Functional Unit of the kidney

Bowman's capsule, collecting tubule, clomerulus, Peritubular capillary bed, afferent arteriole, efferent arteriole

2 Types: Superficial nephron (short henle's loop)
Juxtamedullary Nephron (long hene's loop, associated vasculature, important for urine concentration)

Cx= Ux * V / Px

Cx = clearance

Ux = urine mmole/mL

V = volume of urine formed in a given time

Volume of fluid filtered into bowman's capsule per unit time

GPR = Ux * V / Px

Same as clearance as long as X is freely filtered and the tubules do not absorb, secrete synthesize degrade of accumulate X

Depends on Fx, filtered load Fx = GFR * Px

Rate of reabsorption X(rx) by tubules and Rate of secretion of X(Sx) of tubules

Rx = GFR * Px - Ux * V

Sx = Ux * V - GFR * Px

Fex = Ux * V / Px * GFR

= Cx/GFR

(useful benchmark to find out if something is removed from the plasma)

3 main parts: Afferent arteriole,Macula densa,Thick ascending limb

SNSES NaCl in tubule fluid

Adjusts resistance of arteriole- affects flow and filtration rate which affects NaCl concentration

Cells in afferent arteriole sense stretch (proportional to pressure)

If pressure drops- afferent arteriole directs surrounding cells to make Renin (enzyme, which releases into the blood, converts to circulating angiontensinogen I, II)

This becomes a powerful vasconstrictor (increases presure)

Occurs all around body, but concentration is highest in kidney endothelial cells as the convert from I to II)

Px,a * RPFa = Px,v * RPFv + Ux * V

Ux = concentration of X in urine(mmol/ml)

Px = concentration of x in plasma

RPF = renal plasma flow (ml/min)

V = urine flow(ml/min)

Measuring concentrations one can calculate flows

Px,a * RPFa = 0 + Ux *V
RPF = (Ux * V)/ Pxa

If you have a compound that can be removed 100%(a tracer) can use RPF

10% filtered, 90% secreted

so Cpah = RPF

Glomerulus filtration, tubule resorption, tubule secretion (pertubular capillary)

Ux * V = filtered-resobed+ secreted

Starch from plant, freely filtered, not resorbed or secreted, not metabolized

MW = 5000da

Pin,a = Pin, bowman's

Flomerular filtration rate

GFR = Uin * V / Pina

Passive filtration

passive spread of signal down a neuronal process

processes are not perfectly insulated conductors, signal gets attenuated as it travels

there is a finite resistance between intracellular and extracellular spaces

Constant velocity of propogation

Dendrite

Soma

hillock

Axon

Presynaptic Terminal

Dielectric material that forms a myelin sheath around the axon. Outgrowth of the glial cell. Increases the speed of impulse propegation. If a fiber is severed myelin provides a path to regrow.

Produced by Schwann Cells in the PNS

Produced by Oligodendrocytes in CNS

Acts as an insulator, decrease leak currents

For assumptions = plasma membrane, but not ture, resistance is greater and capacitance is lower

Cm = Q/Vm

C is in Farads C^2/ N*m^2

dictates speed: I = Cm(dVm/dt)

Capture network behavior- understand higher order functions

Occular dominance columns

so we can replace defective neuron networks and repair damaged neuron networks

V = IR or I = gV

Resistance is in ohms

Curret Law: all currents must sum to 0

Voltage law: all voltages must sum to 0

E_x= (RT/zF)ln[X_o]/[X_i]

F = 96500 columb/mole

I = V * g

(V_m - E_x) * g_x

V_m= (g_naE_na + g_KE_K + g_LE_L) / (g_na + g_K + g_L

)

g_k=g_{_k} * n⁴

repolarizes cell after AP fires

Limits the frequency of AP firings

dn/dt = -B_n(n) + a_n(1-n)

n(t) = c₁e^-t/T+ c₂

n(t) = n_inf * (1-e^-t/Tn)

g_na = g__na * m³h

m = activation

h = inactivation

dm/dt = a_m(1-m) - B_m(m)

dh/dt = a_h(1-h) - B_h(h)

Rising phase of AP, depolarizes the cell

Open and close faster than K channels

Causes the refractory period by closing

AP is an all or nothing- magnitude and duration is fixed

Absolute refractory period- a second stimulus cannot elicit an AP if too close to the first stimulus

AP begins when Vm > Vth

I_na i depolarizing

I_K is hyperpolarizing

Vth corresponds to I_na > I_K

initiates positive feedback but stopped when Na channles are shut down

insulation is not perfect

current loss through membrane

Need new model for neuron

Uniform cylindrical core

Length >> diameter

Uniform membrane properties

Uniform core properties

Simple model of plasma membrane

outside resistor, membrane = membrane resistance in parallel with membrane capacitance and then in series with internal resistance

λ = √r_m/(r_o+r_i)

λ= √(a * R_m)/ (2 * R_i)

R_i does not change due to myelin sheath, but R_m is different

τ=c_mr_m

Dependent on radius and electrical properties of lipid

τ = a/y * R_m * y/a * C_m

Ψ = A * e^bx + C

but for a finite solution b must be negative

as x -> inf Ψ = 0, thus C = 0

Ψ=Ψ_oe^-x/λ

r_m  is resistance across membrane times unit length

R_m is resistance times surface area (divide by perimeter to get resistance times unit length)

c_m capacitance of membrane per unit length

C_m is capacitance per unit area (multiply by perimeter, capacitance per unit length)

Dendrite, neurotransmitter binds, opens ion channel, depolarizes the membrane (no action potential, no voltage gated channels, excitory post synaptic potential)

Activates a protien (ion channel and signaling cascade)

Neurotransmitter binds to receptors

channels open to depolarise or hyperpolarize (depending on neurotransmitter)

local change is voltage, transmitted to the cell body (attenuated along way)

determines if an action potential is fired

Initiated at hillock, if V_m > V_th

Propogates by depoarizing the next piece of membrane

Channel opening generates local depoarization, depolarizes next segmetnt by passive propogation

Until V_th is reached, then action potential is regenerated

C_T= C * y/a

where a = n * y

R_T= a/y * R

Myelin is not continuous, Nodes of Ranvier seperate myelin sheaths

No ion channels between myelin sheath (concentrated at nodes of ranvier)

AP jumps from node to node, saltatory conduction

Use cable eq to determine if unmylenated section causes loss of AP

Assume V_th = 1/e Ψ_o

One neuron communicates with next via synapse

electrically isolated from one another, transmissin mediated by release of neurtransmittor

Transmit information about AP (excitory signal propogation only)

No physical connection between cells

message released from pre-synaptic terminal

bind to post synapic cell (pre and post synaptic machines)

Signals can be either excitatory or inhibitory (depends on chemical neurotransmitters

Action potential

Vesicle fusion

transmitter release

free diffusion gap (30nm)

Receptor binding

In the soma by golgi and endoplasmic reticulum (40 - 200nm in diameter)

They bind with the plasma membrane to release. Anchored by three protiens

Synaptotagmin sensed and initias fusion

SNAP-25 and syntaxin bind (still unknown)

Protiens, vesciles and mitocondria transported down axon (400mm/day)

ATP dependent process by motor protiens (kinesin antrograde, dynein retrograde)

AP depolarizes presynaptic terminal

Opens voltage gated Ca⁺⁺ channels

(huge gradiaent 0.1uM, 2mM outside)

This allows for vesicle fusion as it is Ca⁺⁺ dependent

Protiens embedded in plasma membrane bind specifically to certain compounds, altering conformation

Generates specific protiens, presynaptic side could release different NT's, post would express different receptors

Main neurotransmitter is Glutamate (and aspartate)

Have multiple glutamate receptors

Iontropic glutamate receptors (linked w/ ion channels which open when bound to glutamate)

Depolarize cell

Bind clutamate, open cation channel(for positive ions)

both K and Na flow in (net = depolarize)

Nernst potential between E_na and E_K

Occurs in fast excitatory synapses of CNS

Binds glucamate

Opens Cation channel (Na, K and Ca)

Influx of Ca stats many signaling cascades

At normal V_m is blocked by Mg

does not conduct until V_m is depolarised, then glucamate is bound

GABA_A Channels- Site of action for sedatives

y-aminobutyric acid

ionotropic- opens ion channels, specifically Cl, and drives V_m to E_Cl

Hyperpolarizes the membrane by 10mV

Binds to same ligand (Glutamate and GABA)

does not open an ion channel, but activates G-protiens, which initiates signaling cascades.

Amino Acids-glutamate

Monoamines-Acetylchloine, serotonin

Catecholamines-Norepinephrine

Pepties-Endorphin

Exctatory (ionotropic)

Inhibitory (ionotropic)

Modulatory (metabotropic)

Generated in kidney

flows through the ureter

collects in bladder

excreted through the uretha

Suprarenal gland- adrenal (not involved in urine production)

Weight 0.5% of body weight, but 20% of cardiact output

1L/min

renal artery-> main branch of descenting aorta

Renal Vein-> returns through the inferior vena cava

Model 1- Selective secretion, Transporters, channels, exchangers

Active removal of products from the blood

Model 2- Passive Filter, followed by selective resorption-Transporters, exchangers

Special capillary bundle

with resistance arterioles

Leaky capillary- makes a filtrate from plasma

Passive filter (retains blood cells and large protiens, passes water ions and small solutes)

collecting duct

active excretion and resorption proceses

many sections

Resorbs NaCl, NaHCO₃ glucose amino acids + water

Generates an osmotic gradiaent in th medulla

Concentration of urine (only juxtamedullary nephrons contribute)

Net Starling Forces: Hydrostatic pressure, Colloid oncotic pressure (concentration differences on opposites sides of semipermiable membranes)

P_{gc =} Pressure inside capaliary

P_BS = Pressure inside bowman's space

π = onoconic presure

P_gc trying to push fluic out of glomerlous while P_bs is trying to push water out of bowman's space (while onconic forces do the opposite)

Filtration barrier, Fenestrations -> holes in endothelial cells

Basement membrane (negativaely charge)

Filtration slits (space between podocytes)

High flow rates: 125ml/min, 180L/day

1.5>x>4.2nm gets filtered

P_GC - P_{BS =} 50mmHG

normally constant as arrangement of afferent and efferent arterioles (like adjustable resistors)

π_BS is small ~0 (low protien concentrations due to filtration barrier.

π_GC ~ 25mmHG at up stream side (constant efflux of plasma, causes protien conentrations to rise, so it increases pressure from afferent to efferent)

Bout halfway down the capilary (Depends on RPF)

allows for more filtration if needed

Higher RPF, equlib moves farther down the capillary

Afferent arteriole: Constriction leads to increased resistance and thus RPF & P_GC Decreasing, with the net effect of GFR decreasing

Efferent arteriole: Constriction leads to increased resistance, RPF decreases, P_GC increases, thus GFR increases at the beginning, but then decreases when RPF dominates

(surrounds tubule)

Supplies nutirents to intersitial space, resorb fluid from interstital space (obligated water from solute transport)

Resorption is possible because of efferent arteriole adn high resistance element.

Net pressure is ~ -12mmHg thus leads to resorption

Homeostasis of extracellular fluid

Urine can be concentrated or diluted (depends on water intake)

Lungs

Right Heart

Pulmonary circulation

Aveolus

Blood

Hyperosmotic concentrated 4x compared to plamsa

hhyposomonic dilute 10x to plasma

V = C_osm + H₂O

C_osm is osmolal clearance

Production rate of plain water C_H2O

C_osm = U_osm * V / P_osm

U = osmolality of urine

P = osmolality of plasma

If water is added to urine (diluted) (+), water diuresis

if water is removed (concentrated) (-) wter restriction (antidiuresis)

Transporters removes solutes from urine

occurs in the tubules

solutes resorbed by peritubule capilary

No water transporters

only way to remove is through osmosis

requires formation of hypertonic liquid (to pull water out of urine and collects in collecting ducts

Located within the renal medulla (pyramids)

it is generated by Henle's Loop (in juxtamadullary nephrons)

Needed for urine concentration

Generated by Henle's loop

Transport of NaCl (and urea)

differentially permability of tubule segments

counter current multiplier

Only juxtamedullary nephrons

Active transport across the tubule wall (to interstitium

Maximum concentration diff (200mOsm between interior and exterior)

called single effect (cannot explain total concentration gradient of 1200 which is why the countercurrent is the idea to multiply)

PST (top) permeable to water & NaCl

tDLH (permeable to water, low permeability to NaCl) middle section going down

TALH low permeability to water permeabile to NaCl (middle going up)

IC: All segments in equlib (in descending limb and Ascending limb)

TAL transports NaCl (gradients 200mOsm)

After many cycles creates gradient (multipled many times) (parallel difference is only 200mOsm signal effect)

Caused by the spatial orginization of the tubule

AVP levels (released by pituitary in brain into circulatory system)

binds to AVP receptor causing them to be more permeable

reducted ammount of water in body

Gas Exchange

Steps: ventilation: filling and emptying of lungs
Diffusion across aveoli membrane

uptake by red blood cells

transport to the tissue

1: Filling or inflow
2: isovolumic contraction phase
3: Outflow Phase
Isovolumic relaxation 

Systole = 2&3

Diastole = 4&1

rapid ventricular filling (then slow filling)

Ventricle pressure is less than veinous side of system, then equalizes. 

Atrial contraction (complete filling of ventricle)

Mitral and triscupid open 

Outlet valves are held shut by ststemic blood pressure

Aortic and pulmonary

ventricula rpressure must rise before they open
heart contracts to increase pressure (but no change in volume)
terminates with opening of semi-lunar valves

Pressure is greater than systemic

Rapid ejection phase(then slower, dictated by muscle fiber kinetics)
terminates with closing of semi-lunar valves (heart pressure is below systemic pressure

Pressure within the heart is below systemic 
above venous pressure

both inlet and outlet valves are closed (no change in volume)

Heart muscle relaxes, terminates when A/V/ valves open (heart pressures is below venus pressure)

Conservation of energy and momentum

Systolic is highest

Follows pressure and volume cure as a function of time

Cardiac cycle traces the loop

Can read off stroke volume, diastolic (point before linear drop) pressure, systolic pressure (max curve), work performed by heart (area in curve)

Respiration: Transports O, CO

Nutrition: Supplies carbs, amino acids, fats, ect

Excretion: removal of metabolic products, urea, creataine

Maintenance of Hydration

Maintenance of body temperature: supply and removal of heat

Regulation of tissue and organ function

Protection: delivery of antibodies, leukocytes

Responsiveness: meet various demands

Arteries (supply)
veins (return)

Capillaries (mass transport)

Autonomic nervous system

autoregulation

hormonal conrol

Pulmonary - right side (de-oxygenated)

Systemic - left ( oxygenated)

Deoxygenated blood from inferior and superior vena cava into right atrium

Right atrium contracts, blood flows through the triscuspid valve into right ventricle

Right Ventricle contracts: blood flows through the pulmonary valve (3 leafelets) out to the pulmonary arteries to lungs

Pulmonary vein fills left atrium

Left atrium contracts: blood flows through biscuspid (mitral) valve and fills left ventricle

Left ventricle contracts

blood flows through the aortic valve (3 leafelets) into Aorta into systemic cirulation

Mitral and tricuspid

End of leaflets are tethered to the wall by chordare tendinate

tension is regulated by small muscles (papillary muscles) 

Arteries: 25-1mm

Arterioles 30um

Pre-capillary sphincters: control resistance

capillaries 803um (exchange)

venules 30 um

veins 1-30mm

Regulation of pH:  buffer is carbonate

Blood Reserve

Filter: upper airways remove particulates

pulmonary circulation removes emboli and bubbles

Move fresh air into the lungs

move stale air out

System conducts air and has good gas exchange

conduits begin with nose/mouth-pharyn-laryn-trachea

Alveolus: sac 75-300 um diameter
made of very thin membrane

capillaries in close proximity

massive surface area SA = N*4pir^2 = 85m^2

Volume = N *4/3pir^3 = 4.2L

massive SA to V ratio for gas exchange. 

Seperates blood from air with a minimum barrier for diffusion

epithelial cells of the alveolus, Type 1, also surfactant

Spirometer: Measures moving volumes

Residual Volume (RV), Functional residual capacity (FRC)

Gas dilution techniques, Helium

Vl = V(Hei/Hef - 1)

For RV after forced expiration

For RFC after normal tidal breath

Volume of lungs not involved in gas exchange (conductinon airways w/out alveoli)

Use conservation of mass to measure (CO2)
Vin = Vout

Pco2 = Pco2 arterial blood

Vd = Vi * ((Pcoa-Pcol)/Pcoa))

Flow rate is dependent on effort and lung volume

@ full volumes: Dependent on effort

@ low volumes: indepndent on effort (being to collapse from the effort (increasing resistance to decreases flow rate)

inflation generates new surfaces, to overcome energy barrier

formation of the air- liquid interface, energy is supplied in the form of pressure 

lowers the tension at the liquid/air interface

mixture of amphipathic molecules (hydrophobic tail is in the air, hydrophilic head recuees the density of water at the interface.

Reduces the surface tension from 72 to 1 dyne/cm (reduces pressure needed to inflate alveoli)

(Issue w/ pre-mature infants) lungs do not have surfactant, diaphragms are not strong enough to inflate lungs

Energy to generate surfaces

pir^2*delP -2pir * stress

causes to aveoli to collapse and not  re-inflate

1/3 elastic tissue

2/3 surface tension

Edema 

Pneumonia

age

emphysema

Use Poiseuille's law

Q = -pi/8u * delP/L * a^4

Q ~ del P 

flow is laminar (transitional and turbulent too depnding on the velocity and other parameters)

Can be found from reynolds number pVd/u

d = characteristic dimension of the conduit (for long smooth circular pipe)

Rn ~1

Laminar flow del P ~1/Q

Turbulent flow P ~1/Q^2

fluid velocity is non laminar in upper airways

High flow velocities in upper airways (turbulent flow, higher resistances (moderate change in cross sectional area.

Pleural space: filled with fluid (due to elastic recoil & surface tension)

Resistance to flow, compliance dictating volume, pressure driving inflation 

PD= PR + PC

PR = pressure drop due to flow

PC = pressure sustaining inflation

Dependence of lung filling on R and C

Increase R, same C: Does not change max volume = CP_D, increase time constant (takes longer to fill the lungs, asthma)

Increased C, Same R: Max volume is increased, increased time constant (breakdown of elastin)

Movement of gas through alveolar wall -> pulmonary capillaries

Main mechanism is diffusion (transport of a solute in a stationary medium (medium - fluid or tissue, solute = solid/gasses))

P_atm = P_N2+P_o2+P_CO2+P_H2O

Equlibrium of gas and medium is based on partial pressures

α_HB is not a constant, it is a Function of P_o2 

The binding is cooperative 

Increase in alveolar wall thickness

Decrease of the diffusion constant (cystic fibrosis)

Decrease of the surface are (Pulmonary edema)
Decrease of hemocrit:C_{Hb (anemia)}

Decrease in rate constant K (abnormal Hb such as sickle cell anemia)

Main purpose of lung: Supply O2 to body 

Requires: ventilation of lungs for gas movement

perfusion of lungs for gas exchange (and distribution of O2)

Not homogenous (regional distribution of pulmonary blood flow)

Pulmonary circulation if low pressure (hydrostatic pressures affect perfusion)

In an upright position, upper and lower lungs have different flows)