Untitled Quiz

Kidney Functions

• The kidneys perform crucial functions by filtering roughly 200 liters of blood per day, eliminating toxins, metabolic wastes, and excess ions through urine production.
• The kidneys regulate blood volume and chemical composition, ensuring a balanced ratio of water and salts, and acids and bases.

Other Renal Functions

• The kidneys play a role in gluconeogenesis during prolonged fasting, producing glucose from non-carbohydrate sources.
• These organs produce renin, a hormone involved in regulating blood pressure, and erythropoietin, which stimulates red blood cell production.
• The kidneys also activate Vitamin D, essential for calcium absorption.

Other Urinary System Organs

• The urinary bladder acts as a temporary reservoir for urine storage.
• The ureters, paired tubes, transport urine from the kidneys to the bladder.
• The urethra, a single tube, carries urine from the bladder to the exterior of the body.

Kidney Location and External Anatomy

• The bean-shaped kidneys reside in the retroperitoneal space in the superior lumbar region, extending from the 12th thoracic to the 3rd lumbar vertebrae.
• The right kidney is slightly lower than the left due to the liver's presence.
• The external surface of the kidney is convex, while the medial side is concave, featuring a vertical cleft called the renal hilus, which leads to the renal sinus.
• At the hilus, ureters, renal blood vessels, lymphatics, and nerves enter and exit the kidney.

Layers of Tissue Supporting the Kidney

• The renal capsule, a fibrous layer, safeguards the kidney from infection.
• The adipose capsule, a fatty tissue, cushions the kidney and anchors it to the body wall.
• The renal fascia, composed of dense fibrous connective tissue, provides further anchoring.

Internal Anatomy

• A frontal section of the kidney reveals three major regions:
  • The cortex, a light-colored and granular outer region.
  • The medulla, containing cone-shaped medullary (renal) pyramids, which are composed of parallel bundles of urine-collecting tubules.
  • Renal columns, formed by inward extensions of cortical tissue, separate the pyramids.
• A lobe is comprised of a medullary pyramid and its surrounding capsule.
• The renal pelvis, a funnel-shaped tube located lateral to the hilus within the renal sinus, collects urine from the major calyces, which in turn receive urine from the papillae.
• Urine flows through the pelvis and ureters to the bladder.

Blood and Nerve Supply

• Approximately 1200 ml of systemic cardiac output flows through the kidneys per minute, representing about one-fourth of the total.
• Arterial flow into and venous flow out of the kidneys follow a similar path.
• The renal plexus provides the nervous innervation to the kidneys.

The Nephron

• The nephron is the fundamental structural and functional unit of the kidney responsible for urine formation. It consists of two main components:
  • Glomerulus: a tuft of capillaries associated with a renal tubule.
  • Glomerular (Bowman’s) capsule: a blind, cup-shaped end of a renal tubule that fully encloses the glomerulus.
• The glomerulus and Bowman's capsule together constitute the renal corpuscle.
• The glomerular endothelium, a fenestrated (porous) epithelium, allows for the passage of solute-rich, nearly protein-free filtrate from the blood into the glomerular capsule.

Anatomy of the Glomerular Capsule

• The external parietal layer serves as a structural component of the glomerular capsule.
• The visceral layer, made of modified, branching epithelial cells called podocytes, plays a crucial role in filtration.
• Podocytes have extensions called foot processes.
• Filtration slits, openings between the foot processes, allow filtrate to enter the capsular space.

Renal Tubule

• The proximal convoluted tubule (PCT) is comprised of cuboidal cells with numerous microvilli and mitochondria. It is responsible for reabsorption of water and solutes from the filtrate, and secretion of substances into it.
• The loop of Henle, a hairpin-shaped structure, consists of three segments:
  • Proximal part: similar to the proximal convoluted tubule.
  • Thin segment: composed of simple squamous cells.
  • Thick segment: made of cuboidal to columnar cells.
• The distal convoluted tubule (DCT), composed of cuboidal cells without microvilli, primarily functions in secretion rather than reabsorption.

Connecting Tubules

• The distal part of the distal convoluted tubule, near the collecting ducts, is referred to as the connecting tubule.
• Two important cell types are found in this region:
  • Intercalated cells: cuboidal cells with microvilli, responsible for maintaining the body's acid-base balance.
  • Principal cells: cuboidal cells without microvilli, involved in maintaining the body's water and salt balance.

Nephrons

• Two types of nephrons exist:
  • Cortical nephrons: constitute 85% of nephrons and reside in the cortex.
  • Juxtamedullary nephrons:
    • Located at the cortex-medulla junction.
    • Possess loops of Henle that extend deep into the medulla.
    • Have extensive thin segments.
    • Play a vital role in producing concentrated urine.

Capillary Beds of the Nephron

• Each nephron has two capillary beds:
  • Glomerulus: a highly-specialized network where filtration occurs.
  • Peritubular capillaries: a network surrounding the renal tubules, involved in reabsorption.
• The glomerulus is fed by an afferent arteriole and drained by an efferent arteriole.
• The high blood pressure within the glomerulus, resulting from the high resistance of the arterioles and the wider diameter of the afferent arteriole compared to the efferent arteriole, drives the filtration process.
• Fluids and solutes are forced out of the blood throughout the glomerulus, contributing to filtrate formation.

Capillary Beds

• Peritubular capillaries are low-pressure, porous capillaries adapted for absorption.
  • They originate from efferent arterioles.
  • They closely associate with adjacent renal tubules.
  • They drain into the renal venous system.
• Vasa recta are long, straight efferent arterioles of juxtamedullary nephrons.

Vascular Resistance in Microcirculation

• Afferent and efferent arterioles offer high resistance to blood flow.
• Blood pressure drops from 95 mm Hg in the renal arteries to 8 mm Hg in the renal veins.

Vascular Resistance in Microcirculation

• Resistance in afferent arterioles:
  • Protects glomeruli from fluctuations in systemic blood pressure.
• Resistance in efferent arterioles:
  • Reinforces high glomerular pressure.
  • Reduces hydrostatic pressure in peritubular capillaries.

Juxtaglomerular Apparatus (JGA)

• The juxtaglomerular apparatus (JGA) is formed where the distal tubule contacts the afferent (and sometimes efferent) arteriole.
• Arteriole walls contain juxtaglomerular (JG) cells:
  • Enlarged, smooth muscle cells.
  • Secretory granules containing renin.
  • Act as mechanoreceptors sensing pressure changes.
• The macula densa, composed of tall, densely packed distal tubule cells adjacent to JG cells, functions as chemoreceptors or osmoreceptors, sensing changes in solute concentration.
• Mesanglial cells, located within the glomerulus, possess phagocytic and contractile properties, influencing capillary filtration.

Filtration Membrane

• The filtration membrane, separating the blood from the interior of the glomerular capsule, is comprised of three layers:
  • Fenestrated endothelium of the glomerular capillaries.
  • Visceral membrane of the glomerular capsule (podocytes).
  • Basement membrane, a fused basal lamina of the other layers.

Mechanisms of Urine Formation

• The kidneys filter the entire plasma volume of the body approximately 60 times daily.
• The filtrate contains all plasma components except proteins.
• It loses water, nutrients, and essential ions to become urine.
• Urine includes metabolic wastes and unneeded substances.

Mechanisms of Urine Formation

• Urine formation and blood composition adjustments involve three primary processes:
  • Glomerular filtration: the initial filtering of blood into the glomerular capsule.
  • Tubular reabsorption: the reclaiming of essential substances from the filtrate back into the blood.
  • Tubular secretion: the removal of undesirable substances from the blood into the filtrate.

Glomerular Filtration

• Principles of fluid dynamics governing tissue fluid in all capillary beds apply to the glomerulus.
• The glomerulus is more efficient than other capillary beds due to:
  • Its highly permeable filtration membrane.
  • Higher glomerular blood pressure.
  • Higher net filtration pressure.
• Plasma proteins are not filtered, contributing to the oncotic pressure of the blood.

Net Filtration Pressure (NFP)

• The pressure responsible for filtrate formation.
• It is calculated as the difference between glomerular hydrostatic pressure (HPg) and the combined oncotic pressure of glomerular blood (OPg) and capsular hydrostatic pressure (HPc).

Glomerular Filtration Rate (GFR)

• The total amount of filtrate produced by the kidneys per minute.
• It is influenced by:
  • Total surface area available for filtration.
  • Filtration membrane permeability.
  • Net filtration pressure.

Glomerular Filtration Rate (GFR)

• GFR is directly proportional to NFP.
• Changes in GFR typically result from alterations in glomerular blood pressure.

Regulation of Glomerular Filtration

• If the GFR is too high, needed substances cannot be reabsorbed efficiently, leading to losses in urine.
• If the GFR is too low, most substances are reabsorbed, including wastes that should be eliminated.

Regulation of Glomerular Filtration

• Three mechanisms control GFR:
  • Renal autoregulation (intrinsic system): maintains a stable GFR under normal conditions.
  • Neural controls: regulate GFR in response to stress.
  • Hormonal mechanism (the renin-angiotensin system): primarily adjusts GFR in response to blood pressure changes.

Intrinsic Controls

• Under normal circumstances, renal autoregulation maintains a near-constant GFR.
• Autoregulation involves two types of control:
  • Myogenic mechanism: responds to changes in pressure within the renal blood vessels.
  • Flow-dependent tubuloglomerular feedback: senses alterations in the juxtaglomerular apparatus.

Extrinsic Controls

• When the sympathetic nervous system is inactive, renal blood vessels are maximally dilated, allowing for autoregulation to dominate.
• During stress, the sympathetic nervous system releases norepinephrine, and the adrenal medulla releases epinephrine. This leads to constriction of afferent arterioles and inhibits filtration
• The sympathetic nervous system also activates the renin-angiotensin system.

Renin-Angiotensin Mechanism

• Triggered by the release of renin from JG cells.
• Renin converts angiotensinogen into angiotensin I, which is then converted to angiotensin II.
• Angiotensin II increases mean arterial pressure and stimulates the adrenal cortex to release aldosterone, leading to a rise in systemic and glomerular hydrostatic pressure.

Renin Release

• Renin release can be stimulated by:
  • Reduced stretch of the granular JG cells.
  • Stimulation of JG cells by activated macula densa cells.
  • Direct stimulation of JG cells via 1-adrenergic receptors by renal nerves.
  • Angiotensin II itself.

Other Factors Affecting Glomerular Filtration

• Prostaglandins (PGE2 and PGI2), vasodilators produced in response to sympathetic stimulation and angiotensin II, are thought to protect the kidneys during increased peripheral resistance.
• Nitric oxide, a vascular endothelium-derived vasodilator, influences renal blood flow.
• Adenosine, a vasoconstrictor of renal vasculature, can regulate blood flow to the kidneys.
• Endothelin, a potent vasoconstrictor secreted by tubule cells, can also affect renal vascular resistance.

Tubular Reabsorption

• A transepithelial process involving the return of most tubule contents to the blood.
• Transported substances move across three membranes:
  • Luminal and basolateral membranes of tubule cells.
  • Endothelium of peritubular capillaries.
• Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways.

Tubular Reabsorption

• All organic nutrients are reabsorbed.
• Water and ion reabsorption is regulated by hormones.
• Reabsorption can be either active (requiring ATP) or passive.

Sodium Reabsorption: Primary Active Transport

• Sodium reabsorption primarily relies on active transport.
• Na+ enters tubule cells at the luminal membrane and is actively transported out of the tubules by a Na+-K+ ATPase pump.

Sodium Reabsorption: Primary Active Transport

• Na+ then moves to peritubular capillaries due to:
  • Low hydrostatic pressure.
  • High osmotic pressure of the blood.
• Na+ reabsorption provides the energy and mechanism for the reabsorption of most other solutes.

Routes of Water and Solute Reabsorption

• Water and various solutes are reabsorbed through different pathways depending on their characteristics and the location within the nephron.

Reabsorption by PCT Cells

• The active pumping of Na+ drives the reabsorption of:
  • Water by osmosis, assisted by aquaporins, specialized water-filled channels.
  • Cations and fat-soluble substances via diffusion.
  • Organic nutrients and selected cations through secondary active transport.

Nonreabsorbed Substances

• A transport maximum (Tm), reflecting the number of available carriers in the renal tubules, exists for actively reabsorbed substances.
• When carriers are saturated, excess of that substance is excreted in urine.

Nonreabsorbed Substances

• Substances are not reabsorbed if they:
  • Lack carriers.
  • Are not lipid-soluble.
  • Are too large to pass through membrane pores.
• Urea, creatinine, and uric acid are major nonreabsorbed substances.

Absorptive Capabilities of Renal Tubules and Collecting Ducts

• The PCT reabsorbs Sodium, all nutrients, cations, anions, and water, as well as urea, lipid-soluble solutes, and small proteins.
• The loop of Henle reabsorbs different substances in its descending and ascending limbs:
  • Descending limb: H2O, Na+, Cl−, and K+.
  • Ascending limb: Ca2+, Mg2+, and Na+.
• The DCT reabsorbs Ca2+, Na+, H+, K+, and water, as well as HCO3− and Cl−.
• The collecting duct reabsorbs water and urea.

Na+ Entry into Tubule Cells

• Sodium enters tubule cells through various mechanisms depending on the location:
  • Passive entry: Na+-K+ ATPase pump.
  • PCT: facilitated diffusion using symport and antiport carriers.
  • Ascending loop of Henle: facilitated diffusion via Na+-K+-2Cl− symport system.
  • DCT: Na+-Cl− symporter.
  • Collecting tubules: diffusion through membrane pores.

Atrial Natriuretic Peptide Activity

• ANP reduces blood Na+ levels, leading to:
  • Decreased blood volume.
  • Lower blood pressure.
• ANP achieves this by:
  • Directly inhibiting Na+ reabsorption in medullary ducts.
  • Counteracting the effects of angiotensin II.
  • Indirectly stimulating increased GFR, reducing water reabsorption.

Tubular Secretion

• Involves substance movement from the peritubular capillaries or tubule cells into the filtrate, essentially the reverse of reabsorption.
• Tubular secretion is important for:
  • Eliminating substances not already present in the filtrate.
  • Removing undesirable substances like urea and uric acid.
  • Rdding the body of excess potassium ions.
  • Regulating blood pH.

Regulation of Urine Concentration and Volume

• Osmolality: refers to the number of solute particles dissolved in 1 liter of water and reflects its ability to cause osmosis.
• Body fluids are measured in milliosmols (mOsm).
• The kidneys maintain a constant solute load in body fluids at about 300 mOsm.
• This is achieved through the countercurrent mechanism.

Countercurrent Mechanism

• The interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger).
• The solute concentration in the loop of Henle varies from 300 mOsm to 1200 mOsm.
• The medullary osmotic gradient is maintained because the blood in the vasa recta equilibrates with the interstitial fluid.

Loop of Henle: Countercurrent Multiplier

• The descending loop of Henle:
  • Is relatively impermeable to solutes.
  • Is permeable to water.
• The ascending loop of Henle:
  • Is permeable to solutes.
  • Is impermeable to water.
• Collecting ducts in the deep medullary regions are permeable to urea.

Loop of Henle: Countercurrent Exchanger

• The vasa recta, a countercurrent exchanger:
  • Maintains the osmotic gradient.
  • Delivers blood to cells in the area.

Formation of Dilute Urine

• Filtrate is diluted in the ascending loop of Henle.
• Dilute urine is produced when this filtrate continues into the renal pelvis.
• This occurs when antidiuretic hormone (ADH) is not being secreted.

Formation of Dilute Urine

• Collecting ducts remain impermeable to water, preventing further water reabsorption.
• Sodium and selected ions can be removed through active and passive mechanisms.
• Urine osmolality can be as low as 50 mOsm, about one-sixth that of plasma.

Formation of Concentrated Urine

• Antidiuretic hormone (ADH) inhibits diuresis.
• ADH equalizes the osmolality of the filtrate and interstitial fluid.
• In the presence of ADH, 99% of the water in filtrate is reabsorbed.

Formation of Concentrated Urine

• ADH-dependent water reabsorption is known as facultative water reabsorption.
• ADH is the signal for producing concentrated urine.
• The kidneys' ability to concentrate urine depends on the high medullary osmotic gradient.

Diuretics

• Chemicals that increase urinary output include:
  • Any substance not reabsorbed.
  • Substances exceeding the renal tubules' reabsorption capacity.
  • Substances inhibiting Na+ reabsorption.

Diuretics

• Osmotic diuretics include:
  • High glucose levels, carrying water out with the glucose.
  • Alcohol, inhibiting ADH release.
  • Caffeine and most diuretic drugs, inhibiting sodium ion reabsorption.
  • Lasix and Diuril, inhibiting Na+-associated symporters.

Renal Clearance

• The volume of plasma cleared of a specific substance within a given time.
• Renal clearance tests are used to:
  • Determine the GFR.
  • Detect glomerular damage.
  • Monitor the progression of diagnosed renal disease.

Renal Clearance

• Renal clearance rate (RC) is calculated as: RC = UV/P
  • RC = renal clearance rate.
  • U = concentration (mg/ml) of the substance in urine.
  • V = flow rate of urine formation (ml/min).
  • P = concentration of the same substance in plasma.
• The renal clearance rate can be used to assess how well the kidneys are filtering out waste products.

Physical Characteristics of Urine

• Color and transparency:
  • Clear, pale to deep yellow (due to urochrome).
  • Concentrated urine is darker yellow.
  • Drugs, vitamin supplements, and diet can alter urine color.
  • Cloudy urine may indicate a urinary tract infection.

Physical Characteristics of Urine

• Odor:
  • Fresh urine has a slightly aromatic odor.
  • Standing urine develops an ammonia odor.
  • Some drugs and vegetables (asparagus) can change the odor.

Physical Characteristics of Urine

• pH:
  • Slightly acidic (pH 6), with a range of 4.5 to 8.0.
  • Diet can influence pH.
• Specific gravity:
  • Ranges from 1.001 to 1.035.
  • Depends on solute concentration.

Chemical Composition of Urine

• Urine is 95% water and 5% solutes.
• Nitrogenous wastes include urea, uric acid, and creatinine.
• Other normal solutes include:
  • Sodium, potassium, phosphate, and sulfate ions.
  • Calcium, magnesium, and bicarbonate ions.
• Abnormally high levels of any urinary constituent may indicate a medical condition.

Ureters

• Slender tubes that transport urine from the kidneys to the bladder.
• Ureters enter the base of the bladder through the posterior wall, closing their distal ends as bladder pressure rises to prevent backflow of urine.

Ureters

• Ureters have a trilayered wall:
  • Transitional epithelial mucosa.
  • Smooth muscle muscularis.
  • Fibrous connective tissue adventitia.
• Ureters actively propel urine to the bladder through smooth muscle contraction in response to stretch.

Urinary Bladder

• A smooth, collapsible, muscular sac that temporarily stores urine.
• It lies retroperitoneally on the pelvic floor, posterior to the pubic symphysis. In males, the prostate gland surrounds its neck inferiorly. In females, it sits anterior to the vagina and uterus.
• The trigone, a triangular region marked by openings for the ureters and the urethra, is clinically significant as infections tend to persist in this area.

Urinary Bladder

• The bladder wall is composed of three layers:
  • Transitional epithelial mucosa.
  • A thick muscular layer.
  • A fibrous adventitia.
• The bladder is distensible and collapses when empty.
• As urine accumulates, the bladder expands with minimal increase in internal pressure, due to its elasticity.

Urethra

• A muscular tube that:
  • Drains urine from the bladder.
  • Conveys it out of the body.

Urethra

• Sphincters prevent urine leakage when it is not being passed:
  • Internal urethral sphincter: an involuntary sphincter at the bladder-urethra junction.
  • External urethral sphincter: a voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm.
  • Levator ani muscle: a voluntary urethral sphincter.

Urethra

• The female urethra is connected to the anterior vaginal wall.
• Its external opening is located anterior to the vaginal opening and posterior to the clitoris.
• The male urethra has three distinct regions:
  • Prostatic urethra: runs within the prostate gland.
  • Membranous urethra: passes through the urogenital diaphragm.
  • Spongy (penile) urethra: runs through the penis and opens through the external urethral orifice.