Glomerular Filtration Rate and Tubular Function

Intake is greater than Excretion

amount of the substance in the body will increase

Intake is less than Excretion

amount of the substance in the body will decrease

10 mEq/day to 1500 mEq/day

range of sodium intake that the kidney can adjust to

Excretion of varying amounts of sodium and water

The kidney’s method of long-term regulation of arterial pressure

Secretion of hormones and vasoactive factors

The kidney’s method of short-term regulation of arterial pressure

Erythropoietin

Released by the kidneys. Stimulates red blood cell production on the bone marrow.

Hypoxia

Stimulus for erythropoietin secretion.

1,25-dihydroxyvitamin D3 or Calcitriol

• Essential for normal calcium deposisition in bone and calcium reabsorption by the gastrointestinal tract

Excretion

• elimination of waste products (urea, creatinine, uric acid, bilirubin, and hormone metabolite) of metabolism

• elimination of toxins and foreign substances

Filtration

large amount of fluid is filtered from the glomerular capillaries into Bowman’s capsule.

Reabsorption

Filtered fluid leaves Bowman’s capsule and passes through the tubules. Water and solutes are reabsorbed into the blood

Secretion

Filtered fluid secretes other substances from the peritubular capillaries into the renal tubules.

Micturition

Urinary bladder empties when it become filled. first, the bladder fills progressively until tension rises above threshold, then reflex empties the bladder which causes the desire to urinate.

Glomerular Filtrate

fluid filtered from the blood through the glomerular capillaries into the kidney’s nephron. It is protein-free and does not contain cellular elements.

Salts and organic molecules

Contents of glomerular filtrate

Calcium and fatty acids

Low-molecular-weight substances that are partially excluded from glomerular filtrate because they bind to plasma proteins

Endothelium

• Inner later of the glomerular capillary membrane.

• It has small holes known as fenestrae

• Its proteins are richly endowed with fixed negative charges that hinder the passage of plasma proteins

Basement Proteins

• Middle layer of the glomerular capillary membrane

• Made of collagen and proteoglycan fibrillae with large filtration spaces

• Greatly hinders filtration of plasma proteins, because of strong negative electrical charges associated with the proteoglycans

Epithelial Cells or Podocytes

• outer later of glomerular capillary membrane

• has foot-like processes separated by split pores

• provide additional restriction to filtration of plasma proteins via its negative charges

P_bs and Π_gc

Factors that oppose GFR

P_gc and Π_bs

Factors that favor GFR

Increase in Kf and P_gc, and decrease in Π_gc

Capillary filtration rate increases due to these. The reverse can result to edema.

Zero

Π_bs is normally equal to __.

Proteinuria

Presence of protein increases glomerular filtration rate

20%

Normal Filtration Fraction

Increase in P_gc, GFR, RBF, and no change in FF

When an afferent arteriole dilates:

Decrease in P_gc, GFR, RBF, and no change in FF

When an afferent arteriole constricts:

Decrease in P_gc, GFR, FF, and decrease in RBF

When an efferent arteriole dilates:

Increase in P_gc, GFR, FF, and decrease in RBF

When an efferent arteriole constricts:

Efferent arteriole constriction

Gives the highest filtration fraction

Dilation of Afferent

• Prostaglandins

• Kinins

• Dopamine

• Acetylcholine

Constriction of Afferent

• NSAIDs

• Norepinephrine

• Endothelin

Dilation of Efferent

• ACEi inhibitor

• Angiotensin II blockade

Constriction of Efferent

• Angiotensin II

Intrinsic GFR Regulation

• Intra-Renal or only in the Kidney

• Arterial pressure of 80-180

• Goal of maintaining GFR over a wide range of MAP

• Has a myogenic response and a tubuloglomerular feedback

Extrinsic GFR Regulation

• Extra-renal, is system-wide and requires transport in bloodstream

• Arterial pressure of <80

• Goal is to maintain blood volume and pressure

• Happens in Neural and Hormonal

Renal Clearance

the ratio of the product of urine excretion and volume and the concentration of blood plasma.

Renal Clearance is less than GFR

• Net tubular reabsorption of solute V

Renal Clearance is greater than GFR

• Net tubular secretion of solute V

Renal Clearance is equal to GFR

• No net secretion nor reabsorption of solute V

Inulin

• used to calculate GFR since it is freely filtered and neiter reabsorbed nor secreted

Creatinine

• waste product of muscle metabolism, used instead of insulin

• overstimulates GFR because of secretion on proximal convoluted tubule

Nephron

• one unit of a renal tubule and its glomerulus

• one human kidney has approx. 1.3 M

Glomerulus

• invagination of a tuft of capillaries into the Bowman’s Capsule

• Supplied by an afferent arteriole and drained by an efferent arteriole

Macula Densa

• specialized cells at the end of glomerulus

Bowman’s Capsule

• Dilated, blind end of the nephron

Proximal Convoluted Tubule

• made up of a single later of cells that interdigitate with one another and are united by apical tight junctions

Loop of Henle

• straightened portion after the PT

• The descending and ascending portions are made up of thin, permeable cells

• Thick portion of the ascending limb is made up of cells containing mitochondria

Distal Convoluted Tubule

• Starts at macula densa

• Coalesce to form collecting ducts and pass through the renal cortex and medulla

• Empties into the pelvis of kidney and apexes of the medullary pyramids

Glomerulotubular Balance

Direct relationship between GFR and reabsorption of solute in PT

Tubuloglomerular feedback

Autoregulatory mechanism of controlling GFR with tubular filtrate contents of sodium and chloride in DT

Reabsorption

Substances filtered into the kidney tubules are returned to the bloodstream

Secretion

Substances are transported from blood to kidney tubules to be excreted in urine

Secodary Active Transport

• used by most of the handling of solutes

• takes advantage of the sodium gradient established by the Sodium-Potassium pump

• Initial step of tubular functions

• Low sodium concentration inside which creates a gradient for tubular reabsorption

Sodium

• Reabsorbed through PT

• Transported through secondary active transport in Apical side and diffusion in Epithelial sodium channels

• RAAS is involved in active sodium reabsorption

• ANP, urodulatin, uroguanylin and dopamine DECREASE sodium reabsorption

Glucose

• Diffusion of sodium provides energy for the simultaneous active uptake

• Exit across the basolateral membrane by diffusion

• 90% is reabsorbed by SGLT2 in S1 Segment

• 10% is reabsorbed by SGLT1 in S3 Segment

• GLUT2 in S1 and GLUT1 in S3 diffuses it out from tubular lumen

Threshold

At 160-200mg/dl, glycosuria begins

Transport Maxima

At 350mg/dl, all transporters are fully saturated

Splay Phenomenon

deviation from the ideal curve of the diagram. Its magnitude is inversely proportional to the avidity which the transport mechanism binds the substance it transports.

Water

• Aquaporins for water reabsorption are created by exocytosis of vesicles on the apical side through the action of ADH in basolateral membrane.

Aquaporin 2

Highest clinical significance. Plays a role in water reabsorption in the collecting ducts

Cations

• Uses the H+ antiport System

• Secreted in the proximal convoluted tubule

Anions

• Uses the Alpha-Ketoglutarate Antiport System

• Secreted in the proximal convoluted tubule

Para-aminohippuric Acid

• best estimate for renal plasma flow because it is both filtered and excreted in proximal convoluted tubule

• Underestimated by about 10%

Potassium

• backleak into the lumen creates a positive charge which forces magnesium and calcium to diffuse paracellularly

• secretion is dependent on intake and aldosterone

• reabsorbed in the outer medullary collecting duct via H+/K+ ATPase Pump

Calcium

• reabsorbed in the proximal convoluted tubule through solvent drag

• secreted in the distal convoluted tube through stimulation by Vitamin D and PTH

• In the outer medullary collecting duct, it is a factor in stone formation

Magnesium

• reabsorbed in the ascending limb of Henle via the electrochemical gradien by the NaKCl pump pr NaKCl co-transporter

Proximal Convoluted Tubule

• Majority (65%) of reabsorption

• Reabsorbs:

  • Na, Cl, HCO, K, Ca

  • Glucose

  • Amino Acids

  • Water

• Secretes H+, organic acids and bases

• Isosmotic

Thin Descending Lump

• Concentrate filtrate by removing water

• Reabsorbs H2O

• Permeable to water, creates a more concentrated filtrate

• hyperosmotic

Thick Ascending Limb

• Dilutes the filtrate by removing solutes

• Impermeable to water, permeable to sodium

• Reabsorbs:

  • Na, Cl, K

  • Ca, Mg, passively reabsorbed

  • HCO

• Secretes H+

• Hypo-osmotic

Early Distal Tube

• Reaborbs Na, Cl, Ca, Mg

• Regulates ionic balance

Late Distal Tubule and Cortical Collecting Duct

• Principal cells: Reabsorbs Na and H2O, sercretes K

• Type A intercalated cells: Secrete H and reabsorb HCO and K

• Regulated by hormones

Antidiuretric hormone

Acts on beta receptors to create aquaporins for water reabsorption

Medullary Collecting Duct

• final part of nephron where kidney fine-tunes urine

• ensures proper water balance, salt, and pH

• Reabsorbs:

  • Water - ADH

  • Urea - strengthen the osmotic gradient in medulla

  • Na and Cl - electrolyte balance

• Secretion:

  • H - eliminate excess acid, blood pH

  • Bicarbonate - adjusted based on pH

Tubular Fluid/Plasma Ratio

measures tubular solute concentration along the nephron

• More than 1 = Hyperosmotic

• 1 = Isosmotic

• Less than 1 = Hypoosmotic

Peritubular Capillary Reabsorption

• determined by the hydrostatic and colloid osmotic pressure of the peritubular capillaries

• These pressures govern the rate of absorption, just like in the GFR

Increase in Arterial Pressure

• raise PC hydrostatic pressure

• decrease reabsorption rate

Increase in Resistance of Arterioles

• reduce PC hydrostatic pressure

• increase reabsorption rate

Incraese in Systemic Plasma Colloid Osmotic Pressure

• Raise PC colloid osmotic pressure

• Increases reabsorption

Incraese on Filtration Fraction

• Raise the fraction of plasma filtered

• More concentrated protein in plasma

• Raise PC colloid osmotic pressure

• Increase reabsorption

Parasympathetic

• S2-S4

• Transmitted on the pelvic nerves

• Terminate on ganglion cells located in the wall

• Innervate the detrusor muscle

Sympathetic

• L2

• Transmitted through the hypogastric nerve

• Stimulate the blood vessels and not the bladder contraction

• Sensation of fullness or pain

Sensory Parasympathetic fibers

• stimulated and excited by the stretch receptors in the bladder walls when bladder volume reaches 250mL.

• relay information in the sacral region

Parasympathetic motor neurons

• excited and act to contract the detrusor muscles

• bladder pressure increases and the internal sphincter opens

External Sphincter

• motor neurons via the pudendal nerve are inhibited

• This is opened and urine flows out, assisted by gravity