AUBF Part 2

• Nephron


  Functional unit of the urinary system
• Average of 1-1.5 million nephrons per kidney, total of 2-3 million in 2 kidneys

  
• Classification of nephrons according to location in renal tissue

  • Cortical
  • Juxtamedullary

  
• Cortical nephrons


  85% of nephrons, structures localized in the cortex of the kidney, function is immediate reabsorption of essential substances

  
• Juxtamedullary nephrons


  15% of nephrons, have long Henle's loop extending deeper into the medullary region, function is maintenance of the osmotic gradient of the medulla
• Major parts of a nephron

  • Glomerulus
  • Bowman's Capsule
  • Renal Tubule (Proximal Convoluted Tubule, Henle's Loop, Distal Convoluted Tubule, Collecting Duct)
  • Renal Corpuscle

  
• It is important to distinguish the segments of the Loop of Henle as there is reabsorption of solutes
• Descending Loop of Henle (DLH) and Ascending Loop of Henle (ALH)

  Differ in their reabsorptive capacities, selective reabsorption occurs in the Loop of Henle
• Distal Convoluted Tubule (DCT) and Collecting Duct (CD)


  Include the final adjustments in the glomerular filtrate composition, further reabsorption takes place in these two

  
• Juxtaglomerular Apparatus


  Formed by the Juxtaglomerular cells (in ALH) and Macula Densa cells (in DCT), responsible for the secretion of renin as part of the RAAS

  
• Blood vessels in the nephron

  • Afferent Arteriole
  • Efferent Arteriole
  • Peritubular Capillaries
  • Vasa Recta
• Renal Blood Flow (RBF)


  Amount of blood supplied to the kidneys every minute, RBF rate is 1200 mL/min

  
• Glomerular Filtration Rate (GFR)


  The amount of blood filtered per minute, 10% of the RBF is filtered, so GFR is 120 mL/min

  
• GFR is estimated using clearance tests
• Glomerular filtrate (in Bowman's Capsule)


  Isosmotic with plasma, specific gravity of 1.010, no significant amount of proteins and cells
• Net filtration pressure


  10 mmHg, creates the driving force for filtration
• Glomerular filtration barrier


  • Consists of fenestrated endothelium, basement membrane, and podocyte layer
  • Restricts the passage of substances with a MW 70,000 Da or 70 kDa

  
• Shield of negativity


  Repulsion of most plasma proteins by the negatively charged basement membrane
• Renin-Angiotensin-Aldosterone System (RAAS)


  1. Low blood pressure and low plasma sodium content sensed by macula densa

  2. Kidney secretes renin

  3. Renin converts angiotensinogen to angiotensin I

  4. Angiotensin I converted to angiotensin II by ACE

  5. Angiotensin II causes vasodilation of afferent arteriole, vasoconstriction of efferent arteriole and glomerular capillaries
• Tubular reabsorption processes


  • Active transport/Obligatory Reabsorption (glucose, amino acids, salts in PCT, chloride in TAL, sodium in DCT)
  • Passive transport/Facultative Reabsorption (water in all parts except ALH, urea in PCT and ALH, sodium in ALH)
• Countercurrent mechanism


  Carried out by juxtamedullary nephrons through selective reabsorption in the Loop of Henle to maintain the osmotic gradient in the medulla
• Tubular secretion functions


  • Elimination of unfiltered wastes (drug metabolites)
  • Regulation of acid-base balance through secretion of H+ ions
• Tubular reabsorption


  When a substance in the filtrate is returned to the blood
• Tubular secretion


  When a substance in the blood is secreted into the renal tubule

  
• Glomerular filtration tests (clearance tests)

  • β2-microglobulin
  • Cystatin C
• β2-microglobulin


  Small protein freely filterable, but unreliable in patients with autoimmune disorders and malignancy
• Cystatin C


  Small protein readily filtered by the glomerulus and reabsorbed and broken down by RTE cells, recommended for pediatric, diabetic, elderly and critically ill patients
• hindi nafilter kaya napunta sa blood, eh hindi na sya need or hindi sya essential so tinapon na sya sa renal tubule

  
• Back up mechanism para sa mga substance na hindi naman na need pero hindi natapon sa filtrate
• Glomerular Filtration Tests (Clearance Tests)


  Tests to evaluate renal functions

  
• B2 - MICROGLOBULIN


  • Component of HLA, not reliable in patients with immune disorders or malignancy
  • Small protein MW 11,800 kd - freely filterable
  • Endogenous - dissociates from HLA concentrate
• CYSTATIN C


  • Small protein (MW 13, 359) readily filtered by the glomerulus and reabsorbed and broken down by RTE cells
  • Serum marker - no need for 24hr urine collection
  • Normal must have low levels in the blood
  • If impaired → increased levels in the blood

  
• INULIN


  • Reference method/ gold standard, extremely stable, neither reabsorbed nor secreted by the tubules
  • Exogenous substance - needs to be injected in the px since this is a plant polysaccharide
  • MW: 5,200 daltons → half of beta 2 microglobulin (very small)
• CREATININE


  • Recommended method; endogenous procedure
  • Satisfies most criteria for a good clearance substance
  • Provides the laboratory with an endogenous procedure (present in the blood, secreted at a constant rate, normally produces in the muscles, and easily filterable)
  • Minor disadvantage: minimal tubular secretion
• Creatinine Clearance Formula


  • C=UV/P
  • U: urine creatinine (mg/dl)
  • P: plasma/ serum creatinine (mg/dl)
  • V: Volume of 24 hour urine (ml/min)

  
• Normal GFR values


  • Male: 85 -125 ml/min
  • Female: 75-113 ml/min
• Fisherberg test


  Patients are deprived of fluids for 24h prior to measuring the specific gravity
• Mosenthal test


  Compares the volume and SG of day and night samples

  
• Osmometry


  Used to measure the osmolarity of serum and urine by detecting a colligative property change (decreased FB or VP)
• Normal osmolality values


  • Serum: 275 - 300 mOsm/kg
  • Urine: 50-1400 mOsm/kg