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Information. Check Blackboard for information and Power point slides from lectures PP slides are in syllabus Send all class notes to Dr Wall who will forward to lecturer Barry.Wall@va.gov. Introduction. Text: Renal Pathophysiology , Helmut Rennke and Bradley Denker , 3rd edition, 2010

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  1. Information • Check Blackboard for information and Power point slides from lectures • PP slides are in syllabus • Send all class notes to Dr Wall who will forward to lecturer • Barry.Wall@va.gov

  2. Introduction • Text: Renal Pathophysiology, Helmut Rennke and Bradley Denker, 3rd edition, 2010 • Syllabus • Small groups: Group Assignments: attendance strongly encouraged • Blackboard

  3. Examinations • Exam questions come from both small group sessions and lectures • Lectures and slides follow textbook

  4. Role of the Kidney Major function of kidney is to maintain homeostasis for a number of solutes and water Homeostasis maintained despite variations in endogenous production and dietary intake

  5. Homeostasis: maintaining total body contents at a stable and normal level, even in the face of changes in dietary intake or endogenous production rate.

  6. HOMEOSTASIS • Electrolytes: sodium, potassium, chloride • Water (osmolality) • Acid-base: bicarbonate (ECFV buffer) • Minerals: calcium, phosphorus, magnesium • Waste material: urea (protein), creatinine (muscle), uric acid (nucleic acids)

  7. Endocrine Functions • Erythropoietin • 1-alpha hydroxylase to produce 1,25 (OH)2D3 • Renin • Paracrine/autocrine functions a. bradykinin b. prostaglandin c. endothelial factors 1. nitric oxide 2. endothelin

  8. Blood pressure regulation: the kidney is the critical organ in maintaining normal blood pressure. • homeostasis of sodium and water, maintaining normal extracellular fluid volume. 2) control of the renin – angiotensin – aldosterone axis. 3) production of vasodilatory substances

  9. Other Functions of the Kidney • Catabolism of small peptide hormones, such as insulin (decreased nephron mass therefore leads to decreased insulin catabolism and resultant longer circulating half-life of insulin) • Kidney can produce glucose via gluconeogenesis during fasting • Kidney is responsible for elimination of many medications, thus,changes in kidney function will change plasma concentrations of these drugs

  10. Concept of Balance • Neutral balance refers to the state in which dietary intake plus endogenous production equals excretion rate of the kidney. In this situation total body contents of the substance remains stable • Positive balance: intake plus endogenous production >renal excretion rate, leading to increased total body content • Negative balance: intake plus endogenous production <renal excretion rate, leading to decreased total body content

  11. Mechanism of Kidney Function Glomerular level: • massive quantities of plasma ultrafiltrate are formed at the glomerulus (180 liters/d) • this requires an enormous blood flow. ~10-20% of total cardiac output Tubular level: • greater than 99% of glomerular filtrate must be reabsorbed • selective reabsorption and secretion determines urinary excretion rates

  12. Glomerular and tubular levels must operate in concert to achieve normal kidney function (GFR). • Glomerular filtration rate, therefore, is the best index of overall kidney function. • Other kidney functions correlate with GFR

  13. Processes Involved in Renal Function • Filtration Deposition into Bowman’s space of an ultrafiltrate of plasma from glomerular capillary blood • Reabsorption Transport of water and certain solutes from fluid within the tubules into the peritubular capillaries • Secretion Addition of certain solutes (but not of water) to the fluid in the tubules from the peritubular capillaries • Excretion Removal from the body of water and solutes as urine

  14. Starling Forces Promoting filtration out of capillary 1. hydrostatic pressure within capillary 2. oncotic pressure within interstitium Opposing filtration out of capillary 3. oncotic pressure within capillary 4. hydrostatic pressure within interstitium Net fluid flow in or out of capillary Determined by the algebraic sum of the Starling forces, and by the filtration coefficient, Kf

  15. Glomerular Filtrate Formation • GFR = LpS (P - tau) • Lp = capillary wall permeability • S = glomerular capillary surface area available for filtration • P= hydrostatic pressure gradient between capillary and Bowmans space • tau = oncotic pressure gradient between capillary and Bowmans space

  16. Ultrafiltration: Glomerular vs. Other Capillaries The glomerular system has: • Higher hydrostatic pressure in capillary and little decrease in this pressure along the capillary • Low hydrostatic pressure in Bowman’s space (tubular reabsorption) • Lower oncotic pressure in Bowman’s space (protein-free ultrafiltrate) • Higher Kf (permeability factor)

  17. Urine flow rate is not autoregulated • Increased perfusion pressure results in increased urinary flow rate (pressure natriuresis) • Urine flow rate is not a good index of overall kidney function • GFR is the best index of overall kidney function

  18. Definitions • Filtered load (mg/min) = (Px) x GFR • Filtered load represents the amount of substance in plasma that is filtered at the glomerulus per unit of time • Excretion rate (mg/min) = (Ux) x UFR • Excretion rate represents the amount of the substance excreted into the urine per unit of time

  19. Urine flow rate is not autoregulated • Increased perfusion pressure results in increased urinary flow rate (pressure natriuresis) • Urine flow rate is not a good index of overall kidney function • GFR is the best index of overall kidney function

  20. Properties of Marker of GFR • Present in plasma at a constant concentration • Freely filtered at the glomerulus • Once filtered, no reabsorption, secretion, synthesis, or metabolism occurs

  21. GFR • Exogenous example: inulin • Endogenous example: creatinine (~10% secretion, so over-estimates GFR) • Given these properties, the filtered load of inulin is equal to its excretion rate • Pinulin x GFR = Uinulin x UFR • GFR (ml/min) = Uinulin x UFR/Pinulin • GFR is the best overall index of kidney function

  22. Renal Clearance Renal clearance represents the volume of plasma cleared of the substance via elimination into the urine per unit of time Units = ml/min

  23. Renal Clearance • Renal clearance = (Ux x UFR)/Px (ml/min) • The renal clearance (ml/min) of any substance cleared by the kidney can be defined as: (Clearance of substance x) = (urine concentration of x) x (urine flow rate)/plasma concentration of x • “UV/P”

  24. Clearance Ratio • Clearance ratio: defined as the clearance of the particular substance (Cx) divided by GFR • (Cx/GFR)

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