Kidney Anatomy and Function

• The kidneys are in the posterior abdominal cavity, behind the peritoneum (retroperitoneal)
• Renal Capsule: A tough, fibrous capsule protects inner structures, tightly adhering to the kidney, then embedded in fat
• Renal Fascia: Fibrous tissue attaching kidney to the posterior abdominal wall
• Hilum: Indented region where renal artery, veins, nerves, lymphatics, ureter enter and exit

Renal Anatomy

• Renal Cortex: Outer layer, containing glomeruli, proximal tubules, and distal tubule segments
• Renal Medulla: Inner layer with tubules and collecting ducts; contains renal pyramids
• Renal Columns: Extensions from cortex between renal pyramids
• Medulla is divided into 8-10 cone-shaped renal pyramids
• Base of pyramid originates at cortex-medulla border, terminating in papilla
• Papilla projects into renal pelvis
• Renal Pelvis: Funnel-shaped continuation of ureter's upper end
• Outer border of pelvis divides into major and minor calyces, collecting urine from tubules of each papilla

Renal Blood Flow

• Kidneys receive ≈22% of total cardiac output, about 1100 ml/min
• Two kidney capillary beds are separated by efferent arteriole
• High hydrostatic pressure in glomerular capillaries (≈60 mmHg) enables rapid fluid filtration
• Lower hydrostatic pressure in peritubular capillaries (≈13 mmHg) allows for rapid fluid reabsorption
• Resistance adjustment in afferent/efferent arterioles helps maintain GFR.
• Renal artery enters via the hilum branching into interlobar, arcuate, interlobular (radial), then afferent arterioles
• Glomerular capillaries filter fluid and solutes (except plasma proteins) to form urine, distal ends form the efferent arteriole, directing to peritubular capillaries around tubules.
• Two capillary beds, glomerular and peritubular, are in series, separated by efferent arterioles
• The Renal circulation's arterioles regulate hydrostatic pressure in both sets of capillaries
• Peritubular capillaries drain into venous system as interlobular, arcuate, interlobar, then renal vein, beside the renal artery and ureter.
• At any time, two types of fluid move through the kidney: blood and tubular fluid.
• Renal cortex receives ≈90% of renal blood flow (PO2 ≈ 50mmHg)

Bloodflow and Oxygen

• Renal medulla and juxtamedullary nephrons receive about 10% of the renal blood flow (PO2 ≈ 10mmHg)
• Lower PO2 in the medulla makes it more sensitive to ischemia
• Renal blood flow decreases ≈10% per decade of life after age 50 (or 40—book says 40, 10%/10 years)
• Renal blood flow is determined by the pressure gradient across the renal vasculature
• Renal artery pressure is ≈ systemic arterial pressure; renal vein pressure averages ≈3-4 mmHg under most conditions

Resistance and Circulation

• Renal Blood Flow = (Renal artery pressure – Renal vein pressure) / Total Renal Vascular Resistance
• Renal Artery Pressure ≈ MAP
• Renal Vein Pressure ≈ 3 – 4 mmHg
• Most renal vascular resistance is in interlobular arteries, afferent/efferent arterioles
• Sympathetic nervous system, hormones, and local controls all affect resistance
• Increased resistance in kidney vascular segments reduces renal blood flow
• Decreased vascular resistance with constant artery and vein pressures increases renal blood flow
• Kidneys maintain relatively constant renal blood flow and GFR between 80-170 mm Hg via autoregulation
• Autoregulation occurs through mechanisms intrinsic to kidneys and provides constant GFR within (80-170mmHg)
• Increased systemic blood pressure causes afferent arterioles to constrict, preventing filtration pressure increase
• Wide systemic arterial pressure fluctuations are prevented from reaching glomerular capillaries
• Solute/water excretion is maintained uniformly, despite arterial pressure changes
• Glomerular filtration becomes pressure-dependent beyond autoregulation (MAP outside range)
• Reduced renal perfusion leads to autoregulation increase renal blood flow by reducing renal vascular resistance.
• Increased renal perfusion causes autoregulation to decrease renal blood flow by constricting afferent arterioles, preventing increased filtration pressure
• Urine output not autoregulated, linearly related to MAP
• Myogenic mechanism also affects autoregulation
  • Elevated renal artery pressure triggers myogenic mechanism, constricting afferent arteriole to protect glomerulus
  • Low renal artery pressure causes myogenic mechanism to dilate afferent arteriole increasing blood going through the nephron
• Myogenic theory: Sudden stretch in small vessels leads to smooth muscle contraction
• High arterial pressure stretches the vessel, reactive vascular constriction decreases blood flow to normal
• Low pressures cause less vessel stretch, smooth muscle relaxes, reducing vascular resistance and helping flow return

Glomerular Feedback

• Myogenic response inherent to vascular smooth muscle, occurs without neural/hormonal influences and is most pronounced in arterioles (and in arteries, venules, veins, lymphatics)
• Myogenic contraction starts with stretch-induced vascular depolarization, increasing calcium entry and contraction
• Tubuloglomerular feedback is influenced by sodium chloride [NaCl] levels
  • Juxtaglomerular complex includes macula densa cells (initial distal tubule) and juxtaglomerular cells in afferent/efferent arterioles.
  • Low sodium concentration at the macula densa causes decreased resistance to blood flow in afferent arteriole, increasing GFR
  • It will also simulate Renin release from the JG cells.
• Tubuloglomerular feedback mechanism contains two components to control GFR:
  • Afferent arteriolar feedback mechanism
  • Efferent arteriolar feedback mechanism
• These feedback mechanisms rely on juxtaglomerular complex anatomical arrangements.
• Juxtaglomerular complex comprises macula densa cells (initial distal tubule) and juxtaglomerular cells (afferent/efferent arterioles walls)
• Macula densa: specialized epithelial cells in the distal tubules contact afferent and efferent arterioles.
• Macula densa includes Golgi apparatus (intracellular secretory organelles), secreting substances toward the arterioles
• Macula densa cells sense changes in sodium chloride delivered to the distal tubule.
• Decreased GFR is understood to slow flow rate in the loop of Henle, increasing sodium and chloride reabsorption in ascending loop
• Reduced sodium chloride concentration signals macula densa, causing:
  • The macula densa then decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return GFR toward normal
  • Increased renin release from juxtaglomerular cells (afferent/efferent arterioles); major sites for renin stored

Hormones and Regulation

• Renin functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II. Angiotensin II constricts efferent arterioles, increasing glomerular hydrostatic pressure and helping return GFR to normal.
• Neural regulation via sympathetic nervous system:
  • Vasoconstriction decreases RBF and GFR
  • Increases renal tubular sodium and water reabsorption
  • Increases blood pressure
  • Stimulates renin release
  • Stimulates catecholamine release
  • Increases renal tubular absorption (decreased sodium and water excretion)
  • Renalase promotes metabolism of catecholamines
• Renin-angiotensin-aldosterone system (RAAS):
  • Increases systemic arterial pressure and sodium reabsorption.
  • Renin: Enzyme formed and stored in afferent arterioles of the juxtaglomerular apparatus
  • Renin helps form angiotensin I (physiologically inactive)
  • In the presence of angiotensin-converting enzyme (ACE), angiotensin I is converted to angiotensin II.
  • Angiotensin II:
    • Stimulates aldosterone secretion by adrenal cortex
    • Potent vasoconstrictor in efferent rather then afferent arteriole
    • Stimulates ADH secretion and thirst
• Renal arteries supply blood to kidneys
• Interlobar arteries travel down renal columns, between pyramids.
• Arcuate arteries arch over pyramid bases, parallel to kidney surface. Interlobular arteries extend through cortex toward kidney periphery and supply afferent glomerular arterioles
• Glomerular capillaries receive blood from afferent arteriole and feed into efferent arteriole
• Afferent arterioles subdivide into 4–8 glomerular capillaries
• Efferent arterioles convey blood to second capillary bed and Peritubular capillaries surround proximal/distal convoluted tubules and loop of Henle
• Vasa recta is a network of capillaries forming loops and follows loops of Henle; which is only source of blood to medulla (1-2% of total)
• Renal veins follow arterial path in reverse and empty into inferior vena cava
• Glomerulus consists of glomerulus Bowman's capsule, efferent arteriole, and juxtaglomerular apparatus, proximal tubule , distal tubule

Nephron

• The Renal corpuscle is a key filtration unit within the kidney’s nephron, responsible for filtering blood to produce urine
• It contains two main parts: the glomerulus, a network of capillaries, and Bowman's capsule, a cup-shaped structure surrounding the glomerulus.
• Renal corpuscle is in the renal cortex, the kidney's outer layer, and the starting point of the nephron, the kidney's functional unit
• Each nephron contains
  • Glomerulus: Capillary tuft where fluid is filtered from the blood
  • Long tubule: Converts filtered fluid into urine on way to the pelvis of the kidney
• Glomerulus: Branching, anastomosing glomerular capillaries with high hydrostatic pressure (≥60 mm Hg), covered by epithelial cells and encased in Bowman's capsule
• Fluid is filtered from glomerular capillaries flows into Bowman's capsule then proximal tubule (in kidney cortex); then into loop of Henle (renal medulla)
• Each loop consists of a descending and an ascending limb
• Thin segment of loop of Henle consists of walls of descending limb and lower ascending limb walls
• Thick segment of loop of Henle occurs after ascending limb returns to the cortex, its wall becomes thicker
• Thick ascending limb ends in a specialized plaque of cells called macula densa
• After the macula densa, fluid enters into distal tubule (like proximal tubule, in renal cortex)
• Distal tubule is followed into connecting tubule and cortical collecting tubule (lead to cortical collecting duct)
• 8–10 cortical collecting ducts join to form single, larger collecting duct running down into medulla (becomes medullary collecting duct)
• Collecting ducts merge to form progressively larger ducts, which eventually empty into the renal pelvis through the tips of the renal papillae
• Glomerulus: Contains glomerular endothelial cells (synthesize nitric oxide (vasodilator); Synthesize endothelin-1 (vasoconstrictor); Regulate glomerular blood flow)
• Visceral epithelium of Bowman's capsule: composed of cells called podocytes, are footlike projections, and forming filtration slits (modulate filtration)
• Afferent arteriole: Supplies glomeruli
• Efferent arteriole: Drains glomeruli
• Juxtaglomerular apparatus consists of juxtaglomerular cells (specialized cells around both afferent arteriole the enters the glomerulus) and Macula densa (sodium-sensing cells between the afferent and efferent arterioles of distal convoluted tubule:)
• Together, juxtaglomerular cells and macula densa form the juxtaglomerular apparatus (JGA), which controls RBF, glomerular filtration, and renin secretion

Filtration

• Glomerular capillary membrane features three major layers:
  • Fenestrated endothelium of the capillary
  • Basement Membrane of the capillary
  • Epithelial layer (podocytes) around capillary basement membrane
• These layers provide a barrier that hinders filtration of plasma proteins but permits filtration of water/solutes in plasma
• Glomerular filtrate should be protein and cell-free
• Healthy adult GFR is ≈125 ml/min or 180 L/day
• About 20% of plasma that flows through kidney is filtered through glomerular capillaries
• Glomerular filtration membrane filters selected components via three layers:
  • Glomerular capillary endothelium with fenestrae
  • Middle glomerular basement membrane (GBM)
  • Outer layer: visceral endothelial layer (podocytes in Bowman's capsule)
• NFP = Glomerular Hydrostatic Pressure – Bowman's Capsule Hydrostatic Pressure-Glomerular Oncotic Pressure
• Molecule charge and size affects filtration
• Neutral and positively charged molecules filter more easily
• Glomerular capillaries filter fluid at rate determined by:
  • The balance of hydrostatic and colloid osmotic forces acting along the capillary membrane
  • Capillary filtration coefficient (Kf), the production of permeability and filtering surface area
• Glomerular capillaries have greater filtration rate due to high glomerular hydrostatic pressure/large Kf.
• GFR = Kf x Net filtration pressure
• Net filtration pressure represents the sum of hydrostatic and colloid osmotic forces that favor or oppose filtration
• Forces include
  • Hydrostatic pressure (Pg) inside glomerular capillaries, promoting all filtration
  • Hydrostatic pressure in Bowman's capsule (P) outside capillaries, opposing all filtration
  • Colloid osmotic pressure (πg) of glomerular capillary plasma proteins, opposing all filtration
  • Colloid osmotic pressure (πB) of protein in Bowman's capsule, promoting all filtration

GFR

• Under usual conditions, protein concentration in the glomerular filtrate is 0 so that the colloid osmotic pressure is also zero
• GFR = Kf x(Pg - PB - πg + πB) where Kf = GFR/Net filtration pressure
• Normal Kf is about 12.5 ml/min per mm Hg of filtration pressure; This is about 400x greater then other issues
• High Kf contributes to rapid filtration
• Although ↑ Kf raises GFR and ↓Kf reduces GFR changes in Kf do not provide a main mechanism for daily GFR regulation
• Some diseases reduce functional glomerular capillaries lower Kf (thereby reducing filtration surface area)
• For example, chronic hypertension reduces hydraulic conductivity reducing thickness of the glomerular capillary
• Elevated hydrostatic pressure in Bowman's capsule decreases GFR, reducing this pressure raises GFR.
• Tubular obstruction from kidney stones raises Bowman’s capsule pressure to reduce the obstruction is relieved.
• Changes in Bowman's capsule pressure do not mainly regulate GFR.
• Normally, increased pressure in Bowman's capsule decreases GFR including diabetes causing damage to the GBM
  • proteinuria,↓ filtration surface area
  • Glomerulonephritis: Inflammation → decreased GFR decreased RBF from NSAIDs
• ↓ GFR From ↓ PGC= Glomerular capillary Hydrostatic Pressure
• ↓(hypotension, afferent constriction)
  • ↑ PBC = Bowman's Capsule Hydrospatic pressure -(urinary obstruction, tumor, stones) -↑GC (low plasma flow, dehydration) pressure
• ↑ GFR from ↑GIGC= Oncotic pressure
  • glomerular capillaries↑ PGC (efferent constriction, hypervolemia)
• Increased arterial colloid
• Plasma oncotic pressure increases the glomerular capillary colloid osmotic pressure (which reduces the GFR).
• Increasing the filtration fraction increases the rate at which it also increases
• In addition to the normal colloid osmotic pressure the plasma colloid pressure also increases
• Three variables cause for changes in the GFR including hydrostatic pressure
• Arterial pressure tends to raise with an a increased amount of hydrostatic pressure
• Increased afferent arterioles reduces in an increased amount hydrostatic and thus decreases GFR
• Constriction of the efferent arterioles increases hydrostatic raising the outward flow from the capillaries

Kidney Tubules

• Proximal convoluted tubule (PCT)
  • Microvilli for reabsorption/active reabsorption of sodium promoting passive diffusion of water.
  • Reabsorption of water increases urea concentration/Hydrogen ions actively exchanged for sodium ions.
  • Bicarbonate combines with hydrogen in the tubular cell and is reabsorbed as carbon dioxide (CO2) and water.
  • Glomerulotubular balance (GTB)
  • 65% of Na and water reabsorbed in PCT
  • Damaged tubules from metabolic byproducts/drugs accumulate, causing toxicity

Kidney Reabsorption

• In PCT first halt Na is reabsorbed via co-transport with glucose/amino acids/solutes
  • PCT second halt Na mainly reabsorbed with Cl ions
  • Extensie membrane surface of the epithelial brush border has carrier molecules, transports of all sodium ions across the luminal membrane (linked via the co-transport mechanism)
    • Additional sodium is transported from the tubular lumen by counter-transport
      • By reabsorbing hydrogen ions
  • The pump provides for the reabsorption of sodium however there are differences in the mechanisms in which they transported
• Loop of Henle enables kidneys ability to concentrate urine for the body
• The sodium in the tubules remains constant because the water and permibiliity of the solutes are equal so it reabsorbs without too much difficulty
• Certain organic solutes such as Glucose bicarb are more avdid for reabosriton with solutes, amino etc
• Changes in concentration of certain substances along with some glucose in plasma for the tubule which means there has to be a different set
• Amount of h sodium in the fluid drcrwarles alling with Sodium concnetration

Loop of Henle

• Loop is composed of with descending segment into the medulla allows kidney to focus its work of urine to conserve water for the body to
  • Fluid leaving th hyporsomotic
  • Resorb more solute that water into the intestine loop. Almost 20 pcrentbof almost resorb in the descending limb
• loop is impermeable to most parts and for concentrating urine
  • that as the thinner the segment limb
• segment contains high concentration with chloride and
  • The thick segment is not permeable to water