiotensin-converting enzyme (ACE) from lungs & kidneys converts angiotensin I into angiotensin II, which is a hormone with many powerful effects
24 Angiotensin II Effects Systemic Vasoconstriction Constricts afferent & efferent arteriolesStimulates NaCl & water reabsorption by kidneysStimulates aldosterone release by adrenal cortexStimulates antidiuretic hormone (ADH) releaseStimulates thirst center in hypothalamusp 909
26 Proximal Convoluted Tubule (PCT) Longest & most coiled of portion of tubuleSimple cuboidal epithelium with microvilliMany mitochondria provide ATP for high amount of active transportTubular Reabsorption = movement of water and solutes from tubular fluid to bloodTubular Secretion = movement of substances from blood into tubular fluid
27 PCT Sodium (Na+) reabsorption = 60 -70% of total through secondary active transport
28 PCT Chloride (Cl-) reabsorption = % of total mostly by following sodium (electrical attraction)p 910
29 PCT Bicarbonate (HCO3-) reabsorption PCT Bicarbonate (HCO3-) reabsorption? = most of total returned to blood by “slight of hand trick” & carbonic anhydrasep 910
30 PCT Nutrient (glucose, amino acids) reabsorption = Normally 100% returned via cotransport with Na+
31 PCT Nitrogenous waste reabsorption = About half of urea diffuses out of tubular fluid, uric acid diffuses out, NOT creatinine (too large)p 910
32 PCT Water reabsorption = % of total through osmosis, basically by following solutes, called obligatory water reabsorption, (no control/choice)p 910
33 Uptake by Peritubular Capillaries Water = OsmosisBuild up of interstitial H2O from PCT means greater hydrostatic pressureNarrow efferent arteriole means low BHP in peritubular capillaries, about 8 mm HgTrapped proteins (not filtered with water) means higher colloidal osmotic pressure (COP)Solutes = Solvent DragWater “drags” solutes into capillary
34 Transport Maximum (Tm) = maximum rate of reabsorption that is reached when all carrier proteins are saturatedTransport maximum determines the renal threshold, or the plasma concentration at which a specific compound or ion will begin appearing in the urineFor example, renal thresholdfor glucose is about 220 mg/dLUntreated diabetes mellitusmay be 400 mg/dLp 106
35 Nephron LoopThin, descending limb = water permeableReabsorbs about 15% of water, now about 80% of totalThick, ascending limb = water impermeableReabsorbs about 25% of Na+ and Cl-, now about 90% of totalSo tubular fluid becomes more diluteLeaves excess Na+ and Cl- in peritubular fluid (interstitial fluid around tubules)
36 Blood plasma, interstitial fluid, and OsmolarityOsmolarity = amount of dissolved particles in one liter of solutionNormal range of physiological osmolarity is measured in milliosmoles per liter (mOsm/L)Blood plasma, interstitial fluid, andintracellular fluid (cytosol) measure about 300 mOsm/L
38 Distal Convoluted Tubule (DCT) & Collecting Duct Fluid arriving at DCT contains about 20% of water & 10% of salts (mostly NaCl)Reabsorption of remaining water and salts is variable and under the control of hormonesThis allows for the regulation of water and salt balances
39 Aldosterone = “salt-retaining hormone” Secreted by adrenal cortex, triggered by;Low blood Na+Elevated K+Low BP Renin Angiotensin IIPrinciple cells with aldosterone receptors inAscending limb of nephron loopDistal convoluted tubuleCollecting duct (cortical part only)
40 Aldosterone binds nuclear receptors & activates transcription of gene for Na+/K+ pump In 10 to 30 minutes effect of pumps at work in membrane is seenNa+/K+ pump in tubular cell basal membraneMoves Na+ out= Na+ reabsorptionMoves K+ in= K+ secretion
42 which reduces blood pressure Atrial Natriuretic Peptide (ANP)Secreted by atrial myocardium in response to high blood pressureDilates afferent & constricts efferent arteriolesInhibits renin and aldosterone secretionInhibits ADH secretion and action of ADH on kidneysInhibits NaCl reabsorption by collecting ductsReduces blood volumewhich reduces blood pressure
44 Antidiuretic Hormone (ADH) Secreted by posterior pituitary, triggered by;Dehydration & rising blood osmolarityCauses more water to be reabsorbed in collecting duct, so less water lost in urineRelies on high osmolarity in extracellular fluid of inner medullaTotal = 1200 mOsm/LAbout 750 mOsm/L from NaClAbout 450 from urea (papillary region)
45 Resulting in more water being able to pass through the tubule wall ADH causes cells in collecting duct to synthesize aquaporins (water-channel proteins) & install them in plasma membraneResulting in more water being able to pass through the tubule wallWhat determines the highest osmolarity possible for urine?p 915
46 Renal ClearanceRenal Clearance = volume of blood plasma from which a particular waste is completely removed in one minuteGlomerular filtration of waste (125 ml/min)PLUS amount added by tubular secreationMINUS amount removed by tubular reabsorptionRenal ClearanceInulin = 125 ml/minUrea = 60 ml/minCreatinine = 140 ml/min
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