Nephrology
study of the kidneys
Urology
study of male and female urinary systems and male reproductive system
Kidney functions
filters blood production of hormones regulation of ion levels, blood pH, blood pressure, and glucose level during extreme starvation
Urine Characteristics
composition volume pH(4.5-8) specific gravity color and turbidity smell
Urinalysis
Analysis of the volume and physical, chemical and microscopic properties of urineWater accounts for 95% of total urine volumeTypical solutes are filtered and secreted substances that are not reabsorbedIf disease alters metabolism or kidney function, traces of substances normally not present or normal constituents in abnormal amounts may appear
Renal Cortex
outer cortical zone inner juxtamedullary zone renal columns- portions of cortex that extend between renal pyramids
Renal medulla
inner region composed of pyramids
Renal lobe
renal pyramid, overlaying cortex area and half adjacent renal column
Nephron numbers
Number of nephrons never changes, but individual nephrons can grow in sizeSigns of kidney dysfunction do not appear until function is < 25% -- remaining functional nephrons can handle the extra load1 kidney can filter blood at 80% of the rate of 2 normal kidneys
Dialysis
machine that filter blood for the patient when in kidney failure
Renal Corpuscle (nephron)
glomerulus - capillary networkglomerular capsule- surrounds glomerulus Filters blood plasma
Renal tubule (nephron)
proximal convoluted tubule nephron loop- extends into medulla, ascending and descending limbs, thick and thin segments distal convoluted tubule filtered fluid passes into here
Blood Flow (capillaries)
blood flows through 2 capillary beds glomerulus- filtration occurs here, afferent arterioles, efferent arteriolesPeritubular capillaries OR vasa rectaGas/nutrient/waste exchange occurs here
Juxtaglomerular Apparatus Cells
granular cells macula densa
Granular cells
Contract due to stretch or sympathetic stimulationSynthesize, store, & release renin
Macula Densa
Only located on side by afferent arterioleDetect changes in NaClSignal granular cells to release renin
Glomerular filtration
movement of substances from the blood within the glomerulus into the capsular spaceGlomerular filtrate - fluid that enters capsular spaceMore than 99% of filtrate will return to blood in tubular reabsorption
Tubular reabsorption
the movement of substances from the tubular fluid back into the blood
Tubular secretion
the movement of substances from the blood into the tubular fluid
Glomerular filtration membrane
Endothelium of glomerulusBasement membrane of glomerulusVisceral layer of glomerular capsule
Endothelium of glomerulus
Fenestrated - everything smaller than platelets escapes
Basement membrane
Porous - keeps in plasma proteins and anything larger
Visceral layer
Podocytes - specialized cellsPedicels - long processes that wrap around capillariesFiltration slitsseparate the pedicelscovered with membrane that restricts most small proteins
Filtrate
Filtered plasma with certain solutes and minimal proteinMesangial cells are phagocytic and help to keep the filtration membrane clean
Filtrate formation
Freely filteredWater, glucose, AAs, ions, some hormones, vitamins B &C, ketones, nitrogenous wastesNot filteredFormed elements (RBCs, WBCs, platelets)Limited filtrationIntermediate-sized proteins
Pressure and Glomerular filtration
Filtrate is produced due to pressure differences:Hydrostatic pressure of the blood in glomerulusOpposing pressures of:Osmotic blood pressureFluid pressure in capsular space
Hydrostatic pressure
Pushes" water and solutes out of glomerulus and into capsular spacePromotes filtrationDue to size difference in arterioles:Afferent arteriole has larger diameterEfferent arteriole has smaller diameter
Blood colloid pressure
Pressure exerted by blood due plasma proteinsPulls fluid back into glomerulus
Capsular hydrostatic pressure
Pressure in glomerular capsule Due to amount of filtrate already present in capsuleImpedes movement of additional fluid
GFR
The rate at which the volume of filtrate is formed. Influenced by net filtration pressureAs NFP increases, GFR increasesIf GFR is too fast, filtrate has less time to be reabsorbed more is excreted in urine
Regulating GFR
Intrinsic control Renal autoregulationExtrinsic controlNeuralHormonal
Renal Autoregulation
Kidneys themselves maintain constant renal blood flow and GFR2 mechanisms:Myogenic mechanism - Contraction and relaxation of smooth muscle in afferent arterioleTubuloglomerular feedback mechanism - too much NaCl vasoconstriction of afferent arteriole
Tubuloglomerular Feedback Mechanism
Macula densa detects NaCl in tubular fluidIf glomerular blood pressure increases, more NaCl will be in tubular fluidMacula densa signals smooth muscle in afferent arteriole to contract (vasoconstriction)Result: decreased volume of blood entering glomerulusDecreases GFR
Nerve control
Sympathetic stimulation causes:Vasoconstriction of afferent arterioleGranular cells release renin angiotensin II (vasoconstriction)Result: decrease in GFR
Hormonal control
Angiotensin II: increases GFRANP causes:Relaxation of afferent arterioleInhibition of renin releaseResult: increase in GFR
Tubular Reabsorption
most of the filtrate returns to the bloodstreamAbout 65% of filtrate reabsorbedAbout 99% of filtered water reabsorbedPCT cells make largest contribution (microvilli)
Tubular Secretion
transfer of material from blood into tubular fluidHelps eliminate substances from the body
Conditions that affect Reabsorption and Secretion
Barrier to cross: simple epithelium of tubule wallParacellular transport vs. transcellular transport Transcellular transport - must cross 2 cell membranes (luminal & basolateral)Different transport proteins embedded in different membranesPertitubular capillaries have low hydrostatic pressure (facilitates reabsorption)
Principal Cells
Responsive to aldosterone and ADH
Intercalated Cells
Regulate urine pH and blood pHType A eliminate AcidType B eliminate Base
Glucosuria
When blood glucose concentration is very high, renal symporters cannot work fast enough to reabsorb all glucoseSome glucose remains in urine
Transport Maximum
max amount of a substance you can move across the tubule epithelium in a given period of timeDependent on number of transport proteinsEx. Glucosuria
Renal Threshold
max plasma concentration of a substance without appearing in the urine
Sodium Reabsorption
Highly regulated - important for reabsorption of other solutes and waterRegulated by hormones:Aldosterone increases Na+ reabsorptionConcentration gradient established by Na+/K+ pumps
Water Reabsorption
Water movement occurs by osmosisParacellular transport or aquaporinsObligatory water reabsorption - "water follows salt"Water reabsorption also controlled by hormones that affect Na+Aldosterone increases Na+ increases water reabsorptionANP decreases Na+ decreases water reabsorption
ADH
increases water reabsorptionProduces smaller amount of concentrated urineDehydration leads to high ADH concentrationFunctions independently of Na+ regulating hormones
Calcium and Phosphate
Stored as calcium phosphatePTH acts on early DCT to regulate both:Inhibits phosphate reabsorptionIncreases calcium reabsorption
Nitrogenous waste
UreaUric acidCreatinine
Drugs and bioactive substances
Antibiotics, morphine, marijuana, etc.Metabolic wastes (bilirubin, hormone metabolites)Some hormones
Establishing the concentration gradient
ADH secretion is dependent on the concentration gradient in interstitial fluidEstablished and maintained by:Countercurrent multiplier in LoHCountercurrent exchange system in vasa rectaUrea recycling
LoH: countercurrent multiplication
For the first time, reabsorption of water is NOT automatically coupled to reabsorption of solutes because:Descending limb: water moves outPermeable to waterImpermeable to saltsAscending limb: salts pumped outImpermeable to waterPermeable to salts (has salt pumps)
Counter current exchange
Solutes and water are passively exchanged between blood of the vasa recta and interstitial fluid of the renal medullaVasa recta is a countercurrent exchangerJust like tubular fluid flows in opposite directions in the Loop, blood flows in opposite directions in vasa rectaCountercurrent flow allows for exchange of solutes and water between blood and interstitial fluid
Why doesn't water leaving LoHdilute the concentration gradient in the medulla
water is removed by the vasa recta
Urea Recycling
Urea removed from tubular fluid in collecting duct Diffuses into thin segment of ascending limbUrea remains with tubular fluid until it reaches the collecting duct againSome urea remains in interstitial fluid, contributing to concentration gradient
Diuretics
substance that slows renal absorption and causes diuresis Diuresis - elevated urine flow rate Diuretics often used to treat hypertension by lowering blood volumeNaturally occurring diuretics: caffeine inhibits Na+ reabsorptionalcohol inhibits ADH secretion
Measuring GFR
To assess kidney function, you can measure the rate that filtrate is formed per unit of time (GFR)Inject patient with inulin Freely filteredNot reabsorbed or secretedMeasure amount of inulin in urine and blood
Renal Plasma Clearance
Measures volume of plasma that can be completely cleared of a substance in a period of timeCan infer if substance is reabsorbed or secretedUsed to determine amount and timing of drug dosage
Ureters
Each of 2 ureters transports urine from renal pelvis of one kidney to the bladderPeristaltic waves, hydrostatic pressure and gravity move urineNo anatomical valve at the opening of the ureter into bladder - when bladder fills it compresses the opening and prevents backflow
Urinary Bladder
Hollow, distensible muscular organ with rugaeMicturition reflex kicks in around 200 mLMax capacity averages 800 mL
Urethra
Small tube leading from internal urethral orifice in floor of bladder to exterior of the bodyIn males discharges semen as well as urine
Micturition
Discharge of urine from bladderCombination of voluntary and involuntary muscle contractionsWhen volume increases stretch receptors send signals to micturition center in spinal cord triggering spinal reflex - micturition reflexRegulated by autonomic NSIn early childhood we learn to initiate and stop it voluntarily