Human Biology Nephron Functions
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Questions and Answers

What are the three main processes performed by the nephron?

  • Reabsorption, Excretion, Filtration
  • Filtration, Secretion, Filtration
  • Reabsorption, Filtration, Replacement
  • Filtration, Reabsorption, Secretion (correct)

    • Tubular reabsorption and secretion are equally important in determining the final urinary excretion.

    False

    What is the daily rate of filtration in liters that the kidneys typically handle?

    180 liters

    Urinary excretion rate is calculated by the formula: Filtration rate + Secretion rate - ____________ rate.

    <p>Reabsorption</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Filtration = Initial process of blood component separation Reabsorption = Process that returns substances to the blood Secretion = Process of eliminating additional substances from blood Nephron = Functional unit of the kidney</p> Signup and view all the answers

    What percentage of sodium and water reabsorption occurs in the proximal convoluted tubule (PCT)?

    <p>65%</p> Signup and view all the answers

    The Na+/K+ ATPase facilitates the passive transport of sodium in the nephron.

    <p>False</p> Signup and view all the answers

    What is the primary mechanism through which tubular reabsorption occurs?

    <p>Passive and active transport</p> Signup and view all the answers

    The majority of filtrate produced is reabsorbed in the __________ convoluted tubule.

    <p>proximal</p> Signup and view all the answers

    Match the following nephron parts with their primary function:

    <p>Proximal Convoluted Tubule = Major site of sodium and water reabsorption Distal Convoluted Tubule = Fine tuning of solute excretion Loop of Henle = Concentration of urine Collecting Duct = Final regulation of water reabsorption</p> Signup and view all the answers

    Which transporter is crucial for establishing the concentration gradient for reabsorption of substances in the nephron?

    <p>Na+/K+ ATPase</p> Signup and view all the answers

    Water reabsorption is directly linked to sodium reabsorption.

    <p>True</p> Signup and view all the answers

    How many liters of urine does 180 liters of filtrate yield daily?

    <p>1.5 liters</p> Signup and view all the answers

    What is the main site of glucose and amino acid reabsorption in the nephron?

    <p>Proximal Convoluted Tubule</p> Signup and view all the answers

    Tubule fluid leaving the proximal convoluted tubule is hyperosmotic.

    <p>False</p> Signup and view all the answers

    What is the main function of sodium glucose co-transporters (SGLT2)?

    <p>To transport glucose against its concentration gradient.</p> Signup and view all the answers

    If the amount of glucose in filtrate exceeds the transport maximum (Tm), glucose will be lost in the __________.

    <p>urine</p> Signup and view all the answers

    Match the following transport mechanisms with their functions:

    <p>SGLT2 = Glucose co-transport GLUT = Facilitated diffusion of glucose NHE = Na+/H+ exchange Amino Acid Transporters = Amino acid reabsorption</p> Signup and view all the answers

    Which process is linked to sodium reabsorption in the proximal tubule?

    <p>Secondary active transport of hydrogen ions</p> Signup and view all the answers

    There is an unlimited number of SGLT transporters available at all times in the proximal tubule cells.

    <p>False</p> Signup and view all the answers

    What happens when glucose reabsorption reaches its transport maximum (Tm)?

    <p>Glucose is lost in urine.</p> Signup and view all the answers

    Where in the nephron is fractional glucose reabsorption the highest?

    <p>Proximal convoluted tubule</p> Signup and view all the answers

    The ascending limb of the loop of Henle is permeable to water.

    <p>False</p> Signup and view all the answers

    What mechanism primarily allows sodium to leave the lumen of the proximal convoluted tubule?

    <p>Facilitated diffusion coupled with other solutes</p> Signup and view all the answers

    The thin descending limb of the loop of Henle is highly permeable to ______.

    <p>water</p> Signup and view all the answers

    What happens to potassium in the renal tubule?

    <p>Filtered, reabsorbed and secreted</p> Signup and view all the answers

    About 20% of filtered water is reabsorbed in the loop of Henle.

    <p>True</p> Signup and view all the answers

    What hormone controls the extent of water reabsorption in the medullary collecting ducts?

    <p>Antidiuretic hormone (ADH)</p> Signup and view all the answers

    Match the following nephron segments with their primary function:

    <p>Proximal convoluted tubule = Reabsorption of glucose and amino acids Loop of Henle = Water reabsorption and urine concentration Distal convoluted tubule = Regulation of sodium and potassium Collecting ducts = Final concentration of urine</p> Signup and view all the answers

    What is the primary characteristic of the thin descending limb of the Loop of Henle?

    <p>Permeable to water</p> Signup and view all the answers

    The thick ascending limb is characterized by active reabsorption of water.

    <p>False</p> Signup and view all the answers

    What co-transporter is primarily responsible for reabsorbing sodium, potassium, and chloride in the thick ascending limb?

    <p>sodium-potassium-2-chloride co-transporter</p> Signup and view all the answers

    The early distal tubule is impermeable to ______ and contributes to the dilution of the filtrate.

    <p>water</p> Signup and view all the answers

    Match the nephron segments with their key functions:

    <p>Thin descending limb = Water reabsorption Thick ascending limb = Active solute reabsorption Early distal tubule = Dilution of filtrate Medullary collecting duct = Final urine concentration</p> Signup and view all the answers

    Which hormone controls the water permeability of the late distal tubule?

    <p>Antidiuretic hormone (ADH)</p> Signup and view all the answers

    The late distal tubule contains principal cells that are primarily involved in potassium secretion.

    <p>True</p> Signup and view all the answers

    What is the role of urea in the medullary collecting duct?

    <p>Regulate urine concentration</p> Signup and view all the answers

    Sodium reabsorption in the principal cells occurs through ______ sodium channels.

    <p>epithelial</p> Signup and view all the answers

    Match the following nephron sections with their specific features:

    <p>Thin ascending limb = Impermeable to water Thick ascending limb = Reabsorbs 25% of filtered sodium Early distal tubule = Contains macula densa Cortical collecting tubule = Under hormonal control</p> Signup and view all the answers

    What percentage of the filtered sodium load is reabsorbed in the early distal tubule?

    <p>5%</p> Signup and view all the answers

    Hormonal control of sodium reabsorption occurs exclusively in the proximal tubule.

    <p>False</p> Signup and view all the answers

    What mechanisms primarily regulate tubular processes in the nephron?

    <p>Local feedback, hormonal and neural mechanisms</p> Signup and view all the answers

    The reabsorption process in the thick ascending limb dilutes the filtrate as ______ is reabsorbed.

    <p>sodium</p> Signup and view all the answers

    Match the following hormones with their functions:

    <p>Aldosterone = Regulates sodium reabsorption ADH = Controls water permeability Natriuretic peptide = Reduces sodium reabsorption Renin = Increases blood pressure</p> Signup and view all the answers

    Which drug is an angiotensin-II receptor antagonist that blocks cell signaling induced by angiotensin II?

    <p>Losartan</p> Signup and view all the answers

    Nephrotoxic drugs should be used cautiously in patients with renal impairment or disease.

    <p>True</p> Signup and view all the answers

    What is a potential consequence of drug accumulation in patients with reduced renal function?

    <p>Toxic levels of the drug</p> Signup and view all the answers

    The primary role of __________ antagonists is to block mineralocorticoid activation.

    <p>aldosterone</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Angiotensin-II receptor antagonists = Reduces vasoconstriction Aldosterone antagonist = Blockade of mineralocorticoid activation Spironolactone = A type of diuretic Losartan = Blocks cell signaling induced by angiotensin II</p> Signup and view all the answers

    What effect do non-steroidal anti-inflammatory drugs (NSAIDs) have on GFR?

    <p>Reduce GFR by inhibiting prostaglandin production</p> Signup and view all the answers

    AA dilation increases GFR and EA constriction decreases GFR.

    <p>False</p> Signup and view all the answers

    What do ACE inhibitors (ACEi) primarily block in the kidney?

    <p>The action of angiotensin II</p> Signup and view all the answers

    Drugs that block the _____ can act directly on kidney cells to alter local blood pressure.

    <p>RAAS</p> Signup and view all the answers

    Match the following drugs with their effects on GFR:

    <p>NSAIDs = Reduce GFR ACE inhibitors = Reduce GFR Diuretics = Increase urine volume Mineralocorticoid antagonists = Increase sodium excretion</p> Signup and view all the answers

    What is the primary function of Aldosterone in the kidneys?

    <p>Increase sodium reabsorption</p> Signup and view all the answers

    Angiotensin II causes vasodilation and lowers blood pressure.

    <p>False</p> Signup and view all the answers

    What enzyme converts Angiotensin I to Angiotensin II?

    <p>Angiotensin converting enzyme (ACE)</p> Signup and view all the answers

    The hormone that is secreted by the adrenal gland and increases sodium reabsorption is called __________.

    <p>Aldosterone</p> Signup and view all the answers

    Match the following components of the RAAS (Renin-Angiotensin-Aldosterone System) with their functions:

    <p>Renin = Converts Angiotensinogen to Angiotensin I Angiotensinogen = Precursor protein produced by the liver ACE = Converts Angiotensin I to Angiotensin II Angiotensin II = Stimulates aldosterone release</p> Signup and view all the answers

    Where is Renin produced?

    <p>Kidneys</p> Signup and view all the answers

    The principal cells in the collecting duct secrete Na+ in exchange for K+.

    <p>False</p> Signup and view all the answers

    What is the effect of Angiotensin II on sodium and water reabsorption in the kidneys?

    <p>It increases sodium and water reabsorption.</p> Signup and view all the answers

    Which class of diuretics is primarily used for conditions associated with hypertension?

    <p>Thiazide diuretics</p> Signup and view all the answers

    Potassium sparing diuretics promote the excretion of sodium.

    <p>False</p> Signup and view all the answers

    Name one condition for which loop diuretics are commonly prescribed.

    <p>Oedema</p> Signup and view all the answers

    The four main classes of diuretics are loop diuretics, thiazide diuretics, __________ diuretics, and carbonic anhydrase inhibitors.

    <p>potassium sparing</p> Signup and view all the answers

    Match the following RAAS drugs with their functions:

    <p>ACE inhibitors = Block the conversion of angiotensin I to angiotensin II Angiotensin Receptor Blockers = Block the effects of angiotensin II Aldosterone Antagonists = Inhibit the action of aldosterone Combined RAAS agents = Simultaneously block multiple RAAS pathways</p> Signup and view all the answers

    What is the main effect of angiotensin II in the body?

    <p>Increases thirst and fluid retention</p> Signup and view all the answers

    What system is crucial for controlling blood pressure and flow in the kidneys?

    <p>Renin-Angiotensin Aldosterone System (RAAS)</p> Signup and view all the answers

    Carbonic anhydrase inhibitors are commonly used as diuretics in modern medicine.

    <p>False</p> Signup and view all the answers

    What is the main action of aldosterone antagonists like spironolactone and eplerenone?

    <p>Block mineralocorticoid receptor activation by aldosterone</p> Signup and view all the answers

    Potassium-sparing diuretics can lead to hyperkalemia, which is dangerously high potassium levels in the blood.

    <p>True</p> Signup and view all the answers

    What is a common use of potassium-sparing diuretics?

    <p>Chronic heart failure</p> Signup and view all the answers

    Aldosterone antagonists are known to reduce __________ secretion into the tubular lumen.

    <p>potassium</p> Signup and view all the answers

    Match the following drugs to their category:

    <p>Spironolactone = Aldosterone Antagonist Eplerenone = Aldosterone Antagonist Furosemide = Loop Diuretic Hydrochlorothiazide = Thiazide Diuretic</p> Signup and view all the answers

    Why are loop and thiazide diuretics rarely used together?

    <p>They can lead to significant water and potassium losses</p> Signup and view all the answers

    The main purpose of combining a potassium-sparing diuretic with a loop or thiazide diuretic is to promote potassium loss.

    <p>False</p> Signup and view all the answers

    What is the risk associated with the interaction of potassium-sparing diuretics and RAAS drugs?

    <p>Hyperkalemia</p> Signup and view all the answers

    What condition is primarily treated with aldosterone antagonists?

    <p>Congestive heart failure</p> Signup and view all the answers

    Drugs acting on the Renin-Angiotensin-Aldosterone System (RAAS) are crucial for __________ control.

    <p>blood pressure</p> Signup and view all the answers

    What is the main result of phase II reactions in drug metabolism?

    <p>Attachment of a large chemical group that increases hydrophilicity</p> Signup and view all the answers

    Phase II reactions mainly occur in the liver, but can also take place in the lungs and kidneys.

    <p>True</p> Signup and view all the answers

    What are the chemical groups most often involved in conjugate formation during phase II reactions?

    <p>Glucuronyl, acetyl, methyl, sulphate, and glutathione</p> Signup and view all the answers

    The conjugated metabolite formed in phase II reactions is usually __________ and more easily excreted from the body.

    <p>pharmacologically inactive</p> Signup and view all the answers

    Match the following conjugating enzymes with their primary locations:

    <p>Glucuronyl transferases = Endoplasmic reticulum Other conjugating enzymes = Cytosol CYP450s = Endoplasmic reticulum Isoforms = Various tissues</p> Signup and view all the answers

    Which of the following isoforms are involved in drug metabolism and oxidation?

    <p>All of the above</p> Signup and view all the answers

    Cytochrome P450 enzymes require molecular oxygen in order to function.

    <p>True</p> Signup and view all the answers

    What is one example of a Phase I reaction that does not involve the CYP450 system?

    <p>Ethanol metabolism by alcohol dehydrogenase</p> Signup and view all the answers

    Cytochrome P450 catalyses the transfer of one oxygen atom to the substrate while the other oxygen atom is reduced to __________.

    <p>water</p> Signup and view all the answers

    Match the following Cytochrome P450 isoforms with their corresponding approximate percentage of drug metabolism:

    <p>CYP3A = 30-40% CYP2D6 = 20-30% CYP2C9 = 10-20% CYP1A2 = 5-10%</p> Signup and view all the answers

    What is the primary site of drug metabolism in the body?

    <p>Liver</p> Signup and view all the answers

    Phase I metabolism primarily involves conjugation reactions.

    <p>False</p> Signup and view all the answers

    What is the process called when a drug is metabolized into an active form?

    <p>Activation or conversion of pro-drugs</p> Signup and view all the answers

    The ________ system transports orally-administered drugs through the liver for metabolism.

    <p>portal</p> Signup and view all the answers

    Match the following phases of drug metabolism with their descriptions:

    <p>Phase I = Involves oxidation and reduction reactions Phase II = Conjugation reactions to increase water solubility Phase III = Transport and excretion of metabolites</p> Signup and view all the answers

    Which enzyme superfamily is primarily responsible for drug metabolism in the liver?

    <p>Cytochrome P450</p> Signup and view all the answers

    Liver disease can enhance the effects of certain drugs due to impaired metabolism.

    <p>True</p> Signup and view all the answers

    Name one factor that can affect hepatic drug metabolism.

    <p>Age, liver disease, or genetic polymorphisms</p> Signup and view all the answers

    What is the effect of CYP450 enzyme induction on drug metabolism?

    <p>It enhances the rate of drug metabolism.</p> Signup and view all the answers

    CYP450 enzyme inhibition results in increased metabolism of drugs.

    <p>False</p> Signup and view all the answers

    What herbal remedy is known to induce the activity of many P450 enzymes?

    <p>St. John’s Wort</p> Signup and view all the answers

    CYP450 enzyme inhibitors can lead to potentially toxic drug levels and __________ effects.

    <p>adverse</p> Signup and view all the answers

    Match the following drugs with their effects on CYP450 enzymes:

    <p>St. John’s Wort = Induces CYP450 enzymes Omeprazole = Inhibits CYP450 enzymes Warfarin = Requires careful monitoring with CYP450 inducers/inhibitors Phenytoin = Metabolism affected by CYP450 inhibitors</p> Signup and view all the answers

    What is a common result of prolonged CYP450 enzyme induction?

    <p>Decreased therapeutic effect of the drug.</p> Signup and view all the answers

    Pro-drugs are activated by phase I metabolism.

    <p>True</p> Signup and view all the answers

    Which CYP450 enzyme is specifically known to be inhibited by Omeprazole?

    <p>CYP2C19</p> Signup and view all the answers

    What is the primary definition of bioavailability?

    <p>The proportion of administered drug that reaches systemic circulation unchanged</p> Signup and view all the answers

    First-pass metabolism increases the bioavailability of orally administered drugs.

    <p>False</p> Signup and view all the answers

    What impact does cirrhosis have on the drug-metabolizing capacity of the liver?

    <p>It decreases the drug-metabolizing capacity.</p> Signup and view all the answers

    In liver disease, hypoproteinaemia leads to decreased drug-binding capacity, allowing more unbound and __________ drug to circulate.

    <p>pharmacologically active</p> Signup and view all the answers

    Match the following effects of cirrhosis with their descriptions:

    <p>Increased bioavailability = Result of decreased first-pass metabolism Decreased plasma protein binding = Leads to more unbound drug circulation Porto-systemic shunting = Bypasses normal drug metabolism in the liver Hypoproteinaemia = Reduction in plasma protein levels</p> Signup and view all the answers

    Why should initial doses of drugs that are inactivated by first-pass metabolism be smaller than usual in patients with liver disease?

    <p>Increased risk of overdose due to higher plasma levels</p> Signup and view all the answers

    Cirrhosis has no impact on drug action due to compensatory liver function.

    <p>False</p> Signup and view all the answers

    What physiological changes in the liver occur due to porto-systemic shunting in cirrhosis?

    <p>Drugs are directed away from the liver, reducing their metabolism.</p> Signup and view all the answers

    What disorder is most likely indicated by raised levels of protein but normal levels of albumin?

    <p>Multiple myeloma</p> Signup and view all the answers

    Bilirubin is a breakdown product of cholesterol.

    <p>False</p> Signup and view all the answers

    Why would small amounts of bilirubin be expected in blood under normal conditions?

    <p>Normal red blood cell turnover</p> Signup and view all the answers

    Conjugated bilirubin is not normally found in blood and suggests a blockage of the __________.

    <p>bile duct</p> Signup and view all the answers

    Match the following tests to their indicative conditions:

    <p>ALT = Acute liver damage AST = Cirrhosis GGT = Liver or bile duct damage ALP = Bone pathology</p> Signup and view all the answers

    What organ is most likely to have pathology if a patient has raised ALP but normal GGT, along with abnormal calcium levels?

    <p>Bone</p> Signup and view all the answers

    Gamma-glutamyl transferase (GGT) is produced mainly in the kidney.

    <p>False</p> Signup and view all the answers

    ALT levels are generally higher in cases of __________ liver damage.

    <p>acute</p> Signup and view all the answers

    Which of the following tests are part of the basic liver panel? (Select all that apply)

    <p>Total bilirubin</p> Signup and view all the answers

    Total protein in a blood sample measures only enzymes present.

    <p>False</p> Signup and view all the answers

    What is the principal type of protein measured in a total protein test aside from albumin?

    <p>Transport proteins</p> Signup and view all the answers

    Normal liver blood tests may occur even with pathology due to compensation by other parts of the __________.

    <p>liver</p> Signup and view all the answers

    Match the following liver tests with their categories:

    <p>Alanine aminotransferase (ALT) = Liver panel Aspartate aminotransferase (AST) = Liver panel Conjugated bilirubin = Liver panel Prothrombin time (PT) = Other</p> Signup and view all the answers

    Which test is used to assess the functional capacity of the liver?

    <p>Prothrombin time (PT)</p> Signup and view all the answers

    The most abundant protein found in the blood is transport protein.

    <p>False</p> Signup and view all the answers

    Name one reason why liver blood tests may show normal results despite underlying pathology.

    <p>Compensation by other parts of the liver</p> Signup and view all the answers

    Which structure in the kidney is primarily responsible for draining urine into the ureter?

    <p>Minor calyx</p> Signup and view all the answers

    The nephron is the functional unit of the kidney and there are approximately 1 million nephrons per kidney.

    <p>True</p> Signup and view all the answers

    What are the three key processes that epithelial tissue in the kidney is specialised for?

    <p>Filtration, absorption, and secretion</p> Signup and view all the answers

    The uriniferous tubule consists of the nephron and the __________.

    <p>collecting duct</p> Signup and view all the answers

    Match the following kidney structures with their primary function:

    <p>Renal artery = Carries blood to the kidneys Renal vein = Carries blood away from the kidneys Renal pelvis = Collects urine from the major calyx Minor calyx = Collects urine from the renal papilla</p> Signup and view all the answers

    What is the primary characteristic of the cortex in the kidney?

    <p>Contains nephron structures</p> Signup and view all the answers

    The major calyx drains urine directly into the renal pelvis.

    <p>True</p> Signup and view all the answers

    How many uriniferous tubules are typically found in each kidney?

    <p>Approximately 1 million</p> Signup and view all the answers

    What is the main function of the podocytes in the glomerular capillaries?

    <p>Facilitate filtration</p> Signup and view all the answers

    The basemen membrane in the glomerulus is positively charged.

    <p>False</p> Signup and view all the answers

    Which segment of the nephron is primarily responsible for the reabsorption of water, sodium, and various solutes?

    <p>Proximal convoluted tubule</p> Signup and view all the answers

    The thick ascending limb of the Loop of Henle is impermeable to ______.

    <p>water</p> Signup and view all the answers

    Match the parts of the nephron with their main functions:

    <p>Proximal convoluted tubule = Reabsorption of nutrients and water Loop of Henle = Concentration of urine Distal convoluted tubule = Regulation of sodium and potassium levels Juxtaglomerular apparatus = Regulation of blood pressure</p> Signup and view all the answers

    Which cells in the distal convoluted tubule are involved in the secretion of potassium and hydrogen ions?

    <p>Intercalated cells</p> Signup and view all the answers

    The thin descending limb of the Loop of Henle actively reabsorbs sodium and other solutes.

    <p>False</p> Signup and view all the answers

    What determines the variable water permeability in the distal convoluted tubule?

    <p>Antidiuretic hormone (ADH)</p> Signup and view all the answers

    The filtration barrier in the glomerulus limits the passage of substances based on their size, charge, and ______.

    <p>shape</p> Signup and view all the answers

    Match the nephron segments with their primary characteristics:

    <p>Proximal convoluted tubule = Simple cuboidal cells with microvilli Loop of Henle = Generates hyperosmotic interstitium Distal convoluted tubule = Active reabsorption of sodium Juxtaglomerular apparatus = Regulates glomerular filtration rate</p> Signup and view all the answers

    Which cells are involved in tubuloglomerular feedback?

    <p>Extraglomerular mesangial cells</p> Signup and view all the answers

    The collecting duct is primarily responsible for electrolyte reabsorption.

    <p>False</p> Signup and view all the answers

    What role does antidiuretic hormone (ADH) play in the nephron?

    <p>It regulates water permeability in the collecting duct.</p> Signup and view all the answers

    The __________ are responsible for the final site of urine processing in the nephron.

    <p>collecting ducts</p> Signup and view all the answers

    Match the following nephron structures to their primary function:

    <p>Macula densa = Regulation of blood pressure Granular cells = Release of renin Collecting duct = Water reabsorption control Proximal tubule = Major site of reabsorption</p> Signup and view all the answers

    What is the primary role of the loop of Henle in the nephron?

    <p>Regulating urine concentration</p> Signup and view all the answers

    The medullary interstitium is hypoosmolar compared to the filtrate.

    <p>False</p> Signup and view all the answers

    Name one function of the kidney.

    <p>Regulating electrolyte balance.</p> Signup and view all the answers

    What percentage of total body weight does intracellular fluid (ICF) approximately constitute?

    <p>40%</p> Signup and view all the answers

    The main cation in extracellular fluid (ECF) is potassium.

    <p>False</p> Signup and view all the answers

    What are the two main compartments of extracellular fluid (ECF)?

    <p>Interstitial fluid and plasma</p> Signup and view all the answers

    The main anion in intracellular fluid (ICF) is __________.

    <p>phosphate</p> Signup and view all the answers

    Match the following body fluids with their primary characteristics:

    <p>Plasma = Non-cellular component of blood Interstitial Fluid = Surrounds the cells Intracellular Fluid = Fluid in the cells Extracellular Fluid = Fluid outside the cells</p> Signup and view all the answers

    Which ion concentration differs between plasma and interstitial fluid?

    <p>Proteins</p> Signup and view all the answers

    The composition of body fluids is the same across all compartments.

    <p>False</p> Signup and view all the answers

    What is the primary anion found in extracellular fluid (ECF)?

    <p>Chloride</p> Signup and view all the answers

    Which part of the nephron is primarily responsible for the reabsorption of sodium and water?

    <p>Proximal convoluted tubule</p> Signup and view all the answers

    The renal corpuscle consists of the glomerulus and the proximal convoluted tubule.

    <p>False</p> Signup and view all the answers

    What is the function of mesangial cells in the renal corpuscle?

    <p>Provide structural support between glomerular capillaries.</p> Signup and view all the answers

    The renal artery branches into segmental arteries before leaving the ______.

    <p>kidney</p> Signup and view all the answers

    Match the following components of the nephron with their respective roles:

    <p>Distal convoluted tubule = Final adjustment of sodium and potassium Loop of Henle = Creates concentration gradient in the medulla Proximal convoluted tubule = Major site of reabsorption Collecting duct = Regulates final urine concentration</p> Signup and view all the answers

    What type of capillaries are found in the glomerulus?

    <p>High-pressure capillaries</p> Signup and view all the answers

    Podocytes play a significant role in the filtration barrier of the renal corpuscle.

    <p>True</p> Signup and view all the answers

    What is the name of the structure that surrounds and protects the glomerulus?

    <p>Bowman’s capsule</p> Signup and view all the answers

    The ______ artery supplies blood to the interlobular arteries.

    <p>Renal</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>Afferent arteriole = Brings blood to the glomerulus Efferent arteriole = Carries blood away from the glomerulus Peritubular capillaries = Surround nephron tubules for reabsorption Vasa recta = Supplies blood to the loops of Henle</p> Signup and view all the answers

    Which nephron type accounts for approximately 80% of all nephrons?

    <p>Cortical</p> Signup and view all the answers

    The collecting duct is primarily involved in the reabsorption of glucose.

    <p>False</p> Signup and view all the answers

    What are the two primary layers of Bowman’s capsule?

    <p>Parietal layer and Visceral layer</p> Signup and view all the answers

    Blood exits the glomerulus through the ______ arteriole.

    <p>efferent</p> Signup and view all the answers

    Which arteries run along the corticomedullary junction?

    <p>Arcuate arteries</p> Signup and view all the answers

    What is the primary process by which substances are removed from the blood to form urine?

    <p>Filtration</p> Signup and view all the answers

    The kidneys receive approximately 30% of the cardiac output.

    <p>False</p> Signup and view all the answers

    What is the filtration fraction of renal plasma flow?

    <p>20%</p> Signup and view all the answers

    The glomerular filtration barrier is primarily made up of glomerular capillary endothelium and __________.

    <p>podocytes</p> Signup and view all the answers

    Match the nephron processes with their descriptions:

    <p>Filtration = Removal of substances from blood Reabsorption = Return of substances to blood Secretion = Active transport of substances into filtrate</p> Signup and view all the answers

    Which factor is NOT considered in determining the glomerular filtration rate (GFR)?

    <p>Heart rate</p> Signup and view all the answers

    The kidneys filter approximately __________ liters of filtrate daily.

    <p>180</p> Signup and view all the answers

    Glomerular filtration rate (GFR) can be used to assess renal function.

    <p>True</p> Signup and view all the answers

    What determines the glomerular filtration rate (GFR)?

    <p>Glomerular capillary filtration coefficient and net filtration pressure</p> Signup and view all the answers

    Blood cells can easily pass through the filtration barrier in the kidneys.

    <p>False</p> Signup and view all the answers

    What reflects the hydraulic conductivity of the filtration barrier in the kidneys?

    <p>Glomerular capillary filtration coefficient (Kf)</p> Signup and view all the answers

    The GFR can be calculated using the formula: GFR = Kf x ________.

    <p>NFP</p> Signup and view all the answers

    Match each term with its associated description:

    <p>Podocytes = Epithelial cells with filtration slits Filtration barrier = Limits passage of substances based on size and charge NFP = Sum of pressures acting across the filtration barrier GFR = Volume of filtrate formed per unit time</p> Signup and view all the answers

    Which factor can decrease the glomerular filtration rate (GFR)?

    <p>Damage to the filtration barrier</p> Signup and view all the answers

    The composition of filtrate is significantly different from that of plasma.

    <p>False</p> Signup and view all the answers

    What happens to the properties of the filtrate in disease processes?

    <p>They may alter, allowing proteins to appear in the filtrate.</p> Signup and view all the answers

    What is the primary effect of afferent arteriole dilation on GFR?

    <p>Increases GFR</p> Signup and view all the answers

    Efferent arteriole constriction decreases GFR.

    <p>False</p> Signup and view all the answers

    What are the two main factors affecting glomerular hydrostatic pressure (PG)?

    <p>Arterial pressure and arteriolar resistance</p> Signup and view all the answers

    What primarily determines the glomerular filtration rate (GFR)?

    <p>Net filtration pressure across the filtration barrier</p> Signup and view all the answers

    Constriction of the afferent arteriole increases the glomerular filtration rate.

    <p>False</p> Signup and view all the answers

    The regulation of GFR is primarily influenced by changes in ______.

    <p>glomerular hydrostatic pressure</p> Signup and view all the answers

    Match the following concepts with their respective effects on GFR:

    <p>Afferent arteriole dilation = Increases GFR Efferent arteriole constriction = Increases GFR Afferent arteriole constriction = Decreases GFR Efferent arteriole dilation = Decreases GFR</p> Signup and view all the answers

    What is the typical value for net filtration pressure (NFP)?

    <p>10 mmHg</p> Signup and view all the answers

    The equation used to calculate net filtration pressure (NFP) is NFP = PG – PB – πG + πB, where PG represents ________ pressure.

    <p>glomerular</p> Signup and view all the answers

    Which physiological factor can lead to a decrease in GFR?

    <p>Afferent arteriole constriction</p> Signup and view all the answers

    Colloid osmotic pressure (π) has no impact on net filtration pressure (NFP).

    <p>False</p> Signup and view all the answers

    Which pressure most strongly opposes filtration in the glomerulus?

    <p>Colloid osmotic pressure of plasma proteins</p> Signup and view all the answers

    Match the following terms with their definitions:

    <p>GFR = Rate of fluid filtered from the glomeruli to the Bowman's capsule NFP = Overall pressure encouraging filtration at the glomerulus Afferent arteriole = Blood vessel supplying blood to the glomerulus Efferent arteriole = Blood vessel draining blood from the glomerulus</p> Signup and view all the answers

    What is the formula to calculate Net Filtration Pressure (NFP)?

    <p>NFP = PG - PB - πG + πB</p> Signup and view all the answers

    What effect does tubuloglomerular feedback have on glomerular filtration rate?

    <p>It helps maintain a relatively constant GFR despite changes in arterial pressure.</p> Signup and view all the answers

    Net Filtration Pressure (NFP) remains constant regardless of changes in mean arterial pressure.

    <p>False</p> Signup and view all the answers

    What effect does angiotensin II have on the afferent arterioles?

    <p>It constricts afferent arterioles</p> Signup and view all the answers

    The myogenic response is responsible for relaxing the smooth muscle in afferent arterioles.

    <p>False</p> Signup and view all the answers

    What two mechanisms contribute to the autoregulation of GFR?

    <p>Myogenic response and tubuloglomerular feedback</p> Signup and view all the answers

    The __________ feedback mechanism links changes in [NaCl] to control afferent arteriolar resistance.

    <p>tubuloglomerular</p> Signup and view all the answers

    Match the following terms with their corresponding functions:

    <p>Myogenic response = Contraction of smooth muscle in response to increased stretch Tubuloglomerular feedback = Regulates own resistance in afferent arterioles based on [NaCl] Macula densa cells = Sense NaCl concentration in distal tubule Juxtaglomerular apparatus = Links blood pressure changes to renal adjustments</p> Signup and view all the answers

    Which of the following substances is primarily responsible for vasoconstriction of afferent arterioles?

    <p>Endothelin</p> Signup and view all the answers

    Increased arterial blood pressure leads to an increased GFR.

    <p>True</p> Signup and view all the answers

    Which cells in the juxtaglomerular apparatus are responsible for sensing sodium chloride concentration?

    <p>Macula densa cells</p> Signup and view all the answers

    The release of __________ from macula densa cells helps regulate afferent arteriolar resistance.

    <p>paracrine factors</p> Signup and view all the answers

    Which response results from increased stretching of afferent arterioles due to higher blood pressure?

    <p>Vasoconstriction</p> Signup and view all the answers

    What is the typical glomerular filtration rate (GFR) for a young male?

    <p>120 ml/min/1.73m²</p> Signup and view all the answers

    Serum creatinine is less accurate for reflecting GFR compared to serum urea.

    <p>False</p> Signup and view all the answers

    What does a rise in serum creatinine indicate about kidney function?

    <p>Decreased kidney function</p> Signup and view all the answers

    GFR is linked to age, sex, and body size; it often ______ with increasing age.

    <p>declines</p> Signup and view all the answers

    Match the following markers with their relevance in assessing renal function:

    <p>Proteinuria = Indicates kidney damage Serum creatinine = Reflects GFR Estimated GFR = Overall index of kidney function Hematuria = Indicates damage to urinary tract</p> Signup and view all the answers

    Which of the following factors can affect serum creatinine levels?

    <p>All of the above</p> Signup and view all the answers

    Endogenous markers for measuring GFR are more cost-effective compared to exogenous markers.

    <p>True</p> Signup and view all the answers

    What is a common method used to assess renal function?

    <p>Serum urea, serum creatinine, estimated GFR</p> Signup and view all the answers

    What is the primary equation used to estimate glomerular filtration rate (GFR)?

    <p>CKD-EPI equation</p> Signup and view all the answers

    The normal estimated GFR (eGFR) value is less than 90 ml/min/1.73m².

    <p>False</p> Signup and view all the answers

    What parameter is primarily used to calculate estimated GFR?

    <p>serum creatinine</p> Signup and view all the answers

    The __________ increases accuracy in monitoring renal function compared to serum creatinine alone.

    <p>eGFR</p> Signup and view all the answers

    Match the following limitations of eGFR with their descriptions:

    <p>Influenced by muscle mass = Higher eGFR in malnourished individuals due to lower creatinine Limitations in children = Not always accurate for pediatric patients Acute kidney injury = May not reflect true renal function during acute injury Drug dose calculations = Not reliable for highly toxic drug dosing</p> Signup and view all the answers

    Which of the following conditions would likely lead to an inaccurately high eGFR?

    <p>Patient with significant muscle mass loss</p> Signup and view all the answers

    Serum cystatin C is not used in newer tests to estimate GFR.

    <p>False</p> Signup and view all the answers

    What is the relationship between serum creatinine and eGFR results?

    <p>Inversely related</p> Signup and view all the answers

    Study Notes

    Tubular Processing

    • The kidneys play a vital role in regulating body fluid volume and composition.
    • Nephrons are the functional units of the kidneys and perform three main processes: filtration, reabsorption, and secretion.
    • Tubular processing fine-tunes urine volume and composition to prevent excessive fluid and solute losses.
    • Reabsorption is the primary process for most substances in determining final urinary excretion.

    Tubular Reabsorption

    • Tubular reabsorption is a quantitatively large and highly selective process that allows independent regulation of solute excretion.
    • It involves the movement of fluid and solutes from the tubule lumen to the peritubular capillary using both passive and active transport mechanisms.
    • Luminal and basal surfaces of tubule epithelial cells feature different transporter proteins, facilitating the establishment of concentration gradients.
    • The Na+/K+ ATPase plays a crucial role in reabsorption of many substances by providing a concentration gradient along the nephron.
    • Water is passively reabsorbed and closely linked to sodium reabsorption and the permeability of different nephron segments.

    Proximal Convoluted Tubule

    • The majority of sodium and water reabsorption (approximately 65%) occurs in the proximal convoluted tubule (PCT).
    • The PCT has a brush border increasing surface area and mitochondria for energy supply.
    • It is also the site of secretion of metabolic acids, bases, and drugs.
    • Tubular fluid exiting the PCT is isosmotic due to the freely permeable epithelium to water.
    • The PCT is the main site of glucose and amino acid reabsorption.

    Glucose and Amino Acids

    • Almost all glucose and amino acids are reabsorbed in the PCT via secondary active transport (co-transporters) linked to sodium reabsorption.
    • Sodium glucose co-transporters (SGLT2 mainly) on the luminal side move glucose against its concentration gradient.
    • Glucose transporters (GLUT) on the basal side allow facilitated diffusion of glucose into the interstitial fluid.
    • A similar process occurs for amino acids.

    Glucose and Tm

    • There is a finite number of SGLT transporters on proximal tubule cells.
    • They function well under normal physiological plasma glucose levels.
    • When glucose in the filtrate exceeds the transport maximum (Tm), reabsorption cannot keep up, leading to glucose loss in urine.
    • Water is retained in the tubule lumen and excreted along with glucose creating an osmotic effect.

    Secretion of H+

    • Sodium reabsorption is linked to the secondary active transport of hydrogen ions (H+) into the lumen (secretion).
    • This is essential for bicarbonate reabsorption in the proximal tubule.
    • The Na+/H+ exchanger (NHE) functions as an antiporter.

    Loop of Henle

    • The loop of Henle is divided into three parts: the thin descending limb, thin ascending limb, and thick ascending limb.
    • The thin descending limb is permeable to water and does not actively reabsorb or secrete solutes.
    • The thin ascending limb is impermeable to water and also does not actively reabsorb or secrete solutes.
    • The thick ascending limb is impermeable to water and actively reabsorbs sodium (approximately 25% of the filtered load) and other solutes.
    • This dilution of luminal fluid (hypo-osmotic) occurs as solutes are removed/reabsorbed, but water cannot follow.

    Thick Ascending Limb

    • Reabsorption of sodium, potassium, and chloride from the tubule lumen is primarily mediated by the sodium, potassium, 2-chloride co-transporter (Na+K+2Cl-).
    • The positive charge in the lumen encourages paracellular reabsorption of cations, including calcium (Ca2+) and magnesium (Mg2+).
    • As water cannot follow the solutes, the remaining tubular lumen fluid becomes diluted.

    Early Distal Tubule

    • The early distal tubule is impermeable to water and contributes to the dilution of the filtrate.
    • It actively reabsorbs sodium (approximately 5% of the filtered load).
    • The early distal tubule contains the macula densa, a structure sensitive to NaCl levels that forms part of the juxtaglomerular apparatus involved in feedback control of glomerular filtration rate (GFR) and blood pressure.

    Early Distal Tubule 2

    • Sodium-chloride co-transporter on the luminal side further dilutes the tubular lumen fluid.

    Late Distal Tubule and Cortical Collecting Tubule

    • These segments share similar functional characteristics.
    • Water permeability is regulated by antidiuretic hormone (ADH):
      • Water permeable in the presence of ADH.
      • Water impermeable in the absence of ADH.
    • Two main cell types exist:
      • Principal cells: involved in sodium reabsorption (through epithelial sodium channels, ENaC) and potassium secretion.
      • Intercalated cells: involved in potassium reabsorption and hydrogen ion secretion.

    Principal Cells

    • Sodium enters principal cells through ENaC on the luminal side and is transported out of cells by Na+/K+ ATPase to maintain a concentration gradient.
    • The number of ENaC channels and the activity of ATPase are under hormonal control by aldosterone.
    • Principal cells are an important site of regulation and fine-tuning of sodium reabsorption and potassium secretion.

    Medullary Collecting Duct

    • The medullary collecting duct is the final site for urine processing.
    • Water permeability is regulated by ADH.
    • It's surrounded by a medullary interstitium with a high solute concentration.
    • It plays a key role in regulating urine concentration.
    • Urea permeability allows the medullary interstitium to remain concentrated.

    Regulation of Tubular Processes

    • Tubular processes are regulated by local feedback, hormonal, and neural mechanisms.
    • In contrast to GFR regulation, reabsorption of individual solutes can be adjusted independently, particularly by hormones acting on different parts of the nephron.

    Drugs and the Kidney

    • Renal impairment can lead to drug accumulation and toxicity
    • Nephrotoxic drugs should be avoided in patients with renal impairment
    • Drugs can be less effective in patients with impaired renal function
    • Medications may need to be modified for elderly patients

    Diuretics

    • Diuretics promote urine excretion by increasing sodium excretion
    • Loop diuretics, Thiazide diuretics, and Potassium sparing diuretics are the main classes
    • Potassium sparing diuretics can lead to hyperkalemia
    • Loop diuretics and Thiazide diuretics can be combined for improved diuretic effect without K+ loss

    Drugs acting on the RAAS

    • The Renin-Angiotensin-Aldosterone System (RAAS) plays a crucial role in blood pressure and flow regulation
    • Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs), and Aldosterone Antagonists are the main classes
    • Aldosterone antagonists can be used in conjunction with loop or thiazide diuretics to prevent potassium loss

    Potassium sparing diuretics

    • Commonly used for conditions associated with edema and hypertension
    • Can be used to prevent potassium loss from loop or thiazide diuretics
    • Can cause hyperkalaemia

    Aldosterone Antagonists

    • Bind to the mineralocorticoid receptor (MR) and block aldosterone activation
    • Reduce potassium secretion into tubular lumen, leading to potassium retention

    ### Regulation of GFR via vascular control

    • Balance of afferent arteriole (AA) and efferent arteriole (EA) resistances determine GFR
    • Dilation of AA or constriction of EA increases GFR
    • Constriction of AA or dilation of EA reduces GFR

    NSAIDs and GFR

    • NSAIDs inhibit prostaglandin production which promotes dilation of the afferent arteriole and increases GFR
    • NSAIDs can reduce GFR

    ACEi/ARB and GFR

    • ACE inhibitors and ARBs prevent angiotensin II action which drives efferent arteriolar constriction
    • ACEi and ARBs therefore can also reduce GFR

    Drug Metabolism

    • The liver is the primary site for drug metabolism.
    • Orally administered drugs undergo first-pass metabolism in the liver before entering systemic circulation.
    • Drugs can pass through the liver multiple times during systemic circulation, with a fraction metabolized each time.
    • Metabolites can be excreted through the kidneys or bile.

    Biochemical Pathways of Drug Metabolism in the Liver

    • Drug metabolism occurs in two phases:
      • Phase I: Introduces or exposes functional groups (e.g., OH or NH2) to increase polarity and prepare for phase II.
      • Phase II: Conjugation reactions attach large chemical groups to the drug, rendering it inactive and more easily excreted.

    Phase I Metabolism

    • Involves oxidation, reduction, and hydrolysis.
    • Most often decreases drug activity, but can increase activity for pro-drugs.
    • Cytochrome P450 enzymes are a critical component of Phase I metabolism.

    Cytochrome P450 Enzymes

    • A superfamily of enzymes located on the endoplasmic reticulum of hepatocytes.
    • Hundreds of isoforms exist with varying protein structure, regulation, and substrate specificity.
    • Many are inducible, meaning their activity can be increased by exposure to certain substances.
    • These heme-containing enzymes require molecular oxygen, NADPH, and NADPH cytochrome P450 reductase to function.

    Major Cytochrome P450 Isoforms

    • CYP3A: Metabolizes a large proportion of drugs.
    • CYP2D6: Responsible for the metabolism of numerous drugs, including antidepressants and antipsychotics.
    • CYP2C9: Involved in the metabolism of many drugs, such as warfarin and NSAIDs.
    • CYP1A2: Metabolizes several drugs, including caffeine and some antipsychotics.

    Oxidation of a Drug by Cytochrome P450

    • The process involves both chemical oxidation and reduction steps.
    • Cytochrome P450 catalyzes the transfer of one oxygen atom to the drug, while the other atom is reduced to water.

    Other Phase I Reactions

    • Reductions are less common than oxidations.
    • Oxidations that do not involve the CYP450 system occur, such as ethanol metabolism by alcohol dehydrogenase.
    • Monoamine oxidase enzymes inactivate biogenic amines like norepinephrine, serotonin, and dopamine.
    • Hydrolytic reactions occur in plasma and various tissues, such as the hydrolysis of aspirin to salicylic acid.

    Phase II Reactions

    • Conjugation reactions involve attaching a large chemical group to the drug molecule.
    • Most commonly occurs in the liver, but can also occur in other tissues.
    • Common conjugates include glucuronyl, acetyl, methyl, sulphate, and glutathione.
    • Conjugating enzymes can be located on the ER or in the cytosol.

    Drug Interactions at the Level of Hepatic Metabolism

    • Often occur due to interactions at CYP450 enzymes.
    • Various factors (drugs, alcohol, food components, environmental contaminants) can alter CYP450 activity.
    • CYP450 enzyme induction increases drug metabolism, leading to lower plasma levels and potentially reduced therapeutic efficacy.
    • CYP450 enzyme inhibition reduces drug metabolism, leading to higher plasma levels and increased potential for toxicity.

    CYP450 Enzyme Induction

    • Long-term drug administration can induce CYP450 activity by increasing synthesis or decreasing degradation of the enzyme.
    • This results in faster metabolism of the drug and other drugs metabolized by the same enzyme.
    • Plasma levels and biological effects of the drugs decrease.

    St. John's Wort

    • An herbal remedy often used for depression.
    • Induces the activity of multiple CYP450 enzymes, leading to increased metabolism and lower plasma levels of various medications (e.g., warfarin, antiepileptic drugs, oral contraceptives).

    CYP450 Enzyme Inhibition

    • Drugs or other substances can inhibit CYP450 activity.
    • This slows down the metabolism of drugs metabolized by the inhibited enzyme.
    • Plasma levels and biological effects of the drug increase, raising the risk of toxicity.

    Omeprazole

    • A proton pump inhibitor.
    • A weak inhibitor of many CYP450 enzymes, leading to reduced metabolism of endogenous steroids and co-administered drugs (e.g., warfarin, phenytoin).
    • Increased plasma levels of these drugs can lead to toxicity.

    Effects of Liver Disease on Drug Action

    • Impaired liver function reduces drug-metabolizing capacity.
    • Hypoproteinemia reduces drug binding, leading to more unbound and active drug circulating.
    • Porto-systemic shunting bypasses the liver, reducing first-pass metabolism.
    • Increased bioavailability due to decreased first-pass metabolism.
    • Reduced clearance of drugs due to impaired liver function.

    Precautions When Prescribing in Liver Disease

    • Reduced initial doses of drugs metabolized by the liver.
    • Careful monitoring of drug levels and response.
    • Consider alternative medications with lower hepatic metabolism.

    First-Pass Metabolism

    • Orally administered drugs are absorbed into the portal system.
    • The liver can metabolize these drugs before they reach systemic circulation.
    • This significantly affects bioavailability.

    Increased Bioavailability Due to Decreased First-Pass Metabolism

    • Liver disease reduces first-pass metabolism due to impaired hepatocyte function and porto-systemic shunting.
    • Increased bioavailability leads to higher plasma levels and potential toxicity.
    • Initial doses should be reduced for drugs metabolized by the liver in patients with liver disease.

    Decreased Protein Binding

    • Liver disease can cause hypoproteinemia, reducing drug binding capacity.
    • Increased free (unbound) drug levels lead to higher biological effects.

    Liver Blood Tests

    • Basic liver panel includes:

      • Alanine aminotransferase (ALT)
      • Aspartate aminotransferase (AST)
      • Albumin
      • Alkaline phosphatase
      • Total bilirubin
      • Conjugated bilirubin
      • Gamma-glutamyl transferase (GGT)

    • Normal liver blood tests do not always exclude pathology because the liver can compensate for damage.

    Total Protein

    • Total protein measures the sum of all proteins in the blood sample.
    • Albumin is the most abundant protein in blood and is a storage protein.
    • Other principal protein measured in a total protein test is Immunoglobulins.

    Bilirubin

    • Bilirubin is a breakdown product of heme.
    • Small amounts of bilirubin are normal in blood due to the turnover of red blood cells.

    Gamma-Glutamyl Transferase (GGT)

    • Gamma-glutamyl transferase (GGT) is an enzyme primarily found in the liver.
    • Elevated GGT levels indicate liver or bile duct damage.
    • GGT levels are also elevated in individuals with chronic alcohol consumption.

    Liver Enzymes

    • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) are both aminotransferases found in the liver.
    • Elevated levels of both ALT and AST suggest liver damage.
    • ALT is generally elevated in acute liver damage.
    • Clinicians may use higher AST levels over time to indicate cirrhosis.

    Conjugated Bilirubin

    • Conjugated bilirubin is a soluble form of bilirubin, produced in the liver.
    • The presence of conjugated bilirubin in the blood suggests a blockage of the bile duct or liver dysfunction.
    • Conjugated bilirubin is not normally found in the blood.

    Epithelial Tissue Specialization in Kidneys

    • Epithelial tissue in the kidneys plays a crucial role in filtration, absorption, and secretion.
    • Specialised structures like microvilli, cilia, mucoid glands, and keratin contribute to these functions.

    Kidney Macrostructure

    • The kidney consists of a cortex, medulla, renal pyramids, renal papilla, renal artery, renal vein, renal pelvis, and ureter.
    • Minor calyces and major calyces are located within the kidney.

    Kidney Microstructure

    • The kidney is composed of numerous uriniferous tubules and associated blood vessels.
    • The uriniferous tubule is made up of a nephron and a collecting duct.
    • Each kidney contains approximately one million nephrons.
    • Multiple nephrons drain into a common collecting duct.
    • There are slight variations in the definition and naming of different parts of the uriniferous tubule across various sources.

    Nephron Structure

    • The nephron is the functional unit of the kidney.
    • Components of the nephron include the renal corpuscle, proximal convoluted tubule (PT), loop of Henle, and distal convoluted tubule (DT).
    • The cortex primarily contains renal corpuscles, PT, and DT, while the medulla mainly contains loops of Henle and collecting ducts.
    • Nephrons are categorized as cortical or juxtamedullary based on the location of their renal corpuscle, with cortical nephrons comprising around 80% and juxtamedullary nephrons making up approximately 20%.

    Overview of Kidney Microstructure

    • The uriniferous tubule encompasses the nephron and collecting duct.
    • The nephron consists of the renal corpuscle, proximal tubule, loop of Henle, and distal tubule.
    • The renal corpuscle is made up of the glomerulus and Bowman's capsule.
    • The glomerulus is a network of capillaries responsible for filtration.
    • Bowman's capsule is a double-walled cup that surrounds the glomerulus.
    • The parietal layer of Bowman's capsule, composed of simple squamous epithelium, provides containment.
    • The visceral layer of Bowman's capsule is made up of modified simple squamous epithelium called podocytes, which play a crucial role in filtration.
    • Mesangial cells support the glomerular capillaries.

    Blood Supply to the Kidneys

    • Blood enters the kidneys through the renal artery.
    • The renal artery branches into segmental arteries, which further divide into interlobar arteries.
    • Arcuate arteries run along the corticomedullary junction.
    • Interlobular arteries branch off from the arcuate arteries and supply afferent arterioles to the renal corpuscles.
    • Efferent arterioles arise from the glomerular capillaries.
    • Peritubular capillaries surround the renal tubules.
    • Vasa recta, low-pressure capillaries, are found in the medulla.
    • The blood flow through the kidney involves two capillary beds: the high-pressure glomerular capillaries (filtration) and the low-pressure peritubular capillaries (reabsorption and secretion).

    Renal Corpuscle Structure

    • The renal corpuscle consists of the glomerulus and Bowman's capsule.
    • The glomerular capillaries are fenestrated, allowing for filtration.
    • The filtration barrier in the renal corpuscle is composed of three layers: glomerular capillary endothelium, basement membrane, and podocytes with their filtration slits.
    • The filtration barrier restricts the passage of substances from the blood based on their size, charge, and shape.

    Nephron - Simplified Form

    • The nephron consists of the renal corpuscle, proximal convoluted tubule, loop of Henle, and distal convoluted tubule.

    Proximal Convoluted Tubule

    • Unmodified filtrate produced in Bowman's capsule enters the PCT.
    • The PCT is responsible for the reabsorption of the majority of water, sodium, chloride, amino acids, and glucose.
    • The PCT also secretes certain drugs and waste molecules.
    • The PCT is lined by simple cuboidal cells with microvilli, forming a brush border that increases surface area.

    Loop of Henle

    • The loop of Henle, a hairpin-shaped structure, has three main segments: descending limb, thin ascending limb, and thick ascending limb.
    • The descending limb is permeable to water and allows for water reabsorption.
    • The ascending limb is impermeable to water but actively reabsorbs sodium and other solutes.
    • The loop of Henle plays an important role in establishing a hyperosmolar medullary interstitium, which is crucial for urine concentration.

    Distal Convoluted Tubule

    • Divided into early and late segments, the DCT actively reabsorbs sodium and secretes potassium and hydrogen ions.
    • The DCT is lined by simple cuboidal cells.
    • Water permeability varies in the DCT depending on the specific segment and the presence of antidiuretic hormone (ADH).
    • The early DCT loops back to the vascular pole of its own renal corpuscle, forming part of the juxtaglomerular apparatus.

    Juxtaglomerular Apparatus

    • The JGA consists of three components: the macula densa, extraglomerular mesangial cells (Lacis cells), and granular or juxtaglomerular cells.
    • The macula densa, specialized cells in the early DCT, monitors changes in filtrate composition (e.g., sodium concentration).
    • The granular cells in the afferent arteriole produce renin, a key enzyme in the renin-angiotensin-aldosterone system.
    • The JGA plays a crucial role in regulating glomerular filtration rate through tubuloglomerular feedback and blood pressure control.

    Collecting Duct

    • The collecting duct is the final site of urine processing.
    • Water permeability in the collecting duct is regulated by ADH.
    • The collecting duct is surrounded by a medullary interstitium with a high solute concentration, further aiding in urine concentration.
    • It plays a critical role in regulating urine concentration.
    • The collecting duct is lined by simple columnar cells.

    Body Fluid Compartments

    • Approximately 60% of body weight is comprised of water.
    • Water distribution varies with age, sex, and body fat.
    • Body fluids are distributed in various compartments separated by semipermeable membranes.
    • Intracellular fluid (ICF) constitutes approximately 28 liters and represents the fluid within cells.
    • Extracellular fluid (ECF) consists of interstitial fluid, found between cells, and plasma, the non-cellular component of blood.

    Body Fluid Composition

    • The capillary membrane is permeable to water and electrolytes but not most plasma proteins.
    • Interstitial fluid and plasma have similar compositions except for proteins, which remain in plasma.
    • The cell membrane is permeable to water but not most electrolytes.
    • The major cation in ECF is sodium, while the main anion is chloride.
    • Potassium is the primary cation in ICF, and phosphate is the primary anion.
    • Osmotic equilibrium is maintained between different fluid compartments.

    Glomerular Filtration

    • Nephron is the functional unit of the kidney
    • Three main processes performed by the nephron are:
      • Filtration
      • Reabsorption
      • Secretion
    • Urinary excretion rate is the sum of filtration, secretion, and reabsorption
    • Filtration is the first step in the process of urine formation. It is essential for clearing waste products.
    • Kidneys receive approximately 20% of cardiac output, which translates to around 1 litre/min of renal blood flow.
    • Renal plasma flow is approximately 600 ml / min
    • 20% of renal plasma flow passes through the filtration barrier to form filtrate
    • Filtration fraction: ~120 mL/min
    • Glomerular filtration rate (GFR) is the volume of filtrate formed by all the nephrons in both kidneys per unit time.
    • Three main structures compose the glomerular filtration barrier:
      • Glomerular capillary endothelium (fenestrated)
      • Basement membrane (negative charge)
      • Epithelial cells (podocytes)
    • The filtration barrier limits the passage of substances based on their:
      • Size
      • Charge
      • Shape
    • Blood cells and most plasma proteins are excluded from the filtrate
    • Glomerular capillary filtration coefficient (Kf) reflects the:
      • Surface area available for filtration
      • Hydraulic conductivity of the filtration barrier
    • Net filtration pressure (NFP) is the sum of the hydrostatic and colloid osmotic pressures acting across the filtration barrier.
    • NFP equation: PG – PB – πG + πB.
    • Typical value for NFP is 10 mmHg
    • GFR is determined by the glomerular filtration barrier and net filtration pressure
    • Autoregulation of GFR ensures that GFR stays relatively constant across a range of systemic blood pressures, preventing large changes in renal excretion of water and solutes.
    • Two mechanisms of autoregulation:
      • Myogenic response
      • Tubuloglomerular feedback
    • Myogenic response is the inherent ability of smooth muscle in afferent arterioles to respond to changes in vessel circumference.
    • Tubuloglomerular feedback (TGF) links changes in [NaCl] in the tubule lumen to control afferent arteriole resistance. It utilizes the juxtaglomerular apparatus (JGA).
    • The JGA is composed of:
      • Macula densa cells
      • Lacis cells
      • Granular cells

    Factors that Determine GFR

    • The volume of filtrate formed by all the nephrons in both kidneys per unit time.
    • It is determined by:
      • Glomerular capillary filtration coefficient (Kf)
      • Net filtration pressure (NFP)
    • Kf reflects the surface area available for filtration and the hydraulic conductivity of the filtration barrier.
    • NFP is the sum of the hydrostatic and colloid osmotic pressures acting across the filtration barrier.
    • Most physiological regulation of GFR occurs due to changes in glomerular hydrostatic pressure (PG).
    • PG depends on these three factors:
      • Arterial pressure
      • Afferent arteriole resistance
      • Efferent arteriole resistance
    • Afferent arteriole dilation and/or efferent arteriole constriction increases GFR
    • Afferent arteriole constriction and/or efferent arteriole dilation reduces GFR

    Factors that Influence GFR

    • Angiotensin II preferentially constricts the efferent arteriole, thus increasing PG and GFR
    • Prostaglandins and atrial natriuretic peptide (ANP) dilate the afferent arteriole, increasing PG and GFR
    • Noradrenaline (sympathetic nervous system), adenosine, and endothelin tend to vasoconstrict the afferent arteriole, reducing PG and GFR.

    Indicators of Renal Decline

    • Proteinuria / Albuminuria: Indicate damage to kidneys
    • Haematuria: Indicate damage to kidneys
    • Estimated GFR / GFR: Indicate kidney function
    • Serum Creatinine / Urea: Indicate kidney function
    • Calcium / Phosphate: Indicate homeostasis and kidney function, but not quantitive
    • Electrolytes / pH: Indicate kidney function, but not quantitive
    • Fluid balance / Urine volume: Indicate kidney function, but not quantitive
    • Haemoglobin: Indicate kidney function, but not quantitive

    Measuring Renal Function

    • Glomerular Filtration Rate (GFR): Volume of filtrate formed by nephrons in both kidneys per unit time
    • GFR: Directly related to nephron function and declines in all forms of progressive kidney diseases
    • GFR: Accepted as best overall index of kidney function in health and disease
    • GFR: Does not tell you cause or location of kidney problem
    • GFR: Linked to body surface area, typical young male GFR = 120 ml/min/1.73m2
    • GFR: Linked to age, sex, and body size, declines with increasing age
    • GFR: Difficult to measure directly

    Routine Measures of GFR

    • Rationale: If something normally filtered by the kidney builds up in the blood, it indicates decreased GFR and therefore decreased renal function
    • Measurement using exogenous markers: More accurate, but can be time-consuming and expensive (e.g. inulin infusion)
    • Measurement via endogenous markers: More cost-effective and routinely used in clinical practice
    • Three tests routinely used to assess renal function:
      • Serum urea
      • Serum creatinine
      • Estimated GFR (eGFR)
    • All tests: Use a single serum measurement, making them convenient for routine assessment and monitoring of renal function

    Serum Creatinine

    • Serum creatinine: More accurately reflects GFR than urea
    • Creatinine: Formed from breakdown of creatine, a skeletal muscle component
    • Creatinine: Produced at a more steady rate for a given individual
    • Serum creatinine: Still relatively inaccurate as a point measure of GFR, but useful for monitoring trends
    • Inaccuracies with serum creatinine: Result from the way its production varies between individuals and relates to muscle mass
    • Factors affecting muscle mass: Age, sex, amputation, malnutrition, muscle wasting
    • Diet: Also affects creatinine levels (vegetarian diet vs. meat rich diet)

    Estimated GFR (eGFR)

    • eGFR: Uses equations to calculate (estimate) the GFR based on a single serum measurement
    • eGFR calculations: Incorporate simple clinical information along with a single serum measurement
    • Most eGFR calculations: Use serum creatinine, age, sex, and CKD-EPI equation (recommended by NICE)
    • Normal eGFR: >90 ml/min/1.73m2
    • Newer tests available: Use serum cystatin C (eGFRcystatinC)

    Limitations of eGFR

    • eGFR: Does not include a measure of body size
    • eGFR: May be influenced by factors that alter muscle mass (e.g. amputation, malnutrition)
    • Limitations on eGFR use: Children, acute kidney injury, drug calculations
    • eGFR: More accurate than serum creatinine alone
    • eGFR: Useful in monitoring renal function and detecting early decline

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    Description

    Test your knowledge on the critical functions of the nephron, including filtration, reabsorption, and secretion. This quiz will help you understand how the kidneys process and manage fluid and waste. Explore the daily rates of filtration and excretion as you match terms with their descriptions.

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