Chp. 25

• Components of the Urinary System: The system consists of the kidneys, ureters, urinary bladder, and the urethra.

• Primary Functions of the Kidneys:

  • Filtering the blood to remove metabolic wastes.

  • Excretion of wastes in the form of urine.

  • Secretion of hormones and regulatory substances.

  • Regulation of water, electrolyte, and acid-base balance.

  • Production of erythropoietin (hormone for red blood cell production).

  • Long-term blood pressure regulation and maintaining thermal balance.

• Kidney Position: The kidneys are located in a retroperitoneal position, which means they are situated "behind" the peritoneum in the superior lumbar region of the posterior abdominal cavity.

• Supportive Tissues Surrounding the Kidney:

  • Renal fascia: The outermost layer of dense fibrous connective tissue that anchors the kidney and adrenal gland to surrounding structures.

  • Perirenal fat capsule: A fatty mass that surrounds the kidney and cushions it against blows or physical trauma.

  • Fibrous capsule: A transparent capsule that prevents infections in surrounding regions from spreading to the kidneys.

• Renal Hilum: A vertical cleft on the medial side of each kidney where the renal artery, renal vein, and ureter join or exit the organ.

• Internal Anatomy of the Kidney:

  • Cortex: The light-colored, granular superficial region.

  • Medulla: The deeper region containing cone-shaped tissue masses called renal pyramids (or medullary pyramids).

  • Renal Pyramids: Triangular structures in the medulla; the broad base faces the cortex, and the tip (papilla) points internally.

  • Renal Columns: Inward extensions of cortical tissue that separate adjacent pyramids.

  • Renal Pelvis: A funnel-shaped tube continuous with the ureter leaving the hilum.

  • Major Calyces: Branching extensions of the renal pelvis.

  • Minor Calyces: Cup-shaped areas that enclose the papillae of the pyramids and collect urine draining from the papillae into the major calyces.

Blood Supply and Flow Through the Kidney

• Arterial Path (Inward Flow):

  1. Aorta

  2. Renal artery

  3. Segmental artery

  4. Interlobar artery

  5. Arcuate artery (arches over the bases of the pyramids)

  6. Cortical radiate artery (radiates outward into the cortex)

  7. Afferent arteriole

  8. Glomerulus (capillary bed for filtration)

  9. Efferent arteriole

  10. Peritubular capillaries (in cortical nephrons) or Vasa recta (in juxtamedullary nephrons)

• Venous Path (Outward Flow):

  1. Cortical radiate vein

  2. Arcuate vein

  3. Interlobar vein

  4. Renal vein

  5. Inferior vena cava

• Note on Unique Circulation: Blood flows through two capillary beds (the glomerulus and the peritubular capillaries/vasa recta) separated by an efferent arteriole.

Anatomy and Physiology of the Nephron

• Definition: Nephrons are the structural and functional units of the kidney that filter blood and form urine. Each kidney contains approximately 1 million nephrons.

• Main Parts of a Nephron:

  • Renal Corpuscle: Responsible for filtration.

  • Renal Tubule: Responsible for reabsorption and secretion.

• Structural Components of the Renal Corpuscle:

  • Glomerulus: A tuft of fenestrated capillaries.

  • Glomerular capsule (Bowman's capsule): A cup-shaped hollow structure that completely surrounds the glomerulus.

• Structural Components of the Renal Tubule:

  • Proximal Convoluted Tubule (PCT): Regions closest to the corpuscle, located in the cortex, featuring cuboidal epithelial cells with dense microvilli (brush border) for increased surface area.

  • Nephron Loop (Loop of Henle): Consists of a descending limb and an ascending limb.

  • Distal Convoluted Tubule (DCT): Located in the cortex, composed of cuboidal cells which are thinner and lack a prominent brush border compared to the PCT.

• Distinction between Proximal and Distal: "Proximal" indicates the region is closer to the renal corpuscle, while "distal" indicates it is further away.

• Importance of Convolutions: The elaborate coils increase the length and surface area of the tubule, enhancing the processing of filtrate.

• Juxtaglomerular Complex (JGC): A region where the most distal portion of the ascending limb of the nephron loop lies against the afferent arteriole. It contains three cell populations:

  • Macula Densa: Closely packed cells in the ascending limb that act as chemoreceptors to sense the $NaCl$ (sodium chloride) content of the filtrate.

  • Granular Cells (Juxtaglomerular cells): Located in the arteriolar walls; they are enlarged smooth muscle cells acting as mechanoreceptors that sense blood pressure in the afferent arteriole and contain the enzyme renin.

  • Extraglomerular Mesangial Cells: Located between the arteriole and tubule cells, interconnected by gap junctions; they transmit signals between the macula densa and granular cells.

• Comparison of Nephron Types:

  • Cortical Nephrons: Account for $85\%$ of nephrons; renal corpuscles are located superficially in the cortex; have short nephron loops; efferent arterioles supply peritubular capillaries.

  • Juxtamedullary Nephrons: Renal corpuscles lie deep in the cortex near the medulla; contain long nephron loops that invade deeply into the renal medulla; play an essential role in producing concentrated urine; efferent arterioles supply the vasa recta.

The Three Major Renal Processes of Urine Formation

1. Glomerular Filtration: Occurs in the renal corpuscle and produces a cell-free and protein-free filtrate. This is a passive process involving hydrostatic pressure forcing fluids and solutes through a membrane.

2. Tubular Reabsorption: The process of moving substances from the filtrate back into the blood. It occurs in the renal tubules and collecting ducts. Most of the filtrate is reclaimed here.

3. Tubular Secretion: The process of moving specific substances (e.g., $H^{+}$, $K^{+}$, creatinine) from the blood in peritubular capillaries through the tubule cells and into the filtrate.

Glomerular Filtration Mechanics

• Filtration Membrane: A porous membrane between the blood and the interior of the glomerular capsule. It consists of:

  • Glomerular capillary endothelium: Contains fenestrations (pores) that allow all blood components except blood cells to pass.

  • Basement membrane: A physical barrier that blocks all but the smallest proteins; it is negatively charged and electrically repels many anionic macromolecules.

  • Visceral layer of the glomerular capsule: Specifically the foot processes of podocytes that create filtration slits; slit diaphragms prevent the passage of macromolecules.

• Substances passing freely: Water, glucose, amino acids, and nitrogenous wastes.

• Substances excluded: Blood cells and large plasma proteins.

• Glomerular Pressures and Net Filtration Pressure (NFP):

  • Outward Pressure: Glomerular hydrostatic pressure ($HP_{gc}$) is effectively glomerular blood pressure ($55\,mmHg$). Unlike other capillary beds, this stays high along the entire length of the capillary to promote filtration.

  • Inward Pressures: Capsular hydrostatic pressure ($HP_{cs}$) exerted by filtrate in the capsule ($15\,mmHg$) and Colloid osmotic pressure ($OP_{gc}$) resulting from proteins in the blood ($30\,mmHg$).

  • Calculation: $NFP = HP_{gc} - (HP_{cs} + OP_{gc}) = 55 - (15 + 30) = 10\,mmHg$.

• Glomerular Filtration Rate (GFR): The volume of filtrate formed each minute by the combined activity of all 2 million glomeruli ($120\text{ to }125\,ml/min$).

Regulation of Glomerular Filtration

• Intrinsic Controls (Renal Autoregulation): Goal is to maintain GFR despite fluctuations in systemic blood pressure.

  • Myogenic Mechanism: Responds to rising systemic blood pressure; vascular smooth muscle in afferent arterioles contracts when stretched, restricting blood flow to the glomerulus; it relaxes when blood pressure falls.

  • Tubuloglomerular Feedback Mechanism: Macula densa cells sense high flow or high $NaCl$ in the filtrate and cause constriction of the afferent arteriole to lower GFR.

• Extrinsic Controls: Goal is to maintain systemic blood pressure, sometimes at the expense of GFR.

  • Sympathetic Nervous System: During extreme stress or low blood volume, norepinephrine causes intense vasoconstriction.

  • Renin-Angiotensin-Aldosterone Mechanism: Granular cells release renin in response to low systemic blood pressure, sympathetic stimulation, or decreased $NaCl$ sensing by macula densa cells.

Tubular Reabsorption and Secretion

• Reabsorption Mechanisms:

  • Active: Requires energy (ATP). Includes sodium ions ($Na^{+}$), glucose, amino acids, and vitamins. Primary active transport ($Na^{+}/K^{+}$ pump) sets the stage for secondary active transport (co-transport) of other solutes.

  • Passive: Includes water (via osmosis), urea (via diffusion), and lipid-soluble solutes.

• Site of Reabsorption:

  • PCT: Most active; reabsorbs all glucose and amino acids, and $65\%$ of $Na^{+}$ and water.

  • Nephron Loop: Descending limb is permeable to water but not salt; ascending limb is impermeable to water but permeable to solutes ($Na^{+}$, $Cl^{-}$).

  • DCT and Collecting Duct: Reabsorption is regulated by hormones (fine-tuning).

• Hormonal Regulation:

  • Antidiuretic Hormone (ADH): Increases water reabsorption in the collecting duct by inserting aquaporins.

  • Aldosterone: Enhances $Na^{+}$ reabsorption (and water follows) in the DCT and collecting duct; increases $K^{+}$ secretion.

  • Atrial Natriuretic Peptide (ANP): Inhibits $Na^{+}$ reabsorption in the collecting duct to reduce blood volume.

  • Parathyroid Hormone (PTH): Increases $Ca^{2+}$ reabsorption in the DCT.

• Tubular Secretion Importance:

  • Disposing of drugs or metabolites tightly bound to plasma proteins.

  • Eliminating undesirable substances that were passively reabsorbed (like urea).

  • Ridding the body of excess potassium ($K^{+}$).

  • Controlling blood pH by secreting $H^{+}$ and reabsorbing $HCO_{3}^{-}$.

Regulation of Urine Concentration and Volume

• Medullary Osmotic Gradient: An osmotic gradient from the cortex ($300\,mOsm$) to the deep medulla ($1200\,mOsm$), allowing the kidney to vary urine concentration.

• Countercurrent Multiplier: The interaction between filtrate flow in the long nephron loops of juxtamedullary nephrons. It establishes the gradient. The ascending limb actively pumps out salt, which increases interstitial osmolality, which in turn pulls water out of the descending limb.

• Countercurrent Exchanger: The flow of blood through the vasa recta. It maintains the gradient by being highly permeable to water and solutes, preventing the removal of salt from the medullary interstitial space.

• Formation of Dilute vs. Concentrated Urine:

  • Dehydration: Low extracellular fluid volume leads to increased ADH release. This increases aquaporins in collecting ducts, causing high water reabsorption and a small volume of concentrated urine.

  • Overhydration: Decreased ADH release leads to fewer aquaporins. Water stays in the tubule, resulting in a large volume of dilute urine.

Renal Function and Urine Properties

• Renal Clearance: The volume of plasma from which the kidneys clear a particular substance in a given time (usually 1 minute).

  • If clearance is equal to inulin ($125\,ml/min$), the substance is filtered but not reabsorbed or secreted.

  • If clearance is 0, the substance is completely reabsorbed (e.g., glucose).

  • If clearance is less than inulin but greater than 0, the substance is partially reabsorbed.

  • If clearance is greater than inulin, the substance is secreted into the filtrate.

• Urine Composition:

  • Water: Approximately $95\%$ of urine volume.

  • Nitrogenous Wastes: Urea (largest component by weight, derived from amino acid breakdown), Uric acid (nucleic acid metabolism), and Creatinine (metabolite of creatine phosphate).

• Physical Properties:

  • Color: Clear to deep amber. Deeper color indicates higher concentration.

  • pH: Usually slightly acidic (around pH 6).

  • Specific gravity: Usually greater than that of water ($1.001\text{ to }1.035$).

• Abnormal Components:

  • Bile pigments, Plasma proteins (e.g., albuminuria), White blood cells (pyuria), and Erythrocytes (hematuria).

  • Large amounts of glucose in urine (glycosuria) are seen in diabetes mellitus because transport proteins are saturated.

Transport, Storage, and Elimination of Urine

• Ureters: Slender tubes that move urine from the renal pelvis to the bladder via peristalsis. Lined with transitional epithelium to allow stretching.

• Urinary Bladder: A collapsible, muscular sac that stores urine temporarily. Contains the detrusor muscle (smooth muscle) and the trigone (area between ureters and urethra).

• Urethra: A muscular tube that conveys urine to the body exterior. Contains the internal urethral sphincter (smooth muscle, involuntary) and the external urethral sphincter (skeletal muscle, voluntary).

  • Male vs. Female: The female urethra is short ($3\text{ to }4\,cm$) and only transports urine. The male urethra is longer ($20\,cm$) and transports both urine and semen.

• Micturition (Urination):

  1. As urine accumulates, stretch receptors in the bladder wall are activated.

  2. Signals travel to the sacral region of the spinal cord.

  3. Parasympathetic neurons are excited, and sympathetic neurons are inhibited.

  4. The detrusor muscle contracts, the internal sphincter opens, and somatic efferent firing decreases, causing the external sphincter to relax.

  5. The brain's pontine storage center inhibits micturition, while the pontine micturition center promotes it.

• Route of a molecule (e.g., Uric Acid): Afferent arteriole $\\rightarrow$ Glomerulus $\\rightarrow$ Glomerular capsule $\\rightarrow$ Proximal convoluted tubule (PCT) $\\rightarrow$ Nephron loop $\\rightarrow$ Distal convoluted tubule (DCT) $\\rightarrow$ Collecting duct $\\rightarrow$ Minor calyx $\\rightarrow$ Major calyx $\\rightarrow$ Renal pelvis $\\rightarrow$ Ureter $\\rightarrow$ Urinary bladder $\\rightarrow$ Urethra.