Osmoregulation by the kidney

Roles of Kidney

  • filters blood to remove wastes from body

  • osmoregulation (salt and water balance)

  • acid base balance

  • all of the above contributes to making urine

topics covered that the kidney is important for:

  1. Ion concentration

  • need normal Na Cl concentrations in blood

  • too much Na+ outside makes the resting potential less than -70mV, it’s less ready to fire action potentials

    • hypoexcitable

  • hyperexcitable - more likely to fire action potentials, too little Na+

  • important to keep ions normal so action potentials can fire in heart and all over body

  1. Blood pressure

  • kidney’s regulation of salt and water balance also affects blood pressure

  • too much H2O in blood increases blood pressure

  • too little H2O in blood/partially filled blood vessel leads to hypovolemic shock, which can cause a drop in blood pressure and reduced organ perfusion, potentially resulting in serious health complications.

Kidney

  • high O2 blood —>nephron —>ureter —> to bladder

  • processing of blood to make urine occurs at junction of cortex and medulla

  • nephron - renal tubule and blood vessels at the cortex and medulla junction

    • functional unit of the kidney

fluid flow through kidney’s nephron:

  • filtration, then reabsorption of nutrients, then reabsorption of salt and water

  • afferent arteriole —> glomerulus —> proximal renal tubule —> reabsorption or renal tubule —> loop of Henle —> distal renal tubule —> collecting duct

  • Afferent (inward) arteriole - delivers blood to nephron

  • Glomerulus - capillary modified for filtration

    • some blood bypasses for urine production and goes to afferent arteriole

  • Efferent (outward) arteriole - carries blood away from glomerulus

Renal tubule

  • glomerulus —> renal tubule

  • Bowman’s capsule (surrounds glomerulus)

  • Proximal tubule - closest to glomerulus

  • Renal tubule (Henle)

  • Distal tubule - goes down to

  • Collecting duct - now urine

4 processes of kidney:

  • filtration - potential to be urine

    • blood to renal tubule

    • glomerulus to Bowman’s capsule

    • ~20% filtered; 80% efferent arteriole

  • reabsorption - in renal tubule to peritubular capillary

    • saved from urine

    • take good stuff aka nutrients and put in blood

      • H2O, suger, amino acids, etc.

  • secretion - blood to urine tubule

    • K+, H+

    • skipped filtration

  • excretion - urination

    • out of nephron

  • Filtration

    • ~180L fluid filtered everyday

    • 25% of blood supply when sleeping goes to kidneys

    • salt and water balance

    • too much H2O increases blood pressure

  • reabsorption - renal tubule back to blood

  • excretion - out of collecting duct = urine

    • out of nephron

  • end up with 1% of the 180L as urine

  • kidney functions:

    • remove wastes (afferent arteriole, glomerulus)

    • osmoregulation (loop of Henle, distal tubule, collecting duct)

Filtration at Glomerulus

  • plasma enters the afferent arteriole

  • 80% goes to efferent arteriole, (away from glomerulus)

  • 20% goes to glomerulus

  • filtrate goes to Bowman’s capsule then proximal convoluted tubule

The Glomerulus has pores

  • perforated

  • 5nm pores

  • what is filtered?

    • plasma

      • made of water, ions, sugars

    • “plasma-proteins”

  • what is not filtered?

    • proteins (albumin, IgG)

    • cells: RBC, WBC, platelets

How fast does filtration occur?

  • adjusted by pressure

  • Glomerular Filtration Rate (GFR) is determined by Glomerular Filtration Pressure (GFP)

  • afferent arteriole vasoconstricts or vasodilates

  • glomerulus regulated by ANS

    • sympathetic - vasoconstrict

    • parasympathetic - vasodilate

  • PH = hydrostatic, blood pressure

    • ~55 mmHg at capillaries

    • proteins remain in glomerulus

  • Pfluid = fluid pressure, push back from fluid already in Bowman’s capsule

  • π = osmotic pressure, higher osmolarity in glomerulus than in capsule

  • blood ~0.30 Osm = 300mOsm

    • include Na, sugar, Cl, amino acids, K, protein ions

    • everything dissolved added together

  • Osmolarity - all dissolved substances added together

  • glomerulus > capsule because proteins stay behind

  • if dehydrated, want filtration pressure to decrease, how?

  • reduce bp - vasoconstrict afferent arteriole

  • in this situation, sympathetic ns vasoconstricts

Macula densa - modified part of distal tubule

  • a flow meter, measuring flow rate

  • to loop of Henle

paracrine signal - chemical signal

  • tells afferent arterioles to constrict and slow down

  • begin production of urine

  • when flow was too high, now appropriate flow rate

Increase Autoregulation: kidney adjusts its own flow

autoregulation - any organ adjusting itself, digestive system good at it

  • more filtration, lose more urine

Reabsorption - renal lumen tubule back to blood

  • happens across transport epithelium

  • transport - fluid, molecules moving across a tissue

  • epithelia - sheet of cells making a barrier

  • epithelia transport

    • across one side of cell, through cell, then to other side, get through sheet of cells

  • epithelia

    • lined together by tight junctions so no gaps, form a sheet, not easily permeable

    • asymmetrical

      • blood side = basolateral membrane aka serosal side

      • apical membrane - full of microvilli to increase surface area

  • glucose reabsorption

    • pumped from renal tubule to blood

Secondary Active Transport

  1. Na+ K+ pump always on basolateral side

    3 Na+

    2 K+ in

    paired with K+ leak channel

    Na+ concentration becomes low

  2. Na/glucose co transport (diffusion)

    energized by sodium gradient

    strong gradient for Na+ powers this movement

  3. GLUT

    glucose channel - allows you to move down concentration gradient

    facilitated diffusion

    now glucose in blood is sent to muscles, insulin released

Secondary Active Transport

  • common in kidney and intestine

  • most water soluble nutrients use this mechanism

  • reabsorption mechanism for most water soluble nutrients (like glucose)

  • Filtration selectivity is only based on size

    • good and bad molecules

    • small toxins can also get filtered

  • Reabsorption - secondary active transport

    • selectivity for presence of co transporter (Na+ dependent)

      • makes sure nutrients needed are reabsorbed

  • things that get filtered out but not reabsorbed:

    • small enough to get through pores

    • no co transporters

    • gets urinated

Removal of wastes

  • filtered (nonselective) but not reabsorbed (selective)

    • smaller than 5nm but no co transporter

Osmoregulation - loop, distal tubule, collecting duct

Reabsorption in the proximal convoluted tubule is isotonic, and large magnitude (66% of filtrate)

  • 66% of water filtrate reabsorbed in proximal convoluted tubule, 33% in loop/distal tubule/collecting duct

end of Proximal Tubule

  • large volume of H2O reabsorbed

  • no change in osmolarity - concentration of all soluble molecules added together

  • water pulled in by osmosis

    • isotonic

Reabsorption of solutes

  1. Na+ reabsorbed by active transport

  2. electrochemical gradient drives anion reabsorption

  3. H2O moves by osmosis, following solute reabsorption

    concentration of other solutes increases as fluid volume in lumen (tubule) decreases

  4. permeable solutes are reabsorbed by diffusion through membrane transporters/paracellular pathway

Urine composition (water + Na+)

  • osmoregulation - salt and water balance

  • dehydrated - small volume and dark

    • concentrated urine (hypersomatic)

    • > 300 mOsm

  • overhydrated - large volume and clear

    • diluted urine (hyposomatic)

    • < 300 mOsm

  • 300mOsm at end of Proximal tubule = no osmoregulation done

Water gain is mostly via drinking, and water loss is mostly via urine

  • lose some amount of water gained to maintain osmolarity

    • ~1.5L water per day lost through urine

      • amount can be adjustable with hormones

Loop of Henle (renal loop)

Osmolarity of Extracellular fluid

  • in cortex isotonic (300mOsm)

  • gets higher further in renal loop

    • pull water out to make it more concentrated

    • 4x more salty (1200mOsm)

  • then enough salt is pulled out to lower osmolarity

  • waste removal - proximal tubule

  • osmoregulation - loop, distal tubule

  • NaCl reabsorption - active transport

Thiazide

  • diuretics

    • increase urine volume

    • prescribed to lower bp

  • on ppt: b)

  • response to elevated bp & volume

    • increase blood volume

    • increase bp

    • kidney excretes salts (NaCl) and H2O in urine, decreasing blood volume & bp

  • thiazide diuretics block the Na/Cl co transporter of the distal convoluted tubule

  • more Na+ Cl- left in lumen to become urine

  • when co transporter blocked, H2O also blocked so diuretics take out water

    • increases urine output

“Loop diuretics” such as furosemide or bumetanide block the Na/2Cl/K symporter of the thick Ascending limb at the Cl- port

  • loop diuretics block cotransporter

  • Cl- Na+ H2O stays in filtrate

    • output as urine

  • diuretics slightly and chronically increase Na+, Cl-, H2O excretion

Collecting duct function w/out hormones

  • no hormones

  • impermeable to water

Anti diuretic hormone (vasopressin) increases water reabsorption in the renal collecting duct to make concentrated urine

  • makes less urine

  • absence of vasopressin increases bp

  • when release vasopressin increase water reabsorption

  • ADH - decreases urine volume

  • makes concentrated urine

    • >300mOsm

    • removing salts

  • dehydrated

  • water permeable

Vasopressin stimulates Aquaporin-2 movement from intracellular vescicles to the apical membrane

  • vasopressin/ADH

    • increase bp

    • increase water retention

  • vasopressin inserts water channels

    • aquaporin inserted into cell membrane, now cell membrane is permeable to H2O —> reabsorption of H2O

Regulation of blood pressure is acute, intermediary, and chronic - it is integrated across multiple organ systems

  • decrease blood volume —> drop in bp

  • decrease bp

  • so now,

  • kidneys increase blood volume

    • conserve salt & water to minimize blood volume loss

    • decrease urine output

Aldosterone is the “sodium saver” hormone, increase Na+ reabsorption in DCT

  • aldosterone acts on principal cells

  1. aldosterone combines with cytoplasmic receptor

  2. hormone-receptor complex initiates transcription in nucleus

  3. translation and protein synthesis makes new protein channels and pumps

    1. make new proteins

      1. Na+ channels

      2. K+ channels

  4. aldosterone-induced proteins modulate existing channels and pumps

  5. result in increased Na+ reabsorption and K+ secretion

Aldosterone and Atrial Natriuretic Peptide affect urinary Na+

  • aldosterone - sodium saver

    • increase NaCl retention

    • increase water retention

    • exchanged with K+ (pee out more K+)

  • aldosterone released when need to save salt (not take in enough)

Atrial Natriuretic Peptide is the sodium excreter

  • also acts on afferent arteriole, vasodilate

  • made in atria of heart

  • na-uretic = sodium rich urine

  • peptide - fast acting

  • blocks action of aldosterone

    • removes Na+ K+ channels

    • allows Na+ to travel out in urine

  • released when a lot of salt in body

  • decreases bp:

    • decreases Na+, NaCl excreted

    • H2O excreted

    • decreases blood volume

Hormones of salt and water balance

  • Aldosterone - sodium saver (increases Na+ reabsorption)

    • upper ascending loop & distal tubule

    • makes new Na+ channels (&K+ channels)

    • increase bp

  • Vasopressin/ADH - water retention/decrease urine volume

    • insert water channels (aquaporins)

      • increase water permability

    • collecting duct

    • increase bp

  • Atrial Natriuretic Peptide - sodium excreter

    • made in atria

    • opposite function to aldosterone

  • no low ADH -

    • increase water excretions

    • remove H2O channels

    • decrease bp

Changes im plasma volume and osmolarity

  • deviations from osmoregulation

  • pic on ppt

Hormonal responses to changes in plasma volume & NaCl

  • decrease plasma vol & increase osm - high ADH & aldosterone (Na+ saver)

  • increase plasma vol & increase osm - ANP(Na+ excreter) & low ADH

  • no change to H2O & decrease osm - aldosterone & normal ADH(don’t need to change vol)

Angiotensin II

  • the liver makes ANG and goes in plasma

  • renin converts ANG to ANG I

  • angiotensin converting enzyme ACE enzyme converts it to ANG II in plasma

    • ACE II converts ANGII to ANGI

  • low bp initiates afferent arteriole

  • acts on granular cells to make renin

  • next to macula densa are

    • granular cells - modified part of afferent arteriole

    • releases renin

    • aka juxtaglomerular (JG) cell

    • when low bp, renin is released

    • renin is NOT A HORMONE, it is an enzyme that makes the hormone

  • ANGII orchestrates increased bp

    • arterioles vasoconstrict

    • decrease vessel space

    • increase heart effort

    • hypothalamus increase vasopressin

    • ADH increases blood volume

    • hypothalamus increases thirst

    • adrenal cortex increases aldosterone

Covid infection

  • high bp

  • droplets breathed in lungs by COVID-19 spike protein, binds to ACE2 receptor in lungs

  • ACE2 decreases bp

  • eliminates ANG2 balance so a lot of ANG2 in COVID, high bp

Hyponatraemia Paper

  • thiazide induced hyponatraemia

    • increase urinary NaCl

    • increase urine volume

    • block NaCl cotransporter, more NaCl in urine

  • problems with elders taking thiazide:

    • hyponatraemia - low plasma Na+ concentration, normal plasma volume

      • resting potential goes up, hyperexcitability, neurons can fire quickly

  • hyponatraemia associated with

    • increased water intake, they drink more H2O

    • low ADH —> chronic hyponatraemia

  • patients - thiazide causes hyponatraemia

  • control - thiazide and no hyponatraemia

  • patients - low body weight, low plasma Na+ concentration before drug

Study design

  • baseline samples of blood and urine taken

  • one dose of drug, then samples are taken every 0,4,8,24 hours after

  • water & food intake were not regulated, patients drank more water

Table 2

  • patients w past history of hyponatraemia drink more H2O

    b) both groups respond the same to the drug, baseline Na+ just lower in patients

    c) difference occurs before & after drug

    ADH normally released when dehydrated

    patients drank more H2O so lower ADH

  • patients natrually drink more H2O and natrually have low blood sodium

  • may be dangerous

  • no cellular mechanisms differ in groups