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Mammalian Physiology
Diffusion, Kidney Function
88
Physiology
Undergraduate 3
01/25/2011

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Term
Fick Equation
Definition

M/A=J=(D/X)(C1-C2)

M=Molecules/second

A=Area

J=Molecules/cm2sec (net flux)

D=diffusion constant

X=distance of diffusion

Term
Boundary layer
Definition
area just outside the cell where concentration difference is less, which impedes rate of diffusion
Term
Ions are affected by ______ and _________
Definition

voltage

concentration gradient

Term
How do ions cross membranes?
Definition

Ions cross membranes via selective gated ion channels

Gating is affected by voltage, stretch, and chemical interactions (ligand binding, phosphorylation)

Term
When are ions at equilibrium?
Definition
Equilibrium occurs when concentration and electrical gradients are opposite and have equal effects.
Term
Colligative properties
Definition

Properties of a solution that depend on the concentration of dissolved entities.

increase in osmolality

decrease water vapor pressure

decrease freezing point

Term
Isosmotic
Definition
equal osmolarity on both sides of the membrane
Term
Isotonic
Definition
The cell will not change volume in this solution
Term
Osmotic pressure does not create hydrostatic presure, unless...
Definition
Osmotic pressure does not create hydrostatic pressure, unless osmosis occurs from a hyposmotic solution into a confined hyperosmotic solution (e.g. hemolysis)
Term
How does water cross a membrane?
Definition

diffusion through phospholipid

or

channel-mediated water transport through water-specific aquaporitns (rbc, some kidney tubules)

Term
Channel-mediated water transport
Definition

faster than diffusion

faster flux due to bulk flow strreaming, but still passive

 

Term
aquaporin premeability is modulated by
Definition
phosphorylation or insertion/retrieval (vasopressin)
Term
Human cell osmolarity
Definition
approx. 300 mosM
Term
Osmolarity at equilibrium
Definition

Permeant concentrations: in matches out

cell volume changes (water movement) so osmolarity in matches out

total impermeant concentrations in and out balance

Term
Effect of nonpermeating solutes
Definition
Nonpermeating solutes create a persistent osmolarity difference, causing a continuous flow or balancing a hydrostatic pressure
Term
 A lone permeant ion is...
Definition
 A lone permeant ion is non-penetrant because it builds a voltage that stops net movement
Term
Permeant ions are permeant only if...
Definition
Permeant ions are permenat only if part of a permeant pair that can move together without changing voltage
Term
Relationship between [Na+] and [A-]
Definition

A- is impermeant

K+ and Na+ are permeant, but pump makes Na+ non-penetrating

Pump needed for [Na+] to balance [A-] for stable cell volume

The concentration gradient of a permeable ion can create an electrical gradient

Term
Donnan equalibrium
Definition

Involves more than one permeating ion plus nonpermeating ions.

Cell volume is maintained by a double Donnan system (nonpermeating intracellular anions and effectively nonpermeating extracellular Na+)

Term
Carrier-mediated transport: Organic polar (hydrophilic) solutes
Definition

transported by carrier proteins

Ions, sugars, amino acids bind reversibly to specific transporters

transport shows saturation kinetics

conformational changes in the transporter protein are key

Term
Facilitated diffusion
Definition
carrier-mediated, faster than diffusion, but can only transport solutes toward equilibrium
Term
Active carrier-mediated transport
Definition

use energy to transport solutes away from electrochemical equilibrium

 

Term
Electrogenic pump
Definition
active transport mechanism that produces a voltage difference
Term
Electroneutral pump
Definition
active transport mechanism that does not produce a voltage difference
Term
Primary active transport protein
Definition
ATPase with strict coupling between ATP hydrolysis and protein conformational state
Term
Na+ - K+ - ATPase
Definition

-Located in the basolateral membrane of epithelia

Na+ ions bind, phosphorylation changes affinity, Na+ are occluded, then exit. K+ sites increase affinity, K+ bind, dephosphorylation changes affinity, K+ are occluded, then enter

Term
Secondary active transport protein
Definition
Uses energy stored in an electrochemical gradient - symporters (cotransporters) or antiporters (countertransporters)
Term
Characteristics of transport proteins and channels
Definition

can exist in different forms in different tissues and species

can undergo noncovalent and covalent modulation, insertion/retrieval, and changes in gene expression, often under hormonal control

Term
Two types of transepithelial transport
Definition

paracellular- movement through tight junctions

transcellular - through apical and basolateral membranes via various mechanisms

Term
Desmosomes
Definition
strong junctions that attach cells and reinforce cellular attachments
Term
Gap junctions
Definition

Proteins in the membranes of cells that line up and form a channel between them

Permit 1 KD of momement between cell interiors

Term
Basement membrane
Definition

Epithelia rest on a secreted basement membrane

made of glycoproteins and collagen

exchange with capillaries is through basement membrane

Term
Ion concentration regulation
Definition

protein conformation is affected by fluid composition

membrane electrical gradients are affected by fluid composition

humans regulate Na+, K+, Ca2+

Term
Total body water composition
Definition

60% of weight in men, 50% of weight in women

ECF = 1/3 TBW, ICF = 2/3 TBW

Plasma = 20% ECF

Term
Colloid
Definition
solutes that are too big to be crystalloid and sty trapped in plasma, producing colloid osmotic pressure
Term
Water vapor pressure
Definition

Partial pressure of gaseous water in equilibrium with a liquid solution in a closed system at a given temperature

Affected by dissolved solutes (colligative property)

Term

Water vapor pressure from 1 to 2

(body to air)

Definition

J = (K/X)(WVP1-WVP2)

K = permeability of integument

X = thickness of integument

Term
U/P ratios indicate...
Definition

U/P ratios indicate the effect of the kidneys on plasma composition

Kidneys can independently regulate ion concentration, volume, and osmolarity

Term
Human (U/P)osm
Definition

Ranges from .1 to 4

U/P = 1 does not change Plasma concentration

U/P < 1 concentrates Plasma concentration

U/P > 1 dilutes Plasma concentration

Term
Metabolic water
Definition
Water produced in accordance with the stoichiometry of the oxidation reactions of foodstuffs
Term
Obligatory water losses
Definition

Include respiration, urine and feces

-insensible water loss (dry air on skin)

-inspired air may be dry and cold while expired air is warm and saturated

Term
Use of organic molecules in maintaining constant ICFV, ICF solute amout, and osmolarity
Definition

-Permits changes in intracellular solute amount while maintaining cell volume and intracellular ion concentrations

-Compatible solutes (which have minimal side effects on macromolecules) or occur in counteracting pairs (like urea and methylamines)

Permits the intracellular concentrations of inorganic ions to be similar in all animals

Term
ICFV regulation feedback loop
Definition
[image]
Term
ECFV feedback loop
Definition
[image]
Term
Antidiuretic Hormone
Definition

Stimulated by increased osmolarty (or by low blood volume or pressure in emergency)

Promotes retention of solute free water

Term
Obligatory water loss due to solute
Definition
urine solute amount/max Uosm
Term
Aldosterone
Definition

Stimulated by low blood volume, pressure via renin-antiotensin system

controls ECFV including blood plasma volume

INcreased Na+ amt leads to ECFV expansion

also affects salivary, sweat glands, intestines, salt appetite

Term
ICFV =
Definition
ICFV = cell solute/Posm
Term
ECFV =
Definition
ECFV = Na+ amt/[Na+]pl
Term

Atrial Natriuretic Peptide

"P Na"

Definition

Stimulated by atrial stretch (blood volume increase)

Inhibits aldosterone secretion, promotes Na+ and water excretion

Inhibits distal Na+ reabsorption, vasopressin, renin, aldosterone secretion

Increases GFR (glomerular filtration rate)

Term
Function of the glomerulus
Definition
The glomerulus produces a large quantity of plasma ultrafiltrate but retains proteins within the capillaries
Term
GFR
Definition
Glomerular filtration rate = 120 ml/min
Term
Functions of the proximal tubule of nephron
Definition

The proximal tubule reabsorbs "goodies" such as HCO3-, glucose, and amino acids

Isosmotically reabsorbs enough salt and water to reduce the quantity of tubular fluid and solute to amounts that the later nephron segments can manage (about 70% reabsorption)

Term
Function of Loop of Henle
Definition

Makes tubular fluid hyposmotic and medullary interstitial fluid hyperosmotic

Reabsorbs additional salt and water

Term
Function of the distal tubule of nephron
Definition

fine regulation of Na+, K+, and H+ balance

reabsorbs additional salt and water

Term
What happens in the collecting duct of the nephron?
Definition
The collecting duct is the segment where the osmolarity of urine is determined
Term
Ultrafiltration
Definition

Mammals produce primary urine by ultrafiltration

Push:

BP in glomerular capillary: 50mmHg

Colloid osmotic pressure: -25 mmHg

Capsular fluid hydrostatic pressure: -15 mmHg

=total pressure pushing fluid out: 10 mmHg

Term

Glomerular filtration pathway?

Rate?

Definition

Pathway: endothelium, basement membrane, epithelial podocytes - proteins are filtered out on the basis of size and charge

Combined rate = 120 ml/min

Term
Diuresis: osmotic or water
Definition

Increased urine flow

Lack of ADH causes water diuresis: copious dilute urine

Increased solute excretion causes a solute (or osmotic) diuresis

Term
Basic makeup of mammalian kidneys
Definition

Cortex contains glomeruli and convoluted tubules

Medulla contains loops of Henle, collecting ducts, and vasa recta, which are all required to produce concentrated urine.

Term
Recipe for a dilute urine
Definition

reabsorb solute, but make water stay in the tubules (active reabsorption)

-The walls of the TkAL and DCT are water-impermeable and so are the late DT and CD in the absence of ADH

Term
Recipe for a concentrated urine
Definition

Osmotic gradient in the medulla, where osmolarity is higher in the interstitial fluid than the tubules

Single effect: the TkAL reabsorbs solute without water

-Na/K pump causes lower Na concentration inside cell

Na movement helps to bring 2Cl and 1K into the cell using the gradient (secondary active transport)

Term
Countercurrent multiplication
Definition

Results in large end-to-end osmotic gradient

 

Term
Osmotic equilibration between CD fluid and the ISF in the medulla
Definition

Uses gradient created with countercurrent multiplication

occurs if ADH is present to insert aquaporin-2 proteins into CD apical membranes

Urea is concentrated in the CD, then moves from high concentration through UT proteins into the ISF and AL (Urea recycling)

Term
Vasa Recta
Definition

Carry blood into the medulla and back out

Act as countercurrent exchangers: blood loses water and gains solute as it goes toward the turn, and gains water and loses solute as it returns.

Solute from ISF that enters blood in descending limb is returned to ISF from ascending limb, so solute is not carried away blood.

This preserves the osmotic gradient.

Term
_________ protect cell volume in the high osmolarity medulla
Definition
Organic osmolytes
Term
Reabsorption of bicarbonate by Proximal Tubule
Definition
Changed to CO2 so that it can be transported into the cell, and then moved into the interstitial fluid b secondary active transport
Term
Reabsorption of glucose and amino acids by proximal tubule
Definition

Sodium, glucose cotransporter for glucose

Similar pathway for amino acids, but with different proteins.

Facilitated diffusion

Term
Properties of carrier proteins in proximal tubule
Definition

Specificity

Saturation

Inhibition

Competition

Term
How is PT fluid kept isosmotic?
Definition
Water is reabsorbed through constitutive aquaporins
Term
What controls fine regulation of sodium and potassium excretion?
Definition
Aldosterone action on the late DT and CD
Term
Aldosterone
Definition

Steroid hormone produced in adrenal cortes of adrenal gland

Increases expression of genes for basolateral Na/K pumps, apical Na channels, and apical K channels

Increases Na reabsorption and K secretion

Term
Types of nitrogen excretion
Definition

Ammonia

Urea

Uric acid and urates

Term
Ammonia
Definition

Requires little energy to synthesize

Its toxicity means it must be kept at concentrations below .3mM, so it requires a lot of water

most ammonotelic organisms are aquatic

We use ammonia excretion to maintain acid/base balance, but it is not a principal means of nitrogen excretion

Term
Urea
Definition

Requires 4-5 ATP to make one urea (2 N atoms)

Less toxic than ammonia - 5mM

Less water is required to excrete urea than ammonia - most urotelic organisms are terrestrial vertebrates, including mammals

Term
Uric acid/ Urates
Definition

low toxicity and low solubility

can be stored as deposits during a water shortage

can be excreted with less water than urea (birds)

Uric acid requires more energy to make than urea

Term
Water balance in marine mammals
Definition

Marine mammals maintain body fluids that are more dilute than their surroundings

Kidneys can concentrate to a U/P of about 6

Don't lose water through respiration or low-premeability integument

Don't drink sea water

Term
Types of water loss in land mammals
Definition

Evaporative water loss

Respiratory water loss

Excretory water loss

Term
Evaporative water loss in land mammals
Definition

Reduced by lipids in the low-permeability integument (e.g. glycolipids between skin cells)

Increased by larger surface area/kg or high metabolic rate/kg

Term
Respiratory water loss is reduced by...
Definition

-Carrying out respiration in invaginated lungs

-Cooling expired air and retaining the condensed water (countercurrent exchange)

Term
Excretory water loss in land mammals
Definition

Kidneys that concentrate well lose less water

excreting nitrogen in poorly soluble compounds would help, but mammals don't do it

Urea recycling is used to improve the concentrating ability of kidneys

Term
Water loss in small animals
Definition

greater evaporative water loss due to greater surface area to volume ratio

greater respiratory water loss due to greater metabolic rate per kg

greater concentrating ability

turnover more water per gram than large animals

Term

Renal clearance expresses...

What is the formula?

Definition

Renal clearance expresses excretion in terms of the equivalent volume of plasma cleared by the kidney per minute

Cx=VUx/Px=excretion of X/Px

V=urine flow rate

Ux=urine concentration of X

Px=plasma concentration of X

Term
What are the units of renal clearance?
Definition
volume /time
Term
How is GFR related to renal clearance?
Definition

GFR equals the clearance of a substance that is freely filtered but not secreted or reabsorbed.

-Inulin

-to a close approximation, Creatinine

Term
Clearance < GFR
Definition
Clearance is less than GFR for a substance that undergoes net reabsorption
Term
Clearance > GFR
Definition
Clearance is greater than GFR for a substance that undergoes net secretion
Term

Filtered Load equation

Excretion exquation

Definition

Filtered load = (GFR)(Px)

Excretion=VUx

or

Excretion=filtered load + secreted amt - reabsorbed amt

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