Kidney Function and Substance Transport Quiz

Renal Physiology

• Kidneys are the primary organs of the urinary system
• Kidneys receive 20-25% of total cardiac output
• Kidney functions include maintaining blood volume and fluid/electrolyte composition, acid/base balance, elimination of metabolic waste, toxic substances and hormone production
• EPO is responsible for red blood cell production
• Renin is involved in water and salt conservation
• Vitamin D activation involves the hormones Ca2+, PO43- absorption in the small intestine
• Urine is a protein-free filtrate of blood, regulated by the kidneys.
• Urine composition changes according to blood/kidney regulation
• Urine does not normally contain blood cells or large proteins, presence of which can indicate infection or damage to the kidneys
• Urinalysis is the analysis of a urine sample using reagent strips (dipsticks) to test various properties, including clear yellow-amber color, odorless, pH 6-7, and specific gravity 1.001-1.030
• Abnormal results in urinalysis might indicate Urinary Tract Infection (UTI), kidney stone, hyperglycemia (diabetes), starvation, ketoacidosis, infection, kidney disease (heart failure, nephron dysfunction), hemolysis (liver disease), and liver disease.

Nephron Tubules

• The nephron is the functional unit of the kidney responsible for urine production
• Each kidney contains over one million nephrons
• Blood enters the nephron, gets regulated, filtered, and balanced blood is returned to circulation
• Excess waste, toxins, and excess materials are removed in urine
• Nephron contains specialized blood vessels and tubules that regulate exchange of materials with the blood
• Nephron parts include: afferent arteriole, renal corpuscle, glomerulus, bowman's capsule, efferent arteriole, proximal convoluted tubule, peri-tubular capillaries & vasa recta, loop of Henle (descending and ascending limbs), distal convoluted tubule (DCT), collecting duct, and cortical radiate veins

Renal Blood Flow & Filtration

• Renal perfusion is blood flow through the kidneys, including local regulation of the nephron
• Kidneys receive 20-25% of cardiac output
• Renal function is influenced by systemic blood pressure.
• Local blood flow is regulated by factors such as autoregulation, sympathetic nervous system and hormones
• GFR is important in assessing kidney health, kidney disease and kidney failure
• Renal Blood Flow is approximately 1000-1200 mL /min in individuals.

Glomerular Filtration Rate (GFR)

• GFR is the rate of fluid movement from glomerular capillaries into the renal tubules
• It's an essential clinical marker for evaluating kidney health and disease severity

GFR Regulation

• GFR is affected by factors such as plasma protein concentration, hydration, urinary tract obstruction, and Mean Arterial Blood Pressure (MAP).
• GFR regulation involves two main mechanisms:
  • Autoregulation—which includes myogenic mechanism and tubuloglomerular feedback
  • Sympathetic nervous system

Afferent and Efferent Arterioles

• Afferent and efferent arterioles are crucial in maintaining the glomerular filtration rate (GFR).
• Changes in afferent and efferent arteriole pressure directly impacts GFR
• Changes in arteriole constriction lower total renal flow

Autoregulation: Myogenic and Tubuloglomerular Feedback Mechanisms

• Myogenic mechanism is the ability of the afferent arteriole to automatically adjust its diameter in response to changes in blood pressure.
• Tubuloglomerular feedback is a mechanism where cells in the distal tubule (macula densa) sense changes in sodium concentration in the filtrate and signal the afferent arteriole to vasoconstrict or vasodilate, thus regulating glomerular blood flow (GFR).

Sympathetic Nervous System Regulation of GFR

• Stimulation of sympathetic nerves decreases GFR, to conserve fluid and increase blood volume).
• Sympathetic nerves to the afferent arteriole causes vasoconstriction, which lowers GFR by decreasing glomerular blood flow

Juxtaglomerular Apparatus (JGA) and Renin-Angiotensin-Aldosterone System (RAAS)

• The JGA is a cluster of specialized cells in the kidney that plays a crucial role in regulating blood pressure and kidney function.
• The RAAS system is a complex hormonal pathway that involves renin, angiotensin I, angiotensin II, and aldosterone, all influencing blood pressure and sodium balance

Renal Blood Flow and Filtration

• Renal blood flow, the amount of blood flowing to the kidneys, is crucial for glomerular filtration rate (GFR).
• GFR is influenced by factors, including local blood flow regulation.

Clinical Estimation of GFR

• Clinical estimation of GFR uses principles of plasma clearance to track filtration of specific molecules (such as inulin and creatinine)
• Stable plasma concentration, freely filtered at glomerulus, and no reabsorption, secretion, or synthesis by the kidneys are ideal characteristics for a molecule used in GFR assessment

Creatinine Clearance

• Creatinine: a breakdown product of creatine metabolism, commonly used to estimate GFR.
• Factors such as muscle mass, age, and diet influence creatinine levels and interpretation of creatinine clearance, impacting GFR assessment

Plasma Creatinine

• Plasma creatinine levels reflect kidney function.
• Lower GFR results in higher plasma creatinine

Blood Urea Nitrogen (BUN)

• BUN is a metabolic waste product formed via liver metabolism of amino acids.
• It's a simple, routine, and inexpensive method used to assess GFR, although it somewhat underestimates GFR

Glomerular Filtration Rate (GFR) Regulation(page 33)

• GFR depends on total surface area of glomerulus, membrane permeability, and Net Filtration Pressure (NFP)

Surface Area and Permeability of Filtration Membrane

• High surface area of glomerular capillaries is due to their tightly packed nature
• Permeability is influenced by fenestrations of glomerular capillaries and contraction of podocytes

Glomerular Filtration Pressure (page 35)

• Glomerular capillary blood pressure (P_glom) is the primary driving force for glomerular filtration.
• Systemic blood pressure, diameter differences between afferent and efferent arterioles, and plasma-colloid osmotic pressure (P_op) and Bowman's capsule hydrostatic pressure (P_bc) also play roles in influencing GFR.
• Net glomerular filtration pressure (NFP) results from various pressures impacting GFR

Tubular Reabsorption

• Tubular reabsorption is the process of returning essential molecules to the blood from the renal tubules
• Includes returning nutrients (glucose, amino acids, water, and ions) to the blood
• This process is facilitated by active and passive transport mechanisms

Na+/K+ ATPase

• Na+/K+ ATPase sets up a gradient, crucial in maintaining Na concentration high in the tubule lumen and low in tubule cells, and the cell's negative electrical charge.
• This gradient drives the movement of multiple molecules.

Na+-Linked Processes

• Na+-linked processes involve the movement of various molecules linked to Na+ gradients for reabsorption or secretion in the tubules
• Water follows Na+
• Other molecules become more concentrated as they are removed from the filtrate.

Nutrient reabsorption

• Tmax—Maximum absorption rate of transporters in a given time
• Substances are fully reabsorbed, and substances not reabsorbed are excreted in the urine
• Substance reabsorption varies with plasma concentration

Renal Threshold

• Renal threshold is the plasma concentration of a substance that exceeds the reabsorption capacity of transporters, so it passes into the urine

Renal Threshold Levels (page 41)

• Glucose threshold—very high, with glucose largely reabsorbed unless plasma levels greatly exceed normal range
• Phosphate threshold—equal or near normal phosphate intake, with excess eliminated under normal conditions

Diluting and Concentrating Urine

• Kidneys adjust water and ion amounts in blood by controlling water and ion loss in urine.
• Hydration/dehydration status and urinary concentration/dilution are impacted by interactions in the loop of Henle (via vasa recta)

Medullary Osmotic Gradient

• Medulla contains a large osmotic gradient from 300 to 1200 mOsm
• Osmotic gradient increasingly concentrates the fluid progressing through the medulla

Loop of Henle

• The Loop of Henle creates a concentration gradient, facilitating water reabsorption and urine concentration
• Descending limb is permeable to water, allowing water reabsorption
• Ascending limb is impermeable to water, facilitating salt reabsorption

Vasa Recta

• Vasa Recta help preserve the osmotic gradient in the medulla
• Countercurrent exchange within vasa recta helps maintain the osmotic gradient within the medulla

Tubular Filtrate Changes in the Loop of Henle

• Filtrate loses water in the descending limb, becoming progressively concentrated.
• NaCl reabsorption occurs in the ascending limb, making the filtrate isotonic

Collecting Ducts and Gradient

• Collecting ducts use the medullary gradient to adjust urine concentration based on hydration state
• ADH (antidiuretic hormone) regulates water permeability in the collecting ducts, influencing urine concentration

Collecting ducts without water channels

• Collecting ducts can excrete large volumes of dilute urine during hydration states, or more concentrated volumes of urine during states of dehydration
• Diuretics work partially by blocking medullary gradient formation to produce large volumes of dilute urine excretion

Collecting Ducts with Aquaporins

• ADH insertion of aquaporins into collecting ducts increases water reabsorption.
• Body's water balance is maintained by water reabsorption in the collecting ducts, a normal state when kidneys function correctly
• Alcohol directly blocks ADH release

Tubular Secretion

• Tubular secretion is the process of adding molecules to the filtrate from the blood
• Important for excretion of various substances (creatinine, drugs, acid (H+), base (HCO3−), and ions (K+), and urea)
• Essential metabolic waste products, drugs, and excess ions that are not adequately filtered or reabsorbed are secreted into the filtrate by active or passive transport mechanisms

Tubular Secretion: K+

• K+ secretion is regulated to maintain the electrical gradient
• This secretion occurs to regulate heart function and maintenance of Na/K activity and takes place in the Distal Convoluted Tubule (DCT) and Collecting Duct
• The Na+/K+ pumps move K+ into tubules
• K+ leaks into tubules from the DCT and collecting duct lumen
• Aldosterone stimulates this process

Tubular Secretion: H+

• H+ secretion helps balance acid/base levels
• Processes occur primarily in the proximal convoluted tubules (PCT) and collecting ducts
• These processes include H+ ATPase pumps, H+/K+ ATPase pumps, as well as cotransporters/antiporters

Proximal Convoluted Tubule Reabsorption

• Proximal Convoluted Tubule (PCT) reabsorbs 50% of sodium and water
• Na+-linked cotransporters play a crucial role in reabsorbing nutrients like glucose, amino acids, and some organic solutes
• Osmolarity linked passive diffusion—urea, potassium, and calcium are reabsorbed via this process

Micturition

• Bladder progressively fills until its wall tension(pressure) rises above a threshold.
• Reflex called micturition reflex, often unconscious, helps empty the bladder
• Spinal cord initiates the micturition reflex, which can be inhibited/facilitated depending on higher brain center's input.
• Several brain centers including pontine centers and parts of cerebral cortex regulate micturition

Ureterorenal reflex

• Ureterorenal reflex involves low resistance electrical pathways and triggers from sympathetic and parasympathetic nerves in response to bladder filling
• This reflex can be triggered by pressure variations from the sympathetic and parasympathetic nerves, particularly arising from the pelvic nerves in an involuntary and autonomic response

Brain Control of Micturition

• Micturition reflex is primarily controlled by higher brain centers, allowing conscious control
• Higher brain centers exert final control of the micturition reflex, which can be adjusted depending on desire and/or need
• Higher centers inhibit reflex even if reflex is triggered.

Voluntary Urination

• Voluntary control of urination involves abdominal muscle contraction, increasing bladder pressure for efficient emptying.
• Stretching of the bladder neck and posterior urethra during urine flow triggers the micturition reflex
• This reflex inhibits the external urethral sphincter, allowing urination.

Adult Micturition Reflex Diagram

• This diagram illustrates sensory, motor, parasympathetic, and somatic nerve pathways involved in the micturition reflex, which is the coordinated process leading to urination

Hemodialysis

• Hemodialysis is a method for removing wastes and excess fluids from the blood when kidney function is impaired.
• Essential in managing kidney failure. It involves circulating blood through a dialysis machine to filter out waste products.

Test your knowledge on kidney functions and substance transport mechanisms. This quiz explores concepts such as Tmax, renal threshold, and the roles of various substances in the urinary system. Challenge yourself on how kidneys maintain homeostasis and regulate bodily fluids.