Chapter 25: Urinary System and Renal Physiology

kidneys

~200 liters of fluid filtered from blood by _____ every single day

function of kidneys

• Maintaining the composition of the body’s extracellular fluids by filtering the blood. This involves:
• 1) Regulate total body water volume and concentration of solutes in water
• 2) Regulate concentration of ions in ECF
• 3) Acid-base balance
• 4) Remove toxins, metabolic wastes, & other foreign substances
• 5) Hormone production-EPO and renin

gross anatomy of kidneys: external

• Each kidney lies between the parietal peritoneum and dorsal body wall
• Kidneys are retroperitoneal organs
• How is this different from other body organs? Kidneys don’t have a visceral or parietal peritoneum
• Medial portion is concave
• Renal hilum
• Adrenal gland sits immediately superior to each kidney

renal hilum

Ureters, renal blood vessels, lymphatics, and renal nerve supply enter here

supporting external structures of kidneys

• 1) Renal fascia
• 2) Perirenal fat capsule
• 3) Fibrous capsule

renal fascia

• Dense connective tissue
• Function: anchors kidneys to surrounding structures

perirenal fat capsule

• Fat mass surrounding kidneys
• Function: Cushions kidneys from physical trauma

fibrous capsule

• Thin, transparent capsule
• Function: prevents disease from spreading to kidneys from other parts of body

gross anatomy of kidneys: internal

• 3 major internal regions of kidneys:
• 1) Renal Cortex
• 2) Renal Medulla
• 3) Renal Pelvis

renal cortex

Functions: provides area for glomerular capillaries and blood vessel passage, EPO produced here

renal medulla

• Contain renal pyramids
• Seven (7) renal pyramids separated by renal columns

renal pyramids

Packed with capillaries & urine-collecting tubules

kidney lobe

Renal pyramid + surrounding columns

renal pelvis

• Open space in center of each kidney
• Pelvis branches to form major calyces (calyx)
• Major calyces lead into minor calyces at tip of each renal pyramid
• Function of major & minor calyces: urine collection from renal medulla

renal arteries

• _____ deliver to kidneys → divide into smaller blood vessels to serve major regions of kidney:
• 1) Segmental arteries (5)
• 2) Interlobar arteries
• 3) Arcuate arteries
• 4) Cortical radiate arteries

interlobar arteries

Travel between kidney lobes

arcuate arteries

Arch over bases of pyramids

cortical radiate arteries

Supply cortical tissue

veins

• _____ trace arterial supply, but in reverse
• 1) Cortical radiate veins
• 2) Arcuate veins
• 3) Interlobar veins
• 4) Renal veins

renal plexus

• Autonomic nerve fibers & ganglia
• Sympathetic vasomotor fibers regulate blood supply to each kidney
• Function: Adjusts diameter of renal arterioles to adjust blood flow to glomeruli
• What is the importance of changing blood flow to the kidneys? Changes the amount of urine formed and regulates blood pressure

nephron

• The _____ is the functional unit of the kidney
• Function: Responsible for forming filtrate and eventually urine in the kidneys
• General structure of _____:
• Each _____ contains a renal corpuscle and renal tubule

renal corpuscle

Filters blood to form the filtrate

renal tubule

• Reabsorbs what is needed for the body from the filtrate & secretes more substances into the filtrate
• What happens to anything that is secreted into filtrate or not reabsorbed from filtrate? Will be excreted in urine

renal corpuscle

• Located entirely within renal cortex
• Subdivisions:
• 1) Glomerulus
• 2) Glomerular capsule

glomerulus

• Cluster of blood vessels
• Blood enters _____ via afferent arteriole, leave via efferent arteriole
• What is the significance? Arterioles keep _____ high pressure to speed up filtration
• Capillaries are very porous → fluid passes from blood in the glomerular capillaries and into glomerular capsule
• Fluid is called filtrate

filtrate

Raw material used to produce urine

glomerular capsule

• Double-layered structure that completely surrounds glomerular capillaries
• Inner layer has podocytes with foot processes
• What is the function and importance of these 2 structures? Prevent large substances from entering filtrate

renal tubules and collecting duct

• Begins in renal cortex, extends into renal medulla, then returns to renal cortex
• What is the benefit of this hairpin-like structure? Increases surface area
• Subdivisions:
• 1) Proximal convoluted tubule (PCT)
• 2) Nephron Loop (formerly Loop of Henle)
• 3) Distal Convoluted Tubule (DCT)
• 4) Collecting Ducts

proximal convoluted tubule (PCT)

• Leads immediately off from glomerulus
• Located in renal cortex
• Large cuboidal epithelia cells with dense microvilli

nephron loop

• Travel between renal cortex and renal medulla
• Descending limb
• Ascending limb
• Function: allows the kidneys to vary the concentration of urine according to how much water is reabsorbed at _____

descending limb

• Portion continuous with PCT
• High permeability to H2O, low permeability to solutes

ascending limb

• Continuous with DCT
• High permeability to solutes, low permeability to H2O

distal convoluted tubule (DCT)

• Located in cortex, composed of small cuboidal epithelia
• Smaller diameter than PCT, contain no microvilli
• What does the microanatomy of the _____ indicate? Almost no reabsorption happens here

collecting ducts

• Ducts pass through cortex and medulla
• Important cell types in _____:
• 1) Principal cells
• 2) Intercalated cells
• Each _____ receives filtrate from tubules of multiple nephrons
• _____ fuse together, dump urine into minor calyces

principal cells

• Maintain Na+ balance in body
• Would this influence absorption of other substances? Yes

intercalated cells

Help maintain acid-base balance

types of nephrons

• 1) Cortical Nephrons
• 2) Juxtamedullary Nephrons

cortical nephrons

• Located almost entirely in the cortex
• Small portion of nephron loop found in renal medulla

juxtamedullary nephrons

• Nephron loops deeply invade renal medulla
• How does a change in nephron structure affect urine formation? _____ are more useful at reabsorbing water than cortical nephrons

capillary beds of nephrons

• 1) Glomerulus
• 2) Peritubular Capillaries
• 3) Vasa Recta

glomerulus

Maintains high pressure to increase filtrate production

peritubular capillaries

• Low pressure capillaries arising from efferent arteriole
• Cling to proximal & distal tubules of cortical nephrons
• Reabsorb water & solutes from tubule cells
• Empty into venules → filtered blood returns to circulation

vasa recta

• Found only on juxtamedullary nephrons
• Run parallel to long nephron loop
• Help form concentrated urine
• How? Reabsorbs lots of water from nephron loop

juxtaglomerular complex

• Portion of nephron where distal ascending limb lies against arterioles
• Overall function: Regulate blood pressure & filtration rate of the glomerulus
• 3 cellular modifications at this point of contact
• 1) Macula densa
• 2) Granular cells (Juxtaglomerular cells)
• 3) Extraglomerular mesangial cells

macula densa

• Chemoreceptor cells
• Function: Monitor NaCl content of filtrate entering distal convoluted tubule
• How does the rate of filtrate formation affect NaCl concentration in the DCT? What happens to the afferent arteriole to “fix” this problem? If the rate of filtrate formation is low, more NaCl is reabsorbed and afferent arteriole vasodilates; If rate of filtrate formation is high, less NaCl is reabsorbed and afferent arteriole vasoconstricts

granular cells (juxtaglomerular cells)

• Specialized smooth muscle cells
• Found in arteriolar walls of afferent arteriole
• Can sense blood pressure in afferent arteriole
• Also stimulated by macula densa cells
• Contain granules that secrete renin
• Renin mostly affects the efferent arteriole!

increased renin release

low NaCl concentration, low pressure in arteriole

decreased renin release

high NaCl concentration, high pressure in arteriole

extraglomerular mesangial cells

• Packed between tubule and arterioles
• Function: ??

diuresis

urine formation

process of diuresis

• 1) Glomerular Filtration
• 2) Reabsorption
• 3) Secretion

glomerular filtration

• Production of a cell and protein-free filtrate that serves as the raw material for urine
• Where does this occur? Glomerulus
• Pressure forces fluid out of glomerular capillary & into glomerular capsule

filtration membrane

• The _____ allows passage of water, small solutes into glomerular capsule. 3 layers make up this membrane:
• 1) Fenestrated endothelium of capillaries
• 2) Basement membrane
• 3) Foot processes of podocytes

fenestrated endothelium of capillaries

Pores in capillary walls allow all but large proteins and cells to pass through

basement membrane

Negatively charged layer that allows only passage of small molecules & electrically repels other macromolecular anions

foot processes of podocytes

• Foot processes create filtration slits
• Slits prevent passage of macromolecules/large sized materials into filtrate

filtration pressures

Pressures that force fluid into or out of glomerulus

outward pressure

Promotes filtrate formation

hydrostatic pressure in glomerular capillaries (HPgc)

• Blood pressure of the glomerular capillaries that forces fluid into the surrounding space
• Remember: outward pressure here is always HIGH
• Why is this necessary? Ensures kidneys are able to filter blood

inward pressures

Oppose filtrate formation

hydrostatic pressure in capsular space (HPcs)

Pressure exerted by filtrate that is already in the glomerular capsule

colloid osmotic pressure in glomerular capillaries (OPgc)

Proteins that are still in capillaries will “pull” water back in

glomerular filtration rate (GFR)

The total volume of filtrate formed per minute for all nephrons in the kidneys

factors affecting GFR

• 1) Net Filtration Pressure (NFP)
• 2) Surface area of capillaries
• Glomerular mesangial cells adjust surface area of capillaries
• How does this affect GFR? Increased surface area = increased filtrate rate
• 3) Filtration membrane permeability
• Filtration occurs along the entire length of a glomerular capillary
• How is this different from other capillaries in the body? Filtration normally only occurs on one side of capillaries

regulation of GFR

• Tightly regulated for two reasons:
• 1) Kidneys need constant GFR to make filtrate and maintain extracellular homeostasis
• 2) Regulating GFR regulates blood pressure in entire body
• Ex: decreasing GFR will decrease urine output
• Primary variable controlled: HPgc
• Control can be intrinsic (renal) or extrinsic (CNS)

increase in HPgc

increase in NFP and GFR

decrease in HPgc

decrease in NFP and GFR

renal autoregulation

• (Intrinsic): kidneys adjust resistance to blood flow
• Intrinsic controls can maintain GFR for blood pressures ranging 80-180 mm Hg

myogenic mechanism

• Smooth muscle contracts when stretched
• Rising systemic blood pressure stretches afferent arteriole → afferent arteriole constricts
• Blood flow into glomerulus restricted to maintain GFR at desirable rate

tubuloglomerular feedback mechanism

• Controlled by macula densa of juxtaglomerular complex (JGC)
• Remember: macula densa monitor NaCl concentrations
• Increasing GFR = decrease in reabsorption rate
• Macula densa cause vasoconstriction of afferent arteriole → decreases blood flow into glomerulus
• GFR decreases to increase reabsorption rate

neural mechanisms

• (Extrinsic)
• The sympathetic nervous system will override renal autoregulation
• When? Why? When systolic pressure drops below 80 mm Hg in order to maintain filtration rate
• Norepinephrine released by sympathetic system in response to low blood pressure
• Vascular smooth muscle contracts

hormonal mechanisms

• (Extrinsic)
• Renin-Angiotensin-Aldosterone mechanism → overall effect is to increase BP
• Granular cells of JGC stimulated to release renin
• Activation can involve:
• 1) Stimulation by sympathetic nervous system
• 2) Activated macula densa cells
• Macula densa sense low NaCl concentrations in response to decreased GFR
• 3) Reduced stretch of arteriole walls
• Decreased stretch of arteriole walls = low blood flow/pressure

reabsorption

• Selectively moving substances from the filtrate back into the blood
• 99% of filtrate is reabsorbed by the body
• Substances can either move in between kidney tubule cells (paracellular) or through kidney tubule cells (transcellular)

reabsorption of Na+

transcellular, active process

reabsorption of nutrients and ions

• Can be transcellular or paracellular
• Secondary active transport: moves glucose, amino acids, ions, vitamins
• Na+ transported into cell & cotransports another solute with it
• Co-transported molecule moves across basolateral membrane via facilitated diffusion & enters capillary

reabsorption of water

• Passive
• Some H20 absorbed via paracellular route
• Transmembrane protein aquaporin allows water to cross plasma membrane of tubule cell
• PCT has many aquaporins → water is always absorbed here
• Collecting ducts have no aquaporins until antidiuretic hormone (ADH) is present

transport maximum (Tm)

• Any pathway using a transport protein has a _____
• The more transport proteins for a specific molecule, the higher the amount absorbed
• What happens when all the transport proteins for a particular substance are bound? Urine will contain lots of the substance because it can’t be reabsorbed

reabsorption in PCT

• Contain villi and microvilli
• Why is this important for reabsorption? Increases surface area
• All glucose, amino acids, most nutrients reabsorbed here
• Most water and Na+ also reabsorbed here (~65%)
• Most electrolytes reabsorbed here
• Uric acid and urea also reabsorbed here

reabsorption in nephron loop

• Water reabsorption is not coupled to solute reabsorption here
• Water can leave the descending limb, but not the ascending limb
• Solutes can leave the ascending limb, but not the descending limb
• Importance: the difference in permeability between the ascending limb and descending limb allows the nephron to form dilute or concentrated urine

reabsorption in DCT and collecting duct

• Most water and solutes have already been reabsorbed by PCT and nephron loop
• Hormonally controlled
• 1) Antidiuretic hormone (ADH)
• 2) Aldosterone
• 3) Atrial natriuretic peptide (ANP)
• 4) Parathyroid hormone (PTH)

antidiuretic hormone (ADH)

• Inhibits urine formation by increasing water reabsorption to blood
• If water is returned to blood → it will not be put in urine
• Aquaporins inserted into collecting ducts
• Amount of _____ is directly proportional to number of aquaporins inserted

aldosterone

Promotes Na+ reabsorption by principal cells of collecting ducts

atrial natriuretic peptide (ANP)

• Inhibits Na+ reabsorption in collecting ducts
• What hormone has the opposite effect of _____? Aldosterone

parathyroid hormone (PTH)

Increases reabsorption of Ca2+ in the DCT

secretion

• Selectively moving substances from the blood and back into the filtrate (”reabsorption in reverse”)
• Main site: PCT (but also occurs in collecting duct)
• Functions:
• 1) Eliminates waste/undesirable material that are passively reabsorbed
• Ex: nitrogenous wastes urea & uric acid
• 2) Rids body of excess K+ in DCT and collecting ducts
• 3) Controls acid-base balance & blood pH
• Secretion of excess H+ or HCO3-

regulating urine concentration and volume

• The normal solute concentration of body fluids & ICF is ~300 mOsm
• Osmolality is high during dehydration, low during overhydration
• Why? During dehydration, kidneys reabsorb more water and during overhydration, kidneys reabsorb less water
• Kidneys allow body to make constant adjustments based on intake and loss of fluids to maintain this normal osmotic concentration

low fluid intake

kidneys produce small amount of concentrated urine (has low water content)

high fluid intake

kidneys produce large amount of dilute urine (has high water content)

countercurrent exchange mechanism

• Movement of fluids in the opposite direction through the nephron loop allows exchange of material
• Countercurrent multiplier
• Countercurrent exchange

countercurrent multiplier

• Occurs in ascending and descending limb of juxtamedullary nephron loops
• Function: movement of solutes & water out of nephron loop allows for formation of concentrated urine

countercurrent exchange

• Flow of blood through the ascending and descending limb of the vasa recta
• Function: vasa recta reabsorbs water to maintain gradient of multiplier

medullary osmotic gradient

Countercurrent exchange mechanism establishes a _____ → kidneys can vary urine concentration

process of countercurrent multiplier

• The ascending limb transports solutes (NaCl) out of the tubule
• The descending limb transports water out of the tubule
• Solutes are pumped out of the ascending limb filtrate and into the interstitial space
• This creates a gradient! (NaCl concentration is higher outside the tubule than inside)
• Water will follow this gradient from the descending limb and into the interstitial space
• Water is reabsorbed by the vasa recta
• As you approach the hairpin turn, osmolality of the filtrate becomes highest

process of countercurrent exchange

• Maintains the osmotic gradient established in the multiplier by:
• 1) Preventing removal of Na+ and Cl- from the interstitial space
• 2) Removing water from interstitial space (i.e., water is reabsorbed into bloodstream)

urea recycling and osmotic gradient

• Urea enters filtrate in thin ascending limb
• Urea moves into interstitial fluid
• The urea in interstitial fluid eventually moves back into ascending limb (“recycling”)
• Urea increases osmolality → strengthens osmotic gradient

forming dilute urine

• Overhydration leads to dilute urine
• ADH release decreases
• Aldosterone release increases → reabsorb ions from filtrate, leaving mostly water
• **In order for this to work → no aquaporins!

forming concentrated urine

• Dehydration leads to concentrated urine
• ADH release increases → aquaporins allow increased water reabsorption
• Maximal reabsorption brings 99% of water back in from filtrate
• Urine can reach 1200 mOsm to conserve water

homeostatic imbalance of renal function

Chronic renal disease

chronic renal disease

• GFR of <60 ml/min for 3+ months
• Filtrate formation decreases → wastes build up, blood pH decreases
• Caused by: diabetes mellitus, hypertension, pyelonephritis, physical trauma
• Renal failure occurs when GFR <15 ml/min
• Uremia
• Multiple organ failure eventually occurs → EPO release stops, severe ion imbalances, metabolic abnormalities and accumulation of toxins in body
• Treatments: hemodialysis & kidney transplant

uremia

”Urine in the blood” (nausea, muscle cramps, mental changes, fatigue, etc. etc.)