Quiz 7 Physiology

Front 1

functions of the kidney

Back 1

regulation of body fluid osmolality + volumes, regulation of electrolyte balance (Na+, K+, Pi, Ca2+, Mg2+, HCO3-, Cl-; regulation of acid base balance, excretion of metabolic wastes, and foreign substances (urea, uric acid, creatinine, drugs), production of hormones (renin, erythropoietin, calcitriol)

Front 2

fluid compartments

Back 2

intracellular fluid is 40% of body weight; extracellular fluid is 20% body weight

3/4 of the extracellular is the interstitial, and 1/4 of the extracellular is the plasma

the more muscular an individual is the greater the percentage of body water; increases in fat reduce total body water; women have a layer of subcutaneous fat, that reduces their pertanged of total body water to about 50-55%, infants have high water content (70%) & the elderly have lower water content

Front 3

osmolarity

Back 3

number of particles / volume of solution

Front 4

tonicity

Back 4

behavior property of the cell (shape change)

Front 5

volume and osmolarity disturbances

Back 5

rule 1: ECF (osm vol) is always distributed first

rule 2: start with equal osmolarity, end with equal osmolarity

the basic principle governing water movement between the ECF and the ICF is that the osmolality of each must be equal, if not water moves to equalize the osmolality

disturbances are represented by Dannet-Yarrow diagrams

Front 6

hypotonic expansion

Back 6

water typically water

is not given in IV, because the osmolality of the plasma is lowered causing cells to swell and bust

D5W isotonic glucose (5g/100ml) intravenously administered is osmotically equivalent to drinking water; ingested water enter ECF increasing the volume, and decreasing ECF osmolality, water then enters cells via osmosis

SIADH(syndrome of inappropriate ADH release) ADH release is unregulated causing water retention in the body

results in ECF fluid increases and decreases ICF osmolality

Front 7

isotonic expansion

Back 7

isotonic saline (0.9% NaCl ~300 mOsm/kg) or lactated ringer's solution (contains Na+, Cl-, K, Ca2+, HCO3-)

both solutions contain the same osmolality as plasma, ringer's is more similar to ECF than isotonic saline

results in ECF fluid volume increases, does not change ECF osmolality, therefore ICF volume and osmolality does not change

Front 8

hypertonic expansion

Back 8

hypertonic saline IV cause both the ECF volume and osmolality to increase, the latter will cause water to leave the osmosis, thereby decreasing ICF and increasing ICF osmolality

ingestion of NaCl tablet initially increases ECF osmolality but not ECF volume and an increase in ICF osmolality, ultimately will increase ECF volume

Front 9

hypotonic contraction

Back 9

sodium chloride depletion

sweat is a hypotonic NaCl solution, depletion results in low plasma NaCl concentration will decrease ECF osmolality which reduces ADH causing increased excretion of dilute urine; only way to fix this is to restore salt levels, the decrease in ECF osmolality causes water to enter cells increasing ICF volume reducing ICF osmolality

adrenocortical insufficiency the hormone aldosterone is not produced causing a lack of NaCl retention and increased elimination of NaCl via urine

Front 10

isotonic contraction

Back 10

diarrhea

fluid loss is isotonic→ no change in osmolality but ECF volume decreases→ no osmotic gradient is generated across the cell membrane and no net net water movement occurs→ ICF volume and osmolality is therefore unchanged

hemorrhage whole blood is lost during hemorrhage without affecting the osmolality of ECF and ICF, there is no change in ICF volume, ECF volume decreases due to plasma loss

results in ECF volume decrease

Front 11

hypertonic contraction

Back 11

sweat without fluid replacement sweat is hypotonic (dilute NaCl solution) ICF volume decreases and osmolality increases

diabetes insipidus excessive production of dilute urine and excessive thirst due to decreased production of ADH at the level of the brain or insensitivity of ADH at the level of kidneys

result ECF volume decreases

Front 12

urinary system

Back 12

composed of kidneys ureters bladder and urethra, each kidney has a million nephrons which filter the blood

Front 13

kidney surface anatomy

Back 13

Front 14

nephron structure

Back 14

superficial or mid-cortical nephrons are 85% these nephrons do not have a thin ascending limb of the loop of Henle, juxtamedullary nephrons are 15% which are found deep within the medulla and are used to build the medullary osmotic gradient

Front 15

bowman's capsule

Back 15

glomerulus aka bowman's capsule, is doubled walled, parietal layer is made epithelial cells no involved in filtration; visceral layer is made of specialized epithelial cells called podocytes that wrap around the glomerular capillaries, podocytes form filtration slits

Front 16

glomerular basement membrane

Back 16

endothelial layer of the glomerular capillaries are fenestrated with pores that are much larger than other capillaries, blood solutes pass thru the slits of the podocytes excluding the proteins, basement membrane has a negative (-) charge, ultrafiltrate (isotonic) enters the bowman's space which the space between the parietal and visceral layers of the bowman's capsule

Front 17

flow in the kidney

Back 17

renal arteries → interlobar artery → arcuate arteries → interlobular arteries → afferent arterioles→glomerular capillaries → efferent arterioles (portal vessels) → vasa recta (branches off the efferent arterioles of the juxtaglomerular and connect again with the venule) or peritubular capillaries (branch off the efferent arterioles of the superficial or mid cortical nephrons)

Front 18

cells of kidney

Back 18

macula densa found where the macula densa is found where the thick ascending limb of the loop of henle meets the distal convoluted tubule, juxtaglomerular apparatus (JGA) found in the walls of the afferent arteriole and some in the afferent arteriole and some in efferent arteriole, synthesize renin; extraglomerular mesangial cells modified smooth muscle cells that play a role in autoregulation of blood flow

intraglomerular mesangial cells, found among the glomerular capillaries and may regular blow and hence GFR, and may have phagocytic role

Front 19

the fates of the solutes which pass the basement membrane

Back 19

filtration is the movement of ultrafiltrate of plasma into Bowman's space (1 liter a minute);

reabsorption is the movement of water solutes from the tubules to peritubular capillaries; secretion is the movement of water and solutes from the peritubular fluid to the tubules; excretion is the removal of substances from the body in (1 -1.5 liters a day)

filtration = filtration - absorption + secretion

Front 20

Tubular Transport

Back 20

transcellular transport: the transport of solutes through a cell, may be passive or active

paracellular transport is always passive and involves the passage of solutes via the tight junction; always prevents the lateral movement of integral proteins; divide the cell into luminal and basolateral domains

Front 21

Glomerular filtration rate (GFR)

Back 21

GFR = Kf x Pf

Pf= (Pg- Pb) - (πg - πb)

rate at which substances move from glomerular capillary blood into Bowman's space;

filtration barrier has a negative surface prevents large blood proteins (albumin) from crossing;

two factors: the balance of starling forcing (Pf net filtration pressure NFP) filtration coefficient (Kf a combination of glomerular permeability and filtration area)

Front 22

filtration fraction

Back 22

GFR divided by RPF (renal plasma flow) ~20 percent

Front 23

resistance & GFR + Renal blood flow

Back 23

GFR is controlled by Pgc, which is modulated by blood pressure & afferent + efferent resistance; neural & hormonal input affects afferent + efferent arterioles

increase afferent arteriole resistance ⇒ decrease in GFR due to a fall in Pgc; FF does not change GFR and RPF fall together

increase efferent arteriole resistance ⇒ increases FF because GFR rises (due to an increase in Pgc) and RPF falls; increased FF increases πgc

Front 24

kidney autoregulation

Back 24

GFR and RPF remain relatively constant over a range of MAP's; normal MAP is about 93 mmHg

Front 25

myogenic response

Back 25

rapid protection of glomeruli from short term fluctuations in blood pressure; lead to the constriction of afferent arteriole smooth muscle ⇒ minimal ↑ renal blood flow & ↑ GFR

↑ MAP ⇒ ↑afferent arteriole stretch ⇒mechanically gated Na+ & K+ channels open ⇒Na+ influx and K+ efflux ⇒ depolarization ⇒ voltage gated Ca2+ channels open ⇒Ca2+ influx, binds to calmodulin activates MLCK ⇒muscle contracts

Front 26

tubuloglomerular feedback

Back 26

may occur up in up to a minute to help maintain an appropriate filtered load of solutes; an increase in MAP causes an increased GFR therefore an increase in Na+ and Cl- delivery to the macula densa, which causes an increase in ATP (P2) release and adenosine (A1) release; A1 & P2 stimulation causes a rise in Ca2+ levels in extraglomerular mesangial cells which increases Ca2+ in juxtaglomerular cells(secret renin) & in the afferent arteriole smooth muscle (vasoconstriction)

lead to the constriction of afferent arteriole smooth muscle ⇒ minimal ↑ renal blood flow & ↑ GFR

Front 27

sympathetic nervous system stimulation of kidney

Back 27

when MAP falls below 85 mmHg, autoregulation ceases and the sympathetic nervous system overrides it; constricts both the afferent and efferent arterioles to decrease RPF but produces no change in Pgc, therefore the filtration fraction increases

severe sympathetic nervous system activity causes a reduction in Pgc and RPF, acute renal failure may result after 10 days hyperkalemia may result and subsequent death

Front 28

Atrial (ANP) & brain (BNP) natriuretic peptides

Back 28

are released when blood pressure is high (increased vascular volume)

cause decreased Na+ reabsorption in the deep medullary convoluted tubule; afferent arteriole dilation and efferent arteriole constriction

inhibit renin, aldosterone, and ADH release

overall there is an increase in Pgc, GFR, Na+ excretion (helps bring water volume down), & RPF

Front 29

Clearance

Back 29

volume of blood cleared of the substance and excreted into urine per unit time

Cx=(Ux X V) / Px

if a substance is reabsorbed and not secreted it's clearance equals zero (eg glucose)

if a substance is slightly reabsorbed clearance of this substance is less than GFR and RPF

if the kidney removes all of a substance from the blood in one pass through the kidney, the volume of plasma cleared equals RPF;

if secreted the clearance will be greater than GFR, and if the substance is only filtered clearance equals GFR

Front 30

Inulin

Back 30

freely filtered, not reabsorbed or secreted; amount of inulin filtered equals the amount of inulin excreted, rarely used to calculate GFR

Front 31

Creatinine

Back 31

freely filtered not reabsorbed, slightly secreted in the proximal convoluted tubule, clearance is greater than GFR, less than RPF, indicator of renal function; with progressive renal failure GFR decreases and serum creatinine increases: GFR gets halved so the serum creatinine doubles, inverse relationship

Front 32

Para-amino hippuric (PAH)

Back 32

is freely filtered and not reabsorbed, but is secreted into the PCT; clearance of PAH becomes the renal plasma flow

Front 33

carrier mediated reabsorption or secretion

Back 33

limited by the transport maximum (Tm); glucose is an example

Front 34

Na+ Filtration and Reabsorption

Back 34

Na+ is freely filtered at the glomerulus, almost entirely (99.5) reabsorbed and not secreted; largely occurs at the PCT, ascending Loop of Henle, early Distal Collecting, and the CT. Na+ is reabsorbed on the apical (luminal) side of the tubular epithelium down its concentration gradient and against the concentration gradient via the Na+/K+ pump on the basolateral side

Front 35

Na+ at the proximal convoluted tubule (PCT)

Back 35

Na+ reabsorption begins on the luminal membrane via secondary active transporters; diffuses down its concentration gradient to drive Tm dependent substances (glucose, amino acids, lactate, & HPO4 + H2O {keeps tonicity}) against their concentration gradients;the concentration gradient is established on the basolateral membrane via Na+/K+ pump; hydrogen is transported out via secondary active antiport stimulated by hormone angiotensin II

Front 36

Na+ at the Thick ascending Loop of Henle

Back 36

Na+ reabsorption occurs via a Na+/H+ antiporter; Na+/K+/2Cl- symporter on the luminal membrane; moves down it's concentration gradient from tubular lumen to tubular epithelium, which allows secondary active H+ Cl- & K+; concentration gradient is due to Na+/K+ pump on basolateral membrane (became hypertonic at the lowest point between ascending and descending; which then loses it's salt and contains it's water and becomes hypotonic)

Front 37

Loop Diuretics

Back 37

inhibits the Na+/K+/2Cl- symporter preventing water reabsorption in the ascending loop of henle due to osmosis; there are potassium leak channels on both luminal and basolateral membranes; produces more urine, water remains un-reabsorbed because the salt wasn't removed at the thick ascending loop of Henle; glucose acts as an osmotic particle as well resulting in increasing urine production as well

Front 38

Na+ at the Distal Convoluted Tubule

Back 38

Na+ reabsorption occurs via a Na+/Cl- symporter that transports Na+ across the basolateral membrane; water does not follow (diluting)

Front 39

Thiazide-like Diuretics

Back 39

inhibits the Na+/Cl- symporter stimulating the renin-angiotensin-aldosterone system

Front 40

Na+ at the Convoluted Tubule (& late dct)

Back 40

the action of aldosterone (principle cells), will allow Na+ reabsorption stimulating luminal Na+ channels and basolateral Na+/K+ pumps, also increases K+ secretion into the tubular fluid by stimulating luminal K+ channels; water permeability is dependent on ADH

Front 41

Potassium Sparing Diuretics

Back 41

blocks Na+ channels or block aldosterone receptor; indirectly inhibits K+ secretion and excretion; generally used in combination with loop & thiazide-like diuretics

Front 42

RAAS pathway (renin angiotensin aldosterone system)

Back 42

blood volume or pressure decreases, RAAS pathway is activated, sympathetic is stimulated, ANP levels decrease

Front 43

Renin

Back 43

released from the juxtaglomerular cells & part of RAAS pathway; release is stimulated by decreased stretch of afferent arterioles (low blood pressure or volume); decreased Na+ and Cl- delivery to macula densa (due to decrease filtration); hydrolyzes angiotensin (produced in the liver) to angiotensin I; which is converted to angiotensin II by angiotensin converting enzyme

Front 44

Angiotensin II (ang II)

Back 44

actions binds to g-protein linked receptor on smooth muscle activating phospholipase C is activated cleaving PIP2 into IP3 and DAG; IP3 binds to its receptor on the endoplasmic reticulum to cause the release of Ca2+ into the cytoplasm leading to smooth muscle contraction;

stimulates H+ ATPase activity of a-intercalated cells in the CT, increases K+ secretion by stimulating the activity of luminal K+ channels of the principal cells in the CT, increasing Na+ reabsorption by stimulating the activity of luminal Na+ channels and basolateral Na+/K+ pumps on the principle cells of the CT

effects increases blood pressure (vasoconstriction of peripheral vessels) thirst sensation desire to consume salt, increases aldosterone (zona glomerulosa adrenal cortex) & ADH (posterior pituitary) release, increases activity of the Na+/H+ antiporter in the PCT and TAL, decreases GFR and resists renal blood flow; causes the desire to drink water

Front 45

aldosterone

Back 45

aldosterone may be stimulated by increased plasma K+ levels and decreased ANP or BNP; increasing Na+ reabsorption stimulating luminal Na+ channels and basolateral Na+/K+ pumps in the CT, increasing K+ secretion by stimulating luminal K+ channels in the CT, stimulating H+ ATPase activity of a-intercalated cells in the CT

Front 46

regulation of Na+ excretion sympathetic nervous system

Back 46

a1 receptor activation: vasoconstriction of afferent and efferent arterioles decreases, and Na+ reabsorption in the PCT, decreasing in GFR and Na+ filtration

b1 receptor activation: renin release from the juxtaglomerular cells Na+ reabsorption is increased

Front 47

Conn's Syndrome

Back 47

hyperaldosteronism, aldosterone producing adenoma, high concentrations of circulating aldosterone, increased Na+ reabsorption (⇒ hypertension), increased ADH release, increased K+ and secretion leads to hypokalemia, increased H+ ATPase activity increases H+ secretion and HCO3- reabsorption leading in to metabolic alkalosis