Chapter 26

The Urinary System

General Kidney functions

Blood ionic composition - Na+, Cl-, sulfate (SO42-),

phosphate (PO42-)

Blood pH – physical removal of H+ Blood volume – fluid volume regulation Blood pressure - renin Blood osmolarity – ions and fluid levels Hormone production

Calcitrol Erythropoietin

Blood glucose levels - gluconeogenesis Waste removal

Ammonia and urea from deamination Bilirubin from hgb Creatinine Uric acid

Kidney – Internal Macro Anatomy Hilus Cortex Medulla

Pyramid Column

Kidney - Internal Micro Anatomy Nephron - functional unit of kidney

3 functions: 1) filtration2) reabsorption 3) secretion

Different sites different functions: renal corpuscle, renal tubule, collecting duct, peritubular capillaries

Nephron 2 major parts to the

nephron

1. Renal Corpuscle

2. Renal Tubule

Nephron Renal corpuscle

Site of fluid filtration 2 components

Glomerulus group of capillary

loops blood in by afferent

arteriole blood out by efferent

arteriole Glomerular

(Bowman's) capsule double walled

epithelial cup outer wall (parietal

layer) separated from inner wall (visceral layer) by capsular (Bowman's) space

As blood flows through capillary - capillary filtration Water, most solutes pass into capsular space Large proteins, formed elements from blood do not pass

Nephron Renal tubule - where

filtered fluid passes from capsule Proximal convoluted

tubule (PCT) Loop of Henle (nephron

loop) Distal convoluted tubule

(DCT) Short connecting tubules Collecting ducts Merge to papillary duct

Then to minor calyx 30 papillary ducts/papillae

Renal Corpuscle Histology Each nephron portion

has distinctive features Histology of Glomerular

filter Three layers of tissue From inside to out

prevents movement of progressively smaller particles

Physiology of Urine Formation Glomerular filtration -

first step in urine formation forcing of fluids, dissolved

substances through membrane by pressure

same as in caps results in filtrate

180 L/day, about 60x plasma volume

178-179 L/day reabsorbed

Glomerular Filtration Net filtration pressure

(NFP) - depends on 3 pressures:

1) glomerular blood hydrostatic pressure (GBHP)

2) capsular hydrostatic pressure (CHP)

3) blood colloid osmotic pressure (BCOP)

1

23

Glomerular Filtration 3 structural features of renal corpuscles enhance filtering capacity:

1) Glomerular caps very long - surface area for filtration2) Filter (endothelium-capsular membrane) is porous, thin

glomerular caps 50x more permeable than regular cap basement membrane, filtration slits only permit passage of small molecules

3) Cap BP high - efferent arteriole < diameter afferent art - filtration pressure

Glomerular Filtration Rate (GFR) GFR

Amount of filtrate that forms in all renal corpuscles in both kidneys/min

Adults GFR 125 ml/min (180 L/day) Regulation of GFR

When more blood flows into glomerulus GFR Glomerular blood flow (GBF) depends on systemic

blood pressure, diameter of afferent/efferent arterioles

If BP falls to where glomerular capillary pressure is 42 mmHg, no filtration, anuria

Tubule Histology

Juxtaglomerular apparatus (JGA) Ascending LofH contacts afferent arteriole Macula Densa

special cells in this area monitor Na+Cl- content in filtrate able to work w/ JG cells

Juxtaglomerular (JG) cells modified smooth muscle secrete vasodilators

Both work together to regulate BP

Glomerular Filtration Rate (GFR) 3 principal regulators of GFR:

1) Renal autoregulation of GFR ability of kidneys to maintain a constant BP and GFR

despite changes in systemic AP high bp causes afferent arteriole to constrict – keeps

GBF constant negative feedback from JGA – high delivery of filtered

Na+ and Cl- to macula densa causes constriction of afferent arteriole (decrease release of vasodilators)

Glomerular Filtration Rate (GFR) 3 principal regulators of GFR (cont.):

2) Hormonal regulation of GFR1. Angiotensin II

catalyzed from angiotensinogen by renin released from JGA cells

4 important functions vasoconstriction (of afferent arteriole) aldosterone thirst ADH Na+ reabsorption

2. ANP secreted by cells in atria of heart in response to stretch GFR by “relaxing” glomerular cap, promotes excretion of H2O,

Na+

suppresses ADH, aldosterone, renin

Glomerular Filtration Rate (GFR) 3 principal regulators of GFR (cont.):

3) Neural regulation vessels of kidney supplied by vasoconstrictor fibers

from SNS, with strong stim afferent constricts more than efferent

strong SNS stim causes JGA cells to secrete renin and adrenal medulla to secrete Epi

Tubular Reabsorption Movement of water, solutes back into tubule

Filter 180 L/day of fluid and solutes filtering is non-specific much of this (Na+, K+, Glucose, etc.) needed by body must get them back into blood

about 99% of filtrate reabsorbed in tubule Epithelial cells in PCT surface area

(microvilli) for reabsorption – most (65%) reabsorption occurs in PCT

DCT and collecting ducts fine tune reabsorption

PCT site of most reabsorption - more Na+ ions filtered than all but H2O

Mechanisms that aid Na+ reabsorption Na+/ K+ ATPase on

basolateral side very important Keep concentration of Na+

inside tubule cells low Keep interior of cell

negatively charged Double gradient for Na+

movement into cell Requires E!

Reabsorption of Na+ in PCT

100% of filtered glucose, AA's, lactic acid, other useful metabolites reabsorbed by Na+ symporters - secondary active transport

Why are these secondary active transporters?

Reabsorption of Nutrients in PCT

Reabsorption of Na+ Na+ passively diffuses

from fluid in tubule lumen into cells pulls other solutes with it

via secondary active transport

reabsorption of water (osmosis – following solutes)

[ ] of remaining solutes diffusion from lumen

into tubular epithelium of remaining solute

reabsorption of water (osmosis – following solutes)

Reabsorption of Nutrients Transport maximum (Tm)

each type of symporter has upper limit on how fast it can work work is transport of solutes upper limit is max concentration that can still be

transported out of tubule, reabsorbed anything above max is lost in the urine

Renal threshold plasma concentration at which a substance begins

to spill into urine because Tm has been surpassed renal tubule concentration too high, all cannot be

reabsorbed by transporters glucose and diabetics

Reabsorption in the PCT By the end of the PCT the following By the end of the PCT the following

reabsorption has occurred:reabsorption has occurred: 100% of filtered nutrients100% of filtered nutrients 80-90% of filtered HCO80-90% of filtered HCO33

--

65% of Na65% of Na++ and water, and water, 50% of Cl50% of Cl-- and K and K++

Cells in thin descending limb only permeable to water No solute movement out of thin descending limb

Reabsorption in Loop of Henle

Cells in thick ascending LofH feature symporters reabsorb 1 Na+, 1 K+, 2 Cl- dependent on lo [Na+] for function little or no H2O reabsorbed from

thick ascending LofH Creates high osmotic

concentration in kidney medulla L of H reabsorb 30% of KL of H reabsorb 30% of K++ , ,

20% of Na20% of Na++ , 35% of Cl , 35% of Cl-- , 15% of , 15% of H H22OO

HH22O reabsorption not coupled to O reabsorption not coupled to reabsorb of filtered solutes reabsorb of filtered solutes (osmosis)(osmosis)

“Back side sets up the front”

Reabsorption in Loop of Henle

Reabsorption in DCT, Collecting Duct Filtrate reaching DCT has 80% filtered solutes,

H2O reabsorbed DCT

Na+/ Cl- symporter Ca++ reabsorbed here due to PTH reabsorbs another 10-15% of filtrate

Reabsorption in DCT, Collecting Duct Principal cells present in late

DCT and collecting duct 2 hormones act on principal

cells to modify ion and fluid reabsorption Aldosterone

renin, angiotensin system Na+ reabsorption principal cell basolateral Na+/K+

ATPases Anti-Diuretic Hormone (ADH)

generally principal cells have low H2O permeability

hypothalamus monitors osmotic concentration, if conc release ADH through post. pituitary

H2O reabsorption adds H2O pores to apical

membrane to increase H2O permeability

Reabsorption Summary

Tubular Secretion Removes substances from blood, add to filtrate

- includes K+, ammonium (NH4+), creatinine,

penicillin Two primary functions

Helps rid body of substances, generally waste products

Regulate blood pH by secretion of H+

Secretion of K+ Principal cells in collecting ducts secrete variable

amount of K+ due to leaky channels in apical membrane+ (opposite of Na+ reabsorption) Na+/K+ ATPases in basolateral membrane Controlled by:

Aldosterone - aldo, K+ secretion K+ concentration in plasma - levels, secretion Na+ levels in DCT - high levels Na+, Na+ reabsorption, K+

secretion

Secretion of H+ Cells of renal tubule can blood pH 3 ways

Secrete H+ into filtrate Reabsorb filtered HCO3

-

Produce more HCO3-

Secretion of H+ In PCT

CO2 present in cell carbonic anhydrase works in cell end with HCO3

- and H+ Na+/H+ exchanger - H+ secondary

transport with Na+ reabsorption combines w/ HCO3

- in lumen forms CO2 and H2O

CO2 diffuses back in tubule cell for more HCO3

- formation HCO3

- moves back to blood by facilitated transport

Exchanger stimulated by AII for increased Na+ reabsorption

Secretion of H+

Collecting ducts can secrete H+

Primary active transport Generate 1000 fold concentration

gradient (drop pH by 3 units) Carbonic anhydrase Bicarb scavenged by HCO3

-/Cl- antiporter basolateral new HCO3

-

H+ trapped in tubule lumen by buffers

Secretion of NH3 and NH4+

Ammonia (NH3) poisonous waste picked up from deamination, generally converted to urea, much less toxic

Can be used as a buffer for H+ to form NH4+

(ammonium) PCT cells can deaminate and secrete NH4

+ in a Na+/NH4

+ antiporter when blood pH lo

Summary of Nephron Functions

Summary of Nephron Functions

Summary of Nephron Functions

Summary of Nephron Functions

Summary of Nephron Functions

Rate of H2O lost from body dependent on ADH

Mechanism of Urine dilution - No ADH! Normal concentration in PCT

is 300 mOsm/L Glomerular filtrate isosmotic

to plasma Thick ascending LofH

impermeable to water but reabsorbs ions

More ions absorbed in DCT creating hypo-osmotic (hypotonic) urine

Producing Dilute Urine

Producing Concentrated Urine amount of water

reabsorbed - make hyperosmotic (hypertonic) urine

Solute and Water Reabsorption LofH Collecting duct - in

presence of ADH, water moves out

Urea recycling

Producing Concentrated Urine Countercurrent mechanism

Anatomical arrangement of juxtamedullary nephrons and vasa recta

U-shaped tubes have flow in opposite directions

Descending limb impermeable to ions, permeable to H2O ascending vice-versa

Overall effect filtrate more concentrated as it flows

down descending limb more dilute as it moves up

ascending limb

Producing Concentrated Urine Countercurrent mechanism

Also, Na+, K+, Cl- build up osmotic gradient in medulla of kidney

Vasa recta also consist of descending/ascending portions

Helps to remove some of the solutes w/out destroying the gradients

Producing Concentrated Urine

The Final Common Pathway Ureter

extension of kidney pelvis

enter bladder medially from posterior

Physiology transport urine to

bladder peristalsis primarily,

but hydrostatic pressure gravity help

Micturition Voluntary and involuntary

nerve impulses drive process

1. 700-800 ml capacity2. When volume > 200-400

ml stretch receptors fireA. Processed in cortex

– micturition reflex– initiate a conscious desire to

expel urineB. PNS driven 3. Contraction of detrusor,

relaxation of internal sphincter

1

2

A

3

B

The Final Common Pathway Urethra

Physiology - terminal portion of urinary tract, in males also serves as duct through which semen is discharged from the body

Urine Volume

1000-2000 ml/day influenced by blood pressure, blood osmotic pressure,

diet, temperature, diuretics, mental state, general health Chemical Composition - 95% water, 5% solutes