Kidney and Nephron Function

Kidney Basics

• Kidneys are multilobular, numbering around 18 lobes
• Kidneys reside outside the peritoneal cavity

Nephron Structure and Function

• Nephrons are limited in number and incapable of regeneration, leading to a decline with age
• Nephrons have three crucial functions: reabsorption of water and electrolytes, secretion of unneeded materials into tubular filtrate for elimination (including sulfate, phosphate, chloride, and fixed acids), and glomerular filtration
• Tubule segments consist of the proximal convoluted tubule draining into Bowman's capsule, the Loop of Henle, the distal convoluted tubule, and the collecting tubule

Capillary Systems Supplying Nephrons

• The glomerulus capillary system's primary function is filtration
• It acts as a filter, allowing water, ions, and small molecules into the nephron while retaining blood and larger proteins
• The glomerulus is located between afferent and efferent arterioles
• Afferent arterioles bring blood into the glomerulus, while efferent arterioles carry filtered blood away
• High pressure in the arterioles forces fluid and solutes into Bowman's capsule, forming glomerular filtrate, which then becomes urine

Peritubular Capillary System

• The peritubular capillary system facilitates reabsorption of water and solutes back into the blood after filtration
• It originates from the efferent arteriole, forming a low-pressure capillary network
• The low pressure enables reabsorption of nutrients and water back into the bloodstream

Tubular Filtration and Function

• Filtrate flows through the nephron's tubules after exiting the efferent arteriole
• Water and electrolyte concentration changes as filtrate flows through the tubule
• These changes are due to water and solute reabsorption back into the blood, and secretion of waste and excess ions into the filtrate for urine elimination
• Na+/K+ ATPase maintains the concentration gradient by moving Na+ out of the cell and K+ into the cell, using 3 Na+ and ATP
• This process exemplifies antiport, where substances move in opposite directions
• Symport involves two solutes moving in the same direction (e.g., Na+ and glucose)
• Exchange involves swapping ions; Na+ is reabsorbed while H+ is secreted

Normal Urine Concentrations

• Normal urine is clear and amber-colored
• It consists of approximately 95% water and 5% dissolved solids
• Kidneys produce around 1.5L of urine daily
• Urine contains metabolic wastes, with few to no plasma proteins, blood cells, or glucose

Kidney’s Elimination Functions

• The kidney's elimination functions include renal clearance, regulation of Na+, K+ elimination, pH-dependent elimination of organic ions, and uric acid, urea, and drug elimination

Urine Concentration Regulation

• Kidneys regulate urine concentration based on interstitial osmolarity, with a normal value of 1200 mOsm
• ADH (vasopressin) regulates water reabsorption in the collecting duct
• More ADH leads to more water reabsorbed, resulting in more concentrated urine
• Less ADH leads to less water reabsorbed, resulting in diluted urine and more water loss
• ADH binds to vasopressin receptors on tubular cell membranes, opening water channels and moving them to the luminal side of the membrane

Endocrine Functions of the Kidney

• The juxtaglomerular complex aids in regulating blood pressure and filtration rate
• The R.A.A.S. system regulates blood pressure through fluid balance
• Erythropoietin stimulates bone marrow to produce red blood cells when O2 levels are low
• Vitamin D is converted into its active form, enhancing calcium absorption from the GI tract and regulating calcium storage in bone

Juxtaglomerular Complex

• It regulates GFR by adjusting blood flow; low blood pressure results in low GFR meaning too much filtration can occur during high BP
• It is located between afferent and efferent arterioles (glomerulus cap syst)
• It aids in regulating blood pressure and filtration by sensing changes in blood flow and fluid composition in the distal tubule
• It acts as the blood pressure and filtration control center by adjusting kidney function based on blood flow and sodium levels

Renal Casts

• Renal casts are molds of the distal nephron lumen
• They develop when urine has high protein concentration, high osmolarity, and low (acidic) pH

Renal Function Tests

• Urinalysis is conducted to detect infections and abnormalities in pH, protein, blood, and color
• GFR measures the kidney's ability to filter waste
• Blood tests include serum creatinine (high levels indicate poor kidney function) and Blood Urea Nitrogen (BUN), which measures waste buildup related to GFR, protein intake, dehydration, and GI bleed
• Cystoscopy involves using a camera to view the bladder
• Ultrasonography uses sound waves to visualize kidney structure
• Radiologic studies involve X-rays, MRI, and CT scans

Factors Affecting GFR

• Glomerular capillary hydrostatic pressure: higher pressure increases GFR, while lower pressure decreases it
• Glomerular capillary osmotic pressure: high osmotic pressure draws water back into capillaries, reducing GFR
• Hydrostatic and osmotic pressure in Bowman’s capsule: increased pressure opposes filtration, reducing GFR
• Monitoring patient trends over time is more important than individual numbers

Specific Gravity of Urine

• Measures the concentration of urine
• Indicates hydration status and kidney function
• Decreased kidney function: 1.006-1.010
• Normal: 1.010-1.025
• Marked (over) hydration: 1.000
• Healthy kidneys (high concentration): 1.030-1.040

Renal Clearance

• Renal clearance is defined as the volume of plasma completely cleared per minute of any substance that ends up in the urine
• Factors affecting clearance include filtration at the glomerulus and reabsorption/secretion in renal tubules
• Clearance is calculated as (urine concentration x urine flow rate) / plasma concentration

Serum Creatine Levels

• Creatine levels estimate kidney function
• Higher levels indicate reduced kidney function
• If creatine doubles, GFR and renal function decrease to half (50%) of their normal state
• If creatine triples, there is a 75% loss, leaving only 25% kidney function remaining
• Creatine >10mg/dL indicates severe kidney damage, with 90% loss and only 10% function remaining
• Normal creatine levels are 0.7 mg/dL for females and 1 mg/dL for males

How Diuretics Work

• Loop diuretics act on the thick ascending Loop of Henle, blocking sodium, potassium, and chloride reabsorption
• Thiazide diuretics work in the distal convoluted tubule, preventing NaCl reabsorption
• Aldosterone antagonists (potassium-sparing) act on the late distal convoluted and cortical collecting tubules, reducing sodium reabsorption and increasing potassium secretion (retention)

Acid-Base Chemistry

• Acid releases H+ ions
• Base accepts or combines with H+
• Buffer pairs/systems maintain stable pH and consist of weak acid/conjugate base or weak base/conjugate acid
• pH measures H+ concentration: pH = -log[H+]
• Lower H+ concentration means higher pH, and vice versa

Metabolic Acid and Bicarbonate Production

• CO2 reacts with water to form carbonic acid (H2CO3), which then breaks down into bicarbonate (HCO3-) and H+
• Bicarbonate buffers blood and maintains pH
• CO2 is transported as bicarbonate to regulate pH; equal portions leave via the lungs
• Volatile acids (like carbonic acid) convert to CO2 and exit via the lungs
• Nonvolatile acids (sulfate, phosphate, chloride, lactic acids) are buffered by proteins/extracellular buffers (Na+ bicarb) and eliminated by the kidneys

Henderson-Hasselbalch Equation

• pH=6.1 + log10(HCO3-/PCO2 x 0.03)

Chemical Buffer System

• It is a weak base and conjugate acid pair (or vice versa)
• Three major systems stabilize pH:
  • The bicarbonate buffer system which is the most important and powerful buffer that uses bicarbonate as the base and carbonic acid as the acid to maintain pH
  • Proteins can act as acids or bases due to their amino acid side chains
  • Transcellular H+/K+ exchange system regulates H+ and K+ movement between cells and blood, controlling pH in kidneys especially

Regulation of pH

• Intracellular chemical buffers- buffers work inside of cells (i.e. protein)
• Extracellular chemical buffers function in fluids like blood; the bicarbonate system is most important
• Respiratory control mechanisms regulate blood CO2 levels where Increased CO2 lowers pH, and decreased CO2 raises pH
• Renal control mechanisms are utilized where kidneys excrete or reabsorb H+ and bicarb, thus regulating pH in the long-term

Lab Tests on Acids and Bases

• CO2 and bicarbonate levels show how well respiratory and metabolic systems maintain pH balance
• Normal CO2 = 35-45 mmHg, and arterial bicarb = 22-26 mEq/L
• Base excess signifies metabolic alkalosis
• Base deficit signifies metabolic acidosis
• Anion gap identifies causes of acidosis, showing the gap between positive and negative ions (normal gap = 8-16 mEq/L; high gap indicates an unmeasured acid)

Thrombosis vs Bleeding

• Thrombosis: inappropriate blood clotting blocks blood flow
• Bleeding: failure to form blood clots after injury

Why Should Blood Clot?

• It maintains integrity of blood vessels
• Protects the body by: preventing infection, preserving blood volume, maintaining oxygen delivery, limiting tissue damage, and promoting healing

Stages of Hemostasis

1. Vessel spasm: initiated by injury, blood vessel constricts to reduce blood flow, which triggers signals and lasts minutes to hours
2. Formation of platelet plug: Platelet life is 8-12 days where:
   • Platelets stick to the damaged vessel wall
     1. Attracted to the injury site
     2. Activated by endothelial cell signals
     3. Change shape from smooth discs to spiny spheres exposing receptors to stick together
3. Blood coagulation: Cascade of clotting factors activates fibrin, which stabilizes the platelet plug
   • Requires: platelets, von Willebrand factor, and clotting factors made in the liver
4. Clot retraction: 20-60 min after formation, serum squeezes, shrinks, and helps stabilize clot
5. Clot dissolution: vessel heals, clot is dissolved by substrates, enzymes, protein cofactors, and calcium ions

Outcome of Blood Clotting

• Blood flow is reestablished, and tissue repair occurs
• Plasmin digests fibrin strands of clot for fibrinolysis