Overview of the Urinary System and Kidney Functions

Organs of the Urinary System

The urinary system consists of six principal organs: two kidneys, two ureters, the urinary bladder, and the urethra.

Functions of the Kidneys

1. Filter blood and excrete toxic metabolic wastes. 2. Regulate blood volume, pressure, and osmolarity. 3. Regulate electrolyte and acid-base balance. 4. Secrete erythropoietin (EPO). 5. Help regulate calcium homeostasis via calcitriol synthesis. 6. Clear hormones and drugs from the blood. 7. Detoxify free radicals. 8. Synthesize glucose from amino acids (gluconeogenesis) in extreme starvation.

Major Nitrogenous Wastes & Sources

Urea (by-product of protein catabolism), Uric acid (produced by the catabolism of nucleic acids), and Creatinine (produced by the catabolism of creatine phosphate).

Definition of Excretion & Excretory Systems

Excretion is the process of separating wastes from body fluids and eliminating them from the body. It is carried out by four systems: Respiratory (CO2, water), Integumentary (sweat), Digestive (bile, cholesterol), and Urinary (wastes, toxins, drugs).

BUN, Azotemia, and Uremia

BUN (Blood Urea Nitrogen) is the level of nitrogenous waste in the blood (normal is 10-20 mg/dL). Azotemia is an elevated BUN that may indicate renal insufficiency. Uremia is a syndrome of diarrhea, vomiting, dyspnea, and cardiac arrhythmia stemming from the toxicity of nitrogenous wastes.

Location and Position of the Kidneys

The kidneys lie against the posterior abdominal wall at the level of vertebrae T12 to L3. They are retroperitoneal (behind the peritoneum). The right kidney is slightly lower than the left due to the space occupied by the liver.

3 Protective Connective Tissue Layers of the Kidney

1. Fibrous Capsule (encloses the kidney like cellophane). 2. Perinephric Fat Capsule (a layer of adipose tissue that cushions the kidney). 3. Renal Fascia (binds the kidney and associated organs to the abdominal wall).

Gross Anatomy: Renal Cortex & Medulla

The renal parenchyma (glandular tissue) is divided into an outer renal cortex and an inner renal medulla. The medulla is divided into 6 to 10 renal pyramids by extensions of the cortex called renal columns.

Path of Urine Drainage (Internal)

Urine drains from the point of a renal pyramid (renal papilla) into a minor calyx, then several minor calyces converge to form a major calyx, and two or three major calyces converge to form the renal pelvis, which leads to the ureter.

Renal Lobe vs. Renal Sinus

A Renal Lobe consists of one renal pyramid and its overlying cortex. The Renal Sinus is the medial cavity of the kidney, occupied by blood vessels, nerves, and urine-collecting structures like the calyces and renal pelvis.

Trace the Complete Path of Blood Through the Kidney

Aorta -> Renal a. -> Segmental a. -> Interlobar a. -> Arcuate a. -> Cortical radiate a. -> Afferent arteriole -> Glomerulus -> Efferent arteriole -> Peritubular capillaries/Vasa recta -> Cortical radiate v. -> Arcuate v. -> Interlobar v. -> Renal v. -> Inferior Vena Cava.

Trace the Complete Path of Fluid (Filtrate to Urine)

Glomerular capsule -> Proximal Convoluted Tubule (PCT) -> Nephron loop -> Distal Convoluted Tubule (DCT) -> Collecting duct -> Papillary duct -> Minor calyx -> Major calyx -> Renal pelvis -> Ureter -> Urinary bladder -> Urethra.

Two Principal Parts of a Nephron

1. Renal Corpuscle: Filters the blood plasma. 2. Renal Tubule: A long coiled duct that converts the filtrate to urine.

Components of the Renal Corpuscle

It consists of the glomerulus (a ball of capillaries) and the two-layered glomerular (Bowman's) capsule that encloses it. The visceral (inner) layer is made of podocytes.

Visceral Layer

The inner layer made of podocytes.

Proximal Convoluted Tubule (PCT)

The first region of the renal tubule system.

Nephron Loop (Loop of Henle)

The second region of the renal tubule system.

Distal Convoluted Tubule (DCT)

The third region of the renal tubule system.

Collecting Duct

The fourth region of the renal tubule system that receives fluid from many nephrons.

Histology of the PCT

The PCT has a simple cuboidal epithelium with prominent microvilli and abundant mitochondria for absorption and active transport.

Cortical Nephrons

Nephrons that make up 85% of the total, have short nephron loops, and are located mainly in the cortex.

Juxtamedullary Nephrons

Nephrons that make up 15% of the total, have very long nephron loops that extend deep into the medulla and are essential for forming the osmotic gradient to conserve water.

Vasa Recta

A network of capillaries from the efferent arterioles of juxtamedullary nephrons that supply the renal medulla and form the countercurrent exchange system.

Podocytes

Elaborate cells forming the visceral layer of the glomerular capsule with extensions called foot processes that create filtration slits.

Three Stages of Urine Formation

1. Glomerular filtration. 2. Tubular reabsorption and secretion. 3. Water conservation.

Three Layers of the Filtration Membrane

1. The fenestrated endothelium of the capillary. 2. The basement membrane. 3. Filtration slits formed by podocytes.

Function of the Fenestrated Endothelium

The endothelial cells of the glomerular capillaries have large filtration pores (70-90 nm) that are permeable but exclude blood cells.

Function of the Basement Membrane

A proteoglycan gel that excludes molecules larger than 8 nm and repels large anions and plasma proteins.

Function of Filtration Slits

Filtration slits (~30 nm wide) created by foot processes of podocytes that are negatively charged and provide an obstacle to large anions and proteins.

Net Filtration Pressure (NFP)

The overall pressure driving glomerular filtration, calculated from the balance of outward blood hydrostatic pressure and inward pressures.

Forces Involved in Filtration

Blood Hydrostatic Pressure (BHP) of ~60 mm Hg promotes filtration, while Colloid Osmotic Pressure (COP) of ~32 mm Hg and Capsular Pressure (CP) of ~18 mm Hg oppose it.

Why BHP in the Glomerulus is High

The afferent arteriole is larger than the efferent arteriole, creating high resistance to blood outflow and elevating blood pressure inside the glomerulus.

NFP Calculation (Typical Values)

NFP = BHP - (COP + CP) = 60 mm Hg_out - (32 mm Hg_in + 18 mm Hg_in) = 10 mm Hg_out.

Glomerular Filtration Rate (GFR)

The amount of filtrate formed per minute by both kidneys combined; too high can cause dehydration, too low can lead to azotemia.

Renal Autoregulation

The ability of nephrons to adjust their own blood flow and GFR without external control, including the myogenic mechanism and tubuloglomerular feedback.

Myogenic Mechanism

The tendency of smooth muscle to contract when stretched, preventing significant changes in blood flow and GFR when arterial blood pressure rises.

Juxtaglomerular Apparatus (JGA)

A structure at the end of the nephron loop that contacts the afferent and efferent arterioles. It is composed of macula densa cells, granular (juxtaglomerular) cells, and mesangial cells, and it helps regulate GFR and blood pressure.

Tubuloglomerular Feedback

A mechanism where the glomerulus receives feedback on downstream tubular fluid. When GFR is high, macula densa cells sense high NaCl and signal granular cells (via ATP and adenosine) to constrict the afferent arteriole, reducing GFR.

Tubular Reabsorption vs. Secretion

Tubular reabsorption is the process of reclaiming water and useful solutes FROM the tubular fluid and returning them TO the blood. Tubular secretion extracts additional wastes FROM the blood and adds them TO the tubular fluid.

Two Routes of Reabsorption

1. Transcellular route: substances pass through the cytoplasm of the epithelial cells. 2. Paracellular route: substances pass through the leaky gaps between the cells.

Solvent Drag

A process where water, passing through the paracellular route, carries a variety of dissolved solutes along with it.

Role of Sodium in PCT Reabsorption

Sodium reabsorption is the key to almost everything else. It creates an osmotic and electrical gradient that drives the reabsorption of water (osmosis), chloride (electrical attraction), and other solutes like glucose (cotransport).

Glucose Reabsorption Mechanism

Glucose is cotransported with Na+ by symport proteins called Sodium-Glucose Transporters (SGLTs). This is a form of secondary active transport because it depends on the Na+-K+ pump to maintain the sodium gradient.

Transport Maximum (Tm)

The maximum rate of reabsorption for a solute, which is reached when all transport proteins for that solute are saturated. If the amount of a substance filtered exceeds its Tm, the excess appears in the urine.

Glycosuria

The presence of glucose in the urine. It occurs when blood glucose levels exceed about 220 mg/dL, causing the amount of filtered glucose to exceed the transport maximum of the SGLT proteins.

Purposes of Tubular Secretion

1. Waste removal (urea, uric acid, bile acids, ammonia). 2. Acid-base balance by secreting H+ ions. 3. Clearance of drugs and contaminants from the blood (e.g., penicillin, aspirin).

Principal vs. Intercalated Cells

Two cell types in the DCT and collecting duct. Principal cells are more abundant, have hormone receptors, and are involved in salt and water balance. Intercalated cells are involved mainly in acid-base balance by reabsorbing K+ and secreting H+.

Obligatory Water Reabsorption

The reabsorption of water in the PCT that occurs at a constant rate. Water follows the reabsorbed solutes by osmosis and is not under hormonal control.

Primary Function of the Nephron Loop

To generate an osmotic gradient in the renal medulla that enables the collecting duct to concentrate the urine and conserve water.

Countercurrent Multiplier Mechanism

The nephron loop 'multiplies' the osmolarity in the medulla. The ascending limb actively pumps out salt (but not water), making the medulla salty. This salty medulla then causes water to leave the permeable descending limb, which concentrates the fluid inside. This super-concentrated fluid then moves to the ascending limb, providing more salt to be pumped out.

Role of Urea in Medullary Gradient

Urea accounts for about 40% of the high osmolarity in the deep medulla. It is continually cycled from the collecting duct into the medullary ECF and back into the nephron loop, helping to maintain the gradient.

Countercurrent Exchange System Mechanism

The vasa recta prevents the medullary gradient from being washed away.

Role of Antidiuretic Hormone (ADH)

ADH regulates the final volume and concentration of urine. In response to dehydration, ADH makes the collecting duct more permeable to water by causing cells to insert aquaporins into their membranes. This allows for more water to be reabsorbed into the blood, resulting in a smaller volume of concentrated urine.

Role of Aldosterone

Known as the 'salt-retaining hormone,' it is secreted in response to low blood Na+ or high blood K+. It acts on the DCT and collecting duct to stimulate Na+ reabsorption and K+ secretion. Water and Cl- follow the Na+, causing the body to retain NaCl and water and reduce urine volume.

Role of Atrial Natriuretic Peptide (ANP)

Secreted by the heart in response to high blood pressure. It acts to lower blood pressure by increasing GFR and inhibiting the secretion of renin, ADH, and aldosterone. It also inhibits NaCl reabsorption by the collecting duct, leading to increased excretion of salt and water.

Role of Parathyroid Hormone (PTH)

Secreted in response to low blood calcium (hypocalcemia). It acts on the PCT to inhibit phosphate excretion and on the DCT and nephron loop to increase calcium reabsorption, thereby raising blood calcium levels.

Renin-Angiotensin-Aldosterone System (RAAS)

A hormone cascade that is the body's primary mechanism for elevating blood pressure. A drop in BP causes the JGA to secrete renin, which leads to the formation of angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates the secretion of aldosterone and ADH.

Kidney's Role in pH Regulation

The kidneys regulate acid-base balance by secreting hydrogen ions (H+) into the tubular fluid and reabsorbing bicarbonate ions (HCO3-) into the blood. This is accomplished via an Na+-H+ antiport and the generation of H+ from the carbonic anhydrase reaction.

Urochrome

A pigment produced by the breakdown of hemoglobin from expired erythrocytes that gives urine its yellow color.

Abnormal Findings in Urine

Glucose (Glycosuria), Protein (Proteinuria), Ketones (Ketonuria), Erythrocytes (Hematuria), and Leukocytes/Pus (Pyuria).

Polyuria, Oliguria, and Anuria

Polyuria is an output of >2 L/day. Oliguria is an output of <500 mL/day. Anuria is an output of 0 to 100 mL/day.

Renal Clearance

The volume of blood plasma from which a particular waste is completely removed in 1 minute. The formula is C = UV/P, where U is the urine concentration, V is the urine output rate, and P is the plasma concentration of the substance.

Why Inulin is Used to Measure GFR

Inulin is a polysaccharide that is freely filtered by the glomerulus but is neither secreted nor reabsorbed by the renal tubule. Therefore, its renal clearance is exactly equal to the GFR.

Diabetes Mellitus vs. Diabetes Insipidus

Diabetes Mellitus is caused by insulin hyposecretion or insensitivity, leading to hyperglycemia and glycosuria, which causes osmotic diuresis. Diabetes Insipidus is caused by ADH hyposecretion, so the collecting duct cannot reabsorb adequate water, leading to polyuria of dilute urine with no glucose.

Mechanism of Loop Diuretics

Loop diuretics like furosemide act on the thick segment of the ascending limb of the nephron loop to inhibit the Na+-K+-Cl- symport.

Countercurrent Multiplier

This impairs the countercurrent multiplier, reduces the medullary osmotic gradient, and prevents the collecting duct from reabsorbing as much water as usual.

Three Layers of the Ureter Wall

1. Adventitia (connective tissue). 2. Muscularis (smooth muscle that performs peristalsis). 3. Mucosa (lined with transitional epithelium).

Detrusor Muscle

The muscularis of the urinary bladder, consisting of three layers of smooth muscle. Its contraction, stimulated by the parasympathetic nervous system, expels urine from the bladder.

Trigone of the Bladder

A smooth-surfaced triangular area on the bladder floor marked by the openings of the two ureters and the urethra. It is a common site of bladder infection (cystitis).

Epithelium of the Lower Urinary Tract

The ureters, urinary bladder, and the proximal part of the urethra are lined with transitional epithelium (urothelium), which is specialized to stretch and recoil as the bladder fills and empties.

Rugae of the Bladder

Wrinkles of the mucosa in an empty bladder. They flatten as the bladder fills, allowing the bladder to expand its capacity.

Comparison of Male and Female Urethra

The female urethra is short (3-5 cm) and only serves a urinary function. The male urethra is long (18-20 cm), has three regions (prostatic, membranous, spongy), and serves both urinary and reproductive functions (carries semen).

Internal Urethral Sphincter

An anatomical sphincter of smooth muscle at the neck of the bladder in males. It is under involuntary control and contracts during ejaculation to prevent the reflux of semen into the bladder.

External Urethral Sphincter

A ring of skeletal muscle that encircles the urethra where it passes through the urogenital diaphragm. It is under voluntary control and allows for conscious control over urination.

Micturition Reflex (Involuntary)

An involuntary spinal reflex that controls urination in infants or those with spinal cord injuries. Filling of the bladder to ~200 mL excites stretch receptors, which send a signal to the spinal cord. A parasympathetic signal returns, causing the detrusor to contract and the internal sphincter to relax.

Voluntary Control of Micturition

Signals from the bladder's stretch receptors ascend to the micturition center in the pons, which integrates the information with the cerebrum. If the time is appropriate, the brain sends signals via the corticospinal tracts to inhibit the somatic motor neurons that keep the external urethral sphincter contracted, allowing it to relax and urination to occur.

Kidney Stones (Renal Calculi)

Hard granules of calcium, phosphate, oxalate, or uric acid that form in the renal pelvis. Large stones can block the ureter, causing severe pain and pressure buildup in the kidney that can destroy nephrons.

Cystitis

Inflammation of the urinary bladder, a common type of urinary tract infection (UTI). It is more common in females due to the short urethra.

Nephritis

Inflammation of the kidneys. Glomerulonephritis is an autoimmune inflammation of the glomeruli, often following a streptococcus infection, that can lead to proteinuria, hematuria, and renal failure.

Effects of Aging on the Urinary System

Nephrons decrease in number, GFR declines, reduced sensitivity to ADH causes frequent urination, and problems like incontinence (loss of sphincter control) and retention (often due to enlarged prostate) become more common.

Histology of the Ureters

The ureter has three layers: an adventitia, a muscularis (two layers of smooth muscle), and a mucosa lined with transitional epithelium.

Bladder Wall

The bladder wall consists of a mucosa (transitional epithelium and lamina propria), a thick muscularis called the detrusor muscle (three layers of smooth muscle), and an adventitia or peritoneum.

Glomerular Filtrate

Fluid in the capsular space is glomerular filtrate.

Tubular Fluid

Fluid from the PCT through the DCT is tubular fluid.

Urine

Fluid is called urine once it enters the collecting duct, as it undergoes little alteration beyond that point except for changes in water content.

Path of a Urea Molecule

Blood in glomerulus -> Filtration Membrane (fenestrated endothelium, basement membrane, filtration slits) -> Capsular Space -> PCT -> Nephron Loop -> DCT -> Collecting Duct -> Papillary Duct -> Minor Calyx -> Major Calyx -> Renal Pelvis -> Ureter -> Bladder -> Urethra -> Outside the body.

Kidney Role in Blood Pressure Control

The kidneys control blood pressure long-term by regulating blood volume via water and salt retention/excretion (controlled by Aldosterone, ADH, ANP). Short-term, they participate in the RAAS system, where renin secretion leads to Angiotensin II production, a potent vasoconstrictor.

First Urge to Urinate

The first urge to urinate typically occurs when the urinary bladder fills to about 200 mL.

Maximum Bladder Capacity

The maximum capacity of the urinary bladder is approximately 700 to 800 mL.

Urinary Incontinence

Incontinence is the inability to hold urine, often due to loss of sphincter control.

Urinary Retention

Retention is the inability to completely empty the bladder, which can lead to infections and is common in men with an enlarged prostate.

Caffeine as a Diuretic

Caffeine acts by dilating the afferent arteriole, which increases the glomerular filtration rate (GFR) and thus increases urine output.

Alcohol as a Diuretic

Alcohol inhibits the secretion of ADH from the posterior pituitary, which reduces water reabsorption in the collecting duct, leading to a larger volume of dilute urine.

Reabsorption in Nephron Loop

The nephron loop reabsorbs about 25% of the filtrate's Na+, K+, and Cl-, and 15% of its water.

Filtrate Reabsorbed by PCT

The proximal convoluted tubule (PCT) reabsorbs about 65% of the glomerular filtrate.

Renal Fraction

The kidneys receive about 21% of the cardiac output, which is known as the renal fraction.

Gluconeogenesis in Kidneys

In conditions of extreme starvation, the kidneys help to support the blood glucose level by synthesizing glucose from amino acids.

Sympathetic Stimulation of Kidneys

Stimulation by sympathetic fibers tends to reduce glomerular blood flow and therefore the rate of urine production, and also stimulates the kidneys to secrete renin in response to falling blood pressure.

Fluid in DCT

Fluid arriving in the DCT still contains about 20% of the water and 7% of the salts from the glomerular filtrate.

Fluid Leaving Nephron Loop

Because the thick ascending limb is impermeable to water but pumps out salt, the tubular fluid becomes very dilute (hypotonic) by the time it passes from the nephron loop into the DCT.