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Physiology-Renal
Block 3
219
Medical
Graduate
02/09/2009

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Term
responsibilities of the kidney
Definition
1. elimination of waste products; 2. filter blood with end product being urine; 3. return useful substances to blood (water and salts); 4. role in regulation of blood pressure and synthesis and secretion of hormones
Term
steps in formation of urine
Definition
1. filtration of plasma; 2. resorption and secretion of various substances-when body requires water nascent urine is concentrated and urine is dilute when the body is well hydrated
Term
medullary pyramids
Definition
macroscpically visible conical structures with wide base next to cortex and apex facing region of renal pelvis
Term
renal columns (of Bertin)
Definition
cortical material that lies between adjacent pyramids where major divisions of blood vessels lie
Term
look of medulla and cortex in gross specimens
Definition
the cortex has a granular appearance (due to presence of renal corpuscles) and the medulla has a striated appearence to it (parallel arrangements of tubules)
Term
cortical labyrinth (pars convoluta)
Definition
characterized by content of renal corpuscles and sections of proximal and distal convoluted tubules and arched collecting ducts
Term
medullary rays (pars radiata)
Definition
contain proximal and distal straight tubules and collecting ducts which are aligned parallel to each other and continue into the medulla
Term
kidney lobe
Definition
a medullary pyramid the cortex that overlies it and one-half of a renal column on each side
Term
kidney lobule
Definition
centered on a medullary ray and has one-half of the cortical labrynth on each side; starts at an interlobular artery and ends at the next interlobular artery
Term
renal corpuscle
Definition
proximal end of the nephron and consists of the two-layered Bowman's capsule into which the glomerulus is indented
Term
parietal layer of the Bowman's capsule
Definition
simple squamous epithelium and is contunuity with the next portion of the nephron, the proximal convuluted tubule
Term
urinary space
Definition
space between the visceral and parietal layers of Bowmans capsule
Term
blood supply of the renal corpuscle
Definition
blood enters through afferent arteriole-capillary network of the glomerulus-efferent arteriole
Term
capillaries of glomerulus
Definition
are fenestrated and lack diaphragms
Term
parts of Henle loop
Definition
proximal straight tubule, thin limb, and distal straight tubule
Term
glomerular filtrate
Definition
ultrafiltrate of blood enters the urinary space and flows into proximal convuluted tubule; modified as it passes through each successive section of the nephron; and renal corpuscles occur only in the pars convoluta of the cortex
Term
characteristics of proximal convoluted tubule
Definition
longest segment of the nephron and lined by simple columnar epithelium that have well developed microvillar border and extensive basolateral infoldings and associated mitochondria; substances are absorbed and secreted by this segment
Term
thin limb
Definition
has descending and ascending portions and is lined by a thin simple squamous epithelium and is part of loop of Henle
Term
responsibility of loop of Henle
Definition
retention of the water by the body; mostly occurs in medulla but sometimes remains in the cortex
Term
distal convoluted tubule
Definition
continuity with distal straight tubule of loop of Henle; reaches its parent renal corpuscle and passes between afferent and efferent arterioles; lined by simple cubodial that lacks brush border but has extensive basolateral infoldings and secretes and absorbs ions
Term
macula densa
Definition
senses salt concentration in forming urine and may influence the release of renin by JG cells
Term
collecting duct
Definition
where neprhon empties into and is part of medullary ray and composes along with nephron the uriniferous tubule; functions in formation of concentrated urine; lined by pale-staining simple cubodial to columanar epithelium
Term
podocytes
Definition
perch above capillaries and have long (primary) processes from which extend pedicels that surround the capillaries and these pedicels interdiitate with other pedicels of podocyte
Term
filtration slit
Definition
space between adjacent pedicels and closed by thin diaphragm; the basement membrane seperates the processes and pedicels from the endothelial cells
Term
size and characters of filtrate
Definition
blood cells and substances with a radius greater than 4nm of mass of 70kDa remain in capillary lumen and negatively charged molecules fail to be filtered
Term
basement membrane of renal corpuscle
Definition
anchored to surrounding cells and its dense layer contatins collagen type IV and negatively charged proteoglycans; plasma passes through electron lucent layer (lamina rara) then electron dense layer (lamina densa) then lamina rara again and then the diaphragm of the filtration slitto reach urinary space
Term
mesangial cells
Definition
present in the glomerulus which are contractile and can carry out phagocytosis and may help keep basement membrane of filtration barrier clean
Term
ultrafiltrate in the proximal convoluted tubule
Definition
where all glucose, amino acids and 85% of NaCl are resorbed via active Na/K ATPase process; and 85% of water passively flows out in response to the osmotic gradient created; protein also taken into the PCT cells by pinocytosis; also PCT cells secrete waste materials into ultrafiltrate
Term
urine in distal convoluted tubules
Definition
H+ and ammonium ions are secreted into the urine and inpresence of aldosterone, Na is actively absorbed and K is secreted
Term
juxtaglomerular cells
Definition
present in media of afferent arteriole that are smooth muscle cells that synthesize and secrete renin
Term
renin
Definition
involved in the conversion of angiotensinoggen to angiotensin I which in turn is converted to angiotensin II causing adrenal cortex to release aldosterone which acts to bring about sodium and water retention expanding volume of fluid in blood vessels
Term
arteries to the kidney
Definition
renal artery branches into interlobar arteries which lie between renal lobes that give rise to arcuate arteries located between cortex and medulla which send interlobular arteries into the cortex where they lie between lobules (veins accompany arteries)
Term
efferent arteriole
Definition
can drain into peritubular capillary network or form the vasa recta
Term
peritubular capillary network
Definition
happens when parent renal corpuscle is not near the cortico-medullary junction representing an arterial protal system
Term
vasa recta
Definition
if parent renal corpuscle is located near the cortico-medullary junction the efferent breaks up into a network of capillaries that enter the medulla as long parallel vessels
Term
characteristics of ureters
Definition
paired, fibromuscular tubes the convey urine from kidneys to the bladder; has three layers: mucosa, muscularis, and adventitia
Term
ureter mucosa
Definition
consists of transitional epithelium and underlying lamina propria and typically thrown into fold
Term
ureter muscularis
Definition
has two layers of smooth muscle inner longitudinal and outer circular in the upper portion and as approaches the bladder gains an outer longitudinal layer; adventitia consists of fibroelastic connective tissue
Term
bladder characteristics
Definition
has mucosa (transitional epithelium and underyling lamina propria), muscularis (three layers of smooth muscle) and a fibrosa and a serosa
Term
ECF volume regulation
Definition
essential for long-term maintainance of blood pressure and involves regulation of total body Na content
Term
ECF osmolarity regulation
Definition
essential for maintainance of cell volume involves regulation of total body water content
Term
distribution of water
Definition
occurs within in cells (ICF) outside of cells (ECF includes plasma volume and interstitial fluid volume) also within bone and connective tissue and transcellular compartments
Term
% contribution of total body water to body weight
Definition
varies from 40% to 70% and affected by age, gender, and body fat (major factor); the contribution to lean body mass is 73%
Term
normal distributions of hydrated adult
Definition
1. 2/3 of body water is contained in the ICF; 2. 1/3 of body water contained within ECF (75% of ECF is interstitial fluid and 25% is plasma water)
Term
calculation of volume of distribution of body fluid
Definition
done by dye dilution: small amoutn of marker introduced into the body and allowing suitable time for mixing and volume can be calculated using equation: Volume=(Qadded-Qlost)/Cmarker
Term
determination of particular compartments using dye dilution
Definition
1. total body water can be used using tritiated water; 2. ECF can be measured using radioactive sulfate of inulin; 3. plasma fluid volume measured using radioactive albumin or Evans blue dye
Term
determination of blood volume
Definition
BV=plasma volume/(1-hematocrit); hematocrit=RBC volume/total blood volume)
Term
normal values for Na, K, HCO3-, Creatinine, BUN, Cl
Definition
Na-142(135-145); K-4.4(3.5-5.0); HCO3-22 arterial and 24 venous; creatinine-0.7-1.4; BUN-10-20; Cl-102(95-105)
Term
terms that can express the concentration of solutes
Definition
millimolar (mM=mmol/L), millimolal (mmol/KgH2O), milliequivalent (mEq=6x10^20 charges), milliosmole (mOsmol=6x10^20 particles), milliosmolar (mOsmolar=mOsmol/L), milligram/100mL
Term
anion gap
Definition
difference between the sodium concentration and the sum of the bicarbonate and chloride concentrations
Term
normal values of anion gap
Definition
usually between 9-14 mEq/L and composed of lesser anions such as sulfate, phosphate, and ketoacids; in diseased states concentration of ketoacids may increase causing concentration of bicarbonate to decrease and anion gap increases
Term
osmolarity of ECF
Definition
can be estimated by doubling the sodium concentration and when glucose of BUN is highly than normal can be calculated by =2xNa+glucose(mg%)/18+Urea(BUN)/2.8
Term
effective osmoles
Definition
particles that are unable to cross the membrane and which concentration calculated as tonicity important in determining the steady-state change in fluid distribution between ICF and ECF
Term
effect of ingesting excess salt
Definition
NaCl is ingested and absorbed into the ECF and raises osmolarity of ECF and water flows from the ICF to ECF until the osmolarities of two compartments are equal
Term
effect of ingestion of water only
Definition
ingested water enters the ECF reducing osmolarity of the ECF and waters flows from ECF to the ICF to make the osmolarities equal
Term
filtration fraction
Definition
fraction of plasma flowing through the glomerulus that is filtered into the Bowman's space can be changed by altering components of the Starling equation by changing the relative diameters of afferent and efferent arterioles (normally 20% in normal humans)
Term
tubuloglomerular feedback
Definition
glomerulus is able to regulate its filtration rate in response to tubular flow rate and ionic composition of tubular fluid by causing contraction by release of solutes from macula densa and cause afferent arteriole constriction
Term
glomerular filtration rate
Definition
volume of fluid filtered across all the glomerular capillaries per min (this is autoregulated) by changes in the afferent and efferent arteriolar resistance
Term
measurement of GFR and RBF
Definition
inulin used and is filtered across capillary wall and not metabolized or transported across the tubules and equals the amount filtered=amount excreted; and the amount of inulin filtered=plasma concentration x GFR and the amount of inulin excreted=urine conc of inulin x urine volume
Term
clearance equation
Definition
for substances that are freely filtered by not secreted, reabbsorbed, or metabolized clearance X=((X)u*V)/(X)p equals the volume of plasma/min that wouldhave to be completely cleared of the substance to produce the amount excreted in the urine
Term
clearance of substances that are reabsorbed
Definition
the clearance will be less than the GFR and the amount leavin equals T(amount leaving) + amount excreted in the urine
Term
cleareance of substances that are secreted
Definition
will be greater than the GFR the T (secretion) will be added to the amount filtered
Term
renal plasma flow (RPH)
Definition
use PAH since almost all of it is cleare from the plasma that enters the kidney and is excreted in the urine RPF=((PAH)u*V)/(PAH)p
Term
definition of flitration
Definition
movement of water and solutes from blood (glomerular capillaries) to kidney tubules (Bowman's space)
Term
definition of reabsorption
Definition
movement of water and solutes from kidney tubules to blood (peritubular capillaries)
Term
definition of solutes
Definition
movement of solutes from blood (peritubular capillaries) to kidney tubules
Term
definition of excretion
Definition
equals filtration-reabsorption+secretion or E=FL-R+S
Term
movement of water is reabsorption
Definition
moves passively by osmosis and not by an active transport but often follows the movement of solutes that are being actively transported
Term
locations and percentages of reabsorption of Na
Definition
1. most occurs in the proximal tubule (67% of filtered load) but not where regulation takes place; 2. thick ascending limb of loop of Henle (25% of filtered Na); 3. distal convoluted tubule(5% of filtered Na); 4. collecting duct (under hormonal control; 3% of filtered Na)
Term
balance of Na reabsorption
Definition
achieved by regulation of reabsorption in collecting ducts; when conserving Na kidneys reabsorb 99.5% of filtered Na; when trying to reduce Na content of body, kidneys reabsorb 98% of filtered Na
Term
reabsorption of Na in proximal tubule
Definition
about 2/3 of Na is reabsorbed here along with almost all of the glucose and amino acids; glucose and amino acid reabsorption is link to Na reabsorption; also 2/3 of water is absorbed as well
Term
characteristics of proximal tubule histology
Definition
epithelial cells are polarized cells with apical and basolateral surfaces, there are tight junctions between adjacent epithelial cells; also has basolateral spaces and basement membranes with Na/K pumps on basolateral surfaces; have aquaporins-AQP1 present on all surfaces but not affected by ADH
Term
process of ion movement/water movement in proximal tubule
Definition
low Na in cells and Em is negative so electrochemical gradient for Na into cell is large and Na enters cells via channels, leaks, co-transporters or exchangers and Cl follows to maintain electroneutrality and Na is pumped out of epithelial cells by Na/K pump into basolateral spaces and Cl follows for electroneutrality and some Cl goes through tight junctions and H2O follows as well either through tight junctions or through cells and then into the basolateral spaces
Term
osmolarity of fluid leaving proximal tubule
Definition
isotonic and Na conc hasnt changed there is just less fluid because the fluid that crosses the basement membrane and reabsorbed into the peritubular capillary blood is also isosmotic and isotonic
Term
mechanisms for Na to enter the proximal tubule epithelial cells
Definition
1. Na, glucose cotransport (1:1 and 2:1); 2. Na, amino acid cotransport; 3. Na, H exchange (part of process of bicarbonate reabsorption) with angiotensin-II stimulating Na, H exchange
Term
paracellular route of NaCl movement
Definition
movement through tight junctions occuring in late proximal tubule; because in first part of proximal tubule HCO3 is rapidly reabsorbed and Cl remains behind causing an increase in Cl conc to 120mM that causes a gradient from tubular fluid to the ISF and Cl diffuses through the tight junctions and Na follows the Cl because of electroneutrality
Term
reabsorption of Na with Cl by transcellular route
Definition
occurs in late proximal tubule uses the Na/H exchanger and Cl/formate exchanger to move Na and Cl into the cell and Na pumps move Na into the basolateral spaces and Cl leaves the cell through channels; the formate ion in lumen combines with H to make formic acid which diffuses back into the cell to dissociate into H and formate
Term
Na reabsorption in the thick ascending limb of loop of Henle
Definition
reabsorbs about 20-25% of filtered load of Na; Na enters by a Na,K,2Cl co transporter; cotransporter is electroneutral but K channels on apical surface of membrane and K leaks back into the tubular lumen creating a lumen-positive tranepithelial voltage difference (stimulated by ADH and vasopressin)
Term
effect of lumen-positve transepithelial voltage difference
Definition
drives reabsorption of other cations including Ca
Term
Lasix
Definition
diuretic that inhibits Na,K,2Cl cotransporter and prevents reabsorption
Term
Na reabsorption in distal convoluted tubule
Definition
reabsorbs about 5% of filtered load of Na and no water is reabsorbed here and tubular fluid becomes more dilute; uses a Na, Cl cotransporter
Term
thiazide
Definition
diuretic that block Na,Cl cotransporter of distal convoluted tubule
Term
Na reabsorption of collecting tubules and collecting ducts
Definition
principal cells reabsorb about 3% of filtered load; location of sodium reabsorption regulation and Na enters through an apical Na channel (electrogenic uses Na electrochemical Na gradient making urine with Na as low as 5mEq/L)
Term
regulation of Na reabsorption at collecting tubules and collecting ducts
Definition
aldosterone increases sodium reabsorption and atrial natriuretic factor (ANF) decreases sodium reabsorption
Term
amiloride and spironolactone
Definition
diuretics that inhibit sodium channels and reabsorption in collecting ducts/tubules
Term
mechanism of aldosterone
Definition
increases Na reabsorption by increasing the number of functional Na channels by increaseing open time of channel, increase number of channels inserted in membrae and also increase ability of cell to produce ATP
Term
interstitial fluid osmolarity
Definition
in cortex is about 300mOsm but in deepest part of medulla its about 1200mOsm with smooth gradient and fluid leaving the DCT has low osmolarity (100mOsm) and as fluid flows through collecting ducts water wants to leave tubular fluid by osmosis to enter ISF and amount of water reabsorbed depends on how many AQP2 type aquaporins are inserted that depends on the ADH concentration
Term
effect of TAL on osmolarity gradient
Definition
reabsorbs abour 20-25% of Na but does not absorb any water making the tubular fluid dilute and interstitial fluid salty also known as the diluting segment
Term
urea recycling
Definition
as water is reabsorbed in proximal tubule the urea remains behind and becomes more concentrated in tubular fluid and diffuses down its conc gradient from proximal tubular fluid to the ISF then to the peritubular capillary blood, descending limb is permeable to urea so tubular fluid equilibriates with ISF; the ascending limb, DCT, and cortical collecting duct and outer medullary collecting ducts are impermeable to urea so it remains in the tubule; if ADH is present water can be reabsorbed but urea stays in tubular fluid and becomes more concentrated than the ISF; inner medullary collecting duct is permeable to urea and because the tubular fluid has higher urea concentration than ISf the urea diffuses out into the ISF or inner medulla
Term
role of ADH on urea recycling
Definition
increases the permeability of inner medullary collecting ducts as well as water permeability so more urea leaves tubular fluid increasing the osmolarity of the ISF
Term
why is osmolarity of medulla highest at the innermost part of the medulla
Definition
urea is only reabsorbed from the last part of the collecting duct and is added to the ISF of the innermost part of the medulla
Term
parts of urinary system that develop from intermediate mesoderm
Definition
kidney and ureter
Term
parts of the urinary system that develops from urogenital sinus
Definition
bladder and urethra; bladder also develops in part from allantois
Term
kidney development
Definition
originally as pair of structures located in cervical and thoracic region of the developing embryo; originally organized as cords first kidney established is the pronephric kidney
Term
pronephric duct
Definition
series of cords of cells that grow dorsally and laterally and lateral ends open and grow caudally linking together to form this duct and it continues to grow caudally plays important role in development of mesonephric kidney
Term
mesonephric kidney
Definition
arises as another series of tubules that form from intermediate mesoderm and dorsal aorta give rise to tuft of blood vessels that come in contact with the intermediate mesoderm called the glomerulus and tubules that surround the glomerulus elongate and laterally form the mesonephric duct
Term
urogenital bulge
Definition
growth of mesonephros causes a bulge of intermediate mesoderm into the coelomic cavity from the lower cervical to upper lumbar levels
Term
ureter bud
Definition
diverticulum that arises from the mesonephric duct that grows caudally and reaches and empties into the cloaca then the ureter bud grows cranially and contacts the intermediate mesoderm
Term
metanephrogenic blastema
Definition
cap of mesoderm cells that surround the ureter bud and the ureter bud divides many times to give rise to the pelvis of the kidney, the major and minor calyces and the collecting tubules; metanephrogenic blastema becomes cords of cells which eventually give rise to tubules that will be the nephron
Term
distinct developmental structures of the kidney
Definition
1. nephron; 2. collecting system from the arched collecting ducts to the ureter; 3. the glomerulus
Term
location of glucose reabsorption
Definition
only occurs in the proximal tubule and only can absorb a certain amount per minute
Term
transport maximum (Tm)
Definition
similar to Vmax of enzyme kinetics and there is a different one for each solute and when all transporters are saturated the rate cannot be increased by increasing the concentration difference
Term
subtance being filtered is above the Tm
Definition
if exceeds this value then the substance will appear in the urine
Term
filtered load
Definition
amount of any solute being filtered into the tubules in a given time; product of GFR*[solute}
Term
glucose as filtered solute
Definition
the Tm for glucose=375mg/min and in hyperglycemia the filtered load of glucose exceeds the Tm and glucose is excreted
Term
renal plasma threshold
Definition
plasma concentrations at which solute begins to appear in the urine; for glucose reaches 200mg/dL
Term
osmotic diuretic
Definition
if glucose is not completely reabsorbed in the proximal tubule and remains in the tubular fluid; presence increases the urine flow rate which can lead to dehydration and loss of electrolytes
Term
mechanism for glucose reabsorption
Definition
enters epithelial cells by secondary active transport coupled with the reabsorption of Na and be transported uphill from the energy in Na going down its electrochemical gradient
Term
SLGT glucose transporters
Definition
SGLT2 is 1Na/1glucose cotransporter in early proximal tubule (100:1 glucose concentration gradient); SLGT1-2Na/1glucose cotransporter in late proximal tubule (10000:1 gradient); once in the cell glucose leaves the cell and enters BL space via facilitated diffusion by GLUT transporters
Term
trans-epithelial electrical potential
Definition
exists in different parts of the nephron where the tubular fluid in the lumen is a few mV negative to the interstitial fluid in some places and a few positive in other places
Term
electrical potential in early proximal tubule
Definition
lumen is 4mV negative because of the electrogenic Na/glucose cotransport leaving anions
Term
late proximal tubule and thick ascending limb electrical potential
Definition
lumen is 4mV positive because of Cl diffusing from tubular fluid to ISF down concentration gradient
Term
importance of phosphate
Definition
for bone, as a buffer in ECF, as a urinary buffer, and chemistry is intertwined with that of Ca
Term
excretion of phosphate
Definition
binds to Ca and forms complexes if too high it binds too much Ca lowering the free Ca concentration about 80% of filtered load is reabsorbed in proximal tubule by Na dependent cotransporter and remainder excreted in urine where is acts as a urinary buffer
Term
role of parathyroid hormone in phosphate reabsorption
Definition
inhibits phosphate reabsorption and is secreted in response to low plasma Ca concentration
Term
importance in maintaining normal Ca concentrations
Definition
for cardiac muscle, excitability of skeletal and nerve, and bone
Term
Ca in plasma
Definition
much is bound to other solutes and is not free and reported as milligrams total Ca per deciliter (normally 10mg/dL) about 40% bound to plasma proteins another 10% to anions like phosphate; plasma pH affects binding of Ca to plasma proteins and phosphate
Term
Ca in plasma
Definition
much is bound to other solutes and is not free and reported as milligrams total Ca per deciliter (normally 10mg/dL) about 40% bound to plasma proteins another 10% to anions like phosphate; plasma pH affects binding of Ca to plasma proteins and phosphate
Term
reabsorption of Ca
Definition
Ca is reabsorbed passively by diffusion in same places and in same proportion as Na and regulation of reabsorption takes place in distal convoluted tubule occurs through apical Ca channels and transport across BL cell surfaces to ISF by Na/Ca and Ca ATPase pumps
Term
hormonal regulation of Ca reabsorption
Definition
occurs in distal convoluted tubule; low plasma concentration of Ca increase parathyroid hormone secretion and PTH increases Ca reabsorption from distal tubule
Term
reabsorption of Mg
Definition
passive paracellular route driven by lumen-positive voltage difference occurs in thick ascending limb (60% of FL) and lesser amounts reabsorbed by proximal tubule and distal tubule
Term
secretion
Definition
transport of a substance into the tubular fluid from the peritubular capillary blood allows substance to be removed from the ECF rapidly (H,K, and drugs and toxins)
Term
plasma K concentration
Definition
normally about 4.5 mM and kept in narrow range (3.5-5.0); if too high can cause cardiac arrect, decreased excitability or muscle and nerve; if too low can cause decreased excitibility of muscle and nerve and metabolic alkalosis; most (98%) of bodys K is in cells but shifts of K into ECF can cause serious problems
Term
control of K concentration
Definition
rapid buffering of ingested K by uptake into all cells stimulated by insulin and B-adrenergic agonists; K is filtered most is reabsorbed and plasma concentration is regulated by secretion into tubules
Term
K reabsoprtion
Definition
in proximal tubule is passive following Cl (67% of FL); in thick ascending loop of Henle Na/K/2Cl cotransporter on apical surface (20% of FL)
Term
balance of K in kidney tubules
Definition
some K channels on apical surface so some K leaks back into lumen creating positive electrical potential difference; K can also be reabsorbed by distal tubule and can be reabsorbed by intercalated cells of collecting ducts; with normal amount of K in diet balance is acheived through secretion
Term
principal cells in collecting ducts
Definition
secrete K by apical K channels and aldosterone increases K secretion by increasing Na reabsorption and making lumen more negative to have more K flow out of cells and high plasma K directly stimulates adrenal cortex to secrete aldoseterone and causes increased K secretion
Term
ECF osmolarity
Definition
regulation depends on receptors located in the hypothalamus to adjust total body water content
Term
water balance regulation
Definition
regulated and maintained by changes in water excretion (ADH) and water intake (thirst)
Term
ECF volume
Definition
depends upon sensors that reflect the adequacy of circulation-effective circulating blood volume
Term
Na balance
Definition
regulated by neural, hormonal, and hemodynamic factors with short term effects to maintain MBP and long term effects for Na excretion
Term
osmoreceptors
Definition
ECF osmolarity monitored by these located in the hypothalamus and changes in osmolarity are accopanied by changes in cell volume producing changes in plasma ADH levels
Term
effects of changes in osmolarity in osmoreceptors
Definition
increase in ECF osmolarity the osmoreceptors shrink and increase ADH plasma concentration and decrease ECF osmolarity the opposite occurs
Term
ADH synthesis
Definition
synthesized by neurons within the suproptic and paraventricular nuclei of the hypothalamus and stored and released from the posterior pituituary gland
Term
threshold of osmolarity for thirst and maximum ADH
Definition
threshold for release is 280mOsmol/L and maximum release occurs at 290-295 mOsmol/L
Term
action of ADH
Definition
promotes water reabsorption by increasing water permeability in late distal convoluted tubule and collecting ducts; increasing Na-2Cl-K cotransport in thick ascending limb resulting in increase in osmotic gradient between medullary interstitium and collecting duct tubular filtrate; increasing urea reabsorption from inner medullary collecting ducts adding to osmotic gradient
Term
cause of polyuria with ADH
Definition
inability to release ADH from the hypothalamus and inability of kidney to respond to ADH; diabetes inspipidus
Term
ADH secretion in response to decreases in MBP and blood volume
Definition
activation of carotid baroreceptor reflex includes stimulation of hypothalamic paraventricular nuclei and increase in ADH; low pressure baroreceptors in left atrium and pulmonary vessels mediate an increase in ADH in response to decrease in blood volume
Term
changes in MBP and osmolarity to increase plasma ADH
Definition
decrease in MBP/blood volume required to produce and increase in plasma ADH is 10-15% and for decrease in osmolarity is only 1%; amount released is greater in response to change in pressure/volume
Term
factors that affect plasma ADH levels
Definition
1. pain and nausea-increase; 2. stress-increase; 3. infection-increase; 4. nicotine-increase; 5. alcohol-inhibits release
Term
osmolar clearance
Definition
part of urine that is the volume necessary to excrete solute at the same concentration as the plasma
Term
free water
Definition
volume of solute free water that must added/subtracted to the Cosm to account for the actual urine volume
Term
estimation of urine osmolarity
Definition
2*(Na+K)
Term
free water clearance
Definition
Ch2o=V-Cosm and is quantitive measure of how kidneys handle water when positive the urine osmolarity is less than the plasma osmolarity return body osmolarity towards normal values; when negative urine osmolarity is greater than plasma osmolarity and water is being conserved; and when zero urine osmolarity equals plasma osmolarity and kidney not excreting or conserving water
Term
ECF volume regulation
Definition
requires the maintainance of total body sodium; steady state the intake of sodium equals the daily loss of sodium and changes in intake of sodium do not effectECF osmolarity because ADH/thirst mechanisms quickly reestablish the osmolarity to normal
Term
changes in sodium intake
Definition
causes a change in ECF volume and the change in ECF volume is sensed and leads to changes in sodium excretion
Term
factors in delivery of sodium to the nephron
Definition
this is the filtered load and depends on the GFR and plasma Na concentration
Term
factors determining reabsorption of Na in proximal tubule
Definition
1. starling forces surround the nephron; 2. concentration of circulating hormones that influence proximal tubular sodium reabsorption; 3. activity of sympathetic nerve fibers innervating the proximal tubule
Term
factors determining the sodium reabsorbed in the distal nephron
Definition
aldosterone and ANP and there is about 10% of FL of sodium that is reabsorbed in distal nephron
Term
receptors that detect the effective circulating blood volume
Definition
measures the amount of sodium within the plasma and these receptors are sensitive to stretch and are located in 1. renal afferent arterioles; 2. artria and pulmonary vessels (volume); 3. carotid sinus and aortic arch (pressure)
Term
release of renin
Definition
released from the JGA cells in response to 1. reduced renal perfusion pressure causing reduced stretch of afferent arteriolar wall; 2. norepinephrine activating B-receptors on the juxtaglomerular cells; 3. stimulation of macula densa by decreased salt concentration within the ascending limb of the loop of henle
Term
formation of angiotensin II
Definition
renin converts angiotensinogen to angiotensin I which is converted to angiotensin II by angiotensin converting enzyme found within the pulmonary and glomerular endothelial cells
Term
function of angiotensin II
Definition
stimulates sodium reabsorption by proximal tubule by increasing activity of Na-H antiporter; stimulates adrenal cortex to synthesize and release aldosterone; produces contraction of afferent and efferent arterioles and efferent contraction is greater so GFR is maintained even though RBF is decreased
Term
function of aldosterone
Definition
increases Na reabsorption by principal cells of the collecting tubules; increases K secretion from the principal cells of the collecting tubules (also released from adrenal cortex in response to K concentration above 3.5 mEq/L
Term
atrial natriuretic peptide
Definition
synthesized and released from the cardiac muscle cells of both right and left atria; released when increase in blood volume stretches the atria; decreases Na reabsorption by the inner medullary collecting tubules
Term
ways in which ANP may promote excretion of Na
Definition
1. decreasing renin release; 2. inhibiting effect of angiotensin on aldosterone release and Na reabsorption; 3. inhibiting the effect of ADH on water reabsorption
Term
increase of sympathetics to the kidney
Definition
due to low pressure receptors in right atrium that respond to low blood volumes; high pressure receptors in the carotid sinus and aortic arch respond to low blood pressures; and environmental stimuli such as stress and nausea
Term
effect of increased sympathetics to the kidney
Definition
increases Na reabsorption from proximal tubule, loop of Henle, and collecting duct via alpha1 receptors; stimulates renin production by the juxtagomerular granular cells; and produces renal vasoconstriction
Term
integration of reduction in blood volume
Definition
reduces CO and MBP and renal blood flow; activates baroreceptors reflexes-decreased PS and increased SS causing increased HR, increased ventricular contractility, increased arteriolar constriction (TPR) and increased venoconstriction causing increased preload; increased sympathetic to nephron increasing Na reabsorption from proximal tubule and increased renin from JGA; increased release of arginine vasopressin (ADH) increasing reabsorption of water from collecting ducts and increased TPR
Term
effect of activating low blood pressure baroreceptor reflexes
Definition
same response as high pressure baroreceptors but also reduction in the release of ANP resulting in increased reabsorption of Na from the inner medullary collecting ducts
Term
effect of reduced renal flow
Definition
stimulation of afferent arteriole baroreceptors causing release of renin from JGA; and decreased concentration of Na in the luminal fluid at the end of the loop of Henle which stimulates the macula densa which stimulates the release of renin from JGA
Term
volatile acid
Definition
CO2 only one produced and carbonic acid is in equilibrium with CO2 and 12000-24000 mmol per day are produced from metabolism; relativly weak acid and excreted in the lungs if cannot eliminate properly the CO2 concentration in the body rises and body fluids become more acidic
Term
non-volatile acids
Definition
aka fixed acids, are all other acids except CO2 about 70-100 mmols are produced each day; are strong acids and eliminated by kidneys by producing acidic urine; also form of acidity is the loss of alkalinity through normal bicarbonate secretion in the colon or if kidney function is inadequate
Term
mechanisms to preserve pH when acids or bases are introduced
Definition
1. buffering (very fast but limited); 2. respiratory adjustments (few seconds); 3. renal adjustments (slow, may take few days)
Term
normal values of acidity for body fluids
Definition
ECF are normally slightly alkaline (arterial pH is 7.40) normal arterial plasma H conc is 40 nM
Term
acidemia
Definition
when plasma pH is less than 7.4 or H more than 40nM
Term
alkalemia
Definition
plasma pH is greater than 7.4 or H is less than 40nM
Term
extracellular buffers
Definition
major one is bicarbonate and also have plasma proteins and phosphate but are relatively unimportant and have bone as a reservoir in renal failure patients
Term
intracellular buffers
Definition
organic phosphates, intracellular proteins, and hemoglobin in RBC and very important intracellular buffer
Term
control of acid-base balance
Definition
status can be determined by the bicarbonate/CO2 buffer system where [H]=24*PCO2/[HCO3]
Term
control of PCO2
Definition
job of the respiratory system and keeps it at 40mmHg at high altitudes the PCO2 may decreae and in diseased states respiratory system may not be able to elimnate CO2 well enough
Term
control of plasma HCO3
Definition
role of the kidneys to reabsorb all of the bicarb filtered into the tubules and replacing the bicarb that was used elsewhere in the body when it buffered fixed acids and for each new bicarbonate made a H+ is excreted in the urine
Term
Na/H exchanger
Definition
transport mechanism to keep intracellular pH around 7 and not 6.4
Term
carbonic anhydrase
Definition
enzyme that accelerates CO2 combining with H2O; and is such that there is 500 times more CO2 than H2CO3 in body fluids and dissolved CO2 in blood is in equilibrium with alveolar CO2
Term
carbonic acid pool
Definition
consists of H2CO3 and the dissolved CO2 since H2CO3 is only a trace it is considered to be the dissolved CO2
Term
Henderson equation
Definition
relates H PCO2 and HCO3-; written as H=800*10^-9*[CO2]/[HCO3-]; H=800*10^-9*[0.03*PCO2]/[HCO3-]; or H(nmol)=24*PCO2/[HCO3-]
Term
Henderson-Hasselbalch equation
Definition
uses logs and gives pH and pH=pKa+log[HCO3-]/[CO2]; or pH=pKa+log[HCO3]/[0.03*PCO2]; with the pKa is the 6.1 and ratio of HCO3-/CO2 is usually 20:1 (24mM:1.2mM)
Term
isohydric principle
Definition
all the buffer systems in fluid compartment are in equilibrium with the same H concentration and status of other buffer systems can be calculated from bicarbonate and CO2 concentrations
Term
buffering by the bicarbonate system
Definition
fixed acid is being buffered by bicarbonate and consumes bicarb in a 1:1 ratio and if NaOH is added the amount of bicarb increases; kidneys replace bicarb that is used up by buffering daily fixed acid production
Term
increasing CO2 with only bicarb as buffer
Definition
does not change bicarb concentration and doubling PCO2 will double the H concentration
Term
effectiveness of bicarbonate
Definition
it is present in high concentrations in the extracellular fluid; respiratory system eliminates CO2 that is generated when HCO3- buffers fixed acids and keeps PCO2 at a constant level
Term
buffering of volatile acids by non-bicarbonate buffers
Definition
when both buffers are present adding more CO2 increases the HCO3- concentration
Term
non-bicarbonate buffer curve
Definition
primarily the hemoglobin buffer curve and the slope depends on the hemoglobin concentration; CO2 enters RBC forms H2CO3 dissociates and hemoglobin binds H and HCO3- leaves the cell in exchange for Cl- and increases bicarb plasma concentration
Term
buffering of fixed acids by a solution containing both bicarb and non-bicarb buffers
Definition
present in same solution adding more fixed acid causes a decrease in the bicarb concentration and some of the fixed acid is buffered in the ECF and some of the fixed acid is buffered within cells
Term
metabolic acidosis
Definition
addition of excess fixed acid and H of the plasma is increased and H+ is immediately buffered by plasma bicarb and non bicarb buffers of the plasma and red cells and buffering by HCO3 reduces its plasma concentration
Term
movment of H+ in vivo
Definition
after being buffered in the ECF the H+ diffused into the interstitial fluid within 15-30 min and further HCO3- buffering has taken place and H+ moves into the cells and bones more slowly but within 2-4 hours about 50% of added H+ is found within the cells and Na and K move into the ECF; within the cell the H+ is buffered (60% overall and 40% buffered in ECF)
Term
buffering of added volatile acid
Definition
H+ produced by hydration of dissolved CO2 is buffered by hemoglobin and less than 3% by plasma proteins
Term
respiratory acidosis
Definition
when H+ increases due to increased CO2 by hypoventilation and no buffering occurs in the interstitial fluid because no non bicarb buffers found there and CO2 enters the tissues cells where the H+ is buffered by proteins and organic phosphates; so 97% buffered intracellularly
Term
functions of the kidney to maintain acid-base balance
Definition
1. reabsorb HCO3- filtered at the glomerulus; 2. resynthesize HCO3 that was used in buffering fixed acid; 3. secrete H+ into the urine
Term
renal bicarbonate reabsorption
Definition
HCO3 freely filtered at glomerulus and essentially all reabsorbed to maintain plasma concentration; with about 85-90% reabsorbed at the PCT and 10-15% in the distal nephron; carbonic anhydrase inside cells provides H+ for Na+/H+ antiporter and HCO3 leaves cell via basolateral membrane and enters blood (1Na/HCO3 cotransport); carbonic anhydrase on brush border combines secreted H+ and filtered HCO3 to form H2O and CO2 and CO2 freely enters the cell to react with carbonic anhydrase (rapid reaction prevents progressive acidification that would decrease Na/H exchange and decrease HCO3 reabsorption); little net HCO3 synthesize occurs
Term
reabsorption in distal nephron
Definition
type A intercalated cells and reabsorbs about 10-15% of filtered HCO3; similar except that H+ secretion into lumen is via ATPase pump which is electrogenic and not coupled to Na transport and exit of HCO3 is via HCO3/Cl- exchange and no carbonic anhydrase on luminal membrane
Term
parameters relating to HCO3 reabsorption
Definition
amount of HCO3 reabsorbed=amount HCO3 filtered-amount HCO3 excreted in urine; threshold for HCO3 is the plasma concentration of HCO3 where a significant amount of HCO3 first appears in the urine; Tm is maximum rate of HCO3 reabsorption under a given set of conditions and it can change (for whole system not just a specific carrier); normal threshold near plasma concentration of HCO3
Term
factors which modify HCO3 reabsorption (Tm)
Definition
1. factors which acidify the tubular cells-more H+ available for secretion; 2. factors which alkalinize the tubular cells decrease HCO3 reabsorption-less H+ available for secretion; 3. PaCO2-hypercapnia increases HCO3 reabsorption and hypocapnia decreases it; 4. ECF volume-expansion decreases whereas ECF contraction enhances HCO3 reabsorption; 5. potassium-hyperkalemia decreases HCO3 reabsorption and hypokalemia increases HCO3 reabsorption
Term
synthesis of new bicarbonate
Definition
fixed acid destroys about 70mEq/day and CO2 is blown off and kidneys must synthesize 70 mEq/day; occurs when proximal tubule secretes NH4+ that is excreted and distal nephron secretes H+ which binds to titratable acids; so when H+ ion is excreted in urine than the HCO3 generated is "new" bicarb
Term
ways in which H+ is excreted in the urine
Definition
1. as free H+(decreasing pH)-insignifficant; 2. buffered by NH3; 3. buffered by titratable acids (HPO4)
Term
Net acid excretion (NAE)
Definition
equals H+ excreted as ammonium plus H+ excreted as titratable acid plus free H+ minus any HCO3 excreted in the urine; NAE=[U(NH4)*Vu]+[U(TA)*Vu]-[U(HCO3)*Vu]; amount of free H+ is negligible compared to the total H+ excreted and is ignored and the net acid excretion is equal to the net bicarbonate generation
Term
urine pH
Definition
reflection of free hydrogen ion concentration, major factor in determining ammonium ion and titratable acid excretion and changes along the tubules; along the proximal tubule stays high-b/c carbonic anhydrase allows rapid reaction of H+ and HCO3 lumen and little buildup of H+ in lumen High H+ secretory volume (at end of PT=6.4); distal nephron- no luminal carbonic andhydrase high H+ gradient maximum of 1000:1 lowest urine pH of 4.4 low H+ secretory volume
Term
factors affecting urinary pH and H+ excretion in distal nephron
Definition
factors which enhance Na reabsorption enhance H+ secretion and negative potenital in lumen of tubules enhances H+ secretion (due to lag of Cl behind sodium and presence of poorly reabsorbed anion); 3. acid-base status-decreases in intracellular pH to enhance H+ secretion and lower urinary pH; 4. aldosterone-stimulates H+ ion pump in cells of cortical collecting tubule and enhances Na reabsorption
Term
titratable acids
Definition
anions of weak acids can buffer H+ secreted into tubular lumen; quantity of H+ buffered can be measured titrating urine sample with NaOH; phosphate is major titratable acid with minor ones as creatinine, urate, beta hydroxybutyrate, lactate; availability of buffers effects TA excretion because at pH of 4.4 TA only can be increased by the amount of phosphate filtered (depends upon dietary phophate intake)
Term
ammonia
Definition
major urinary buffer and produced in proximal tubular cells mainly from glutamine metabolism and binds H to make NH4+ and when excreted eliminates H+ from body; can be increased to deal with acidosis
Term
chemistry of ammonia
Definition
NH3 is lipid-soluble gas and can diffuse freely through membranes because pKa is 9.2 nearly all is ammonia is present in ammonium ions and this cannot cross membranes easily
Term
production of ammonia
Definition
produced from glutamine in cells of proximal tubule by the enzyme glutaminase; another NH4+ is produced when glutamate is converted to alpha-KG and when alpha-KG metabolized to CO2 and water and 2HCO3 are formed
Term
reabsorption of NH4+
Definition
thick ascending limp of loop of Henle by substitutin for K+ of Na/K/2Cl transporter and once inside the cell exits the BL surface by diffusion of uncharged ammonia; and NH3 and NH4+ accumulate and become more concentrated in the interstitial fluid of medulla
Term
movement of NH3 from medullary interstitium
Definition
from interstitium into the collecting tubules; can diffuse across the walls of the medullary collecting tubules down its concentration gradient and as urine becomes acidified NH3 combines with H+ which is not permeable and is trapped and NH4+ is excreted
Term
control of ammonia excretion and production
Definition
1. urine pH-the lower the pH the more effective the trapping of H+ as NH4+; 2. arterial pH-metabolic acidosis causes an increase in NH3 production; 3. potassium-hypokalemia increases NH# excretion and production and hyperkalemia decreases NH3 exretion and production
Term
renal tubular acidiosis
Definition
metabolic acidosis that is caused by inability of kidneys to excrete enough acid; Type 1-distal urine cannot be acidified below 5.3; Type 2-proximal proximal tubule cnnot reabsorb adequate amounts of HCO3; Type 4- involves either aldosterone deficiency or aldosterone resistance hyperkalemia results which decreases NH3 production and leads to acidosis
Term
relationship between PCO2 and alveolar ventilation
Definition
PaCO2=rate of CO2 production of the body (VCO2)/alveolar ventilation(VA); alveolar ventilation primarily controlled by central chemoreceptors; if metabolic activity of body is increased, alveolar ventilation is increased and PaCO2 remains normal; when fixed acid is added the CO2 by buffered bicarbonate is blown off and PaCO2 remains normal
Term
compensation
Definition
restoration of PaCO2/[HCO3] ratio towrds normal but the concentrations remain abnormal; buffering is always first line of defense; when disturbance metabolic compensation after buffering is generally due to respiratory changes (with renal compensations); when disturbance is respiratory origin compensation after buffering is primarily result of renal activity
Term
correction
Definition
not only is the PaCO2/[HCO3] ratio returned to normal but the concentrations of HCO3 and CO2 are returned to normal
Term
causes of metabolic acidosis
Definition
increase in the fixed or metabolic acid load; loss of HCO3
Term
compensation in metabolic acidosis
Definition
1.buffering (rapid)-H+ which is produced by metabolic acids buffered by HCO3 and conc reduced in ECF and also buffered by non-bicarb buffers; 2. response of respiratory system- peripehral chemoreceptors immediately stimulated by high H+ and alveolar ventilation increases and PaCO2 is reduced below 40mmHg and ratio of PaCO2/[HCO3] improved and H+ returned towards normal; 3. renal response (slow) all filtered HCO3 is reabsorbed and urinary H+ increases and new bicarb is generated and over time NH3 production increases and H+ excretion increases further
Term
plasma electrolytes in metabolic acidosis
Definition
anion gap is greatly increased when plasma concentration of fixed acids is increased; when acidosis is due to the loss of HCO3 the gap remains normal
Term
causes of metabolic alkalosis
Definition
loss of fixed acid from the body (vomiting); secondary to hypokalemia; and secondary to volume depletion
Term
compensation in metabolic alkalosis
Definition
cheifly excretion of HCO3 by the kidney; some compensatory hypoventilation may occur but limited due to hypoexmia
Term
respiratory acidosis
Definition
an increase in PaCO2 causing an increase in H+ due to hypoventilation such as with COPD
Term
compensation of respiratory acidosis
Definition
immediately is buffering of excess H+ by hemoglobin and other NBB; cannot have respiratory compensation; renal compensation is slow takin 3-5 days to reach max: new HCO3 generated and PaCO2/[HCO3] is improved; H+ is excreted and [H+] is returned to normal
Term
plasma electrolytes in respiratory acidosis
Definition
anion gap is normal the [HCO3] is increases and[CL-] is decreased
Term
respiratory alkalosis
Definition
decrease in PaCO2 causes a decrease in H+ caused by hypeventilation; caused by high altitudes, pregnancy, fever, pain, CNS lesions, and psychological stress
Term
compensations in respiratory alkalosis
Definition
immediate defense is buffering-intracellular buffers supply H+ which enters the ECF in exchange for Na and K and H combines with HCO3 reducing its concentration; kidneys excrete HCO3 and ratio of PaCO2/[HCO3] is improved and H returns toward normal; in chronic respiratory alkalosis the pH may be restored almost to normal by the renal compensation
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