Physiology Unit 4 - Renal - Fofi
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| Functions of kidney | regulation of body fluid osmolality, volume; excretion of H20 & NaCl regulated w/ cardiovascular, endocrine, & CNS
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| Regulation of electrolyte balance | daily intake of organic ions should be matched by daily excretion through kidneys
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| Regulation of acid-base balance | kidneys work in concert with lungs to regulate the pH in narrow limits of buffers within body fluids
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| Excretion of metabolic products and foreign substances | urea from amino acid metabolism, uric acid from nucleic acids, creatinine from muscles, end products of hemoglobin metabolism, hormone metabolites, foreign substances
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| Renin | activates the renin-angiotensin-aldosterone system (RAAS), thus regulating blood pressure & Na+K+ balance
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| Prostaglandins/kinins-braykinin | vasoactive, leading to modulation of renal blood flow and along w/ angiotensin II affect systemic blood flow
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| Erythropoietin | stimulates RBC formation by bone marrow
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| Functional unit of the kidney | nephron
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| Nephron function | production of filtrate, reabsorption of organic nutrients, reabsorption of water and ions, secretion of waste products into tubular fluid
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| Types of nephrons | cortical and juxtamedullary
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| Cortical nephrons | 85% of all nephrons; located in cortex
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| Juxtamedullary nephrons | closer to renal medulla; loops of Henle extend deep into renal pyramids
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| Blood supply to kidnesy | blood travels from afferent arteriole to capillaries in nephron (glomerulus); blood leaves nephron via efferent arteriole; blood travels from efferent arteriole to peritubluar capillaries and vasa recta
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| Glomerular filtration | produced from blood plasma; must pass thru pores b/t entothelial cells of glomerular capillary, basement membrane, podocyte filtration slits
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| Filtrate | similar to plasma in terms of concentrations of salts, organic molecules, but it is essentially protein free.
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| Glomerular filtration barrier | restricts filtration of molecules on basis of size and electrical charge
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| What drives filtration? | starling forces across glomerular capillaries; changes in these forces and in renal plasma flow alter glomerular filtration rate (GFR)
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| Glomerulus is more efficient than other capillary beds…why? | filtration membrane is significantly more permeable, glomerular blood pressure is higher, higher net filtration pressure
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| Plasma proteins and filtrate | not filtered and are used to maintain oncotic (colloid osmotic) pressure of the blood
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| Net filtration pressure (NFP) | pressure responsible for filtrate formation; equals the glomerular hydrostatic pressure (HPg) minus the oncotic pressure of glomerular blood (OPg) plus capsular hydrostatic pressure (HPc); NFP = HPg- (OPg + HPc)
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| Glomerular filtration rate (GFR) | total amt filtrate formed/min by kidneys; factors include total surface area available for filtration & membrane permeability, net filtration pressure (NFP); GFR directly proportional to NFP; changes in GFR result of changes in glomerular capillary BP
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| GFR too high | needed substances cannot be reabsorbed quickly enough and are lost in urine
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| GFR too low | everything is reabsorbed, including wastes that are normally disposed of
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| Control of GFR | normally result from adjusting glomerular capillary blood pressure; 3 mechanisms—renal autoregulation (intrinsic system), neural controls, hormonal mechanism (renin-angiotensin)
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| Autoregulation of GFR | two mechanisms—myogenic mechanism, tubuloglomerular feedback
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| Myogenic mechanism | autoregulation of GFR; arterial pressure rises, afferent arteriole stretches, vascular smooth muscles contract, arteriole resistance offsets pressure increase; RBF & hence GFR remain constant
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| Tubularglomerular feedback mechanism | autoregulation of GFR; feedback loop of flow rate (increased NaCL) sensing mechanism in macula dena of juxtaglomerular apparatus; increased GFR & RBF triggers release of vasoactive signals; constricts afferent arteriole leading to decreased GFR & RBF
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| Juxtaglomerular apparatus | arterial walls have JG cells—enlarged smooth muscle cells; have secretory granules containing renin; act as mechanoreceptors
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| Macula densa | tall, closely packed distal tubule cells; lie adjacent to JG cells; function as chemoreceptors or osmoreceptors
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| Extrinsic controls at rest | renal blood vessels are maximally dilated, autoregulation systems prevail
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| Extrinsic controls under stress | Norepi released by sympathetic NS; Epi released by adrenal medulla; afferent arterioles constrict, filtration inhibited; drop in filtration pressure stimulates JGA to release renin and erythropoietin
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| Renin-angiontensin mechanism | renin release triggered by reduced stretch of JG cells, stimulation of JG cells by macula densa cells, direct stimulation of JG cells by renal nerves; renin acts on angiotensin to release angiotensin I, which is converted to angiotensin II
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| Angiotensin II | causes mean arterial pressure to rise; stimulates adrenal cortex to release aldosterone; results in both systemic & glomerular hydrostatic pressure to rise
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| Prostaglandins | affect glomerular filtration; vasodilators produced in response to sympathetic stimulation and angiotensin II; thought to prevent renal damage when peripheral resistance increased
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| Nitric oxide | vasodilator produced by vascular endothelium
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| Adenosine | vasoconstrictor of renal vasculature
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| Control of surface area | mesangial cells have contractile properties, influence capillary filtration by closing some of the capillaries; effects surface area; podocytes change size of filtration slits
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| Process of urine formation | glomerular filtration, tubular reabsorption of substance from tubular fluid into blood, tubular secretion of substance from blood into tubular fluid
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| Mass balance | amount excreted in urine = amount filtered through glomeruli into renal proximal tubule minus amount reabsorbed into capillaries plus amount secreted into tubules
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| Reabsorption and secretion | accomplished via diffusion, osmosis, active and facilitated transport; carrier proteins have transport max Tm which determines renal threshold for reabsorption of substances in tubular fluid; carriers saturation = excess of that substance is secreted
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| Transport maximum (Tm) | reflects the number of carriers in the renal tubules available; exists for nearly every substance actively reabsorbed
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| Sodium reabsorption | almost always by active transport via NKATpase pump; provides energy and means for reabsorbing most other solutes, i.e. water by osmosis, organic nutrients & selected cations by secondary active transport
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| Reabsorption—secondary active transport | Na linked secondary active transport; key site is proximal convoluted tubule (PCT); reabsorption of glucose, ions, amino acids
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| Non-reabsorbed substances | substances that lack carriers, are not lipid soluble, too large to pass through membrane pores; urea, creatinine, uric acid most important
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| Tubular secretion | basically reabsorption in reverse; substances move from peritubular capillaries/tubule cells into filtrate; important for disposal of substances not already in filtrate, eliminating undesirable substances (urea, uric acid); controlling blood pH
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| PCT reabsorption & secretion | glomerular filtration produces fluid similar to plasma (but no proteins); PCT reabsorbs 60-70% of filtrate produced; Na, all nutrients, cations, ions, water, urea, lipid soluble solutes, small proteins; H+ secretion also occurs here
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| DCT reabsorption & secretion | performs final adjustment of urine; active absorption of Na and Cl; secretion of K and H based on blood pH; water regulated by ADH/vasopressin; Na and K regulated by aldosterone
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| Atrial natriuretic peptide activity (ANP)—reduces Na | decreases blood volume, lowers blood pressure
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| ANP lowers blood Na by | acting on medullary ducts to inhibit Na reabsorption; antagonistic to aldosterone & angiotensin II; promotes Na and H20 excretion in urine by kidney; indirectly stimulates increase in GFR reducing H20 reabsorption
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| Regulation by ADH | released by posterior pituitary when osmoreceptors detect increase in plasma osmolality; dehydration or excess salt intake produces thirst sensation; stimulates H20 reabsorption from urine
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| Control of urine volume & concentration | regulated by controlling water and sodium reabsorption; precise control allowed via facultative water reabsorption
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| Osmolality | number of solute particles dissolved in 1L water; reflects solution’s ability to cause osmosis; body fluids measured in milliosmols (mOsm); kidneys keep solute load of body fluids at about 300mOsm by countercurrent mechanism
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| Countercurrent mechanism | interaction b/t filtrate flow through loop of Henle (countercurrent multiplier) and flow of blood through vasa recta (countercurrent exchanger)
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| Countercurrent multiplication—loop of Henle | vasa recta prevents loss of medullary osmotic gradient—equilibrates w/ interstitial fluid; maintains osmotic gradient, delivers blood
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| Descending loop of Henle | relatively impermeable to solutes; highly permeable to water
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| Ascending loop of Henle | permeable to solutes; impermeable to water
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| Collecing ducts of deep medullary region | permeable to urea
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| Countercurrent multiplier and exchange | medullary osmotic gradient; H20ECFvasa recta vessels
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| Formation of concentrated urine | ADH inhibits diuresis; equalizes osmolarity of filtrate, interstitial fluid; presence of ADH99% filtrate water reabsorbed; ADH is signal to produce concentrated urine; kidney ability to respond depends on high medullary osmotic gradient
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| Facultative water reabsorption | ADH dependent water reabsorption
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| Formation of dilute urine | diluted in ascending loop if ADH not secreted; created by allowing filtrate to continue into renal pelvis; collecting ducts remain impermeable to water—no further water reabsorption occurs; Na and selected ions removed via active/passive mechanisms
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| ADH mechanism action | formation of water pores; ADH dependent water reabsorption is called facultative water reabsorption
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| Renal clearance | volume of plasma that is cleared of a particular substance in a given time; =UV/P; U = conc mg/ml of certain substance in urine; v = flow rate of urine (ml/min); P = conc of same substance in plasma
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| Renal clearance tests | used to determine GFR, detect glomerular damage, follow progress of diagnosed renal disease
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| Creatinine clearance | amount of creatinine in urine, divided by concentration in blood plasma, over time. UcreatininV/Pcreatinine
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| Glomerular filtration | can be calculated by measuring any chemical that has a steady level in the blood, and is filtered but neither actively absorbed or excreted by the kidneys; creatinine fulfills these requirements and is produced naturally by the body
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| Inulin | freely filtered @ glomerulus & neither reabsorbed/secreted; therefore its clearance measures GFR; substances filtered and reabsorbed will have lower clearances than inulin (Ux¯); substances filtered and secreted have greater clearances than inulin (Ux)
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| PAH | freely filtered at glomerulus; most of remaining PAH actively secreted into tubules so that >90% plasma is cleared of its PAH in one pass through kidney; can be used to measure plasma flow through kidneys (renal plasma flow)
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| Excretion | all filtration products not reabsorbed; excess ions, H20, molecules, toxins, excess urea, “foreign molecules,” kidneyureterbladderurethraout of body
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| Characteristics of urine | color and transparency; yellow due to urocrhome; concentrated = deep yellow; drugs, vitamin supplements, diet, can change color of urine; cloudy urine may indicate UTI
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| pH of urine | slightly acidic (pH 6); diet can alter pH
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| specific gravity of urine | ranges from 1.001 to 1.035; dependent on solute concentration
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| Chemical Composition of Urine | 95% water, 5% solutes; Nitrogenous wastes include urea, uric acid, & creatinine; Other normal solutes--Na, K, phosphate, and sulfate ions, Ca, Mg, and HCO3 ions; Abnormally high concentrations of urinary constituents may indicate pathology
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| Micturition | from kidneys, urine flows down ureters to bladder (peristalsis); fills bladder; contraction of detrusor muscle empties bladder; greater volumes stretch bladder walls—initiate micturition reflex
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| Micturition reflex | spinal reflex; Psymp stimulation causes bladder to contract; internal sphincter opens, external sphincter relaxes due to inhibition
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