Functions and Anatomy of the Kidneys

Functions of the Kidneys

• Primary function: formation of urine
• Remove waste products from the body (ingested or metabolized)
• Eliminating unwanted substances and retaining needed substances
• Control the composition and volume of body fluids:
  • Regulation of water and electrolyte balance (ECF)
  • Regulation of fluid osmolality
  • Regulation of acid-base balance (strongest & slowest)
• Regulation of arterial blood pressure
• Metabolism and excretion of hormones
• Secretion of hormones (erythropoietin, renin)
• Gluconeogenesis and activation of vitamin D

Physiologic anatomy

• Size of a clenched fist (150 grams)
• Capsule, outer cortex, and inner medulla
• Medulla (renal pyramids) → papilla → renal pelvis → ureter → bladder→ urethra
• Urine drains into the renal pelvis and is channeled into the ureter
• Urine stores temporarily in the urinary bladder and is emptied through the urethra
• The urethra serves both the urinary and reproductive systems in males

Renal blood supply

• Supplied by the renal artery and renal vein
• The kidney processes plasma that flows through it
• 22% of cardiac output goes to the kidneys
• Renal blood flow = 1100 ml/min
• Renal plasma flow = 625 ml/min
• Renal artery → interlobar arteries → arcuate arteries → interlobar arteries → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries

Nephron

• Functional unit of the kidney
• 1 million nephrons per kidney (2 million total)
• After 40 years of age, the number of nephrons decreases by 1% per year
• Composed of:
  • Vascular components:
    • Afferent arteriole: carries blood into the glomerulus
    • Glomerulus: a network of capillaries surrounded by Bowman's capsule
    • Efferent arteriole: carries blood away from the glomerulus
    • Peritubular capillaries: supply renal tissue and are involved in reabsorption and secretion
  • Tubular components:
    • Bowman's capsule: collects glomerular filtrate
    • Proximal convoluted tubule
    • Loop of Henle (LOH): descending and ascending limbs
    • Distal convoluted tubule
    • Collecting duct (CD) (250 per kidney): each collects from 4000 nephrons

Types of nephrons

• Cortical nephrons:
  • 70-80% of nephrons
  • Glomeruli in the outer cortex
  • Short loop of Henle
  • Travel a short distance in the medulla
  • Surrounded by peritubular capillaries
  • Form diluted urine
• Juxtamedullary nephrons:
  • 20-30% of nephrons
  • Glomeruli in the inner cortex
  • Long loop of Henle
  • Travel through the entire medulla
  • Surrounded by Vasa Recta
  • Form concentrated urine

Glomerular filtration

• A random and passive process that takes place in the glomerulus
• Protein-free plasma is filtered from the glomerulus into the Bowman's capsule
• Blood cells and proteins are not normally filtered
• The size and charge of a substance determine its filterability
• 20% of renal plasma flow is filtered
• The remaining 80% enters the efferent arteriole

Glomerular filtrate

• Composition is similar to plasma but lacks proteins and red blood cells
• Contains less calcium and fatty acids (bind partially to proteins)
• Makes up 20% of the renal plasma flow
• Glomerular filtrate production rate is 125 ml per minute (180 liters per day)
• Glomerular filtration rate (GFR) = 125 ml per minute (180 liters per day)
• Filtration fraction = GFR/renal plasma flow = 125/625 = 20%
• GFR is high for the following reasons:
  • Removing waste products rapidly
  • Filtering body fluids many times each day
  • Providing precise and rapid control over body fluids (volume and composition)

Tubular reabsorption

• A highly selective and variable process
• Filtered substances move from the inside of the tubular part of the nephron into the blood of the peritubular capillaries (tubular lumen → peritubular capillary lumen)
• The return of substances to the blood is necessary to maintain the composition of the ECF
• High reabsorption rates:
  • 124 of 125 ml of filtered fluid per minute
  • 100% for glucose
  • 99.5% for salts
  • 99% for water
  • 50% for urea

Tubular secretion

• A very selective process to eliminate toxic substances rapidly
• Substances from the peritubular capillaries enter the lumen of the nephron tubule

Handling of substances by the nephron

• A - Filtration only:
  • Plasma clearance = GFR
  • Ex: creatinine and inulin
• B - Filtration and partial reabsorption:
  • Plasma clearance < GFR
  • Ex: plasma electrolytes
• C - Filtration and complete reabsorption:
  • Plasma clearance = zero
  • Ex: glucose and amino acids
• D - Filtration and secretion:
  • Plasma clearance > GFR
  • Ex: para-amino-hippuric acid (PAH)

Glomerular filtration layers

• The pores (fenestra) in the wall (endothelium) of the glomerular capillaries
  • 400 times more permeable than other capillaries
• The basement membrane: negatively charged gelatinous layer between glomerulus & Bowman's capsule (collagen and proteoglycans)
• The inner epithelial layer of Bowman's capsule (through filtration slits between podocytes that encircle the glomerulus tuft)

Factors influencing glomerular filtration

• Glomerular capillary hydrostatic pressure (55 mm Hg):
  • Result of blood pressure
  • Causes the filtration process
  • Pushes plasma from glomerulus into Bowman's capsule
  • The main parameter controlling the filtration process
  • Increased by:
    • Increasing arterial blood pressure
    • Afferent vasodilation (reduced afferent resistance)
    • Moderate efferent vasoconstriction
  • Decreased by:
    • Reducing arterial blood pressure
    • Afferent vasoconstriction (increased afferent resistance)
    • Severe efferent vasoconstriction
• Glomerular plasma-colloid osmotic (oncotic) pressure (30 mm Hg):
  • Due to the retention of plasma proteins in the glomerular blood
  • Opposes the filtration process
  • Determined by:
    • Arterial plasma colloid osmotic pressure (directly proportional)
    • Filtration fraction (directly proportional): Increased by ↑ GFR or ↓ RPF
• Hydrostatic pressure of the Bowman's capsule (15 mm Hg):
  • Moves fluids from Bowman's capsule into the glomerulus
  • Opposes the filtration process
  • Increases with tubular obstruction (kidney stones)

Net filtration pressure

• Glomerular capillary pressure - (plasma colloid osmotic pressure + Bowman's capsule hydrostatic pressure) = 55 - (30 + 15) = 10 mmHg

Glomerular filtration rate (GFR)

• GFR = Filtration coefficient (Kf) x Net filtration pressure
• GFR = 12.5 x 10 = 125 ml/min:
  • 125 ml/min = 180 L/day
  • Plasma Volume = 3 liters
  • Plasma is filtered 60 times daily

Filtration coefficient

• Determined by properties of the glomerular membrane:
  • The glomerular surface area for penetration
  • The permeability of the glomerular membrane

Factors affecting GFR

• Reduction in filtration coefficient (Kf) reduces GFR: chronic uncontrolled HTN & DM
• Increased Bowman’s capsule hydrostatic pressure reduces GFR: kidney stones
• Increased glomerular capillary colloid osmotic pressure reduces GFR
• Increased glomerular capillary hydrostatic pressure increases GFR

Factors affecting renal blood flow

• Sympathetic nervous system (SNS):
  • Strong activation: reduces RBF and GFR
  • Moderate activation: little effect
• Hormones and autocoids:
  • Afferent and efferent vasoconstrictors (NE, EN, endothelin): reduce RBF and GFR
  • Efferent vasoconstrictor (angiotensin II): increase RBF and GFR
  • Vasodilators (prostaglandin, bradykinin, nitric oxide): increase RBF and GFR

Autoregulation of GFR and RBF

• GFR remains constant as arterial pressure ranges from 75 to 160 mmHg
• Normally: filtration= 180 L/day, reabsorption = 178.5 L/day, and urine =1.5 L/day
• Without autoregulation:
  • If pressure ↑ by 25% → GFR = 225 L/day
  • If reabsorption is constant → urine= 46.5 L/day
  • 30 folds increase in urine formation depletes the body
• Autoregulation mechanisms aren't 100% effective
• ↑ BP always leads to ↑ GFR (pressure diuresis or pressure natriuresis)
• Myogenic mechanism:
  • Responds to changes in the nephron's vascular component
  • Altering the caliber of the afferent arterioles due to stretch of smooth muscle
  • ↑ GFR by ↑ arterial pressure → afferent arterioles constrict to lower the GFR
  • ↓ GFR by ↓ arterial pressure → afferent arterioles dilate to increase the GFR
• Tubuloglomerular feedback:
  • Senses changes in flow in the nephron's tubular parts
  • Done by the juxtaglomerular apparatus:
    • Formed as the DCT passes between afferent & efferent arterioles
    • Composed of two components: macula densa and granular cells
      • Macula densa: monitors the NaCl concentration in the DCT
      • Juxtaglomerular (granular) cells: secrete renin
  • ↓ GFR due to ↓ arterial pressure → ↑ Na reabsorption & ↓ filtrate [NaCl]:
    • Macula densa will sense the low [NaCl] and activate granular cells
    • Granular cells will secrete renin:
      • Renin causes vasodilation of the afferent arteriole (↑ GFR)
      • Renin converts angiotensinogen into angiotensin I