chapter 26rnrausch.com/25x/pdf/253/chapter_26.pdf · 2. elimination! • discharge wastes! 3....

Chapter 26 – Urinary system!

1!

Chapter 26!The Urinary System!

2!

SECTION 26-1!Consisting of the kidneys, ureters, urinary bladder, and urethra, the urinary system has three primary functions!

Renal gross anatomy was/is being covered in lab.!

3!

Urinary System Functions – 1!

1. Excretion!•  Remove organic wastes from body fluids!

2. Elimination!•  Discharge wastes!

3. Regulate plasma volume and solute concentration!•  Regulate blood volume and pressure!

ü  Adjust volume of water in urine!ü  Secrete erythropoietin!ü  Secrete renin!


2!

4!

Urinary System Functions – 2!

3. Plasma volume and solute concentration (cont.)!•  Regulates plasma Na+, K+, Cl-, Ca2+, etc.!•  Helps regulate blood pH!

ü  Excrete or conserve H+ and HCO3-!

•  Conserve valuable nutrients!•  Assist liver in detoxifying poisons,

deaminating amino acids, activating Vitamin D!

5!

Renal gross anatomy and basic nephron anatomy!was or will be covered in lab.!

•  About 1 million nephrons per kidney!•  Nephron = renal corpuscle + renal tubule!

!

SECTION 26-2!Kidneys are highly vascular structures containing functional units called nephrons, which perform filtration, reabsorption, and secretion!

6!

Representative Nephron Figure 26-6!


3!

7!

Nephron Functions!

1. Filtration•  Occurs at renal corpuscle (Bowman’s capsule +

glomerulus)!•  Anything but large proteins and blood cells can

be filtered into glomerular filtrate!2. Secretion

•  Occurs in renal tubule and collecting duct!•  “Unwanted” substances added to filtrate by

active transport!3. Reabsorption

•  Occurs in renal tubule and collecting duct!•  Remove “wanted” substances from filtrate!

8!

Nephron Anatomy!

Renal corpuscle = glomerulus + Bowman’s capsule!

Glomerulus = capillary bed!•  Blood enters via afferent arteriole!•  Blood exits via efferent arteriole!•  Next enters peritubular capillaries!

Bowman’s (glomerular) capsule!•  Has visceral and parietal layers!•  Layers define Bowman’s space!

Bowman’s space continuous with lumen of renal tubule at PCT!

9!

Nephron Anatomy – 2!

Renal tubule!Contains tubular fluid (i.e. the filtrate in tubule)!Three main sections!

1. Proximal convoluted tubule (PCT) in cortex!2. Loop of Henle in medulla (variable)!

•  Descending limb!•  Ascending limb!

3. Distal convoluted tubule (DCT) in cortex!


4!

10!

Collecting System (Ducts)!

DCTs of several nephrons empty into a collecting duct (CD)!→ CDs empty into papillary ducts!

→ Papillary ducts empty into minor calyces!→ Minor calyces empty into major calyces!

→ Major calyces empty into the renal pelvis!

→ Renal pelvis empties into ureter!

11!

Types of Nephrons – 1 Figure 26-7a!

1.  Cortical nephrons (80– 85% of all nephrons)!•  Renal corpuscle in

outer cortex!•  Have short loops of

Henle that are mainly in cortex and superficial medulla!

•  Efferent arteriole sends blood to peritubular capillaries that surround entire tubule!

12!

Types of Nephrons – 2!2.  Juxtamedullary nephrons (15–20%)!

•  Allow production of concentrated or dilute urine•  Renal corpuscle is deep in cortex!•  Efferent arterioles send blood to:!

•  Peritubular capillaries!•  Vasa recta!

•  Have long loops of Henle which:!•  Penetrate deep into medulla!•  Are surrounded by vasa recta!•  Ascending and descending limbs of loop of

Henle have different permeability characteristics !


5!

13!

Cortical and Juxtamedullary Nephrons Fig. 26-7b, c!

Cortical nephron!

Juxtamedullary nephron!

cortex!medulla! medulla!

14!

Renal Corpuscle!

Bowman’s (glomerular) capsule!1. Visceral layer!•  Simple squamous epithelium!•  Cells called podocytes!

Have pedicels (“little feet”). Form filtration slits that wrap around glomerulus!

2. Parietal layer!•  Simple squamous epithelium!

3. Bowman’s (capsular) space!4. Glomerular capillaries and filtration

membrane!

15!

The Renal Corpuscle Figure 26-8a!

Filtration slit!

Podocyte with pedicels!


6!

16!

Filtration Membrane!

1. Glomerular endothelial cells!•  Leaky capillaries - large fenestrations!

Do not let blood cells and platelets pass into filtrate!

•  Mesangial (supporting) cells!ü  Between adjacent capillaries!ü  Contractile cells!ü  Regulate capillary diameter and therefore

surface area currently available for filtration!

17!

Filtration Membrane – 2!

2. Basal lamina (lamina densa)!•  Acellular glycoprotein layer!•  Between endothelium and podocytes!•  Prevents filtration of large proteins!

3. Filtration slits (formed by podocyte “feet”)!•  Cells have thousands of pedicels on

capillaries!•  Space between pedicels = filtration slits!

ü  A slit membrane spans each slit!

18!

Filtration Membrane – Overall Function!

1. Hydrostatic pressure forces fluid and solutes through the membrane!

2. Prevents filtration of albumin (plasma protein)!3. Allows filtration of very small proteins, water,

glucose, amino acids, ions, etc.!


7!

19!

The Renal Corpuscle Figure 26-8b from 7th edition!

20!

Functional Anatomy Figure 26-6!

21!

Characteristics of Parts of the Renal Tubule!

1. Proximal convoluted tubule (PCT)!•  Simple cuboidal epithelium!•  Cells have brush border (microvilli)!

Increase surface area for secretion and absorption!

2. Descending limb and thin ascending limb of loop of Henle!•  Simple squamous epithelium!•  Permeable to water, but not to salts


8!

22!

Characteristics of Parts of the Renal Tubule – 2!

3. Thick ascending limb of loop of Henle!•  Simple cuboidal or low columnar epithelium!•  Moves Na+ and Cl- out of tubule, into

peritubular fluid. Figure 26-13, later.•  Not permeable to water SEE SLIDE 57

4. Distal convoluted tubule and collecting duct!•  Simple cuboidal epithelium!•  Few microvilli!(continued on next slide)!

23!


4.  DCT and CD (cont.)!•  Initial portion of DCT contacts afferent

arteriole!•  Forms macula densa (“dense spot”)!

ü  Afferent arteriole contains smooth muscle cells called juxtaglomerular (JG) cells!

ü  JG cells + macula = juxtaglomerular apparatus (JGA)!

ü  JGA releases renin (remember decreased blood flow, pressure, volume stimuli from chapter 18?)!

24!


4.  DCT and CD (cont.)!Final portion of DCT and the CDs!A. Principal cells!

•  Most numerous!•  Have ADH and Aldosterone receptors!

ü  Affect permeability to water and ions!B. Intercalated cells!

•  Microvilli at apical surface!•  Many mitochondria!•  Function in pH regulation!


9!

25!

The point is to regulate the volume and composition of blood by varying the volume

and composition of urine.!

SECTION 26-3!Different segments of the nephron form urine by filtration, reabsorption and secretion!

26!

Overview of Urine Formation Figure 26-9!

27!

Basic Processes!

1. Filtration (of blood) - renal corpuscle only!2. Reabsorption - mostly in PCT!

•  Of water and “wanted” materials!•  Absorption is selective!

ü  Solutes: diffusion or transport protein!ü  Water: osmosis allowed (or not)!


10!

28!

Basic Processes – 2!

3. Secretion - mostly PCT and DCT!•  Of “unwanted” substances (e.g. metabolic

wastes)!4. Volume and solute concentration of urine!

•  Long loops of Henle (juxtamedullary nephrons)!

•  Final portion of DCT; Collecting ducts!Reabsorption and secretion involve carrier-

mediated transport

29!

Types of Carrier-mediated Transport!

1. Facilitated diffusion!2. Active transport (primary)!3. Cotransport (secondary active transport)!

•  Two substances move in same direction!•  ATP not used at site of transport!•  At least one substance moves down its

concentration gradient!4. Countertransport!

•  Substances move in opposite directions!

30!

Carrier-Mediated Transport – Characteristics!

1. Specific substrate binds specific carrier!2. Transporters are normally unidirectional in situ!3. Carriers may differ on different portions of a

cell’s membrane!•  E.g. apical (luminal) membrane of PCT cells!

ü  Amino acids transported into cell by cotransport with Na+ (secondary active transport)!

•  Basolateral membrane of PCT cells!ü  Amino acids leave cells by facilitated

diffusion!


11!

31!

Carrier-Mediated Transport – 2!

4. Single cells may contain many types of transporters!

5. Carriers can be saturated!i.e. they have a maximum rate of function called

the transport (or tubular) maximum (Tm)!•  Secretory transporters - not usually a

problem!•  Reabsorption transporters - may saturate•  Tm determines renal threshold!

= the plasma concentration of a substrate at which the substrate begins to appear in the urine (and will be lost)!

32!

SECTION 26-4!Hydrostatic and colloid osmotic pressures influence glomerular filtration pressure, which in turn affects the glomerular filtration rate!

Glomerular filtration rate must be maintained or the kidneys cannot perform their vital functions. !

33!

Glomerular Filtration!Note: All solutes except plasma proteins and

formed elements of blood can pass into the filtrate so the initial concentrations of small organic molecules and ions in filtrate in the PCT is about the same as that of blood. !

Filtration pressures!•  Balance between hydrostatic and colloid

osmotic pressures!•  This works on the same principle that we saw for

filtration and reabsorption at other capillaries in Chapter 21 (Figure 21-11).!


12!

34!

Glomerular Hydrostatic Pressures!GHP = glomerular hydrostatic pressure!

•  Outward force from blood into capsular space!•  Higher than in systemic capillaries!

Efferent arteriole smaller diameter than afferent arteriole: Avg. GHP about 50 torr

CsHP = (Bowman’s) capsular hydrostatic pressure!•  Inward force from capsular space into blood!•  Resists flow into tubule, causes flow along

tubule: average pressure about 15 torrNet hydrostatic pressure (NHP) = GHP - CsHP = 35 torr

35!

Glomerular Osmotic Pressures!

BCOP (blood colloid osmotic pressure)!•  Due to plasma proteins trapped in blood!•  Inward force from capsular space into blood!•  About 25 torr!•  Because large proteins don’t enter capsular

space, but other solute concentrations are the same in blood and filtrate, this is the net colloid osmotic pressure!

•  (Capsular COP is only important if the glomerulus is damaged and proteins leak out so assume it is zero.)!

36!

Glomerular Filtration Figure 26-10b!


13!

37!

Glomerular Filtration Rate (GFR)!

GFR = volume of filtrate produced by both kidneys in one minute!

Huge filtration surface area (6m2 / kidney)!•  I.e. lots of filtration!•  Average = 125 ml/min = 180 l/day!!!!•  99% of filtrate is reabsorbed!

GFR depends upon net filtration pressure:!↓ GHP → ↓ net filtration pressure → ↓ GFR!↑ GHP→ ↑ net filtration pressure → ↑ GFR!

38!

Control of GFR – Autoregulation!1. Autoregulation - change diameters of afferent

and efferent arterioles and capillaries!Maintains GFR when BP and blood flow change!a)  Decreased glomerular BP or blood flow →!

•  Dilation of afferent arterioles!•  Constriction of efferent arterioles!•  ↑ blood flow and GHP (BP) → ↑ GFR!

b)  Increased glomerular BP or blood flow →!•  ↑ Stretch on afferent arterioles → these

contract → ↓ BP and → ↓ GFR!

39!

Autoregulation Figure 26-11 bottom!

If GFR not restored, initiate hormonal response.!

??

Immediate, initial response to decreased GFR!


14!

40!

Hormonal Regulation of GFR!If autoregulation does not restore GFR → Renin-

angiotensin system and natriuretic peptides a) ↓ blood volume, ↓ BP or blocked renal artery

→ ↓ blood flow to glomerulus → ↓ GFR !b) ↓ GFR → Lower flow rate through tubule → fluid

spends more time in tubule → more Na+ and Cl- absorbed → ↓ [osmotic] of fluid of DCT!

(see slide #57 for clarification)c) Macula densa (DCT) senses this, signals JGA!d)  Renin released by JGA → ↑ BP → ↑ GFRe)  The JGA also senses ↓ BP and is also

sympathetically innervated!

41!

Angiotensin II Effects That Increase GFR!

1. Renin release results in formation of ANG II!2. Brief vasoconstriction of systemic arterioles and

precapillary sphincters → ↑ BP → ↑ GFR!3. Constriction of efferent arteriole →!

•  ↑ glomerular BP!•  ↑ GFR!

4. PCT effects: more Na+ and Cl- reabsorbed → water follows → ↑ blood volume and BP → ↑ GFR!

Stimulus: Low BP, low BV caused ↓GFR!Response: Act to increase GFR!

42!

Angiotensin II Effects - 2!

5. Stimulates adrenals to release aldosterone !•  ↑ Na+ and Cl- reabsorption by DCT and CD!•  Water follows if ADH is present → ↑ blood

volume and BP → ↑ GFR!6. CNS effects!

a) Causes thirst!b) Stimulates release of ADH

•  ↑ water reabsorption in DCT and CD → ↑ blood volume and BP → ↑ GFR!

c) ↑ sympathetic tone → systemic vasoconstriction → ↑ BP → ↑ GFR!


15!

43!

Response to a Reduction in GFR Figure 26-11 top!

44!

Response to an Increase in GFR!

1. ↑ BP → ↑ GFR → ↑ urine output → return to normal blood volume and BP → ↓GFR

2. ANP/BNP: next slide!

Stimulus: High BP, high BV caused ↑ GFR!Response: Act to reduce GFR !

45!

ANP and BNP – Response to Increased GFR!

2. Atrial and Brain natriuretic peptides (ANP, BNP)!ANP from atria; BNP from ventricles!!ANP mechanism at kidney!•  High BP and blood volume → ↑ venous

return → ↑ atrial stretch → release ANPa)  Dilate afferent arterioles → ! ↑ GHP → ↑ GFR → ↑ urine output → ! ↓ volume and BP → ↓ GFR!a)  Constrict efferent arterioles - same effects!


16!

46!

Sympathetic Response to ↑ BP → ↑ GFR!

3.  Autonomic regulation!•  Most renal innervation is sympathetic!•  Emergency: → sympathetic response → ↑

blood pressure → ↑ GFR !•  Sympathetic stimulation:!

•  Constrict afferent arterioles → ↓ GHP → ↓ GFR

•  Crisis situation…maintain blood volume and pressure!

47!

Reabsorption and secretion involve carrier-mediated transport.!

SECTION 26-5!Countercurrent multiplication, antidiuretic hormone, and aldosterone affect reabsorption and secretion

48!

Transport in the PCT!

Reabsorbs 60–70% of filtrate!Substances enter peritubular fluid!

•  Diffuse into peritubular capillaries!Major functions:!

1. Reabsorb organic nutrients!•  99% of glucose and amino acids!

2. Active reabsorption of ions!•  Na+, K+, phosphates, HCO3

-, etc.!3. Reabsorption of water (>100 l/day)!


17!

49!

Transport in the PCT – 2!4. Passive reabsorption of ions!

Active transport of some substances results in the passive (diffusional) transport of others.!a) Solutes are actively removed from filtrate!b) Water follows salt…!

•  This increases the concentrations of solutes that remain in the lumen!

•  This favors diffusion of ions out of lumen down their individual concentration gradients!

•  Cl- is especially important here…!

50!

Transport in the PCT – 3!

4.  (continued) !Importance of Cl- diffusion

•  Cl- is ion in highest concentration remaining in tubule!

•  Diffusion of Cl- into peritubular (interstitial) fluid carries negative charge!

•  Cations follow because they are attracted to Cl-!

i.e., both concentration differences and electrical forces are important to diffusional reabsorption

51!

Transport in the PCT – 4!

5. Angiotensin II stimulates Na+ reabsorption!•  Stimulate Na+/K+ pumps at basal membrane!•  Stimulate Na+/H+ transport at apical

membrane (no evidence that ATP is required)!

6. Secretion (into tubule)!•  H+, NH4

+, creatine, drugs, toxins!


18!

52!

Transport at the PCT Figure 26-12!

Water reabsorbed by osmosis! Note

importance of [Na+] gradient

What enzyme would you expect to be present in the basilar membrane of PCT cells?

Basal membrane

Apical membrane

Active transport!

53!

Loop of Henle – The Countercurrent Multiplier!

Fluid in descending and ascending limbs runs in opposite directions (i.e. countercurrent)!

Limbs have different permeability characteristics!•  Thin descending limb and thin portion of

ascending limb!Permeable to water, only very slightly permeable to salts

•  Thick ascending limb!Not permeable to water, pumps salts out

54!

Sodium and Chloride Cotransport!

Na+-K+/2Cl- transporter - thick ascending limb

Reabsorb Na+ and Cl-.!Secrete K+. Ions are reabsorbed from fluid, but water cannot follow!Na+/K+ pump!

Active trnsprt!

1!

2!2° active trnsprt!


19!

55!

Sodium and Chloride Cotransport – 2!Thick ascending limb of loop of Henle!1. Na+/K+ exchanger pumps 3 Na+ out of tubular

cell into peritubular fluid and 2 K+ from peritubular fluid into cell!

2. K+ diffuses across cell and into tubule lumen!3. 2 Cl-, 1 K+ and 1 Na+ cotransported into tubular

cell. Secondary active transport. Na+ moving down its concentration gradient drives transport.!

4. 2 Cl- and K+ leave cell into peritubular fluid by cotransport ([high] → [low])!

5. Water cannot follow!

56!

Countercurrent Multiplier !Mechanism operating in thick ascending loop of

Henle:!1. Na+ and Cl- transported out of thick ascending

limb!2. ↑ osmotic concentration in medulla!3. Water leaves thin descending limb by osmosis!4. ↑ osmotic concentration of fluid in descending

limb!5. More Na+ and Cl- reach thick ascending limb!6. Na+/Cl- transport works faster (positive

feedback) !

57!

Countercurrent Multiplier Figure 26-13b!

Numbers in boxes:! , , etc.,!indicate the osmotic concentration of the peritubular fluid in the medulla. !

600!300!

First!

Second!

Go back and look at slide 40!

End of PCT: same [osmotic] as blood!


20!

58!

Countercurrent Multiplier – “Bottom Lines”!

•  Cl- and Na+ are transported out of lumen of thick ascending limb and into medulla (peritubular fluid)!

•  Osmotic concentration increases along the descending loop of Henle!

•  Osmotic concentration decreases along the thick ascending limb of Henle!

•  Fluid reaching DCT is dilute (100 mOsm/l)!•  The osmotic concentration increases deeper in the

medulla!•  This high osmotic concentration in the medulla

allows for the production of a concentrated urine if ADH is present (below)!

59!

Countercurrent Multiplier Figure 26-13c!

60!

Reabsorption and Secretion in the DCT!

1. Basic pattern:!a. Na+ pumped out of tubular cell at basolateral

surface in exchange for K+ !b. Na+ and Cl- cotransported in at luminal

surface!c. Na+ pumped out (see a., above) into medulla!d. Cl- diffuses out into medulla!e. K+ diffuses through cell into tubule lumen!

2. Aldosterone stimulates synthesis of Na+/K+ pumps and channels!•  Promotes Na+ reabsorption and K+ secretion!


21!

61!

Secretion and Reabsorption by DCT Figure 26-14!

1!

2!With aldosterone:!!

More Na+/K+ pumps and channels produced!

!More Na+ and Cl- reabsorbed, K+

secreted !

62!

H+ Secretion Involves Carbonic Anhydrase!

1. CO2 (from tubular fluid) + H20 combine within cell → H2CO3 –– carbonic acid → H+ + HCO3

-!2. H+ exchanged for Na+!

•  H+ enters basilar surface from peritubular fluid!

•  H+ leaves apical surface into tubular fluid!3. HCO3

- leaves cell for peritubular fluid in exchange for Cl-!

Blood pH rises because:!•  H+ leaves blood!•  HCO3

- enters blood!

63!

H+ Secretion and HCO3- Reabsorption!

Figure 26-14c!

But know that the DCT is

important for H+

secretion


22!

64!

Control of Urine Volume and Osmotic Concentration!

Antidiuretic hormone and Aquaporins !

65!

Formation of Dilute Urine - Low [ADH]!

•  ADH levels low!•  Blood [osmotic] ≈ 300 mOsm/l !•  PCT [osmotic] ≈ 300 mOsm/l !•  Loop of Henle!

ü  [osmotic] increases in descending loop!ü  [osmotic] decreases in ascending loop!

•  DCT!ü  [osmotic] about 100 mOsm/l!

•  CD and papillary ducts!ü  Cells impermeable to H2O → dilute urine!

66!

Effects of ADH on DCT and CD Figure 26-15a!

1!2!

3!

MEDULLARY!osmotic

concentrations!

! Low [ADH] !!


23!

67!

Formation of Concentrated Urine!

•  Increased ADH (from posterior pituitary)!•  Aquaporin-2 (“water channels”) inserted into

apical membranes of principal cells of DCT and CDs!

•  DCT and CD ducts now permeable to water!•  Water exits into medulla down concentration

gradient!•  Concentrated urine produced!

68!

Effects of ADH on DCT and CD Figure 26-15b!

ADH causes aquaporins “water channels” to be inserted into DCT and CD membranes.!!DCT and CD are now permeable to water.!!Water follows its concentration gradient into the medulla.!!Water is returned to the circulation by the vasa recta of juxtamedullary nephrons.!

MEDULLARY!osmotic

concentrations!

69!

Aquaporins!

http://arbl.cvmbs.colostate.edu/hbooks/molecules/aquaporins.html!


24!

70!

Dilute vs. Concentrated Urine Figure 26-15!

Low [ADH]! High [ADH]!

MEDULLARY!osmotic

concentrations!

71!

Where Does the Salt and Water Go??!

Figure 26-16!

72!

Gross anatomy will be learned in lab.!

SECTION 26-6!Urine is transported via the ureters, stored in the bladder, and eliminated through the urethra, aided by the micturition reflex!


25!

73!

Ureters!

•  Carry urine from renal pelvis to urinary bladder!•  Retroperitoneal!•  Lined by transitional epithelium!•  Urine moved by:!

Peristalsis (smooth muscle)!Hydrostatic pressure (urine formation)!Gravity!

•  Mucus from mucosa protects cells!

74!

Urinary Bladder!

•  Retroperitoneal!•  Lining is transitional epithelium!•  Smooth muscle in wall known as detrusor

muscle!•  Trigone located in floor of bladder!

Entrance to bladder from 2 ureters!•  Physiological sphincter!

Exit for urethra!2 ureters + 1 urethra = 3 = trigone!

75!

Micturition Reflex !

•  Stretch receptors in wall activated as bladder fills!

•  Parasympathetic input sent to spinal cord!•  Reflex causes:!

1. Contraction of detrusor muscle (including internal sphincter)!

2. Message sent to cortex - awareness of need to urinate!

3. External sphincter contracted (somatic reflex)!4. External sphincter = can be voluntarily

controlled (Again, Dr. Guyton’s “socially appropriate moment.”)!


26!

76!

Micturition Reflex – 2 Figure 26-20!

Micturition Reflex Link

chapter 26rnrausch.com/25x/pdf/253/chapter_26.pdf · 2. elimination! • discharge wastes! 3....

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