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Renal Exam 1
PCC: Based on Schmidt notes
126
Physiology
Professional
11/12/2010

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Term
Starling
Definition
Recognized kidneys as regulatory, rather than excretory organs
Term
Kidneys regulate
Definition

composition of body fluid

volume of body fluid

Term
Excretion
Definition
= process of separating wastes from body fluids and eliminating them
Term
1. Regulation of Body Fluid Osmolality and Volume
Definition

osmolality controlled in order to: maintain cell volume, carry on normal cardiovascular function.

 Done by regulating excretion of water and NaCl

Term
2. Regulation of Electrolyte Balance
Definition

Inorganic Ions: Na, K, Cl, HCO3, H, Ca, P

Organic Ions: citrate, succinate excretion must match intake

Term
3. Regulation of Acid-Base Balance
Definition
pH must be kept between 6.8-7.8 accomplished by: buffers, coordinated action of lungs and kidneys
Term
4. Excretion of Metabolic Products and Foreign Substances
Definition

Metabolic wastes (Amino acids to Urea (50% of nitrogen products), Nucleic acid to uric acid, Phosphocreatine to creatine, Metabolites to hormones, hemoglobin end products) 

  Foreign substances: - chemicals in food - drugs - insecticides and herbicides

Elimination rate matches production

Term
5. Production and Secretion of Hormones
Definition
kidney may be considered an endocrine organ, secreting: - renin - calcitriol (vit. D3) - erythropoeitin
Term
Renin
Definition

proteolytic enzyme

activates renin-angiotensin-aldosterone system

 regulates blood pressure with Na-K balance 

Term
Calcitriol
Definition
facilitates normal reabsorption of Ca+ by GI tract (impairment as in renal disease can lead to abnormal formation)
Term
Erythropoietin
Definition

stimulates RBC production by bone marrow, indirectly controlling O2 carrying capacity of blood

Anemia can be caused by dietary insufficiency of Fe or erythropoeitin problem

Term
Urine Production
Definition
normally 1.2 nephrons per kidney
urine volume: 1-2L/day (can vary 5-18L/day)
urine conc: 50 mOsm/L - 1200 mOsm/L
polyuria: >2 L/day
oliguria: <500 mL/day
anuria: 0-100 mL/day (kidney disease, prostate enlargement, dehydration)
Term
Waste
Definition
= substance useless to the body or present in excess of body’s needs
Term
Metabolic waste
Definition
= waste substance produced by the body
toxic examples: ammonia, urea, uric acid, creatinine, CO2
Term
Azotemia
Definition

accumulation of nitrogenous wastes in blood

can result in uremia (diarrhea, vomiting, arrhythmia) leads to convulsion, coma, and death

Term
BUN
Definition
= blood urea nitrogen test measure of kidney function
Term
Molarity
Definition

The amount of a substance dissolved in a solution relative to its molecular weight

 mmol/L = mM used for uncharged solutes

Term
Equivalence
Definition

For charged solutes such as NaCl which dissociates in solution refers to interaction between cations and anions

Molarity multiplied by valence mEq or ions/L

Term
Osmosis
Definition

Passage of water from a region of high water concentration to low water concentration through a semi-permeable membrane

 Osmotic pressure difference is driving force for movement of water across cell membranes

Experiment: - high concentration of particles in chamber A - low concentration of particles in chamber B - H2O moves into A by osmotic pressure - At equilibrium, hydrostatic pressure (pressure of water volume in chamber) stops movement of water from B to A and is equal and will be opposite the osmotic pressure exerted by solute particles in chamber A

Term
Osmotic Pressure
Definition
determined by number of solute particles (not by size, mass or chemical nature)
Term
van’t Hoff’s Law
Definition

osmotic pressure =  = nCRT

n = number of dissociable particles per molecule

C = total solute concentration (mol/L)

R = gas constant

T = temp (degrees Kelvin)

Term
Osmolarity
Definition

Number of dissociable particles per L of solvent

Esxpressed as milliosmoles/L

(mOsm/L)

Term
Osmolality
Definition

Number of solute particles per Kg solvent

not temperature dependent (based on mass rather than volume)

Expressed as Osm/kg H2O but

mOsm/kgH2O in physiology

Term
Tonicity
Definition

Solutions effect on the volume of a cell

Hypotonic solution: causes cell to swell

Hypertonic: solution causes cell to shrink (crenate)

factors that affect tonicity:

permeability, osmolality

Term
Effective Osmole
Definition

Not permiable to cell membrane. Exerts an osmotic pressure equal and opposite to the osmotic pressure generated by the contents of Rbc

Ex. Glucose

Term
Ineffective Osmole
Definition

permeates cell membrane cannot exert osmotic pressure to balance that generated by solutes of ICF

ex. Urea

Term
Modified van’t Hoff’s equation
Definition

 = a(nCRT)

a= reflection/osmotic coefficient  (ability to cross a cell membrane)

 a = 0 solute freely crosses, no osmotic pressure exerted

a = 1 solute cannot cross cell membrane

Term
Oncotic Pressure
Definition
Osmotic pressure generated by large molecules (especially proteins)  Human plasma oncotic pressure: 26-28 mmHg = 1.4 mOsm/kg H2O Important force involved in fluid movement across capillaries (even though small)
Term
Specific Gravity
Definition

Weight of volume of solution divided by the weight of equal volume distilled H2O

specific gravity of human plasma: 1.008-1.010

used to assess the concentrating ability of the kidneys varies in proportion to its osmolality depends on both the number and weight of solute particles

Term
Total Body Water (TBW)
Definition
= 0.6 X body weight
Term
ECF
Definition
= 0.2 X body weight
Term
ICF
Definition
= 0.4 X body weight
Term
Plasma
Definition
1/4 of ECF
Term
Major cation of ECF
Definition
Na+ (major determinant of ECF osmolality)
Term
Plasma Osmolality
Definition

provides a measure of ECF and ICF because water is in osmotic equilibrium across capillary endothelium and cell membrane

Rough estimate: 2X plasma [Na+]

Term
Major cation of ICF
Definition
K+
Term
2 forces determining movement of water between body fluid compartments
Definition

1. Hydrostatic pressure – from pumping of heart; across capillary wall only

2. Oncotic pressure = osmotic pressure due to plasma proteins; across capillary wall and cell membrane

Term
Starling Forces of Capillary Fluid Exchange
Definition

vary among tissues and organs 

Fluid movement = Kf[(Pc – Pi) – σ(πc – πi)]

Kf = filtration coefficient of capillary wall

Pc = hydrostatic pressure in cap lumen (force for mvmt of fluid from lumen to interstitium)

πc = oncotic pressure of plasma (retards mvmt of fluid out of cap)

Pi = hydrostatic pr of interstitium (normally moves fluid out of cap)

πi = oncotic pr of the ISF – proteins that leak out of cap move fluid out of cap into interstitium

σ = reflection coefficient for proteins across the cap wall (value for ability of solute to cross cell membrane values for typical skeletal muscle capillary bed drawing

Term
Cellular Fluid Exchange
Definition
Cell membrane is highly permeable to water, thus there is osmotic equilibrium between ICF and ECF. Movement of ions across cell membrane depends on - specific membrane transporters - membrane permeability Examples: 1. 0.9% NaCl sol’n has osmolality of 290 mOsm/kgH2O (both ECF and ICF osmolality is approx 290) 2L added intravenously ECF volume increases by 2L because solution is isotonic; there is no driving force Na+ does go in but gets pumped out in proportion 2. 0.45% NaCl sol’n has osmolality of 145 mOsm/kgH2O 2L added intravenously ECF volume decreases because osmolality of ECF is decreased by the solution, water moves into ICF After equilibration, - osmolalities of ICF and ECF are equal but lower than before infusion - volume of each is increased with most increase in ICF (cells increase in volume) 3. 3% NaCl sol’n has osmolality of 1,000 mOsm/kgH2O 2L added intravenously ECF volume increases because osmolality of ECF is increased, water moves out of cells After equilibration: - osmolalities of ICF and ECF will be equal - volume of ECF is increased - volume of ICF is decreased
Term
Different Intravenous Solutions
Definition

1. 5% albumin used to increase patient’s vascular volume – albumin molecules don’t readily cross cap, volume retained

2. 0.9% NaCl (isotonic saline solution) used to expand ECF – entire volume of infused sol’n remains in ECF

3. hypotonicsolutions

(0.45% NaCl or D5W) used for patients with hyperosmotic body fluids – increases both ICF and ECF 4. hypertonic solutions (3% or 5% NaCl) used for patients with hypoosmotic body fluids – expand ECF volume, decrease ICF volume

Term
Gross Anatomy (of Kidneys)
Definition

paired, retroperitoneal

115-170 g each (<.5 % of total body weight)

11cmX6cmX3cm thick

 Composed of nephrons, blood vessels, lymphatics, and nerves.

Term
Renal Blood Flow
Definition
about 25% of cardiac output flows to the kidneys, about 1.25L/min Progression of vessels: - renal artery - interlobar artery - arcuate artery - interlobular artery - afferent arteriole - glomerular capillaries (glomerulus) - efferent arteriole - peritubular capillaries (supply blood to nephron) - Vasa Recta - ascending recti - arcuate vein - interlobar vein - renal vein – courses beside the ureter
Term
Vasa Recta
Definition

Long hairpin-shaped vessels

Follows course of loop of Henle  Function: concentrate/dilute urine

Term
Nephron
Definition

Functional unit of the kidney

1.2 million nephrons in each kidney Consists of: 1. glomerular capillaries (capillary tufts from afferent arteriole inside bowmans membrane, site of ultrafiltration of blood into Bowman’s capsule)

2. Bowman's membrane

Term
Podocytes
Definition
epithelial cells which cover the glomerular capillaries; form the visceral layer of Bowman’s capsule; Endocytic, can phagocytize
Term
Filtration Barrier
Definition

Formed of:

Endothelium- fenustrated, allowing water Na+, urea, glucose, and small protiens through

Basement membrane- pourous matrix of extracellular proteins, type IV collagen, Laminin, Fibronectin, and other negative charged proteins

Filtration slits-Retard filtration of some macromolecules, 40-140 A

Term
Mesangium
Definition

consists of:

1. Mesangial Cells-

phagocytic

Secrete prostaglandins and cytokines

Can contact and influence GFR

2. Mesangial marix

Term
Renal Tubule
Definition

lined with epithelial cells, specialized for transport functions Segments:

1. proximal tubule

2. Henle’s Loop . descending thin limb . ascending thin limb . thick ascending limb (with macula densa) 3. distal tubule

4. cortical collecting duct (from 2 or more nephrons)

5. collecting duct . principal cells – invaginated basolateral membrane, few mitochondria . intercalated cells – high density of mitochondria

Term
Brush Border
Definition

present only in proximal tubule 

Extensions of cell membrane which increase surface area for reabsorption

Dense in mitochondria

Term
2 Types of Nephrons
Definition

1. Superficial Cortical Nephrons - glomerulus located in outer cortex - short loop of Henle extends only into outer medullary region

2. Juxtamedullary Nephrons - glomerulus located near corticomedullary boder - larger renal corpuscle, long loop of Henle extend deep into inner medullary region - function to concentrate urine

Term
Juxtaglomerular Apparatus
Definition

comprised of:

1. macula densa of thick ascending limb; actually a plaque in its walls

2. extraglomerular mesangial cells

3. granular cells of afferent arteriole involved in autoregulation of blood pressure through tubuloglomerular feedback mechanism

Term
Granular Cells
Definition
modified smooth muscle cells which produce and secrete renin [Renin converts circulating angiotensinogen to angiotensin I which travels to lungs to be converted by ACE to angiotensin II. Angiotensin II has the effect of stimulating aldosterone secretion by adrenal cortex, arteriolar vasoconstriction, stimulating ADH secretion, enhancement of NaCl reabsorption by proximal tubule—all increasing blood pressure.]
Term
Innervation of Kidneys
Definition
sympathetics only (no parasympathetics) – from celiac plexus
help regulate RBF, GFR, Na and water reabsorption by nephron
Adrenergic fibers which release norepinephrine and dopamine; release has 3 effects:
1. stimulates contraction of smooth muscle cells of renal artery and afferent arterioles
2. stimulates secretion of renin from granular cells of afferent arterioles
3. enhances Na reabsorption by nephron segments
Term
Nephrotic Syndrome
Definition
characterized by increase in protein permeability in glomerular capillaries (=leaky glomerulus)
Proteinuria = protein in urine of >3.5 g/day (may see protein foam upon collection)
also see hypoalbuminemia and severe edema
Risk Factors:
- diabetes is #1 (uncontrolled)
- membranous glomerulopathy
- foot process disease (too far apart)
- amyloidosis
Term
Alport’s Syndrome
Definition
Hematuria
can be due to glomerulonephritis—cause of 1-2% of renal failure; result of genetic defect in type IV collagen of basement membrane
Term
Ureters
Definition
muscular tubes 30 cm long
enter bladder on posterior aspect, near base but above bladder neck
Term
Bladder
Definition
1. Fundus – body
2. Neck – 2-3 cm long funnel, connects to urethra
Trigone – above posterior urethra, below ureters
Detrusor Muscle
- smooth muscle surrounding transitional epithelium
- forms distinct layers close to bladder neck, fibers arranged randomly:
. inner and outer longitudinal
. middle circular
- smooth muscle cells are electrically coupled, contract when stretched, so entire bladder contracts at once for entire emptying of bladder
- under autonomic control
Rugae – folds which make bladder highly distensible; assisted by transitional epithelium; volume can go from 10 ml to >400 mL with pressure change of 5cm H2O
Term
3 Types of Cells of Renal Calyces, Pelvis, Ureter and Bladder
Definition
all lined with transitional epithelium
1. basal columnar cells
2. intermediate cuboidal cells
3. superficial squamous cells
Term
Internal Sphincter
Definition
smooth muscle of bladder neck
stops urine flow for storage (also autonomic)
Term
External Sphincter
Definition
skeletal muscle (under voluntary control)
can prevent or interrupt urination
better developed in males
Term
Innervation of Bladder
Definition
1. Sympathetic – from hypogastric nerves; -adrenergic receptors cause contraction of bladder neck and urethra, causing closure
2. Parasympathetic – from pelvic nerves; muscarinic receptors cause sustained bladder contraction
3. Sensory fibers – pelvis visceral afferent; carry input from receptors that detect bladder fullness, pain, temp sensation
4. Sacral Pudendal Nerves – innervate the skeletal muscle of external sphincter
Term
Nephrolithiasis
Definition
= Kidney Stones = renal calculi
5-10% Americans
Composition: 80-90% Ca salts
10-20% uric acid, Mg, NH4, acetate, cysteine
Formed as crystallation of super-saturated urine
Caused by:
- hypercalcemia
- constant dehydration
- frequent UTIs
- prostate enlargement
Lithotripsy – ultrasound vibrations to shatter stone into granules
Disease manifests when stones block ureter – get severe flank pain due to reflex constriction of ureter; pain perceived by sensory pelvic nerves
Term
Passage of Urine
Definition
Kidney to ureter:
urine collects in renal calyces
pacemaker activated by stretch (peristaltic contraction)
urine pushed from pelvis to ureter
Micturition:
1. progressive filling of bladder until critical pressure is reached (bladder wall stretched)
2. Neuronal/Micturition Reflex initiated by bladder wall stretch, an autonomic spinal cord reflex, empties the bladder
[Micturition reflex can be inhibited or facilitated by centers in brainstem and/or cortex]
3. parasympathetic stimulation of detrusor muscle causes smooth muscle cells in neck of bladder to contract, opening the neck of the bladder; urine flows through posteiror urethra
4. voluntary relaxation of external sphincter by cortical inhibition of pudendal nerves initiates micturation
Reflex can be altered by destruction of parasympathetic nerves resulting in complete bladder dysfunction, but not by interruption of hypogastric sympathetic nerves or of pudendal nerves.
Term
Urine Volume
Definition
average: 1-2 L/day
possible range: 0.5L/day – 18L/day (not normal)
Term
UTI
Definition
= cystitis
common in women due to E. coli traveling from perineum up short urethra
untreated, bacteria can spread up ureters, cause
pyelitis = infection of renal pelvis, then
pyelonephritis – inflammation of nephrons and cortex (entire kidney infected—could also be bloodborne)
Kidney stones, prostate enlargement can cause urine stagnation, increased risk of UTI.
Term
Urinary Incontinence
Definition
= inability to hold urine, involuntary leakage from bladder
caused by:
- urinary sphincter incompetence
- bladder irritation (eg UTI)
- brief surges in bladder pressure due to stress, neurological incontinence
- pressure on bladder in pregnancy
- spinal cord injury
Term
Urine
Definition
= ultrafiltrate of plasma across the glomerular capillaries
Term
Glomerular Filtration Rate
Definition
GFR = sum of filtration rates of all functioning nephrons (2.4 million)
can indicate severity and course of kidney disease, index of kidney function
Fall in GFR indicates disease is progressing.
Increase in GFR after previous fall, suggests recovery/healing.
Term
Renal Clearance
Definition
= the rate at which substances are removed from the plasma
= the volume of plasma completely cleared of a substance by the kidney per unit time
A concept based on the Fick Principle (mass balance or conservation of mass): input = output
Input to kidney: renal artery
output: renal vein and ureter
C = [U] x V [P]  [U] x V
[P]
C = clearance (ml/min)
[U] = urine concentration of x (mg/ml)
V = urine flow rate (ml/min)
[P] = plasma concentration of x (mg/ml)
Clearance can be used to:
- measure GFR
- measure RPF (renal plasma flow)
- determine whether a substance is reabsorbed or secreted
Term
Excretion Rate
Definition
= [U] x V (ml/min)
Term
Criteria for Marker for Measurement of GFR
Definition
1. filttered freely across glomerulus into Bowman’s space
2. not reabsorbed or secreted
3. not metabolized or produced by kidney
4. does not alter GFR in any way
Term
Clearance of Inulin
Definition
polymer of fructose
molecular weight = 5,000 g/mol
not produced by the body
meets above criteria, so
amount filtered = amount excreted (used to determine GFR)
therefore:
GFR = [U] x V
[P]
Term
Filtration Fraction
Definition
FF = GFR/RPF
percent of plasma entering glomerulus which is filtered
normally 15-20%
[10% of plasma does not pass through a glomerulus]
Term
Creatinine
Definition
byproduct of skeletal muscle creatine metabolism
used to estimate GFR (reasonably accurately)
Production: produced endogenously at a constant rate in proportion to muscle mass
Secretion: from peritubular capillary blood to renal tubules and to a small extent by proximal tubule cells (doesn’t meet all criteria for a marker)—this adds an error of about 10% overestimation of renal tubule creatinine
Error in claculation: about 10% overestimation of plasma creatinine (cancels above error due to secretion)
Term
Albumin Clearance
Definition
ZERO – not filtered across the glomerular capillaries
Term
Glucose Clearance
Definition
ZERO – filtered but reabsorbed 100%
Term
Na, Urea, P, Cl Clearance
Definition
>zero – filtered and partially absorbed
Term
PAH Clearance
Definition
highest clearance rate of all substances
both filtered and secreted
Term
Glomerular Filtration/Formation of Urine
Definition
Formation of ultrafiltrate:
a. renal blood flow enters glomerular capillaries
b. a portion of renal blood flow is filtered (result of Starling Forces) into Bowman’s capsule = the ultrafiltrate; contains water and solutes, no cells or proteins
Term
Autoregulation
Definition
GFR and RPF (renal plasma flow) are held within very narrow ranges
Term
Glomerular Filtration Barrier
Definition
GFB
= physical structure of glomerular capillary wall
determines what is filtered, how much is filtered and the composition of the plasma ultrafiltrate
consists of:
- capillary endothelium
- basement membrane
- filtration slits of podocytes
restricts filtration of molecules on the basis of
1. Size – 20-40A neutral molecules are filtered freely
2. Charge – cations are readily filtered as negatively charged glycoproteins line the ouside surface of the glomerular capillaries
Term
Proteinuria
Definition
In the case of glomerular disease, inflammation and/or immunological damage can increase protein filtration, leading to protein in the urine.
Term
Determinants of the GFR
Definition
1. net filtration pressure = sum of all Starling Forces
2. glomerular filtration coefficient = Kf

GFR = Kf x [(Pg – Pb) – (πg – πb)]

Kf – reflects:
- intrinsic permeability of capillary wall
- surface area available for filtration
Normal pressure values:
Pg = 60 mmHg =hydrostatic pr of glomerular capillary – favors filtration
Pb = 18 mmHg =hydrostatic pr of Bowman’s caps – opposes filtration
πg = 32 mmHg =colloid osmotic pr of glom. cap - opposes filtration
πb = 0 = colloid osmotic pr of Bowman’s caps – no effect; favors filtration if >0 (abnormal conditions)
Normal Net Filtration = +10 mmHg
Kf = 12.5 mL/min/mmHg
GFR = 125 mL/min = 180 L/day
Term
Effects of Changes in Pressures/Kf
Definition
1. Increase in Kf increases GFR
2. Increase in Pb decreases GFR – ex: obstruction of urinary tract (stones due to deposit of Ca or uric acid) causes serious reduction of GFR and damage to kidney
3. Decrease in Pb increases GFR
4. Increase in Pg increases GFR; decrease in Pg decreases GFR; 3
variables determine Pg:
- arterial pressure (increase in a.p. increases Pg)
- afferent arteriolar resistance – increase in aar, decreases Pg; dilation of afferent arterioles increases Pg, increasing GFR
- efferent arteriole resistance:
. modest constriction of efferent arterioles increases Pg and GFR
. severe condtriction reduces blood flow, decreasing Pg and GFR
5. πg>Pg, decreased net force for filtration, decreased GFR
Term
Urine Formation
Definition
result of 3 processes:
1. glomerular filtration (fomation of ultrafiltrate into tubules)
2. secretion from blood into renal tubules – of unwanted solutes which were not filtered in glomerulus
3. reabsorption from renal tubules into blood

urinary excretion rate = filtrate rate – reabsorption rate + secretion rate
Term
Ultrafiltrate
Definition
= tubular fluid = luminal fluid
large amount of protein-free fluid
approximately same solute concentration as plasma
180 L/day formed
amounts filtered daily:
180 L water
22,500 mEq/L Na
19,800 Cl
4,320 HCO3
14,400 mg glucose
Term
Filtered Load
Definition
= amount of a substance filtered into Bowman’s space per unit time
filtered load = GFR x [P]x
Term
Reabsorption
Definition
of water and solutes
from glomerular filtrate in renal tubules into blood
substances pass through:
- luminal/apical membrane of tubule cell
- basolateral membrane of tubule cell
- (ISF)
- capillary endothelial cell
Inorganic solutes: Na, Cl, HCO3, Ca, Mg, P, urea
organic solutes: aas, citrate, lactate
Requires transporters in membranes of renal epithelial cells
Term
Secretion
Definition
Organic acids, organic bases and K are secreted from peritubular capilary blood into tubular fluid (into urine).
Requires transporters in membranes o epithelial cells
Term
Excretion rate
Definition
= amount of a substance excreted per unit time
net result of filtration, reabsorption and secretion
excretion rate = V x [U]x
(reabsorption/secretion rate = filtered load – excretion rate)
Term
Tubular Transport Maximum
Definition
Tm = concentration at which transporters are saturated
Term
Glucose Reabsorption Example
Definition
normal blood glucose: 70-100 mg/dL
Glucose is transported by 2o active transport: Na-glucose transporters which use Na gradient to move glucose against glucose gradient
All glucose is reabsorbed via transporters (until threshold reached)
Tm = 350
threshold = plasma concentration at which glucose first appears in urine (glucosuria); threshold is lower than Tm
see Guyton figure + p. 232 case study
Causes of glucosuria:
1. uncontrolled diabetes mellitus – plasma glucose conc is abnormally high due to insulin deficiency; filtered load of glucose exceeds reabsorptive capacity
2. pregnancey – GFR is increased, increasing filtered load which may exceed reabsorptive capacity
3. congenital abnormalities of Na-glucose co-transporters in apical/luminal membrane of proximal tubule cells; lowered Tm, glucose excreted in urine at lower than normal plasma conc of glucose
Term
Urea Reabsorption
Definition
filtered freely across the blomerular cpillaries
reabsorbed in most segments of nephron by simple diffusion
rate determined by:
- concentration difference for urea between tubular fluid and blood
- permeability of epithelial cells to urea
Term
PAH Secretion
Definition
= para-aminohippuric acid = hippurate
used to measure RPF
not produced in body
unbound PAH is both filtered and secreted (90% of PAH is bound to plasma proteins)
Filtered load of PAH increases linearly as unbound concentration of PAH increases.
Transporters in basolateral membrane of proximal tubule cells, can become saturated. Excretion increases linearly with increase in plasma PAH only until Tm is reached. Then excretion increases only with subsequent increase in filtration rate as no additional secretion can occur (transporters saturated).
Term
Renal Blood Flow
Definition
25% of cardial output
1800 L/day = 1.25 L/min

Q = ΔP/R ΔP = mean arterial pressure-renal venous pressure
R = resistance of flow through organ
Term
Functions of Kidneys
Definition
1. determine GFR
2. modify rate of solute and water reabsorption by proximal tubules
3. participate in concentration and dilution of urine
4. deliver O2, nutrients, and hormones to cells of nephron
5. return CO2 and reabsorbed fluid and solutes to circulation
6. deliver substrates for excretion in urine
Term
Autoregulation of RBF and GFR
Definition
1. absent at arterial pressure <90 mmHg
2. not perfect – RBF and GFR change slightly as arterial b.p. rises
3. GFR and RBF can be changed under appropriate conditions by several hormones.
2 Mechanisms:
1. Myogenic Mechanism
2. Tubuloglomerular Feedback
Term
1. Myogenic Mechanism
Definition
intrinsic property of vascular smooth muscle: response to changes in arterial pressure
inc arterial pressure  renal afferent areriole stretched  smooth muscle contracts, increasing resistance to offset the increase in pressure, thus maintaining constant RBF and GFR
Term
2. Tubuloglomerular Feedback
Definition
reponse to change in NaCl concentraiton of tubular fluid
macula densa of juxtablomerular apparatus senses NaCl conc of tubular fluid, signals afferent arteriole, altering resistance, example:
- increased GFR causes increase in NaCl conc in tubular fluid in Henle’s loop
- sensed by macula densa, converted into signal
- increase in resistance of afferent arteriole
- lowered GFR
Term
Sympathetic Nerves and RBF/GFR
Definition
Norepinephrine vasoconstricts by binding to receptors on afferent arterioles, decreasing RBF and GFR
released in cases of fear or pain
Term
Epinephrine
Definition
from adrenal medulla
vasoconstricts in same manner as norepinephrine
Term
Angiotensin II
Definition
produced by kidneys
constricts afferent and efferent arterioles, decreasing RBF and GFR
Term
Prostanglandins
Definition
(may not regulate RBF or GFR in healthy individuals)
In hemorrhage (decrease in effective circulating volume), PGI2 and PGE2 are produced within kidneys.
They dampen the vasoconstrictor effects of sympathetic nerves and angiotensin II, increasing RBF with no change in GFR
This prevents severe and potentially harmful vasoconstriction and renal ischemia.
Term
Nitric Oxide
Definition
endothelium-derived relaxing factor
released by endothelial cells when arterioles are stretched
counteracts vasoconstriction producd by angiotensin II and catecholamines (NE, EPI) by causing vasodilation of both afferent and efferent arterioles; decreases total peripheral resistance
Hormones and neurotransmitters also increase NO production (Ach, histamine, bradykinin, ATP).
Term
Endothelin
Definition
secreted by endothelial cells of renal vessels, mesangial cells, and distal tubular cells in response to:
- antiotensin II
- bradykinin
- epinephrine
- stretch
vasoconstricts afferent and efferent arterioles, decreasing GFR and RBF
(may not influence GR and RBF in basal state)
elevated in glomerular diseased states such as diabetes mellitus, very damaging.
Term
Bradykinin
Definition
produced by kidneys
vasodilator
stimulates release of NO and PGs
increases GFR and RBF
Term
Adenosine
Definition
produced in kidneys
vasoconstrictor of afferent arterioles, decreasing RBF and GFR
may play a role in tubuloglomerular feedback
Term
Atrial Natriuretic Peptide
Definition
ANP
secreted by heart with hypertension and expansion of ECV
causes:
- vasodilation of afferent arteriole
- vasoconstriciton of efferent arteriole
with net effect of modest increase in GFR, little change in RBF
Term
ATP
Definition
2 effects:
- constriction of afferent arteriole, decreasing RBF and GFR, with a role in tubuloglomerular feedback
- may stimulate NO produciton at other times, increasing GFR and RBF
Term
Glucocorticoids
Definition
therapeutic doses increase GFR and RBF
Term
Histamine
Definition
local release may increase RBF without elevating GFR by decreasing afferent and efferent arteriolar resistance with slight vasodilation
Term
Dopamine
Definition
produced by proximal tubule
vasodilator hormone
increases RBF
inhibits renin secretion, causing net vasodilation
Term
RENAL TRANSPORT MECHANISMS
Definition
1. Passive Diffusion
a. diffusion – via conc gradient or electrical gradient
b. osmosis
c. solvent drag
d. facilitated diffusion
2. Active Transport
a. coupled transport
b. endocytosis
Term
Osmosis
Definition
movement of water from high conc to low conc through pores in membrane with some displacement of lipids
driven by osmoic pressure gradient (solute concentration)
Term
Solvent Drag
Definition
substantial amount of solutes get dragged in with water between cells into proximal tubule
Term
Facilitated Diffusion
Definition
uses carrier
uniport – movement in one direction only (ex: urea, glucose)
Term
Primary Active Transport
Definition
= direct active transport
moves solute up concentration gradient
requires ATP
Term
Secondary Active Transport
Definition
= indirect active transport
requires ionic gradient energy
Term
Coupled Transport
Definition
1. Symport – carrier moves 2 solutes in the same direction; one or both molecules pumped by carrier, 0 or one diffuses
- Na-glucose
- Na-amino acid
- Na-phosphate
- 1Na-1K-2Cl in thick ascending limb of Henle’s loop
2. Antiport – carrier moves 2 solutes in opposite directions
- Na-H antiporter in proximal tubule (apical membrane); uphill movement of H out of cell into tubular lumen using Na gradient as energy source (secondary active transport)
- Na-K-ATPase – active transporter in basolateral membrane
- H-ATPase
- H-K-ATPase – last 2 secrete H in collecting ducts
- Ca-ATPase – moves Ca from cytoplasm into blood
Term
Endocytosis
Definition
(pinocytosis) = invagination of membrane, engulgind and pinching off an endocytic vesicle
used to reabsorb larger molecules: small proteins than may have been filtered and some macromolecules
ATP required
Term
Paracellular Pathway
Definition
reabsorption or secretion of substances between cells (Renal cells are held together by tight junctions.)
Ex: Ca and K are reabsorbed by solvent drag between cells
Term
Transcellular Pathway
Definition
reabsorption or secretino of substances through the cells
2-step process of reabsorption of Na:
1. movement across apical membrane into cell down electrochemical gradient established by the Na-K pump
2. movement across basolateral membrane out of cell against electrchemical gradient via the Na-K pump
Term
Adaptation to Nephron loss
Definition

Kidney response to homeostatic need

Urine may be diluted 50m OSM/L

Concentrated 120m OSM/L 

Term
One Difference between composition of ISF and Plasma in ECF
Definition
Lots more proteins
Term
What causes fluid to leave the lumen (filtration) along its entire length?
Definition

The ballance of starling forces across muscle capillaries

The filtered fluid is then returned to circulation via lymphatics

Term
Nephrin
Definition

Transmembrane protein of slit diaphragm

Mutation in Nephrin gene causes abnormal slit diaphragm and leads to massive proteinuria and renal failure

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