Renal physiology

• 1. Excretion of waste (urea, allantion, creatinine, bile pigments)
• 2. excretion of foreign chemicals
• 3. maintain electolyte composition
• 4. maintain body fluid composition
• 5. produce renin (regulate BP, water, ions)
• 6. secrete erythropoietin (stimulates RBC production)
• 7. activate vitamin D (calcium and phosphate)
• 8. regulate acid-base balance

secreted in urine, made from breakdown of amino acids

• secreted in urine, made from breakdown of purine nucleic acids (A and G)
• Primates and some dogs (Dalmations) secrete uric acid instead (lack metabolic pathway)

urea, allantoin (uric acid), creatinine, bile pigements

enzyme that plays key role in regulating blood pressure and levels of water and many ions in body fluids. 

water you know you're losing, like urine

water you can't tell you're losing--can't perceive or measure.  Transdermal, respiratory. 

heart shaped

kidney-shaped

lobulated

smooth muscular tube that conveys urine from renal pelvis to urinary bladder

at entrance to bladder, prevens urine from going backwards. 

hollow muscular organ with smooth muscle (detrusor) and transitional epithelium lining

smooth muscle of urinary bladder

low near cortex, high near renal pelvis

smooth muscle and elastic fibers of narrow part of bladder leading to urethra act as internal sphincter. 

• caudal continuation of neck of bladder to exterior. 
• External sphincter: skeletal muscle that encircles urethra to separate bladder from urethra. 

• functional unit of the kidney.  Glomerulus, bowman's capsule, proximal convoluted tubules, loop of henle, distal convoluted tubules, collecting duct. 
• 2 different kinds, identified based on location of glomerulus and how deep loops into medulla are.
• Cortical (corticomedullary) nephron
• Juxtamedullary nephron

• glomerulus is in outer and middle cortexes
• Loops of henle are at junction of cortex and medulla

tuft of capillaries surrounded by Bowman's capsule, place where blood transfers waste, etc.

• glomeruli are in the cortex close to the medulla (lower)
• loops of henle extend more deeply into the medulla
• develop and maintain osmotic gradient

enters collecting tubes, exposed to effects of medullary osmotic gradient

where blood enters glomerulus.  Branch of branch (one of many) of renal artery.

where blood leaves glomerulus.  Leads all around convoluted tubules to second capillary bed (peritubular and vasa recta) becomes branch of renal vein

second capillary bed after glomerulus, making kidney a portal system.  Includes vasa recta

part of blood flow to nephron, the lower loop of renal vein that entertwines with loop of henle.

Afferent/efferent arterioles, glomerulus, bowman's capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule, collecting duct., peritubular capillaries, vasa recta

• the junction between the distal tubule and glomerulus
• Regulates blood flowing to the kidney, amount of filtration, secretion of renin
• Includes juxtaglomerular cells (secrete renin), macula densa (in distal tubule, control amt of renin and glomerular filtrate), extraglomerular mesangial cells (erythropoietin?)

secrete renin.  At juxtaglomerular apparatus.

• contained in distal tubule at juxtaglomerular apparatus. 
• Control/influence amount of renin produced and amount of glomerular filtrates.

between macula densa and arterioles.  Possibly responsible for secretion of erythropoeitin.

• Not urine until it hits the renal pelvis. 
• three processes: Glomerular filtration, tubular reabsorption, tubular secretion

bulk flow of fluid from glomerular capillaries into Bowman's capsule.  Travels nephron, subject to reabsorption and secretion

Movement of useful substances from the flitrate in renal tubules back into capillaries around the tubules.  Stuff you want to keep (water, glucose, amino acids, vitamins, bicarbonate ions, chloride salts of calcium, magnesium, sodium, potassium. 

• substances that are actively secreted into the tubules.  Stuff you want to get rid of. 
• ammonia, hydrogen ions, potassium, drugs

• Filtration, reabsorption, secretion, excretion
• Excretion = filtration - reabsorption + secretion

• ions are smallest (Na+, Cl-, glucose)
• Albumin
• globulins (beta and gamma)
• lipoproteins (alpha and beta)
• fibrinogen
• red blood cell is HUGE

• filtration barrier that separates the glomerular capillaries from the capsular space.  Filtration occurs through this membrane, restricting based on size and charge.
• 3 layers include Fenestrated capillary endothelium, Glomerular basement membrane, filtration slit diaphragm of epithelial foot processes

• Weights below ~65,000 (below albumin, glucose and NaCl)
• positively charged molecules easier than negative
• NOT albumin

water, amino acids, glucose, urea, allantoin, uric acid, creatinine, ions

volume of filtrate formed per unit time

• passive process, Starling's law (capillary surface area, permeability, hydrostatic and oncotic pressure gradients determine movement)
• Filtration rate is determined by pressure gradients between two spaces

• Pressure exerted by a liquid. 
• High in capillary
• low in bowman's space.  drive filtration into Bowman's space

• osmotic pressure exerted by colloids.  opposes movement of fluid out. 
• none in Bowman's space (no big molecules)
• higher in capillary.  So fluid won't move out of capillary
• Net filtration pressure is positive.

hydrostatic pressure in glomerulus capillary - oncotic pressure in glomerulus capillary - hydrostatic pressure in bowman's capsule = net filtration flow

P_GC - Pi_GC - P_BC = Net Filtration Flow

• Processes that prevent blood flow from increasing when pressure increases.  Stops massive dehydration when exercising, for example.  Work well but not perfectly.  Can't work at arterial pressure below 70 mmHg, can't fix neuroendocrine factors like sympathetic NS or angiotensin II
• Myogenic mechanism
• Tubulogloermular feedback

• BP increase, smooth muscle stretches, vessel constricts. (or opposite) Like a rubber band.
• To keep GFR (P/R) constant, if pressure increases, resistance has to increase.  Afferent arteriole constricts to increase resistance.  Increased arteriole (BP) pressure raise renal blood flow and GFR.  Afferent arteriole constriction lowers these.  Cancel out (stretch a rubber band, pushes back).

When blood pressure increases, GFR increases, flow rate increases, less time to reabsorb NaCl in tubules, high osmolarity in tubules, the macula densa senses change, releases vasoconstrictor, constricting the afferent arteriole, raising resistance and keeping GFR steady.  Or opposite

• humoral mechanism moderating GFR in normal animals
• Renin released, turns liver's angiotensinogen into angiotensin I, ACE turns I into angiotensin II

• released from juxtaglomerular cells in afferent arterioles when
• systemic arterial BP goes down so renal BF goes down so pressure in glomerular capillary goes down
• low Na+ concentration in blood plasma
• activation of sympathetic nervous system

• Does a LOT of things, ultimately raises blood pressure back towards normal. 
• stimulates sympathetic NS (up HR, up contractility, up arteriolar constriction = up CO, up BP)
• constricts arterioles (up PVR = up BP)
• Constricts efferent arteriole (up GC pressure)
• reabsorbs Na+ and H2O from proximal tubule (up plasma volume = up VR and preload = up CO, up PVR = up BP)
• stimulates posterior pituitary to secrete ADH (up plasma volume, up VR)
• Stimulates adrenal cortex to secrete aldosterone (up plasma volume, up VR)

• Sympathetic neurons release high levels of NEpi--override. 
• Constricts afferent and efferent arterioles, temporarily suspends kidney function to move blood to more useful areas.
• Lowers GFR and RBF (more RBF) and stimulates sodium and water absorption in proximal tubules, raising arterial pressure toward normal. 
• Also release renin (constrict renal arterioles via angiotensin II)

• movement of substances from tubular lumen into peritubular capillaries.  Reabsorbed substances re-enter systemic circulation. 
• Reabsorb glucose and amino acids with secondary active transport into interstitial space then diffusion into peritubular capillaries. 
• Secondary active reabsorption with sodium also includes amino acids, inorganic phosphate, sulfate, organic nutrients
• water by osmosis into ISF (toward higher osmolarity), increasing concentration, increasing diffusion

• movement of substances from peritubular capillaries into tubular lumen to be removed from the body in urine.
• H+ throughout length of nephron except henle.  Coupled with HCO3-
• K+ secretion coupled with Na+ reabsorption (pump)
• ammonia
• organic molecules (bile salts, fatty acids, urate, creatinine, dopamine, drugs)

• Solutes are reabsorbed (amino acids, glucose, Na+)
• osmolarity decreases in tubular lumen
• water moves out of tubular lumen by osmosis
• more concentrated makes more diffusion. 
• Both solutes and water absorbed in same percentage.

• reabsorbs more sodium and chloride than water.  DIFFERENT than proximal tubules.
• Responsible for concentration gradient in medulla of kidney.  Concentrated near renal pelvis, dilute in cortex.
• Fluid is dilute compared to plasma when it leaves

does not absorb sodium or chloride, permeable to water.  tubular fluid becomes hyperosmotic/hyperconcentrated

reabsorbs sodium and chloride not water.  Diluting segment.  Tubular fluid becomes hypoosmotic

• sodium and chloride reabsorbed via cotransport
• water permeability low and unchanging. 
• Diluting segment. 

• Principal cells (latter distal tubule) reabsorb sodium, secrete K+
• type-B-intercalated cells (medullary collecting duct) reabsorb chloride (also acid base, also Type A)
• water permiability is hormone-controlled (ADH).

dilute urine

concentrated urine

• Hormone secreted by adrenal cortex.  Stimuli for secretion are angiotensin II or high K+ in blood plasma. 
• Acts on principal cells to up Na and down K+

• decide how acidic or alkaline the urine is. 
• Type A is for too acidic (H+ in urine)
• Type B is too alkaline (bicarb in urine)

• where final concentration of urine is determined. 
• Hormone (ADH) controlled, changes permiability of membrane to water to concentrate or dilute urine. 

Makes membrane very permeable to water, lots of aquaporins, so less water and very concentrated by the end.  Done when dehydrated. 

membrane less permeable to water, few aquaporins, more water in urine, dilute urine. 

• Lots of water, low ADH in collecting tubule, hypotonic, hypo-osmotic
• specific gravity 1.000-1.008

• Conservation of water.  Hyperosmotic, hypertonic. 
• Specific gravity higher than 1.014

• antidiuretic hormone (vasopressin).  Changes the H2O permiability of the collecting duct to water. 
• Secreted by pituitary posterior lobe. 
• Secretion stimulated by high plasma osmolarity (thick blood sensed by osmoreceptors), low blood volume or pressure, Angiotensin II

• Posterior pituitary secretes when osmoreceptors or baroreceptors recognize: 
• High osmolarity, low blood volume, low blood pressure, angiotensin II

• Acts on the collecting ducts on the pricipal cells (absorb sodium and secrete potassium), which have vasopressin (V2) receptors. 
• On the vasolateral side, vasopressin stimulates V2 receptor which releases cAMP which inserts vesicles with aquaporin channels into the wall. 
• Increases permeability.
• Without ADH, endocytosis pulls channels back in. 

• plasma osmolarity decreases, inhibits osmoreceptors in anterior hypothalamus, decreases secretion of ADH, decreases water permeability of late distal tubule and collecting duct, decreases water reabsorption,
• decreases urine osmolarity and increases urine volume (dilute)
• increases plasma osmolarity (less water in blood)

• increases plasma osmolarity, stimulates osmoreceptors in anterior hypothalamus, increases secretion of ADH from posterior pituitary, increases water permeability of late distal tubule and collecting duct, increases water reabsorption
• increases urine osmolarity and decreases urine volume (concentrated)
• Decreases plasma osmolarity (more water)

• Ratio that compares the weight of a fluid to the weight of an equal volume of pure water.  Used to test kidney function. 
• Total solute concentration in a solution. 

1.009-1.012

1.000-1.008

• 1.009-1.012
• SAME as blood plasma--may mean that the kidneys are not doing anything if blood is not also normal. 

greater than 1.014

Through aquaporins made by ADH, with simple diffusion, using a concetration gradient created by the counter current multiplier mechanism in the loop of henle (fluid must be hyperosmotic to attract water)

establishes hyperosmolarity gradient in renal medulla.  Uses ascending loop of henle which is impermeable to water, so solute (sodium) is reabsorbed into medullary interstital, acts to separate solute from water. 

• blood supply to renal medulla.  2 functions
• Provide nutrients and oxygen to tubules in medulla
• help maintain medullary interstitial osmotic gradient (countercurrent exchanger)

• Angiotensin II (ups reabsorption of NA, Cl, H2O)
• Aldosterone (ups reabsorption of NA, Cl, HCO3, H2O)
• ADH (ups reabsorption of H2O)

Proximal tubules

hydrogen-ion secretion

in collecting tubules.  H+ is secreted, Bicarb and K+ are reabsorbed, acidic urine

• Kidney can create it.  2 methods. 
• involved with H+ secreted in tubular lumen
• related to ammonium production and secretion by proximal tubular cells. 

• excrete HCO3- and K+, H+ reabsorbed. 
• Alkalize urine
• increases filtered load of bicarb
• returns body pH to normal.