Urinary System and Acid-Base Balance

Functions and Overview of the Urinary System

• Regulation of Body Fluid Composition:     * The kidneys regulate body water volume, blood osmolarity (the concentration of dissolved solutes in the blood), and the ion concentration of various bodily fluids.     * Kidneys filter out excess water or ions present in plasma to maintain osmolarity.     * They conserve water and ions if levels in the body are too low.
• Regulation of Blood Pressure:     * The kidneys regulate water volume, which directly influences blood volume.     * They synthesize and secrete the hormone renin.     * Renin initiates a chain reaction producing Angiotensin II, which leads to:         * Vasoconstriction.         * Secretion of aldosterone.         * Stimulation of thirst.         * Stimulation of Antidiuretic Hormone (ADH) secretion.
• Acid-Base Balance:     * The kidneys maintain a stable blood $pH$ range by generating or excreting bicarbonate ($HCO_3^-$) as needed.     * They also excrete or conserve acid according to the body's requirements.
• Excretion of Waste and Toxins:     * The kidneys clear the blood of built-up metabolic waste, toxins, and drugs.
• Production of Erythropoietin (EPO):     * The kidney produce EPO, a hormone that stimulates red blood cell ($RBC$) production.
• Vitamin D Activation:     * The kidneys convert the inactive form of Vitamin D (cholecalciferol) into its active form, Calcitriol.     * Kidney cells contain the enzyme 1-alpha-hydroxylase to perform this conversion.     * Calcitriol is essential for calcium absorption by the small intestines.
• Gluconeogenesis:     * During periods of prolonged fasting, kidney cells can synthesize glucose from non-carbohydrate sources such as amino acids and lactate to maintain normal blood glucose levels.

General Anatomy of the Urinary System

• Main Structures and Functions:     * Kidney: Functions to filter the blood and form urine.     * Ureter: Paired tubes that transport urine from the kidney to the urinary bladder.     * Urinary Bladder: Serves as a temporary storage reservoir for urine.     * Urethra: The tube that carries urine from the urinary bladder to the exterior of the body.
• Location and External Anatomy:     * The kidneys are located in the posterior abdominal wall at levels $T12$ to $L3$.     * They are retroperitoneal (located behind the peritoneum).     * The right kidney is slightly lower than the left (often due to the space occupied by the liver).     * Above each kidney sit the adrenal glands.     * The lateral surface of the kidney is convex, while the medial surface is concave.     * Renal Hilum: An opening on the medial surface that leads into the renal sinus. It serves as the entry and exit point for ureters, blood vessels, and nerves.

Gross Anatomy and Internal Regions of the Kidney

• Renal Cortex: The most superficial region. It is lighter in color compared to the medulla.
• Renal Medulla: The middle region, formed by multiple cone-shaped renal pyramids.     * Renal Columns: Areas of tissue that separate the renal pyramids.     * Renal Pyramids: The base of the pyramid points toward the cortex, while the tip points toward the renal pelvis.
• Renal Pelvis: The deepest region located in the renal sinus. It is a medial expansion of the ureter.     * Urine Collection Path: Urine flows from minor calices into major calices, which merge to form the renal pelvis.

Renal Blood Supply

• Arterial Supply Path (to the nephron):     1. Aorta     2. Renal artery     3. Segmental artery     4. Interlobar artery     5. Arcuate artery     6. Cortical radiate artery     7. Afferent arteriole     8. Glomerulus (capillaries)
• Venous Drainage Path (from the nephron):     1. Efferent arteriole     2. Peritubular capillaries or vasa recta     3. Cortical radiate vein     4. Arcuate vein     5. Interlobar vein     6. Renal vein     7. Inferior vena cava

The Nephron: Functional Unit of the Kidney

• Definition: Nephrons are the structural and functional units of the kidney responsible for filtering blood.
• Components of a Nephron:     * Renal Corpuscle: The site of blood filtration. It consists of:         * Glomerulus: A ball of fenestrated capillaries. "Fenestrated" means they contain pores that allow for high permeability.         * Glomerular (Bowman's) Capsule: A cup-shaped structure of epithelial cells surrounding the glomerulus. It receives filtrate in the capsular space. It features podocytes, specialized cells with foot processes that interdigitate to form filtration slits.     * Renal Tubule: Extends from the corpuscle and consists of three regions:         * Proximal Convoluted Tubule (PCT): Receives filtrate from the corpuscle. It is lined with cuboidal epithelial cells with dense microvilli, highly adapted for reabsorption and secretion. It reclaims approximately $65\%$ of filtered water and solutes ($NaCl$, glucose, $HCO_3^-$, $Cl^-$, etc.).         * Nephron Loop (Loop of Henle): U-shaped with descending and ascending limbs. These limbs help concentrate urine.         * Distal Convoluted Tubule (DCT): Contains cuboidal cells lacking microvilli. Limited reabsorption and secretion occur here.
• Collecting Duct (CD):     * Filtrate from the DCT drains here before entering the renal pelvis.     * Principal Cells: Responsible for water and sodium balance; they are targets for ADH and Angiotensin II.     * Intercalated Cells: Two types (alpha and beta) that regulate acid-base balance.
• Classes of Nephrons:     * Cortical Nephrons ($85\%$): Most of the nephron resides in the cortex.     * Juxtamedullary Nephrons ($15\%$): Loops dip deep into the medulla; essential for generating a medullary concentration gradient to concentrate urine.

Nephron Capillary Beds and the Juxtaglomerular Complex

• Peritubular Capillaries: Arise from the efferent arteriole, surround the renal tubule, and reabsorb filtered solutes and water.
• Vasa Recta: Surround the loop of Henle of juxtamedullary nephrons. They dip deep into the medulla and play a major role in forming concentrated urine via countercurrent multiplication.
• Juxtaglomerular Complex (JGC): A contact point between the distal ascending limb and the afferent arteriole. It contains:     * Macula Densa Cells: Chemoreceptors that monitor $NaCl$ concentration in the filtrate (a marker for GFR and blood pressure).     * Granular Cells (Juxtaglomerular Cells): Mechanoreceptors in the afferent arteriole that monitor stretch. They synthesize and secrete renin.

Major Renal Processes and Urine Formation

• The Three Major Processes:     1. Filtration: Occurs exclusively at the glomerulus; produces cell-free and protein-free filtrate.     2. Reabsorption: Occurs along the renal tubule; reclaims needed substances from the filtrate.     3. Secretion: Occurs along the renal tubule; moves unwanted substances from the blood into the filtrate.
• Filtration Membrane: A passive process driven by hydrostatic pressure. It consists of:     1. Fenestrated endothelium of glomerular capillaries (allows passage of ions, water, amino acids, glucose, metabolites).     2. Basement membrane (fused physical barrier, negatively charged to repel proteins).     3. Podocytes (cells with filtration slits/diaphragms).
• Clinical Note: Glomerulonephritis: Inflammation of the glomerulus. Damage to the filtration membrane leads to proteinuria (protein in urine) and hematuria (blood in urine), resulting in hypoproteinemia and tissue edema due to loss of osmotic pressure.
• Filtration Pressures:     * Outward Pressure: Hydrostatic pressure in glomerular capillaries ($HP_{GC}$) = $55\,mmHg$.     * Inward Pressures: Capsular space hydrostatic pressure ($HP_{CS}$) = $15\,mmHg$ and Colloid osmotic pressure in glomerular capillaries ($OP_{GC}$) = $30\,mmHg$.     * Net Filtration Pressure (NFP): $55 - (15 + 30) = 10\,mmHg$ promoting filtration.
• Glomerular Filtration Rate (GFR):     * Amount of filtrate formed per minute. Normal GFR is $≥ 90\,ml/min$.     * GFR is directly proportional to NFP, total surface area, and membrane permeability.

Regulation of GFR

• Intrinsic Controls (Renal Autoregulation):     * Myogenic Response: Increased stretch ($\uparrow$ BP) causes afferent arteriole constriction to reduce flow; decreased stretch ($\downarrow$ BP) causes dilation to maintain flow.     * Tubuloglomerular Feedback: High $NaCl$ in filtrate (indicating high GFR) causes macula densa cells to release ATP, causing afferent arteriole vasoconstriction to decrease GFR. Low $NaCl$ causes vasodilation to increase GFR.
• Extrinsic Controls:     * Neural: High sympathetic tone causes vasoconstriction of the afferent arteriole, decreasing GFR.     * Hormonal: Low $NaCl$ or $BP$ triggers granular cells to release renin. Renin-Angiotensin-Aldosterone System ($RAAS$) increases blood pressure and GFR.

Tubular Reabsorption and Secretion Specifics

• Reabsorption Routes:     * Transcellular: Across apical membrane, through cytosol, across basolateral membrane, through interstitial fluid into capillary. Used for glucose, amino acids, and some ions.     * Paracellular: Between cells through leaky tight junctions (common in PCT). Used for urea and some ions.
• Specific Reabsorption Mechanisms:     * Water: Reabsorbed via aquaporins following an osmotic gradient generated by sodium.     * Nephron Loop: Descending limb is permeable to water only; ascending limb is permeable to solutes ($NaCl$) only.     * Hormonal Fine-Tuning (DCT and CD):         * ADH: Increases aquaporins in CD for water reabsorption.         * Aldosterone: Increases sodium channels in CD and DCT; reabsorbs $Na^+$ while secreting $K^+$ (electrical neutrality).         * Atrial Natriuretic Peptide (ANP): Inhibits $Na^+$ reabsorption in CD.         * Parathyroid Hormone (PTH): Increases $Ca^{2+}$ reabsorption in DCT.
• Tubular Secretion: Secretion of $H^+$, $K^+$, $NH_4^+$, creatinine, and drug metabolites into the tubule.

Osmotic Gradient and Urine Concentration

• Countercurrent Multiplier (Nephron Loop): Establishes the medullary osmotic gradient. Filtrate enters at $300\,mOsm$. Water leaves the descending limb (up to $1200\,mOsm$). Salt is removed in the ascending limb, diluting urine (down to $100\,mOsm$).
• Countercurrent Exchanger (Vasa Recta): Preserves the gradient while ensuring blood remains isosmotic to surrounding fluid.
• Urea Recycling: Urea moves into the ascending limb and is concentrated in the CD. In the deep medulla, it moves back out into the interstitial fluid, helping maintain the gradient.
• Hydration Status:     * Overhydrated: Reduced ADH, dilute urine ($100\,mOsm$).     * Dehydrated: Increased ADH and Aldosterone, concentrated urine ($1200\,mOsm$).

Renal Function Evaluation and Urine Properties

• Renal Clearance ($C$): Volume of plasma cleared of a substance per minute. Normal is $125\,ml/min$.     * $C < 125$: Substance reabsorbed.     * $C = 125$: No net reabsorption/secretion.     * $C > 125$: Substance secreted.
• Urine Composition: $95\%$ water, $5\%$ solutes (Nitrogenous wastes: Urea, Uric Acid, Creatinine).
• Physical Characteristics:     * Color: Clear to deep yellow (from urobilin).     * Odor: Sightly aromatic; turns to ammonia smell due to bacteria metabolizing urea. Fruity smell in diabetes (acetone).     * $pH$: Usually slightly acidic (avg $6.0$, range $4.5 - 8.0$). Alkaline $pH$ may indicate UTI.     * Specific Gravity: $1.001$ to $1.035$ (density relative to water).

Transport, Storage, and Elimination of Urine

• Ureters: Tubes from renal pelvis to bladder starting at $T2$. Three layers: Mucosa (transitional epithelium), Muscularis (smooth muscle for peristalsis), and Adventitia.     * Calculi: "Kidney stones." Nephrolithiasis (in kidney) or Ureterolithiasis (in ureters). Treated with lithotripsy.
• Urinary Bladder: Muscular sac for storage. Located posterior to pubic symphysis.     * Trigone: Triangular area between two ureter openings and the urethra; common site of UTIs.     * Detrusor: Thick muscular layer for contraction.     * Distensibility: Facilitated by rugae and transitional epithelium.
• Urethra: Drains the bladder.     * Sphincters: Internal (involuntary/autonomic) and External (voluntary/skeletal muscle).     * Female vs. Male: Female is short ($3-4\,cm$). Male is long ($20\,cm$) with three regions: Prostatic, Intermediate (membranous), and Spongy (running through the penis).
• Micturition (Urination):     * Requires detrusor contraction, internal sphincter opening, and external sphincter opening.     * Stretch receptors signal the sacral spinal cord, exciting parasympathetic/inhibiting sympathetic neurons.     * Incontinence: Inability to control urination (e.g., stress incontinence). Retention: Inability to expel urine (e.g., prostate hypertrophy).

Acid-Base Balance (Chapter 26)

• Optimal $pH$: Blood range is $7.35 - 7.45$. Arterial $pH \approx 7.4$. Venous $pH \approx 7.35$. ICF $pH \approx 7.0$.     * Alkalosis: $pH > 7.45$.     * Acidosis: $pH < 7.35$.
• Chemical Buffer Systems:     * Bicarbonate Buffer: Most important in blood/ECF; uses bicarbonate as an alkaline reserve.     * Phosphate Buffer: Effective in urine and ICF.     * Protein Buffer: Proteins are amphoteric (act as acid or base).
• Regulation of $pH$:     * Respiratory Regulation: Regulates $CO_2$ levels. Acidosis triggers increased respiration to expel $CO_2$ (shifting equilibrium left to lose $H^+$).     * Renal Regulation: Long-term mechanism. Kidneys reabsorb $HCO_3^-$ and secrete $H^+$ (Acidosis) or excrete $HCO_3^-$ (Alkalosis).     * Ammoniagenesis: Breakdown of glutamine to generate new $HCO_3^-$ and secrete ammonium ion ($NH_4^+$).
• Acid-Base Abnormalities:     * Respiratory Acidosis: $P_{CO_2} > 45\,mmHg$ (too much $CO_2$).     * Respiratory Alkalosis: $P_{CO_2} < 35\,mmHg$ (too little $CO_2$).     * Metabolic Acidosis: $HCO_3^- < 22\,mEq/L$.     * Metabolic Alkalosis: $HCO_3^- > 26\,mEq/L$.     * Systemic compensation usually occurs (e.g., respiratory compensation for metabolic issues).