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Function of Kidneys
Major ____ organ that maintain body’s ____ environment by:
Regulating total WATER volume + total ____ [ ] in water
Regulating ion [ ] in ECF
Ensuring long-term acid-base balance
Excreting metabolic wastes, toxins, drugs
Producing:
Erythropoietin → regulates RBC production
____ → regulates BP
Activating vitamin D
Carrying out gluconeogenesis (during prolonged fasting)
excretory, internal, solute, renin
Kidneys
____ → transport urine FROM kidneys to urinary bladder
Urinary bladder → temp ____ reservoir for urine
____ → transport urine OUT of body
ureters, storage, urethra
ANATOMY of KIDNEYS
Location and External Anatomy
Retroperitoneal + in SUPERIOR lumbar region (b/w T12 and L5)
Right kidney is crowded by liver + LOWER than left
____ (suprarenal) gland sits on top of each kidney
Convex lateral surface
Concave medial surface w/ vertical ____ ____ leads to internal space → renal sinus
Ureters, renal blood vessels, lymphatics, and nerves ENTER and EXIT at ____
adrenal, renal hilum, hilum
INTERNAL ANATOMY - kidneys (3 regions)
Renal ____ → granular-appearing superficial region
cortex
INTERNAL ANATOMY - kidneys (3 regions)
Renal ____ → deep to cortex, composed of cone-shaped medullary (renal) pyramids
Broad base of pyramid faces cortex
____ → TIP of pyramid + points internally
Pyramids are separated by ____ ____ (inward extensions of cortical tissue)
____ = medullary pyramid + its surrounding cortical tissue, abt 8/kidney
medulla, papilla, renal columns, lobe
INTERNAL ANATOMY - kidneys (3 regions)
Renal ____ → funnel-shaped tube continuous with ____
Minor calyces = cup-shaped areas that collect urine draining from ____ ____
Major calyces = areas that collect urine from ____ ____ + empty urine into renal pelvis
Urine flow: renal pyramid → minor calyx → major calyx → renal pelvis → ureter
pelvis, ureter, pyramidal papillae, minor calyces
Blood & Nerve Supply
Blood = kidneys cleanse blood + adjust its composition, SO it has a RICH blood supply
Renal arteries deliver about ¼ (1200mL) of CO to kidneys per MINUTE
Arterial flow = renal → segmental → ____ → ____ → cortical radiate (interlobular)
Venous flow = cortical radiate → ____ → ____ → renal veins
NO ____ veins
Nerve Supply = through sympathetic fibers from ____ ____
interlobar, arcuate, arcuate, interlobar, segmental, renal plexus
NEPHRONS - Renal Corpuscle (2)
Glomerulus
Tuft of ____ composed of fenestrated endothelium
Highly porous
Allows for efficient FILTRATE formations
Filtrate = plasma-derived fluid that ____ ____ process to form urine
capillaries, renal tubules
NEPHRONS - Renal Corpuscle (2)
Glomerular Capsule
Aka Bowman’s capsule → cup-shaped, hollow structure surrounding ____
2 layers:
Parietal = simple ____ epithelium
Visceral = clings to glomerular caps + branches epithelial ____
Extensions end (terminate) in foot processes that cling to basement membrane
____ ____ b/w foot processes allow filtrate to pass into capsular space
glomerulus, squamous, podocytes, filtration slits
NEPHRONS - Renal Tubule (3)
____ ____ Tubule (PCT)
CLOSEST to renal corpuscle
____ cells w/ dense microvilli that form brush border
Increase surface area
Also have large ____
Functions = ____ + ____
Confined to cortex
proximal convoluted, cuboidal, mitochondria, reabsorption, secretion
NEPHRONS - Renal Tubule (3)
____ ____
Aka loop of Henle
U-shaped structure consisting of 2 limbs
Descending limb = proximal part of it is continuous w/ proximal tubule
Distal portion aka descending ____ limb → simple ____ epithelium
Ascending limb
THICK ascending limb → thin in some nephrons
Cuboidal or columnar cells
nephron loop, thin, squamous
NEPHRONS - Renal Tubule (3)
Distal convoluted tubule (DCT)
FARTHEST from renal corpuscle
Cuboidal cells w/ very FEW ____
Function = more in ____ (than reabsorb)
Confined to cortex
drains into ___
microvilli, secretion, collecting duct
Collecting Ducts
2 cells types:
____ cells = maintain WATER and Na+ balance
Not that much + with SHORT microvilli
____ cells = help maintain ____ balance of BLOOD
Cuboidal cells w/ LOTS of microvilli
2 types → A and B (both help)
Receive filtrate from many nephrons
Run through medullary pyramids → give pyramids their ____ look
Ducts fuse together to deliver urine through ____ into ____ calyces
principal, intercalated, acid-base, striped, papillae, minor
Classes of Nephrons (2)
____ Nephrons
85% of nephrons
Almost entirely IN cortex
____ Nephrons
Long nephron loops deeply go through (invade) ____
Ascending limbs have thick and thin segments
Important in production of ____ urine
More prominent in desert animals
cortical, juxtamedullary, medulla, concentrated
NEPHRON CAPIS BEDS (3)
Renal tubules have 2 cap beds → ____ + ____ caps
Juxta nephrons have 1 → ____ ____
glomerulus, peritubular, vasa recta
NEPHRON CAPIS BEDS (3)
1. Glomerulus
Specialized for ____
Diff from other cap beds b/c they are fed and drained by arteriole
Afferent arteriole ____ glomerulus via efferent arteriole
Afferent arises from ____ radiate arteries
Efferent feed into either peritubular caps or vasa recta
BP is ____ in glomerulus b/c:
Afferent arterioles are LARGER in ____ than efferent
Arterioles are high-resistance vessels
filtration, enters, cortical, high, diameter
NEPHRON CAPIS BEDS (3)
2. Peritubular Capillaries
____ -____ , porous caps adapted for ____ of water and solutes
Arise from ____ arterioles
Cling to adjacent renal tubules in cortex
Empty into ____
low-pressure, absorption, efferent, venules
NEPHRON CAPIS BEDS (3)
3. Vasa Recta
Long, THIN-walled vessels parallel to long nephron loops of juxta nephrons
Arise from ____ arterioles serving ____ nephrons
Instead of peritubular caps
Function = formation of ____ urine
efferent, juxtamedullary, concentrated
Juxtaglomerular Complex (JGC)
EACH nephron has ____ JGC
Involves modified positions of:
Distal portion of ____ limb of nephron loop
Afferent (sometime efferent) arteriole
Important in regulating rate of ____ ____ and ____
one, ascending, filtrate formation, BP
CELLS in JGC (3)
____ ____
Tall + closely packed cells of ascending limb
Has ____ that sense NaCl content of filtrate
macula densa, chemoreceptors
CELLS in JGC (3)
____ cells (juxtaglomerular, of JG cells)
Enlarged + smooth muscle cells of arteriole
Acts as ____ to sense BP in ____ arteriole
Contain secretory granules that contain enzyme ____
granular, mechanoreceptors, efferent, renin
CELLS in JGC (3)
Extraglomerular ____ cells
Located b/w arteriole and tubule cells
Interconnected with ____ ____
May pass signals b/w macula densa and granular cells
mesangial, gap junctions
Physiology of Kidney
180L of fluid processed daily but ONLY 1.5L of urine is formed
Kidneys filter body’s ENTIRE plasma volume 60x each day
Consume 20-25% of O2 used by body at ____
Filtrate (produced by glomerular filtration) → basically blood plasma WITHOUT ____
Urine is produced from filtrate:
Urine is ____ than 1% of OG filtrate
Contains metabolic wastes + unneeded substances
rest, proteins, less
Processes of Urine Formation & Blood Composition Adjustment
____ ____ → produces FILTRATE (w/o cells and proteins)
Tubular ____ → selectively returns 99% of substances from filtrate to blood in renal ____ and ____ ____
Tubular ____ → selectively moves substances from blood to filtrate in renal tubules and collection ducts
glomerular filtration, reabsorption, tubule, collecting ducts, secretion
STEP 1: Glomerular Filtration (urine formation)
A ____ process → NO metabolic energy needed
Hydrostatic pressure forces fluids and solutes through ____ ____ into glomerular capsule
NO reabsorption into capillaries of glomerulus occurs
passive, filtration membrane
Filtration Membrane
Porous membrane b/w blood and interior of glomerular capsule
Allows water + solutes (smaller than plasma proteins) to pass → normally NO cells can pass
3 layers:
____ ____ of glomerular capillaries
____ membrane → fused basal laminae of 2 other layers
____ ____ of podocytes w/ filtration slits → slit diaphragms REPEL macromolecules
Macromolecules “stuck” in filtration membrane are engulfed by glomerular ____ cells
Allows molecules smaller than 3 nm to pass → so water, glucose, amino acids, nitrogenous wastes
Plasma proteins remain in blood to maintain colloid osmotic pressure
Prevents loss of all water to capsular space
Proteins in filtrate indicate membrane problem
fenestrated endothelium, basement, foot processes, mesangial
Pressures Affecting Filtration (2)
Outward Pressures
____ filtrate formation
hydrostatic pressure in ____ ____ (HPgc) → basically glomerular BP
MAIN force pushing water and solutes OUT of blood
HIGH BP→ 55mm Hg
Compared to 26 mm Hg seen in most caps beds
High b/c ____ arteriole is a high-resistance vessels w/ a diameter ____ than afferent arteriole
promote, glomerular capillaries, efferent, smaller
Pressures Affecting Filtration (2)
Inward Pressures
____ filtrate formation
Hydrostatic pressure in ____ ____ (HPcs) → filtrate pressure in capsule (15 mm Hg)
____ osmotic pressure in ____ (OPgc) → “pull” of proteins in blood (30 mm Hg)
Net filtration pressure (NFP) = SUM of forces
55 mm Hg forcing OUT minus 45 mm Hg opposing = net outward force of 10 mm Hg
Pressure responsible for ____ formation
Main controllable factor determining ____ ____ ____ (GFR)
inhibit, capsular space, colloid, capillaries, filtrate, glomerular filtration rate
Glomerular Filtration Rate (GFR)
The ____ of filtrate formed per MINUTE by BOTH kidneys
Normal = 120-125 ml/min
Directly proportional to:
NFP → primary pressure is glomerular hydrostatic pressure
Total ____ ____ available for filtration → glomerular mesangial cells control by contracting
____ ____ permeability→ much MORE permeable that other capis
volume, surface area, filtration membrane
Regulation of Glomerular Filtration
CONSTANT GFR is important b/c it allows kidneys to make filtrate and maintain ____ ____
Goal of local intrinsic controls (renal autoregulation) = maintain ____ in kidney
GFR affects systemic BP
Increased GFR → causes increased ____ ____ → LOWERS BP (and vice versa)
Goal of extrinsic controls = maintain ____ ____
NS and endocrine mechanisms are main extrinsic controls
extracellular homeostasis, GFR, urine output, systemic BP
Regulation of Filtration - Intrinsic Controls: Renal Autoregulation (2)
Maintains nearly constant GFR when MAP is in range of 80-180 mm Hg
Autoregulation STOPS if out of that range
____ Mechanism
Local SMOOTH muscle contracts when stretched
Increased BP causes muscle to stretch → leads to constriction of ____ arterioles
Restricts blood flow into ____
Protects glomeruli from damaging high BP
Decreased BP → ____ of afferent arterioles
Both help maintain normal GFR despite normal fluctuations in BP
myogenic, afferent, glomerulus, dilation
Regulation of Filtration - Intrinsic Controls: Renal Autoregulation (2)
____ feedback mechanism
Flow-dependent mechanism directed by ____ ____ cells
Respond to filtrate’s NaCl [ ]
If GFR INCREASES → filtrate flow rate ____
Leads to ____ reabsorption time = HIGH NaCl levels in ____
Feedback mechanism causes ____ of afferent arteriole → lowers NFP and GFR → allow more time for NaCl reabsorb
Opposite mechanism for DECREASED GFR
tubuloglomerular, macula densa, increases, decreased, filtrate, constriction
Regulation of Filtration - Extrinsic Controls: Neural & Hormonal
Purpose = regulate GFR to maintain systemic BP
Extrinsic controls will override intrinsic if blood volume needs to be INCREASED
Sympathetic NS
Under normal conditions at rest:
Renal blood vessels ____
Renal autoreg mechanisms win (prevail)
ABRNOMAL conditions (extremely low ECF volume, low BP):
Norepinephrine is released by sympathetic NS
Epinephrine is released by adrenal medulla
Systemic ____ → increases BP
Constriction of afferent arterioles → decreases GFR
Blood volume + pressure ____
Sympathetic NS is activated
dilated, vasoconstriction, increase
Regulation of Filtration - Extrinsic Controls: Neural & Hormonal
RAA (renin-angiotensin-aldosterone)
MAIN mechanism for increasing BP
3 pathways to renin release by ____ cells
Direct stimulation of granular cells by sympathetic NS
Stimulation by activated ____ ____ cells when filtrate NaCl [ ] is LOW
Reduced ____ of granular cells
granular, macula densa, stretch
STEP 2: Tubular Reabsorption (urine formation)
This quickly reclaims most of tubular contents and returns them to BLOOD
Selective transepithelial process
Almost all ____ nutrients are REABSROBED
Water and ion reabsorption is ____ regulated and adjusted
____ + ____ tubular reabsorption
organic, hormonal, active, passive
Routes for Substances (2)
____ route
Solute enters apical membrane of tubule cells
Diffusion through cytosol
Transport across ____ membrane
Often involves lateral intercellular spaces b/c membrane transporters transport ions into these spaces
Enters blood through ____ of ____ capillaries
transcellular, basolateral, endothelium, peritubular
Routes for Substances (2)
____ route → BETWEEN tubule cells
Movement through leaky ____ ____ , particularly in the ____
Limited by tight junctions
Movement through interstitial fluid and into capis
Water, Ca, Mg, K, and some Na in the PCT move through this route
paracellular, tight junction, PCT
Tubular Reabsorption of Sodium (2)
Sodium Transport across ____ membrane
Na is most abundant cation in filtrate
Transport of Na across basolateral membrane of tubule cell is via ____ ____ transport
Na-K ATPase pumps Na into interstitial space
Na is swept by bulk flow into ____ capis
basolateral, primary active, peritubular
Tubular Reabsorption of Sodium (2)
Transport across ____ membrane
Na enters tubule cell at apical surface via ____ ____ transport (cotransport) or facilitated diffusion through channels
Active pumping of Na at basolateral membrane = strong electrochemical gradient within tubule cell
Result = LOW ____ Na levels that facilitate Na diffusion
K leaks OUT of cell into interstitial fluid → leaves a net ____ charge inside cell → which also pulls Na IN
apical, secondary active, intracellular, negative
Tubular Reabsorption of Nutrients, Water, and Ions
Na reabsorption by primary active transport provides ____ and means for reabsorbing almost every other substance
energy
Tubular Reabsorption of Nutrients, Water, and Ions
Secondary Active Transport
Electrochemical gradient created by pumps at ____ surface give “push” needed for transport of other solutes
____ nutrients reabsorbed by secondary active transport → are ____ w/ Na
Ex. glucose, amino acids, some ions, vitamins
basolateral, organic, cotransported
Tubular Reabsorption of Nutrients, Water, and Ions
Passive tubular reabsorption of WATER
Movement of Na and other solutes creates osmotic gradient for water
Water is reabsorbed by osmosis → helped by water-filled pores called ____
____ water reabsorption → aquaporins ALWAYS present in PCT
____ water reabsorption → aquaporins are inserted in collecting ducts only if ____ is present
aquaporins, obligatory, facultative, ADH
Tubular Reabsorption of Nutrients, Water, and Ions
Passive tubular reabsorp of SOLUTES
Solute [ ] in filtrate ____ as water is reabsorbed
Creates [ ] gradients for solutes → drive their entry into tubule cell and peritubular capis
Fat-soluble substances, some ions, and urea → will ____ water into peritubular capis down their [ ] gradients
Which is why lipid-soluble drugs and environmental pollutants are reabsorbed even though its bad
increases, follow
Transport Maximum
Transcellular transport systems are specific and limited
Transport maximum (Tm) exists for almost EVERY reabsorbed substances
Reflects number of ____ in renal tubules that are available
When carriers for a solute are ____ → excess is excreted in ____
Ex. ____ leads to high blood glucose that exceed Tm = so glucose spills over into urine
carriers, saturated, urine, hyperglycemia
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
PCT
Site of MOST reabsorption:
All ____ (like glucose and amino acids)
65% of Na and water
Many ions
Almost all ____ acid
About HALF of ____ (later secreted back into filtrate)
nutrients, uric, urea
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
Nephron Loop
____ limb → water can leave, solutes CANNOT
____ limb → water CANNOT leave, solutes can leave
THIN segment is ____ to Na movement
THICK segment has Na-K-2Cl symporters and Na-H antiporters that transport Na INTO cell
Some Na can pass into cell by ____ route in this area of the limb
descending, ascending, passive, paracellular
Reabsorptive Capabilities of Renal Tubules and Collecting Ducts
Distal Convoluted tubule and collecting duct
Reabsorption is ____ regulated in these areas:
hormonally
DCT & CD Hormone regulation (4)
ADH aka vasopressin
Released by ____ pituitary gland
Causes ____ cells of collecting ducts to insert aquaporins in apical membranes → increase water absorption
Increased ADH levels = increase in water absorption
posterior, principal
DCT & CD Hormone regulation (4)
Aldosterone
Targets collecting ducts (principal cells) and distal CT
Promotes ____ of apical Na and K channels + basolateral Na-K ATPases → for Na reabsorption (water follows)
Result = little Na leaves the body
Without aldosterone → daily loss of filtered Na would be 2% which is incompatible with life (can’t survive)
Functions = ____ BP and ____ K levels
synthesis, increase, decrease
DCT & CD Hormone regulation (4)
____ Natriuretic Peptide
REDUCES blood Na → decreases blood volume and BP
Released by cardiac atrial cells if blood volume or pressure is ____
atrial, elevated
DCT & CD Hormone regulation (4)
Parathyroid hormone
Acts on DCT to increase ____ reabsorption
Ca
Step 3: Tubular Secretion (urine formation)
REVERSE of reabsorption
Occurs almost completely in ____
Selected substances are moved from peritubular capis through tubule cells → then OUT into filtrate
K, H, NH4, creatine, organic acids and bases
Substances ____ in tubule cells are also SECRETED (ex. HCO3)
PCT, synthesized
Tubule Secretion Important for:
Disposing substances (ex. drugs or metabolites) that are bound to plasma ____
Eliminating undesirable substances that were passively absorbed (ex. urea and uric acid)
Getting rid of excess ____ (aldosterone effect)
Controlling ____ ____ by altering amounts of H+ or HCO2 in urine
proteins, K+, blood pH
Regulating of Urine [ ] and Volume
One main function of kidneys → make adjustments needed to maintain body fluid osmotic [ ] (at around 300mOsm)
Osmolarity = number of solute particles in 1 kg of H2O
1 osmol = 1 mole of particle per kg H2O
Body fluids have much smaller amounts → so expressed in milioosmols (mOsm)
1 mOsm = 0.001 osmol
Kidneys produce only ____ amounts of urine if body is dehydrated or ____ urine if overhydrated
Accomplish this by using ____ mechanism
Fluid flows in opposite directions in 2 adjacent segments of SAME tube with ____ turn (U-shape bend)
small, diluted, countercurrent, hairpin
Countercurrent Mechanisms (2 types)
2 countercurrent mechanisms work together to:
Establish + maintain medullary ____ ____ from renal cortex through medulla
Gradient runs from 300 mOsm in cortex to 1200 mOsm at bottom of medulla
Countercurrent MULTIPLIER ____ gradient
Exchanger ____ gradient
Collecting ducts can then ____ gradient to vary urine [ ]
Countercurrent multiplies → interaction of filtrate flow in ascending/descending limbs of nephron loops of ____ nephrons
Countercurrent exchanger → blood flow in ascending/descending limbs of ____ ____
osmotic gradient, creates, preserves, use, juxtamedullary, vasa recta
Countercurrent Multiplier
Involves the nephron loop and depends on:
Filtrate FLOW in opposite directions (descending/ascending)
Difference in ____ b/w descending and ascending loop
____ transport of solutes out of ascending limb
Limbs of nephron loop are NOT in direct contact but are CLOSE enough to influence each other’s exchange w/ surrounding interstitial fluid
permeabilities, active
Countercurrent Multiplier
Ascending limb of nephron loop is IMPERMEABLE to water and selectively permeable to solutes
Na and Cl are ACTIVELY absorbed in ____ segment (some passively reabsorbed in THIN segment)
Descending limb lets in water but NOT solutes
Water passes out filtrate into hyperosmotic medullary interstitial fluid
Causes remaining filtrate osmolarity to ____ to 1200 mOsm
thick, increase
Countercurrent Multiplier Mechanism
The MORE NaCl ascending limb actively transports into interstitial fluid = the more water diffuses ____ of descending limb
The more water that diffuses OUT of descending limb = the saltier the filtrate becomes
Ascending limb then uses salty filtrate to further ____ osmolarity of medullary interstitial fluid
Constant difference of ____ mOsm ALWAYS exists b/w the 2 limbs and between ascending and interstitial fluid
Difference is “multiplied” along length of loop
From 300 to 1200 mOsm = difference of 900mOsm
out, raise, 200
Countercurrent Exchanger
Uses vasa recta → vasa recta is HIGHLY permeable to water and solutes
Flow of blood in vasa recta is also countercurrent (hairpin turn) so blood can exchange NaCl and water with surrounding interstitial fluid as it moves through adjacent parallel section of gradient
Blood inside vasa recta remains ____ w/ surrounding interstitial fluid
Vasa recta is able to reabsorb water and solutes w/o ____ osmotic gradient created by countercurrent multiplies
isosmotic, undoing
Countercurrent Exchanger Mechanism
preserves gradient (2 things):
Prevents rapid removal of ____ from interstitial space
____ reabsorbed water
Water in ascending vasa recta comes from descending vasa recta or is reabsorbed from nephron loop + collecting duct
Result = volume of blood at END of vasa recta is ____ than at beginning
salt, removes, greater
Formation of Dilute or [ ] Urine
Established medullary osmotic gradient can now be used to form ____ or ____ urine
WITHOUT gradient → would NOT be able to raise urine [ ] more than 300 mOsm to ____ water
dilute, concentrated, conserve
Mechanisms
Overhydration = ____ volume of ____ urine
ADH production ____ → urine about 100 mOsm
If aldosterone is present → additional ions can be ____ causing water to dilute to 50 mOsm
Dehydration = ____ volume of ____ urine
Maximal ADH released → urine 1200 mOsm
Severe dehydration → 99% of water reabsorbed
large, dilute, decreases, removed, small, concentrated
Urea Recycling & Medullary Osmotic Gradient
Urea helps gradient
Urea enters filtrate in ____ ____ limb by facilitated diffusion
Cortical collecting duct reabsorbs water → leaves urea behind
In deep medullary region → NO highly concentrated urea leaves ____ ____ → enters interstitial fluid of ____
Urea then moves back into ascending thin limb
Contributes to HIGH osmolarity in medulla
ascending thin, collecting duct, medulla
Diuretics
Chemicals that ____ urinary output (make u pee more)
____ ADH (ex. alcohol)
Na reabsorption ____ (and resultant water reabsorption) → ex. Coffee or drugs for hypertension or edema
Loop diuretics inhibit ____ ____ formation
____ ____ = substance NOT reabsorbed so water remains in urine
Ex. in a diabetic patient, high glucose [ ] pulls water from body
enhance, inhibit, inhibitors, medullary gradient, osmotic diuretics