Urinary System and Kidney Function Notes

Organic/metabolic waste and the urinary system

• Organic waste is produced during normal metabolism (e.g., CO₂ from Krebs cycle, urea and ammonia from protein metabolism).
  • These waste products must be eliminated from body fluids, the blood, and ultimately the body.
  • Distinction: waste should be removed from the body entirely (excreted), not just kept in blood.
• Role of urinary system: hold onto useful substances, remove waste, and regulate fluid and solute concentrations.
• Key idea: different organs regulate blood contents in distinct ways (liver and spleen vs. kidneys).

Liver, spleen, and kidneys: different blood-regulation roles

• Liver:
  • Detoxifies the blood by converting toxic chemicals to less toxic forms.
  • Produces most blood proteins (e.g., albumin, clotting factors).
  • Can remove some blood cells, but not the primary regulator of filtering blood.
• Spleen:
  • Regulates blood by removing old red blood cells and pathogens (bacteria, viruses, fungi).
• Kidneys:
  • Maintain the chemical environment of the blood and regulate the composition of body fluids.
  • Filter the blood to remove waste while conserving needed substances.
  • Adjust pH and electrolyte levels; regulate water balance and blood volume/pressure.

Urinary system structure and flow: overall pathway

• Structures (overview):
  • Kidneys (two bean-shaped organs in the abdominal cavity, retroperitoneal) with adrenal glands atop each.
  • Ureters (two tubes) transport urine from kidneys to bladder.
  • Urinary bladder stores urine.
  • Urethra carries urine out of the body.
• Blood supply and drainage:
  • Renal artery branches from the abdominal aorta to supply the kidney.
  • Renal vein drains into the inferior vena cava.
• Functional relationships:
  • Kidneys filter the blood; urine is formed and then transported via the ureters to the bladder, stored, and excreted via the urethra.
• Important distinction:
  • Blood going to the kidney via the renal artery is unfiltered yet to be filtered;
  • Blood leaving via the renal vein is filtered.

Kidney anatomy and nephron: structural units

• Kidneys consist of cortex (outer) and medulla (inner) with medullary pyramids; hilum is the entry/exit site for vessels and the ureter.
• Each kidney contains many nephrons, the functional units of filtration and urine formation.
  • Nephron components: renal corpuscle and renal tubule.
  • Renal corpuscle includes the glomerulus (capillary network) and Bowman's capsule (glomerular capsule).
  • Afferent arteriole brings blood to the glomerulus; efferent arteriole drains blood away.
  • Peritubular capillaries surround the tubule and participate in reabsorption and secretion; vasa recta are the straight capillaries in the medulla.
• Pathway of filtrate/urine:
  • Blood enters via the afferent arteriole → glomerulus → Bowman's capsule (filtrate formed) → proximal convoluted tubule → loop of Henle (descending and ascending limbs) → distal convoluted tubule → collecting duct → renal pelvis → ureter → bladder → urethra.
• Key structures and their roles:
  • Glomerulus: site of filtration via pressure-driven movement of fluid and solutes from blood into Bowman's capsule.
  • Bowman's capsule: collects filtrate from the glomerulus.
  • Proximal convoluted tubule (PCT): major site of reabsorption; Na⁺, glucose, amino acids, and water reabsorb here.
  • Loop of Henle: creates medullary osmotic gradient; descending limb permeable to water, ascending limb permeable to ions (Na⁺, K⁺, Cl⁻) but not water.
  • Distal convoluted tubule (DCT): fine-tuning of reabsorption/secretion; sites of aldosterone action for Na⁺ (and K⁺) handling.
  • Collecting ducts: final adjustments of water reabsorption (ADH/vassopressin dependent) and solute handling.
• Amounts and scale:
  • There are thousands of nephrons per kidney; each nephron handles filtration and selective reabsorption/secretion.

Filtration, reabsorption, secretion, and excretion: core nephron processes

• Filtration (glomerular filtration):

  • Occurs in the renal corpuscle (glomerulus + Bowman's capsule).
  • Substances move from blood in the glomerular capillaries into Bowman's capsule.
  • Filtrate composition is plasma-like (initially): predominantly water; ions (K⁺, Na⁺, Cl⁻); nitrogenous wastes (urea, uric acid, creatinine); organic molecules like glucose and amino acids.
  • Large molecules and cells (e.g., plasma proteins, red blood cells) remain in the blood because they are too large to pass through the filtration barrier.

• Forces in glomerular filtration:

  • Hydrostatic pressure in the glomerulus (P_g) pushes filtrate out.
  • Colloid osmotic pressure of blood (π_g) pulls fluid back into the capillary.
  • Capsular hydrostatic pressure (P_c) within Bowman's capsule opposes filtration.
  • Net filtration pressure (NFP):
    ext{NFP} = Pg - ( ext{COP}g + P_c )
  • If NFP is positive and hydrostatic pressure dominates, filtration proceeds.

• Tubular reabsorption:

  • Contents move from the tubular lumen back into the blood via peritubular capillaries or vasa recta.
  • Major reabsorbed substances include glucose, amino acids, and many Na⁺/Ca²⁺ ions; water follows by osmosis (obligatory water movement) with Na⁺ reabsorption.
  • Reabsorption is mostly active (Na⁺ transport) for many solutes; water reabsorption is often passive (osmosis) following Na⁺.
  • The proximal tubule reabsorbs most of the filtrate; significant reabsorption also occurs along the loop of Henle, DCT, and collecting duct depending on hormonal signals.

• Tubular secretion:

  • Contents move from the blood into the tubule lumen (opposite direction of reabsorption).
  • Secretion helps eliminate unwanted metabolites, drugs, hydrogen ions (H⁺), potassium ions (K⁺), and other wastes.
  • Most secretion occurs in the proximal tubule; potassium secretion largely occurs in the distal tubule and collecting duct under aldosterone control.

• Excretion:

  • Final urine is formed after filtration, reabsorption, and secretion, and is excreted from the collecting ducts, through the renal pelvis and ureter to the bladder.

The loop of Henle and countercurrent multiplier

• Loop of Henle components:
  • Descending limb: permeable to water only (facilitates water reabsorption and filtrate concentration).
  • Ascending limb: permeable to ions (Na⁺, K⁺, Cl⁻) but impermeable to water (dilutes filtrate).
• Osmotic gradient:
  • The bottom of the loop becomes highly concentrated (approx. 1,200 mOsm) while the top cortex is relatively dilute (approx. 300 mOsm).
  • This gradient is essential for concentrating urine when needed.
• Countercurrent multiplier:
  • The descending and ascending limbs run in opposite directions and interact to establish and maintain the medullary osmolarity gradient.
  • This gradient enables water reabsorption from the collecting duct under the influence of ADH (vasopressin).

Regulation of glomerular filtration rate (GFR)

• GFR basics:
  • Normal GFR in healthy adults is about ext{GFR}
    oughly 120rac{ ext{mL}}{ ext{min}} (for both kidneys together).
  • GFR represents the rate at which the kidneys filter plasma into the tubules.
  • GFR should be maintained near 120 mL/min under varied conditions; large deviations can cause problems.
• Autoregulation (local control):
  • The kidneys automatically adjust afferent and efferent arteriolar tone to keep GFR around 120 mL/min despite changes in blood pressure.
  • If GFR falls (low filtration): afferent arteriole dilates and the efferent arteriole constricts to raise pressure and restore GFR.
  • If GFR rises (high filtration): afferent arteriole constricts and efferent arteriole dilates to lower pressure and reduce GFR.
  • This local mechanism is mediated by the juxtaglomerular apparatus (JG cells and macula densa) that compare inputs from the afferent and efferent arterioles.
• Hormonal regulation:
  • Renin-angiotensin-aldosterone system (RAAS) adjusts GFR and blood pressure via angiotensin II, aldosterone, and ADH, among others.
  • Angiotensin II can constrict both afferent and efferent arterioles (predominantly efferent constriction to boost filtration pressure) and stimulates aldosterone release.
  • Aldosterone increases Na⁺ reabsorption (and thus water via osmosis) in the distal tubule/collecting duct, which can influence GFR via changes in blood volume and pressure.
  • Antidiuretic hormone (ADH, vasopressin) increases water reabsorption in collecting ducts by promoting aquaporin insertion, affecting plasma volume and indirectly GFR.
  • Atrial natriuretic peptide (ANP) is released with increased atrial stretch (volume overload) and tends to reduce Na⁺ reabsorption, lowering blood volume and BP, opposing RAAS.
• Nervous system regulation:
  • Sympathetic activation (fight/flight) can constrict afferent arterioles and reduce GFR to redirect blood to vital organs during stress or exercise; can impair renal filtration temporarily.
  • Parasympathetic influence is less prominent in GFR regulation but part of integrated control.

The renin-angiotensin-aldosterone system (RAAS) in detail

• Trigger for RAAS:
  • Drop in renal blood pressure or renal perfusion stimulates juxtaglomerular (JG) cells to release renin.
• Cascade:
  • Renin converts angiotensinogen (from the liver) to angiotensin I: ext{Renin} + ext{Angiotensinogen}
    ightarrow ext{Angiotensin I}
  • Angiotensin-converting enzyme (ACE) in the lungs converts Angiotensin I to Angiotensin II: ext{Angiotensin I}
    ightarrow ext{Angiotensin II} ext{ (via ACE)}
• Effects of Angiotensin II:
  • Direct vasoconstriction of blood vessels → raises blood pressure.
  • Stimulates aldosterone release from the adrenal cortex → increases Na⁺ reabsorption and K⁺ secretion in the distal tubule/collecting duct.
  • Stimulates ADH release from the posterior pituitary → increases water reabsorption in collecting ducts.
  • Increases thirst and overall blood volume.
• Aldosterone action:
  • In distal convoluted tubule and collecting duct, increases Na⁺ reabsorption and K⁺ secretion; water follows Na⁺, increasing blood volume and BP.
• Antidiuretic hormone (ADH) action:
  • ADH promotes insertion of aquaporins in the collecting duct walls, increasing water reabsorption and concentrating urine.

Atrial natriuretic peptide (ANP) and other regulators

• ANP is released from the atria in response to excessive blood volume/stretch.
  • Promotes natriuresis (sodium excretion) and diuresis (water excretion); antagonizes RAAS effects by reducing Na⁺ reabsorption.
• Antidiuretic hormone (ADH) and water balance:
  • ADH increases water reabsorption by inserting aquaporin channels in collecting ducts, concentrating urine and preserving body water.
• A note on osmolarity regulation:
  • Antidiuretic hormone helps regulate plasma osmolality by adjusting water reabsorption; converse actions (e.g., RAAS) adjust both volume and osmolality via Na⁺/water balance.

Erythropoietin (EPO) and oxygen sensing

• Erythropoietin (EPO) production:
  • Kidneys sense low blood oxygen (hypoxia) and release EPO from interstitial fibroblasts.
  • EPO stimulates bone marrow to increase red blood cell production, improving oxygen delivery.
• Clinical relevance:
  • EPO production can be a diagnostic/therapeutic target in anemia and chronic kidney disease.

Calcium, phosphate, and acid-base regulation by the kidney

• Calcium regulation:
  • Parathyroid hormone (PTH) and calcitriol (active vitamin D) regulate calcium handling in the kidney.
  • Calcitonin and calcitriol influence calcium reabsorption and calcium phosphate balance in the kidney.
• pH regulation:
  • Kidneys contribute to acid-base balance by reabsorbing bicarbonate and secreting hydrogen ions (H⁺) into the tubule lumen; distal nephron segments are key sites for this adjustment.
• Overall importance:
  • The kidney’s ability to regulate electrolytes (Na⁺, K⁺, Ca²⁺, Cl⁻), pH, and acid-base balance is essential for homeostasis.

Glucose, protein, and nutrient handling in the kidney

• Glucose and amino acids:
  • Normally reabsorbed in the proximal tubule; glucose reabsorption has a transport maximum (not discussed in detail here), and glucose in urine can indicate high blood glucose (e.g., diabetes mellitus).
  • Diabetes mellitus (glycosuria) is evidenced by glucose in urine; it reflects overwhelmed reabsorption capacity.
• Proteins and albumin:
  • Normally retained in blood; minimal protein should appear in urine; significant proteinuria indicates renal issues.
• Diabetes insipidus (DI):
  • Condition where lack of ADH or kidney response to ADH prevents water reabsorption, leading to large volumes of dilute urine and excessive thirst.

Filtration pressures, filtrate composition, and filtration concepts

• Filtration forces recap:
  • Hydrostatic pressure (P_g) pushes filtrate out of capillaries into Bowman's capsule.
  • Colloid osmotic pressure (π_g) pulls fluid back into capillaries due to plasma proteins.
  • Capsular hydrostatic pressure (P_c) is the pressure within Bowman's capsule opposing filtration.
• Desired balance:
  • Under normal conditions, hydrostatic pressure dominates to favor filtration: filtration proceeds when Pg > (πg + P_c).
• Filtrate composition (initial):
  • Water, ions (K⁺, Na⁺, Cl⁻), nitrogenous wastes (urea, uric acid, creatinine), glucose, amino acids.
  • Plasma proteins and red blood cells remain in the blood due to size/charge barriers.

Clinical implications and reminders

• GFR as a clinical indicator:
  • Maintaining a stable GFR (~120 mL/min) is essential for stable filtration and homeostasis.
  • A drop in GFR can indicate impaired kidney function; a high GFR may indicate overfiltration or physical activity effects but is less common.
• Ureter vs. urethra mnemonic:
  • Ureter: two tubes that transport urine from kidneys to bladder.
  • Urethra: single tube that transports urine out of the body.
• Filtration vs reabsorption terminology:
  • Reabsorption: movement from tubule back into blood.
  • Secretion: movement from blood into tubule.
  • Absorption in the kidney context is often called reabsorption to reflect initial filtration away from the blood.

Quick reference: key equations and numbers

• Glomerular filtration rate (GFR):
  • ext{GFR} \,\approx\, 120\ \frac{\text{mL}}{\text{min}}
• Net filtration pressure (NFP):
  • \text{NFP} = Pg - \left( \pig + P_c \right)
• Osmolarity gradient in loop of Henle (approximate):
  • Descending limb creates high water permeability and concentrates filtrate: bottom ~ 1{,}200\ \text{mOsm}
  • Top cortex around ~ 300\ \text{mOsm}
• Notes on homeostasis:
  • Water reabsorption often follows Na⁺ reabsorption (obligatory water movement).
  • ANP, RAAS, ADH, and other hormones integrate to regulate blood volume, pressure, and electrolyte balance.

Summary: integrated view of kidney function

• The kidneys form urine by filtering blood, then selectively reabsorbing needed substances and secreting wastes to be excreted.
• The nephron’s functional subunits (glomerulus/Bowman’s capsule and renal tubules) perform filtration, reabsorption, secretion, and excretion.
• The Loop of Henle creates and maintains a medullary osmotic gradient essential for concentrating urine when needed.
• GFR is tightly regulated by autoregulation, RAAS, ADH, aldosterone, ANP, and autonomic nervous system to maintain fluid, electrolyte, and acid-base balance.
• EPO links kidney function to red blood cell production; calcium, phosphate, and pH are also tightly regulated by renal processes.
• Pathophysiology cues (e.g., glucose in urine, DI) reflect disruptions in these tightly regulated processes and have clinical implications.