Renal Physiology

• The kidneys regulate fluid balance, electrolytes, and waste products
• Kidneys filter blood to create urine
• They maintain blood pressure and acid-base balance
• Kidneys also secrete hormones

Kidney Anatomy and Structure

• Kidneys are bilateral organs on either side of the spine

Nephron

• Nephron: the functional unit of the kidney responsible for filtering blood and forming urine
• Each kidney contains about one million nephrons

Components of the Nephron

• Glomerulus: a network of capillaries where blood is first filtered
• Bowman’s Capsule: encapsulates the glomerulus and receives the filtrate

Tubules

• Proximal Convoluted Tubule (PCT): reabsorbs nutrients, electrolytes, and water
• Loop of Henle: creates a concentration gradient for water and salt reabsorption
• Distal Convoluted Tubule (DCT): fine-tunes reabsorption and secretes substances like H+ and K+
• Collecting Duct: collects urine from multiple nephrons and plays a major role in water reabsorption, influenced by hormones like antidiuretic hormone (ADH)

Renal Cortex and Medulla

• Renal cortex: the outer region where most nephrons' glomeruli reside, playing a crucial role in early filtration and reabsorption
• Renal medulla: beneath the cortex, contains loops of Henle and collecting ducts, primarily involved in concentrating urine and regulating water balance

Key Renal Functions

• Filtration, reabsorption, secretion, and excretion

Filtration

• Filtration occurs in the glomerulus, where blood enters through the afferent arteriole and is filtered into the Bowman’s capsule
• The filtrate contains water, ions, glucose, and waste products like urea
• High blood pressure increases the filtration rate, potentially damaging the glomeruli
• Low blood pressure reduces filtration, causing waste accumulation

Reabsorption

• Reabsorption primarily occurs in the proximal convoluted tubule (PCT), but also in the loop of Henle, distal convoluted tubule (DCT), and collecting duct
• Water, glucose, amino acids, and electrolytes (Na+, K+, Cl-) are reabsorbed into the bloodstream
• Reabsorption helps maintain homeostasis by regulating the body's levels of nutrients and electrolytes
• The loop of Henle uses a countercurrent exchange mechanism to create a concentration gradient, crucial for water and salt balance

Secretion

• Substances like hydrogen ions (H+), potassium (K+), and certain drugs are secreted into the filtrate, especially in the DCT and collecting ducts
• Secretion helps remove waste products from the bloodstream and regulates pH by controlling H+ levels

Excretion

• After filtration, reabsorption, and secretion, waste products form urine
• Urine contains excess water, urea, uric acid, and other waste products
• Kidneys excrete urine through the ureters, which transport it to the bladder for storage before elimination via the urethra

Regulation of Kidney Functions

Autoregulation of GFR

• Kidneys adjust the diameter of afferent and efferent arterioles to maintain a constant glomerular filtration rate (GFR)
• When blood pressure increases, the kidneys constrict the afferent arteriole to prevent an increase in glomerular filtration

Hormonal Regulation

• Renin-Angiotensin-Aldosterone System (RAAS) helps regulate blood pressure and sodium balance
• Low blood pressure causes juxtaglomerular cells to release renin, activating angiotensin II
• Angiotensin II triggers aldosterone release (increases sodium reabsorption) and causes vasoconstriction to raise blood pressure
• Antidiuretic Hormone (ADH) controls water reabsorption in the collecting ducts
• In the presence of ADH, water reabsorption increases, leading to more concentrated urine
• ADH release is triggered by increased blood osmolarity or decreased blood volume
• Atrial Natriuretic Peptide (ANP) inhibits the RAAS system and promotes sodium excretion
• ANP is released by the heart in response to increased blood volume
• It reduces sodium reabsorption and relaxes afferent arterioles, increasing GFR and urine production to reduce blood volume
• Parathyroid Hormone (PTH) regulates calcium and phosphate balance by increasing calcium reabsorption and inhibiting phosphate reabsorption in the kidneys

Interaction with Other Body Systems

Cardiovascular System

• Blood pressure directly affects the kidneys' ability to filter blood
• The kidneys use renin to influence blood pressure (via RAAS), demonstrating a close relationship with the cardiovascular system in regulating fluid balance

Endocrine System

• Kidneys release erythropoietin (EPO) for red blood cell production
• The kidneys participate in the activation of vitamin D, which influences calcium balance

Respiratory System

• Kidneys and lungs contribute to acid-base balance where kidneys excrete H+ ions and reabsorb bicarbonate (HCO₃-) to help regulate pH
• The lungs control CO2 levels in the blood

Nervous System

• Kidneys are regulated by the sympathetic nervous system (for blood flow control)
• Kidneys also regulated by signaling from the hypothalamus, to regulate ADH secretion in response to hydration status

Homeostasis and Kidney Disease

• Kidneys central to homeostasis by regulating blood volume, pressure, and composition
• Disruption in kidney function—such as in chronic kidney disease (CKD), acute renal failure, or glomerulonephritis—can lead to imbalanced fluid levels, electrolyte disturbances, and toxin accumulation
• Severe cases may require dialysis or kidney transplants

Detailed functions

Kidney Structure and Anatomy

• Each kidney contains around a million nephrons
• Nephrons are microscopic units responsible for filtering blood and forming urine
• Each nephron consists of a renal corpuscle (glomerulus and Bowman’s capsule) and a renal tubule (proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct)

Renal Cortex and Medulla

• Renal Cortex: outer region housing glomeruli and proximal/distal convoluted tubules, where most filtration and the beginning of reabsorption occur
• Renal Medulla: deeper region containing loops of Henle and collecting ducts, important for establishing concentration gradients and fine-tuning water and electrolyte reabsorption

Vascular Supply

• Blood enters through the renal artery and branches into smaller arterioles, supplying blood to each nephron via the afferent arteriole, leading to the glomerulus
• Blood exits the glomerulus via the efferent arteriole
• Remaining blood flows through the peritubular capillaries surrounding the renal tubules

Renal Function in Detail

Glomerular Filtration

• Filters blood through the glomerular membrane into the Bowman’s capsule, with small molecules passing into the filtrate and larger molecules retained

Mechanism

• Filtration barrier consists of:
• Endothelium of glomerular capillaries with fenestrations
• Basement membrane acting as a charge and size filter
• Podocytes with foot processes regulating filtration
• Filtration is driven by glomerular hydrostatic pressure, opposed by colloid osmotic pressure and capsular hydrostatic pressure

Filter Load and GFR

• Glomerular filtration rate (GFR) is the rate at which plasma is filtered into the Bowman’s capsule, typically around 120-125 mL/min in a healthy adult
• GFR is a key measure of kidney function, reflecting the kidneys’ ability to filter blood

Reabsorption of Solutes and Water

Proximal Convoluted Tubule (PCT)

• The site of bulk reabsorption, reabsorbing about 65% of filtered sodium, chloride, and water, along with 100% of glucose and amino acids through active and passive transport
• Sodium is actively transported out via Na+/K+ ATPase, with water following passively due to osmosis

Loop of Henle

• Integral in concentrating urine and establishing a medullary concentration gradient
• The descending loop is permeable to water but impermeable to ions, so water is reabsorbed as the filtrate moves through the hyperosmolar medulla
• The ascending loop is impermeable to water but actively reabsorbs sodium, chloride, and potassium through Na+/K+/2Cl- symporters, creating high osmolarity in the medulla

Distal Convoluted Tubule (DCT)

• Selective reabsorption of sodium, chloride, and calcium occurs, regulated by hormones like aldosterone (increases sodium reabsorption) and parathyroid hormone (PTH, promotes calcium reabsorption)

Collecting Duct

• The final site of water reabsorption regulated by antidiuretic hormone (ADH), which inserts aquaporins into the membrane of the collecting duct
• Aldosterone acts here to increase sodium reabsorption in exchange for potassium secretion

Secretion

• Active transport of substances from the peritubular capillaries into the nephron tubule, eliminating waste and regulating electrolytes/acid-base balance

Substances Secreted

• Potassium (K+): secreted in the DCT and collecting duct in exchange for sodium to maintain electrolyte balance
• Hydrogen ions (H+): secreted in the DCT to regulate blood pH
• Ammonia (NH3) and urea are secreted as part of nitrogenous waste elimination

Importance of Secretion

• Electrolyte Balance: H+ and K+ secretion vital to maintain acid-base/potassium homeostasis
• Detoxification: substances like drugs, toxins, and excess ions that were not filtered by the glomerulus are secreted here to be excreted

Regulatory Mechanisms of Kidney Function

Renal Autoregulation

• Kidneys have intrinsic mechanisms to maintain a stable GFR despite fluctuations in blood pressure, through changes in afferent and efferent arteriole diameter

Myogenic Mechanism

• If blood pressure increases, the afferent arteriole constricts to prevent an increase in filtration pressure

Tubuloglomerular Feedback

• The macula densa in the distal tubule detects flow rate and sodium concentration
• If the flow rate is too high, it signals the afferent arteriole to constrict

Hormonal Regulation

Renin-Angiotensin-Aldosterone System (RAAS)

• Triggered when blood volume or pressure drops
• The kidneys release renin, converting angiotensinogen (from the liver) into angiotensin I
• Angiotensin I is converted to angiotensin II by ACE (angiotensin-converting enzyme) in the lungs
• Angiotensin II stimulates aldosterone release (increasing sodium reabsorption) and causes vasoconstriction to raise blood pressure
• It also stimulates thirst and ADH secretion, enhancing water retention

Antidiuretic Hormone (ADH)

• When blood osmolarity is high, ADH is released from the posterior pituitary to promote water reabsorption in the collecting ducts

Atrial Natriuretic Peptide (ANP)

• ANP is released from the heart in response to increased blood volume, promoting natriuresis (sodium excretion) and increasing urine output
• ANP also inhibits RAAS, reducing blood pressure

Interactions with Other Body Systems

Cardiovascular System

• The kidneys regulate blood volume and blood pressure through RAAS and ADH
• Blood pressure affects GFR directly, and the kidneys’ autoregulatory mechanisms ensure consistent filtration

Endocrine System

• The kidneys regulate blood calcium levels by converting vitamin D into its active form, calcitriol
• Erythropoietin is produced by the kidneys in response to low oxygen levels, stimulating red blood cell production in the bone marrow

Respiratory System

• The kidneys contribute to acid-base balance by excreting hydrogen ions (H+) and reabsorbing bicarbonate (HCO₃-)

Renal Dysfunction and Diseases

• Kidney diseases like CKD or AKI affect the kidney’s ability to filter blood, reabsorb nutrients, and excrete waste, leading to fluid retention, electrolyte imbalances, and toxin accumulation
• These issues can affect the cardiovascular and nervous systems

Key Term Definitions

Kidney

• Organs that filter blood to remove waste and excess substances, maintaining balance in the body

Nephron

• The functional unit of the kidney, filtering blood, reabsorbing useful substances, and excreting waste as urine

Glomerulus

• A network of tiny blood vessels (capillaries) in the nephron where blood is filtered

Bowman's Capsule

• A cup-like structure that surrounds the glomerulus, collecting filtered blood plasma (filtrate)

Proximal Convoluted Tubule (PCT)

• The first part of the nephron where most reabsorption of water, ions, and nutrients happens back into the blood

Loop of Henle

• A U-shaped part of the nephron, responsible for creating a concentration gradient in the kidney to conserve water

Distal Convoluted Tubule (DCT)

• The part of the nephron where more ions are reabsorbed and waste products are secreted into urine

Collecting Duct

• A tube where urine from several nephrons collects, adjusting the concentration of urine by reabsorbing water

Glomerular Filtration Rate (GFR)

• The rate at which the kidneys filter blood, helping evaluate kidney

Filtrate

• The liquid that is filtered from the blood, needing further processing in the nephron to form urine

Reabsorption

• The process of moving substances from the filtrate back into the blood

Secretion

• The process of moving waste products and excess substances from the blood into the filtrate

Urine

• The final product excreted by the kidneys, consisting of waste products

Renin-Angiotensin-Aldosterone System (RAAS)

• A hormone system that regulates blood pressure, blood volume, and sodium balance

Antidiuretic Hormone (ADH)

• A hormone that controls water reabsorption by the kidneys, concentrating the urine

Aldosterone

• A hormone that acts on the kidneys to increase sodium and water reabsorption and potassium excretion

Countercurrent Mechanism

• A process in the loop of Henle that helps create a concentration gradient

Filtration Fraction

• The fraction of plasma entering the kidneys that gets filtered into the nephron

Renal Blood Flow (RBF)

• The amount of blood delivered to the kidneys per minute

Efferent Arteriole

• The blood vessel that carries blood away from the glomerulus after filtration

Afferent Arteriole

• The blood vessel that carries blood toward the glomerulus

Peritubular Capillaries

Small blood vessels that surround the renal tubules, allowing reabsorption and secretion

Vasa Recta

• Specialized capillaries that surround the loop of Henle

Excretion

• The removal of waste products from the body through urine

Nephron Clearance

• The rate at which a substance is cleared from the blood by the kidneys per minute

Tubular Fluid

• The fluid within the nephron resulting from blood filtration

Pressure Natriuresis

• The process by which increased blood pressure leads to increased excretion of sodium and water

Macula Densa

• Specialized cells in the distal convoluted tubule that regulate GFR

Urea

• A nitrogenous waste product formed by the breakdown of proteins

Creatinine

• A byproduct of muscle metabolism, used to estimate kidney function

Kidney Dialysis

• A medical procedure that artificially removes waste and excess fluid from the blood

Hyperfiltration

• A condition where the kidneys filter more blood than normal

Ureter

• The tube that carries urine from the kidneys to the bladder

Bladder

A muscular sac that stores urine

Urethra

• The tube through which urine is excreted from the bladder

Diuresis

• The increased production of urine

Polydipsia

• Excessive thirst

Polyuria

• Excessive urine production

Osmolarity

• The concentration of solutes in a solution

Acid-Base Balance

• The process by which the kidneys regulate the blood's pH

Glucose Reabsorption

• The process by which the kidneys reabsorb glucose from the filtrate

Urinous GFR (Filtration) Rate

• A measure of how much urine is produced as a function of filtration by the kidneys

Additional Terms

Portal System (Renal Portal System)

• Blood flows through two capillary networks (glomerulus → peritubular capillaries/vasa recta) for filtration, reabsorption, and secretion

High Osmolarity

• More solutes, produces concentrated urine

Low Osmolarity

• Fewer solutes, produces diluted urine

Juxtaglomerular Cells

• Monitor BP & sodium, releasing Renin to increase BP and sodium retention

Hypovolemia

• Low blood volume, leading to retaining water & sodium and activating RAAS

Hypoperfusion

• Low blood flow to kidneys, activating RAAS, and reducing urine production with risk of kidney damage