Renal Physiology Dr Heddwen Brooks Department of Physiology
[email protected] Reading material BME 511 Sherwood, Chapters 13-14 PSIO 603 Boron and Boulpaep, Chapters 32-39
Renal Structure
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Position of Kidneys in Body Cavity
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Structure of Kidney
Basic Functions of the Kidneys • • • • • • • • • •
Eliminate METABOLIC WASTE PRODUCTS Eliminate FOREIGN COMPOUNDS Regulate BODY FLUID OSMOLALITY Regulate plasma IONIC COMPOSITION Regulate EXTRACELLULAR FLUID VOLUME Help regulate ARTERIAL PRESSURE Help maintain ACID-BASE BALANCE Synthesize GLUCOSE Metabolize/degrade POLYPEPTIDE HORMONES Act as an ENDOCRINE organ: – Erythropoietin – 1,25-(OH)2vitamin D3 – Renin
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Fundamental Processes Involved in Urine Formation
Kidney: blood supply Glomerulus Afferent arteriole Efferent arteriole peritubular capillary plexus (cortex) or vasa recta (medulla)
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Blood in
Blood out
Capillaries (vasa recta)
Filtrate made ions, H20 reabsorbed toxins, waste secreted 20-25% of plasma that enters the glomerulus is filtered
To venous system Urine formation
Kidney: the nephron
Connecting tubule
Collecting duct
Bowman’s capsule (Renal corpuscle)
Proximal convoluted tubule An ultrafiltrate of blood plasma is forced through into Bowman’s capsule
Distal convoluted tubule
As the ultrafiltrate travels along the nephron most components are selectively reabsorbed by the cells of the nephron
Loop of Henle
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Quantitative Relationship between Filtration, Reabsorption, Secretion & Excretion
Filtered/min /min –– Reabsorbed/min /min ++ Secreted/min /min == Excreted/min /min Filtered Reabsorbed Secreted Excreted Filtered/min Reabsorbed/min Secreted/min Excreted/min
Strategy for Understanding Renal Physiology
• Learn the basic mechanisms involved in filtration, filtration reabsorption and secretion, and understand how secretion these processes can be regulated. • Apply this information to describe the renal handling of specific substances (Na+, H2O, K+, etc). • Place these processes in the context of the role of the kidneys in maintaining the optimum internal environment.
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Filtration • Glomerulus is made up of capillaries • Fluid has to flow from capillaries (Starling Forces) into Bowman’s capsule • Fluid that enters the Bowmans capsule has the same ionic composition as blood, but is almost protein free…….in the normal kidney • No Cells are filtered • Filtration is size and charge selective
Ultrafiltration The formation of a virtually proteinprotein-free filtrate of plasma as blood passes through the glomerular capillaries
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Structural Components of the Ultrafiltration Barrier
Kidney: renal corpuscle Parietal layer Visceral layer
Bowman's capsule
Capillary wall
podocytes
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Kidney: renal corpuscle
podocyte Glomerular basement membrane
pedicel
endothelium Capillary lumen
Kidney: renal corpuscle 1. Fenestrated endothelium allows passage of most elements of plasma, retains formed elements 2. GBM filters plasma (molecules the size of albumin and larger are held back) 3. Podocytes secrete GBM, contribute to Glomerular basement membrane barrier function, provide structural reinforcement (pressures up to 40 mm mercury)
endothelium Capillary lumen
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Kidney:
glomerular basement membrane pedicels
Lamina rara interna Lamina densa Type IV collagen Lamina rara externa endothelium
Laminin, Fibronectin Proteoglycans (polyanions) • Most proteins cannot pass through GBM
Capillary lumen • Glucose, ions, water – pass into ultrafiltrate
Glomerular basement membrane is damaged in disease
Glomerular basement membrane
Glomerulonephritis
The GBM is susceptible to damage by bound proteins, especially immunoglobulins Damage to the GBM causes leakage of protein into urine (proteinuria)
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Cross-sectional View of the Glomerular Capillary Wall
Size and Charge barrier for macromolecular passage
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Which is more important: Size/Shape or Charge? • Estimates from Mathematical Models: – 30% ↓ in charge density → 25-fold ↑ in albumin filtration – 100% ↑ in “pore” radius → 5-fold ↑ in albumin filtration
• Loss of fixed negative charges probably results in a physical rearrangement of proteins that contribute to the size barrier. – Glycoproteins contribute to the Basal Lamina structural meshwork (a component of the size barrier) as well as contributing fixed negative charges
• But does this really matter?? – Glomerular disease: Not really as both size- and chargeselective components of the filtration barrier are compromised → protein in the ultrafiltrate – If filtration of protein > protein reabsorption → proteinuria
– Proteinuria (or albuminuria) is the hallmark of glomerular injury!
Strategy for Understanding Renal Physiology
• Learn the basic mechanisms involved in filtration, filtration reabsorption and secretion, and understand how secretion these processes can be regulated.
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Absorption and Secretion Absorption: removal of substances from the urine. Movement of solutes or water from lumen to blood
Transcellular (across both cell membranes) Paracellular (between cell membranes)
Secretion: addition of substances to the urine Movement of solutes from blood to lumen Toxins Urea, Creatinine
Flexibility in how the kidney can handle different substances
Filtered: Reabsorbed: Secreted: Excreted:
inulin glucose
sodium penicillin
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Transcellular v Paracellular Water Movement ¾ All epithelial cells serve as selective permeability barriers, separating fluids on each side that have different chemical compositions. ¾ The epithelial cells lining the lumen transport selected ions across the cell, from the lumen into the extracellular fluid, where they diffuse into small blood vessels
= Transcellular transport
Transcellular Transport ¾ Transcellular transport depends on two sets of membrane-bound carrier proteins: ¾ One on apical surface of the epithelial cell (facing the lumen) which moves selected molecules into the cell from the lumen of the kidney ¾ One on the basolateral surface, which allows the same molecules to leave the cell to enter the extracellular fluid on the other side.
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Water follows the movement of solutes down its concentration gradient
Transcellular Transport Important for Salt and H20
Na+ Channels Exchangers
Na+
H20
H20
Aquaporins
Lumen
H20
H20 Aquaporins
Blood
(urine, chyme)
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Fluid Compartments of the Body Intracellular and Extracellular Space/Fluid Intracellular space is the space within cell membranes Extracellular space is the space between cells (interstitial fluid) and within blood vessels (plasma) Electrolyte composition (e.g. salt and water content) of interstitial fluid and plasma is identical
Compartmentalization of Body Fluids Total body water (TBW)= 60% of body weight
60% x 60kg = 36L
Intracellular water (ICF) = 2/3 of total body water
2/3 x 36L = 24 L
Extracellular water (ECF) = 1/3 of total body water 1/3 x 36L = 12 L
Extracellular Fluid Plasma water = ¼ of extracellular water
1/4 x 12L = 3 L
Interstitial fluid = ¾ extracellular water
3/4 x 12L = 9 L
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Osmotic Composition of Major Fluid Compartments
Osmolarity Osmoles refers to the number of impermeable particles dissolved in a solution, regardless of charge. This is important for determining the diffusional movement of water. For substances that maintain their molecular structure when they dissolve (e.g. glucose), the osmolarity and the molarity are essentially the same. For substances that dissociate when they dissolve, the osmolarity is the number of free particles times the molarity. Thus for a pure NaCl solution, a 1 Molar solution would be 2 Osmolar (1 for Na, and 1 for Cl).
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¾ osmolarity (Osm) is defined as moles of dissolved solute per volume of solution in liters ¾ In human plasma the concentration of dissolved particles is about 290 X 10-3 M.
Osmotic gradient • Osmotic gradient is required in order to achieve net water movement between ECF and ICF • Because water can move freely between compartments, a change in the osmolarity of a single compartment results in redistribution of TBW between compartments (driven by the osmotic gradient) until osmotic equilibrium is restored.
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Major Function of Kidney: Homeostasis Maintain optimal fluid environment in the body
Regulates H20 - osmolarity NaCl Most ions Maintains plasma volume = long term regulation of blood pressure
Balance Concept Net gain must equal net loss if substance remains in a steady state (e.g. water, salt) Ingestion
+
(External gain) food air
Production (Internal gain) metabolism
=
Excretion
+ Consumption
(External loss) urine stool expired air sweat
(Internal loss) metabolism
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Water balance
Electrolytes and Water Salt is not produced or consumed by the body so balance is maintained by regulating the amounts excreted in body fluids (urine, sweat, stool) such that they equal the amounts ingested (ingestion = excretion)
Kidneys maintain water and salt balance in the body by regulating output of both in the urine
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