2130 unit 5

What are seven different functions of the kidney?

• (1) Regulation of ECF volume & BP

• (2) Regulation of osmolarity

  • remove extra solutes to maintain balance

• (3) Maintenance of ion balance

  • examine each ion to conserve OR excrete ions not needed

• (4) Maintenance of body pH

  • keep body in narrow range otherwise die (work w/ lungs to regulate)

• (5) Excretion of wastes

  • remove waste from blood plasma (urea, ammonia, creatinine)

    recover essential substances → glucose, AAs, water, ions, Na, Cl

    waste can accumulate BUT X = death

• (6) Production of hormones

  • make erythropoietin (EPO) → helps RBC maturation

  • make vit D → activated by kidney

• (7) Gluconeogenesis

  • makes new glucose molecules from non carb sources

What is the most important function of the kidney?

Regulation of total body water and salt balance (of blood plasma in ECF)

• w/o = X survive if ECF, osmolarity & ions dissolved in plasmas unregulated

• EX → INC H2O intake = INC ECF volume = INC blood plasma volume = INC BP & need to remove CDF to DEC BP to normal

What are three ways the kidneys contribute to homeostasis?

• Balance ECF volume

• regulate osmolarity

• maintain ion balance

urinary system anatomy

• kidney → filter blood, process it & unabsorbed items excreted via urine

• renal artery → 1 on inner concave side of each kidney, big blood vessel brings O2 blood inside

• renal vein → 1 on inner concave side of each kidney, send blood to body w/ nutrients to conserve/return to blood

• ureter → 1 on each kidney, filter blood X absorbed & take urine out

• bladder → collects urine made from both kidneys

• urethra → tube releases urine from body (INC length M)

kidney anatomy

• renal vein → blood sent back to body to be used

• renal artery → brings in blood & flow thru smaller blood vessels to cortex

• cortex → outer layer, granular b/c of nephron

• medulla → inner layer, straited b/c of nephron

• nephron → structures filter blood, make urine, collected in minor calyces & collected to rental pelvis

• calyces minor → in medulla & collects urine from nephron & funnel into calyces major

• calyces major → funnel in urine from minor calyces & send to renal pelvis

• renal pelvis → center of kidney, hollow, collects urine & leave via ureter

• ureter → bring urine to bladder & out of body

How are the kidneys positioned?

• retroperitoneally → outside abdominal cavity & btwn membrane lining of abdomen & back bone/muscles

• posterior to abdomen each side of spine @ 11/12th rib

What happens at the inner concave side of the kidney?

Where blood supply enters w/ renal artery and exists via renal vein

What is the function of the ureter?

• Where urine produced by kidneys is removed

• located on the inner concave side of the kidney

What is the function of the bladder?

• Collects urine produced by both kidneys

• Stores the urine until it is full and triggers the urge to urinate

What is the urethra?

• tube where urine exits the body from the bladder

kidney stones

• precipitation & crystallization of INC than regular [minerals] = stones

• occur in diff locations on urinary tract → renal pelvis, ureter & urethra

  • renal pelvis → if VV big, stuck here & hard exit kidney via ureter

• EX → oxalate, P, Ca, uric acid

TREATEMENT

• lithotripsy = E waves pulverize stones to smaller parts

• ureteroscopy = use laser break apart & grab out of ureter

• surgery

nephron

• functional unit of kidney

• each kidney = 1M nephrons

• IRL = twist on itself & covered in blood vessels

• (1) renal corpuscle

• (2) tubule (proximal, loop of Henle, distal convoluted tubule, collecting duct)

What is the renal corpuscle?

• filters blood

• makes filtrate & it travels through tubule

• (1) Bowman's Capsule → where fluid filters into

• (2) Glomerulus → specialized leaky capillaries

• (3) Juxtaglomerular Apparatus (JGA) → junction of tubule & arterioles around bowman’s capsule

What is the Bowman's Capsule?

• fluid filled ball hollow structure

• surround glomerulus & connects to proximal tubule

• (1) bowman’s/capsular space → inside of capsule, where filtrate collects

• (2) epithelial cells → outside

• (3) podocytes → contact glomerulus

What are podocytes?

• cells that wrap around the glomerulus

• stop excess leaking & filters fluid from blood → bowman’s space (all has to go thru this)

What is the function of the glomerulus?

• leaky capillaries bed 4 filtration from blood → bowman’s space

• blood enter = Afferent arteriole

• blood leave = Efferent arteriole (X all blood filtered b/c moving & exits)

What is the juxtaglomerular apparatus (JGA)?

• junction of =

  • (1) late ascending limb of Henle (touches corpuscle)

    • macula densa cells → detect [Na] & [Cl] & speed filtrate pass

  • (2) arterioles → afferent (IN) & efferent (OUT)

    • limb passes thru these blood vessels

• around Bowman's Capsule

• secretes renin from granular/juxtaglomerular cells

what is the afferent arteriole?

• bring blood from renal artery → each nephron’s afferent arteriole → glomerulus (travels to bowman’s space OR out w efferent arteriole)

• juxtaglomerular/glandular cells → behind macula densa, make & release renin

what is the efferent arteriole?

• blood exit from renal corpuscle

What is the tubule?

• tube-like structure made up of a single layer of epithelial cells

• wraps around itself & forms JGA

• process & modifies fluid → varies based on each part

• (1) proximal tubule = close to corpuscle

• (2) loop of Henle = descending & ascending limbs

• (3) distal convoluted tubules

• (4) collecting duct = connects w/ many nephrons on 1 collecting duct

What is the direction that filtrate travels?

renal artery → smaller blood vessels → nephron [ Renal corpuscle → proximal tubule → descending limb of Henle → ascending limb of Henle → distal convoluted tubule → collecting duct] → minor calyces → major calyces → renal pelvis → ureter → bladder → urethra

where are nephrons found?

• within layers of cortex & medulla in kidney

• fits with smaller blood vessels branches (1M nephrons in 1 kidney)

  • from renal artery surrounds medulla & fills in cortex

what are the types of nephrons?

based on position & anatomical differences BUT → filter blood, process fluid same as tubules

1. cortical nephron

   • 80% of all

   • short loop of Henle

   • renal corpuscle upper part of cortex

   • peritubular capillaries → reabsorb filtrate

2. juxtamedullary nephron

   • 20% of all

   • longer loop of Henle

   • renal corpuscle next to medulla

   • vasa recti capillaries → reabsorb filtrate & [] urine

What are peritubular capillaries?

Capillaries next to cortical nephrons that help reabsorb filtrate.

What are vasa recti?

Capillaries next to juxtamedullary nephrons that help reabsorb filtrate and concentrate urine.

In the renal corpuscle, what are the layers that connect the blood vessels to Bowman's capsule?

Podocytes

How much cardiac output is sent to the kidneys?

20%

• then filtered in nephrons

• large amt needed b/c → keep blood V & efficient ion balance

components of blood sent to kidney?

(1) PLASMA → H2O, proteins, glucose, hormones, CO2, O2, ions

(2) RBC

(3) WBC

What is the order of blood vessels in and around the nephron?

Renal artery --> afferent arteriole --> glomerulus (capillary bed) --> efferent arteriole --> peritubular capillaries/vasa recti --> venule --> renal vein

---

difference from rest of body = go to 2 diff arterioles & capillaries before venules & veins

• impt bc both can contract & dilate

• peritubular capillaries/vasa recti = reabsorb glucose back to body

what is the process of the nephron?

• most of filtrate reabsorbed back in body → 180L make, 1.5-2L urine

• PROCESS

  • (1) F = filtration

  • (2) R = reabsorption

  • (3) S = secretion

  • (4) E = excreted

What is filtration?

• movement of fluid & items dissolved in blood

• from glomerulus → Bowman's space (filtrate enters)

• ONLY IN RENAL CORPUSCLE

What is reabsorption?

• movement of items from filtrate within tubules → surrounding capillary bed (peritubular capillaries/vasa recti capillaries)

• most filtered fluid reabsorbed

• reabsorbed filtrate = H2O, ions, glucose, AAs

What is secretion?

• movement of items dissolved in blood from capillary bed → filtrate in tubule

• things dissolved in blood & X filtered in corpuscle

What is excretion?

• amount of solute excreted in urine

• filtrate collected in renal pelvis → collect to bladder = urine

What is the formula for excretion?

E = F - R + S

solute excreted = filtered - reabsorbed + secreted

what are the filtration barriers?

• glomerulus capillary bed has many FENESTRATIONS (pores)

• THUS → leaky & everything filters into bowman’s space

• THUS → barriers in corpuscle so proteins X filtered

How does the glomerulus serve as a filtration barrier?

• has endothelial pores (fenestration) → holes on endothelial cells & spaces btwn endothelial cells

• USE → size filter items filter out b/c leaky everything except proteins

How does the basal lamina serve as a filtration barrier?

• spaces in btwn fibers = further filter & exclude plasma proteins enter Bowman's capsule

• FORM → collagen & (-) charged glycoproteins structure connect endothelial cells of glomerulus to podocytes

How do podocytes serve as a filtration barrier?

• use pedicels → wrap & interlace glomerulus w narrow slits

• narrow slits btwn each podocyte → narrow or widen & limit SA 4 filtration

• THUS → only 20% blood entering glomerulus filtered in bowman space

how does the filtration in the renal capsule work?

blood ENTER renal capsule & nephron via afferent arteriole to make filtrate→

1. glomerulus’ fenestration sizes + spaces btwn endothelial cells

2. basal lamina’s space in btwn fibers

3. podocytes’ spaces in btwn

THEN → blood not filtered exit via efferent arteriole to kidney & to main circuit

What are three methods used for urinalysis measurement?

GOAL = test if healthy based on whats in urine

1. Visual inspection (colour & clarity)

   • clear = overhydration

   • bright yellow = excess multi vitamins (B2)

   • dark yellow = dehydration

   • brown = liver/kidney disease, antibiotics, drugs, malaria

   • frothy = proteinuria, meds (INC BP)

   • particles/frothing = bacteria, proteins & kidney stones

2. microscopic evaluation

   • test if seen w/o microscope, crystal, cell types

   • small crystals = kidney stones

   • bacteria, RBC = UTI

   • RBC = UT cancer

3. chemical analysis

   • pH, density w colorimetric strip

   • WBC/leukocytes = infection

   • glucose = DM

   • bilirubin = liver disease/ gallstones (excrete digestive normally)

net filtration pressure

• healthy = 10 mmHg

• collection of 4 forces that control amt of fluid filtered into bowman’s space

What are the four pressures in the renal corpuscle that contribute to net filtration pressure?

1. Hydrostatic Pressure of Glomerular Capillaries (PGC)

2. Colloid Osmotic Pressure of Glomerular Capillaries (πGC)

3. Hydrostatic Pressure of Bowman's Capsule (PBC)

4. Colloid Osmotic Pressure of Bowman's Capsule (πBC)

What is the formula for NFP?

NFP = (PGC + πBC) - (PBC + πGC)

What is Hydrostatic Pressure of Glomerular Capillaries (PGC)?

• heart’s pressure push blood → leaky glomerular capillaries → capsule space

• FAVOURS filtration

• #1 force promotes filtration

What is Colloid Osmotic Pressure of Glomerular Capillaries (πGC)?

• water's pressure from its affinity 4 proteins in plasma → draw water to self & stay in capillaries

• INHIBITS filtration

What is Hydrostatic Pressure of Bowman's Capsule (PBC)?

• fluid’s back pressure when try to leave capsule

• INHIBITS filtration → limits more fluid filtering into capsule space

What is Colloid Osmotic Pressure of Bowman's Capsule (πBC)?

• when protein in capsular space pull fluid itself BUT X often exist

• FAVOURS filtration

what affects the net filtration rate?

• INC renal blood flow/BP INC = INC NFR

• DEC healthy = DEC filter

• INC healthy = INC filter = rupture capillaries

• (+) = fluid filter into bowman’s space

• 0/(-) = fluid X filter into bowman’s space

What is the glomerular filtration rate (GFR)?

• # of water/fluid & solutes dissolved in water get filtered per unit time → Bowman's space from the glomerular capillaries

• affects amt salt & H2O exerted from body

what affects the GFR?

• NFP → blood flow & BP

• filtration coefficient

• fenestration

filtration coefficient

• affects leakiness of glomerular capillaries

• hard to measured

• affected by →

  • (1) SA of glomerular capillaries 4 filtration

  • (2) permeability btwn capillaries

what results when there in an INC/DEC in the GFR?

high = INC solutes & H2O excreted

• CAUSE → INC BP (= INC PGC), INC blood in kidneys

low = DEC solutes & H2O excreted

• CAUSE → INC basal lamina thickness, smaller slits btwn podocytes

What are the two autoregulatory mechanisms that regulate GFR?

• techqs to keep GRF if overall BP changes

  • USE → protect kidney damage b/c INC BP = damage blood vessels

1. Myogenic response

2. tubuloglomerular feedback

What activates myogenic response?

• INC blood flow to nephrons = INC pressure each glomerulus = INC GFR

• THEN → myogenic response kicks in to keep GFR constant

• THUS → reflexive contraction of afferent arteriole & DEC blood flow to each glomerulus = DEC GFR

---

• related to myogenic theory from CV system → INC BP = INC blood flow = stretch arteriole = vasocontraction = DEC blood flow after

What activates the tubuloglomerular feedback?

• filtrate in tubule based on macula densa cells → detect [Na] & fluid flow rate

• THEN → INC solute [Na+] & [Cl-] filtered & fluid flow INC

• THUS → macula densa cells release paracrine factor= stimulate afferent arteriole constriction = DEC fluid filtration rate

GFR INC detected = adenosine released

GFR DEC detected = nitric oxide released

What would happen to GFR if there was vasoconstriction of the AFFERENT arteriole?

Vasoconstriction --> DEC blood enter glomerulus --> DEC pressure --> DEC GFR

What would happen to GFR if there was vasoconstriction of the EFFERENT arteriole?

Vasoconstriction --> DEC blood leave glomerulus --> INC pressure --> INC GFR

What would happen to GFR if there was vasoconstriction of both arterioles?

angiotensin II released = vasoconstriction afferent & efferent arterioles = DEC blood enter glomerulus = DEC fluit filtration = DEC GFR

how can we accurately measure GFR?

• X measure fluid filters in nephrons noninvasively

• measure w/ creatinine (good for most)

  • (1) find [creatine] in plasma

  • (2) find creatinine in urine

  • (3) find total urine/yr

  • (4) calc

([creatine in urine] x urine/day) / [creatine in blood plasma]

what is the issue with using creatinine to calc GFR?

• can free filter & X reabsorb BUT some secreted into tubule

• THUS → amt creatinine excreted = filtered + extra secreted into filtrate

• THUS → overestimate GFR

• also → INC skeletal muscle = INC creatinine

what are the ways to measure GFR?

1. creatine urine & plasma

2. inulin

   • IV infusion so [inulin] = blood & filtered by kidneys (100% excreted)

3. blood urea nitrogen (BUN)

   • blood plasma [urea] lvl use w/ N measure in urea

   • DEC filter = INC urea = DEC kidney f(x)/INC protein diet/heavy exercise

4. serum creatinine

   • quick check w normal blood lvl → BUT normal vary

   • INC blood creative = DEC filter

What information is provided by the filtered load calculation?

How much of each substance is filtered and how each filtered substance is handled by the tubules.

what GFR value is healthy?

• 180L/day or 125mL/min

• kidney f(x) DEC overtime → DEC GFR = INC chance kidney disease/failure

what is renal handling?

• reabsorption of substances dissolved in blood & X uptake by bowman’s space

• diff processes for each filtered substance

• use filtered load to assess amt pxd filtered

What is the filtered load?

• how much each substance in blood is filtered

• assess if tubules f(x) normal

• (1) find GFR

• (2) [substance] in plasma x GFR

what are the common excretion rates of Na, K, Mg?

Na = 0.5 - 2.5

K = 6 - 9

Mg = 3 - 5

What is the formula for percent excreted?

Total excreted / filtered load

What is happening when excretion rate < filtered load?

DEC levels of ions in blood plasma than normal

• hyponatremia → Na+

• hypomagnesemia → Mg2+

• hypokalemia → K+

What is happening when excretion rate > filtered load?

INC levels of ions in blood plasma than normal

• hypernatremia → Na+

• hyperkalemia → K+

• hypermagnesemia → Mg2+

how does the tubule work?

• 180L filtrate made each day w/ 99% reabsorbed

• diff f(x) of filtrate based on type of tubule

• V reabsorbed (H2O + solutes)

  • PROXIMAL = 65%

  • loop of Henle = 20%

  • distal tubule & collecting duct= 14%

What is the overall function of the proximal tubule?

• reabsorbs → glucose, AAs, H2O, Na+, K+, Cl-

• reabsorb 65% of total volume

What is the overall function of the descending limb of the loop Henle?

• reabsorbs most H2O & little Na+

• reabsorbs 20% of total volume w/ ascending limb

What is the overall function of the ascending limb of the loop Henle?

• reabsorbs Na+, K+, Cl-

• X H2O reabsorb

• reabsorbs 20% of total volume w/ descending limb

What is the overall function of the distal tubule?

• reabsorb Na+, K+, Cl-, and Ca++

• reabsorbs 14% of total volume w/ collecting duct

What is the overall function of the collecting duct?

• reabsorbs Na+ & H2O

• secretes K+ some cases

• reabsorbs 14% of total volume w/ collecting duct

what are the cells of the tubule?

• 1 layer of polar epithelial cells → linked w tight junctions

• (1) luminal/apical → membrane inside tubule touch filtrate

• (2) basolateral → membrane outside near interstitium

tight junctions in btwn epithelial cells → proteins adhere cells together (vary if allow transport or not)

What are the two types of transport mechanisms?

• Paracellular transport → btwn epithelial cells

• transcellular transport → across cell in luminal & basolateral membrane

What is paracellular transport?

• transport btwn epithelial cells

• move substances from lumen & filtrate → interstitium → blood

• movement based on tight junction proteins

What is transcellular transport?

• transport across cell w/ channels/protein carriers from →

  • (1) filtrate across luminal

  • (2) cytosol across basolateral

• GOAL → reabsorb OR secret (rare)

• can have same or diff channels

• EX → ions, H2O

what are the types of transport mechanisms?

1. CHANNEL

   • small protein lined pores 4 specfic molecules

   • H → L passive w/ [ ]/elector chem gradient

     ---

2. UNIPORTER

   • facilitated w H → L

   • move 1 molecule thru membrane by bind & release

     ---

3. SYMPORTER/CO TRANSPORT

   • facilitated move 2+ molecules

   • 1st = down [gradient] H → L

   • 2nd = against [gradient] L → H w/ 2nd active transport (X ATP self)

     ---

4. ANTIPORTER/EXCHANGER

   • facilitated move 2 molecules opp ways

   • 1st = down [gradient] H → L

   • 2nd = against [gradient] L → H w/ 2nd active transport (X ATP self)

     ---

5. 1ST ACTIVE TRANSPORTER

   • use ATP move against [gradient] L → H

   • kidney = Na/K ATPase w/ Na out tubule & K in

What is required for both symporters and antiporters?

1+ molecule moving down its [gradient] from H → L in 2 opp directions

1. What are the 6 transporters in the kidney?

1. H2O CHANNEL →

   • osmosis w aquaporins in membrane

   • kidney w 4 types → only aquaporin II hormonally regulated

     ---

2. Na+ CHANNEL →

   • mediated diffusion of Na H → L [] across membrane

   • AKA ENaCs (epithelial Na⁺ channels)

     ---

3. glucose UNIPORTER →

   • only move glucose w facilitated protein carrier H → L []

     ---

4. Na+/glucose SYMPORTER →

   • reabsorb from filtrate

   • diff types & facilitate transport w Na⁺gradient for glucose

     ---

5. Na+/H+ ANTIPORTER →

   • AKA exchanger

   • facilitate export protons (H+ ions) out & Na+ in w/ Na+ gradient

     ---

6. Na+/K+ ATPase →

   • primary active transporter w ATP

   • move Na/K L → H

   • keep Na+ gradient for other transporters

Which aquaporin is regulated by ADH?

Aquaporin II

How does the Na+/glucose symporter move the molecules?

Reabsorbs glucose & Na+ from the filtrate

driven by the Na+ gradient

How does the Na+/H+ antiporter move the molecules?

Exports protons out of the tubule in exchange for Na+ entering the cell

driven by the Na+ gradient

regulated transporter

• hormone changes f(x) for a specific transporter/channel

• vary → based on hormone, type of transporter, OR nonregulated & constant

What are the different ways that channels and protein carriers can be changed due to the signaling by hormones?

1. CELLULAR LOCATION

   • only work when on cell membrane even if transporter same

2. ACTIVITY

   • hormones INC activity in protein carriers = INC speed w/ INC molecules across a membrane

3. GENE EXPRESSION

   • Stimulating cell to produce INC copies of mRNA = INC amt translated into channels or protein carriers = INC molecules move across membrane

How does the sodium gradient help with the reabsorption of other molecules within the tubule?

• epithelial tubule cell → Na DEC in cell, K INC outside cell

• filtrate in lumen → from blood plasma & INC in Na

• THUS → Na+ leave filtrate & enter tubule cells

  • balanced w/ (1) ion channel/protein carriers for Na move INTO luminal (2) primary active protein carrier on basolateral moves Na OUT

• THUS →

  • help reabsorption of glucose (symporter)

  • help secretion of H+ (antiporter)

  • help secretion of K+ (ATPase)

direction of protein carrier movement based on [gradient]

what are the channels/transporters on the PROXIMAL tubule?

1. Na/AA symporter

   • bind & conformation change w both 1 direction move

   • facilitated transport based on Na detection & AA follow

   • LUMINAL

     ---

2. Na/glucose symporter

   • bind & conformation change w both 1 direction move

   • facilitated filtrate move to tubule b/c of Na & help glucose enter

   • LUMINAL

     ---

3. Na/H exchanger

   • protein carrier & hormone responsive

   • reabsorb Na + move lumen → tubule (H-L)

   • antiport of H secreted + move tubule → lumen

   • LUMINAL

     ---

4. Na/K ATPase

   • ATP conformation w against gradient → 3Na move out, 2K move in

   • hormone responsive

   • BASOLATERAL

     ---

5. AQ1 LUMINAL

   • move via osmosis from filtrate → tubule

     ---

6. AQ1 BASOLATERAL

   • reabsorb by move H2O from tubule cell → interstitial into capillaries

     ---

7. AA uniporter

   • AA move cytosol → interstitial space by self w transcellular reabsorb

   • BASOLATERAL

     ---

8. glucose uniporter

   • glucose move H -> L where DEC outside cell w facilitated transporter

   • BASOLATERAL

     ---

9. paracellular

What four channels/transporters are located on the LUMINAL of the PROXIMAL tubule?

• Na+/AA symporter

• Na+/glucose symporter

• Na+/H+ exchanger

• AQ I

What four channels/transporters are located on BASOLATERAL of the PROXIMAL tubule?

• Na+/K+ ATPase

• AQ I

• AA uniporter

• glucose uniporter

What kind of paracellular transport occurs on the proximal tubule?

Reabsorption of water, K+, and Cl-

• X hormone affect bc gaps btwn cells

Which two channels/transporters are responsive to hormones on the proximal tubule?

angiotensin II → release when Na DEC in blood than normal, change speed of exchange

1. Na+/H+ exchanger

2. Na+/K+ ATPase

What channel is located on the luminal membrane of the descending limb of loop of Henle?

AQ I.

What two channels/transporters are located on the basolateral membrane of the descending limb of loop of Henle?

AQ I and Na+/K+ ATPase.

What two channels/transporters are located on the luminal membrane of the ascending limb of loop of Henle?

Na+ uniporter and Na+/Cl-/K+ symporter

What two channels/transporters are located on the basolateral membrane of the ascending limb of loop of Henle?

Na+/K+ ATPase and K+/Cl- symporter.

What kind of paracellular transport occurs on the ascending limb?

Paracellular transport of Na+ from the tubule lumen to the blood stream.

What three channels/transporters are located on the luminal membrane of the distal convoluted tubule?

Ca++ uniporter, Na+ uniporter, and Na+/Cl- symporter.