major kidney functions (8)
- 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)
Waste products of cellular metabolism secreted from kidney
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.
Sensible body fluid loss
water you know you're losing, like urine
insensible water loss
water you can't tell you're losing--can't perceive or measure. Transdermal, respiratory.
Horse's right kidney
horse's left kidney
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
Concentration gradient of medulla
low near cortex, high near renal pelvis
neck of bladder
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
Corticomedullary nephron (cortical 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.
Parts of a nephron
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.
Extraglomerular mesangial cells
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
4 processes of urine formation
- Filtration, reabsorption, secretion, excretion
- Excretion = filtration - reabsorption + secretion
Relative sizes of the constituents of blood (6, 3 important)
- ions are smallest (Na+, Cl-, glucose)
- globulins (beta and gamma)
- lipoproteins (alpha and beta)
- 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
What gets through glomerular membrane?
- Weights below ~65,000 (below albumin, glucose and NaCl)
- positively charged molecules easier than negative
- NOT albumin
Major components of glomerular filtration
water, amino acids, glucose, urea, allantoin, uric acid, creatinine, ions
Glomerular filtration rate (GFR)
volume of filtrate formed per unit time
How does fluid move across glomerular membrane?
- 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
Hydrostatic pressure in the kidney
- Pressure exerted by a liquid.
- High in capillary
- low in bowman's space. drive filtration into Bowman's space
Oncotic pressure in kidney
- 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.
Glomerular filtration equation
hydrostatic pressure in glomerulus capillary - oncotic pressure in glomerulus capillary - hydrostatic pressure in bowman's capsule = net filtration flow
PGC - PiGC - PBC = 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
Myogenic mechanism of autoregulation
- 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
Renin-angiotensin aldosterone system (RAS)
- 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
Affects of angiotensin II
- 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 NS on severe hypotension
- 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)
- 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.
Henle's loop reabsorption
- 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
Descending loop of Henle
does not absorb sodium or chloride, permeable to water. tubular fluid becomes hyperosmotic/hyperconcentrated
Ascending loop of Henle
reabsorbs sodium and chloride not water. Diluting segment. Tubular fluid becomes hypoosmotic
Distal convoluted tubules
- 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).
- 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+
Intercalated cells of collecting ducts, 2 types
- 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.
High ADH incollecting tubule
Makes membrane very permeable to water, lots of aquaporins, so less water and very concentrated by the end. Done when dehydrated.
Low ADH in collecting tubule
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
Secretion of ADH
- Posterior pituitary secretes when osmoreceptors or baroreceptors recognize:
- High osmolarity, low blood volume, low blood pressure, angiotensin II
Effect of ADH
- 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.
Drink water, then...
- 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.
Specific gravity of plasma
specific gravity of dilute urine
specific gravity of isosthenuric urine
- SAME as blood plasma--may mean that the kidneys are not doing anything if blood is not also normal.
concentrated urine specific gravity
greater than 1.014
How does water leave collecting duct?
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)
Countercurrent multiplier mechanism
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)
Hormones regulating tubular reabsorption and secretion
- Angiotensin II (ups reabsorption of NA, Cl, H2O)
- Aldosterone (ups reabsorption of NA, Cl, HCO3, H2O)
- ADH (ups reabsorption of H2O)
Where is filtered bicarbonate (80%) reabsorbed?
How does the Loop of Henle absorb bicarb?
Type-A intercalated cells
in collecting tubules. H+ is secreted, Bicarb and K+ are reabsorbed, acidic urine
How is new bicarb made?
- Kidney can create it. 2 methods.
- involved with H+ secreted in tubular lumen
- related to ammonium production and secretion by proximal tubular cells.
Type B intercalated cells
- excrete HCO3- and K+, H+ reabsorbed.
- Alkalize urine
- increases filtered load of bicarb
- returns body pH to normal.