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Lecture: Renal Physiology I. Overview of Nephron Structure and Function A. General Nephron Structure 1. glomerulus – site of filtration from arterial blood 2. proximal convolute tubule – first tube off glomerulus 3. Loop of Henle – U-turn connecting tubules 4. distal convoluted tubule – to the Collecting Tubule 5. collecting tubule (duct) – urine from many nephrons 6. peritubular capillaries – “around” the “tubes” 7. 80% of nephrons are in the cortex – “cortical” 8. 20% of nephrons dip down into the medulla – “juxtamedullary”

Lecture: Renal Physiology€¦ · Web viewglomerular filtration 2. tubular reabsorption 3. tubular secretion C. Fluid Processing in the Kidneys 180 liters of blood fluid processed

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Page 1: Lecture: Renal Physiology€¦ · Web viewglomerular filtration 2. tubular reabsorption 3. tubular secretion C. Fluid Processing in the Kidneys 180 liters of blood fluid processed

Lecture: Renal Physiology

I. Overview of Nephron Structure and Function

A. General Nephron Structure

1. glomerulus – site of filtration from arterial blood2. proximal convolute tubule – first tube off glomerulus3. Loop of Henle – U-turn connecting tubules4. distal convoluted tubule – to the Collecting Tubule5. collecting tubule (duct) – urine from many nephrons6. peritubular capillaries – “around” the “tubes”

7. 80% of nephrons are in the cortex – “cortical”

8. 20% of nephrons dip down into the medulla – “juxtamedullary”

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B. General Nephron Function1. glomerular filtration

2. tubular reabsorption3. tubular secretion

C. Fluid Processing in the Kidneys1. 180 liters of blood fluid processed each day2. 1.5 liters of urine produced each day

II. Functions of the Kidney

A. Regulation of water, inorganic ion balance, acid-base balanceB. Removal of metabolic wastes and their excretion into urineC. Removal of foreign chemicals (e.g. drugs) and their excretion into urineD. Gluconeogenesis during prolonged fastingE. Production of hormones and enzymes

a. erythropoietin – controls formation of red blood cellsb. renin – a hormone that controls the level of angiotensin in the blood

and its subsequent effects on blood pressure and sodium balance

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III. Overview of Components Functions

A. Bowman’s Capsule – 180 L fluid filtered per day; osmolarity of filtrate is identical in composition and isosmotic to blood plasma (300 mosm)

B. Proximal Convoluted Tubule - 70% reabsorbed in peritubular capillaries by transporting solutes out of the proximal tubule (water follows by osmosis) => osmolarity of entering & leaving fluid in proximal tubule stays the same => Primary function of proximal tubule: Bulk reabsorption of isosmotic fluid.

C. Loop of Henle - Primary site for diluting urine. More solute than water is reabsorbed while passing thru the loop => filtrate hyposmotic related to plasma (100 mOsm) and vol=18 L/day

D. Distal Tubule & Collecting Duct - Regulation of salt & water balance under control of hormones. Osmolarity: 50-1200 mOsm & vol: 1.5 L/day depending on the need of body to conserve or excrete water.

III. Glomerular Filtration

A. Renal Corpuscle – components

1. Glomerulus – tuft of capillaries through which filtration occurs2. Glomerular (Bowman’s) capsule – cup-shaped end of a renal tubule that surrounds the glomerulus3. Glomerular endothelium – fenestrated (has pores) epithelium with large pores that allows water and solute-rich, virtually blood-free and protein-free filtrate to pass from the blood into the glomerular capsule4. afferent arteriole – supplies blood to the glomerulus5. efferent arteriole – drains blood from the glomerulus6. peritubular capillaries – surround the all of the tubules

B. Filtration Membrane

1. hydrostatic pressure – forces 1/5 of blood fluid through capillary walls into glomerular capsule

2. filtration membrane – has three partsa. fenestrated capillary endothelium (prevents passage of blood

cells)b. basal membrane (allows most solutes but not larger proteins)c. visceral layer of glomerular capsule with podocytes and

filtration slits

3. solutes that can pass into glomerular capsule< 3 nm easily pass (water, sugar, amino acids, nitrogenous waste molecules) 9 nm larger proteins cannot pass through proteinuria – proteins in the urine

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B. Net Filtration Pressure

NFP = force OUT of blood – force to remain IN blood

NFP = glomerular – (glomerular + capsular ) hydrostatic osmotic hydrostatic pressure pressure pressure

NFP = 55 mm Hg – ( 30 mm Hg + 15 mm Hg )

NFP = 55 mm Hg – ( 45 mm Hg )

NFP = net filtration pressure = 10 mm Hg

[This is the NET forces pushing fluid/solutes OUT of blood]

C. Glomerular Filtration Rate (GFR)

1. glomerular filtration rate = milliliters of blood fluid filtered by glomerulus each minute

Factors effecting the GFR:a. total filtration surface areab. membrane permeability to fluid/solutesc. Net Filtration Pressure

2. Normal GFR = 125 ml/min (7.5 L/hr, 180 L/day)

Page 5: Lecture: Renal Physiology€¦ · Web viewglomerular filtration 2. tubular reabsorption 3. tubular secretion C. Fluid Processing in the Kidneys 180 liters of blood fluid processed

3. NFP – primary factor controlling GFRa. bleeding – NFP drops because of lower glomerular H.P.b. dehydration – NFP drops because of lower glomerular H.P.

4. If GFR is too high > needed substances cannot be reabsorbed quickly enough and are lost in the urine

5. If GFR is too low > everything is reabsorbed including nitrogenous waste compounds.

D. Intrinsic Controls: Regulation of Glomerular Filtration

1. renal autoregulation – rate of FILTRATE production must be coordinated with systemic blood pressure changes

2. myogenic mechanism – circular muscle around the glomerular arterioles reacts to pressure changes

a. increased systemic blood pressure -> vasoconstriction of afferent arterioles

b. decreased systemic blood pressure -> vasodilation of afferent arterioles

3. tubuloglomerular feedback mechanism – macula densa cells (of juxtaglomerular apparatus in walls of distal tubules) sense the solute concentration and rate of flow of the FILTRATE

a. low filtrate osmolarity or flow rate -> vasodilation of afferent arteries

b. high filtrate osmolarity or flow rate -> vasoconstriction of afferent arteries

4. renin-angiotensin mechanism

renin (released by juxtoglomerular cells) -> anigiotensinogen -> angiotensin I -> (Angiotensin Converting Enzyme (ACE))-> angiotensin II -> global vasoconstrictor (rise in blood pressure) -> aldosterone (reabsorption of more Na+)

Factors causing release of Renin:

a. reduced stretch of juxtaglomerular cellsb. stimulation by macula densa cells (as above)c. stimulation of juxtaglomerular cells by sympathetics

E. Extrinsic Controls: Sympathetic Innervation

1. sympathetics – cause increased release of renin2. epinephrine – causes increased vasoconstriction

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IV. Tubular Reabsorption: Reabsorbing the Glomerular Filtrate

A.Overview of Reabsorption

1. filtrate - all fluid and its solutes pushed into the capsule2. urine - filtrate minus reabsorbed substances

3. route of reabsorption (transepithelial process)

luminal surface of tubule cells >>basolateral membrane of tubule cells >>interstitial fluid between tubule cells and capillaries >>endothelium of the peritubular capillary

4. most sugars and amino acids are reabsorbed5. water and ion reabsorption depends on hormonal control (see below)

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B. Active Tubular Reabsorption

1. glucose, amino acids, lactate, vitamins, ions

a. move across luminal surface by diffusionb. actively transported across basolateral membrane

i. contransported with Na+

c. diffuse into capillary by diffusion

2. transport maximum (Tm) - when “ carrier proteins” for specific solute becomes saturated and cannot carry the substance across the membrane

a. diabetes mellitus – lower Tm (glucose lost)

3. renal threshold – the plasma concentration at which substrate (e.g. glucose) first appears in the urine;

a. glycosuria – excessive concentration of glucose in the urine; carriers are saturated with glucose and cannot carry any more

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C. Passive Tubular Resorption

1. Na+ driven into interstitial space actively (above)2. HCO3

- and Cl- follow Na+ into the interstitial space3. obligatory water reabsorption – water follows ions into the interstitial space between tubule & capillary

4. solvent drag – solutes will begin to move into tubule from filtrate, following water (especially some urea and lipid-soluble molecules)

Page 9: Lecture: Renal Physiology€¦ · Web viewglomerular filtration 2. tubular reabsorption 3. tubular secretion C. Fluid Processing in the Kidneys 180 liters of blood fluid processed

D. Nonreabsorbed Substances

1. urea, creatinine, ammonia, uric acid – most is not reabsorbed because of the following reasons

a. no carrier molecules for active transportb. not lipid-solublec. too large (as with most proteins)

E. Absorption in Different Regions of Renal Tubule

1. proximal tubule – closest to the glomerular capsule

a. almost all glucose & amino acidsb. 75-80% of water and Na+c. most active transport of ions

2. Loop of Henle – connects proximal & distal tubules

Regulates Total water retained or lost:a. descending limb – relatively impermeable to solutes but freely

permeable to waterb. ascending limb – very permeable to solutes, but not to water

3. distal tubule & collecting duct – final passageway

a. antidiuretic hormone (ADH) – causes increased permeability of collecting duct to water, resulting in more reabsorption (B.P. ??? )

b. aldosterone – stimulated by renin-angiotensin, enhances Na+ reabsorption, resulting in increased water reabsorption (B.P. ??? )

i. in response to lower blood pressureii. in response to low blood Na+ concentration (hyponatremia)

c. atrial natriuretic factor (protein) (ANF) – reduces Na+ permeability, less water reabsorption (B.P. ??? )

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V. Tubular Secretion

A. Movement from Capillaries to Tubular Cells

1. K+, creatinine, ammonia, organic acids, drugs2. Primary functions of tubular secretion:

a. moving drugs into the urineb. moving more urea & uric acid into urinec. removing excess K+ and Na+ from bloodd. regulating pH (H+ ion removal)

VI. Regulation of Urine Concentration & Volume

A. Osmolarity – Number of Solute particles in 1 Liter water

1. independent of size of solute (Na+, glucose)2. 1 osmol = 6.02 X 10^23 particle in 1 Liter3. milliosmol (mosm) = 0.001 osmol4. normal body fluids = 300 mosm

B. Countercurrent Multiplier Mechanism for Maintenance of Blood/Urine Osmolarity

1. Water moves out along Descending Limb of the Loop of Henle, creating 1200 mosm urine at the base

2. Na+Cl- moves out along the Ascending Limb of the Loop of Henle, creating 100 mosm urine at distal end. This salt helps pull more water out of the Descending Limb in positive feedback mechanism.

3. In times of dehydration, Collecting Tubules leak urea to interstitial space, further increasing water retention by increasing osmolarity.

4. Vasa recta (capillaries around Loop of Henle) have no Net Effect on water/salt balance

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C. Formation of Dilute Urine

1. When water removal is needed, no ADH is released, so that the Distal and Collecting Tubules will not actively transport Na+ out; no water moves out

2. Urine may be as low as 50 mosm

D. Formation of Concentrated Urine (Water Conservation)

1. antidiuretic hormone (ADH) – stimulates reabsorption of water in the Distal and Collecting Tubules

E. Diuretics (Stimulate Water Loss)

1. alcohol – inhibits action of ADH2. caffeine – causes renal vasodilation; increases GFR3. Na + reabsorption blockers – block Na+ movement

VII. Renal Clearance

A. Renal Clearance (RC) – the rate at which the kidney can remove a substance from the blood

RC = U/P X V

concentration of substance in urine (mg/ml)U/P = - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - concentration of substance in plasma (mg/ml)

V = rate of the formation of urine (ml/minute) (normal = 1 ml/minute)

B. Glomerular Filtration Rate = 125 ml/minute; (determined by challenge with “Inulin” – inert polysaccharide not reabsorbed or secreted)

1. RC < 125 – reabsorption is occurring2. RC > 125 – tubule cells secrete into the urine3. RC = 0 – substance completely reabsorbed or not filtrated

VIII. Characteristics and Composition of Urine

A. Physical Characteristics

1. color – clear to yellowish; influenced by diet, drugs, and health state2. odor – slightly aromatic; influenced by diet, drugs, and health state3. pH (H + conc.) – usually about 6; changes in diet can effect the pH

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4. specific gravity – compared density to distilled water; urine slightly heavier (with solutes)

B. Chemical Composition

1. 95% water

2. 5% solutes – urea (breakdown of amino acids); uric acid; creatinine;Na+, K+, PO4

3–, and SO42–, Ca2+, Mg2+ and HCO3

3. Abnormally high concentrations of any constituent, or abnormal components, e.g., blood proteins, WBCs, bile pigments, may indicate pathology

IX. Disorders of the Urinary System

A. Urinary Tract Infection (UTI) – women are more prone to develop a UTI because urethra is short and close to the large intestine.

B. Kidney stones – mostly made of calcium oxalate but there are also stones made up of Ca phosphate and uric acid; these chemicals are common in the urine but sometimes crystalize; they can obstruct urinary flow causing intense pain; treated by shock-wave lithotripsy or surgery.

X. Urination: Micturition Reflex

A. The act of emptying the bladder – can contain 500 ml of urineB. Internal sphincter – smooth muscle; external sphincter – skeletal muscleC. External sphincter controlled by somatic motor division of nervous systemD. Internal sphincter controlled by autonomic nervous systemE. Urination a simple spinal reflex subject to conscious and unconscious control;

parasympathetic neurons cause contraction of smooth muscles of bladder

F. Overactive bladder : Detrusor muscle is contracted at a certain volume.

G. Men : Enlargement of the prostate (benign prostate hyperplasia - BPH)H. Women : Pelvic floor may lower with aging or after childbirth causing the

neck of the bladder to descend and increase the pressure against the urethral sphincters.

I. Treatment: ACh inhibitors (ACh is normally released to contract the detrusor muscle)