Ch 37- Structure & Function of the Renal & Urologic Systems

• The kidneys' primary function is to maintain a stable internal environment for optimal cell and tissue metabolism.
• Mechanisms of action include balancing solute and water transport, excreting metabolic waste products, conserving nutrients, and regulating acids and bases.

Endocrine Function

• Hormones secreted include renin, erythropoietin, and 1,25-dihydroxy-vitamin D3.
• These hormones regulate blood pressure, erythrocyte production, and calcium metabolism.

Glucose Synthesis

• Kidneys synthesize glucose from amino acids, performing gluconeogenesis.

Urine Formation

• Glomerular filtration, tubular reabsorption, and secretion occur within the kidney.
• Urine travels through ureters to the bladder for storage, then exits the body.

Kidney Anatomy

• Paired organs located in the posterior abdominal cavity, behind the peritoneum.
• They lie on either side of the vertebral column, spanning approximately the 12th thoracic to 3rd lumbar vertebrae.
• The right kidney sits slightly lower than the left due to the liver's displacement.
• The approximate dimensions of each kidney are 11cm long, 5-6cm wide, and 3-4cm thick.

Renal Capsule

• Surrounds and embeds each kidney in a mass of fat.
• The capsule and fatty layer attach the kidney to the posterior abdominal wall.
• Kidney position and fat cushion protect from trauma.

Hilum

• It is a medial indentation in the kidney,

Hilum Functions

• Acts as the entry/exit point for renal blood vessels, nerves, lymphatic vessels, and the ureter.

Kidney Structures

Cortex

• The outer layer containing glomeruli, most proximal tubules, and some distal tubule segments.

Medulla

• It constitutes the inner part of the kidney.
• Consists of regions called pyramids.

Renal Columns

• Extensions of the cortex lie between the pyramids and extend to the renal pelvis.

Apexes of the Pyramids

• They project into minor calyces.
• Unite to form major calyces.

Minor Calyces

• Cup-shaped cavities, receive urine from collecting ducts through the renal papilla.

Major Calyces

• Join with minor calyces to form the renal pelvis connecting to the ureter's proximal end.

Calyces, Pelvis, and Ureter Walls

• Lined with epithelial cells and contain smooth muscle cells that contract to move urine to the bladder.

Lobe

• It is the structural unit of the kidney.
• Each lobe comprises a pyramid and the overlying cortex.
• About 14 lobes exist in each kidney on average

Nephron

• Each kidney has approximately 1.2 million nephrons

Functional unit

• The collective tubular structures and subunits all contribute to urine formation.

Nephron Subunits

• Renal corpuscle
• Proximal convoluted tubule
• Loop of Henle (nephron ansa)
• Distal convoluted tubule
• Collecting duct

Nephron - Epithelial Cells

• Different epithelial cells line various segments of the tubule.
• These cells facilitate the special functions of reabsorption and secretion.
• Proximal convoluted tubule cells reabsorb ≈60% of the glomerular filtrate.
• Intercalated cells either secrete H+ to reabsorb HCO3 or secrete HCO3 to reabsorb K+.
• Principle cells reabsorb Na+ and water while secreting K+.

Types of Nephrons

Superficial Cortical Nephrons

• They make up approximately 85% of all nephrons.
• The extend partially into the medulla.

Midocortical Nephrons

• Have short and long loops.

Juxtamedullary Nephrons

• Lie close to, and extend deep into, the medulla.
• Important for urine concentration.

Renal Corpuscle

Glomerulus

• This tuft of capillaries loops into the circular Bowman capsule, akin to fingers pushed into bread dough.
• Supplied by the afferent arteriole.

Juxtaglomerular Cells

• Located around the afferent arteriole.
• The cells release renin.

Macula densa

• The sodium sensing cells of the distal convoluted tubule.
• These lie between the afferent and efferent arterioles
• Juxtaglomerular cells + macula dense cells = juxtaglomerular apparatus (JGA) controls blood flow, glomerular filtration, and renin secretion.
• Drained by the efferent arteriole.

Bowmans Capsule

• Composed of a visceral epithelium which forms podocytes.
• The visceral epithelium reflects back at the vascular pole becoming the outer parietal epithelium.

Mesangial Cells and Matrix

• A combination of mesangial cells and matrix lie between and support the glomerular capillaries.
• Mesangial cells are shaped like smooth muscle cells.
• The Mesangial matrix is a type of connective tissue.
• Contract like smooth muscle cells to regulate glomerular capillary blood flow.
• They have phagocytic properties, releasing inflammatory cytokines and growth factors.

Glomerular Filtration Membrane

• Separates blood in glomerular capillaries from fluid in Bowman space.
• Allows filtration of blood components, except cells and large plasma proteins (MW > 70,000).
• Glomerular filtrate passes through three layers, forming primary urine.

Glomerular Filtration Membrane Layers

Inner Capillary Endothelium

Middle Glomerular Basement Membrane

Outer Visceral Epithelium

• Forms the inner layer of Bowman's capsule.

Inner Capillary Endothelium

• Composed of cells with continuous contact with the basement membrane.
• Synthesizes nitric oxide (vasodilator) and endothelin-1 (vasoconstrictor).
• Functions to help regulate glomerular blood flow.
• Contains pores maintained by vascular epithelial growth factor (VEGF) produced by visceral epithelium.

Middle Glomerular Basement Membrane

• Composed of a selectively permeable network of proteoglycans (type IV collagen).
• Secreted and maintained by the epithelial cells.

Outer Visceral Epithelium

• Composed of specialized cells called podocytes with pedicles.
• The pedicles radiate and adhere to the basement membrane.

Filtration Slits or Slit Membranes

• Pedicles of 1 podocyte interlock with pedicles of adjacent podocytes.
• This forms a network of intercellular clefts that modulates filtration.
• Nephrin, podocin, CD2-associated protein molecules function to ensure proper function of the filtration slits.
• When altered, glomerular disease results.

Bowman Space (Urinary Space)

• It is a space between visceral and parietal epithelia, continuous with the renal tubule lumen.
• The endothelium, basement membrane, and podocytes are covered with protein molecules.
• These protein molecules bear negative/anionic charges.
• This retards the filtration of anionic proteins preventing proteinuria

Proximal Convoluted Tubule

• Continues from the Bowman capsule Has initial convoluted (pars convolute) and straight segments (pars recta).
• The latter of the two descends toward the medulla.
• The tubule wall comprises one layer of cuboidal epithelial cells with microvilli.
• It increases reabsorptive surface area.

Distal Tubule

• This part contains straight and convoluted segments.
• Extends from the macula densa to the collecting duct which descends down the cortex.
• This part extends to renal pyramids of the inner and outer medullae, draining into the minor calyx.
• Composed of principal cells (secrete K+, reabsorb Na+ and water) and intercalated cells (secrete hydrogen, reabsorb K+).

Loop of Henle

• Proximal convoluted tubule joins the "hairpin-shaped.”
• This segment is composed of:

Thin descending segment

• Squamous cells, no active transport; permeable to water.

Thin ascending segment

• Permeable to ions, but not water.

Thick ascending segment

• Actively transports ions into interstitium, passing urine into distal convoluted tubule.
• Major structural difference between nephrons: the length of the Loop of Henle.

Cortical Nephrons

• More numerous; glomeruli close to cortex surface or in midcortex.
• Loops are short and may not extend into the medulla.

Juxtamedullary Nephrons

• Glomeruli located deep in cortex, close to medulla.
• May extend the whole length of medulla (approx. 40mm).
• Represent ~12% of nephrons.
• They are important for concentrating and diluting urine.

Cardiac output and the Kidneys

• Kidneys receive ≈20-25% of cardiac output in adults; about 1000-1200 mL of blood/minute.

Renal Bloodflow Regulation

• Interlobular artery → afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries → venules → interlobular vein.

Blood Vessels of the Kidneys

Renal Arteries

• The fifth branches of the abdominal aorta.
• Divide into anterior and posterior branches at renal hilum.
• Subdivide into lobar arteries supplying the lower, middle, and upper kidney thirds.

Interlobar Artery

• Subdivisions descend renal columns, between pyramids.
• Forms afferent glomerular arteries.

Arcuate Arteries

• Branches of interlobar arteries at the corticomedullary junction
• They arch over the base of pyramids, and run parallel to the surface.

Glomerular Capillaries

• Consist of four to eight vessels in a fist-like arrangement.
• Their vessels arise from the afferent arteriole, and empty into the efferent arteriole.
• These vessels carry blood to peritubular capillaries.
• Major resistance vessels regulate intrarenal blood flow.

Peritubular Capillaries

• Surround convoluted portions of proximal and distal tubules and the loop of Henle.
• Adapted for cortical and juxtamedullary nephrons.

Vasa Recta

• A network of capillaries that forms loops and closely follow the loops of Henle.
• The sole blood supply to medulla, necessary for concentrated urine.

Renal Veins

• They follow the arterial path in reverse and have the same names as corresponding arteries.
• Eventually empty into the inferior vena cava.
• Lymphatic vessels tend to follow the blood vessels' distribution.

Normal Hematocrit

• Is about 45%, about 600-700 mL of plasma flows through kidney/minute.

Renal Plasma Flow

• Approximately 20% (120-140 mL/min) of plasma is filtered at the glomerulus into the Bowman capsule.
• The remaining 80% (≈480 mL/min) flows through efferent arterioles to peritubular capillaries.
• Normally, ≈1-2 mL/min of glomerular filtrate is not reabsorbed, and instead returns to circulation via peritubular capillaries.

Glomerular Filtration Rate (GFR):

• Direct relation to perfusion pressure in glomerular capillaries.
• Directly related to renal blood flow (RBF).
• Regulation is through intrinsic autoregulatory, neural and hormonal regulatory mechanisms.
• Filtration Fraction is the GFR to RPF ratio per minute 120/600 = 0.20).

Arteriovenous Pressure

• Differences determine blood flow.
• Decreased mean arterial pressure or increased vascular resistance causes RBF decline and decreased urinary output.
• Normal urinary output = 30 mL/hour minimum in adults (0.5 to 1.0 mL/kg/hour).

Autoregulation

• Local mechanism maintaining constant GFR between 80-180 mmHg.
• Changes in afferent arteriolar pressure and resistance occur similarly.
• The Intrarenal blood flow + GFR remain constant despite changes in perfusion pressure.
• This is maintained by intrinsic autoregulatory myogenic contraction from blood vessel stretching.
• Autoregulation functions to maintain constant RBF and GFR during systemic blood pressure fluctuations.
• It also regulates solute and water excretion and It prevents barotrauma from high systemic blood pressure.

Neural Regulation

• Kidney blood vessels possess are innervated by sympathetic nerve fibers, primarily on afferent arterioles).
• Decreased systemic arterial pressure increases renal sympathetic nerve activity.
• This is mediated reflexively.
• Occurs through the carotid sinus and aortic arch baroreceptors.
• Sympathetic nerves release catecholamines which: stimulate afferent renal arteriolar vasoconstriction to decreases RBF and GFR.
• As well as increased renal tubular sodium and water reabsorption.
• In addition, increased blood pressure can result in regulation to water and sodium balance.
• Renalase is a hormone released by the kidney and the heart
• Ultimately this is to promote the metabolism of catecholamines.

RAAS (Renin-Angiotensin-Aldosterone System)

• Functions as a hormonal regulator and affects renal blood flow.
• It can increase arterial pressure, sodium and water reabsorption, and RBF
• Renin is secreted from the juxtaglomerular apparatus in response to diminished blood pressure, triggering vasoconstriction.
• Renin secretion also occurs due to decreased sodium chloride concentrations, sympathetic nerve stimulation, and release of prostaglandins.
• Renin cleaves angiotensinogen into angiotensin I.
• Angiotensin I is converted to angiotensin II ACE.
• It is mainly found in pulmonary and renal endothelium.
• Angiotensin II effects include Vasoconstriction of systemic arterioles increasing filtration pressure and systemic vascular resistance.
• Additionally stimulates aldosterone secretion increasing sodium reabsorption and water retention.
• Effects also includes Stimulating antidiuretic hormone (ADH) release which increases water reabsorption in collecting ducts.
• Stimulating thirst promotes drinking.
• Increased sympathetic activity also results.
• Aldosterone promote: Sodium reabsorption in distal tubules and collecting ducts, Potassium excretion, and Hydrogen ion excretion.
• Overall, these functions contribute to increasing blood pressure and electrolyte stasis.
• ADH is made and stores in the hypothalamus and posterior pituitary gland:
• Key components promotes permeability in collection ducts.
• At higher concentrations, ADH also causes vasoconstriction increasing systemic vascular resistance.
• Netriuretic Peptides such at Atrial Nitriuretic Peptide are antagonists to the RAAS.
• It has a collection of functions related to inhibiting reabsorption and increasing vasodilation that enhance the production of urine and salt excretion.
• Brain Natriuretic Peptide mirrors this, vasodilating and helping to prevent the formation of excess liquid.
• C-Type promotes vasodilation, and Urodilatin helps enahnce the release of more urine and salt.
• Vitamin D, primarily known for bone synthesis, also acts as a regulator to blood pressure gene, further reducing issues in the blood and electrolytes.
• Several other hormones in play here include:
• Adenosine
• Angiotensin II
• Atrial/Brain Netriuretic Peptide
• Bradykinin
• Dopamine
• Endothelin
• Histamine
• Nitric Oxide
• Prostaglandins
• Urodilatin
• Some related and relevant drug interactions in this area include ACE inhibitors, ARBs and SLGT2 inhibitors.
• Relevant concepts include the relation to RAAS over activation, which occurs through various issues and disseases like the development of heart issues.