CH 25 - Urinary System

kidneys - description

• retroperitoneal (between the dorsal body wall and the parietal peritoneum)

• superior lumbar region (T12 to L4)

• right kidney lies slightly lower than the left due to liver

kidneys - function

• Regulating the total volume/pressure of water in the body and the total concentration of solutes in that water (osmolality)

• Regulating the concentrations of the various ions in the extracellular fluids

• Ensuring long-term acid-base balance (pH)

• Excreting metabolic wastes and foreign substances such as drugs or toxins

• Producing erythropoietin and renin, important molecules for regulating red blood cell production and blood pressure, respectively

• Converting vitamin D to its active form

• Carrying out gluconeogenesis during prolonged fasting

ureters - function

• paired tubes that transport urine from the kidneys to the urinary bladder

• Incoming urine distends the ureter and stimulates its muscularis to contract, propelling (peristaltic waves) urine into the bladder

• sympathetic and parasympathetic fibers innervate each ureter, but neural control of peristalsis is less common

ureter - histology

• mucosa = transitional epithelium

• muscularis

  • 2 smooth muscle sheets

  1. internal longitudinal layer

  2. external circular layer

  • external longitudinal layer (smooth muscle layer)

• adventitia =fibrous CT

ureter - description

• begins at the level of L2

• descends behind the peritoneum

• runs obliquely through posterior bladder wall

  • prevents backflow of urine

urinary bladder - function

• temporary storage reservoir for urine

• when empty = collapsed (pyramidal shape)

• when full = expands to pear shape and rise superiorly

urinary bladder - histology

• mucosa = transitional epithelium

• muscular (detrusor) = intermingled smooth muscle fibers

  • inner and outer longitudinal

  • middle circular layer

• adventitia = fibrous CT

  • except superior surface covered by peritoneum

urinary bladder - description

• retroperitoneally on the pelvic floor just posterior to the pubic symphysis

• smooth, collapsible, muscular sac

• has opening for both ureters and urethra

trigone - bladder

• contains 2 ureteric orifices = where the ureters enter the bladder

• contains 1 internal urethra orifice = where urine exits the bladder into the urethra

urethra - function

• thin-walled muscular tube that carries urine from the bladder to the body exterior

urethra - histology

• mucosal lining = pseudostratified columnar epithelium

  • near bladder becomes transitional epithelium

  • near external opening becomes protective stratified squamous epithelium

*female = long & fibrous CT

internal urethral sphincter - urethra

• smooth muscle

• involuntary sphincter controlled by the ANS

  • keeps the urethra closed when urine is not being passed and prevents leaking

external urethral sphincter - urethra

• skeletal muscle

• voluntarily controlled

renal hilum

• entry/exit point of the kidneys

  • entry = renal artery

  • exit = renal vein & ureter

• medial side of each kidney

renal sinus

• occupied mostly by fat

• calyces, blood vessels, and nerves are embedded

renal capsule

• enclose kidney

• transparent capsule that prevents infection in surrounding regions from spreading to the kidney

adipose capsule

• provide cushioning

• fatty mass that surrounds the kidney and cushions it against blows

renal fascia

• provide stability and protection

• outer layer of dense fibrous CT that anchors the kidney and the adrenal gland to surrounding structures

renal cortex

• light-colored

• granular appearance

• outer part of kidney

medulla

• deep to the cortex

• darker, reddish-brown

pyramids

• cone shaped tissue masses that contains kidney tubules

• broad base of each pyramid faces toward the cortex

• appear striped due to urine-collecting tubules and capillaries

papilla

• apex point of renal pyramids

• drains into calyx

columns

• inward extensions of cortical tissue that separate the pyramids

• contains blood vessels going to/from cortex

renal pelvis

• funnel-shaped tube, continuous with the ureter leaving the hilum

Calyces

• collect urine, which drains continuously from the papillae, and empty it into the renal pelvis

major calyces

• branching of the renal pelvis

minor calyces

• subdivision of each major calyx

• cup-shaped areas that enclose the papillae

urine flow through the kidneys

1. Nephron: Blood is filtered in the nephron to form urine.

2. Collecting Ducts: Urine from several nephrons flows into the collecting ducts.

3. Minor Calyx: Collecting ducts empty urine into the minor calyces.

4. Major Calyx: Minor calyces merge to form major calyces.

5. Renal Pelvis: Major calyces drain into the renal pelvis.

6. Ureter: The renal pelvis funnels urine into the ureter, which carries it to the bladder.

path of blood flow through kidneys

• Aorta

  • Blood is pumped from the heart through the aorta.

• Renal Artery

  • Blood enters the kidneys through the renal artery, which branches off from the abdominal aorta.

• Segmental Arteries

  • The renal artery divides into segmental arteries as it enters the kidney.

• Interlobar Arteries

  • Segmental arteries further branch into interlobar arteries, which pass between the renal pyramids.

• Arcuate Arteries

  • Interlobar arteries arch over the bases of the renal pyramids to form arcuate arteries.

• Cortical Radiate (Interlobular) Arteries

  • Arcuate arteries give rise to cortical radiate arteries that extend into the renal cortex.

• Afferent Arterioles

  • Cortical radiate arteries branch into afferent arterioles, which supply blood to the glomeruli.

• Glomerulus (Capillaries)

  • The afferent arterioles lead into the glomerulus, where blood is filtered.

• Efferent Arterioles

  • After filtration in the glomerulus, blood exits via the efferent arterioles.

• Peritubular Capillaries or Vasa Recta

  • Efferent arterioles form two networks:

    • Peritubular Capillaries: Surround the proximal and distal convoluted tubules in the cortex.

    • Vasa Recta: Surround the loop of Henle in the medulla.

• Cortical Radiate (Interlobular) Veins

  • Blood from the peritubular capillaries drains into cortical radiate veins.

• Arcuate Veins

  • Cortical radiate veins drain into arcuate veins.

• Interlobar Veins

  • Arcuate veins drain into interlobar veins.

• Renal Vein

  • Interlobar veins converge into the renal vein, which exits the kidney.

• Inferior Vena Cava

  • The renal vein drains into the inferior vena cava, returning blood to the heart.

  • inferior vena cava lies to the right of the vertebral column, the left renal vein is about twice as long as the right.

renal plexus

• autonomic nerve fibers (sympathetic) and ganglia

• sympathetic fibers from the most inferior thoracic and first lumbar splanchnic nerves

• sympathetic vasomotor fibers regulate renal blood flow by adjusting the diameter of renal arterioles and also influence the formation of urine by the nephron

• nerve supply of the kidney and ureter

components of the kidney nephron

• renal corpuscle

  • glomerular capsule

  • glomerulus

• proximal convoluted tubule

• nephron loop (loop of Henle)

  • descending limb

  • ascending limb

• distal convoluted tubule

• collecting duct

nephrons

• creates cell & protein free filtrate from blood

• from the filtrate, recovers chemicals the body needs while also secreting chemicals that the body needs to get rid of

• empty their processed filtrate into collecting duct

renal corpuscle

• all located in renal cortex

renal tubules

• begin in the cortex and then pass into medulla before returning to the cortex

• continuous with renal tubule and completely surrounds the glomerulus

• all parts of nephron tubules have single layer but different epithelium on basement membrane

glomerular capsule

• external parietal layer

  • plays no part in forming filtrate

• visceral layer

  • clings to the glomerulus capillaries

  • consists of highly modified branching epithelial cells = podocytes

glomerular capsule - histology

• parietal layer: simple squamous epithelium

• visceral layer:

  • fenestrated endothelium = large diameter pores that allow passage of all plasma components, except blood cells

  • basement membrane = negative charge to limit loss of [-] ions

  • filtration slits = between pedicles of podocytes that limit particle passage based on size (<6-9nm) and prevent passage of small proteins

glomerulus

• endothelium is fenestrated which makes these capillaries porous

• allows large amounts of solute-rich but protein-free fluid to pass from the blood into the glomerular capsule (creates a filtrate)

• fed and drained by afferent & efferent arterioles

  • maintains high pressure that is needed for filtration

  • afferent arterioles arise from the cortical radiate arteries

peritubular capillaries

• empty into nearby venules

• arise from the efferent arterioles (which have high resistance), so have low pressure

• due to low pressure, porous capillaries, they absorb solutes and water from the tubule cells

vasa recta

• extend deep into the medulla

• supply oxygen and nutrients to the tissue

• form concentrated urine

juxtaglomerular complex

• region where the most distal portion of the ascending limb of the nephron loop lies against the afferent arteriole

macula densa

• group of tall packed cells in the ascending limb that lies adjacent to the granular cells

• are chemoreceptors that monitor the NaCl content of the filtrate entering the DCT

granular cells

• in arteriolar walls

• enlarged smooth muscle cells with prominent secretory granules containing the enzyme renin

• act as mechanoreceptors that sense the blood pressure in the afferent arteriole

extraglomerular mesangial cells

• lie between the arteriole and tubule cells

• interconnected by gap junctions

• pass regulatory signals between macula densa and granular cells

proximal convoluted tubule

• most active absorbers

• reabsorbed into cell:

  • 65% of filtrate volume

  • H2O, Na+, HCO3-, and other ions

  • all of glucose, amino acids, other nutrients

• secreted into filtrate: H+, NH4+, uric acid, drugs

proximal convoluted tubule - histology

• cuboidal epithelial cells

• have large mitochondria

• apical surface have dense microvilli

• brush border increases the surface area and capacity for reabsorbing water and solutes from the filtrate and secreting substances into it

descending limb - nephron loop

• reabsorbed into cell: H2O

• no solute reabsorption

descending limb of nephron loop - histology

• thick descending limb: proximal part have similar cells as proximal convoluted tubule

• thin descending limb: simple squamous epithelium

thin ascending limb - nephron loop

• secreted into filtrate: urea

• reabsorbed into cell: sodium moves passively from filtrate into the tubule cells down its concentration gradient created by the reabsorption of water

thick ascending limb - nephron loop

• reabsorbed into cell: Na⁺-K⁺-2Cl⁻ symporter is the main means of sodium, potassium, and chloride entry at the apical surface

• has Na⁺-H⁺ antiporters and about 50% of sodium is reabsorbed through the paracellular route

ascending limb of nephron loop - histology

• thick ascending limb: cuboidal or low columnar

distal convoluted tubule

• confined in the cortex

• most of the filtered water and solutes have been reabsorbed by the time the DCT is reached

• reabsorbed into cell:

  • Na+ (by aldosterone; Cl- follows)

  • Ca2+ (by parathyroid hormone)

• secreted into filtrate: K+ (by aldosterone)

distal convoluted tubule - histology

• cuboidal epithelium

• thinner than PCT and lack microvilli

collecting duct

• principal cells (more common): maintain the body’s water and Na+ balance (osmolarity)

• intercalated cells: maintain acid-base balance of the blood

• run side by side through the medullary pyramids

• reabsorbed into cell:

  • H2O (by ADH)

  • Na+ (by aldosterone; Cl- follows)

  • urea (increased by ADH)

• secreted into filtrate: K+ (by aldosterone)

collecting duct - histology

• principal cells (more common): sparse, short microvilli

• intercalated cells: cuboidal cells with abundant microvilli

cortical nephrons

• 85% of the nephrons

• Except for small parts of their nephron loops that dip into the outer medulla, they are located entirely in the cortex

• short nephron loop

• glomerulus further from the cortex-medulla junction

• efferent arteriole supplies peritubular capillaries

juxtamedullary nephrons

• produce urine that’s concentrated (which conserve water)

• ascending limb has both thin and thick segments

• long nephron loop

• glomerulus closer to the cortex-medulla junction

• efferent arteriole supplies vasa recta

glomerular filtration

• takes place in the renal corpuscle

• produces a cell and protein free filtrate

tubular reabsorption

• selectively move substances from the filtrate back into the blood (transepithelial process)

• takes place in the renal tubules and collecting ducts

• reclaims almost everything filtered

  • all of glucose, amino acids, 99% of water, salt

• 2 route: transcellular & paracellular

transcellular route - tubular reabsorption

• lipid soluble substances

• transport across the apical membrane

• diffusion through the cytosol

• transport across the basolateral membrane

  • often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces

• movement through the interstitial fluid and into the capillary

paracellular route - tubular reabsorption

• various ions (Cl-, Ca2+, K+, Mg2+, Na+) & urea

• movement through leaky tight junctions, particularly in the PCT

• movement through the interstitial fluid and into the capillary

active tubular reabsorption

• requires ATP either directly (primary active transport) or indirectly (secondary active transport) for at least one of its steps

passive tubular reabsorption

• diffusion, facilitated diffusion, and osmosis—processes in which substances move down their electrochemical gradients

tubular secretion

• selectively moving substances from the peritubular capillaries through the tubule cell into the filtrate

  • H+, K+, NH4+, ammonium, creatine, acids & bases

• substances (HCO3-) that are synthesized in the tubular cells are secreted

• occurs along the PCT and collecting duct

importance of tubular secretion

1. disposing of substances (drugs, metabolites) that are tightly bound to plasma proteins

   • because plasma proteins are generally not filtered

2. eliminating undesirable substances or end products that have been reabsorbed by passive process = urea & uric acid

3. ridding the body of excess K+

   • Most potassium in the filtrate is reabsorbed, so potassium in urine comes from active secretion driven by aldosterone

4. controlling blood pH

   • when blood pH becomes acidic, renal tubule actively secrete H+ into filtrate and retain more HCO3-

   • when blood pH becomes basic, Cl- is reabsorbed instead of HCO3-

glomerular filtration

• passive process in which hydrostatic pressure forces fluids and solutes through a membrane

  • doesn’t directly consume metabolic energy

filtration membrane

• lies between the blood and and the interior of glomerular capsule

• porous membrane that allows free passage of water and solutes smaller than plasma proteins

• 3 layer

  1. fenestrated endothelium of the glomerular capillaries

  2. basement membrane

  3. foot processes of podocytes of the glomerular capsule

fenestrated endothelium of the glomerular capillaries - filtration membrane

• fenestrations (capillary pores) allow all blood components except blood cells to pass through

basement membrane - filtration membrane

• composed of the other 2 layer’s fused basal laminae

• forms a physical barrier that blocks all but the smallest proteins while still permitting most other solutes to pass

• glycoproteins of basement membrane give it a negative charge

  • repels many negatively charged macromolecular anions (plasma protein)

foot processes of podocytes of the glomerular capsule - filtration membrane

• lies on visceral layer of glomerular capsule

• any macromolecules that manage to make it through the basement membrane, slit diaphragms - thin membrane that extend across the filtration slits prevent almost all of them traveling further

hydrostatic pressure in glomerular capillaries

• glomerular blood pressure (55 mm hg)

• high blood pressure due to glomerular capillaries drained by high-resistance efferent arteriole (smaller diameter)

  • filtration occurs but no reabsorption

• force pushing water and solutes out the the blood and across the filtration membrane

• if its pressure rise, NFP & GFR rise

osmotic pressure in glomerular capillaries

• pressure exerted by the proteins in the blood that sucks water in the capillary (30 mm hg)

• proteins in the capillaries maintains it

hydrostatic pressure in capsular space

• pressure exerted by filtrate in the glomerular capsule

• pressure is much higher than most capillaries because filtrate is confined in a small space with a narrow outlet (15 mm hg)

net filtration pressure

NFP = outward pressure - inward pressure

(HPgc) - (HPcs + OPgc)

(55) - (15+30)

= 10 m Hg

• largely determines the glomerular filtration rate

Glomerular filtration rate

• volume of filtrate formed each minute by the combined activity of all glomeruli of kidneys

• can be controlled by changing glomerular hydrostatic pressure

• directly proportional to:

  • net filtration pressure

  • total surface area available for filtration

  • filtration membrane permeability

net filtration pressure

• main controllable factor

• hydrostatic pressure in glomerulus determines NFP the most

  • can be controlled by changing the diameter of the afferent (and sometimes efferent) arterioles

total surface area available for filtration

• glomerular mesangial cells surrounding these capillaries can fine-tune GFR by contracting to adjust the total surface area available for filtration

filtration membrane permeability

• glomerular capillaries are thousands of times more permeable than other capillaries because of their fenestrations

regulation of glomerular filtration

• kidneys need a constant GFR to make filtrate do their job while body needs a constant blood pressure

• increase in GFR increases urine output, which reduces blood volume and blood pressure

• 2 controls:

  1. intrinsic

  2. extrinsic

Intrinsic control (renal autoregulation)

• act locally within the kidney to maintain GFR

  • adjust its own resistance to blood flow

• mean arterial pressure between 80-180 mm Hg

• mechanism: myogenic & tubuloglomerular feedback

myogenic mechanism

• vascular smooth muscle contracts when stretched and relaxes when not stretched

  
  

• rising bp stretches vascular smooth muscle in the arteriolar walls, causing the afferent arterioles to constrict

  • constriction restricts blood flow into the glomerulus and keeps the GFR at ideal rate

• declining systemic bp causes dilation of afferent arterioles and raises glomerular hydrostatic pressure

tubuloglomerular feedback mechanism

• directed by the macula densa cells of the juxtaglomerular complex

  • located in the walls of ascending limb

  • respond to filtrate NaCl concentration

• When GFR increases, there is not enough time for reabsorption and the concentration of NaCl in the filtrate remains high, so macula densa cells respond to high levels of NaCl in filtrate by releasing vasoconstrictor chemicals (ATP ) that cause intense constriction of the afferent arteriole, reducing blood flow into the glomerulus

  • drop in blood flow decreases the NFP and GFR, slowing the flow of filtrate and allowing more time for filtrate processing (NaCl reabsorption)

• low NaCl concentration of slowly flowing filtrate inhibits ATP release from macula densa cells, causing vasodilation of the afferent arterioles which allow more blood to flow into the glomerulus, increasing NFP and GFR

extrinsic control

• nervous and endocrine systems maintain blood pressure

• mean arterial pressure <80 or >180 mm Hg

  • in extreme changes of bp, extrinsic control takes over

• mechanism: sympathetic nervous system controls & Renin-Angiotensin-Aldosterone Mechanism

sympathetic nervous system controls

• blood pressure falls, norepinephrine released by sympathetic nerve fibers & epinephrine released by the adrenal medulla causes vascular smooth muscle to constrict, increasing peripheral resistance and bringing blood pressure back up toward normal = baroreceptor reflex

• afferent arterioles also constrict, decreasing GFR and help restore blood volume and blood pressure to normal

Renin-Angiotensin-Aldosterone Mechanism

• body’s main mechanism for increasing BP & blood NaCl content

• low BP causes the granular cells of juxtaglomerular complex to release renin

  • enzyme released by kidneys that raise BP by initiating Renin-Angiotensin-Aldosterone Mechanism

• 3 pathways that stimulate granular cells:

  1. sympathetic nervous system

  2. activated macula densa cells

  3. reduced stretch

sympathetic nervous system - pathway that stimulate granular cells

• part of the baroreceptor reflex

• renal sympathetic nerves activate B1-adrenergic receptors that cause the granular cells to release renin

activated macula densa cells - pathway that stimulate granular cells

• when macula densa sense low [NaCl], they signal the granular cells to release renin

• may signal by releasing less ATP, by releasing more prostaglandin PGE2, or both

reduced stretch - pathway that stimulate granular cells

• granular cells act as mechanoreceptors

• drop in mean arterial blood pressure reduces the tension in the granular cells’ plasma membranes and stimulates them to release more renin.

other factors affecting GFR

• release paracrine chemicals affecting renal arterioles

  • adenosine

  • prostaglandin E2 (PGE2)

• kidney makes its own locally acting angiotensin II

Antidiuretic hormone (ADH)

• inhibits urine output

• makes the principal cells of the collecting ducts more permeable to water by causing aquaporins to be inserted into their apical membranes

• increases urea reabsorption by the collecting ducts

Angiotensin II

• Constriction of Efferent Arterioles:

  • Increases glomerular hydrostatic pressure, raising GFR.

• Stimulates Aldosterone Release:

  • Enhances sodium and water reabsorption, increasing blood volume and supporting GFR.

• Promotes Antidiuretic Hormone(ADH) Secretion:

  • Increases water reabsorption & blood volume, maintaining GFR.

• Contracts Mesangial Cells:

  • Reduces filtration surface area, adjusting GFR as needed.

Aldosterone

• fine-tunes reabsorption of remaining Na+

• increase blood volume/pressure by enhancing Na+ reabsorption and K+ secretion

• targets the principal cells of the collecting ducts and cells of the distal portion of the DCT

• released by decreased blood volume/pressure, high extracellular [K+]

natriuretic peptides

• Dilation of Afferent Arterioles:

  • Increases blood flow into the glomerulus, raising GFR.

• Constriction of Efferent Arterioles:

  • Increases glomerular hydrostatic pressure, enhancing GFR.

• Inhibits Renin and Aldosterone Secretion:

  • Reduces sodium reabsorption, increasing sodium and water excretion, lowering blood volume, and indirectly regulating GFR.

• Reduces Mesangial Cell Contraction:

  • Increases filtration surface area, raising GFR.

• released by cardiac arterial cells

Parathyroid hormone (PTH)

• acting primarily at the DCT, PTH increase the reabsorption of Ca2+

sodium transport across the basolateral membrane

• Na+ transported by primary active transport = Na+ K+ ATPase pump in the basolateral membrane

• bulk flow of water sweeps Na+ into adjacent peritubular capillaries

  • rapid due to blood there having low hydrostatic pressure and high osmotic pressure

sodium transport across the apical membrane

• Active pumping of Na+ from the tubule cells results in a strong electrochemical gradient that favors its entry at the apical face via secondary active transport (cotransport) carriers or via facilitated diffusion through channel

• pump maintains the intracellular Na+ concentration at low levels

• K+ pumped into the tubule cells almost immediately diffuses out into the interstitial fluid via leakage channels, leaving the interior of the tubule cell with a net negative charge.

secondary active transport

• the push that comes from the gradient created by Na+ K+ pumping at the basolateral membrane

• glucose, amino acids, some ions, vitamins

• apical carrier moves Na+ down its concentration gradient as it cotransports another solute

  • cotransported solutes move across the basolateral membrane by facilitated diffusion via other transport proteins

passive tubular reabsorption of water

• movement of Na+ and other solutes establishes a strong osmotic gradient, and water moves by osmosis into the peritubular capillaries

• aquaporins act as water channels across plasma membrane

• water permeable regions (PCT) always have aquaporins in tubule cell membrane

• Aquaporins are absent in the apical membranes of the collecting duct unless antidiuretic hormone (ADH) is present

obligatory water reabsorption

• absorb water in the proximal nephron regardless & descending limb of the loop of Henle of its state of over- or under-hydration

• follows solute reabsorption through osmosis

facultative water reabsorption

• water reabsorption that depends on ADH

• in distal convoluted tubule & collecting duct

passive tubular reabsorption of solutes

• As water leaves the filtrate, it becomes more concentrated with solutes, and these solutes can follow their concentration gradients into the peritubular capillaries

• As Na+ ions move through the tubule cells into the peritubular capillary blood, they also establish an electrical gradient that favors passive reabsorption of anions (primarily Cl−) to restore electrical neutrality in the filtrate and plasma

• lipid soluble substances are hard to secrete since they easily pass through cell membranes and are reabsorbed