Module 4 - Lecture 6
Urine Formation
Concept of Urine Formation:
Involves altering the composition of blood and filtrate that pass through nephrons.
Achieved through renal blood flow:
Renal Blood Flow: Approximately 1.2 L/min, ~25% of cardiac output, with kidneys weighing only 1-2% of body weight.
Ensures high plasma filtration rate.
Key Formula:
Urinary excretion = Filtration – Reabsorption + Secretion
Filtration Rates:
Entire plasma volume ~3 L filtered ~60 times a day through the kidneys.
Glomerular filtration = 125 mL/min or 180 L/day.
Three Renal Processes that Produce Urine
Glomerular Filtration:
Produces cell- and protein-free filtrate.
Tubular Reabsorption:
Selectively reabsorbs 99% of substances from filtrate back into blood within renal tubules and collecting ducts.
Tubular Secretion:
Selectively moves substances from blood to filtrate.
Glomerular Filtration Rate (GFR)
Definition:
Volume of plasma filtered per minute by all glomeruli.
An important indicator of kidney function.
GFR declines in kidney disease.
Filtration Fraction:
The fraction of renal plasma flow that is filtered in the glomerulus during a single pass through the kidney, calculated as:
Of plasma volume entering the afferent arteriole, 20% is filtered by the glomerulus, and 80% continues back through the efferent arteriole into capillaries.
>99% of filtrate is typically reabsorbed.
Glomerular Filtration Process
Filtration Membrane
Components:
Separates blood in glomerular capillaries from filtrate in glomerular capsule.
Porous membrane allows free passage of water and solutes smaller than proteins.
Composed of three layers:
Fenestrated Endothelium: of glomerular capillaries.
Basement Membrane: Prevents protein passage.
Podocytes: Specialized cells with foot processes.
Filtrate Composition:
Blood plasma minus proteins.
Process Type:
Glomerular filtration is a passive, non-selective process.
Driving Force:
Hydrostatic pressure forces fluids and solutes out of glomerular capillaries into the glomerular capsule through the filtration membrane.
Pressures Affecting Glomerular Filtration
Net Filtration Pressure (NFP):
Responsible for filtrate formation, resulting from a balance of outward and inward pressures.
Outward Pressures:
Promote filtrate formation.
Hydrostatic Pressure in Glomerular Capillaries (HPgc):
Typical value: 55 mmHg, higher than usual for capillaries (28 mmHg).
Inward Pressures:
Inhibit filtrate formation.
Hydrostatic Pressure in Capsular Space (HPcs) and Colloid Osmotic Pressure in Glomerular Capillaries (OPgc):
OPgc exerts pressure by proteins in blood, 'sucking' water into capillaries.
NFP Calculation:
Main controllable factor determining GFR.
Regulation of Glomerular Filtration
Purpose:
Maintain filtration and systemic blood pressure.
Determination of GFR:
Regulated by the volume of blood (BV) flowing into the glomerulus, which affects glomerular hydrostatic pressure.
Changes in GFR:
Affect filtrate formation, urine output, and systemic blood pressure.
Increasing GFR will increase urinary output, thus decreasing blood volume and blood pressure.
Intrinsic Mechanisms of Regulation
Myogenic Stretch of Afferent Arteriole Smooth Muscle:
Fluid volume entering arterioles alters arteriole diameter.
Vascular smooth muscle contracts when stretched and relaxes when not stretched.
High blood volume/stretch triggers vasoconstriction → decreases GFR; low blood volume/stretch triggers vasodilation.
Tubuloglomerular Feedback:
Macula densa cells monitor filtrate [NaCl].
High GFR reduces reabsorption time; results in high NaCl in filtrate.
Vasoactive secretions from macula densa constrict afferent arterioles, which decreases GFR.
Extrinsic Mechanisms of Regulation
Renin-Angiotensin-Aldosterone System (RAAS):
Primary mechanism for increasing blood pressure.
If blood volume is abnormally low (e.g., due to hemorrhage or dehydration), several pathways activate granular cells to release renin:
Activated Macula Densa: Low blood pressure correlates to low GFR, meaning slow filtrate flow in tubules → more NaCl reabsorption; decreased [NaCl] signals granular cells.
Reduced Stretch: Granular cells act as mechanoreceptors that secrete renin under low pressure.
Sympathetic Nervous System (SNS) & Baroreceptor Reflex:
In resting state, renal arterioles are typically dilated.
If blood volume is low, the baroreceptor reflex is inhibited (normally promotes vasodilation); SNS gets activated.
Results in vasoconstriction to increase total peripheral resistance, constriction of afferent arterioles decreases blood flow and GFR, leading to increased blood volume and blood pressure.
Tubular Reabsorption of Filtrate
Process:
Active transport is used to facilitate Na+ reabsorption across apical and basolateral membranes.
Substances such as glucose, amino acids, vitamins, and ions (e.g., K+, Cl-) are co-transported alongside Na+ transporters.
Osmotic diffusion of water occurs via aquaporins present at the proximal convoluted tubule (PCT).
Varying Reabsorption Across Tubules
Proximal Convoluted Tubule:
Reabsorbs all glucose, amino acids, and approximately two-thirds of Na+ and water.
Nephron Loop:
Water is reabsorbed from the descending limb and not the ascending limb (aquaporins are present only in descending limb).
Solutes are reabsorbed in the ascending limb but not in descending limb.
Distal Convoluted Tubule & Collecting Duct:
Regulated reabsorption occurs, based on the body's needs.
Antidiuretic Hormone (ADH, or vasopressin) increases water reabsorption by inserting aquaporins in the collecting duct.
Aldosterone promotes Na+ reabsorption in DCT and collecting duct, increasing water reabsorption due to osmosis following Na+.
Urine Characteristics and Formation
Urine Composition:
95% water, 5% solutes including:
Urea: Product of amino acid breakdown
Uric Acid: Waste product of amino acid metabolism
Creatinine: Metabolite of creatinine phosphate.
Concentration Levels in Urine:
Urea > Na+ > K+ > creatinine > uric acid
Physical and Chemical Characteristics of Urine:
Healthy urine is clear and varies from pale to deep yellow due to urochrome (pigment from hemoglobin breakdown).
Aromatic when fresh, often develops an ammonia odor due to bacterial metabolism of urea.
Slightly acidic (~pH 6.0); high-protein diets lead to more acidity while vegetarian diets lead to more alkalinity.
Mechanism of Osmotic Gradient in Urine Formation
Osmotic Gradients:
Determined by water movement and solute concentration in the medulla of the kidneys.
Countercurrent mechanisms affect urine volume and concentration.
Countercurrent Mechanisms:
The direction of fluid flow in adjacent segments of a connected tube (descending & ascending loops).
Countercurrent multiplier first concentrates and then dilutes the filtrate.
Changes in filtrate concentration in the descending limb facilitate water loss to interstitial fluid, affecting solute secretion in the ascending limb.
Urea recycling from the collecting duct contributes to high osmolality in the medulla.
Dilute vs Concentrated Urine
Well-Hydrated State:
The body can dilute urine to $\frac{1}{6}$ the concentration of blood plasma.
Dehydrated State:
Up to 99% water reabsorbed yielding 0.5 L of concentrated urine at 1200 mOsmol/L.
Countercurrent Exchange via Vasa Recta
Function:
The vasa recta, a series of capillaries that surround the nephron loops, perform countercurrent exchange, preserving osmotic gradients in the renal medulla.
Capillaries exchange solutes and water in opposing directions, maintaining equilibrium between capillaries and interstitial fluid at each section, upholding the concentration gradient throughout the renal medulla.