physiology

• Osmosis and osmotic pressure

  • Osmosis: The movement of water across cell membranes occurs by osmosis. Driving force for the movement of water is the osmotic pressure difference across the cell membrane. Osmotic pressure is determined solely by the number of solute particles in the solution.
  • Osmolarity = Concentration X number of dissociable particles
  • mOsm/L = mmol/L X number of particles/mol
  • e.g. 150 mmol/L NaCl = 300 mOsm/L
• Lecture objectives

  • Understand basic concepts of osmolarity, osmotic pressure, oncotic pressure
  • Understand gross anatomy of kidneys and segments of nephron
  • Understand renal hemodynamics: GFR and RBF
  • Understand determinants and regulation of GFR
• Body fluid compartments

  • Body fluid is compartmentalized in extracellular and intracellular compartments. The intracellular compartment is two-thirds of total, and extracellular fluid compartment is one-third of total. Extracellular compartment is further divided into plasma (1/4) and interstitial compartments (3/4). It is sodium and water in the plasma compartment which is regulated.
• Physical aspects that regulate filtration of substances

  • Substances Size > 70,000 Daltons mwt., is not filtered
  • Electrical charge: Negatively charged molecules are less filtered. This is because the surfaces of the filtration barrier are coated with polyanions which tend to repel negative charges.
• Glomerular filtration rate is the rate at which blood is filtered through the glomerulus
• Kidney function

  • Maintain constant body fluid volume
  • Maintain constant fluid composition
  • Endocrine organ
  • Acid-base balance
• Oncotic pressure

  • Oncotic pressure is the osmotic pressure generated by large molecules such as proteins (has the symbol π). It is an important force in the kidneys which regulates fluid movement across the glomerulus and peritubular capillaries
• Juxtaglomerular (JG) apparatus

  • Portion of tubule where the late thick ascending limb of Henle's loop courses between the arterioles. Made up of at least 2 cell types: granular cells - differentiated smooth muscle cells in the walls of the arterioles, macula densa cells. Granular cells secrete the hormone renin. Macula densa contributes to control of glomerular filtration rate and to the secretion of renin.
• Glomerular filtration

  Bulk flow of fluid from glomerular capillaries into Bowman's capsule. The glomerular filtrate - fluid within Bowman's capsule normally doesn't contain cells, essentially protein-free and contains most inorganic ions and low molecular weight organic solutes. Filtered substances go through (in order): 1. Fenestrae in the glomerular-capillary endothelial layer, 2. Basement membrane, 3. Slit diaphragms between podocyte foot processes.
• Negatively charged molecules are less filtered due to the surfaces of the filtration barrier being coated with polyanions which repel negative charges
• Direct determinants of GFR

  1. Rate of filtration = permeability x surface area x Net filtration pressure (NFP)

  2. Kf = Permeability X Surface area

  3. GFR = Kf (permeability x surface area) X Net filtration pressure (NFP)
• Regulation of GFR is important for regulating the amount of fluid going into the nephron
• Net Filtration Pressure (NFP)

  • PGC = glomerular-capillary hydrostatic pressure
  • πBC = oncotic pressure of fluid in Bowman's capsule
  • PBC = hydrostatic pressure in Bowman's capsule
  • πGC = oncotic pressure in glomerular-capillary plasma
• Overall equation for GFR is GFR = Kf x NFP (PGC - PBC - πGC)
• RBF is determined by mean arterial pressure and the contractile state of renal arterioles
• Functions of RBF

  • Indirectly determines GFR
  • Modifies the rate of solute and water reabsorption by the proximal tubule
  • Participates in the concentration (and dilution) of urine
  • Delivers oxygen, nutrients and hormones to nephron cells; returns CO2 and reabsorbed fluid and solutes to circulation
  • Delivers substrates for excretion in urine
• Kf

  Ultrafiltration coefficient (permeability X surface area of glomerular capillaries)
• Substances Size > 70,000 Daltons mwt., is not filtered
• Because there is virtually no protein in Bowman's capsule, πBC may be taken as zero
• Renal Blood flow is approximately 1.1 L/min and constitutes 20-25% of total cardiac output
• Physical aspects of glomerulus-endothelial cell barrier that regulate filtration of substances

  • Permeability
  • Size of space/fenestra between endothelial cells
  • Size of spaces between epithelial podocytes of Bowman’s capsule
  • Volume of filtrate formed per unit time is known as glomerular filtration rate, GFR
  • Normal GFR is approximately 180L/day
• Regulation of GFR

  1. Factors that influence afferent and efferent arteriolar caliber

  2. Renal sympathetic nerves

  3. Renin-angiotensin system

  4. Autoregulation

  5. Prostaglandins
• Regulation of RBF is influenced by mean arterial pressure and the contractile state of renal arterioles
• Functions controlling fluid volume and composition

  • Help control fluid volume and composition
• Control of renin secretion

  Controlled by 4 major inputs: Intrarenal baroreceptors, Macula densa, Renal sympathetic nerves, Ang II
• Actions of Angiotensin II (AII)


  • Constricts both efferent and afferent arterioles (but has more effect on efferent), increasing PGC, but reduction in RBF causes decrease in PGC. Ang II decreases Kf by acting on mesangial cells, tends to decrease GFR in normal situations. In pathological situations like renal artery stenosis, Ang II serves to maintain GFR
• Regulation of GFR

  Factors that influence afferent and efferent arteriolar caliber: Renal sympathetic nerves, Renin-angiotensin system, Autoregulation, Prostaglandins
• Nitric oxide (NO)

  • Important vasodilator in control of renal blood flow, counteracts Ang II and catecholamines, production increases with greater shear force on endothelial cells
• Importance of GFR regulation

  • Regulates the amount of fluid going into nephron tubules which helps regulate the amount of fluid being excreted/reabsorbed, clearance of specific molecules e.g. toxins, drugs, certain metabolites
• Prostaglandins

  Local metabolites of arachidonic acid produced by renal sympathetic stimulation and AII. Major prostaglandins produced in the endothelial cells of renal arterioles are PGI2 (prostacyclin) and PGE2. Vasodilatory agents important to prevent excessive vasoconstriction during cardiovascular stress
• Dopamine


  • Vasodilator produced by the proximal tubule, increases renal blood flow, inhibits renin secretion
• Renin-angiotensin system

  Renin produced from JG cells converts angiotensinogen to angiotensin I. Angiotensin I converted to angiotensin II by action of angiotensin converting enzyme (ACE). Levels of angiotensin II dependent on levels of renin
• Effects of Angiotensin II on renal arteries

  Significant effects on efferent arteriole, maintains GFR, ensures reduction is not severe
• Autoregulation of renal blood flow and GFR

  myogenic response, tubuloglomerular feedback
• Oncotic pressure

  The osmotic pressure generated by large molecules such as proteins. It is an important force in the kidneys which regulates fluid movement across the glomerulus and peritubular capillaries
• It is sodium and water in the plasma compartment which is regulated
• Osmolarity

  Concentration X number of dissociable particles
• If the ECF becomes hyperosmotic (increased Na)


  Then water moves from the ICF into the ECF. There is a contraction of the ICF and an enlargement of the ECF (hyperosmotic volume expansion)
• If hypotonic saline was injected i.v.

  There was decreased osmolarity in ECF first which will equilibrate with ICF. Volume obviously increases (hypoosmotic volume expansion)
• Drinking Gatorade results in isosmotic volume expansion